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MIT HAN Lab 71

Nonuniform muscle fiber orientation causes spiral wave drift in a finite element model of cardiac action potential propagation. Reentrant tachyarrhythmias are thought to involve spiral waves of excitation and recovery that may be nonstationary. The effect of muscle fiber curvature on spiral and planar wave propagation was studied using a computational model. Two-dimensional anisotropic cardiac propagation was modeled using a finite element method to solve a modification of the FitzHugh-Nagumo equations. Spiral waves that propagated stably about a fixed core in tissue with a uniform fiber orientation were found to drift at an oblique angle to the fibers when the fibers curved. The drift velocity was linearly related to the fiber angle gradient and was 10% of the longitudinal propagation velocity with a gradient of 4 degree/cm. Planar wavefronts were also affected by fiber curvature. The maximal upstroke rate, propagation velocity, and the action potential amplitude all increased when the fibers curved toward the wavefront and decreased when they curved away. For example, when the fibers curved toward the wavefront with a moderate gradient of 15 degree/cm, maximal upstroke rate increased 74%, transverse propagation velocity increased 65%, and action potential amplitude increased 9%. This phenomenon caused the spiral wave drift: As a spiral wave traverses a cycle, the angle between the wavefront at the wavetip and the fibers changes periodically, thus altering the propagation parameters. These periodic changes affect the instantaneous radius of curvature of the wavetip path, which results in drift. Spiral and planar waves are affected by muscle fiber curvature. The resulting dynamics may be important in determining the lifetime and stability of reentrant arrhythmias.

Despite her obsessivequest to get Americans catching, spreading and, as a consequence, dying from coronavirus, Laura Ingraham also hopes nobody has the right to sue a business or employee that passed it on. After Donald Trump dangerously suggested injecting disinfectant as a treatment for COVID-19, then pretended he had been sarcastic when he clearly hadn’t, Laura Ingraham and her two-Trump worshiping guests shrugged off any possible deaths that might result, along with Trump's cowardly lie once he faced a backlash – and attacked anyone who might dare criticize Dear Leader. It hasn’t been 24 hours since Trump’s last medical improv show (press conference) during which Trump suggested that disinfectant injections just might be the ticket to a COVID-19 cure. But Trump’s Fox News website cheerleaders aren’t wasting any time defending Trump’s absurdist comedy stylings!

Q: yii2 losing user identity after login redirect i have looked at the other similar questions, and while this one (Yii2 user identity loss after page redirection) asks pretty much the same question, there is no solution that applies to my situation. i have created a new identity class, i have implemented all the necessary methods and implemented the IdentityInterface. note that it does NOT extend ActiveRecord, but rather extends my own base Model class that does not derive from AR. everything seems to work fine, i can log in and be correctly authenticated. i have traced the code and i can see that my identity class is correctly set in Yii::$app->user after IdentityInterface::validatePassword() and User::login() have been called. however, once the login succeeds and the user is redirected, Yii::$app->user contains an empty IdentityInterface, rather than the one that was there immediately prior to the redirect. in SiteController::actionLogin(), i have modified the code from: return $this->goHome(); to: $tmp = $this->goHome(); // echo '<pre>';var_dump(Yii::$app->user);echo '</pre>';exit; return($tmp); and i can see that Yii::$app->user still has the correct identity up until the return() statement. can anyone tell me why i am losing my identity? i have traced through everything i can think of: yii\web\Controller, yii\base\Controller, yii\web\Response, SiteController, yii\web\User, etc... any help at all would be greatly appreciated. thanks! A: Same problem, after 3 days find solution and I it working. My User model is: namespace app\models; use Yii; class User extends \yii\db\ActiveRecord implements \yii\web\IdentityInterface { public $username; /** * @inheritdoc */ public static function tableName() { return 'tbl_users'; } /** * @inheritdoc */ public function rules() { return [ [['name', 'email', 'password'], 'required'], [['email'], 'unique'], [['role', 'status'], 'integer'], [['created', 'last_update'], 'safe'], [['name', 'email', 'password'], 'string', 'max' => 250] ]; } /** * @inheritdoc */ public function attributeLabels() { return [ 'id' => 'ID', 'name' => 'Name', 'email' => 'Email', 'password' => 'Password', 'role' => 'Role', 'status' => 'Status', 'created' => 'Created', 'last_update' => 'Last Update', ]; } public function getAuthKey() { } public function getId() { return $this->id; } public function validateAuthKey($authKey) { } public static function findIdentity($id) { } public static function findIdentityByAccessToken($token, $type = null) { } public static function findByEmail($email) { return static::findOne(array('email'=>$email)); } public function validatePassword($password) { return $this->password === $password; } } I change: public static function findIdentity($id) { } to: public static function findIdentity($id) { return self::findOne(array('id'=>$id)); } It working for me. A: I had the same problem. I had my custom class implementing yii\web\IdentityInterface. I made sure that session was enabled and enableAutologin was also true, but I had no luck at all. Finally, I realized that in config/web.php there's a setting 'user' => [ 'identityClass' => 'app\models\User', 'enableAutoLogin' => true] Of course, the identityClass is the default in a basic yii application. After setting this value to my custom class, identity was finally persisted.

Gremio vs Cerro Porteno: Preview and Predictions Cerro Porteno are leading the group A of the 2018 Copa Libertadores by 2 points against Gremio. The Brazilians will be keen to reclaim the spot making use of the home advantage and with a win when these two teams meet on Tuesday evening. Gremio’s lone home match in the competition saw a dominant 4-0 victory over the Venezuelan outfit Monagas. But they had little luck in away trips so far, as they were held to a 1-1 draw at Defensor Sporting on matchday 1 before the goal-less stalemate at their Tuesday’s visitors Cerro Porteno. On the other hand, the Paraguayan club are performing above expectations up to this point. The draw against Gremio in a huge point, while away win at Monagas 2-0 and home win against Defensor set the platform for knockout qualification going into the second leg of fixtures. As we mentioned earlier, the teams are separated by 2 points at kick-off. A draw will do well to Porteno, but Gremio must win here since Defensor Sporting at third are at a 1 point gap. Gremio vs Cerro Porteno: Head-to-head Overall three meetings between the two teams at Copa Libertadores. Before the goal-less stalemate this season, Gremio won back to back games by 1-0 margins in 2007. So we are yet to see a match with more than 2 goals in their head-to-head clashes. Gremio vs Cerro Porteno: Predictions Historic data throw light to the fact that Gremio are a consistent home side in the competition. They won 7 of the last 8 here and lost just 2 of their last 19. Cerro Porteno did start their campaign with an away win at Monagas, but this is their first road win in the competition since 2011. They had lost in 10 of the previous 15 outings. Therefore, Gremio can be backed with confidence to win this fixture in style. Gremio vs Cerro Porteno: Bet Tips FT – Gremio to win @ 1.41 odd is a banker. Brave punters can give a shot at home win with Asian handicap -1.5 for 2.15 odds.

The BBC has been severely criticised on social media after ruling that BBC Breakfast presenter Naga Munchetty breached impartiality guidelines by suggesting that Donald Trump’s “Go home” comments directed at a number of BAME Congresswomen were “embedded in racism“. In off-script comments made earlier this year on the BBC Breakfast programme, Munchetty said she was “absolutely furious” about tweets posted by Donald Trump which suggested that four BAME Democratic Congresswomen – three of whom were actually born in the USA, with another arriving to the country as a child refugee – should “go home“: “Every time I have been told, as a woman of colour, to “go home” or “go back to where I came from”, that was embedded in racism.” “Now I’m not accusing anyone of anything here, but you know what certain phrases mean.” Munchetty went on to say: “I can imagine lots of people in this country will be feeling absolutely furious that a man in that position feels it’s OK to skirt the line of using language like that.” "I've been told as a woman of colour to 'go home'…"@BBCNaga shares her experience as we discuss the reaction to comments made by President Trump. pic.twitter.com/u0HL5tEdgt — BBC Breakfast (@BBCBreakfast) July 17, 2019 Immediately following her comments, Munchetty received praise on social media for calling out Donald Trump’s “blatant racism“. Sign up to be notified of new Evolve Politics articles Name Email* However, following a number of complaints made to the corporation, the BBC has now decided to rebuke Munchetty, declaring that her comments breached their impartiality guidelines. In an official statement, the BBC stated: “The ECU ruled that while Ms Munchetty was entitled to give a personal response to the phrase ‘go back to your own country’ as it was rooted in her own experience, overall her comments went beyond what the guidelines allow for.” The BBC’s decision to rebuke a BAME presenter for calling out unequivocally racist comments made by the US President came in for stinging criticism on social media, with one user stating: “I saw this interview live and thought @BBCNaga’s comments were balanced and relevant given the topic and her experiences as a woman of colour. I challenge anyone to provide an example where telling a person to “go home” to a different country isn’t steeped in racism or prejudice.” I saw this interview live and thought @BBCNaga's comments were balanced and relevant given the topic and her experiences as a woman of colour. I challenge anyone to provide an example where telling a person to "go home" to a different country isn't steeped in racism or prejudice. — Andrea Smart (@ThatSmartPerson) September 25, 2019 Whilst another Twitter user simply stated: “How can you ever be impartial over bigotry?“ Miqdaad Versi, a spokesman for the Muslim Council of Britain, said the BBC’s decision was “appalling“, writing on Twitter: “The BBC has ruled that factually stating Trump’s racist call (4 politicians to “go back” to their home countries), is “embedded in racism”, is apparently not OK for BBC journalists like the brilliant @BBCNaga Calling out racism is not partisan Appalling” The BBC has ruled that factually stating Trump's racist call (4 politicians to “go back” to their home countries), is "embedded in racism", is apparently not OK for BBC journalists like the brilliant @BBCNaga Calling out racism is not partisan Appallinghttps://t.co/ZoMJJNadzf — Miqdaad Versi (@miqdaad) September 25, 2019 Whilst Jess Brammar, the former Deputy Editor of the BBC’s Newsnight programme – now the Executive Editor for HuffPost – said she also thought her former employer’s decision was wrong, stating: “Been writing and deleting longer tweets on this, because it’s depressing and/but I love BBC & often defend it. I think Naga talking about her experience of racism was powerful television, I think it was fair for her to reference Trump’s comments in that context, which were racist” Been writing and deleting longer tweets on this, because it's depressing and/but I love BBC & often defend it. I think Naga talking about her experience of racism was powerful television, I think it was fair for her to reference Trump's comments in that context, which were racist — Jess Brammar (@jessbrammar) September 25, 2019 Munchetty herself has not yet responded to the BBC’s decision.

Fifty years ago evangelicals in Germany formed what became known as the Confessing Church. They opposed the German Christian Church Movement sponsored by the Nazis between 1933 and 1945. As Nazi dominance increased, the Confessing Church was forced underground. In 1935 the Confessing Church formed a preachers’ seminary near Zingst on the Baltic Sea, which soon moved to Finkenwalde. The principal and main teacher of the twenty-five students was Dietrich Bonhoeffer, a 29-year-old pastor and university professor from Berlin. Bonhoeffer led the students in a disciplined life together that included daily prayers, meditation, worship, study, recreation, and work. All the seminarians knew they lived on the edge of eternity in those frightening days. In September 1937 the seminary was closed by the Nazi police, and in November the seminarians were put under arrest. That same year Bonhoeffer published a book entitled, The Cost of Discipleship, and in September of 1938 put in book form the lessons of Finkenwalde entitled, Life Together. Here we have insights into how to be Christians in a community when life is being lived on the brink. In March 1943 Bonhoeffer participated in an attempt to assassinate Adolf Hitler. He was arrested April 5, and two years later, April 9, 1945, Bonhoeffer was hanged by the Gestapo in the Flossenberg concentration camp at the age of 39. One of his students in the Finkenwalde days recollected, Bonhoeffer wanted a genuine, natural community in the Preacher’s Seminary, and this community was practiced in play, in walks through the richly wooded and beautiful district of Pomerania, during evenings spent in listening to someone reading, . . . in making music and singing, and last not least in worship together and holy communion. He kept entreating us to live together naturally and not to make worship an exception. He rejected all false and hollow sentiment. (I Knew Dietrich Bonhoeffer, 155) The Testimony of Bonhoeffer’s Life Together Bonhoeffer’s little book, Life Together, is a word for our times because we are plagued in America by a kind of laissez-faire Christianity that lacks the vigorous camaraderie and discipline that unites a kingdom in wartime. We don’t have a wartime mentality and therefore our young men and women do not gather late at night in basement rooms and plot their strategies to detonate Satan’s bridgehead and liberate some of his captives. We don’t see ourselves as insurgents in the alien territory of sin planting explosives of righteousness and truth at every fortified wall; and so our eyes don’t meet with a flame of eternal friendship on Nicollet Mall and say without a word amid a thousand aliens: “You and I will die for this cause and join hands in the resurrection.” We don’t feel like a fifth column devoted with all our strength to sabotage the rule of Satan in this world; and therefore our life together is not intense but petty. There are no coded handshakes of joy, or secret passwords. And there are few tearful embraces and songs of thanks because a squad of witnesses has returned safely even bringing some liberated captives home. Bonhoeffer’s words about “life together” have the ring of authenticity for us because they were written not at the nerve center of comfort but on the brink. They have the taste of radical commitment that all of us dream about, many of us crave, and only a few pursue. He wrote, The physical presence of other Christians is a source of incomparable joy and strength to the believer . . . It is true, of course, that what is an unspeakable gift for the lonely individual is easily disregarded and trodden underfoot by those who have the gift every day . . . Among earnest Christians in the Church today there is a growing desire to meet together with other Christians in the rest periods of their work for common life under the Word. Communal life is again being recognized by Christians today as the grace that it is, as the extraordinary, the “roses and lilies” of the Christian life. (Life Together 8–10) Then Bonhoeffer comes to a very solemn point that I want to emphasize this morning. He writes, If somebody asks [a Christian], Where is your salvation, your righteousness? he can never point to himself. He points to the Word of God in Jesus Christ, which assures him of salvation and righteousness. He is as alert as possible to this Word. Because he daily hungers and thirsts for righteousness, he daily desires the redeeming Word . . . But God has put this Word into the mouth of men in order that it may be communicated to other men. When one person is struck by the Word, he speaks it to others. God has willed that we should seek and find His living Word in the witness of a brother, in the mouth of a man. Therefore, the Christian needs another Christian who speaks God’s Word to him. He needs him again and again when he becomes uncertain and discouraged, for by himself he cannot help himself without belying the truth. He needs his brother man as a bearer and proclaimer of the divine word of salvation. He needs his brother solely because of Jesus Christ. The Christ in his own heart is weaker than the Christ in the word of his brother; his own heart is uncertain; his brother’s is sure. (Life Together, 11–12) The Means of Persevering to the End Turn with me to Hebrews 3:12. I want to show you from Scripture how true and essential Bonhoeffer’s words are for us today at Bethlehem. The question to ask yourself as we read these verses is: How important is it to live with other Christians in such a way that I can give to them and receive from them the word of God every day? Take care, brethren, lest there be in any of you an evil, unbelieving heart, leading you to fall away from the living God. But exhort one another every day, as long as it is called “today,” that none of you may be hardened by the deceitfulness of sin. For we share in Christ, if only we hold our first confidence firm to the end. Three observations from this tremendously important text: Sin wages a constant battle to deceive and harden the hearts of professing Christians. If it succeeds, a person slips into unbelief and falls away from the living God. The evidence and confirmation of whether we have any share in Christ is whether we hold our first confidence firm to the end. Hebrews sees two possibilities for professing Christians: either they hold fast their first confidence to the end and show that they have really become sharers in the life of Christ, or they become hardened by the deceitfulness of sin and fall away from God with a heart of unbelief and show that they did not have a share in Christ. The means appointed by God to enable the saints to persevere to the end is daily exhortation from other saints. “Exhort one another every day as long as it is called ‘today,’ that none of you may be hardened by the deceitfulness of sin.” “The saints will persevere to the end and be saved.” Twitter Tweet Share on Facebook It is written that the saints will persevere to the end and be saved. Those who have become sharers in Christ by the new birth will hold their first confidence to the end and be saved. But one of the evidences that you are among that number is that when God reveals in his holy word the means by which you will persevere, you take him very seriously, you thank him, and you pursue those means. This text makes it very clear that the means by which God intends to guard us for salvation (1 Peter 1:5) is Christian community. Eternal security is a community project. Not just prayer, not just worship, not just the sacraments, not just Bible reading, but daily exhortation from other believers is God’s appointed means to enable you to hold your first confidence firm to the end. The Imperative of Meeting Together One of the most important questions facing the leadership of this church is: What should we do to encourage and enable you to live together or meet together in smaller groups where you can obey this text and exhort each other with the promises and warnings and commands of Scripture? How can we make the priesthood of all believers a reality? How can we help you to form the kind of group life or community life that makes Hebrews 3:13 a fact and not a fairy tale? “Exhort one another every day, as long as it is called ‘today,’ that none of you may be hardened by the deceitfulness of sin.” Part of the answer for us at Bethlehem is given in Hebrews 10:23–25. Here the writer is concerned not only how to help people hold fast their faith but also how to help them become ablaze with love. Faith toward God and love toward men — how shall they be stirred up and preserved? Let us hold fast the confession of our hope without wavering, for he who promised is faithful; and let us consider how to stir up one another to love and good works, not neglecting to meet together, as is the habit of some, but encouraging (same word as in 3:13) one another, and all the more as you see the Day drawing near. The closer we get to the second coming of Christ, the more we ought to meet together to encourage each other to hold fast our hope and to pour ourselves into acts of love. The text envisions not just haphazard meetings on the street but planned gatherings for the purpose of exhortation. Bonhoeffer said, “The physical presence of other Christians is a source of incomparable joy and strength to the believer.” Hebrews says: “Meet together!” “Meet together!” Meet in homes. Meet at work. Meet in restaurants. Don’t neglect meeting. How else can we exhort each other to hold fast to our confidence? How else can we stir each other up to love and good works? And when you meet, don’t throw it away with glib conversation: Consecrate it with the Word of God and prayer. Do you see the warning in this text? “Don’t neglect to meet together, as is the habit of some.” Professing Christians are always in danger of forming the habit of not meeting with other Christians to encourage and be encouraged in faith and love. Have you fallen out of that habit? Are you a part of a regular gathering of Christians which is small enough so that you can give and receive personal exhortation from Scripture? Bonhoeffer was speaking biblical truth when he said, “A Christian needs another Christian who speaks God’s Word to him. He needs him again and again when he becomes uncertain and discouraged.” Three Relationships Every Believer Must Pursue Let me try to put this ministry in a wider context. Over the past year, the pastoral staff has worked through a philosophy of ministry that shapes what we do and how we plan. That philosophy says that there are three relationships of life which every maturing believer must pursue. First, and most important, is your personal relationship with God, characterized by trust, devotion, worship, and obedience. Second is your relationship with other believers in the body of Christ, characterized by mutual exhortation to strengthen each others’ faith and stir each other up to love. Third, and flowing out from the first two, is your relationship to unbelievers and to Christ’s global purpose of redemption, characterized by witness in words of hope and deeds of love. Now you can see the wider context of today’s message. Last Sunday provided the biblical foundation of priority number one: going hard after the holy God. Today provides the biblical foundation for priority number two: helping each other endure to the end as believers. Next Sunday, Lord willing, will provide the biblical foundation for priority three: extending to unbelievers the joy of salvation. “Our relationships will be deepened if we focus our attention and affection on God himself.” Twitter Tweet Share on Facebook A radical, all out God-centeredness will remain priority number one under our leadership at Bethlehem — I don’t think you would have it any other way. That’s why we stress worship and seek to guard this one hour in the week from the ever-present encroachments of the horizontal. All our relationships with each other and with the world will be deepened and empowered and purified if in this hour we focus our minds’ attention and our hearts’ affection on God himself. Even when I preach, as I am today, about the horizontal dimension of life in Christ, I try to do it in such a way that it is not chatty or familiar, but rather has behind it the authority of God, the aroma of his sovereignty, and the tremendous seriousness of heaven and hell. The Calling of Pastors-Teachers From this philosophy of ministry and from Ephesians 4:12 we believe that we are called as pastor-teachers to study the word of God and to pray and to equip you to do the work of the ministry — ministry toward God in worship, ministry toward each other in biblical exhortation, and ministry to the world in witness. Nothing will bring us more joy than to see our people growing to maturity in each of these priorities while the Lord adds many people to the church. We will be praying and thinking and planning in this year how we can better help you to exhort each other every day lest there be in any of you an evil heart of unbelief. We will be studying how we can successfully urge you all to be a part of a regular meeting of Christians small enough to allow you to give and receive personal biblical exhortation to help you fight the fight of faith and be fired up to love and good works. We Are in Wartime In the meantime, why don’t you go ahead and take the initiative to seek out some fellow-believers? If we knew that the Gestapo was closing in on us, if we knew that at any time some could disappear from our number never to be heard from again, we would gather often in our homes and in secret rendezvous to strengthen our hands in God. And love would cover a multitude of sins, and our handshakes and embraces and the meetings of our eyes would be like gifts of roses and lilies from the bottom of the heart. Well, we are in wartime. We are in enemy territory. Thousands of lives hang in the balance. The danger of hard hearts and unbelief and cool love and American luxury lurks everywhere. Oh, how we need to exhort one another every day to have strong confidence of victory in Christ, and to dream of new strategies of love to sabotage the enemy’s concentration camps of unbelief! Last Friday I called Daniel Fuller in Pasadena to ask if I could quote a letter he sent me a few weeks ago. He is a priceless friend and Professor of Hermeneutics at Fuller Seminary, and son of Charles Fuller. He is a mature Christian with more knowledge of Scripture than anyone in this room. Therefore what he says should inspire all of us to obey Hebrews 3:13. He wrote,

Many systems require digital processing even when the input and/or output signals are analog signals. This is often the case, for example, in the context of conventional speed or transmission (e.g., engine transmission) sensing systems. In at least some such conventional sensing systems, speed is sensed by detecting zero crossings of a magnetic field that occur as magnetic teeth on a wheel rotate past a magnetic sensor (e.g., a Hall sensor, an anisotropic magnetoresistance (AMR) sensor, a tunnel magnetoresistance (TMR) sensor, or a giant magnetoresistance (GMR) sensor) and induce change(s) in the output voltage of the magnetic sensor. In such embodiments, after each zero crossing, the supply current of the sensor is set to a new level. Additionally, in such embodiments, all calculations on the incoming signal are performed digitally, so the supply current can only change after an edge of the internal clock signal. This limits the accuracy of the zero-crossing detection, and the quantization in the time domain adds to the overall jitter of the system. Referring to FIG. 1, a first graph 100, second graph 102, and third graph 104 collectively illustrate how variations in the timing of a clock signal relative to the timing of an input signal 106 can result in significantly different output signals and corresponding jitter. More particularly, the first graph 100, second graph 102, and third graph 104 respectively illustrate a first clock signal 108, second clock signal 110, and third clock signal 112, respectively. Although the first, second, and third clock signals 108, 110, and 112 share in common the same frequency, the three clock signals are slightly out of phase relative to one another. Consequently, as shown in the first, second, and third graphs 100, 102, and 104, the first, second, and third clock signals 108, 110, and 112 respectively have first, second, and third values 114, 116, and 118, respectively that differ from one another at a time 120 at which the input signal 106 crosses zero occurs. More particularly, the first value 114 of the first clock signal 108 is a minimum value of that clock signal at the time 120, the third value 118 of the third clock signal 112 is a maximum value of that clock signal at the time 120, and the second value 116 of the second clock signal 110 is a transitional (downward edge) value of that clock signal at the time 120 that can be considered to be in between (e.g., a zero value) of the second clock signal 110. Because of this variation in the relative timing of the first, second, and third clock signals 108, 110, and 112 relative to one another and relative to the input signal 106, as further illustrated in FIG. 1 virtual phase error is introduced into output signals generated based upon the interplay of the input signal 106 and the clock signals 108, 110, and 112. More particularly, in the first graph 100, it can be seen that a first output signal 122 is step-shaped and includes a series of steps 124 that are each of equal height and width relative to the preceding step, that a first step 126 of the series of steps 124 occurs a first time differential 128 after the time 120, and that the series of steps has an effective slope represented by a dashed line 130. By comparison, in the second graph 102, it can be seen that a second output signal 132 also is step-shaped and includes a series of steps 134 that are each of equal height and width relative to the preceding step, that a first step 136 of the series of steps 134 occurs a second time differential 138 after the time 120, and that the series of steps has an effective slope represented by a dashed line 140. Additionally by comparison, in the third graph 104, it can be seen that a third output signal 142 also is step-shaped and includes a series of steps 144 that are each of equal height and width relative to the preceding step, that a first step 146 of the series of steps 144 occurs a third time differential 148 after the time 120, and that the series of steps has an effective slope represented by a dashed line 150. In view of these considerations, as further illustrated in FIG. 1, the first, second, and third output signals 122, 132, and 142 are not in phase within one another even though the three output signals are all generated based upon the same input signal, namely, the input signal 106. More particularly, it can be seen from the first graph 100 that a first virtual starting point 152 of the first output signal 122, namely, the point at which the dashed line 130 crosses an initial (e.g., zero) level 154 of the first output signal, occurs a first time amount 156 in advance of the time 120. By contrast, it can be seen from the second graph 102 that a second virtual starting point 162 of the second output signal 132, namely, the point at which the dashed line 140 crosses an initial (e.g., zero) level 164 of the second output signal, occurs a second time amount 166 in advance of the time 120 that is less than the first time amount 156. And further by contrast, it can be seen from the third graph 104 that a third virtual starting point 172 of the third output signal 142, namely, the point at which the dashed line 150 crosses an initial (e.g., zero) level 174 of the third output signal, occurs a third time amount 176 in advance of the time 120 that is less than each of the first time amount 156 and the second time amount 166. Accordingly, because of the differences in the timing of the clock signals 108, 110, and 112, the output signals 122, 132, and 142 are out of phase relative to one another, and such differences correspond to the producing of jitter in the overall output signal during operation in which a given clock signal varies in its phase over time. Although efforts have been made to develop modified systems and methods for signal processing to alleviate such concerns, such modified systems and methods have other disadvantages. For example, one manner of addressing the above-discussed problems relating to jitter and associated inaccuracy involves increasing the clock frequency to a level at which the clock is no longer the dominant jitter source. However, this strategy can result in increased total power consumption and necessitate higher timing constraints on the digital signal processing, neither of which are desirable. For at least these reasons, therefore, it would be advantageous if one or more improved systems and methods for signal processing could be developed that addressed one or more of these concerns or disadvantages relating to jitter, and/or one or more other concerns or disadvantages.

Our APK Insight into the new Google Home app this week revealed a new “Gaming preferred” setting for Google and Nest Wifi. Intended for Stadia, a support document now details what network prioritization will be occurring when this preference is enabled. Google describes how the “best gaming experience” requires a “fast pathway to and from cloud servers without being overly delayed by an underperforming router or competing traffic on the same network.” The former is a ding on other networking devices, while the latter is unavoidable in a modern smart home. With “Gaming preferred” enabled, Nest Wifi (and presumably the first-generation Google Wifi given their interoperability) “automatically optimizes your Stadia traffic.” This works regardless of whether you’re using a Chromecast Ultra, desktop, laptop, or mobile device, and does not require any other user tuning. Gaming preferred prioritizes Stadia so your gameplay doesn’t get slowed down by other devices or activities on your network, like someone streaming TV or browsing the web in the other room. Gaming preferred will work when you’re playing games on Stadia. While the setting is on by default after setting up Made by Google routers, the company notes how it’s only active when you’re streaming a game from Stadia. This being a feature exclusive to first-party connectivity equipment speaks to how Stadia could possibly advertise Made by Google gear as ensuring the absolute best gaming experience come November 19th. Full instructions for toggling on/off are available below: Open the Google Home app . Choose Wi-Fi . Select Settings in the top corner. Toggle “Gaming preferred” on or off . Update 12/11: First available in the Google Home app for the new Nest Wifi, “Gaming preferred” is now available for the old Google Wifi following an update (version BV10175_RC0005) to the companion app. Disabled by default, the option is somewhat hidden: Settings tab > Network & General > Advanced networking > Gaming preferred (at the very bottom) More about Google Stadia: FTC: We use income earning auto affiliate links. More. Check out 9to5Google on YouTube for more news:

Q: sharing a single service across multiple angular 5 applications I'm running multiple small angular 5 applications as widgets inside my backbase application. Now I'm trying to write a global service, which is at window level, and share across all applications. Currently, I'm making the service static and using in each widget and using webpack to create widget specific bundle. Here I was able to achieve http caching with rxjs operators. But I feel this might not be the right way to implement it. Is there any better way to share a singleton service across multiple angular 5 applications in a single project. A: Previously if you want to share something between multiple Angular projects that was pretty tricky. You'll have to do one of the following: Create a package contains shared code and publish it to private or public NPM registry Create a GIT submodule and reference it on both of your projects But now I'm guessing the Library support introduced in Angular 6 would suits your needs the best. For details see: Angular - Creating Libraries It's similar to publish your shared package to NPM but Angular CLI (and ng-packagr) really made it super simple. A: Technically one of your modules ("main" module) can export its own service via window object, other modules ("clients") can inject wrapper service: class ServiceWrapper implements IService { private readonly instance:IService; constructor(){ this.instance = window['myService'] as IService; } public someMethod():void { this.instance.someMethod(); } }

Q: Is this considered bad attitude? In my post Imagine I'm on a spacecraft that was accelerated to 1.0$c$ could I only move backwards?, I asked something that came into my mind and I wasn't able to find an answer for it here. After I posted it, the list of related posts (the list under the title before posting didn't!) showed a question what seemed to be the same. I had a look, found there my answer and marked my post as dupe of that one. Now after that was done I'm getting more and more downvotes for it. What might this reason be? Should I have deleted the post instead? A: No, you have done the right thing. With some many questions on the site it's very easy to miss the fact that a duplicate exists, and to be fair the site search isn't as great as it could be. Don't attach too much significance to the downvotes. It's easy to feel that downvotes are a personal criticism, but really they are just a statement that the question isn't appropriate for the site. Personally I don't downvote duplicates just because they are duplicates, though I know some site members feel differently. Downvoting does remove the question from the site home page, so there is an argument that a question should be downvoted when we don't want it to appear there. Maybe that's why you have the two downvotes. I believe that it's generally bad form to delete a question. I can't remember the reasons for this, but I'm sure I have seen comments from the moderators that in general questions shouldn't deleted. Just leave the question - there is an automated cleanup process for downvoted questions that springs into life after a couple of weeks. For what it's worth you should be congratulated for responding to the duplicate link, reviewing the duplicate and deciding that your question is indeed answered by the existing one. Too many people just abandon their duplicate questions and leave it to the moderators to close. A quick footnote to summarise David's comments below: I was a bit hasty to suggest you shouldn't delete your question. The Stack Exchange has various checks to detect users who it thinks aren't being serious, and it will eventually block those users from asking any more questions. One of the criteria it uses is the number of times the user asks a question then deletes it - hence my vague memory that deleting your own questions is a bad thing. However deleting one question, or even a few questions, isn't likely to cause a problem. So you should feel free to delete your question if you want to. A footnote to the footnote: As it happens the issue of how deleted questions affect your status has just arisen in the question What is the "positive question record"?. This explains why having lots of deleted question is bad.

[Cite as Parma v. Horky, 2019-Ohio-4886.] COURT OF APPEALS OF OHIO EIGHTH APPELLATE DISTRICT COUNTY OF CUYAHOGA CITY OF PARMA, : Plaintiff-Appellee, : No. 107968 v. : ZACHARY P. HORKY, : Defendant-Appellant. : JOURNAL ENTRY AND OPINION JUDGMENT: VACATED RELEASED AND JOURNALIZED: November 27, 2019 Criminal Appeal from the Parma Municipal Court Case Nos. 18-CRB-03100 and 18-CRB-03492 Appearances: Timothy G. Dobeck, Parma Law Director, and John J. Spellacy, Assistant Prosecuting Attorney, for appellee. Mark A. Stanton, Cuyahoga County Public Defender, and Cullen Sweeney, Assistant Public Defender, for appellant. KATHLEEN ANN KEOUGH, J.: Defendant-appellant, Zachary P. Horky (“Horky”), appeals his convictions in two cases that were consolidated for appeal. For the reasons that follow, we vacate his convictions and order Horky discharged.  In 2018, Horky was charged in the Parma Municipal Court in two different cases with one count each of criminal child enticement in violation of Parma Codified Ordinances 636.075. He pleaded not guilty in both cases, and the matter proceeded to a bench trial. During its opening statement, the city amended the charge in each case to criminal child enticement in violation of R.C. 2905.05, the state statute containing nearly identical language to that of Parma Codified Ordinances 636.075. After hearing all the evidence, the court found Horky guilty in both cases and sentenced him in each case to a $250 fine and 180 days in jail; the sentences were ordered to be served consecutively. Horky’s sentence was immediately ordered into execution. The trial court subsequently denied Horky’s request for bond and to stay execution of his sentence pending appeal. Subsequently, this court granted Horky’s motion for an appellate bond and suspended the execution of his sentence pending appeal. Horky now appeals, raising three assignments of error of our review. I. Final Appealable Order At the outset, the city of Parma contends that Horky’s judgment entries of conviction are not final appealable orders; thus, this court lacks jurisdiction to consider his appeal. Specifically, the city contends, without citation to any authority, that because the judgment entries of conviction do not identify the subsection of R.C. 2905.05 of which Horky was found to be in violation, there is an ambiguity that renders the entries not final or appealable. We disagree.  Crim.R. 32(C) specifies what a judgment entry of conviction must contain: “A judgment of conviction shall set forth the plea, the verdict, or findings, upon which each conviction is based, and the sentence.” “A judgment of conviction is a final order subject to appeal under R.C. 2505.02 when it sets forth (1) the fact of the conviction, (2) the sentence, (3) the judge’s signature, and (4) the time stamp indicating the entry upon the journal by the clerk.” State v. Lester, 130 Ohio St.3d 303, 2011-Ohio-5204, 958 N.E.2d 142, paragraph one of the syllabus. In this case, the judgment entries of conviction satisfy all four requirements: (1) each provides that Horky was convicted of criminal child enticement, (2) states his sentence for the offense, (3) is signed by the trial judge, and (4) is time stamped. The fact that they do not contain the code subsection of the charge upon which Horky was found guilty does not make the judgment entries not final nor unappealable. See, e.g., State v. Baker, 119 Ohio St.3d 197, 2008-Ohio- 3330, 893 N.E.3d 163 (journal entry of conviction final and appealable where it only identified the names of the offenses the defendant was convicted; not the code section). Accordingly, this appeal is properly before this court. II. Unconstitutional Statute In his first assignment of error, Horky contends that his convictions violate due process and are otherwise invalid because they are based on R.C. 2905.05(A) — a statute that has been declared unconstitutional by the Ohio Supreme Court in State v. Romage, 138 Ohio St.3d 390, 2014-Ohio-783, 7 N.E.3d 1156. The state contends that the Ohio Supreme Court did not find R.C. 2905.05 unconstitutional in its entirety, but rather only declared subsection (A) unconstitutional. The city seems to contend that Horky’s journal entries of conviction do not indicate the subsection of which Horky was found guilty; thus, Horky’s convictions should be upheld because it is possible he was convicted of R.C. 2905.05(B) or (C). R.C. 2905.05, criminal child enticement, provides, in relevant part: (A) No person, by any means and without privilege to do so, shall knowingly solicit, coax, entice, or lure any child under fourteen years of age to accompany the person in any manner, including entering into any vehicle or onto any vessel, whether or not the offender knows the age of the child, if both of the following apply: (1) The actor does not have the express or implied permission of the parent, guardian, or other legal custodian of the child in undertaking the activity. (2) The actor is not a law enforcement officer, medic, firefighter, or other person who regularly provides emergency services, and is not an employee or agent of, or a volunteer acting under the direction of, any board of education, or the actor is any of such persons, but, at the time the actor undertakes the activity, the actor is not acting within the scope of the actor’s lawful duties in that capacity. (B) No person, with a sexual motivation, shall violate division (A) of this section. (C) No person, for any unlawful purpose other than, or in addition to, that proscribed by division (A) of this section, shall engage in any activity described in division (A) of this section. In Romage, the Ohio Supreme Court held that R.C. 2905.05(A) is unconstitutionally overbroad because it “sweeps within its prohibitions a significant amount of constitutionally protected activity.” Id. at syllabus. See also Cleveland v. Cieslak, 8th Dist. Cuyahoga No. 92017, 2009-Ohio-4035 (finding that Cleveland Codified Ordinances 609.09, criminal child enticement, is unconstitutionally overbroad). In this case, the city does not dispute that R.C. 2905.05(A) was declared unconstitutional, but contends that Horky’s convictions should be upheld because it is possible he was found guilty of R.C. 2905.05(B) or (C), which was not stricken by Romage. The city, however, ignores a plain reading of the record that reveals that the city undoubtedly prosecuted Horky for violating R.C. 2905.05(A). First, at the time that the city amended the charge from the city code to the state code of R.C. 2905.05, the prosecutor stated: And it says that no person by any means and without privilege to do so shall knowingly solicit, coax, entice or lure any child under 14 years of age to accompany the person in any manner including entering into a vehicle or onto any vessel whether or not the offender knows the age of the child if both of the following apply and so it mimics, it is the exact same language that’s contained in the Parma Codified Ordinance. (Tr. 4-5.) This quoted language is expressly derived from subsection (A) of R.C. 2505.05. At no time did the city add the additional elements contained in subsections (B) or (C) of R.C. 2505.05 when making the amendment. Additionally, during both opening and closing arguments, the city maintained that Horky was guilty of criminal child enticement by continuing to quote from R.C. 2905.05(A). During opening statements, the prosecutor stated: Your honor we believe that the City will prove beyond a reasonable doubt each and every essential element of the crime of Child Enticement and that is that Mr. Horky did knowingly solicit, coax, entice, or lure a child under 14 years of age to accompanying [sic] the person in any manner. And then it goes on to say if both of the  following apply and (a) no express or implied permission of any parent or guardian and [b] the actor is not a law enforcement officer. (Tr. 3-4.). During closing argument, the prosecutor stated: I believe the evidence is pretty clear that the Defendant is Guilty of Two Counts of Child Enticement. One on or about July 13th 2018, one from July 16th 2018, the statute is pretty clear, specifically the elements are to knowingly solicit, coax, entice or lure a child under 14 years of age to accompany the person in any manner if both of the following apply [a)] there is no expressed or implied permission of the parent or guardian and b) the actor is not a law enforcement officer, etc., well he certainly is not a law enforcement officer, he certainly, clearly did not have permission contrary to his testimony. (Tr. 108.) Based on these arguments at trial, the record clearly demonstrates that the city prosecuted Horkey under R.C. 2505.02(A). Finally, the record does not support the city’s theory that Horky may have been convicted of either R.C. 2905.05(B) or (C) because at no time during trial did the city argue or even mention the presence of the additional element found in subsection (B) — prohibiting a violation of subsection of (A) “with a sexual motivation;” or the additional element found in subsection (C) — prohibiting a violation of subsection (A) “for any unlawful purpose.” In fact, the record clearly rebuts the possibility that Horky was convicted of violating either subsections (B) or (C), both of which require some unlawful intent, because the prosecutor specifically stated during closing that: Whether [Horky’s] intentions were completely good or not doesn’t matter pursuant to the statute, has no bearing on the statute, this is for the protection of kids and he violated the statue. (Tr. 108.)  Based on the record before this court, we find that Horky’s due process rights were violated when he was prosecuted and convicted of violating a statute that was previously declared unconstitutional. The assignment of error is sustained. Because we find merit to his first assignment of error, Horky’s second and third assignments of error, which challenge the effectiveness of his trial counsel and sufficiency of the evidence, are rendered moot. See App.R. 12(A)(1)(c). Judgment vacated; Horky is ordered discharged from the sentences imposed. It is ordered that appellant recover from appellee costs herein taxed. The court finds there were reasonable grounds for this appeal. It is ordered that a special mandate issue out of this court directing the Parma municipal court to carry this judgment into execution. A certified copy of this entry shall constitute the mandate pursuant to Rule 27 of the Rules of Appellate Procedure. KATHLEEN ANN KEOUGH, JUDGE MARY J. BOYLE, P.J., and RAYMOND C. HEADEN, J., CONCUR 

Since saying "I do" to the International Olympic Committee in 1998 the National Hockey League and Winter Games have endured an often tumultuous relationship, one that ended last year in an acrimonious separation. In sporting terms this had been an arranged marriage and after five consecutive Winter Games together the NHL, feeling unappreciated and taken advantage of, told the IOC their players would not compete at the Games in Pyeongchang, South Korea. During protracted negotiations to get the world's best ice hockey players to the Olympics there had been plenty of finger pointing and take-it-or-leave-it ultimatums. The NHL, already convinced it could get by just fine without the exposure offered by the Olympics, relaunched its World Cup of Hockey in 2016 and made that tournament its top international commitment. The jilted IOC huffed and warned NHL Commissioner Gary Bettman not to come knocking in four years time when the 2022 Olympics will be in Beijing, a market that every major sports league covets. While NHL players will not be in South Korea for the Feb. 9-25 Olympics, the league has already begun flirting with China having staged their first exhibition games there last September. International Ice Hockey Federation president Rene Fasel said this month it is his mission to get the NHL back on Olympic ice while NHL Players Association head Donald Fehr said the players want to return to the Winter Games. "The Olympics is a unique event and it provides not only an opportunity to play at an elite level but there's a real element of patriotism and national pride that's involved and it matters a lot," Fehr told Reuters. "I think that it is very likely as we go forward that getting back into the Olympics will be something the players will want to pursue." "It will be a significant issue." New CBA could impact future Olympics Significant enough that the Olympics will be a carrot dangled when players and owners negotiate a new collective bargaining agreement sometime between now and 2022. It remains to be seen what the players might be willing to give up to get back on the global stage that is offered by the Winter Games. When the NHL dangled Pyeongchang participation in front of the NHLPA in exchange for an extension of the current CBA the proposal was flatly rejected. "From my personal standpoint not only do the players want to participate in it but I think that participation in the Olympic Games, if it is handled right, is a very significant potential marketing and exposure opportunity for NHL players and therefore NHL hockey," said Fehr. "I would hope that we get to the point where that is recognised." 'Huge opportunity' in China While the NHL saw little upside in shutting down operations for almost three weeks to accommodate Olympic participation, the 2022 Beijing Games represent a gateway into the Chinese market. To grow hockey in China the NHL will need infrastructure and the Chinese government and businesses have already displayed a keen interest in helping the cause by building ice rinks. "I guess they [NHL] are a little late to the [China] party but better to do it right than do it fast," David Carter, executive director at the USC Sports Business Institute and a member of the Los Angeles Kings advisory board, told Reuters. "They would more likely look back and rue the day they didn't figure this thing out than looking back and saying it was a wise move to forego the Games. "It is a big market to penetrate and it is something that has captivated people in sport business for awhile. "But that doesn't get you anywhere unless the home country is willing to spend time, money and invest capital in it." The key to getting the NHL back on board for the 2022 Games will not be as simple as the lure of tapping into a new market. The NHL has long bristled at paying for the privilege of competing at the Olympics while, in their view, getting very little in return beyond the prestige and a two-week global platform for their product. "China is a completely different economic opportunity than South Korea," Neal Pilson, head of Pilson Communications and former president of CBS Sports, told Reuters. "There was really no way to figure out any possible benefit for the NHL allowing its players to play in South Korea but the league could negotiate a much better deal for its ownership when you are talking about teams, the league, the sport growing in China. "I know they are thinking about how they can develop hockey in that nation. "China is a huge opportunity for the NHL."

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Eslamabad-e Sofla, Ilam Eslamabad-e Sofla (, also Romanized as Eslāmābād-e Soflá; also known as Eslāmābād) is a village in Zarrin Dasht Rural District, in the Central District of Darreh Shahr County, Ilam Province, Iran. At the 2006 census, its population was 940, in 212 families. References Category:Populated places in Darreh Shahr County

Carntown, Kentucky Carntown is an unincorporated community in Pendleton County, in the U.S. state of Kentucky. History A variant name was Motier. A post office called Motier was established in 1839, the name was changed to Carntown in 1891, and the post office closed in 1920. Jacob Carnes, one of the early postmasters, gave the community its present name. References Category:Unincorporated communities in Pendleton County, Kentucky Category:Unincorporated communities in Kentucky

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Q: $E[X^4]+E[X]^4 \geq 2E[X^2]^2$ for $X \geq 0$ I was wondering whether this inequality is actually true. It seems to hold for discrete distributions, for the Normal and the Poisson distribution. Furthermore, after applying AM-GM, it can be seen that a sufficient condition for this inequality to hold is the following inequality $$ \|X\|_4 \|X\|_1 \geq \|X\|_2^2 $$ where the norms are the respective norms in $L_p$. A: No. Consider $X$ following a Bernoulli distribution with parameter $p\in[0,1]$. Then, since $X^4 =X^2 = X$, your inequality is equivalent to $\mathbb{E}[X]+\mathbb{E}[X]^4 \geq 2\mathbb{E}[X]^2$, i.e., $$ p + p^4 \geq 2p^2 $$ which is not always true for $p\in[0,1]$. (E.g., it fails for $p=3/4$).

Charly's Column Incoming TCP connections do not always end up where they are supposed to. A freely configurable redirector points digital debris in the direction of a new and better place. Just a little while back we discussed Rinetd [1], a TCP redirector. Rinetd is lean, reliable, and easy to configure; on the downside, it lacks some advanced features. This month I’ll examine Portfwd, a tool that includes some of those features missing from Rinetd. Portfwd (Port Forwarding Daemon, [2]) takes the form of a 116K tarball, which you can build and install in the normal way: ./configure; make; make install or almost. The all-important binary went into hiding in the src directory after I typed make install. A symlink (ln -s /usr/local/portfwd-0.27/src/portfwd/usr/bin/portfwd) took care of that. Checking email for viruses is typically the domain of the SMTP gateway or a server directly downstream of it. In this month’s column, Charly decides to move this protection to the other side – that is, to the client connectionswith their SMTP and POP servers. If you do not receive a response to a ping, or if the response is seriously delayed, you might like to take this as a warning. But who wants to ping all day? You need a ping-based monitoring utility like Smokeping.

You will need to sign on with your LLLID (La Leche League ID) before you can post. If you have never claimed your LLLID, create your LLLID now. To sign in, click the LLLID Sign On button in the upper right corner. Enter your LLLID Alias and click the button again. Re: Random BLS rambles we are not quite ready for solids, jack is 5 months. he is actually grabbing everything i eat though, is that a sign for readiness? he sits in his high chair but he stiil needs to get better at picking things up. i am not going to do purees but should i start giving him a few things on his tray? like mashed potatoes or something? i feel like i want to wait a bit more, he's just so crazy when i eat anything that i am unsure. also, i think i would have no idea what to do if he did start choking. Susan, did you actually need to hit gavin on the back? Re: Random BLS rambles Originally Posted by @llli*mtmama also, i think i would have no idea what to do if he did start choking. Susan, did you actually need to hit gavin on the back? Contact your local red cross and take an infant CPR class before you start. You will never need it but you will feel much more comfortable. I have BLS 2 kids and the only time I ever needed it was when DS (the one who ate NOTHING) ate a dime proud but exhausted working mammy to two high needs babies my surprise baby: the one and only D-Man born 3 weeks late (5/5/08) at 9 lbs 14 oz and 21.5 inches, and the shock H-Girl born about a week late (10/7/09) at 8lbs 15oz and 20.75 inches. If I am here I am covered in baby (probably two) and fighting for control of the keyboard. Family beds are awesome Wondering if you have PPD? Take the screening and see your doctor. You deserve to feel better. Re: Random BLS rambles Originally Posted by @llli*mtmama a dime??? fell out of DH's pocket. apparently it is perfect size to block the airway. I has my not quite one year old upside down before he turned blue though. I have never personally known a BLS baby choke on actual food proud but exhausted working mammy to two high needs babies my surprise baby: the one and only D-Man born 3 weeks late (5/5/08) at 9 lbs 14 oz and 21.5 inches, and the shock H-Girl born about a week late (10/7/09) at 8lbs 15oz and 20.75 inches. If I am here I am covered in baby (probably two) and fighting for control of the keyboard. Family beds are awesome Wondering if you have PPD? Take the screening and see your doctor. You deserve to feel better. Re: Random BLS rambles No choking here either, gagging yes, but choking no. Susan I second the mesh feeder, I don't know why they wouldn't be safe. Unless you leave LO unattended :Shrug We used one for X now and then, I would just buy one and a few packs of extra mesh bags. They aren't too terribly expensive IIRC ~Meg~Wife to Ray (09/07/07)and Mama to:Xander (01/19/07) nursed for 30 monthsLiam (12/12/09) still nursing through the night and in the mornings!Sebastian (7/29/12) my newest little nursling who graciously shares his milk with big brother! Re: Random BLS rambles Susan, sorry for all the solids trouble I would wait awhile. Connor is doing amazing. But you wouldn't KNOW it if you saw all the malarky my mother picks up for him. No jars, but all sorts of snacks, etc. Pouches of organic puree. Some of the Gerber variety that I made her take back. She just doesn't seem to understand that all these foods (even the healthy organic ones) are a marketing ploy. I tried the arrowroot cookies and they taste no different than Lorna Doone's. I'm fine with him having some more snackish things when he is older, but she doesn't get it. And she thinks I am making him "fend for himself" I am just so SICK of telling her to STOP. It is making me scared for when I go back to school. Re: Random BLS rambles Originally Posted by @llli*mtmama also, i think i would have no idea what to do if he did start choking. Susan, did you actually need to hit gavin on the back? I have taken a CPR class, and there, we learned how to unchoke a baby. And yep, I thumped him on the back when he stopped breathing. I've never had to do that before, with three BLS babies. This is entirely due to that stupid cleft and pretty common for cleft babies to choke until they figure it out. Originally Posted by @llli*meganbeth Susan I second the mesh feeder, I don't know why they wouldn't be safe. Unless you leave LO unattended :Shrug We used one for X now and then, I would just buy one and a few packs of extra mesh bags. They aren't too terribly expensive IIRC I was going to get one today, and I forgot. Oh well. I'll be out running errands again Thursday or Friday. And then yesterday, I gave him a cracker, and he was fine. I don't know. Re: Random BLS rambles I've never used a mesh feeder. I had this weird impression that those weren't safe I don't know where that idea came from. I probably read it a long time ago the dog will miss the feeding. I hurled that tray will all the food away, and it went everywhere He cleaned up for me. I didn't even care The mesh feeders never really worked for us. They always seemed to get dropped on the floor within a couple minutes. With pets in the house, they just ended up a sticky furry mess. At least with small pieces of food, I just give more if some ends up on the floor. The mesh feeder was just too much of a hassle to clean every time it was dropped. I tried hooking it onto the highchair with DD using rings, but she hated it being hooked onto the tray. DD's newest thing to do when she is done eating is to drop the leftover food piece by piece down her shirt . It usually all ends up in the front of her diaper. Re: Random BLS rambles sounds like he's doing well considering and really the puree was the main problem did he like the cracker? It was OK, but then I repeated yesterday, and he choked again. But he got this one out, and I didn't have to help. Originally Posted by @llli*wdsmom The mesh feeders never really worked for us. They always seemed to get dropped on the floor within a couple minutes. With pets in the house, they just ended up a sticky furry mess. At least with small pieces of food, I just give more if some ends up on the floor. The mesh feeder was just too much of a hassle to clean every time it was dropped. I tried hooking it onto the highchair with DD using rings, but she hated it being hooked onto the tray. DD's newest thing to do when she is done eating is to drop the leftover food piece by piece down her shirt . It usually all ends up in the front of her diaper. And I could see that happening here too...Or the dog snatching it, mid-air, and me having to haul him down to the clinic to remove it from his stomach He doesn't look. He just swallows.

How it feels to have a stroke Page Navigation Main Profile At A Glance How it feels to have a stroke http://www.ted.com Neuroanatomist Jill Bolte Taylor had an opportunity few brain scientists would wish for: One morning, she realized she was having a massive stroke. As it happened -- as she felt her brain functions slip away one by one, speech, movement, understanding -- she studied and remembered every moment. This is a powerful story about how our brains define us and connect us to the world and to one another. Length: 20:12 Contact Questions about How it feels to have a stroke Want more info about How it feels to have a stroke? Get free advice from education experts and Noodle community members.

Restriction fragment length polymorphisms in isolates of Aspergillus fumigatus probed with part of the intergenic spacer region from the ribosomal RNA gene complex of Aspergillus nidulans. Differences in restriction fragment length polymorphisms (RFLPs) have been detected in isolates of Aspergillus fumigatus. Genomic DNA from 11 isolates was digested with EcoRI, separated by electrophoresis, Southern blotted and probed with DNA from the intergenic spacer or non-transcribed spacer region of the rRNA gene complex of Aspergillus nidulans. Three distinct RFLP patterns were detected which differed from the control patterns observed with A. nidulans, Aspergillus flavus and Aspergillus niger hybridized with the same probe. Furthermore, the differences in RFLP patterns in the A. fumigatus isolates were not detected when probed with DNA coding for the rRNA complex in Saccharomyces cerevisiae. These findings may be of use in the study of the epidemiology and pathogenesis of infections caused by A. fumigatus.

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The Computer for the 21st Century (1991) - t0dd http://www.ubiq.com/hypertext/weiser/SciAmDraft3.html ====== bhauer _Pads differ from conventional portable computers in one crucial way. Whereas portable computers go everywhere with their owners, the pad that must be carried from place to place is a failure. Pads are intended to be "scrap computers" (analogous to scrap paper) that can be grabbed and used anywhere; they have no individualized identity or importance._ That sounds eerily appealing. It speaks to my preference for a multi-device lifestyle where portable devices are but terminals to my network of applications running on my singular compute host. And yet, that's nothing quite like that today. Today, despite my desire to buy what I call a "subservient tablet," [1] I have no such option. Instead, tablets are first- order computers on their own right, adding to the number of devices in my life that want constant attention. I find it a shame that in the real present-day, we're off on this curious tangent where every device has to stand on its own as a silo of computing. In fact, it's a shame many of the concepts described in this article from 1991 still don't exist. Most notably, I am especially interested in large form- factor displays. [1] [http://tiamat.tsotech.com/microsoft](http://tiamat.tsotech.com/microsoft) ------ rootbear Mark Weiser was a professor of mine at the University of Maryland before he went to PARC. It was an awful tragedy that he died at such a young age (46). With the rise of tablets and small, powerful computers like the Raspberry Pi and the Arduino, I'm often reminded of his ideas about ubiquitous computing. He'd be having a ball today with all of the power one can now get in such tiny, efficient packages. It would be great if more of his UC ideas were to get into the mainstream of computing.

Nashville Predators The Nashville Predators are a professional ice hockey team based in Nashville, Tennessee. They compete in the National Hockey League (NHL) as a member of the Central Division of the Western Conference. The Predators have played their home games at Bridgestone Arena since 1998. Their television broadcasting rights are held by Fox Sports Tennessee, and radio broadcasting rights are held by WPRT-FM. The club was founded in 1998 when the NHL granted an expansion franchise to Craig Leipold. After five seasons, the Predators qualified for their first Stanley Cup playoffs during the 2003–04 season. In 2008, ownership of the club was transferred from Leipold to a locally based ownership group. The Predators advanced to their first Stanley Cup Finals in 2017, but were defeated by the Pittsburgh Penguins in six games. In the following season, the Predators won their first Presidents' Trophy and Central Division title. The Predators are presently affiliated with the minor league teams Milwaukee Admirals of the American Hockey League and Florida Everblades of the ECHL. History Bringing the NHL to Nashville In late 1995, rumors began to circulate that the New Jersey Devils would be relocating to the planned Nashville Arena. Nashville offered a $20 million relocation bonus to any team that would relocate, and the Devils attempted to terminate their lease with the NJSEA before ultimately restructuring it to stay in New Jersey. After the attempt to get the Devils, NHL Commissioner Gary Bettman stated Nashville would probably be considered in upcoming expansion. The arena was opened in 1996, and after an attempt to bring the National Basketball Association's Sacramento Kings did not materialize, the city instead went after a hockey team. In January 1997, a group led by Wisconsin businessman Craig Leipold made a formal presentation before the NHL requesting an expansion franchise. When Bettman and league officials visited Nashville to tour the arena, thousands gathered on the arena plaza to greet them. In June, the league granted conditional franchises to Nashville, Columbus, Ohio, Atlanta and Minneapolis–Saint Paul. The Nashville team would be scheduled to begin play in 1998 if they met the NHL requirement of selling 12,000 season tickets before March 31, 1998. Of the four cities, Nashville was the only one with a completed arena and therefore began play first. One month later, Leipold named former Washington Capitals general manager David Poile as the franchise's first general manager. Portland Pirates' head coach Barry Trotz was named the franchise's first head coach on August 6. On September 25, 1997, Leipold and team president Jack Diller held a press conference where they unveiled the franchise's new logo, a saber-toothed cat (Smilodon floridanus). The logo was a reference to a partial Smilodon skeleton found beneath downtown Nashville in 1971 during construction of the First American National Bank building, now the UBS Tower. Once the logo was unveiled, the franchise held a vote among fans to choose a name. Three candidates were culled from 75: "Ice Tigers," "Fury" and "Attack." Leipold added his own submission to the vote, "Predators." On November 13, Leipold revealed at a press conference that his submission had won out and that the new franchise would be known as the "Nashville Predators." When awarded a franchise, the city of Nashville paid 31.50% of the $80 million fee to join the league. The city has engaged an affiliate of the team to operate the arena, and that agreement protects the city against annual arena operating losses over approximately $3.8 million. The $15 million payroll of the team was the lowest of the NHL. Early years (1998–2005) The Predators began play during the 1998–99 season, taking to the ice for the first time on October 10, 1998, where they lost 1–0 at home to the Florida Panthers. It was the only sold out game of the Predators' first five bouts in Nashville. Three nights later, on October 13, they defeated the Carolina Hurricanes 3–2 for their first win. Forward Andrew Brunette scored the first goal. The Predators, in their first year of existence, finished second-to-last in the Western Conference with a 28–47–7 record. In the 1999–2000 season, the Predators finished with a similar record to the previous season, and finished last in the Western Conference behind the Calgary Flames. However, during a game versus the New York Islanders on February 20, 2000, the Predators scored four goals in 3 minutes and 38 seconds. To begin the 2000–01 season, the Predators played two games in Japan against the Pittsburgh Penguins. Each team won a game in front of the largest crowds ever to see a hockey game in Japan. Backed by the goaltending duo of Mike Dunham and Tomas Vokoun, Nashville finished the season in tenth place in the Western Conference, ten points out of a playoff spot with a total of 80 total points. During the 2001–02 season, the Predators recorded their 100th victory on December 6, 2001. With that win, Nashville became the second-fastest expansion team of the 1990s to reach the 100-win plateau. In the 2002–03 season, head coach Barry Trotz broke the record for most games coached by the original coach of an expansion team (392 games). The club had failed to qualify for the Stanley Cup playoffs for their first five years as a franchise. However, in the 2003–04 season, the Predators finished eighth in the Western Conference, qualifying for their first post-season berth. The Predators were eliminated by the Detroit Red Wings in six games in the first round of the 2004 Stanley Cup playoffs. The following 2004–05 season was wiped out by a labor dispute between NHL owners and players. After the lockout (2005–2014) In the 2005–06 season, the Predators set an NHL record by winning their first four games by one goal each (although two of those were shootout victories, which would have been tie games in previous seasons). They also became only the fourth NHL franchise to start the season 8–0; the last time a team did so was the Toronto Maple Leafs, who set the mark with a 10–0 start in the 1993–94 season. The Predators set the franchise mark for wins in a season with a 2–0 shutout of the Phoenix Coyotes on March 16, 2006. In that match, Chris Mason became the ninth goaltender to score a goal. By the end of the season, the Predators had accumulated 106 points—their first 100-point season—and clinched home ice advantage in the first round of the playoffs for the first time in team history. They finished the season with an NHL-best 32–8–1 record at home. However, the Predators would be eliminated by the San Jose Sharks in five games in the first round of the 2006 playoffs. During the off-season, the Predators acquired veteran center Jason Arnott from free agency on July 2, 2006. In the following season, Arnott and David Legwand led the team in goals with 27 each. Late in the season, the Predators traded two former first round draft picks, Scottie Upshall and Ryan Parent, plus their first and third-round pick in the 2007 NHL Entry Draft, to the Philadelphia Flyers for five-time NHL All-Star Peter Forsberg. The Predators finished the season ranked fourth in the Western Conference with a franchise record 110 points, finishing third overall behind the Buffalo Sabres and the Red Wings. They were defeated by the Sharks in the first round of the 2007 playoffs for the second year in a row, losing the series 4–1. The roster saw a depletion in talent during the off-season. With multiple potential buyers, and rumors of the franchise moving hounding the team until almost mid-season, the Predators were not expected to be successful during the 2007–08 season. Chris Mason, former backup goaltender to Tomas Vokoun (who was traded to the Florida Panthers) had a shaky season and shared net-minding duties with Dan Ellis. Ellis, who was signed from the Dallas Stars before the season began, had a 233:39 long shutout streak (fifth longest in league history) nearing the end of the season that helped Nashville attain the eighth playoff spot with 91 points. The Predators met the Presidents' Trophy-winning (and eventual Stanley Cup winners) Red Wings in the first round of the playoffs and were defeated 4–2, their fourth-straight first-round knockout. New ownership group The first off-season of settling in under new ownership was a quiet one for the Predators with little personnel movement. As such, the Predators began the 2008–09 season with little expectation. Following a strong push after the All-Star break and no movement at the trade deadline, the team found themselves still battling for a playoff spot into the last week of the season. Buoyed by the return of Steve Sullivan after almost two seasons recovering from a back injury, the Predators finished with 88 points, settling for tenth place in the Western Conference, missing the playoffs for the first time in five seasons. The Predators made few major additions to their roster in the 2009 off-season, signing former San Jose Sharks forward Marcel Goc (who was extended for another year by the club in mid-season) and former Montreal Canadiens defenseman Francis Bouillon. The 2009–10 season also saw the much-anticipated debut of top prospect Colin Wilson. However, due to a groin injury suffered in training camp, Wilson spent the first week-and-a-half of the season on the sidelines, and was sent to the Milwaukee Admirals of the American Hockey League (AHL) in November. He returned to the club in February and scored 11 points in his next 15 games and finished the season with 15 points in 35 games. 2010 also saw a breakout year for the last pick in the 2005 Draft, Patric Hornqvist, as the 23-year-old Swede scored 30 in the 2009–10 season, becoming the fourth Predator to do so (the others being Steve Sullivan, Paul Kariya and Jason Arnott). The Predators qualified for the 2010 playoffs, facing the Chicago Blackhawks in the first round. The Predators earned their first postseason road win on April 16, 2010 when they beat the Blackhawks 4–1 at the United Center, although they lost the overall series in six games. On July 9, 2010, the Predators announced that defenseman Shea Weber would become the club's fifth captain. In the following years' playoffs, the Predators advanced to the second round of the playoffs for the first time in franchise history. They defeated the Anaheim Ducks in the first round, winning the fourth game of the series at Bridgestone Arena on April 24, 2011. Two days prior, Predators' goaltender Pekka Rinne was nominated as a Vezina Trophy finalist for his performance during the 2010–11 season. The Predators played against the number-one ranked team in the NHL in the second round, the Vancouver Canucks. The Predators lost the series 4–2. On June 22, 2011, the Predators unveiled their modified logo set for the 2011–12 season. With the color scheme simplified to blue, gold and white and eliminating orange, silver and steel, the Predators cleaned up their primary logo and wordmark. A new alternate logo incorporating elements from a guitar pick and the Tennessee state flag was also introduced. In the beginning of the 2011–12 season, on November 3, 2011, the Predators signed goaltender Pekka Rinne to a seven-year, $49 million deal. It was the largest contract awarded in Predators' history, as well as making Rinne the highest paid goaltender in the NHL that year. On February 27, 2012, during the NHL's trade deadline, the Predators acquired Andrei Kostitsyn and Paul Gaustad from the Montreal Canadiens and the Buffalo Sabres, respectively. The Predators surrendered draft picks to bolster their team for the 2012 playoffs. The season also saw the return of Russian forward Alexander Radulov to the Predators after a four-year hiatus to play in the Kontinental Hockey League (KHL). For the second year in a row, and the second time in the team's history, the Predators won a first-round series in the Stanley Cup playoffs, defeating the Red Wings in a best-of-seven series 4–1. However, for the second year in a row, the Predators were ousted in the Western Conference second round, this time to the Phoenix Coyotes. The following 2012–13 season as a result of the 2012–13 NHL lockout. The Predators failed to qualify for the playoffs in the shortened season, the first time they failed to do so since the 2008-09 season. After the season, the Predators signed Weber through a front-loaded $110 million, 14-year offer sheet, $68 million of it as a signing bonus, from the Philadelphia Flyers on July 19. The offer sheet was the richest in NHL history in terms of total money, money per season, and length, surpassing the previous offer sheet record set by Thomas Vanek. The following season saw the departure of center David Legwand, the first player ever drafted by the Predators, the club's all-time leading scorer, and was co-leading scorer for the season at the time. Agreeing to waive his "no-trade clause", he was traded on March 5, 2014, to his hometown team, the Detroit Red Wings, in exchange for prospect forward Calle Jarnkrok, forward Patrick Eaves and a third-round pick in the upcoming 2014 NHL Entry Draft. After missing the playoffs for a second season in a row, the Predators opted not to renew the contract of Barry Trotz as its head coach after 15 years, although he was offered an unnamed position within the organization. On May 6, 2014, the Predators announced Peter Laviolette as their new head coach. Peter Laviolette era (2014–2020) In Peter Laviolette's first season as the Predators' head coach, the Predators finished second in the Central Division. Despite having home advantage in the first round of the 2015 playoffs, they lost the first round in six games to the Chicago Blackhawks, who went on to win the Stanley Cup. For the following 2015–16 season, the Predators name Sean Henry CEO and then finished as the Western Conference's first wild-card, earning 96 points. When they advanced to the second-round after beating the Anaheim Ducks in Game 7, it was the franchise's first seven-game series and seven-game series win. They were eliminated in seven games by the San Jose Sharks, who went on to win the conference. In the 2016 off-season, on June 29, 2016, the Predators traded Weber to the Montreal Canadiens in exchange for defenseman P. K. Subban. The trade surprised many hockey fans because the details to this trade were kept strictly confidential until the deal was already made. On September 7, 2016, the Predators announced Mike Fisher would replace Weber as the sixth captain of the club. In the 2016–17 season, the Predators finished fourth in the Central Division with 94 points, which earned them the second wild card spot in the Western Conference. The 2016–17 season marked the first time the Predators sold out all 41 regular season home games. Their eighth-place finish in the conference gave them a first-round Stanley Cup playoff matchup against the Chicago Blackhawks, who finished first in the conference during the regular season. The Predators swept the Blackhawks in four games. This was the first time that an eighth seed swept a playoff series against the top seed in the conference in NHL history as well as the first time that there had been a sweep by an eighth seed against a top seed in a best-of-seven playoff series in the history of North American major league professional sports. In the second round of the Stanley Cup playoffs, the Predators defeated the St. Louis Blues in six games, marking the first time the team advanced to the Western Conference Finals. On May 16, the Predators became the first team in 20 years (since the Detroit Red Wings in 1997) to achieve ten-straight wins at home in the postseason. On May 22, 2017 the Predators defeated the Anaheim Ducks 6–3 and won the series four games to two, winning the Western Conference, and advancing to the club's first Stanley Cup Finals. In the 2017 Stanley Cup Finals, the Predators went down 2–0 against the Penguins before battling back and leveling the series at two, winning games 3 and 4 at home. Returning to Pittsburgh, the Predators lost 6–0 before being eliminated at home 2–0 in game 6. On April 5, 2018, the Predators clinched their first division title in team history while also claiming their first Presidents' Trophy. They defeated the Colorado Avalanche in the first round of the playoffs in six games, and then lost to the Winnipeg Jets in seven games in the second round. The Predators fired head coach Laviolette in the middle of the 2019–20 season on January 6, 2020, with the team sitting at sixth place in the division at the time and a record of 19–15–7. John Hynes era (2020–present) On January 7, 2020, John Hynes was hired as the third head coach in the Predators' franchise history. Team information Facilities The Nashville Predators have played their home games at Bridgestone Arena since their inaugural season in 1998. Opened in 1996, Bridgestone Arena is a multi-purpose venue in downtown Nashville. The Predators' practice facility is located at Centennial Sportsplex, a multi-use athletic complex located next to Centennial Park. Both facilities are owned by the Metropolitan Government of Nashville and Davidson County. Fan traditions Fans of the Nashville Predators have modified the octopus-throwing tradition of Detroit Red Wings fans to show their support: on occasion, a fan will throw a catfish onto the ice. The Tennessean newspaper of Nashville cites the first instance of this as being on October 30, 2003. On May 16, 2017, during Game 3 of the Western Conference Final at Bridgestone Arena, country music singer, songwriter, and record producer Keith Urban, who had performed the National Anthem prior to the game, was seen on the Jumbotron hoisting a massive catfish that Tennessee Titans left tackle, Taylor Lewan had with him at the game. Lewan, along with fellow Titans offensive linemen Jack Conklin, Quinton Spain, Ben Jones, and Josh Klein, and Titans quarterback Marcus Mariota, served as the hype men prior to the game, another Predators playoff tradition prior to home games, which included them waving gold Predators towels, Mariota encouraging the crowd to get louder, Lewan hoisting the catfish, and the offensive linemen chugging beer. Section 303 is where a section of fans at the Bridgestone Arena sit, stand, and cheer, colloquially known as The Cellblock. The group refers to themselves as "the loudest section of the loudest arena in the NHL." The fan-based organization has been recognized by the Predators' front office. A large banner was produced by the front office for posting on the wall behind the section. On April 3, 2008, with the Predators clinging to a 3–2 lead with 4:30 in their final home game of the regular season, a sellout crowd at what was then known as the Sommet Center, gave the team a standing ovation through the entirety of the final TV timeout. The Predators went on to win the game against the St. Louis Blues and advanced to the playoffs that year, where the "standing O" during the final TV timeout has since become a fan tradition. The mascot of the Predators is Gnash, a blue saber-toothed cat. Introduced in 1998, Gnash's trademark includes stunts, such as very fast rappels, zip lines, and a pendulum swing that takes him under the scoreboard and just inches off the ice. To go along with the saber-toothed cat mascot, Predators fans proudly use their Fang Fingers during each power play of the game. There are foam saber-fang gloves that can be purchased, but most fans simply curl their index and middle fingers on each hand into fang shapes and brandish them in an up-and-down motion. Fang Fingers are done to the horror sounds from the Alfred Hitchcock movie, Psycho. Fans are also known for a variety of chants taunting players of the opposing team, particularly the goalie. For example, after each Predators goal, fans call the opposing goalie's name, accompanied by shouts of "It's all your fault" and other epithets. These cheers are sometimes said to originate from tradition at college football games, but some of these derive from traditions held by fans of Nashville's former pre-NHL hockey teams Nashville Dixie Flyers, Nashville South Stars, Nashville Knights, and Nashville Nighthawks/Nashville Ice Flyers. Nashville's fanbase is said by many to be among the loudest in the National Hockey League, with sound levels reaching over 120 dB during the playoffs. This has contributed to the team also being called "Smashville". Jersey and logo The original Predators uniforms were worn from 1998 to 2007 and both featured a silver yoke on the shoulder. Navy and white were the base uniform colors while gold was used only as an accent color. The white uniforms featured the primary Predators logo outside a navy triangle while the navy uniforms use the same logo minus the triangle. From 1998 to 2004 the secondary logo featuring the Gaylord Center (now Bridgestone Arena) tower adorned the shoulders. From 2001 to 2007 the Predators wore mustard gold third jerseys featuring the front-facing saber-toothed cat logo. The logo then replaced the tower alternate logo on the shoulders of their primary uniforms in 2005. Switching to Reebok's Edge template in 2007, the Predators made minor tweaks to their uniforms. Most notably, the white uniforms no longer featured a contrasting nameplate color, while the city name was added above the Predators logo. From 2009 to 2011, the Predators wore navy third jerseys but with black replacing gold as trim color. A roundel logo featuring the fossilized cat adorned the shoulders while a checkerboard pattern of black and navy squares adorned the sleeves, tail stripes and socks. For the 2011–12 season, the Nashville Predators changed their jersey design and color scheme. The home jerseys are a bright gold with navy and white highlights, while the away jerseys are white with gold and navy highlights. Furthermore, the Predators changed their logo, making it purely white, gold and navy. The jerseys have a guitar pick on the shoulder with the Tennessee state tri-star inside it, lines reminiscent of guitar strings on the numbers, and piano keys along the neck line inside the jersey as a nod to Nashville's internationally-known music heritage. From the 2016–17 season gold helmets became a permanent part of the home uniform, after they first used them on Saturday home games the prior season. In the 2017–18 season the Predators changed their uniform style to fit with the new Adidas template. While the gold home uniforms received minimal alterations, the away white uniforms featured more gold accents in the sleeves, shoulders and tail while navy was relegated to trim color. The Predators unveiled a special edition uniform for the 2020 NHL Winter Classic, featuring a design inspired from the uniforms of the defunct EHL team Nashville Dixie Flyers. Heavy gold stripes with navy trim adorn the chest and sleeves while a script rendition of the team name was inserted to the gold chest stripe. A navy felt-rendered saber-toothed cat logo was also added on the left shoulder. Ownership The franchise was initially owned by a group led by Craig Leipold. On May 23, 2007, Leipold was reported to have reached a tentative agreement to sell the team to Research in Motion chairman and co-CEO Jim Balsillie. At the time, Leipold indicated that the team would play the 2007–08 season in Nashville but that the future of the team after that was not clear. On June 23, information was leaked by several sources indicating that Leipold no longer wanted to sell the Predators to Balsillie. Subsequently, a campaign to land the team in Kansas City, Missouri, received a boost in late June 2007. The Canadian National Post, citing anonymous sources, reported that Leipold planned to sell the team to San Jose venture capitalist William "Boots" Del Biaggio III, who wanted to relocate the club to Kansas City's new Sprint Center for the 2008–09 season. Del Biaggio, who had a contract with Anschutz Entertainment Group to own an NHL club that would play home games in Sprint Center, had made an offer reported to be for about $190 million for the Predators. Del Biaggio had entered an agreement two years earlier, in 2005, to purchase the Pittsburgh Penguins, but the club backed out of the deal after it won the NHL draft lottery and took Sidney Crosby with the first overall pick. On July 19, 2007, a group of local business owners known as Our Team Nashville held a rally at the Sommet Center to encourage fans to buy season tickets in order to help the Predators meet the attendance figures needed to keep the team in Nashville. They drew approximately 7,500 fans and sold the equivalent of 726 full season tickets during the rally. The rally was heavily supported by George Plaster, then a sportscaster on WGFX 104.5 "The Zone" sports radio in Nashville. On August 1, 2007, the group released a letter of intent from Craig Leipold. After negotiations with the City of Nashville, the local group headed by David Freeman reached an agreement with Nashville Mayor Karl Dean, and the NHL Board of Governors approved the sale on November 29, 2007. The $172 million acquisition of the Nashville Predators included repayment of existing debt of approximately $61 million and $2.2 million in fees and expenses. The sale of the Predators to the Tennessee-based group included Del Biaggio, who had been trying to move the team to Kansas City. The locally based buyers held 73% of the team, while Del Biaggio and a minority partner acquired about 27% of the club. In June 2008, Del Biaggio ran into legal trouble over a multitude of unpaid loans, culminating in his filing for Chapter 11 bankruptcy. Furthermore, it was alleged that Del Biaggio acquired the loans he used to buy his stake in the team through fraudulent means, prompting an FBI investigation and criminal charges. The charges culminated in a 97-month prison sentence for Del Biaggio. Under United States bankruptcy law, a trustee was appointed to sell Del Biaggio's assets, including his stake in the Predators, to pay off his creditors. In November 2011, it was announced that Calgary businessman W. Brett Wilson had purchased a 5% interest in the Nashville Predators. On March 1, 2010, during the 2009–10 season, the Predator's front office saw Freeman stepped down as chairman of the Nashville Predators in favor of Thomas Cigarran. Cigarran announced on September 2 that the local ownership group had completed the purchase of the Del Biaggio stake. Ownership dispute On June 23, 2016, Freeman filed a $250 million lawsuit against the Nashville Predators and Cigarran. His claim was that his ownership stake has been improperly diluted by Cigarran failing to notify him of capital calls, and that he had not received loan guaranty fees that the ownership group had agreed to pay him. The lawsuit stated that Freeman initially owned a 48% share, while the holding company for the Nashville Predators stated that Freeman controlled less than 1% of ownership in the team at the time of the suit. This dilution was exacerbated by the existence of two classes of investments in the Predators: the common units owned by Freeman were subject to capital calls; the Series A units originally owned by Del Biaggio and his minority partner were not subject to capital calls. The dispute was sent to court-ordered arbitration on July 29, 2016, under the supervision of NHL commissioner Gary Bettman. As of January 25, 2018, arbitration was continuing in the unresolved dispute. The outcome may remain undisclosed, as the arbitration is private. Season-by-season record This is a partial list of the last five seasons completed by the Predators. For the full season-by-season history, see List of Nashville Predators seasons. GP = Games played, W = Wins, L = Losses, T = Ties, OTL = Overtime Losses, Pts = Points, GF = Goals for, GA = Goals against Retired numbers Other than 99, retired league-wide to honor Wayne Gretzky in 2000, there are no retired Predators numbers. Players Current roster Team captains Tom Fitzgerald, 1998–2002 Greg Johnson, 2002–2006 Kimmo Timonen, 2006–2007 Jason Arnott, 2007–2010 Shea Weber, 2010–2016 Mike Fisher, 2016–2017 Roman Josi, 2017–present First-round draft picks Franchise scoring leaders These are the top-ten point-scorers, goal scorers, and assist leaders in franchise regular season history. Figures are updated after each completed NHL regular season. Note: Pos = Position; GP = Games played; G = Goals; A = Assists; Pts = Points; P/G = Points per game; – current Predators player NHL awards and trophies Clarence S. Campbell Bowl 2016–17 Presidents' Trophy 2017–18 Lester Patrick Trophy David Poile: 2000–01 Bill Masterton Memorial Trophy Steve Sullivan: 2008–09 NHL Foundation Player Award Mike Fisher: 2011–12 Mark Messier Leadership Award Shea Weber: 2015–16 Wayne Simmonds: 2018–19 Vezina Trophy Pekka Rinne: 2017–18 NHL First All-Star Team Shea Weber: 2010–11, 2011–12 Pekka Rinne: 2017–18 NHL Second All-Star Team Pekka Rinne: 2010–11 Shea Weber: 2013–14, 2014–15 P. K. Subban: 2017–18 NHL All-Rookie Team Filip Forsberg: 2014–15 Juuse Saros: 2017–18 NHL All-Star Game selections Sergei Krivokrasov: 1998–99 Kimmo Timonen: 1999–2000, 2003–04, 2006–07 Tomas Vokoun: 2003–04 Jason Arnott: 2007–08 Shea Weber: 2008–09, 2010–11, 2011–12, 2014–15, 2015–16 Ryan Suter: 2011–12 Pekka Rinne: 2014–15, 2015–16, 2017–18, 2018-19 Filip Forsberg: 2014–15 Roman Josi: 2015–16, 2018-19, 2019-20 James Neal: 2015–16 P. K. Subban: 2016–17, 2017–18 Franchise individual records Most games played: David Legwand, 956 Most games played, goaltender: Pekka Rinne, 630 Most goals in a season: Viktor Arvidsson, 34 (2018–19) Most assists in a season: Paul Kariya, 54 (2005–06) Most points in a season: Paul Kariya, 85 (2005–06) Most penalty minutes in a season: Patrick Cote, 242 (1998–99) Most goals in a season, defenseman: Shea Weber, 23 (2008–09 and 2013–14) Most points in a season, defenseman: Roman Josi, 61 (2015–16) Most goals in a season, rookie: Filip Forsberg, 26 (2014–15) Most points in a season, rookie: Filip Forsberg, 63 (2014–15) Most wins in a season: Pekka Rinne, 43 (2011–12) Most shutouts in a season: Pekka Rinne, 8 (2017–18) See also List of Nashville Predators general managers List of Nashville Predators head coaches Nashville Predators Radio Network List of Nashville Predators broadcasters References External links Category:1998 establishments in Tennessee Category:Central Division (NHL) Category:Ice hockey clubs established in 1998 Category:Ice hockey teams in Tennessee Category:National Hockey League in the Sun Belt Category:Sports in Nashville, Tennessee

$\begingroup$ Many famous results were discovered through non-rigorous proofs, with correct proofs being found only later and with greater difficulty. One that is well known is Euler's 1737 proof that $1+\frac{1}{2^2}+\frac{1}{3^2}+\frac{1}{4^2}+\cdots =\frac{\pi^2}{6}$ in which he pretends that the power series for $\frac{\sin\sqrt{x}}{\sqrt{x}}$ is an infinite polynomial and factorizes it from knowledge of its roots. Another example, of a different type, is the Jordan curve theorem. In this case, the theorem seems obvious, and Jordan gets credit for realizing that it requires proof. However, the proof was harder than he thought, and the first rigorous proof was found some decades later than Jordan's attempt. Many of the basic theorems of topology are like this. Then of course there is Ramanujan, who is in a class of his own when it comes to discovering theorems without proving them. I'd be interested to see other examples, and in your thoughts on what the examples reveal about the connection between discovery and proof. Clarification. When I posed the question I was hoping for some explanations for the gap between discovery and proof to emerge, without any hinting from me. Since this hasn't happened much yet, let me suggest some possible explanations that I had in mind: Physical intuition. This lies behind results such as the Jordan curve theorem, Riemann mapping theorem, Fourier analysis. Lack of foundations. This accounts for the late arrival of rigor in calculus, topology, and (?) algebraic geometry. Complexity. Hard results cannot proved correctly the first time, only via a series of partially correct, or incomplete, proofs. Example: Fermat's last theorem. I hope this gives a better idea of what I was looking for. Feel free to edit your answers if you have anything to add.

/** * Copyright Amazon.com, Inc. or its affiliates. All Rights Reserved. * SPDX-License-Identifier: Apache-2.0. */ #pragma once #include <aws/iotthingsgraph/IoTThingsGraph_EXPORTS.h> #include <aws/core/utils/memory/stl/AWSString.h> namespace Aws { namespace IoTThingsGraph { namespace Model { enum class FlowTemplateFilterName { NOT_SET, DEVICE_MODEL_ID }; namespace FlowTemplateFilterNameMapper { AWS_IOTTHINGSGRAPH_API FlowTemplateFilterName GetFlowTemplateFilterNameForName(const Aws::String& name); AWS_IOTTHINGSGRAPH_API Aws::String GetNameForFlowTemplateFilterName(FlowTemplateFilterName value); } // namespace FlowTemplateFilterNameMapper } // namespace Model } // namespace IoTThingsGraph } // namespace Aws

Osteoporosis is a common skeletal disease, affecting millions of individuals worldwide, and the prevention of fractures is an important public health goal. Currently, the osteoporosis treatments that are used substantially reduce vertebral fracture risk, whereas nonvertebral fracture risk has only moderately been improved by the osteoporosis drugs used, defining an unmet medical need ([@B1], [@B2]). Although cortical bone mass and composition are major determinants of bone strength and fracture risk in humans ([@B1], [@B3], [@B4]), only a limited number of studies have focused on the cellular and molecular mechanism specifically regulating cortical bone mass ([@B2]). However, it is known that the periosteal surface of the cortical bone is regulated by growth hormone (GH), insulin-like growth factor I (IGF-I), and periostin ([@B5][@B6][@B7]--[@B8]). Wingless-type MMTV integration site family members (WNTs) belong to a family of secreted cysteine-rich glycoproteins that signal *via* either the WNT/β-catenin pathway, also termed the canonical WNT pathway, or the noncanonical WNT pathways. A crucial step for WNT signaling is the interaction between WNTs and their transmembrane receptor proteins frizzled. When WNT proteins are synthesized, an acyl group from palmitoleic acid is attached at a serine amino acid residue ([@B9]). This lipid modification of WNT is necessary for its function because the frizzled proteins contain a cleft that specifically interacts with the acyl group. Recent *in vitro* studies have demonstrated that an extracellular enzyme (secreted lipase) called NOTUM renders WNT inactive by specifically removing the acyl group from WNT ([@B9], [@B10]). It has been described that NOTUM is a circulating protein, but the relative importance of circulating *vs.* local NOTUM is unknown ([@B11]). In a previous report, lifelong NOTUM inactivation in mice, using the less precise gene trapping technique, resulted in developmental defects involving the kidneys (unilateral agenesis) and teeth (dental dysplasia) as well as reduced embryonic viability ([@B12]). Referring to this mouse model of NOTUM inactivation, developed in a large-scale screen of multiple mouse models, it was recently reported that the mice surviving to adulthood had increased cortical bone mass, but the underlying mechanisms for the skeletal phenotype in these mice were not evaluated ([@B13]). Because several WNTs and modulators of WNT activity are major regulators of bone mass ([@B1], [@B4], [@B14], [@B15]), we hypothesized that NOTUM might modulate bone mass *via* an inhibition of WNT activity. To characterize the possible role of endogenous NOTUM as a physiologic modulator of bone mass, we developed global, cell-specific, and inducible *Notum*-inactivated mouse models using homologous recombination, allowing precise manipulation of genetic sequences in the mouse. In addition, we determined the cellular and molecular effects of *Notum* using cultured osteoblasts and osteoclasts. Finally, we aimed to determine if genetic variation in the *NOTUM* locus is associated with bone mass in humans. MATERIALS AND METHODS {#s1} ===================== Generation of global *Notum^−/−^ and Notum^+/−^* mice {#s2} ----------------------------------------------------- The global *Notum^−/−^* and *Notum^+/−^* mice were generated by breeding male *Notum^flox/flox^* mice (kindly provided by Prof. Christine Perret, INSERM, Institut Cochin) ([@B16]), with female mice expressing Cre recombinase ubiquitously and from an early embryonic stage under the control of the phosphoglycerate kinase-1 promoter (PGKcre) ([@B17]). In PGKcre-expressing female mice, the Cre activity starts in the diploid phase of oogenesis, and thereby a complete recombination of *LoxP* sites occurs also in *Cre^−^* offspring. In the *Notum^flox^* mice, *LoxP* sites are introduced upstream from *Notum* exon 2 and downstream from *Notum* exon 8 and in the presence of an active Cre recombinase, the DNA fragment from exon 2 to exon 8 of the *Notum* gene is excised ([@B16]). Presence or absence of the *Notum^flox^* allele was determined by use of multiplex real-time PCR analysis (StepOnePlus Real-Time PCR System, Thermo Fisher Scientific, Waltham, MA, USA). The following primers and carboxyfluorescein-labeled probe were used for detection of the *Notum^flox^* allele: forward (5′-CCATGATCCTGTGCCTTTCT-3′), reverse (5′-CGACGCGTGAAGTTCCTATT-3′), and probe (5′-GGCCGCGAAGTTCCTATACT-3′), whereas the following primers and VIC-labeled probe were used for detection of the *Notum*^*+*^ allele: forward (5′-CCATGATCCTGTGCCTTTCT-3′), reverse (5′-AGTGGCATCGGAGACAAATC-3′), and probe (5′-TTGGCAGCCCCAAAATATAG-3′). Genotyping for the presence of PGKcre was done using forward (5′-AACATGCTTCATCGTCGG-3′) and primer (5′-TTCGGATCATCAGCTACACC-3′). Briefly, male *Notum^flox/flox^* mice were bred with PGKcre-expressing female mice generating *Notum^+/−^* offspring. To generate *Notum^−/−^, Notum^+/−^*, and littermate wild-type (WT) control mice for the experiment, *Notum^+/−^* female and male mice were mated. Male and female mice included in the experiment were euthanized at 15 wk of age. The degree of *Notum* deletion at the DNA level in different tissues was determined by multiplex real-time PCR analysis using the following primers and carboxyfluorescein-labeled probe: forward (5′-TGGCTTCCCAGCCCATTAAG-3′), reverse (5′-GGCATGCTACAGACAGGTTG-3′), and probe (5′-AGTCTCACCACCCTGCCCTGT-3′). The following primers and VIC-labeled probe were used as a reference because they detect a sequence present in all mice: forward (5′-AGGTCTCAGACGGCAATCAT-3′), reverse (5′-CCTCCACTGCCTGCTAAGAT-3′), and probe (5′-ACCCAGCATGGTGAGGCCTGCC-3′). Generation of *Runx2cre-Notum^flox/flox^* mice {#s3} ---------------------------------------------- To generate specific inactivation of *Notum* in the osteoblast lineage, *Notum^flox/flox^* mice were bred with the previously described *Runx2-cre* mice ([@B2], [@B18]). These *Runx2-creNotum*^*flox/flox*^ mice display early osteoblast-specific *Cre* expression and have the capacity to recombine *LoxP*-flanked DNA sequences in an early osteoblast-specific manner, and an efficient recombination occurs at all sites of endochondral and intramembranous bone formation (particularly in periosteal cells, osteoblasts, and osteocytes but not osteoclasts) when *Runx2-cre* mice were crossed to a Rosa26 reporter strain ([@B18]). To generate mice depleted of *Notum* in osteoblasts, female mice with 2 floxed *Notum* alleles (*Notum^flox/flox^*) were mated with male mice having 1 floxed *Notum* allele and 1 allele of *Runx2-cre* (*Runx2-creNotum^+/flox^*). The littermate control mice were *Notum^flox/flox^*. *Runx2-cre* mice have an unchanged skeletal phenotype compared to WT mice ([@B2]). Genotyping of *Notum^flox^* mice was performed as described above, whereas the presence of the *Runx2-cre* gene was determined using a 3-primer strategy. The common 5′ primer (5′-CCAGGAAGACTGCAAGAAGG-3′) binds to the *Runx2* promoter of the endogenous gene and the transgene. The 3′ primer (5′-TGGCTTGCAGGTACAGGAG-3′) binds to the *Cre* sequence, and another 3′ primer (5′-GGAGCTGCCGAGTCAATAAC-3′) binds to the endogenous *Runx2*. Male and female *Runx2-creNotum^flox/flox^* mice included in the experiment were euthanized at 17 wk of age. Generation of mice with inducible *Notum* inactivation {#s4} ------------------------------------------------------ In order to study the acute adult effects of *Notum*, avoiding confounding developmental effects, inducible *Notum* knockout mice were created by breeding the *Notum^flox/flox^* mice with the previously described B6.Cg-Tg(CAG-Cre/Esr1\*)5Amc/J (CAGGCre-ER, 004682; The Jackson Laboratory, Bar Harbor, ME, USA) transgenic mice ([@B19]). Briefly, a male transgenic mouse expressing a tamoxifen-inducible Cre-mediated recombinase, and a *Notum*^+/flox^ allele (hereafter called *CAGGCre-ER-Notum^+/flox^*) were bred with female *Notum^flox/flox^* mice, creating *CAGGCre-ER-Notum^flox/flox^* mice. *Notum^flox/flox^* littermates were used as controls. Genotyping of the *Notum^flox/flox^* mice was done as previously described, and the presence of the Cre construct was determined using the following primers: Cre forward: 5′-GCGGTCTGGCAGTAAAAACTATC-3′; Cre reverse: 5′-GTGAAACAGCATTGCTGTCACTT-3′; WT forward: 5′-CTAGGCCACAGAATTGAAAGATCT-3′; and WT reverse: 5′-GTAGGTGGAAATTCTAGCATCATCC-3′. To study the adult effects of NOTUM on cortical bone thickness and bone strength, avoiding confounding developmental effects, a long-term study using female *CAGGCre-ER-Notum^flox/flox^* mice was performed. Female 11-wk-old *CAGGCre-ER-Notum^flox/flox^* and *Notum^flox/flox^* littermate control mice were injected with tamoxifen (50 mg/kg; T5648; MilliporeSigma, Burlington, MA, USA) for 3 consecutive days to activate the Cre construct. The mice were euthanized 31 d after the first tamoxifen injection at the age of 15 wk. To mechanistically study the importance of NOTUM in a short-term study, 20-wk-old male *CAGGCre-ER-Notum^flox^*^/flox^ and *Notum^flox/flox^* littermate control mice were injected with tamoxifen for 3 consecutive days. The mice were euthanized 11 d after the first tamoxifen injection at the age of 22 wk. The experimental procedures involving animals were approved by the Ethics Committee at the University of Gothenburg, and the care of the animals was in accordance with its guidelines. The mice were housed in a standard animal housing facility with 12-h dark/light periods. The temperature was controlled (22°C), and food and water were available *ad libitum*. At termination, the animals were anesthetized with Ketador/Dexdomitor (Richter Pharma, Wels, Austria/Orion Oyj, Espoo, Finland), bled, and euthanized by cervical dislocation. Long bones and vertebrae were dissected and stored for future analyses, and soft tissues were collected, weighed, and snap-frozen in liquid nitrogen. Assessment of murine bone parameters {#s5} ------------------------------------ ### Dual-energy X-ray absorptiometry {#s6} Total body and femur bone mineral density (BMD) were assessed using Lunar PIXImus densitometer (Wipro GE Healthcare, Chicago, IL, USA), or the UltraFocus^DXA^ (Faxitron Bioptics, Tucson, AZ, USA) ([@B2], [@B20]). ### High-resolution micro--computed tomography {#s7} High-resolution micro--computed tomography (μCT) was used to analyze distal femur, proximal tibia, and vertebrae L5 (Skyscan 1172; Bruker MicroCT, Aartselaar, Belgium) ([@B2]). The cortical region was analyzed in the diaphyseal region of femur and tibia, starting at a distance of ≈5.2 mm from the growth plate and continuing a further 134 μm in proximal direction for femur and in the distal direction for tibia. Trabecular bone was analyzed in the metaphyseal region of the femur and tibia, starting ≈650 μm from the growth plate and continuing a further 134 μm in proximal direction for femur and in distal direction for tibia. In the L5 vertebral body, the trabecular bone caudal of the pedicles was selected for analysis commencing at a distance of approx. 4.5 μm caudal of the lower end of the pedicles, and extending a further longitudinal distance of 230 μm in the caudal direction. Within the trabecular region, the trabecular bone was manually separated from the cortical bone by contouring the irregular anatomic structure adjacent to the endocortical boundary on a slice-by-slice basis. The grayscale µCT images were processed by a global threshold segmentation using the CTAn software (Bruker MicroCT) ([@B2]). ### Peripheral quantitative computed tomography {#s8} Computed tomography (CT) scans were performed using the peripheral quantitative computed tomography XCT Research M (v.4.5B; Norland Stratec, Pforzheim, Germany) with a voxel size of 70 μm, as previously described by Windahl *et al.* ([@B21]). To measure trabecular volumetric BMD, the scan was positioned in the metaphysis of the femur at a distance corresponding to 3.4% of the total femur length, proximal from the distal growth plate. This area contained trabecular and cortical bone, and the trabecular region was therefore defined as the inner 45% of the total cross-sectional area. The cortical bone parameters were analyzed in the middiaphyseal region of the femur, which is an area that contains only cortical bone. The threshold for cortical bone was set to 710 mg/cm^3^ ([@B22]). ### Mechanical strength {#s9} After dissection, the humerus was frozen at −20°C. Three-point bending was performed with a span length of 4.5 mm and a loading speed of 0.155 mm/s using an Instron 3366 (Instron, Norwood, MA, USA). Biomechanical parameters, based on the recorded load deformation curves, were calculated from Bluehill 2 software v.2.6 (Instron) with custom-made Excel (Microsoft, Redmond, WA, USA) macros ([@B2]). ### Bone histomorphometry {#s10} For dynamic histomorphometry, the mice were intraperitoneally injected with the fluorochromes calcein and alizarin (Merck GmbH, Darmstadt, Germany) 9 and 2 d prior to termination, respectively ([@B2]). Upon dissection, femur and tibia were fixated in 4% formaldehyde, dehydrated in 70% EtOH, and imbedded in methyl methacrylate. The femur and tibia were cut in 200-μm-thick transverse cross-sectional sections in the middiaphyseal region (for dynamic cortical histomorphometry), as well as in 4-μm-thick longitudinally coronary sections (for static histomorphometry). The analyses of dynamic cortical bone parameters were performed without any staining. For analyses of cellular parameters, the 4-µm-thick sections were stained with Masson-Goldner trichrome. Osteoclasts were defined in Masson-Goldner trichrome--stained sections as bone-resorbing multinucleated cells (2 or more nuclei) in contact with cortical bone surface. The bone-resorbing nature was identified using the shape of the cell (compared to other endosteal cells, including flat mononuclear bone lining cells and cuboidal mononuclear osteoblasts) and the possible presence of eroded surface ([@B23], [@B24]). All parameters were measured using the OsteoMeasure Histomorphometry Analysis System software v.2.2 (Osteometrics, Atlanta, GA, USA), following the guidelines of the American Society for Bone and Mineral Research ([@B25]). Measurement of serum markers {#s11} ---------------------------- To assess bone resorption, serum levels of C-terminal type I collagen (CTX) fragments were measured using an ELISA RatLaps Kit (Immunodiagnostic Systems, East Boldon, United Kingdom). Serum levels of procollagen type I N-terminal propeptide were measured using a Rat/Mouse EIA Kit (Immunodiagnostic Systems) as a marker of bone formation. Cell cultures {#s12} ------------- ### Silencing of Notum in MC3T3-E1 osteoblasts {#s13} Gene expression analyses in primary calvarial cell cultures from WT mice showed that expression of *Notum* mRNA was down-regulated during culture to an expression level similar to that in cells from *Runx2-creNotum^flox/flox^* mice ([Supplemental Fig. S1*A*](#SM1){ref-type="supplementary-material"}). The mRNA expression of *Notum* was also decreased in primary cultures of osteoblasts from long bones ([Supplemental Fig. S1*B*](#SM1){ref-type="supplementary-material"}). This finding, together with the fact that these cells are a mixture of *Runx2*-expressing cells and other cell types present in the bones used for isolation, made us select the murine preosteoblastic cell line MC3T3-E1 for studies on the role of endogenous NOTUM in osteoblast differentiation. An important observation for this selection was the finding that the *Notum* mRNA expression in the MC3T3-E1 cells was not decreased in cell cultures over 11 d ([Supplemental Fig. S2](#SM1){ref-type="supplementary-material"}), in contrast to primary bone cell cultures. MC3T3-E1 (CRL-2593, subclone 4; American Type Culture Collection, Manassas, VA, USA) was maintained in α-minimum essential medium (α-MEM, M0450; Thermo Fisher Scientific; MilliporeSigma) supplemented with 10% heat inactivated fetal bovine serum (16000-044; Thermo Fisher Scientific), 2 mM L-glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin. For experiments, cells were seeded at an initial density of 10,000 cells in 500 μl of culture medium in 48-well culture dishes (Corning, Corning, NY, USA). To induce osteogenic differentiation, osteogenic medium was prepared by further supplementation with 50 μg/ml [l]{.smallcaps}-ascorbic acid and 4 mM β-glycerophosphate (MilliporeSigma). Medium was replaced every 2 d for the duration of all experiments. All cells were maintained at 37°C in a humidified 5% CO~2~ environment. To assess the role of NOTUM in osteoblast differentiation, *Notum* mRNA was silenced using a specific small interfering RNA (siRNA) sequence (Invitrogen Silencer Predesigned siRNA 4390771, S95064; Thermo Fisher Scientific). A scrambled sequence (AM4635) was used as negative control. Twenty-four and 72 h after seeding, the cells were transfected with 30 nM of the siRNA using lipofectamine RNAiMax (Thermo Fisher Scientific) in serum-free OptiMEM (Thermo Fisher Scientific). Cells were harvested 24 h after the first and second transfection for gene expression analyses. For quantification of alkaline phosphatase (ALP) activity and ALP staining, cells were exposed to osteogenic media 24 h after the second silencing, with an additional silencing 3 d later. Seven days after exposure to osteogenic media, cells were stained for ALP and enzyme activity was analyzed quantitatively. ### ALP analyses {#s14} At the end of osteogenic treatment, the cells were fixed with 70% ethanol for 10 min and stained for ALPase activity using a commercial kit (86R; MilliporeSigma) following the manufacturer's instructions and photographed. For quantification of ALPase activity, proteins from another plate were extracted using 200 μl of ultrapure water and exposed to 5 thermal shock cycles for 20 min at −20°C and 15 min at 37°C. Proteins were quantified using Bicinchoninic Acid Assay Kit (23235; Thermo Fisher Scientific). For ALPase activity measurement, a commercial kit based on the ability of ALP to hydrolyze thymolphthalein monophosphate releasing thymolphthalein was used (Labtest Diagnostica, Lagoa Santa, Brazil). Briefly, 10 μg of proteins were used in a final volume of 80 μl of the reaction buffer (pH 10.1) containing 2.75 mM of thymolphthalein monophosphate and incubated at 37°C for 90 min in a 96-well ELISA plate (Corning). After the reaction period, 200 μl of color reagent was added to each well and the absorbance was measured at 580 nM using a spectrophotometer (Epoch; Biotek, Winooski, VT, USA). ### Primary bone cell cultures {#s15} Primary calvarial periosteal bone cells from 3- to 5-d-old C57BL/6N *Notum*^*flox/flox*^ and *Runx2-creNotum*^*flox/flox*^ mice were isolated by sequential enzymatic digestion as previously described in refs. [@B26] and [@B27]. Isolated periosteal bone cells were cultured in complete α-MEM (22561-021; Thermo Fisher Scientific) supplemented with 10% heat inactivated fetal bovine serum (F7524; MilliporeSigma), 2 mM GlutaMax (35050-038; Thermo Fisher Scientific), 50 µg/ml gentamicin (15750-037; Thermo Fisher Scientific), 100 U/ml penicillin and 100 µg/ml streptomycin (15140-148; Thermo Fisher Scientific) for 3--5 d prior to experiment start. At the start of the experiment, cells were seeded at 20,000 cells/cm^2^ in 48 well plates and incubated in osteogenic media \[complete α-MEM supplemented with 10 mM β-glycerophosphate disodium salt hydrate (BGP, G9422; MilliporeSigma) and 0.2 mM [l]{.smallcaps}-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (Asc-2P, A8960; MilliporeSigma)\]. Culture media were replenished after 4 d and cells were harvested for RNA analysis after 4 and 7 d of culture. Primary bone cell cultures from femur and tibia from 8- to 12-wk-old C57BL/6N mice were isolated by outgrowth of cells from collagenase-treated diaphyseal cortical bone as previously described by Bakker and Klein-Nulend ([@B27]). Primary bone cells from femur and tibia were isolated in complete α-MEM, and thereafter experiments were performed in osteogenic medium as for calvarial bone cells above. ### Primary osteoclast cell cultures {#s16} Bone marrow cells from 8- to 12-wk-old *Notum^flox/flox^* and *Runx2-creNotum^flox/flox^* mice were cultured in suspension culture discs (Corning) in complete α-MEM with 30 ng/ml macrophage colony-stimulating factor (M-CSF) (416-ML-050; R&D Systems, Minneapolis, MN, USA) for 2 d, and the adherent bone marrow--derived macrophages (BMMs) were used as osteoclast progenitors ([@B28], [@B29]). BMMs were detached and spot seeded in 24-well plates (40,000 cells/well) and cultured in complete α-MEM with 30 ng/ml M-CSF with or without the addition of 4 ng/ml receptor activator of nuclear factor κ-B ligand (RANKL) (462-TEC; R&D Systems) to induce osteoclast differentiation. The medium was changed after 3 d and cells harvested for RNA isolation by lysis in RLT buffer (Qiagen, Germantown, MD, USA) 4 d after seeding. ### Treatment of osteoclasts with recombinant NOTUM {#s17} Osteoclasts were differentiated from BMMs as described above. Cells were cultured in M-CSF and RANKL with or without the addition of 10 or 100 ng/ml recombinant human NOTUM (9118-NM; R&D Systems) for 3--4 d before staining for expression of tartrate-resistant acid phosphatase (TRAP) using a commercial staining kit (387A; MilliporeSigma) or lysis in RLT buffer for RNA purification. To study osteoclast formation and activity on bone, 20,000 BMMs were seeded on bovine bone discs (IDS Nordic, Copenhagen, Denmark) in 96-well plates. Media were changed and saved for analysis every 3--4 d, and staining for TRAP was performed after 10 d. The total amount of TRAP5b in the culture media were analyzed as a measure of osteoclastogenesis using a commercial kit (IDS Nordic). Resorptive activity, as assessed by the release of C-terminal telopeptides of type I collagen (CTX-I) from the bone slices, was measured using commercial CTX ELISA (IDS Nordic). Lipase activity measurement of recombinant NOTUM {#s18} ------------------------------------------------ Functional enzyme activity of recombinant human NOTUM was tested using the fluorogenic substrate 8-Octanoyloxypyrene-1-3-6-trisulfonic acid trisodium salt (74875; MilliporeSigma). Recombinant NOTUM (50 ng) dissolved in 0.1% bovine serum albumin in PBS (25 µl) was mixed with an equal volume of 5 mM 8-Octanoyloxypyrene-1-3-6-trisulfonic acid trisodium salt in 2 times reaction buffer (10 mM CaCl~2~, 1 mM MgCl~2~, 50 mM TrisHCl, pH 7.4). Fluorescence intensity at 535 nm was measured after 10, 20, and 30 min using a SpectraMax i3 (Molecular Devices, Sunnyvale, CA, USA). Wheat germ lipase (L3001, 250 ng; MilliporeSigma) was used as positive control and 0.1% bovine serum albumin in PBS was used as blank. Real-time quantitative PCR {#s19} -------------------------- Total mRNA was prepared from bone using Trizol reagent (15596018; Thermo Fisher Scientific) and RNeasy Mini Kit (74106; Qiagen). For preparation of total mRNA from cultured cells, the RNeasy Micro Kit (74004; Qiagen) or Total RNA Purification Kit (DPK-108L; Cellco, Basking Ridge, NJ, USA) were used. The mRNA was reversed transcribed into cDNA (4368814; Thermo Fisher Scientific), and real-time PCR analyses were performed using the StepOnePlus Real-Time PCR System (Thermo Fisher Scientific) and Assay-on-Demand primer and probe sets (*Notum*: Mm01253273_m1, *Alpl*: Mm00475834_m1, *Acp5 (Trap)*: Mm00475698_m1, *Nfatc1:* Mm00479445_m1, *Ctsk:* Mm00484036_m1; Thermo Fisher Scientific). The expression of each gene was adjusted to 18S ribosomal subunit (4310893E; Thermo Fisher Scientific) or *Actb* custom-made primers: forward (5′-GGACCTGACGGACTACCTCATG-3′), reverse (5′-TCTTTGATGTCACGCACGATTT-3′), used as an internal standard. All assays had 90--100% efficiency, thus the 2^−ΔΔ^*^Ct^* method was used to calculate the relative gene expression. Statistical analyses {#s20} -------------------- Values are given as means ± [sem]{.smallcaps}. The statistical difference between *Runx2-creNotum^flox/flox^* mice and *Notum^flox/flox^* mice, between *CAGGCre-ER-Notum^flox/flox^* and *Notum^flox/flox^* mice, as well as between *Notum^+/−^* mice and WT mice, were calculated using an unpaired, 2-tailed Student's *t* test. Statistical differences between cell culture treatment groups were calculated using an unpaired, 2-tailed Student's *t* test when there were 2 groups (cells from 2 mouse strains or 2 treatment groups) and using 1-way ANOVA and Tukey's multiple comparison test when there were more than 2 treatment groups. A difference was considered statistically significant if *P* \< 0.05. Large-scale human genetic analyses using the UK Biobank {#s21} ------------------------------------------------------- In 2006--2010, the UK Biobank recruited 502,647 individuals aged 37--76 yr from across the United Kingdom. All participants provided information regarding their health and lifestyle *via* touch screen questionnaires, consented to physical measurements, and agreed to have their health followed. They also provided blood for future analysis. UK Biobank has ethical approval from the Northwest Multicenter Research Ethics Committee, and informed consent was obtained from all participants. ### Estimated BMD using ultrasound {#s22} Quantitative ultrasound of the heel was used to obtain a noninvasive estimate of BMD that predicts fracture ([@B30], [@B31]). A Sahara Clinical Bone Sonometer (Hologic, Marlborough, MA, USA) was used for quantitative ultrasound assessment of calcanei in UK Biobank participants. Details of the complete protocol are publicly available on the UK Biobank website (*<https://www.ukbiobank.ac.uk/>*). Estimated BMD (eBMD; g/cm^2^) was derived as a linear combination of speed of sound (SOS in the following equation) and bone ultrasound attenuation (BUA in the following equation) \[eBMD = 0.0025926 × (BUA + SOS) − 3.687\] ([@B31]). ### Genotyping {#s23} Genotype data are available for ≈488,000 participants in the UK Biobank cohort. Genotyping was performed using the Affymetrix UK BiLEVE Axiom array on an initial set of ≈50,000 participants; the remaining ≈450,000 participants were genotyped using the Affymetrix UK Biobank Axiom array. The 2 arrays are extremely similar (with over 95% common content). Quality control and imputation \[to over 39 million Haplotype Reference Consortium single nucleotide polymorphisms (SNPs) including more than 8 million SNPs with a minor allele frequency \>1%\] were performed centrally by UK Biobank. IMPUTE2 (*<https://mathgen.stats.ox.ac.uk/impute/impute_v2.html#home>*) was used for imputation to the Haplotype Reference Consortium v.1.1 panel. ### Model used for genetic associations {#s24} The recently released version of BOLT-LMM Bayesian mixed model association method (*<https://www.biorxiv.org/content/early/2017/09/27/194944>*) was used for the associations between imputed SNPs and eBMD (on a BMD T-score scale). This method was developed to produce highly powered, robust test statistics when run on all European samples (retaining related individuals) in the UK Biobank. The model was adjusted for sex, age, and weight. The genome-wide association study of estimated ultrasound BMD using this methodology was recently made available for public download (*<https://data.broadinstitute.org/alkesgroup/UKBB/>*). For the present study, we used these downloaded data and searched for possible associations specifically between imputed SNPs (minor allele frequency (MAF) \>1%) in the *NOTUM* locus ±25 kb from the genes' start/end limits and eBMD. In total, 125 SNPs with a minor allele frequency \> 1% were tested, and we applied a conservative Bonferroni correction for these SNPs, setting a value of *P* = 0.05/125 = 4.0 × 10^−4^ as a significance threshold. RESULTS {#s25} ======= Heterozygous female *Notum*-inactivated mice have increased cortical bone thickness {#s26} ----------------------------------------------------------------------------------- To determine the role of NOTUM in the skeleton, we developed a mouse model with global *Notum* inactivation (*Notum*^−/−^). This model had exons 2--8 of the *Notum* gene deleted (*Notum*^−/−^; [**Fig. 1*A***](#F1){ref-type="fig"}). A majority of *Notum*^−/−^ mice (≈90%) died during embryonal development, and the few mice surviving until 13 wk of age were severely growth inhibited. However, heterozygous *Notum*^+/−^ mice had normal embryonic development and were born apparently healthy and had a normal body weight growth until 13 wk of age ([Fig. 1*B*](#F1){ref-type="fig"}). In addition, *Notum*^+/−^ mice displayed normal bone length of femur ([Fig. 1*C*](#F1){ref-type="fig"}) and normal weights of several visceral organs ([Fig. 1*D*](#F1){ref-type="fig"}). When comparing the *Notum* expression in different tissues, the highest expression in WT mice was observed for liver and diaphyseal cortical bone ([Fig. 1*E*](#F1){ref-type="fig"}). *Notum*^+/−^ mice had reduced *Notum* mRNA levels in both liver and bone compared with WT mice ([Fig. 1*E*](#F1){ref-type="fig"}), and no *Notum* expression was observed in the few surviving severely growth-inhibited *Notum*^−/−^ mice. As expected, the recombination of the *Notum* allele in liver and bone was complete in the *Notum*^−/−^ mice, and it was ≈50% in these 2 tissues of *Notum*^+/−^ mice ([Fig. 1*F*](#F1){ref-type="fig"}). ![Heterozygous female *Notum*-inactivated mice have increased cortical bone thickness. *A*) Schematic drawing of the global *Notum*-inactivated mouse model. *B*) Normal body weight in both male and female *Notum^+/−^* mice (*n* = 8) when comparing with WT mice (*n* = 7) at 4, 6, and 13 wk of age. *C*) *Notum^+/−^* mice (*n* = 8) have normal femur length compared to WT mice (*n* = 7). *D*) Soft tissue weights over body weight in male and female *Notum^+/−^* (*n* = 8) and WT (*n* = 7) mice. *E*) mRNA expression analyses of *Notum* in liver, cortical bone, vertebral body, spleen, and gonadal fat, as normalized to WT liver, in male *Notum^+/−^* (*n* = 8) and WT (*n* = 7) mice. *F*) Degree of deletion in purified DNA from male WT (*n* = 7), *Notum^+/−^* (*n* = 8), and *Notum^−/−^* (*n* = 2) mice in cortical bone and liver. *G*, *H*) Femur BMD (females, *G*) and total body BMD (*H*) as measured by DXA in *Notum^+/−^* (female, *n* = 8) and WT mice (female, *n* = 7). *I*--*M*) Cortical bone area (*I*), cortical thickness (*J*), mean polar moment of inertia (*K*), cortical porosity (*L*), and cortical volumetric BMD (*M*) of the femur as measured by μCT in female *Notum^+/−^* (*n* = 8) and WT (*n* = 7) mice. *N*) Maximal load (F max) of the humerus as measured by 3-point bending analyses in female *Notum^+/−^* (*n* = 8) and WT (*n* = 7) mice. *O*, *P*) Trabecular bone volume/tissue volume (BV/TV) of the femur (*O*) and of the vertebrae L5 (*P*) as measured by μCT in female *Notum^+/−^* (*n* = 8) and WT (*n* = 7) mice. Unless otherwise stated, the results refer to 13-wk-old mice. N.D., not detectable; Sem Ves, seminal vesicles. All values are given as means ± [sem]{.smallcaps}. (\*)*P* = 0.09, \**P* \< 0.05, \*\**P* \< 0.01, \*\*\**P* \< 0.001 *vs.* WT mice (Student's *t* test[)]{.smallcaps}.](fj.201900707Rf1){#F1} Dual-energy X-ray absorptiometry (DXA) analyses revealed that the total femur BMD was significantly increased in female *Notum*^+/−^ mice compared with WT mice ([Fig. 1*G*](#F1){ref-type="fig"}), and a similar nonsignificant trend was observed for total body BMD ([Fig. 1*H*](#F1){ref-type="fig"}). We next evaluated the cortical and trabecular bone compartments separately using high-resolution µCT analyses. The femur middiaphyseal cortical bone area ([Fig. 1*I*](#F1){ref-type="fig"}), cortical thickness ([Fig. 1*J*](#F1){ref-type="fig"}), and the estimated bone strength polar moment of inertia ([Fig. 1*K*](#F1){ref-type="fig"}) were significantly increased in female *Notum*^+/−^ mice compared with WT mice, whereas cortical porosity ([Fig. 1*L*](#F1){ref-type="fig"}) and cortical volumetric BMD ([Fig. 1*M*](#F1){ref-type="fig"}) were unaffected. Three-point bending analyses of the diaphyseal region of the humerus revealed increased cortical bone strength in female *Notum*^+/−^ mice compared with WT mice ([Fig. 1*N*](#F1){ref-type="fig"}). In contrast, female *Notum*^+/−^ mice had normal trabecular bone volume/tissue volume (BV/TV) fraction in both the distal metaphyseal region of femur ([Fig. 1*O*](#F1){ref-type="fig"}) and in the L5 vertebral body ([Fig. 1*P*](#F1){ref-type="fig"}). Thus, heterozygous female *Notum*-inactivated mice have specifically increased cortical bone thickness and bone strength. There was no significant bone phenotype in the male *Notum*^+/−^ mice compared with male WT mice ([Supplemental Table S1](#SM2){ref-type="supplementary-material"}). Osteoblast-derived NOTUM is the principal source of NOTUM in bone {#s27} ----------------------------------------------------------------- Because *Notum* expression was high in cortical bone, we hypothesized that the cortical bone phenotype in the heterozygote female *Notum*-inactivated mice might be caused by lack of *Notum* expression by osteoblast lineage cells in cortical bone. However, a role of other contributing cell types in the bone compartment or by circulating factors such as liver-derived *Notum* or other indirect systemic effects could not be excluded. To determine the source of NOTUM in cortical bone and the function of osteoblast-derived NOTUM *in vivo*, we generated a conditional *Notum*-inactivated mouse model targeting osteoblasts and osteocytes. A mouse model with exons 2--8 of *Notum* flanked by *LoxP* sites (*Notum*^*flox/flox*^,[**Fig. 2*A***](#F2){ref-type="fig"}) was used ([@B16]). To achieve inactivation of NOTUM early in the osteoblast lineage, we generated *Runx2-creNotum^flox/flox^* mice, which express Cre recombinase driven by the Runx2 promoter, a promoter that is expressed specifically in early osteoblast lineage cells but not in osteoclasts ([Fig. 2*A*](#F2){ref-type="fig"}) ([@B18]). *Runx2-creNotum^flox/flox^* mice had substantial and specific recombination of the *Notum^flox^* allele in bone ([Fig. 2*B*](#F2){ref-type="fig"}), resulting in 98 ± 0.4 and 79 ± 9.5% lower *Notum* mRNA levels in cortical bone of female and male mice, respectively, compared to corresponding *Notum^flox/flox^* mice ([Fig. 2*C*](#F2){ref-type="fig"}). Analyses of isolated calvarial cells, containing a large proportion of osteoblasts, showed that cells from *Runx2-creNotum^flox/flox^* mice had substantially lower levels of *Notum* mRNA expression compared with cells from *Notum^flox/flox^* mice ([Fig. 2*D*](#F2){ref-type="fig"}). Expression of *Notum* mRNA in bone marrow macrophages was close to the detection limit and was not affected by osteoblast lineage--specific *Notum* inactivation ([Fig. 2*D*](#F2){ref-type="fig"}). These findings demonstrate that osteoblast lineage--derived NOTUM is the principal source of NOTUM in cortical bone. ![Osteoblast-derived NOTUM is the principal source of NOTUM in bone. *A*) Schematic drawing of the conditional osteoblast lineage--specific *Notum*-inactivated mouse model. *B*) Degree of deletion of *Notum* DNA in cortical bone and liver in *Runx2-creNotum^flox/flox^* (*n* = 15) and *Notum^flox/flox^* (*n* = 11) male mice. *C*) mRNA expression analyses of *Notum* in the cortical bone and liver in *Runx2-creNotum^flox/flox^* (females, *n* = 11; males, *n* = 15) and *Notum^flox/flox^* (females, *n* = 13; males, *n* = 11) mice. *D*) mRNA expression analyses of *Notum* in cultured calvarial osteoblasts (cOBL) and bone marrow macrophage--derived osteoclasts (BMMOCLs) from *Runx2-creNotum^flox/flox^* and *Notum^flox/flox^* mice. (Representative experiment, *n* = 3 wells/cell type and mouse strain.) *E*) Normal body weight in *Runx2-creNotum^flox/flox^* mice (female, *n* = 11; male, *n* = 15) compared to *Notum^flox/flox^* mice (female, *n* = 13; male, *n* = 11) at 5, 12, and 17 wk of age. *F*) Normal femur length in *Runx2-creNotum^flox/flox^* mice (female, *n* = 11; male, *n* = 15) compared to *Notum^flox/flox^* mice (female, *n* = 13; male, *n* = 11). *G*) Soft tissue weights over body weight in *Runx2-creNotum^flox/flox^* mice (females, *n* = 11; males, *n* = 15) and *Notum^flox/flox^* mice (females, *n* = 13; males, *n* = 11). *H*) Total body BMD as measured by DXA in 5-wk-old and 17-wk-old *Runx2-creNotum^flox/flox^* mice (female, *n* = 11; male, *n* = 15) and *Notum^flox/flox^* mice (female, *n* = 13; male, *n* = 11). *I*) Femur BMD as measured by DXA in 17-wk-old *Runx2-creNotum^flox/flox^* mice (female, *n* = 11; male, *n* = 15) and *Notum^flox/flox^* mice (female, *n* = 13; male, *n* = 11). Unless otherwise stated, the results refer to 17-wk-old mice. All values are given as means ± [sem]{.smallcaps}. \**P* \< 0.05, \*\**P* \< 0.01 *vs.* *Notum^flox/flox^* mice (Student's *t* test).](fj.201900707Rf2){#F2} *Runx2-creNotum^flox/flox^* mice displayed normal embryonic development and were born apparently healthy and had a normal body weight growth through 17 wk of age ([Fig. 2*E*](#F2){ref-type="fig"}). In addition, *Runx2-creNotum^flox/flox^* mice had normal bone length of femur ([Fig. 2*F*](#F2){ref-type="fig"}) and normal weights of several visceral organs ([Fig. 2*G*](#F2){ref-type="fig"}). DXA analyses revealed that both *male and female Runx2-creNotum^flox/flox^* mice developed increased total body BMD during sexual maturation ([Fig. 2*H*](#F2){ref-type="fig"}). Total femur BMD was also significantly increased in both adult male and adult female *Runx2-creNotum^flox/flox^* mice compared with corresponding *Notum^flox/flox^* mice ([Fig. 2*I*](#F2){ref-type="fig"}). Thus, osteoblast-derived NOTUM is the principal source of NOTUM in bone and decreases total body BMD. Osteoblast-derived NOTUM reduces cortical but not trabecular bone mass {#s28} ---------------------------------------------------------------------- Detailed CT analyses of the cortical diaphyseal bone in femur revealed increased cortical bone area ([**Fig. 3*A***](#F3){ref-type="fig"}), cortical bone thickness ([Fig. 3*B*](#F3){ref-type="fig"}), and cortical polar moment of inertia ([Fig. 3*C*](#F3){ref-type="fig"}) in adult *Runx2-creNotum^flox/flox^* mice compared to control mice. However, neither the cortical porosity ([Fig. 3*D*](#F3){ref-type="fig"}) nor the cortical volumetric BMD ([Fig. 3*E*](#F3){ref-type="fig"}) were affected in the *Runx2-creNotum^flox/flox^* mice. Furthermore, the cortical thickness and cortical area of vertebral body L5 were increased in female *Runx2-creNotum^flox/flox^* mice compared to control mice and a similar nonsignificant trend (*P* = 0.09) was observed for the cortical bone area in male mice ([Supplemental Table S2](#SM2){ref-type="supplementary-material"}). The increased amount of cortical bone resulted in a substantial increase in mechanical strength (maximum load; [Fig. 3*F*](#F3){ref-type="fig"}) and whole-bone work-to-fracture ([Fig. 3*G*](#F3){ref-type="fig"}) of the cortical bone, whereas the structural stiffness ([Fig. 3*H*](#F3){ref-type="fig"}) was not significantly affected when evaluated by using 3-point bending in the diaphyseal region of the humerus. *Runx2-creNotum^flox/flox^* male mice had normal BV/TV in both the distal metaphyseal region of femur ([Fig. 3*I*](#F3){ref-type="fig"}) and in the L5 vertebral body ([Fig. 3*J*](#F3){ref-type="fig"}). *Runx2-creNotum^flox/flox^* female mice had also a normal BV/TV in the distal metaphyseal region of femur ([Fig. 3*I*](#F3){ref-type="fig"}) but a slightly decreased BV/TV in the L5 vertebral body ([Fig. 3*J*](#F3){ref-type="fig"}). The increased cortical thickness but not trabecular bone mass is a phenocopy, although slightly more pronounced, of the heterozygote female global *Notum*-inactivated mice. The increased cortical bone thickness in both the male and the female mice with osteoblast lineage--specific *Notum* inactivation was the result of an increased periosteal circumference ([Fig. 3*K*](#F3){ref-type="fig"}), whereas the endocortical circumference was not reduced ([Fig. 3*L*](#F3){ref-type="fig"}). However, cortical histomorphometric analyses performed at 17 wk of age did not identify any significant effects on bone formation rate or on numbers of osteoblasts or osteoclasts per bone surface ([Supplemental Table S3](#SM2){ref-type="supplementary-material"}). ![Osteoblast-derived NOTUM reduces cortical but not trabecular bone mass. *A*--*E*) Cortical bone area (*A*), cortical thickness (*B*), mean polar moment of inertia (*C*), cortical porosity (*D*), and cortical volumetric BMD (*E*) of the femur as measured by μCT in *Runx2-creNotum^flox/flox^* (female, *n* = 11; males, *n* = 15) and *Notum^flox/flox^* (females, *n* = 13; males, *n* = 11) mice. *F*--*H*) Maximal load (F max) (*F*), whole-bone work-to-fracture (*G*), and (*H*) structural stiffness (*H*) of the humerus as measured by 3-point bending in *Runx2-creNotum^flox/flox^* (female, *n* = 11; males, *n* = 15) and *Notum^flox/flox^* (females, *n* = 13; males, *n* = 11) mice. All biomechanical data are whole-bone data. *I*, *J*) Trabecular BV/TV in the femur (*I*) and vertebral body L5 (*J*) in *Runx2-creNotum^flox/flox^* mice (females, *n* = 11; males, *n* = 15) and *Notum^flox/flox^* mice (females, *n* = 13; males, *n* = 11). *K*, *L*) Periosteal (*K*) and endocortical circumference (*L*) of the femur as measured by µCT in *Runx2-creNotum^flox/flox^* (females, *n* = 11; males, *n* = 15) and *Notum^flox/flox^* (females, *n* = 13; males, *n* = 11) mice. Unless otherwise stated, the results refer to 17-wk-old mice. All values are given as means ± [sem]{.smallcaps}. \**P* \< 0.05, \*\**P* \< 0.01 *vs.* *Notum^flox/flox^* mice (Student's *t* test).](fj.201900707Rf3){#F3} Inducible inactivation of *Notum* increases cortical periosteal bone formation {#s29} ------------------------------------------------------------------------------ Although very informative, the studies using osteoblast lineage--specific *Notum* inactivation could not separate between developmental effects of NOTUM and its effects on adult bone metabolism. Therefore, to evaluate the effect of *Notum* specifically on adult cortical bone homeostasis and the underlying mechanisms, we developed a mouse model with tamoxifen-inducible *Notum* inactivation in adult mice. To this end, we bred *Notum^flox/flox^* mice with *CAGGCre-ER* transgenic mice ([@B19]) expressing a tamoxifen-inducible Cre-mediated recombination system ([**Fig. 4*A***](#F4){ref-type="fig"}). We have previously shown that *CAGGCre-ER* mice do not have a skeletal phenotype ([@B32]). All mice evaluated were treated with the same tamoxifen regime, using daily intraperitoneal injections during 3 consecutive days and the phenotype of *CAGGCre-ER-Notum^flox/flox^* and *Notum^flox/flox^* mice were compared ([Fig. 4*A*](#F4){ref-type="fig"}). The *Notum* mRNA levels in cortical bone were substantially lower (−63 ± 5%; *P* \< 0.01) in tamoxifen-treated *CAGGCre-ER-Notum^flox/flox^* mice compared with tamoxifen-treated *Notum^flox/flox^* mice, demonstrating efficient *Notum* inactivation ([Fig. 4*B*](#F4){ref-type="fig"}). To determine the skeletal phenotype in the inducible *Notum* knockout mice, 11-wk-old *Notum^flox/flox^* and *CAGGCre-ER-Notum^flox/flox^* mice were treated with tamoxifen and the phenotype was evaluated 31 d after the first tamoxifen dose. The inducible inactivation of *Notum* did not affect body weight, weights of liver, gonadal fat, kidney, spleen or uterus, or the lengths of femur or tibia ([Supplemental Table S4](#SM2){ref-type="supplementary-material"}). Detailed skeletal analyses using DXA and CT revealed that the total femur BMD (*P* \< 0.05) and several diaphyseal cortical bone mass parameter (cortical area, cortical thickness, and cortical moment of inertia; *P* \< 0.05) but not BV/TV in the metaphyseal region of tibia were significantly increased in tamoxifen-treated *CAGGCre-ER-Notum^flox/flox^* mice compared with tamoxifen-treated *Notum^flox/flox^* mice ([**Table 1**](#T1){ref-type="table"}). ![Inducible inactivation of the *Notum* gene increases cortical periosteal bone formation. *A*) Schematic drawing of the inducible *Notum* inactivation model. *B*) mRNA expression analyses of *Notum* in cortical bone in *CAGGCre-ER-Notum^flox/flox^* mice (22-wk-old male mice, *n* = 10) and *Notum^flox/flox^* mice (*n* = 12). *C*--*E*) Mineralizing surface per bone surface (*C*), mineral apposition rate (*D*), and bone formation rate per bone surface (*E*) on the periosteal side of tibia as measured by histomorphometry in *CAGGCre-ER-Notum^flox/flox^* mice (15-wk-old female mice, *n* = 11) and *Notum^flox/flox^* mice (*n* = 6). *F*--*H*) Mineralizing surface per bone surface (*F*), mineral apposition rate (*G*), and bone formation rate per bone surface (*H*) on the endocortical side of tibia as measured by histomorphometry in *CAGGCre-ER-Notum^flox/flox^* mice (15-wk-old female mice, *n* = 11) and *Notum^flox/flox^* mice (*n* = 6). *I*) Levels of procollagen type I N-terminal propeptide (P1NP, left) and (CTX) fragments (right) measured in serum in *CAGGCre-ER-Notum^flox/flox^* mice (22-wk-old male mice, *n* = 12) and *Notum^flox/flox^* mice (*n* = 10). *J*) mRNA expression analyses of ALP (*Alpl,* left) and TRAP (*Trap/Acp5*, right) in cortical bone of *CAGGCre-ER-Notum^flox/flox^* mice (22-wk-old male mice, *n* = 10) and *Notum^flox/flox^* mice (*n* = 12). All values are given as means ± [sem]{.smallcaps}. \**P* \< 0.05, \*\**P* \< 0.01, \*\*\**P* \< 0.001 *vs.* *Notum^flox/flox^* mice (Student's *t* test).](fj.201900707Rf4){#F4} ###### *Increased cortical bone mass in mice with inducible* Notum *inactivation* Variable *Notum^flox/flox^* *CAGG-Cre-ER-Notum^flox/flox^* ------------------------------------------- -------------------- -------------------------------- DXA  Femur BMD (mg/cm^2^) 104.2 ± 1.8 109.2 ± 1.5\*  Total body BMD (mg/cm^2^) 73.2 ± 0.8 75.4 ± 0.7^\#^ CT (tibia)  Cortical bone area (mm^2^) 0.87 ± 0.02 0.93 ± 0.02\*  Cortical bone thickness (µm) 222 ± 5 234 ± 3\*  Mean polar moment of inertia (mm^4^) 0.33 ± 0.01 0.37 ± 0.02\*  Cortical porosity (%) 6.4 ± 0.8 5.8 ± 0.6  Cortical volumetric BMD (g/cm^3^) 1.22 ± 0.02 1.23 ± 0.02  Trabecular bone volume/tissue volume (%) 20.1 ± 1.5 21.6 ± 0.7 Values are given as means ± [sem]{.smallcaps}. (*Notum^flox/flox^*, *n* = 10; *CAGG-Cre-ER*-*Notum^flox/flox^*, *n* = 12; 15-wk-old female mice; ^\#^*P* = 0.056). \**P* \< 0.05 *vs.* *Notum^flox/flox^* (Student's *t* test). Dynamic cortical histomorphometry was performed to determine if inducible *Notum* inactivation increased cortical bone thickness *via* increased cortical bone formation. Periosteal mineralized surface (+32 ± 4%; *P* \< 0.01; [Fig. 4*C*](#F4){ref-type="fig"}), mineral apposition rate (+65 ± 16%; *P* \< 0.05; [Fig. 4*D*](#F4){ref-type="fig"}), and bone formation rate (+113 ± 25%; *P* \< 0.01; [Fig. 4*E*](#F4){ref-type="fig"}) were substantially increased in tamoxifen-treated *CAGGCre-ER-Notum^flox/flox^* mice compared with tamoxifen-treated *Notum^flox/flox^* mice. In contrast, endocortical bone formation was not significantly affected by inducible *Notum* inactivation ([Fig. 4*F*--*H*](#F4){ref-type="fig"}). Static histomorphometry revealed that the periosteal number of osteoblasts (+183 ± 68%; *P* \< 0.05) and the periosteal surface covered by osteoblasts (+183 ± 66%; *P* \< 0.05) were significantly increased by inducible *Notum* inactivation, whereas the number of osteoblasts on the endocortical side was unchanged ([**Table 2**](#T2){ref-type="table"}). These mechanistic studies using inducible *Notum* inactivation demonstrate that *Notum* deficiency increases bone formation at the periosteal, but not at the endocortical, side of the cortical bone. For further mechanistic studies including analyses of serum bone markers and gene transcripts, *Notum^flox/flox^* and *CAGGCre-ER-Notum^flox/flox^* mice were induced with tamoxifen and evaluated 11 d after the first tamoxifen dose. Although serum levels of the bone resorption marker CTX fragments ([Fig. 4*I*](#F4){ref-type="fig"}) and the mRNA levels of the osteoclast-specific transcript *Acp5* in cortical bone ([Fig. 4*J*](#F4){ref-type="fig"}) were reduced, neither the number of periosteal osteoclasts nor the number of endocortical osteoclasts were significantly altered by *Notum* inactivation ([Table 2](#T2){ref-type="table"}). Thus, inducible *Notum* inactivation does not seem to influence the number of osteoclasts, but we cannot exclude the possibility that an inhibitory effect on osteoclast activity might have contributed to increased cortical bone thickness. ###### *Increased number of periosteal osteoblasts in mice with inducible* Notum *inactivation* Variable *Notum^flox/flox^* *CAGG-Cre-ER-Notum^flox/flox^* ------------------------------------------- -------------------- -------------------------------- Periosteal  Number of osteoblasts/perimeter (mm^−1^) 1.9 ± 0.6 5.6 ± 1.3\*  Osteoblast surface/bone surface (%) 4.0 ± 1.3 11.5 ± 2.7\*  Number of osteoclasts/perimeter (mm^−1^) 0.8 ± 0.1 0.9 ± 0.1  Osteoclast surface/bone surface (%) 2.7 ± 0.4 2.7 ± 0.4 Endocortical  Number of osteoblasts/perimeter (mm^−1^) 23.3 ± 2.7 18.0 ± 2.1  Osteoblast surface/bone surface (%) 46.4 ± 5.8 34.5 ± 4.1  Number of osteoclasts/perimeter (mm^−1^) 1.3 ± 0.2 1.2 ± 0.2  Osteoclast surface/bone surface (%) 4.1 ± 0.7 3.4 ± 0.5 Values are given as means ± [sem]{.smallcaps}. (*Notum^flox/flox^*, *n* = 12; *CAGG-Cre-ER-Notum^flox/flox^*, *n* = 10; 22-wk-old male mice). \**P* \< 0.05 *vs.* *Notum^flox/flox^* (Student's *t* test). Silencing of NOTUM increases osteoblast differentiation {#s30} ------------------------------------------------------- To determine if osteoblast-derived NOTUM has the capacity to exert local effects on osteoblasts, *Notum* expression was silenced in osteoblasts using the preosteoblast cell line MC3T3-E1. The cells were silenced 1 and 3 d after seeding and treated with osteogenic medium for 7 d, starting 24 h after the second silencing. Expression of *Notum* mRNA was decreased by 82 ± 9% (*P* \< 0.001) and 95 ± 2% (*P* \< 0.05) after the first and second silencing ([**Fig. 5*A***](#F5){ref-type="fig"}). Analyses of osteoblast differentiation showed that silencing of *Notum* resulted in enhanced mRNA expression of *Alpl* already 24 h after the second silencing ([Fig. 5*B*](#F5){ref-type="fig"}) and an increased ALP staining ([Fig. 5*C*](#F5){ref-type="fig"}) and a 7-fold increase of ALP activity ([Fig. 5*D*](#F5){ref-type="fig"}) at the end of the cultures, indicating that NOTUM is a negative regulator of osteoblastic differentiation. These findings clearly demonstrate that osteoblast-derived NOTUM has the capacity to exert local effects on osteoblast differentiation. ![Silencing of NOTUM in MC3T3-E1 cells increases osteoblastic differentiation. *A*) mRNA expression analyses of *Notum* in MC3T3-E1 cells 24 h after first (d 2) and second (d 4) silencing using siRNA. *B*) mRNA expression analyses of *Alpl* in MC3T3-E1 cells 24 h after second silencing of *Notum* using siRNA. *C*) ALP staining of MC3T3-E1 cells after silencing of *Notum* and cultured in osteogenic medium for 7 d. *D*) ALP enzymatic activity in MC3T3-E1 cells after silencing of *Notum* and cultured in osteogenic medium for 7 d. *E*) TRAP staining of osteoclasts cultured in the presence or absence of recombinant NOTUM protein for 3 d. *F*--*H*) Expression of *Acp5* (*F*), *Ctsk* (*G*), and *Nfatc1* (*H*) in osteoclasts cultured in the presence or absence of recombinant NOTUM for 3 d. *I*) TRAP5b protein released into osteoclast culture media during d 7--10 of culture on bone discs in the presence or absence of recombinant NOTUM. *J*) CTX released into osteoclast culture medium during d 7--10 of culture on bone discs in the presence or absence of recombinant NOTUM. M, M-CSF; RL, RANKL; siSCR, control scramble siRNA; siNOTUM, NOTUM-specific siRNA. All values are given as means ± [sem]{.smallcaps}. \**P* \< 0.05, \*\**P* \< 0.01, \*\*\**P* \< 0.001 *vs.* siSCR \[Student's *t* test (*A*, *B*, *D*)\]; \*\*\**P* \< 0.001 *vs.* the M treatment \[1-way ANOVA and Tukey's multiple comparison test (*F*--*H*)\]; *n* = 4 wells/treatment. All cell culture experiments were repeated at least twice with similar results.](fj.201900707Rf5){#F5} Recombinant NOTUM protein does not affect osteoclast differentiation or activity {#s31} -------------------------------------------------------------------------------- Because the NOTUM expression is very low in osteoclasts, we wanted to explore the possibility that paracrine or endocrine NOTUM might exert effects on osteoclasts. To determine if preosteoclasts or osteoclasts have the capacity to respond to NOTUM, we treated BMMs with M-CSF/RANKL in the absence and presence of recombinant human NOTUM. First, we demonstrated that the used recombinant human NOTUM had effective lipase activity ([Supplemental Fig. S3](#SM1){ref-type="supplementary-material"}). Recombinant human NOTUM did not affect the formation of TRAP-positive multinucleated osteoclasts ([Fig. 5*E*](#F5){ref-type="fig"}) or M-CSF/RANKL-induced expression of the osteoclastic genes *Acp5*, *Ctsk*, and *Nfatc1* ([Fig. 5*F*--*H*](#F5){ref-type="fig"}), when BMMs were cultured on plastic dishes. Recombinant NOTUM affected neither osteoclast formation on bone disc as assessed by release of TRAP5b ([Fig. 5*I*](#F5){ref-type="fig"}) nor osteoclast resorption activity analyzed by release of CTX ([Fig. 5*J*](#F5){ref-type="fig"}), suggesting that NOTUM does not exert any direct effects on osteoclasts. These data, however, do not exclude the possibility that NOTUM could have indirect effects on osteoclasts *in vivo.* Large-scale human genetic analyses reveal that the *NOTUM* locus is associated with BMD {#s32} --------------------------------------------------------------------------------------- To determine if the *NOTUM* locus is also associated with bone mass in humans, we used the complete UK Biobank data set, currently the most powerful available resource for human genetic analyses of a bone phenotype (*<https://www.biorxiv.org/content/early/2017/09/27/194944>*). We searched for possible associations between imputed SNPs specifically in the *NOTUM* locus (defined as ± 25 kb from the gene start and end limits) and BMD as estimated by quantitative ultrasound of the heel (eBMD; available in 445,921 European subjects). In total, we tested 125 SNPs with a minor allele of \>1% and identified 2 independent genetic signals located upstream of *NOTUM* ([**Table 3**](#T3){ref-type="table"} and [Supplemental Fig. S4*A, B*](#SM1){ref-type="supplementary-material"}) both associated with a *P* value of \<10^−10^, providing compelling statistical evidence that genetic variation arising from the *NOTUM* locus is associated with eBMD in humans. One of the identified SNPs, rs35344256 ([Supplemental Fig. S4*A*](#SM1){ref-type="supplementary-material"}; C allele associated with reduced eBMD), is a common variant with minor allele frequency of 31%, whereas the other SNP, rs147901986 ([Supplemental Fig. S4*B*](#SM1){ref-type="supplementary-material"}; G allele associated with increased eBMD), is a low-frequency variant with minor allele frequency of 2.9% ([Table 3](#T3){ref-type="table"}). ###### Genetic variants in the NOTUM locus are associated with BMD SNP Chr Position A1 A2 AF β SE P N ------------- ----- ---------- ---- ---- ------ --------- -------- --------- -------- rs35344256 17 79934194 C A 0.69 −0.0134 0.0020 1.5E−11 445921 rs147901986 17 79921522 G A 0.97 0.0386 0.0059 4.6E−11 445921 Large-scale human genetic analyses revealed that genetic variants in the *NOTUM* locus are associated with BMD. We specifically searched for possible associations between imputed SNPs (minor allele frequency \>1%) in the *NOTUM* locus ±25 kb (in total 125 SNPs with a minor allele frequency \>1% were evaluated) and BMD as estimated by quantitative ultrasound of the heel. A1, effect allele; A2, other allele; AF, allele frequency of allele 1. Independent SNPs associated with BMD and with *P* \< 1 × 10^−10^. β given as [sd]{.smallcaps} change in eBMD per effect allele. DISCUSSION {#s33} ========== NOTUM is a secreted WNT lipase reducing WNT activity ([@B9], [@B10]). As the role of NOTUM *in vivo* is essentially unknown, we developed global, cell-specific, and inducible *Notum*-inactivated mouse models. We herein demonstrate that osteoblast lineage--derived NOTUM is a crucial determinant specifically of cortical bone mass and strength *via* regulation of periosteal bone formation in mice and that genetic variants in the *NOTUM* locus are robustly associated with BMD in humans. WNT proteins signal through both the canonical WNT pathway and the noncanonical WNT pathways ([@B1], [@B2], [@B14], [@B33], [@B34]). Activation of canonical β-catenin signaling increases bone mass, and rare human genetic mutations affecting bone have been identified in components of the canonical and noncanonical WNT signaling machinery ([@B1], [@B4], [@B35][@B36][@B37][@B38]--[@B39]). Recent *in vitro* studies demonstrate that NOTUM inactivates WNTs by removing their attached lipid group essential for activation of Frizzled receptors ([@B9], [@B10]). To evaluate if NOTUM may be a local factor in bone, we first developed and characterized a mouse model with global *Notum* inactivation. Because a majority of *Notum^−/−^* mice died during embryonal development, it was not possible to determine the physiologic role of NOTUM for any phenotype in adult *Notum^−/−^* mice. However, heterozygous Notum-inactivated mice, having significantly reduced *Notum* expression in multiple tissues, were born apparently healthy and displayed a normal body weight and longitudinal bone growth. The female mice with heterozygous global *Notum* inactivation had increased cortical bone thickness and bone strength but normal BV/TV. Although our studies using heterozygous female mice with global *Notum* inactivation indicated that NOTUM reduces cortical but not trabecular bone mass, these studies were difficult to interpret. First, a majority of homozygous *Notum*-inactivated mice died during embryonic development, demonstrating that NOTUM is required for normal development and that it therefore is not possible to use this mouse model to determine the effect of NOTUM on adult bone metabolism. Second, although female mice with global *Notum* inactivation had increased cortical bone thickness, no significant bone phenotype was observed in heterozygous male mice. Finally, the experiments using global *Notum* inactivation could not determine the source of NOTUM with an impact on cortical bone. Because *Notum* expression was high in the cortical bone, we hypothesized that the cortical bone phenotype in the heterozygote female *Notum*-inactivated mice might be caused by lack of *Notum* expression by osteoblast lineage cells in cortical bone. However, a role of other contributing cell types in the bone compartment or by circulating factors, such as liver-derived Notum, or other indirect systemic effects could not be excluded using this mouse model. To determine if the relatively high *Notum* expression in cortical bone is osteoblast-derived and to determine the *in vivo* role of osteoblast-derived NOTUM, we developed a conditional *Notum*-inactivated mouse model with inactivation of *Notum* in both osteoblasts and osteocytes. Using this model, we clearly demonstrated that osteoblast lineage cells are the principal source of NOTUM in cortical bone, and we next determined the functional role of osteoblast-derived NOTUM. In contrast to homozygous mice with global *Notum* inactivation, those with osteoblast lineage--specific *Notum* inactivation were born healthy and displayed a normal body weight and longitudinal bone growth. These findings demonstrate that the severe developmental effects in the global *Notum*-inactivated homozygous mice are caused by lack of NOTUM in other cells than osteoblast lineage cells. CT analyses, separating the cortical and trabecular bone compartments revealed that both adult male and adult female mice with osteoblast lineage--specific inactivation of *Notum* had increased cortical bone thickness in the long bones, whereas no increase was observed on BV/TV in the vertebrae or in the long bones. Although slightly more pronounced, this specific cortical bone phenotype in mice with osteoblast lineage--specific *Notum* inactivation is very similar to the cortical bone phenotype observed in the female mice with heterozygous global Notum inactivation, supporting the concept that osteoblast-derived NOTUM is mediating the effects on cortical bone thickness. Three-point bending analyses revealed substantially increased whole-bone mechanical bone strength in mice with osteoblast lineage--specific inactivation of *Notum* compared with control mice, demonstrating that the increased cortical bone thickness resulted in increased bone strength. It is a limitation with the present study that the cortical bone quality was only evaluated by cortical porosity measurements, whereas no analyses of the tissue material properties were performed, precluding statements on the cortical bone quality. Another limitation with the present study is that the cortical tissue organization estimated by informative collagen type I orientation analyses was not performed ([@B40][@B41]--[@B42]). The increased cortical bone thickness in both the male and the female mice with osteoblast lineage--specific *Notum* inactivation was the result of an increased periosteal circumference, whereas the endocortical circumference was not reduced, suggesting that the increased cortical bone thickness was caused by cortical periosteal bone formation. However, the lack of significant effects on cortical bone formation rates and number of osteoclasts in 17-wk-old adult mice with lifelong osteoblast lineage--specific *Notum* inactivation indicated that the increased cortical bone thickness of these mice was a result of effects occurring earlier in life. Therefore, to evaluate the effect of NOTUM on adult cortical bone homeostasis and the underlying mechanisms, we developed a mouse model with tamoxifen-inducible *Notum* inactivation in adult mice. An increase specifically of cortical bone mass was observed only 4 wk after the inducible *Notum* inactivation in adult mice, excluding confounding developmental effects and demonstrating that endogenous NOTUM exerts crucial effects on cortical bone homeostasis in adult mice. The mechanistic studies using the mouse model with inducible inactivation of *Notum* revealed that NOTUM deficiency increases periosteal bone formation as a result of a combination of increased periosteal mineralized surface, reflecting the number of active osteoblasts, and increased periosteal mineral apposition rate, reflecting the activity of osteoblasts. An effect on cortical periosteal bone formation was further supported by the observed increased number of osteoblasts on the periosteal surface in mice with inducible *Notum* inactivation. Collectively, the acute mechanistic data, using inducible *Notum* inactivation, demonstrate that the increased periosteal cortical circumference, observed in mice with lifelong chronic osteoblast lineage--specific inactivation of *Notum,* is primarily caused by increased periosteal bone formation. A local effect of osteoblast-derived *Notum* on osteoblasts is supported by our finding that *Notum* silencing enhanced osteoblast differentiation in cultured MC3T3-E1 osteoblasts. In contrast, very low *Notum* expression was observed in osteoclast cultures and recombinant human NOTUM did not exert any significant direct effect on osteoclast formation or activity *in vitro*. Although serum levels of the bone resorption marker CTX and the mRNA levels of the osteoclast-specific transcript *Acp5* in cortical bone were reduced by inducible *Notum* inactivation, we were unable to detect any decrease of the number of osteoclasts in cortical bone. Thus, NOTUM does not seem to exert any effect on osteoclastogenesis in cortical bone. Our findings overall demonstrate that the principal mechanism for the increased cortical bone thickness in *Notum*-inactivated mice is an increased periosteal bone formation *via* depletion of local inhibitory effects of osteoblast-derived NOTUM on osteoblast number and activity. Very similar increases on cortical bone thickness and cortical bone strength were observed in male and female mice for the mouse model with osteoblast lineage--specific *Notum* inactivation. In contrast, for the mouse model with heterozygous global *Notum* inactivation, a significant cortical bone phenotype was only observed in female mice, suggesting that female mice might be more sensitive to changes in *Notum* expression. It is a limitation with the present study that possible sex differences in the effect on cortical bone thickness were not investigated in the inducible *Notum*-inactivated mouse model. Cortical bone mass is a major determinant of bone strength and therefore of susceptibility to fractures ([@B3], [@B43]). With aging, the mass of cortical bone may decrease more than the mass of trabecular bone, and fractures occurring in older persons result to a large extent from cortical bone fragility ([@B43], [@B44]). Although progress has been made in therapeutic approaches to reduce the risk of vertebral fracture (which occurs at sites rich in trabecular bone), currently available treatments do little to reduce the risk of nonvertebral fracture, which results mostly from cortical bone fragility ([@B4], [@B43], [@B45], [@B46]). Thus, there is a medical need to improve the therapy for nonvertebral fractures, and our present finding that osteoblast-derived *Notum* reduces cortical bone mass suggests that methods inhibiting the effect of NOTUM might increase cortical bone mass and thereby reduce nonvertebral fracture risk. Mice with osteoblast- or osteocyte-specific inactivation of *Wntless* (*Wls*, previously known as Gpr177), which is required for the secretion of WNT ligands from cells, have substantially reduced bone mass, illustrating the crucial role of osteoblast lineage--derived WNTs for bone homeostasis ([@B47]). In contrast to mice with osteoblast lineage--specific *Wls* inactivation (displaying a marked reduction of both trabecular and cortical bone mass) ([@B47]), osteoblast lineage--specific *Notum* inactivation resulted specifically in increased cortical bone thickness without affecting trabecular bone mass. Combined, these findings suggest that NOTUM mainly renders WNTs inactive in cortical bone, and this notion is supported by our observation that the *Notum* expression is higher in cortical than in trabecular bone. The fact that patients with Pyle's disease, caused by recessive mutation in the *SFRP4* gene, encoding a soluble WNT inhibitor, have thin cortical but dense trabecular bone, further demonstrates that WNTs and WNT modulators exert site-specific effects in the skeleton ([@B46]). Previous studies have demonstrated that osteoblast-derived WNT16 increases cortical but not trabecular bone mass, and it is therefore possible that osteoblast-derived WNT16 is inactivated by osteoblast-derived NOTUM in cortical bone ([@B2], [@B48]). We recently observed that inducible *Wnt16* inactivation in adult mice reduces periosteal cortical bone formation ([@B32]). In addition, we herein demonstrate that inducible inactivation of the WNT lipase *Notum* in adult mice increases periosteal cortical bone formation, suggesting that there may be a local periosteal interaction between WNT16 and NOTUM for the regulation of bone formation. We propose that in adult mice, WNT16-mediated periosteal bone formation might be inhibited by a local NOTUM-mediated negative feedback. A role of intact palmitoleoylation of WNTs for periosteal bone growth is supported by our recent finding that inhibition of Porcupine, the enzyme responsible for palmitoleoylation of WNTs, reduces periosteal but not endocortical bone formation ([@B49]). The trabecular bone phenotype in mice with osteoblast lineage--specific inactivation of *Wls* most likely is mediated by loss of WNTs not inactivated by NOTUM within the trabecular bone microenvironment ([@B47]). Collectively, these findings demonstrate that WNTs may exert compartment-specific effects on bone homeostasis and that NOTUM most likely inactivates WNTs with a crucial effect specifically on cortical bone. It has recently been reported that substances inhibiting the lipase activity of NOTUM increased cortical bone thickness ([@B13], [@B50], [@B51]). These substances, selected based on their capacity to inhibit lipase activity and canonical signaling specifically by WNT3A, increased cortical bone thickness mainly *via* an increased endocortical bone formation, whereas inactivation of endogenous NOTUM in the present study increased cortical bone thickness mainly *via* increased periosteal bone formation. This difference in the predominant cortical bone surface involved might be caused by differences in the effects of inactivation of endogenous NOTUM and the effects of pharmacological inhibition of lipase activity, resulting in enhanced WNT3A-mediated canonical signaling. First, endogenous NOTUM may exert lipase independent effects; second, the lipase substrate specificity, both regarding WNTs known to control cortical bone homeostasis such as WNT16 and other non-WNT proteins, may differ between endogenous NOTUM and the pharmacological effect of the developed substances. Finally, we evaluated if the *NOTUM* locus is associated with bone mass also in humans. To this end, we used the recently released complete UK Biobank data set (*n* = 445,921 European subjects) to test genetic variation in the *NOTUM* locus for association with eBMD variation in the most powered setting available. We identified 2 independent genetic variants in the *NOTUM* locus that are associated with eBMD. This finding is the first indication that the *NOTUM* locus is involved in the regulation of bone mass also in humans. Subsequent studies assessing whether these genetic variants in the *NOTUM* locus are specifically associated with cortical bone thickness are warranted in deeper phenotyped cohorts assessed by computer tomography. In summary, we demonstrate that osteoblast-derived NOTUM is an essential regulator of cortical bone mass *via* effects on periosteal bone formation in adult mice and that genetic variation in the *NOTUM* locus is associated with BMD in humans. Therapies targeting osteoblast-derived NOTUM may constitute useful and specific treatments to reduce the risk of nonvertebral fractures. Supplementary Material {#s35} ====================== This article includes supplemental data. Please visit *<http://www.fasebj.org>* to obtain this information. ###### Click here for additional data file. ###### Click here for additional data file. This article includes supplemental data. Please visit *<http://www.fasebj.org>* to obtain this information. The authors thank Lotta Uggla, Biljana Aleksic, Anna Westerlund, and Anette Hansevi (all from the University of Gothenburg) for excellent technical assistance, and Carolina Medina-Gomez (Erasmus University Rotterdam) for support in the human genetic analyses. This study was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement in Gothenburg (Grants 238261, 226481, and 237551), the IngaBritt and Arne Lundberg Foundation, the Royal 80 Year Fund of King Gustav V, the Torsten and Ragnar Söderberg's Foundation, the Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, and São Paulo Research Foundation (Grant 2014/05283-3). J.T. was supported by the Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (CRC) 1149, and G.C.N. was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Finance Code 001). S.M.-S. and K.H.N. share first authorship. The authors declare no conflicts of interest. α-MEM : α-minimum essential medium μCT : micro--computed tomography ALP : alkaline phosphatase BMD : bone mineral density BMM : bone marrow--derived macrophage BV/TV : bone volume/tissue volume CT : computed tomography CTX : C-terminal type I collagen DXA : dual-energy X-ray absorptiometry eBMD : estimated bone mineral density M-CSF : macrophage colony-stimulating factor PGK-1 : phosphoglycerate kinase 1 RANKL : receptor activator of nuclear factor κ-B ligand siRNA : small interfering RNA TRAP : tartrate-resistant acid phosphatase SNP : single nucleotide polymorphism Wls : Wntless WNT : Wingless-type MMTV integration site family member WT : wild type AUTHOR CONTRIBUTIONS {#s34} ==================== S. Movérare-Skrtic and K. H. Nilsson were responsible for the animal experiments; P. Henning and T. Funck-Brentano assisted with animal experiments; M. Nethander, F. Rivadeneira, and C. Ohlsson performed the human genetic analyses; A. Koskela and J. Tuukkanen performed the 3-point bending experiments; G. Coletto Nunes and P. P. C. Souza performed studies using MC3T3-E1 osteoblasts; P. Henning and U. H. Lerner were responsible for primary cell cultures of osteoblasts and osteoclasts; J. Tuckermann provided the *Runx2-cre* mice; C. Perret provided the *Notum*^*flox*^ mice; S. Movérare-Skrtic, U. H. Lerner, and C. Ohlsson designed and supervised the project; and S. Movérare-Skrtic, K. H. Nilsson, U. H. Lerner, and C. Ohlsson wrote the manuscript. [^1]: These authors contributed equally to this work.

You are here How can I observe Sukkot if I do not have a sukkah? It is a mitzvah to build a sukkah and to celebrate in a sukkah. The Torah (Leviticus 23:42-43) tells us that we are to live in a booth for seven days. Of course, it is not always possible to build a sukkah of one's own. Those who live in apartments may not have the outdoor space necessary for a sukkah. We are also instructed (Deuteronomy 16:14-15) to celebrate in the sukkah. We do this by eating our meals in a sukkah. Synagogues and Jewish community centers often have sukkot (plural of sukkah) that are open to the public, where one can eat a meal. Even if we dine outdoors often, eating a meal in a sukkah is a wonderful reminder of the fall harvest and our connection to the world around us. Like Thanksgiving, it is an opportunity for us to express our gratitude for all that sustains us. Even if there is no sukkah near you, consider ways to celebrate the change of seasons and how the bounty of the harvest can be shared with others. A donation to a food pantry or to a shelter for the homeless is a wonderful way of celebrating Sukkot. One of the mitzvot of Sukkot is to rejoice during the holiday. Another tradition, ushpizin, involves inviting symbolic guests to the sukkah. Plan a festive meal, inviting family and friends, featuring food common to the fall harvest.Another important mitzvah of Sukkot is the gathering of the four species represented by the lulav (palm branches) and the etrog (a citron). There are many lovely stories associated with these symbols, which help to emphasize the agricultural basis of this holiday.

「い・ろ・は・す」から「い・ろ・は・す サイダー」が登場します。サイダー!!!!! 「い･ろ･は･す サイダー」はほんのりとした甘みとやさしい刺激の炭酸が特徴の新ラインアップ。100％国産素材にこだわって作られたサイダーで、きめ細かな泡がしゅわしゅわと口の中を踊ります。保存料不使用なのもうれしい！ 3月14日より全国のコンビニエンスストア、自動販売機・スーパーマーケットなどで販売開始。515mlと1.5Lペットボトルの同時発売です。 ちなみに「い･ろ･は･す サイダー」のペットボトルには、植物由来の素材を一部に使用したプラントボトルを採用。さらに、ボトルの軽量化により515mlペットボトルでは樹脂使用量を10％削減、1.5Lペットボトルでは約5％削減し、環境にも配慮しています。 （太田智美）

The incorporation of the A2 protein to produce novel Qβ virus-like particles using cell-free protein synthesis. Virus-like particles (VLPs) have been employed for a number of nanometric applications because they self-assemble, exhibit a high degree of symmetry, and can be genetically and chemically modified. However, high symmetry does not allow for a single unique modification site on the VLP. Here, we demonstrate the co-expression of the cytotoxic A2 protein and the coat protein of the bacteriophage Qβ to form a nearly monodispersed population of novel VLPs. Cell-free protein synthesis allows for direct access and optimization of protein-synthesis and VLP-assembly. The A2 is shown to be incorporated at high efficiency, approaching a theoretical maximum of one A2 per VLP. This work demonstrates de novo production of a novel VLP, which contains a unique site that has the potential for future nanometric engineering applications.

--- abstract: 'We study cryptography based on operator theory, and propose quantum no-key (QNK) protocols from the perspective of operator theory, then present a framework of QNK protocols. The framework is expressed in two forms: trace-preserving quantum operators and natural presentations. Then we defined the information-theoretical security of QNK protocols and the security of identification keys. Two kinds of QNK protocols are also proposed. The first scheme is constructed based on unitary transformation, and the other is constructed based on two multiplicative commutative sets.' address: - 'State Key Laboratory of Information Security, Institute of Information Engineering, Chinese Academy of Sciences, Beijing 100093, China' - 'Data Communication Science and Technology Research Institute, Beijing 100191, China' author: - Li Yang - Min Liang title: 'Cryptography based on operator theory (): quantum no-key protocols' --- quantum cryptography ,quantum no-key protocol ,man-in-the-middle attack,information-theoretical security Introduction ============ The earliest group of quantum message oriented protocols is suggested in [@Boykin00; @Ambainis00; @Nayak07], which can be regarded as a quantum version of one-time pad, the sender and the receiver must preshare secretly a classical key. Later, a public-key encryption scheme of quantum message is proposed [@Yang03]. Recently, this kind of public-key cryptosystems has been developed [@Yang10]. Here we consider another technique to securely transmit quantum message, so called quantum no-key (QNK) protocol. No-key protocol was first proposed by Shamir [@Menezes97]. It is a wonderful idea to transmit classical messages secretly in public channel, independent of the idea of public-key cryptosystem and that of secret-key cryptosystem. However, the protocol presented is computationally secure, cannot resists a man-in-the-middle(MIM) attack. [@Yangli02a; @Yangli02] develop a quantum from of no-key protocol based on single-photon rotations, which can be used to transmit classical and quantum messages secretly. It can be seen that the security of the QNK protocol is based on the laws of quantum mechanics, so it is beyond computational hypothesis. Ref. [@Yangli03] proposed a protocol based on quantum computing of Boolean functions. This protocols is constructed with inherent identifications in order to prevent MIM attack. Similar to the idea of QNK protocol, Kanamori et al.[@Kanamori05] proposed a protocol for secure data communication, Kye et al.[@Kye05] proposed a quantum key distribution scheme, and Kak [@Subhash07] proposed a three-stage quantum cryptographic protocol for key agreement. Wu and Yang [@Wu09] presents a practical QNK protocol, and studied a new kind of attack named unbalance-of-information-source (UIS) attack. This kind of attack may also be effective to quantum secure direct communication protocols, such as those in [@Beige01; @Bostrom02; @Deng2003; @Deng2004]. In the paper, the theory of QNK protocols is studied, and a framework of QNK protocols is presented. Then we defined the information-theoretical security of QNK protocols, and the security of identification keys. Finally, two kinds of QNK protocols are presented. Quantum no-key protocols ======================== Framework --------- Let us consider a general framework of quantum no-key protocol, in which two ancillary states are used. Suppose Alice will send quantum message $\rho\in H_M$. The ancillary states used by Alice and Bob are $\rho_A$ and $\rho_B$, respectively. The framework of QNK protocol is described as (see Figure \[fig1\]): ![\[fig1\] A general framework of quantum no key protocol. This figure is divided into two part by a dashed line. The part above the dashed line describes Alice’s operations, and the other part describes Bob’s operations. The quantum state $\rho$ is the plain state, and $\rho_1,\rho_2,\rho_3$ represents the three cipher states transmitted between Alice and Bob. $\rho_A,\rho_B$ are two ancillary states generated randomly by Alice and Bob, respectively.](quantum-no-key){width="12cm"} 1. Alice randomly prepare a quantum state $\rho_A$, then performs $U_A$ on the quantum states $\rho_A\otimes\rho$ and gets $U_A(\rho_A\otimes\rho)U_A^\dagger$. Then she sends to Bob the first cipher state $\rho_1$, $$\rho_1=tr_A(U_A(\rho_A\otimes\rho)U_A^\dagger)\triangleq \mathcal{E}_A(\rho).$$ She retains the state $\rho_A'=tr_M(U_A(\rho_A\otimes\rho)U_A^\dagger)$. 2. Bob randomly prepares a quantum state $\rho_B$, then performs $U_B$ on the quantum states $\rho_1\otimes\rho_B$ and gets $U_B(\rho_1\otimes\rho_B)U_B^\dagger$. Then he sends to Alice the second cipher state $\rho_2$, $$\rho_2=tr_B(U_B(\rho_1\otimes\rho_B)U_B^\dagger)\triangleq \mathcal{E}_B(\rho_1).$$ He retains the state $\rho_B'=tr_M(U_B(\rho_1\otimes\rho_B)U_B^\dagger)$. 3. Alice performs $U_A'$ on $\rho_A'\otimes\rho_2$, and sends to Bob the third cipher state $\rho_3$, $$\rho_3=tr_A(U_A'(\rho_A'\otimes\rho_2)U_A'^\dagger)\triangleq\mathcal{E}_A'(\rho_2).$$ 4. Bob performs $U_B'$ on $\rho_3\otimes\rho_B'$, and gets the message $\rho\prime$, $$\rho'=e^{i\phi}\rho=tr_B(U_B'(\rho_3\otimes\rho_B')U_B'^\dagger)\triangleq\mathcal{E}_B'(\rho_3).$$ In the above protocols, the four quantum operations $\mathcal{E}_A,\mathcal{E}_B,\mathcal{E}_A',\mathcal{E}_B'$ are all trace-preserving quantum operators. This protocol is correct if and only if the four quantum operators satisfy this condition: $$\label{eqn5} \mathcal{E}_B'\circ\mathcal{E}_A'\circ\mathcal{E}_B\circ\mathcal{E}_A=e^{i\phi}\mathcal{I}.$$ [**Remark:**]{} As a special case, the unitary transformations $U_A$,$U_B$ can be chosen as bitwise controlled-unitary transformations where the message qubits act as control qubits, and $U_A'=U_A^\dagger$,$U_B'=U_B^\dagger$. In this case, $(I\otimes U_B)(U_A \otimes I)=(U_A \otimes I)(I\otimes U_B)$, and $(I\otimes U_B')(U_A' \otimes I)(I\otimes U_B)(U_A \otimes I)=I$. Natural Representation ---------------------- Trace-preserving quantum operator $\mathcal{E}$ can be written as the form of operator-sum representation $$\begin{aligned} \mathcal{E}(\rho)=\sum_i E_{i}\rho E_{i}^\dagger.\end{aligned}$$ Its natural representation [@Watrous08] is $$\begin{aligned} \label{eqn7} \overrightarrow{\mathcal{E}}(\rho)= \sum_i (E_{i}\otimes E_{i}^*)\overrightarrow{\rho} \triangleq B\overrightarrow{\rho},\end{aligned}$$ where $\overrightarrow{\rho}$ is a the column vector, and represents the vector form of the density matrix $\rho$. The quantum operations $\mathcal{E}_1$ and $\mathcal{E}_2$ are trace-preserving quantum operator, and their natural representations are denoted as $A,B$ respectively. Because trace-preserving quantum operator can be realized physically, the operators $A,B$ can be realized physically. Suppose four operators $A,B,A',B'$ represent the natural representation of the four trace-preserving quantum operators $\mathcal{E}_A,\mathcal{E}_B,\mathcal{E}_A',\mathcal{E}_B'$. Next we deduce the expressions of the natural representation $A,B,A',B'$. Let the ancillary states of Alice and Bob are $\rho_A=\rho_B=|0\rangle\langle 0|$, the orthogonal basis on the ancillary space is the set $\{e_k\}_k$. From the trace-preserving quantum operator $\mathcal{E}_A(\rho)=tr_A(U_A(|0\rangle\langle 0|\otimes\rho)U_A^\dagger)$, it can be inferred that $$\begin{aligned} \mathcal{E}_A(\rho)&=&\sum_k\langle e_k|U_A(|0\rangle\langle 0|\otimes\rho)U_A^\dagger|e_k\rangle \\ &=&\sum_k E_k\rho E_k^\dagger,\end{aligned}$$ where $E_k\equiv\langle e_k|U_A|0\rangle$ is an operator acting on the message space $H_M$. Thus, according to Eq.(\[eqn7\]), one know that the natural representation of trace-preserving quantum operator $\mathcal{E}_A$ is as follows $$A=\sum_k E_k\otimes E_k^*=\sum_k \langle e_k|U_A|0\rangle\otimes\langle e_k|U_A^*|0\rangle.$$ Similarly, one can present the natural representations of the other three trace-preserving quantum operators, for example $B=\sum_k \langle e_k|U_B|0\rangle\otimes\langle e_k|U_B^*|0\rangle$. From the above analysis, the four transformations to the quantum message $\rho$ in the quantum no-key protocol can be described in the form of natural representation. $$\begin{aligned} \overrightarrow{\rho}&\longrightarrow&\overrightarrow{\rho_1}=A\overrightarrow{\rho}\\ &\longrightarrow&\overrightarrow{\rho_2}=B\overrightarrow{\rho_1}\\ &\longrightarrow&\overrightarrow{\rho_3}=A'\overrightarrow{\rho_2}\\ &\longrightarrow&\overrightarrow{\rho}'=B'\overrightarrow{\rho_3}\end{aligned}$$ Quantum no-key protocol can be described in the form of trace-preserving quantum operators or natural representation, and the two forms are equivalent. In the following sections, we use the natural representation, and the operators $A$ and $B$ are both natural representations of trace-preserving quantum operators. $\mathcal{E}_1\circ\mathcal{E}_2=\mathcal{E}_2\circ\mathcal{E}_1$ if and only if $AB=BA$. The additive commutator $A,B$ satisfy $$AB=BA+K;$$ The multiplicative commutator $A,B$ satisfy $$BA=e^{i\lambda}AB, \lambda\neq 0,$$ or be written as $B^{-1}A^{-1}BA=e^{i\lambda}I, \lambda\neq 0$. When $K=\lambda=0$, the additive commutator equals to multiplicative commutator. The multiplicative commutator $BA=e^{i\lambda}AB$ is just additive commutator when $\lambda=0$; Multiplicative commutator is different from additive commutator in only a global phase $e^{i\lambda}$ when $\lambda \neq 0$, and they have no difference in physical implementation. [**Theorem 1**]{}: The multiplicative commutators $A,B$ are unitary matrices. If $BA=e^{i\lambda}AB$, where $\lambda\neq 0$, then the sum of the eigenvalues of the operators $A,B$ are zero, respectively. [**Proof**]{} It means to prove: if $A=\sum_j e^{i\varphi_j}|a_j\rangle\langle a_j|$, then $\sum_j e^{i\varphi_j}=0$; if $B=\sum_j e^{i\phi_j}|b_j\rangle\langle b_j|$, then $\sum_j e^{i\phi_j}=0$. The proof is as follows. From $BA=e^{i\phi_{AB}}AB$ where $A,B$ are both unitary, one know that $A=e^{i\phi_{AB}}B^\dagger AB$. Because $A$ is a unitary transformation, it has spectral decomposition $A=\sum_j\lambda_j|j\rangle\langle j|$, and each eigenvalue $\lambda_j$ can be written as $e^{i\phi_j}$. Thus, $\sum_j\lambda_j|j\rangle\langle j|=\sum_je^{i\phi_{AB}}\lambda_jB^\dagger |j\rangle\langle j|B$. Then $$\label{eqn8} \lambda_k=\sum_je^{i\phi_{AB}}\lambda_j\langle k|B^\dagger|j\rangle\langle j|B|k\rangle=\sum_je^{i\phi_{AB}}\lambda_j|\langle j|B|k\rangle|^2.$$ Let the $j$-th row and $k$-th column of $B$ is $b_{jk}$. The two side of Eq.(\[eqn8\]) is added with the variable $k$, and obtains $\sum_k\lambda_k=e^{i\phi_{AB}}\sum_j\lambda_j\sum_k|b_{jk}|^2=e^{i\phi_{AB}}\sum_j\lambda_j$. Thus, $\sum_j\lambda_j(e^{i\phi_{AB}}-1)=0$. If $\phi_{AB}\neq 0$, then $\sum_j\lambda_j=0$, that means the sum of the eigenvalues of $A$ is 0. Similarly, one can prove that the sum of the eigenvalues of $B$ is 0.$~\hfill{}\Box$ In the next part of this paper, we consider the case that $A'=A^{-1},B'=B^{-1}$. In this case, Eq.(\[eqn5\]) can also be expressed as $B^{-1}A^{-1}BA=e^{i\phi}I$. It can be seen that $A,B$ are multiplicative commutator. In order to identify personal identification in the protocols, Alice and Bob must preshare a secret key $k,i$, and the multiplicative commutator $A,B$ should satisfy: $$B^{-1}A^{-1}BA=e^{i\phi}N_k(i).$$ Alice and Bob preshare secret identification key $k,i$, where $k\in\mathcal{K}$. From the value of $k$, a operator $N_k$ can be obtained and a set $I(k)$ can be constructed, and the secret key $i\in I(k)$. From $k,i$, we can get a set $L(k,i)$ and a set of operators satisfying $$S_k(i)=\{A_l^{(i)}(k)|l\in L(k,i)\}\cup \{B_l^{(i)}(k)|l\in L(k,i)\}.$$ The set of operators $S_k(i)$ should satisfy the condition: for any two elements $A_{l_1}^{(i)}(k),B_{l_2}^{(i)}(k)\in S_k(i)$, it holds that $$\label{eqn1} [B_{l_2}^{(i)}(k)]^{-1}[A_{l_1}^{(i)}(k)]^{-1} B_{l_2}^{(i)}(k) A_{l_1}^{(i)}(k) =e^{i\phi(l_1,l_2)}N_k(i).$$ Alice and Bob communicates according to $k,i$ and the set $S_k(i)$. The process is as follows 1. Alice randomly selects $l_1\in L(k,i)$, and performs an operator $A_{l_1}^{(i)}(k)$ on quantum message $\overrightarrow{\rho}$, then obtains a state $\overrightarrow{\rho_1}$. She sends it to Bob. 2. Bob randomly selects $l_2\in L(k,i)$, and performs an operator $B_{l_2}^{(i)}(k)$ on quantum state $\overrightarrow{\rho_1}$, then obtains a state $\overrightarrow{\rho_2}$. He sends it to Alice. 3. According to $l_1$, Alice performs an operator $[A_{l_1}^{(i)}(k)]^{-1}$ on quantum state $\overrightarrow{\rho_2}$, then obtains a state $\overrightarrow{\rho_3}$. She sends it to Bob. 4. According to $l_2$, Bob performs an operator $[B_{l_2}^{(i)}(k)]^{-1}$ on quantum state $\overrightarrow{\rho_3}$, then obtains a state $\overrightarrow{\rho_4}$. From the condition satisfied by $S_k(i)$, it is deduced that $$\overrightarrow{\rho_4}=[B_{l_2}^{(i)}(k)]^{-1} [A_{l_1}^{(i)}(k)]^{-1} B_{l_2}^{(i)}(k) A_{l_1}^{(i)}(k) \overrightarrow{\rho} = e^{i\phi(l_1,l_2)}N_k(i) \overrightarrow{\rho}.$$ Thus, the quantum state obtained by Bob in the end is $N_k(i) \overrightarrow{\rho}$. He can recovery the quantum message $\overrightarrow{\rho}$ by performing the inverse transformation of $N_k(i)$. Through the value of $l_1$ is unknown by Bob, Bob randomly selects a value of $l_1'\in L(k,i)$, then it can satisfy the relation in Eq.(\[eqn1\])(only a little difference on total phase). Thus, the inverse transformation of $N_k(i)$ can also be replace by $$N_k^{-1}(i)=[A_{l_1'}^{(i)}(k)]^{-1}[B_{l_2}^{(i)}(k)]^{-1}A_{l_1'}^{(i)}(k)B_{l_2}^{(i)}(k), \forall l_1'\in L(k,i).$$ Because the operators $A_l^{(i)}(k)$, $B_l^{(i)}(k)$ are all trace-preserving quantum operators and can be implemented physically, the quantum operator $N_k^{-1}$ is physically implementable. Thus, Bob can recovery the quantum message $\overrightarrow{\rho}$ by performing $N_k^{-1}(i)$ on the state $\overrightarrow{\rho_4}$. In order to enhance the security of this protocol, we can select a group of similarity transformations $\{T_i|i\in L(k,i)\}$. The set $S_k(i)$ in the above protocol is replaced with another set $$\tilde{S}_k(i)=\{T_iA_l^{(i)}(k)T_i^{-1}|l\in L(k,i)\}\cup \{T_iB_l^{(i)}(k)T_i^{-1}|l\in L(k,i)\}.$$ Similarly, $N_k(i)$ is replaced with $T_iN_k(i)T_i^{-1}$, but it is still denoted as $N_k(i)$ for convenient. Then according to Eq.(\[eqn1\]), we know $$T_i[B_{l_2}^{(i)}(k)]^{-1}[A_{l_1}^{(i)}(k)]^{-1} B_{l_2}^{(i)}(k) A_{l_1}^{(i)}(k)T_i^{-1}=e^{i\phi(l_1,l_2)}N_k(i).$$ From the following relation $$\begin{aligned} & T_i[B_{l_2}^{(i)}(k)]^{-1}[A_{l_1}^{(i)}(k)]^{-1} B_{l_2}^{(i)}(k) A_{l_1}^{(i)}(k)T_i^{-1} \nonumber\\ =& [T_iB_{l_2}^{(i)}(k)T_i^{-1}]^{-1}[T_iA_{l_1}^{(i)}(k)T_i^{-1}]^{-1} T_iB_{l_2}^{(i)}(k)T_i^{-1} T_iA_{l_1}^{(i)}(k)T_i^{-1},\end{aligned}$$ it is inferred that: any two elements in $\tilde{S}_k(i)$ such as $T_iA_{l_1}^{(i)}(k)T_i^{-1},T_iB_{l_2}^{(i)}(k)T_i^{-1}$ satisfy the following relation $$[T_iB_{l_2}^{(i)}(k)T_i^{-1}]^{-1}[T_iA_{l_1}^{(i)}(k)T_i^{-1}]^{-1} T_iB_{l_2}^{(i)}(k)T_i^{-1} T_iA_{l_1}^{(i)}(k)T_i^{-1}=e^{i\phi(l_1,l_2)}N_k(i).$$ Security -------- In QNK protocol, there are 3 times of transmitting quantum ciphers through public quantum channel. Denote $\rho_i$ as the $i$-th quantum cipher with respect to the attackers, where $i=1,2,3$. [**Definition 1:**]{} QNK protocol is information-theoretically secure, if the three quantum ciphers $\rho_1,\rho_2,\rho_3$ satisfy the following condition: for any positive polynomial $p(.)$, and all sufficiently big number $n$, it holds that $$D\left(\rho_i,\rho_j\right)<\frac{1}{p(n)},\forall i,j\in\{1,2,3\},$$ where $\rho_1,\rho_2,\rho_3$ are all $n$-qubit ciphers. In fact, this definition equals to the following definition. [**Definition 2:**]{} QNK protocol is information-theoretically secure, if the three quantum ciphers $\rho_1,\rho_2,\rho_3$ satisfy the following condition: there exists a quantum state $\tau$, such that for any positive polynomial $p(.)$ and all sufficiently big number $n$, it holds that $$D\left(\rho_i,\tau\right)<\frac{1}{p(n)},\forall i\in\{1,2,3\},$$ where $\rho_1,\rho_2,\rho_3$ are all $n$-qubit ciphers. In one hand, if QNK protocol satisfies Definition 2, it can be deduced that $D\left(\rho_i,\rho_j\right)<D\left(\rho_i,\tau\right)+D\left(\rho_j,\tau\right)<\frac{2}{p(n)},\forall i,j\in\{1,2,3\}$, then the protocol satisfies Definition 1; In the other hand, if QNK protocol satisfies Definition 1, and let $\tau=\rho_1$, we know that $D\left(\rho_i,\tau\right)=D\left(\rho_i,\rho_1\right)<\frac{1}{p(n)},\forall i\in\{1,2,3\}$, then the protocol satisfies Definition 2. Thus, the two definitions are equivalent to each other. Here, $\rho_i$ is the $i$-th quantum cipher with respect to the attackers, where $i=1,2,3$. In the QNK protocol, $\overrightarrow{\rho_1}$ is obtained by performing quantum transformation $A_{l_1}^{(i)}(k)$ on quantum state $\overrightarrow{\rho}$. However, with regard to the attackers, the random number $l_1$ and authentication key $i,k$ used by Alice cannot be obtained, so $$\overrightarrow{\rho_1}=\sum_{i,k,l_1}p_i p_k p_{l_1} A_{l_1}^{(i)}(k)\overrightarrow{\rho},$$ where $p_i, p_k$ are the probability of selecting the authentication key $i,k$, and $p_{l_1}$ is the probability of the local number $l_1$ being selected by Alice. Similarly, the attackers cannot obtain the random number $l_2$ and authentication key $i,k$ used by Bob, so $$\overrightarrow{\rho_2}=\sum_{i,k,l_1,l_2}p_i p_k p_{l_1} p_{l_2}B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)\overrightarrow{\rho},$$ where $p_{l_2}$ is the probability of the local number $l_2$ being selected by Bob. $$\overrightarrow{\rho_3}=\sum_{i,k,l_1,l_2}p_i p_k p_{l_1} p_{l_2}(A_{l_1}^{(i)}(k))^{-1}B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)\overrightarrow{\rho}.$$ [**Definition 3:**]{} QNK protocol is information-theoretically secure, if the three operators $\sum_{i,k,l_1}p_i p_k p_{l_1}A_{l_1}^{(i)}(k)$, $\sum_{i,k,l_1,l_2}p_i p_k p_{l_1} p_{l_2}B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)$, and\ $\sum_{i,k,l_1,l_2}p_i p_k p_{l_1} p_{l_2}(A_{l_1}^{(i)}(k))^{-1}B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)$ satisfy the condition: for any positive polynomial $p(.)$, and all sufficiently large number $n$, it holds that $$\begin{aligned} &&||\sum_{i,k,l_1}p_i p_k p_{l_1} A_{l_1}^{(i)}(k)-\sum_{i,k,l_1,l_2}p_i p_k p_{l_1} p_{l_2}B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)||_{\diamondsuit}<\frac{1}{p(n)},\\ &&||\sum_{i,k,l_1,l_2}p_i p_k p_{l_1} p_{l_2}\left(B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)-(A_{l_1}^{(i)}(k))^{-1}B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)\right)||_{\diamondsuit}<\frac{1}{p(n)},\\ &&||\sum_{i,k,l_1}p_i p_k p_{l_1}A_{l_1}^{(i)}(k)-\sum_{i,k,l_1,l_2}p_i p_k p_{l_1} p_{l_2}(A_{l_1}^{(i)}(k))^{-1}B_{l_2}^{(i)}(k)A_{l_1}^{(i)}(k)||_{\diamondsuit}<\frac{1}{p(n)}.\end{aligned}$$ where the notation $||*||_{\diamondsuit}$ represents diamond norm. It is obvious that a sufficient condition for information-theoretical security is as follow: $$\begin{aligned} &&||I-\sum_{l_2}p_{l_2}B_{l_2}^{(i)}(k)||_{\diamondsuit}<\frac{1}{p(n)},\forall i,k,\\ &&||I-A_{l_1}^{(i)}(k)^{-1}||_{\diamondsuit}<\frac{1}{p(n)}, \forall i,k,l_1, \\ &&||I-\sum_{l_2}p_{l_2}(A_{l_1}^{(i)}(k))^{-1}B_{l_2}^{(i)}(k)||_{\diamondsuit}<\frac{1}{p(n)}, \forall i,k,l_1.\end{aligned}$$ For the QNK protocol which uses authentication key, when considering its security, besides analyzing the security of quantum message, we also should analyze the security of the authentication key. Here we present a definition of the security of authentication key in QNK protocol. [**Definition 4:**]{} The authentication key in QNK protocol is secure, if for any positive polynomial $p(.)$, and all sufficiently large number $n$, it holds that $$\begin{aligned} &&||\sum_{l_1}A_{l_1}^{(i_1)}(k_1)-\sum_{l_1}A_{l_1}^{(i_2)}(k_2)||_{\diamondsuit}<\frac{1}{p(n)}, \forall i_1,i_2,k_1,k_2.\\ &&||\sum_{l_1,l_2}B_{l_2}^{(i_1)}(k_1)A_{l_1}^{(i_1)}(k_1)-\sum_{l_1,l_2}B_{l_2}^{(i_2)}(k_2)A_{l_1}^{(i_2)}(k_2)||_{\diamondsuit}<\frac{1}{p(n)}, \forall i_1,i_2,k_1,k_2.\\ &&||\sum_{l_1,l_2}(A_{l_1}^{(i_1)}(k_1))^{-1}B_{l_2}^{(i_1)}(k_1)A_{l_1}^{(i_1)}(k_1)-\sum_{l_1,l_2}(A_{l_1}^{(i_2)}(k_2))^{-1}B_{l_2}^{(i_2)}(k_2)A_{l_1}^{(i_2)}(k_2)||_{\diamondsuit}\\ &&<\frac{1}{p(n)}, \forall i_1,i_2,k_1,k_2.\end{aligned}$$ Two schemes of quantum no-key protocols ======================================= First scheme ------------ Unitary transformation is a special kind of trace-preserving quantum operator. Here we assume the quantum operators used by Alice and Bob in QNK protocols are all unitary. Let $N_k(i)=I$. The sets of operators $\{A_l|l\in\{1,2,\ldots,n_A\}\}$ and $\{B_k|k\in\{1,2,\ldots,n_B\}\}$ are natural representations of unitary operator used by Alice and Bob. The two set satisfy the relation: $$\label{eqn4} B_{l_2}^{-1}A_{l_1}^{-1}B_{l_2}A_{l_1}=e^{i\phi(l_1,l_2)}I.$$ The above formula can also be written as $B_{l_2}A_{l_1}=e^{i\phi(l_1,l_2)}A_{l_1}B_{l_2}$. $A_l,B_k$ are natural representations of unitary operators. So we can assume $A_l=E_l\otimes E_l^*,B_k=F_k\otimes F_k^*$, where $E_l, F_k$ are unitary transformations, and $l\in\{1,2,\ldots,n_A\}$, $k\in\{1,2,\ldots,n_B\}$. Then $$\begin{aligned} B_{l_2}^{-1}A_{l_1}^{-1}B_{l_2}A_{l_1}&=&(F_{l_2}\otimes F_{l_2}^*)^{-1}(E_{l_1}\otimes E_{l_1}^*)^{-1}(F_{l_2}\otimes F_{l_2}^*)(E_{l_1}\otimes E_{l_1}^*)\nonumber\\ &=& (F_{l_2}^{-1}E_{l_1}^{-1}F_{l_2}E_{l_1})\otimes(F_{l_2}^{-1}E_{l_1}^{-1}F_{l_2}E_{l_1})^*\nonumber\\ &\triangleq&V_{l_1,l_2}\otimes V_{l_1,l_2}^*,\end{aligned}$$ where $V_{l_1,l_2}=F_{l_2}^{-1}E_{l_1}^{-1}F_{l_2}E_{l_1}$ is unitary transformation. According to Eq.(\[eqn4\]), we have $V_{l_1,l_2}\otimes V_{l_1,l_2}^*=e^{i\phi(l_1,l_2)}I_{2^{2n}}$. From the identity $I_{2^{2n}}=I_{2^n}\otimes I_{2^n}$, it has $V_{l_1,l_2}\otimes V_{l_1,l_2}^*=aI_{2^n}\otimes bI_{2^n}$, where $ab=e^{i\phi(l_1,l_2)}$, and $b=a^*$. So $e^{i\phi(l_1,l_2)}=aa^*=|a|^2$, then $e^{i\phi(l_1,l_2)}=1$. That means it is impossible to produce a global phase in Eq.(\[eqn4\]). Thus the Eq.(\[eqn4\]) is rewritten as follows $$\label{eqn6} B_{l_2}^{-1}A_{l_1}^{-1}B_{l_2}A_{l_1}=I.$$ Based on this relation, we construct a QNK scheme, which is described as follows. Firstly, two sets of operators are selected, such as $$S(A)=\{A_l|l\in\{1,2,\ldots,n_A\}\},$$ $$S(B)=\{B_k|k\in\{1,2,\ldots,n_B\}\}.$$ By using the two sets, Alice and Bob communicate following this QNK protocol. 1. Alice randomly selects a number $l_1\in\{1,2,\ldots,n_A\}$, then performs quantum operator $A_{l_1}$ on quantum message $\overrightarrow{\rho}$, and obtains the state $\overrightarrow{\rho_1}$. She sends it to Bob. 2. Bob randomly selects a number $l_2\in\{1,2,\ldots,n_B\}$, then performs quantum operator $B_{l_2}$ on quantum message $\overrightarrow{\rho_1}$, and obtains the state $\overrightarrow{\rho_2}$. He sends it to Alice. 3. According to the value of $l_1$, Alice performs quantum operator $A_{l_1}^{-1}$ (or $A_{l_1}^\dagger$) on quantum message $\overrightarrow{\rho_2}$, and obtains the state $\overrightarrow{\rho_3}$. She sends it to Bob. 4. According to the value of $l_2$, Bob performs quantum operator $B_{l_2}^{-1}$ (or $B_{l_2}^\dagger$) on quantum message $\overrightarrow{\rho_3}$, and obtains the state $\overrightarrow{\rho_4}$. According to the relation (Eq.(\[eqn6\])) of the two sets $S(A),S(B)$, we know that $$\overrightarrow{\rho_4}=B_{l_2}^{-1} A_{l_1}^{-1} B_{l_2} A_{l_1} \overrightarrow{\rho} = \overrightarrow{\rho}.$$ Thus, the quantum state obtained by Bob’s performing quantum transformation $B_{l_2}^{-1}$ is just the quantum message sent by Alice. Second scheme ------------- Denote the operation of two operators $A,B$: $(A,B)=B^{-1}A^{-1}BA$. Suppose there exists two groups of operators $S(A)=\{A_i|i=1,\cdots,n_A\}$ and $S(B)=\{B_i|i=1,\cdots,n_B\}$, which satisfy the following condition $$\label{eqn2} (A_i,B_j)=N, \forall i\in\{1,\cdots,n_A\},j\in\{1,\cdots,n_B\},$$ where $N$ is an operator that is independent of $i,j$. [**Proposition 1:**]{} Suppose two sets of operators $S(A),S(B)$ satisfy the condition Eq.(\[eqn2\]), then the following relations hold: $\forall i,j$ $$\begin{aligned} && (A_i^{-1},B_jB_i^{-1})=I,\\ && (A_j^{-1},B_jB_i^{-1})=I,\\ && (B_i,A_jA_i^{-1})=I,\\ && (B_j,A_jA_i^{-1})=I.\end{aligned}$$ [**Proof:**]{} See the appendix.$\hfill{}\Box$ [**Proposition 2:**]{} Suppose two sets of operators $S(A),S(B)$ satisfy the condition Eq.(\[eqn2\]), then the following relations hold: $\forall i,j,k,l$ $$(A_iA_j,B_kB_l)=(A_j^2,B_l^2).$$ [**Proof:**]{} See the appendix.$\hfill{}\Box$ According to Proposition 2, we know the relation $(A_{l_1}A_{k_1},B_{l_2}B_{k_2})=(A_{k_1}^2,B_{k_2}^2)$. Based on this relation, a QNK scheme is constructed as follows. Suppose the set of similarity transformations $\{T_i|i\in I\}$ is selected. Firstly we construct a set of operators $S_k(i)$ as follows: $$\begin{aligned} S_{k_1||k_2}(i)&=&\{T_iA_lA_{k_1}T_i^{-1}|l\in\{1,\cdots,n_A\}\} \nonumber\\ &&\cup\{T_iB_lB_{k_2}T_i^{-1}|l\in\{1,\cdots,n_B\}\}.\end{aligned}$$ In the set $S_k(i)$, any two elements $A_{l_1}^{(i)}(k_1||k_2)=T_iA_{l_1}A_{k_1}T_i^{-1}$ and $B_{l_2}^{(i)}(k_1||k_2)=T_iB_{l_2}B_{k_2}T_i^{-1}$ satisfy the following relation $$\begin{aligned} (A_{l_1}^{(i)}(k_1||k_2),B_{l_2}^{(i)}(k_1||k_2))&=& (T_iA_{l_1}A_{k_1}T_i^{-1},T_iB_{l_2}B_{k_2}T_i^{-1}) \nonumber\\ &=& T_i(A_{l_1}A_{k_1},B_{l_2}B_{k_2})T_i^{-1} \nonumber\\ &=& T_i(A_{k_1}^2,B_{k_2}^2)T_i^{-1}.\end{aligned}$$ Denote $N_{k_1||k_2}=(A_{k_1}^2,B_{k_2}^2)$, $N_{k_1||k_2}(i)=T_i N_{k_1||k_2} T_i^{-1}$, then $$(A_{l_1}^{(i)}(k_1||k_2),B_{l_2}^{(i)}(k_1||k_2))=N_{k_1||k_2}(i), ~\forall l_1,l_2.$$ Alice and Bob communicate according to $k_1||k_2,i$ ($k_1\in\{1,\cdots,n_A\},k_2\in\{1,\cdots,n_B\}$, $i\in I$) and the set of operators $S_{k_1||k_2}(i)$. The process is as follows. 1. Alice randomly selects a number $l_1\in\{1,\cdots,n_A\}$, and performs quantum transformation $A_{l_1}^{(i)}(k_1||k_2)$ on quantum message $\overrightarrow{\rho}$, then obtains $\overrightarrow{\rho_1}$. She sends it Bob. 2. Bob randomly selects a number $l_2\in \{1,\cdots,n_B\}$, and performs quantum transformation $B_{l_2}^{(i)}(k_1||k_2)$ on quantum state $\overrightarrow{\rho_1}$, then obtains $\overrightarrow{\rho_2}$. He sends it to Alice. 3. According to $l_1$, Alice performs quantum transformation $[A_{l_1}^{(i)}(k_1||k_2)]^{-1}$ on quantum state $\overrightarrow{\rho_2}$, and obtains $\overrightarrow{\rho_3}$. She sends it to Bob. 4. According to $l_2$, Bob performs quantum transformation $[B_{l_2}^{(i)}(k_1||k_2)]^{-1}$ on quantum state $\overrightarrow{\rho_3}$, and obtains $\overrightarrow{\rho_4}$. From the condition satisfied by $S_{k_1||k_2}(i)$, it can be deduced that $$\overrightarrow{\rho_4}=N_{k_1||k_2}(i)\overrightarrow{\rho}=T_i (A_{k_1}^2,B_{k_2}^2) T_i^{-1}\overrightarrow{\rho}.$$ Bob performs the inverse transformation of $N_{k_1||k_2}(i)$, which is $[N_{k_1||k_2}(i)]^{-1}=T_i (B_{k_2}^2,A_{k_1}^2) T_i^{-1}$, then the quantum message $\overrightarrow{\rho}$ is recovered. [**Proposition 3:**]{} $(A_{j_1}A_{j_2}A_{j_3},B_{i_1}B_{i_2}B_{i_3})=(A_{j_3}A_{j_2}A_{j_3},B_{i_3}B_{i_2}B_{i_3})$, $\forall i_1,i_2,i_3$, $\forall j_1,j_2,j_3$. [**Proof:**]{} See the appendix.$\hfill{}\Box$ According to Proposition 3, we know the relation $(A_{l_1}A_{k_1}A_{k_2},B_{l_2}B_{k_3}B_{k_4})=(A_{k_2}A_{k_1}A_{k_2},B_{k_4}B_{k_3}B_{k_4})$. Suppose the set of similarity transformations $\{T_i|i\in I\}$ is selected. We construct the set of operators $S_k(i)$ as follows: $$\begin{aligned} S_{k_1||k_2||k_3||k_4}(i)&=&\{T_iA_lA_{k_1}A_{k_2}T_i^{-1}|l=1,\cdots,n_A\} \nonumber\\ &&\cup\{T_iB_lB_{k_3}B_{k_4}T_i^{-1}|l=1,\cdots,n_B\}.\end{aligned}$$ When the set of operators $S_{k_1||k_2||k_3||k_4}(i)$ is used in the QNK communication, $l$ is a random number selected locally, and $k_1,k_2,k_3,k_4,i$ are authentication keys preshared by Alice and Bob. If Alice selects a local random number $l_1$, then she should perform quantum transformation $T_iA_{l_1}A_{k_1}A_{k_2}T_i^{-1}$; if Bob selects a local random number $l_2$, then he should perform quantum transformation $T_iB_{l_2}B_{k_3}B_{k_4}T_i^{-1}$. The detailed process of the three interactive communication is the same as the last scheme. After the fourth step, Bob obtains a quantum state $$\overrightarrow{\rho_4}=T_i (A_{k_2}A_{k_1}A_{k_2},B_{k_4}B_{k_3}B_{k_4}) T_i^{-1}\overrightarrow{\rho}.$$ Then Bob performs quantum transformation $T_i (B_{k_4}B_{k_3}B_{k_4},A_{k_2}A_{k_1}A_{k_2}) T_i^{-1}$ and obtains the quantum message $\overrightarrow{\rho}$ sent by Alice. In general, we have the following relation $$(A_{l_1}A_{k_1}A_{k_2}\cdots A_{k_n},B_{l_2}B_{k_1'}B_{k_2'}\cdots B_{k_n'})=(A_{k_n}A_{k_1}A_{k_2}\cdots A_{k_n},B_{k_n'}B_{k_1'}B_{k_2'}\cdots B_{k_n'}).$$ According to this relation, a new QNK scheme can be constructed similarly. In the new scheme, more operators can be used by Alice and Bob. Construction of the sets $S(A)$ and $S(B)$ ------------------------------------------ Suppose there exists two groups of operators such as $S(A)=\{A_i|i=1,\cdots,n_A\}$ and $S(B)=\{B_i|i=1,\cdots,n_B\}$, and they satisfy the relation expressed in Eq.(\[eqn2\]), then $A_i^{-1}B_jA_i=B_jN,\forall j$. Thus $A_{i_1}^{-1}B_jA_{i_1}=A_{i_2}^{-1}B_jA_{i_2}$. That is $$\label{eqn3} (A_{i_2}A_{i_1}^{-1})B_j=B_j(A_{i_2}A_{i_1}^{-1}),$$ or written as $(A_{i_2}A_{i_1}^{-1},B_j)=I$ or $[A_{i_2}A_{i_1}^{-1},B_j]=0$. (Denote $[A,B]=AB-BA$) According to Eq.(\[eqn2\]) and the similar deduction, it can be inferred that $\forall i,j,k$, $$\begin{aligned} && [A_iA_j^{-1},B_k]=0, \\ && [A_iA_j^{-1},B_k^{-1}]=0, \\ && [B_iB_j^{-1},A_k]=0, \\ && [B_iB_j^{-1},A_k^{-1}]=0,\end{aligned}$$ From $[A_iA_j^{-1},B_k]=0,\forall i,j,k$, it can be deduced that $$\label{eqn3} [A_iA_j^{-1},B_kB_l^{-1}]=[A_iA_j^{-1},B_k]B_l^{-1}+B_k[A_iA_j^{-1},B_l^{-1}]=0+0=0.$$ That means $(A_iA_j^{-1},B_kB_l^{-1})=I, \forall A_i,A_j\in S(A), B_k,B_l\in S(B)$. Thus, we can extend the two sets of operators $S(A),S(B)$ to two new sets of operators $\tilde{S}(A),\tilde{S}(B)$ as follows: $$\begin{aligned} & \tilde{S}(A)=\{A_{i||j}=A_iA_j^{-1}|A_i,A_j\in S(A)\}, \\ & \tilde{S}(B)=\{B_{i||j}=B_iB_j^{-1}|B_i,B_j\in S(B)\},\end{aligned}$$ According to Eq.(\[eqn3\]), if we select one element from each of the two new sets $\tilde{S}(A),\tilde{S}(B)$, such as $A_{i||j},B_{k||l}$ (where $i,j\in\{1,\cdots,n_A\}$, $k,l\in\{1,\cdots,n_B\}$), then the two elements satisfy the relation $(A_{i||j},B_{k||l})=I$. Thus, the new sets extended from $S(A),S(B)$ can also be used in QNK protocol. When $n_A=n_B=2$, the extended sets of operators are $\tilde{S}(A)=\{A_1A_2^{-1}, \\A_2A_1^{-1},A_1A_1^{-1}=I,A_1A_1^{-1}=I\}$ and $\tilde{S}(B)=\{B_1B_2^{-1},B_2B_1^{-1},B_1B_1^{-1}=I,B_1B_1^{-1}=I\}$. Because the identity operator $I$ in the two sets is meaningless, the number of the operators in the two extended sets does not increase through the above method (The number of the operators in each set remains 2). Thus the extension is meaningless. However, the extension is meaningful when $n_A,n_B\geq 3$. Discussions and Conclusions =========================== We study the theory of quantum no-key protocols. Firstly, a framework of quantum no-key protocols is presented. The framework is expressed in two forms: trace-preserving quantum operators and natural presentations. Secondly, we defined the information-theoretical security of quantum no-key protocol, and the security of authentication keys. Finally, two kinds of quantum no-key protocols are presented. In the first scheme, the quantum operators used by Alice and Bob are all unitary. In the second scheme, Alice and Bob use trace-preserving quantum operators, and the two sets of operators used by Alice and Bob are constructed based on two multiplicative commutative sets. In the paper, there exists the following questions. 1. $k,i$ are secret identification key. How to use them to identify the personal identification of Alice, Bob, or attackers. How to identify in each of the three transformations? 2. How to construct operator $N_k$ and a set $I(k)$ from a given number $k$? 3. How to construct a set $L(k,i)$ and a set of operators $S_k(i)$ from the given $k$ and $i\in I(k)$? 4. In the quantum no-key protocols, the numbers $l_1,l_2\in L(k,i)$ are selected randomly. Whether the random selection of $l_1,l_2$ can prevent from the leakage of identification keys $k\in\mathcal{K}$ and $i\in I(k)$ during the communication? Acknowledgements {#acknowledgements .unnumbered} ================ This work was supported by the National Natural Science Foundation of China (Grant No. 61173157). Appendix {#appendix .unnumbered} ======== [**Proposition 1:**]{} Suppose two sets of operators $S(A),S(B)$ satisfy the condition Eq.(\[eqn2\]), then the following relations hold: $\forall i,j$ $$\begin{aligned} && (A_i^{-1},B_jB_i^{-1})=I,\\ && (A_j^{-1},B_jB_i^{-1})=I,\\ && (B_i,A_jA_i^{-1})=I,\\ && (B_j,A_jA_i^{-1})=I.\end{aligned}$$ [**Proof:**]{} According to the condition Eq.(\[eqn2\]), $\forall i\neq j$ $$\begin{aligned} && (A_i,B_i)=N,\\ && (A_i,B_j)=N,\\ && (A_j,B_i)=N,\\ && (A_j,B_j)=N.\end{aligned}$$ From the identity $(A_i,B_i)=N=(A_i,B_j)$, it can be deduced $B_i^{-1}A_i^{-1}B_iA_i=B_j^{-1}A_i^{-1}B_jA_i$, then $$B_i^{-1}A_i^{-1}B_i=B_j^{-1}A_i^{-1}B_j.$$ Thus, it can be known that $(B_jB_i^{-1})A_i^{-1}=A_i^{-1}(B_jB_i^{-1})$, that is $(A_i^{-1},B_jB_i^{-1})=I$. The other three relations can be obtained in the same way.$\hfill{}\Box$ [**Proposition 2:**]{} Suppose two sets of operators $S(A),S(B)$ satisfy the condition Eq.(\[eqn2\]), then the following relations hold: $\forall i,j,k,l$ $$(A_iA_j,B_kB_l)=(A_j^2,B_l^2).$$ [**Proof:**]{} In the deduction of this proof, the four identities such as $B_lA_i=A_iB_lN$ (that is $(A_i,B_l)=N$), $A_i^{-1}B_kA_i=B_kN$ (that is $(A_i,B_k)=N$), $B_k^{-1}A_j^{-1}B_k=B_l^{-1}A_j^{-1}B_l$, and $B_lN=A_j^{-1}B_lA_j$ (that is $(A_j,B_l)=N$) are used in turn. The deduction is as follows. $\forall i,j,k,l$, $$\begin{aligned} (A_iA_j,B_kB_l)&=& (B_l^{-1}B_k^{-1})(A_j^{-1}A_i^{-1})B_kB_lA_iA_j \\ &=& (B_l^{-1}B_k^{-1})A_j^{-1}A_i^{-1}B_kA_iB_lNA_j \\ &=& B_l^{-1}B_k^{-1}A_j^{-1}B_kNB_lNA_j \\ &=& B_l^{-1}B_l^{-1}A_j^{-1}B_lNB_lNA_j \\ &=& (B_l^{-1})^2 A_j^{-1}A_j^{-1}B_lA_jA_j^{-1}B_lA_jA_j \\ &=& (B_l^{-1})^2 (A_j^{-1})^2B_l^2A_j^2 \\ &=& (A_j^2,B_l^2).\end{aligned}$$ $\hfill{}\Box$ [**Proposition 3:**]{} $(A_{j_1}A_{j_2}A_{j_3},B_{i_1}B_{i_2}B_{i_3})=(A_{j_3}A_{j_2}A_{j_3},B_{i_3}B_{i_2}B_{i_3})$, $\forall i_1,i_2,i_3$, $\forall j_1,j_2,j_3$. [**Proof:**]{} It can be inferred from the formula $A_i^{-1}B_kA_i=A_j^{-1}B_kA_j$ that $$\begin{aligned} A_i^{-1}B_{k_1}B_{k_2}B_{k_3}A_i &=& A_i^{-1}B_{k_1}A_iA_i^{-1}B_{k_2}A_iA_i^{-1}B_{k_3}A_i \\ &=& A_j^{-1}B_{k_1}A_jA_j^{-1}B_{k_2}A_jA_j^{-1}B_{k_3}A_j \\ &=& A_j^{-1}B_{k_1}B_{k_2}B_{k_3}A_j.\end{aligned}$$ Similarly, it can be inferred $$\begin{aligned} B_i^{-1}A_{k_1}^{-1}A_{k_2}^{-1}A_{k_3}^{-1}B_i &=& B_j^{-1}A_{k_1}^{-1}A_{k_2}^{-1}A_{k_3}^{-1}B_j.\end{aligned}$$ Thus, the following result holds $$\begin{aligned} (A_{j_1}A_{j_2}A_{j_3},B_{i_1}B_{i_2}B_{i_3})&=& B_{i_3}^{-1}B_{i_2}^{-1}B_{i_1}^{-1}A_{j_3}^{-1}A_{j_2}^{-1}A_{j_1}^{-1}B_{i_1}B_{i_2}B_{i_3}A_{j_1}A_{j_2}A_{j_3} \\ &=& B_{i_3}^{-1}B_{i_2}^{-1}B_{i_1}^{-1}A_{j_3}^{-1}A_{j_2}^{-1}A_{j_2}^{-1}B_{i_1}B_{i_2}B_{i_3}A_{j_2}A_{j_2}A_{j_3} \\ &=& B_{i_3}^{-1}B_{i_2}^{-1}B_{i_2}^{-1}A_{j_3}^{-1}A_{j_2}^{-1}A_{j_2}^{-1}B_{i_2}B_{i_2}B_{i_3}A_{j_2}A_{j_2}A_{j_3} \\ &=& B_{i_3}^{-1}B_{i_2}^{-1}B_{i_2}^{-1}A_{j_3}^{-1}A_{j_2}^{-1}A_{j_3}^{-1}B_{i_2}B_{i_2}B_{i_3}A_{j_3}A_{j_2}A_{j_3} \\ &=& B_{i_3}^{-1}B_{i_2}^{-1}B_{i_3}^{-1}A_{j_3}^{-1}A_{j_2}^{-1}A_{j_3}^{-1}B_{i_3}B_{i_2}B_{i_3}A_{j_3}A_{j_2}A_{j_3} \\ &=& (A_{j_3}A_{j_2}A_{j_3},B_{i_3}B_{i_2}B_{i_3}).\end{aligned}$$ $\hfill{}\Box$ [99]{} P. Boykin and V. Roychowdhury, Optimal Encryption of Quantum Bits, arXiv: quant-ph/0003059. A. Ambainis, M. Mosca, A. Tapp, and R. De Wolf, Private quantum channels, 41st Annual Symposium on Foundations of Computer Science, Proceedings: 547-553, 2000. A. Nayak and P. Sen, Invertible quantum operations and perfect encryption of quantum states, Quantum Information & Computation 7(1-2): 103-110, 2007. L. Yang, Quantum public-key cryptosystem based on classical NP-complete problem, arXiv: quant-ph/0310076. L. Yang, et al, Quantum public-key cryptosystems based on induced trapdoor one-way transformations, arXiv: 1012.5249. A. J. Menezes, P. C. van Oorschot, and S. A. Vanstone, Handbook of Applied Cryptography, CRC Press, Boca Raton,1997 L. Yang, L. A. Wu, Transmit Classical and Quantum Information Secretly. arXiv: quant-ph/0203089. L. Yang, L. A. Wu, and S. H. Liu, Proc. SPIE, 4917(2002), 106-111. L. Yang, Quantum no-key protocol for direct and secure transmission of quantum and classical messages. arXiv: quant-ph/0309200, 28 Sep 2003. L. Yang and L. Hu, Quantum no-key protocol with inherent identification, Proc. SPIE Vol. 6305, pp. 63050J (2006). Y. Kanamori, S. M. Yoo and Mohammad, A Quantum No-Key Protocol for Secure Data Communication, 43rd ACM SE Conference, March 18-20, 2005 W. H. Kye, C. M. Kim, M. S. Kim and Y. J. Park, Quantum Key Distribution with Blind Polarization Bases, Phys.Rev.Lett. 95 (4), 2005, 040501. S. Kak, A Three-Stage Quantum Cryptography Protocol, Foundations of Physics Letters, Vol. 19, No. 3, June 2006. Y. Wu and L. Yang, Practical quantum no-key protocol with identification. IAS 2009: 540-543, IEEE Computer Society. A. Beige, B. G. Englert, C. Kurtsiefer, and H. Weinfurter, Secure communication with a publicly known key. Acta physica Polonica. A 101(3): 357-368. (see also arXiv:quant-ph/0101066). K. Boström and T. Felbinger. 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--- abstract: 'The Dirac oscillator in a homogenous magnetic field exhibits a chirality phase transition at a particular (critical) value of the magnetic field. Recently, this system has also been shown to be exactly solvable in the context of noncommutative quantum mechanics featuring the interesting phenomenon of re-entrant phase transitions. In this work we provide a detailed study of the thermodynamics of such quantum phase transitions (both in the standard and in the noncommutative case) within the Maxwell-Boltzmann statistics pointing out that the magnetization has discontinuities at critical values of the magnetic field even at finite temperatures.' author: - '<span style="font-variant:small-caps;">A. M. Frassino</span>' - '<span style="font-variant:small-caps;">D. Marinelli</span>' - '<span style="font-variant:small-caps;">O. Panella</span>' - '<span style="font-variant:small-caps;">P. Roy</span>' bibliography: - 'DiracOscillator.bib' title: Thermodynamics of Quantum Phase Transitions of a Dirac oscillator in a homogenous magnetic field --- Introduction {#sec:introduction} ============ Quantum Phase Transitions (QPT) [@Sachdev201105] are a class of phase transitions that can take place at zero temperature when the quantum fluctuations, required by the Heisenberg’s uncertainty principle, cause an abrupt change in the phase of the system. The QPTs occur at a critical value of some parameters of the system such as pressure or magnetic field. In a QPT, the change is driven by the modification of particular couplings that characterise the interactions between the microscopic elements of the system and the dynamics of its phase near the quantum critical point. For a quantum system at finite temperature $T$, both the thermal and the quantum fluctuations are present. The interplay between the quantum and the thermal fluctuations can either smooth out the differences between the phases (namely, no phase transition occurs at finite temperature) or there can be regimes in which some discontinuities hold, and a phase transition appears. Eventually, the thermal fluctuations prevail [@Sachdev201105]. In this paper, we focus on a particular quantum system, namely the Dirac oscillator, at finite temperature $T$ and with an additional constant magnetic field $\textbf{B}$. The Dirac oscillator system including an interaction in the form of a homogeneous magnetic field is an exactly solvable system [@PhysRevLett.99.123602; @2007PhRvA76Delgado; @PhysRevA.77.033832; @Mandal:2009we; @Mandal:2012wp] and shows interesting properties. In particular, at zero temperature, if the magnitude of the magnetic field either exceeds or is less than a critical value $B_{\text{cr}}$ (which depends on the oscillator strength), this combined system shows a *chirality phase transition* [@2008PhRvA77:Delgado; @Quimbay:2013gta]. Because of the phase transition, the energy spectrum is different for $B>B_{\text{cr}}$ and $B<B_{\text{cr}}$ where $B$ is the magnetic field strength. The $(2+1)$-dimensional Dirac oscillator in the presence of a constant magnetic field has also been studied at zero temperature in the framework of noncommutative space coordinates and momenta [@Panella:2014hga]. It has been shown that in this case $B_{\text{cr}}$ depends not only on the oscillator strength but also on the noncommutative parameters. An interesting consequence of the noncommutative scenario is that, apart from the left- and right-chiral phases of the commutative case [@PhysRevA.77.033832], there is also a third left phase and thus a second quantum phase transition (right-left) [@Panella:2014hga] (see Fig. \[fig:CNNcom\]). The presence of the third phase with left chirality leads to what is called a Re-entrant Phase Transition (RPT) [@2016:PanellaRoyReE] first observed in nicotine/water mixture [@hudson1904gegenseitige] as noted in [@Mann2016]. This phenomenon has been recently found also in gravitational systems [@Altamirano:2013ane; @Frassino:2014pha]. In this work, we analyze the Dirac oscillator in the presence of a constant magnetic field at finite temperature. While in the first part of the paper we consider the standard system at finite $T$, the second part will be dedicated to the noncommutative Dirac oscillator. To study what kind of QPT the Dirac oscillator at finite $T$ undergoes, we will investigate the system at high temperatures when the statistics can be approximated with the Maxwell-Boltzmann one [@Kubo1990]. We find that in this regime the QPT does not disappear and therefore the quantum fluctuations prevail upon the thermal ones (as can be seen in the noncommutative case in Fig. \[fig:CNNcom\]). Only in the limit of very high temperatures ($\beta \rightarrow0$) the QPT disappears. The organization of the paper is as follows: in Sec.\[sec:System\] we shall present the system to be analyzed and discuss the spectrum of the two phases, namely, the left and the right phase; in Sec. \[sec:FiniteT\], we present the method to calculate the partition function that characterizes the chiral phases at finite temperature and describes the phase transition as the strength of the magnetic field varies; in Sec. \[sec:magnetiz\] we scrutinize in details the magnetization at finite temperature and in Sec. \[sec:NCoscillator\] we study the thermodynamic of a noncommutative Dirac Oscillator with a constant magnetic field. Finally, Sec. \[sec:conclusions\] is devoted to conclusions. The Quantum System: Dirac Oscillator with a constant magnetic field {#sec:System} =================================================================== The non-relativistic version of the $\left(2+1\right)$-dimensional Dirac oscillator with a constant magnetic field and zero temperature can be associated to a chiral harmonic oscillator [@2008PhRvA77:Delgado], that have been studied in [@Banerjee:1998em]. Moreover, in [@HortaBarreira:1992ec; @Dunne:1989hv] a possible connection to topological Chern-Simons gauge theories has been pointed out. The case of the system presented in this paper can be seen as a relativistic extension of the chiral harmonic oscillators [@2008PhRvA77:Delgado; @Quimbay:2013gta], at finite temperature. A relativistic spin-1/2 fermion constrained in a 2-dimensional plane with mass $m$, charge $e$, Dirac oscillator frequency $\omega$ and subjected to a a constant magnetic field orthogonal to the plane, is described by the Hamiltonian: $$H= c\, \bm{ \sigma} \cdot (\bm{p}-im\omega\sigma_z \bm{x}+\frac{e}{c}\bm{\,A}) +\sigma_z \,mc^{2}\,, \label{eq:hamiltonian}$$ where $c$ stands for the speed of light and $\bm{\sigma}=\left(\sigma_x,\sigma_y\right)$, $\sigma_z$ denotes the Pauli matrices. As in the usual notation, the $\bm{p}$ and the $\bm{x}$ represent the momentum and the position operators while the vector potential is related to the magnetic field through $$\bm{A}=(-B{y}/2,B{x}/2)\,.$$ This set-up offers an intriguing interplay: while the two-dimensional Dirac oscillator coupling endows the particle with an intrinsic left-handed chirality [@2007PhRvA76Delgado], the magnetic field coupling favors a right-handed chirality [@PhysRevLett.99.123602]. The interplay between opposed chirality interactions culminates in the appearance of a relativistic quantum phase transition, which can be fully characterized [@2008PhRvA77:Delgado]. Energy levels {#sec:energy-levels} ------------- In this section, we shall recall the spectrum and the degeneracy of the various energy levels of a two-dimensional relativistic Dirac oscillator in the two phases defined by $B>B_{\text{cr}}$ and $B<B_{\text{cr}}$. The spectum of the system is characterized by two quantum numbers: $n_r = 0,1,2,...$, the radial quantum number and $M=0,\pm 1, \pm 2,...$, the 2-dimensional angular momentum quantum number. In what we call the *left phase*, the energy level corresponding to the zero mode has positive energy $E=\, mc^2$ and infinite degeneracy with respect to the non-negative magnetic quantum number $M\ge 0$ (the negative magnetic numbers are forbidden [@Panella:2014hga]). The excited states are $$\begin{aligned} E_{N}^{\pm}=\,\pm mc^{2}\sqrt{1+\,\xi_{L}\,N}\,,\quad\\ N=n_{r}+\frac{|M|-M}{2},\quad N=1,2,\,,\dots\,\label{spectrumL1}\end{aligned}$$ where $N$ labels the energy levels, $\xi_L$ is a constant encoding the parameters of the system that for the standard commutative case simply reads $$\begin{gathered} \xi_L = -4\,X, \quad X := \frac{1}{mc^{2}}\left(\mu\, B - \hbar\omega\right) \label{eq:xiLcomm}\end{gathered}$$ and $\mu=e \hbar / (2 m\, c)$ denotes the Bohr magneton. The energy levels in are degenerate. In particular, every level has infinite degeneracy, with respect to the non-negative values of $M$, and $D=N+1$ finite degeneracy with respect to the negative values of $M$.\ The *right phase*, on the other hand, has zero mode degeneracy with respect to the non-positive magnetic quantum number $M \le 0$ and the value of the energy is in the negative branch: $E = - m\, c^2$. Similarly, the excited states have an infinite degeneracy with respect to non-positive values of $M$, while the degeneracy is $D=N+1$ with respect to $M>0$ and the energies read $$\begin{gathered} E_{N}^{\pm}=\,\pm mc^{2}\sqrt{1+\,\xi_{R}\,N}\,,\\ N=n_{r}+\frac{|M|+M}{2}\quad N=1,2,\dots\,,\label{spectrumR}\end{gathered}$$ where the parameter $\xi_{R}$ is related to $\xi_{L}$ by the relation $\xi_{R}=-\xi_{L}$. Note that, when $\xi_{R} = \xi_{L} = 0$, that is when $$B = B_{\text{cr}} =\hbar\, \mu \, \omega, \label{eq:BcrComm}$$ all the energy levels collapse to the energy $E=\pm mc^2$ and the *quantum phase transition* happens [@2008PhRvA77:Delgado; @Panella:2014hga]. Finite Temperature Quantum Phase Transition {#sec:FiniteT} =========================================== To study the interplay between thermal and quantum fluctuations for this two-dimensional relativistic Dirac oscillator, we focus on the system at high temperatures when the electron-states statistics can be described with the Maxwell-Boltzmann statistics. We will show that in this regime the QPT will not disappear. Partition Function ------------------ The partition function for the positive branch of the energy levels (\[spectrumL1\]) and (\[spectrumR\]) and the zero mode, has to take into account the degeneracy of each single energy level. Thus, it is defined by the product of the density of the states and the Boltzmann factor $$\begin{gathered} Z_{L,R} = \sum_{M,n_r}\, \mathtt{g} \, e^{-\beta\, E^{+}_{N}}, \quad N=0,1,\dots\,, \label{eq:Z-LR}\end{gathered}$$ where $E^{+}_{N}$ are the values given by (\[spectrumL1\]) and (\[spectrumR\]), and $\beta$ is the inverse temperature. [0.25/0.75/0.5,0.75/1.25/1.0,1.55/2.05/1.8]{} //iin //in in [0,0.05,...,0.5]{} [ ($(\xz,\from)+(0,\k)$) to ($(\xs,\from)+(0,\k)$) ; ($(\xs,\from)+(0,\k)$) to\[out=0,in=180\] (,) ; ]{} in [0,0.05,...,0.25]{} [ ($(\xz,0)+(0,\k)$) to ($(\xs,0)+(0,\k)$) ; ($(\xs,0)+(0,\k)$) to\[out=0,in=180\] (,0) ; ]{} (0.5,1.28) – (0.5,1.50) ; (3.0,1.3) – (3.0,1.7) ; (0.5,2.1) – (0.5,2.250) ; (3.0,2.1) – (3.0,2.25) ; (,0) to node\[above,sloped,font=,pos=0.8\] [$mc^2\sqrt{1+p^2}$]{} node\[above,sloped,font=,pos=0.2\] [$\omega=B=0$]{} (,2.255) ; iin To evaluate the density of the states $ \mathtt{g}$, we can split every chiral phase of the system (left and right introduced in the previous section) into two different sub-systems with respect to the sign of the quantum number $M$. If we consider a free electron with $M>0$ or alternatively $M<0$, in a standard commutative spacetime and confined to a finite area $\mathtt{L}^{2}$, the number of energy levels in the region $dp_{x}dp_{y}$ around $p_{x}$ and $p_{y}$ is $ d\mathtt{g} = \mathtt{L}^{2}/\left( 2 h^{2} \right)dp_{x}dp_{y}$ [@Kubo1990]. Note that it can be proved that the phase-space volume element $dp_{x}\wedge dp_{y}$ in the relativistic case is invariant for Lorentz transformations [@hakim2011introduction]. Moreover, $\mathtt{L}$ is the length in a rest-frame. #### Left Phase. For $M\ge0$, the degeneracy of each energy level (\[spectrumL1\]) defined in the region $\mathscr{K}$ of the momenta $(p_x,p_y)$ such that $E_N<E_{\text{free}}(p_x,p_y)<E_{N+1}$ (see Fig.\[fig:spectrum\]), where $E_{\text{free}}$ is the energy of the free electron, is given by $$\begin{aligned} \mathtt{g}_{M>0}&=& \frac{1}{2}\left(\frac{\mathtt{L}}{h}\right)^{2} \iintop_{\mathscr{K}}dp_{x}dp_{y} \nonumber \\ &=& \pi\left(\frac{\mathtt{L}}{h}\right)^{2}\left[p^{2}\right]_{\frac{p^{2}}{m^{2}c^{2}}=\,\xi_{L}N}^{\frac{p^{2}}{m^{2}c^{2}}=\,\xi_{L}\left(N+1\right)} = \left(\frac{\mathtt{L}mc}{h}\right)^{2}\,\pi\xi_{L} .\end{aligned}$$ and $N$ depends only on the quantum number $n_{r}$ because the difference in is zero. In the case $M<0$, the number of levels collapsing into the level $N$ is still equal to $\mathtt{g}_{M>0}$. However, one should consider that, when $M<0$, as shown in (\[spectrumL1\]), $N$ depends on both the quantum number $M$ and $n_{r}$, namely $N = n_r + M $. Therefore, one needs to keep into account, for each energy level $N$, the degeneracy $D$, i.e. $ \mathtt{g}_{M<0}= \mathtt{g}_{M>0}/D$. Thus, the number of states $$\mathtt{g}_{M<0}= \left(\frac{\mathtt{L}mc}{h}\right)^{2}\,\frac{\pi\xi_{L}}{\left(n_{r}-M+1\right)},\label{eq:StateDensity}$$ is not constant along the spectrum, but depends on the energy level. Taking into account the degeneracy, using the spectrum (\[spectrumL1\]) and its zero point energy, the partition function with Boltzmann statistics of the states of a single oscillator[^1] for the left phase is $$\begin{aligned} Z_L &=& \left(\frac{\mathtt{L}mc}{h}\right)^{2}\,\pi\xi_{L} \left[ e^{-\beta mc^{2}}+ \sum_{n_{r}=1}^{\infty} \ e^{-\beta mc^{2}\sqrt{1+\,\xi_{L}\,n_{r}}}+\right.\nonumber\\ &+&\left. \sum_{n_{r}=1}^{\infty} \sum_{M=0}^{-\infty} \frac{e^{-\beta mc^{2}\sqrt{1+\,\xi_{L}\,\left(n_{r}-M\right)}}} {\left(n_{r}-M+1\right)} \right]. \label{eq:ZSingleOscillator}\end{aligned}$$ Notice that the contribution to the partition function of the zero mode energy appears only for $M\ge 0$ [@Panella:2014hga] and, as we will see later in sec. \[sec:CriticalPoint\], this will be the source of the non-analiticty of the partition function at the phase point. The sum in the third term of coincides with the second if we introduce $M'$ and $N'$ such that $M'=-M$ then $n_{r}+M'=N'$, obtaining $$\label{doublesum} \sum_{n_{r}=1}^{\infty}\sum_{N'=n_{r}}^{\infty} \frac{e^{-\beta mc^{2}\sqrt{1+\,\xi_{L}\,\left(N'\right)}}} {\left(N'+1\right)} =\sum_{N'=1}^{\infty}e^{-\beta mc^{2}\sqrt{1+\,\xi_{L}\,\left(N'\right)}},$$ so, over all, the two sectors ($M>0$ and $M<0$) equally contribute to the partition function. #### Right Phase The partition function for the right phase, defined by the energy levels (\[spectrumR\]), is equal to (\[eq:ZSingleOscillator\]) except for the zero mode term. This is because, as explained in Sec. \[sec:System\], the zero mode contributes only to the negative energies branch. Zeta-function representation \[sub:mellin\] ------------------------------------------- A different representation of the defining series in the partition function that will reveal itself to be more effective when the phase switches from left to right, can be obtained using the Cahen-Mellin integral, as suggested for different systems in [@Brevik:2005ys] and reviewed in [@Dariescu:2007; @boumali2015one]. The Cahen-Mellin integral is defined as [@ParisKaminski200109] $$e^{-x}=\frac{1}{2\pi i}\int_{\mathfrak{c}-i\infty}^{\mathfrak{c}+i\infty}\Gamma\left(s\right)\: x^{-s}\ ds \quad \left(\left|\arg x\right|<\frac{1}{2}\pi;\, x\neq0\right)\label{eq:CahenMellinIntegral}$$ where $\mathfrak{c}$ is real and $\mathfrak{c}>0$. The argument of the integral has poles for all $x=-n$, $n\in \mathbb{N}_0$ and the residuals at the negative poles are $\left(-1\right)^{n}/n!$ (see Fig. \[fig:figure1\]). [cc]{} (-5,0) – (5,0) node\[right\] [$\mathfrak{Re}\left(x\right)$]{}; (0,-5) – (0,5) node\[above\] [$\mathfrak{Im}\left(x\right)$]{}; (1.5,-5) – (1.5,5) node\[right\] ; at (1.5,0) ; in [0,...,5]{} [ ( [-]{} , 0 ) node [$\times$]{}; ]{} & (-5,0) – (5,0) node\[right\] [$\mathfrak{Re}\left(s\right)$]{}; (0,-5) – (0,5) node\[above\] [$\mathfrak{Im}\left(s\right)$]{}; (2.5,-) to node\[above,sloped,font=,pos=0.75\] [$R\rightarrow\infty$]{} (2.5,); (2.5,) arc (90:270:) node\[right,font=\] ; at (2.5,0) ; in [0,...,5]{} [ ( [-]{} , 0 ) node [$\times$]{}; ]{} ( 2 , 0 ) node [$\times$]{}; [\ ]{} Using (\[eq:CahenMellinIntegral\]) to calculate the second term in the partition function (\[eq:ZSingleOscillator\]) and including the sum into the integral, we have that the term $$\xi_{L}\sum_{n_{r}=1}^{\infty}\ e^{-\beta mc^{2}\sqrt{1+\,\xi_{L}\, n_{r}}}$$ can be rewritten as $$\frac{\xi_{L}}{2\pi i}\int_{\mathfrak{c}-i\infty}^{\mathfrak{c}+i\infty} \frac{\Gamma\left(s\right)}{\left(\beta mc^{2}\right)^{s}}\:\sum_{n_{r}=1}^{\infty}\frac{1}{\left(1+\,\xi_{L}\, n_{r}\right)^{s/2}}\ ds. \label{eq:term2}$$ The series in (\[eq:term2\]) can be recognized as the series representation of the Hurwitz-$\zeta$ function $\zeta\left(v,a\right)=\sum_{n=0}^{\infty}\frac{1}{\left(n+a\right)^{v}}$ that converges only if $\ensuremath{\mathfrak{Re}\left(v\right)}>1$. Under this condition the integral (\[eq:term2\]) becomes $$\frac{\xi_{L}}{2\pi i}\int_{\mathfrak{c}-i\infty}^{\mathfrak{c}+i\infty} \frac{\Gamma\left(s\right)}{\left(\beta mc^{2}\xi_{L}^{1/2}\right)^{s}}\:\:\zeta\left(\frac{s}{2},\frac{1}{\xi_{L}}+1\right)\ ds. \label{eq:IntegrandZeta}$$ In contrast to what has been proposed in the recent literature on the topic (see [@boumali2015one] and references therein), we notice that the condition for the convergence of the series $s/2>1$ implies $\mathfrak{c} >2$. The integral can therefore be evaluated with the method of residue once a proper closed path has been identified. Because of the presence of the $\Gamma$-function that diverges as $\Gamma(s)=\left(2\pi\right)^{1/2}e^{-s}s^{s-\frac{1}{2}}\left[ 1-\mathcal{O}\left(s^{-1}\right)\right] $, the integration in can be closed only on the left part of the complex plane, allowing to use the Cauchy’s residue theorem on the poles $\left\{ s=2,0,\mathbb{Z}^{-}\right\} $ represented in Fig. \[fig:figure1\]. Introducing the adimensional variable $\tilde{\beta}=\beta m\, c^2$, the partition functions for both the phases becomes $$\begin{gathered} Z_{L,R}=2\pi\left(\frac{\mathtt{L}mc}{h}\right)^{2}\times\\ \times\left[\left(\frac{2}{\tilde{\beta}^{2}}-1\right)+\left(\frac{\Theta e^{-\tilde{\beta}}}{2}-\frac{1}{2}\right)\xi_{L,R}+\right.\\ \left.+\sum_{n=1}^{\infty}\frac{\left(-\tilde{\beta}\right)^{n} \xi_{L,R}^{\frac{n}{2}+1}}{n!}\zeta\left(-\frac{n}{2},1+\frac{1}{\xi_{L,R}}\right)\right], \label{eq:Zzeta}\end{gathered}$$ where now we use the subscript $L,R$ to indicate both the left and right phase and $\Theta$ is a step function that is equal to zero (one) for the right phase (left phase). This series representation can be seen as a series expansion in power of $\beta$, namely a high-temperature power expansion. From now on the quantity in the square brackets of will be called $\tilde{Z}_{L,R}$ $$Z_{L,R}=2\pi\left(\frac{\mathtt{L}mc}{h}\right)^{2} \tilde{Z}_{L,R}.$$ The series representations of the partition function $ \tilde{Z}_{L,R}$ in terms of the $\zeta$-function and the Boltzmann representation introduced in can be both evaluated numerically considering only a finite number of terms in the series. However, the Boltzmann representation encounters obvious numerical issues for small values of $\xi_{L,R}$, i.e. close to the value where the phase transition happens. These issues do not affect the $\zeta$-function representation of the partition function and, as we will see in the next subsection, the partition function can be evaluated analytically for small values of $\xi_{L,R}$. Fig. \[fig:2\] shows $ \tilde{Z}_{L,R}$ in the $\zeta$-function representation keeping $n_{\text{max}}=100$ terms of the series in . Partition function near the critical point {#sec:CriticalPoint} ------------------------------------------ The partition function can be used to calculate the asymptotic expansion near the critical point, namely when $\xi_{L,R}\rightarrow 0$. This allows to analytically explore the regimes close to the phase transition and study the interplay between thermal and quantum fluctuations. The asymptotic expansion of the Hurwitz-$\zeta$ function [@MR2124202; @magnus2013formulas] is $$\zeta\left(s,a\right)=\frac{a^{1-s}}{s-1}+\frac{1}{2}a^{-s}+\frac{\mathtt{Z}\left(s,a\right)}{\Gamma\left(s\right)}\label{eq:ZetaExp}$$ where the large-$a$ (Poincaré) asymptotic expansion of the function $\mathtt{Z}\left(s,a\right)$ $$\mathtt{Z}\left(s,a\right)\sim\sum_{k=1}^{\infty}\frac{B_{2k}}{\left(2k\right)!}\frac{\Gamma\left(2k+s-1\right)}{a^{2k+s-1}},\qquad\left|a\right|\rightarrow\infty \label{eq:ZetaExp2}$$ is valid in $|\text{arg}\;\; a| < \pi$ and $B_{2k}$ denote the even-order Bernoulli numbers. Writing explicitly the sum in the partition function $\tilde{Z}_{L,R}$ gives $$\begin{gathered} \tilde{Z}_{L,R}=\frac{2}{\tilde{\beta}^{2}}-1-\left(1-\Theta e^{-\tilde{\beta}}\right)\frac{\xi_{L,R}}{2}+\\ +\sum_{n=1}^{\infty}\frac{\left(-\tilde{\beta}\right)^{n}}{n!}\left\{ \left[\frac{1}{2}\xi_{L,R}-\frac{2\left(\xi_{L,R}+1\right)}{n+2}\right]\left(\xi_{L,R}+1\right)^{\frac{n}{2}}+\right.\\ \left.+\sum_{k=1}^{\infty}\frac{B_{2k}}{\left(2k\right)!}\frac{\Gamma\left(2k-\frac{n}{2}-1\right)\:}{\Gamma\left(-\frac{n}{2}\right)}\frac{\xi_{L,R}^{2k}}{\left(\xi_{L,R}+1\right)^{2k-\frac{n}{2}-1}}\right\} . \label{eq:ZtildPreBinomial}\end{gathered}$$ Using the binomial series and the relation between Euler gamma functions $$\Gamma\left( -\frac{n}{2} \right) \; \Gamma\left( 1 + \frac{n}{2} \right) = \frac{\pi}{\sin\left( - \pi n/2 \right)},$$ one can rewrite the terms in the curly brackets in (\[eq:ZtildPreBinomial\]) as $$\begin{gathered} \sum_{w=0}^{\infty} \frac{1}{w!} \left\{ \left[\frac{1}{2}\xi_{L,R}-\frac{2\left(\xi_{L,R}+1\right)}{n+2}\right] \frac{\Gamma \left(1+ \frac{n}{2} \right)}{\Gamma \left(1+ \frac{n}{2} - w \right)} \xi_{L,R}^{w} + \right.\\ \left.+\sum_{k=1}^{\infty}\frac{B_{2k}}{\left(2k\right)!}\frac{\Gamma\left( 1+ \frac{n}{2} \right)\:}{\Gamma\left( -2k +\frac{n}{2}+2-w \right)} \xi_{L,R}^{2k+w} \right\}\end{gathered}$$ defining in this way the partition function at all orders in $\xi_{L,R}$ near the critical point. At the second order in $\xi_{L,R}$, one can sum the partition function at all orders in $\beta$, so that, near the critical point, it reads $$\begin{gathered} \tilde{Z}_{L,R} =\frac{2e^{-\tilde{\beta}}}{\tilde{\beta}}\left[1+\frac{1}{\tilde{\beta}}+\left(\Theta-1\right)\frac{\tilde{\beta} \xi_{L,R}}{4}+\frac{\tilde{\beta}^{2}\,\xi_{L,R}^{2}}{48}\right] + \\ +{\cal O}\left(\xi_{L,R}^{3}\right).\label{eq:Z2ndOrder}\end{gathered}$$ This expression is a continuous but non-analytic function in $\xi_{L,R}$ and, in fact, $\Theta$ brings a discontinuity in the first order derivatives. The function to the second order is compared with in Fig. \[fig:2\]. Magnetization at finite temperature {#sec:magnetiz} =================================== At this point, it is possible to use the derived expression for the partition function to calculate a physical observable quantity like the magnetization [@Yoshioka1992; @Andersen1995]. Indeed, in [@Panella:2014hga] the magnetization has been proposed as the quantity able to distinguish between the phases of the system. The magnetization for a system at finite temperature, can be defined as [@Kubo1990] $$\begin{gathered} M=k_{B}T\frac{\partial\log Z}{\partial B}=\frac{1}{\beta\,Z}\frac{\partial Z}{\partial\xi}\frac{\partial\xi}{\partial X}\frac{\partial X}{\partial B}.\label{eq:Mformula}\end{gathered}$$ In order evaluate the derivative $\partial Z/\partial\xi_{L.R}$ one can use in the following identity [@NIST:DLMF] $$\begin{gathered} \frac{\partial\zeta\left(s,a\right)}{\partial a}=-s\:\zeta\left(s+1,a\right)\ \mbox{for }s\neq0,1\,\mathfrak{Re}a>0. \end{gathered}$$ The magnetization evaluated numerically with $n_\text{max}=60$ is illustrated in Fig. \[fig:MagnComm\]. Interestingly, we find that the magnetization in the left phase, has opposite sign with respect to the single state result obtained at $T=0$ [@Panella:2014hga]. At finite temperature, in $\xi_L =\xi_R = 0$ the magnetization manifests a discontinuity. Analogously to what has been done for the partition function in the previous sections, we now inspect the magnetization behaviour at values of the magnetic field close to the critical values. To approximate the full partition function in the neighborhood of $\xi_L=\xi_R=0$, we can either follow the steps described in subsection \[sec:CriticalPoint\] for the full partition function resulting of , or we can use in . At the critical point, the magnetization is not a continuous function of the magnetic field and can be written as a series expansion around $X=0$ at all order in $\beta$ as $$\begin{gathered} \frac{M_{R,L}}{\mu}= -\frac{\tilde{\beta}}{\tilde{\beta}+1}H\left(X\right)+\\ +\left(\frac{\tilde{\beta}}{\tilde{\beta}+1}\right)^{2}\left[\frac{2}{3}+\tilde{\beta}\left(H\left(-X\right)-\frac{1}{3}\right)\right]\,X + \mathcal{O}\left(X^{2}\right) ,\end{gathered}$$ where $H(x) $ is the Heaviside step function. The discontinuity with respect to the magnetic field at the critical point $X=0$ is $$|\Delta M_{\text{cr}}| = \mu\, \frac{\, \tilde{\beta} }{ (1+\tilde{\beta} )}. \label{eq:Mgap}$$ In the limit $\tilde{\beta} \rightarrow 0 $, the thermal fluctuations overcome the quantum ones, the gap disappears and the magnetization is zero for both the chiralities. Other thermodynamic functions ============================= Once the partition function has been calculated, the thermodynamics of the system can be fully explored. Using $$\begin{aligned} F=-\frac{1}{\beta}\ln Z,\qquad U=-\frac{\partial}{\partial\beta}\ln Z,\\ S=\, k_{B}\beta^{2}\frac{\partial F}{\partial\beta},\qquad C=-k_{B}\beta^{2}\frac{\partial U}{\partial\beta}, \end{aligned}\label{eq:ThermQuant}$$ in Fig. \[fig:Free\], we plot the thermodynamic quantities for the commutative system. The specific heat as function of the $\beta$ manifests a non-monotonic behaviour in the left phase, while it becomes monotonic in the right phase. Noncommutative Dirac Oscillator with a constant magnetic field {#sec:NCoscillator} ============================================================== In the previous sections we described the Dirac oscillator under a uniform magnetic field and its associated QPT in a $2D$ space-time. Now, we move to the noncommutative system, indeed, studies in quantum gravity and string theory propose that the space-time can be fundamentally or effectively described by a generalization of geometry where, locally, coordinates do not necessarily commute [@Bertolami2005; @Gamboa2002; @Ito1967; @Bellucci2001b; @Duval2000; @Gamboa2001a; @Gamboa2001; @Horvathy:2010wv; @Nair2001; @Smailagic2002; @Smailagic2002a]. Moreover, recent developments in condensed matter physics, suggest the use of the noncommutative geometry framework to encode geometrical properties of topological quantum systems [@2012PhRvB..86c5125N; @Haldane:2011ia; @2012PhRvB..85x1308P; @2012PhRvB..85g5128B]. The study of the Dirac oscillator in the presence of noncommutative coordinates and momenta and a constant magnetic field in a $2$-dimensional space at zero-temperature has been carried out in [@Panella:2014hga]. The system that in the commutative case undergoes a quantum phase transition at finite magnetic field, also exhibits in the noncommutative case another phase transition at a higher magnetic field. The third region appears to have the same chirality of the first one providing a re-entrant quantum phase transition [@2016:PanellaRoyReE]. In this section, we will study the noncommutative system at finite temperature, the parametrization that has been used for the exact calculation of the spectrum in [@Panella:2014hga] will allow us to exploit all the calculation done in the previous sections and easily study the QPTs in the noncommutative space. Energy levels {#energy-levels} ------------- The Hamiltonian for the $(2 + 1)$-dimensional Dirac oscillator in the noncommutative plane with a homogeneous magnetic field can be written in a way similar to (\[eq:hamiltonian\]) $$\hat{H}= c\bm{\sigma}. (\hat{\bm{p}}-im\omega\sigma_z\hat{\bm{x}}+\frac{e}{c}\,\hat{\bm{A}}) +\sigma_{z}\,mc^{2}\,,\label{h1}$$ where now the *hat* indicates the noncommutative operators. In this framework, the commutation relation between coordinates and momenta are given by [@Bertolami2005] $$[{\hat{x}},{\hat{y}}]=i\theta, ~~~~[{\hat{p}}_{x},{\hat{p}}_{y}]=i\eta, ~~~~[{\hat{x}}_{i},{\hat{p}}_{j}]=i\hbar(1+\frac{\theta\eta}{4\hbar^{2}})\delta_{ij}, \label{NCEQ}$$ where $\theta,\eta\in\mathbb{R}$. The noncommuting coordinates and momenta can be expressed in terms of commuting ones using the Seiberg-Witten map and are given by $$\begin{aligned}{\hat x}=\displaystyle {x-\frac{\theta}{2\hbar}p_y,~~~~{\hat p}_x=p_x+\frac{\eta}{2\hbar}y}\,,\\ {\hat y}=\displaystyle{y+\frac{\theta}{2\hbar}p_x,~~~~{\hat p}_y=p_y-\frac{\eta}{2\hbar}x}\label{rel}\,. \end{aligned}$$ The Hamiltonian (\[h1\]) can be rewritten as $$H= c\left(\begin{array}{cc} mc & {\hat{\Pi}}_{-}\\ {\hat{\Pi}}_{+} & -mc \end{array} \right),\label{h2}$$ where $\hat{\Pi}_{\pm}$ are given by $$\begin{gathered} {\hat\Pi}_{\pm} = \left( 1- \frac{\tilde{\omega}-\omega}{\omega_\theta}\right)(p_x \pm i\, p_y)\,\pm \\ \pm\, i\, m\, (\tilde{\omega} -\omega -\omega_\eta) (x \pm i y)\end{gathered}$$ after introducing the following frequencies out of the parameters of the system: $$\tilde{\omega}=\frac{eB}{2mc},\,\qquad \omega_\theta = \frac{2\,\hbar}{m\theta},\, \qquad \omega_\eta=\frac{\eta}{2\hbar m}.$$ With this paramatrization it is clear that there are two critical values of the magnetic field $$\begin{gathered} \label{bc} B_{\text{cr}}=\frac{2 mc}{e} (\omega +\omega_\eta)=\frac{2c}{e}(m\omega+\frac{2\eta}{\hbar}) \,,\\ \label{bcrit*} B_{\text{cr}}^*=\frac{2 mc}{e} (\omega +\omega_\theta)=\frac{2c}{e}(m\omega+\frac{\hbar}{\theta}) \, .\end{gathered}$$ such that for both $B=B_{\text{cr}}$ and $B=B_{\text{cr}}^*$, there are no interactions in the model and the Hamiltonian represents a free particle (only kinetic energy). Since the critical value $B_{\text{cr}}$ depends on the momentum noncommutative parameter $\eta$, this shifts the value of the critical field relative to the value in .The space noncommutativity ($\theta \ne 0$) instead introduces the additional critical value for the magnetic field ($B_{\text{cr}}^*$) [@Panella:2014hga]. Interestingly, the parameters used in the noncommutative massive Dirac oscillator can be re-assorbed in such a way that one can study the single phases independently. In fact, the behaviour of the single phases can be described regardless of the parameters encoding the noncommutative physics [@Panella:2014hga]. Therefore, although the noncommutative system has two more parameters, they can recast into the parameter $\xi_{L,R}$ allowing us to use most of the calculations performed in the previous sections for the commutative case. The main difference now is that the magnetic field and the noncommutative parameters are related by $$\begin{aligned} \xi_{L}&=&-4\frac{mc^{2}}{\omega_{\theta}\hbar}\left(\frac{\omega_{\theta}\hbar}{mc^{2}}-X\right)\left(X-\frac{\omega_{\eta}\hbar}{mc^{2}}\right) \label{eq:xiL} \end{aligned}$$ while it is still valid the relation $\xi_R = -\xi_L$. Phase changes occur at critical values of the magnetic field that makes the parameter $\xi_{L,R}$ null. Note that, differently from the commutative case , in the noncommutative case the equation is quadratic in $B$ and consequently it admits two critical points. Energy levels and partition function ------------------------------------ In Section \[sec:energy-levels\] we reviewed the spectrum of the system as a function of the parameter $\xi_{L,R}$. As mentioned above, for the noncommutative case, the spectrum remains equal to and as a function of the parameter $\xi_{L,R}$ that now becomes , quadratic in $B$. Since the density of the energy states is also a function of the parameters $\xi_{L,R}$, its contribution to the partition function of each energy level in the noncommutative case coincides with the one in the commutative case . The resulting partition function is illustrated in Fig. \[fig:ZNonComm\]. In the plot is also represented the outcome of the approximation once the constant $\xi_{L,R}$ in is replaced in . The partition function can be used to calculate the other thermodynamic quantities using . In particular, the heat capacity is shown in Fig. \[fig:CNNcom\]. In [@boumali2013thermal] a different noncommutative model has been studied without considering the degeneracy of the states. Magnetization ------------- The magnetization for the noncommutative Dirac oscillator case is illustrated in Fig. \[fig:Magn\]. The figure shows the presence of a fixed point at $M=0$ for every $T$. The point where the magnetization changes its sign appears only in the noncommutative case and is a consequence of the term $ \partial \xi / \partial X $ in , that is a non constant function of $X$: $$\begin{gathered} \frac{\partial\xi_{L,R}}{\partial X}=\pm 4\frac{mc^{2}}{\omega_{\theta}\hbar}\left[2\, X-\frac{\hbar\left(\omega_{\eta}+\omega_{\theta}\right)}{mc^{2}}\right]= \\ =\pm 4\sqrt{\frac{m\,c^{2}}{\hbar\,\omega_{\theta}} \xi_{L,R} \pm \frac{(\omega_{\eta}-\omega_{\theta})^{2}}{\omega_{\theta}{}^{2}}} \label{eq:Derxix}\end{gathered}$$ where the plus sign is for the $L$ phase and the minus sign is for the $R$ phase. From the first line of , we find that at the point $X_0 = \frac{\hbar (\omega_\eta +\omega_\theta )}{2 mc^2}$ the magnetization change[**s**]{} sign. Therefore, the point where the magnetization smoothly vanishes is the midpoint between the two critical points. This feature of the noncommutative system is independent of the temperature and was also present in the analysis at $T=0$ [@Panella:2014hga]. Near the critical point, we can evaluate the magnetization in $\xi_{L,R}$ using the second line of and in , obtaining: $$\begin{gathered} \frac{\partial\xi_{L,R}}{\partial X} = \pm\,4\,\left[\left|\frac{(\omega_{\eta}-\omega_{\theta})}{\omega_{\theta}}\right|\pm\frac{1}{2}\frac{m\,c^{2}}{\hbar\,}\frac{\xi_{L,R}}{\left|\omega_{\eta}-\omega_{\theta}\right|}+\mathcal{O}(\xi^{2})\right],\end{gathered}$$ and the other terms in read $$\begin{gathered} \frac{1}{\tilde{\beta}}\frac{1}{Z}\frac{\partial Z}{\partial\xi} = \frac{\tilde{\beta}}{4(\tilde{\beta}+1)}\left(\Theta-1\right)+ \\ + \left[\frac{\tilde{\beta}}{4(\tilde{\beta}+1)}\right]^{2}\left[\frac{2}{3}+\tilde{\beta}\left(\Theta-\frac{1}{3}\right)\right]\xi+ \mathcal{O}\left(\xi^{2}\right).\end{gathered}$$ Then the discontinuity of the magnetization at the two critical points, for the noncommutative case is $$\begin{gathered} \Delta M=\pm\mu\, \left|\frac{(\omega_{\eta}-\omega_{\theta})}{\omega_{\theta}}\right|\frac{\tilde{\beta}}{(\tilde{\beta}+1)},\end{gathered}$$ and we can notice that if $\eta$, the noncommutative parameter related with the momenta, vanishes then the transitions become independent from $\theta$, the coordinates noncommutative parameter. Conclusions {#sec:conclusions} =========== Over the years, the Dirac oscillator has become a valuable tool for various branches of physics, mostly because it is one of the few relativistic systems whose exact solutions are known. The $(2+1)$-dimensional case, namely when an electron is constrained to live in a plane, manifests an intrinsic chiral behavior of its states. An external magnetic field interacts at the quantum level with the chirality properties of the system and, if strong enough, it forces an abrupt switch in the electron chirality. This behavior studied at zero temperature, distinguish two phases of the electron at different regimes, and their change is recognized to be a quantum phase transition [@2008PhRvA77:Delgado]. Magnetization shows a discontinuity at a finite value of the magnetic field [@Panella:2014hga]. The quantum nature of this behavior raises the question on how thermal fluctuations interacts with the system and when the thermal disorder destroys these quantum effects. In this paper, we analyze the interplay between these two physical phenomena. In particular, we quantify the discontinuity of the magnetization of the QPT at finite temperature $\Delta M \propto \hbar \left[ \frac{1}{k_B\,T}+O(\frac{1}{k_B\,T})^2\right]$. This discontinuity is a quantum phenomenon that tends to zero for high temperatures. While the critical values of the system are not affected by changes in temperature, we noticed a crucial difference from the system at $T=0$ studied in [@Panella:2014hga]: the magnetization at finite temperature has regimes with opposite sign with respect to the single state (zero-temperature) case. This opens to the possibility of a second phase transition at low temperatures, where the statistics of the states becomes quantum and cannot be described by Boltzmann statistics. In Fig. \[fig:Free\] we report various thermodynamic quantities that can be evaluated once the partition function is provided. The specific heat shows different behaviors at different phases of the system. The series representations of the partition function proposed in this paper allow to explore the system in diverse regimes: far, close and at the critical points. The representation in terms of the Hurwitz-zeta function fixes some misunderstandings present in the literature regarding which poles play a role in the evaluation of the partition function. We also generalize our calculations to the Dirac oscillator in noncommutative momenta and coordinates. The interest for this system comes from the fact that at zero temperature it manifests a re-entrant quantum phase transition, that we find is present also at finite temperature. Interestingly, there are systems in condensed matter physics that in certain regimes appear to have behavior similar and some times mathematically equivalent to systems living in a noncommutative space-time [@2012PhRvB..86c5125N; @Haldane:2011ia; @2012PhRvB..85x1308P; @2012PhRvB..85g5128B]. This opens the avenue of an *analogue noncommutativity* that is the possibility of studying, also experimentally, systems that are mathematically equivalent to those with noncommutating coordinates and/or momenta but are condensed matter systems living in an ordinary commutative space. The “analogue” approach to theoretical models that are too extreme or too weak to be measured directly has already been successfully employed in high-energy physics, and in particular in gravity with the so called analogue gravity [@Barcelo:2005fc]. This program is in constant development and already lead to important successes such as the measures of the analogue Hawking radiation [@Weinfurtner:2010nu; @Belgiorno:2010wn; @Steinhauer:2014dra; @Steinhauer:2015saa], phenomenon that seemed to be only a theoretical model. It is interesting and challenging to find an analogue system that would allow the experimental measure of the re-entrant phase transition described in this paper, and we leave it for future investigation. Acknowledgements {#acknowledgements .unnumbered} ================ A.M.F. would like to thank the Stiftung Giersch for the generous support during this work. D.M. acknowledges L. Malagò for discussions and support. [^1]: The classical multi-oscillator states partition function is simply $ (Z_L)^n / n! $ for $n$ electrons [@Kubo1990].

FadeSlideShow not showing 1 of 9 images in Chrome and Firefox, works fine in Safari If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. FadeSlideShow not showing 1 of 9 images in Chrome and Firefox, works fine in Safari 3) Describe problem: I have used this slideshow in the past (on the same website where I'm having trouble now) with no problems. I even think when I changed the images recently it was working fine. But NOW (a few weeks later I think) I've noticed that 1 of 9 images is not showing up on Chrome and Firefox. It works perfectly in Safari though. I've looked at the code for the problem image, and it is following the same format as the other images and the image is uploaded. I checked this before I found that it worked fine in Safari. Here is the site where I am having the trouble. The slideshow is on the right, almost half way down the home page: If you are looking at this in Safari, the image that doesn't show on Chrome and Firefox is of a side view of a man in Native American clothing playing a woodwind instrument. It comes just after 2 images, 1 of a man, and 1 of a woman, both posing against a palm tree trunk. In Chrome and Firefox this space just comes up with a beige color. My Safari (for Win 7) cannot show it either, but perhaps one on a Mac could. That image (I downloaded it): ojaiworldmusic.org/images/owmf2013/RCarlosNakai_525.jpg doesn't appear to actually be a JPEG type image. I have several image editing programs. Two are fairly sophisticated. The Gimp opens it and reports it as a "Photoshop image", and shows it at 525 × 300 pixels. The other is Paint Shop Pro 7 (old but still reliable) it opens it as a jpg, but at only 160 x 91 pixels, which I'm thinking is an embedded thumbnail, these can often be embedded in an image's EXIF or other data. So, I suspect that you saved it in Photoshop or some other image editor as a Photoshop formatted image and just put a .jpg extension on it. What I would do is load it back into the image editor and save it as a JPEG formatted .jpg image. Or, if that's not something you know how to do, use this version (right click and 'Save As' - First make a backup copy of your version, just in case): BTW, the PSD version of the image (what's currently on the website) is about 888K, the above is about 49K. The PSD version is "lossless", I also saved a true JPEG version at 100% quality (virtually "lossless"), it's about 117K, if you're interested in that version, let me know. The 49K version is about 95% quality with Image Optimizer Pro's "Magic Compression" applied, except to the face. I preserved what I think is the original date of the image in its EXIF data's 'DateTimeOriginal' field for both of the JPEG versions - 6/19/2013. I'm on a Mac: Firefox says it can't show it because "it has errors". Safari does display it. At first glance, it's hard to tell what's going on. That's partly because the file extension is only one cue on a Mac so you can still read a file in format X with extension Y. Preview (the main image viewer) can open it without problems. I'd guess it's the same image-reading engine as in Safari (and Finder, where you see a thumbnail). It's possible that this could happen when an image is simply corrupt. That's happened for me a few times with a digital camera, where only half of the data is saved and most of the image is random colors (usually blocks) or gray. Or I've even had that happen where the image is visually clear but still has some corrupt data in the file (maybe invisible information in the image, maybe metadata, I'm not sure). In that case, it's best to extract what you see (eg, via a screen capture or cut-and-paste as long as you're not accidentally then copying bad data too). Then it'll work. Anyway, back to Preview-- it showed it just fine. But in the "Info" window I could see something about Adobe Photoshop Format. It also listed a couple layers in the image (a clear indication that it's not a JPEG). So I tried Photoshop. Still on the Mac, where Photoshop isn't really a Mac program (just running there), so it probably does rely on the file extension. Sure enough, I got "Could not complete your request because an unknown or invalid JPEG marker type is found." Renaming it to PSD allowed me to open the file in PS. And there was the answer: it really is a Photoshop Document. It has two layers: one is the image, and the other is the white 'border' (actually a full rectangle filling the whole background underneath). So that's the complete explanation if it matters. John, your JPEG looks fine to me. So that's solved. But I just wanted to add the "whole story". John and Daniel - thank you both for your quick detective work. I'll have to add this issue to my tool belt of problem solving. You were both absolutely right! I don't remember if the original image was given to me by the site owner, or if I acquired it from the performer. I went back out to find another copy, and apparently there is a corrupted version out there floating around. One I tried to use gave me a similar "can't be opened in Photoshop" message. I was able to find an uncorrupted version and the slideshow now works perfectly in Firefox and Chrome. While you were answering me I found out it hadn't been working in IE either, so I'm assuming that is working fine now as well. Thank you SO much! This is my first time in the forum and I had no expectation of receiving a solution within an hour. Amazing!

2018 hot sale high quality peanut sunflower oil making Peanut Oil Machine Easy Way to Set Up and Run a Mini Oil Mill Plant On Sell Automatic Linseed Oil Skip to content Main Menu Home About Our factory Communication With Client Products Animal Oil 2018 hot sale high quality peanut sunflower oil making Peanut Oil Machine Easy Way to Set Up and Run a Mini Oil Mill Plant On Sell Automatic Linseed Oil Skip to content Main Menu Home About Our factory Communication With Client Products Animal Oil

Q: How To: View MFC Doc File in Python I want to use Python to access MFC document files generically? Can CArchive be used to query a file and view the structure, or does Python, in opening the document, need to know more about the document structure in order to view the contents? A: I think that the Python code needs to know the document structure. Maybe you should make a python wrapper of your c++ code. In this case, I would recommend to use http://sourceforge.net/projects/pycpp/>pycpp which is my opinion a great library for making python extensions in c++.

Kakhaber Sidamonidze Kakhaber Sidamonidze (born 17 April 1971) is a retired Georgian professional football player. External links Category:1971 births Category:Living people Category:Soviet footballers Category:Footballers from Georgia (country) Category:Georgia (country) international footballers Category:FC Guria Lanchkhuti players Category:FC Dinamo Batumi players Category:Association football defenders

Q: If in a turing machine, whenever the head tries to move left, it gets rewinded all the way to the leftmost cell. ASSUMPTION : Turing Machine has one sided infinite tape(right to be precise). Given following constrained (deterministic single-tape) Turing Machine, what is the class of language recognized by it. Restraint: The Turing machine, on each transition can perform three operations(wrt moving L,R,S) 1.) It can move right by one cell. 2.) It can stay on current cell. 3.) It can move to the leftmost cell. (restraint) So Does this turing machine accepts all the languages accepted by a Unrestrained turing machine or not. I think it accepts all that an unrestricted turing machine can accept, but I am still doubtful. A: This type of machines is indeed equivalent in power to ordinary Turing machines. In fact, even if you remove the ability to perform the second type of moves (stay on the current cell), the power of the machine will not be affected. Here is how such a restricted TM can be converted to an unrestricted one. When the machine needs to move the head to the right, it first puts a special mark, e.g. $\sim$, upon the current symbol. Then it goes all the way back to the leftmost cell, and starts moving rightward. While the machine does so, if another special mark, e.g. $\bullet$, is discovered on a symbol, it gets removed from it. Once the head encounters $\sim$, the machine replaces it with $\bullet$ and moves the head one cell to the right. This combination of moves is equivalent to one move to the right performed by an ordinary TM. Note that the symbol in the left adjacent cell is now marked with $\bullet$. When the head needs moving to the left, there are three possibilities. The head points to the leftmost cell. In this case the tape contains no symbols marked with $\bullet$. The head points to the cell adjacent to the leftmost cell. In this case the tape does contain a symbol marked with $\bullet$, which is located in the leftmost cell. The head points to neither the leftmost cell nor its adjacent cell. In this case the tape also contains a symbol marked with $\bullet$, which is not in the leftmost cell. This is the symbol the head needs to move to. The first case can be handled by marking the current symbol with $\sim$, moving the head to the leftmost cell and checking if the current symbol has $\sim$ upon it. If it does, remove it and remain in this cell, the move is now complete. Otherwise, check if the current symbol has $\bullet$ upon it. If it does, remove it, move the head to the adjacent cell, remove $\sim$ from the symbol in that cell and move to the leftmost cell again. This handles the second case. To deal with the last case perform the following steps. Mark the current symbol with $\bullet$. Move the head one cell to the right. Check if the current symbol is marked with $\bullet$. If it is, remove $\bullet$, move the head one cell to the right, remove $\sim$, move the head to the leftmost cell and scan the tape for an occurrence of $\bullet$. Once it is found, move the head one cell to the right and finish. Otherwise, put $\bullet$ upon it, move the head to the leftmost cell and scan the tape for the first occurrence of $\bullet$. Once it is found, remove it, move the head one cell to the right and proceed with step 2. This simulates one move leftward performed by an ordinary TM. Note, that unless the head is pointing to the leftmost cell, the symbol in the left adjacent cell is marked with $\bullet$.

Feeding oleamide to lactating Jersey cows 1. Effects on lactation performance and milk fatty acid composition. Oleamide was previously reported to resist ruminal biohydrogenation and elevate milk oleic acid concentration when fed to lactating Holstein cows. To determine if Jersey cows responded similarly to oleamide, four lactating Jersey cows (mean 417 kg of body weight and 64 days in milk) were fed four diets in a 4x4 Latin square with 2-wk periods. Diets were total mixed ration containing 47% corn silage and 53% concentrate (dry matter basis) and were supplemented with no added fat (control), or with 3.5% added fat from either higholeic canola oil, a commercial source of oleamide, or oleamide synthesized from oleic acid and urea. The canola oil supplement had no effect on milk yield or composition. Compared to canola oil, the oleamide supplements reduced milk yield, dry matter intake, and milk fat and protein contents. Milk oleic acid concentration increased from 17.4% of total fatty acids for the control diet to 22.1% for the canola oil diet. Both oleamides further increased milk oleic acid to 30.0 and 27.1% of total fatty acids for the commercial and synthesized oleamides, respectively. Milk palmitic acid was reduced and stearic acid was increased by all fat supplements but more so by the oleamides than by the canola oil. Consistent with previous reports that fatty acyl amides resist ruminal biohydrogenation, feeding oleamide to Jersey cows in this study increased milk oleic acid concentration but had negative effects on feed intake and milk yield.

De Blasio likens Trump’s comments to a 'third-world dictator' New York City Mayor Bill de Blasio said Donald Trump’s refusal to say whether he would concede if he loses the presidential election in November is something expected from a “third world dictator, not from an American presidential candidate.” During an interview with CNN on Thursday morning, de Blasio, a surrogate for Hillary Clinton, said Trump’s remarks made during the third and final presidential debate are “dangerous” and “something you’d expect from a military leader about to attempt a coup in a foreign country.” Trump’s comments came after spending months spreading the unsubstantiated claim that the election will be “rigged” against him, and suggesting that he will contest the results. Still, his campaign manager, Kellyanne Conway, has repeated that she does not think the election will be “rigged” and said after the debate that he will concede if he loses the election fair and square. But his comments sparked wide criticism and concern, even among some Republicans. Sen. Lindsey Graham issued a statement saying, “Trump is doing a great disservice by continuing to suggest the outcome of this election is out of his hand.” He added, ”If he loses it will not be because the system is rigged, but because he failed as a candidate.” Other Republicans leaped to Trump's defense, saying he wouldn't be the first candidate to contest an election. “This is exactly what Al Gore did,” former New York City Mayor Rudy Giuliani said to reporters in the spin room Wednesday night after the debate. “It was their Democrat, Al Gore.”

within Modelica.Mechanics.MultiBody.Frames.Quaternions; function relativeRotation "Return relative quaternions orientation object" extends Modelica.Icons.Function; input Quaternions.Orientation Q1 "Quaternions orientation object to rotate frame 0 into frame 1"; input Quaternions.Orientation Q2 "Quaternions orientation object to rotate frame 0 into frame 2"; output Quaternions.Orientation Q_rel "Quaternions orientation object to rotate frame 1 into frame 2"; algorithm Q_rel := [ Q1[4], Q1[3], -Q1[2], -Q1[1]; -Q1[3], Q1[4], Q1[1], -Q1[2]; Q1[2], -Q1[1], Q1[4], -Q1[3]; Q1[1], Q1[2], Q1[3], Q1[4]]*Q2; annotation(Inline=true, Documentation(info="<html> <h4>Syntax</h4> <blockquote><pre> Q_rel = Quaternions.<strong>relativeRotation</strong>(Q1, Q2); </pre></blockquote> <h4>Description</h4> <p> This function returns <a href=\"modelica://Modelica.Mechanics.MultiBody.Frames.Quaternions.Orientation\">quaternions orientation</a>&nbsp;Q_rel that describes the orientation to rotate frame&nbsp;1 to frame&nbsp;2 from the <a href=\"modelica://Modelica.Mechanics.MultiBody.Frames.Quaternions.Orientation\">quaternions orientation</a>&nbsp;Q1 that describes the orientation to rotate from frame&nbsp;0 to frame&nbsp;1 and from the <a href=\"modelica://Modelica.Mechanics.MultiBody.Frames.Quaternions.Orientation\">quaternions orientation</a>&nbsp;Q2 that describes the orientation to rotate from frame&nbsp;0 to frame&nbsp;2. </p> <h4>See also</h4> <p> <a href=\"modelica://Modelica.Mechanics.MultiBody.Frames.relativeRotation\">Frames.relativeRotation</a>, <a href=\"modelica://Modelica.Mechanics.MultiBody.Frames.TransformationMatrices.relativeRotation\">TransformationMatrices.relativeRotation</a>. </p> </html>")); end relativeRotation;

The gunners at Fort McHenry readied the 3-ton cannon known as Messenger, heaving it into position behind a wooden wall with a block-and-rope pulley system and loading it with gunpowder and a substitute cannonball of peat moss. The call came: "Clear!" and the gunners stepped to the side, with one touching a slow match to the gunpowder inside the cannon. The boom rocked the air and echoed across Baltimore's harbor as a geyser of fire and smoke poured from the cannon's mouth. Park ranger Tyler Mink said the first time he set off a cannon, the experience was "a little nerve-racking. Major League Lacrosse Berger, Buchanan shine in 16-15 Cannons victory Stephen Berger (Washington College, Mount St. Joseph) and Kevin Buchanan (Calvert Hall) each had four goals and an assist, and the host Boston Cannons held on for a 16-15 win over the Florida Launch on Saturday afternoon at Harvard. The win moved the Cannons (6-7) ahead of the Launch (6-8) in the race for the fourth and final playoff berth in Major League Lacrosse. Heading into Saturday night's game, the Ohio Machine (6-6) On February 11, 2003, JOSEPH E.; dear brother of Leroy L. Cannon and his wife Dolores Helen, Patricia Ann Winterling and the late James I. Cannon; dear uncle of Kathleen Cannon Saini, Stephen L. Cannon, Daniel and Timothy Winterling. Also survived by many friends at the Christ Church Harbor Apartments. Relatives and friends are invited to call at the Schimunek Funeral Home, Inc., 3331 Brehms Lane (at Erdman and Mannosota Avenues), on Wednesday, from 2 to 4 and 7 to 8 P.M. A Funeral Mass will be held at the Shrine of the Little Flower Church, on Thursday, at 11 A.M. Interment Garrison Forest Maryland Veteran's Cemetery. The gunners at Fort McHenry readied the 3-ton cannon known as Messenger, heaving it into position behind a wooden wall with a block-and-rope pulley system and loading it with gunpowder and a substitute cannonball of peat moss. The call came: "Clear!" and the gunners stepped to the side, with one touching a slow match to the gunpowder inside the cannon. The boom rocked the air and echoed across Baltimore's harbor as a geyser of fire and smoke poured from the cannon's mouth. Park ranger Tyler Mink said the first time he set off a cannon, the experience was "a little nerve-racking. On March 22, 2004, BRO. GABRIEL T. CANNON, F.S.C., 78 years as a Christian Brother, of which 12 were spent as Principal of Calvert Hall College High School. Beloved son of the late Dorothy Burns Cannon and Patrick J. Cannon, uncle of Sheila Bryant and Peter Mellett of Maywood, NJ. Friends may call at the Calvert Hall College High School Fine Arts Theatre on Friday from 6:30 to 8 P.M., at which time a Funeral Mass will be celebrated and at La Salle Hall, Ammendale, Beltsville, MD, on Saturday from 11 to 12 noon, at which time a Funeral Mass will be celebrated. You would think that a 27mm cannon might help a man protect his property from a siege, but modern-day suburban invaders apparently aren't the least bit daunted by heavy artillery.Since Benfield Road resident Jack Colleran placed a World War II vintage Japanese cannon in his side yard in 1970, he and housemate Caroline Cox have stood by in despair besieged by a half a dozen different enemies.In the last 20 years:* Their home has been broken into four times.* The county condemned a wide strip of their land to expand Benfield Road. Derrick "OOH" Jones, aka Yo Slick and member of the influential Baltimore rap group Brown F.I.S.H., died Sunday. He was 38. Al Shipley's obituary in City Paper , which first reported Jones' death (cause of death has not yet been released), is essential reading to understand Jones' impact on Baltimore. Jones was an excellent rapper and live performer, but his reach extended well beyond hip-hop fans. He was a teacher at Gilmor Elementary and the director of the Baltimore Youth Advocate Program. Today they endure climbing children and have bicycles chained to them, but the cannons that flank Patterson Park's Pagoda were used in wars as much as 350 years ago, park officials have found. A cannon expert surveyed the seven historic weapons last fall and will soon undertake their restoration after finding they aren't just reproductions, as many had thought in the century since they were installed to commemorate the War of 1812 centennial. Some were likely used in the Battle of Baltimore, on land or sea, and in the Revolutionary War - or earlier. Major League Lacrosse announced on Monday that Fifth Third Bank Stadium at Kennesaw State University in Kennesaw, Ga., will host the 2014 MLL championship game Aug. 23. “We are thrilled to return to Fifth Third Bank Stadium and the Atlanta region,” MLL commissioner David Gross said. “We believe in the growth of the sport in the area and having the championship game there is the next step as we contemplate future expansion.” Last season, more than 4,000 fans traveled to Fifth Third Bank Stadium to watch the Rochester Rattlers play the Boston Cannons in the first-ever MLL game in Georgia. The two-time defending Major League Lacrosse champion Chesapeake Bayhawks will open their 2014 schedule with a road game against Paul Rabil (Johns Hopkins) and the Boston Cannons on April 26. The Bayhawks return for their sixth summer at Navy-Marine Corps Memorial Stadium in Annapolis for their home opener on May 3 against Rookie of the Year Rob Pannell and the New York Lizards. The regular season will again be 14 games -- seven home and seven away. “We are excited about our schedule this season,” coach Dave Cottle said. Madge R. Cannon, a retired Social Security Administration worker and longtime member of Fulton Baptist Church, died Oct. 22 of heart failure at Envoy of Pikesville nursing home. She was 86. The daughter of Willie Rice, a factory worker, and Clara Fernandez Rice, a housekeeper, Madge Rice was born in Baltimore and then moved to Jonesville, S.C. In 1937, she and her family moved back to Baltimore. She attended Frederick Douglass High School, from which she graduated in 1947. She attended what is now Coppin State University and later Baltimore City Community College. Chase Winter , who recently finished his playing career as a Johns Hopkins midfielder, had four goals and an assist and was named Most Valuable Player of the Men's Open 1 championship game at the Lake Placid Summit Classic in North Elba, N.Y. on Sunday. Winter led Power-Tek, a team that featured 2012 Tewaaraton Award winner Peter Baum and several other players with Colgate ties, to a 13-10 win over the Big Red Steelheads for their second straight Open 1 title. It was Winter's first time playing in the event, which has been held annually since 1990. The already prodigious legacy of Casey Powell grew Thursday night in the Bayhawks' 13-12 victory over the Boston Cannons. The former four-time All-American and Major League Lacrosse's second-leading scorer all time had three goals and an assist for the Bayhawks in his first game of the season, but it took just one goal to remind fans of what they've been missing while he's been gone. With Chesapeake trailing 12-11 with less than 10 seconds to go, Powell raced behind the Cannons net with the ball in his stick.

p0c has asked for the wisdom of the Perl Monks concerning the following question: Hey all, I'm looking for some modules or example script on how to capture packets, modify and then send them further. Net::Packet is good for capturing, but I can't see how to edit the packets. I can only manage to look at the packet itself, but the packet itself is already send to it final destination then. Maybe Net::Packet isn't the right way to go? Say for example I want to replace <img src=bla.jpg> to <img src=lala.jpg> in every HTTP packet.. Can anyone give me some pointers in the right direction? Are you planning on piecing the individual packets together first, doing your substitution, and then re-splitting the packets? If not, I think you will run into complications on the splitting points of the packets. How will you know that the entire URL of your image is contained in one single packet, all of the time? Do packets always respect URLs in such a way as to make sure that they will not get chopped in two? I don't think so. As one website put it: TCP/IP implementations differ in the approach they take to deciding on packet size. It is fairly common for implementations to use 576-byte packets whenever they can't verify that the entire path is able to handle larger packets. The problem is that many implementations have bugs in the code to reassemble pieces. So many implementors try to avoid ever having splits occur. Different implementors take different approaches to deciding when it is safe to use large packets. Some use them only for the local network. Others will use them for any network on the same campus. 576 bytes is a safe size, which every implementation must support. So, what are the odds of your URL always landing somewhere in the middle of that packet, and never on the joint between two packets? Yes, but the thing is that i can't use a proxy for this. The only thing I can do is intercept the packets. The thing I want to do looks like what ettercap filters do. Like this: http://www.irongeek.com/i.php?page=security/ettercapfilter Yes, but the thing is that i can't use a proxy for this. The only thing I can do is intercept the packets. I take it that you mean you cannot reconfigure the clients to direct their queries to the proxy explicitly. This does not prevent you using software that provides easy access to the HTTP protocol layer and HTML documents therein. Software that allows you to intercept relevant packets on the network and manipulate the communications protocols without configuration of the clients are sometimes called "transparent" or "intercepting" proxies. You can do this with ettercap but there are other packages that provide easier access to the HTTP protocol layer. There are Perl modules that do this and many other applications, as ikegami has pointed out in Re: Packet editing. There are Perl modules that provide rich features for inspecting and modifying HTTP protocol communications and HTML documents. There are intercepting proxies that are not written in Perl that provide access to the HTTP protocol and HTML documents and may provide better performance than you could achieve with Perl. Wikipedia has links to some of these. The squid proxy is popular and I have successfully used it many times. It can be used as an intercepting proxy, though I have not used it to manipulate the HTML myself. But, as noted previously, there are many others that you might investigate. I suggest that you cannot create a reasonably competent proxy to manipulate HTML documents in HTTP protocol streams by manipulation of individual IP packets, whether with ettercap or any other packet filtering software. You will have better results with less effort if you start with a better tool.

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Todd Akin Compares Opponent To A Dog More sensitive phrasing from the man who brought you "legitimate rape." Claire McCaskill "fetches" government from Washington, he says. (Via PoliticMO)

Coyotes Vs. Jessica Simpson Amelie Gillette & Matt Kirsch discuss important terrible things. It's Telepathy Awareness Week on the Hater podcast! To celebrate, Amelie Gillette and Onion web producer Matt Kirsch didn't speak a single word when recording this week. Instead, they just had a thought conversation about Jessica Simpson's eternal, coyote-related sadness; The stupid Ellen/American Idol debate; and the ongoing animosity between TV and the Internet, trusting that this conversation would be communicated to the listeners via their incredible telepathic powers. Go ahead: click Play and find out if telepathy is real!

The computed tomographic appearance of subcutaneous nodules occurring in metastatic neuroblastoma. The authors report a case of subcutaneous nodules in a 2-month-old girl with metastatic neuroblastoma; the appearance of the nodules in computed tomography scans is described. Such nodules are sometimes overlooked by clinicians and radiologists, even though they almost always occur in disseminated disease. In patients with neuroblastoma and other neoplasms subcutaneous nodules may be an easily accessible source of samples for histopathologic examination.

National Association of County Behavioral Health & Developmental Disability Directors The voice of local authorities in the nation's capital News Article Details County addressing mental health needs in the community Mar. 2--As the conversation regarding mental health continues at the state and national levels, local leaders are taking action to implement solutions in hopes to better the community. In 2019, the Platte County Board of Supervisors budgeted almost $13,000 to address mental health issues those in the law enforcement and justice fields have come across through their everyday work. The decision to fund these efforts came after a presentation by then-Platte County Deputy Attorney Elizabeth Lay in mid-2019. Lay handled various mental health commitments on behalf of the county attorney's office before stepping away from county employment recently. "I am so excited about this programming," Lay told The Telegram. "We already have people utilizing the funding and I think it is going to help a lot of people get on the path towards better choices and a better life." The Supervisors put money toward three aspects of mental health programs to address local needs. First, the board approved $5,000 in the Platte County Sheriff's Office budget to fund evaluations for defendants in criminal cases that cannot afford the evaluation on their own. To be eligible, defendants must be part of a pending adult case, be appointed an attorney by the court, and participating in a plea deal that contemplates an evaluation and treatment to be eligible for the funds. The board also approved $5,000 in the General Assistance budget for counseling services for defendants in criminal cases that cannot afford treatment on their own. The same eligibility requirements exist for these funds as for the other. The county will pay up to three sessions for a defendant, according to Lay. The board put an additional $2,500 toward mental health treatment costs in the Adult Diversion Program, which aims to provide an alternative to court for eligible adult offenders charged with lower-level offenses. "I think it is safe to say that they understand how big of an issue this is for our community," Lay said about the Board of Supervisors. Funding mental health programs was important when considering the future of the county as a whole, according to Platte County Board of Supervisors Chairman Jerry Engdahl. He said more people are facing mental health problems in the area each year, noting that it's unfortunate some of those folks end up in a prison cell because of it. "We need to look after everybody, including those with mental health problems," Engdahl said. "We're striving and hoping to make a positive influence." Coming from Lincoln, Lay moved to town seven years ago and said she has seen firsthand what happens when people with mental illness don't have the support they need to get better. "It's awful to see that cycle -- it's a vicious cycle," she said. "They do things they normally wouldn't do. It's really important to have someone who is sitting back and trying to figure out how we solve that." Platte County Sheriff Ed Wemhoff said he believes there is a direct correlation to mental health and criminal activity, noting there have been many people who have served time in the local facility that have mental health problems, substance abuse issues, and sometimes, both. Although the sheriff's office was already working with a mental health professional, Wemhoff said he was all ears when Lay approached him about how the sheriff's office could help identify mental health problems in the area. The goal was to develop a plan that would have minimal impact on the day-to-day operations of the sheriff's office, while also being able to make something like an evaluation work within officers' other duties. "It was beneficial having other supervisors here at the sheriff's office understanding and recognizing the benefits of working with such a program," he said. Mental health hits home for Lay. She suffered from postpartum depression and anxiety after the birth of her first child, and though her anxiety went away, for the most part, she acknowledged she struggles with it to some degree even today. "I, however, am lucky enough to have had needed resources available to me and to know where to find resources when I needed them," Lay said, noting she has seen family members and friends deal with depression, bipolar disorder, anxiety and more and watched how the effects of those diseases radiate through family units and wreak havoc in people's lives. "So many people don't know where to turn when things go south. So many people don't have resources available to them." Having lived in larger communities, Lay emphasized there is a gap right now between what can be done for mental health in urban areas and the rural ones. Lay said she has seen more and more people she deals with in the mental health system enter the criminal system and vice-versa. "That is why I am so passionate about making sure people have the help they need when they need it," Lay said. "People are dying, and if we can save lives, then we have a duty to do so. I am so proud that our county now has a hand in that. I think it's a really big step for a smaller county to take initiative on that and say, 'OK, we're not getting enough help in this area. We need to do something.'" Wemhoff said he doesn't believe the issue will ever go away completely and the impact of the funds might not be seen for a while. But, he noted, he believes they will make a difference down the line. "I would say these funds will be more likely to benefit the County Attorney's Office as they evaluate and access each case, as they attempt to do what is best for the community as a whole," Wemhoff said. "Together we recognize that many individuals currently incarcerated are suffering from mental health and if we can get them the help and support they need to keep them out of jail, this would be a direct relation to less criminal activity." Matt Lindberg is the managing editor of The Columbus Telegram. Reach him via email at [email protected]. NEED HELP? National Suicide Prevention Lifeline, 1-800-273-TALK (8255) If you or someone you know is suicidal or in emotional distress, contact the National Suicide Prevention Lifeline. Trained crisis workers are available to talk 24 hours a day, 7 days a week. Your confidential and toll-free call goes to the nearest crisis center in the Lifeline national network. These centers provide crisis counseling and mental health referrals. Special education families fear that children will not receive enough help during a prolonged school delay due to the coronavirus pandemic Plunge more than just special Wellness Recovery Action Planning (WRAP) Learn more about Mary Ellen Copeland's Wellness Recovery Action Planning (WRAP), the format for organizing wellness tools into action plans in order to deal with Life's challenges, especially those related to mental illness.

Validation of a prediction model to estimate health utilities index Mark 3 utility scores from WOMAC index scores in patients with osteoarthritis of the hip. To examine the validity of a newly developed prediction model translating osteoarthritis (OA)-specific health-related quality of life (HRQL) scores measured using the Western Ontario and McMaster Osteoarthritis Index (WOMAC) into generic utility-based HRQL scores measured using the Health Utilities Index Mark 3 (HUI3). Preintervention data from 145 patients with hip OA and complete WOMAC and HUI3 baseline assessments from the Alberta Hip Improvement Project study were used to validate three utility prediction models. These models were estimated using data from a previous study of knee OA patients. Predictive performance was assessed using the mean absolute prediction error (MAE) criterion and several other criteria. The validation sample appeared healthier (on the basis of the HUI3 and WOMAC) than the subjects used toestimate the prediction models. Nevertheless, the validation sample outperformed the predictive performance of the model sample. The results from the validation sample support the conclusions from the original study in that the primary model identified during model development (a model using WOMAC subscales, their interactions, their square terms, age, OA duration, their square terms, and gender) performed better on the MAE criterion than competing models. These results support the external validity of the prediction model for the retrospective estimation of HUI3 utility scores for use in economic evaluation.

Android: Sundroid is a simple but effective tool for checking the cycles of the sun and moon based on your physical location, right from your Android phone. If your work or recreational activities are dependent on markers like sunrise or sunset (the shooting range I belong to, for example, shuts down the outdoor ranges at sunset) Sundroid will keep you abreast of the times. Sundroid comes in free and premium flavors. The free version displays the sunrise, sunset, moonrise, and moonset times for your location. The $2 premium version adds in twilight times, azimuths, a lunar calendar, and a home screen widget. Sundroid uses your GPS or WiFi network IP location for geolocation. Advertisement Download the free version by scanning the QR code at right or search for "Sundroid" on the Android Market.

Magento 2 Enterprise The HiPay Enterprise module for Magento 2 is a PHP module which allows you to accept payments in your Magento 2 online store. It offers innovative features to reduce shopping cart abandonment rates, optimize success rates and enhance the purchasing process on merchants’ sites in order to significantly increase business volumes without additional investments in the Magento 2 e-commerce CMS solution. To use this module, you will need valid HiPay Enterprise account credentials: please contact HiPay to get them. Platform configuration Before using the HiPay Enterprise module for Magento 2, the following settings are required and must be configured. To do so, log in to your HiPay Enterprise back office. Configure your secret passphrase A secret passphrase is required to allow notifications.In your HiPay Enterprise back office, click on the “Integration” tab, then on “Security Settings”. Enter your secret passphrase in the “Data Verification” section. Allow your servers’ IP address(es) When a request is sent to the HiPay Enterprise servers, the IP address or IP address range from where the connection was made is verified. If it matches with the IP address previously provided by the merchant, the request will be processed. In case of missing or incorrect information, the server will respond with an appropriate error message, indicating the error in the request. In your HiPay Enterprise back office, click on the “Integration” tab, then on “Security Settings” and enter your IP address(es) in the “IP Restriction” section. Important! When changing your IP addresses, make sure that all the new ones are configured for your account. If not, your server requests will be rejected. Configure redirect URLs To use the HiPay Enterprise module for Magento 2, you need to configure default redirect URLs in your HiPay Enterprise back office in “Integration” -> “Redirect Pages”.Yet, these are not used by the HiPay Enterprise module for Magento 2 as it sends its own URLs. Accept Page: http://notused.com/accept Decline Page: http://notused.com/decline Pending Page: http://notused.com/pending Cancel Page: http://notused.com/cancel Exception Page: Empty Also, check the “Feedback Parameters” box and apply changes. Configure the notification URL In your HiPay Enterprise back office, click on the “Integration” tab, then on “Notifications”. Then, you need to enter your credentials. You will find them on your HiPay Entreprise back office (Integration > Security Settings) Anti-fraud emails configuration Based on the screening results of HiPay Sentinel, our advanced anti-fraud solution, emails can be sent to end customers. There are 3 email templates. Fraudulent: This email is sent to the customer if the payment is fraudulent. Accepted: This email is sent to the customer if the payment is approved by the merchant. Denied: This email is sent to the customer if the payment is denied by the merchant. Field name Description Enabled Enables/disables sending Payment Fraud Email Sender Sets the email sender Payment Fraud Template Sets the email template. You can customize it in your Magento 2 Admin Panel. To do so, go to “Marketing” => “Communications” [Email Templates]. Click on “Add New Template”, then upload the HiPay email template you want and modify it. Send Payment Fraud Email Copy To Email addresses you want to add in copy Send Payment Fraud Email Copy Method Selects the email copy method (Cc or Bcc) Customer’s cart items configuration This section addresses customer’s cart items sending to the HiPay Enterprise back office during the transaction. Enabling this option applies to all enabled payment methods on your site. The information of the customer’s cart, containing the shipping method, the discounts and each product with the quantity, as well as the SKU and the tax, is sent with the transaction. For Oney Facily Pay, sending this information is mandatory. This option is therefore ignored if the transactions are made with this payment method. Oney’s anti-fraud system requires additional configuration for the shipping method and product categories. The configuration is explained in the following paragraph. Please note that “Adjustment Fee” or “Adjustment Refund” are not supported with carts for refunds. Mapping categories Go to the setup screen HiPay Enterprise > Mapping Categories. Only the top level categories are displayed and must be mapped. If the mapping is not done, transactions will be refused by Oney. It is therefore important to check your mapping regularly when adding or modifying a category. Mapping shipping method Go to the setup screen HiPay Enterprise > Mapping Shipping method. A list of all the shipping methods activated on the site is displayed. This mapping is necessary to indicate a match between your shipping methods and the shipping methods defined by HiPay. For each customer’s order, depending on the chosen configuration, this information is sent as a supplement to the customer’s cart. For each mapping, you have to fill out the following information: Order preparation delay: Estimated time for order preparation, Delivery time estimated: Estimated time for delivery. From this information, an estimated delivery day is calculated and sent with the transaction. Non-working days are not taken into account in this calculation. As with the mapping of categories, all shipping methods must be mapped. Therefore, it is important to update your list if you change the configuration of your shipping methods. Other configurations Field name Description Device fingerprint Defines if a fingerprint is sent with the transaction (“YES” by default) URL of HiPay’s JavaScript Technical parameter not to be modified. Send cart Activates customer’s cart items sending or not (“NO” by default) EAN attribute EAN is not a Magento attribute by default: you must define your custom attribute if you want to send it in the cart PSD2 & SCA Given the strong growth of the e-commerce in Europe, the second Payment Services Directive (PSD2) redefines the security standards for online payments, aiming to increase security during the payment process, while fighting more actively against fraud attempts. For more details on the regulations, we invite you to read our guide on PSD2 compliance. As from September 14, 2019, the issuer will now decide if a payment is processed depending on the analysis of more than 150 data collected during purchasing. Thanks to our Magento 2 module, we handle most of the data without you having to develop anything. Discover all the new parameters on our API explorer. Adding or overriding PSD2 data The accuracy of the information sent is key for making sure that your customers have a frictionless payment process. That’s why we give you the possibility to add or override PSD2 data, using a plugin on the “HiPay\FullserviceMagento\Model\Request\Order” class which can intercept the “mapRequest” method. You can either implement the plugin in your own modules or use the one that we provide. You can find this additional plugin in our GitHub repository. You can install this plugin in a standard way, then directly modify the “ThreeDSPlugin.php” file and the “afterMapRequest” method to add your information. Please note: If there is an update of this plugin, remember to save your information so that it is not overwritten. Finally, although we do our best to retrieve all relevant data for you, we cannot get the following information as it depends on the modules installed on your CMS or on your workflow. Merchant risk statement Field name Description delivery_time_frame By default, we send “1” (Electronic delivery) if it is a downloadable or an intangible product. Depending on your carrier and delivery methods, you can refine this information. Payment methods configuration Before describing the configuration fields for each payment method, please note the difference between the HOSTED and API modes. General configuration All payment methods have a basic configuration like the native Magento 2 payment methods configuration or the general HiPay Enterprise configuration. Field name Description Enabled Enables/disables the payment method Title Desired name of the payment method as displayed during checkout Payment Action Authorization or Sale. See more configuration details below. New Order Status Order status to set when the order is created before payment. Pending by default. Order status when payment accepted Order status to set when the transaction is successful. Processing by default. Order status when payment refused Order status to set when the transaction fails. On Hold by default. Order status when payment cancelled Order status to set when the transaction is canceled by the user. Canceled by default. HiPay status to validate order By default, all orders are validated/invoiced upon notification when the Capture status (118) is sent from the HiPay Enterprise platform (around 10 min after capture is requested). You can change this pattern by selecting “Capture Requested”. In this case, the order is validated/invoiced directly upon the Capture Requested (117) status. Capture When making a purchase with the “Sale” mode, the capture is automatically requested right after authorization. If the payment fails, the customer is redirected to an error page and the status is defined as “CANCELED”. If the payment is successful, the customer is redirected to the success page and the status is defined as “CAPTURE REQUESTED”. “Authorization” mode When making a purchase with the “Authorization” mode, the transaction status will be “AUTHORIZED” until you ask for the capture. Customers are not charged directly: you have 7 days to “capture” the order and charge the customer. Otherwise, the order is cancelled. If the authorization fails, the customer is redirected to an error page and the status is defined as “CANCELED”. If the authorization is successful, the customer is redirected to the success page and the status is defined as “AUTHORIZED”. To capture a transaction in your Magento Admin Panel, select “Sales” -> “Orders” -> “View” to see the details of the order and choose to submit an “invoice”.On the “New Invoice” page, select “Capture online” and save your invoice.Please note: If you select a custom item quantity, you can do a partial capture. You can also do the “capture” directly in your HiPay Enterprise back office. The order will then be automatically updated in your Magento Admin Panel.Please note: It only works for total captures (not partial). Refund Some HiPay Enterprise payment methods allow for a refund. To do so, in your Magento Admin Panel, select “Sales” -> “Orders” -> “View” to see the details of the order, then choose an invoice to refund and click on “Credit Memos”. Please note: If you select a custom item quantity, you can do a partial refund. You can also do the “refund” directly in your HiPay Enterprise back office. The order will then be automatically updated in your Magento Admin Panel.Please note: It only works for total refunds (not partial). One-click If the One-click option is enabled, your system will create an “alias” for the credit card. Customers will thus be able to use a saved credit card for their second transaction and won’t need to fill in all the payment data again. Customers can delete their saved credit cards from their account. Split payments When an order is created with a HiPay Enterprise split payment method, x installments are created (x depending on the selected payment profile). A split order is validated when the payment is captured. Upon payment capture, x installments are generated for this order. The order is fully invoiced (but not fully captured in the HiPay Enterprise platform) and you can get ready for shipment. The first installment is always debited on the payment date in Capture mode or when you capture manually in Authorization mode. Then, with a Cron task, each installment is debited on its respective payment date. Split payment methods The HiPay Enterprise module for Magento 2 includes two payment methods for split payments: Custom data It is possible to send additional information in the transaction that can then be viewed in the HiPay back office. To do so, you can use the functionality of Magento 2 which relies on the notion of plugin. To add custom information to transactions, you need to create a plugin in your custom module. This plugin must observe HiPay\FullserviceMagento\Model\Request\Order and extend the method getCustomData with afterGetCustomData. You can put what you want in the $result variable. You can get inspiration from our CustomDataPlugin plugin located in our module. Payment notifications During the payment workflow, the order status is updated only through HiPay Enterprise notifications. The endpoint for notifications is http://yourawesomewebsite.com/hipay/notify/index. It is protected by an encrypted passphrase: don’t forget to enter it in your Magento Admin Panel and HiPay Enterprise back office. For more information, please see the process in the Notify model. Transaction statuses All HiPay Enterprise transaction statuses are processed, but not all of them interact with Magento order statuses. This process only occurs when a notification is received. When a status is in process, a Magento payment transaction is created. Otherwise, we just add a new order history record with notification information. Actions according to statuses BLOCKED (110) and DENIED (111) The transaction order “Denied” status is created. The transaction order is closed. Any invoice in Pending status is cancelled. The order status changes to the status selected in configuration for the current payment method. AUTHORIZED AND PENDING (112) and PENDING PAYMENT (200) The transaction order “Authorization” status is created. The transaction order is Pending. The order status changes to Pending Review. The invoice is not created. AUTHORIZATION REQUESTED (142) The transaction order is not created. The order status changes to Authorization Requested. Notification details are added to the order history. REFUSED (113), AUTHORIZATION_REFUSED (163), CAPTURE_REFUSED (163) The transaction order is not created. The order is set to the configured status. If an invoice exists, it is cancelled. CANCELLED (115) The transaction order is not created. The order is set to the configured status. If an invoice exists, it is cancelled. EXPIRED (114) The transaction order “Void” status is created if a parent transaction exists and is in status “Authorization”. The order is set to status Processing by Magento 2. AUTHORIZED (116) The transaction order “Authorization” status is created. The order status changes to Authorized. The invoice is not created. CAPTURE REQUESTED (117) If the validation status is set to Capture: – The transaction order is not created. – The order status changes to Capture requested. – Notification details are added to the order history. Otherwise, if the validation status is set to Capture requested, please see the Captured status related actions below. CAPTURED (118) and PARTIALLY CAPTURED (119) The transaction order “Captured” status is created. The transaction order is closed. The order status changes to Processing or Partially captured. A complete/partial invoice is created. In case of a split payment, a new transaction is created. REFUND REQUESTED (124) The transaction order is not created. The order status changes to Refund requested. Notification details are added to the order history. REFUNDED (125) and PARTIALLY REFUNDED (126) The transaction order “Captured” status is created. The transaction order is closed. The order status changes to Processing or Partially refunded. A complete/partial invoice is created. REFUND REFUSED (117) The transaction order is not created. The order status changes to Refund refused. Notification details are added to the order history. OTHER STATUSES CREATED (101) CARD HOLDER ENROLLED (103) CARD HOLDER NOT ENROLLED (104) UNABLE TO AUTHENTICATE (105) CARD HOLDER AUTHENTICATED (106) AUTHENTICATION ATTEMPTED (107) COULD NOT AUTHENTICATE (108) AUTHENTICATION FAILED (109) COLLECTED (120) PARTIALLY COLLECTED (121) SETTLED (122) PARTIALLY SETTLED (123) CHARGED BACK (129) DEBITED (131) PARTIALLY DEBITED (132) AUTHENTICATION REQUESTED (140) AUTHENTICATED (141) ACQUIRER FOUND (150) ACQUIRER NOT FOUND (151) CARD HOLDER ENROLLMENT UNKNOWN (160) RISK ACCEPTED (161) The transaction order is not created. The order status does not change. Notification details are added to the order history Cron configuration Several HiPay Enterprise features require at least one cron job, which schedules activities to occur in the future. A partial list of these activities follows: – clear pending orders, – pay installment for split payments. Therefore, the Magento cron:run command must be added to your crontab. To do so, please refer to the Magento 2 Configuration Guide. Clear pending orders This cron job runs every 15 minutes. If configuration is enabled for any payment method, this cron job cancels all the orders which are paid with HiPay Enterprise and are in Pending status (API mode) or Pending Payment status (HOSTED mode) for more than 30 minutes. Pay installment for split payments This cron job runs once a day. For each split payment in Pending status, this cron job sends an API query to pay each installment. Test suites The HiPay Enterprise module for Magento 2 includes unit and functional test suites. Unit tests Unit tests are located in HiPay\FullserviceMagento\Test\Unit namespace. You can run them with the following command lines.

Up And Running Every industry, and every profession, maintains a kind of ongoing conversation among its members. The topics tend to remain the same but, at any moment, some have moved up to the foreground while others have receded. The foreground is where immediate threats and promises reside. At present, the conversation seems to be centered on management tools, often developed by rethinking an old concept and applying new technology to it, and on health. "Health" has meant everything from safe water to electrical safety; at the moment, it involves nutrition. Whatever the question of the day, there is enough threat and promise in the foreground to keep everyone busy and alert. At the risk of violating the prudent warning about sleeping dogs, we'd like to bring an old topic back to the top of the stack. That topic, broadly, is the effect that the vending machine has on the prospective customer. It provoked a lot of discussion during the full-line vending boom, 40 years ago, and culminated in the approach (and the slogan) "Clean, Filled and Working." Coined by two innovative operators in Indiana, it was picked up by the National Automatic Merchandising Association, and it never has been quite forgotten. Still, many vendors today do not remember the urgency with which industry leaders called on their peers to install coin mechanisms that held the patron's money in escrow until the vend was made; to post a telephone number that a customer could call to report a failure and request a refund; to make sure their drivers were cleaning the machines adequately and replacing burnt-out lamps; and so on and on. Today's equipment is a great deal more reliable and easier to service than the pioneering designs of the 1960s, and it is understandable that operators today expect it to work well enough, nearly all the time, unless it is vandalized. The challenge, though, is to see the vending machine as the customer sees it. While steady progress in coin and bill validation, and the rapid adoption of sense-and-feedback systems to verify that the vend was made, have taken the edge off many of the old complaints about "one-armed bandits," it remains true that anything accessible to large numbers of people and offering openings to the outside world is not always going to work properly. Operators know all the things that can go wrong, and may take quiet satisfaction in preventing most of them from happening. The general public doesn't have this informed view, and just wants the machines to work, every single time. We need to keep in mind that returning the customer's money in case of failure is only half the battle. It's important, but from the purchaser's perspective, it is not enough. If the product was not delivered, the operation was not successful. The vending industry always has known that "downtime can kill you," that an out-of-order machine is not making the sales needed to produce a return on the investment in it. They also know that frequent breakdowns annoy locations, who often cite undependable service as a prime reason for wanting to change operators. But the strategic cost is even steeper. In the past, informal surveys of vending patrons suggested that simple lack of confidence in vending machines was a major reason for not buying things from them. It was argued, eloquently, that a machine on which someone has taped a handwritten "out of order" sign is not only failing to generate any revenue, but also is sending a negative message about the reliability of any nearby vending machines - indeed, about vending machines in general. As vending finds more applications in the retailing mainstream, and so must handle a wide range of merchandise at prices far higher than the old blue-collar-based business could have imagined, confidence in vending machines becomes more and more important. All the old correctives , fast dispatch of well-trained technicians, good records of service calls and their dispositions, effective preventive maintenance programs, selection of machines and components on the basis of reliability and durability , remain important, and new ones (like telemetry) deserve study. Most important, though, is management's ability to communicate its insistence on equipment that works right, all the time. Performance will never be perfect, but perfection has to be the goal.

[Familial infantile myofibromatosis]. Infantile myofibromatosis (IM) is the most common fibrous disorder of infancy and childhood. It is characterized by congenital tumours of the skin, striated muscle, bones and viscera. Most cases are sporadic and few familial cases have been reported. We describe a 5-month-old girl presenting with two congenital nodules. The diagnosis of infantile myofibromatosis was based on clinical and histopathological examination. Surgical excision was performed and there was no relapse at six years. The patient's brother presented multiple nodules and toe necrosis at birth due to infantile myofibromatosis. Two months later, the congenital nodules increased in size and new nodules developed. Surgical excision was performed. At 11 months of age, the boy presented with cranial relapse and bone resorption at P3 of the third right toe. The clinical and radiological investigations were normal. Three clinical forms of IM have been described: solitary cutaneous nodules, multiple cutaneous nodules and generalized MI with visceral involvement. The prognosis is good except in generalized MI. All familial cases of MI may be interpreted as autosomal dominant or alternatively there may be genetic heterogeneity. Strict follow-up is recommended to identify potentially life-threatening complications. Spontaneous regression usually occurs but in some cases the treatment of choice is surgical removal.

Robert of Aumale Robert of Aumale (fl. 1086) (alias d'Amarell, Damarell, etc., Latinised to de Albemarle, de Albamara, etc. ) was one of the Devon Domesday Book tenants-in-chief of King William the Conqueror (1066-1087). His lands, comprising 17 entries in the Domesday Book of 1086, later formed part of the very large Feudal barony of Plympton, whose later barons were the Courtenay family, Earls of Devon. Origins He was lord of Aumale in Normandy, now in the département of Seine-Maritime, France. Descendants Various junior branches of the Damarell family split off to establish separate families, most notably at Milton Damarell; at Damarell in the parish of North Huish; at Woodbury and at Aveton Giffard. Sir William Pole (d.1635) wrote that in his time "Theire is remayning on of this name of meane quality". References Category:Devon Domesday Book tenants-in-chief

The demoltion of a civil war-era log cabin has caused tension among the Detroit Land Bank Authority and local historians and archaeologists. Before the cabin had been razed, it had been discovered by an archaeologist late last year. Located on the 2000 Block of Halleck, it was at one time a part of Hamtramck Township. One wouldn't have noticed the structure however, due to another century-old house being built around the cabin. Upon studying it, history buff Greg Kowalski said moves were in place to relocate the cabin to Hamtramck. "We took every step that was proper because as soon as we saw what was here, we contacted the landbank and asked them to put a hold on the demoltion and we supplied them with information," said the Hamtramck Historical Museum historian. Except, a few days later demo crews came through and knocked it down. Because the house's demolition had been contracted out by the land bank, officials with the authority say there was little they could do without losing money already contracted out. "By the time we found out about it, it was already listed for demo, at that stage an average of about $10,000 in taxpayers money has already been spent on the process and we would have no way to recoup those costs," said Alyssa Strickland, spokewoman for the Detroit Land Bank. Strickland said the authority wouldn't be able to get that money back. However, preservationists say they wish they were given more time. "There was never any mention of a demolition, so had we known that there would’ve been a demolition we could’ve at least gone in there one more time and gotten more information about the property," said Krysta Ryzewski, a Wayne State associate professor of Archaeology. The land bank did however save another cabin similar to the one that had been knocked down. The reason? They say its because they had more time to work with historians. "Unfortunately in this case it wasn’t about not being able to work with them, it was simply too far into the process," Strickland said, "too much taxpayer money had already been spent for us to pull it out of demolition at that time.

This is an archived article and the information in the article may be outdated. Please look at the time stamp on the story to see when it was last updated. DENVER — Murder suspect Robert Feldman officially fired his public defender Monday and rehired private defense attorney David Kaplan. The move was made possible by a Colorado Supreme Court decision in June that says the law firm is an independent third party who was given the funds legally before the Probate Court tried to have them frozen. Feldman, 55, was charged with first-degree murder in 2018, three years after his wife Stacy was found dead in the couple’s shower. Investigators say Feldman staged his wife’s death to look like she slipped and fell. Prosecutors say Stacy was strangled to death hours after she confronted her husband about an extramarital affair. Soon after Feldman was charged, he agreed to pay David Kaplan’s law firm $550,000 to defend him, using funds from Stacy’s $751,000 life insurance policy. Stacy’s family sued in Probate Court, citing Colorado’s slayer statute. The measure is intended to prevent murderers from profiting off their crimes, usually through a movie or book deal. Denver’s Probate Court sided with Stacy’s family and ruled the life insurance funds should not be allowed to benefit Feldman. Soon after, Kaplan withdrew from the case and Feldman was forced to rely on a public defender. However, Feldman appealed to the Colorado Supreme Court, which ruled Stacy’s family acted too late to stop Feldman from using the funds. “The Probate Court, according to the Supreme Court, can’t freeze the money already given to a third party. If Robert Feldman had the money in his account, Probate Court did have jurisdiction to freeze that money but it was already with the law firm,” said criminal defense attorney Dan Recht, who interpreted the ruling for FOX31. Recht said the high court found Kaplan’s law firm acted properly in accepting funds for a legitimate purpose even if it seems unseemly to Stacy’s family. “Let’s say the killer takes the proceeds of an insurance policy and buys a car. [The] car dealership doesn’t know anything is wrong, they haven’t done anything wrong. They just received money and gave somebody a car. Well, should they have to give the money back if he’s (Feldman) found guilty of murder? Arguably not,” Recht said. But Democratic state Rep. Jonathan Singer of Longmont says he finds the practical result of the ruling troubling. “We need to go back to the legislature next year and revisit this and reopen those books and look at the real intent of this (Colorado Slayer Statute), which was to make sure that killers never profit from their victims,” Singer said. Monday morning, Kaplan officially rejoined the case as legal counsel for Feldman. A judge set Feldman’s arraignment for October and set aside two weeks in April 2020 to hold the murder trial.

１週間の価格変動率を予想するオプション市場で、ユーロに対して円の下落を見込む取引が22日、過去最高水準に達した。日本銀行が政策決定会合で一段の緩和策を導入するとの観測が広がっている。市場の持ち高とセンチメントの指標とされるボラティリティ・スキューは急速にスティープ化し、円のプットオプション（売る権利）がコールオプション（買う権利）を0.74ポイント上回って取引されている。これはブルームバーグがデータの集計を開始して以来、投資家心理が円に最も弱気に傾いていることを示す。 原題：Yen Downside Bets Hit Record High as BOJ Seen Easing: Chart （抜粋）

Q: How does Russell's paradox affect Cantor's set theory? I've been studying naive set theory and I have been told that Russell's paradox causes problems in Cantor's set theory when sets get "too big". I don't understand why this causes a problem. I know how the paradox effected Frege's work in terms of logic but not Cantor. Any help will be appreciated, Thanks A: Maybe they meant that due to Russell's paradox there cannot be a 'universal set': a set of 'everything'. Here's why: Assuming there would be a set of everything $U$, then we can consider the set $D$ defined as $\{ x \in U | x \not \in x \}$. We could thus say that $D$ contains all 'normal' sets, where a 'normal' set is a set that does not contain itself as an element. Now, since $U$ is universal, we have $D \in U$. But is $D \in D$? Well, if $D \in D$, then by definition of $D$, we don't put $D$ in $D$, i.e. $D \not \in D$. But if $D \not\in D$, then by definition of $D$ we would put $D$ in $D$, i.e. $D \in D$. Hence, we obtain $D \in D$ if and only if $D \not \in D$, which is a contradiciton. So, using the logic behind Russell's paradox, there cannot be a universal set. ... And yes, that would certainly be a set that can be said to be 'too big'.

Q: How to save the value of textarea to localstorage then display it in the same textarea I'm creating a simple note storing application and would like the values of all text areas to be saved to the local storage when the user hits a save button. When the user returns I would like the textareas to display the saved notes. Below I will add the relevent code. As for now, when I reload the page the textareas aren't filled with the notes and I can't figure out why. JSLint errors: https://gyazo.com/c2271b41e83a7d3f81ee024386832e5b HTML: <div id="container"> <button id="note1btn" data-role="button">Note #1</button> <textarea id="note1input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note2btn" data-role="button">Note #2</button> <textarea id="note2input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note3btn" data-role="button">Note #3</button> <textarea id="note3input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note4btn" data-role="button">Note #4</button> <textarea id="note4input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note5btn" data-role="button">Note #5</button> <textarea id="note5input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note6btn" data-role="button">Note #6</button> <textarea id="note6input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note7btn" data-role="button">Note #7</button> <textarea id="note7input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note8btn" data-role="button">Note #8</button> <textarea id="note8input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note9btn" data-role="button">Note #9</button> <textarea id="note9input" class="textarea hide" rows="10" cols="50"></textarea> <button id="note10btn" data-role="button">Note #10</button> <textarea id="note10input" class="textarea hide" rows="10" cols="50"></textarea> <button id="savenotesbtn" data-role="button">Save</button> </div> JS: $(document).ready(function () { var savesnotesbtn = document.getElementById("savenotesbtn"); //FILL TEXT AREAS WITH NOTES for (var i = 1; i < 11; i++) { $("#note" + i + "input").val(localStorage.getItem("note" + i)); } //SWIPE LEFT $(document).on('swipeleft', '.ui-page', function (event) { if (event.handled !== true) { // This will prevent event triggering more then once var nextpage = $.mobile.activePage.next('[data-role="page"]'); // swipe using id of next page if exists if (nextpage.length > 0) { $.mobile.changePage(nextpage, {transition: "slide", reverse: false}, true, true); } event.handled = true; } return false; }); //SWIFE RIGHT $(document).on('swiperight', '.ui-page', function (event) { if (event.handled !== true) { // This will prevent event triggering more then once var prevpage = $(this).prev('[data-role="page"]'); if (prevpage.length > 0) { $.mobile.changePage(prevpage, {transition: "slide", reverse: true}, true, true); } event.handled = true; } return false; }); //DISPLAY NOTE $("body").on('click', '[id^="note"]', function (e) { $(this).next('textarea').toggleClass("hide"); }); $(".textarea").on('input', function () { $("#savenotesbtn").addClass("notSaved"); }); savesnotesbtn.addEventListener("click", saveNotes); }); //SAVE NOTES function saveNotes() { //Change styles of button $("#savenotesbtn").removeClass("notSaved").addClass("Saved"); //Save notes in local storage for (var i = 1; i < 11; i++) { localStorage.getItem("note" + i, $("#note" + i + "input").val()); } } A: Get values by .val() instead of value (value is property from vanilla javascript, not jQuery): $(document).ready(function () { var savesnotesbtn = document.getElementById("savenotesbtn"); //FILL TEXT AREAS WITH NOTES for (var i = 1; i < 11; i++) { $("#note" + i + "input").val(localStorage.getItem("note" + i)); } function saveNotes() { //Change styles of button $("#savenotesbtn").removeClass("notSaved").addClass("Saved"); // Save data to localstorage for (var i = 1; i < 11; i++) { localStorage.setItem("note" + i, $("#note" + i + "input").val()); } }; savesnotesbtn.addEventListener("click", saveNotes); });

Share this: Description The “Temple of Pallas” is an old illustration by Samuel Prout, taken from a 19th Century book. It has been clarified and darkened to improve the beautiful detail. —Details— Resizable, up to 10” x 13”. Black and white illustration. Instant download. Use as many times as you wish. —Possible Uses— Junk Journals Various other Journals (prayer, gratitude, pregnancy, reflective, or travel). Poetry Book Wall Art Card-making Illustrated Content (article, poetry, short stories). Greeting Cards Certificates or Commemorative Letters Itineraries or Programs and much more! —General License— You agree to the following terms when you purchase and download my files: You can use these images, pages, or wall hangings for any personal project, as many times as you like. You can use these images in physical products you then sell (such as: albums, junk journals, diaries, wall art, scrapbooks, other physical art work) You can resize these images to suit your projects. You agree not to digitally reproduce these images, not to share or sell these images, and not to use them for ulterior commercial purposes. You may not claim this ephemera is your own work, regardless of use. Reviews There are no reviews yet. Only logged in customers who have purchased this product may leave a review.

[Enzyme activity of thiamine pyrophosphate in the rat after oxythiamine administration]. Intraperitoneal injection of hydroxythiamine to rats (1 mmol per kg bw) resulted after 2-4 h in a more than 4-fold decrease in the activity of the oxoglutarate dehydrogenase complex, pyruvate dehydrogenase complex and NADP-dependent isocitrate dehydrogenase in adrenal mitochondria. Inhibition of hyaloplasmic transketolase, 6-phosphogluconate dehydrogenase and NADP-dependent malate dehydrogenase occurred later. Based on the correlation of the time course of enzymatic activity in the adrenals and the decreased concentration of 11-hydroxycorticosteroids in the blood the paramount role in the maintenance of the steroidogenesis among thiamine pyrophosphate-containing enzymes is assigned to the oxoglutarate dehydrogenase and pyruvate dehydrogenase complexes.

Introduction {#s1} ============ Surgical endodontic retreatment is essential in cases of failed endodontic treatment or when conventional endodontic treatment cannot be undertaken. Endodontic surgery entails raising a mucoperiosteal flap and performing osteotomy, followed by root-end resection, root-end preparation, and root-end filling. A root-end filling material is considered effective when it provides a complete apical seal, preventing the passage of microorganisms into the root canal system and leading to the throwing out of microorganisms and their by-products from the root canal system.^[@R01]^ Various materials have been suggested and used for root end filling. They include zinc oxide eugenol cements, glass ionomer cement, super EBA, polyvinyl resins, composite resins, resin-glass ionomer hybrids, and mineral trioxide aggregate (MTA).^[@R02]-[@R06]^ Microleakage studies have confirmed MTA has the best apical sealing ability. However, despite its excellent sealing ability and biocompatibility when compared with other root-end filling materials, MTA is expensive, has delayed setting time, and poor handling properties.^[@R07],[@R08]^ Asgary et al^[@R09]^ have introduced a novel endodontic cement with sealing ability comparable to MTA. This biomaterial was formulated using different calcium compounds such as calcium hydroxide, calcium oxide, calcium phosphate, calcium sulfate, calcium silicate, and calcium carbonate. Studies have demonstrated that the calcium-enriched mixture (CEM) cement comprises water-soluble calcium and phosphate which immediately forms hydroxyapatite during and after setting.^[@R09]^ The composition and surface characteristics as well as the physical and chemical properties of CEM cement have been examined. CEM cement has been shown to have a sealing ability comparable to MTA and superior to IRM.,^[@R06],[@R10]^ The cement exhibits several advantages including high tissue biocompatibility, hard tissue induction, effective sealing ability against the entry of microorganisms, ability to set in an aqueous environment, antibacterial effects, and resistance to washout.^[@R10]-[@R11],[@R13]^ *In-vitro* studies have documented the equivalence of CEM cement and MTA properties.^[@R10],[@R14],[@R15]^ *In-vivo* studies have also produced successful results with CEM cement.^[@R11],[@R12],[@R16]-[@R20]^ In an *in-vitro* study, the influence of the thickness of mineral trioxide aggregate on the sealing ability of root-end fillings was assessed by Valois et al^[@R21]^ The results revealed a thickness of 4 mm as most adequate when using MTA as a root-end filling material.^[@R21]^ In a previous study by Rahimi et al,^[@R22]^ the microleakage with MTA as root-end filling material was not found to be significantly different among various thicknesses. Investigations of the sealing ability of CEM cement through dye penetration have revealed that the sealing properties of this root-end filling material parallel those of commercial types of MTA.^[@R23]^ The aim of this study was to compare the sealing ability associated with three different thicknesses of CEM cement as a root-end filling material in cavities prepared by ultrasonic retro-tips. Materials and Methods {#s2} ===================== Seventy single-rooted human premolar teeth extracted for periodontal or orthodontic purposes were selected for this study. The teeth were evaluated under stereomicroscope and radiography. Any teeth with caries, cracks, resorption, fractures, morphologic anomalies, and open apices were excluded from the study. The selected teeth were decoronated at cemento-enamel junction (CEJ) level with a diamond disk (D&Z, Darmstadt, Germany) under running water and air spray. Working length was determined with a \#15 K-type file (Mani, Utsunomiya, Japan) 1 mm short of the apical foramen. The canals were prepared up to size \#40 using the step-back technique and the shaping of the middle and coronal thirds was carried out by Gates Glidden burs 1, 2, and 3. During instrumentation procedures, root canals were irrigated with 10 ml of saline solution. All canals were obturated using gutta percha (Diadent, Korea) and AH-26 sealer (Dentsply, Konstanz, Germany) with the lateral compaction technique. The teeth were stored at 37°C and 100% humidity for 48 hours (Heratherm, Thermo Inc., Switzerland). The apical 3 mm of each tooth was resected perpendicular to the long axis of the tooth with a diamond bur under continuous water and air spray. Teeth were randomly divided into three experimental groups each containing 20 samples, and 5 positive and 5 negative controls. In group 1, root-end cavities were prepared to a depth of 1mm perpendicular to the long axis using ultrasonic retrotips Kis-3D (Spartan, Missouri, USA). In samples of groups 2 and 3, the same procedure was done to depths of 2 mm and 3 mm, respectively. In positive controls, the cavities were prepared to a depth of 3 mm. The cavities were then irrigated and dried by paper cones. The CEM cement was mixed according to the manufacturer's instructions on a sterile glass slab and filled into the cavities with the aid of a small condenser (Kerr Hawe, Orange, CA, USA). Any excess material was removed with a sterile cotton swab. The quality of the root-end fillings was confirmed by radiographs in two directions (mesiodistal and buccolingual), while the root-end cavities of controlled groups remained empty. In all experimental and positive control groups, two layers of nail varnish were applied to the surface of the teeth up to the level of the resected root-end. In negative controls, the entire surface of the teeth was covered with two layers of nail varnish. All teeth were kept at 37°C and 100% humidity for 48 hours, and then immersed into synthetic tissue fluid (STF) with pH=7 for 48 hours. The specimens were placed horizontally in 2% Rhodamine B (Merk, Darmstadt, Germany) for 48 hours. Then the samples were rinsed for 10 min under running water. After that, two facial and lingual fissures were created along the long axis of the roots using a diamond disc and the roots were longitudinally resected into two mesial and distal halves. The maximum amount of linear dye penetration was measured under a stereomicroscope (Zeiss, Munich, Germany) at ×16 magnification with 0.1 mm accuracy and using Image J software (35d; National Institutes of Health, USA). The data were analyzed with one-way ANOVA analysis and the Bonferroni post-hoc test was utilized to reveal specific group differences. The level of significance was set at P \< 0.05. Results {#s3} ======= No dye microleakage was noted in the negative control samples. The mean ± standard deviation of dye penetration in the 1, 2, and 3 mm groups were 3395.58 ± 1893.44, 3410.47 ± 1440.58, and 2581.65 ± 1852.90 micrometers, respectively ([Figure 1](#F01){ref-type="fig"}). {#F01} Significant 'Skewness' and 'Kurtosis' tests confirmed non-normal data distribution. Natural logarithmic transformation provided normal distribution of the data. Analysis of variance indicated significant differences among the tested groups (P = 0.000). However, Bonferroni post-hoc test revealed that only the positive control group differed from the experimental groups (P = 0.000; [Table 1](#T1){ref-type="table"}). Consequently, there was no significant difference among sealing ability of 1, 2 and 3 mm CEM cement as a retrofilling material. ###### Mean dye leakage (upper and lower 95% confidence interval) of experimental groups (micrometer) ---------- ------------------- ------------------- ------------------- Groups Variable 1 mm 2 mm 3 mm Leakage 3395.58\ 3410.47\ 2581.65\ (4281.74-2509.42) (4084.68-2736.25) (3448.84-1714.47) ---------- ------------------- ------------------- ------------------- Discussion {#s4} ========== The success of periradicular surgery directly depends on the achievement of a good apical seal, utilizing a well-adapted root-end filling material that prevents the leakage of irritants from the root canal system into the periradicular region.^[@R24]^ In this study, the microleakage of three different thicknesses of CEM cement as a root-end filling material was evaluated by the dye penetration method. Findings indicated no significant differences among 1, 2, and 3 mm of CEM cement as a root end filling material. But in 1-mm and 2-mm depths, the leakage was more than the root-end filling material's depth; in other words, only 3-mm depth was capable of providing adequate seal. Apical microleakage has been assessed using various methods including dye/ink, bacterial/endotoxin leakage, radioisotope tracing, and fluid filtration technique.^[@R25]-[@R31]^ There is no evidence to favor the superiority of any particular method. However, the dye penetration technique is widely used for microleakage studies because dyes are cheap, safe, easily available, and also relatively easy to be stored, used and to have their penetration assessed quantitatively.^[@R32],[@R33]^ Different dyes have been employed for dye penetration test as India ink and methylene blue. In this study, the extension of dye (2% Rhodamine B) penetration was used as the criteria for evaluation. The use of methylene blue in marginal sealing studies has been debated, due to its incompatibility with alkaline substances, which may induce discoloration of the dye.^[@R34]^ It is known that methylene blue dye presents an acid character and Rhodamine B, a basic one. Rhodamine B is a basic intense organic dye, soluble in water at room temperature, also solvent in alcohols and common organic solvents, in addition to being highly stable.^[@R35]^ Since color stability of organic dyes is an important factor that must be observed in microleakage studies, and because of alkali conditions around CEM cement, in this study Rhodamine B dye was used for leakage assessment. An ideal root-end cavity preparation is a class I cavity at least 3 mm deep with parallel walls.^[@R36]^ Achieving this with the classical method in surgical endodontics is held back by several difficulties such as limited access, root anatomy, and tooth angulation. To avoid these problems, Piezoelectric ultrasonic devices for root-end preparation have been developed and are nowadays used as standard tools for retrograde cavity preparation.^[@R37]-[@R39]^ In another *in-vitro* study, the influence of the thickness of mineral trioxide aggregate on the sealing ability of root-end fillings was assessed by Valois et al.^[@R21]^ The 1-mm-thick MTA was the least effective in preventing apical leakage. No significant difference was found between 2- and 3-mm-thick MTA. Four-millimeter-thick MTA was found to be significantly more effective than the other thicknesses tested. These researchers suggested a thickness of 4 mm as most adequate when MTA is used as a root-end filling material.^[@R21]^ Similar findings were obtained in our study and CEM cement in 3-mm thickness present the most effective sealing ability. The apical sealing ability of CEM cement has been reported to be similar to different commercial types of MTA.^[@R23]^ In a previous study, microleakage in the 3-mm and 2-mm root-end cavities was less than that in 1 mm depth cavities, but analysis of variance revealed no significant differences across the three different thicknesses.^[@R22]^ The current study led to similar results but with CEM cement used as root-end filling material. Conclusion {#s5} ========== Based on the findings of this in vitro study, the CEM cement demonstrated adequate root-end sealing ability in 3-mm thickness. Acknowledgement {#s6} =============== The authors would like to extend their appreciation to the Office of the Vice Chancellor for Research, Tabriz University of Medical Sciences, for the financial support of this study.

Always Be with You (film) Always Be With You is a 2017 Hong Kong horror film written and directed by Herman Yau. It is the 20th instalment in the Troublesome Night film series and was produced specially to mark the 20th anniversary of the first movie. The film stars Louis Koo, Julian Cheung, Gordon Lam, Charlene Choi and Charmaine Sheh. Plot David, a taxi driver with lung cancer, kills vacation property owner Patrick in a freak car accident. Off-duty police officer Sam, his wife Si and Si's aunt seemingly were able to avoid the collision after Si's aunt warned him to drive away from the road they were on. At the same time, Siu-hung, who broke up with her fiancé, committed suicide by jumping off a building, landing right on top of Patrick's car. Chi-keung is a crematorium worker who is saddled with huge gambling debts. He steals a pair of pricey gold bracelets, the funerary objects of Siu-hung, to pay off his debts. Chi-keung fails to sell off the gold bracelets as the buyer was crushed by a concrete block while on his way to meet Chi-keung. Later, while crossing a street, a lorry loses control and veers into him and a couple who he recognises as Siu-hung's younger sister and brother in law. Chi-keung and Siu-hung's younger sister survives the accident. The bracelets which fell out while he was unconscious, were retrieved by the police as evidence. Meanwhile, Patrick's fiancée, Yu Xin, after recovering from the tragedy, hopes to fulfil Patrick's last wish in running a suburban vacation house. However, a series of strange happenings keeps on occurring in the vacation house. Her first tenants, two lovers, commits suicide during their stay. Sam, accompanying Si, to investigate the scene, realises the presence of a disfigured female spirit. Later, David appears at the vacation home, offering to help Yu Xin. She at first declines but later, accepts him as a long term tenant. Back home, Chi-keung is haunted by Siu-hung's ghost and at the same time, was visited by the loansharks whom he owes money. Chi-keung escapes through the window and ends up at Yu Xin's vacation home. He proceeds to commit suicide by gassing and suffocating himself, and is later discovered by David. The next morning, Yu Xin feels anxious as she has not seen her tenant, Chi-keung since the previous day. She decides to go to his room, worried that there may be another suicide. Accompanied by David, they both enter Chi-keung's rented room but discovered no one and Chi-keung's belongings gone. David tries to comfort Yu Xin and tells her he may have just ran off, not wanting to pay the rent. Much later, a part of Chi-keung's dismembered body was discovered and Sam and Si once again makes a visit to Yu Xin's vacation home. They questioned David and Yu Xin about Chi-keung but both denied meeting him. Later that night, Sam spots Chi-keung's ghost and it is revealed that David got rid of Chi-keung's body but did not burn it according to Chi-keung's wishes left in a note. That same night, David gave himself up at a police station and commits suicide in his cell, leaving a note to Yu Xin explaining his terminal illness. After that, Sam discovers singer Jamie's vinyl, which Si got from a second hand shop, was haunted by her ghost. They decide to dispose it but it keeps appearing at Sam and Si's apartment after a few times. They eventually return it to the shop owner, who was Jamie's uncle and the vinyl, a personal gift from Jamie for him. The next evening, Sam rhetorically asks Si what she'd do if he were to leave her. The question surprises and frightens Si as she had found his behaviour changed ever since the freak car accident as Sam was being especially sweet to her. She embraces him tightly and urges him to tell her what was happening. Sam notices two men approaching them, breaks from her embrace and runs off down the street. Si gives chase and points her gun to the two men dragging Sam away by his arms. Sam then tells her that the two men are from the otherworld and he has been dead the three weeks since the night of the accident. That night, after avoiding the collision, Sam had gotten down from the car to report the crash. A passing car with the second hand shop owner and his wife in front and singer Jamie at the back spots the crash. Jamie, leaning out to capture the crash was hit by a lorry from the opposite direction. Her torso flies off from the impact, hitting Sam who falls and his skull pierced by a long, upright nail and dies on the spot. Cast Starring Louis Koo as Sam Julian Cheung as David Gordon Lam as Chi-keung Charlene Choi as Yu-xin Charmaine Sheh as Si Others Ava Yu as Siu-hung Bonnie Wong as Siu-hung's mother Wiyona Yeung as Siu-man Ben Yeung as Lam Pui Tony Ho as Agent Chiu Jamie Lee as Nancy Aaron Chow as Peter Pancy Chan as Miss Chan Brian Lee as Mysterious man Renci Yeung as Student Special appearance Alex Lam as Patrick Heidi Lee as Jamie Lam Suet as Record owner Law Lan as Sam's aunt Kingdom Yuen as Record owner's wife Guest appearance Ken Lo as Fung Elena Kong as Doctor Kong Cheung Tat-ming as Residential Guard Emily Kwan as Plastic surgeon Fire Lee as Man seeking haunted vacation mansion Terence Siufay as Man seeking haunted vacation mansion References External links Category:2017 films Category:Cantonese-language films Category:2017 horror films Category:Hong Kong horror films Category:Hong Kong films Category:Films directed by Herman Yau Category:Troublesome Night Category:Hong Kong ghost films

The invention relates to a packaging box obtained through a related method and to the blank for obtaining this box.

Q: How to find the used characters in a subsetted font? I have PDF files which are dynamically generated, with text, vectors, and subsetted fonts. I can see which fonts are used in various viewers - is there a way of displaying the actual subsetted characters of those fonts? For example, I see the document contains the subsetted subsetted fonts "AAAAAC+FreeMono" and "AAAAAD+DejaVuSans". How do I find how many characters were subsetted from these fonts, and what characters they were? (I tried loading the fonts in FontForge, but it just crashes while opening the file) A: The solution is to save the font data to a file and load it into a font editor. A subset font file is still a valid font file but it is possible that FontForge expects some data in the font that is not there. I have seen also many fonts that are not properly subset and this could also cause loading problems in a font editor.

Estamel's Modified Torpedo Launcher Locations A massive launcher designed for extended bombardments of hard targets like battleships and stations. Contains a huge missile capacity, but has a slow firing rate and trouble targeting small, fast ships.

Q: How to create a new instance from a class object in Python I need to dynamically create an instance of a class in Python. Basically I am using the load_module and inspect module to import and load the class into a class object, but I can't figure out how to create an instance of this class object. Please help! A: I figured out the answer to the question I had that brought me to this page. Since no one has actually suggested the answer to my question, I thought I'd post it. class k: pass a = k() k2 = a.__class__ a2 = k2() At this point, a and a2 are both instances of the same class (class k). A: Just call the "type" built in using three parameters, like this: ClassName = type("ClassName", (Base1, Base2,...), classdictionary) update as stated in the comment bellow this is not the answer to this question at all. I will keep it undeleted, since there are hints some people get here trying to dynamically create classes - which is what the line above does. To create an object of a class one has a reference too, as put in the accepted answer, one just have to call the class: instance = ClassObject() The mechanism for instantiation is thus: Python does not use the new keyword some languages use - instead it's data model explains the mechanism used to create an instantance of a class when it is called with the same syntax as any other callable: Its class' __call__ method is invoked (in the case of a class, its class is the "metaclass" - which is usually the built-in type). The normal behavior of this call is to invoke the (pseudo) static __new__ method on the class being instantiated, followed by its __init__. The __new__ method is responsible for allocating memory and such, and normally is done by the __new__ of object which is the class hierarchy root. So calling ClassObject() invokes ClassObject.__class__.call() (which normally will be type.__call__) this __call__ method will receive ClassObject itself as the first parameter - a Pure Python implementation would be like this: (the cPython version is of course, done in C, and with lots of extra code for cornercases and optimizations) class type: ... def __call__(cls, *args, **kw): constructor = getattr(cls, "__new__") instance = constructor(cls) if constructor is object.__new__ else constructor(cls, *args, **kw) instance.__init__(cls, *args, **kw) return instance (I don't recall seeing on the docs the exact justification (or mechanism) for suppressing extra parameters to the root __new__ and passing it to other classes - but it is what happen "in real life" - if object.__new__ is called with any extra parameters it raises a type error - however, any custom implementation of a __new__ will get the extra parameters normally) A: This is how you can dynamically create a class named Child in your code, assuming Parent already exists... even if you don't have an explicit Parent class, you could use object... The code below defines __init__() and then associates it with the class. >>> child_name = "Child" >>> child_parents = (Parent,) >>> child body = """ def __init__(self, arg1): # Initialization for the Child class self.foo = do_something(arg1) """ >>> child_dict = {} >>> exec(child_body, globals(), child_dict) >>> childobj = type(child_name, child_parents, child_dict) >>> childobj.__name__ 'Child' >>> childobj.__bases__ (<type 'object'>,) >>> # Instantiating the new Child object... >>> childinst = childobj() >>> childinst <__main__.Child object at 0x1c91710> >>>

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190 Mich. App. 686 (1991) 476 N.W.2d 487 BLOEMSMA v. AUTO CLUB INSURANCE ASSOCIATION Docket Nos. 121616, 123235. Michigan Court of Appeals. Decided August 19, 1991, at 9:35 A.M. Giddy & Associates (by Ronald J. Giddy), for the plaintiff. Cunningham, Mulder & Breese, P.C. (by Kenneth B. Breese), for the defendant. Before: DOCTOROFF, P.J., and MAHER and CAVANAGH, JJ. *688 AFTER REMAND DOCTOROFF, P.J. Plaintiff appeals as of right from orders of the circuit court awarding attorney fees and costs to plaintiff. Plaintiff argues that the trial court erred in not awarding attorney fees for services provided during trial, after trial, and on appeal and in not awarding actual costs. Defendant cross appeals, asserting that plaintiff's claim for appellate attorney fees and costs is vexatious and frivolous and, therefore, it is entitled to reasonable attorney fees. The appeals were consolidated by the Court of Appeals. We reverse and remand. This case is before us for the second time. In its first opinion, this Court held that the trial court erred in finding that defendant's delay in making personal injury protection benefit payments to plaintiff was reasonable and remanded for recalculation of penalty interest and judgment interest. Bloemsma v Auto Club Ins Co, 174 Mich App 692; 436 NW2d 442 (1989). This Court also ordered the trial court to award reasonable attorney fees to plaintiff. Id., p 698. On remand, the trial court issued an opinion dated Friday, June 2, 1989, and filed Monday, June 5, 1989, awarding plaintiff attorney fees in the amount of $4,269. This award was based on a statement submitted by plaintiff's attorney during trial on December 5, 1986, which itemized services provided through December 4, 1986. The court determined that $75 an hour was a reasonable fee for the 56.92 hours expended. On June 5, 1989, plaintiff, before receiving notice of the trial court's order, filed a motion for attorney fees and costs, claiming attorney fees for the December 5, 1986, trial and for hours expended after the December 5, 1986, trial. At a hearing on June 12, 1989, the trial court denied *689 plaintiff's request for additional attorney fees, but granted plaintiff's request for costs, including those incurred on appeal. An order in accordance with the trial court's ruling was entered on September 21, 1989. A third order was entered on November 2, 1989, setting forth the costs allowed. Plaintiff argues that the trial court erred in not awarding attorney fees for services provided during trial and on appeal. Plaintiff contends that he is entitled to an award of those fees because the time spent during trial and on the two appeals was expended in an effort to collect the benefits claimed. In this case, attorney fees were granted pursuant to MCL 500.3148(1); MSA 24.13148(1), which states: An attorney is entitled to a reasonable fee for advising and representing a claimant in an action for personal or property protection insurance benefits which are overdue. The attorney's fee shall be a charge against the insurer in addition to the benefits recovered, if the court finds that the insurer unreasonably refused to pay the claim or unreasonably delayed in making proper payment. In determining the reasonableness of an attorney's fee, the trial court should consider (1) the professional standing and experience of the attorney, (2) the skill, time, and labor involved, (3) the amount in question and results achieved, (4) the difficulty of the case, (5) the expenses incurred, and (6) the nature and length of the professional relationship between the attorney and client. Wood v DAIIE, 413 Mich 573, 588; 321 NW2d 653 (1982). However, the trial court is not limited to these factors and need not detail its findings with regard to each specific factor. Id. An award of attorney fees will be upheld on appeal unless the *690 trial court's determination regarding the "reasonableness" issue was an abuse of discretion. Id.; Smolen v Dahlmann Apartments, Ltd, 186 Mich App 292, 296; 463 NW2d 261 (1990). The trial court's denial of plaintiff's request for fees other than those itemized in the statement submitted on the day of trial was based on its conclusion that the case had been remanded for the recalculation of attorney fees and not to allow the presentation of additional evidence. We agree with plaintiff that the trial court erred. This matter was remanded to the trial court with instructions that it award reasonable attorney fees to plaintiff. The determination of reasonable attorney fees requires that the trial court take into account the totality of the circumstances of the case. Id., p 297. We are unable to find any authority for the trial court's conclusion that plaintiff's attorney was prohibited on remand from presenting evidence related to the time, labor, and expenses involved in advising and representing plaintiff during trial and thereafter. Clearly, plaintiff was entitled to a reasonable attorney fee for the services rendered on this matter up to and including trial. Plaintiff also argues that the trial court erred in not awarding attorney fees for the services rendered on appeal. We agree. This Court has held that a statutory provision for attorney fees applies to appellate proceedings when the statute does not place any restrictions on the recovery of attorney fees and does not limit attorney fees to services rendered at the trial court level. Smolen, supra (provision for attorney fees under the Michigan Consumer Protection Act, MCL 445.901 et seq.; MSA 19.418(1) et seq., applies to appellate proceedings). Although the provision for attorney fees at issue here, MCL 500.3148(1); *691 MSA 24.13148(1), restricts an award of attorney fees to cases in which the court finds that the insurer unreasonably refused to pay the claim or unreasonably delayed in making proper payment, no other restrictions are imposed, and the award of attorney fees is not limited to services rendered at the trial court level. We conclude that attorney fees for services on appeal can be awarded under MCL 500.3148(1); MSA 24.13148(1). Thus, on remand, the trial court is to consider services rendered on appeal. Plaintiff also argues that the trial court abused its discretion in determining that $75 an hour was reasonable and that it failed to consider the contingency fee arrangement. In its opinion, the trial court stated that it considered the factors listed in Wood in determining a reasonable fee, but did not indicate its findings on any of the factors. We are not convinced and will not assume that the trial court abused its discretion in determining that $75 an hour was reasonable. We also decline to address plaintiff's assertion that the trial court failed to consider the contingency fee arrangement. The record provided to this Court indicates that plaintiff sought attorney fees based upon the time and labor expended by counsel, and not based upon a contingency fee arrangement. Error requiring reversal must be that of the trial court, and not error to which the appellant contributed by plan or negligence. Smith v Musgrove, 372 Mich 329, 337; 125 NW2d 869 (1964); Harrigan v Ford Motor Co, 159 Mich App 776, 786; 406 NW2d 917 (1987), app dis 431 Mich 905 (1988). Plaintiff next claims that the trial court erred in not awarding actual costs. In its December 1986 opinion, January 1987 order, and June 1989 opinion, the trial court awarded plaintiff statutory costs. Attached to plaintiff's motion for attorney *692 fees and costs was an itemized statement listing actual costs apparently incurred both in presenting the original action to the trial court and to this Court on appeal. At the June 12, 1989, hearing and in its September 21, 1989, order, the trial court awarded plaintiff taxable costs incurred on appeal. Plaintiff claims that the trial court erred in allowing only taxable costs, arguing that, by providing for an award of a reasonable attorney fee, MCL 500.3148(1); MSA 24.13148(1) authorizes an award of actual costs. Plaintiff's argument is without merit. The power to tax costs is wholly statutory. Herrera v Levine, 176 Mich App 350, 357; 439 NW2d 378 (1989); Brown v Dep't of State Hwys, 126 Mich App 392, 396; 337 NW2d 76 (1983). Costs are not recoverable where there is no statutory authority for awarding them. Id. Where the language of a statute is clear and unambiguous, judicial interpretation is precluded, and this Court should not look beyond the ordinary meaning of the unambiguous language in giving effect to the statute. Wills v Iron Co Bd of Canvassers, 183 Mich App 797, 801; 455 NW2d 405 (1990). MCL 500.3148(1); MSA 24.13148(1) clearly provides for only an award of attorney fees. There is no express authorization for an award of actual costs. We also reject as untimely plaintiff's argument that the trial court should have awarded actual costs pursuant to MCL 600.2591; MSA 27A.2591. Issues and arguments raised for the first time on appeal are not subject to review. Petrus v Dickinson Co Bd of Comm'rs, 184 Mich App 282, 288; 457 NW2d 359 (1990). We must, however, reverse the trial court's award of taxable costs incurred on appeal. The *693 trial court was without jurisdiction to tax costs incurred on appeal. Lopez-Flores v Hamburg Twp, 185 Mich App 49, 53; 460 NW2d 268 (1990); Oscoda Chapter of PBB Action Committee, Inc v Dep't of Natural Resources, 115 Mich App 356, 365; 320 NW2d 376 (1982). Furthermore, by failing to file a bill of costs with this Court as required by MCR 7.219, plaintiff waived his right to costs incurred on the first appeal. Defendant's claim on cross appeal that plaintiff's claims on appeal are frivolous and vexatious is without merit. Reversed and remanded for proceedings consistent with this opinion. We do not retain jurisdiction.

Q: Mathematica not evaluating q derivative of Jacobi theta function Jacobi theta functions, $\theta_a(u,q)$ for $a=1,2,3,4$ are defined in the unit disk $|q|<1$. For some reason that I would like to understand, Mathematica does not evaluate numerically the $q$ derivatives of these functions, regardless the value of $u$ (at least for the dozen of values that I tried). Plotting their imaginary and real parts shows that all of them undergo the same problem. Plot[{Re[(EllipticTheta^(0,0,1))[1,-.5,q]],Im[(EllipticTheta^(0,0,1))[1,-.5,q]]},{q,0,1}] Plot[{Re[(EllipticTheta^(0,0,1))[2,-.5,q]],Im[(EllipticTheta^(0,0,1))[2,-.5,q]]},{q,0,1}] Plot[{Re[(EllipticTheta^(0,0,1))[3,-.5,q]],Im[(EllipticTheta^(0,0,1))[3-.5,q]]},{q,0,1}] Plot[{Re[(EllipticTheta^(0,0,1))[4,-.5,q]],Im[(EllipticTheta^(0,0,1))[4,-.5,q]]},{q,0,1}] Heuristically, the limit point is 0.52830188679244577999999999999999...999... D[EllipticTheta[1,-0.28I,q],q]/.q->0.52830188679244577999999999 0. +0.909738 I Evaluation above it returns no result; D[EllipticTheta[1,-0.28I,q],q]/.q->0.52830188679244578 (EllipticTheta^(0,0,1))[1,0. -0.28 I,0.528302] A: As it turns out, one can use the PDE satisfied by the Jacobi theta functions to compute the required values: With[{z = -7 I/25, q = 0.52830188679244577999999999}, {Derivative[0, 0, 1][EllipticTheta][1, z, q], -Derivative[0, 2, 0][EllipticTheta][1, z, q]/(4 q)}] {0.9097375919067572916312 I, 0.*10^-23 + 0.90973758336986133322032 I} (Note that there is a discrepancy between the two evaluations, but I am more inclined to trust the second result instead of the first, since computing the $z$-derivatives for theta functions is much more numerically well-behaved.) Now, for the case in the OP that could not be numerically evaluated: With[{z = -7 I/25, q = 0.52830188679244578}, -Derivative[0, 2, 0][EllipticTheta][1, z, q]/(4 q)] 9.99066*10^-16 + 0.909738 I

// Sexy LED animation. #include "quantum.h" #define LED_INTERVAL 160 #define LED_RADIUS 6 void dmc12_start(uint32_t color, bool reset); void dmc12_process(void);

Movie News After Dark: Avengers Brings Out the Worst in Fans, Fringe Presses On, Chuck Norris, Texting in Theaters and How to Build a Web-Shooter What is Movie News After Dark? It’s a nightly column that assembles the heroes of movie and entertainment news every night. Marvel has only assembled its team once. Take that, Marvel. We begin tonight with several items on The Avengers. First — embargo be damned — it’s so much fun. There is also a new image of the team completely assembled amidst the rubble of the film’s massive third act war scene. And then there’s the disappointing news of the day. Matt Singer reports on CriticWire about angry nerds attacking a female critic over a negative review of The Avengers. Not only did the lash out at the otherwise lovely Amy Nicholson of Boxoffice Magazine, they did so in a terrible, misogynistic way. If this was you, be very ashamed of yourself. Every critic gets their say, and just because she didn’t like the movie, that doesn’t mean you get to be a shit about it. It’s truly sad. Please grow up. The folks at JoBlo have a new (to me) column on their site called Ink & Pixel, which explores the world of animated film — a world that is a constant source of joy for film fans the world over. This week, author Steve Seigh takes an in-depth look at Pixar’s Finding Nemo, a film that I was sadly reminded is yet to be released on Blu-ray. Come on, Disney. Lets get on that. Remember the Steve Jobs movie that will star Ashton Kutcher as the visionary entrepreneur and mock turtle neck enthusiast who founded Apple? That’s still very much happening. And now like the real life Jobs, Ashton may have his Woz. Book of Mormon star Josh Gad is in talks to play Steve Wozniak in Jobs. The real Woz could not be reached for comment, as he’s currently waiting outside the Valley Fair Apple Store for the next iPhone’s indefinite launch. (Haha… nerd inside joke.) Now that the 23rd James Bond film is almost wrapped up and ready for theaters, MGM and Sony are looking to minimize the gap between this one and the next. Assuming MGM doesn’t go belly-up again, Bond 24 will hit theaters in 2014. As I’ve always said, the more Bond we get, the safer I feel. One of the hot topics of debate this week amongst movie people came of Theater Owners Considering Letting People Text During Movies. This, in my opinion, is only one step below the berating of a female critic because she didn’t like a movie based on your favorite comic heroes. As it turns out, theater owners are bigger morons than some of the people who comment on Rotten Tomatoes. I’m spoiled living near an Alamo Drafthouse, where this sort of thing is punishable by death. That said, we all know that it’s wrong to be holding a shiny, backlight anything in a dark room where people are trying to enjoy a performance, right?… Right?… And now for some things that you can hang on your wall. Or think about hanging on your wall, if you don’t have a large printer. First is one of twelve Expendables 2 character posters. This one’s got a little Chuck Norris in it. Because Chuck Norris allows it: The folks at Movielicious have a list of 10 Faux Posters for 10 Non-Existent Movies, including this one for a movie called Dad of the Dead starring Robert Englund as George A. Romero. Why that hasn’t been made yet is beyond me… Don’t Forget… You can now follow Movie News After Dark on Pinterest, a place where our FSR scavengers will pin awesome movie-related things to a board in the cloud. It’s very New Age, we assure you. Just click the button below. More from Around the Web: Reject Nation 2 Comments Leave a comment Comment Policy: No hate speech allowed. If you must argue, please debate intelligently. Comments containing selected keywords or outbound links will be put into moderation to help prevent spam. Film School Rejects reserves the right to delete comments and ban anyone who doesn't follow the rules. We also reserve the right to modify any curse words in your comments and make you look like an idiot. Thank You!

package images // import "github.com/docker/docker/daemon/images" import ( "github.com/docker/docker/builder" "github.com/docker/docker/image/cache" "github.com/sirupsen/logrus" ) // MakeImageCache creates a stateful image cache. func (i *ImageService) MakeImageCache(sourceRefs []string) builder.ImageCache { if len(sourceRefs) == 0 { return cache.NewLocal(i.imageStore) } cache := cache.New(i.imageStore) for _, ref := range sourceRefs { img, err := i.GetImage(ref) if err != nil { logrus.Warnf("Could not look up %s for cache resolution, skipping: %+v", ref, err) continue } cache.Populate(img) } return cache }

Fellow offensive linemen Ryan McFarland, left, and Jameel Griffin, have been teammates since their freshman year. They are the only two seniors on the roster who have played all four years for the Largo High School Packers. Both agree it has been hard work but they’ve enjoyed it. Ryan McFarland remembers his first day of football practice. He was nervous. He was excited. • A freshman at the time, his parents never allowed him to play Little League football, only basketball. McFarland would attend his older brother's Largo High practices and games and long for the day when he too could step foot on the gridiron. • Jameel Griffin also remembers that day. He too was a freshman and ready for high school football. Griffin remembers all the other rising ninth- and 10th-graders there on the first day. But then on the second day, the numbers got smaller. The third, the numbers were even smaller. • "A couple of my friends had to quit," Griffin, 17, said. "They had to get jobs to help their families." • McFarland and Griffin are oddities on the 2008 Largo High School football team. • Of the 13 seniors listed on this year's roster, they are the only two to have played Packer football all four years. Related News/Archive "It's hard," offensive lineman McFarland, 17, said. "It's a commitment you have to make. It's like getting a job." "It feels good," said Griffin, a lineman. "I made it through all four years of playing. It was hard but I stuck to it." Friday night football brings the body-painted students to the stands. There's the band and doting mothers, fathers, uncles and cousins, cheering in support. There's the gathering at the concession stand to gossip. There's the final score. But the work put in before the lights are lit is often forgotten. There are the daily summer workouts in the weight room and the running of suicide sprints. There's standing outside a local Publix to raise money for practice shorts and T-shirts. "There's a lot that we do that people have no idea about," said McFarland. "They just know we play football." The padded and helmeted students bring in the most money to athletic programs, with $433,057 made in the Pinellas school system last season. Football brings most of the exposure, the most scholarships. Pinellas athletic director Nick Grasso said the money football generates supports many of the other athletic programs. But he said it's the lessons the students take away from the game that makes it great. "It's about goal setting and the sacrifices it takes to meet the goal," Grasso said. "You have a collective blend of our society from all different backgrounds that kids bring with them, from race to financial backgrounds. You reduce the amount of barriers for tolerance for one another when you work together for a common goal. You're a team." And at Largo, the goals and expectations are high. The Packers had their first undefeated regular season since 1977 last year, with a final record of 13-1 after losing in the state semifinal. They've won three consecutive district championships and have lost just three games in the last three seasons. Winning is expected. Griffin and McFarland know the pressure is on and they are ready for it. But they say they are dealing with other pressures as well. "People see us and they just think we are all about football," said McFarland, who also works as a server on the weekends at a retirement home. "But it's my senior year and I'm thinking about college. I'm taking the SAT in September. I want to be a police officer." Griffin, who also is preparing for the SAT and looking at colleges, agreed. "In order to play football, you have to keep your grades up," he said. "You have to know how to act and behave in school. Anything you do off the field can stop you from playing on Friday nights." That's the lesson Largo coach Rick Rodriguez wants the players to take with them. He said he wants them to understand commitment and that in life, you don't quit and that hard work is rewarded, whether it's on or off field. The two seniors who stuck to the game on the field and made sure they did the right things off the field take those lessons with them into their senior year. "It's been hard work but it's taught me that you never quit," Griffin said. "Whether you are on the field or off the field, you don't quit." Demorris A. Lee can be reached at 445-4174 or [email protected] About this series Every week during the regular season, Beyond the Gridiron: Largo will take a different approach to the Packer football program. Fast facts Packer football District 10, Class 5A Head Coach: Rick Rodriguez 2007 record: 13-1, lost in state semifinal to Fort Lauderdale St. Thomas Aquinas There is a reason why the air in Tampa Bay is filled with playoff talk. If Thursday night's 12-8 Bucs preseason win over the Jaguars is any indication, it's also going to be filled with footballs thrown by quarterback Jameis Winston. TORONTO — Two pitches RHP Chris Archer didn't execute are the ones that stood out Thursday as Josh Donaldson hit them out of the park. But the two solo home runs aside, Archer turned in a sterling outing that went atop the pile of good pitching the Rays keep wasting. CLEARWATER — Tracey Fritzinger has seen Tim Tebow play baseball a few times this year. The 40-year-old St. Petersburg resident went to two of his games against the Tampa Yankees, along with Joy, her little sister from Big Brothers Big Sisters of America.

//===- BugDriver.cpp - Top-Level BugPoint class implementation ------------===// // // The LLVM Compiler Infrastructure // // This file is distributed under the University of Illinois Open Source // License. See LICENSE.TXT for details. // //===----------------------------------------------------------------------===// // // This class contains all of the shared state and information that is used by // the BugPoint tool to track down errors in optimizations. This class is the // main driver class that invokes all sub-functionality. // //===----------------------------------------------------------------------===// #include "BugDriver.h" #include "ToolRunner.h" #include "llvm/IR/Module.h" #include "llvm/IR/Verifier.h" #include "llvm/IRReader/IRReader.h" #include "llvm/Linker/Linker.h" #include "llvm/Pass.h" #include "llvm/Support/CommandLine.h" #include "llvm/Support/FileUtilities.h" #include "llvm/Support/Host.h" #include "llvm/Support/SourceMgr.h" #include "llvm/Support/raw_ostream.h" #include <memory> using namespace llvm; namespace llvm { Triple TargetTriple; } // Anonymous namespace to define command line options for debugging. // namespace { // Output - The user can specify a file containing the expected output of the // program. If this filename is set, it is used as the reference diff source, // otherwise the raw input run through an interpreter is used as the reference // source. // cl::opt<std::string> OutputFile("output", cl::desc("Specify a reference program output " "(for miscompilation detection)")); } /// setNewProgram - If we reduce or update the program somehow, call this method /// to update bugdriver with it. This deletes the old module and sets the /// specified one as the current program. void BugDriver::setNewProgram(Module *M) { delete Program; Program = M; } /// getPassesString - Turn a list of passes into a string which indicates the /// command line options that must be passed to add the passes. /// std::string llvm::getPassesString(const std::vector<std::string> &Passes) { std::string Result; for (unsigned i = 0, e = Passes.size(); i != e; ++i) { if (i) Result += " "; Result += "-"; Result += Passes[i]; } return Result; } BugDriver::BugDriver(const char *toolname, bool find_bugs, unsigned timeout, unsigned memlimit, bool use_valgrind, LLVMContext &ctxt) : Context(ctxt), ToolName(toolname), ReferenceOutputFile(OutputFile), Program(nullptr), Interpreter(nullptr), SafeInterpreter(nullptr), cc(nullptr), run_find_bugs(find_bugs), Timeout(timeout), MemoryLimit(memlimit), UseValgrind(use_valgrind) {} BugDriver::~BugDriver() { delete Program; if (Interpreter != SafeInterpreter) delete Interpreter; delete SafeInterpreter; delete cc; } std::unique_ptr<Module> llvm::parseInputFile(StringRef Filename, LLVMContext &Ctxt) { SMDiagnostic Err; std::unique_ptr<Module> Result = parseIRFile(Filename, Err, Ctxt); if (!Result) { Err.print("bugpoint", errs()); return Result; } if (verifyModule(*Result, &errs())) { errs() << "bugpoint: " << Filename << ": error: input module is broken!\n"; return std::unique_ptr<Module>(); } // If we don't have an override triple, use the first one to configure // bugpoint, or use the host triple if none provided. if (TargetTriple.getTriple().empty()) { Triple TheTriple(Result->getTargetTriple()); if (TheTriple.getTriple().empty()) TheTriple.setTriple(sys::getDefaultTargetTriple()); TargetTriple.setTriple(TheTriple.getTriple()); } Result->setTargetTriple(TargetTriple.getTriple()); // override the triple return Result; } // This method takes the specified list of LLVM input files, attempts to load // them, either as assembly or bitcode, then link them together. It returns // true on failure (if, for example, an input bitcode file could not be // parsed), and false on success. // bool BugDriver::addSources(const std::vector<std::string> &Filenames) { assert(!Program && "Cannot call addSources multiple times!"); assert(!Filenames.empty() && "Must specify at least on input filename!"); // Load the first input file. Program = parseInputFile(Filenames[0], Context).release(); if (!Program) return true; outs() << "Read input file : '" << Filenames[0] << "'\n"; for (unsigned i = 1, e = Filenames.size(); i != e; ++i) { std::unique_ptr<Module> M = parseInputFile(Filenames[i], Context); if (!M.get()) return true; outs() << "Linking in input file: '" << Filenames[i] << "'\n"; if (Linker::linkModules(*Program, std::move(M))) return true; } outs() << "*** All input ok\n"; // All input files read successfully! return false; } /// run - The top level method that is invoked after all of the instance /// variables are set up from command line arguments. /// Error BugDriver::run() { if (run_find_bugs) { // Rearrange the passes and apply them to the program. Repeat this process // until the user kills the program or we find a bug. return runManyPasses(PassesToRun); } // If we're not running as a child, the first thing that we must do is // determine what the problem is. Does the optimization series crash the // compiler, or does it produce illegal code? We make the top-level // decision by trying to run all of the passes on the input program, // which should generate a bitcode file. If it does generate a bitcode // file, then we know the compiler didn't crash, so try to diagnose a // miscompilation. if (!PassesToRun.empty()) { outs() << "Running selected passes on program to test for crash: "; if (runPasses(Program, PassesToRun)) return debugOptimizerCrash(); } // Set up the execution environment, selecting a method to run LLVM bitcode. if (Error E = initializeExecutionEnvironment()) return E; // Test to see if we have a code generator crash. outs() << "Running the code generator to test for a crash: "; if (Error E = compileProgram(Program)) { outs() << toString(std::move(E)); return debugCodeGeneratorCrash(); } outs() << '\n'; // Run the raw input to see where we are coming from. If a reference output // was specified, make sure that the raw output matches it. If not, it's a // problem in the front-end or the code generator. // bool CreatedOutput = false; if (ReferenceOutputFile.empty()) { outs() << "Generating reference output from raw program: "; if (Error E = createReferenceFile(Program)) { errs() << toString(std::move(E)); return debugCodeGeneratorCrash(); } CreatedOutput = true; } // Make sure the reference output file gets deleted on exit from this // function, if appropriate. std::string ROF(ReferenceOutputFile); FileRemover RemoverInstance(ROF, CreatedOutput && !SaveTemps); // Diff the output of the raw program against the reference output. If it // matches, then we assume there is a miscompilation bug and try to // diagnose it. outs() << "*** Checking the code generator...\n"; Expected<bool> Diff = diffProgram(Program, "", "", false); if (Error E = Diff.takeError()) { errs() << toString(std::move(E)); return debugCodeGeneratorCrash(); } if (!*Diff) { outs() << "\n*** Output matches: Debugging miscompilation!\n"; if (Error E = debugMiscompilation()) { errs() << toString(std::move(E)); return debugCodeGeneratorCrash(); } return Error::success(); } outs() << "\n*** Input program does not match reference diff!\n"; outs() << "Debugging code generator problem!\n"; if (Error E = debugCodeGenerator()) { errs() << toString(std::move(E)); return debugCodeGeneratorCrash(); } return Error::success(); } void llvm::PrintFunctionList(const std::vector<Function *> &Funcs) { unsigned NumPrint = Funcs.size(); if (NumPrint > 10) NumPrint = 10; for (unsigned i = 0; i != NumPrint; ++i) outs() << " " << Funcs[i]->getName(); if (NumPrint < Funcs.size()) outs() << "... <" << Funcs.size() << " total>"; outs().flush(); } void llvm::PrintGlobalVariableList(const std::vector<GlobalVariable *> &GVs) { unsigned NumPrint = GVs.size(); if (NumPrint > 10) NumPrint = 10; for (unsigned i = 0; i != NumPrint; ++i) outs() << " " << GVs[i]->getName(); if (NumPrint < GVs.size()) outs() << "... <" << GVs.size() << " total>"; outs().flush(); }

Cricket is not a game where you can practise everything and hope to win tomorrow. There may be no match tommorrow. Here's a preview of second One day International between India and South Africa on India's tour of South Africa 2006. The Weather forecast : Not good. It started with SriLanka's rained off tri-series, then to Malaysia and now to South Africa. Rain god seems to love Indian team a little too much and he is expected to have an effect in this 2nd ODI at Durban. The weather forecast says morning and evening showers - which means this being a Day/Night match, we will get some play in the afternoon and then some after the rain break. I expect umpires and both captain to be smart and start a match of not 50 overs but 30 overs. This will mean we only need 4 and half hours of playing time and little lunch break - which rain god is sure to provide. The pitch : Easily the fastest in South Africa and probably second fastest in World after Perth in Australia. What makes Durban pitch even more dangerous for the batsmen is the dew factor. They don't play Day/Night games at Perth. But Kingsmead Durban has been hosting Day night ODI's for a long time and whenever the second innings start underlight - ball not only bounces more, but swings extensively. Toss is very important here but what's more important is believe. Even if you bat first and make 200 - you should believe you can defend it. And even when you bowl first - you must know you can't let them score more than 150. The short boundaries : Makes Durban even more harder play for spinners to make a mark. The start time : This 2nd India v SA ODI will start at 1800hrs India time. But the important factor here is if there is a delay in the start of this one day International - the last time to start the match is 2245 India time. This means if rain again haunts this match, 2245 is the last till when you can wait. FastCricket welcomes your feedback : *** Related Articles If you watched Day 4 of Cape town test between India and South Africa, you will know two things for sure that Mr. Sourav Ganguly is in very good form, whereas Mr. Sachin Tendulkar is fighting within himself about what is his role in the team.. Sehwag and Jaffer departed early Indian team have their flight booked just a few hours after 5pm on 6th January - the 5th and last day of their 2006-07 tour of South Africa. Which means that last 48 hours in African nation will decide how our boys will feel on that flight back home.. and When we started the South African tour, everyone wanted Team India to do well, but also knew we actually had very little chance of beating South Africa in their own den.We lost the test series 4-0 and only consolation came in a twenty20 match. The script for the test We had a similar chance at the same time, just before last World Cup in Australia when we were 1-0 up in that "Steve Waugh farewell" 4 test match series....We blew it. Now we have exactly same chance to show the World that we - the Indians as a cricket Great people or teams, win one battle and their hunger to win the war grows. Whereas common/average people go so mad upon a single triump that they forget what more they could have done with their only lives..I feared the same when our team won the first test

Study Highlights**WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?**☑ More than half of ulcerative colitis (UC) patients fail to achieve mucosal healing with conventional drug therapy.☑ The efficacy of probiotics in the treatment of UC remains controversial.☑ We previously identified a long‐chain polyphosphate from *Lactobacillus brevis* SB88 and suggested that it was effective for improving the intestinal barrier function and inflammation.**WHAT QUESTION DID THIS STUDY ADDRESS?**☑ All drugs that are clinically available for the treatment of UC are antiinflammatory or immunomodulatory agents; none directly improve the intestinal barrier function.☑ The safety and efficacy of oral enteric capsules containing long‐chain polyphosphates in humans remain unclear.**WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?**☑ No adverse reactions occurred in association with long‐chain polyphosphate treatment in our first‐in‐human trial.☑ Among the 10 enrolled patients for whom conventional drug therapy had failed, 7 acquired a clinical response, 4 of whom achieved endoscopic remission.**HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?**☑ Because of their high safety and efficacy, long‐chain polyphosphates are strongly believed to be useful for the treatment of refractory ulcerative colitis. {#cpt1628-sec-0002} Ulcerative colitis (UC) is a condition of chronic intestinal inflammation, the pathogenesis of which is largely unknown. While steroids and mesalamine are the standard treatments for relieving symptoms, a treatment strategy for curing the disease has not yet been established. Most patients experience relapses repeatedly and suffer from abdominal pain, diarrhea, and hematochezia for more than 50 years. "Mucosal healing," which is defined by a sufficient intestinal barrier function, leads to a significantly long‐term remission;[1](#cpt1628-bib-0001){ref-type="ref"} however, more than half of UC patients fail to achieve mucosal healing, even when using recently developed anti--tumor necrosis factor (TNF)--α treatments.[2](#cpt1628-bib-0002){ref-type="ref"} Probiotics are live microorganisms that confer a health benefit on the host when administered in adequate amounts[3](#cpt1628-bib-0003){ref-type="ref"} and are used as functional foods as well as drugs for the treatment of acute intestinal inflammation and necrotizing enterocolitis.[4](#cpt1628-bib-0004){ref-type="ref"}, [5](#cpt1628-bib-0005){ref-type="ref"}, [6](#cpt1628-bib-0006){ref-type="ref"} Probiotics possess sufficient safety to be used for a long time; however, their efficacy as a treatment for inflammatory bowel diseases remains controversial[7](#cpt1628-bib-0007){ref-type="ref"} because the function of live bacteria is influenced by the intestinal conditions in individual patients. To solve this weak point of probiotic treatment, we have considered using the bioactive molecules produced by probiotics, which enhance the intestinal barrier function regardless of the intestinal conditions, as do drugs. A method for identifying bioactive molecules[8](#cpt1628-bib-0008){ref-type="ref"} was used to identify the probiotic‐derived molecule responsible for improving the intestinal barrier function. Briefly, fraction‐inducing HSP27, which is known to increase the intestinal barrier function, in human Caco2/BBE cells was separated from the conditioned media of *Lactobacillus brevis SBC8803* using spin columns equipped with several molecular weight cutoff membranes, diethylaminoethyl anion‐exchange chromatography, and size‐exclusion chromatography. The amino acid composition and peptidoglycan content of the HSP27‐inducible fractions were shown to be extremely low; however, the fraction contained a large amount of phosphorus (90% weight for weight) and oxygen. Based on these results, we assumed that the HSP27‐inducible fraction was a polyphosphate. Synthesized polyphosphate poly P significantly induced HSP27 in Caco2/BBE cells, and the HSP27 induction by the culture supernatant of *L. brevis* was diminished by the degradation of polyphosphate using polyphosphate kinase, indicating that poly P was the molecule responsible for the induction of HSP27.[9](#cpt1628-bib-0009){ref-type="ref"} We proposed that the administration of long‐chain polyphosphate led to the localization of cell‐adherent molecules along the tight junction in intestinal epithelia and thereby improved the intestinal barrier function and inflammation *in vitro* and in chemical‐induced colitis mice through the epithelial endocytosis of long‐chain polyphosphate‐integrin β1‐caveolin‐1 complex (patent nos. JP5660508, EP2559437).[10](#cpt1628-bib-0010){ref-type="ref"}, [11](#cpt1628-bib-0011){ref-type="ref"}, [12](#cpt1628-bib-0012){ref-type="ref"} This was the first study to show that long‐chain polyphosphate was able to improve the intestinal barrier function and ameliorate intestinal injury under inflammatory conditions, although short‐polyphosphate is known to enhance the proliferation of human fibroblasts by stabilizing fibroblast growth factors[13](#cpt1628-bib-0013){ref-type="ref"} and to exert antibacterial activity against many bacteria and fungi.[14](#cpt1628-bib-0014){ref-type="ref"}, [15](#cpt1628-bib-0015){ref-type="ref"}, [16](#cpt1628-bib-0016){ref-type="ref"}, [17](#cpt1628-bib-0017){ref-type="ref"} A subsequent study also showed that polyphosphate produced by a marine cyanobacterium, *Synechococcus*, exerted an antiinflammatory function.[18](#cpt1628-bib-0018){ref-type="ref"} The present study identified the most suitable chain length of polyphosphate for the enhancement of the intestinal barrier function and confirmed the efficacy of long‐chain polyphosphate in inflammation models (including a genetically induced mouse colitis model and inflammation‐induced human macrophages). Furthermore, the safety of long‐chain polyphosphate was confirmed by preclinical tests, and we conducted the first‐in‐human trial to determine the safety and efficacy of long‐chain polyphosphate in patients with refractory UC. Results {#cpt1628-sec-0003} ======= The reinforcement of the intestinal barrier by polyphosphate was dependent on the chain length {#cpt1628-sec-0004} ---------------------------------------------------------------------------------------------- To determine the chain lengths of polyphosphate that might enhance the intestinal barrier function, an *ex vivo* ^3^H‐mannitol study was performed using 12.5, 65, 300, 450, and 700‐mer polyphosphates. The barrier function was enhanced by the polyphosphates in a concentration‐dependent manner (**Figure** [**S1**](#cpt1628-sup-0001){ref-type="supplementary-material"}). The grade of the barrier function when using the 450‐mer polyphosphate did not differ from that when using the 700‐mer polyphosphate (**Figure** [1](#cpt1628-fig-0001){ref-type="fig"} **a**). A transepithelial electric resistance (TER) test was performed to assess the effect of polyphosphates on the epithelial barrier function. The permeability of the Caco2 cell layer was increased by TNF‐α treatment, and both preventive and simultaneous treatments with the 450‐mer and 700‐mer polyphosphates improved the TER at 7.5 hours (**Figure** [1](#cpt1628-fig-0001){ref-type="fig"} **b**), indicating that treatment with the 450‐mer polyphosphate sufficiently increased the intestinal barrier function in comparison with longer polyphosphates. Thus, the 450‐mer polyphosphate was used as the long‐chain polyphosphate for the subsequent studies. The incubation of long‐chain polyphosphate under acidic conditions (pH 1.2) for 2 hours failed to reduce ^3^H‐mannitol leakage (**Figure** [1](#cpt1628-fig-0001){ref-type="fig"} **c**). A high‐performance liquid chromatography spectrum analysis revealed that the retention time of polyphosphate had shifted from 16.701 to 18.826 minutes, indicating that fragmentation of polyphosphate occurred under acidic conditions (**Table** [1](#cpt1628-tbl-0001){ref-type="table"}). These findings suggest that the protection of long‐chain polyphosphates from gastric juice in the stomach, which has a low pH, is necessary for them to effectively enhance the intestinal barrier function. ![Polyphosphate enhanced the intestinal barrier function in a chain length‐dependent manner. (**a**) An *ex vivo* study revealed that the intestinal permeability induced by oxidative stress was significantly attenuated by treatment with 300‐mer, 450‐mer, and 700‐mer polyphosphates (*n* = 5). (**b**) The TER test is a method of assessing the resistance between the upper and lower sides of the transwell *in vitro*. The TER test showed that the permeability induced by TNF‐α treatment was reduced by long‐chain polyphosphate treatment (*n* = 3). (**c**) Long‐chain polyphosphates incubated under acidic conditions (pH 1.2) for 2 hours did not enhance the intestinal barrier function in an *ex vivo* study. \**P* \< 0.05 by Student\'s *t*‐test. The error bars show the standard deviation. BSA, bovine serum albumin; LCP, long‐chain polyphosphate; NT, no treatment; TER, transepithelial electrical resistance; TNF‐α, tumor‐necrosis factor alpha. \[Colour figure can be viewed at <http://wileyonlinelibrary.com>\]](CPT-107-452-g001){#cpt1628-fig-0001} ###### Shortening of polyphosphates under acidic conditions   R. Time (minutes) LCP/BSA (R. Time) 50%‐width (minutes) 10%‐width (minutes) ----------------------- ------------------- ------------------- --------------------- --------------------- LCP 16.701 0.971 1.358 2.948 LCP treated with acid 18.826 1.095 2.107 3.163 BSA 17.195 --- --- --- 10%‐width, width of the wave 10% from the bottom of the wave; 50%‐width, width of the wave 50% from the bottom of the wave; BSA, bovine serum albumin; LCP, long‐chain polyphosphate; R. Time, retention time. John Wiley & Sons, Ltd Long‐chain polyphosphate exerted an antiinflammatory effect in human‐derived M1 macrophages, an IL‐10 KO transfusion mouse model, and a DSS‐induced colitis rat model {#cpt1628-sec-0005} --------------------------------------------------------------------------------------------------------------------------------------------------------------------- To clarify the antiinflammatory effects in active macrophages, M1 macrophages were treated with the polyphosphate and Lipopolysaccharide (LPS). The LPS‐inducible production of TNF‐α in M1 macrophages was inhibited by treatment with 0.1 μm long‐chain to 3.0 μm long‐chain polyphosphates (≥450 mer) but not short‐chain polyphosphates (≤65 mer) ([**Figure S2**](#cpt1628-sup-0002){ref-type="supplementary-material"}), suggesting that long‐chain polyphosphate exerted an antiinflammatory effect as well as enhanced the intestinal barrier function. To clarify the treatment effect of long‐chain polyphosphate *in vivo*, an interleukin (IL)‐10 knockout (KO) transfusion mouse model was constructed. The diarrhea score in IL‐10 KO transfusion mice transanally treated with long‐chain polyphosphate showed a significant improvement, and the colon weight in the IL‐10 KO transfusion group was significantly increased in comparison with the no‐transfusion group but was significantly reduced by the transanal treatment with long‐chain polyphosphate (**Figure** [2](#cpt1628-fig-0002){ref-type="fig"} **a**). The diarrhea score, but not the colon weight, of IL‐10 KO transfusion mice that received oral long‐chain polyphosphate recovered in comparison with the phosphate‐buffered saline (PBS) group (**Figure** [2](#cpt1628-fig-0002){ref-type="fig"} **b**). These data suggested that, in order to achieve sufficient efficacy, it was important to prevent the reduction of the activity of polyphosphates under acidic conditions. To overcome this issue, an enteric‐coated capsule containing long‐chain polyphosphate was generated, and the treatment effect of the capsule was analyzed in a dextran sodium sulfate (DSS)‐induced colitis rat model. The DSS‐treated rats showed shortening of the colon, and recovered following treatment with capsules in a dose‐dependent manner (**Figure** [2](#cpt1628-fig-0002){ref-type="fig"} **c**). A reverse transcription polymerase chain reaction revealed that the messenger RNA (mRNA) expression of proinflammatory cytokines, including TNF‐α and IL‐1β, and the histopathological scores of intestinal damage were reduced by the administration of the capsules (**Figure** [2](#cpt1628-fig-0002){ref-type="fig"} **d,e**). These findings suggest that an enteric‐coated capsule containing long‐chain polyphosphate may be useful for the treatment of intestinal inflammation. {#cpt1628-fig-0002} Preclinical tests {#cpt1628-sec-0006} ----------------- A nonrodent (beagle) repeated‐dose toxicity study using long‐chain polyphosphate (328 and 2,296 mg/body/day) for 4 weeks, a rodent single‐dose toxicity study using long‐chain polyphosphate (40, 200, and 1,000 mg/kg/day) for 2 weeks, a rodent single‐dose toxicity study using long‐chain polyphosphate (10 and 90 mg/body/day), a mutagenicity test, an *in vitro* micronucleus test of long‐chain polyphosphate in TK6 cells, and safety pharmacology studies to investigate the effects of long‐chain polyphosphate on the central nervous and respiratory systems in rats revealed no adverse events (details are shown in the study protocol). First‐in‐human trial {#cpt1628-sec-0007} -------------------- After confirming the effects and safety of long‐chain polyphosphate with preclinical studies, a first‐in‐human trial was conducted. In this study, no adverse reactions associated with the intake of long‐chain polyphosphate were observed on any electrocardiograms, urinary tests, or blood examinations (including abnormal serum levels of phosphates). In step 1, the partial Mayo scores of four of five patients were decreased. Two of the patients achieved a clinical remission (partial Mayo score ≤2) as well as endoscopic remission (Mayo endoscopic subscore ≤1, corresponding to mucosal healing). These two patients who achieved remission had shown either treatment failure or intolerance to anti‐TNF‐α agents. In step 2, the partial Mayo scores of three of five patients were decreased, including two patients with failure or intolerance of anti‐TNF‐α agents. Among the 10 patients in the study population, long‐chain polyphosphate relieved the disease activity in 7 patients, including 4 who achieved endoscopic remission at the end of the 4‐week drug administration period. Long‐chain polyphosphate was able to induce clinical and endoscopic remission in patients with refractory UC regardless of the failure or intolerance of anti‐TNF‐α agents (**Table** [2](#cpt1628-tbl-0002){ref-type="table"}). The mRNA expression of inflammatory cytokines decreased in six of seven patients, thereby relieving their disease activity. In the three patients who did not respond to long‐chain polyphosphate therapy, the partial Mayo score at one week after starting the treatment did not improve, and the mRNA expression of inflammatory cytokines did not decrease (data not shown). ###### The prestudy evaluation and Mayo scores before and after long‐chain polyphosphate treatment Step Case Age Sex Type Treatment history Before treatment After treatment ------ ------ ----- ----------- ----------- ------------------- ------------------ ----------------- ---- --- --- ---- --- --- ---- ---- --- 1 1 58 M Left side D \+ − − 8 5 3 5 3 2 \+ − 2 72 M Proctitis D \+ − − 5 3 2 5 3 2 − − 3 39 F Total D \+ \+ \+ 6 4 2 3 2 1 \+ \+ 4 36 F Left side D \+ \+ − 6 4 2 2 1 1 \+ \+ 5 55 F Left side R \+ − − 7 5 2 5 3 2 \+ − 2 1 69 M Left side D \+ \+ \+ 8 6 2 5 3 2 \+ − 2 53 F Left side D \+ \+ − 6 4 2 3 2 1 \+ \+ 3 19 F Total D \+ \+ − 7 5 2 10 7 3 − − 4 54 F Total D \+ \+ − 7 5 2 5 4 1 \+ \+ 5 44 F Left side R \+ − − 7 5 2 10 7 3 − − 5‐ASA, aminosalicylic acid (mesalamine); Anti‐TNF, anti‐TNF‐α agents; CI, calcineurin inhibitor; CR, clinical response; D, steroid‐dependent; MES, Mayo endoscopic subscore; MH, mucosal healing; PMS, partial Mayo score; R, steroid‐resistant; TMS, total Mayo score. John Wiley & Sons, Ltd Case presentation (Case 4 in step 1) {#cpt1628-sec-0008} ------------------------------------ A 36‐year‐old woman with an onset of UC at 22 years of age visited our hospital because of recurrence with a high frequency of bowel movements and hematochezia. Despite receiving 12 subcutaneous injections of adalimumab, she failed to achieve clinical remission. Before the administration of long‐chain polyphosphate, her partial Mayo score and Mayo endoscopic subscore had been 4 and 2, respectively. After 4 weeks of long‐chain polyphosphate treatment (300 mg, daily) her partial Mayo score and Mayo endoscopic subscore decreased to 2 and 1, respectively (**Figure** [3](#cpt1628-fig-0003){ref-type="fig"} **a**). Colonoscopy revealed an edematous mucosa and multiple small depressions in the sigmoid colon and rectum before long‐chain polyphosphate treatment. These findings disappeared after the administration of the drug (**Figure** [3](#cpt1628-fig-0003){ref-type="fig"} **b**). A clinical remission has been maintained for more than one year since the treatment. {#cpt1628-fig-0003} Discussion {#cpt1628-sec-0009} ========== Probiotics possess sufficient safety to be used for a long time, but their efficacy in UC treatment remains controversial[7](#cpt1628-bib-0007){ref-type="ref"} due to the diversity of intestinal conditions among patients. To resolve the issue and develop a drug that is effective against UC, regardless of intestinal conditions, we developed a method for identifying bioactive molecules from probiotic‐conditioned media[8](#cpt1628-bib-0008){ref-type="ref"} and isolated the bioactive long‐chain polyphosphate molecule from media conditioned with *L. brevis* SB88.[9](#cpt1628-bib-0009){ref-type="ref"} Our findings suggested that long‐chain polyphosphate treatment enhanced the intestinal barrier function and relieved the intestinal injury under inflammatory conditions both *in vitro* and in an IL‐10 KO transfusion mouse model. The function of polyphosphates is known to depend on their chain length. Short‐chain‐length polyphosphates have been shown to enhance the proliferation of human fibroblasts by stabilizing fibroblast growth factors[13](#cpt1628-bib-0013){ref-type="ref"} and exert antibacterial effects against microorganisms.[14](#cpt1628-bib-0014){ref-type="ref"}, [15](#cpt1628-bib-0015){ref-type="ref"}, [16](#cpt1628-bib-0016){ref-type="ref"}, [17](#cpt1628-bib-0017){ref-type="ref"} The present study showed that long‐chain (chain length ≥ 450) polyphosphates improved the intestinal barrier function under conditions of oxidative stress, while short‐chain polyphosphates (chain length ≤ 65) exerted no significant effect on the intestinal barrier function. We therefore developed a procedure for fashioning long‐chain polyphosphates for clinical trials and conducted the first‐in‐human trial to assess the outcomes of long‐chain polyphosphate therapy for refractory UC in 10 patients who responded poorly to currently available treatments. Seven patients achieved a clinical response, and four achieved endoscopic remission after 4 weeks of treatment with long‐chain polyphosphate. The response and remission induction rates were almost the same as those in previous studies using anti‐TNF‐α agents[2](#cpt1628-bib-0002){ref-type="ref"} or recently developed biological drugs, including Janus kinase inhibitors and vedolizumab.[19](#cpt1628-bib-0019){ref-type="ref"}, [20](#cpt1628-bib-0020){ref-type="ref"} Because our human trial was a single‐arm study, it is difficult to compare the effects of long‐chain polyphosphate therapy with a control group, such as the achievement of spontaneous remission. However, Travis, *et al*.[21](#cpt1628-bib-0021){ref-type="ref"} showed in a phase III study of budesonide that the remission rates at 8 weeks were 4.5% among patients in the placebo group. In a phase III study of budesonide, Sandborn, *et al*.[22](#cpt1628-bib-0022){ref-type="ref"} showed that the remission rates at 8 weeks were 6.2% among patients in the placebo group. These recent studies suggested that the spontaneous remission rate was quite low. Thus, the remission rate of 40% in our study is thought to be higher in comparison with the general spontaneous remission rate. It is notable that efficacy was observed in patients with failure or intolerance to anti‐TNF‐α agent therapy, as well as in naïve patients. Our *ex vivo* intestinal loop study and *in vitro* TER test showed that long‐chain polyphosphate improved the intestinal barrier function impaired by not only TNF‐α but also monochloramine (NH~2~CL), suggesting that long‐chain polyphosphate does not directly target TNF‐α. Thus, long‐chain polyphosphate therapy has a function that is distinct from that of anti‐TNF‐α agents and is a feasible alternative to costly biological drugs for treating refractory UC. The drugs that are currently available for the treatment of UC in the clinical setting are all antiinflammatory or immunomodulating agents, and none have directly improved the intestinal barrier function. We previously reported the mechanisms of action of long‐chain polyphosphates on the improvement of intestinal injuries. Briefly, long‐chain polyphosphates bind to the integrin β1 expressed on the intestinal epithelia,[9](#cpt1628-bib-0009){ref-type="ref"} forming a complex with caveolin‐1 (phosphate‐integrin β1‐caveolli‐1 complex). Thereafter, the complex is endocytosed into the cytosol of the intestinal epithelia and p38 mitogen‐activated protein kinase is activated. Then, cell‐adhesion‐associated molecules are strongly upregulated and the intestinal barrier function is increased.[11](#cpt1628-bib-0011){ref-type="ref"} Based on our results, the effect of long‐chain polyphosphate on the intestinal barrier function was thought to be due to the upregulation of cell‐adhesion‐associated molecules. The impairment of the intestinal barrier function is known to lead to the translocation of bacteria and virulence, thereby aggravating the disease status of intestinal disorders, including inflammatory bowel diseases. A recent study showed that mesalamine targeted polyphosphate kinase in pathogenic bacteria but did not show that mesalamine enhanced the intestinal barrier function at all.[23](#cpt1628-bib-0023){ref-type="ref"} Long‐chain polyphosphates may be the first drugs to help prevent the invasion of bacteria and virulence through the direct enhancement of the intestinal barrier function. We also confirmed that long‐chain polyphosphates reduced the expression of inflammatory cytokines, including TNF‐α and IL‐12, in human M1 macrophages and in the colon of DSS‐induced and IL‐10 KO transfusion mouse models. This suggests that long‐chain polyphosphate possesses an antiinflammatory function both *in vitro* and *in vivo*. Regarding the function in relation to macrophages, we previously showed that long‐chain polyphosphates reduced the expression of TNFα in LPS‐stimulated THP‐1 cells that were pretreated with macrophage colony‐stimulating factor and IFNγ. We also confirmed that long‐chain polyphosphate improved the intestinal injury in a 2,4,6‐Trinitrobenzenesulfonic acid--induced colitis model[10](#cpt1628-bib-0010){ref-type="ref"} as well as a DSS‐induced colitis model. While the mechanisms of the antiinflammatory effect are still being explored, our previous study showed that long‐chain polyphosphates might target M1 macrophages. Based on these findings in experimental models, long‐chain polyphosphates are expected to exhibit an antiinflammatory effect in patients with inflammatory bowel diseases. Regarding the safety of long‐chain polyphosphates, preclinical studies, including nonrodent repeated‐dose toxicity studies, rodent single‐dose toxicity studies, mutagenicity tests, and safety pharmacology tests, revealed no adverse events. In addition, the present study showed no adverse events in 10 UC patients with active inflammation. These data suggest that long‐chain polyphosphates are a safe drug. In conclusion, long‐chain polyphosphate was safe and effective for the treatment of refractory UC in the first‐in‐human study. The next phase of this study has been prepared and will provide stronger evidence concerning the safety and efficacy of long‐chain polyphosphate in the treatment of UC, including appropriate targets for treatment. Materials and Methods {#cpt1628-sec-0010} ===================== Animals {#cpt1628-sec-0011} ------- Details are provided in the [**Supplementary Material**](#cpt1628-sup-0004){ref-type="supplementary-material"}. Polyphosphate {#cpt1628-sec-0012} ------------- Polyphosphates with a length of 12.5 (BENX‐PolyP‐S), 65 (BENX‐PolyP), and 700 (BENX‐EPolyP) mers were purchased from BIOENEX, Higashihiroshima, Japan, while 300‐mer and 450‐mer polyphosphates were obtained by enzymatic reactions.[9](#cpt1628-bib-0009){ref-type="ref"} Calculating the chain length of the polyphosphates {#cpt1628-sec-0013} -------------------------------------------------- Polyphosphates were incubated in reaction buffer containing 50 mM Tris‐HCl pH 7.5, 0.01% N,N‐Bis(4‐sulfobutyl)‐3‐methylaniline disodium salt, 0.01% 4‐aminoantipyrine, 2 mM adenosine diphosphate, 2 mM MgCl~2~, 10 mM glycerol, 10 U/mL glycero‐3‐P oxidase, 5 U/mL peroxidase, 1 U/mL glycerol kinase, and 0.1 mg/mL polyphosphate kinase at 37°C for 10 minutes. Two reaction volumes of 2% sodium dodecyl sulfate were then added, and detection was performed at an optical density of 550 nm. The chain length of the polyphosphates was calculated using a 700‐mer polyphosphate as the standard. The HPLC spectrum analysis of the polyphosphates {#cpt1628-sec-0014} ------------------------------------------------ The polyphosphates were separated using an HPLC system (Shimadzu Corporation, Kyoto, Japan) with a TSKgel GMPW XL (φ7.8 mm × 300 mm) column at 30°C and eluted with 10 mM phosphate buffer containing 0.5 M sodium chloride, at a flow rate of 0.5 mL/minute. The eluent was monitored by ultraviolet spectrophotometry at 260 nm. Bovine serum albumin was used as a standard. TER test {#cpt1628-sec-0015} -------- Details are provided in the [**Supplementary Material**](#cpt1628-sup-0004){ref-type="supplementary-material"}. Human peripheral blood‐derived macrophages {#cpt1628-sec-0016} ------------------------------------------ Details are provided in the [**Supplementary Material**](#cpt1628-sup-0004){ref-type="supplementary-material"}. The *ex vivo* intestinal loop study {#cpt1628-sec-0017} ----------------------------------- C57Bl/6 mice were euthanized, and the small intestine was divided into three pieces, with each end ligated with silk sutures and the loops filled with RPMI 1640 medium containing the sample. The loops were incubated for 2 hours at 37°C in a 5% CO~2~ incubator. To assess the permeability effects, the loops were filled with RPMI 1640 medium containing 1 mCi/mL \[3H\]‐mannitol with or without 0.3 mM freshly prepared NH~2~Cl. The loops were placed into the middle section of the organ culture dish in 4 mL of RPMI 1640 without NH~2~Cl. To assess the permeability, samples were taken at 5, 20, and 35 minutes to determine the flux of mannitol from the lumen to the media outside the loops. Radioactivity was measured using a scintillation spectrometer. Isotope‐labeled polyphosphate {#cpt1628-sec-0018} ----------------------------- Details are provided in the [**Supplementary Material**](#cpt1628-sup-0004){ref-type="supplementary-material"}. Pharmacokinetics study {#cpt1628-sec-0019} ---------------------- Mice were treated with ^32^P‐labeled long‐chain polyphosphate (500 μg) orally or through the duodenum and then euthanized 2, 5, or 24 hours later. The organs, stool, urine, inferior vena cava blood, and portal blood were collected at euthanizing, and the radioactivity was measured using a scintillation spectrometer. Enteric‐coated capsules {#cpt1628-sec-0020} ----------------------- Details are provided in the [**Supplementary Material**](#cpt1628-sup-0004){ref-type="supplementary-material"}. DSS‐induced colitis {#cpt1628-sec-0021} ------------------- Details are provided in the [**Supplementary Material**](#cpt1628-sup-0004){ref-type="supplementary-material"}. The real‐time polymerase chain reaction {#cpt1628-sec-0022} --------------------------------------- Details are provided in the [**Supplementary Material**](#cpt1628-sup-0004){ref-type="supplementary-material"}. The IL‐10 KO‐derived T‐lymphocyte transfusion (IL‐10 KO transfusion) mouse model {#cpt1628-sec-0023} -------------------------------------------------------------------------------- CD4‐positive cells were purified from the spleen, mesenteric lymph node, and sacral lymph node of IL‐10 KO mice. A total of 5 × 10^6^ CD4‐positive cells were suspended in 1 mL PBS, and 0.2 mL/mouse of cell suspension was transferred to SCID mice. Starting on day 1, long‐chain polyphosphate or PBS was transanally administered to the mice every day. The diarrhea score was assessed at day 15. The scores were determined as follows: score 0, solid stool that was not deformed when pushed by finger; score 1, solid stool that was deformed when pushed by finger; score 3, solid stool that was easily collapsed when pushed by finger; score 3, soft stool that was easily deformed and stuck to container; score 4, muddy or watery stool. The mice were euthanized on day 15 under isoflurane anesthesia, the colon was sampled, and the weight of the colon was measured. First‐in‐human trial {#cpt1628-sec-0024} -------------------- We designed an investigator‐initiated, nonrandomized, open‐label pilot study of long‐chain polyphosphate (University Hospital Medical Information Network number, UMIN000021555) involving 10 adult patients with refractory UC. The study was approved by the ethics committee of Asahikawa Medical University (Number, 15189), and each patient provided their written informed consent. We developed a double‐capsule formulation using size 0 and 2 DRcaps capsules (Capsugel Japan, Tokyo, Japan) containing 100 mg of long‐chain polyphosphate in a capsule. Ten UC patients, including two steroid‐resistant and eight steroid‐dependent cases (refractory UC), who visited Asahikawa Medical University Hospital from May 2016 to December 2017 and who showed a disease activity with a Mayo score ranging from 3 to 8 with obvious hematochezia were enrolled in this study. The first five patients orally took 300 mg of long‐chain polyphosphate once daily for 4 weeks (step 1); the second five patients orally took 900 mg of long‐chain polyphosphate once daily for 4 weeks (step 2). Anti‐TNF‐α agent treatments were fixed at 20 weeks before taking the study drugs, and other medications were fixed 2 weeks before taking the study drugs. All treatments used before the enrollment were continued during the study. In the patients enrolled in the present study, biologics were fixed ≥20 weeks before taking the study drugs, and all other medications were fixed ≥4 weeks before taking the study drugs, except for antibiotics, which were fixed 2 weeks before taking the study drugs in one case (case 2 in step 2). Therefore, none of the enrolled patients were excluded due to concomitant medications. The disease activity of the enrolled patients was assessed using the Mayo score (the calculation of the Mayo and partial mayo scores is described in the [**Supplementary Methods**](#cpt1628-sup-0003){ref-type="supplementary-material"}). The partial Mayo score was assessed before starting the study and every week until the administration schedule was completed. The Mayo endoscopic subscore was assessed before and after the study. Before enrollment, pan‐colonoscopy was performed in all patients to determine the most severe inflammation site, which was set as the assessment area. The severity of the inflammation was then assessed based on the Mayo endoscopic subscore. After long‐chain polyphosphate treatment, the subscore of the assessment area evaluated by initial colonoscopy was reassessed. Pan‐colonoscopy was performed as second colonoscopy only if the endoscopist concluded that other sites needed to be evaluated. The mRNA expression of inflammatory cytokines, including TNF‐α, IFN‐γ, and IL‐1β, in biopsy samples obtained from the rectosigmoid colon were measured before and after this study. The primary endpoint was the safety of the long‐chain polyphosphate, and the secondary endpoint was the efficacy of this drug in patients with refractory UC. Monitoring and inspection of this study were performed by a third‐party organization (MRS Planning, Tokyo, Japan). Steroids, mesalamine, anti‐TNF‐α agents, and calcineurin inhibitors were used by 10, 10, 6, and 2 of the enrolled patients, respectively, before their entry in this study. In step 1, the disease activity was classified as follows: Mayo 5, *n* = 1; Mayo 6, *n* = 2 patients; Mayo 7, *n* = 1 patient; and Mayo 8, *n* = 1. In step 2, the activity at the beginning of this study was classified as Mayo 6, *n* = 1; Mayo 7, *n* = 3; and Mayo 8, *n* = 1 (**Table** [1](#cpt1628-tbl-0001){ref-type="table"}). Blood examinations performed before starting this study revealed no abnormalities, with the exception of slight C‐reactive protein elevation in three patients. Statistical analyses {#cpt1628-sec-0025} -------------------- Details are provided in study protocols of the first‐in human trial. Funding {#cpt1628-sec-0027} ======= This study was partially supported by Ministry of Education, Culture, Sports, Science and Technology Grants‐in‐Aid for Scientific Research, No. 26460956 (M.F.), Translational Research Network Program of Japan Agency for Medical Research and Development, No. C40 (M.F.), and Development and Intractable Disease Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare. This study was partially supported as a joint research project of Asahikawa Medical University and EA Pharma Co., Ltd. Conflict of Interest {#cpt1628-sec-0028} ==================== M.F. reports grants from Japanese Grants‐in‐Aid for Scientific Research, grants from Translational Research Network Program of Japan Agency for Medical Research and Development, nonfinancial support from Development and Intractable Disease Health, and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare. During the conduct of the study: grants and personal fees from Yakult Honsha Co., Ltd, grants and personal fees from Nippon Kayaku Co., Ltd., grants, personal fees, and nonfinancial support from EA Pharma Co., Ltd., personal fees from Novartis Pharmaceuticals, grants from Boehringer Ingelheim GmbH, personal fees from Technical Information Institute Co., Ltd, personal fees from Pfizer Inc., grants and personal fees from Takeda Pharmaceutical Company Limited, grants and personal fees from Daiichi Sankyo Company, Limited, grants from Shionogi & Co., Ltd, personal fees from Olympus Co., Ltd., personal fees from Janssen Pharmaceutical K.K., personal fees from Kyorin Pharmaceutical Co., Ltd., personal fees from Taisho Toyama Pharmaceutical Co., Ltd., grants from AstraZeneca, personal fees from Tomakomai Minpo Co., Ltd., personal fees from Meiji Seika Pharma Co., Ltd., grants and personal fees from Mochida Pharmaceutical Co., Ltd, grants from Astellas Pharma Inc., personal fees from Mitsubishi Tanabe Pharma Corporation, grants from Baxter International Inc, personal fees from Bristol‐Myers Company, grants and personal fees from Chugai Pharmaceutical Co., Ltd., grants from MSD K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd, grants and personal fees from Kyowa Hakko Kirin Co., Ltd., grants from Taiho Pharmaceutical Co., Ltd, personal fees from Zeria Pharmaceutical Co., Ltd., grants from Alexion Pharmaceutical Co., Ltd., grants, personal fees, and nonfinancial support from Ajinomoto Pharmaceutical Co., Ltd., personal fees from Asahi Kasei Corporation, grants and nonfinancial support from Sapporo Breweries Ltd., grants and personal fees from Eisai Co., Ltd., grants from GlaxoSmithKline K.K., grants from AbbVie Inc, grants from Sumitomo Dainippon Pharma Co., Ltd., grants from Asuka Pharmaceutical Co., Ltd., grants from Boston Scientific Corporation or its affiliates, grants and nonfinancial support from Kamui Pharma. Inc., outside the submitted work. In addition, M.F. has been issued patents for intestinal protectants (JP 5660508 and EP 2559437). The other authors declared no conflicts of interest in association with the present study. Author Contributions {#cpt1628-sec-0029} ==================== M.F. and N.U. wrote the manuscript; M.F. and N.U. designed the research; M.F, N.U., S.K., K.T, K.A., Ke.M., H.K., N.K., Y.T., Tom.O. and Ka.M. performed the research; M.F, N.U., A.S., M.T., and Tos.O. analyzed the data. Supporting information ====================== ###### **Figure S1.** The effects of several concentrations of long‐chain polyphosphate on the improvement of the intestinal barrier function. ###### Click here for additional data file. ###### **Figure S2.** Long‐chain polyphosphate inhibited the anti--tumor necrosis factor--α production in Lipopolysaccharide‐stimulated M1 macrophages. ###### Click here for additional data file. ###### **Supplementary Methods** ###### Click here for additional data file. ###### **Clinical Trial Protocol** ###### Click here for additional data file. We thank Miyuki Sato, Kuninori Iwayama, Naoya Kamiyama, Takashi Ono, and other members of the Department of Hospital Pharmacy and Pharmacology and the Clinical Research Support Center of Asahikawa Medical University, Professor Hiroshi Funakoshi, Professor Yasuaki Saijyo, and Professor Nobuyuki Sato, and Atsushi Yonezawa and Takayuki Nakagawa and other members of the Department of Clinical Pharmacology and Therapeutics of Kyoto University Hospital for their great support of this study. [^1]: MF and NU contributed equally to this study.

Añade soporte para decodificar por VP9 y refresco variable sobre HDMI 2.1 para monitores Gsync entre otras características Nos llegan noticias de que Nvidia acaba de lanzar un nuevo driver beta para Linux con numeración 440.26, y que trae novedades interesantes entre las que destacan el soporte para decodificación VP9 para el driver VDPAU, el refresco variable sobre HDMI 2.1 para monitores que soporten frecuencia adaptativa GSYNC y enlazado paralelo de shaders GLSL. Además, trae mejoras específicas para los juegos Saints Row IV y Saints Row: The Third, soporte para nuevas extensiones multicast de Vulkan y las correspondientes mejoras y parches a todos los niveles. Una vez que sea estable, el driver debería aparecer en pocos días en los repositorios habituales de cada distribución. Si quieres saber más en profundidad lo que trae este nuevo driver tienes toda la información en este enlace.

In the latter half of the twentieth century, there began a phenomenon known as the information revolution. While the information revolution is a historical development broader in scope than any one event or machine, no single device has come to represent the information revolution more than the digital electronic computer. The development of computer systems has surely been a revolution. Each year, computer systems grow faster, store more data, and provide more applications to their users. A modern computer system is an enormously complex machine, usually having many sub-parts or subsystems. Typically, the system comprises one or more central processing units (CPUs) which form the heart of the system, and which execute instructions contained in computer programs stored in memory. The system further includes data storage devices, such as rotating disk drives, and hardware necessary to communicate with the outside world, such as input/output controllers; I/O devices attached thereto such as keyboards, monitors, printers, and so forth; and external communication devices for communicating with other digital systems. Computer systems, and particularly large multi-user computer systems, typically have many components which can be configured to operate or interact in a variety of different ways. Various configuration parameters specify modes of operation, resource allocation, operating speeds, limits, and so forth, of these components. These configuration parameters are subject to change, sometimes as a result of automated processes, sometimes through manual intervention by a system administrator, user, or other person. One example of configuration variability is logical partitioning. Conceptually, logical partitioning means that multiple discrete partitions are established in a single hardware system, and the system resources of certain types are assigned to respective partitions. For example, processor resources of a multi-processor system may be partitioned by assigning different processors to different partitions, by sharing processors among some partitions and not others, by specifying the amount of processing resource measure available to each partition which is sharing a set of processors, and so forth. Memory or other resources may also be partitioned. In general, tasks executing within a logical partition can use only the resources assigned to that partition, and not resources assigned to other partitions. Nearly any configuration parameter of a computer system may affect how executing tasks perform, and ultimately the efficiency of the system as a whole. These effects may be severe, causing drastic loss of system efficiency and/or unacceptable response time. Different components interact in many complex ways, so that a parameter with respect to one component may affect the performance of many others. It is extremely difficult to model or predict in advance the effect of configuration changes or the performance of hypothetical configurations. Moreover, the computer system and its environment are very dynamic. Some configuration parameters are subject to frequent change by automated processes. Workload changes, randomly, periodically, and as a result of long-term trends. User expectations change. Managing system configuration parameters for optimum efficiency in a large computer system can therefore be a daunting task. Conventional methods for managing configuration parameters often involve gathering substantial amounts of performance data over relatively long intervals and analyzing that data to model the system, identify probable sources of system inefficiency, and predict the effect of configuration changes. This analysis is often performed manually by human experts, although there are analytical programs which can be used for this purpose, either alone or in conjunction with human expertise. The use of human experts necessarily means that considerable cost is involved in this process. Moreover, the need to collect a large amount of data and perform complex analysis generally means that the analysis and consequent actions are performed well after the data collection, and can not respond to rapid changes in real time. Finally, modeling of hypothetical configurations is difficult to perform reliably and accurately for all possible permutations of system hardware and software, workload, and configuration parameters. With increasing complexity of computer systems, there is a need for improved techniques for managing configuration parameters in a computer system.

Milesburg, Pennsylvania Milesburg is a borough in Centre County, Pennsylvania. It is part of the State College, Pennsylvania Metropolitan Statistical Area. The population was 1,123 at the 2010 census. History Milesburg, as well as nearby Miles Township was named after Colonel Samuel Miles, who co-owned the Centre Furnace Iron Works, along with Colonel John Patton and John Dunlop. Milesburg is on (or near) the site of a former Lenape Indian settlement known as Bald Eagle's Nest. The Iddings-Baldridge House was added to the National Register of Historic Places in 1977. Geography Milesburg is located at (40.942533, -77.789207). According to the United States Census Bureau, the borough has a total area of , all of it land. Demographics As of the census of 2010, there were 1,123 people, 459 households, and 305 families residing in the borough. The population density was 2,503.4 people per square mile (966.8/km²). There were 489 housing units at an average density of 1,090.1 per square mile (421.0/km²). The racial makeup of the borough was 98.7% White, 0.4% Black or African American, 0.1% Native American, 0.4% Asian, 0.2% other, and 0.2% from other races. Hispanic or Latino of any race were 0.3% of the population. There were 459 households, out of which 29.8% had children under the age of 18 living with them, 47.3% were married couples living together, 6.2% had a male householder with no wife present, 12.9% had a female householder with no husband present, and 33.6% were non-families. 26.6% of all households were made up of individuals, and 8.5% had someone living alone who was 65 years of age or older. The average household size was 2.45 and the average family size was 2.77. In the borough the population was spread out, with 19.1% under the age of 18, 8.8% from 18 to 24, 25.3% from 25 to 44, 29.3% from 45 to 64, and 17.5% who were 65 years of age or older. The median age was 42 years. For every 100 females there were 89.1 males. For every 100 females age 18 and over, there were 87.8 males. The median income for a household in the borough was $45,588, and the median income for a family was $51,597. The per capita income for the borough was $19,310. About 5.0% of families and 7.2% of the population were below the poverty line, including 1.7% of those under age 18 and 3.4% of those age 65 or over. References Category:Populated places established in 1793 Category:Boroughs in Centre County, Pennsylvania Category:1843 establishments in Pennsylvania

Coordinated transformation of the gut microbiome and lipidome of bowhead whales provides novel insights into digestion. Whale digestion plays an integral role in many ocean ecosystems. By digesting enormous quantities of lipid-rich prey, whales support their energy intensive lifestyle, but also excrete nutrients important to ocean biogeochemical cycles. Nevertheless, whale digestion is poorly understood. Gastrointestinal microorganisms play a significant role in vertebrate digestion, but few studies have examined them in whales. To investigate digestion of lipids, and the potential contribution of microbes to lipid digestion in whales, we characterized lipid composition (lipidomes) and bacterial communities (microbiotas) in 126 digesta samples collected throughout the gastrointestinal tracts of 38 bowhead whales (Balaena mysticetus) harvested by Alaskan Eskimos. Lipidomes and microbiotas were strongly correlated throughout the gastrointestinal tract. Lipidomes and microbiotas were most variable in the small intestine and most similar in the large intestine, where microbiota richness was greatest. Our results suggest digestion of wax esters, the primary lipids in B. mysticetus prey representing more than 80% of total dietary lipids, occurred in the mid- to distal small intestine and was correlated with specific microorganisms. Because wax esters are difficult to digest by other marine vertebrates and constitute a large reservoir of carbon in the ocean, our results further elucidate the essential roles that whales and their gastrointestinal microbiotas play in the biogeochemical cycling of carbon and nutrients in high-latitude seas.

Kelly Frederick Kelly Frederick (born October 7, 1978) is an Antigua and Barbudan football player. He plays for Antigua and Barbuda national team. National team statistics References Category:1978 births Category:Living people Category:Antigua and Barbuda footballers Category:Antigua and Barbuda international footballers Category:Association football forwards

Studies on metabolic regulation using NMR spectroscopy. The effects of hypoxia and hypoglycaemia on cerebral metabolism and calcium have been studied using multinuclear magnetic resonance spectroscopy. 13C MRS showed that severe hypoxia did not cause any further increase in metabolic flux into lactate seen in mild hypoxia, but there was a further increase in 13C labelling of alanine and glycerol 3-phosphate. These results are discussed in terms of the ability of lactate dehydrogenase to maintain normal levels of NADH in mild hypoxia, but not in severe hypoxia. We conclude that glycerol 3-phosphate and alanine may provide novel means of monitoring severe hypoxia whereas lactate is a reliable indicator only of mild hypoxia. 19F- and 31P NMR spectroscopy showed that neither hypoxia nor hypoglycaemia alone caused any significant change in [Ca2+]i. Combined sequential insults (hypoxia, followed by hypoxia plus hypoglycaemia), or vice versa, produced a 100% increase in [Ca2+]i, whereas immediate exposure to the combined insult (hypoxia plus hypoglycaemia) resulted in a large 5-fold increase in [Ca2+]i, with severe irreversible effects on the energy state. These results are discussed in terms of metabolic adaptation to the single type of insult, which renders the tissue less vulnerable to the combined insult. The effects of this combined insult are far more severe than those caused by glutamate or NMDA, which throws doubt on the current excitoxic hypothesis of cell damage.

Earlier this month one of my new FB friends, Maria, who actively participates on my SB Canning page challenged me to come up with a jam that had the flavor that she loved during the holidays. That flavor was gingerbread. Now being a long time lover of making gingerbread houses, gingerbread cookies, and gingerbread pumpkin bread I instantly had an idea of the ingredients needed and took that challenge. I did a small batch and presented it for her to try. I thought the flavors were, as they say spot on, and on a scale of simple to complex, this was easy even for the beginner. Maria then went into action and create her version which has many layers of flavor and the amount of different ingredients and spices gave hers a very gourmet feel and flavor. A bit more complex for a beginning canner, but at our canning group today the verdict was in. I wanted to make sure that I didn’t cloud the group by telling them about the challenge but had them do Maria’s recipe as part of their extravaganza today. Once the recipe was complete I pulled out the jar I had of my recipe for them to try. They thought they were tasting what the end result would be that was in the pot, so I had to explain. Here are the two recipes, mine now converted to a full batch, for you to try and decide for yourself. I don’t want to cloud your judgement by telling you which they liked best. If you get a chance to make both, please comment below on which you like! Enjoy! Gingerbread Jam Gingerbread Jam (SB Canning version) Print Recipe Pin Recipe Prep Time 10 mins Cook Time 1 hr Total Time 1 hr 10 mins Course Dessert Cuisine American Servings 30 Ingredients 6 cups apples, peeled and chopped (Sweet apples not tart!) 4 T. crystallized ginger, minced 1 cup molasses, original (not unsulfured) 1 1/2 cup sugar 1 t. ground ginger 2 T. bottled lemon juice Instructions Cook down apples for 20 minutes in a stainless steel pot till soft adding 1/2 cup water(or apple juice) so the apples don't burn. Add all the rest of the ingredients and continue to cook, mashing the apples, and creating a smooth consistency. You can use an immersion blender to get the texture you want. Ladle the recipe into a 5 sterilize half pint jar leaving 1/4" headspace. Remove air, wipe rims, and add hot lids/rings. Water bath for 10 minutes once the water has come back to a full boil. Keyword Gingerbread Jam

Q: L-series of difference of two cusp forms Let $f=\sum_{n\geq 1} a_nq^n$ and $g=\sum_{n\geq 1} b_nq^n$ be two distinct cusp eigenforms of same weight $k\geq 2$ with real Fourier coefficients. We normalize the coefficients by defining: $\widetilde {a_n}:=\frac{a_n}{n^{(k-1)/2}}$ and similarly $\widetilde{b_n}:=\frac{b_n}{n^{(k-1)/2}}$. I was wondering if there is a quick way to see that $$\sum_{p-prime}\frac {\widetilde{a_p}-\widetilde{b_p}}{p^s}$$ is bounded as $s\to 1^{+}$. A: Let $L(s,f)$ denote the $L$-function of a Hecke eigenform $f$, normalised so that the critical line is $\Re(s) = 1/2$. Then for $\Re(s) > 1$, \[L(s,f) = \prod_p \frac{1}{1 - \lambda_f(p) p^{-s} + p^{-2s}} = \prod_p \frac{1}{(1 - \alpha_f(p) p^{-s}) (1 - \beta_f(p) p^{-s})},\] where $\lambda_f(p)$ is the normalised $p$-th Hecke eigenvalue and $\alpha_f(p) + \beta_f(p) = \lambda_f(p)$, $\alpha_f(p) \beta_f(p) = 1$; by Deligne's proof of the Ramanujan conjecture, $|\alpha_f(p)| = |\beta_f(p)| = 1$. It follows that for $\Re(s) > 1$, \[\log L(s,f) = \sum_{p} \frac{\lambda_f(p)}{p^s} + \sum_{p} \sum_{k = 2}^{\infty} \frac{\alpha_f(p)^k + \beta_f(p)^k}{kp^{ks}},\] and the second term is uniformly bounded as $s \searrow 1$ (in fact, this only requires the weaker bound $|\alpha_f(p)|, |\beta_f(p)| \leq p^{1/2 - \delta}$ for some $\delta > 0$). Moreover, the $L$-function $L(s,f)$ is nonvanishing and has no poles on the line $\Re(s) = 1$ (by the usual proof of the prime number theorem; see chapter 5 of Iwaniec and Kowalski), so $\log L(s,f) \to \log L(1,f)$ as $s \searrow 1$. In particular, it follows that $\sum_{p} \frac{\lambda_f(p)}{p^s}$ is bounded as $s \searrow 1$, and the same is obviously true for $\sum_{p} \frac{\lambda_f(p) - \lambda_g(p)}{p^s} = \sum_{p} \frac{\lambda_f(p)}{p^s} - \sum_{p} \frac{\lambda_g(p)}{p^s}$. Similarly, let $L(s,\mathrm{sym}^2 f)$ denote the symmetric square $L$-function, so that for $\Re(s) > 1$, \[L(s,f) = \prod_p \frac{1}{1 - \lambda_f(p^2) p^{-s} + \lambda_f(p^2) p^{-2s} - p^{-3s}} = \prod_p \frac{1}{(1 - \alpha_f(p)^2 p^{-s}) (1 - p^{-s}) (1 - \beta_f(p)^2 p^{-s})}.\] Then for $\Re(s) > 1$, \[\log L(s,\mathrm{sym}^2 f) = \sum_{p} \frac{\lambda_f(p^2)}{p^s} + \sum_{p} \sum_{k = 2}^{\infty} \frac{\alpha_f(p)^{2k} + 1 + \beta_f(p)^{2k}}{kp^{ks}}.\] Again, $L(s,\mathrm{sym}^2 f)$ is nonvanishing and has no poles on the line $\Re(s) = 1$ (though when the nebentypus is nonprincipal, there may be a pole; see this question). So the same argument goes through (though this time, we need bounds towards the generalised Ramanujan conjecture of the form $|\alpha_f(p)|, |\beta_f(p)| \leq p^{1/4 - \delta}$ for some $\delta > 0$, which is certainly known).

From ... From: Erik Naggum Subject: Re: clisp: compile Lisp program to stand alone binary? Date: 1998/10/05 Message-ID: <[email protected]>#1/1 X-Deja-AN: 397865928 References: <[email protected]> mail-copies-to: never Organization: Naggum Software; +47 8800 8879; http://www.naggum.no Newsgroups: comp.lang.lisp * [email protected] (David Steuber "The Interloper") | Can clisp create a binary executable that can be distributed without | relying on lisp being on the other machine? no. (the same is true for all other languages, incidentally. C just happens to have its run-time system pre-shipped with many systems.) what is the problem with shipping a file to be loaded into CLISP? | cmu doesn't seem to be available for Linux. Am I blind, or is this true? can't say you aren't blind, but CMUCL is available for Linux. #:Erik

Awards Tangaroa Blue Foundation and the Australian Marine Debris Initiative have been acknowledged on local, state and national platforms. Each award acknowledges the vast numbers of Tangaroa Blue volunteers and Australian Marine Debris Initiative partners who assist in removing tonnes of marine debris from our environment every year, documenting the hundreds of thousands of items removed for the Australian Marine Debris Database, and work tirelessly in their communities to prevent marine debris and litter by stopping it at the source. The Department of Agriculture, Fisheries and Forestry (DAFF) recently presented a Regional Biosecurity Commendation award to Tangaroa Blue for their cooperation and contribution in maintaining Australia's biosecurity status in northern Australia. Tangaroa Blue is a not-for-profit environmental charity that has a large network of volunteers and conducts beach monitoring/clean-up and logs data on marine debris collected. As NAQS also conducts coastal marine debris surveillance, Tangaroa Blue agreed to place important biosecurity information in their training materials, detailing the reporting process of biosecurity risk material to the department.

Rotational energy Rotational energy or angular kinetic energy is kinetic energy due to the rotation of an object and is part of its total kinetic energy. Looking at rotational energy separately around an object's axis of rotation, the following dependence on the object's moment of inertia is observed: where is the angular velocity is the moment of inertia around the axis of rotation is the kinetic energy The mechanical work required for or applied during rotation is the torque times the rotation angle. The instantaneous power of an angularly accelerating body is the torque times the angular velocity. For free-floating (unattached) objects, the axis of rotation is commonly around its center of mass. Note the close relationship between the result for rotational energy and the energy held by linear (or translational) motion: In the rotating system, the moment of inertia, I, takes the role of the mass, m, and the angular velocity, , takes the role of the linear velocity, v. The rotational energy of a rolling cylinder varies from one half of the translational energy (if it is massive) to the same as the translational energy (if it is hollow). An example is the calculation of the rotational kinetic energy of the Earth. As the Earth has a period of about 23.93 hours, it has an angular velocity of 7.29×10−5 rad/s. The Earth has a moment of inertia, I = 8.04×1037 kg·m2. Therefore, it has a rotational kinetic energy of 2.138×1029 J. A good example of actually using earth's rotational energy is the location of the European spaceport in French Guiana. This is within about 5 degrees of the equator, so space rocket launches (for primarily geo-stationary satellites) from here to the east obtain nearly all of the full rotational speed of the earth at the equator (about 1,000 mph, sort of a "sling-shot" benefit). This saves significant rocket fuel per launch compared with rocket launches easterly from Kennedy Space Center (USA), which obtain only about 900 mph added benefit due to the lower relative rotational speed of the earth at that northerly latitude of 28 degrees. Part of the earth's rotational energy can also be tapped using tidal power. Additional friction of the two global tidal waves creates energy in a physical manner, infinitesimally slowing down Earth's angular velocity ω. Due to the conservation of angular momentum, this process transfers angular momentum to the Moon's orbital motion, increasing its distance from Earth and its orbital period (see tidal locking for a more detailed explanation of this process). See also Flywheel List of energy storage projects Rigid rotor Rotational spectroscopy References Category:Forms of energy Category:Rotation

NGC 3227 NGC 3227 is an intermediate spiral galaxy that is interacting with the dwarf elliptical galaxy NGC 3226. The two galaxies are one of several examples of a spiral with a dwarf elliptical companion that are listed in the Atlas of Peculiar Galaxies. Both galaxies may be found in the constellation Leo. Sir William Herschel already recognised them as a 'double nebula' and they were jointly listed as Holm 187 in the Catalogue of Double and Multiple Galaxies and as Arp 94 in the Atlas of Peculiar Galaxies. Amateur telescopes can discern them but require magnification of about 100 times. They are situated 50′ east of the well-known double star system Gamma Leonis (i.e. Algieba). Nucleus NGC 3227 contains a Seyfert nucleus, a type of active galactic nucleus (AGN). Such Seyfert nuclei typically contain supermassive black holes. This object has an estimated mass of . As is typical of many AGN, the nucleus of NGC 3227 has been identified as a source of variable X-ray emission. This variability occurs on time scales ranging from a few hours to a few months. The variability may be caused by variations in the density or ionization of gas and dust near the AGN that absorb the X-ray emission. A substantial amount of the X-ray-absorbing gas may lie within 0.4 parsec (1.3 light-years) of the nucleus. An observed change in the shape of the X-ray spectrum in 2000 and 2001 suggests that some of the X-ray absorbing gas is located within 10–100 light-days of the nucleus. The luminosity of the nucleus reached a maximum in 1977 when evidence suggesting long-lived one-sided or two-sided gas streams was obtained. X-ray radiation of the central accretion disc is reprocessed in one to two days to be re-emitted in the optical spectrum. Infra-red light emission from the hot dust torus lags optical light emission from the nucleus by about 20 days in NGC 3227. The temperature of the dust torus is estimated at 1500 K to 1800 K in NGC 3227 and similar galaxies. This galaxy was studied by the Multicolor Active Galactic Nuclei Monitoring 2m telescope. References Catalogue of Double and Multiple Galaxies, Erik Holmberg, 1937 A catalogue of dwarf galaxy candidates around interacting galaxies, Astron. Astrophys., Suppl. Ser., 129, 455-462 (1998) - May(I) 1998, Deeg, H.J. et al. Long-term variability of the optical emission lines in the nuclear spectrum of the Seyfert galaxy NGC 3227, Active Galaxies Newsletter, No 98, Pronik I., Metik L., May 2005 Reverberation Measurements of the Inner Radius of the Dust Torus in Nearby Seyfert 1 Galaxies, M. Suganuma et al., Astrophysical Journal, vol 639, March 2006 External links Glen Youman's Astrophotos of NGC 3226 and NGC 3227 Cosmic Voyages webpage on NGC 3226 and NGC 3227 Spitzer observations of the interacting galaxy pair Long-term variability of the optical emission lines in the nuclear spectrum of the Seyfert galaxy NGC 3227, Pronik et al., Active Galaxies Newsletter, No. 98 Reverberation Measurements of the Inner Radius of the Dust Torus in Nearby Seyfert 1 Galaxies, Suganuma et al., ApJ, March 2006, vol. 639 Category:Seyfert galaxies Category:Intermediate spiral galaxies Category:Peculiar galaxies Category:Leo (constellation) 3227 05620 30445 094 17840215

Q: Is it idiomatic to say "please always close the door behind you"? my sister's bedroom is face to my bedroom and she play music loudly, which is disturbing me. So, I said to her, please always close the door behind you. I would like to have her remember this, and close the door next time without my reminder, close our own doors to avoid disturbing each other. Is it an idiomatic expression? A: "Always" may sound more commanding than you want and actually if you are not her boss, it may not be justifiable to say that. "Behind you" is redundant when it's obvious, so you end up with "Close the door, please." If she's a decent human being, she'll understand even better if you give here some reasoning: I try to study (sleep, or so), and your music is disturbing me, so would you...? If you have a good reason, you'll find the right words.

Q: Chrome Extension webRequest.onBeforeRequest Cancel Page I am attempting to create a chrome extension that queries an external source as a reference to block or allow through a particular page. The following is part of my code. I am new to javascript, and scope always seems to be something that screws me up. chrome.webRequest.onBeforeRequest.addListener( function(details) { var http = new XMLHttpRequest(); var url = "http://xxx.xx.xxxx"; var params = "urlCheck="+encodeString_(details.url); http.open("POST", url, true); //Send the proper header information along with the request http.setRequestHeader("Content-type", "application/x-www-form-urlencoded"); http.onreadystatechange = function() { if(http.readyState == 4 && http.status == 200) { guilt = 0; console.log(guilt); }else if(http.readyState == 4 && http.status == 404){ guilt = 1; console.log(guilt); } } http.send(params); if(guilt == 1){ return {cancel: true}; }else{ return {cancel: false}; } }, {urls: ["<all_urls>"], types:["main_frame"] }, ["blocking"] ); Any help would be greatly appreciated! Thanks. A: You can't do that. Your code does not work as expected because XHR is asynchronous; your onreadystatechange is executed after the whole outer function finishes. So guilt will be undefined or, worse, stale (from the last request). For more information, see this canonical question: Why is my variable unaltered after I modify it inside of a function? However, if you try to fix this, you'll notice that you can't return a response from within the async handler. This is intentional: there is no function to pass and then call later (like sendResponse in Messaging API), because Chrome will not wait for you. You are expected to respond to a blocking call in a deterministic and fast way. If the optional opt_extraInfoSpec array contains the string 'blocking' (only allowed for specific events), the callback function is handled synchronously. That means that the request is blocked until the callback function returns. You could try to bypass it by using synchronous XHR calls. That is not a very good idea in general, since loading a remote response takes a long time, and synchronous XHR is considered deprecated. Even though you limited your queries to "main_frame" requests, this still adds an uncertain delay to each load. A proper way to do that would be to load a set of rules from a server and update it periodically, and when a request occurs validate it against this local copy of rules. This is the approach extensions like AdBlock use.

Ranger Independent School District Ranger Independent School District is a public school district based in Ranger, Texas (USA). Located in Eastland County, a small portion of the district extends into Stephens County. Schools Ranger ISD has three campuses - Ranger High School (grades 9-12), Ranger Middle School (grades 6-8) and Ranger Elementary School (grades PK-5). Ranger College was part of the district until 1950, when it became a separate community college entity. Walter Prescott Webb (1888-1963), historian of the American West and author of the classic The Great Plains (1931), graduated from Ranger High School about 1905. In 2009, the school district was rated "academically acceptable" by the Texas Education Agency. References External links Ranger ISD Category:School districts in Texas Category:School districts in Eastland County, Texas Category:School districts in Stephens County, Texas

How to stop an if statement i have these two if statements. if a the updateUser.text = "Add User" And LicenseDB.AddUser(userProfile) then step one should run =============================================one========== If btnUpdateUser.Text = "Add User" And LicenseDB.AddUser(userProfile) Then Me.ClearFields() lblmsg.Text = "The user has been added." Else lblmsg.Text = "That user details already exists." End If else two should run ==========================two============================ If btnUpdateUser.Text = "Update User" And LicenseDB.UpdateUser(userProfile) Then Me.ClearFields() lblmsg.Text = "The user has been updated." Else lblmsg.Text = "That user details already exists." End If Me.SetControlState(ControlState.NoSelection) LoadData() the proble is that when i add a user it displays lblmsg.Text = "That user details already exists." ============from step two. If btnUpdateUser.Text = "Add User" then if LicenseDB.AddUser(userProfile) Then Me.ClearFields() lblmsg.Text = "The user has been added." Else lblmsg.Text = "That user details already exists." end if End If If btnUpdateUser.Text = "Update User" then if LicenseDB.UpdateUser(userProfile) Then Me.ClearFields() lblmsg.Text = "The user has been updated." Else lblmsg.Text = "That user details already exists." end if End If 1.0 - Introduction Converting Visual Basic 6.0 (VB6) to Visual Basic 2008+ (VB.NET). If ever there was a subject full of murkiness and bad decisions, it is this one! The first problem seems to be that people considering this task of converting… It was really hard time for me to get the understanding of Delegates in C#. I went through many websites and articles but I found them very clumsy. After going through those sites, I noted down the points in a easy way so here I am sharing that unde… If you’ve ever visited a web page and noticed a cool font that you really liked the look of, but couldn’t figure out which font it was so that you could use it for your own work, then this video is for you! In this Micro Tutorial, you'll learn yo… Have you created a query with information for a calendar? ... and then, abra-cadabra, the calendar is done?! I am going to show you how to make that happen. Visualize your data! ... really see it To use the code to create a calendar from a q…

package io.digdag.standards.auth.jwt; import com.google.inject.Inject; import io.digdag.spi.Authenticator; import io.jsonwebtoken.Claims; import io.jsonwebtoken.JwsHeader; import io.jsonwebtoken.JwtException; import io.jsonwebtoken.Jwts; import io.jsonwebtoken.SignatureException; import io.jsonwebtoken.SigningKeyResolver; import org.slf4j.Logger; import org.slf4j.LoggerFactory; import javax.crypto.spec.SecretKeySpec; import javax.ws.rs.container.ContainerRequestContext; import java.security.Key; import java.util.Map; public class JwtAuthenticator implements Authenticator { private static final Logger logger = LoggerFactory.getLogger(JwtAuthenticator.class); private final JwtAuthenticatorConfig config; @Inject public JwtAuthenticator(JwtAuthenticatorConfig config) { this.config = config; } @Override public Result authenticate(ContainerRequestContext requestContext) { int siteId; boolean admin; String auth = requestContext.getHeaderString("Authorization"); if (auth == null) { if (config.isAllowPublicAccess()) { // OK siteId = 0; admin = true; } else { return Result.reject("Authorization is required"); } } else { String[] typeData = auth.split(" ", 2); if (typeData.length != 2) { return Result.reject("Invalid authorization header"); } if (!typeData[0].equals("Bearer")) { return Result.reject("Invalid authorization header"); } String token = typeData[1]; try { Map<String, UserConfig> userMap = config.getUserMap(); String subject = Jwts.parser().setSigningKeyResolver(new SigningKeyResolver() { @Override public Key resolveSigningKey(JwsHeader header, Claims claims) { Object keyType = header.get("knd"); if (keyType == null || !"ps1".equals(keyType)) { throw new SignatureException("Invalid key type"); } UserConfig user = userMap.get(claims.getSubject()); if (user == null) { throw new SignatureException("Invalid subject"); } return new SecretKeySpec(user.getApiKey().getSecret(), header.getAlgorithm()); } @Override public Key resolveSigningKey(JwsHeader header, String plaintext) { throw new SignatureException("Plain text JWT authorization header is not allowed"); } }) .parseClaimsJws(token) .getBody() .getSubject(); UserConfig user = userMap.get(subject); if (user == null) { throw new SignatureException("Invalid subject"); } siteId = user.getSiteId(); admin = user.isAdmin(); } catch (JwtException ex) { logger.trace("Authentication failed: ", ex); return Result.reject("Authorization failed"); } } return Result.builder() .siteId(siteId) .isAdmin(admin) .build(); } }

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The common mold, Aspergillus fumigatus, is an opportunistic pathogen and the most frequently isolated causative agent of invasive aspergillosis. The disease is often contracted by immunocompromised hosts, including cancer patients, with reported mortality rates >80%. Our long-term goals are to develop a vaccine and to provide better means for the early diagnosis and monitoring of aspergillosis. Our specific hypotheses are: 1) certain aspergillus antigens have an immunoprotective effect, and 2) some antigens may serve as indicators of early stages of aspergillus infections. We base our hypotheses on the following observations. First, mice vaccinated with crude fungal protein extracts or viable conidia survive infection following immunosuppression (e.g., with corticosteroid treatment). Second, the fungus actively secretes a variety of specific proteins and peptides at different stages of its lifecycle. More than 60 antigens and allergens of Aspergillus have been described (1-4). However, only one of them, the polysaccharide galactomannan, is routinely assayed to diagnose Aspergillus infections. Based on these observations, our experimental focus is on the identification and structural and immunological characterization of A. fumigatus antigens. We plan to utilize and improve novel mass spectrometric techniques to detect and identify proteins and peptides of fungal origin from complex mixtures such as culture supernatants, bronchoalveolar lavage (BAL) fluid, blood and urine.

Induction of DNA damage and p21-dependent senescence by Riccardin D is a novel mechanism contributing to its growth suppression in prostate cancer cells in vitro and in vivo. Our previous studies had shown that Riccardin D (RD) exhibited cytotoxic effects by induction of apoptosis and inhibition of angiogenesis and topoisomerase II. Here, we reported that apoptosis is not the sole mechanism by which RD inhibits tumor cell growth because low concentrations of RD caused cellular senescence in prostate cancer (PCa) cells. Low concentrations of RD were used to treat PCa cells in vitro and in vivo, and senescence-associated β-galactosidase activity, DNA damage response markers, and/or colony-forming ability, cell cycle were analyzed, respectively. We then used siRNA knockdown to identify key factor in RD-triggered cellular senescence. RD treatment caused growth arrest at G0/G1 phase with features of cellular senescence phenotype such as enlarged and flattened morphology, increased senescence-associated-beta-galactosidase staining cells, and decreased cell proliferation in PCa cells. Induction of cellular senescence by RD occurred through activation of DNA damage response including increases in the phosphor-H2AX, inactivation of Chk1/2, and suppression of repair-related Ku70/86 and phosphor-BRCA1 in PCa cells in vitro and in vivo. Analysis of expression levels of p53, p21(CIP1), p16(INK4a), p27(KIP1), pRb and E2F1 and genetic knockdown of p21(CIP1) demonstrated an important role of p21(CIP1) in RD-triggered cellular senescence. Involvement of the DNA damage response and p21(CIP1) defines a novel mechanism of RD action and indicates that RD could be further developed as a promising anticancer agent for cancer therapy.

of 7 and -488. -3416 Calculate -25.5*-2.8. 71.4 Product of -1 and 0.184. -0.184 -0.081*4 -0.324 Multiply -1.5 and -9. 13.5 79 times 0 0 Product of 0.1553 and 0.9. 0.13977 What is -4966 times -1? 4966 Multiply 0 and 786. 0 -11.42 * -0.12 1.3704 Multiply 0.38 and 0.063. 0.02394 What is 0.04079 times -0.2? -0.008158 0.078 * -0.2 -0.0156 What is the product of 3.8 and -1.39? -5.282 -2224 * -2 4448 What is 0.859 times -41? -35.219 276.8*-2 -553.6 -16*-2.1 33.6 What is the product of -0.8062 and 1? -0.8062 Calculate -12.8*0.2. -2.56 Work out -4.6 * 94. -432.4 Calculate 4*723. 2892 Multiply 5035 and 2. 10070 What is -1 times 275? -275 1.255*0.1 0.1255 0.38*-1 -0.38 Product of 0.05 and 9.7. 0.485 5 times -446 -2230 Calculate 0.3*0.53. 0.159 -1148 * 3 -3444 2*-59 -118 Multiply 0.1 and -1.363. -0.1363 -9 * 4.9 -44.1 What is -3.6 times -0.14? 0.504 -0.12 * -1.4 0.168 Calculate 0.025*-101. -2.525 What is the product of -2 and 0.6? -1.2 What is 0.68 times -0.2? -0.136 -25 * -2.02 50.5 What is the product of 685 and -0.3? -205.5 -0.5 times -55 27.5 0.284 times -0.15 -0.0426 Calculate -157*0.07. -10.99 -0.063 * -3 0.189 What is the product of -0.2 and -0.2? 0.04 Work out -0.16 * -2.3. 0.368 Work out -0.895 * 0. 0 -0.4 * 0.24 -0.096 Product of -13 and -1.3. 16.9 Multiply 0.04 and 179. 7.16 -873 times -4 3492 Multiply -0.1 and 72.4. -7.24 Product of 2.04 and 33. 67.32 Work out -212.2 * -0.06. 12.732 Calculate -0.38*11. -4.18 -1.1631 * -5 5.8155 Multiply 0.3984 and -0.4. -0.15936 -4523 * -0.3 1356.9 What is -0.06772 times 1? -0.06772 Product of 0.54 and 0.9. 0.486 What is -0.0463 times -4? 0.1852 Calculate 80*-5. -400 1.9 times 0.64 1.216 Calculate 0.1*5. 0.5 -5*-3.83 19.15 Calculate -0.576*0.1. -0.0576 Product of 15739 and 5. 78695 Work out 2574 * -1. -2574 Work out -0.4 * -26. 10.4 What is -2 times -180? 360 What is -14976 times 0.5? -7488 Multiply 5.2 and -5. -26 Multiply -38451 and -5. 192255 What is 171.35 times -0.5? -85.675 4*4321 17284 10*91.1 911 What is 0.48 times 3? 1.44 What is -0.5 times 0.05? -0.025 Multiply -1.3 and -100. 130 -0.6 times -96 57.6 Product of 1 and -0.214. -0.214 -17.7 * -4 70.8 Product of 9 and 0.2. 1.8 -1 * -180 180 Multiply 21 and 13. 273 Product of 115 and 1.5. 172.5 Work out 0 * 263. 0 Work out 4 * 54.6. 218.4 Work out -2.5 * 0.01. -0.025 Multiply 21 and -4. -84 What is the product of 1407 and -0.1? -140.7 -0.2*210 -42 Calculate 77*0.04. 3.08 What is 0.4 times 0.328? 0.1312 Multiply 0.7 and 124. 86.8 -4*-120 480 What is 0.55 times -0.6? -0.33 Product of -2125 and 0.3. -637.5 What is 250 times 5? 1250 -12 * -4 48 -797 * 0.2 -159.4 Work out -0.1 * 2728. -272.8 What is the product of -0.5 and 10.2? -5.1 Product of 0.06 and -4.6. -0.276 Work out -2.34 * 0.4. -0.936 What is the product of 52 and 0.023? 1.196 Multiply 5 and -3225. -16125 Work out -0.2 * -50. 10 -157 * -0.5 78.5 What is the product of 0.2 and 0.04? 0.008 Calculate -0.56*0.3. -0.168 Calculate -4*-6. 24 Multiply -1 and 0.0583. -0.0583 2 times -60 -120 What is 0.81 times -0.1? -0.081 Multiply 0 and 9. 0 What is the product of -0.1 and -0.014? 0.0014 Calculate 0*-28. 0 -1003 * -4 4012 What is 9 times 2915? 26235 Product of 1.3 and 5. 6.5 What is the product of -1.45 and 0.19? -0.2755 What is the product of -33 and 23.8? -785.4 Product of -2 and 58.4. -116.8 Multiply 0.14 and 13.4. 1.876 1292*0.02 25.84 Product of 49 and 3. 147 Calculate 0.3*-1.904. -0.5712 What is -1.24 times 7? -8.68 Work out -6 * 18.83. -112.98 What is 1661 times 5? 8305 Multiply -0.056 and -0.01. 0.00056 What is the product of 217 and -2? -434 What is -0.0806 times -0.4? 0.03224 Work out -620 * 0.5. -310 What is the product of -247 and 4? -988 Multiply -3 and -5. 15 Product of 20.97 and 5. 104.85 Work out -5.05 * -0.3. 1.515 Multiply -0.4 and -3188. 1275.2 Work out 0.2 * -735. -147 Calculate 5*20. 100 Multiply 0.2 and -0.0178. -0.00356 What is the product of -2 and 4133? -8266 0 * -943 0 Multiply 202 and -0.01. -2.02 -28 times -0.4 11.2 Product of 7837 and 3. 23511 Product of 1.2 and 4. 4.8 15237*0.4 6094.8 What is the product of -0.1 and -60? 6 Work out -0.1 * 1.3. -0.13 Multiply -66580 and 5. -332900 -7915 times 0.2 -1583 What is the product of 17 and -4? -68 0.4*-274 -109.6 Multiply 1.4 and -1.7. -2.38 What is the product of 51 and 0.2? 10.2 What is the product of -5 and 2.7? -13.5 Work out -1 * -95. 95 Work out -11.8 * 29. -342.2 Calculate 14967*0.1. 1496.7 What is the product of 2514 and -0.1? -251.4 What is -2 times 58? -116 Product of -5 and -4. 20 Work out -0.1 * 0.56. -0.056 What is 12.24 times 0.2? 2.448 Multiply 107 and -0.2. -21.4 Multiply 15 and -8. -120 Work out 0.04 * 35. 1.4 What is 76 times 227? 17252 Work out -4235 * -0.2. 847 -4337*-1 4337 What is 0.1 times -0.037? -0.0037 What is -60 times -0.03? 1.8 180 times -0.4 -72 -0.15 times 1.7 -0.255 Calculate 5*25. 125 1392 * -0.1 -139.2 Calculate -1.13*-0.12. 0.1356 16 * 148 2368 Work out -5327 * -0.7. 3728.9 -0.3 times 86 -25.8 -0.2 * -767 153.4 0.37 times -28 -10.36 What is -8 times -270? 2160 -0.29 times -10.6 3.074 -40 times 0.37 -14.8 Product of -0.98 and 7. -6.86 What is -0.03 times -3.4? 0.102 Multiply -5398 and -0.5. 2699 Product of 2 and -18.3. -36.6 Calculate -15.5*-1.7. 26.35 What is 2.93 times 5? 14.65 0.14739 times -0.4 -0.058956 Calculate -955*0.09. -85.95 -84 times -0.03 2.52 What is the product of -0.01 and -56? 0.56 -48 * -1 48 Product of 0 and -2810. 0 Multiply -0.131 and -82. 10.742 Work out 217 * -87. -18879 What is the product of 5 and 3543? 17715 Multiply 38 and -2.9. -110.2 Calculate 0*-32. 0 -0.5 * 226.9 -113.45 Work out -0.3 * -346. 103.8 4.521*-0.5 -2.2605 Product of -12 and -0.053. 0.636 Multiply -0.004 and -16. 0.064 What is -83.32 times 0.2? -16.664 Work out -4 * 0.504. -2.016 Product of -247 and 0.4. -98.8 -1 times -2312 2312 Multiply -439 and -4. 1756 Product of -232 and -0.18. 41.76 -2 * 0.23 -0.46 Calculate -1.5*-0.4. 0.6 5 times 134.2 671 What is the product of -0.08 and 0.72? -0.0576 -0.1*-0.089 0.0089 What is the product of 1 and -5.1? -5.1 What is the product of 0.01 and -7.3? -0.073 0.048 * -0.48 -0.02304 Product of 2.3 and 8. 18.4 Multiply -0.5 and -7. 3.5 Product of -0.4 and 454. -181.6 Calculate 0.6*-0.0653. -0.03918 What is -116 times 0.1? -11.6 Work out 44.1 * -0.3. -13.23 85*-1.26 -107.1 Product of 0.4 and -0.773. -0.3092 0.058*0.5 0.029 Work out 0.2 * 0.2472. 0.04944 What is -0.159 times 0.07? -0.01113 Calculate -8*9.35. -74.8 0.4 * -96 -38.4 Multiply -0.2 and -1648. 329.6 2 * -17 -34 0.7 * -0.11 -0.077 324*-19 -6156 Product of -0.8 and -5. 4 What is the product of 5 and -0.036? -0.18 150.6*-5 -753 Calculate 135*0.5. 67.5 -5.2 times -0.5 2.6 Multiply -0.4 and -3.6. 1.44 Calculate 21.36*0. 0 What is 0.5 times -0.53? -0.265 Calculate 365*0.04. 14.6 What is the product of -3.7 and -0.5? 1.85 5 times -1209 -6045 Calculate 0.1*33. 3.3 Multiply 24.7 and -5. -123.5 What is the product of 0.04 and -22? -0.88 Product of 268 and -20. -5360 Work out 18 * -6. -108 What is -4.3 times -28? 120.4 -0.8*37 -29.6 0.2*-0.128 -0.0256 Calculate -1.22*-3. 3.66 What is 2 times -1.002? -2.004 0.06 times -5.3 -0.318 What is 0.2 times 1408? 281.6 Product of 0.2 and 0.1. 0.02 Work out -28 * 0. 0 294 times -5 -1470 Calculate 2*-60.5. -121 Multiply -4 and -43.8. 175.2 0.8*0.0038 0.00304 2.98*0.3 0.894 Multiply -0.55 and -0.04. 0.022 Calculate 624*-3. -1872 Calculate 1*552. 552 Work out 13 * 99.6. 1294.8 What is -28492 times 0.4? -11396.8 Multiply 780 and -5. -3900 20 * -7 -140 Multiply -0.076 and -146. 11.096 Work out -0.1 * -0.281. 0.0281 15.41 * 0.1 1.541 What is the product of -0.6 and 23.03? -13.818 Product of -0.5 and -0.045. 0.0225 0.04 times 11 0.44 What is -72 times 0.01? -0.72 Work out -5 * 0.077. -0.385 Calculate 0.06*3626. 217.56 What is the product of 1068 and -1.9? -2029.2 Calculate 8*-18. -144 What is -2 times 2221? -4442 Calculate 0*-1587. 0 0.16 * 4 0.64 What is the product of -0.021 and -0.2? 0.0042 -0.06 times 6.2 -0.372 Product of -53 and 5. -265 Product of -284 and 0.1. -28.4 0.08 times -0.342 -0.02736 Calculate 0.19*-14. -2.66 Multiply 2 and -0.517. -1.034 Multiply 1.03 and 5. 5.15 Work out 16 * -13. -208 202 times 3 606 Calculate -1.2*-0.015. 0.018 -15 * -73 1095 Calculate 0.05*-1.6. -0.08 Work o

879 A.2d 526 (2005) 91 Conn.App. 26 Myra J. KRAMER et al. v. Robert J. PETISI et al. No. 24698. Appellate Court of Connecticut. Argued February 23, 2005. Decided August 23, 2005. *527 William F. Gallagher, with whom, on the brief, was Hugh D. Hughes, for the appellant (named plaintiff). *528 Robert B. Bellitto, Fairfield, for the appellees (named defendant et al.). Laura Pascale Zaino, with whom, on the brief, was Thomas J. Hagarty, Jr., Hartford, for the appellees (defendant Patricia Abagnale et al.). SCHALLER, FLYNN and GRUENDEL, Js. SCHALLER, J. The plaintiff Myra J. Kramer[1] appeals from the judgment of the trial court rendered in favor of the defendants[2] following the jury trial of a case involving the negligent or fraudulent misrepresentation of property boundary lines. On appeal, the plaintiff claims that the court improperly (1) instructed the jury on the applicability of comparative negligence and (2) refused to set aside the verdict as to the defendants Patricia Abagnale, Country Living Associates, Inc., Robert J. Petisi and Carole W. Petisi. The plaintiff asserts that the jury improperly found that she was not entitled to damages on the basis of its finding that she was negligent in relying on a 1982 survey of the property instead of obtaining a current survey before purchasing the property. We affirm the judgment of the trial court. The following facts are relevant to our resolution of the plaintiff's appeal. In 1978, John P. Edel and Jacque-line P. Edel, the owners of a four and one-half acre estate on North Street in Fairfield, subdivided the parcel of land into two parcels, which became known as 2250 North Street and 2228 North Street. The Edels had a fenced-in horse paddock, which was located on both parcels. The paddock area of the land is the focus of the current dispute. In 1991, the Petisis purchased 2228 North Street from the Edels. When the Petisis purchased the property, the horse paddock was still in existence, but because of the overgrown condition of the paddock land, the Petisis dismantled the portion of the fence that enclosed the paddock on their property. They asked the owners of the other parcel, 2250 North Street, if they could mow the tall grass up to the remaining portion of the fence, which was located on the other parcel. The owners granted permission and, between 1992 and 1994, the Petisis maintained that parcel of land. On June 1, 1994, the Petisis listed their property for sale with Abagnale, an agent of Country Living Associates, Inc. The Petisis provided Abagnale and Country Living Associates, Inc., with a written disclosure document. In response to the disclosure document question regarding encroachments, boundary disputes or easements affecting the property, the Petisis replied that a "[s]ection of [the] backyard is fenced in including [a ten foot by fifty foot section of the] neighbor's property." In July, 1994, the plaintiff and her husband decided to move from New Mexico to Connecticut. The couple looked at several homes in a ten day period between July 11 and 20. After attending a broker's open house at the Petisis' home, Nancy W. Thorne, the plaintiff's real estate agent, took the plaintiff to look at the house. Although Thorne had spoken with Abagnale, *529 she did not wait for Abagnale before taking the plaintiff to view the property. Shortly thereafter, the plaintiff visited the property with members of her family, Thorne and Abagnale. There were three to five additional visits in the days that followed. At one of the visits, the plaintiff and Thorne walked around the property. The plaintiff asked Thorne about the location of the boundaries. When Thorne replied that she did not know the boundaries of the property, she told the plaintiff that she would go inside and ask Abagnale. Upon her return, Thorne told the plaintiff that the boundary was the western side of the fence, which actually was located on the adjoining parcel, 2250 North Street. The plaintiff offered to purchase the property for $1.25 million. After some difficult negotiations, the parties agreed on a sale price of $1.4 million. After the inspection of the property revealed a variety of problems, the Petisis signed the sales contract and an addendum dated August 24, 1994, promising, among other items, a $3000 credit at closing. In addition, the addendum provided that the Petisis would remove an inground oil tank and kerosene tank, and provide for the extermination of wasps, bats, carpenter ants and mice. The sales contract also provided that any improvements or appurtenances located on the Petisis' land were entirely within the boundaries of the property to be conveyed. The parties closed on September 26, 1994. Prior to the closing, the plaintiff did not obtain a survey of the property. Instead, she relied on a 1982 survey of the property, which indicated the boundaries of the property without the fence. There is some dispute as to whether the plaintiff's attorney advised her to get a new survey done or whether it was suggested that the old survey be updated. Regardless, instead of obtaining a new survey, the plaintiff obtained an affidavit in lieu of a survey in which the Petisis stated that they had no knowledge of adverse rights, including easements, rights-of-way or encroachments. Despite the affidavit, the seller's disclosure statement indicated that a portion of the land, which was partially fenced-in, was not part of the property. The sellers' disclosure form, however, was not given to the plaintiff. Abagnale did not provide this to Thorne or to the plaintiff. On April 23, 1996, the plaintiff received notice from the owners of 2250 North Street, the adjacent property, that they were asserting their rights to prevent her from adversely possessing a portion of their property. At issue was a .22 acre portion of the property that was fenced in and used by the plaintiff. Thereafter, the plaintiff, by complaint dated September 20, 1996, filed an action against the Petisis and the other parties involved in the sale of 2228 North Street. On February 5, 1997, Abagnale and Country Living Associates, Inc., filed an answer and, pursuant to Practice Book § 10-53, affirmatively pleaded contributory negligence as a special defense. At trial, the jury found in favor of the Petisis but against Abagnale and Country Living Associates, Inc. The jury determined that Abagnale negligently had misrepresented the boundary lines of the property, but the jury also concluded that the plaintiff was 60 percent contributorily negligent. Consequently, Abagnale and Country Living Associates, Inc., were not liable for damages. On June 23, 2003, the plaintiff filed a motion to set aside the verdict as to Abagnale, Country Living Associates, Inc., and the Petisis. The motion was denied and *530 this appeal followed. Additional facts will be set forth as needed. I On appeal, the plaintiff claims that the court improperly denied her request to instruct the jury regarding the inapplicability of comparative negligence. The plaintiff first claims on appeal that the court improperly denied her request to charge. The requested supplemental charge[3] provided that the jury could not find the plaintiff contributorily negligent for failing to obtain a survey if the plaintiff relied on the defendants' misrepresentations regarding the property boundaries. The plaintiff contends that the law of Connecticut is well settled that if the failure to obtain a survey is a direct result of a negligent or intentional misrepresentation as to property boundary lines and if that misrepresentation is not open to discovery by inspection, the plaintiff's failure to obtain a survey does not constitute negligence. The plaintiff maintains that the case law on which she relies has not been overturned; therefore, contributory negligence does not apply. Accordingly, the plaintiff argues that the court was incorrect in omitting her requested instruction and charging the jury with an instruction that allowed for a finding of contributory negligence. We disagree. "We begin with our standard of review. A request to charge which is relevant to the issues of the case and which is an accurate statement of the law must be given.... When reviewing the challenged jury instruction ... we must adhere to the well settled rule that a charge to the jury is to be considered in its entirety, read as a whole, and judged by its total effect rather than by its individual component parts.... [T]he test of a court's charge is not whether it is as accurate upon legal principles as the opinions of a court of last resort but whether it fairly presents the case to the jury in such a way that injustice is not done to either party under the established rules of law.... As long as [the instructions] are correct in law, adapted to the issues and sufficient for the guidance of the jury ... we will not view the instructions as improper." (Citation omitted, internal quotation marks omitted.) 1525 Highland Associates, LLC v. Fohl, 62 Conn.App. 612, 621, 772 A.2d 1128, cert. denied, 256 Conn. 919, 774 A.2d 137 (2001). The following additional facts are relevant to our resolution of the plaintiff's claim. In their special defense to negligent misrepresentation, the defendants alleged that the plaintiff was contributorily negligent and that any damages suffered by the plaintiff were the result of her negligence because she failed to obtain a survey or review a survey map on file at *531 the Fairfield town hall prior to purchasing the property. The plaintiff denied this special defense, but later made a supplemental request to charge that, in essence, rendered the special defense inapplicable. On appeal, the defendants maintain that the case law and rule of law relied on by the plaintiff in her requested supplemental charge is inapplicable because it relates solely to fraudulent misrepresentation cases. Furthermore, they argue that such cases have been implicitly overruled by tort reform and the introduction of comparative negligence principles. The court instructed the jury that the determination of whether the plaintiff was contributorily negligent is a question of fact.[4] Furthermore, the court instructed that if the defendants could prove that the plaintiff was negligent by failing to obtain a survey prior to the closing and that her negligence contributed to more than 50 percent of her loss, then recovery would be barred. If the plaintiff's negligence was found to account for less than 50 percent of her loss, then the plaintiff's recovery would be merely reduced. We have reviewed the court's charge on comparative negligence in the context of the entire instruction, keeping in mind the *532 allegations of the defendants' special defense and the law. On the basis of our review, we conclude that the court's instruction on comparative negligence did not mislead the jury. The defendants contend that the same common-law rules applied in cases involving negligence are applied to cases involving negligent misrepresentation. Consequently, comparative negligence principles are applicable to cases involving acts of negligent misrepresentation. Connecticut courts have "long recognized liability for negligent misrepresentation. [Our courts] have held that even an innocent misrepresentation of fact may be actionable if the declarant has the means of knowing, ought to know, or has the duty of knowing the truth.... The governing principles are set forth in similar terms in § 552 of the Restatement (Second) of Torts (1977): One who, in the course of his business, profession or employment ... supplies false information for the guidance of others in their business transactions, is subject to liability for pecuniary loss caused to them by their justifiable reliance upon the information, if he fails to exercise reasonable care or competence in obtaining or communicating the information." (Citations omitted; internal quotation marks omitted.) Williams Ford, Inc. v. Hartford Courant Co., 232 Conn. 559, 575, 657 A.2d 212 (1995). Because negligent misrepresentation is a tort sounding in negligence, it is "consistent with [the] goal[s] for ... comparative negligence [principles] to apply to the tort of negligent misrepresentation...." Id., at 586, 657 A.2d 212.[5] As a result of tort reform, "the legislature abolished the common-law rule of joint and several liability and replaced it with a system based on principles of comparative fault." Lostritto v. Community Action Agency of New Haven, Inc., 269 Conn. 10, 23, 848 A.2d 418 (2004). "The purpose of comparative negligence is to ameliorate the harshness of the complete bar to liability resulting from the common law defense of contributory negligence.... This change in policy was accomplished by mandating a comparison by the fact finder of the relative degrees of negligence of the plaintiff and the defendant. [Section] 52-572h(b) provides that contributory negligence shall not bar recovery in an action by any person ... to recover damages resulting from personal injury [or damage to property] ... if the negligence was not greater than the combined negligence of the person or persons against whom recovery is sought.... The purpose of the comparative negligence statute was to replace the former rule, under which contributory negligence acted as a complete defense, with a rule under which contributory negligence would operate merely to diminish recovery of damages based upon the degree of the plaintiff's own negligence." (Citation omitted, internal quotation marks omitted.) Williams Ford, Inc. v. Hartford Courant Co., supra, 232 Conn. at 585-86, 657 A.2d 212. It is consistent with the purposes of comparative negligence principles to apply them to cases involving negligent misrepresentation. The plaintiff maintains that despite the applicability of comparative negligence principles to actions for negligent misrepresentation, we should find an exception to that rule that would render the defense inapplicable in cases concerning misrepresentations of property boundary lines. In support of her claim, the plaintiff cites a variety of cases concerning the fraudulent misrepresentation of property conditions *533 in which a plaintiff's failure to obtain a survey prior to purchasing the property did not serve as a defense to a misrepresentation claim.[6] The plaintiff maintains that because our Supreme Court did not address that line of cases when it addressed the application of comparative negligence principles to negligent misrepresentation cases, we should treat a negligent misrepresentation claim in those types of cases as if it were a fraudulent misrepresentation claim. Although the plaintiff is correct that comparative negligence principles do not apply to cases involving fraudulent misrepresentation, we are not persuaded by her argument. Merely because our Supreme Court did not directly address the cases cited by the plaintiff when ruling on the applicability of comparative negligence principles to negligent misrepresentation claims does not mean that comparative negligence principles should not apply to cases involving the negligent misrepresentation of property boundary lines. The plaintiff suggests that the determination as to whether comparative negligence principles apply is not made on the basis of whether the misrepresentation was negligent or fraudulent, but rather on whether the misrepresentation was material to the transaction. We decline, however, to adopt the plaintiff's suggestion and conclude that the court properly instructed the jury. II A The plaintiff next claims that the court improperly denied her motion to set aside the verdict as to Abagnale and Country Living Associates, Inc. Even though the jury found that Abagnale and Country Living Associates, Inc., were negligent, they were not held liable because the jury found that their negligence caused less than 50 percent of the plaintiff's loss. Our standard of review concerning a motion to set aside a verdict is well settled. "[T]he proper appellate standard of review when considering the action of a trial court granting or denying a motion to set aside a verdict ... [is] the abuse of discretion standard.... In determining whether there has been an abuse of discretion, every reasonable presumption should be given in favor of the correctness of the court's ruling.... Reversal is required only where an abuse of discretion is manifest or where injustice appears to have been done.... We do not ... determine whether a conclusion different from the one reached could have been reached.... A verdict must stand if it is one that a jury reasonably could have returned and the trial court has accepted." (Internal quotation marks omitted.) Maag v. Homechek Real Estate Services Inc., 82 Conn.App. 201, 211-12, 843 A.2d 619, cert. denied, 269 Conn. 908, 852 A.2d 737 (2004). The plaintiff's argument as to her claim is identical to her argument regarding the court's denial of her request to charge. Because we did not conclude that the instruction regarding comparative negligence was incorrect, we conclude that the court did not abuse its discretion in denying the plaintiff's motion to set aside the verdict. B The plaintiff next claims that the court improperly denied her motion to set aside *534 the verdict as to the Petisis. The plaintiff contends that the verdict absolving the Petisis of liability was unreasonable, illogical and contrary to the evidence and, therefore, the court improperly denied her motion to set aside the verdict. The standard of review concerning a motion to set aside a verdict is set forth in part II A. The plaintiff contends that the Petisis should have been found liable for negligent or intentional misrepresentation because they made two written representations concerning the western boundary of the property that directly contravened the written property disclosure that they gave to Abagnale. Specifically, the plaintiff refers to the real estate rider for the contract for sale and the affidavit in lieu of survey. The Petisis provided Abagnale with a written disclosure document in which they noted that a section of property that was partially fenced in was not part of their property. Abagnale failed to give this document to the plaintiff. In the real estate rider for the contract for sale dated August 24, 1994, the Petisis represented that any improvements were within the boundary of the property. Shortly thereafter, before the closing, the plaintiff obtained an affidavit from the Petisis in lieu of obtaining a survey. In the affidavit, dated September 28, 1994, the Petisis represented that they were not aware of any encroachments on the property. The plaintiff maintains that the last two documents were in direct conflict with the Petisis' statements in the initial disclosure document and, therefore, that the Petisis intentionally or negligently misrepresented the property boundary lines. At trial, the Petisis maintained that they did not encroach on the land of the adjoining landowners, nor did they perform any act that changed or attempted to change the property boundary lines, and, therefore, they did not misrepresent the property boundary lines to the plaintiff. The Petisis pointed out that the plaintiff's continued focus on the remaining portion of the fence on the adjoining property is misplaced. The Petisis did not build the fence, nor did they encroach on the portion of land that they did not own. The adjoining landowner gave the Petisis permission to mow the grass. There was no attempt by the Petisis to take this portion of the land for their own use. Merely because the Petisis pointed out, in a voluntary written disclosure that the remaining portion of the fence was not located on their property, does not mean that the Petisis were making misrepresentations as to the boundary of the property line when they made a written representation that there were no encroachments on the property. We conclude, therefore, that the jury reasonably could have determined that the Petisis did not misrepresent the boundary lines and, therefore, that the court did not abuse its discretion in denying the plaintiff's motion to set aside the verdict. The judgment is affirmed. In this opinion the other judges concurred. NOTES [1] Kramer's husband, Gary Kramer, a plaintiff at trial, died while this action was pending in the trial court and is not a party to this appeal. We therefore refer in this opinion to Myra Kramer as the plaintiff. [2] At trial, the defendants were Robert J. Petisi, Carole W. Petisi, Patricia Abagnale, Country Living Associates, Inc., Nancy W. Thorne and Dunlap-Hibbs Real Estate, Inc. On appeal, the plaintiff raises claims relating only to Abagnale, Country Living Associates, Inc., and the Petisis. [3] The supplemental request to charge provided: "1. Defendants claim plaintiff was negligent in failing to get a survey. If you find that there was a misrepresentation, whether negligent or intentional, about the westerly boundary, and if you find that the correct boundary was not open to discovery by inspection, then the failure of the plaintiff to obtain a survey is not contributorily negligent and you may not consider it. Stevens v. Giddings, 45 Conn. 507 (1878); Lovejoy v. Isbell, 73 Conn. 368 [47 A. 682] (1900); Clark v. Haggard, 141 Conn. 668, [109 A.2d 358] (1954). "2. If the defendants, or any one of them, misrepresented the boundary by stating that the rail fence formed the westerly boundary toward the rear of the property, the failure of the plaintiff to get a survey was a natural consequence of the misrepresentation. That is why her failure to get a survey under these circumstances doesn't matter. Clark v. Haggard, [supra, 141 Conn. at 673, 109 A.2d 358] (`It matters not that the plaintiff had the opportunity to have the land surveyed. His omission to have a survey made was a natural consequence of the fraudulent misrepresentations.')." [4] The court's instruction to the jury regarding comparative negligence provided: "The defendants, when they responded to this lawsuit, denied all the claims..... [A]mong the claims they denied was the claim of negligent misrepresentation. When they filed that denial, they also filed what is called a special defense. In this special defense, they state that if there was a negligent misrepresentation, any loss that the plaintiff suffered was caused not by the negligent misrepresentation, but was caused by the plaintiff's own negligence. They claim that the [plaintiff] should have obtained a survey. This is called a defense of contributory negligence. The defendants claim that any harm that befell the plaintiff with respect to this claim came to her through her own contributory negligence. "Whether she was contributorily negligent is a question of fact for you to decide. Whether the [plaintiff] should have gotten a survey depends upon the facts as you find them. Whether the survey would have disclosed the problem with respect to the western boundary is a question for you to decide. The defendants have the burden on this issue. There's a presumption that a person is acting in due care.... That presumption survives unless and until the defendants prove by the fair preponderance of the evidence that she was not acting in due care, that she was careless. The defendants have the burden of persuasion on their special defense of contributory negligence, and this special defense only applies to the claim of negligent misstatement. "If the defendants have proven that [the plaintiff] was contributorily negligent, then two possibilities exist; either her claim of negligent misrepresentation is barred entirely or any recovery on that claim would be reduced in proportion to her negligence. If you find that she has proven the claim of negligent misstatement, and if you further find that she was contributorily negligent herself, then you would have to combine the negligence of all the parties, call that 100 percent, and then decide how much is attributable, how much fault is attributable to [the plaintiff]. "If [the plaintiff] was more than 50 percent at fault, she could not—she cannot recover under the negligent misrepresentation claim. If she was 50 percent or less at fault, then she could still-she would still recover under this claim, but her recovery would be reduced by her percentage of fault.... "Now, that's the second type of claim, negligent misrepresentation. The defendants, acting in the course of a transaction in which [they] had a financial interest, supplied false information for the guidance of the other. The defendants failed to exercise reasonable care in obtaining or communicating the information, and the plaintiff justifiably relied on the information. The plaintiff suffered a monetary loss. With respect to this claim, you would consider whether or not the plaintiff was contributorily negligent. If she was—if she was greater than 50 percent, then she would be barred from recovering on this claim. If she was 50 percent or less at fault, then her recovery under this claim would be reduced by her percentage of fault." [5] See also annot., 22 A.L.R.5th 464, 471 (1994); Gilchrist Timber Co. v. ITT Rayonier, Inc., 696 So.2d 334, 339 (Fla.1997). [6] See Gibson v. Capano, 241 Conn. 725, 733, 699 A.2d 68 (1997); Johnson v. Healy, 176 Conn. 97, 101-102, 405 A.2d 54 (1978); Warman v. Delaney, 148 Conn. 469, 473-74, 172 A.2d 188 (1961); Clark v. Haggard, 141 Conn. 668, 673, 109 A.2d 358 (1954); Foley v. Huntington Co., 42 Conn.App. 712, 722, 682 A.2d 1026, cert. denied, 239 Conn. 931, 683 A.2d 397 (1996).

/* ----------------------------------------------------------------------------- This source file is part of OGRE (Object-oriented Graphics Rendering Engine) For the latest info, see http://www.ogre3d.org/ Copyright (c) 2000-2014 Torus Knot Software Ltd Permission is hereby granted, free of charge, to any person obtaining a copy of this software and associated documentation files (the "Software"), to deal in the Software without restriction, including without limitation the rights to use, copy, modify, merge, publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons to whom the Software is furnished to do so, subject to the following conditions: The above copyright notice and this permission notice shall be included in all copies or substantial portions of the Software. THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER DEALINGS IN THE SOFTWARE. ----------------------------------------------------------------------------- */ #ifndef __D3D9PIXELBUFFER_H__ #define __D3D9PIXELBUFFER_H__ #include "OgreD3D9Prerequisites.h" #include "OgreHardwarePixelBuffer.h" #include "Threading/OgreThreadHeaders.h" namespace Ogre { class D3D9Texture; class D3D9RenderTexture; class _OgreD3D9Export D3D9HardwarePixelBuffer: public HardwarePixelBuffer { protected: struct BufferResources { /// Surface abstracted by this buffer IDirect3DSurface9* surface; /// AA Surface abstracted by this buffer IDirect3DSurface9* fSAASurface; /// Volume abstracted by this buffer IDirect3DVolume9* volume; /// Temporary surface in main memory if direct locking of mSurface is not possible IDirect3DSurface9* tempSurface; /// Temporary volume in main memory if direct locking of mVolume is not possible IDirect3DVolume9* tempVolume; /// Mip map texture. IDirect3DBaseTexture9 *mipTex; }; typedef map<IDirect3DDevice9*, BufferResources*>::type DeviceToBufferResourcesMap; typedef DeviceToBufferResourcesMap::iterator DeviceToBufferResourcesIterator; /// Map between device to buffer resources. DeviceToBufferResourcesMap mMapDeviceToBufferResources; /// Mipmapping bool mDoMipmapGen; bool mHWMipmaps; /// Render target D3D9RenderTexture* mRenderTexture; // The owner texture if exists. D3D9Texture* mOwnerTexture; // The current lock flags of this surface. DWORD mLockFlags; // Device access mutex. OGRE_STATIC_MUTEX(msDeviceAccessMutex); protected: /// Lock a box PixelBox lockImpl(const Image::Box lockBox, LockOptions options); PixelBox lockBuffer(BufferResources* bufferResources, const Image::Box &lockBox, DWORD flags); /// Unlock a box void unlockImpl(void); void unlockBuffer(BufferResources* bufferResources); BufferResources* getBufferResources(IDirect3DDevice9* d3d9Device); BufferResources* createBufferResources(); /// updates render texture. void updateRenderTexture(bool writeGamma, uint fsaa, const String& srcName); /// destroy render texture. void destroyRenderTexture(); void blit(IDirect3DDevice9* d3d9Device, const HardwarePixelBufferSharedPtr &src, const Image::Box &srcBox, const Image::Box &dstBox, BufferResources* srcBufferResources, BufferResources* dstBufferResources); void blitFromMemory(const PixelBox &src, const Image::Box &dstBox, BufferResources* dstBufferResources); void blitToMemory(const Image::Box &srcBox, const PixelBox &dst, BufferResources* srcBufferResources, IDirect3DDevice9* d3d9Device); public: D3D9HardwarePixelBuffer(HardwareBuffer::Usage usage, D3D9Texture* ownerTexture); ~D3D9HardwarePixelBuffer(); /// Call this to associate a D3D surface or volume with this pixel buffer void bind(IDirect3DDevice9 *dev, IDirect3DSurface9 *mSurface, IDirect3DSurface9* fsaaSurface, bool writeGamma, uint fsaa, const String& srcName, IDirect3DBaseTexture9 *mipTex); void bind(IDirect3DDevice9 *dev, IDirect3DVolume9 *mVolume, IDirect3DBaseTexture9 *mipTex); /// @copydoc HardwarePixelBuffer::blit void blit(const HardwarePixelBufferSharedPtr &src, const Image::Box &srcBox, const Image::Box &dstBox); /// @copydoc HardwarePixelBuffer::blitFromMemory void blitFromMemory(const PixelBox &src, const Image::Box &dstBox); /// @copydoc HardwarePixelBuffer::blitToMemory void blitToMemory(const Image::Box &srcBox, const PixelBox &dst); /// Internal function to update mipmaps on update of level 0 void _genMipmaps(IDirect3DBaseTexture9* mipTex); /// Function to set mipmap generation void _setMipmapping(bool doMipmapGen, bool HWMipmaps); /// Get rendertarget for z slice RenderTexture *getRenderTarget(size_t zoffset); /// Accessor for surface IDirect3DSurface9 *getSurface(IDirect3DDevice9* d3d9Device); /// Accessor for AA surface IDirect3DSurface9 *getFSAASurface(IDirect3DDevice9* d3d9Device); /// Notify TextureBuffer of destruction of render target virtual void _clearSliceRTT(size_t zoffset); /// Release surfaces held by this pixel buffer. void releaseSurfaces(IDirect3DDevice9* d3d9Device); /// Destroy resources associated with the given device. void destroyBufferResources(IDirect3DDevice9* d3d9Device); // Called when device state is changing. Access to any device should be locked. // Relevant for multi thread application. static void lockDeviceAccess(); // Called when device state change completed. Access to any device is allowed. // Relevant for multi thread application. static void unlockDeviceAccess(); }; }; #endif

873 F.2d 1443 Martin (Michael L.)v.Duckworth (Jack R.) NO. 88-2394 United States Court of Appeals,Seventh Circuit. APR 06, 1989 1 Appeal From: N.D.Ind. 2 AFFIRMED.

@(urlMsgs: List[String] = List.empty, fileMsgs: List[String] = List.empty)(implicit request: RequestHeader, context: model.ApplicationContext) @import conf.switches.Switches.R2PagePressServiceSwitch @admin_main("R2 page presser (archiver)", isAuthed = true) { <form action="/press/r2" method="POST" class="form-horizontal redirect-form"> <fieldset> <legend>Press (archive) an individual page</legend> <div class="form-group"> <label for="r2url" class="control-label col-sm-1">R2 URL:</label> <div class="col-sm-6"> <input type="text" class="form-control" id="r2url" name="r2url" value="" placeholder="http://www.theguardian.com/an/r2/path" /> </div> </div> <div class="form-group"> <label for="is-takedown" class="control-label col-sm-1">Takedown:</label> <div class="col-sm-6"> <input type="checkbox" class="form-control" id="is-takedown" name="is-takedown"/> </div> </div> <div class="form-group"> <label for="is-from-preserved-source" class="control-label col-sm-1">From preserved src:</label> <div class="col-sm-6"> <input type="checkbox" class="form-control" id="is-from-preserved-source" name="is-from-preserved-source" checked/> </div> </div> <div class="form-group"> <label for="is-convert-to-https" class="control-label col-sm-1">Make HTTPS compatible:</label> <div class="col-sm-6"> <input type="checkbox" class="form-control" id="is-convert-to-https" name="is-convert-to-https" checked/> </div> </div> <div class="form-group"> <div class="controls col-sm-offset-1 col-sm-11"> @if(R2PagePressServiceSwitch.isSwitchedOn) { <input class="btn btn-default" type="submit" value="Press" /> } else { <div class="col-sm-6"> This feature is currently switched off (use the switchboard to re-enable it) </div> } </div> </div> @if(urlMsgs.nonEmpty) { <div class="form-group label-warning"> <div id="server-message" class="controls col-sm-offset-1 col-sm-11"> @urlMsgs.mkString </div> </div> } </fieldset> </form> <form action="/press/r2/batchupload" method="POST" class="form-horizontal redirect-form" enctype="multipart/form-data"> <fieldset> <legend>Press a batch of pages from a file of urls</legend> <div class="form-group"> <label for="r2urlfile" class="control-label col-sm-1">File:</label> <div class="col-sm-6"> <input type="file" class="form-control" id="r2urlfile" name="r2urlfile" /> </div> </div> <div class="form-group"> <label for="is-takedown" class="control-label col-sm-1">Takedown:</label> <div class="col-sm-6"> <input id="is-takedown" name="is-takedown" type="checkbox"/> </div> </div> <div class="form-group"> <label for="is-from-preserved-source" class="control-label col-sm-1">From preserved src:</label> <div class="col-sm-6"> <input type="checkbox" class="form-control" id="is-from-preserved-source" name="is-from-preserved-source" checked/> </div> </div> <div class="form-group"> <label for="is-convert-to-https" class="control-label col-sm-1">Make HTTPS compatible:</label> <div class="col-sm-6"> <input type="checkbox" class="form-control" id="is-convert-to-https" name="is-convert-to-https" checked/> </div> </div> <div class="form-group"> <div class="controls col-sm-offset-1 col-sm-11"> @if(R2PagePressServiceSwitch.isSwitchedOn) { <input class="btn btn-default" type="submit" value="Upload & Press" /> } else { <div class="col-sm-6"> This feature is currently switched off (use the switchboard to re-enable it) </div> } </div> </div> @if(fileMsgs.nonEmpty) { <div class="form-group label-warning"> <div id="server-message" class="controls col-sm-offset-1 col-sm-11"> @fileMsgs.mkString </div> </div> } </fieldset> </form> }