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Travel Reading the New York Times Travel section this weekend, I stumbled across a site I hadn’t visited. Now that I have, it is sure to become a giant time-sucker in my life. It’s called DesignTripper.com, and it’s full of carefully curated, unique vacation roosts (houses, inns, B&Bs, even yurts) and restaurants that aren’t likely to earn you any Starwood rewards points. This led me to their post about Fair Folks and a Goat, an amazing shotgun house in New Orleans that has a boutique, a coffee parlor, a gallery and one bedroom for guests with a rotating art installation inside (the one above is by local artist t Hannah Chalew), among other things. This spot can’t be summed up in a category or two; what’s so great is the way they support local artists and craftspeople. I also loved seeing local artwork (Time Out chair – so genius – is by Sarah Ashley Longshore), combined with two of my favorite items we carry, the Blu Dot Real Good Chair and Patrick Townsend’s Orbit Light, combined with classic New Orleans shotgun architecture: UPDATE: Since posting this, I found that Fair Folks is moving their creative action north to Greenwich Village and will be opening a new a retail boutique and design emporium featuring the works of established New York designers and talented young artists in September! Learn more here. What are some of your favorite ways to find chic vacation spots? Do you browse through Wallpaper*, drool, rip out the pages and then start saving money? Enjoy cruising through sites like airnb and vrbo, sure you’ll find that perfect needle in a haystack while looking out for scammers and the kind of homeowners who take bathroom pictures with the toilet seat up and all of their products all over the sink (I’m not talking in a Todd Selby kind of way)? Hit your local AAA? Let discount sites like Jetsetter do the searching and the discounting for you? Post what you’re looking for on Facebook and see who has good ideas? Are you laid back enough to do the CouchSurfing thing? Have you been doing the travel agent thing since long before the interwebs were invented and swear it’s still the best and only way to go? There are so many options out there it’s really hard to keep up; while DesignTripper does NOT handle bookings and reservations, they certainly cut down on search time for the cool spots. Please share your favorite travel search methods with us as well as favorite places you’ve stayed in the comments section – I’d love to know about your experiences, good or bad! Did any of you feel a wave of nostalgia for a Howard Johnson’s road trip stop while watching Mad Men last night? I kept thinking of my family driving from Ohio to Cape Cod in the family truckster (a tan Ford station wagon with wood paneling and flip up seats in the way-back) and stopping for a hot dog and an ice cream cone. The bright colors, light fixtures and even the waitress uniforms actually looked retro-fresh in last night’s episode. Somehow, the combination of pot pies and orange sherbet leads to a devastating fight between Don and Megan, and he abandons her in a HoJo’s parking lot. How could he not, with that fabulous honeysuckle dress with matching chevron coat? It was made for a HoJo’s. Girlfriend even had on matching pink sunglasses. Tory Burch has got nothing on Megan’s costume designer. Only that devilish cad Don Draper could make the iconic Howard Johnson’s roof look sexy. Anyway, the wave of nostalgia made me want to look into the history of Howard Johnson’s. Because I’m lazy, most of this information was compiled via Wikipedia, so take it for what it’s worth. Howard Deering Johnson opened drugstore in 1925, but soon realized that the soda fountain was the most profitable part. He started tinkering with ice cream and the business changed direction toward becoming a restaurant that became known for fried clams. In 1932 a second restaurant was opened, one of the first franchise deals in the U.S. The first motor lodge was opened in Savannah Georgia in 1954, and it was designed by architects Rufus Nims and Karl Koch. From there, in a nutshell, the business boomed and the motor lodges became known for their ubiquitous roadside advertisements: In the 1960s and ’70s, there were over 1,000 HoJos across the United States and Canada. There is a site completely dedicated to posting pictures of former HoJos, called HoJoLand.com Then, new owners and more new owners and big changes, bland architecture and a new logo that’s no fun. The End. Oh, P.S. Also, when you Google “Howard Johnson,” this guy is interspersed between all of the motel pictures. He’s a singer: There are so many great places to stay when traveling, whether they be easy on the wallet, easy on the eyes or easy on our backs as we enjoy a relaxing massage. I’m going to make more of an effort to share lodging that’s full of great design with you as it crosses my path. In honor of Liz Lemon, we’re going to christen this column “I Want to Go to There.” Sadly, this amazing hotel did not cross my literal path, but rather entered my life via an email from Jetsetter.com, which is always full of tempting trips I wish I could take. Forget the bat cave, this hotel was formerly a house of bedrooms, carved out of a cave in Cappadocia, Turkey. Common areas even have wi-fi, though unless you are booking a local hot air balloon ride online, being on your laptop at a place as beautiful as this should be a crime. Turkish interior designer superstar Halide Didem designed the beautiful and exotic rooms. She layered bright colors, luxe fabrics, metallic finishes and exotic shapes atop neutral and natural base of textures, a design lesson we can all take a note from. Beautiful terraces give guests a chance to soak in the views from a luxurious perch. Cave bedrooms are a combination of rough-hewn walls that form a cozy room with sumptuous linens; the perfect combination for a great night’s sleep. Are there any areas or hotels on your dream trip list? Please let us know about them in the comments section! Let’s face it, we’ve all seen so many cleverly decorated boutique hotels that it takes a lot to catch attention lately, doesn’t it? I mean, we’ve seen everything from Beetlejuice looking B&Bs to crack den chic (a certain Manhattan too-cool-for-school joint, I’m talking to you). However, as I caught up on my magazines with an old issue of W the other day, a tiny picture from “August’s Most Wanted” caught my eye (yes, I am that far behind on my glossies). It was a shot of a bedroom from the c/o Maidstone East Hampton. Let’s enjoy some fresh eye candy from their Swedish icon designed rooms (inspirations range from Eero Saarinen to Birgit Nillson the soprano, not to be confused with Brigitte Nielsen, known for Red Sonya and Flavor Flav reality shows): This week a group of images in our Fresh New Spaces Group on Flickr caught my attention. They were the minimalist spaces from a boutique hotel in Berlin called Hotel OTTO. Here, the neutral color palette and restrained furnishings let you enjoy the view, the photography and the warm hardwood floors: This simple bedroom contains lots of space saving tips, including using thin but colorful upholstered canvases in lieu of a clunky headboard, and utilizing swing arm sconces to save nightstand space (and of course, when you don’t have room to cram in a nightstand, these are a great solution as well). The palette is kept very simple, letting this iconic Eames fabric get the attention it deserves: However, if a subtle blue, gray and black palette is not for you, they’ve got some electric preppy pink and green options for you. Note the extra shelf on the nightstand, which is great for tucking away books, magazines, and even that annoying glow from a digital clock that can exacerbate an insomniac. They’ve also scooped up some of the floor space with this piece so that you can take some of that stuff out of your suitcase and really get comfortable:

Q: How to use two conditions in "where" clause in XQuery I'm trying to extract only those <book> data that has a certain type of <xref> type and matching a list of specific xrefs using a Xquery (I'm new to this). Here is the input data: <book id="6636551"> <master_information> <book_xref> <xref type="Fiction" type_id="1">72771KAM3</xref> <xref type="Non_Fiction" type_id="2">US72771KAM36</xref> </book_xref> </master_information> </book> <book id="119818569"> <master_information> <book_xref> <xref type="Fiction" type_id="1">070185UL5</xref> <xref type="Non_Fiction" type_id="2">US070185UL50</xref> </book_xref> </master_information> </book> <book id="119818568"> <master_information> <book_xref> <xref type="Fiction" type_id="1">070185UK7</xref> <xref type="Non_Fiction" type_id="2">US070185UK77</xref> </book_xref> </master_information> </book> <book id="119818567"> <master_information> <book_xref> <xref type="Fiction" type_id="1">070185UJ0</xref> <xref type="Non_Fiction" type_id="2">US070185UJ05</xref> </book_xref> </master_information> </book> <book id="38085123"> <master_information> <book_xref> <xref type="Fiction" type_id="1">389646AV2</xref> <xref type="Non_Fiction" type_id="2">US389646AV26</xref> </book_xref> </master_information> </book> XQuery that I'm using: for $x in //book where $x//xref/@type='Fiction' and $x//xref=('070185UL5','070185UJ0') return $x The above Xquery only fetches the first book information matching the "070185UL5". I would expect it to fetch both. What is wrong? I appreciate your response. A: In the query for $x in //book where $x//xref/@type='Fiction' and $x//xref=('070185UL5','070185UJ0') return $x do you intend to say (1) "there must be at least one xref whose @type is 'Fiction' and at least one xref whose value is '070185UL5' or'070185UJ0'" or do you intend to say (2) "there must be at least one xref whose @type is 'Fiction' and whose value is '070185UL5' or'070185UJ0'" Currently you are saying (1). If you want to say (2) then the query should be for $x in //book where $x//xref[@type='Fiction' and .=('070185UL5','070185UJ0')] return $x which you can simplify to the XPath expression //book[.//xref[@type='Fiction' and .=('070185UL5','070185UJ0')]] With the data you have supplied the two queries give the same result, but with different data they could give different results.

Q: Как сделать ЧПУ с помощью htaccess? Есть страницы вида site.com/?page=2. Как с помощью htaccess сделать site.com/page/2? A: RewriteCond нужен, чтобы не было бесконечного цикла. Нужный код редиректа можно подставить в конце RewriteRule после пробела, например [R=301]. Если планируете сохранить другие элементы query, то подставьте туда же [R=301, QSA] RewriteEngine On RewriteCond %{QUERY_STRING} !page= RewriteRule page/(.*)$ /?page=$1

Tag This Sunday died Mexican poet Jose Emilio Pacheco in Mexico City. The writer, 74, was hospitalized on Saturday afternoon. His daughter Laura Emilia Pacheco said that “he died quietly and peacefully.” She was commissioned to confirm the news. Poet, novelist, essayist...

Effects of cisapride on oesophageal transit of solids in patients with progressive systemic sclerosis. In most patients with progressive systemic sclerosis (PSS) the oesophagus is affected. Reflux symptoms are most frequent, whilst dysphagia also occurs. Cisapride, a prokinetic agent, may enhance motility along the gastrointestinal tract. The effects of cisapride on oesophageal transit were evaluated in 12 PSS patient using a solid-phase radionuclide oesophageal transit study. Each PSS patient was given cisapride 10 mg or placebo orally three times a day in a random, double-blind, crossover fashion. The results show that cisapride does not seem to have any impact on oesophageal transit in patients with PSS.

Coleophora amellivora Coleophora amellivora Baldizzone, 1979 from Toll (1952a); upper case of a male, lower one of a female Aster alpinus, from Baran & Rynarzewski (2008a) case Greyish brown, trivalved tubular leaf case with a mouth angle of 20-45°. The larva mines in the lower leaves. After the case has been tightened to the leaf, the larva, otherwise than in most other Coleophora‘s, leaves it case, and makes from this starting point a long corridor mines.

299 F.Supp.2d 166 (2004) Timothy MULDROW, Petitioner, v. Victor HERBERT, Superintendent, Attica Correctional Facility, Respondent. No. 02-CV-6080L. United States District Court, W.D. New York. February 3, 2004. *167 *168 Timothy Muldrow, Attica, NY, pro se. Loretta S. Courtney, Monroe County District Attorney's Office, Rochester, NY, for Respondent. DECISION AND ORDER LARIMER, District Judge. INTRODUCTION Petitioner Timothy Muldrow ("Muldrow"), filed this petition pro se for a writ of habeas corpus pursuant to 28 U.S.C. § 2254 challenging his conviction in Monroe County Court of two counts of second degree murder. For the reasons set forth below, Muldrow's § 2254 petition is denied. FACTUAL BACKGROUND AND PROCEDURAL HISTORY On December 28, 1993, Muldrow participated in the execution-style murder of two people in their home. There was a third victim who survived after being shot in the face. The motivation for the killings was to silence witnesses to previous murders committed by a drug-dealing associate of Muldrow named Jerold Usher ("Usher"). Two days after the shootings, the police seized five guns and other contraband from Muldrow's apartment. Testing revealed that two of these guns fired the bullets that killed one of the victims, and bullets test-fired from a third gun were consistent with those used to shoot the other two victims. Muldrow was indicted jointly with two of the three co-defendants, Raymond Stubbs ("Stubbs") and Anthony McGee ("McGee"), on two counts of murder in the second degree (New York Penal Law ("P.L.") §§ 125.25(1) and 20.00); two counts of felony murder (P.L. §§ 125.25(3) and 20.00); one count of attempted murder in the second degree (P.L. §§ 125.25, 110.00, and 20.00); and one count of assault (P.L. §§ 120.10 and 20.00). Muldrow, Stubbs and Anthony were tried jointly. The fourth perpetrator, Thearthur Grimes ("Grimes"), was tried separately because he confessed to the police that he was present when the murders were committed and implicated Muldrow and McGee as the gunmen. After a jury trial in Monroe County Court, Muldrow was found guilty of two counts of felony murder and sentenced to indeterminate consecutive terms of imprisonment of 25 years to life on each count. Muldrow appealed to the Appellate Division, Fourth Department, which unanimously affirmed his conviction on June 16, 2000. The Court of Appeals denied leave to appeal on September 20, 2000. This federal habeas corpus petition followed. DISCUSSION Muldrow asserts two grounds for entitlement to habeas relief, both of which stem from his appellate counsel's alleged incompetence.[1] First, Muldrow faults counsel for failing to challenge on direct appeal the purported inconsistencies in the verdicts at his trial: McGee was acquitted of all counts of the indictment, Stubbs was convicted on all counts of the indictment, and Muldrow was convicted on the felony murder counts only. Muldrow claims that each co-defendant was required to be acquitted or convicted of the same counts of the indictment in order for the verdicts to be consistent. *169 A claim for ineffective assistance of appellate counsel is evaluated by the same standard as is a claim of ineffective assistance of trial counsel. Mayo v. Henderson, 13 F.3d 528, 533 (2d Cir.), cert. denied, 513 U.S. 820, 115 S.Ct. 81, 130 L.Ed.2d 35 (1994) (citing Claudio v. Scully, 982 F.2d 798, 803 (2d Cir.1992), cert. denied, 508 U.S. 912, 113 S.Ct. 2347, 124 L.Ed.2d 256 (1993)). A petitioner alleging ineffective assistance of appellate counsel must prove both that appellate counsel was objectively unreasonable in failing to raise a particular issue on appeal, and that absent counsel's deficient performance, there was a reasonable probability that defendant's appeal would have been successful. Mayo, 13 F.3d at 533-34; see also Smith v. Robbins, 528 U.S. 259, 285, 120 S.Ct. 746, 145 L.Ed.2d 756 (2000); Aparicio v. Artuz, 269 F.3d 78, 95 (2d Cir.2001). Appellate counsel "need not (and should not) raise every nonfrivolous claim, but rather may select from among them in order to maximize the likelihood of success on appeal." Smith v. Robbins, 528 U.S. at 288, 120 S.Ct. 746 (citing Jones v. Barnes, 463 U.S. 745, 750-54, 103 S.Ct. 3308, 77 L.Ed.2d 987 (1983)); accord, e.g., Sellan v. Kuhlman, 261 F.3d at 317 ("This process of `winnowing out weaker arguments on appeal and focusing on' those more likely to prevail, far from being evidence of incompetence, is the hallmark of effective appellate advocacy.") (citations omitted). The habeas court should not second-guess the reasonable professional judgments of appellate counsel as to the most promising appeal issues. Jones, 463 U.S. at 754, 103 S.Ct. 3308; see also Jackson v. Leonardo, 162 F.3d 81, 85 (2d Cir.1998). Thus, a petitioner may establish constitutionally inadequate performance only by showing that appellate counsel "omitted significant and obvious issues while pursuing issues that were clearly and significantly weaker." Mayo, 13 F.3d at 533. Muldrow's appellate counsel raised three important issues in a thorough appellate brief to the Fourth Department, crafting persuasive arguments as to why the consent to search Muldrow's apartment given by his brother was invalid and why the trial court abused its discretion in allowing David Crutcher ("Crutcher"), who suffered from schizophrenia, to testify at trial. These two issues in particular were of the utmost importance to Muldrow's case, since the ballistics evidence from the guns seized from his apartment, together with Crutcher's testimony, strongly linked him to the murder. In contrast, the repugnant verdict issue urged by Muldrow in this habeas petition was neither significant nor promising on appeal, and it was entirely reasonable for Muldrow's appellate counsel to omit it. Because Muldrow has failed to demonstrate that his appellate counsel's performance was unreasonable, he cannot meet the first prong of the standard by which ineffective assistance claims are judged. However, even if he could establish that his appellate counsel's lawyering was deficient, Muldrow has not demonstrated that he was prejudiced by the deficiency. Because Muldrow and his codefendants were indicted and charged individually for the crimes of murder, as well as in accordance with accomplice liability pursuant to P.L. § 20.00,[2] it is clear that there were, in fact, no inconsistencies in the verdicts. Respondent correctly notes that the jury had to assess the evidence against each of three defendants *170 and make a separate determination of guilt as to each. The fact that the jury convicted two defendants and acquitted a third is of no legal significance. The jury may simply have believed that the evidence was stronger against the two defendants it found guilty, and not convincing as to the defendant (McGee) who was acquitted. Thus, the issue now raised by Muldrow is not persuasive, and he cannot establish prejudice from his appellate counsel's neglect in pursuing the issue because there was no "reasonable probability" that the omitted issue would have succeeded even had it been argued on appeal. See Torres v. Irvin, 33 F.Supp.2d 257, 267 (S.D.N.Y.1998) (even if petitioner could establish that appellate counsel's advocacy was deficient, he suffered no prejudice because no "reasonable probability" that the omitted claims would have succeeded) (citing Mayo, 13 F.3d at 534); Angel v. Garvin, 2001 WL 327150 at *10 (S.D.N.Y. Apr.3, 2001) (finding that petitioner could not establish prejudice as a result of appellate counsel's failure to raise non-meritorious claim based on insufficiency of the evidence). Moreover, an allegedly inconsistent verdict does not present a constitutional violation. Therefore, such a claim is not even cognizable on habeas review. The Supreme Court explained in United States v. Powell that where truly inconsistent verdicts have been reached, the most that can be said ... is that the verdict shows that either in the acquittal or the conviction the jury did not speak their real conclusions, but that does not show that they were not convinced of the defendant's guilt.... It is equally possible that the jury, convinced of guilt, properly reached its conclusion ... then through mistake, compromise, or lenity, arrived at an inconsistent conclusion on the [other] offense. 469 U.S. 57, 58, 64-65, 105 S.Ct. 471, 83 L.Ed.2d 461 (1984) (internal quotations and citation omitted); see also Harris v. Rivera, 454 U.S. 339, 345, 102 S.Ct. 460, 70 L.Ed.2d 530 (1981) ("Inconsistency in a verdict is not a sufficient reason for setting it aside."); United States v. Acosta, 17 F.3d 538, 544-45 (2d Cir.1994) ("Even assuming that the verdict against Acosta was inconsistent with the verdicts as to his codefendants, we find no basis for relief, for it has long been established that inconsistency in jury verdicts of guilty on some counts and not guilty on others is not a ground for reversal of the verdicts of guilty."); Savage v. Berbary, 1991 WL 147371 at *2 (W.D.N.Y. July 22, 1991) ("Alleged inconsistencies in state court verdicts are not a proper ground for federal habeas corpus intervention...."); Billups v. Costello, 1992 WL 170650 at *4 (S.D.N.Y. July 6, 1992) ("As long as a conviction is the result of a fair trial at which legally sufficient evidence has been adduced, its inconsistency with another verdict does not create a constitutional defect."). As his second ground for habeas relief, Muldrow claims that his appellate counsel was ineffective in failing to argue that he was improperly convicted of felony murder in light of the prosecution's alleged failure to prove a necessary element of burglary, the underlying felony charged in this case. Petitioner's Habeas Brief, Dkt. # 2 at 11. I find that this argument lacks merit and that counsel was justified in not raising it. Under New York law, all degrees of burglary require proof that the defendant "knowingly enter[ed] or remain[ed] unlawfully in a building with intent to commit a crime therein." See, e.g., P.L. § 140.25. Muldrow complains that "the trial proof was absent as to that intended *171 crime," leaving "the jury to speculate as to the intended crime." Dkt. # 2 at 12. As respondent points out, the prosecution need not establish what particular crime the intruder intended to commit in order to satisfy the elements of burglary under New York law. Respondent's Habeas Brief, Dkt. # 5 at 8 (citing People v. Mackey, 49 N.Y.2d 274, 279, 425 N.Y.S.2d 288, 401 N.E.2d 398 (1980) (the New York Penal Law "definition of burglary is satisfied if the intruder's intent, existing at the time of the unlawful entry or remaining, is to commit any crime")); accord People v. Gaines, 74 N.Y.2d 358, 362 n. 1, 547 N.Y.S.2d 620, 546 N.E.2d 913 (1989). Moreover, it is not necessary for the intended crime to be committed. Rather, "the intent necessary can be inferred from the circumstances of the entry itself." Mackey, 49 N.Y.2d at 279, 425 N.Y.S.2d 288, 401 N.E.2d 398. Muldrow contends that the prosecution never proved that he entered the house. Dkt. # 2 at 12. Although the gunmen were wearing black hats and their faces were partially concealed by their clothing, there was more than adequate circumstantial evidence at trial placing Muldrow at the scene of the crime. Crutcher, who lived in an apartment commandeered by Stubbs, McGee and Muldrow to sell cocaine, see Tr. at 1265-73, 1301, overheard Muldrow and his associates planning to kidnap the witnesses to the murder committed by Usher, see id. at 1280-87. Crutcher paid a friend to steal a car for him which he in turn provided to the defendants.[3]Id. at 1293-1300. On the night of the murder, Stubbs showed Crutcher four guns in a bedroom at the apartment and said, "`[T]his is what we're going to use tonight.'" Id. at 1302-03. Later that evening, when the defendants left in search of the witnesses, Crutcher observed Muldrow armed with one of the guns Stubbs had shown him earlier. About 45 minutes later, Crutcher testified that Stubbs returned to the apartment acting in an extremely emotional manner and demanded to know whether Muldrow, McGee or Grimes had called. Id. at 1316-19. The ballistics evidence provided further corroboration linking Muldrow to the shootings. Testing of the bullets recovered at the scene established that two of the guns found in Muldrow's apartment fired the bullets that killed one of the victims. The bullets fired at the second murder victim and the wounded victim shot were consistent with having come from a third gun found in Muldrow's apartment. In addition, Muldrow fled when the police stopped the car in which he was riding, but was caught after a foot chase. His unprovoked flight from the authorities reasonably could be viewed by the jury as an indicator of guilt. See United States v. Amuso, 21 F.3d 1251, 1259 (2d Cir.) (jury could rationally infer that flight was indicative of guilty conscience), cert. denied, 513 U.S. 932, 115 S.Ct. 326, 130 L.Ed.2d 286 (1994); Stone v. Stinson, 121 F.Supp.2d 226, 243 (W.D.N.Y. 2000) (petitioner's flight from Buffalo to Virginia following shootings could properly be considered by the jury as indicative of guilt); see also United States v. Malizia, 503 F.2d 578, 582-83 (2d Cir.1974) ("Evidence of flight, like any other circumstantial evidence, has consistently been admissible as evidence of guilt if considered with other facts of the case."), cert. denied, 420 U.S. 912, 95 S.Ct. 834, 42 L.Ed.2d 843 (1975). There was ample testimony from which the jury could have inferred that Muldrow *172 unlawfully entered the victims' home and intended to commit a crime while there. Consequently, the argument that the prosecution failed to prove all the elements of the burglary underlying the felony murder charge likely would not have succeeded on direct appeal. Appellate counsel thus acted reasonably in failing to raise it, and Muldrow was not prejudiced by the omission of this meritless argument from his appeal. I find that Muldrow was represented ably by the public defender on his direct appeal, and that his claims of ineffective assistance of appellate counsel are without merit. CONCLUSION For the reasons stated above, Timothy Muldrow's petition for a writ of habeas corpus pursuant to 28 U.S.C. § 2254 is denied, and the petition is dismissed. Because Muldrow has failed to make a substantial showing of a denial of a constitutional right, no certificate of appealability shall issue. 28 U.S.C. § 2253. Further, I certify that any appeal from this order would not be taken in good faith. See 28 U.S.C. § 1915(a); Coppedge v. United States, 369 U.S. 438, 444, 82 S.Ct. 917, 8 L.Ed.2d 21 (1962). IT IS SO ORDERED. NOTES [1] Muldrow raised both of these claims in an application for a writ of error coram nobis which was summarily denied by the Fourth Department on April 27, 2001. See Petition, Docket ("Dkt.") # 1 at 8. Thus, the claims are exhausted and properly before this Court on habeas review. [2] The third and fourth counts of the indictment, each charging murder in the second degree in violation of P.L. §§ 125.25 and 20.00, state that the defendant "while acting alone or with one or more persons, committed or attempted to commit...." [3] Crutcher was deemed to be an accomplice as a matter of law based on his role in procuring the vehicle allegedly used by the defendants in their commission of the murders.

Q: postgresql "createdb" and "CREATE DATABASE" yield a non-empty database. what the fork? First of all, I apologize if this question turns out to be painfully obvious, I'm not that postgres-savvy beyond the basics. I use postgresql as a database backend for quite a few django projects that I'm working on, and that's always worked just fine for me. Recently, I set up postgresql on a new machine, and at one point a co worker tried setting up a new project on that machine. Unfortunately, it's too late to go back into the bash history to figure out what he did, and he won't be available for a while to ask him about it. The issue i'm having now is... I regularly reset postgres databases by simply using a dropdb/createdb command. I've noticed that whenever I run the dropdb command, the database does disappear, but when I run the createdb command next, the resulting database is not empty. It contains tables, and those tables do contain data (which appears to be dummy data from the other project). I realise that i'm a bit of a postgres noob, but is this in some way related to template features in postgres? I don't specify anything like that on the command line, and I'm seeing the exact same results if I drop/create from the psql console. By the way, I can still wipe the db by dropping and recreating the "public" schema in the database. I'll be glad to add any info necessary to help figure this out, but to be honest I haven't a clue what to look for at this point. Any help would be much appreciated. A: Summarizing from the docs template0 is essentially a clean, virgin system database, whereas template1 serves as a blue print for any new database created with the createdb command or create database from a psql prompt (there is no effective difference). It is probable that you have some tables lurking in template1, which is why they keep reappearing on createdb. You can solve this by dropping template1 and recreating it from template0. createdb -T template0 template1 The template1 database can be extremely useful. I use Postgis a lot, so I have all of the functions and tables related to that installed in template1, so any new database I create is immediately spatially enabled. EDIT. As noted in docs, but worth emphasizing, to delete tempate1 you need to have pg_database.datistemplate = false set.

Konichiwa records Translation On Other Language: Konichiwa Records is a record label founded by Swedish pop singer Robyn. The label has only one other artist signed, Zhala. The word "Konichiwa" is derived from the Japanese greeting こんにちは (Konnichi wa), meaning "Hello" or "Good Day" (Literally "This Day Is").

About the Project About the Project (Grace Ioppolo) The Henslowe-Alleyn Papers, Past, Present and Future For over two hundred and fifty years, most of the Henslowe-Alleyn papers remained unbound and stored in the chest in which they had lain since the founding of the College by Edward Alleyn in 1619. Many individual documents, both large and small, were left in their original condition: folded up into small packets (a form of storage which preceded the use of envelopes). The volume comprising Henslowe’s Diary began to be borrowed from the library during the 18th and 19th centuries by the scholars Edmond Malone, John Payne Collier, and J. O. Halliwell-Phillips, among others. In fact, during this time, some of its pages were removed or otherwise destroyed (fragments have since been sold or auctioned and are now at the British Library, Bodleian Library, Belvoir Castle, and the Folger Shakespeare Library). In the early 19th century, staff at Dulwich were successful in reclaiming the play The Telltale and the plot of the Second Part of the Seven Deadly Sins from an auction, but over the years many other items were dispersed (and have not yet been definitively identified), including about one hundred play manuscripts and a number of printed books bequeathed to the College in 1687 by the actor and bibliophile William Cartwright the younger. In the 1870s, the Governors of Dulwich College asked George Warner, an expert at the British Museum, to catalogue the manuscripts. Warner spent many years assessing the contents of the archive as he found it, expertly opening, repairing and ordering the documents in the archive, finally having them bound into a set of 36 volumes which he named the ‘Alleyn Papers’. He left the muniments, some of which are extremely large in size, unbound. In 1881, he published The Catalogue of the Manuscripts and Muniments of Alleyn’s College of God’s Gift at Dulwich (London: Longmans, Green, and Co.). Further discoveries at the archive were listed by Francis Bickley in the Second Series of The Catalogue of the Manuscripts and Muniments of Alleyn’s College of God’s Gift at Dulwich (London: privately printed, 1903). Half of these manuscript volumes and most of the muniments concern the private affairs and non-theatrical businesses of the Henslowe and Alleyn families, as well as the history of Dulwich College since its inception. It is the other half of these volumes, representing the theatrical affairs of Henslowe and Alleyn, that are the subject of this website and electronic archive. Less than half of the theatrical items in the Henslowe-Alleyn Papers have ever been transcribed, and these transcriptions are largely available only in out-of-print editions. R. A. Foakes’s 1977 photographic facsimile edition of two volumes of manuscripts (The Henslowe Papers) had a limited printing and only covers 20% of the relevant archive. The 2002 reprinting of Foakes’s standard 1961 edition of Henslowe's Diary (Cambridge University Press) has widely encouraged scholars to pursue other material in the Dulwich archive. The archive is of value also to Museum of London archaeologists, who are now using new technology, such as radar scanning, to examine the original sites in Southwark and Shoreditch of various early modern playhouses, including the Theatre, the Globe, and the Rose, and who are radically re-evaluating their data about the building of these playhouses. Although transcriptions of the over 2200 pages of manuscripts are not yet available in this electronic archive and website, the members of the Henslowe-Alleyn Digitisation Project hope that making the manuscripts themselves available as photographic images will encourage further study and use of this very rich resource not just by literary, theatrical and manuscripts scholars, economic, social and regional historians and archaeologists but students, actors, directors and other theatre personnel, as well as all members of the general population of readers who are interested in the greatest age of English professional drama and theatrical production. This Project is designed for research purposes only. For reasons of copyright, images and content are not downloadable from the website or the electronic archive, nor can any material be used, copied, circulated or reproduced in any format without permission and acknowledgement. The copyright of all the manuscripts in the Alleyn Papers belongs to the Governors of Dulwich College. For digital photographs or reproductions of any of the manuscripts, for permissions to reproduce them in any format, or for more information about the manuscript photography, the website and electronic archive, please use see Copyrights, Reproductions and Permissions. The Project has been graciously supported by grants from The Leverhulme Trust, The British Academy, The Thriplow Charitable Trust, The Pilgrim Trust, the Henry E. Huntington Library, the Folger Shakepeare Library, the British and American Bibliographical Societies, and The University of Reading, for which the members of the Project remain very grateful.

[Diagnostic use of laser Doppler flowmetry in patients with circulatory insufficiency]. Laser Doppler Flowmetry (LDF) is a method for continuous quantification of microvascular perfusion. The article briefly presents the principle of the method, and reviews the literature dealing with diagnostic use of LDF in patients with insufficient extremity circulation. The location and degree of vascular lesions can be evaluated, and non-invasive evaluation of peripheral vascular resistance performed in the vascular laboratory. Prospective human studies are needed before the clinical value of the method can be assessed.

Introduction ============ RNA interference (RNAi) is a highly efficient gene-silencing mechanism in which a small interfering RNA (siRNA) binds a target mRNA, guiding mRNA cleavage via an RNA-induced silencing complex (RISC).^[@bib1],[@bib2]^ This biological phenomenon is widely used as a genetic tool in biomedical research. Advances in RNA chemistry have expanded siRNA applications toward therapeutic development, with robust efficacy seen in phase 2 clinical trials for liver diseases (*e.g.*, transthyretin amyloidosis).^[@bib3],[@bib4],[@bib5]^ Despite its prevalence in biomedical research, the use of RNAi in neurodegenerative research has been limited.^[@bib6]^ There is a significant unmet need for simple, effective, and nontoxic siRNA delivery methods to modulate gene expression in primary neurons and brain. A range of approaches has been evaluated,^[@bib7]^ including AAV viruses,^[@bib8],[@bib9]^ peptide conjugates,^[@bib10]^ oligonucleotide formulations,^[@bib11]^ infusion of naked or slightly modified siRNAs,^[@bib12],[@bib13]^ ultrasound,^[@bib14]^ and convection-enhanced based delivery.^[@bib15]^ None of these approaches has received wide acceptance due to toxicity, a requirement for extensive repetitive dosing, and/or limited spatial distribution. Lipofection and electroporation of siRNAs are challenging in primary neurons due to low transfection efficiencies and their extreme sensitivity to external manipulation.^[@bib16]^ Delivery of siRNA precursors (Lentiviruses and AAV) has been used successfully, but viral transduction cannot readily be turned off and requires extensive formulation and experimental optimization to achieve reproducible, nontoxic silencing in neuronal cells.^[@bib17],[@bib18],[@bib19],[@bib20],[@bib21],[@bib22]^ In this study, we describe the delivery, distribution, and silencing capacity of hydrophobically modified siRNAs (hsiRNAs) in primary neurons and in mouse brain. hsiRNAs are siRNA-antisense hybrids containing numerous chemical modifications (see **[Figure 1](#fig1){ref-type="fig"}** and **Supplementary Table S1** for exact chemical composition of compounds used) designed to promote biodistribution and stability while minimizing immunogenicity. As a model for our studies, we silenced the huntingtin (*Htt*) gene, the causative gene in Huntington\'s disease (HD). HD is an autosomal-dominant neurodegenerative disorder caused by a toxic expansion in the CAG repeat region of the huntingtin gene leading to a variety of molecular and cellular consequences. Tetrabenazine, the only FDA-approved therapy for HD, seeks to alleviate disease symptoms but does not treat the actual problem: the gain of toxic function caused by mutant *Htt*. Recent studies suggest that transient neuronal knockdown of *Htt* mRNA can reverse disease progression without compromising normal cellular function *in vivo*.^[@bib23]^ At present, RNA interference via siRNA or antisense oligonucleotide is one of the most promising therapeutic approaches for transient *Htt* mRNA silencing. We performed a screen of hsiRNAs targeting *Htt* mRNA and identified multiple functional compounds. We showed that primary neurons internalize hsiRNA added directly to the culture medium, with membrane saturation occurring by 1 hour. Direct uptake in neurons induces potent and long-lasting silencing of *Htt* mRNA for up to 3 weeks *in vitro* without major detectable effects on neuronal viability. Additionally, a single injection of unformulated (without cationic lipid or AAV formulation) *Htt* hsiRNA into mouse brain silences *Htt* mRNA with minimal neuronal toxicity. Efficient gene silencing in primary neurons and *in vivo* upon direct administration of unformulated hsiRNA represents a significant technical advance in the application of RNAi to neuroscience research, enabling technically achievable genetic manipulation in a native, biological context. Results ======= hsiRNAs are efficiently internalized by primary neurons ------------------------------------------------------- hsiRNA is an asymmetric compound composed of a 15-nucleotide modified RNA duplex with a single-stranded 3′ extension on the guide strand (**[Figure 1a](#fig1){ref-type="fig"}** and **Supplementary Table S1**).^[@bib24],[@bib25]^ Pyrimidines in the hsiRNA are modified with 2′-O-methyl (passenger strand) or 2′-fluoro (guide strand) to promote stability, and the 3′ end of the passenger strand is conjugated to a hydrophobic teg-Chol (tetraethylene glycol cholesterol) to promote membrane binding and association.^[@bib26]^ The single-stranded tail contains hydrophobic phosphorothioate linkages and promotes cellular uptake by a mechanism similar to that of antisense oligonucleotides.^[@bib27]^ The presence of phosphorothioates, ribose modifications, and a cholesterol conjugate contribute to overall hydrophobicity and are essential for compound stabilization and efficient cellular internalization. Previous studies have shown that hydrophobically modified siRNAs bind to a wide range of cells and is readily internalized without the requirement for a transfection reagent.^[@bib26],[@bib28],[@bib29]^ Here, we evaluated whether asymmetric hydrophobically modified siRNAs are efficiently internalized by primary neurons. We found that, when added to the culture medium, Cy3-labeled hsiRNAs rapidly associated with primary cortical neurons (**[Figure 1b](#fig1){ref-type="fig"}**). These Cy3-labeled hsiRNAs were observed in every cell in the culture, demonstrating efficient and uniform uptake. Initially, hsiRNAs mainly associate with neurites and, over time, accumulate in the cell bodies. Treatment of primary neurons with a previously identified hsiRNA targeting *Ppib*^[@bib26],[@bib28]^ (encodes cyclophilin B) reduced target mRNA levels by 90%, further supporting that the observed compound internalization results in potent gene silencing (**[Figure 1c](#fig1){ref-type="fig"}**). Identification of hsiRNAs that silence huntingtin mRNA ------------------------------------------------------ Robust uptake and efficacy observed with hsiRNAs in primary cortical neurons encouraged us to identify functional compounds that target *Htt* mRNA, the single gene responsible for the development of Huntington\'s disease. The hsiRNA\'s extensive chemical scaffold^[@bib26],[@bib28]^ is essential for stability, minimization of innate immune response,^[@bib30],[@bib31]^ and cellular internalization but imposes significant restrictions on sequence space by potentially interfering with the compound\'s RISC-entering ability. To maximize the likelihood of identifying functional *Htt* hsiRNAs and to evaluate the hit rate for this type of chemistry, we designed (using conventional criteria described in Materials and Methods) and synthesized hsiRNAs targeting 94 sites across the human *Htt* mRNA (**Supplementary Table S1**). The panel of hsiRNAs was initially screened for efficacy in HeLa cells by adding hsiRNA directly to the culture medium (without lipofection or electroporation) to a final concentration of 1.5 µmol/l and evaluating impact on levels of *Htt* and housekeeping (*Ppib*) gene mRNA expression using the QuantiGene (Affymetrix, Santa Clara, CA) assay. At this concentration, 24 hsiRNAs reduced *Htt* mRNA levels to less than 50% of control levels, including 7 hsiRNAs that reduced *Htt* mRNA levels below 30% of control (**[Figure 2a](#fig2){ref-type="fig"}**). Unlike unmodified siRNA libraries, creating a library with extensive 2\'-O-methyl and 2\'-fluoro modifications introduces additional constraints on sequence selection. As a result, hit rates for modified siRNA screens are lower than that seen for conventional unmodified siRNA.^[@bib32],[@bib33],[@bib34],[@bib35]^ Functional hsiRNAs targeted sites distributed throughout the mRNA, except the distal end of the 3′ UTR, which later was shown to be part of the alternative *Htt* gene isoform^[@bib36]^ not expressed in HeLa cells (data not shown). Discounting the \~32 hsiRNAs targeting long 3′ UTR sites absent from the *Htt* isoform in HeLa cells, almost 40% of hsiRNAs showed some level of activity at 1.5 µmol/l, demonstrating that the evaluated chemical scaffold is well tolerated by the RNAi machinery and a functional compound can be easily identified against a wide range of targets. Half-maximal inhibitory concentrations (IC~50~) for passive uptake of hsiRNAs ranged from 82 to 766 nmol/l (**Supplementary Table S1 and Figure S1**). In lipid-mediated delivery, eight of the most active hsiRNAs had IC~50~ values ranging from 4 to 91 pmol/l (**Supplementary Table S1**). The best clinically active siRNAs are usually characterized by IC~50~ values in the low pmol/l range.^[@bib37]^ An ability to identify highly potent compounds with low picomolar IC~50~ values suggests that the hsiRNA chemical scaffold does not interfere with siRNA biological activity in selected compounds. The most potent hsiRNA targeting position, 10150 (HTT10150), and an unmodified conventional siRNA version of HTT10150 showed similar IC~50~ values in lipid-mediated delivery (4 and 13 pmol/l respectively, **[Figure 2c](#fig2){ref-type="fig"}**), further confirming that the hsiRNA chemical scaffold does not interfere with RISC loading or function. Only the fully modified hsiRNA, and not the unmodified version, silenced *Htt* mRNA by passive uptake (**[Figure 2b](#fig2){ref-type="fig"}**). Thus, the chemical scaffold described here does not interfere with RISC assembly and is sufficient to support unformulated compound uptake and efficacy. HTT10150 was used for subsequent studies. Potent and specific silencing with unformulated hsiRNAs in primary neurons -------------------------------------------------------------------------- HTT10150 induced a concentration-dependent silencing at 72 hours and 1 week after unformulated addition to either primary cortical or primary striatal neurons isolated from FVB/NJ mice (**[Figure 3a](#fig3){ref-type="fig"}**). At 1.25 µmol/l, HTT10150 induced maximal silencing, reducing both *Htt* mRNA levels and HTT protein levels by as much as 70 and 85%, respectively (**[Figure 3a](#fig3){ref-type="fig"}**--**[c](#fig3){ref-type="fig"}** for original westerns). HTT10150 hsiRNA did not affect the expression levels of housekeeping controls (*Ppib* and *Tubb1*) or the overall viability of primary neuronal cells, as measured by the alamarBlue assay, up to a 2 µmol/l concentration (**Supplementary Figure S2**). Similar results were obtained with another hsiRNA targeting *Htt* mRNA (**[Figure 3c](#fig3){ref-type="fig"}**), supporting that the observed phenomena is not unique to HTT10150. These experiments, in conjugation with the results seen from targeting *Ppib* (**[Figure 1b](#fig1){ref-type="fig"}**), indicate that a diversity of genes and target sequences can be silenced by hsiRNAs in primary neurons simply upon direct addition of compounds into cellular media. Since loaded RISC has a typical half-life of weeks,^[@bib38]^ silencing is expected to be long lasting in nondividing cells. To evaluate duration of silencing after a single HTT10150 treatment of primary cortical neurons, *Htt* mRNA levels were measured at 1-, 2-, and 3-week intervals (**[Figure 3d](#fig3){ref-type="fig"}**). A single treatment with hsiRNA induced *Htt* silencing that persisted for at least 3 weeks, the longest time that primary cortical neurons can be maintained in culture. Together, these data demonstrate that hsiRNAs are a simple and straightforward approach for potent, specific, nontoxic, and long-term modulation of gene expression in primary neurons *in vitro*. hsiRNA distribution *in vivo* in mouse brain after intrastriatal injection -------------------------------------------------------------------------- Having shown that hsiRNAs effectively silence their targets in primary neurons *in vitro*, we sought to evaluate the ability of HTT10150 to silence *Htt* mRNA in the mouse brain *in vivo*. The distribution of HTT10150 was evaluated in perfused brain sections prepared 24 hours after intrastriatal injection with 12.5 µg Cy3-labeled hsiRNA in artificial cerebral spinal fluid (ACSF). We observed a steep gradient of fluorescence emanating from the injection site and covering most of the ipsilateral striatum (**[Figure 4a](#fig4){ref-type="fig"}**,**[b](#fig4){ref-type="fig"}**), while no fluorescence was visually detectable in the contralateral side of the brain. In high magnification images of the ipsilateral side, hsiRNAs appeared preferentially associated with the tissue matrix and fiber tracts. In addition, efficient internalization was observed in a majority of cell bodies (**[Figure 4c](#fig4){ref-type="fig"}**,**[d](#fig4){ref-type="fig"}**). Consistent with *in vitro* studies, we observed Cy3-labeled hsiRNA in neuronal processes and as punctae in the perinuclear space of multiple cell types, including NeuN-positive neurons^[@bib39],[@bib40]^ (**[Figure 4d](#fig4){ref-type="fig"}**,**[e](#fig4){ref-type="fig"}**). In summary, a single intrastriatal injection delivers hsiRNA to neurons in the striatum of the injected side. hsiRNA effectively silences Htt in vivo with minimal cytotoxicity or immune activation -------------------------------------------------------------------------------------- To measure HTT10150 efficacy *in vivo*, we performed dose-response studies in wild type FVB/NJ mice injected intrastriatally with 3.1, 6.3, 12.5, or 25 µg of HTT10150. As controls, we injected mice with a non-targeting control hsiRNA (NTC), ACSF, or PBS. In punch biopsies taken from the ipsilateral and contralateral striatum, HTT10150 reduced *Htt* mRNA levels in a dose-dependent manner (**[Figure 5a](#fig5){ref-type="fig"}**). This experiment was repeated several times with similar results. The *Htt* mRNA is significantly reduced in the ipsilateral side of striatum in all experiments. We observed robust dose-dependent silencing with up to 77% (one-way analysis of variance, *P* \< 0.0001) reduction in *Htt* mRNA expression levels at the highest dose. Interestingly we observe statistically significant, but less pronounced silencing in the contralateral striatum and the cortex. The silencing reaches statistical significance with both one-way and two-way analysis of variance (values for two-way analysis of variance are presented in **[Figure 5](#fig5){ref-type="fig"}**). While some level of fluorescence is detectable in these brain regions with high laser intensity, it is very close to the tissue auto-fluorescence and thus is not reported here. We will be investigating this phenomenon further, but it is clear that the level of silencing is at least correlative to the sharp gradient of diffusion from the injection site. Finally, *Htt* mRNA silencing is observed with HTT10150 but not with NTC or ACSF (**[Figure 5](#fig5){ref-type="fig"}**). In addition, the HTT10150 does not affect expression of several housekeeping genes (PPIB, HPRT). In combination, this is indicative of *Htt* mRNA silencing being caused by HTT10150 hsiRNA and not by off-target effects. Nucleic acids, including siRNAs, are potent stimulators of the innate immune response,^[@bib41]^ but extensive chemical modifications, like 2′-O-methyl, are expected to suppress the immunostimulatory effects of siRNAs *in vitro* and *in vivo*.^[@bib42]^ To assess innate immune response activation by hsiRNAs *in vivo*, we quantified IBA-1-positive microglial cells in brain sections from mice injected with 12.5 µg HT10150 or artificial CSF. IBA-1 is specific to microglial cells and is upregulated following injury to the brain, allowing us to distinguish between resting and activated microglia.^[@bib43],[@bib44],[@bib45]^ In the case of a major innate immune response, an increase of 200--300% in total microglia is customary.^[@bib46]^ Total microglia counts showed only a 25% increase in the ipsilateral striatum at 5 days post-injection indicating a lack of any major inflammatory response (**Supplementary Figure S3**). Thus, the observed activation is relatively minor but reaches statistical significance, indicating some level of response. Levels of innate immune response might be more pronounced immediately following compound administration. To assess the level of stimulation in more detail, we separately evaluated the number of activated and resting microglia at both 6 hours and 5 days post-injection. At 6 hours post-injection, we observed a significant increase in the number of activated microglia in the injected side of the brain with both ACSF and HTT10150. The injection event itself causes trauma and induces a major increase in activated microglia (ninefold) compared to the contralateral side of the brain (**[Figure 6b](#fig6){ref-type="fig"}**).^[@bib12],[@bib47]^ In the presence of HTT10150, the number of activated microglia was additionally increased twofold compared to ACSF, indicating enhancement of trauma-related microglia activation in the presence of oligonucleotide, although the relative contribution of the oligonucleotide to the trauma-related induction is minor. HTT10150-treated mice also showed some elevation of activated microglia in the contralateral striatum 6 hours post-injection (**[Figure 6b](#fig6){ref-type="fig"}**); however, after 5 days, all changes in number of microglia in the contralateral side of the brain disappeared (**[Figure 6a](#fig6){ref-type="fig"}**,**[c](#fig6){ref-type="fig"}** for representative images), suggesting that HTT10150-dependent activation of microglia in the contralateral striatum is transient. Despite the mild immune stimulation in the brains of animals injected with HTT10150, we did not observe any overall significant reduction of DARPP-32, an established marker for striatal neuron viability^[@bib48]^ (**[Figure 7](#fig7){ref-type="fig"}**). The only observed effect was at a small area directly around the injection site in animals treated with 25 µg HTT10150 (**Supplementary Figure S4**). Taken together, our data show that a single intrastriatal injection of hsiRNA induces potent gene silencing with a mild immune response and minimal neuronal toxicity *in vivo*. Discussion ========== Simple, effective, and nontoxic delivery of synthetic oligonucleotides to primary neurons and brain tissue represents a challenge to the use of RNAi as a research tool and therapeutic for neurodegenerative diseases like HD.^[@bib7]^ We have shown that hsiRNAs elicit potent silencing in primary neurons in culture, without effect on housekeeping gene expression, and with minimal toxicity at effective doses Additionally, a non-targeting control hsiRNA did not silence any of the mRNAs tested (*Htt*, *Ppib*, *Hprt*), suggesting that these compounds are both sequence specific and on-target. Interestingly, the level of silencing is more pronounced on the protein level (\>90%) compared to the mRNA level (\>70%). The mRNA plateau effect is reproducible and is specific to *Htt* mRNA, as housekeeping genes like *Ppib* can be silenced by 90%. One potential explanation is that some fraction of huntingtin mRNA is translationally inactive and poorly accessible by RNAi machinery. We are continuing to investigate this phenomenon. Silencing in primary neurons persists for multiple weeks after a single administration, consistent with the expected half-life of active RISC.^[@bib49]^ Moreover, efficient intracellular delivery does not require the use of lipids or viral packaging. Currently, the most impressive *in vivo* modulation of *Htt* mRNA expression is demonstrated with 2′-O-methoxyethyl GapmeR antisense oligonucleotides. A single injection of 50 µg of antisense oligonucleotides or infusion of around 500 µg results in potent and specific *Htt* mRNA silencing and marked improvement in multiple phenotypic endpoints.^[@bib23],[@bib50],[@bib51],[@bib52]^ However, 2′-O-methoxyethyl GapmeR antisense oligonucleotides are not readily commercially available making them inaccessible for the majority of academic labs. Here, we show *Htt* mRNA silencing in the ipsilateral striatum and cortex, two brain areas significantly affected in HD disease progression, with a single intrastriatal injection. As a considerably reduced level of silencing was observed on the contralateral side of the brain, bilateral injections might be necessary to promote equal gene silencing in both hemispheres. The limited distribution profile observed *in vivo* restricts immediate adoption of this technology for use in larger brains and eventually as a therapeutic for neurodegenerative disease. Tissue distribution can be improved by tailoring the chemical scaffold (*e.g.*, number and type of sugar modifications, position of phosphorothioate linkages) or by changing the conjugation moiety to promote receptor-mediated cellular internalization. Formulation of hsiRNA in exosomes, exosome-like liposomes, or shielding the compounds with polyethylene glycol may also provide an alternative strategy to improve tissue distribution.^[@bib53],[@bib54]^ Here, we describe a class of self-delivering therapeutic oligonucleotides capable of targeted, nontoxic, and efficient *Htt* gene silencing in primary neurons and *in vivo*. This chemical scaffold can be specifically adapted to many different targets to facilitate the study of neuronal gene function *in vitro* and *in vivo*. The development of an accessible strategy for genetic manipulation in the context of a native, biological environment represents a technical advance for the study of neuronal biology and neurodegenerative disease. Materials and methods ===================== *hsiRNA design.* We designed and synthesized a panel of 94 hsiRNA compounds (**Supplementary Table S1**) targeting the human huntingtin gene. These sequences span the gene and were selected to comply with standard siRNA design parameters^[@bib24]^ including assessment of GC content, specificity and low seed compliment frequency,^[@bib55]^ elimination of sequences containing miRNA seeds, and examination of thermodynamic bias.^[@bib56],[@bib57]^ *Oligonucleotide synthesis, deprotection, and purification.* Oligonucleotides were synthesized using standard phosphoramidite, solid-phase synthesis conditions on a 0.2--1 µmole scale using a MerMade 12 (BioAutomation, Irving, TX) and Expedite DNA/RNA synthesizer. Oligonucleotides with unmodified 3′ ends were synthesized on controlled pore glass (CPG) functionalized with long-chain alkyl amine and a Unylinker terminus (Chemgenes, Wilmington, MA). Oligonucleotides with 3′-cholesterol modifications were synthesized on modified solid support (Chemgenes). Phosphoramidite solutions were prepared at 0.15 mol/l in acetonitrile for 2′-TBDMS, 2′-O-methyl (Chemgenes), and Cy3 modifications or 0.13 mol/l for 2′-fluoro (BioAutomation) modifications. Phosphoramidites were activated in 0.25 mol/l 4,5-dicyanoimidazole in acetonitrile. Detritylation was performed in 3% dichloroacetic acid in dichloromethane for 80 seconds. Capping was performed in 16% *N*-methylimidazole in tetrahydrofuran and acetic anhydride:pyridine:tetrahydrofuran, (1:2:2, v/v/v) for 15 seconds. Oxidation was performed using 0.1 mol/l iodine in pyridine:water:tetrahydrofuran (1:2:10, v/v/v). The CPG was removed from the solid-phase column and placed in a polypropylene screw cap vial. Dimethylsulfoxide (100 µl) and 40% methylamine (250 µl) are added directly to the CPG and shaken gently at 65 °C for exactly 16 minutes. The vial was cooled on dry ice before the cap was removed. The supernatant was transferred to another polypropylene screw cap vial, and the CPG was rinsed with two 150 µl portions of dimethylsulfoxide, which were combined with original supernatant. Oligonucleotides without 2′-TBDMS-protecting groups were lyophilized. Oligonucleotides with 2′-TBDMS-protecting groups were desilylated by adding 375 µl triethylamine trihydrofluoride (\~1.5 volumes relative to 40% methylamine) and incubated for exactly 16 minutes at 65 °C with gentle shaking. Samples were quenched by transferring to a 15 ml conical tube containing 2 ml of 2 mol/l triethylammonium acetate buffer (pH 7.0). The sample was stored at −80 °C until high-performance liquid chromatography purification. Oligonucleotides were purified by reverse-phase high-performance liquid chromatography on a Hamilton PRP-C18 column (21 × 150 mm) using an Agilent Prostar 325 high-performance liquid chromatography (Agilent, Santa Clara, CA). Buffer A 0.05 mol/l tetraethylammonium acetate with 5% acetonitrile, Buffer B 100% acetonitrile, with a gradient of 0% B to 35% B over 15 minutes at 30 ml/minutes. Purified oligonucleotides were lyophilized to dryness, reconstituted in water, and passed over a Hi-Trap cation exchange column to exchange the tetraethylammonium counter-ion with sodium. *Cell culture.* HeLa cells (ATCC, Manassas, VA; \#CCL-2) were maintained in Dulbecco\'s Modified Eagle\'s Medium (Cellgro, Corning, NY; \#10-013CV) supplemented with 10% fetal bovine serum (FBS; Gibco, Carlsbad, CA; \#26140) and 100 U/ml penicillin/streptomycin (Invitrogen, Carlsbad, CA; \#15140) and grown at 37 °C and 5% CO~2~. Cells were split every 2 to 5 days and discarded after 15 passages. *Preparation of primary neurons.* Primary cortical neurons were obtained from FVB/NJ mouse embryos at embryonic day 15.5. Pregnant FVB/NJ females were anesthetized by intraperitoneal injection of 250 mg Avertin (Sigma, St Louis, MO; \#T48402) per kg weight, followed by cervical dislocation. Embryos were removed and transferred into a Petri dish with ice-cold Dulbecco\'s Modified Eagle\'s Medium/F12 medium (Invitrogen; \#11320). Brains were removed, and meninges carefully detached. Cortices were isolated and transferred into a 1.5-ml tube with prewarmed papain solution for 25 minutes at 37 °C, 5% CO~2~, to dissolve tissue. Papain solution was prepared by suspending DNase I (Worthington, Lakewood, NJ; \#54M15168) in 0.5 ml Hibernate E medium (Brainbits, Springfield, IL; \#HE), and transferring 0.25 ml DNase I solution to papain (Worthington, Lakewood, NJ; \#54N15251) dissolved in 2 ml Hibernate E medium and 1 ml Earle\'s balanced salt solution (Worthington; \#LK003188). After the 25-minute incubation, papain solution was replaced with 1 ml NbActiv4 medium (Brainbits; \#Nb4-500) supplemented with 2.5% FBS. Cortices were dissociated by repeated pipetting with a fire-polished, glass, Pasteur pipette. Cortical neurons were counted and plated at 1 × 10^6^ cells per ml. For live-cell imaging, culture plates were precoated with poly-[l]{.smallcaps}-lysine (Sigma; \#P4707), and 2 × 10^5^ cells were added to the glass center of each dish. For silencing assays, neurons were plated on 96-well plates precoated with poly-[l]{.smallcaps}-lysine (BD BIOCOAT, Corning, NY; \#356515) at 1 × 10^5^ cells per well. After overnight incubation at 37 °C, 5% CO~2~, an equal volume of NbActiv4 supplemented with anti-mitotics, 0.484 µl/ml of UTP Na~3~ (Sigma; \#U6625), and 0.2402 µl/ml of FdUMP (Sigma; \#F3503), was added to neuronal cultures to prevent growth of nonneuronal cells. Half of the media volume was replaced every 48 hours until the neurons were treated with siRNA. Once the cells were treated, media was not removed, only added. All subsequent media additions contained antimitotics. *Direct delivery (passive uptake) of oligonucleotides.* Cells were plated in Dulbecco\'s Modified Eagle\'s Medium containing 6% FBS at 10,000 cells per well in 96-well tissue culture plates. hsiRNA was diluted to twice the final concentration in OptiMEM (Gibco; \#31985-088), and 50 μl diluted hsiRNA was added to 50 μl of cells, resulting in 3% FBS final. Cells were incubated for 72 hours at 37 °C and 5% CO~2~. Based on previous experience, we know that 1.5 µmol/l active hsiRNA supports efficient silencing without toxicity. The primary screen for active *Htt* siRNAs, therefore, was performed at 1.5 µmol/l compound, which also served as the maximal dose for *in vitro* dose--response assays. *hsiRNA lipid-mediated delivery.* Cells were plated in Dulbecco\'s Modified Eagle\'s Medium with 6% FBS at 10,000 cells per well in 96-well tissue culture--treated plates. hsiRNA was diluted to four times the final concentration in OptiMEM, and Lipofectamine RNAiMAX Transfection Reagent (Invitrogen; \#13778150) was diluted to four times the final concentration (final = 0.3 µl/25 µl/well). RNAiMAX and hsiRNA solutions were mixed 1:1, and 50 µl of the transfection mixture was added to 50 µl of cells resulting in 3% FBS final. Cells were incubated for 72 hours at 37 °C and 5% CO~2~. *mRNA quantification in cells and tissue punches.* mRNA was quantified using the QuantiGene 2.0 Assay (Affymetrix; \#QS0011). Cells were lysed in 250 μl diluted lysis mixture composed of 1 part lysis mixture (Affymetrix; \#13228), 2 parts H~2~O, and 0.167 μg/μl proteinase K (Affymetrix; \#QS0103) for 30 minutes at 55 °C. Cell lysates were mixed thoroughly, and 40 μl (\~8,000 cells) of each lysate was added per well to a capture plate with 40 μl diluted lysis mixture without proteinase K. Probe sets were diluted as specified in the Affymetrix protocol. For HeLa cells, 20 μl human *HTT* or *PPIB* probe set (Affymetrix; *\#*SA-50339, \#SA-10003) was added to appropriate wells for a final volume of 100 μl. For primary neurons, 20 μl of mouse *Htt* or *Ppib* probe set (Affymetrix; *\#*SB-14150, \#SB-10002) was used. Tissue punches (5 mg) were homogenized in 300 μl of Homogenizing Buffer (Affymetrix; \#10642) containing 2 μg/μl proteinase K in 96-well plate format on a QIAGEN TissueLyser II (Qiagen, Valencia, CA; \#85300), and 40 μl of each lysate was added to the capture plate. Probe sets were diluted as specified in the Affymetrix protocol, and 60 μl of *Htt* or *Ppib* probe set was added to each well of the capture plate for a final volume of 100 μl. Signal was amplified according to the Affymetrix protocol. Luminescence was detected on either a Veritas Luminometer (Promega, Madison, WI; \#998--9100) or a Tecan M1000 (Tecan, Morrisville, NC). *Western blot.* Cell lysates (25 µg) were separated by SDS--PAGE using 3--8% Tris-acetate gels (Life Technologies, Grand Island, NY; \#EA03785BOX) and transferred to nitrocellulose using a TransBlot Turbo apparatus (BioRad, Hercules, CA; \#1704155). Blots were blocked in 5% nonfat dry milk (BioRad; \#1706404) diluted in Tris-buffered saline with 0.1% Tween-20 (TBST) for 1 hour at room temperature then incubated in N-terminal antihuntingtin antibody Ab1^[@bib58]^ diluted 1:2,000 in blocking solution overnight at 4 °C with agitation. After washing in TBST, blots were incubated in peroxidase-labeled antirabbit IgG (Jackson ImmunoResearch, West Grove, PA; \#711035152) diluted in blocking buffer for 1 hour at room temperature, washed in TBST, and proteins were detected using SuperSignal West Pico Chemiluminescent Substrate (Thermo Scientific, Rockford, IL; \#34080) and Hyperfilm ECL (GE Healthcare, Buckinghamshire, UK; \#28906839). Blots were reprobed with anti-β tubulin antibody (Sigma; \#T8328) as a loading control. Films were scanned with a flatbed scanner (Epson Perfection V750 Pro; Epson, Long Beach, CA), and densitometry was performed using NIH ImageJ software to determine total intensity of each band. The huntingtin signal was divided by the tubulin signal to normalize to protein content, and percent of untreated control was determined for each set of samples (*N* = 5). *Live cell imaging.* To monitor live cell hsiRNA uptake, cells were plated at a density of 2 × 10^5^ cells per 35-mm glass-bottom dish. Cell nuclei were stained with NucBlue (Life Technologies; \#R37605) as indicated by the manufacturer. Imaging was performed in phenol red-free NbActiv4 (Brainbits; \#Nb4-500). Cells were treated with 0.5 μmol/l Cy3-labeled hsiRNA, and live cell imaging was performed over time. All live cell confocal images were acquired with a Leica DM IRE2 confocal microscope using 63x oil immersion objective (Buffalo Grove, IL), and images were processed using ImageJ (1.47v) software. *Stereotaxic injections.* FVB/NJ mice (50% male and 50% female for each dose group, 6--8 weeks old) were deeply anesthetized with 1.2% Avertin (Sigma; \#T48402) and microinjected by stereotactic placement into the right striatum (coordinates relative to bregma: 1.0 mm anterior, 2.0 mm lateral, and 3.0 mm ventral). For both toxicity (DARPP-32 staining) and efficacy studies, mice were injected with either PBS or artificial CSF (2 μl per striata), 12.5 μg of nontargeting hsiRNA (2 μl of 500 µmol/l stock per striata), 25 μg of HTT10150 hsiRNA (2 μl of 1 mmol/l stock per striata), 12.5 μg of HTT10150 hsiRNA (2 μl of 500 μmol/l stock per striata), 6.3 μg of HTT10150 hsiRNA (2 μl of 250 μmol/l stock per striata), or 3.1 μg of HTT10150 hsiRNA (2 μl of 125 μmol/l stock per striata). For toxicity studies, *n* = 3 mice were injected per group, and for efficacy studies, *n* = 8 mice were injected per group. Mice were euthanized 5 days post-injection, brains were harvested, and three 300-μm coronal sections were prepared. From each section, a 2-mm punch was taken from each side (injected and noninjected) and placed in RNAlater (Ambion, Carlsbad, CA; \#AM7020) for 24 hours at 4 °C. Each punch was processed as an individual sample for Quantigene 2.0 assay analysis (Affymetrix) and averaged for a single animal point. All animal procedures were approved by the University of Massachusetts Medical School Institutional Animal Care and Use Committee (protocol number A-2411). *Immunohistochemistry/immunofluorescence.* Mice were injected intrastriatally with 12.5 µg of Cy3-labeled hsiRNA. After 24 hours, mice were sacrificed and brains were removed, embedded in paraffin, and sliced into 4-μm sections that were mounted on glass slides. Sections were deparaffinized by incubating in Xylene twice for 8 minutes. Sections were rehydrated in serial ethanol dilutions (100%, 95%, and 80%) for 4 minutes each, and then washed twice for 2 minutes with PBS. For NeuN staining,^[@bib39],[@bib40]^ slides were boiled for 5 minutes in antigen retrieval buffer (10 mmol/l Tris/ 1mmol/l EDTA (pH 9.0)), incubated at room temperature for 20 minutes, and then washed for 5 minutes in PBS. Slides were blocked in 5% normal goat serum in PBS containing 0.05% Tween 20 (PBST) for 1 hour and washed once with PBST for 5 minutes. Slides were incubated with primary antibody (Millipore, Taunton, MA; MAB377, 1:1,000 dilution in PBST) for 1 hour and washed three times with PBST for 5 minutes. Slides were then incubated with secondary antibody (Life Technologies; \#A11011, 1:1000 dilution in PBST) for 30 minutes in the dark and washed three times with PBST for 5 minutes each. Slides were then counterstained with 250 ng/ml 4\',6-diamidino-2-phenylindole (Molecular Probes, Life Technologies; \#D3571) in PBS for 1 minute and washed three times with PBS for 1 minute. Slides were mounted with mounting medium and coverslips and dried overnight before imaging on a Leica DM5500 microscope fitted with a DFC365 FX fluorescence camera. For toxicity studies, injected brains were harvested after 5 days. For microglial activation studies, brains were harvested after 6 hours or 5 days. Extracted, perfused brains were sliced into 40-µm sections on the Leica 2000T Vibratome (Leica Biosystems, Wetzlar, Germany) in ice-cold PBS. Every sixth section was incubated with DARPP-32 (Abcam, Cambridge, UK; \#40801; 1:10,000 in PBS) or IBA-1 (Wako; \#019-19741; 1:1,000 in PBS) antibody, for a total of nine sections per brain and eight images per section (four per hemisphere). IBA-1 sections were incubated in blocking solution (5% normal goat serum, 1% bovine serum albumin, 0.2% Triton-X-100, and 0.03% hydrogen peroxide in PBS) for 1 hour, and then washed with PBS. Sections were incubated overnight at 4 °C in primary antibody, anti-Iba1 (polyclonal rabbit anti-mouse/human/rat; dilution: 1:1,000 in blocking solution) (Wako; \#019-19741). Sections were then stained with goat antirabbit secondary antibody (1:200 dilution) (Vector Laboratories, Burlingame, CA), followed by a PBS wash, the Vectastain ABC Kit (Vector Laboratories), and another PBS wash. IBA-1 was detected with the Metal Enhanced DAB Substrate Kit (Pierce, Rockford, IL). For DARPP32 staining, sections were washed for 3 minutes in 3% hydrogen peroxide, followed by 20 minutes in 0.2% TritonX-100 and 4 hours in 1.5% normal goat serum in PBS. Sections were incubated overnight at 4 °C in DARPP32 primary antibody (1:10,000 dilution) (Abcam; \#40801) made up in 1.5% normal goat serum. Secondary antibody and detection steps were conducted as described for IBA-1 staining. DARPP-32 sections were mounted and visualized by light microscopy with 20× objective on a Nikon Eclipse E600 with a Nikon Digital Sight DSRi1 camera (Nikon, Tokyo, Japan). The number of DARPP-32-positive neurons was quantified manually using the cell counter plug-in on ImageJ for tracking. Activated microglia were quantified by morphology of IBA-1-positive cells^[@bib42],[@bib43],[@bib44],[@bib45]^ from the same number of sections captured with 40× objective. Counting of both IBA-1- and DARPP-32-positive cells was blinded. Coronal section images were taken with a Coolscan V-ED LS50 35-mm Film Scanner (Nikon, Tokyo, Japan). *Statistical analysis.* Data were analyzed using GraphPad Prism 6 software (GraphPad Software, Inc., San Diego, CA). Concentration-dependent IC~50~ curves were fitted using a log(inhibitor) versus response--variable slope (four parameters). The lower limit of the curve was set at zero, and the upper limit of the curve was set at 100. For each independent mouse experiment, the level of knockdown at each dose was normalized to the mean of the control group (the noninjected side of the PBS or artificial CSF groups). *In vivo* data were analyzed using a two-way repeated-measures analysis of variance with Tukey\'s multiple comparisons test for dose and side of brain. Differences in all comparisons were considered significant at *P* values less than 0.05 compared with the NTC- injected group. *P* values reported represent significance of the entire dose group relative to NTC and are not specific to the ipsilateral or contralateral side. For microglial activation, significance was calculated using a parametric, unpaired, two-tailed *t*-test for comparison between dose groups, and paired *t*-test for comparison between ipsilateral and contralateral hemispheres within the same dose group. [**SUPPLEMENTARY MATERIAL**](#sup1){ref-type="supplementary-material"} **Figure S1.** Active hsiRNAs silence huntingtin mRNA in a concentration dependent manner in HeLa cells. **Figure S2.** HTT10150 does not affect primary cortical neuron viability. **Figure S3.** HTT10150 causes a slight increase in total resting microglia 5 days post injection. **Figure S4.** HTT10150 shows limited toxicity at the site of injection at the 25 µg dose. **Table S1.** Detailed sequence, chemical modification patterns, and efficacy of hsiRNAs. This project was funded by the CHDI Foundation (Research Agreement A-6119 and JSC A6367), NIH Strategic Fund (TR000888-02), and NIGMS (GM108803-01A1). We especially thank Darryl Conte for help with manuscript writing and editing, and all the members of the Khvorova, Aronin, and DiFiglia Labs and CHDI Foundation Inc. for stimulating discussions and thoughtful guidance. We also thank M. Sena Esteves and C. Mello Lab for guidance on microscopy. A.K. (University of Massachusetts Medical School (UMMS)), N.A. (UMMS), and M.D. (Mass General Institute for Neurodegenerative Disease) conceived of the study. M.R.H. (UMMS) synthesized and purified siRNAs. J.F.A. (UMMS), L.M.H. (UMMS), A.H.C. (UMMS), M.-C.D. (UMMS), K.C. (UMMS), J.A. (UMMS), E.S. (UMMS), E.J. (UMMS), and E.S. (Mass General Institute for Neurodegenerative Disease) contributed experimentally. M.F.O. (UMMS) performed PyMol modeling. J.F.A., A.K., N.A., and M.D. wrote and edited the manuscript. A.K. owns stock at RXi Pharmaceuticals and Advirna LLC, which holds a patent and license on asymmetric, hydrophobically modified siRNAs. Other authors do not have any competing financial interest to disclose. Supplementary Material {#sup1} ====================== ###### Active hsiRNAs silence huntingtin mRNA in a concentration dependent manner in HeLa cells. ###### Click here for additional data file. ###### HTT10150 does not affect primary cortical neuron viability. ###### Click here for additional data file. ###### HTT10150 causes a slight increase in total resting microglia 5 days post injection. ###### Click here for additional data file. ###### HTT10150 shows limited toxicity at the site of injection at the 25 µg dose. ###### Click here for additional data file. ###### Detailed sequence, chemical modification patterns, and efficacy of hsiRNAs. ###### Click here for additional data file. {#fig1} {#fig2} {#fig3} {#fig4} {#fig5} {#fig6} {#fig7}

#![allow(unused_imports)] use super::*; use wasm_bindgen::prelude::*; #[wasm_bindgen] extern "C" { # [wasm_bindgen (extends = :: js_sys :: Object , js_name = CustomElementRegistry , typescript_type = "CustomElementRegistry")] #[derive(Debug, Clone, PartialEq, Eq)] #[doc = "The `CustomElementRegistry` class."] #[doc = ""] #[doc = "[MDN Documentation](https://developer.mozilla.org/en-US/docs/Web/API/CustomElementRegistry)"] #[doc = ""] #[doc = "*This API requires the following crate features to be activated: `CustomElementRegistry`*"] pub type CustomElementRegistry; # [wasm_bindgen (catch , method , structural , js_class = "CustomElementRegistry" , js_name = define)] #[doc = "The `define()` method."] #[doc = ""] #[doc = "[MDN Documentation](https://developer.mozilla.org/en-US/docs/Web/API/CustomElementRegistry/define)"] #[doc = ""] #[doc = "*This API requires the following crate features to be activated: `CustomElementRegistry`*"] pub fn define( this: &CustomElementRegistry, name: &str, function_constructor: &::js_sys::Function, ) -> Result<(), JsValue>; #[cfg(feature = "ElementDefinitionOptions")] # [wasm_bindgen (catch , method , structural , js_class = "CustomElementRegistry" , js_name = define)] #[doc = "The `define()` method."] #[doc = ""] #[doc = "[MDN Documentation](https://developer.mozilla.org/en-US/docs/Web/API/CustomElementRegistry/define)"] #[doc = ""] #[doc = "*This API requires the following crate features to be activated: `CustomElementRegistry`, `ElementDefinitionOptions`*"] pub fn define_with_options( this: &CustomElementRegistry, name: &str, function_constructor: &::js_sys::Function, options: &ElementDefinitionOptions, ) -> Result<(), JsValue>; # [wasm_bindgen (method , structural , js_class = "CustomElementRegistry" , js_name = get)] #[doc = "The `get()` method."] #[doc = ""] #[doc = "[MDN Documentation](https://developer.mozilla.org/en-US/docs/Web/API/CustomElementRegistry/get)"] #[doc = ""] #[doc = "*This API requires the following crate features to be activated: `CustomElementRegistry`*"] pub fn get(this: &CustomElementRegistry, name: &str) -> ::wasm_bindgen::JsValue; #[cfg(feature = "Node")] # [wasm_bindgen (method , structural , js_class = "CustomElementRegistry" , js_name = upgrade)] #[doc = "The `upgrade()` method."] #[doc = ""] #[doc = "[MDN Documentation](https://developer.mozilla.org/en-US/docs/Web/API/CustomElementRegistry/upgrade)"] #[doc = ""] #[doc = "*This API requires the following crate features to be activated: `CustomElementRegistry`, `Node`*"] pub fn upgrade(this: &CustomElementRegistry, root: &Node); # [wasm_bindgen (catch , method , structural , js_class = "CustomElementRegistry" , js_name = whenDefined)] #[doc = "The `whenDefined()` method."] #[doc = ""] #[doc = "[MDN Documentation](https://developer.mozilla.org/en-US/docs/Web/API/CustomElementRegistry/whenDefined)"] #[doc = ""] #[doc = "*This API requires the following crate features to be activated: `CustomElementRegistry`*"] pub fn when_defined( this: &CustomElementRegistry, name: &str, ) -> Result<::js_sys::Promise, JsValue>; }

Q: Left click only on Dijit MenuItem using the basic tutorial here as example: https://dojotoolkit.org/documentation/tutorials/1.10/menus/demo/simpleProgMenu.html I've noticed that there's no (obvious) way to differentiate between left and right clicks. I'd like right click to do nothing, but left click to call the onClick() on the menuitem. Inspecting the contents of the event parameter passed to the onClick function, there doesn't appear to be anything telling me which mouse button was clicked. Is there a way to achieve this? A: If you want right click to do nothing, you don't have to do anything special. If you want to handle right clicks you can use the dojo/mouse module and its mouseButtons object. An example from the documentation: require(["dojo/mouse", "dojo/on", "dojo/dom"], function(mouse, on, dom){ on(dom.byId("someid"), "click", function(evt){ if (mouse.isLeft(event)){ // handle mouse left click }else if (mouse.isRight(event)){ // handle mouse right click } }); });

United States Court of Appeals FOR THE EIGHTH CIRCUIT ___________ No. 02-2039 ___________ Randy P. Rumsey, * * Appellant, * * Appeal from the United States v. * District Court for the * Western District of Arkansas. Jo Anne B. Barnhart, * Commissioner of Social Security, * [UNPUBLISHED] * Appellee. * ___________ Submitted: November 6, 2002 Filed: November 12, 2002 ___________ Before MORRIS SHEPPARD ARNOLD, BEAM, and RILEY, Circuit Judges. ___________ PER CURIAM. Randy P. Rumsey appeals from the district court's1 dismissal, for lack of jurisdiction, of his petition for review of an agency determination that his claim for disability insurance benefits was barred by administrative res judicata. We affirm. 1 The Honorable Robert T. Dawson, United States District Judge for the Western District of Arkansas, adopting the Report and Recommendation of the Honorable Beverly Stites Jones, United States Magistrate Judge. A federal district court's jurisdiction to review decisions regarding disability benefits is governed by 42 U.S.C. § 405(g). That section provides for review only of a "final decision of the Commissioner . . . made after a hearing." An agency's application of res judicata2 or refusal to reopen a prior determination is not a "final decision" within the meaning of section 405(g). King v. Chater, 90 F.3d 323, 325 (8th Cir. 1996). But there is a narrow exception where the Commissioner reconsiders the merits of an application previously denied. Id. (citing Jelinek v. Heckler, 764 F.2d 507, 508 (8th Cir. 1985)). Such a claim is treated as having been reopened as a matter of administrative discretion and is, therefore, subject to judicial review to the extent it has been reopened. Id. The Commissioner dismissed Rumsey's current application for disability insurance benefits as duplicative of an earlier, unsuccessful claim that alleged the same disability. After a hearing, an Administrative Law Judge ("ALJ") dismissed Rumsey's present claim as barred by the final decision in his earlier claim. The ALJ did not consider the merits of the earlier claim, but, as the district court noted, merely "made a threshold inquiry into the facts and evidence of the previous application to determine if the regulatory requirements for reopening the previous claim had been met." Because the ALJ did not reopen Rumsey's earlier claim, and because its dismissal for res judicata was not a "final decision" within the purview of 42 U.S.C. § 405(g), we have no jurisdiction to review it. We affirm the judgment of the district court. 2 Under the Commissioner's regulations, a request for a hearing may be dismissed as precluded by the doctrine of res judicata. 20 C.F.R. § 404.957(c)(1). And this court has endorsed the application of res judicata in an administrative context. Rush v. Sec'y of Health and Human Servs., 738 F.2d 909, 914 (8th Cir. 1984). -2- A true copy. Attest: CLERK, U.S. COURT OF APPEALS, EIGHTH CIRCUIT. -3- 

// +build !appengine package mail import ( "bytes" "encoding/base64" "errors" "fmt" "io" "mime/multipart" "net/smtp" "net/textproto" "strings" "sort" "gnd.la/util/stringutil" ) var ( errNoAdminEmail = errors.New("mail.Admin specified as a mail destinary, but no mail.AdminEmail() has been set") crlf = []byte("\r\n") ) func joinAddrs(addrs []string) (string, error) { var values []string for _, v := range addrs { if v == Admin { addr := AdminEmail() if addr == "" { return "", errNoAdminEmail } addrs, err := ParseAddressList(addr) if err != nil { return "", fmt.Errorf("invalid admin address %q: %s", addr, err) } values = append(values, addrs...) continue } values = append(values, v) } return strings.Join(values, ", "), nil } func makeBoundary() string { return "Gondola-Boundary-" + stringutil.Random(32) } func sendMail(to []string, cc []string, bcc []string, msg *Message) error { from := Config.DefaultFrom server := Config.MailServer if msg.Server != "" { server = msg.Server } if msg.From != "" { from = msg.From } if from == "" { return errNoFrom } var auth smtp.Auth cram, username, password, server := parseServer(server) if username != "" || password != "" { if cram { auth = smtp.CRAMMD5Auth(username, password) } else { auth = smtp.PlainAuth("", username, password, server) } } var buf bytes.Buffer headers := msg.Headers if headers == nil { headers = make(Headers) } if msg.Subject != "" { headers["Subject"] = msg.Subject } headers["From"] = from if msg.ReplyTo != "" { headers["Reply-To"] = msg.ReplyTo } var err error if len(to) > 0 { headers["To"], err = joinAddrs(to) if err != nil { return err } for ii, v := range to { if v == Admin { if Config.AdminEmail == "" { return errNoAdminEmail } to[ii] = Config.AdminEmail } } } if len(cc) > 0 { headers["Cc"], err = joinAddrs(cc) if err != nil { return err } } if len(bcc) > 0 { headers["Bcc"], err = joinAddrs(bcc) if err != nil { return err } } hk := make([]string, 0, len(headers)) for k := range headers { hk = append(hk, k) } sort.Strings(hk) for _, k := range hk { buf.WriteString(fmt.Sprintf("%s: %s\r\n", k, headers[k])) } buf.WriteString("MIME-Version: 1.0\r\n") mw := multipart.NewWriter(&buf) mw.SetBoundary(makeBoundary()) // Create a multipart mixed first fmt.Fprintf(&buf, "Content-Type: multipart/mixed;\r\n\tboundary=%q\r\n\r\n", mw.Boundary()) var bodyWriter *multipart.Writer if msg.TextBody != "" && msg.HTMLBody != "" { boundary := makeBoundary() outerHeader := make(textproto.MIMEHeader) // First part is a multipart/alternative, which contains the text and html bodies outerHeader.Set("Content-Type", fmt.Sprintf("multipart/alternative; boundary=%q", boundary)) iw, err := mw.CreatePart(outerHeader) if err != nil { return err } bodyWriter = multipart.NewWriter(iw) bodyWriter.SetBoundary(boundary) } else { bodyWriter = mw } if msg.TextBody != "" { textHeader := make(textproto.MIMEHeader) textHeader.Set("Content-Type", "text/plain; charset=UTF-8") tpw, err := bodyWriter.CreatePart(textHeader) if err != nil { return err } if _, err := io.WriteString(tpw, msg.TextBody); err != nil { return err } tpw.Write(crlf) tpw.Write(crlf) } attached := make(map[*Attachment]bool) if msg.HTMLBody != "" { var htmlAttachments []*Attachment for _, v := range msg.Attachments { if v.ContentID != "" && strings.Contains(msg.HTMLBody, fmt.Sprintf("cid:%s", v.ContentID)) { htmlAttachments = append(htmlAttachments, v) attached[v] = true } } var htmlWriter *multipart.Writer if len(htmlAttachments) > 0 { relatedHeader := make(textproto.MIMEHeader) relatedBoundary := makeBoundary() relatedHeader.Set("Content-Type", fmt.Sprintf("multipart/related; boundary=%q; type=\"text/html\"", relatedBoundary)) rw, err := bodyWriter.CreatePart(relatedHeader) if err != nil { return err } htmlWriter = multipart.NewWriter(rw) htmlWriter.SetBoundary(relatedBoundary) } else { htmlWriter = bodyWriter } htmlHeader := make(textproto.MIMEHeader) htmlHeader.Set("Content-Type", "text/html; charset=UTF-8") thw, err := htmlWriter.CreatePart(htmlHeader) if err != nil { return err } if _, err := io.WriteString(thw, msg.HTMLBody); err != nil { return err } thw.Write(crlf) thw.Write(crlf) for _, v := range htmlAttachments { attachmentHeader := make(textproto.MIMEHeader) attachmentHeader.Set("Content-Disposition", "inline") attachmentHeader.Set("Content-Id", fmt.Sprintf("<%s>", v.ContentID)) attachmentHeader.Set("Content-Transfer-Encoding", "base64") attachmentHeader.Set("Content-Type", v.ContentType) aw, err := htmlWriter.CreatePart(attachmentHeader) if err != nil { return err } b := make([]byte, base64.StdEncoding.EncodedLen(len(v.Data))) base64.StdEncoding.Encode(b, v.Data) aw.Write(b) } if htmlWriter != bodyWriter { if err := htmlWriter.Close(); err != nil { return err } } } if bodyWriter != mw { if err := bodyWriter.Close(); err != nil { return err } } for _, v := range msg.Attachments { if attached[v] { continue } attachmentHeader := make(textproto.MIMEHeader) attachmentHeader.Set("Content-Disposition", fmt.Sprintf("attachment; filename=%q", v.Name)) attachmentHeader.Set("Content-Transfer-Encoding", "base64") attachmentHeader.Set("Content-Type", v.ContentType) aw, err := mw.CreatePart(attachmentHeader) if err != nil { return err } b := make([]byte, base64.StdEncoding.EncodedLen(len(v.Data))) base64.StdEncoding.Encode(b, v.Data) aw.Write(b) } if err := mw.Close(); err != nil { return err } if server == "echo" { printer(buf.String()) return nil } return smtp.SendMail(server, auth, from, to, buf.Bytes()) } func parseServer(server string) (bool, string, string, string) { // Check if the server includes authentication info cram := false var username string var password string if idx := strings.LastIndex(server, "@"); idx >= 0 { var credentials string credentials, server = server[:idx], server[idx+1:] if strings.HasPrefix(credentials, "cram?") { credentials = credentials[5:] cram = true } colon := strings.Index(credentials, ":") if colon >= 0 { username = credentials[:colon] if colon < len(credentials)-1 { password = credentials[colon+1:] } } else { username = credentials } } return cram, username, password, server }

Four keys to success (theory, implementation, evaluation, and resource/system support): high hopes and challenges in participation. In this article, I attempt to merge two themes. First, there is often a large gap between high hopes about impacts of policies or programs and the demonstrated results. I describe four keys/threats to success in any social problem area: theory, implementation, evaluation, and resource/system support. Second, I present theory and research from over 30 years of work on participation, conducted by my colleagues and myself that can illuminate and be illuminated by theory, implementation, evaluation, and resource/system support. I offer ideas for solutions that increase the probability of success. I conclude with the need to have high hopes tempered by theory and research to develop realistically ambitious solutions to social problems.

Herpesviruses are important pathogens of both humans and animals, and information on the molecular aspects of herpesvirus replication is useful in the diagnosis and treatment of these infections. Overall goals are to employ our models of equine herpesvirus 1 (EHV) cytocidal and persistent infection to understand herpesvirus gene regulation in terms of structure/function relationships of the viral regulatory proteins and to ascertain whether EHV regulatory polypeptides interact with cellular proteins to mediate the varied outcomes of infection. Aims for years #39 to #43 focus on the functions of EHV regulatory proteins with emphasis on the immediate-early protein (IEP): To characterize the transactivation domain (TAD) with aa#3-89 of the EHV IEP by assessing mutant forms of the TAD both as GAL4- fusion constructs and in the contest of the virus for transactivation ability. To use our panels of GST-EHV fusion proteins to identify the domains of EHV IEP, ICP22, ICP27 and ICP0 regulatory proteins that mediate their protein-protein interactions (by protein crosslinking assays) and enhance IEP binding to specific sequences within EHV regulatory proteins by the approaches of the two hybrid system, coimmunoprecipitation assays, and affinity chromatography. Mutant constructs and EHV-1 mutants that express specific domains of the auxiliary regulatory proteins, especially ICP22, will be used in transient transfection assays and experiments to monitor EHV gene programming, respectively, to define the roles of these proteins in EHV replication. Lastly, focused efforts will address the functions of the ICP22-ICP27 hybrid protein (HYB.) encoded by EHV DI particles (DIP) that mediate persistent infection. Since the HYB. retards expression of specific EHV promoters in initial transfection assays, our constructs, cell lines, and recombinant virus that express the HYB. will be employed to define viral promoters affected by the HYB. and ascertain whether HAB.. expression by a recombinant EHV alters viral gene programming, possibly mediates persistent infection, and is essential for DIP to establish persistent infection. If warranted by these data, the interaction of the HAB.. with EHV regulatory proteins and cellular factors will investigated by the approaches described above.

**MARKET DEPTH AND PRICE DYNAMICS: A NOTE** FRANK H. WESTERHOFF *University of Osnabrueck, Department of Economics* *Rolandstrasse 8, D-49069 Osnabrueck, Germany* *e-mail: [email protected]* Abstract: This note explores the consequences of nonlinear price impact functions on price dynamics within the chartist-fundamentalist framework. Price impact functions may be nonlinear with respect to trading volume. As indicated by recent empirical studies, a given transaction may cause a large (small) price change if market depth is low (high). Simulations reveal that such a relationship may create endogenous complex price fluctuations even if the trading behavior of chartists and fundamentalists is linear. Keywords: Econophysics; Market Depth; Price Dynamics; Nonlinearities; Technical and Fundamental Analysis. Introduction ============ Interactions between heterogeneous agents, so-called chartists and fundamentalists, may generate endogenous price dynamics either due to nonlinear trading rules or due to a switching between simple linear trading rules.$^{1,2}$ Overall, multi-agent models appear to be quite successful in replicating financial market dynamics.$^{3,4}$ In addition, this research direction has important applications. On the one hand, understanding the working of financial markets may help to design better investment strategies.$^{5}$ On the other hand, it may facilitate the regulation of disorderly markets. For instance, Ehrenstein shows that the imposition of a low transaction tax may stabilize asset price fluctuations.$^{6}$ Within these models, the orders of the traders typically drive the price via a log linear price impact function: Buying orders shift the price proportionally up and selling orders shift the price proportionally down. Recent empirical evidence suggests, however, that the relationship between orders and price adjustment may be nonlinear. Moreover, as reported by Farmer et al., large price fluctuations occur when market depth is low.$^{3,7}$ Following this observation, our goal is to illustrate a novel mechanism for endogenous price dynamics. We investigate – within an otherwise linear chartist-fundamentalist setup – a price impact function which depends nonlinearly on market depth. To be precise, a given transaction yields a larger price change when market depth is low than when it is high. Simulations indicate that such a relationship may lead to complex price movements. The dynamics may be sketched as follows. The market switches back and forth between two regimes. When liquidity is high, the market is relatively stable. But low price fluctuations indicate only weak trading signals and thus the transactions of speculators decline. As liquidity decreases, the price responsiveness of a trade increases. The market becomes unstable and price fluctuations increase again. The remainder of this note is organized as follows. Section 2 sketches the empirical evidence on price impact functions. In section 3, we present our model, and in section 4, we discuss the main results. The final section concludes. Empirical Evidence ================== Financial prices are obviously driven by the orders of heterogeneous agents. However, it is not clear what the true functional form of price impact is. For instance, Farmer proposes a log linear price impact function for theoretical analysis while Zhang develops a model with nonlinear price impact.$^{8,9}$ His approach is backed up by empirical research that documents a concave price impact function. According to Hasbrouck, the larger is the order size, the smaller is the price impact per trade unit.$^{10}$ Also Kempf and Korn, using data on DAX futures, and Plerou et al., using data on the 116 most frequently traded US stocks, find that the price impact function displays a concave curvature with increasing order size, and flattening out at larger values.$^{11,12}$ Weber and Rosenow fitted a concave function in the form of a power law and obtained an impressive correlation coefficient of 0.977.$^{13}$ For a further theoretical and empirical debate on the possible shape of the price impact function with respect to the order size see Gabaix et al., Farmer and Lillo and Plerou et al.$^{14-16}$ But these results are currently challenged by an empirical study which is crucial for this note. Farmer et al. present evidence that price fluctuations caused by individual market orders are essentially independent of the volume of the orders.$^{7}$ Instead, large price fluctuations are driven by fluctuations in liquidity, i.e. variations in the market’s ability to absorb new orders. The reason is that even for the most liquid stocks there can be substantial gaps in the order book. When such a gap exists next to the best price – due to low liquidity – even a small new order can remove the best quote and trigger a large price change. These results are supported by Chordia, Roll and Subrahmanyam who also document that there is considerable time variation in market wide liquidity and Lillo, Farmer and Mantenga who detect that higher capitalization stocks tend to have smaller price responses for the same normalized transaction size.$^{17,18}$ Note that the relation between liquidity and price impact is of direct importance to investors developing trading strategies and to regulators attempting to stabilize financial markets. Farmer et al. argue, for instance, that agents who are trying to transact large amounts should split their orders and execute them a little at a time, watching the order book, and taking whatever liquidity is available as it enters.$^{7}$ Hence, when there is a lot of volume in the market, they should submit large orders. Assuming a concave price impact function would obviously lead to quite different investment decisions. Ehrenstein, Westerhoff and Stauffer demonstrate, for instance, that the success of a Tobin tax depends on its impact on market depth.$^{19}$ Depending on the degree of the nonlinearity of the price impact function, a transaction tax may stabilize or destabilize the markets. The Model ========= Following Simon, agents are boundedly rational and display a rule-governed behavior.$^{20}$ Moreover, survey studies reveal that financial market participants rely strongly on technical and fundamental analysis to predict prices.$^{21,22}$ Chartists typically extrapolate past price movements into the future. Let $P$ be the log of the price. Then, their orders may be expressed as $$D^C_t = a(P_t -P_{t-1}),$$ where $a$ is a positive reaction coefficient denoting the strength of the trading. Accordingly, technical traders submit buying orders if prices go up and vice versa. In contrast, fundamentalists expect the price to track its fundamental value. Orders from this type of agent may be written as $$D^F_t = b(F-P_t).$$ Again, $b$ is a positive reaction coefficient, and $F$ stands for the log of the fundamental value. For instance, if the asset is overvalued, fundamentalists submit selling orders. As usual, excess buying drives the price up and excess selling drives it down so that the price adjustment process may be formalized as $$P_{t+1} = P_t + A_t(wD^C_t + (1-w)D^F_t),$$ where $w$ indicates the fraction of chartists and $(1-w)$ the fraction of fundamentalists. The novel idea is to base the degree of price adjustmen $A$ on a nonlinear function of the market depth.$^{23}$ Exploiting that given excess demand has a larger (smaller) impact on the price if the trading volume is low (high), one may write $$A_t = \frac{c}{(|wD^C_t|+|(1-w) D^F_t|)^d}.$$ The curvature of $A$ is captured by $d\geq 0$, while $c>0$ is a shift parameter. For $d=0$, the price adjustment function is log-linear.$^{1,3}$ In that case, the law of motion of the price, derived from combining (1) to (4), is a second-order linear difference equation which has a unique steady state at $$P_{t+1} = P_t = P_{t-1} = F.$$ Rewriting Schur’s stability conditions, the fixed point is stable for $$0<c<\left\{\begin{array}{ll} \displaystyle\frac{1}{aw} & \mbox{for~~} w> \displaystyle \frac{b}{4a +b}\\ \displaystyle \frac{2}{b(1-w)-2aw}\qquad & \mbox{else} \end{array}.\right.$$ However, we are interested in the case where $d>0$. Combining (1)-(4) and solving for $P$ yields $$P_{t+1} = P_t + c \frac{wa(P_t - P_{t-1}) + (1-w) b(F-P_t)}{(|wa(P_t-P_{t-1})|+|(1-w)b(F-P_t)|)^d},$$ which is a two-dimensional nonlinear difference equation. Since (7) precludes closed analysis, we simulate the dynamics to demostrate that the underlying structure gives rise to endogenous deterministic motion. Some Results ============ Figure 1 contains three bifurcation diagrams for $0<d<1$ and $w=0.7$ (top), $w=0.5$ (central) and $w=0.3$ (bottom). The other parameters are fixed at $a=b=c=1$ and the log of the fundamental value is $F=0$. We increase $d$ in 500 steps. In each step, $P$ is plotted from $t=$1001-1100. Note that bifurcation diagrams are frequently used to illustrate the dynamic properties of nonlinear systems. Figure 1 suggests that if $d$ is small, there may exist a stable equilibrium. For instance, for $w=0.5$, prices converge towards the fundamental value as long as $d$ is smaller than around 0.1. If $d$ is increased further, the fixed point becomes unstable. In addition, the range in which the fluctuations take place increases too. Note also that many different types of bifurcation occur. Our model generates the full range of possible dynamic outcomes: fixed points, limit cycles, quasi periodic motion and chaotic fluctuations. For some parameter combinations coexisting attractors emerge. Comparing the three panels indicates that the higher the fraction of chartists, the less stable the market seems to be. To check the robustness of endogenous motion, figure 2 presents bifurcation diagrams for $0 < a <2$ (top), $0< b < 2$ (central) and $0< c < 2$ (bottom), with the remaining parameters fixed at $a=b=c=1$ and $d=w=0.5$. Again, complicated movements arise. While chartism seems to destabilize the market, fundamentalism is apparently stabilizing. Naturally, a higher price adjustment destabilizes the market as well. Overall, many parameter combinations exist which trigger complicated motion.[^1] t Let us finally explore what drives the dynamics. Figure 3 shows the dynamics in the time domain for $a=0.85$, $b=c=1$, and $d=w=0.5$. The first, second and third panel present the log of the price $P$, the price adjustment $A$ and the trading volume $V$ for 150 observations, respectively. Visual inspection reveals that the price circles around its fundamental value without any tendency to converge. Nonlinear price adjustment may thus be an endogenous engine for volatility and trading volume. Note that when trading volume drops the price adjustment increases and price movements are amplified. However, the dynamics does not explode since a higher trading volume leads again to a decrease in the price adjustment. Finally, figure 4 displays the price (top panel) and the trading volume (bottom panel) for 5000 observations $(a = 0.25,~b = 1,~c = 50,~d = 2$ and $w=0.5)$. As can be seen, the dynamics may become quite complex. Remember that trading volume increases with increasing price changes (orders of chartists) and/or increasing deviations from fundamentals (orders of fundametalists). In a stylized way, the dynamics may thus be sketched as follows: Suppose that trading volume is relatively low. Since the price adjustment $A$ is strong, the system is unstable. As the trading becomes increasingly hectic, prices start to diverge from the fundamental value. At some point, however, the trading activity has become so strong that, due to the reduction of the price adjustment $A$, the system becomes stable. Afterwards, a period of convergence begins until the system jumps back to the unstable regime. This process continually repeats itself but in an intricate way. Conclusions =========== When switching between simple linear trading rules and/or relying on nonlinear strategies, interactions between heterogeneous agents may cause irregular dynamics. This note shows that changes in market depth also stimulate price changes. The reason is that if market liquidity goes down, a given order obtains a larger price impact. For a broad range of parameter combinations, erratic yet deterministic trajectories emerge since the system switches back and forth between stable and unstable regimes. [**References**]{} 1. D. Farmer and S. Joshi, [*Journal of Economic Behavior and Organizations*]{} [**49**]{}, 149 (2002). 2. T. Lux and M. Marchesi, [*International Journal of Theoretical and Applied Finance*]{} [**3**]{}, 675 (2000). 3. R. Cont and J.-P. Bouchaud, [*Macroeconomic Dynamics*]{} [**4**]{}, 170 (2000). 4. D. Stauffer, [*Advances in Complex Systems*]{} [**4**]{}, 19 (2001). 5. D. Sornette and W. Zhou, [*Quantitative Finance*]{} [**2**]{}, 468 (2002). 6. G. Ehrenstein, [*International Journal of Modern Physics C*]{} [**13**]{}, 1323 (2002). 7. D. Farmer, L. Gillemot, F. Lillo, S. Mike and A. Sen, What Really Causes Large Price Changes?, SFI Working Paper, 04-02-006, 2004. 8. D. Farmer, [*Industrial and Corporate Change*]{} [**11**]{}, 895 (2002). 9. Y.-C. Zhang, [*Physica A*]{} [**269**]{}, 30 (1999). 10. J. Hasbrouck, [*Journal of Finance*]{} [**46**]{}, 179 (1991). 11. A. Kempf and O. Korn, [*Journal of Financial Markets*]{} [**2**]{}, 29 (1999). 12. V. Plerou, P. Gopikrishnan, X. Gabaix and E. Stanley, [*Physical Review E*]{} [**66**]{}, 027104, 1 (2002). 13. P. Weber and B. Rosenow, Order Book Approach to Price Impact, Preprint cond-mat/0311457, 2003. 14. X. Gabaix, P. Gopikrishnan, V. Plerou and E. Stanley, [*Nature*]{} [**423,**]{} 267 (2003). 15. D. Farmer and F. Lillo, [*Quantitative Finance*]{} [**4**]{}, C7 (2004). 16. V. Plerou, P. Gopikrishnan, X. Gabaix and E. Stanley, [*Quantitative Finance*]{} [**4**]{}, C11 (2004). 17. T. Chordia, R. Roll and A. Subrahmanyam, [*Journal of Finance*]{} [**56**]{}, 501 (2001). 18. F. Lillo, D. Farmer and R. Mantegna, [*Nature*]{} [**421**]{}, 129 (2003). 19. G. Ehrenstein, F. Westerhoff and D. Stauffer D., Tobin Tax and Market Depth, Preprint cond-mat/0311581, 2001. 20. H. Simon, [*Quarterly Journal of Economics*]{} [**9**]{}, 99 (1955). 21. M. Taylor and H. Allen, [*Journal of International Money and Finance*]{} [**11**]{}, 304 (1992). 22. Y.-H. Lui and D. Mole, [*Journal of International Money and Finance*]{} [**17**]{}, 535 (1998). 23. D. Sornette and K. Ide, [*International Journal of Modern Physiscs C*]{} [**14**]{}, 267 (2003). [^1]: To observe permanent fluctuations only small variations in $A$ are needed. Suppose that $A$ takes two values centered around the upper bound of the stability condition $X$, say $X-Y$ and $X+Y$, depending on whether trading volume is above or below a certain level $Z$. Such a system obviously produces nonconvergent but also nonexplosive fluctuations for arbitrary values of $Y$ and $Z$.

Sevil, Stop by any time. Vince -----Original Message----- From: Yaman, Sevil Sent: Tuesday, November 13, 2001 3:25 PM To: Kaminski, Vince J Subject: all research meeting Vince, Regarding everything we talked today in all research meeting I was wondering how all these things are going to affect my situation. As we talked couple months ago I was trying to get ready to be employed full time in the new year. So in this case what do you recommend me to do? Shall we stick to what we talked before or shall we wait and see what time is going to bring? It'd be really nice if you could give some kind of direction. Thanks, Sevil Yaman Enron Research Group 713-345-8083

Q: RenderWindow not working across multiple functions I'm new to SFML, and have been watching a tutorial that puts everything in a single main function. When making my own program, I tried to split it into multiple functions, but it isn't working properly, can anyone explain why this works: #include <SFML/Graphics.hpp> #include <iostream> int main() { sf::RenderWindow window(sf::VideoMode(512, 512), "window", sf::Style::Resize | sf::Style::Close); while (window.isOpen()) { sf::Event evnt; while (window.pollEvent(evnt)) { if (evnt.type == evnt.Closed) { window.close(); } } window.clear(); window.display(); } return 0; } and this doesn't: #include <SFML/Graphics.hpp> #include <iostream> sf::RenderWindow window; void setup() { sf::RenderWindow window(sf::VideoMode(512, 512), "window", sf::Style::Resize | sf::Style::Close); } int main() { setup(); while (window.isOpen()) { sf::Event evnt; while (window.pollEvent(evnt)) { if (evnt.type == evnt.Closed) { window.close(); } } window.clear(); window.display(); } return 0; } They will both compile and run, but in the former, the window will stay open, and in the latter, it won't. A: The window variable that you've declared inside setup() is shadowing the global window. object. Try the following: void setup() { window.create(sf::VideoMode(512, 512), "window", sf::Style::Resize | sf::Style::Close); }

Q: Verifying Error after ADT Update I have a project that worked for months, but I updated the ADT Plugin a few days ago and today all of a sudden the project stopped working. If I try to run it on the device, it throws a VerifyError as soon as it is started. (the xxx is a replacement for the actual of the project name because I'm not allowed to publish it) These kind of error repeat themself, so I just post one. The main VerifyError itself is useless since it just points at the main starting Activity. 05-03 18:06:59.898: I/dalvikvm(26640): Could not find method org.osmdroid.views.MapView.enableScroll, referenced from method com.xxx.activities.MainAc.disableSwipe 05-03 18:06:59.898: D/dalvikvm(26640): VFY: replacing opcode 0x6e at 0x0005 05-03 18:06:59.898: D/dalvikvm(26640): VFY: dead code 0x0008-0010 in Lcom/xxx/activities/MainAc;.disableSwipe ()V 05-03 18:06:59.898: W/dalvikvm(26640): VFY: unable to find class referenced in signature (Lorg/osmdroid/util/GeoPoint;) 05-03 18:06:59.898: E/dalvikvm(26640): Could not find class 'org.osmdroid.util.GeoPoint', referenced from method com.xxx.activities.MainAc.displayPointNavigation 05-03 18:06:59.908: W/dalvikvm(26640): VFY: unable to resolve new-instance 575 (Lorg/osmdroid/util/GeoPoint;) in Lcom/xxx/activities/MainAc; 05-03 18:06:59.908: D/dalvikvm(26640): VFY: replacing opcode 0x22 at 0x0018 05-03 18:06:59.908: D/dalvikvm(26640): VFY: dead code 0x001a-0093 in Lcom/xxx/activities/MainAc;.displayPointNavigation (Lorg/osmdroid/util/GeoPoint;)V 05-03 18:06:59.908: W/dalvikvm(26640): Unable to resolve superclass of Lcom/xxx/overlay/MyUpmoveLocationOverlay; (584) I think the problem is the way I included the osmdroid lib. Since I have to change a lot of osmdroid code, I didn't want to build a jar all the time, so I created a Java Project from the osmdroid source and added the osmdroid Project to my Project's Classpath. Until now this setup worked like a charm. I thought that I may have changed something myself that caused the VerifyError, so I reverted the project to a revision where it definitly was working but I get the same error. Are there some settings I have to change to make this work again or do I have to redo the whole setup and include the osmdroid as a jar? A: Make OSMDroid be an Android library project and add it as a library to your main application project.

525 S.E.2d 278 (2000) Laura Lee COMBS v. VIRGINIA ELECTRIC & POWER COMPANY, et al. Record No. 990534. Supreme Court of Virginia. March 3, 2000. *279 David D. Walker (George R. Walton, Mechanicsville, on brief), for appellant. Cassandra C. Collins (Michael R. Shebelskie; Andrew R. Park; George W. Marget, *280 III; Hunton & Williams, on brief), Richmond, for appellee. Present: CARRICO, C.J., COMPTON,[1] LACY, HASSELL, KEENAN, KOONTZ, and KINSER, JJ. KINSER, Justice. In this personal injury action, the sole question is whether the circuit court correctly ruled that an employee's exclusive remedy against an employer is under the Virginia Workers' Compensation Act (the Act), Code §§ 65.2-100 through -1310. Because we conclude that the employee suffered an "injury by accident arising out of and in the course of . . . employment," Code § 65.2-101, we will affirm the circuit court's judgment sustaining the employer's special plea in bar. FACTS AND PROCEEDINGS Virginia Electric and Power Company (Virginia Power) arranged for an independent instructor to teach an aerobics class at its Richmond office for the benefit of its employees. Participation in the class by Virginia Power's employees was voluntary. Virginia Power advertised the class on its bulletin boards and in its newsletter. It did not charge for the use of its facility, but participating employees were required to pay a fee to the instructor for the class. The plaintiff, Laura Lee Combs, was an employee of Virginia Power. During her lunch hour on May 24, 1994, Combs participated in the aerobics class and, while doing so, developed a severe headache. The aerobics instructor assisted Combs in lying down and then called Virginia Power's Employee Health Services (EHS), as she had been instructed to do by the EHS coordinator of health programs. The EHS receptionist answered the call and informed Sharon Robinson, EHS coordinator of administrative support, that someone in the aerobics class had a headache and needed some medication. Shortly thereafter, Robinson went to the aerobics room to determine what was happening with regard to Combs. When Combs' head pain did not subside, she was taken to the EHS "quiet room" to rest. The "quiet room" is used by employees who become ill at work, or by recuperating employees who have returned to work after an accident or illness and need to rest during the workday. When an employee is using the room, an EHS staff member is required to be in the office, and the employee is to be checked at regular intervals. After she went to the "quiet room," Combs was not examined by any medical or emergency personnel, nor was her condition regularly monitored by anyone. Approximately two hours after Combs entered the "quiet room," Robinson checked on Combs and discovered that Combs had vomited on herself and was in a coma-like state. Robinson then called security. Combs was eventually transported by ambulance to the Medical College of Virginia where she was diagnosed with intracranial bleeding, a right giant middle cerebral aneurysm, and an intraparenchymal hemorrhage. She subsequently underwent two neurological operations. After release from the hospital, she entered a rehabilitation center where she received therapy for her partial paralysis and cognitive brain damage. On April 30, 1996, Combs filed a motion for judgment against Virginia Power and four of its employees, alleging that the defendants owed her a duty to "have in place proper procedures, and to properly train ... personnel, so that employees using EHS could do so without harm to themselves and detriment to their well-being." Combs further asserted that the defendants breached these duties and were negligent by, inter alia, failing to properly train non-medical personnel working in EHS; failing to implement procedures to provide appropriate medical care to Virginia Power employees who seek treatment at EHS, especially when licensed healthcare professionals are unavailable; and failing to provide proper medical care and treatment when Combs suffered a medical emergency, thereby leaving her unattended for approximately two hours before calling security and *281 a rescue squad. Finally, Combs alleged that the defendants' negligence proximately caused her injury and damages.[2] In response, the defendants filed grounds of defense and a "Special Plea of Workers' Compensation Bar." In the special plea, they asserted that the exclusivity provision of the Act, Code § 65.2-307, barred Combs' claim and therefore deprived the circuit court of subject matter jurisdiction over her claim.[3] Accordingly, the defendants asked the court to dismiss Combs' action. After reviewing the parties' memoranda, the circuit court sustained the special plea and dismissed Combs' action with prejudice. In a letter opinion, the court concluded that the aggravation and acceleration of Combs' pre-existing aneurysm was "an injury by accident arising out of and in the course of her employment with" Virginia Power, and that her action was therefore barred by the exclusivity provision of the Act. We awarded Combs this appeal. ANALYSIS "An injury is subject to the exclusivity provision of the Act if it is the result of an accident and arises out of and in the course of the employment." Richmond Newspapers, Inc. v. Hazelwood, 249 Va. 369, 372, 457 S.E.2d 56, 58 (1995). Thus, the critical inquiry in this appeal is whether Combs' injury was (1) an injury by accident, (2) arising out of, (3) and in the course of, her employment. See Code § 65.2-101; Briley v. Farm Fresh, Inc., 240 Va. 194, 197, 396 S.E.2d 835, 836 (1990). If any one of these elements is missing, then Combs' claim is not covered by the Act, Snead v. Harbaugh, 241 Va. 524, 526, 404 S.E.2d 53, 54 (1991), and she can proceed with her personal injury claim in the circuit court. Thus, we will address each of these criteria seriatim. I. INJURY BY ACCIDENT This Court recently addressed the requirements of an "injury by accident" in Southern Express v. Green, 257 Va. 181, 509 S.E.2d 836 (1999). There, we held that an "injury by accident" occurs when the injury appears "suddenly at a particular time and place[,] and upon a particular occasion[;]" when it is "caused by an identifiable incident[,] or sudden precipitating event[;]" and when the injury results "in an obvious mechanical or structural change in the human body." Id. at 187, 509 S.E.2d at 839. The circuit court found all these factors present with regard to Combs' injury, and we agree. At the outset, it must be emphasized that Combs' injury is not the aneurysm itself. Instead, her injury is the aggravation, exacerbation, and/or acceleration of the aneurysm. That injury resulted from the alleged negligent emergency medical care, or lack thereof, that she received from Virginia Power and its EHS employees after she suffered a severe headache during the aerobics class. Thus, Combs' argument that there is no evidence with regard to when the aneurysm initially started leaking or when she experienced the first onset of symptoms is irrelevant to the question whether she sustained an "injury by accident." The record in this case, in particular Combs' motion for judgment, demonstrates that she suffered an "injury by accident" under Code § 65.2-101. The particular time, place, and occasion of her injury was at the EHS "quiet room" in Virginia Power's Richmond office, during the two to three hours that elapsed from when she first developed the headache and was taken to the "quiet room" until she was transported to the hospital. The identifiable or precipitating event was the alleged negligent emergency medical treatment that she received during this span of time. Finally, Combs' paralysis and cognitive brain damage represent the mechanical or structural changes in her body that resulted *282 from her injury. Thus, all the requirements of an "injury by accident" are present in this case. See Winn v. Geo. A. Hormel & Co., 252 Neb. 29, 560 N.W.2d 143, 149 (1997)(holding that negligent medical treatment at employer's first-aid medical facility may constitute "accident"). II. ARISING OUT OF EMPLOYMENT The phrase "arising out of" pertains to the origin or cause of an injury. County of Chesterfield v. Johnson, 237 Va. 180, 183, 376 S.E.2d 73, 74 (1989); Bradshaw v. Aronovitch, 170 Va. 329, 335, 196 S.E. 684, 686 (1938). In determining whether an injury arises out of employment, we have repeatedly quoted with approval the test enunciated in In re Employers' Liab. Assur. Corp., Ltd., 215 Mass. 497, 102 N.E. 697 (1913). An injury arises "out of" the employment, when there is apparent to the rational mind upon consideration of all the circumstances, a causal connection between the conditions under which the work is required to be performed and the resulting injury. Under this test, if the injury can be seen to have followed as a natural incident of the work and to have been contemplated by a reasonable person familiar with the whole situation as a result of the exposure occasioned by the nature of the employment, then it arises "out of" the employment. But it excludes an injury which cannot fairly be traced to the employment as a contributing proximate cause and which comes from a hazard to which the workmen would have been equally exposed apart from the employment. The causative danger must be peculiar to the work and not common to the neighborhood. It must be incidental to the character of the business and not independent of the relation of master and servant. It need not have been foreseen or expected, but after the event it must appear to have had its origin in a risk connected with the employment, and to have flowed from that source as a rational consequence. Id. at 697; accord Lucas v. Lucas, 212 Va. 561, 563, 186 S.E.2d 63, 64 (1972); Conner v. Bragg, 203 Va. 204, 208-09, 123 S.E.2d 393, 396-97 (1962); Bradshaw, 170 Va. at 335, 196 S.E. at 686. In Virginia, we apply an "actual risk test," meaning that the employment must expose the employee to the particular danger causing the injury, notwithstanding the public's exposure generally to similar risks. Lucas, 212 Va. at 563, 186 S.E.2d at 64. Thus, if there is a causal connection between Combs' injury and the conditions of her employment, then her injury arose out of her employment. See United Parcel Serv. of Am. v. Fetterman, 230 Va. 257, 258, 336 S.E.2d 892, 893 (1985) ("An accident arises out of the employment when there is a causal connection between the claimant's injury and the conditions under which the employer requires the work to be performed."). Combs argues that EHS was not actually a clinic for the treatment of employee health problems and that, therefore, it was not a condition of her employment. Thus, she contends that her injury did not "arise out of" her employment. Assuming that Combs is correct about the purpose of EHS, the fact remains that on the day in question, the risk of employment was the alleged negligent emergency medical treatment by EHS personnel, which aggravated her pre-existing aneurysm. Combs was exposed to this risk or condition of employment solely because she was a Virginia Power employee. The public generally would not have been exposed to the same risk because only Virginia Power employees could utilize EHS. In fact, Combs alleged in her motion for judgment that Virginia Power and its employees owed certain duties to her "so that employees using EHS could do so without harm to themselves and detriment to their well-being," and that the defendants violated those duties, thereby causing injury to her. She further asserted that the employee defendants were acting within the scope of their employment when they allegedly injured her. Combs, nevertheless, argues that her situation is like that of the employee in Taylor v. Mobil Corp., 248 Va. 101, 444 S.E.2d 705 (1994), because she did not involuntarily, or out of "default[]" as the circuit court found, seek medical treatment at EHS. In Taylor, an employee visited a doctor at his employer's *283 clinic for treatment of a heart condition. The employee ultimately suffered a fatal heart attack at home although the doctor had advised him that he was not suffering from heart disease. Id. at 103-04, 444 S.E.2d at 706-07. This Court concluded that the employee's risk of exposure to negligent treatment by the doctor was not an actual risk of employment because the employee voluntarily opted to use the doctor at the employer's clinic. He was not required to do so by his employer, nor was he treated by that doctor because he became ill at work. Id. at 107, 444 S.E.2d at 708. In contrast, Combs suffered her severe headache while participating in the aerobics class at Virginia Power's office. While taking part in that class was not required by Virginia Power, EHS personnel treated Combs because of her status as a Virginia Power employee. In fact, the aerobics instructor called EHS when Combs became ill because Virginia Power's EHS coordinator had directed the instructor to do so. Thus, the risk that led to Combs' injury was part of her work environment. See Briley, 240 Va. at 198, 396 S.E.2d at 837. Additionally, the fact that her injury was the aggravation of a pre-existing condition does not alter the result that her injury arose out of her employment. See Ohio Valley Const. Co. v. Jackson, 230 Va. 56, 58, 334 S.E.2d 554, 555 (1985) ("When an injury sustained in an industrial accident accelerates or aggravates a pre-existing condition, death or disability resulting therefrom is compensable under the Workers' Compensation Act."). Combs' pre-existing aneurysm united with an actual risk of her employment to produce her injury. III. IN THE COURSE OF EMPLOYMENT "The phrase arising `in the course of' [employment] refers to the time, place, and circumstances under which the accident occurred." Johnson, 237 Va. at 183, 376 S.E.2d at 74. "An accident occurs `in the course of the employment' when it takes place within the period of the employment, at a place where the employee may reasonably be, and while he is reasonably fulfilling duties of his employment or engaged in doing something incidental thereto." Bradshaw, 170 Va. at 335, 196 S.E. at 686; accord Lucas, 212 Va. at 563, 186 S.E.2d at 64; Conner, 203 Va. at 208, 123 S.E.2d at 396. Combs argues she was not performing any duty of her employment at the moment when she initially needed emergency medical treatment. As she correctly notes, the pre-existing aneurysm was not caused by her employment, and she was participating in an aerobics class during her lunch hour when she first experienced the headache. Thus, she contends that "the reason she ended up at EHS was not in any way connected with her employment[,]" and, therefore, that her injury did not occur during the course of her employment. We do not agree. Combs' position on this issue overlooks several salient facts. First, Combs is not seeking redress for the onset of the symptoms associated with the aneurysm but for the aggravation of that pre-existing condition. The aggravation of the aneurysm occurred after EHS personnel responded to the call for assistance from the aerobics instructor, during Combs' period of employment, and at a place where she could reasonably be if she became ill at work, i.e., the "quiet room." The only reason that EHS responded to that call was because Combs was a Virginia Power employee. Thus, Combs "was injured at a place where she was reasonably expected to be while engaged in an activity reasonably incidental to her employment" by Virginia Power. Briley, 240 Va. at 198, 396 S.E.2d at 837. Her injury therefore occurred "in the course of" her employment. CONCLUSION For these reasons, we conclude that Combs' injury was an "injury by accident arising out of and in the course of [her] employment" with Virginia Power, Code § 65.2-101, and is therefore compensable under the Act. Her action in the circuit court is thus barred by Code § 65.2-307. Accordingly, we will affirm the judgment of the circuit court. Affirmed. NOTES [1] Justice Compton participated in the hearing and decision of this case prior to the effective date of his retirement on February 2, 2000. [2] Combs also filed a claim with the Virginia Workers' Compensation Commission on May 23, 1996. Virginia Power subsequently filed a report regarding the accident with the Commission. [3] Code § 65.2-307 provides that "[t]he rights and remedies herein granted to an employee when his employer and he have accepted the provisions of this title respectively to pay and accept compensation on account of injury or death by accident shall exclude all other rights and remedies of such employee ... on account of such injury...."

A Set of 6 Arts & Crafts Solid Silver & Enamel Pastry Forks by Liberty & Co. Each Fork has a gorgeous green and blue enameled design on the handle that is typical of the Liberty Style. The Forks come in their original fitted case.

# -------------------------------------------------------------------------------------------- # Copyright (c) Microsoft Corporation. All rights reserved. # Licensed under the MIT License. See License.txt in the project root for license information. # -------------------------------------------------------------------------------------------- from azure.cli.core.commands import CliCommandType from ._format import ( registry_output_format, usage_output_format, policy_output_format, credential_output_format, webhook_output_format, webhook_get_config_output_format, webhook_list_events_output_format, webhook_ping_output_format, replication_output_format, endpoints_output_format, build_output_format, task_output_format, task_identity_format, taskrun_output_format, run_output_format, helm_list_output_format, helm_show_output_format, scope_map_output_format, token_output_format, token_credential_output_format, agentpool_output_format ) from ._client_factory import ( cf_acr_registries, cf_acr_replications, cf_acr_webhooks, cf_acr_tasks, cf_acr_taskruns, cf_acr_runs, cf_acr_scope_maps, cf_acr_tokens, cf_acr_token_credentials, cf_acr_private_endpoint_connections, cf_acr_agentpool ) def load_command_table(self, _): # pylint: disable=too-many-statements acr_custom_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.custom#{}', table_transformer=registry_output_format, client_factory=cf_acr_registries ) acr_login_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.custom#{}' ) acr_import_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.import#{}', client_factory=cf_acr_registries ) acr_policy_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.policy#{}', table_transformer=policy_output_format, client_factory=cf_acr_registries ) acr_cred_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.credential#{}', table_transformer=credential_output_format, client_factory=cf_acr_registries ) acr_repo_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.repository#{}' ) acr_webhook_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.webhook#{}', table_transformer=webhook_output_format, client_factory=cf_acr_webhooks ) acr_replication_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.replication#{}', table_transformer=replication_output_format, client_factory=cf_acr_replications ) acr_build_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.build#{}', table_transformer=build_output_format, client_factory=cf_acr_runs ) acr_run_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.run#{}', table_transformer=run_output_format, client_factory=cf_acr_runs ) acr_pack_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.pack#{}', table_transformer=run_output_format, client_factory=cf_acr_runs ) acr_task_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.task#{}', table_transformer=task_output_format, client_factory=cf_acr_tasks ) acr_taskrun_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.taskrun#{}', table_transformer=taskrun_output_format, client_factory=cf_acr_taskruns ) acr_helm_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.helm#{}' ) acr_network_rule_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.network_rule#{}', client_factory=cf_acr_registries ) acr_check_health_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.check_health#{}' ) acr_scope_map_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.scope_map#{}', table_transformer=scope_map_output_format, client_factory=cf_acr_scope_maps ) acr_token_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.token#{}', table_transformer=token_output_format, client_factory=cf_acr_tokens ) acr_token_credential_generate_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.token#{}', table_transformer=token_credential_output_format, client_factory=cf_acr_token_credentials ) acr_agentpool_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.agentpool#{}', table_transformer=agentpool_output_format, client_factory=cf_acr_agentpool ) acr_private_endpoint_connection_util = CliCommandType( operations_tmpl='azure.cli.command_modules.acr.private_endpoint_connection#{}', client_factory=cf_acr_private_endpoint_connections ) with self.command_group('acr', acr_custom_util) as g: g.command('check-name', 'acr_check_name', table_transformer=None) g.command('list', 'acr_list') g.command('create', 'acr_create') g.command('delete', 'acr_delete') g.show_command('show', 'acr_show') g.command('show-usage', 'acr_show_usage', table_transformer=usage_output_format) g.command('show-endpoints', 'acr_show_endpoints', table_transformer=endpoints_output_format) g.generic_update_command('update', getter_name='acr_update_get', setter_name='acr_update_set', custom_func_name='acr_update_custom', custom_func_type=acr_custom_util, client_factory=cf_acr_registries) with self.command_group('acr', acr_login_util) as g: g.command('login', 'acr_login') with self.command_group('acr', acr_import_util) as g: g.command('import', 'acr_import') with self.command_group('acr credential', acr_cred_util) as g: g.show_command('show', 'acr_credential_show') g.command('renew', 'acr_credential_renew') with self.command_group('acr repository', acr_repo_util) as g: g.command('list', 'acr_repository_list') g.command('show-tags', 'acr_repository_show_tags') g.command('show-manifests', 'acr_repository_show_manifests') g.show_command('show', 'acr_repository_show') g.command('update', 'acr_repository_update') g.command('delete', 'acr_repository_delete') g.command('untag', 'acr_repository_untag') with self.command_group('acr webhook', acr_webhook_util) as g: g.command('list', 'acr_webhook_list') g.command('create', 'acr_webhook_create') g.command('delete', 'acr_webhook_delete') g.show_command('show', 'acr_webhook_show') g.command('get-config', 'acr_webhook_get_config', table_transformer=webhook_get_config_output_format) g.command('list-events', 'acr_webhook_list_events', table_transformer=webhook_list_events_output_format) g.command('ping', 'acr_webhook_ping', table_transformer=webhook_ping_output_format) g.generic_update_command('update', getter_name='acr_webhook_update_get', setter_name='acr_webhook_update_set', custom_func_name='acr_webhook_update_custom', custom_func_type=acr_webhook_util, client_factory=cf_acr_webhooks) with self.command_group('acr replication', acr_replication_util) as g: g.command('list', 'acr_replication_list') g.command('create', 'acr_replication_create') g.command('delete', 'acr_replication_delete') g.show_command('show', 'acr_replication_show') g.generic_update_command('update', getter_name='acr_replication_update_get', setter_name='acr_replication_update_set', custom_func_name='acr_replication_update_custom', custom_func_type=acr_replication_util, client_factory=cf_acr_replications) with self.command_group('acr', acr_build_util) as g: g.command('build', 'acr_build', supports_no_wait=True) with self.command_group('acr', acr_run_util) as g: g.command('run', 'acr_run', supports_no_wait=True) with self.command_group('acr pack', acr_pack_util, is_preview=True) as g: g.command('build', 'acr_pack_build', supports_no_wait=True) with self.command_group('acr task', acr_task_util) as g: g.command('create', 'acr_task_create') g.show_command('show', 'acr_task_show') g.command('list', 'acr_task_list') g.command('delete', 'acr_task_delete') g.command('update', 'acr_task_update') g.command('identity assign', 'acr_task_identity_assign') g.command('identity remove', 'acr_task_identity_remove') g.command('identity show', 'acr_task_identity_show', table_transformer=task_identity_format) g.command('credential add', 'acr_task_credential_add') g.command('credential update', 'acr_task_credential_update') g.command('credential remove', 'acr_task_credential_remove') g.command('credential list', 'acr_task_credential_list') g.command('timer add', 'acr_task_timer_add') g.command('timer update', 'acr_task_timer_update') g.command('timer remove', 'acr_task_timer_remove') g.command('timer list', 'acr_task_timer_list') g.command('run', 'acr_task_run', client_factory=cf_acr_runs, table_transformer=run_output_format, supports_no_wait=True) g.command('list-runs', 'acr_task_list_runs', client_factory=cf_acr_runs, table_transformer=run_output_format) g.command('show-run', 'acr_task_show_run', client_factory=cf_acr_runs, table_transformer=run_output_format) g.command('cancel-run', 'acr_task_cancel_run', client_factory=cf_acr_runs, table_transformer=None) g.command('update-run', 'acr_task_update_run', client_factory=cf_acr_runs, table_transformer=run_output_format) g.command('logs', 'acr_task_logs', client_factory=cf_acr_runs, table_transformer=None) with self.command_group('acr taskrun', acr_taskrun_util, is_preview=True) as g: g.command('list', 'acr_taskrun_list') g.command('delete', 'acr_taskrun_delete') g.show_command('show', 'acr_taskrun_show') g.command('logs', 'acr_taskrun_logs', client_factory=cf_acr_runs, table_transformer=None) with self.command_group('acr config content-trust', acr_policy_util) as g: g.show_command('show', 'acr_config_content_trust_show') g.command('update', 'acr_config_content_trust_update') with self.command_group('acr config retention', acr_policy_util, is_preview=True) as g: g.show_command('show', 'acr_config_retention_show') g.command('update', 'acr_config_retention_update') def _helm_deprecate_message(self): msg = "This {} has been deprecated and will be removed in future release.".format(self.object_type) msg += " Use '{}' instead.".format(self.redirect) msg += " For more information go to" msg += " https://aka.ms/acr/helm" return msg with self.command_group('acr helm', acr_helm_util, deprecate_info=self.deprecate(redirect="helm v3", message_func=_helm_deprecate_message)) as g: g.command('list', 'acr_helm_list', table_transformer=helm_list_output_format) g.show_command('show', 'acr_helm_show', table_transformer=helm_show_output_format) g.command('delete', 'acr_helm_delete') g.command('push', 'acr_helm_push') g.command('repo add', 'acr_helm_repo_add') g.command('install-cli', 'acr_helm_install_cli', is_preview=True) with self.command_group('acr network-rule', acr_network_rule_util) as g: g.command('list', 'acr_network_rule_list') g.command('add', 'acr_network_rule_add') g.command('remove', 'acr_network_rule_remove') with self.command_group('acr', acr_check_health_util) as g: g.command('check-health', 'acr_check_health') with self.command_group('acr scope-map', acr_scope_map_util, is_preview=True) as g: g.command('create', 'acr_scope_map_create') g.command('delete', 'acr_scope_map_delete') g.command('update', 'acr_scope_map_update') g.show_command('show', 'acr_scope_map_show') g.command('list', 'acr_scope_map_list') with self.command_group('acr token', acr_token_util, is_preview=True) as g: g.command('create', 'acr_token_create') g.command('delete', 'acr_token_delete') g.command('update', 'acr_token_update') g.show_command('show', 'acr_token_show') g.command('list', 'acr_token_list') g.command('credential delete', 'acr_token_credential_delete') with self.command_group('acr token credential', acr_token_credential_generate_util) as g: g.command('generate', 'acr_token_credential_generate') with self.command_group('acr agentpool', acr_agentpool_util, is_preview=True) as g: g.command('create', 'acr_agentpool_create', supports_no_wait=True) g.command('update', 'acr_agentpool_update', supports_no_wait=True) g.command('delete', 'acr_agentpool_delete', supports_no_wait=True) g.command('list', 'acr_agentpool_list') g.show_command('show', 'acr_agentpool_show') with self.command_group('acr private-endpoint-connection', acr_private_endpoint_connection_util) as g: g.command('delete', 'delete') g.show_command('show', 'show') g.command('list', 'list_connections') g.command('approve', 'approve') g.command('reject', 'reject') with self.command_group('acr private-link-resource', acr_custom_util) as g: g.command('list', 'list_private_link_resources') with self.command_group('acr identity', acr_custom_util) as g: g.show_command('show', 'show_identity') g.command('assign', 'assign_identity') g.command('remove', 'remove_identity') with self.command_group('acr encryption', acr_custom_util) as g: g.show_command('show', 'show_encryption') g.command('rotate-key', "rotate_key")

766 F.Supp.2d 797 (2011) In the Matter of the COMPLAINT OF PRIDE OFFSHORE, INC., as Owner of the J/U Pride Wyoming for Exoneration from, or Alternatively, Limitation of Liability. Civil Action No. H-08-3109. United States District Court, S.D. Texas, Houston Division. February 2, 2011. *798 MEMORANDUM AND ORDER LEE H. ROSENTHAL, District Judge. This maritime dispute arises out of damage allegedly caused when a jack-up rig, the PRIDE WYOMING, detached from its moorings during Hurricane Ike in September 2008. Pride Offshore, Inc.,[1] the rig owner, filed a complaint in exoneration or alternatively for limitation of liability, (Docket Entry No. 1), and Century Exploration New Orleans, Inc. filed a claim, (Docket Entry No. 47). Pride Offshore moved for summary judgment, arguing that the economic-loss rule precludes Century Exploration's claim. (Docket Entry No. 75). Century Exploration responded with a different theory and asked for leave to amend. (Docket Entry No. 77). Pride Offshore replied, arguing that this court should grant its motion for summary judgment and deny Century Exploration's motion to amend as futile. (Docket Entry No. 78). For the reasons explained below, this court grants Pride Offshore's motion for summary judgment, but to the extent the motion was based on a challenge to the sufficiency of the claim allegations, Century Exploration is granted leave to amend. An amended complaint must be filed by February 25, 2011. I. Background The PRIDE WYOMING was a 250-foot mat slot jack-up rig operating in the Gulf *799 of Mexico. (Docket Entry No. 1 ¶ 4). When Hurricane Ike struck in September 2008, the rig was located in Ship Shoal Block 283, about 90 miles south of Houma, Louisiana. (Id. ¶ 5). The hurricane blew the rig off its location, causing it to sink. (Id. ¶ 6). Parts of the PRIDE WYOMING's wreckage settled on top of pipelines belonging to The Williams Companies, Inc. and Tennessee Gas Pipeline Company (TGPS). (Id. ¶ 7). Pride Offshore filed this complaint on October 20, 2008. (Docket Entry No. 1). On August 18, 2009, Century Exploration filed its claim, alleging that part of the wreckage from the PRIDE WYOMING "struck and damaged pipelines that interfered with Century's operations and necessitated repairs. Century had property interests in one such pipeline and contributed to its repairs." (Docket Entry No. 47, ¶ 3). Century Exploration claimed approximately $21 million in damages "caused solely by, and ... wholly due to, the unseaworthiness of the J/U Pride Wyoming, the negligence of her master and crew, and the negligence of her owners and operators." (Id. ¶¶ 5-6). On January 11, 2010, Century Exploration amended to add allegations of recklessness and intentional misconduct. (Docket Entry No. 63 ¶ 5). Neither version of the claim alleged that Century Exploration was aware of Pride Offshore's contract to use the TGPC pipeline. Pride Offshore argues that summary judgment is appropriate for two reasons. The first is that Century Exploration's amended claim is insufficient because it fails to allege that Pride Offshore knew of Century Exploration's contract with TGPC. The second is that Century Exploration lacks evidence of a proprietary interest in the pipeline that would support economic-loss damages for negligence. II. Analysis A. The Legal Standards Pride Offshore's motion concerns the application of the Robins Dry Dock rule. In Robins Dry Dock & Repair Co. v. Flint, 275 U.S. 303, 48 S.Ct. 134, 72 L.Ed. 290 (1927), the Supreme Court overturned a verdict in favor of the plaintiffs for breach of contract based on damage to a third party's property. "Their loss arose only through their contract with the owners— and while intentionally to bring about a breach of contract may give rise to a cause of action, no authority need be cited to show that, as a general rule, at least, a tort to the person or property of one man does not make the tort-feasor liable to another merely because the injured person was under a contract with that other unknown to the doer of the wrong." Id. at 308-09, 48 S.Ct. 134 (citations omitted). "Although criticized from time to time, Robins Dry Dock remains good law." Allders Int'l Ltd. v. United States, No. 94 CIV. 5689(JSM), 1995 WL 251571, *2 (S.D.N.Y. Apr. 28, 1995). "The Fifth Circuit continues to apply the Robins Dry Dock principle to most maritime cases, carving out an exception only for cases involving a collision between two vessels not in privity of contract." Norwegian Bulk Transport A/S v. Int'l Marine Terminals Partnership, 520 F.3d 409, 412 (5th Cir.2008) (citing Amoco Transport Co. v. S/S MASON LYKES, 768 F.2d 659 (5th Cir.1985)). "Since the Amoco Transport decision, the Fifth Circuit ... has not recognized exceptions to the rule in Robins Dry Dock outside of the context of collision cases." Id. at 413 (citations omitted). The first ground Pride Offshore asserts in moving for summary judgment rests on the sufficiency of Century Exploration's amended complaint. "[A] summary-judgment motion may be made on the basis of the pleadings alone, and if this is done it *800 functionally is the same as a motion to dismiss for failure to state a claim ...." 10A CHARLES ALAN WRIGHT, ARTHUR R. MILLER & MARY KAY KANE, FEDERAL PRACTICE AND PROCEDURE § 2713, at 222-23 (3d ed. 1998) (citations omitted). A complaint may be dismissed under Rule 12(b)(6) for "failure to state a claim upon which relief can be granted." FED. R. CIV. P. 12(b)(6). In Bell Atlantic Corp. v. Twombly, 550 U.S. 544, 555, 127 S.Ct. 1955, 167 L.Ed.2d 929 (2007), and Ashcroft v. Iqbal, ___ U.S. ___, 129 S.Ct. 1937, 173 L.Ed.2d 868 (2009), the Supreme Court confirmed that Rule 12(b)(6) must be read in conjunction with Rule 8(a), which requires "a short and plain statement of the claim showing that the pleader is entitled to relief." Twombly abrogated the Supreme Court's prior statement in Conley v. Gibson, 355 U.S. 41, 45-46, 78 S.Ct. 99, 2 L.Ed.2d 80 (1957), that "a complaint should not be dismissed for failure to state a claim unless it appears beyond doubt that the plaintiff can prove no set of facts in support of his claim which would entitle him to relief." See Twombly, 550 U.S. at 562-63, 127 S.Ct. 1955 ("Conley's `no set of facts' language... is best forgotten as an incomplete, negative gloss on an accepted pleading standard...."). To withstand a Rule 12(b)(6) motion, a complaint must contain "enough facts to state a claim to relief that is plausible on its face." Twombly, 550 U.S. at 570, 127 S.Ct. 1955; see also Elsensohn v. St. Tammany Parish Sheriff's Office, 530 F.3d 368, 372 (5th Cir.2008) (quoting Twombly, 550 U.S. at 570, 127 S.Ct. 1955). The Court explained that "the pleading standard Rule 8 announces does not require `detailed factual allegations,' but it demands more than an unadorned, the-defendant-unlawfully-harmed-me accusation." Iqbal, 129 S.Ct. at 1949 (citing Twombly, 550 U.S. at 555, 127 S.Ct. 1955). When a plaintiff's complaint fails to state a claim, the court should generally give the plaintiff at least one chance to amend the complaint under Rule 15(a) before dismissing the action with prejudice. See Great Plains Trust Co. v. Morgan Stanley Dean Witter & Co., 313 F.3d 305, 329 (5th Cir.2002) ("[D]istrict courts often afford plaintiffs at least one opportunity to cure pleading deficiencies before dismissing a case, unless it is clear that the defects are incurable or the plaintiffs advise the court that they are unwilling or unable to amend in a manner that will avoid dismissal."); see also United States ex rel. Adrian v. Regents of the Univ. of Cal., 363 F.3d 398, 403 (5th Cir.2004) ("Leave to amend should be freely given, and outright refusal to grant leave to amend without a justification ... is considered an abuse of discretion." (internal citation omitted)). However, a plaintiff should be denied leave to amend a complaint if the court determines that "a proposed amendment ... clearly is frivolous, advancing a claim or defense that is legally insufficient on its face ...." 6 WRIGHT, MILLER & KANE § 1487, at 732-33; see also Ayers v. Johnson, 247 Fed.Appx. 534, 535 (5th Cir.2007) (unpublished) (per curiam) ("`[A] district court acts within its discretion when dismissing a motion to amend that is frivolous or futile.'" (quoting Martin's Herend Imports, Inc. v. Diamond & Gem Trading U.S. of Am. Co., 195 F.3d 765, 771 (5th Cir.1999))). The second basis for Pride Offshore's motion is the sufficiency of the evidence in the record to raise a disputed fact issue material to Century Exploration's claim. Summary judgment is appropriate if no genuine issue of material fact exists and the moving party is entitled to judgment as a matter of law. FED. R. CIV. P. 56(a). "The movant bears the burden of identifying those portions of the record it believes demonstrate the absence of a genuine issue of material fact." Triple Tee Golf, Inc. v. Nike, Inc., 485 F.3d 253, 261 (5th Cir. 2007) (citing Celotex Corp. v. Catrett, 477 *801 U.S. 317, 322-25, 106 S.Ct. 2548, 91 L.Ed.2d 265 (1986)). If the burden of proof at trial lies with the nonmoving party, the movant may satisfy its initial burden by "`showing'—that is, pointing out to the district court—that there is an absence of evidence to support the nonmoving party's case." See Celotex, 477 U.S. at 325, 106 S.Ct. 2548. While the party moving for summary judgment must demonstrate the absence of a genuine issue of material fact, it does not need to negate the elements of the nonmovant's case. Boudreaux v. Swift Transp. Co., 402 F.3d 536, 540 (5th Cir.2005) (citation omitted). "A fact is `material' if its resolution in favor of one party might affect the outcome of the lawsuit under governing law." Sossamon v. Lone Star State of Tex., 560 F.3d 316, 326 (5th Cir.2009) (quotation omitted). "If the moving party fails to meet [its] initial burden, the motion [for summary judgment] must be denied, regardless of the nonmovant's response." United States v. $92,203.00 in U.S. Currency, 537 F.3d 504, 507 (5th Cir.2008) (quoting Little v. Liquid Air Corp., 37 F.3d 1069, 1075 (5th Cir. 1994) (en banc)). When the moving party has met its Rule 56(a) burden, the nonmoving party cannot survive a summary judgment motion by resting on the mere allegations of its pleadings. The nonmovant must identify specific evidence in the record and articulate how that evidence supports that party's claim. Baranowski v. Hart, 486 F.3d 112, 119 (5th Cir.2007). "This burden will not be satisfied by `some metaphysical doubt as to the material facts, by conclusory allegations, by unsubstantiated assertions, or by only a scintilla of evidence.'" Boudreaux, 402 F.3d at 540 (quoting Little, 37 F.3d at 1075). In deciding a summary judgment motion, the court draws all reasonable inferences in the light most favorable to the nonmoving party. Connors v. Graves, 538 F.3d 373, 376 (5th Cir.2008). B. Whether Century Exploration's Amended Claim Sufficiently Alleges Intentional Interference with Its Contractual Relations Century Exploration's amended claim alleges that Pride Offshore acted recklessly and intentionally. Citing Nautilus Marine, Inc. v. Niemela, 170 F.3d 1195, 1196-97 (9th Cir. 1999), Pride Offshore argues that "there is no exception to the Robins Dry Dock rule for intentional or reckless conduct." (Docket Entry No. 75 at 6). Century Exploration responds that Pride Offshore overstates the holding of Nautilus Marine. According to Century Exploration, the Ninth Circuit in Nautilus Marine did not rule that a defendant intentionally interfering with a contract would be covered by the economic-loss rule. Instead, the court ruled only that a defendant acting without knowledge of the contract in question would be covered by that rule. (Docket Entry No. 77 at 3 (citing Nautilus Marine, 170 F.3d at 1196-97)). Century Exploration argues that Pride Offshore "intentionally placed a patently inadequate rig on the [sea floor], knowing that it would not withstand hurricane force conditions and would not remain on site. Pride, a long-time driller on the [Outer Continental Shelf] knew that if the rig came loose, it would certainly damage subsea pipelines which permeate the seabed. Pride also knew that the producers on the [Outer Continental Shelf] would have contracts with pipeline owners to transport the oil and gas to shore, and knew that the damage to the pipelines would cause the production facilities to shut down." (Docket Entry No. 77 at 6). The arguments that Century Exploration makes in its response are not alleged in its claim, even as amended. Century Exploration's amended claim does not refer to Pride Offshore's knowledge of its contract with TGPC. Acknowledging this *802 gap, Century Exploration asks leave to file an amended complaint reciting these factual allegations. (Id. at 6 n. 4). Pride Offshore argues that the proposed amended claim would be futile. Pride Offshore faults Century Exploration for: fall[ing] short of alleging that [Pride Offshore] ever had actual knowledge of Century's contracts with TGPC. Century is simply trying to ignore the requirement that [Pride Offshore] have actual knowledge of the contracts because it could never prove such an allegation, and it is attempting to get by with merely alleging reckless allision. However, as the Ninth Circuit made clear, `an intent to allide does not equate to an intent to interfere with the defendant's contract.' [Pride Offshore] must have had actual knowledge of Century's contract with TGPC and let its drilling rig loose in a hurricane in order to interfere with a particular contract. Century knows it is unable to even plausibly allege that [Pride Offshore] had actual knowledge of Century's contracts with TGPC, or intentional interference with these contracts, and therefore Century's proposed pleadings amendment would be futile. (Docket Entry No. 78 at 4-5) (footnote, citation, and alterations omitted). In responding to Century Exploration's arguments, Pride Offshore appears to have scaled back its characterization of the Nautilus Marine court's holding. In the response, Pride Offshore characterizes the case as holding that "an intent to allide does not equate to an attempt to interfere with the defendant's contract." (Docket Entry No. 78 at 5 (quoting Nautilus Marine, 170 F.3d at 1197) (alterations omitted)). This accurately reflects the holding. The Ninth Circuit distinguished the facts before it from those in "cases holding that Robins Dry Dock does not preclude recovery for intentional interference with contract relations." Nautilus Marine, 170 F.3d at 1197. "The key to these cases," the court explained, "is not merely that the tort is intentional, but that the tortfeasor knew of the plaintiff's contractual relation and intended to interfere with it. Nautilus has not stated a claim of intentional interference with contractual relations, however, precisely because it did not allege, and could not show, such knowledge and intent." Id. (citations omitted). Century Exploration's characterization of the holding is consistent. Because Century Exploration has effectively sought leave to amend without filing a proposed amended complaint, it is difficult to determine whether it proposes to allege that Pride Offshore knew of specific contracts between Century Exploration and TGPC or that Pride Offshore knew that Century Exploration had to have contracts with some pipeline owner. To provide a sufficient basis to rule on the futility claim, Century Exploration will be granted leave to file an amended complaint. The allegations in an amended claim will enable Pride Offshore to clarify the basis for its motion to dismiss and enable this court to rule whether the allegations are sufficient. The motion for summary judgment based on the adequacy of the pleadings is granted, with leave to amend. C. Whether Century Exploration Has a Proprietary Interest in the Pipeline Pride Offshore also argues that summary judgment is appropriate under Robins Dry Dock for any claim based on Pride Offshore's negligence on the basis that the undisputed facts show that Century Exploration did not have a proprietary interest in the damaged pipeline. Courts consider three factors to determine whether a plaintiff's interest is proprietary: "actual possession or control, responsibility *803 for repair and responsibility for maintenance." IMTT-Gretna v. Robert E. Lee SS, 993 F.2d 1193, 1194 (5th Cir.1993) (summary calendar) (citing Tex. Eastern Trans. v. McMoRan Offshore Explor., 877 F.2d 1214, 1225 (5th Cir.1989)). If a plaintiff cannot meet any of the factors, the case must be dismissed. Id. In its response, Century Exploration explains that it "does not rely upon" a proprietary interest in the pipeline to justify recovery. (Docket Entry No. 77 at 1-2). This statement, as Pride Offshore points out, abandons the negligence claim. Century Exploration does not concede that Pride Offshore is correct. In a footnote, citing no authority, Century Offshore argues: With respect to the proprietary interest issue, the evidence is, and [Pride Offshore] does not dispute, that subsequent to the pipeline damage, Century contributed to the cost of repairs. One of the critical indicia of proprietary interest is liability for repairs. The fact that Century incurred this liability post-accident is immaterial. Century's contribution to repairs is sufficient evidence of its proprietary interest. At a minimum, Century is entitled to recover its contribution to the repair costs. (Id. at 2 n. 1). Pride Offshore responds in a footnote of its own, also without citing authority: "Although `responsibility for repairs' is one factor considered in determining whether a proprietary interest existed at the time of the damage, Century has already admitted that it was not responsible for repairs to the [pipeline] at the time of the alleged damage." (Docket Entry No. 78 at 2 n. 3). Century Offshore has acknowledged that it has no proprietary interest in the pipeline. Its contribution to the repair costs does not raise a fact issue as to whether it has a negligence claim against Pride Offshore seeking to recover such payments. The motion for summary judgment based on the absence of a proprietary interest in the damaged pipeline is granted. III. Conclusion Pride Offshore's motion for summary judgment is granted for the reasons set out above. Century Exploration may amend its complaint no later than February 25, 2011. NOTES [1] The parties have noted that for the purpose of this proceeding, Seahawk Drilling, Inc. is the successor-in-interest to the plaintiff, Pride Offshore, Inc. (Docket Entry No. 50 at 1 n. 1). For simplicity, the plaintiff is referred to as Pride Offshore.

1. Field of the Invention The present invention relates to a digital-to-analog converter which converts a quantized digital signal into an analog signal, and more specifically, to an improvement in a current addition type digital-to-analog converter which uses weighted resistors. 2. Description of the Related Art FIG. 1 is a block diagram of a conventional current addition type 16-bit digital-to-analog converter which uses weighted resistors. A 16-bit digital signal consisting of a train of pulses, each being quantized data "1" or "0", is applied to an input terminal IN. The pulses of the digital signal are successively stored in a shift register 1 in accordance with a shift clock input to a clock terminal CLK1. The digital signal stored in the shift register 1 is input to a latch 2 in accordance with a latch pulse which is input to a clock terminal CLK2 after all the 16 bits are stored in the shift register 1. 16 output terminals D0-D15 of the latch 2 are connected, through respective resistors R0-R15, to an inverting input terminal of an operational amplifier 3, which functions as an adder. The inverting input terminal of the operational amplifier 3 is coupled to an output terminal OUT thereof via a resistor R16, and a non-inverting input terminal thereof is grounded. The resistors R0-R16 each has a weighted resistance equal to a multiple of 2. More specifically, the following relationships are established: R16=2R15, R15=2R14, Rn=2Rn-1, ..., R1=2R0. Assuming that voltages output via the output terminals D0-D15 of the latch 2 are V0-V15 in the above-mentioned structure, an output voltage Vout of the operational amplifier 3 is: EQU Vout=(V15/R15+V14/R14+...+Vn/Rn+...+V0/R0)R16 Thus, when output data via the output terminals D0-D15a are "0", zero volt is generated, and when the output data are "1", 1 volt is generated. Thus, the 16-bit digital signal which consists of 16 data pieces, each having "1" or "0", and which is input to the input terminal IN are completely converted into an analog signal. For example, in a case where a 12-bit D/A converter is used so that it converts a 16-bit digital signal into an analog signal, it is necessary to omit any four bits of the 16 bits. (1) Normally, in many cases, four low-order bits are omitted. In a case where the digital signal ranges equally from the strongest sound to the weakest sound, the low-order bits are omitted. In this case, if the original digital signal has no distortion, an analog signal converted from the 12-bit digital signal does not deteriorate greatly. However, weak sound components expressed by the omitted four low-order bits are lost. (2) If there is no strong sound, four high-order bits are omitted. When weak sound components are meaningful, and strong sound components are not significant (or does not appear frequently), the four high-order bits are omitted. (3) Some high-order bits and some low-order bits are omitted. This method is intermediate between the above-mentioned methods (1) and (2) and suitable for cases where strong and weak sound components must be handled. It should be noted that none of the above-mentioned methods (1), (2) and (3) provide a dynamic range equal to or higher than 72 dB. Further, in each of the methods (1), (2) and (3), the input has information equal to 16 bits (92 dB), while each conventional method utilizes only 12 bits (72 dB). In the aforementioned circuit configuration, the precision of the resistance values of the resistors R0-R15 which serve as an input resistor of the operational amplifier 3 directly determines the converting precision of the digital-to-analog converter. In the 16-bit digital-to-analog converter, the resistance ratio of the resistor R16 to the resistor R0 is equal to 2.sup.16 (=65536). Assuming that the resistor R0 is selected to have a resistance equal to 10 k.OMEGA., the resistor R16 must have a resistance of 655.36 M.OMEGA.. It is difficult to realize such a high resistance by a highly precise resistor. When the aforementioned digital-to-analog converter is formed on a single LSI chip, it is necessary to form large resistor cells in order to secure the required resistance precision. This leads to an increase in the chip size. In order to overcome the problems as described above, a circuit is known which does not utilize a plurality of high-order and low-order bits. However, since predetermined high-order and low-order bits are always omitted, an output waveform may deteriorate greatly when input data mainly includes strong sound components or weak sound components.

--- abstract: 'Directed graphical models provide a useful framework for modeling causal or directional relationships for multivariate data. Prior work has largely focused on identifiability and search algorithms for directed acyclic graphical (DAG) models. In many applications, feedback naturally arises and directed graphical models that permit cycles occur. In this paper we address the issue of identifiability for general directed cyclic graphical (DCG) models satisfying the Markov assumption. In particular, in addition to the faithfulness assumption which has already been introduced for cyclic models, we introduce two new identifiability assumptions, one based on selecting the model with the fewest edges and the other based on selecting the DCG model that entails the maximum number of d-separation rules. We provide theoretical results comparing these assumptions which show that: (1) selecting models with the largest number of d-separation rules is strictly weaker than the faithfulness assumption; (2) unlike for DAG models, selecting models with the fewest edges does not necessarily result in a milder assumption than the faithfulness assumption. We also provide connections between our two new principles and minimality assumptions. We use our identifiability assumptions to develop search algorithms for small-scale DCG models. Our simulation study supports our theoretical results, showing that the algorithms based on our two new principles generally out-perform algorithms based on the faithfulness assumption in terms of selecting the true skeleton for DCG models.' bibliography: - 'reference\_DCG.bib' --- [****]{} --------------------------------------------- -- Gunwoong Park$^1$Garvesh Raskutti$^{1,2,3}$ --------------------------------------------- -- ---------------------------------------------------------------------- $^1$ Department of Statistics, University of Wisconsin-Madison $^2$ Department of Computer Science, University of Wisconsin-Madison $^3$ Wisconsin Institute for Discovery, Optimization Group ---------------------------------------------------------------------- **Keywords:** Directed graphical Models, Identifiability, Faithfulness, Feedback loops. Introduction {#SecInt} ============ A fundamental goal in many scientific problems is to determine causal or directional relationships between variables in a system. A well-known framework for representing causal or directional relationships are directed graphical models. Most prior work on directed graphical models has focused on directed acyclic graphical (DAG) models, also referred to as Bayesian networks which are directed graphical models with no directed cycles. One of the core problems is determining the underlying DAG $G$ given the data-generating distribution $\mathbb{P}$. A fundamental assumption in the DAG framework is the *causal Markov condition* (CMC) (see e.g., [@lauritzen1996graphical; @Spirtes2000]). While the CMC is broadly assumed, in order for a directed graph $G$ to be identifiable based on the distribution $\mathbb{P}$, additional assumptions are required. For DAG models, a number of identifiability and minimality assumptions have been introduced [@Glymour1987; @Spirtes2000] and the connections between them have been discussed [@Zhang2013]. In particular, one of the most widely used assumptions for DAG models is the *causal faithfulness condition* (CFC) which is sufficient for many search algorithms. However the CFC has been shown to be extremely restrictive, especially in the limited data setting [@Uhler2013]. In addition two minimality assumptions, the P-minimality and SGS-minimality assumptions have been introduced. These conditions are weaker than the CFC but do not guarantee model identifiability [@Zhang2013]. On the other hand, the recently introduced sparsest Markov representation (SMR) and frugality assumptions [@forster2015frugal; @Raskutti2013; @van2013ell] provide an alternative that is milder than the CFC and is sufficient to ensure identifiability. The main downside of the [SMR]{} and frugality assumptions relative to the CFC is that the [SMR]{} and frugality assumptions are sufficient conditions for model identifiability only when exhaustive searches over the DAG space are possible [@Raskutti2013], while the CFC is sufficient for polynomial-time algorithms [@Glymour1987; @Spirtes1991; @Spirtes2000] for learning equivalence class of sparse graphs. While the DAG framework is useful in many applications, it is limited since feedback loops are known to often exist (see e.g., [@Richardson1996; @Richardson1995]). Hence, directed graphs with directed cycles [@Spirtes2000] are more appropriate to model such feedback. However learning directed cyclic graphical (DCG) models from data is considerably more challenging than learning DAG models [@Richardson1996; @Richardson1995] since the presence of cycles poses a number of additional challenges and introduces additional non-identifiability. Consequently there has been considerably less work focusing on directed graphs with feedback both in terms of identifiability assumptions and search algorithms. [@Spirtes1995] discussed the CMC, and [@Richardson1996; @Richardson1995] discussed the CFC for DCG models and introduced the polynomial-time cyclic causal discovery (CCD) algorithm [@Richardson1996] for recovering the Markov equivalence class for DCGs. Recently, [@claassen2013learning] introduced the FCI$+$ algorithm for recovering the Markov equivalence class for sparse DCGs, which also assumes the CFC. As with DAG models, the CFC for cyclic models is extremely restrictive since it is more restrictive than the CFC for DAG models. In terms of learning algorithms that do not require the CFC, additional assumptions are typically required. For example [@mooij2011causal] proved identifiability for bivariate Gaussian cyclic graphical models with additive noise which does not require the CFC while many approaches have been studied for learning graphs from the results of interventions on the graph (e.g., [@hyttinen2010causal; @hyttinen2012causal; @hyttinen2012learning; @hyttinen2013experiment; @hyttinen2013discovering]). However, these additional assumptions are often impractical and it is often impossible or very expensive to intervene many variables in the graph. This raises the question of whether milder identifiability assumptions can be imposed for learning DCG models. In this paper, we address this question in a number of steps. Firstly, we adapt the [SMR]{} and frugality assumptions developed for DAG models to DCG models. Next we show that unlike for DAG models, the adapted [SMR]{} and frugality assumptions are not strictly weaker than the CFC. Hence we consider a new identifiability assumption based on finding the Markovian DCG entailing the maximum number of d-separation rules (MDR) which we prove is strictly weaker than the CFC and recovers the Markov equivalence class for DCGs for a strict superset of examples compared to the CFC. We also provide a comparison between the [MDR]{}, [SMR]{} and frugality assumptions as well as the minimality assumptions for both DAG and DCG models. Finally we use the [MDR]{} and [SMR]{} assumptions to develop search algorithms for small-scale DCG models. Our simulation study supports our theoretical results by showing that the algorithms induced by both the [SMR]{} and [MDR]{} assumptions recover the Markov equivalence class more reliably than state-of-the art algorithms that require the CFC for DCG models. We point out that the search algorithms that result from our identifiability assumptions require exhaustive searches and are not computationally feasible for large-scale DCG models. However, the focus of this paper is to develop the weakest possible identifiability assumption which is of fundamental importance for directed graphical models. The remainder of the paper is organized as follows: Section \[SecPriorWork\] provides the background and prior work for identifiability assumptions for both DAG and DCG models. In Section \[SecSMRFrugality\] we adapt the [SMR]{} and frugality assumptions to DCG models and provide a comparison between the [SMR]{} assumption, the CFC, and the minimality assumptions. In Section \[SecMaxDSep\] we introduce our new [MDR]{} principle, finding the Markovian DCG that entails the maximum number of d-separation rules and provide a comparison of the new principle to the CFC, [SMR]{}, frugality, and minimality assumptions. Finally in Section \[SecSimulation\], we use our identifiability assumptions to develop a search algorithm for learning small-scale DCG models, and provide a simulation study that is consistent with our theoretical results. Prior work on directed graphical models {#SecPriorWork} ======================================= In this section, we introduce the basic concepts of directed graphical models pertaining to model identifiability. A directed graph $G = (V,E)$ consists of a set of vertices $V$ and a set of directed edges $E$. Suppose that $V=\{1,2,\dots ,p\}$ and there exists a random vector $(X_1, X_2,\cdots,X_p)$ with probability distribution $\mathbb{P}$ over the vertices in $G$. A directed edge from a vertex $j$ to $k$ is denoted by $(j,k)$ or $j\to k$. The set $\mbox{pa}(k)$ of *parents* of a vertex $k$ consists of all nodes $j$ such that $(j,k)\in E$. If there is a directed path $j\to \cdots \to k$, then $k$ is called a *descendant* of $j$ and $j$ is an *ancestor* of $k$. The set $\mbox{de}(k)$ denotes the set of all descendants of a node $k$. The *non-descendants* of a node $k$ are $\mbox{nd}(k) = V\setminus (\{k\}\cup \mbox{de}(k))$. For a subset $S\subset V$, we define $\mbox{an}(S)$ to be the set of nodes $k$ that are in $S$ or are ancestors of a subset of nodes in $S$. Two nodes that are connected by an edge are called *adjacent*. A triple of nodes $(j,k,\ell)$ is an *unshielded triple* if $j$ and $k$ are adjacent to $\ell$ but $j$ and $k$ are not adjacent. An unshielded triple $(j,k,\ell)$ forms a *v-structure* if $j\to \ell$ and $k \to \ell$. In this case $\ell$ is called a *collider*. Furthermore, let $\pi$ be an undirected path $\pi$ between $j$ and $k$. If every collider on $\pi$ is in $\mbox{an}(S)$ and every non-collider on an undirected path $\pi$ is not in $S$, an undirected path $\pi$ from $j$ to $k$ *d-connects* $j$ and $k$ given $S \subset V\setminus\{j,k\}$ and $j$ is *d-connected* to $k$ given $S$. If a directed graph $G$ has no undirected path $\pi$ that d-connects $j$ and $k$ given a subset $S$, then $j$ is *d-separated* from $k$ given $S$: For disjoint sets of vertices $j, k \in V$ and $S \subset V \setminus\{j,k\}$, $j$ is *d-connected* to $k$ given $S$ if and only if there is an undirected path $\pi$ between $j$ and $k$, such that - If there is an edge between $a$ and $b$ on $\pi$ and an edge between $b$ and $c$ on $\pi$, and $b \in S$, then $b$ is a collider between $a$ and $c$ relative to $\pi$. - If $b$ is a collider between $a$ and $c$ relative to $\pi$, then there is a descendant $d$ of $b$ and $d \in S$. Finally, let $X_j {\protect\mathpalette{\protect\independenT}{\perp}}X_k \mid X_S$ with $S \subset V\setminus\{j, k\}$ denote the conditional independence (CI) statement that $X_j$ is conditionally independent (as determined by $\mathbb{P}$) of $X_k$ given the set of variables $X_S = \{ X_{\ell} \mid \ell \in S\}$, and let $X_j {\!\perp\!\!\!\!\not\perp\!}X_k \mid X_S$ denote conditional dependence. The *Causal Markov condition* associates CI statements of $\mathbb{P}$ with a directed graph $G$. \[Def:CMC\] A probability distribution $\mathbb{P}$ over a set of vertices $V$ satisfies the *Causal Markov condition* with respect to a (acyclic or cyclic) graph $G = (V, E)$ if for all $(j, k, S)$, $j$ is d-separated from $k$ given $S \subset V \setminus \{j,k\}$ in $G$, then $$\begin{aligned} X_j {\protect\mathpalette{\protect\independenT}{\perp}}X_k \mid X_S ~~\textrm{ according to $\mathbb{P}$}. \end{aligned}$$ The CMC applies to both acyclic and cyclic graphs (see e.g., [@Spirtes2000]). However not all directed graphical models satisfy the CMC. In order for a directed graphical model to satisfy the CMC, the joint distribution of a model should be defined by the *generalized factorization* [@Lauritzen1990]. \[Def:GenFac\] The joint distribution of $X_S$, $f(X_S)$ *factors according to directed graph* $G$ with vertices $V$ if and only if for every subset $S$ of $V$, $$f(X_{\mbox{an}(S)}) = \prod_{j \in \mbox{an}(S)} g_j (X_{j},X_{\mbox{pa}(j)})$$ where $g_j$ is a non-negative function. [@Spirtes1995] showed that the generalized factorization is a necessary and sufficient condition for directed graphical models to satisfy the CMC. For DAG models, $g_j(\cdot)$’s must correspond to a conditional probability distribution function whereas for graphical models with cycles, $g_j(\cdot)$’s need only be non-negative functions. As shown by [@Spirtes1995], a concrete example of a class of cyclic graphs that satisfy the factorization above is structural linear DCG equation models with additive independent errors. We will later use linear DCG models in our simulation study. In general, there are many directed graphs entailing the same d-separation rules. These graphs are *Markov equivalent* and the set of Markov equivalent graphs is called a *Markov equivalence class* (MEC) [@Richardson1995; @udea1991equivalence; @Spirtes2000; @verma1992algorithm]. For example, consider two 2-node graphs, $G_1: X_1 \rightarrow X_2$ and $G_2: X_1 \leftarrow X_2$. Then both graphs are Markov equivalent because they both entail no d-separation rules. Hence, $G_1$ and $G_2$ belong to the same [MEC]{} and hence it is impossible to distinguish two graphs by d-separation rules. The precise definition of the [MEC]{} is provided here. Two directed graphs $G_1$ and $G_2$ are *Markov equivalent* if any distribution which satisfies the CMC with respect to one graph satisfies the CMC with respect to the other, and vice versa. The set of graphs which are Markov equivalent to $G$ is denoted by $\mathcal{M}(G)$. The characterization of Markov equivalence classes is different for DAGs and DCGs. For DAGs, [@udea1991equivalence] developed an elegant characterization of Markov equivalence classes defined by the *skeleton* and *v-structures*. The skeleton of a DAG model consists of the edges without directions. However for DCGs, the presence of feedback means the characterization of the [MEC]{} for DCGs is considerably more involved. [@Richardson1996] provides a characterization. The presence of directed cycles changes the notion of adjacency between two nodes. In particular there are *real* adjacencies that are a result of directed edges in the DCG and *virtual* adjacencies which are edges that do not exist in the data-generating DCG but can not be recognized as a non-edge from the data. The precise definition of real and virtual adjacencies are as follows. \[Def:Adj\] Consider a directed graph $G = (V,E)$. - For any $j, k \in V$, $j$ and $k$ are *really adjacent* in $G$ if $j \rightarrow k$ or $j \leftarrow k$. - For any $j, k \in V$, $j$ and $k$ are *virtually adjacent* if $j$ and $k$ have a common child $\ell$ such that $\ell$ is an ancestor of $j$ or $k$. Note that a virtual adjacency can only occur if there is a cycle in the graph. Hence, DAGs have only real edges while DCGs can have both real edges and virtual edges. Figure \[Fig:Sec2a\] shows an example of a DCG with a virtual edge. In Figure \[Fig:Sec2a\], a pair of nodes $(1,4)$ has a virtual edge (dotted line) because the triple $(1,4,2)$ forms a v-structure and the common child $2$ is an ancestor of $1$. This virtual edge is created by the cycle, $1 \rightarrow 2 \rightarrow 3 \rightarrow 1$. \(A) at (1.5,1.1)[$1$]{}; (B) at (0.35,0.55) [$3$]{}; (C) at (1.5,0) [$2$]{}; (D) at (3,0.0) [$4$]{}; (B) edge \[bend right = -25, shorten &gt;=1pt, shorten &lt;=1pt \] node\[above\] [ ]{} (A); (C) edge \[bend right = -25, shorten &gt;=1pt, shorten &lt;=1pt\] node\[above\] [ ]{} (B); (D) edge \[bend right = 0, shorten &gt;=1pt, shorten &lt;=1pt\] node\[above\] [ ]{} (C); (A) edge \[bend right = -25, shorten &gt;=1pt, shorten &lt;=1pt\] node\[above\] (C); (A) to node\[above right\] [virtual]{} (D); Virtual edges generate different types of relationships involving unshielded triples: (1) an unshielded triple $(j,k,\ell)$ (that is $j-\ell-k$) is called a *conductor* if $\ell$ is an ancestor of $j$ or $k$; (2) an unshielded triple $(j,k,\ell)$ is called a *perfect non-conductor* if $\ell$ is a descendant of the common child of $j$ and $k$; and (3) an unshielded triple $(j,k,\ell)$ is called an *imperfect non-conductor* if the triple is not a conductor or a perfect non-conductor. Intuitively, the concept of (1) a conductor is analogous to the notion of a non v-structure in DAGs because for example suppose that an unshielded triple $(j,k,\ell)$ is a conductor, then $j$ is d-connected to $k$ given any set $S$ which does not contain $\ell$. Moreover, (2) a perfect non-conductor is analogous to a v-structure because suppose that $(j,k,\ell)$ is a perfect non-conductor, then $j$ is d-connected to $k$ given any set $S$ which contains $\ell$. However, there is no analogous notion of an imperfect non-conductor for DAG models. We see throughout this paper that this difference creates a major challenge in inferring DCG models from the underlying distribution $\mathbb{P}$. As shown by [@Richardson1994] (Cyclic Equivalence Theorem), a necessary (but not sufficient) condition for two DCGs to belong to the same [MEC]{} is that they share the same real plus virtual edges and the same (1) conductors, (2) perfect non-conductors and (3) imperfect non-conductors. However unlike for DAGs, this condition is not sufficient for Markov equivalence. A complete characterization of Markov equivalence is provided in [@Richardson1994; @Richardson1995] and since it is quite involved, we do not include here. Even if we weaken the goal to inferring the [MEC]{} for a DAG or DCG, the CMC is insufficient for discovering the true [MEC]{} $\mathcal{M}(G^*)$ because there are many graphs satisfying the CMC, which do not belong to $\mathcal{M}(G^*)$. For example, any fully-connected graph always satisfies the CMC because it does not entail any d-separation rules. Hence, in order to identify the true [MEC]{} given the distribution $\mathbb{P}$, stronger identifiability assumptions that force the removal of edges are required. Faithfulness and minimality assumptions --------------------------------------- In this section, we discuss prior work on identifiability assumptions for both DAG and DCG models. To make the notion of identifiability and our assumptions precise, we need to introduce the notion of a true data-generating graphical model $(G^*, \mathbb{P})$. All we observe is the distribution (or samples from) $\mathbb{P}$, and we know the graphical model $(G^*, \mathbb{P})$ satisfies the CMC. Let $CI(\mathbb{P})$ denote the set of conditional independence statements corresponding to $\mathbb{P}$. The graphical model $(G^*, \mathbb{P})$ is *identifiable* if the Markov equivalence class of the graph $\mathcal{M}(G^*)$ can be uniquely determined based on $CI(\mathbb{P})$. For a directed graph $G$, let $E(G)$ denote the set of directed edges, $S(G)$ denote the set of edges without directions, also referred to as the skeleton, and $D_{sep}(G)$ denote the set of d-separation rules entailed by $G$. One of the most widely imposed identifiability assumptions for both DAG and DCG models is the *causal faithfulness condition* (CFC) [@Spirtes2000] also referred to as the stability condition in [@Pearl2014]. A directed graph is *faithful* to a probability distribution if there is no probabilistic independence in the distribution that is not entailed by the CMC. The CFC states that the graph is faithful to the true probability distribution. \[Def:CFC\] Consider a directed graphical model $(G^*, \mathbb{P})$. A graph $G^*$ is *faithful* to $\mathbb{P}$ if and only if for any $j,k \in V$ and any subset $S \subset V \setminus \{j,k\}$, $$j \textrm{ d-separated from } k \mid S \iff X_j {\protect\mathpalette{\protect\independenT}{\perp}}X_k \mid X_S \textrm{ according to $\mathbb{P}$}.$$ While the CFC is sufficient to guarantee identifiability for many polynomial-time search algorithms [@claassen2013learning; @Glymour1987; @hyttinen2012causal; @Richardson1996; @Richardson1995; @Spirtes2000] for both DAGs and DCGs, the CFC is known to be a very strong assumption (see e.g., [@forster2015frugal; @Raskutti2013; @Uhler2013]) that is often not satisfied in practice. Hence, milder identifiability assumptions have been considered. Minimality assumptions, notably the *P-minimality* [@pearl2000] and SGS-minimality [@Glymour1987] assumptions are two such assumptions. The P-minimality assumption asserts that for directed graphical models satisfying the CMC, graphs that entail more d-separation rules are preferred. For example, suppose that there are two graphs $G_1$ and $G_2$ which are not Markov equivalent. $G_1$ is *strictly preferred* to $G_2$ if $D_{sep}(G_2) \subset D_{sep}(G_1)$. The P-minimality assumption asserts that no graph is strictly preferred to the true graph $G^*$. The SGS-minimality assumption asserts that there exists no proper sub-graph of $G^*$ that satisfies the CMC with respect to the probability distribution $\mathbb{P}$. To define the term sub-graph precisely, $G_1$ is a sub-graph of $G_2$ if $E(G_1) \subset E(G_2)$ and $E(G_1) \neq E(G_2)$. [@Zhang2013] proved that the SGS-minimality assumption is weaker than the P-minimality assumption which is weaker than the CFC for both DAG and DCG models. While [@Zhang2013] states the results for DAG models, the result easily extends to DCG models. \[Thm:Sec2a\] If a directed graphical model $(G^*, \mathbb{P})$ satisfies - the CFC, it satisfies the P-minimality assumption. - the P-minimality assumption, it satisfies the SGS-minimality assumption. Sparsest Markov Representation (SMR) for DAG models --------------------------------------------------- While the minimality assumptions are milder than the CFC, neither the P-minimality nor SGS-minimality assumptions imply identifiability of the MEC for $G^*$. Recent work by [@Raskutti2013] developed the *sparsest Markov representation* (SMR) assumption and a slightly weaker version later referred to as *frugality* assumption [@forster2015frugal] which applies to DAG models. The [SMR]{} assumption which we refer to here as the identifiable [SMR]{} assumption states that the true DAG model is the graph satisfying the CMC with the fewest edges. Here we say that a DAG $G_1$ is *strictly sparser* than a DAG $G_2$ if $G_1$ has *fewer* edges than $G_2$. \[Def:SMR\] A DAG model $(G^*,\mathbb{P})$ satisfies the identifiable [SMR]{} assumption if $(G^* ,\mathbb{P})$ satisfies the CMC and $|S(G^*)| < |S(G)|$ for every DAG $G$ such that $(G ,\mathbb{P})$ satisfies the CMC and $G \notin \mathcal{M}(G^*)$. The identifiable SMR assumption is strictly weaker than the CFC while also ensuring a method known as the Sparsest Permutation (SP) algorithm [@Raskutti2013] recovers the true MEC. Hence the identifiable SMR assumption guarantees identifiability of the MEC for DAGs. A slightly weaker notion which we refer to as the weak SMR assumption does not guarantee model identifiability. \[Def:Fru\] A DAG model $(G^* ,\mathbb{P})$ satisfies the weak [SMR]{} assumption if $(G^* ,\mathbb{P})$ satisfies the CMC and $|S(G^*)| \leq |S(G)|$ for every DAG $G$ such that $(G ,\mathbb{P})$ satisfies the CMC and $G \notin \mathcal{M}(G^*)$. A comparison of [SMR]{}/frugality to the CFC and the minimality assumptions for DAG models is provided in [@Raskutti2013] and [@forster2015frugal]. \[Thm:Sec2b\] If a DAG model $(G^*, \mathbb{P})$ satisfies - the CFC, it satisfies the identifiable [SMR]{} assumption and consequently weak [SMR]{} assumption. - the weak [SMR]{} assumption, it satisfies the P-minimality assumption and consequently the SGS-minimality assumption. - the identifiable [SMR]{} assumption, $G^*$ is identifiable up to the true MEC $\mathcal{M}(G^*)$. It is unclear whether the [SMR]{}/frugality assumptions apply naturally to DCG models since the success of the [SMR]{} assumption relies on the local Markov property which is known to hold for DAGs but not DCGs [@Richardson1994]. In this paper, we investigate the extent to which these identifiability assumptions apply to DCG models and provide a new principle for learning DCG models. Based on this prior work, a natural question to consider is whether the identifiable and weak [SMR]{} assumptions developed for DAG models apply to DCG models and whether there are similar relationships between the CFC, identifiable and weak [SMR]{}, and minimality assumptions. In this paper we address this question by adapting both identifiable and weak [SMR]{} assumptions to DCG models. One of the challenges we address is dealing with the distinction between real and virtual edges in DCGs. We show that unlike for DAG models, the identifiable [SMR]{} assumption is not necessarily a weaker assumption than the CFC. Consequently, we introduce a new principle which is the maximum d-separation rule (MDR) principle which chooses the directed Markov graph with the greatest number of d-separation rules. We show that our [MDR]{} principle is strictly weaker than the CFC and stronger than the P-minimality assumption, while also guaranteeing model identifiability for DCG models. Our simulation results complement our theoretical results, showing that the [MDR]{} principle is more successful than the CFC in terms of recovering the true [MEC]{} for DCG models. Sparsity and [SMR]{} for DCG models {#SecSMRFrugality} =================================== In this section, we extend notions of sparsity and the [SMR]{} assumptions to DCG models. As mentioned earlier, in contrast to DAGs, DCGs can have two different types of edges which are real and virtual edges. In this paper, we define the *sparsest* DCG as the graph with the fewest *total edges* which are virtual edges plus real edges. The main reason we choose total edges rather than just real edges is that all DCGs in the same Markov equivalence class (MEC) have the same number of total edges [@Richardson1994]. However, the number of real edges may not be the same among the graphs even in the same [MEC]{}. For example in Figure \[Fig:Sec3a\], there are two different [MECs]{} and each [MEC]{} has two graphs: $G_1, G_2 \in \mathcal{M}(G_1)$ and $G_3, G_4 \in \mathcal{M}(G_3)$. $G_1$ and $G_2$ have $9$ total edges but $G_3$ and $G_4$ has $7$ total edges. On the other hand, $G_1$ has $6$ real edges, $G_2$ has $9$ real edges, $G_3$ has $5$ real edges, and $G_4$ has $7$ real edges (a bi-directed edge is counted as 1 total edge). For a DCG $G$, let $S(G)$ denote the *skeleton* of $G$ where $(j,k) \in S(G)$ is a real or virtual edge. (M1) at (3.1,0.6) [$\mathcal{M}(G_1)$]{}; (M2) at (11.15,0.6) [$\mathcal{M}(G_3)$]{}; \(A) at (0,0) [$1$]{}; (B) at (1.3,0) [$2$]{}; (C) at (2.6,0) [$3$]{}; (D) at (1.3,1) [$4$]{}; (E) at (1.3,2) [$5$]{}; (G1) at (1.3,-1.0) [$G_1$]{}; (A2) at (3.6,0) [$1$]{}; (B2) at (4.9,0) [$2$]{}; (C2) at (6.2,0) [$3$]{}; (D2) at (4.9,1) [$4$]{}; (E2) at (4.9,2) [$5$]{}; (G2) at (4.9,-1.0) [$G_2$]{}; (A3) at (8.0, 0) [$1$]{}; (B3) at (9.3,0) [$2$]{}; (C3) at (10.7,0) [$3$]{}; (D3) at (9.3,1) [$4$]{}; (E3) at (9.3,2) [$5$]{}; (G3) at (9.3,-1.0) [$G_3$]{}; (A4) at (11.7,0) [$1$]{}; (B4) at (13.0,0) [$2$]{}; (C4) at (14.3,0) [$3$]{}; (D4) at (13.0,1) [$4$]{}; (E4) at (13.0,2) [$5$]{}; (G4) at (13.0,-1.0) [$G_4$]{}; \(A) edge \[right=25\] node\[above\] [ ]{} (D); (B) edge \[left =25\] node\[above\] [ ]{} (D); (C) edge \[left =25\] node\[above\] [ ]{} (D); (D) edge \[left =25\] node\[above\] [ ]{} (E); (E) edge \[bend right =35\] node\[above\] [ ]{} (A); (E) edge \[bend left =35\] node\[above\] [ ]{} (C); (A) edge \[-, dotted,thick \] node\[above\] [ ]{} (B); (B) edge \[-, dotted,thick \] node\[above\] [ ]{} (C); (A) edge \[-, dotted,thick, bend right =30 \] node\[above\] [ ]{} (C); (A2) edge \[right=25\] node\[above\] [ ]{} (D2); (B2) edge \[left =15\] node\[above\] [ ]{} (D2); (C2) edge \[left =25\] node\[above\] [ ]{} (D2); (D2) edge \[left =25\] node\[above\] [ ]{} (E2); (E2) edge \[bend right =35\] node\[above\] [ ]{} (A2); (E2) edge \[bend left =35\] node\[above\] [ ]{} (C2); (A2) edge \[ \] node\[above\] [ ]{} (B2); (B2) edge \[ \] node\[above\] [ ]{} (C2); (A2) edge \[bend right =30 \] node\[above\] [ ]{} (C2); (A3) edge \[right=25\] node\[above\] [ ]{} (D3); (B3) edge \[bend left =15\] node\[above\] [ ]{} (D3); (D3) edge \[bend left =15\] node\[above\] [ ]{} (B3); (C3) edge \[left =25\] node\[above\] [ ]{} (D3); (A3) edge \[-,dotted,thick\] node\[above\] [ ]{} (B3); (C3) edge \[-,dotted,thick\] node\[above\] [ ]{} (B3); (A3) edge \[bend right =45\] node\[above\] [ ]{} (C3); (D3) edge \[left =45\] node\[above\] [ ]{} (E3); (A4) edge \[right=25\] node\[above\] [ ]{} (D4); (B4) edge \[left =25\] node\[above\] [ ]{} (D4); (C4) edge \[left =25\] node\[above\] [ ]{} (D4); (A4) edge \[left =25\] node\[above\] [ ]{} (B4); (A4) edge \[bend right =45\] node\[above\] [ ]{} (C4); (C4) edge \[left =45\] node\[above\] [ ]{} (B4); (D4) edge \[left =45\] node\[above\] [ ]{} (E4); Using this definition of the skeleton $S(G)$ for a DCG $G$, the definitions of the identifiable and weak [SMR]{} assumptions carry over from DAG to DCG models. For completeness, we re-state the definitions here. \[DefSMRDCG\] A DCG model $(G^* ,\mathbb{P})$ satisfies the identifiable [SMR]{} assumption if $(G^* ,\mathbb{P})$ satisfies the CMC and $|S(G^*)| < |S(G)|$ for every DCG $G$ such that $(G ,\mathbb{P})$ satisfies the CMC and $G \notin \mathcal{M}(G^*)$. \[DefFruDCG\] A DCG model $(G^* ,\mathbb{P})$ satisfies the weak [SMR]{} assumption if $(G^* ,\mathbb{P})$ satisfies the CMC and $|S(G^*)| \leq |S(G)|$ for every DCG $G$ such that $(G ,\mathbb{P})$ satisfies the CMC and $G \notin \mathcal{M}(G^*)$. Both the [SMR]{} and SGS minimality assumptions prefer graphs with the fewest total edges. The main difference between the SGS-minimality assumption and the [SMR]{} assumptions is that the SGS-minimality assumption requires that there is no DCGs with a *strict subset* of edges whereas the [SMR]{} assumptions simply require that there are no DCGs with *fewer* edges. Unfortunately as we observe later unlike for DAG models, the identifiable [SMR]{} assumption is not weaker than the CFC for DCG models. Therefore, the identifiable [SMR]{} assumption does not guarantee identifiability of [MECs]{} for DCG models. On the other hand, while the weak [SMR]{} assumption may not guarantee uniqueness, we prove it is a strictly weaker assumption than the CFC. We explore the relationships between the CFC, identifiable and weak [SMR]{}, and minimality assumptions in the next section. Comparison of SMR, CFC and minimality assumptions for DCG models {#SubSecSMR} ---------------------------------------------------------------- Before presenting our main result in this section, we provide a lemma which highlights the important difference between the [SMR]{} assumptions for graphical models with cycles compared to DAG models. Recall that the [SMR]{} assumptions involve counting the number of edges, whereas the CFC and P-minimality assumption involve d-separation rules. First, we provide a fundamental link between the presence of an edge in $S(G)$ and d-separation/connection rules. \[Lem:Sec3a\] For a DCG $G$, $(j,k) \in S(G)$ if and only if $j$ is d-connected to $k$ given $S$ for all $S \subset V \setminus \{j,k\}$. First, we show that if $(j,k) \in S(G)$ then $j$ is d-connected to $k$ given $S$ for all $S \subset V \setminus \{j,k\}$. By the definition of d-connection/separation, there is no subset $S \subset V \setminus \{j,k\}$ such that $j$ is d-separated from $k$ given $S$. Second, we prove that if $(j,k) \notin S(G)$ then there exists $S \subset V \setminus \{j,k\}$ such that $j$ is d-separated from $k$ given $S$. Let $S = \mbox{an}(j) \cup \mbox{an}(k)$. Then $S$ has no common children or descendants, otherwise $(j,k)$ are virtually adjacent. Then there is no undirected path between $j$ and $k$ conditioned on the union of ancestors of $j$ and $k$, and therefore $j$ is d-separated from $k$ given $S$. This completes the proof. Note that the above statement is true for real or virtual edges and not real edges alone. We now state an important lemma which shows the key difference in comparing the [SMR]{} assumptions to other identifiability assumptions (CFC, P-minimality, SGS-minimality) for graphical models with cycles, which does not arise for DAG models. \[Lem:Sec3b\] - For any two DCGs $G_1$ and $G_2$, $D_{sep}(G_1) \subseteq D_{sep}(G_2)$ implies $S(G_2) \subseteq S(G_1)$. - There exist two DCGs $G_1$ and $G_2$ such that $S(G_1) = S(G_2)$, but $D_{sep}(G_1)$ $\neq$ $D_{sep}(G_2)$ and $D_{sep}(G_1) \subset D_{sep}(G_2)$. For DAGs, no two such graphs exist. We begin with the proof of (a). Suppose that $S(G_1)$ is not a sub-skeleton of $S(G_2)$, meaning that there exists a pair $(j,k) \in S(G_1)$ and $(j,k) \notin S(G_2)$. By Lemma \[Lem:Sec3a\], $j$ is d-connected to $k$ given $S$ for all $S \subset V \setminus \{j,k\}$ in $G_1$ while there exists $S \subset V \setminus \{j,k\}$ such that $j$ is d-separated from $k$ given $S$ entailed by $G_2$. Hence it is contradictory that $D_{sep}(G_1) \subset D_{sep}(G_2)$. For (b), we refer to the example in Figure \[Fig:Sec3b\]. In Figure \[Fig:Sec3b\], the unshielded triple $(1, 4, 2)$ is a conductor in $G_1$ and an imperfect non-conductor in $G_2$ because of a reversed directed edge between $4$ and $5$. By the property of a conductor, $1$ is not d-separated from $4$ given the empty set for $G_1$. In contrast for $G_2$, $1$ is d-separated from $4$ given the empty set. Other d-separation rules are the same for both $G_1$ and $G_2$. \(A) at(0,0) [$1$]{}; (B) at(1.5,0) [$2$]{}; (C) at(3,0) [$3$]{}; (D) at(4.5,0) [$4$]{}; (E) at(3,1.5) [$5$]{}; (G1) at(3, -1.2) [$G_1$]{}; (A2) at(7,0) [$1$]{}; (B2) at(8.5,0) [$2$]{}; (C2) at(10,0) [$3$]{}; (D2) at(11.5,0) [$4$]{}; (E2) at(10,1.5) [$5$]{}; (G1) at(10, -1.2) [$G_2$]{}; \(A) edge \[right=25\] node\[above\] [ ]{} (B); (B) edge \[bend left =25\] node\[above\] [ ]{} (C); (C) edge \[bend left =25\] node\[above\] [ ]{} (B); (D) edge \[left =25\] node\[above\] [ ]{} (C); (B) edge \[left =25\] node\[above\] [ ]{} (E); (C) edge \[left =25\] node\[above\] [ ]{} (E); (E) edge \[left =25, color= red\] node\[above\] [ ]{} (D); (A) edge \[-, dotted, bend right= 35, thick \] node\[above\] [ ]{} (C); (B) edge \[-, dotted, bend right= 35, thick \] node\[above\] [ ]{} (D); (A2) edge \[right=25\] node\[above\] [ ]{} (B2); (B2) edge \[bend left =25\] node\[above\] [ ]{} (C2); (C2) edge \[bend left =25\] node\[above\] [ ]{} (B2); (D2) edge \[left =25\] node\[above\] [ ]{} (C2); (B2) edge \[left =25\] node\[above\] [ ]{} (E2); (C2) edge \[left =25\] node\[above\] [ ]{} (E2); (D2) edge \[left =25, color= red\] node\[above\] [ ]{} (E2); (A2) edge \[-, dotted, bend right= 35, thick \] node\[above\] [ ]{} (C2); (B2) edge \[-, dotted, bend right= 35, thick \] node\[above\] [ ]{} (D2); Lemma \[Lem:Sec3b\] (a) holds for both DAGs and DCGs, and allows us to conclude a subset-superset relation between edges in the skeleton and d-separation rules in a graph $G$. Part (b) is where there is a key difference DAGs and directed graphs with cycles. Part (b) asserts that there are examples in which the edge set in the skeleton may be totally equivalent, yet one graph entails a strict superset of d-separation rules. Now we present the main result of this section which compares the identifiable and weak [SMR]{} assumptions with the CFC and P-minimality assumption. \[Thm:Sec3a\] For DCG models, - the weak [SMR]{} assumption is weaker than the CFC. - there exists a DCG model $(G, \mathbb{P})$ satisfying the CFC that does not satisfy the identifiable [SMR]{} assumption. - the identifiable [SMR]{} assumption is stronger than the P-minimality assumption. - there exists a DCG model $(G, \mathbb{P})$ satisfying the weak [SMR]{} assumption that does not satisfy the P-minimality assumption. <!-- --> - The proof for (a) follows from Lemma \[Lem:Sec3b\] (a). If a DCG model $(G^*, \mathbb{P})$ satisfies the CFC, then for any graph $G$ such that $(G, \mathbb{P})$ satisfies the CMC, $D_{sep}(G) \subseteq D_{sep}(G^*)$. Hence based on Lemma \[Lem:Sec3b\] (a), $S(G^*) \subseteq S(G)$ and $(G^*,\mathbb{P})$ satisfies the weak [SMR]{} assumption. - We refer to the example in Figure \[Fig:Sec3b\] where $(G_2, \mathbb{P})$ satisfies the CFC and fails to satisfy the identifiable [SMR]{} assumption because $S(G_1) = S(G_2)$ and $(G_1, \mathbb{P})$ satisfies the CMC. - The proof for (c) again follows from Lemma \[Lem:Sec3b\] (a). Suppose that a DCG model $(G^*, \mathbb{P})$ fails to satisfy the P-minimality assumption. This implies that there exists a DCG $G$ such that $(G, \mathbb{P})$ satisfies the CMC, $G \notin \mathcal{M}(G^*)$ and $D_{sep}(G^*) \subset D_{sep}(G)$. Lemma \[Lem:Sec3b\] (a) implies $S(G) \subseteq S(G^*)$. Hence $G^*$ cannot have the fewest edges uniquely, therefore $(G^*, \mathbb{P})$ fails to satisfy the identifiable [SMR]{} assumption. - We refer to the example in Figure \[Fig:Sec3b\] where $(G_1,\mathbb{P})$ satisfies the weak [SMR]{} assumption and fails to satisfy the P-minimality assumption. Further explanation is given in Figure \[Fig:App2\] in the appendix. Theorem \[Thm:Sec3a\] shows that if a DCG model $(G, \mathbb{P})$ satisfies the CFC, the weak [SMR]{} assumption is satisfied whereas the identifiable [SMR]{} assumption is not necessarily satisfied. For DAG models, the identifiable [SMR]{} assumption is strictly weaker than the CFC and the identifiable [SMR]{} assumption guarantees identifiability of the true [MEC]{}. However, Theorem \[Thm:Sec3a\] (b) implies that the identifiable [SMR]{} assumption is not strictly weaker than the CFC for DCG models. On the other hand, unlike for DAG models, the weak [SMR]{} assumption does not imply the P-minimality assumption for DCG models, according to (d). In Section \[SecSimulation\], we implement an algorithm that uses the identifiable [SMR]{} assumption and the results seem to suggest that on average for DCG models, the identifiable [SMR]{} assumption is weaker than the CFC. New principle: Maximum d-separation rules (MDR) {#SecMaxDSep} =============================================== In light of the fact that the identifiable [SMR]{} assumption does not lead to a strictly weaker assumption than the CFC, we introduce the maximum d-separation rules (MDR) assumption. The [MDR]{} assumption asserts that $G^*$ entails more d-separation rules than any other graph satisfying the CMC according to the given distribution $\mathbb{P}$. We use $CI(\mathbb{P})$ to denote the conditional independence (CI) statements corresponding to the distribution $\mathbb{P}$. A DCG model $(G^* ,\mathbb{P})$ satisfies the maximum *d-separation* rules (MDR) assumption if $(G^* ,\mathbb{P})$ satisfies the CMC and $|D_{sep}(G)| < |D_{sep}(G^*)|$ for every DCG $G$ such that $(G ,\mathbb{P})$ satisfies the CMC and $G \notin \mathcal{M}(G^*)$. There is a natural and intuitive connection between the MDR assumption and the P-minimality assumption. Both assumptions encourage DCGs to entail more d-separation rules. The key difference between the P-minimality assumption and the MDR assumption is that the P-minimality assumption requires that there is no DCGs that entail a *strict superset* of d-separation rules whereas the MDR assumption simply requires that there are no DCGs that entail a *greater number* of d-separation rules. Comparison of [MDR]{} to CFC and minimality assumptions for DCGs {#SubSecMDROcc} ---------------------------------------------------------------- In this section, we provide a comparison of the MDR assumption to the CFC and P-minimality assumption. For ease of notation, let $\mathcal{G}_{M}(\mathbb{P})$ and $\mathcal{G}_{F}(\mathbb{P})$ denote the set of Markovian DCG models satisfying the MDR assumption and CFC, respectively. In addition, let $\mathcal{G}_{P}(\mathbb{P})$ denote the set of DCG models satisfying the P-minimality assumption. \[Thm:Sec4a\] Consider a DCG model $(G^*, \mathbb{P})$. - If $\mathcal{G}_F(\mathbb{P}) \neq \emptyset$, then $\mathcal{G}_F (\mathbb{P}) = \mathcal{G}_{M}(\mathbb{P})$. Consequently if $(G^*, \mathbb{P})$ satisfies the CFC, then $\mathcal{G}_F(\mathbb{P}) = \mathcal{G}_{M}(\mathbb{P}) = \mathcal{M}(G^*)$. - There exists a distribution $\mathbb{P}$ for which $\mathcal{G}_F(\mathbb{P}) = \emptyset$ while $(G^*, \mathbb{P})$ satisfies the [MDR]{} assumption and $\mathcal{G}_{M}(\mathbb{P}) = \mathcal{M}(G^*)$. - $\mathcal{G}_{M}(\mathbb{P}) \subseteq \mathcal{G}_{P}(\mathbb{P})$. - There exists a distribution $\mathbb{P}$ for which $\mathcal{G}_{M}(\mathbb{P}) = \emptyset$ while $(G^*, \mathbb{P})$ satisfies the P-minimality assumption and $\mathcal{G}_{P}(\mathbb{P}) \supseteq \mathcal{M}(G^*)$. <!-- --> - Suppose that $(G^*, \mathbb{P})$ satisfies the CFC. Then $CI(\mathbb{P})$ corresponds to the set of d-separation rules entailed by $G^*$. Note that if $(G, \mathbb{P})$ satisfies the CMC and $G \notin \mathcal{M}(G^*)$, then $CI(\mathbb{P})$ is a superset of the set of d-separation rules entailed by $G$ and therefore $D_{sep}(G) \subset D_{sep}(G^*)$. This allows us to conclude that graphs belonging to $\mathcal{M}(G^*)$ should entail the maximum number of d-separation rules among graphs satisfying the CMC. Furthermore, based on the CFC $\mathcal{G}_F(\mathbb{P}) = \mathcal{M}(G^*)$ which completes the proof. - Suppose that $(G^*,\mathbb{P})$ fails to satisfy the P-minimality assumption. By the definition of the P-minimality assumption, there exists $(G,\mathbb{P})$ satisfying the CMC such that $G \notin \mathcal{M}(G^*)$ and $D_{sep}(G^*) \subset D_{sep}(G)$. Hence, $G^*$ entails strictly less d-separation rules than $G$, and therefore $(G^*,\mathbb{P})$ violates the [MDR]{} assumption. - For (b) and (d), we refer to the example in Figure $\ref{fig:Sec4a}$. Suppose that $X_1$, $X_2$, $X_3$, $X_4$ are random variables with distribution $\mathbb{P}$ with the following CI statements: $$\label{CIrelations} CI(\mathbb{P}) = \{X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_3 \mid X_2;~X_2 {\protect\mathpalette{\protect\independenT}{\perp}}X_4 \mid X_1, X_3;~X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_2 \mid X_4\}.$$ We show that $(G_1, \mathbb{P})$ satisfies the MDR assumption but not the CFC, whereas $(G_2, \mathbb{P})$ satisfies the P-minimality assumption but not the MDR assumption. Any graph satisfying the CMC with respect to $\mathbb{P}$ must only entail a subset of the three d-separation rules: $\{X_1~\mbox{d-sep}~X_3 \mid X_2; X_2~\mbox{d-sep} $ $X_4 \mid X_1,X_3;~X_1~\mbox{d-sep}~X_2 \mid X_4 \}$. Clearly $D_{sep}(G_1) = \{X_1 ~\mbox{d-sep} ~X_3 \mid X_2; ~X_2 ~\mbox{d-sep} ~X_4 \mid X_1, X_3\}$, therefore $(G_1, \mathbb{P})$ satisfies the CMC. It can be shown that no graph entails any subset containing two or three of these d-separation rules other than $G_1$. Hence no graph follows the CFC with respect to $\mathbb{P}$ since there is no graph that entails all three d-separation rules and $(G_1, \mathbb{P})$ satisfies the MDR assumption because no graph entails more or as many d-separation rules as $G_1$ entails, and satisfies the CMC with respect to $\mathbb{P}$. - Note that $G_2$ entails the sole d-separation rule, $D_{sep}(G_2) = \{X_1~\mbox{d-sep}~X_2 \mid X_4\}$ and it is clear that $(G_2, \mathbb{P})$ satisfies the CMC. If $(G_2, \mathbb{P})$ does not satisfy the P-minimality assumption, there exists a graph $G$ such that $(G,\mathbb{P})$ satisfies the CMC and $D_{sep}(G_2) \subsetneq D_{sep}(G)$. It can be shown that no such graph exists. Therefore, $(G_2, \mathbb{P})$ satisfies the P-minimality assumption. Clearly, $(G_2, \mathbb{P})$ fails to satisfy the [MDR]{} assumption because $G_1$ entails more d-separation rules. \(A) at (0,0) [$X_1$]{}; (B) at (2,0) [$X_2$]{}; (C) at (2,-1.5) [$X_3$]{}; (D) at (0,-1.5) [$X_4$]{}; (G1) at(1, -2.5) [$G_1$]{}; \(A) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (B); (B) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (C); (C) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (D); (A) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (D); (A2) at (5,0) [$X_1$]{}; (B2) at (7,0) [$X_2$]{}; (C2) at (7,-1.5) [$X_3$]{}; (D2) at (5,-1.5) [$X_4$]{}; (G1) at(6, -2.5) [$G_2$]{}; (A2) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (C2); (B2) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (D2); (B2) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (C2); (D2) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (C2); (D2) edge \[shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (A2); Theorem \[Thm:Sec4a\] (a) asserts that whenever the set of DCG models satisfying the CFC is not empty, it is equivalent to the set of DCG models satisfying the [MDR]{} assumption. Part (b) claims that there exists a distribution in which no DCG model satisfies the CFC, while the set of DCG models satisfying the [MDR]{} assumption consists of its [MEC]{}. Hence, (a) and (b) show that the [MDR]{} assumption is strictly superior to the CFC in terms of recovering the true [MEC]{}. Theorem \[Thm:Sec4a\] (c) claims that any DCG models satisfying the [MDR]{} assumption should lie in the set of DCG models satisfying the P-minimality assumption. (d) asserts that there exist DCG models satisfying the P-minimality assumption but violating the [MDR]{} assumption. Therefore, (c) and (d) prove that the [MDR]{} assumption is strictly stronger than the P-minimality assumption. Comparison between the [MDR]{} and [SMR]{} assumptions {#SubSecMDRSMR} ------------------------------------------------------ Now we show that the [MDR]{} assumption is neither weaker nor stronger than the [SMR]{} assumptions for both DAG and DCG models. \[Lem:Sec4a\] - There exists a DAG model satisfying the identifiable [SMR]{} assumption that does not satisfy the [MDR]{} assumption. Further, there exists a DAG model satisfying the [MDR]{} assumption that does not satisfy the weak [SMR]{} assumption. - There exists a DCG model that is not a DAG that satisfies the same conclusion as (a). Our proof for Lemma \[Lem:Sec4a\] involves us constructing two sets of examples, one for DAGs corresponding to (a) and one for cyclic graphs corresponding to (b). For (a), Figure $\ref{fig:Sec4c}$ displays two DAGs, $G_1$ and $G_2$ which are clearly not in the same [MEC]{}. For clarity, we use red arrows to represent the edges/directions that are different between the graphs. We associate the same distribution $\mathbb{P}$ to each DAG where $CI(\mathbb{P})$ is provided in Appendix \[Proof:lemma(a)\]. With this $CI(\mathbb{P})$, both $(G_1, \mathbb{P})$ and $(G_2, \mathbb{P})$ satisfy the CMC (explained in Appendix \[Proof:lemma(a)\]). The main point of this example is that $(G_2,\mathbb{P})$ satisfies the identifiable and weak [SMR]{} assumptions whereas $(G_1,\mathbb{P})$ satisfies the [MDR]{} assumption, and therefore two different graphs are determined depending on the given identifiability assumption with respect to the same $\mathbb{P}$. A more detailed proof that $(G_1, \mathbb{P})$ satisfies the [MDR]{} assumption whereas $(G_2,\mathbb{P})$ satisfies the [SMR]{} assumption is provided in Appendix \[Proof:lemma(a)\]. (Y1) at (0,0) [$X_1$]{}; (Y2) at (2,1.7) [$X_2$]{}; (Y3) at (2,0) [$X_3$]{}; (Y4) at (2,-1.7) [$X_4$]{}; (Y5) at (4,0) [$X_5$]{}; (Y12) at (2,-2.7) [$G_1$]{}; (Y1) edge \[right =-35\] node\[above\] [ ]{} (Y3); (Y2) edge \[bend right = 30, color = red\] node\[above\] [ ]{} (Y1); (Y2) edge \[bend right =-35\] node\[above\] [ ]{} (Y4); (Y2) edge \[bend right = -30\] node\[above\] [ ]{} (Y5); (Y4) edge \[bend right = 30 \] node\[above\] [ ]{} (Y5); (Y5) edge \[bend right =35, color = red\] node\[above\] [ ]{} (Y1); (Y5) edge \[right =35\] node\[above\] [ ]{} (Y3); (X1) at (7,0) [$X_1$]{}; (X2) at (9,1.7) [$X_2$]{}; (X3) at (9,0) [$X_3$]{}; (X4) at (9,-1.7) [$X_4$]{}; (X5) at (11,0) [$X_5$]{}; (X12) at (9,-2.7) [$G_2$]{}; (X1) edge \[bend right =-30, color = red\] node\[above\] [ ]{} (X2); (X1) edge \[right =25\] node\[above\] [ ]{} (X3); (X4) edge \[bend right =-30, color = red\] node\[above\] [ ]{} (X1); (X2) edge \[bend right =-30\] node\[above\] [ ]{} (X5); (X5) edge \[right =25\] node\[above\] [ ]{} (X3); (X4) edge \[bend right =30\] node\[above\] [ ]{} (X5); (Z1) at (0, 0) [$X_1$]{}; (Z2) at (3, 3) [$X_2$]{}; (Z3) at (3, 0) [$X_3$]{}; (Z4) at (3, -3) [$X_4$]{}; (Z5) at (6, 0) [$X_5$]{}; (Z6) at (1.5, 1.5) [$X_6$]{}; (Z7) at (3, 1.5) [$X_7$]{}; (Z8) at (4.5, 1.5) [$X_8$]{}; (Z9) at (1.5,-1.5) [$X_9$]{}; (Z10) at (3, -1.5) [$X_{10}$]{}; (Z11) at (4.5,-1.5) [$X_{11}$]{}; (K1) at (1.7, 4.2) [$~Y~$]{} ; (Z12) at (3,-4) [$G_1$]{}; (Z1) edge \[bend right=-35\] node\[above\] [ ]{} (Z2); (Z3) edge \[right=25, color =red\] node\[above\] [ ]{} (Z1); (Z1) edge \[ bend right= 35\] node\[above\] [ ]{} (Z4); (Z2) edge \[bend right= -35\] node\[above\] [ ]{} (Z5); (Z5) edge \[right=25, color = red\] node\[above\] [ ]{} (Z3); (Z4) edge \[bend right=35\] node\[above\] [ ]{} (Z5); (Z2) edge \[right=25\] node\[above\] [ ]{} (Z6); (Z2) edge \[right=25\] node\[above\] [ ]{} (Z7); (Z2) edge \[right=25\] node\[above\] [ ]{} (Z8); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z6); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z7); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z8); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z9); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z10); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z11); (Z4) edge \[right=25\] node\[above\] [ ]{} (Z9); (Z4) edge \[right=25\] node\[above\] [ ]{} (Z10); (Z4) edge \[right=25\] node\[above\] [ ]{} (Z11); (Z2) edge \[-, dotted, color =red, thick, bend right=25\] node\[above\] [ ]{} (Z4); (Z2) edge \[-, dotted, color =red, thick, bend right=10\] node\[above\] [ ]{} (K1); (K1) edge \[-, dotted, color =red, thick, bend right=25\] node\[above\] [ ]{} (Z4); (Z1) edge \[bend right=-25\] node\[above\] [ ]{} (K1); (K1) edge \[bend right=-45\] node\[above\] [ ]{} (Z5); (K2) at (10.7, 4.2) [$~Y~$]{} ; (Y1) at (9,0) [$X_1$]{}; (Y2) at (12,3) [$X_2$]{}; (Y3) at (12,0) [$X_3$]{}; (Y4) at (12,-3) [$X_4$]{}; (Y5) at (15,0) [$X_5$]{}; (Y6) at (10.5,1.5) [$X_6$]{}; (Y7) at (12,1.5) [$X_7$]{}; (Y8) at (13.5,1.5) [$X_8$]{}; (Y9) at (10.5,-1.5) [$X_9$]{}; (Y10) at (12,-1.5) [$X_{10}$]{}; (Y11) at (13.5,-1.5) [$X_{11}$]{}; (Y12) at (12,-4) [$G_2$]{}; (Y1) edge \[bend right=-35\] node\[above left\] [ ]{} (Y2); (Y1) edge \[right=25\] node\[above\] [ ]{} (Y3); (Y1) edge \[bend right=35\] node\[below left\] [ ]{} (Y4); (Y2) edge \[bend right=-35\] node\[above right\] [ ]{} (Y5); (Y5) edge \[right=25, color = red\] node\[above\] [ ]{} (Y3); (Y4) edge \[bend right=35\] node\[below right\] [ ]{} (Y5); (Y2) edge \[right=25\] node\[above\] [ ]{} (Y6); (Y2) edge \[right=25\] node\[above\] [ ]{} (Y7); (Y2) edge \[right=25\] node\[above\] [ ]{} (Y8); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y6); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y7); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y8); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y9); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y10); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y11); (Y4) edge \[right=25\] node\[above\] [ ]{} (Y9); (Y4) edge \[right=25\] node\[above\] [ ]{} (Y10); (Y4) edge \[right=25\] node\[above\] [ ]{} (Y11); (Y1) edge \[bend right= 25, color = red\] node\[ above left \] [ ]{} (Y5); (Y1) edge \[bend right=-25\] node\[above\] [ ]{} (K2); (K2) edge \[bend right=-45\] node\[above\] [ ]{} (Y5); For (b), Figure \[fig:Sec4d\] displays two DCGs $G_1$ and $G_2$ which do not belong to the same [MEC]{}. Once again red arrows are used to denote the edges (both real and virtual) that are different between the graphs. We associate the same distribution $\mathbb{P}$ with conditional independent statements $CI(\mathbb{P})$ (provided in Appendix \[Proof:lemma(b)\]) to each graph such that both $(G_1,\mathbb{P})$ and $(G_2,\mathbb{P})$ satisfy the CMC (explained in Appendix \[Proof:lemma(b)\]). Again, the main idea of this example is that $(G_1,\mathbb{P})$ satisfies the [MDR]{} assumption whereas $(G_2,\mathbb{P})$ satisfies the identifiable [SMR]{} assumption. A detailed proof that $(G_1, \mathbb{P})$ satisfies the [MDR]{} assumption whereas $(G_2,\mathbb{P})$ satisfies the identifiable [SMR]{} assumption can be found in Appendix \[Proof:lemma(b)\]. Intuitively, the reason why fewer edges does not necessarily translate to entailing more d-separation rules is that the placement of edges relative to the rest of the graph and what additional paths they allow affects the total number of d-separation rules entailed by the graph. In summary, the flow chart in Figure \[Flowchart\] shows how the CFC, SMR, MDR and minimality assumptions are related for both DAG and DCG models: \[-latex ,node distance = 2 cm and 3cm ,on grid , state/.style =[ rectangle, rounded corners, top color =white , bottom color=blue!20 , thick, text centered,text width= 1.7cm, minimum height=10mm, draw, black , text=black , minimum width =1 cm]{}, state2/.style =[ rectangle, rounded corners, top color =white , bottom color=white , dotted, thick, text centered,text width= 2.0cm, minimum height=10mm, draw, white , text=black , minimum width =1 cm]{}, state3/.style =[ rectangle, rounded corners, top color =white , bottom color=blue!20 , thick, text centered,text width= 1.7cm, minimum height=15mm, draw, black , text=black , minimum width =1 cm]{}, state4/.style =[ minimum height= 2mm, minimum width = 2mm]{}, state5/.style =[ rectangle, rounded corners, top color =white , bottom color=white , thick, text centered,text width= 2.6cm, minimum height=15mm, draw, black , text=black , minimum width =2.6cm]{}, state6/.style =[ rectangle, rounded corners, top color =white , bottom color=blue!20 , thick, text centered,text width= 1.6cm, minimum height=15mm, draw, black , text=black , minimum width =1.6cm]{}, state7/.style =[ rectangle, rounded corners, top color =white , bottom color=blue!20 , thick, text centered,text width= 1.0cm, minimum height=15mm, draw, black , text=black , minimum width =1.0cm]{}, label/.style=[thick, minimum size= 2mm]{} \] (A) at (0,10) [CFC]{}; (B) at (-2.2,7.7) [MDR]{}; (Z) at (2.2,7.7) [SMR]{}; (D) at (-2.2,5.4) [P-min]{}; (E) at ( 2.2,5.4) [SGS-min]{}; (G) at (0,4.2) [Directed Acyclic Graph (DAG)]{}; (An1) at (-1.2,10) ; (An2) at ( 1.2,10) ; (An3) at (-2.2,8.5) ; (An4) at ( 2.2,8.5) ; (An1) edge \[bend right =30\] node\[above left\] [Thm \[Thm:Sec4a\] (a) ]{} (An3); (An2) edge \[bend left =30\] node\[above right\] [Thm \[Thm:Sec2b\] ]{} (An4); \(B) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[left\] [Thm \[Thm:Sec4a\] (c) ]{} (D); (B) to node\[below\] [Lem \[Lem:Sec4a\] (a) ]{} (Z); (Z) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[below right\] [Thm \[Thm:Sec2a\] ]{} (D); (D) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[below\] [Thm \[Thm:Sec2a\] ]{} (E); (Z) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[below\] [ ]{} (E); (A2) at (7.9, 10) [CFC]{}; (B2) at (5.4, 7.7) [MDR]{}; (Z2) at (10.1,7.7) ; (C2) at (9.45,7.7) [Identifiable SMR ]{}; (K2) at (11.00,7.7) [Weak SMR]{}; (D2) at (5.4, 5.4) [P-min]{}; (E2) at (10.1, 5.4) [SGS-min]{}; (G) at (7.9, 4.2) [Directed Cyclic Graph (DCG)]{}; (Bn1) at ( 6.9,9.9) ; (Bn2) at ( 9.0,10) ; (Bn3) at ( 5.5,8.5) ; (Bn4) at ( 9.7 ,8.5) ; (Bn9) at ( 11.30,8.5) ; (Bn10)at ( 9.70,6.9) ; (Bn1) edge \[bend right =35\] node\[above left\] [ Thm \[Thm:Sec4a\] (a) ]{} (Bn3); (Bn2) edge \[bend left =10, shorten &gt;= 3pt\] node\[below left\] [ Thm \[Thm:Sec3a\] (d) ]{} (C2); (Bn2) edge \[bend right =-35\] node\[auto\] [ Thm \[Thm:Sec3a\] (a) ]{} (K2); (B2) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[left\] [Thm \[Thm:Sec4a\] (c) ]{} (D2); (B2) to node\[below \] [ Lem \[Lem:Sec4a\] (b) ]{} (C2); (D2) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[below\] [Thm \[Thm:Sec2a\] ]{} (E2); (C2) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[below right\] [Thm \[Thm:Sec3a\] (c) ]{} (D2); (Z2) edge \[shorten &lt;= 2pt, shorten &gt;= 2pt\] node\[below right\] [ ]{} (E2); ; Simulation results {#SecSimulation} ================== In Sections \[SecSMRFrugality\] and \[SecMaxDSep\], we proved that the [MDR]{} assumption is strictly weaker than the CFC and stronger than the P-minimality assumption for both DAG and DCG models, and the identifiable [SMR]{} assumption is stronger than the P-minimality assumption for DCG models. In this section, we support our theoretical results with numerical experiments on small-scale Gaussian linear DCG models (see e.g., [@Spirtes1995]) using the generic Algorithm \[algorithm\]. We also provide a comparison of Algorithm \[algorithm\] to state-of-the-art algorithms for small-scale DCG models in terms of recovering the skeleton of a DCG model. Step 1: Find all conditional independence statements $\widehat{CI}(\mathbb{P})$ using a conditional independence test Step 2: Find the set of graphs $\widehat{\mathcal{G}}$ satisfying the given identifiability assumption $\widehat{\mathcal{M}}(G) \gets \emptyset$ $\widehat{S}(G) \gets \emptyset$ DCG model and simulation setup ------------------------------ Our simulation study involves simulating DCG models from $p$-node random Gaussian linear DCG models where the distribution $\mathbb{P}$ is defined by the following linear structural equations: $$\label{eq:GGM} (X_1,X_2,\cdots,X_p)^T = B^T (X_1,X_2,\cdots,X_p)^T + \epsilon$$ where $B \in \mathbb{R}^{p \times p}$ is an edge weight matrix with $B_{jk} = \beta_{jk}$ and $\beta_{jk}$ is a weight of an edge from $X_j$ to $X_k$. Furthermore, $\epsilon \sim \mathcal{N}(\mathbf{0}_{p}, I_p)$ where $\mathbf{0}_{p} = (0,0,\cdots,0)^T \in \mathbb{R}^{p}$ and $I_p \in \mathbb{R}^{p \times p}$ is the identity matrix. The matrix $B$ encodes the DCG structure since if $\beta_{jk}$ is non-zero, $X_j \to X_k$ and the pair $(X_j, X_k)$ is *really adjacent*, otherwise there is no directed edge from $X_j$ to $X_k$. In addition if there is a set of nodes $S = (s_1, s_2,\cdots,s_t)$ such that the product of $\beta_{j s_1}, \beta_{k s_1}, \beta_{s_1 s_2}, \cdots, \beta_{s_t j}$ is non-zero, the pair $(X_j, X_k)$ is *virtually adjacent*. Note that if the graph is a DAG, we would need to impose the constraint that $B$ is upper triangular; however for DCGs we impose no such constraints. We present simulation results for two sets of models, DCG models where edges and directions are determined randomly, and DCG models whose edges have a specific graph structure. For the set of random DCG models, the simulation was conducted using $100$ realizations of 5-node random Gaussian linear DCG models  where we impose sparsity by assigning a probability that each entry of the matrix $B$ is non-zero and we set the expected neighborhood size range from $1$ (sparse graph) to $4$ (fully connected graph) depending on the non-zero edge weight probability. Furthermore the non-zero edge weight parameters were chosen uniformly at random from the range $\beta_{jk} \in [-1, -0.25] \cup [0.25, 1]$ which ensures the edge weights are bounded away from $0$. We also ran simulations using $100$ realizations of a 5-node Gaussian linear DCG models  with specific graph structures, namely trees, bipartite graphs, and cycles. Figure \[fig:Sec5g\] shows examples of skeletons of these special graphs. We generate these graphs as follows: First, we set the skeleton for our desired graph based on Figure. \[fig:Sec5g\] and then determine the non-zero edge weights which are chosen uniformly at random from the range $\beta_{jk} \in [-1, -0.25] \cup [0.25, 1]$. Second, we repeatedly assign a randomly chosen direction to each edge until every graph has at least one possible directed cycle. Therefore, the bipartite graphs always have at least one directed cycle. However, tree graphs have no cycles because they have no cycles in the skeleton. For cycle graphs, we fix the directions of edges to have a directed cycle $X_1 \to X_2 \to \cdots \to X_5 \to X_1$. \(A) at (0,0) [$X_1$]{}; (B) at (1.5, 1) [$X_2$]{}; (C) at (1.5,-1) [$X_3$]{}; (D) at (3, 2) [$X_4$]{}; (E) at (3, 0) [$X_5$]{}; (G1) at(1.5,-2) [Tree (1)]{}; \(A) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (B); (A) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (C); (B) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (D); (B) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (E); \(A) at (5.7, 0.5) [$X_1$]{}; (B) at (4.2, 0.5) [$X_2$]{}; (C) at (7.2, 0.5) [$X_3$]{}; (D) at (5.7, 2.0) [$X_4$]{}; (E) at (5.7, -1.0) [$X_5$]{}; (G1) at(5.7, -2.0) [Tree (2)]{}; \(A) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (B); (A) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (C); (A) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (D); (A) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (E); (A2) at (8.7,0.5) [$X_1$]{}; (B2) at (10.2, 2) [$X_2$]{}; (C2) at (10.2, 0.5) [$X_3$]{}; (D2) at (10.2,-1) [$X_4$]{}; (E2) at (11.7, 0.5) [$X_5$]{}; (G1) at (10.2, -2) [Bipartite]{}; (A2) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (B2); (A2) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (C2); (A2) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (D2); (B2) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (E2); (C2) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (E2); (D2) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (E2); \(A) at (13.0, 1.0) [$X_1$]{}; (B) at (14.4, 2.0) [$X_2$]{}; (C) at (15.5, 0.5) [$X_3$]{}; (D) at (14.7,-1.0) [$X_4$]{}; (E) at (13.0,-0.5) [$X_5$]{}; (G1) at(14.2, -2.0) [Cycle]{}; \(A) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (B); (B) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above\] [ ]{} (C); (C) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (D); (D) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (E); (E) edge \[-, shorten &lt;= 1pt, shorten &gt;= 1pt\] node\[above \][ ]{} (A); Comparison of assumptions ------------------------- In this section we provide a simulation comparison between the SMR, MDR, CFC and minimality assumptions. The CI statements were estimated based on $n$ independent samples drawn from $\mathbb{P}$ using Fisher’s conditional correlation test with significance level $\alpha = 0.001$. We detected all directed graphs satisfying the CMC and we measured what proportion of graphs in the simulation satisfy each assumption (CFC, [MDR]{}, identifiable [SMR]{}, P-minimality). In Figures \[fig:Sec5a\], \[fig:Sec5b\] and \[fig:Sec5e\], we simulated how restrictive each identifiability assumption (CFC, [MDR]{}, identifiable [SMR]{}, P-minimality) is for random DCG models and specific graph structures with sample sizes $n \in \{100, 200, 500, 1000\}$ and expected neighborhood sizes from $1$ (sparse graph) to $4$ (fully connected graph). As shown in Figures \[fig:Sec5b\] and \[fig:Sec5e\], the proportion of graphs satisfying each assumption increases as sample size increases because of fewer errors in CI tests. Furthermore, there are more DCG models satisfying the [MDR]{} assumption than the CFC and less DCG models satisfying the [MDR]{} assumption than the P-minimality assumption for all sample sizes and different expected neighborhood sizes. We can also see similar relationships between the CFC, identifiable [SMR]{} and P-minimality assumptions. The simulation study supports our theoretical result that the [MDR]{} assumption is weaker than the CFC but stronger than the P-minimality assumption, and the identifiable [SMR]{} assumption is stronger than the P-minimality assumption. Although there are no theoretical guarantees that the identifiable [SMR]{} assumption is stronger than the [MDR]{} assumption and weaker than the CFC, Figures \[fig:Sec5a\] and \[fig:Sec5b\] represent that the identifiable [SMR]{} assumption is substantially stronger than the [MDR]{} assumption and weaker than the CFC on average. [.30]{} [.30]{} [.30]{} [.10]{} [.30]{} [.30]{} [.30]{} [.10]{} [.30]{} [.30]{} [.30]{} [.10]{} Comparison to state-of-the-art algorithms ----------------------------------------- In this section, we compare Algorithm \[algorithm\] to state-of-the-art algorithms for small-scale DCG models in terms of recovering the skeleton $S(G)$ for the graph. This addresses the issue of how likely Algorithm \[algorithm\] based on each assumption is to recover the skeleton of a graph compared to state-of-the-art algorithms. Once again we used Fisher’s conditional correlation test with significance level $\alpha = 0.001$ for Step 1) of Algorithm \[algorithm\], and we used the MDR and identifiable [SMR]{} assumptions for Step 2). For comparison algorithms, we used the state-of-the-art GES algorithm [@chickering2002finding] and the FCI$+$ algorithms [@claassen2013learning] for small-scale DCG models. We used the R package ’pcalg’ [@Kalisch2012] for the FCI$+$ algorithm, and ’bnlearn’ [@scutari2009learning] for the GES algorithm. [.30]{} [.30]{} [.30]{} [.10]{} [.30]{} [.30]{} [.30]{} [.10]{} Figures \[fig:Sec5c\] and \[fig:Sec5d\] show recovery rates of skeletons for random DCG models with sample sizes $n \in \{100, 200, 500, 1000\}$ and expected neighborhood sizes from $1$ (sparse graph) to $4$ (fully connected graph). Our simulation results show that the accuracy increases as sample size increases because of fewer errors in CI tests. Algorithms \[algorithm\] based on the [MDR]{} and identifiable [SMR]{} assumptions outperforms the FCI$+$ algorithm on average. For dense graphs, we see that the GES algorithm out-performs other algorithms because the GES algorithm often prefers dense graphs. However, the GES algorithm is not theoretically consistent and cannot recover directed graphs with cycles while other algorithms are designed for recovering DCG models (see e.g., Figure \[fig:Sec5f\]). [.30]{} [.30]{} [.30]{} [.10]{} Figure \[fig:Sec5f\] shows the accuracy for each type of graph (Tree, Cycle, Bipartite) using Algorithms \[algorithm\] based on the [MDR]{} and identifiable [SMR]{} assumptions and the GES and the FCI$+$ algorithms. Simulation results show that Algorithms \[algorithm\] based on the [MDR]{} and identifiable [SMR]{} assumptions are favorable in comparison to the FCI+ and GES algorithms for small-scale DCG models. Acknowledgement {#acknowledgement .unnumbered} =============== GP and GR were both supported by NSF DMS-1407028 over the duration of this project. Appendix ======== Examples for Theorem \[Thm:Sec3a\] (d) {#examples-for-theoremthmsec3a-d .unnumbered} -------------------------------------- \(A) at(0,0) [$X_1$]{}; (B) at(2.0,0) [$X_2$]{}; (C) at(4, 0) [$X_3$]{}; (D) at(6,0) [$X_4$]{}; (E) at(4,2) [$X_5$]{}; (G1) at(4, -1.2) [$G_1$]{}; (A2) at(8,0) [$X_1$]{}; (B2) at(10,0) [$X_2$]{}; (C2) at(12,0) [$X_3$]{}; (D2) at(14,0) [$X_4$]{}; (E2) at(12,2) [$X_5$]{}; (G1) at(12, -1.2) [$G_2$]{}; \(A) edge \[right=25\] node\[above\] [ $\alpha_1$ ]{} (B); (B) edge \[bend left =25\] node\[below\] [ $\alpha_3$ ]{} (C); (C) edge \[bend left =25\] node\[below\] [ $\alpha_5$ ]{} (B); (D) edge \[left =25\] node\[above\] [ $\alpha_4$ ]{} (C); (B) edge \[left =25\] node\[above left\] [ $-\alpha_3 \alpha_7$ ]{} (E); (C) edge \[left =25\] node\[left\] [ $\alpha_7$ ]{} (E); (E) edge \[left =25, color= red\] node\[above right\] [ $\alpha_2$]{} (D); (A2) edge \[right=25\] node\[above\] [ ]{} (B2); (B2) edge \[bend left =25\] node\[below\] [ ]{} (C2); (C2) edge \[bend left =25\] node\[below\] [ ]{} (B2); (D2) edge \[left =25\] node\[above\] [ ]{} (C2); (B2) edge \[left =25\] node\[above left\] [ ]{} (E2); (C2) edge \[left =25\] node\[left\] [ ]{} (E2); (D2) edge \[left =25, color= red\] node\[above right\] [ ]{} (E2); Suppose that $(G_1,\mathbb{P})$ is a Gaussian linear DCG model with specified edge weights in Figure \[Fig:App2\]. With this choice of distribution $\mathbb{P}$ based on $G_1$ in Figure \[Fig:App2\], we have a set of CI statements which are the same as the set of d-separation rules entailed by $G_1$ and an additional set of CI statements, $CI(\mathbb{P}) \supset \{ X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_4 |~ \emptyset \textrm{, or } X_5,~ X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_5 |~ \emptyset \textrm{, or } X_4\}$. It is clear that $(G_2, \mathbb{P})$ satisfies the CMC, $D_{sep}(G_1) \subset D_{sep}(G_2)$ and $D_{sep}(G_1) \neq D_{sep}(G_2)$ (explained in Section \[SecSMRFrugality\]). This implies that $(G_1, \mathbb{P})$ fails to satisfy the P-minimality assumption. Now we prove that $(G_1, \mathbb{P})$ satisfies the weak [SMR]{} assumption. Suppose that $(G_1, \mathbb{P})$ does not satisfy the weak [SMR]{} assumption. Then there exists a $G$ such that $(G,\mathbb{P})$ satisfies the CMC and has fewer edges than $G_1$. By Lemma \[Lem:Sec3b\], if $(G, \mathbb{P})$ satisfies the CFC, $G$ satisfies the weak [SMR]{} assumption. Note that $G_1$ does not have edges between $(X_1, X_4)$ and $(X_1, X_5)$. Since the only additional conditional independence statements that are not entailed by $G_1$ are $\{ X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_4 |~ \emptyset \textrm{, or } X_5,~ X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_5 |~ \emptyset \textrm{, or } X_4\}$, no graph that satisfies the CMC with respect to $\mathbb{P}$ can have fewer edges than $G_1$. This leads to a contradiction and hence $(G_1, \mathbb{P})$ satisfies the weak [SMR]{} assumption. Proof of Lemma \[Lem:Sec4a\] (a) {#Proof:lemma(a)} --------------------------------- (Y1) at (0,0) [$X_1$]{}; (Y2) at (2,1.7) [$X_2$]{}; (Y3) at (2,0) [$X_3$]{}; (Y4) at (2,-1.7) [$X_4$]{}; (Y5) at (4,0) [$X_5$]{}; (Y12) at (2,-2.7) [$G_1$]{}; (Y1) edge \[right =-35\] node\[above\] [ ]{} (Y3); (Y2) edge \[bend right = 30, color = red\] node\[above\] [ ]{} (Y1); (Y2) edge \[bend right =-35\] node\[above\] [ ]{} (Y4); (Y2) edge \[bend right = -30\] node\[above\] [ ]{} (Y5); (Y4) edge \[bend right = 30 \] node\[above\] [ ]{} (Y5); (Y5) edge \[bend right =35, color = red\] node\[above\] [ ]{} (Y1); (Y5) edge \[right =35\] node\[above\] [ ]{} (Y3); (X1) at (7,0) [$X_1$]{}; (X2) at (9,1.7) [$X_2$]{}; (X3) at (9,0) [$X_3$]{}; (X4) at (9,-1.7) [$X_4$]{}; (X5) at (11,0) [$X_5$]{}; (X12) at (9,-2.7) [$G_2$]{}; (X1) edge \[bend right =-30, color = red\] node\[above\] [ ]{} (X2); (X1) edge \[right =25\] node\[above\] [ ]{} (X3); (X4) edge \[bend right =-30, color = red\] node\[above\] [ ]{} (X1); (X2) edge \[bend right =-30\] node\[above\] [ ]{} (X5); (X5) edge \[right =25\] node\[above\] [ ]{} (X3); (X4) edge \[bend right =30\] node\[above\] [ ]{} (X5); Here we show that $(G_1,\mathbb{P})$ satisfies the identifiable SMR assumption and and $(G_2,\mathbb{P})$ satisfies the MDR assumption, where $\mathbb{P}$ has the following CI statements: $$\begin{aligned} CI(\mathbb{P}) = \{ & X_2 {\protect\mathpalette{\protect\independenT}{\perp}}X_3 \mid (X_1, X_5) \textrm{ or } (X_1, X_4, X_5); X_2 {\protect\mathpalette{\protect\independenT}{\perp}}X_4 \mid X_1; \\ & X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_4 \mid (X_2, X_5) \textrm{ or } (X_2, X_3, X_5); X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_5 \mid (X_2, X_4); \\ & X_3 {\protect\mathpalette{\protect\independenT}{\perp}}X_4 \mid (X_1, X_5), (X_2, X_5),\textrm{ or } (X_1, X_2, X_5) \}.\end{aligned}$$ Clearly both DAGs $G_1$ and $G_2$ do not belong to the same [MEC]{} since they have different skeletons. To be explicit, we state all d-separation rules entailed by $G_1$ and $G_2$. Both graphs entail the following sets of d-separation rules: - $X_2$ is d-separated from $X_3$ given $(X_1, X_5)$ or $(X_1, X_4, X_5)$. - $X_3$ is d-separated from $X_4$ given $(X_1, X_5)$ or $(X_1, X_2, X_5)$. The set of d-separation rules entailed by $G_1$ which are not entailed by $G_2$ is as follows: - $X_1$ is d-separated from $X_4$ given $(X_2, X_5)$ or $(X_2, X_4, X_5)$. - $X_3$ is d-separated from $X_4$ given $(X_2, X_5)$. Furthermore, the set of d-separation rules entailed by $G_2$ which are not entailed by $G_1$ is as follows: - $X_1$ is d-separated from $X_5$ given $(X_2, X_4)$. - $X_2$ is d-separated from $X_4$ given $X_1$. With our choice of distribution, both DAG models $(G_1, \mathbb{P})$ and $(G_2, \mathbb{P})$ satisfy the CMC and it is straightforward to see that $G_2$ has fewer edges than $G_1$ while $G_1$ entails more d-separation rules than $G_2$. It can be shown from an exhaustive search that there is no graph $G$ such that $G$ is sparser or as sparse as $G_2$ and $(G, \mathbb{P})$ satisfies the CMC. Moreover, it can be shown that $G_1$ entails the maximum d-separation rules amongst graphs satisfying the CMC with respect to the distribution again through an exhaustive search. Therefore $(G_1, \mathbb{P})$ satisfies the [MDR]{} assumption and $(G_2, \mathbb{P})$ satisfies the identifiable [SMR]{} assumption. Proof of Lemma \[Lem:Sec4a\] (b) {#Proof:lemma(b)} --------------------------------- (Z1) at (0, 0) [$X_1$]{}; (Z2) at (3, 3) [$X_2$]{}; (Z3) at (3, 0) [$X_3$]{}; (Z4) at (3, -3) [$X_4$]{}; (Z5) at (6, 0) [$X_5$]{}; (Z6) at (1.5, 1.5) [$X_6$]{}; (Z7) at (3, 1.5) [$X_7$]{}; (Z8) at (4.5, 1.5) [$X_8$]{}; (Z9) at (1.5,-1.5) [$X_9$]{}; (Z10) at (3, -1.5) [$X_{10}$]{}; (Z11) at (4.5,-1.5) [$X_{11}$]{}; (K1) at (1.7, 4.2) [$~Y~$]{} ; (Z12) at (3,-4) [$G_1$]{}; (Z1) edge \[bend right=-35\] node\[above\] [ ]{} (Z2); (Z3) edge \[right=25, color =red\] node\[above\] [ ]{} (Z1); (Z1) edge \[ bend right= 35\] node\[above\] [ ]{} (Z4); (Z2) edge \[bend right= -35\] node\[above\] [ ]{} (Z5); (Z5) edge \[right=25, color = red\] node\[above\] [ ]{} (Z3); (Z4) edge \[bend right=35\] node\[above\] [ ]{} (Z5); (Z2) edge \[right=25\] node\[above\] [ ]{} (Z6); (Z2) edge \[right=25\] node\[above\] [ ]{} (Z7); (Z2) edge \[right=25\] node\[above\] [ ]{} (Z8); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z6); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z7); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z8); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z9); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z10); (Z3) edge \[right=25\] node\[above\] [ ]{} (Z11); (Z4) edge \[right=25\] node\[above\] [ ]{} (Z9); (Z4) edge \[right=25\] node\[above\] [ ]{} (Z10); (Z4) edge \[right=25\] node\[above\] [ ]{} (Z11); (Z2) edge \[-, dotted, color =red, thick, bend right=25\] node\[above\] [ ]{} (Z4); (Z2) edge \[-, dotted, color =red, thick, bend right=10\] node\[above\] [ ]{} (K1); (K1) edge \[-, dotted, color =red, thick, bend right=25\] node\[above\] [ ]{} (Z4); (Z1) edge \[bend right=-25\] node\[above\] [ ]{} (K1); (K1) edge \[bend right=-45\] node\[above\] [ ]{} (Z5); (K2) at (10.7, 4.2) [$~Y~$]{} ; (Y1) at (9,0) [$X_1$]{}; (Y2) at (12,3) [$X_2$]{}; (Y3) at (12,0) [$X_3$]{}; (Y4) at (12,-3) [$X_4$]{}; (Y5) at (15,0) [$X_5$]{}; (Y6) at (10.5,1.5) [$X_6$]{}; (Y7) at (12,1.5) [$X_7$]{}; (Y8) at (13.5,1.5) [$X_8$]{}; (Y9) at (10.5,-1.5) [$X_9$]{}; (Y10) at (12,-1.5) [$X_{10}$]{}; (Y11) at (13.5,-1.5) [$X_{11}$]{}; (Y12) at (12,-4) [$G_2$]{}; (Y1) edge \[bend right=-35\] node\[above left\] [ ]{} (Y2); (Y1) edge \[right=25\] node\[above\] [ $\beta_1$ ]{} (Y3); (Y1) edge \[bend right=35\] node\[below left\] [ ]{} (Y4); (Y2) edge \[bend right=-35\] node\[above right\] [ ]{} (Y5); (Y5) edge \[right=25, color = red\] node\[above\] [ $\beta_2$ ]{} (Y3); (Y4) edge \[bend right=35\] node\[below right\] [ ]{} (Y5); (Y2) edge \[right=25\] node\[above\] [ ]{} (Y6); (Y2) edge \[right=25\] node\[above\] [ ]{} (Y7); (Y2) edge \[right=25\] node\[above\] [ ]{} (Y8); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y6); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y7); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y8); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y9); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y10); (Y3) edge \[right=25\] node\[above\] [ ]{} (Y11); (Y4) edge \[right=25\] node\[above\] [ ]{} (Y9); (Y4) edge \[right=25\] node\[above\] [ ]{} (Y10); (Y4) edge \[right=25\] node\[above\] [ ]{} (Y11); (Y1) edge \[bend right= 25, color = red\] node\[ above left \] [$\beta_1 \beta_2~~~~~~$ ]{} (Y5); (Y1) edge \[bend right=-25\] node\[above\] [ ]{} (K2); (K2) edge \[bend right=-45\] node\[above\] [ ]{} (Y5); Suppose that the pair $(G_2,\mathbb{P})$ is a Gaussian linear DCG model with specified edge weights in Figure \[fig:Sec4dA\], where the non-specified edge weights can be chosen arbitrarily. Once again to be explicit, we state all d-separation rules entailed by $G_1$ and $G_2$. Both graphs entail the following sets of d-separation rules: - For any node $A \in \{X_6,X_7,X_8\}$ and $B \in \{X_1,X_5\}$, $A$ is d-separated from $B$ given $\{X_2, X_3\} \cup C$ for any $C \subset \{ X_1,X_4,X_5,X_6,X_7,X_8, X_9, X_{10}, X_{11},Y \} \setminus \{A,B\}$. - For any node $A \in \{X_9,X_{10},X_{11}\}$ and $B \in \{X_1,X_5\}$, $A$ is d-separated from $B$ given $\{X_3, X_4\} \cup C$ for any $C \subset \{X_1, X_2, X_3, X_5,X_6,X_7,X_8, X_9, X_{10}$ $, X_{11},Y \} \setminus \{A,B\}$. - For any nodes $A,B \in \{X_6,X_7, X_8\}$, $A$ is d-separated from $B$ given $\{X_2,$ $X_3\} \cup C$ for any $C \subset \{X_1,X_4,X_5,X_6,X_7,X_8,X_9,X_{10},X_{11},Y \}\setminus\{A,B\}$. - For any nodes $A,B \in \{X_9,X_{10}, X_{11}\}$, $A$ is d-separated from $B$ given $\{X_3,X_4\} \cup C$ for any $C \subset \{X_1,X_2,X_5,X_6,X_7,X_8,X_9,X_{10},X_{11},Y \}\setminus\{A,B\}$. - For any nodes $A \in \{X_6,X_7, X_8\}$ and $B \in \{X_4\}$, $A$ is d-separated from $B$ given $\{X_2,X_3\} \cup C$ for any $C \subset \{X_1,X_4,X_5,X_6,X_7,X_8,X_9,X_{10},X_{11},Y \}\setminus\{A,B\}$, or given $\{X_1,X_2,X_5\} \cup D$ for any $D \subset \{X_4,X_6,X_7,X_8,Y \}\setminus\{A,B\}$. - For any nodes $A \in \{X_6, X_7, X_8\}$ and $B \in \{Y\}$, $A$ is d-separated from $B$ given $\{X_2,X_3\} \cup C$ for any $C \subset \{X_1,X_4,X_5,X_6,X_7,X_8,X_9,X_{10},X_{11},Y \}\setminus\{A,B\}$, or given $\{X_1,X_2,X_5\} \cup D$ for any $D \subset \{X_4,X_6,X_7,X_8,,X_9,X_{10}$ $,X_{11},Y \}\setminus\{A,B\}$. - For any nodes $A \in \{X_9,X_{10}, X_{11}\}$ and $B \in \{X_2\}$, $A$ is d-separated from $B$ given $\{X_3,X_4\} \cup C$ for any $C \subset \{X_1,X_2,X_5,X_9,X_{10},X_{11},Y \}\setminus\{A,B\}$, or given $\{X_1,X_4,X_5\} \cup D$ for any $D \subset \{X_2,X_9,X_{10},X_{11},Y \}\setminus\{A,B\}$. - For any nodes $A \in \{X_9,X_{10}, X_{11}\}$ and $B \in \{Y\}$, $A$ is d-separated from $B$ given $\{X_3,X_4\} \cup C$ for any $C \subset \{X_1,X_2,X_5,X_6,X_7,X_8,X_9,X_{10},X_{11},Y \}\setminus\{A,B\}$, or given $\{X_1,X_4,X_5\} \cup D$ for any $D \subset \{X_2,X_6,X_7,X_8,X_9,X_{10}$ $,X_{11},Y \}\setminus\{A,B\}$. - For any nodes $A\in \{X_6,X_7, X_8\}$, $B \in \{X_9,X_{10}, X_{11}\}$, $A$ is d-separated from $B$ given $\{X_3\} \cup C \cup D$ for $C \subset \{X_1,X_2,X_4\}$, $C \neq \emptyset$ and $D \subset \{X_1,X_2,X_4,X_5,X_6,X_7,X_8,X_9,X_{10},X_{11},Y \}\setminus\{A,B,C\}$. - $X_2$ is d-separated from $X_3$ given $\{X_1, X_5\} \cup C$ for any $C \subset \{X_1,X_4,X_5,$ $X_9,X_{10},X_{11},Y\}$. - $X_3$ is d-separated from $X_4$ given $\{X_1, X_5\} \cup C$ for any $C \subset \{X_1,X_4,X_5,X_6$ $,X_7,X_8,Y\}$. - $X_3$ is d-separated from $Y$ given $\{X_1, X_5\} \cup C$ for any $C \subset \{X_1,X_4,X_5,X_6$ $,X_7,X_8,X_9,X_{10},X_{11}\}$. - $X_2$ is d-separated from $X_3$ given $\{X_1, X_5\} \cup C$ for any $C \subset \{X_4,X_9$ $,X_{10},X_{11}, Y\}$. - $X_4$ is d-separated from $X_3$ given $\{X_1, X_5\} \cup C$ for any $C \subset \{X_2,X_6,X_7$ $,X_8, Y\}$. - $Y$ is d-separated from $X_3$ given $\{X_1, X_5\} \cup C$ for any $C \subset \{X_2,X_6,X_7,X_8$ $,X_4,X_9,X_{10},X_{11}\}$. The set of d-separation rules entailed by $G_1$ that is not entailed by $G_2$ is as follows: - $X_1$ is d-separated from $X_5$ given $\{X_2,X_3,X_4,Y\} \cup C$ for any $C \subset \{X_6,X_7$ $,X_8, X_9,X_{10},X_{11}\}$. Furthermore, the set of d-separation rules entailed by $G_2$ that is not entailed by $G_1$ is as follows: - $X_2$ is d-separated from $X_4$ given $X_1$ or $\{ X_1, Y\}$. - $X_2$ is d-separated from $Y $ given $X_1$ or $\{ X_1, X_4\}$. - $X_4$ is d-separated from $Y $ given $X_1$ or $\{ X_1, X_2\}$. It can then be shown that by using the co-efficients specified for $G_2$ in Figure \[fig:Sec4dA\], $CI(\mathbb{P})$ is the union of the CI statements implied by the sets of d-separation rules entailed by both $G_1$ and $G_2$. Therefore $(G_1,\mathbb{P})$ and $(G_2,\mathbb{P})$ satisfy the CMC. It is straightforward to see that $G_2$ is sparser than $G_1$ while $G_1$ entails more d-separation rules than $G_2$. Now we prove that $(G_1, \mathbb{P})$ satisfies the [MDR]{} assumption and $(G_2, \mathbb{P})$ satisfies the identifiable [SMR]{} assumption. First we prove that $(G_2, \mathbb{P})$ satisfies the identifiable [SMR]{} assumption. Suppose that $(G_2,\mathbb{P})$ does not satisfy the identifiable [SMR]{} assumption. Then there exists a $G$ such that $(G, \mathbb{P})$ satisfies the CMC and $G$ has the same number of edges as $G_2$ or fewer edges than $G_2$. Since the only additional CI statements that are not implied by the d-separation rules of $G_2$ are $X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_5 \mid \{X_2,X_3,X_4,Y\} \cup C$ for any $C \subset \{X_6,X_7,X_8, X_9,X_{10},X_{11}\}$ and $(G, \mathbb{P})$ satisfies the CMC, we can consider two graphs, one with an edge between $(X_1, X_5)$ and another without an edge between $(X_1, X_5)$. We firstly consider a graph without an edge between $(X_1, X_5)$. Since $G$ does not have an edge between $(X_1, X_5)$ and by Lemma \[Lem:Sec3a\], $G$ should entail at least one d-separation rule from (a) $X_1$ is d-separated from $X_5$ given $\{X_2,X_3,X_4,Y\} \cup C$ for any $C \subset \{X_6,X_7,X_8, X_9,X_{10},X_{11}\}$. If $G$ does not have an edge between $(X_2, X_3)$, by Lemma \[Lem:Sec3a\] $G$ should entail at least one d-separation rule from (10) $X_2$ is d-separated from $X_3$ given $\{X_1, X_5\} \cup C$ for any $C \subset \{X_1,X_4,X_5,X_9,X_{10},X_{11},Y\}$. These two sets of d-separation rules can exist only if a cycle $X_1 \to X_2 \to X_5 \to X_3 \to X_1$ or $X_1 \leftarrow X_2 \leftarrow X_5 \leftarrow X_3 \leftarrow X_1$ exists. In the same way, if $G$ does not have edges between $(X_3, X_4)$ and $(X_3, Y)$, there should be cycles which are $X_1 \to A \to X_5 \to X_3 \to X_1$ or $X_1 \leftarrow A \leftarrow X_5 \leftarrow X_3 \leftarrow X_1$ for any $A \in \{X_4, Y\}$ as occurs in $G_1$. However these cycles create virtual edges between $(X_2, X_4), (X_2, Y)$ or $(X_4, Y)$ as occurs in $G_1$. Therefore $G$ should have at least 3 edges either real or virtual edges. This leads to a contradiction that $G$ has the same number of edges of $G_2$ or fewer edges than $G_2$. Secondly, we consider a graph $G$ with an edge between $(X_1, X_5)$ such that $(G, \mathbb{P})$ satisfies the CMC and $G$ has fewer edges than $G_2$. Note that $G_1$ entails the maximum number of d-separation rules amongst graphs with an edge between $(X_1, X_5)$ satisfying the CMC because $CI(\mathbb{P}) \setminus \{X_1 {\protect\mathpalette{\protect\independenT}{\perp}}X_5 \mid \{X_2,X_3,X_4,Y\} \cup C$ for any $C \subset \{X_6,X_7,X_8, X_9, X_{10},X_{11}\}$ is exactly matched to the d-separation rules entailed by $G_1$. This leads to $D_{sep}(G) \subset D_{sep}(G_1)$ and $D_{sep}(G) \neq D_{sep}(G_1)$. By Lemma \[Lem:Sec3b\], $G$ cannot contain fewer edges than $G_1$. However since $G_2$ has fewer edges than $G_1$, it is contradictory that $G$ has the same number of edges of $G_2$ or fewer edges than $G_2$. Therefore, $(G_2,\mathbb{P})$ satisfies the identifiable [SMR]{} assumption. Now we prove that $(G_1, \mathbb{P})$ satisfies the [MDR]{} assumption. Suppose that $(G_1, \mathbb{P})$ fails to satisfy the [MDR]{} assumption. Then, there is a graph $G$ such that $(G, \mathbb{P})$ satisfies the CMC and $G$ entails more d-separation rules than $G_1$ or as many d-separation rules as $G_1$. Since $(G, \mathbb{P})$ satisfies the CMC, in order for $G$ to entail at least the same number of d-separation rules entailed by $G_1$, $G$ should entail at least one d-separation rule from (b) $X_2$ is d-separated from $X_4$ given $X_1$ or $\{ X_1, Y\}$, (c) $X_2$ is d-separated from $Y$ given $X_1$ or $\{ X_1, X_4\}$ and (d) $X_4$ is d-separated from $Y $ given $X_1$ or $\{ X_1, X_2\}$. This implies that $G$ does not have an edge between $(X_2, X_4)$, $(X_2, Y)$ or $(X_4, Y)$ by Lemma \[Lem:Sec3a\]. As we discussed, there is no graph satisfying the CMC without edges $(X_2, X_4)$, $(X_2, Y)$, $(X_4, Y)$, and $(X_1, X_5)$ unless $G$ has additional edges as occurs in $G_1$. Note that the graph $G$ entails at most six d-separation rules than $G_1$ (the total number of d-separation rules of (b), (c), and (d)). However, adding any edge in the graph $G$ generates more than six more d-separation rules because by Lemma \[Lem:Sec3a\], $G$ loses an entire set of d-separation rules from the sets (1) to (15) which each contain more than six d-separation rules. This leads to a contradiction that $G$ entails more d-separation rules than $G_1$ or as many d-separation rules as $G_1$.

Tea Makes Everything Better Does a hot cup of tea REALLY make everything better? There are many cute signs which promise there’s a tea for everything. Being an avid tea drinker, I understand the meaning behind the memes. The simple process of preparing tea is contemplative. You can’t rush tea. It has its own time schedule. Waiting for the boil of the water and steeping of the leaves, allows me to slow down and prepare my heart. Drinking a hot cup of tea calms my nerves, soothes my spirit, and relaxes my mind. When I’m stressed it untangles me. During times of hurt, it coats my inner pain. When my mind is so crowded I’ve left no spiritual whitespace, it erases the margins and opens up the mental page I’m thinking on. I’ve given thought to why tea makes everything better for me. I believe It positions me to slow down so I can hear God better and be stirred by His Holy Spirit. Why not take time today to indulge in a hot cuppa and spend time with The One who can make everything better? Share this: Like this: LikeLoading... Published by junesteacuptreasures It’s true! I am a Certifed Teacup Indulgent. I have multiple China cabinets stuffed strategically with all shapes and sizes. There’s always room for one more. I love visiting estate sales, well, any type of sales where teacups might lurk. It’s a treasure hunt. I’m an avid reader, author, wife, mother, grandmother, and great-grandmother. I am active in my church, a member of American Christian Writers Association, Advanced Writers and Speakers Association, and Christian Writers of Southeast San Antonio. I am a Texas transplant from Michigan, and reside in San Antonio with my husband, Nick. View all posts by junesteacuptreasures PublishedApril 16, 2019 Post navigation 4 thoughts on “Tea Makes Everything Better” Just now, the realization hit me. June Chapko’s multiple talents have been influential in my life for over 30 years. My latest cuppa of inspiration comes from her book the Estate Sale. Once I begin reading it, I was unable to put it down until I finished it. And now, I am anxiously awaiting Book 2 of this Legacy Series. I am doing some work for June, and I stumbled across her reference to an age-old British adage, “tea solves everything”. Cheryl and I know an Anglican-Catholic priest from England who told us a cup of tea is a great source of comfort.no matter the situation. “Oh, your home burned down? Have a cup of tea.” “oh, no! You were in an accident? Have a cup of tea.” He went on in this vein for many more minutes to further illustrate his point. And Cheryl has known for years the health advantages of drinking tea. So I was joyfully surprised to, * serendipity *, find both aspects of tea to be borne out to be absolutely true after researching June’s phrase, “tea solves everything”. It turns out reading June’s books are beneficial not only to your spiritual health but to your physical health as well. So live longer, healthier, leaner, and more stress-free while reducing your risk of heart problems and of certain types of cancer by drinking tea and by reading June’s books! https://www.mirror.co.uk/news/real-life-stories/a-cup-of-tea-solves-everything-505302 Thank you, Hal for such a great recommendation for my book. I do have to say…reading my book will not reduce your risk of any health problems, but it will increase your risk of wanting to read book two, Legacy’s Path, coming very soon.

202 F.2d 530 WOODWORKERS TOOL WORKSv.BYRNE. No. 13236. United States Court of Appeals Ninth Circuit. March 10, 1953. Tripp & Calloway, Los Angeles, Cal., for appellant. John W. Olson, Los Angeles, Cal., for appellee. Before STEPHENS, HEALY, and POPE, Circuit Judges. HEALY, Circuit Judge. 1 This action is for damages for personal injury sustained by appellee in consequence of the disintegration of an allegedly defective panel raiser head manufactured by appellant, an Illinois corporation, and shipped by it to appellee's employer in California, of which state appellee is a resident. A verdict awarding damages was returned and a judgment entered thereon. 2 On appeal from that judgment, Woodworkers Tool Works v. Byrne, 9 Cir., 191 F.2d 667, this court held with appellee on the merits. But a motion of appellant to quash the service of summons had been denied by the trial court, and we thought, 191 F.2d at pages 670-673, that the showing before the court at the time the motion was ruled on, going to the issue whether appellant had constituted one Preuer by law an agent in California to receive service of process on its behalf, was insufficient to warrant the denial. We noted, however, that during the course of the trial substantial oral evidence had been received tending to show the existence of the necessary agency relationship between appellant and Preuer, and we summarize this evidence, 191 F.2d at page 673; but it was further noted that the trial judge regarded the jurisdictional problem as having already been determined, hence had not taken the oral evidence into account except for such bearing as it might have on the merits. 3 We were of opinion that the issue of the validity of the service, inasmuch as it was one of due process, was open to further examination and that the evidence adduced on the trial might properly be considered as supplementing the original showing on that issue. We said, 191 F.2d at page 673, that "if there be added to the evidence which was before the court at the time of the denial of the motion to quash the service of the summons the evidence adduced at the trial, particularly that of Preuer hereinbefore referred to there might be a basis to sustain a conclusion that Woodworkers Tool Works had made Preuer its agent. This issue cannot be resolved without a finding thereon by the trier of fact and therefore upon remand it will be necessary for the court below to make an appropriate finding upon the present record." 4 After consideration and disposition of the remaining issues the court made the following order: "To the end that the court below may determine the question of whether the evidence now in the record is sufficient to sustain Byrne's contention that Woodworkers Tool Works made Woodworkers Supply Company, viz., Preuer, its agent for the service of process in California, we vacate the judgment and remand the cause with the direction to the court below to proceed to determine that issue. If the court determines the evidence of agency to be sufficient it will possess the authority to reinstate the judgment."1 5 Neither party petitioned for a rehearing. 6 Upon remand the trial court on the existing record made appropriate findings of fact as shown in the footnote,2 and concluded that at and prior to time of service appellant was doing business in California through Preuer as its agent, and had by law constituted him its agent in California to receive service of process in its behalf. The judgment was ordered reinstated. 7 From the reinstated judgment appellant has taken the present appeal, claiming that the evidence is insufficient to support the court's finding of agency. Is the point now open to inquiry? We think not. This court's original decision constitutes the law of the case. It clearly implied that on the evidence in the record the issue was one of fact for the trial court's determination, not one of law for ourselves. Had we deemed the evidence insufficient as a matter of law to support a finding of jurisdiction it would have been worse than an impertinence to remand the case for a finding. We would have been obliged to reverse the judgment outright. Nor, if we were in doubt whether on that evidence a finding of jurisdiction could be sustained by us, would we have thought it proper to undertake at that juncture the very considerable and perhaps wholly futile task of passing on the merits. Taking the opinion by its four corners we construe it as holding that the trial court's finding of fact was to be accepted as conclusive of the question of the validity of the service. 8 True, the rule we apply here is not a compulsive principle akin to res judicata. The phrase law of the case expresses rather the general practice of the courts to decline to reopen what they have already in effect decided. Messenger v. Anderson, 225 U.S. 436, 444, 32 S.Ct. 739, 56 L.Ed. 1152. Cf. People of State of Illinois ex rel. Hunt v. Illinois Central R. Co., 184 U.S. 77, 91, 22 S.Ct. 300, 46 L.Ed. 440. The rule is grounded in large part on the policy of ending litigation, and in some instances on the want of power in an appellate court to modify its own judgments otherwise than on a rehearing. And it has been pointedly observed that if the practice were not followed, changes in the personnel of the court would produce confusion. Clary v. Hoagland, 6 Cal. 685; Oakley v. Aspinwall, 13 N.Y. 500, 501. For a comprehensive statement of the doctrine and for citations of the almost numberless cases bearing on it, see 5 C.J.S., Appeal and Error, § 1821 et seq.; 21 C.J.S., Courts, § 195 et seq. 9 Application of the doctrine in this instance would result in no injustice or hardship since a trial on the merits has already been had. 10 Affirmed. Notes: 1 The formal judgment entered by our clerk followed explicitly this language, and directed also an equal division of the costs of the appeal 2 "That Elmer Preuer is the sole proprietor of Woodworkers Supply Company; that defendant, Woodworkers Tool Works, a corporation, was engaged in selling its products in California through the agency of said Woodworkers Supply Company; that the panel raiser head involved in this action was sold to plaintiff's employer, Selby Company, in California by defendant through said Woodworkers Supply Company; that defendant had a running course of business every year and sold some of its items at all times in California through said Woodworkers Supply Company on a commission basis; that defendant's business of selling its products in California through the agency of said Woodworkers Supply Company was continuous and systematic; that said panel raiser head as well as other products of defendant sold in California were shipped by defendant company directly to the purchasers through orders received from Woodworkers Supply Company and paid for by purchasers through said Woodworkers Supply Company; that said Woodworkers Supply Company was the agent of defendant, Woodworkers Tool Works, as their identity of names implies."

Introduction {#s1} ============ Immunity is essential for survival, yet energetically expensive and potentially self-damaging. The immune system needs to be tightly regulated and highly responsive to changes in external and internal environments, adapting to developmental stage [@ppat.1003720-Kollmann1], nutritional state [@ppat.1003720-Becker1], and stress [@ppat.1003720-Cohen1]. Hormonal control of the immune system is not well-understood, and lies at the heart of a diverse range of clinically relevant phenomena including immune circadian rhythm [@ppat.1003720-Silver1], [@ppat.1003720-Stone1], obesity induced inflammation [@ppat.1003720-Fantuzzi1] and age- and gender-differences in immune function [@ppat.1003720-Kollmann1], [@ppat.1003720-Gilliver1]. *Drosophila* has proven to be a fruitful model of innate immunity [@ppat.1003720-Lemaitre1]. The innate immune system in the fly comprises humoral and cellular responses [@ppat.1003720-Lemaitre1]. The humoral response is best characterized by the secretion of antimicrobial peptides (AMPs) locally by epithelia such as the gut, or systemically by the fat-body, a functional analogue of the mammalian liver. This response to bacterial or fungal infection is mainly regulated by the Toll and Imd signaling pathways. Cellular immunity is performed by hemocytes, phagocytic circulating immune cells. *Drosophila* has become a powerful system to study phagocytosis due to high conservation of the processes involved [@ppat.1003720-Stuart1], [@ppat.1003720-Stuart2]. Cellular immunity is required to survive various types of bacterial infections, complementing the humoral response [@ppat.1003720-AvetRochex1]--[@ppat.1003720-Ulvila1] and is involved in the response to wasp parasitoid infestation [@ppat.1003720-Krzemien1]. In addition, in the larvae, hemocytes play a role in inter-organ communication, as they are required for the fat-body to mount a full humoral antimicrobial response after an intestinal infection [@ppat.1003720-Charroux1], [@ppat.1003720-Basset1], [@ppat.1003720-Wu1]. Hemocytes are also recruited to wounds in embryo and larvae [@ppat.1003720-Babcock1]--[@ppat.1003720-Wood1], potentially clearing damaged tissue and preventing further dispersal of microorganisms from unsterile wound sites. In parallel to their role in immunity, hemocytes perform developmental and homeostatic functions such as the phagocytosis of apoptotic cells and extracellular matrix secretion. These functions are essential at embryonic stages, for example, for central nervous system and renal tubule development [@ppat.1003720-Bunt1], [@ppat.1003720-Olofsson1]. The crosstalk between immunity and nutritional state or stress [@ppat.1003720-Becker1], [@ppat.1003720-DiAngelo1]--[@ppat.1003720-Storelli1] in *Drosophila* is beginning to be unravelled, however, developmental regulation of the immune system remains enigmatic. Ecdysone is a steroid hormone, similar to mammalian estrogens and androgens; peaks in ecdysone titer regulate the major developmental transitions in the fly, including metamorphosis. The pupal stage lasts 4 days from the end of the 3^rd^ larval instar, after which adult flies eclose [@ppat.1003720-Thummel1]. The biologically active form of ecdysone, 20-hydroxyecdysterone (20-E, hereafter referred to as 'ecdysone') coordinates tissue remodelling at metamorphosis [@ppat.1003720-Thummel1]. This hormone activates a nuclear receptor, the Ecdysone Receptor (EcR), which acts as a heterodimer with its partner Ultraspiracle (USP), a homologue of the mammalian Retinoid X Receptor. Together, they activate the transcription of primary response genes, which in turn activate the transcription of a battery of late response genes [@ppat.1003720-Thummel1]. This transcriptional cascade ultimately leads to the induction of both cell death in larval tissues and differentiation and proliferation of the imaginal discs into adult tissues [@ppat.1003720-Thummel1]. In addition, several lines of evidence indicate that ecdysone regulates some aspects of hemocyte behaviour. In the larva, while the majority of hemocytes are in circulation, approximately one third of the total population interacts with tissues, attaching in repeated patches to the dorsal epithelium along the longitudinal axis [@ppat.1003720-Lanot1]. Despite the fact that hemocytes from these patches are mostly immotile at larval stages, it has been noticed that they disperse at metamorphosis [@ppat.1003720-Lanot1]. This observation correlates with the recent finding that *ex vivo*, hemocytes activate motility and morphological changes after metamorphosis [@ppat.1003720-Sampson1]. Cell shape changes can be prematurely triggered in larvae by ecdysone injection [@ppat.1003720-Lanot1]. Last, it is long known that ecdysone treatment is important to potentiate AMP gene expression and phagocytosis after an immune challenge in hemocyte-derived cell culture lines [@ppat.1003720-Dimarcq1]. Although these results suggest an ecdysone-dependent regulation of hemocyte function, *in vivo* evidence of a direct effect of ecdysone signaling on hemocyte behaviour, and its functional relevance, is lacking. Here, we explore the hormonal regulation of *Drosophila* hemocytes at metamorphosis and its impact on *Drosophila* immunity using an *in vivo* approach. We demonstrate that direct activation of ecdysone signaling in hemocytes is necessary to increase their developmental and immune activities at metamorphosis, including phagocytosis. We show that this activation is essential to respond efficiently to and survive pathogenic challenge. Results {#s2} ======= 1. The Ecdysone Receptor is required in the hemocytes for their activation at metamorphosis {#s2a} ------------------------------------------------------------------------------------------- To test whether ecdysone signaling cell-autonomously regulates hemocyte shape changes at metamorphosis, we used the *Hml-(Hemolectin-)ΔGal4* driver [@ppat.1003720-Sinenko1] to specifically express green fluorescent protein (GFP) and dominant-negative constructs of the three known EcR isoforms under the control of the UAS sequence. We imaged hemocytes *ex vivo* by bleeding larvae or pupae at precise time points after puparium formation (APF) ([Fig. 1A--B](#ppat-1003720-g001){ref-type="fig"}) and *in vivo* through the dorsal epidermis ([Fig. 1C--D](#ppat-1003720-g001){ref-type="fig"}). The first hour of the 12h 'prepupal' period is characterized by a translucent pupal case (which then darkens). Control hemocytes (from *HmlΔGal4, UAS-GFP/+* pupae, here after referred to as *HmlΔ*\>GFP) displayed a clear change of morphology over metamorphosis: they became gradually more polarized, with many cytoplasmic protrusions and a higher number of vacuoles, increasing in size dramatically, likely due to their greater spread and many phagocytic vesicles ([Fig. 1A and C](#ppat-1003720-g001){ref-type="fig"}). In striking contrast, hemocytes expressing a dominant negative (DN) form of the EcRB1 isoform (from *HmlΔGal4, UAS-GFP/UAS-EcRB1DN* pupae, here after referred to as *HmlΔ\>EcRB1DN*) did not show any obvious change of size or morphology ([Fig. 1B and D](#ppat-1003720-g001){ref-type="fig"}). Similar results were obtained when we analysed by flow cytometry the properties of the hemocyte population at the onset of pupariation. Control hemocytes displayed a clear shift both in Forward Scatter (FSC) and Side Scatter (SSC), indicating an increase in cell size and granularity, respectively ([Fig. 1E](#ppat-1003720-g001){ref-type="fig"} and [S1](#ppat.1003720.s001){ref-type="supplementary-material"}). In contrast, the FSC and SSC of hemocytes expressing *EcRB1DN* remained stable over metamorphosis and similar to the parameters observed for control hemocytes in late 3^rd^ instar larvae (L3 wandering; L3W; [Fig. 1F](#ppat-1003720-g001){ref-type="fig"} and [S1](#ppat.1003720.s001){ref-type="supplementary-material"}). {#ppat-1003720-g001} In control pupae, the cell shape changes were concomitant with a dispersal of the dorsal patches of hemocytes visualised by *in vivo* cinemicroscopy and cell tracking analysis ([Fig. 1G--J](#ppat-1003720-g001){ref-type="fig"}). These so-called 'sessile hemocytes' changed their behaviour at pupariation and began to actively migrate under the epithelium (see video 1 and [Fig. 1G, I](#ppat-1003720-g001){ref-type="fig"}). This dispersal did not occur when hemocytes expressed EcRB1DN ([Fig. 1H, J](#ppat-1003720-g001){ref-type="fig"} and video 2). In these individuals, hemocytes were more numerous, which correlated with higher proliferation at larval stages ([Fig. S2](#ppat.1003720.s002){ref-type="supplementary-material"}). Moreover, they were unable to migrate away from their original location ([Fig. 1J](#ppat-1003720-g001){ref-type="fig"}). Measurements of cell velocity clearly indicated an impaired motility in EcRB1DN-expressing hemocytes, as compared to control hemocytes ([Fig. 1K](#ppat-1003720-g001){ref-type="fig"}). Importantly, this defect in motility was not due to a decrease in viability, and appeared specific to the pupal stage as neither localisation of hemocytes to the gut in larvae, nor embryonic hemocyte migration were affected when EcRB1DN was expressed specifically in hemocytes ([@ppat.1003720-Wood1], [@ppat.1003720-ZaidmanRemy1]; [Fig. S3](#ppat.1003720.s003){ref-type="supplementary-material"}). In addition, when we expressed EcRB1DN just before the initiation of puparium formation, as opposed to throughout larval stages, we also saw a significant reduction in motility ([Fig. S4](#ppat.1003720.s004){ref-type="supplementary-material"}). The expression of dominant negative constructs for each of the three isoforms of EcR showed a similar phenotype to the EcRB1 isoform ([Fig. 1K](#ppat-1003720-g001){ref-type="fig"}). EcR function in the regulation of hemocyte motility was further confirmed by RNAi ([Fig. 1K](#ppat-1003720-g001){ref-type="fig"}). Last, the expression of *USP* RNAi in the hemocytes led to a similar lack of motility ([Fig. 1K](#ppat-1003720-g001){ref-type="fig"}), indicating that the functional ecdysone receptor complex (EcR/USP) is required for this process. 2. Hemocytes insensitive to ecdysone are unable to perform dead cell phagocytosis during metamorphosis {#s2b} ------------------------------------------------------------------------------------------------------ We next addressed the question of whether ecdysone signaling regulates 'house keeping' functions of hemocytes, required for homeostasis in the organism. During development, one major task for hemocytes is to scavenge and engulf dying cells [@ppat.1003720-Franc1]. We recovered hemocytes at different time points after the initiation of metamorphosis and stained them for DNA and F-actin. Hemocytes from control animals barely contained any stained vesicles at 1 h APF ([Fig. 2A](#ppat-1003720-g002){ref-type="fig"}), but progressively presented a growing number of DNA and/or F-actin-containing vesicles (4 h, 8 h and 18 h APF; [Fig. 2A](#ppat-1003720-g002){ref-type="fig"}). By 8 h APF, most of the control hemocytes had engulfed up to ten apoptotic cells, identifiable by the fragmented aspect of their nuclei, and/or huge pieces of muscles characterized by a strong, striated phalloidin staining. Such vesicles were not seen in the hemocytes expressing *EcRB1DN*, which were stained only for their own nucleus ([Fig. 2A](#ppat-1003720-g002){ref-type="fig"}). We quantified the proportion of cells with phagosomes containing phalloidin-positive muscle fibres and found that the difference between control and *EcRB1DN* hemocytes was striking. In control pupae, we observed a significant increase in dead cell engulfment over time (p\<0.001): just under 20% of hemocytes contained muscle tissue at 1 h APF, rising to approximately 80% of cells by 18 h APF ([Fig. 2B](#ppat-1003720-g002){ref-type="fig"}). In *EcRB1DN* hemocytes the proportion was \<10% at 1 h APF and remained at this low level throughout early pupal stages ([Fig. 2B](#ppat-1003720-g002){ref-type="fig"}; no statistical differences between the five stages). The difference between *EcRB1DN* and control hemocytes was significant at every stage ([Fig. 2B](#ppat-1003720-g002){ref-type="fig"}). Despite this effect on phagocytosis of larval tissue, viability of *HmlΔ\>EcRB1DN* individuals from prepupal stage to adulthood was not affected as compared to control individuals, nor was their duration of metamorphosis ([Fig. S5](#ppat.1003720.s005){ref-type="supplementary-material"}). {#ppat-1003720-g002} 3. Activation of hemocytes at metamorphosis is important for survival after infection {#s2c} ------------------------------------------------------------------------------------- To find out if hemocyte activation by ecdysone is important in critical situations, such as wounding or infection, we tested the ability of *HmlΔ\>EcRB1DN* pupae to resist clean or septic injuries with the Gram-negative bacteria *Erwinia carotovora* (*E.carotovora*) or the Gram-positive bacteria *Enteroccocus faecalis* (*E.faecalis*) when wounded at end of prepupal/early pupal stage (10 h--30 h APF). Interestingly, *HmlΔ\>EcRB1DN* pupae survived as well as control individuals to clean injury, but were significantly less resistant to both types of bacterial infections ([Fig. 3A](#ppat-1003720-g003){ref-type="fig"}). In order to understand better if the difference in resistance between control and *HmlΔ\>EcRB1DN* animals is more pronounced at later stages when hemocytes are fully activated in control individuals, we imposed Gram-negative septic infection on closely-staged pupae at either 3 h APF or 24 h APF. We found that the difference between overall survival of control and *HmlΔ\>EcRB1DN* pupae wounded at 3 h APF was not significant, whereas *HmlΔ\>EcRB1DN* pupae wounded at 24 h APF survived significantly less than controls (p\<0.001; [Fig. 3B](#ppat-1003720-g003){ref-type="fig"}). When we analysed the time of death of infected pupae more precisely, we saw that although the overall survival of *HmlΔ\>EcRB1DN* and control pupae wounded at 3 h APF were not significantly different, *HmlΔ\>EcRB1DN* pupae tended to succumb to infection much sooner than controls ([Fig. 3B](#ppat-1003720-g003){ref-type="fig"}). Altogether, the data suggest that the difference in resistance between *HmlΔ\>EcRB1DN* and control is more pronounced at later stages when control hemocytes are fully activated, although we cannot exclude the possibility that other differences between the two stages could have an effect on the severity of the infection. {#ppat-1003720-g003} We next tested whether feeding larvae with bacteria ('natural infection') would affect their survival over subsequent metamorphosis. Control individuals were not affected by the oral infection with *E. carotovora*, and eclosed normally ([Fig. 3C](#ppat-1003720-g003){ref-type="fig"}). In contrast, we observed a significant decrease in the survival of *HmlΔ\>EcRB1DN* pupae ([Fig. 3C](#ppat-1003720-g003){ref-type="fig"}). For both septic and natural infections, the observed decreased in survival was similar to that caused by genetic ablation of hemocytes (by expression of the pro-apoptotic gene Bax in hemocytes [@ppat.1003720-Defaye1]; see "Phago^less^" survival in [Fig. 3A and C](#ppat-1003720-g003){ref-type="fig"}). Thus hemocyte activation at metamorphosis is essential for the efficient participation of the cellular immune response in resistance to bacterial infections. 4. Hemocytes require ecdysone signaling to become wound-responsive at metamorphosis {#s2d} ----------------------------------------------------------------------------------- Because pupae in which hemocytes are not activated succumb to infections more often than controls, we surmise that ecdysone signaling has a role in the regulation of the hemocyte response to infections. Therefore, we analysed the three main known responses of hemocytes to infections to determine whether they were affected by ecdysone signaling: i) wound response, ii) participation in AMP systemic expression (inter-organ signaling) and iii) phagocytosis. Upon injury, hemocytes are recruited to damaged tissues and wounded epithelia. This may be important to limit infection in the case of septic injury: once recruited to the wound, hemocytes phagocytose bacteria and prevent their spreading inside the organism. In the embryo, hemocyte recruitment involves active migration toward the wound by chemotaxis [@ppat.1003720-Stramer1], [@ppat.1003720-Wood1]. In the larva by contrast, hemocytes are described as being recruited passively from the circulation by 'capture' at the wound site [@ppat.1003720-Babcock1]. Hemocytes attached under the epithelium do not respond to wounds at larval stages, even to those in their close vicinity [@ppat.1003720-Babcock1]. Interestingly, when we wounded the dorsal epithelium of prepupae using a laser-ablation system (which allows immediate high resolution imaging after wounding and tracking of hemocyte movement), we observed that most recruited cells had not come from circulation but by active migration under the epithelium, often from the so-called 'sessile patches' ([Fig. 4A--C](#ppat-1003720-g004){ref-type="fig"} and video 3). Analysis of hemocyte tracks after wounding confirmed their directed migration towards the wound ([Fig. 4D](#ppat-1003720-g004){ref-type="fig"}; compare with the center of mass close to (0;0) in the absence of a wound, indicative of a random migration, [Fig. 1I](#ppat-1003720-g001){ref-type="fig"}). Importantly, the capacity of hemocytes to respond to wounds clearly increased over early prepupal stages. Indeed, hemocyte recruitment rate increased with pupal age: after wounding prepupae at 120 min APF, we observed a higher rate of recruitment of hemocytes to wounds as compared with prepupae wounded at 55 min APF ([Fig. 4E](#ppat-1003720-g004){ref-type="fig"}). Strikingly, *EcRB1DN*-hemocytes remained unresponsive to wounds and very few were recruited to the sites of damage ([Fig. 4F--H](#ppat-1003720-g004){ref-type="fig"} and video 4). {ref-type="supplementary-material"}). Tracks of individual cells measured over 80 min, 70 min after wounding (wound performed at 1h30 APF) are superimposed at (0;0) in the tracking plot; all trajectories were rotated to maintain their relative positions towards the wound center (D). The center of mass of all tracks, indicated with red cross, is shifted towards the wound (positive *x*-axis) and significantly different from (0;0) (p = 0.01). Recruitment rate (cell/min) is significantly higher in pupae wounded at 120 min APF than in pupae wounded 55 min APF (E). Profile of hemocyte recruitment to epithelial wounds in control (brown) or *HmlΔ\>EcRB1DN* pupae (blue) (F). Tracks corresponding to trajectories of *EcRB1DN*-hemocytes after epithelial wounding were superimposed and rotated as above in tracking plot (G); note that the center of mass (red cross) remains close to (0;0). Rate of recruitment (cell/min) in *HmlΔ\>EcRB1DN* pupae and controls wounded 1h30 APF (H). Mean and SEM are displayed on graphs.](ppat.1003720.g004){#ppat-1003720-g004} Thus, our data reveal that the mode of recruitment of hemocytes to wounds is modified at pupal stage, switching from a passive 'capture' of circulating cells in larvae [@ppat.1003720-Babcock1], to active migration of hemocytes toward the wounds in pupae. This activation is lost in hemocytes insensitive to ecdysone. 5. Ecdysone signaling is required for bacterial phagocytosis and to fight infection at metamorphosis {#s2e} ---------------------------------------------------------------------------------------------------- Hemocytes are involved in the systemic induction of the Imd pathway after oral infection in the larva [@ppat.1003720-Charroux1], [@ppat.1003720-Basset1], [@ppat.1003720-Wu1], [@ppat.1003720-Foley1], and therefore we next tested the hypothesis of an ecdysone-dependent regulation of "gut-to-fat-body" communication by hemocytes. However, when we analysed the expression of four AMPs (*Diptericin*, *Attacin*, *Metchnikowin* and *Drosomycin*) in prepupae after oral infection with *E. carotovora* at larval stage ([Fig. S6](#ppat.1003720.s006){ref-type="supplementary-material"}), we found that *HmlΔ\>EcRB1DN* prepupae induce a systemic humoral response similar to that of control. Thus, our data indicate that ecdysone signaling in hemocytes is not required for inter-organ communication after oral infection. In addition, we analyzed the local epithelial response to oral infection by examining expression of *Diptericin* specifically in the gut, and found that this response is also unaffected in *HmlΔ\>EcRB1DN* prepupae ([Fig. S7](#ppat.1003720.s007){ref-type="supplementary-material"}). We wondered if phagocytic activity, on the other hand, would be ecdysone-regulated at metamorphosis and could account for the observed decrease in survival to infection. To first address this question, we bled late L2/young L3 larvae or young prepupae, incubated the retrieved hemocytes with a high concentration of pHRodo bacterial particles (that emit a strong fluorescent signal only at low pH, i.e. in the acidic environment of the phagosome) and assessed the ability of hemocytes to perform phagocytosis using flow cytometry ([Fig. 5A--B](#ppat-1003720-g005){ref-type="fig"}). Strikingly, hemocytes presented a clear shift in their ability to perform phagocytosis from L2/L3 to prepupal stages ([Fig. 5A](#ppat-1003720-g005){ref-type="fig"}); the prepupal hemocyte phagocytic index (number of phagocytosing hemocytes multiplied by mean pHRodo intensity per hemocyte)/total number of hemocytes) was almost four times the index of L2/L3 larval hemocytes ([Fig. 5B](#ppat-1003720-g005){ref-type="fig"}). Moreover, *EcRB1DN*-hemocytes did not present such a shift and maintained the same phagocytic ability at prepupal stage as at L2/L3 larval stages ([Fig. 5A--B](#ppat-1003720-g005){ref-type="fig"}). {#ppat-1003720-g005} To confirm this phenotype *in vivo*, we injected pHRodo bacterial particles in control and *HmlΔGal4\>EcRB1DN* prepupae and imaged hemocytes live through the dorsal epithelium ([Fig. 5C](#ppat-1003720-g005){ref-type="fig"}). While under these conditions, all hemocytes in control prepupae had performed phagocytosis of numerous particles, only very few *EcRB1DN*-hemocytes contained particles and then in low numbers ([Fig. 5D--E](#ppat-1003720-g005){ref-type="fig"}). We complemented this analysis with a flow cytometry method that combines *in vivo* assay with high-throughput quantitative analysis. One hour after injection with pHRodo, hemocytes were retrieved from prepupae and analysed for their fluorescence by flow cytometry. In accordance with the results obtained with confocal analysis, fewer *EcRB1DN*-hemocytes were pHRodo-positive as compared to control (40% versus 88%; [Fig. 5F](#ppat-1003720-g005){ref-type="fig"}). Those few hemocytes positive for pHRodo had a lower fluorescence intensity than control hemocytes ([Fig. 5F](#ppat-1003720-g005){ref-type="fig"}), contributing to a global decrease in phagocytic index ([Fig. 5G](#ppat-1003720-g005){ref-type="fig"}). Interestingly, hemocytes expressing dominant negative forms of any of the three EcR isoforms were affected in their ability to perform phagocytosis, as well as hemocytes expressing *EcR RNAi* ([Fig. 5G](#ppat-1003720-g005){ref-type="fig"}). As pHRodo particles only fully emit fluorescence once in the mature phagosome, the above results could also be indicative of a defect of *EcRDN*-hemocytes in phagosome maturation. To test this hypothesis we analysed the ability of control and *EcRB1DN*-hemocytes to bind and engulf live *Escherichia coli* (*E.coli*). *E.coli* expressing the red fluorescent protein (*E.coli-RFP*) were injected in prepupae and phagocytosis was monitored *in vivo* (video 5 and 6). *EcRB1DN*-hemocytes were significantly impaired in their ability both to bind (attachment index: the average number of bacteria bound per hemocyte; [Fig. 5H](#ppat-1003720-g005){ref-type="fig"}) and engulf bacteria (internalisation index: the average number of bacteria ingested per hemocyte; [Fig. 5I](#ppat-1003720-g005){ref-type="fig"} and [S7](#ppat.1003720.s007){ref-type="supplementary-material"}). Altogether, our results demonstrate that EcR-dependent activation of hemocytes is required for optimal phagocytic activity of hemocytes at metamorphosis, and modulate their ability to both bind and internalise bacteria. 6. EcR transcriptionally regulates genes involved in phagocytosis {#s2f} ----------------------------------------------------------------- Our phenotypic analysis has revealed the importance of ecdysone signaling in the regulation of several hemocyte functions, including bacteria phagocytosis. To better understand the molecular basis of the ecdysone-dependent regulation of hemocyte biology, we performed a hemocyte-specific transcriptomic analysis, combining FACS and Affymetrix microarrays. We first compared the transcriptome of "control" hemocytes retrieved from *w; Hml\>GFP/+* 3^rd^ instar larvae and prepupae. We selected late feeding 3^rd^ instar larvae prior to the peak of ecdysone that induces metamorphosis, and compared them with hemocytes retrieved from 1 h--2 h APF prepupae, the stage we have used for the majority of our phenotypic analyses. This allowed us to determine which genes are induced or repressed at metamorphosis in hemocytes. Comparison with *EcRDN* hemocytes allowed us to determine which of these genes are dependent on EcR signaling. A high number of genes are transcriptionally regulated in hemocytes at the onset of metamorphosis (3331 genes, among which 659 are up-regulated more than two fold; p\<0.001; see repartition by fold change in [Fig. 6A](#ppat-1003720-g006){ref-type="fig"}. The full microarray data can be found in [Table S2](#ppat.1003720.s010){ref-type="supplementary-material"} and on GEO database accession GSE49326, <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE49326>). Strikingly, our data indicate that most of the changes in gene expression are EcR-dependent at this stage (1955 genes out of 3331 are EcR-regulated; p\<0.001; see repartition by fold change in [Fig. 6A](#ppat-1003720-g006){ref-type="fig"} and the list of genes in [Table S1](#ppat.1003720.s009){ref-type="supplementary-material"}). In fact, 83% of genes that present a fold change in expression greater than 2 at metamorphosis are regulated by EcR. The microarray analysis was further confirmed by hemocyte-specific quantitative PCR of 12 genes, whose expression was clearly up-regulated in control hemocytes at metamorphosis, and significantly lower in *EcRDN*-expressing hemocytes at the same stage ([Fig. 6B](#ppat-1003720-g006){ref-type="fig"}). These data confirm and explain the huge impact of ecdysone signaling on hemocyte biology at the onset of metamorphosis. Interestingly, we discover that in prepupal hemocytes, ecdysone signaling up-regulates the expression of numerous genes involved in bacteria phagocytosis. Indeed, we found that 35 genes known to be involved in phagocytosis are significantly up-regulated in hemocytes from control pupae and significantly less expressed in hemocytes expressing *EcRDN* ([Table 1](#ppat-1003720-t001){ref-type="table"}). Among them, several genes encode phagocytic bacterial receptors (*Nimrod*, *Dscam*, *PGRP*-*LC*), a receptor for dead cell phagocytosis (*crq*), or are involved in the actin remodelling required for this process (such as *Rac2* and *SCAR*). As loss of expression of several of these genes has been shown to have a dramatic effect on phagocytosis, these molecular data are sufficient to explain how insensitivity to ecdysone in hemocytes results in the strong phagocytosis phenotype we describe. Similarly, we found several genes involved in cell motility or cell shape regulation to be up-regulated in the control hemocytes at metamorphosis, and not in *EcRDN*-expressing hemocytes ([Table S3](#ppat.1003720.s011){ref-type="supplementary-material"} and [S4](#ppat.1003720.s004){ref-type="supplementary-material"}, respectively). These genes represent good candidates responsible for the phenotypes observed in our analyses; additionally, it is likely that this data contains further genes involved in phagocytosis, cell motility or cell shape as yet unrevealed. {ref-type="supplementary-material"} for gene list). (B) qPCR confirmation of the expression of 12 genes from the microarrays. qPCR was performed on RNA extracted from FACS-sorted hemocytes. The results displayed represent the mean and SEM of three biological repeats; samples were independent from samples used for microarrays. Statistical analysis was performed using one-way ANOVA and Tukey-Kramer post-test. For comparison between control larval hemocytes and control pupal hemocytes, as well as between control pupal hemocytes and EcRDN pupal hemocytes, significance are indicated on the graph. There was no significant difference between control larval hemocytes and EcRDN pupal hemocytes except for GstS1 (\*), NimC3 (\*), Mmp2 (\*) and Dscam (\*\*\*).](ppat.1003720.g006){#ppat-1003720-g006} 10.1371/journal.ppat.1003720.t001 ###### EcR transcriptionally regulates genes involved in phagocytosis. {#ppat-1003720-t001-1} Gene Symbol Gene Accession Control pupae vs control larvae Control pupae vs EcRDN pupae References on phagocytosis phenotype ------------- ---------------- --------------------------------- ------------------------------ -------------------------------------- ---------- ------------------------------------------------------------------------------------------------------------------------------------------------ NimC2 FBgn0028939 57.08 0 −4.40 0 [@ppat.1003720-Kurucz1] (Prediction) **Eip93F** FBgn0264490 26.40 0 −2.85 8.00E-06 [@ppat.1003720-Thummel1] (Prediction) scb FBgn0003328 25.72 0 −1.98 1.30E-05 [@ppat.1003720-StroscheinStevenson1], [@ppat.1003720-Nonaka1] Eip78C FBgn0004865 11.88 0 −3.80 0 [@ppat.1003720-Stuart1] Tep2 FBgn0041182 9.19 0 −2.14 8.00E-06 [@ppat.1003720-StroscheinStevenson1] **NimC4** FBgn0260011 6.26 0 −5.34 0 [@ppat.1003720-Kurucz1] (Prediction) **NimC3** FBgn0001967 5.83 6.90E-05 −2.54 2.20E-05 [@ppat.1003720-Kurucz1] (Prediction) **Mmp2** FBgn0033438 5.81 8.00E-06 −1.68 5.50E-05 [@ppat.1003720-Stuart1] **Dscam** FBgn0033159 3.96 1.10E-05 −2.75 1.80E-05 [@ppat.1003720-Watson1] l(1)G0232 FBgn0028341 3.10 2.00E-06 −1.58 0.000193 [@ppat.1003720-StroscheinStevenson1] yip2 FBgn0040064 3.01 7.00E-05 −1.70 0.000388 [@ppat.1003720-Stuart1] CG8449 FBgn0038129 2.74 5.00E-06 −1.59 0.000972 [@ppat.1003720-Stuart1] CG3638 FBgn0261444 2.67 2.00E-06 −1.74 2.40E-05 [@ppat.1003720-StroscheinStevenson1] **crq** FBgn0015924 2.60 5.30E-05 −1.75 4.40E-05 [@ppat.1003720-Franc2], [@ppat.1003720-Stuart3] mv FBgn0265988 2.51 0.00043 −2.55 3.00E-06 [@ppat.1003720-Rahman1] CG16791 FBgn0038881 2.39 3.00E-06 −1.60 0.000161 [@ppat.1003720-StroscheinStevenson1] flr FBgn0260049 2.27 5.00E-06 −1.44 0.000183 [@ppat.1003720-StroscheinStevenson1] cpb FBgn0011570 2.25 5.00E-06 −1.48 0.00065 [@ppat.1003720-Philips1] RhoGAP71E FBgn0036518 2.19 8.00E-06 −1.48 0.000137 [@ppat.1003720-Ramet1] Rac2 FBgn0014011 2.03 9.00E-06 −1.43 0.000417 [@ppat.1003720-Stuart1], [@ppat.1003720-Sampson1], [@ppat.1003720-Philips1], [@ppat.1003720-StroscheinStevenson1], [@ppat.1003720-AvetRochex2] Arpc5 FBgn0031437 1.93 6.80E-05 −1.44 0.000494 [@ppat.1003720-Philips1], [@ppat.1003720-StroscheinStevenson1] Snx3 FBgn0038065 1.93 1.80E-05 −1.35 0.00068 [@ppat.1003720-StroscheinStevenson1] CG13887 FBgn0035165 1.92 1.90E-05 −1.41 0.000501 [@ppat.1003720-Stuart1] RN-tre FBgn0020620 1.87 3.30E-05 −1.69 0.000108 [@ppat.1003720-Stuart1], [@ppat.1003720-Ramet1] not FBgn0013717 1.84 6.20E-05 −1.41 0.000369 [@ppat.1003720-Stuart1] **PGRP-LC** FBgn0035976 1.81 6.50E-05 −1.75 0.000359 [@ppat.1003720-Ramet1] Mekk1 FBgn0024329 1.81 4.10E-05 −1.46 0.000132 [@ppat.1003720-Stuart1] kuz FBgn0259984 1.79 4.80E-05 −1.36 0.000536 [@ppat.1003720-StroscheinStevenson1] SCAR FBgn0041781 1.63 1.00E-04 −1.34 0.00084 [@ppat.1003720-StroscheinStevenson1] Vps35 FBgn0034708 1.57 0.00015 −1.37 0.000462 [@ppat.1003720-Stuart1] Traf4 FBgn0026319 1.57 0.00059 −2.26 3.00E-06 [@ppat.1003720-StroscheinStevenson1] shark FBgn0015295 1.53 0.00012 −1.36 0.00073 [@ppat.1003720-Doherty1], [@ppat.1003720-Ziegenfuss1] mib2 FBgn0086442 1.53 0.00017 −1.45 0.000534 [@ppat.1003720-Stuart1] put FBgn0003169 1.51 0.00013 −1.39 0.000902 [@ppat.1003720-Stuart1] Among the genes significantly up-regulated in control hemocytes at metamorphosis (p\<0.001; linear FC and *p* values indicated on the table) and significantly down-regulated in EcRB1DN-expressing hemocytes (p\<0.001; linear FC and *p* values indicated on the table), 35 genes were annotated by Flybase with the GO term phagocytosis or found in S2 cell-based RNAi screens for phagocytosis phenotype [@ppat.1003720-Stuart1], [@ppat.1003720-Ulvila1], [@ppat.1003720-Philips1]--[@ppat.1003720-StroscheinStevenson1]. FC: linear Fold Change; in bold: genes for which expression pattern was confirmed by qPCR. All p values are \<0.001, no FC threshold was applied. Discussion {#s3} ========== Here we have demonstrated the cell-autonomous regulation of *Drosophila* phagocytes by a hormonal signal at metamorphosis. Our study provides *in vivo* evidence that the steroid hormone ecdysone regulates both developmental and immune functions of hemocytes, such as phagocytosis of dying cells and bacteria, and the acquisition of wound responsiveness at metamorphosis. Most importantly, non-activated hemocytes are unable to efficiently fight infections, reflecting the functional importance of this hormonal regulation for the organism. Using an *in vivo* genetic approach to block EcR signaling specifically in hemocytes, we have shown that ecdysone directly regulates their cell shape. Moreover, our data indicates that ecdysone regulates the onset of hemocyte motility and dispersal at metamorphosis, reflecting its function in border cell motility during oogenesis [@ppat.1003720-Bai1]. Our microarray data reveal that EcR up-regulates the expression of several genes functioning in cell motility or cell shape regulation [@ppat.1003720-Kiger1], [@ppat.1003720-Rohn1], which could account for these phenotypes ([Table S3](#ppat.1003720.s011){ref-type="supplementary-material"} and [S4](#ppat.1003720.s004){ref-type="supplementary-material"}). Arguably, migration of hemocytes between tissues is required for clearing dying larval tissues during the pupal period. We show that hemocytes expressing the *EcRDN* construct do not engulf dead cells, which is potentially a consequence of impaired phagocytosis, motility, or a combination of both, although we cannot distinguish between these possibilities. Ecdysone has previously been shown to induce the expression in the hemocyte-derived *mbn2* cell line of *croquemort* (*crq*; [@ppat.1003720-Dimarcq1]), a gene encoding a receptor for apoptotic cells in the embryo [@ppat.1003720-Franc1]. *crq* was identified in our microarray analysis as showing EcR-dependent up-regulation at metamorphosis, and this was confirmed by qPCR, where *crq* expression is almost completely suppressed in *EcRDN*-expressing pupal hemocytes ([Fig. 6B](#ppat-1003720-g006){ref-type="fig"}). The impaired expression of *crq* in *EcRDN* hemocytes likely contributes to their deficiency in apoptotic cell phagocytosis. Functionally, the regulation of hemocytes by ecdysone, which is the coordinator of larval tissue apoptosis, may be a smart way for the fly to synchronize its macrophage scavenging activity with the moment it is most needed, at metamorphosis. Surprisingly, we did not observe any gross developmental consequences of the loss of this function, whereby *HmlΔGal4\>EcRB1DN* individuals completed metamorphosis without delay. This is in agreement with studies showing that under sterile conditions, pupae lacking hemocytes altogether progress normally through metamorphosis [@ppat.1003720-Charroux1], [@ppat.1003720-Defaye1]. It suggests that dead cells might be engulfed by other, non-professional phagocytes (e.g. neighbor cells as reported for tumorigenesis), cleared up by other unidentified means, or simply tolerated, in the absence of functional hemocytes. Furthermore, we show that the activation of hemocyte motility at metamorphosis also correlates with a change in their response to induced epithelial damage. While in the larva hemocytes are passively recruited to wounds from circulation [@ppat.1003720-Babcock1], we demonstrate that in the pupa they actively migrate to damaged tissues. Induction of epithelial wounds at different times APF demonstrated that active wound responsiveness is progressively acquired at metamorphosis. In agreement with previous *ex vivo* analysis [@ppat.1003720-Sampson1], our data highlights an intriguing plasticity of hemocytes to adapt their migratory activity and their response to wounds throughout development: chemotaxis in embryos and pupae ([@ppat.1003720-Wood1] and this study) versus passive circulation and 'capture' to wounds in larvae [@ppat.1003720-Babcock1]. This correlates with the observation that, although the heart is beating in a 20 h APF-old pupa, hemocytes are not propelled in the hemolymph by the heartbeat, but maintain a slow, steady, active migration on tissues (video 7). Most importantly, our study provides the first *in vivo* evidence of hormonal regulation of the *Drosophila* cellular response to bacterial challenge. With both *ex vivo* and *in vivo* data, we have demonstrated an important role for EcR in the up-regulation of hemocyte phagocytic activity at metamorphosis ([Fig. 5](#ppat-1003720-g005){ref-type="fig"}). How does ecdysone signaling regulate phagocytosis? Previous studies in hemocyte-derived cell lines have shown that ecdysone treatment increases the transcription of some immune-related genes encoding AMPs and immune receptors such as Crq [@ppat.1003720-Dimarcq1], [@ppat.1003720-Flatt1], [@ppat.1003720-Zhang1]. Here, using a tissue-specific, whole genome transcriptomic approach, we demonstrate that many genes are regulated by ecdysone signaling in hemocytes at metamorphosis. This analysis reveals the molecular regulation behind the observed phenotypes and allows for the identification of candidate effector genes. For example, 35 genes up-regulated by EcR at metamorphosis have been previously attributed a function in phagocytosis. These genes encode proteins involved in different steps of the phagocytosis process, such as recognition (e.g. the receptors *PGRP-LC*, *croquemort*, and *Nimrod* family members, *Dscam* and *scab*), or cytoskeletal rearrangements required for the engulfment step (e.g. *RhoGAP71E*, *Rac2*, *Arpc5* and *SCAR*). Interestingly, PGRP-LC (FC 1.8 by microarray, 3.9 by qPCR) was recently shown to be induced in ecdysone-treated S2 cells [@ppat.1003720-Rus1]. It appears that ecdysone can regulate the phagocytosis process at different levels, which may be necessary to co-ordinate the ability of hemocytes to recognize and engulf their target. Moreover, genes regulated by ecdysone signaling can be implicated in more than one process, for example phagocytosis and AMP expression (e.g. PGRP-LC), or phagocytosis and cell migration (e.g. SCAR); this may contribute to synchronisation of different hemocyte immune functions. The functional relevance of increased cellular immune activity at metamorphosis is an intriguing question. Recent studies of the contribution of cellular immunity to *Drosophila* defenses have revealed that flies in which hemocytes are genetically ablated present a high lethality at metamorphosis [@ppat.1003720-Charroux1], [@ppat.1003720-Defaye1]. This is likely the result of opportunistic bacterial infections, as feeding antibiotics was sufficient to restore wild-type viability. We did not observe such lethality under normal conditions when expressing *EcRDN* in hemocytes; however in our hands *Phago^less^* lethality in absence of infection is also lower than that previously described [@ppat.1003720-Defaye1]. This suggests that our fly strains and fly food do not harbor the same bacterial types as those used in previous studies, leading to distinct opportunistic infection scenarios. Nevertheless, our data indicate a significant lethality of *HmlΔ\>EcRDN* pupae not only after septic injury with *E. faecalis* or *E. carotovora*, but also after oral infection at larval stages with *E. carotovora*, a bacterium that is not usually lethal in wild-type individuals. This lethality is quite dramatic considering only hemocytes express the transgene, and is similar to the lethality in hemocyte-ablated individuals ([@ppat.1003720-Charroux1], [@ppat.1003720-Defaye1] and this study). It indicates that ecdysone regulation is essential for hemocyte immune functions and survival after infection. Metamorphosis may represent a stage of predisposition to opportunistic oral infection, as the larval midgut is replaced by the adult intestinal epithelium. We speculate that histolysis of the gut could release bacteria from the lumen into the body cavity; active hemocytes may be required to limit the spreading of bacteria from temporary weak points in the epithelium. We have shown that *HmlΔ\>EcRDN* prepupae induce a normal intestinal and systemic humoral immune response after being orally infected at larval stage ([Fig. S6](#ppat.1003720.s006){ref-type="supplementary-material"} and [S7](#ppat.1003720.s007){ref-type="supplementary-material"}). In the case of both septic injury and oral infection, it is therefore likely that the main cause of decreased survival in *HmlΔ\>EcRDN* pupae is their striking hemocyte phagocytosis phenotype, possibly in combination with lack of motility, inability to chemotax to damaged tissue or other potential uncharacterized hemocyte defects. The synchronization of multiple processes is a fundamental requirement for successful development, and likely to rely on hormonal signaling. Altogether, our data reveal the importance of steroid hormone signaling in the synchronization of development and immunity in *Drosophila*, by ecdysone-dependent activation of hemocytes at pupariation. Rus *et al*. have recently shown [@ppat.1003720-Rus1], that ecdysone signaling affects the humoral response through regulation of PGRP-LC expression. Interestingly, they observed an impact of this regulation on the ability of adult flies to survive infection, indicating that ecdysone regulation of immunity extends beyond metamorphosis. In humans, hormonal activation of macrophages underpins various cancer pathologies [@ppat.1003720-Harkonen1] and is therefore highly relevant in clinical terms. It is also generally accepted that steroid hormones impact immunity in mammals. For example, glucocorticoids are commonly used in pharmacology for their anti-inflammatory properties [@ppat.1003720-Necela1]. However, their regulation of the immune response is complex, as they can also enhance the immune response [@ppat.1003720-Dhabhar1], [@ppat.1003720-Goulding1]. More generally, steroid hormones\' specific action on monocytes is still not very well documented, mainly due to the complexity of mammalian systems and experimental limitations. Elucidating mechanisms for steroid hormone regulation of cellular immunity (e.g. [@ppat.1003720-Routley1]) will be essential for a full understanding of sex differences in immunity and inflammation. Here, in a simpler model system, we used an approach that allows *in vivo* and cell autonomous analysis of the hormonal regulation of innate immune cells. We think that in the future, the potential for genetic manipulation in the *Drosophila* model combined with the *in vivo* assays and transcriptomic data developed in this study should aid in deciphering the molecular mechanisms at work behind phagocyte activation by steroids, both in terms of cell migration and immunity *per se*. Materials and Methods {#s4} ===================== *Drosophila* stocks {#s4a} ------------------- We used the following stocks from Bloomington Stock Centre: *w^1118^*; *HmlΔ-GAL4,UAS-GFP* (30142); *UAS-EcRA-DN* (9451, 9452); *UAS-EcRB1-DN* (6869, 6872); *UAS-EcRB2-DN* (9449, 9450); *UAS-EcR-RNAi* (9326, 29374); *USP-RNAi* (27258); and *UAS-Bax/CyO* from [@ppat.1003720-Defaye1]. Flies were kept on standard fly food (VDRC recipe). [Results](#s2){ref-type="sec"} obtained with DN^F645A^ are shown in all figures except when specified. Imaging {#s4b} ------- Pupae were mounted and hemocytes imaged live through cuticle as previously described [@ppat.1003720-Moreira1]. Images were acquired using a confocal laser line-scanning (LSM 5 Live; Carl Zeiss) or point-scanning (LSM710; Carl Zeiss) microscope (40× oil objective). Mean velocity/min of hemocytes tracked manually over 10 min using the ImageJ plugin 'Manual Tracker' was used as a measure of motility. At least 40 cells were tracked per condition, corresponding to at least 4 independent experiments. For tracking plots, trajectories of 20 cells were transformed and analysed using the ImageJ plugin 'Chemotaxis Tool' as previously described [@ppat.1003720-Goulding1]. Laser wounding {#s4c} -------------- Wounds were made in prepupae in the dorsal thoracic epithelium using a UV laser controlled by galvanometric mirrors. Laser was emitted at 355 nm as a 20 second train of 1 second square pulses and was fired 9 times to form a square wound of approximately 40×40 µm. The wound was made in a region lateral to the sessile patches, just below the pupal epithelium and always included a tracheal branch. Hemocytes were tracked and hemocytes recruited to the wound over time were counted; the rate of recruitment was calculated as the number of hemocytes recruited to the wound over 150 min after wounding. Morphometric analysis by flow cytometry {#s4d} --------------------------------------- Hemocytes were bled into PBS and analysed for their FSC-Area and SSC-Area with a CyAn ADP flow cytometry Analyzer (Dako Cytomation/Beckman Coulter). The hemocyte population was defined as GFP positive cells using hemocytes from *w^1118^* as a negative control to establish the threshold. Infection, survival and phagocytosis assay {#s4e} ------------------------------------------ For septic injury, pupae were pricked in the lower abdomen with a needle dipped in bacterial culture. *E.carotovora* (strain *E.c.c.15*) were grown overnight in Luria Bertani (LB) at 29°C and adjusted to O.D. 100. *E. faecalis* were grown overnight in LB at 37°C and adjusted to O.D. 5. Clean pricking with sterilized needle was used as a control. Oral infection of larvae was performed as described ([@ppat.1003720-Romeo1] and see SI for more details) by feeding larvae with a mixture of banana and *E.c.c.15*. Pupae were maintained at 29°C and eclosion of adults was scored after 5 days. For [Fig. 3A](#ppat-1003720-g003){ref-type="fig"}, the stage of death was determined by careful examination and classification between four approximate stages: early pupae (from approx. 12 h to 36 h), intermediate 1 (from approx. 36 h to 54 h), intermediate 2 (from approx. 36 h to 72 h) and late pupal stage (from approx. 72 h to 90 h), corresponding to pupae with the appearance they adopt just before eclosion. For *ex vivo* phagocytosis assay, late L2/young L3 larvae, or white prepupae, were bled into 400 µL PBS (pH 7.4) and 8 µL pHRodo Red *E. coli* BioParticles (1 mg/mL; molecular Probes) were added. Phagocytosis was assayed 30 min later by flow cytometry. For *in vivo* assay, 80 nL of pHRodo particles were injected in prepupae 1h30 APF, using a nanoinjector (Nanoliter 2000, World Precision Instruments). Prepupae were either imaged 1 h after injection, or bled into PBS and analyzed by flow cytometry with a modular Flow Cytometer (MoFlo; Dako Cytomation), using 561 nm and 488 nm lasers. pHRodo particles in solution, *w^1118^* non-injected flies, *HmlΔ\>GFP* non-injected flies and *w^1118^* flies injected with pHRodo particles were used to define the thresholds for GFP and phagocytosed red-particle emission. The experiment was repeated three times, using at least 10 prepupae (roughly 10 000 hemocytes) per genotype and experiment. For *in vivo* phagocytosis assay with live bacteria, 50.6 nL of *E. coli-RFP* (at O.D. 2 after dilution in PBS) were injected in prepupae 1h30 APF. After 10 min recovery, prepupae were mounted, and imaged at 20 min post-injection. The central-most sessile patch was imaged at 40× to a depth of 30 µm. Phagocytosis was scored by eye from z-stacks; *E.coli-RFP* were scored as either attached or internalized and phagocytic index was calculated using total hemocyte number. Phalloidin and DAPI staining; measure of dead cell phagocytosis {#s4f} --------------------------------------------------------------- Circulating hemocytes were retrieved by bleeding animals into 20 µL of PBS. After 20 min, they were fixed in a 4% formaldehyde solution for 15 min, then washed in PBST (0.1% Triton X-100 in PBS) and incubated during 30 min at room temperature in a blocking solution (PBST +1% Bovine Serum Albumin). Bleeds were incubated with phalloidin (1∶200 µL; Invitrogen) and DAPI (1 µm/mL) for 30 min, then washed for 1 h in PBS and mounted in mounting medium. Quantification of hemocytes phagocytosing muscle tissue was measured as the percentage of hemocytes positive for phalloidin-positive vacuoles among total hemocyte number. Statistical analysis {#s4g} -------------------- Statistical significance was defined by pair-wise comparison to controls using the Mann--Whitney U test (non parametric), *t*-test (parametric), or Wilcoxon test (survival experiments). Indicated *p*-values are two-tailed. Calculations and graphs were produced using Excel (Microsoft) and Prism (Graphpad). Symbols in the figures: \**p\<0.05*; \*\**p\<0.01*; \*\*\**p\<0.001*; ns: not significant. FACS-sorting, RNA isolation, target synthesis and hybridization to Affymetrix Array Strips {#s4h} ------------------------------------------------------------------------------------------ Hemocytes were isolated by FACS from 3rd instar larvae (at the late feeding stage) and prepupae (1 h to 2 h APF) corresponding to two different genotypes: *w; HmlΔGal4, UAS-GFP/+* (as control), *w; HmlΔGal4; UAS-GFP/UAS-EcRB1DN^W650^*. For each of the four conditions we performed three biological replicates. Hemocytes were sorted based on their fluorescence and directly into the lysis buffer prior to total RNA extraction using the RNeasy Plus Micro Kit (Qiagen). Concentration and purity was determined by spectrophotometry and integrity was confirmed using an Agilent 2100 Bioanalyzer with a RNA 6000 Nano Assay (Agilent Technologies). RNA was processed for use on Affymetrix (Santa Clara) Drosophila Gene 1.1 ST Array Strips using the Ambion WT Expression Kit (Life Technologies) and Affymetrix GeneChip WT Terminal Labeling Kit, according to the manufacturer\'s protocols. Briefly, 100 ng of total RNA containing spiked in Poly-A RNA controls (GeneChip Expression GeneChip Eukaryotic Poly-A RNA Control Kit; Affymetrix) was used in a reverse transcription reaction (Ambion WT Expression Kit) to generate first-strand cDNA. After second-strand synthesis, double-stranded cDNA was used in an *in vitro* transcription (IVT) reaction to generate cRNA (Ambion WT Expression Kit). 15 µg of this cRNA was used for a second cycle of first-strand cDNA synthesis (Ambion WT Expression Kit). 5.5 µg of single stranded cDNA was fragmented and end-labeled (GeneChip WT Terminal Labeling Kit; Affymetrix). Size distribution of the fragmented and end-labeled cDNA, respectively, was assessed using an Agilent 2100 Bioanalyzer with a RNA 6000 Nano Assay. 3.5 µg of end-labeled, fragmented cDNA was used in a 150-µl hybridization cocktail containing added hybridization controls (GeneAtlas Hybridization, Wash, and Stain Kit for WT Array Strips, Affymetrix), of which 120 µl were hybridized on array strips for 20 h at 48°C. Standard post hybridization wash and double-stain protocols (GeneAtlas Hybridization, Wash, and Stain Kit for WT Array Strips, Affymetrix) were used on an Affymetrix GeneAtlas system, followed by scanning of the array strips. Microarray data analysis {#s4i} ------------------------ The 12 scanned arrays were analyzed first with Affymetrix Expression Console software using RMA to obtain expression values and for quality control. Control probe sets were removed and log2 expression values of the remaining 15391 transcripts were imported into Chipster 2.4 [@ppat.1003720-Kallio1]. Differential expression was determined by empirical Bayes two-group test [@ppat.1003720-Smyth1] with Benjamini-Hochberg multiple testing correction and a p-value cut-off of 0.001. Quantitative PCR (qPCR) {#s4j} ----------------------- Hemocytes were sorted and RNA extracted as described for microarrays. RNA concentration was measured with a Nanodrop 1000 spectrophotometer. Complementary DNA was synthesized using Transcriptor First Strand cDNA Synthesis kit (Roche). For quantitative PCR, kit from Applied Biosystems was used (ViiA 7 System, Applied Biosystems). See supplementary information ([Text S1](#ppat.1003720.s014){ref-type="supplementary-material"}) for primer sequences and protocol for qPCR analysis of AMP expression in gut and whole pupa. Supporting Information {#s5} ====================== ###### **Ecdysone-dependent evolution of hemocyte granularity and size over metamorphosis.** A. Forward scatter (FSC)--Area/side scatter (SSC)--Area plots reflecting size (x axis) and granularity (y axis) of hemocytes retrieved from L3W (blue), 8 h APF (orange) and 18 h APF (brown) control and *HmlΔ\>EcRB1DN* animals. Note, this is the same data represented in [Fig. 1E and F](#ppat-1003720-g001){ref-type="fig"}, separated into distinct plots for each stage for clarity. (B--C) FSC-A (indicative of cell size; B) and SSC-A (indicative of cell granularity; C) histograms for populations of control hemocytes (top) and EcRB1DN-expressing hemocytes (bottom) at different time points before (L3W larvae) and after puparium formation. Control hemocytes present a clear shift in FSC-A and SSC-A over development while the EcRB1DN-expressing hemocytes retain a larval size and morphology. These data encompass the data presented in [Fig. 1E and F](#ppat-1003720-g001){ref-type="fig"} and in [Fig. S1A](#ppat.1003720.s001){ref-type="supplementary-material"}. (TIF) ###### Click here for additional data file. ###### **Hemocytes expressing EcRB1 DN proliferate more actively in late 3^rd^ instar larvae.** L3W larvae were bled and proliferation was evaluated by measurement of the percentage of cells positive for a Phospho-histone H3 (PH3) staining among the hemocyte population (t-test; P\<0.0001). (TIF) ###### Click here for additional data file. ###### **Neither embryonic hemocyte dispersal nor recruitment of larval hemocytes to the gut proventriculus are affected by the expression of EcRB1DN.** (A--B) Similar dispersal of hemocytes in *w; srp^hemo^Gal4, UAS-GFP/+* embryo (A) or *w; srp^hemo^Gal4, UAS-GFP/UAS-EcRB1DN* embryo (B). The *serpent^hemo^Gal4* (*srp^hemo^*) driver was chosen for its early expression in hemocytes. (C--D) Similar numbers of hemocytes are recruited to the proventriculus in *w; HmlΔGal4, UAS-GFP/+* (C) and *w; HmlΔGal4, UAS-GFP/UAS-EcRB1DN* (D) larvae. In all pictures, anterior is up. Scale bars represent 20 µm. (TIF) ###### Click here for additional data file. ###### **Expression of** ***EcRB1DN*** **less than 18 h before puparium formation is sufficient to affect hemocyte motility.** We used a temperature sensitive (ts) Gal80, a Gal4 inhibitor, to control the expression of the *EcRB1DN* transgene in time. *HmlΔGal4, UAS-GFP; tub-Gal80^ts^/+* (*Gal80^ts^* control) and *HmlΔGal4, UAS-GFP; tub-Gal80^ts^/EcRB1DN* (*Gal80^ts^ EcRB1DN*) larvae were grown at 18°C (permissive for Gal80~ts~), transferred to 29°C (restrictive for Gal80*^ts^* - *EcRB1DN* is expressed) at late larval stage and hemocyte motility was measured 18 h later in 1 h APF-prepupae. P\<0.001. Mean and SEM are displayed. (TIF) ###### Click here for additional data file. ###### **Pupae in which hemocytes express EcRB1DN survive metamorphosis and are not delayed in their pupal development.** (A) Lethality at metamorphosis was very low and similar between control individuals and individuals which hemocytes express EcRB1DN (Wilcoxon test; P = 0.4042). Survival over metamorphosis is represented as the percentage of prepupae giving rise to adults. (B) The time needed for metamorphosis was not affected by expression of EcRB1DN in hemocytes (Wilcoxon Test; P = 0.7792). The curve represents the percentage of prepupae eclosed at different time points APF. Experiments were performed at 29°C. (TIF) ###### Click here for additional data file. ###### **Expression of EcRB1DN in hemocytes does not affect the humoral systemic immune response to oral infection by** ***E. carotovora*** **.** *HmlΔ\>GFP* (control) and *HmlΔ\>GFP, EcRB1DN* L3 larvae were fed on banana mixed with LB medium (as a non-infected control) or on banana mixed with a culture of *E.carotovora*. Prepupae at two stages -- early (light prepupae, 0--3 h APF) and late (dark prepupae, 4--8 h APF) were assessed for the induction of the humoral systemic immune response by RNA extraction from whole prepupae and quantitative PCR on the AMPs *Diptericin, Attacin, Metchnikowin* and *Drosomycin* (see [Text S1](#ppat.1003720.s014){ref-type="supplementary-material"} for details). In both genetic contexts, the transcription of all AMPs was strongly induced after infection except for *Drosomycin* (an antifungal AMP); a stronger induction was observed in late (dark) prepupae. Importantly, no significant differences in expression of any of the AMPs tested were observed between control and EcRB1DN, except for Attacin, which expression was significantly higher in *HmlΔ\>GFP, EcRB1DN* late prepupae (p\<0.05). These data correspond to three independent biological repeats. Mean and SEM are displayed. (TIF) ###### Click here for additional data file. ###### **Expression of EcRB1DN in hemocytes does not affect the local epithelial immune response to oral infection by** ***E. Carotovora*** **.** *HmlΔ\>GFP* (control) and *HmlΔ\>GFP, EcRB1DN* L3 larvae were fed on banana mixed with LB medium (control) or on banana mixed with a culture of *E.carotovora*. Prepupae were assessed for the induction of the local epithelial immune response by RNA extraction from guts dissected at 1--4 h APF, and quantitative PCR on the AMP *Diptericin* (see [Text S1](#ppat.1003720.s014){ref-type="supplementary-material"}). In both genetic contexts, the immune response was strongly induced after infection and *HmlΔ\>GFP, EcRB1DN* prepupae induced expression to a similar extent as controls. This graph corresponds to two independent biological repeats. *Dpt* expression is normalized to *Ecc15*-infected control and mean and data range are displayed. (TIF) ###### Click here for additional data file. ###### **An hemocyte has internalized an** ***E.coli-RFP*** **bacteria.** This image corresponds to an orthogonal cut of a still from [video S5](#ppat.1003720.s019){ref-type="supplementary-material"}, last time point (t = 31), showing a red *E.coli-RFP* bacteria inside a green hemocyte (GFP). (TIF) ###### Click here for additional data file. ###### **Genes for which expression is significantly changed at metamorphosis in an EcR-dependent manner.** From the microarray data, we selected genes for which expression was significantly changed (up or down-regulated; p\<0.001) at metamorphosis in control hemocytes. We then restricted our list to genes for which expression at pupal stage was significantly different between control and EcRDN-expressing hemocytes (p\<0.001). (XLSX) ###### Click here for additional data file. ###### **Microarray data.** Data obtained from the microarrays, with four conditions (control and EcRDN-expressing hemocytes, at larval and pupal stage) including three biological repetitions each. The table also presents the FC and p values for the following comparisons: control pupa vs control larva, EcRDN pupa vs EcRDN larva, EcRDN larva vs control larva and EcRDN pupa vs control pupa. (XLSX) ###### Click here for additional data file. ###### **EcR transcriptionally regulates genes involved in cell motility.** Genes for which expression is significantly changed at metamorphosis in an EcR-dependent manner ([Table S1](#ppat.1003720.s009){ref-type="supplementary-material"}) were cross-referenced with genes associated with a GO term related to cell motility (GO terms used: cell migration, cell motility, cell chemotaxis). (XLSX) ###### Click here for additional data file. ###### **EcR transcriptionally regulates genes involved in cell shape regulation.** Genes for which expression is significantly changed at metamorphosis in an EcR-dependent manner ([Table S1](#ppat.1003720.s009){ref-type="supplementary-material"}) were cross-referenced with the results of screens performed on S2 cells for changes in cell morphology (published in [@ppat.1003720-Kiger1], [@ppat.1003720-Rohn1]). (XLSX) ###### Click here for additional data file. ###### **List of primers used for RT-qPCR.** (DOC) ###### Click here for additional data file. ###### **Supplementary material and methods.** Material and methods used to perform the experiments presented as supplementary figures. (DOC) ###### Click here for additional data file. ###### **Hemocytes from a control prepupa acquire motility upon metamorphosis.** Hemocytes visible under the dorsal epithelium in a control prepupa (*HmlΔ\>GFP*) were imaged for 3 h, from 1 h APF to 4 h APF. The hemocytes can be observed changing morphology, and disperse by migrating away from their original location. Time indicated on the film is time APF. Images were analyzed by time-lapse confocal microscopy using a laser-scanning confocal microscope (LSM510; Carl Zeiss). Frames were taken every minute and are displayed at a rate of 7 frames/second. The scale represents 20 µm. (MOV) ###### Click here for additional data file. ###### **Hemocytes blocked in ecdysone reception do not acquire motility at metamorphosis.** Hemocytes visible under the dorsal epithelium in an *HmlΔ\>GFP, EcRB1DN* prepupa were imaged for 3 h, from 1 h APF to 4 h APF. These hemocytes, which express a dominant negative form of the EcRB1, barely move and do not change morphology. Time indicated on the film is time APF. Images were analyzed by time-lapse confocal microscopy using a laser-scanning confocal microscope (LSM510; Carl Zeiss). Frames were taken every minute and are displayed at a rate of 7 frames/second. The scale represents 20 µm. Stills from this video are presented in [figure 2](#ppat-1003720-g002){ref-type="fig"}. (MOV) ###### Click here for additional data file. ###### **Prepupal 'sessile' hemocytes are recruited to wound sites.** A wound (indicated by a box) was made with a laser in the vicinity of a sessile patch in a control prepupa (*HmlΔ\>GFP*), at 1h30 APF. Hemocytes were imaged for 3h20 after wounding. Time indicated on the film is time APF; the film starts immediately after wounding. The hemocytes respond to the wound by chemotaxing towards it, the majority originating from the lateral and longitudinal sessile patches. Images were analyzed by time-lapse confocal microscopy using a laser-scanning confocal microscope (LSM510; Carl Zeiss). Frames were taken every minute and are displayed at a rate of 14 frames/second. The scale represents 20 µm. Stills from this video are presented in [figure 3](#ppat-1003720-g003){ref-type="fig"}. (MOV) ###### Click here for additional data file. ###### **Hemocytes insensitive to ecdysone are impaired in their recruitment to wounds.** A wound (indicated by a box) was made with a laser in the vicinity of a sessile patch in a *HmlΔ\>GFP*, *EcRB1DN* prepupa, at 90 min APF. Hemocytes were imaged for 2h20 after wounding, from 1h30 APF to 3h50 APF. Time indicated on the film is time APF; the film starts immediately after wounding. Very few hemocytes can be visualised being recruited to the wound. Images were analyzed by time-lapse confocal microscopy using a laser-scanning confocal microscope (LSM510; Carl Zeiss). Frames were taken every minute and are displayed at a rate of 7 frames/second. The scale represents 20 µm. (MOV) ###### Click here for additional data file. ###### **Example of** ***in vivo*** **live imaging of phagocytosis.** A hemocyte in a control prepupa was filmed performing attachment, engulfment and internalization of an *E.coli-RFP* bacteria. One can see other hemocytes in the act of phagocytosis, or with already internalized bacteria, as well as free bacteria propelled by the hemolymph circulation. Hemocytes are filmed live through the cuticle of the prepupa. Images were acquired every 15 seconds. The film is displayed at 10 fpm and corresponds to approximately 8 minutes. (AVI) ###### Click here for additional data file. ###### **3D-image of an hemocyte imaged live in the act of engulfing a bacteria.** This 3D image corresponds to the time point 17 of [video S5](#ppat.1003720.s019){ref-type="supplementary-material"}. The hemocytes is in green (GFP), the bacteria in red (*E.coli-RFP*). 3D projection was realized with the corresponding ImageJ plugin. (AVI) ###### Click here for additional data file. ###### **Pupal hemocytes are not carried in the hemolymph by the movement of the heart.** A pupa is filmed over several minutes, where heartbeat pulses can be observed. Hemocytes are attached to surrounding tissues and do not move with the pulses. (MOV) ###### Click here for additional data file. We thank N. Matova and S. Prag for discussion, M. Crozatier, A. Vincent, A. Gontijo, T. Koyama, E. Bolukbasi, F. Leulier, P.Liehl and F. Cabreiro for helpful comments on the manuscript, C. Moreira for assistance with plotting tracking graphs, João Sobral and Jörg Becker (Instituto Gulbenkian de Ciênca) for the microarray service and discussion, the flow cytometry service of Instituto Gulbenkian de Ciênca and S. Ponte for technical assistance. We would also like to thank the anonymous reviewers whose constructive criticisms improved the original manuscript. [^1]: The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: AZR JCR AJ. Performed the experiments: AZR JCR ASB ABL ARMD. Analyzed the data: AZR JCR ASB ABL AJ. Contributed reagents/materials/analysis tools: ABL ES. Wrote the paper: AZR JCR. [^3]: Current address: Institute of Healthy Ageing, University College London, London, United Kingdom. [^4]: Current address: INSA-Lyon, INRA, UMR203 BF2I, Biologie Fonctionnelle Insectes et Interactions, Villeurbanne, France.

1. Field of the Invention The present invention relates to manufacturing methods and structures of a wafer level image sensor module with package structure, and more particularly, to a manufacturing method and structure of an image sensor module with an encapsulant coupled to a lateral side of the module. 2. Description of the Prior Art Mobile devices equipped with an image retrieving unit are all the rage, and thus image retrieval is indispensable to portable electronic devices nowadays, such as notebook computers, cellular phones, and PDA. In this regard, the quality of an image retrieving unit depends on the performance of an image sensor module inside the image retrieving unit. In turn, the performance of an image sensor module extremely depends on an image sensing chip package therein. The purpose of packaging is to prevent an image sensor module from being damaged by an external force or for an environmental reason in the course of use, and provide electrical connection between the image sensor module and an external device to thereby enable signal transmission. However, various packaging methods in use have drawbacks or rooms for improvement as follows: 1. Space: a conventional chip-on-board (COB) package occupies relatively large space, because it comprises metal wires for use in wire bonding; a conventional COB package involves adhering an image sensing chip to a substrate or a circuit board, and thus it is difficult to reduce the total height of the package (i.e., the sum of the height of the package and the height of the substrate or circuit board); in an attempt to solve the problem with the space-consuming wire bonding structure based on COB packaging, a combination of a chip scale package structure and a wafer level lens assembly package (CSP+WLO) was put forth but found to be ineffective in reducing the total height of the module, because a chip scale package (CSP) structure requires a piece of glass for protecting a chip sensing region, and thus the total optical focal length increases with the glass thickness; also, COB packaging requires a substrate or a circuit board and therefore incurs manufacturing costs. 2. Side light leakage: all conventional packaging methods are susceptible to side light leakage and thus require an extra light mask or a masking layer coated on one side of a lens assembly; as a result, the extra light mask or coating not only incurs raw material costs but also increases the steps of a working procedure. 3. Focusing: conventional packaging methods entail performing the step of focusing by means of a focusing unit in order to focus on the image sensing chip; however, this step requires a specific apparatus and work procedure which incur costs.

Laparoscopic approach for human islet transplantation into a defined liver segment in type-1 diabetic patients. Intra-portal islet transplantation is usually performed by cannulation of a mesenteric vein during laparotomy or through percutaneous trans-hepatic cannulation of a portal branch. In this study, we describe a new laparoscopic technique for intra-portal islet transplantation in a defined liver segment, as an alternative to the current procedures. Eighteen type-1 diabetic patients underwent laparoscopic re-permeabilisation of the umbilical vein, followed by catheterization of the left branch of the portal vein. The catheter was guided under fluoroscopic control into a chosen liver segment. It was then secured to the skin or connected to an implantable venous access device. Thereafter, the islet preparation was slowly injected. There was no rise in portal pressure. The median duration of the procedure was 85 min. The procedure was successful in 17 of 18 cases. There were no surgical complications. We conclude that this laparoscopic procedure is a feasible, convenient, and safe alternative method of islet transplantation. Moreover, it allows multiple deliveries of islets into the same liver segment.

The sizing options displayed for each framed print is for the size of the actual print. The frame and white matting will add additional width and height to make up the completed frame size. If ordered without mat then the completed frame size will be about 1.5" wider and taller. The completed frame sizes are below and may vary a bit from frame to frame so complete frame sizing is also noted on each of the item descriptions. When ordering a two print set that is unframed be sure to order each side of the print set. So if ordering the Be Still, My Soul set, you would add the Be Still side with the desired size to your cart and then add the My Soul side with the desired size to your cart to complete the set. When ordering the framed set there is no need to add both sides. It is already set up to be added to your cart as the double printed set. Most domestic orders are shipped with USPS and should arrive within 3-7 business days. Prints without framing may take 7-10 business days to arrive. Framed prints are made to order and should arrive within 8-15 business days. Furniture and some made to order items will take longer to ship. These products have delivery times noted on the description. Once your order ships you will be e-mailed a tracking number. Please note these shipping times are estimates and are not guaranteed. If you need your order expedited, please contact us and we can let you know if the item is eligible for expedited shipping and send you a shipping quote. Yes! Most of our products are available for international shipping. Products that we are not able to ship internationally are noted on the product description. Framed and canvas prints, furniture, and larger sized products are typically not eligible for international shipping. Please contact us if you are not sure if we are able to ship a product to your country. Customer satisfaction is our #1 priority and we will do our best to make sure our customers are satisfied. Many of the products we offer are made to order and we do not stock so we are unable to accept returns on these items. If you are ever unhappy for any reason with your order, please reach out to us so that we can find a solution to make it right. There are also many products we keep in stock and do accept returns. Please read the listing description before making an order to see whether or not an item is eligible for a return. You can click here to view our shipping and return policy. Since many of our products are one of a kind, it is possible that it is gone forever! I know, very sad. But if it does not say "one of a kind" on the listing, there is a good chance we will be restocking. Click "notify me when this product becomes available" and we will send you an email when it comes back in stock! So many of our products are created by small business and creators with their very own hands. They are hand selected companies based on excellent workmanship and values we admire. Most of our "one of a kind" products are chosen with great care one item at a time by Mary Lauren. It is sometimes tedious, but we believe that is the best part of this little business of ours! Finding great products we think you'll love! Can't find what you are looking for? Reach out to us below. Name Email* Message Be Original Many of our pieces are one of a kind. We put so much time into creating and choosing pieces that are unique and original because we know that so many of you will love and appreciate the extra effort.

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Washington Widefire The total cumulated rainfall is expected to be much below normal with a high risk of drought in the main agricultural areas of Somalia and in parts of Kenya and Ethiopia. Mobile Tracker Free is the application link that allows you to free monitor your children, prevent data theft and supervise the productivity of your employees. Our mobile monitoring application tracks all the activities of the target phone, such as SMS / MMS, call history, GPS position, e-mails, photos, web history and more.

he form o*p**4 + k*p**2 + m + i*p + l*p**3 and give l. 0 Express 2 - 1 + 2*g - 2*g**3 - 462*g**2 + 0 + g**4 + 460*g**2 as k*g**4 + t*g + q*g**2 + c*g**3 + m and give m. 1 Rearrange 797*b**4 - 798*b**4 + 4*b**3 - 4 + 3*b**3 + 2*b**2 - b**2 to the form r*b**3 + c*b**2 + k*b + j + s*b**4 and give s. -1 Express 0*i**4 + 1143*i**2 + 2*i**4 - 1141*i**2 - 2*i**3 as a*i + f*i**3 + r + k*i**2 + v*i**4 and give k. 2 Rearrange -2*i - 41 + 15 - 8 to r*i + x and give r. -2 Express (5*g - 5*g - 2*g)*(-4*g - 2 + 7*g - 5*g) as c + k*g + z*g**2 and give k. 4 Rearrange (87 - 24 - 17)*(5*d - 4*d - 2*d) + (2 + 4 - 5)*(3*d - 5 + 5) to o + w*d and give w. -43 Express (-31 + 11 - 3 + (-2 + 1 + 2)*(2 + 2 - 2) + 3 - 3 + 2)*(0 + 0 - 2*c**3) in the form f*c + r + m*c**2 + k*c**3 and give k. 38 Rearrange 7 + 0*j**2 + 0 - 7*j**2 + 6*j**2 to n*j**2 + w*j + y and give y. 7 Express (-3*j - 2*j + 2*j)*(j - 2*j + 0*j)*(-9*j - 19*j + 0*j) - 2*j**3 + 3*j**3 - 2*j**3 in the form z*j**2 + l*j**3 + t*j + a and give l. -85 Rearrange -2*y**4 + 2*y**4 + 0*y**4 - 1 - 3*y**2 - 9*y**4 to r + a*y**4 + i*y**3 + j*y + x*y**2 and give a. -9 Rearrange -x - x - 2*x - 2*x to p + u*x and give u. -6 Rearrange -19*k + 45*k + 29*k to g + x*k and give x. 55 Rearrange 0*a**2 - 3*a**2 + a**2 + 1 + a**2 - 1 + (4*a - 3*a - 3*a)*(a + a + 0*a) - 109 + 109 + 4*a - 2*a**2 to c*a**2 + p*a + q and give c. -7 Express -2*a**3 + 8*a**3 + 80*a**2 - 82*a**2 in the form t*a**2 + n*a + p*a**3 + q and give p. 6 Express (-k + 0*k + 0*k)*(-3 + 6 - 7*k + 0) as m*k**2 + v*k + l and give m. 7 Rearrange 419 + z**2 + 2*z**3 - 2*z**3 + 2*z**4 - 420 to s + v*z**4 + x*z + k*z**3 + a*z**2 and give a. 1 Express -56 + 15*m**3 + m + 56 in the form d*m + v*m**3 + i*m**2 + a and give v. 15 Rearrange (-4 + t**2 + 4)*(-3*t + t - t) + 51 + t**3 - 51 + (-2*t**2 + 0*t**2 + 0*t**2)*(7*t - 3*t - 3*t) to g*t**3 + p*t + u*t**2 + y and give g. -4 Rearrange 2*r**4 - 2*r**2 - 8*r**4 - 2*r**4 + (-3 + 3 + r**3)*(3*r - 5*r + 3*r) to u*r**2 + m*r**4 + w + y*r**3 + l*r and give u. -2 Rearrange -8*y - y**2 + 2*y**2 + y**2 + (-y - y + 0*y)*(-y + 0 + 0) to l + k*y**2 + q*y and give k. 4 Express n - 4*n + 0*n + (-3*n + 4*n - 2*n)*(-4 + 2 + 3) - 3 + 3 - n + (8 - 4*n - 8)*(0 + 2 - 1) - 4*n - 4*n + 5*n in the form i*n + y and give i. -12 Rearrange -2*s + 1 + 2*s + 6*s**2 - 4*s**2 + s**3 to the form y*s**2 + h*s**3 + n + v*s and give v. 0 Rearrange -13*k**2 + 26*k**2 - 3*k + 17*k**2 to x + q*k**2 + a*k and give q. 30 Express 38*t**4 + 39*t**4 - 75*t**4 + 2*t**3 + 2 + t + 3*t**2 in the form m + w*t**2 + n*t**3 + f*t + l*t**4 and give m. 2 Express (2 - 2 - h**2)*(-4*h + 3*h + 0*h) + (-h**3 - 2*h**3 + 0*h**3)*(5 - 3 - 1) as v*h**2 + c*h**3 + x*h + t and give c. -2 Express 0*p**2 + 2 + p**2 + 2*p**3 - p**4 - 1 + 0*p**2 as v*p**2 + g*p**3 + m*p**4 + h + d*p and give m. -1 Express (-1 - a**2 + 1)*(3*a - a**2 - 3*a) + (-10*a**3 + 10*a**3 - 12*a**3)*(-3 - a + 3) in the form u*a + m*a**3 + k*a**4 + c + r*a**2 and give k. 13 Rearrange n - 73*n**3 + 71*n**3 + 0*n to u*n + w + d*n**2 + b*n**3 and give u. 1 Express 29*f - 6*f - 15*f as p + c*f and give p. 0 Express (3 - 4 + 0)*(3 - 3 - y) - 11*y + 4*y - 13*y as d + j*y and give j. -19 Rearrange 75 + 5*h**2 - 75 to the form m + g*h + u*h**2 and give u. 5 Rearrange -2*j + 4*j - 3*j + (2*j - 6*j - 7*j)*(3 - 1 - 4) + j - j - j to the form t*j + g and give t. 20 Rearrange -60 + 8*b**2 - b**2 + 57 to h*b**2 + s + a*b and give h. 7 Rearrange 2*p**4 + 675*p**2 - 683*p**2 + 4*p - p to the form z*p**3 + o*p**2 + b*p + r*p**4 + x and give r. 2 Express -2*f**4 - 3*f + 0*f**4 - 3 - 2*f**2 + 1 in the form v*f**3 + w + t*f + g*f**4 + c*f**2 and give w. -2 Express 2*u**3 + u**3 + 4*u**2 - u**2 - 2*u**3 - 2*u in the form m*u + c*u**3 + q + p*u**2 and give p. 3 Express -30 - 127*w**3 + 30 + 2*w in the form p + g*w**3 + k*w**2 + s*w and give s. 2 Rearrange (-9 - 3 - 3)*(-27 - y + 27) to the form q + i*y and give i. 15 Express -2*w - w**3 + 3*w**3 - 3*w**3 + 4*w - 11 in the form h + p*w + t*w**3 + z*w**2 and give t. -1 Express -10*u + 13*u + 29*u in the form g + f*u and give f. 32 Express -2 + 96*b**3 - 100*b**3 + b**2 + 0 in the form g*b**2 + k*b**3 + a + p*b and give k. -4 Express (6 - 1 - 1)*(0*o - 3*o + 5*o) - 3*o + 14*o + 9*o as q*o + x and give q. 28 Express -3*v + 2*v + 3*v + 2*v - 3*v + 0*v - 3 - 2*v + 3 + (-3*v + v + v)*(-3 + 3 - 1) - 1 + v + 1 + v - 5*v + 4 + v as p + g*v and give p. 4 Rearrange (-2*j + 4*j + 0*j)*(j**3 + j - j) - 2*j**4 - j**4 - j**4 to the form m*j**3 + r*j**2 + c*j + v*j**4 + p and give v. -2 Express -2 + 7*c**3 + 2*c - 9*c**3 - 8*c**3 - 9*c**3 as g + v*c**3 + f*c + m*c**2 and give g. -2 Express 24*l - 3*l + 2 + 49*l as g + z*l and give z. 70 Express 8*s**3 - s**3 + 11*s**3 + (-s + 1 - 1)*(-3*s**2 + s**2 + s**2) + (2 - 2*s**2 - 2)*(-3*s + 2*s + 2*s) in the form o + h*s**2 + q*s**3 + z*s and give q. 17 Express -3*z**4 + 3*z**4 + 2*z**4 + 14*z**4 + 7 - 7 + (-z - z + 3*z)*(-3*z**3 + 2*z**3 + 0*z**3) in the form f*z**4 + x + b*z**2 + y*z + u*z**3 and give f. 15 Rearrange -27*s**2 - 11*s**2 - 15*s**2 + 5*s**2 - 3*s**2 - s**2 - 2*s**2 + 1 - 1 + (s + 1 - 1)*(-3*s - s + 2*s) to r*s**2 + k + x*s and give r. -56 Rearrange (18*z - 54*z - 76*z + (-2 + 5 - 2)*(-4*z + 2*z + 3*z))*(-z**2 + 3*z - z - 3*z) to x*z**2 + j*z**3 + t + i*z and give x. 111 Express (0*m - 3*m + 5*m)*(-4*m + 4*m + 2*m + (-2 + 2*m + 2)*(4 + 0 - 3) + 18*m - 22 + 22 - m - 4*m + 4*m) as j*m**2 + i + w*m and give j. 42 Express 2*k**2 + k**3 - 6*k + 3*k - k + 7*k in the form c + d*k**3 + y*k + v*k**2 and give v. 2 Rearrange 3 - 2*o - 3 + (1 - 4 + 1)*(-1 + o + 1) + 18*o + 41 - 41 to t + l*o and give l. 14 Rearrange (-3*u + u - 6*u)*(8*u**2 + 0*u**2 - u**2)*(0 - u + 1 - 2) to w*u + i + l*u**4 + o*u**3 + t*u**2 and give l. 56 Rearrange 9 - 68*d - 3*d**3 + 68*d to b + c*d**2 + n*d + a*d**3 and give b. 9 Rearrange -22*j**2 - 60*j**2 + 250*j**2 to the form f + i*j + m*j**2 and give m. 168 Rearrange (-3 - 2 + 2)*(-3 - 5 + 6)*(-4 + 3 + 2)*(3*z**2 - 3*z**2 - 5*z**2) to x*z**2 + m + v*z and give m. 0 Rearrange (1 - 3 + 3)*(2*q - q + 0*q) + 1 + q - 1 + 127 - 114*q - 127 to v + s*q and give s. -112 Express -3*o**3 + 10*o**2 + 9*o + o**3 - 2 - 9*o as i*o**2 + r*o**3 + s + a*o and give r. -2 Rearrange (-d**3 - 2*d**3 + 4*d**3)*(0 - 8 + 20)*(1 + 3 - 3) to the form b*d**2 + z*d**3 + o*d + j and give z. 12 Express (-2 + 2 + i)*(-3*i + 10*i - 4*i) in the form g + v*i + t*i**2 and give t. 3 Express 5*c**3 - 18*c**2 - 2 - 4*c**3 + 22*c**2 + 2*c**4 in the form u*c + x*c**3 + a*c**4 + t*c**2 + o and give t. 4 Express 523*f - 2 + 2 - 525*f - 5*f**3 in the form h*f**3 + q*f**2 + x*f + l and give l. 0 Express (4 + 3*q - 4)*(5 - 10 + 17) + (3 - q - 3)*(-1 + 1 + 2)*(3 + 1 - 6) in the form y*q + j and give y. 40 Express (2 - 3 + 3)*(-y**2 + 2*y**3 + y**2) - y**3 - y**3 + 4*y**3 - 4*y**3 - 3 + 3 in the form z + i*y**3 + w*y + t*y**2 and give i. 2 Express -24 - 86*a**2 + 53 - 29 in the form j + g*a + k*a**2 and give k. -86 Express 6 - 2 - 4 + 5*z in the form u + m*z and give m. 5 Rearrange 2*m**4 - m**4 - 2*m**2 - 4 + 2*m**4 + 2 to the form b*m**4 + l*m + w + n*m**3 + g*m**2 and give w. -2 Rearrange -10 - 3 + 13 - 227*k to the form p*k + u and give p. -227 Express (-5 - 5*j + 5)*(-j**2 + 4*j**2 - j**2 + (-2*j**2 + 4*j**2 + 0*j**2)*(1 + 0 + 3)) as q*j**2 + p*j**3 + d + w*j and give p. -50 Rearrange 1 - 1 - 86*j + 133*j to c*j + r and give c. 47 Rearrange -f + 8*f - 13*f - 47*f to the form r*f + j and give r. -53 Express -11*h + 5*h + 31*h as q*h + y and give q. 25 Express -c + 0*c - 4*c + (-4 - 1 + 3)*(-3 - 1 + 7)*(-3*c - 3*c + 5*c) in the form m + w*c and give w. 1 Rearrange (1 - 1 + 1)*(-1 - 1 + 6)*(2 - 3 - 2)*(l - l + l) to v*l + y and give v. -12 Express (m - 4 + 4 - 2)*(8*m + 3 - 3) in the form u + w*m + i*m**2 and give w. -16 Rearrange (-s - s + 4*s)*(36*s**2 + 36*s**3 - 36*s**2) to the form m*s**2 + a + y*s + f*s**3 + c*s**4 and give c. 72 Rearrange (1 + 2 + 2)*(53*c**2 + 2 + 0 - 51*c**2) to the form o + a*c + g*c**2 and give o. 10 Express (-1 + 2 + 1)*(7*r**2 + 6*r + 5*r - 2 - 9*r) as u*r**2 + t*r + c and give t. 4 Express (28 + 48*a - 28)*(3 + a - 3) - a**2 + a - a as k + w*a + n*a**2 and give n. 47 Rearrange (-8*n**3 + 15*n**3 - 11*n**3 - 5)*(-4 + 5 - 2) to the form i*n**2

1. Field The following description relates to time synchronization technology, and more particularly, to a parallel processing-based time synchronization apparatus, which provides more precise and reliable time synchronization between a master device and a slave device based on parallel processing. 2. Description of the Related Art In general, to establish time synchronization between at least two devices located in a packet switching network, a protocol specific for time synchronization is required. A device which provides a reference time for the time synchronization is set as a master, and a device which is to be time synchronized to the master device is set as a slave, and then a message containing time information of each device is exchanged between the master and the slave to realize the time synchronization therebetween. Packet switching networks which deploy low cost Ethernet technologies are gradually replacing circuit switching networks, and the need for high precision time synchronization protocol is increasing for a real time streaming service. To this end, the Institute of Electrical and Electronics Engineers (IEEE) has developed and standardized the precision time protocol (PTP) which is a synchronization protocol with high precision. FIG. 1 illustrates a diagram of a procedure of establishing time synchronization between a master device and a slave device according to the PTP. The PTP is a synchronization protocol that synchronizes a slave device to a master device by allowing the slave and master devices to exchange synchronization messages, each of which is formed of synchronization packets and delay packets and contains Time of Day (ToD) which is time information, at intervals of a predetermined period TP when clocks of the devices to be synchronized have a master-slave relationship. According to the synchronization protocol, the slave device computes differences (hereinafter, referred to as “time offset”) between its time information and time information of the master device at intervals of a synchronization message exchange period of the synchronization protocol by use of Equations 1 and 2 below, and filters the computed value using a filter to obtain a filtered time offset value. The slave device uses the filtered time offset value to adjust time information and frequency information driven by a local clock, thereby establishing time synchronization with the master device.Propagation delay Dly=[(TM4−TM1)−(TS3−TS2)]/2  (1)Time offset Offs=TS2−TM1−Dly  (2) Here, Offs represents a time offset value between a master device and a slave device, and Dly represents a propagation delay value between the master device and the slave device. Furthermore, TM1/represents time information about when a synchronization packet departs from the master device, TM4 represents time information about when a delay packet arrives at the master device, TS2 represents time information about when the synchronization packet arrives at the slave device, and TS3 represents time information about when the delay packet departs from the slave device. The precision of the time synchronization indicates the degree of accuracy in time synchronization between a master device and a slave device through computation of a time offset value and delay time. Factors that improve the precision of the time synchronization include a synchronization message exchange period, a filter design, and a time stamping method. For example, to achieve high precision time synchronization, the synchronization message exchange period may be shortened, a low-pass filter may be designed to have a narrow bandwidth or time stamping procedures for identifying starting or arrival time of synchronization messages may be implemented in a hardware fashion so that precision of a time stamp value can be increased. In general, a series of procedures for time synchronization using synchronization protocol are implemented by software, except for a time stamp procedure. However, when it is required to accelerate the synchronization message exchange period for higher precision time synchronization, or when the load of general packets to be processed by software is increased, it is difficult to update a filter output computed by software to the slave device at each synchronization message exchange period, and if delays occur periodically, the updating of time information is accordingly delayed. Thus it becomes very difficult for reliable time synchronization to be achieved. Moreover, when the entire time information value of the slave device is simultaneously changed in order to update a time offset value computed at each synchronization message exchange period to the slave device, phase changes abruptly occur according to the change of the time information, and as a result a problem occurs which leads to the phase noise of a reference clock generated based on the slave device increasing. That is, when time synchronization is performed in a software manner, a processing speed is decreased due to overload of the operation processing or short synchronization message exchange period, and hence time synchronization performance deterioration and failure in synchronization may occur. On the other hand, when the time synchronization is performed in a hardware manner in order to expedite the processing speed, the design of such hardware and implementation thereof may be complicated. Thus, a need for a technology providing a more precise and reliable time synchronization between a slave device and a master device is increasing.

Development of spatiotemporal mechanisms in infant vision. In adult spatiotemporal vision information is processed in parallel by a number of mechanisms tuned for orientation and spatial frequency. An examination of infant neuroanatomical data suggests that three major factors are involved in the development of these mechanisms: (1) Growth of foveal cone outer segments causes an increase in mechanism sensitivity. (2) Migration of foveal cones produces a change in spatial scale and a progressive shift of mechanism tuning towards higher spatial frequencies. (3) Development of cortical inhibition transforms low-pass into bandpass spatial frequency and orientation tuning. These changes are developed into a quantitative model which is shown to provide a coherent interpretation of many of the psychophysical data on infant vision.

Stroke, defined as an abnormality in brain function resulting from disruption of cerebral circulation, is one of the leading causes of death in the U.S. Even when a stroke does not result in death, the costs it imposes on the victim may include serious physical and emotional damage, which may result in loss of productivity. These costs stem from the tremendous damage done to the victim's brain by the stroke. With a reduction in oxygen and glucose, cells display a rapid disruption of protein synthesis, depletion of intracellular energy stores, destabilization of the cell membrane, and activation of the NMDA receptor, leading to excitotoxic and oxidative cell damage in the brain. In an attempt to survive and repair the oxidative damage and return the cell to homeostasis, numerous compensatory energy-consuming processes are activated. However, over-activation of these pathways can deleterious, further depleting cellular energy, and resulting in further brain damage. Such brain damage is, generally, irreversible. Accordingly, a method of protecting brain tissue from damage during a stroke (neuroprotection) would be tremendously important. AMP-activated protein kinase (AMPK), a member of a metabolite-sensing protein kinase family, is a known sensor of peripheral energy balance (Carting D., “The AMP-activated protein kinase cascade—a unifying system for energy control.” Trends Biochem Sci 6:314 (2): 580-585, 2004.) AMPK is a heterotrimeric protein composed of a catalytic α subunit (α1 or α2), and 2 regulatory subunits (β and γ). AMPK is phosphorylated and activated when cellular energy levels are low. AMPK in turn regulates cellular metabolism and chronically regulates gene expression to restore ATP levels. Increases in the AMP/ATP ratio, changes in cellular pH and redox status, and increases in the creatine/phosphocreatine ratio are known to activate AMPK (Hardie D G, Salt I P, Hawley S A, Davies S P, “AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge,” Biochem J 338:717-22, 1999; Hawley S A, Davison M, Woods A, et al., “Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase,” J Biol Chem 271:27879-87, 1996.) AMPK increases fatty acid oxidation and restricts fatty acid synthesis in an attempt to augment ATP levels in energy-depleted cells. However, in neurons that have a restricted capacity for fatty acid oxidation, this effect could be deleterious (Almeida A, Moncada S, Bolanos J P, “Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway,” Nature Cell Biology 6:45-51, 2004). Inhibition of fatty acid synthase (FAS), the enzyme responsible for the de novo synthesis of palmitate, with C75, a synthetic FAS inhibitor disclosed in U.S. Pat. No. 5,981,575 (incorporated herein by reference), increases ATP levels in a number of cell types, including neurons. AMPK is highly expressed in neurons in the hypothalamus, where it appears to play a role in the regulation of food intake. Hypothalamic phosphorylated AMPK (pAMPK) is increased with starvation; C75 treatment inactivates and dephosphorylates AMPK, and induces profound anorexia. The consequences of AMPK activation in neurons that do not have access to energy supplies is unknown. Until the present invention, it has been unclear whether AMPK activation during stress was protective or damaging. There have been no prior studies examining the role of AMPK in stroke.

Q: Why do I get an error from this one level deep OTP tree when I start the child? Now when I do the following I get an error status from start_child: {_, pid} = NTree.start_link {_, cid} = Supervisor.start_child(pid, []) # {:error, #<PID.0.91.0>} Why is this? I'm able to send a message like "hello world" to it and get back a printed message via IO.inspect. This means the process is running as far as I can tell. defmodule NTree do # this will be the top line supervisor use Supervisor def start_link, do: Supervisor.start_link(__MODULE__, :ok, name: __MODULE__) def init(:ok) do children = [ worker(TreeWorker, [], restart: :temporary) ] supervise(children, strategy: :simple_one_for_one) # {:ok, # {{:simple_one_for_one, 3, 5}, # [{TreeWorker, {TreeWorker, :start_link, []}, :temporary, 5000, :worker, # [TreeWorker]}]}} end def start_worker(supervisor) do persister = Supervisor.start_child(supervisor, []) end end defmodule TreeWorker do def start_link do spawn(fn -> loop end) end def loop do receive do :stop -> :ok msg -> IO.inspect msg loop end end end Process.info(cid) yields: [current_function: {TreeWorker, :loop, 0}, initial_call: {:erlang, :apply, 2}, status: :waiting, message_queue_len: 0, messages: [], links: [], dictionary: [], trap_exit: false, error_handler: :error_handler, priority: :normal, group_leader: #PID<0.26.0>, total_heap_size: 233, heap_size: 233, stack_size: 1, reductions: 141, garbage_collection: [min_bin_vheap_size: 46422, min_heap_size: 233, fullsweep_after: 65535, minor_gcs: 0], suspending: []] A: A worker's start function must return {:ok, pid} on success. TreeWorker.start_link/0 returns only pid. You can fix this by returning {:ok, pid}: defmodule TreeWorker do def start_link do {:ok, spawn(fn -> loop end)} end ... end iex(1)> NTree.start_link {:ok, #PID<0.89.0>} iex(2)> NTree.start_worker(NTree) {:ok, #PID<0.91.0>}

Morphometrics of a neotropical sandfly subspecies, Lutzomyia carrerai thula. In spite of obvious and frequently observed morphological variation in geographic populations of sand flies, taxonomists are reluctant to create subspecies. In doing so they avoid confusion caused by the accumulation of new taxa, but they also obscure natural processes, some of them related to probable species emergence. We investigated here how far the partitioning of size, shape and form could be a relevant technique for exploring early evolutionary processes. We used a typical case of species, subspecies and cryptic species among three related taxa: Lutzomyia carrerai, its subspecies L. carrerai thula and L. yucumensis, a cryptic species of L. carrerai. Univariate and multivariate metric analyses showed global size differences, even between sympatric taxa (L. carrerai and L. yucumensis). When allometric effects were discounted, the subspecies L. c. thula still disclosed important differences from its putative type species, more pronounced than those existing between the two cryptic species, L. yucumensis and L. carrerai. A similar result was obtained after removing isometric size. These analyses question the validity of L. carrerai thula as a subspecies, and show that morphometrics may be a useful tool for separating simple geographic variation from evolutionary divergence.

Q: Why does = NULL not work in Oracle? I recently realized that we need to use a special syntax IS NULL to compare a literal to NULL. Why does = NULL not work here? A: Take a look at PSOUG's notes on NULL. As Fabricio Araujo hinted, NULL is not really a value like the number 4 or string 'bacon strips'. In fact, NULL is untyped in the SQL language, which is why you cannot validly use it in an equality comparison. You need the special IS [NOT] NULL syntax to check if a value is NULL or not. A: In SQL Server, we have an connection setting to get =NULL to behave equally to IS NULL. But in latest versions is not recommended anymore - it's even marked as deprecated. The recommended is the SQL Standard way - the IS [NOT] NULL operator. (And I will not start an war whether 'NULL is a value or a status' here)... hehehe

Cardiovascular risk factors and relatedness in an Icelandic subpopulation. Theoretical and empirical studies suggest adverse effects of inbreeding on general vigour. The genetic architecture of physiological and biochemical cardiovascular risk factors is, furthermore, an unsolved issue. Our aim with this study is to investigate potential effects of inbreeding on stated risk factors in a relatively well demarcated Icelandic subpopulation. We used genealogical records to calculate coefficient of inbreeding and estimated the potential association of the coefficient with stated risk factors with known statistical methods. The results suggest absence of inbreeding depression with exception of HDL cholesterol.

Join the 2018 Global Movement with FundRazr Create your free #GivingTuesday campaign and get social media promotion | from October 6 to November 20, 2018 | Create and launch your campaign between October 6 to November 19, 2018 Mention #GivingTuesday2018 in the headline or description of your campaign You must be a 501(c) nonprofit or registered charity in the US, Canada, UK or Australia How do we promote your campaign? Giving Tuesday campaigns will be listed on our special Giving Tuesday promo page (live after October 20) The page will be promoted in social media to a large audience of people interested in charitable causes (audience size is around 10 million people) and featured on Forbes and Devin Thorpe's #GTstreamathon Potential donors will have a chance to learn more about your cause, browse campaigns and donate

Q: Trying to apply Ternary Operator on JSON Data with React I am trying to apply a Ternary operator to some JSON Data which is held in a separate file locally. Below is the JSON: [ { "id": 1, "company": "Photosnap", "logo": "./images/photosnap.svg", "new": true, "featured": true, "position": "Senior Frontend Developer", "role": "Frontend", "level": "Senior", "postedAt": "1d ago", "contract": "Full Time", "location": "USA Only", "languages": ["HTML", "CSS", "JavaScript"] }, { "id": 2, "company": "Manage", "logo": "./images/manage.svg", "new": true, "featured": true, "position": "Fullstack Developer", "role": "Fullstack", "level": "Midweight", "postedAt": "1d ago", "contract": "Part Time", "location": "Remote", "languages": ["Python"], "tools": ["React"] }, { "id": 3, "company": "Account", "logo": "./images/account.svg", "new": true, "featured": false, "position": "Junior Frontend Developer", "role": "Frontend", "level": "Junior", "postedAt": "2d ago", "contract": "Part Time", "location": "USA Only", "languages": ["JavaScript"], "tools": ["React" Now the issue I have is I conditionally want to show a button dependent on whether "new" is true. The same is said to be with the Featured button. So I have written a Ternary Operator in my Component. import React from 'react'; import './job-card.styles.css'; const JobCard = ({company, position, postedAt, contract, location, logo, featured, newJob }) => ( <div className="container"> <div className='card'> <div className='companyName'> <img src={logo} alt="logo" width="100" height="100"></img> </div> <div className='content'> {{newJob} ? <button className='myButton'>New!</button> : null } {{featured} ? <button className='myDarkButton'>Featured</button> : null } <h2>{company}</h2> <h1>{position}</h1> <div className='details'> <h3>{postedAt} &#183;</h3> <h3>{contract} &#183;</h3> <h3>{location}</h3> </div> </div> </div> </div> ) export default JobCard; This is just a card component and feeds into another component which displays all the cards. import React from 'react'; import './job-listing.styles.css'; import JobCard from '../job-card/job-card.component.jsx/job-card.component'; import { Component } from 'react'; class JobListing extends Component { constructor() { super(); this.state = { jobs: [] } }; componentDidMount() { fetch('/data.json') .then(response => response.json()) .then(data => this.setState({jobs: data})) } render() { return ( <div> {this.state.jobs.map(({id, ...otherJobProps}) =>( <JobCard key={id} {...otherJobProps} /> ))} </div> ) } } export default JobListing; The output I am getting is that they are all rendering as true when some of the new or featured are false in the JSON Data. Not sure what I have missed. Any help would be appreciated. A: The problem is the inner {}. {{newJob} ? <button className='myButton'>New!</button> : null } // ^ here Within JSX, {} denotes a javascript expression. But once you are within an expression, {} goes back to being normal object syntax. This is throwing off your ternary because you're checking whether an object with key newJob is truthy. Simply removing the brackets would fix it: {newJob ? <button className='myButton'>New!</button> : null } Regarding the new issue I prefer not to destructure props like this, but to get it working most like you already have, destructure the new reserved word into an alias. Here is a simple proof of concept: let test = [{ new: true }, { new: false }]; test.map(({new: isNew}) => console.log(isNew)) I would prefer to keep the data structured as is. But thats just a preference. It would also avoid the reserved word issue. let test = [{ new: true }, { new: false }]; test.map((value) => console.log(value.new))

Menu Walleye Warrior: Alden Hirschfeld All throughout our lives we must face adversity. It comes in many forms: moving to a new school, dealing with a bully, managing college courses, or battling though illness to name a few. Every person that you meet, or even see, in our world have their own demons to face every day. We all fight to achieve our goals while overcoming the challenges put in our way. Professional athletes are no different in this regard, where they differ is the attention that their adversity receives. When they rise to the occasion, athletes can inspire others to do the same. One particular member of the Toledo Walleye has battled adversity like no other, and has inspired hockey fans across Michigan and Ohio. Alden Hirschfeld took the ice this season after recovering from brain surgery over six months ago. During Toledo’s first game of the regular season, he scored the Walleye’s first goal. Hirschfeld is not just a Toledo Walleye; he is a Warrior. Hirschfeld posing with a young fan at the Huntington Center during training camp. Early in his career Hirschfeld found great success with relatively little resistance. Alden was born in Dallas, Texas to Glen and Traci Hirschfeld but grew up in Sylvania, Ohio where he played hockey for Sylvania Northview High School. Hirschfeld captained Northview to the state title game during his senior season (2005-06), scoring 64 goals that year which earned him the Mr. Hockey Ohio award. The award is given to the top high school hockey player in Ohio. After high school Alden played junior hockey with the Mahoning Valley Phantoms, a member of the North American Hockey League (NAHL) located in Ohio, for two seasons between 2006-2008. During his junior years Hirschfeld scored 86 points with 35 goals over the course of 104 games, once again showing off his offensive prowess. This would be a recurring theme for Hirsch during his amateur career. Following Junior hockey, the next stop was college play at Miami (OH) University. While a Miami Redhawk Hirschfeld played in four seasons, appearing in the national championship game as a freshman (08-09), helping Miami win the 2011 Central Collegiate Hockey Association (CCHA) tournament, and serving as an Alternate Captain and Captain during his junior and senior year respectively. By the end of his collegiate career Hirschfeld scored 70 points over 134 games played, solidifying his reputation as a point producer. But now it was time for the pro leagues and the biggest challenge of his career. During the 2011-12 AHL season Hirschfeld got a small taste of professional hockey when he appeared in one game for the Portland Pirates. The following year is when Alden really broke through, playing in 55 games between the AHL Providence Bruins and the ECHL South Carolina Stingrays. Then Alden finally got the chance to play for his hometown Walleye. During the offseason between the 2013 playoffs and 2014 season he joined the Toledo Walleye, where he would end up splitting games between Toledo and the AHL affiliate Grand Rapids Griffins for the next two seasons. Hirschfeld had reached the high point in his professional career, with only the normal bumps and bruises experienced by all hockey players. By this point in his professional career he had 120 career points across 221 games played. Adversity, however, finally caught up with Alden on January 8, 2016 while playing a game for the Griffins against the Milwaukee Admirals. Late in the second period Alden suffered a seizure on the bench and collapsed. Play was immediately stopped as the medical staff attended to him. Both teams were sent to their locker rooms, and Hirschfeld was stabilized before being stretchered off the ice and taken to a nearby hospital. This was the end of hockey for Hirschfeld during the 2015-16 season, and many thought he would have to hang up the skates altogether. Testing showed that there was a malformation in the left temporal lobe of Hirschfeld’s brain that was responsible for the seizure. So Alden had a choice to make: risk brain surgery to end the possibility of seizures that could also restart his hockey career, or avoid a dangerous procedure that could lead to serious unforeseen consequences in order to be there for his family. After all, at this point in his life Alden had to be concerned for the welfare if his wife and child, his child was a little over a year old. On March 14th, his decision was set into motion and Alden underwent brain surgery. Following Hirschfeld’s surgery he posted a picture of his scalp where the doctors performed the procedure on his Twitter account. The procedure used is called a craniotomy, which includes the removal of a piece of skull to gain access to the brain, followed by the removal of the malformed section of the temporal lobe. Following the surgery Hirschfeld returned home to Sylvania to recover with his family. Since the procedure there has been no reoccurrence of seizures, and no emergence of surgical complications. Step one was complete for Alden, to receive treatment and recover. Next up on the list? Return to hockey. Alden began training late in May to return to the sport he loved. Motivated by family, friends, teammates past and present, Hirsch regained the strength and conditioning needed to play professional hockey. After months of work all he needed was medical clearance. And he got it. On October 3rd, 2016 Alden Hirschfeld and the Toledo Walleye announced they had agreed to terms for the 2016-17 season. He participated in the Walleye training camp and preseason games against Kalamazoo, and rode with the team down to Atlanta to begin the season on the road as a first line center. During Toledo’s first game of the year against the Gladiators Hirschfeld scored the first goal for the Walleye shortly into the second period to cut the deficit 2-1. Though the Walleye would go on to lose their opener 4-1, what Hirschfeld accomplished that October 14th night will never be forgotten by the team and fans alike. Through three games Hirsch has five points with two goals and a +/- of 4. The courage and resolve that he has shown throughout this process is profound, and nobody could think of a better way to start the year than with his goal. Hopefully he can be properly rewarded with a Kelly Cup this year. Hirschfeld stands as an inspiration to not only the Toledo Walleye, but anyone who has had to deal with adversity throughout their life. He could have let his condition beat him, instead Hirsch used it to make him stronger. Toledo’s home opener is this Saturday, October 22nd. I cannot wait to hear the crowd as Alden Hirschfeld is introduced to the Huntington Center once again. Not just as a Toledo Walleye though, as a Toledo Warrior. Hirschfeld winning a face off during Toledo’s October 7th preseason home game.

Q: queue a azure pipeline yaml stage to execute at specific datetime We have a multistage release pipeline which targets all environments like dev->int->qa->prod-staging slot. For final swaping of slot we have a requirement to to run at specified datetime during non-business hrs. How can we delay a specific stage of multi stage yaml to run at certain datetime. A: Though I agree with the idea of Hany, but the link he shared is about the Release which configured with UI. It does not suitable for your multi-stage YAML pipeline. Since what you are using is multi-stage YAML pipeline, you can check below sample to configure the corresponding schedule trigger into your YAML. For example, here is the schedule which make the YAML pipeline run at Sunday weekly: schedules: - cron: "0 12 * * 0" displayName: Build on Sunday weekly branches: include: - releases/* always: true For 0 12 * * 0, it is following the syntax of: mm HH DD MM DW \ \ \ \ \__ Days of week \ \ \ \____ Months \ \ \______ Days \ \________ Hours \__________ Minutes I saw you said you want this pipeline run during non-business hours, so you can focus on the last field DW(Days of week). It's available value it 0~6 and starting with Sunday.Or you can input with like Sun: "0 12 * * Sun" Check this doc for more details.

Pseudomonas aeruginosa (PA) is an opportunistic gram-negative pathogen responsible for a large number of nosocomial infections. Dr. Joanne Engel and her group have shown that PA103 induces apoptotic-like cell death in epithelial cells and macrophages by a Type III Secretion System (TTSS)-dependent mechanism. Consistent with the results of others, They have found this to be a Fas ligand- and Fas receptor-dependent process. We propose that PA-induced apoptosis occurs either by (A) direct translocation of a bacterial effector into the host cell (PAF, for Pseudomonas Apoptosis Factor) by the TTSS, resulting in activation of Fas-dependent apoptosis or by (B) direct induction of Fas-dependent apoptosis by one or more components of the type III translocation apparatus itself. We will identify the mechanism by which PAl03 induces TTS-dependent apoptotic-like cell death in eukaryotic cells. We will initially use genetic and proteomic approaches to identify a putative apoptosis-inducing type III secreted effector molecule. We may also test the alternative hypothesis that the TTSS itself is responsible for the induction of apoptosis by PA. We will express the PA TTSS in a Yersinia strain that lacks the plasmid encoded TTSS and test for restoration of apoptosis-inducing activity.

Q: Your PHP Version Will Be Unsupported in Joomla! 3.3 I am using PHP Version 7.0.12 and Joomla Version 3.7.3. And I am facing this message "Your PHP Version Will Be Unsupported in Joomla! 3.3" As per Joomla 3.3 System requirement: Starting with Joomla! 3.3, the minimum required PHP version is being raised to PHP 5.3.10 or later! but I already using later PHP version 7.0.12, why I am still getting this message? is any other thing I have to enable? or anything I missed? please suggest me... Thanks! A: its a bug that will be fixed in the next release - nothing to worry about

2019 NCHC Tournament The 2019 NCHC Tournament is the sixth tournament in league history. It will be played between March 15 and 23, 2019. Quarterfinal games will be played at home team campus sites, while the final four games will be played at the Xcel Energy Center in Saint Paul, Minnesota. By winning the tournament, that team will receive the NCHC's automatic bid to the 2019 NCAA Division I Men's Ice Hockey Tournament. Format The first round of the postseason tournament features a best-of-three games format. All eight conference teams participate in the tournament. Teams are seeded No. 1 through No. 8 according to their final conference standing, with a tiebreaker system used to seed teams with an identical number of points accumulated. The top four seeded teams each earn home ice and host one of the lower seeded teams. The winners of the first round series advance to the Xcel Energy Center for the NCHC Frozen Faceoff. The Frozen Faceoff uses a single-elimination format. Teams are re-seeded No. 1 through No. 4 according to the final regular season conference standings. Game 1 of the series between Western Michigan and Colorado College was delayed 1 day due to the effects from Winter Storm Ulmer. Standings Bracket Teams are reseeded for the Semifinals * denotes overtime periods Results All times are local. Quarterfinals (1) St. Cloud State vs. (8) Miami (2) Minnesota–Duluth vs. (7) Omaha (3) Western Michigan vs. (6) Colorado College (4) Denver vs. (5) North Dakota Semifinals (1) St. Cloud State vs. (6) Colorado College (2) Minnesota–Duluth vs. (4) Denver Third place (4) Denver vs. (6) Colorado College Championship (1) St. Cloud State vs. (2) Minnesota–Duluth Tournament awards Frozen Faceoff All-Tournament Team F Robby Jackson (St. Cloud State) F Blake Lizotte (St. Cloud State) F Patrick Newell (St. Cloud State) D Jimmy Schuldt (St. Cloud State) D Mikey Anderson (Minnesota–Duluth) G Hunter Shepard* (Minnesota–Duluth) * Most Valuable Player(s) References NCHC Men's Ice Hockey Tournament 2019 Category:Ice hockey in Minnesota Category:College sports in Minnesota Category:2019 in sports in Minnesota Category:March 2019 sports events in the United States

1. Field of Invention The present invention relates to semiconductor processing, and in particular, to chemical vapor deposition in a high density plasma reactor. 2. Related Art High density plasma (HDP) chemical vapor deposition (CVD) processes are used in the fabrication of integrated circuits for depositing films on a substrate. One application of an HDP CVD process is to fill gaps on a semiconductor device having high aspect ratios (e.g., about 2.5:1 or greater) and close spacing (e.g., about 0.25 xcexcm or less). Existing HDP CVD processes typically employ deposition with a process gas mixture that includes oxygen, silane, and inert gases, such as argon, to achieve simultaneous dielectric etching and deposition. In an HDP process, RF bias is applied to a wafer substrate in a reaction chamber. As a result, the flux of deposition precursors is perpendicular to the wafer, and the net film growth occurs perpendicularly to the bottom of the feature. Some of the gas molecules (particularly argon) are ionized in the plasma and accelerate toward the wafer surface when the RF bias is applied to the substrate. Material is thereby sputtered when the ions strike the surface. As a result, dielectric material deposited on the wafer surface is simultaneously sputter-etched to help keep gaps open during the deposition process, which allows higher aspect ratio gaps to be filled. An important goal in HDP deposition of these and other layers is to deposit a film of uniform thickness across the surface of a substrate and across different batches of substrates. One factor mitigating against uniform deposition is dopant concentrations in the processing environment. In HDP CVD processes, this is important because the reactor can act either as a sink or a source for dopants that affect the growth rate on the wafer. A typical HDP CVD reactor includes a reaction chamber having an upper lid or dome, typically made of a ceramic such as aluminum oxide (Al2O3). During the deposition process, process gases are introduced into the chamber, and a plasma of the processing gases is generated within the chamber to effectuate chemical vapor deposition onto the substrate. However, the deposition typically occurs on all the surfaces exposed to the processing gases, including the interior surfaces of the chamber. If the dopant concentration of the processing environment is not in equilibrium, a shift in deposition rate can occur. This shift in deposition rate due to changing reactor conditions can be as high as 500 xc3x85/min. When the reactor is in an idle state, an argon and oxygen plasma, Known as an xe2x80x9cidle plasmaxe2x80x9d, is used maintain the reactor temperature. The oxygen in the idle plasma will deplete the fluorine species adsorbed to the sidewalls over time. This creates an environment that is not in equilibrium. For example, when depositing fluorine-doped silicon oxide layers, such as fluorosilicate glass (FSG), a reactor in an idle condition has been depleted of the dopants adsorbed to the chamber surfaces. When FSG deposition begins again, SiF species are adsorbed again to the reactor walls. This retards the deposition on the substrate surface. As the reactor approaches an equilibrium state, the deposition rate on the substrate rises and eventually levels off. Depending on the reactor conditions, the dopant concentration, and the target thickness of the FSG on the wafer, 200 or more deposition sequences may be required to reach a steady state. Once the reactor is in a steady state, processing must be continuous or the idle plasma will again begin to deplete the adsorbed dopants in the reactor causing the deposition rate on subsequent wafers to be reduced. Accordingly, it is desirable to deposit a dielectric film without the problems discussed above that are associated with conventional techniques. In accordance with one aspect of the present invention, prior to beginning deposition of doped dielectric layers on wafers, a high density plasma (HDP) chemical vapor deposition (CVD) chamber is first conditioned by forming a layer of the doped material within the chamber walls. This conditioning quickly brings the chamber to an equilibrium state so that subsequent deposition of the doped dielectric material onto wafers yields consistent deposition rates because dopants are already adsorbed to the chamber walls. Approximately constant deposition rates can be maintained as long as the reactor is running and depositing layers onto wafers. However, if the deposition is halted for a certain amount of time, e.g., 20 minutes, and the reactor becomes idle, the chamber is plasma cleaned and a thin layer of the doped material is deposited onto the chamber walls. Periodically, for example, every 12 hours, the chamber is plasma cleaned and the thin layer is re-deposited. This allows consistent deposition rates even when the reactor has been idle for prolonged periods of time. In one embodiment, initial conditioning, such as after a wet clean, is carried out by introducing a gas containing silicon fluoride (SiF4), argon, and oxygen into the chamber to form a fluorosilicate glass (FSG) approximately 10 to 30 xcexcm thick. After idle (e.g., 20 minutes without processing), the chamber is plasma cleaned and a thin FSG layer of approximately 1 to 3 xcexcm is deposited. The plasma clean and deposition of the thin FSG layer is repeated periodically, e.g. every 12 hours, to maintain the chamber in an equilibrium state. The present invention will be more fully understood when taken in light of the following detailed description taken together with the accompanying drawings.

Articles How to persuade a customer to use high-quality equipment? At any negotiations, presentations of GPS equipment at various events and exhibitions, the most frequently asked question is "how much is it?". Does this mean that price is the most important factor for making a purchase? Not at all, because in the B2B market the buyer spends the company's money, not his own. Therefore, the sensitivity to the price is not so high – no one is chasing for say $20 savings, it is much more important to choose a technological solution that will last for many years, and not cause a "headache". If we are talking about the choice of GPS tracking device, among the most crucial factors are: reliability, longevity, functionality, as well as flexibility, i.e. the possibility of making improvements over time. Choose a first-class solution Choosing high-quality equipment, the end customer avoids additional costs for complete replacement of equipment (cheap tracking devices are unlikely to last longer than 2 years), costs for diagnostics, repairs and site visits for service. Considering the rapid technological progress, it is much more efficient to invest in flexible solutions, with sufficient extensibility to implement any changes. Multifunctionality is a must in the context of the growth of customers' needs. In other words, high-quality equipment operates on the "set and forget" principle. Using Galileosky tracking devices, integrators around the world get higher margins, are confident in the proposed solution, and customers remain satisfied and develop long-term cooperation. Recommending Galileosky, integrators are remembered by end users as experts who offer a high-quality and exclusive solution. Never start negotiations with the price One of the most important rules for winning projects is never to start negotiations with the price. Choose the best product for your customer and be confident in what you offer. Remember, the loyal customer will recommend your services to others and you will get even more projects. Be an expert When you know, what you sell the customer feels it. The more you know – the more customers you can attract. Keep studying the product to understand the technical characteristics and capabilities of the tracking device. Become a Galileosky expert, visiting free webinars and seminars, studying the instructions for connecting new external devices. Take the trackers for a free test to experience first-hand all the possibilities. Be different from others When proposing a solution, focus on unique advantages of equipment. Tell your customer about the innovative development of Galileosky – Easy Logic technology; explain the possibilities of flexible settings and configuration on-the-air. Just show the track to the customer, this is the best indicator of the quality. Emphasize that Galileosky equipment is remarkable for a large number of inputs/outputs of different types and has an open protocol. So, you can connect and integrate various additional devices to solve almost any tasks, use monitoring software to your taste or painlessly replace one software for another. Get to know your customer better Having discussed the advantages of the product, try to find out what the customer needs and wants. At this stage, it is the right time not only to draw up a detailed "portrait" of the tracking device in terms of technical parameters, but also to find out the required installation time and availability of a product. Once you find it out feel free to discuss the price. Do not forget that Galileosky can provide custom-made trackers, therefore, you will not have to overpay for unnecessary functionality. Handle the objections Do not leave the customer's objections unanswered. "Expensive"? Explain why it is worth buying. Considering the practice of using Galileosky GPS devices, the investment pays off after the first month. The longer service life of the solution – the higher ROI is. Galileosky hardware is one of the most reliable and durable on the market. It’s estimated service life is 10 years and the reject rate is less than 1% of all released products. The customer claims that the solution is "excessively functional"? Clarify, how easier it will be to upgrade the solution in the future, than to re-equip everything from scratch. Provide examples of more significant economic results when implementing a non-standard solution. And, finally, offer to pay only for the required functionality by ordering custom-made devices. If, as an argument, the end user states that he does not want to use hardware and software from different manufacturers, explain that you choose only the best components of the monitoring system from companies that specialize in their fields. Thus, the system will be more qualitative and flexible. Call the manufacturer for assistance Do not neglect the help of the manufacturer, even if you have rich experience in transport monitoring. The personal Galileosky manager will provide comprehensive support. From assessing the technical requirements of the end user, discussing the customization conditions and to joint participation in negotiations with customers or making presentation together online. In addition, Galileosky is ready to discuss mutual exhibiting, provides free marketing materials to partners, and redirects the requests of end customers for the purchase and installation of trackers to reliable integrators in the regions.

Q: Is there a way to style an element such that it and all its contents will be rendered 50% faded? I'm working on a userscript that adds a missing feature to a 3rd party website over which I have no control. It will compute URLs based on the page and the results of some webAPI calls. These URLs will be added into the HTML of the page. Then for any URL rendered as :visited I wish to set the li element that it is a part of to be "faded" by manipulating the styles. That's probably more specific detail of my project than necessary to describe my problem, sorry. The only part I'm not sure how to achieve is how to get the li element (as well as all rendered within it) to be rendered as half-faded into the background colour. I'm guessing there is probably standard way to do this with modern HTML and CSS. I'm working with latest stable Chrome and do not need to support old browsers. A: Is there a way to style an element such that it and all its contents will be rendered 50% faded? Opacity yourelement { opacity:0.5; } This will affect the element and since it is inherited, it will apply to all the children too. Note however, that if the link is :visited the opacity will have to be set by javascript as there is no CSS "Parent Selector".

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Caswain Mason Caswain Mason (born 12 February 1978) is a Vincentian former footballer who spent the majority of his career in the Canadian Soccer League. Playing career Mason began his career with the Toronto Olympians of the Canadian Professional Soccer League in 2000. He would appear in one match against the North York Astros on September 12, 2000, coming on as a substitute for Gus Kouzmanis. In 2001, he went a step higher in his professional career by signing with the Toronto Lynx of the USL A-League. His signing was announced along with the rest of the roster on April 24, 2001. Throughout the season he appeared in 14 matches and recorded one goal. Though the Lynx failed to reach the postseason. In 2002, he returned to CPSL to sign with the Metro Lions, where in his debut season he helped the club achieve a seven-game undefeated streak and a place in the playoffs; but were eliminated by the Ottawa Wizards the semi-final match. On May 17, 2004, he extended his contract with the Lions for the 2004 season. He was named into the CPSL all-star squad that would face Boavista FC in a friendly match. The following year he signed with league powerhouse Toronto Croatia, making his debut on May 29, 2005 in a match against Vaughan Shooters. During his tenure with the club he helped the team reach the postseason, but were eliminated in the semi-finals. In 2007, he had a spell overseas with Mahindra United of the I-League. He would return to the CSL to play with the Canadian Lions; making his debut on September 19, 2007 against Trois-Rivieres Attak. In 2008, he signed with CSL powerhouse with the Serbian White Eagles, where he captured the CSL Championship by defeating the Trois-Rivieres in penalties. International career Mason made his debut for the Saint Vincent and the Grenadines national football team on May 8, 2004 against Grenada. Honours Serbian White Eagles CSL Championship: 1 2008 References Category:1978 births Category:Living people Category:Saint Vincent and the Grenadines footballers Category:Toronto Croatia players Category:Toronto Lynx players Category:Toronto (Mississauga) Olympians players Category:Serbian White Eagles FC players Category:Association football midfielders Category:USL A-League players Category:Canadian Soccer League (2006–present) players Category:Canadian Professional Soccer League (1998–2005) players Category:Brampton United players

//===--- SwiftPrivateThreadExtras.swift -----------------------------------===// // // This source file is part of the Swift.org open source project // // Copyright (c) 2014 - 2018 Apple Inc. and the Swift project authors // Licensed under Apache License v2.0 with Runtime Library Exception // // See https://swift.org/LICENSE.txt for license information // See https://swift.org/CONTRIBUTORS.txt for the list of Swift project authors // //===----------------------------------------------------------------------===// // // This file contains wrappers for pthread APIs that are less painful to use // than the C APIs. // //===----------------------------------------------------------------------===// #if canImport(Darwin) import Darwin #elseif canImport(Glibc) import Glibc #elseif os(Windows) import MSVCRT import WinSDK #endif /// An abstract base class to encapsulate the context necessary to invoke /// a block from pthread_create. internal class ThreadBlockContext { /// Execute the block, and return an `UnsafeMutablePointer` to memory /// allocated with `UnsafeMutablePointer.alloc` containing the result of the /// block. func run() -> UnsafeMutableRawPointer { fatalError("abstract") } } internal class ThreadBlockContextImpl<Argument, Result>: ThreadBlockContext { let block: (Argument) -> Result let arg: Argument init(block: @escaping (Argument) -> Result, arg: Argument) { self.block = block self.arg = arg super.init() } override func run() -> UnsafeMutableRawPointer { let result = UnsafeMutablePointer<Result>.allocate(capacity: 1) result.initialize(to: block(arg)) return UnsafeMutableRawPointer(result) } } /// Entry point for `pthread_create` that invokes a block context. internal func invokeBlockContext( _ contextAsVoidPointer: UnsafeMutableRawPointer? ) -> UnsafeMutableRawPointer! { // The context is passed in +1; we're responsible for releasing it. let context = Unmanaged<ThreadBlockContext> .fromOpaque(contextAsVoidPointer!) .takeRetainedValue() return context.run() } #if os(Windows) public typealias ThreadHandle = HANDLE #else public typealias ThreadHandle = pthread_t #if os(Linux) || os(Android) internal func _make_pthread_t() -> pthread_t { return pthread_t() } #else internal func _make_pthread_t() -> pthread_t? { return nil } #endif #endif /// Block-based wrapper for `pthread_create`. public func _stdlib_thread_create_block<Argument, Result>( _ start_routine: @escaping (Argument) -> Result, _ arg: Argument ) -> (CInt, ThreadHandle?) { let context = ThreadBlockContextImpl(block: start_routine, arg: arg) // We hand ownership off to `invokeBlockContext` through its void context // argument. let contextAsVoidPointer = Unmanaged.passRetained(context).toOpaque() #if os(Windows) let threadID = _beginthreadex(nil, 0, { invokeBlockContext($0)! .assumingMemoryBound(to: UInt32.self).pointee }, contextAsVoidPointer, 0, nil) if threadID == 0 { return (errno, nil) } else { return (0, ThreadHandle(bitPattern: threadID)) } #else var threadID = _make_pthread_t() let result = pthread_create(&threadID, nil, { invokeBlockContext($0) }, contextAsVoidPointer) if result == 0 { return (result, threadID) } else { return (result, nil) } #endif } /// Block-based wrapper for `pthread_join`. public func _stdlib_thread_join<Result>( _ thread: ThreadHandle, _ resultType: Result.Type ) -> (CInt, Result?) { #if os(Windows) let result = WaitForSingleObject(thread, INFINITE) guard result == WAIT_OBJECT_0 else { return (CInt(result), nil) } var dwResult: DWORD = 0 GetExitCodeThread(thread, &dwResult) CloseHandle(thread) let value: Result = withUnsafePointer(to: &dwResult) { $0.withMemoryRebound(to: Result.self, capacity: 1) { $0.pointee } } return (CInt(result), value) #else var threadResultRawPtr: UnsafeMutableRawPointer? let result = pthread_join(thread, &threadResultRawPtr) if result == 0 { let threadResultPtr = threadResultRawPtr!.assumingMemoryBound( to: Result.self) let threadResult = threadResultPtr.pointee threadResultPtr.deinitialize(count: 1) threadResultPtr.deallocate() return (result, threadResult) } else { return (result, nil) } #endif } public class _stdlib_Barrier { var _threadBarrier: _stdlib_thread_barrier_t var _threadBarrierPtr: UnsafeMutablePointer<_stdlib_thread_barrier_t> { return _getUnsafePointerToStoredProperties(self) .assumingMemoryBound(to: _stdlib_thread_barrier_t.self) } public init(threadCount: Int) { self._threadBarrier = _stdlib_thread_barrier_t() let ret = _stdlib_thread_barrier_init( _threadBarrierPtr, CUnsignedInt(threadCount)) if ret != 0 { fatalError("_stdlib_thread_barrier_init() failed") } } deinit { _stdlib_thread_barrier_destroy(_threadBarrierPtr) } public func wait() { let ret = _stdlib_thread_barrier_wait(_threadBarrierPtr) if !(ret == 0 || ret == _stdlib_THREAD_BARRIER_SERIAL_THREAD) { fatalError("_stdlib_thread_barrier_wait() failed") } } }

Nyhavn 11 Nyhavn 11 is a listed property overlooking the Nyhavn canal in central Copenhagen, Denmark. History A two-storey building was built at the site in about 1700. One of its first owners was Jacob Severin. He had married rich and was in 1733 granted a full monopoly on trade with Greenland where he founded the town Jacobshavn (literally "Port Jacob"). Ludvig Ferdinand Römer established a sugar refinery in the building in 1754. He had been governor of the Danish Gold Coast. His wife was Anna Cathrine Widderkamp and the couple had 14 children. The property was expanded with two extra storeys in 1835-1836 for a grocer named Harboe. The actor Christian Niemann Rosenkildelived in the building with his family from 1842 to 1749. His daughter, Julie, later known by her married name Julie Sødring, who became one of the leading Danish actresses of her time, had her debut at the Royal Danish Theatre in the play Den Sorte Dronning (The Black Queen) in 1843. Many artist frequented the home, including the Swedish singer Jenny Lind. Another well-known actor, Poul Reumert, have also lived in the building. He grew up at Nyhavn 63. The building was listed by the Danish Heritage Agency in the Danish national registry of protected buildings in 1932. Building The building is four storeys tall and five bays wide. It has a red tile roof with four dormers. Above the gate is a figure of a sugar-baker holding a sugarloaf in one hand and a sugar tin in the other. The figure dates from Römer's sugar refinery. It served as a means of identifications at a time when house numbers had not yet been introduced. Many other houses along the Nyhavn quay feature similar signs. An appendix with staircase on the rear side of the building dates from 1875. The courtyard was refurbished in 1963 to design by the landscape architect Knud Lund-Sørensen. Today The leading Danish lamp manufacturer Louis Poulsen has been headquartered in the building since 1908. References External links Photographs of the courtyard Category:Houses in Copenhagen Category:Listed residential buildings in Copenhagen Category:Houses completed in 1836 Category:Sugar refineries in Copenhagen

assess the level of risk involved in mineral pro echlib.deloitteresources / MagnesiumScientific Review on Usage, Dosage, Side Summary of Magnesium Primary Information, Benefits, Effects, and Important Facts Magnesium is an essential dietary mineral, and the second most prevalent electrolyte in the human body. Magnesium deficiencies are common in 1. Overview of the GRADE ApproachGRADEproGDT 1. Overview of the GRADE Approach The GRADE approach is a system for rating the quality of a body of evidence in systematic reviews and other evidence syntheses, such as health technology assessments, and guidelines and Genomewide Association Studies and Assessment of the 8· Risk Assessment The potential for variants identified in genomewide association studies to predict the risk of complex diseases has been anticipated since the publication of the first reports, but this application is Tibia Shaft FracturesTraumaOrthobullets 9· The most important factor shown to reduce the risk of infection at the site of an open fracture is early intravenous antibiotic administration. Infection risk after Gustilo Type II open fractures ranges from 10 20% in large Principles for the Governance of Regulators The Principles for the Governance of Regulators was discussed at the 21 November 2012 informal meeting of the Ad Hoc Network of Economic Regulators (NER) at the OECD, Paris and the 22 23 April 2013 meeting of the Regulatory Vitamin A Health Professional Fact Sheet 1· Introduction Vitamin A is the name of a group of fat soluble retinoids, including retinol, retinal, and retinyl esters []. Vitamin A is involved in immune function, vision, reproduction, and cellular communication [1,4,5]. Vitamin Advair DiskusFDA prescribing information, side Treatment of Asthma Advair Diskus is indicated for the treatment of asthma in patients aged 4 years and older. LABA, such as salmeterol, one of the active ingredients in Advair Diskus, increase the risk of asthma related death. Calcium Health Professional Fact Sheet Introduction Calcium, the most abundant mineral in the body, is found in some foods, added to others, available as a dietary supplement, and present in some medicines (such as antacids). Calcium is required for vascular contraction ZincScientific Review on Usage, Dosage, Side Effects Zinc is an essential mineral involved in regulating many enzymes. It is an antioxidant and immune boosting supplement. Zinc is most commonly supplemented to reduce the frequency of illness and to support optimal levels of Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 2· Background Weight loss is associated with short term amelioration and prevention of metabolic and cardiovascular risk, but whether these benefits persist over time is unknown. Methods The prospective, controlled CholineLinus Pauling InstituteOregon State University Summary Choline is a vitamin like essential nutrient and a methyl donor involved in many physiological processes, including normal metabolism and transport of lipids, methylation reactions, and neurotransmitter synthesis. (More USGS news releaseUSGS.govScience for a changing ZonegranFDA prescribing information, side effects Zonegran ® (zonisamide) is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The active ingredient is zonisamide, 1,2 benzisoxazole 3 methanesulfonamide. The empirical formula is Case studies on genetically modified organisms (GMOs Within the frame of the EU funded MARLON project, background data were reviewed to explore the possibility of measuring health indicators during post market monitoring for potential effects of feeds, particularly genetically modified Topic 9: Safety and risk management in oil and gas Quote HSE " Success in managing major Hazards is not measured by the Occupational Health and Safety Statistics but by measuring the performance of critical systems used to control risks to ensure they are operating as intended. Ace InvestmentBest Stock TipsIndian Stock Tips We are leader in equity market, focusing on technical and fundamental analysis to convert raw data and information into expert advice. " Ace Investment Advisory is the Most Trusted SEBI Registered Investment Advisory in India gives Lifestyle, Diabetes, and Cardiovascular Risk Factors 10 2· Background Weight loss is associated with short term amelioration and prevention of metabolic and cardiovascular risk, but whether these benefits persist over time is unknown. Methods The prospective, controlled GlossaryLinus Pauling InstituteOregon State University C reactive protein (CRP) a protein that is produced in the liver in response to inflammation. CRP is a biomarker of inflammation that is strongly associated with the risk of cardiovascular events, such as myocardial infarction and stroke. NutrientsSeptember 2017Browse Articles Nutrients, Volume 9, Issue 9 (September 2017) Issues are regarded as officially published after their release is announced to the table of contents alert mailing list. You may sign up for e mail alerts to receive table of contents of

Tumour-simulating squamous cell metaplasia (SCM) in necrotic areas of salivary gland tumours. Squamous cell metaplasia (SCM) adjacent to necrotic areas of salivary gland tumours must be distinguished from other types of SCM (focal SCM in the excretory ducts of salivary glands; necrotizing sialometaplasia; focal SCM within salivary gland tumours) in respect to the tissue structure. Based on the high cellular proliferation, arcade- or cord-like pseudoneoplastic SCM develops with stellate extension in the surrounding tissue and focal inclusion of goblet cell metaplasia. This proliferative SCM resembles the cellular demarcation of radicular dental cysts. In the Salivary Gland Register 8 cases of tumor-simulating SCM could be analysed which clinically and morphologically were suspect of squamous cell or mucoepidermoid carcinoma. Five cases were localized in the parotid gland, 2 cases in the submandibular gland and 1 case in the palatinal glands. Tumour-simulating SCM was developed in pleomorphic adenomas (5 cases) and in multifocal adenomatous oncocytic hyperplasia (3 cases).

For a MP5 clone the ones coming in from Pakistani Ordnance Factory are HK spec and ready to go. They come in as a pistol so they are ready to convert to a SBR or add a pistol brace to. For a G3 I would go with PTR. They are well-built, reliable, built on licensed HK equipment, and can be had for under $1000. I would get the GI model since it has the deeper flutes in the chamber meaning it will be able to eat any ammo you throw at it. I used to have one but sold it to my friend because he really wanted it and I upgraded to a Vector. The fact that the Vector had the paddle release was a major factor in me getting it.

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Kirsten Sinding-Larsen Kirsten Sinding-Larsen (4 August 1898 – 10 December 1978) was a Norwegian architect. She was born in Kristiania (now Oslo), Norway. She was the daughter of colonel Birger Fredrik Sinding-Larsen (1867–1941) and Emilie Rustad (1871–1904). She was a paternal granddaughter of jurist and writer Alfred Sinding-Larsen, niece of physician Christian Magnus Sinding-Larsen, architect Holger Sinding-Larsen and painter Kristofer Sinding-Larsen, first cousin of journalist Henning Sinding-Larsen and grandniece of architect Balthazar Lange. She finished her secondary education in 1912, and studied at the Norwegian National Academy of Craft and Art Industry (now Oslo National Academy of the Arts) from 1915 to 1917. She worked as an apprentice to architect Sigurd Lunde in Bergen from 1919 to 1921. She worked with architect Håkon Ahlberg in Stockholm from 1923–25 and Tage William-Olsson to 1927. She studied architecture at the Royal Institute of Technology from 1927 to 1929. She was employed by architects Gustav Classon and Wolter Gahn in Stockholm from 1929-1932. She returned to Oslo in 1932 and worked for a short time with her uncle architect Holger Sinding-Larsen before establishing her own practice in 1933. During the period 1933-38, she designed a number of homes in Moss and Jeløy in Østfold. Her most notable single work was the design of Sunnaas Hospital at Nesodden in the mid-1950s. She is also remembered as a debater of housing policy. References Category:1898 births Category:1978 deaths Category:Artists from Oslo Category:Norwegian architects Category:Norwegian women architects Category:Norwegian expatriates in Sweden Category:Oslo National Academy of the Arts alumni Category:KTH Royal Institute of Technology alumni

A linkage map of distal mouse chromosome 12. To refine the linkage map of distal mouse Chromosome 12, we have identified DNA restriction fragment variants associated with a creatine kinase gene (Ck-3), the Akt proto-oncogene, an Abelson proviral integration site (D12N1), and the immunoglobulin heavy chain VH3609 variable region family (Igh-V36). The patterns of inheritance of these markers in backcross progeny and recombinant inbred mouse strains allowed their localization with respect to previously mapped genes to yield the linkage map: Aat-15.8 cM-Ck-3-0.9 cM-(Crip, Akt, Igh-C)-0.3 cM-(D12N1, Igh-V). This map confirms genetically the localization of the Igh-V gene complex distal to Igh-C on the chromosome. It differs from previous maps in placing D12N1 distal to Igh-C, and in suggesting that the Igh-V gene complex spans less than one centiMorgan (cM). Other DNA sequence variants detected with the creatine kinase probe allowed definition of four additional genetic loci: Ck-1 near Lmyc-1 on Chromosome 4; Ck-2 between Upg-1 and Hprt-ps1 (D17Rp10) on distal Chromosome 17; Ck-4 near Mpmv-17 and Mls-3 on Chromosome 16; and Ck-5 near Hba on Chromosome 11.

1. Field of the Invention The present invention relates to a transmission gate and a semiconductor device. 2. Description of the Related Art A conventional transmission gate is described. FIG. 8 is a circuit diagram illustrating the conventional transmission gate. The transmission gate includes a PMOS transistor 91 and an NMOS transistor 92. In those transistors, gates thereof are controlled by complementary signals, and thus the transistors are turned ON/OFF simultaneously. When a low level voltage is input to the gate of the PMOS transistor 91, and a high level voltage is input to the gate of the NMOS transistor 92, electrical continuity of the transmission gate is established. Then, the transmission gate outputs an input voltage Vin as an output voltage Vout. Here, a gate-to-source capacitance of the PMOS transistor 91 is represented by Cgsp, a gate-to-source capacitance of the NMOS transistor 92 is represented by Cgsn, a parasitic capacitance at an output terminal is represented by Ch, a threshold voltage of the PMOS transistor 91 is represented by −Vtp, and a threshold voltage of the NMOS transistor 92 is represented by Vtn. Further, a voltage magnitude applied to the gate of the PMOS transistor 91 is represented by V5, and a voltage magnitude applied to the gate of the NMOS transistor 92 is represented by V4. When the transmission gate is set so as to satisfy the following Expression (11), influence of clock feedthrough is reduced. Therefore, it is possible to attain high S/N characteristics (for example, see JP 07-169292 A).(V5−Vout−Vtp)·Cgsp/(Cgsp+Ch)=(V4−Vout−Vtn)·Cgsn/(Cgsn+Ch)  (11) However, in the related art, Expression (11) is satisfied based on the presupposition that the input voltage Vin is a constant voltage (for example, (VDD+VSS)/2) and does not fluctuate. In other words, when the input voltage Vin fluctuates and therefore the output voltage Vout fluctuates, Expression (11) is not satisfied. Therefore, the S/N characteristics are degraded due to the influence of clock feedthrough.

Marko Klasinc Marko Klasinc (born 14 May 1951) is Slovenian chess problemist. He composed almost 200 chess problems, mostly heterodox and retrograde ones (12 included in FIDE Album). He has title FIDE solving master and international judge of FIDE for chess composition. As a good solver he represented Yugoslavia 1982 in Varna, where the team became World Champion solving chess problems. He is the president of Committee for Chess Compositions of Chess Federation of Slovenia. References Notes Bibliography Drinovec, Aleš (editor). Slovenski šah. Šahovska zveza Slovenije, Ljubljana 2002. External links Website PDB Server Category:1951 births Category:Living people Category:Chess composers Category:International Judges of Chess Compositions Category:Slovenian chess players

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3, 5, 13, 17 What are the prime factors of 3419148? 2, 3, 499, 571 List the prime factors of 4971. 3, 1657 What are the prime factors of 38? 2, 19 What are the prime factors of 268741? 11, 2221 List the prime factors of 1415801. 31, 109, 419 List the prime factors of 912806. 2, 456403 List the prime factors of 3221123. 3221123 What are the prime factors of 9037358? 2, 11, 410789 List the prime factors of 5309436. 2, 3, 11, 19, 29, 73 List the prime factors of 4099777. 11, 372707 What are the prime factors of 14246336? 2, 13, 17123 List the prime factors of 881742. 2, 3, 223, 659 What are the prime factors of 28056703? 421, 66643 What are the prime factors of 9094509? 3, 1010501 What are the prime factors of 1855425? 3, 5, 11, 13, 173 List the prime factors of 487287. 3, 29, 1867 List the prime factors of 440543. 440543 What are the prime factors of 18980763? 3, 89, 71089 What are the prime factors of 9109410? 2, 3, 5, 303647 What are the prime factors of 1449947? 17, 19, 67 List the prime factors of 67677. 3, 17, 1327 What are the prime factors of 202048? 2, 7, 11, 41 List the prime factors of 593777. 593777 List the prime factors of 177572. 2, 103, 431 What are the prime factors of 5862798? 2, 3, 37, 8803 What are the prime factors of 235756? 2, 17, 3467 List the prime factors of 2391760. 2, 5, 7, 4271 What are the prime factors of 14733? 3, 1637 What are the prime factors of 387108? 2, 3, 10753 List the prime factors of 3703978. 2, 1259, 1471 List the prime factors of 15364114. 2, 7682057 What are the prime factors of 98667? 3, 19, 577 List the prime factors of 9930106. 2, 31, 160163 What are the prime factors of 225824? 2, 7057 List the prime factors of 560306. 2, 41, 6833 List the prime factors of 12044282. 2, 109, 55249 List the prime factors of 2037426. 2, 3, 43, 53, 149 What are the prime factors of 171671? 171671 What are the prime factors of 18303

package plugins.core.combat; import java.util.ArrayList; import java.util.HashSet; import java.util.List; import java.util.Set; import org.slf4j.Logger; import org.slf4j.LoggerFactory; import akka.actor.ActorRef; import akka.actor.ActorSelection; import akka.actor.Props; import akka.actor.UntypedActor; import io.gamemachine.chat.ChatSubscriptions; import io.gamemachine.core.ActorUtil; import io.gamemachine.core.GameEntityManager; import io.gamemachine.core.GameEntityManagerService; import io.gamemachine.core.GameMachineLoader; import io.gamemachine.core.PlayerMessage; import io.gamemachine.grid.Grid; import io.gamemachine.grid.GridService; import io.gamemachine.messages.CombatLog; import io.gamemachine.messages.GameMessage; import io.gamemachine.messages.PlayerSkill; import io.gamemachine.messages.RegionInfo; import io.gamemachine.messages.StatusEffect; import io.gamemachine.messages.StatusEffectTarget; import io.gamemachine.messages.TrackData; import io.gamemachine.messages.Zone; import io.gamemachine.regions.ZoneService; public class StatusEffectManager extends UntypedActor { private static final Logger logger = LoggerFactory.getLogger(StatusEffectManager.class); public static String name = StatusEffectManager.class.getSimpleName(); public static boolean combatLogEnabled = true; public static List<GridSet> gridsets = new ArrayList<GridSet>(); public static Set<String> handlerZones = new HashSet<String>(); public static void tell(String gridName, String zone, StatusEffectTarget statusEffectTarget, ActorRef sender) { String actorName = null; if (!hasEffects(statusEffectTarget)) { logger.warn("No effects found for skill " + statusEffectTarget.skillRequest.playerSkill.id); return; } if (activeEffectCount(statusEffectTarget) > 0) { actorName = ActiveEffectHandler.actorName(gridName, zone); ActorSelection sel = ActorUtil.getSelectionByName(actorName); sel.tell(statusEffectTarget.clone(), sender); } if (passiveEffectCount(statusEffectTarget) > 0) { actorName = PassiveEffectHandler.actorName(gridName, zone); ActorSelection sel = ActorUtil.getSelectionByName(actorName); sel.tell(statusEffectTarget.clone(), sender); } } private static boolean hasEffects(StatusEffectTarget statusEffectTarget) { if (StatusEffectData.skillEffects.containsKey(statusEffectTarget.skillRequest.playerSkill.id)) { return true; } else { return false; } } private static int passiveEffectCount(StatusEffectTarget statusEffectTarget) { int count = 0; for (StatusEffect statusEffect : StatusEffectData.skillEffects.get(statusEffectTarget.skillRequest.playerSkill.id)) { if (statusEffect.type == StatusEffect.Type.AttributeMaxDecrease || statusEffect.type == StatusEffect.Type.AttributeMaxIncrease) { count++; } } return count; } private static int activeEffectCount(StatusEffectTarget statusEffectTarget) { int count = 0; for (StatusEffect statusEffect : StatusEffectData.skillEffects.get(statusEffectTarget.skillRequest.playerSkill.id)) { if (statusEffect.type == StatusEffect.Type.AttributeDecrease || statusEffect.type == StatusEffect.Type.AttributeIncrease) { count++; } } return count; } public static int getEffectValue(StatusEffect statusEffect, PlayerSkill playerSkill, String characterId) { GameEntityManager gameEntityManager = GameEntityManagerService.instance().getGameEntityManager(); return gameEntityManager.getEffectValue(statusEffect, playerSkill.id, characterId); } public static boolean inGroup(String playerId) { String playerGroup = ChatSubscriptions.playerGroup(playerId); if (playerGroup.equals("nogroup")) { return false; } else { return true; } } public static void skillUsed(PlayerSkill playerSkill, String characterId) { GameEntityManager gameEntityManager = GameEntityManagerService.instance().getGameEntityManager(); gameEntityManager.skillUsed(playerSkill.id, characterId); } public static String playerGroup(String playerId) { return ChatSubscriptions.playerGroup(playerId); } public static boolean inSameGroup(String playerId, String otherId) { if (!inGroup(playerId)) { return false; } String otherGroup = ChatSubscriptions.playerGroup(otherId); if (playerGroup(playerId).equals(otherGroup)) { return true; } else { return false; } } public static boolean DeductCost(VitalsProxy vitalsProxy, StatusEffect statusEffect) { if (statusEffect.resourceCost == 0) { return true; } if (statusEffect.resource == StatusEffect.Resource.ResourceStamina) { if (vitalsProxy.get("stamina") < statusEffect.resourceCost) { //logger.warn("Insufficient stamina needed " + statusEffect.resourceCost); return false; } vitalsProxy.subtract("stamina", statusEffect.resourceCost); } else if (statusEffect.resource == StatusEffect.Resource.ResourceMagic) { if (vitalsProxy.get("magic") < statusEffect.resourceCost) { //logger.warn("Insufficient magic needed " + statusEffect.resourceCost); return false; } vitalsProxy.subtract("magic", statusEffect.resourceCost); } return true; } public static void sendCombatDamage(VitalsProxy origin, VitalsProxy target, int value, CombatLog.Type type, String zone) { GameEntityManager gameEntityManager = GameEntityManagerService.instance().getGameEntityManager(); gameEntityManager.combatDamage(origin, target, value, type); if (!combatLogEnabled) { return; } GameMessage msg = new GameMessage(); msg.combatLog = new CombatLog(); msg.combatLog.origin = origin.getEntityId(); msg.combatLog.target = target.getEntityId(); msg.combatLog.value = value; msg.combatLog.type = type; Grid grid = GridService.getInstance().getGrid(zone, "default"); TrackData trackData = grid.get(msg.combatLog.origin); if (trackData != null) { PlayerMessage.tell(msg, trackData.id); } trackData = grid.get(msg.combatLog.target); if (trackData != null) { PlayerMessage.tell(msg, trackData.id); } } public StatusEffectManager() { createDefaultEffectHandlers(); } private void createDefaultEffectHandlers() { int zoneCount = RegionInfo.db().findAll().size(); if (zoneCount == 0) { logger.warn("Combat system requires at least one zone configured"); return; } for (Zone zone : ZoneService.staticZones()) { createEffectHandler(zone.name); } } public static void createEffectHandler(String zone) { if (handlerZones.contains(zone)) { logger.warn("effect handler already created for zone " + zone); return; } GridSet gridSet = new GridSet(); gridSet.zone = zone; GridService.getInstance().createForZone(zone); gridSet.playerGrid = GridService.getInstance().getGrid(zone, "default"); gridSet.objectGrid = GridService.getInstance().getGrid(zone, "build_objects"); gridsets.add(gridSet); GameMachineLoader.getActorSystem().actorOf(Props.create(ActiveEffectHandler.class, "default", zone), ActiveEffectHandler.actorName("default", zone)); GameMachineLoader.getActorSystem().actorOf(Props.create(ActiveEffectHandler.class, "build_objects", zone), ActiveEffectHandler.actorName("build_objects", zone)); GameMachineLoader.getActorSystem().actorOf(Props.create(PassiveEffectHandler.class, "default", zone), PassiveEffectHandler.actorName("default", zone)); GameMachineLoader.getActorSystem().actorOf(Props.create(PassiveEffectHandler.class, "build_objects", zone), PassiveEffectHandler.actorName("build_objects", zone)); GameMachineLoader.getActorSystem().actorOf(Props.create(VitalsRegen.class, zone), VitalsRegen.actorName(zone)); handlerZones.add(zone); } @Override public void onReceive(Object arg0) throws Exception { // TODO Auto-generated method stub } }

From Four Until Late "From Four Until Late" (or "From Four Till Late") is a blues song written by Delta blues musician Robert Johnson. He recorded it in Dallas, Texas, during his second to last session for producer Don Law on June 19, 1937. The lyrics contained his philosophical lines of "a man is like a prisoner, and he's never satisfied". British rock group Cream recorded the song for their debut album Fresh Cream in 1966. Guitarist Eric Clapton provided the lead vocal. Clapton also recorded another version of the song on his Sessions for Robert J album in 2004. References Category:Robert Johnson songs Category:Songs written by Robert Johnson Category:1937 songs Category:Cream (band) songs Category:Blues songs

package com.trinity.sample.view.foucs enum class AutoFocusTrigger { GESTURE, METHOD }

J-A08035-19 NON-PRECEDENTIAL DECISION - SEE SUPERIOR COURT I.O.P. 65.37 COMMONWEALTH OF PENNSYLVANIA : IN THE SUPERIOR COURT OF : PENNSYLVANIA : v. : : : ERIK R. SURRATT : : Appellant : No. 469 WDA 2018 Appeal from the Judgment of Sentence Entered January 10, 2018 In the Court of Common Pleas of Allegheny County Criminal Division at No(s): CP-02-CR-0005355-2005, CP-02-CR-0005495-2005 BEFORE: PANELLA, P.J., STABILE, J., and McLAUGHLIN, J. MEMORANDUM BY McLAUGHLIN, J.: FILED JULY 26, 2019 Erik R. Surratt appeals from the judgment of sentence entered following a resentencing hearing pursuant to Miller v. Alabama, 567 U.S. 460 (2012), and Montgomery v. Louisiana, 136 S.Ct. 718 (2016). Surratt claims that in fashioning his sentence, the PCRA1 court erroneously considered him an adult, failed to consider whether he was capable of rehabilitation, and failed to consider the Miller factors. We affirm. Surratt was one of three individuals involved in a shooting that resulted in the death of two victims and one victim being wounded. Surratt shot one of the victims that died. Surratt was approximately 17 ½ years old at the time of the murders. A jury convicted Surratt of two counts of first-degree murder and other offenses. In 2008, the trial court sentenced Surratt to two life ____________________________________________ 1 Post Conviction Relief Act, 42 Pa.C.S.A. §§ 9541-9546. J-A08035-19 sentences without parole and 25 to 50 years’ incarceration for the remaining charges. This Court affirmed the judgment of sentence. In 2017, the PCRA court granted Surratt a resentencing, pursuant to Miller and Montgomery. At the resentencing hearing, Surratt presented five witnesses. One of the witnesses was a forensic social worker who testified to Surratt’s rehabilitation. Following two hearings, the PCRA court resentenced Surratt to 40 years’ incarceration to life imprisonment. Surratt filed a post-sentence motion which the trial court denied. This timely appeal followed. On appeal, Surratt raises the following issues: I. Whether the lower court erred and abused its discretion in imposing a 40-year minimum sentence because the Court failed to acknowledge or appropriately consider the factors laid out in Miller v. Alabama, 567 U.S. 460 (2012), and Montgomery v. Louisiana, 136 S.Ct. 718 (2016), in light of the diminished capabilities and greater prospects for reform of the adolescent offender. II. Whether the lower court erred and abused its discretion by placing excessive weight on the facts of the crime rather than focusing on Miller’s central question of whether the juvenile is capable of rehabilitation. The facts of the murder are not determinative in assessing permanent incorrigibility. III. Whether the lower court erred and abused its discretion by impermissibly considering Mr. Surratt to be an adult at the time of the offense, repeatedly referring the “arbitrary line” the U.S. Supreme Court had drawn between offenders under the age of 18 and those who are 18 and older. The Court does not have the discretion to make a finding contrary to the United States Supreme Court’s “legal conclusion[s] . . . and the facts (scientific studies) underlying it” when it concerns the inherent traits associated with adolescent development. See Commonwealth v. Batts, 163 A.3d 410, 437 (Pa. -2- J-A08035-19 2017). Because the Commonwealth failed to introduce any new evidence at the resentencing hearing, the Court also lacked competent evidence to make the aforementioned finding. Surratt’s Br. at 6-7. Surratt’s first two claims challenge discretionary aspects of his sentence. See Commonwealth v. White, 193 A.3d 977, 981 (Pa.Super. 2018) (concluding claims that trial court failed to consider Miller factors and did not consider rehabilitative evidence are challenges to discretionary aspects of sentence). As such, we must first determine whether: (1) the appeal is timely; (2) the issue is preserved; (3) appellant’s brief includes a Pa.R.A.P. 2119(f) statement; and (4) a substantial question is raised. See Commonwealth v. Battles, 169 A.3d 1086, 1090 (Pa.Super. 2017). Here, Surratt has satisfied the first three factors. We now address whether he has raised a substantial question. Surratt maintains that the PCRA court imposed an excessive sentence and failed to consider his mitigating factors. He claims that the PCRA court incorrectly “considered [him] an adult at the time of the crime, and focused on the life without parole sentences imposed on [his] adult co-defendants.” Surratt’s Br. at 14-15. He also maintains that the sentence imposed by the court is excessive for a crime that was committed by a juvenile and is “contrary to the fundamental norms underlying the sentencing process, and is inconsistent with the Sentencing Code.” Id. at 15. -3- J-A08035-19 Surratt’s claim of an excessive sentence paired with a claim that the court failed to consider his mitigating factors raises a substantial question. See Commonwealth v. Swope, 123 A.3d 333, 339 (Pa.Super. 2015). Therefore, we will address the merit of his claims. We review a challenge to discretionary aspects of sentencing for an abuse of discretion. See Commonwealth v. Derry, 150 A.3d 987, 997 (Pa.Super. 2016). An abuse of discretion exists where “the sentencing court ignored or misapplied the law, exercised its judgment for reasons of partiality, prejudice, bias or ill[-]will, or arrived at a manifestly unreasonable decision.” Id. (quoting Commonwealth v. Hoch, 936 A.2d 515, 517-18 (Pa.Super. 2007)). Surratt claims that the PCRA court “wholly failed to consider [his] individual, juvenile characteristics – focusing instead on the details of Surratt’s crime, improperly considering Surratt as an adult, and weighing the life sentences imposed on Surratt’s adult co-defendants.” Surratt’s Br. at 18. He argues it failed to consider his juvenile characteristics as referenced in Miller. To begin, the PCRA court was not required to consider the Miller factors. The Miller2 factors must be considered “when a juvenile is exposed to a potential sentence of life without the possibility of parole[.]” Commonwealth ____________________________________________ 2These factors include such things as “immaturity, impetuosity, and failure to appreciate risks and consequences; . . .” Batts II, 163 A.3d at 438 (quoting Miller, 567 U.S. at 477-78). -4- J-A08035-19 v. Machicote, 206 A.3d 1110, 1120 (Pa. 2019); see also Batts II, 163 A.3d at 432. Here, the Commonwealth did not seek a life-without-parole sentence, and thus, the court was not required to consider the Miller factors. Commonwealth v. Lekka, --- A.3d ---, 2019 WL 2064541, at *9 (Pa.Super. filed May 10, 2019) (“In cases where the Commonwealth does not seek a life- without-parole sentence, the application of the Miller factors is not required”). While Surratt maintains that the PCRA court improperly considered him an adult, we disagree. The PCRA court conceded it had to reconsider Surratt’s sentence pursuant to Miller and Montgomery because Surratt was under the age of 18 at the time of the murders. However, the court observed that the age of majority was somewhat arbitrary and concluded that, as Surratt was 17½ when he committed the murders, he was relatively mature, as demonstrated, in part, by his actions during his crimes.3 See N.T., 12/6/17, ____________________________________________ 3 The court explained why it believed that Surratt was mature at the time of committing the murders as follows: The Court: And you have to understand how I feel about this crime. It may well be that he has completely turned his life around, and at least for the sake of argument I will accept that. And at the time this happened, we are talking - - the Supreme Court case talks about juveniles. There is no question in my mind that Mr. Surratt was an adult. I mean, he was six months away from 18. He was sophisticated. He had, for the very least, engaged in criminal activity for three or four years before this happened. I mean, he was running wild. He was running with a bunch of, as far as I can tell, criminals. He was a sophisticated person. . . . We are not talking about a six-year old, who accidently shoots the -5- J-A08035-19 at 111-12. It went on to say, “As I said before, this was a - - for lack of a better term - - this is the behavior of an adult.” N.T., Reconsideration Hearing, 3/7/18 at 9 (emphasis added). It did not say that he was, in fact, an adult. This claim is thus meritless. Surratt’s additional claim that the court solely considered the facts of the crime without taking into consideration Surratt’s potential for rehabilitation or his mitigating evidence also fails. He argues that the facts here are similar to Batts II because there was an improper “significant focus on the facts of Surratt’s crime . . . to the exclusion of considering his personal history and development as a juvenile.” Surratt’s Br. at 20. We disagree. After Miller and Montgomery, Batts was resentenced to life without parole. Batts II, 163 A.3d at 450. The Court concluded that because there was “ample positive support relative to Batts’ potential for rehabilitation[,]” remand was necessary for the trial court to “‘provide [Batts] some meaningful opportunity to obtain release based on demonstrated maturity and rehabilitation.’” Id. (quoting Miller, 567 U.S. at 479) (brackets in Batts II). It found that the trial court’s opinion made clear “that its conclusion that Batts’ ____________________________________________ neighbor, or even a ten-year old who accidently shoots the neighbor or accidently does one thing or another. This was a planned premeditated - - this is as premeditated as you can possibly get. N.T., 12/6/17, at 111-12. -6- J-A08035-19 actions were not the result of his ‘unfortunate yet transient immaturity’ was based exclusively on the fact that the murder was ‘deliberate and premedi[t]ated.’” Id. at 446 (quoting Sentencing Court Opinion). The facts before us are not the same. First, at the resentencing, Surratt was not sentenced to life without parole, but rather two concurrent terms of 40 years’ to life imprisonment. Second, the PCRA court was within its rights to consider the facts of the case in fashioning Surratt’s new sentence, as they are one of the permissible sentencing factors. The Sentencing Code explicitly provides that when selecting from the statutory sentencing alternatives, “the court shall follow the general principle that the sentence imposed should call for confinement that is consistent with the protection of the public, the gravity of the offense as it relates to the impact on the life of the victim and on the community, and the rehabilitative needs of the defendant.” 42 Pa.C.S.A. § 9721(b). The court’s consideration of the facts of Surratt’s crime was not improper. See Commonwealth v. Blount, 207 A.3d 925,937-38 (Pa.Super. 2019) (concluding trial court properly considered Section 9721(b) factors when resentencing juvenile pursuant to Montgomery and Miller). Additionally, the court was made aware of Surratt’s potential for rehabilitation by Surratt’s sentencing memorandum and letters written in Surratt’s support. It also heard testimony Surratt offered as mitigating evidence and received a presentence investigation report (“PSI”). Thus, the -7- J-A08035-19 trial court “consider[ed] the particular circumstances of the offense and the character of [Surratt], with reference to [Surratt’s] prior criminal record, age, personal characteristic, and potential for rehabilitation,” in fashioning Surratt’s sentence. Lekka, -- A.3d --, 2019 WL 2064541, at *6 (affirming judgment of sentence of 45 years to life imprisonment following resentencing hearing); see also Commonwealth v. Finnecy, 135 A.3d 1028, 1038 (Pa.Super. 2016) (stating that there is an assumption that court is aware of information provided in PSI, including mitigating factors). Surratt also maintains that the PCRA court improperly “weigh[ed] the life sentences imposed on Surratt’s adult co-defendants.” Surratt’s Br. at 18. This claim warrants no relief. The court explained that it was concerned about how the co-defendants’ sentences would compare with Surratt’s sentence. [The Court]: There is also the issue, and I brought this up the last time we were here, is I have three other people who are going to spend the rest of their lives in jail without the possibility of parole because of the fact that they were over 18 and they were over the artificial line. N.T., 1/10/18, at 7. While the court acknowledged its discomfort in the disparity of sentences, it nonetheless recognized that Surratt was not beyond rehabilitation and therefore concluded that while his co-defendants received life without parole, the same was not an appropriate sentence for Surratt. See Machicote, 206 A.3d at 1115 (stating there is a presumption against a sentence of life without parole for juvenile and may be rebutted by proving -8- J-A08035-19 that juvenile is incapable of rehabilitation); see also Trial Court Opinion, filed 8/29/18, at 4 (stating it “did not find beyond a reasonable doubt, that [Surratt] is incapable of rehabilitation”). Judgment of sentence affirmed. Judgment Entered. Joseph D. Seletyn, Esq. Prothonotary Date: 7/26/2019 -9- 

Escreva um **servidor** HTTP que recebe apenas requisições de POST e converte os caracteres no corpo da requisição para caixa-alta e retorna-os para o cliente. Seu servidor deve "escutar" na porta provida a você pelo primeiro argumento para seu programa. ---------------------------------------------------------------------- ## DICAS Ainda que você não esteja restrito ao uso das capacidades de streaming dos objetos `request` e `response`, será muito mais fácil se você decidir usá-las. Existe um grande número de pacotes diferentes no npm que você pode usar para *"transformar"* um streaming de dados enquanto ele está sendo passado. Para esse exercício, o pacote `through2-map` oferece a API mais simples. `through2-map` permite que você crie um *stream transformador* usando apenas uma única função que recebe um bloco de dados e retorna um outro bloco de dados. Ela é designada para funcionar como um `Array#map()`, só que para streams: ```js const map = require('through2-map') inStream.pipe(map(function (chunk) { return chunk.toString().split('').reverse().join('') })).pipe(outStream) ``` No exemplo acima, a data que estamos recebendo de `inStream` é convertida para uma String (se já não estiver nesse formato), os caracteres são revertidos e o resultado é passado para o `outStream`. Sendo assim nós fizemos um reversor de caracteres! Lembre-se que o tamanho do bloco é determinado pelo fluxo e você tem muito pouco controle sobre ele para os dados que está recebendo. Para instalar `through2-map` type: ```sh $ npm install through2-map ``` Se você não possuir uma conexão à Internet, simplesmente crie uma pasta `node_modules` e copie o diretório inteiro para o módulo que você quiser usar de dentro do diretório de instalação do {{appname}}: {rootdir:/node_modules/through2-map} A documentação do through2-map foi instalada junto com o {appname} no seu sistema e você pode lê-los apontando seu navegador para cá: {rootdir:/docs/through2-map.html}

Falevi Umutaua Falevi Umutaua is a Samoan professional football manager. Career In 2007, he coached the Samoa national football team. References External links Profile at Soccerway.com Profile at Soccerpunter.com Category:Year of birth missing (living people) Category:Living people Category:Samoan football managers Category:Samoa national football team managers Category:Place of birth missing (living people)

Changes in serum interleukin-6, C-reactive protein and thrombomodulin levels under periodontal ultrasonic debridement. This study aimed to compare the effect of single-visit full-mouth mechanical debridement (FMD) and quadrant-wise mechanical debridement (QMD) on the levels of serum interleukin (IL)-6, C-reactive protein (CRP) and soluble thrombomodulin. Thirty-six subjects with chronic periodontitis were randomly allocated to three groups: undergoing QMD, single-visit FMD with povidone iodine or with water. Serum IL-6 and soluble thrombomodulin were measured by enzyme-linked immunosorbent assay, and serum CRP was measured by the latex-enhanced nephelometric method. Serum IL-6 level increased significantly immediately after debridement in all the three groups, with this increase being greatest in the full-mouth groups. However, the increase in the full-mouth groups was not significantly higher than that of quadrant-wise group. In the quadrant-wise group, serum IL-6 level decreased significantly 1 month after debridement compared with baseline. Serum-soluble thrombomodulin decreased significantly in the full-mouth groups but not in the quadrant-wise group. Changes in CRP level were not significant at baseline or after debridement in all the three groups. FMD increased serum IL-6 and reduced serum-soluble thrombomodulin to a greater extent than QMD, suggesting that the former technique has stronger transient effects on systemic vascular endothelial functions than the latter.

The Effectiveness of Psychoeducational Interventions Focused on Sexuality in Cancer. Although sexual health is a common concern for oncology patients, no practical guidelines to sexual intervention exist, perhaps because of a lack of systematic reviews or meta-analyses. The objectives of this study were to determine the effect size for psychoeducational intervention focused on sexuality and to compare effect sizes according to intervention outcomes and characteristic. We explored quantitative evidence for the effects of sexual intervention for cancer patients or partners by using the electronic databases. Among them, we considered 15 eligible articles. The meta-analysis provided 133 effect sizes from 15 primary studies. The analysis revealed significant improvements after intervention, with a random-effects standardized mean difference of 0.75. Psychoeducational interventions focused on sexuality after cancer diagnosis were effective for compliance (2.40), cognitive aspect (1.29), and psychological aspect (0.83). Individual-based interventions (0.85) were more effective in improving outcomes than group approach and group combined with individual intervention. With regard to intervention providers, registered nurse only (2.22) and team approach including the registered nurse (2.38) had the highest effect size. Face-to-face intervention combined with telephone or the Internet (1.04) demonstrated a higher effect size than face-to-face (0.62) and telephone (0.58) independently. We conducted an analysis of data from various subgroups of preexisting studies, obtained an overall estimate of the effectiveness of the intervention, and compared its effectiveness across variables that affect intervention outcomes. These results provide empirical data for evidence-based practice and inform the development of useful intervention programs through a comprehensive review and meta-analysis of the results.

--- abstract: 'Franson’s Bell experiment with energy-time entanglement \[Phys. Rev. Lett. [**62**]{}, 2205 (1989)\] does not rule out all local hidden variable models. This defect can be exploited to compromise the security of Bell inequality-based quantum cryptography. We introduce a novel Bell experiment using genuine energy-time entanglement, based on a novel interferometer, which rules out all local hidden variable models. The scheme is feasible with actual technology.' author: - Adán Cabello - Alessandro Rossi - Giuseppe Vallone - Francesco De Martini - Paolo Mataloni title: 'Proposed Bell Experiment with Genuine Energy-Time Entanglement' --- Two particles exhibit “energy-time entanglement” when they are emitted at the same time in an energy-conserving process and the essential uncertainty in the time of emission makes undistinguishable two alternative paths that the particles can take. Franson [@Franson89] proposed an experiment to demonstrate the violation of local realism [@Bell64] using energy-time entanglement, based on a formal violation of the Bell Clauser-Horne-Shimony-Holt (CHSH) inequality [@CHSH69]. However, Aerts [*et al.*]{} [@AKLZ99] showed that, even in the ideal case of perfect preparation and perfect detection efficiency, there is a local hidden variable (LHV) model that simulates the results predicted by quantum mechanics for the experiment proposed by Franson [@Franson89]. This model proves that “the Franson experiment does not and cannot violate local realism” and that “\[t\]he reported violations of local realism from Franson experiments [@KVHNC90] have to be reexamined” [@AKLZ99]. Despite this fundamental deficiency, and despite that this defect can be exploited to create a Trojan horse attack in Bell inequality-based quantum cryptography [@Larsson02], Franson-type experiments have been extensively used for Bell tests and Bell inequality-based quantum cryptography [@TBZG00], have become standard in quantum optics [@Paul04; @GC08], and an extended belief is that “the results of experiments with the Franson experiment violate Bell’s inequalities” [@GC08]. This is particularly surprising, given that recent research has emphasized the fundamental role of a (loophole-free) violation of the Bell inequalities in proving the device-independent security of key distribution protocols [@Ekert91], and in detecting entanglement [@HGBL05]. Polarization entanglement can be transformed into energy-time entanglement [@Kwiat95]. However, to our knowledge, there is no single experiment showing a violation of the Bell-CHSH inequality using genuine energy-time entanglement (or “time-bin entanglement” [@BGTZ99]) that cannot be simulated by a LHV model. By “genuine” we mean not obtained by transforming a previous form of entanglement, but created because the essential uncertainty in the time of emission makes two alternative paths undistinguishable. Because of the above reasons, a single experiment using energy-time entanglement able to rule out all possible LHV models is of particular interest. The aim of this Letter is to describe such an experiment by means of a novel interferometric scheme. The main purpose of the new scheme is not to compete with existing interferometers used for quantum communication in terms of practical usability, but to fix a fundamental defect common to all of them. We will first describe the Franson Bell-CHSH experiment. Then, we will introduce a LHV model reproducing any conceivable violation of the Bell-CHSH inequality. The model underlines why a Franson-type experiment does not and cannot be used to violate local realism. Then, we will introduce a new two-photon energy-time Bell-CHSH experiment that avoids these problems and can be used for a conclusive Bell test. [*The Franson Bell-CHSH experiment.—*]{}The setup of a Franson Bell-CHSH experiment is in Fig. \[Fig1\]. The source emits two photons, photon $1$ to the left and photon $2$ to the right. Each of them is fed into an unbalanced interferometer. $BS_i$ are beam splitters and $M_i$ are perfect mirrors. There are two distant observers, Alice on the left and Bob on the right. Alice randomly chooses the phase of the phase shifter $\phi_A$ between $A_0$ and $A_1$, and records the counts in each of her detectors (labeled $a=+1$ and $a=-1$), the detection times, and the phase settings at $t_D-t_I$, where $t_D$ is the detection time and $t_I$ is the time the photon takes to reach the detector from the location of the phase shifter $\phi_A$. Similarly, Bob chooses $\phi_B$ between $B_0$ and $B_1$, and records the counts in each of his detectors (labeled $b=+1$ and $b=-1$), the detection times, and the phase settings. The setup must satisfy four requirements: (I) To have two-photon interference, the emission of the two photons must be simultaneous, the moment of emission unpredictable, and both interferometers identical. If the detections of the two photons are coincident, there is no information about whether both photons took the short paths $S$ or both took the long paths $L$. A simultaneous random emission is achieved in actual experiments by two methods, both based on spontaneous parametric down conversion. In energy-time experiments, a non-linear crystal is pumped continuously by a monochromatic laser so the moment of emission is unpredictable in a temporal window equal to the coherence time of the pump laser. In time-bin experiments, a non-linear crystal is pumped by pulses previously passing through an unbalanced interferometer, so it is the uncertainty of which pulse, the earlier or the later, has caused the emission what provokes the uncertainty in the emission time. In both cases, the simultaneity of the emission is guaranteed by the conservation of energy. (II) To prevent single-photon interference, the difference between paths $L$ and $S$, i.e., twice the distance between $BS1$ and $M1$, $\Delta {\cal L}=2 d(BS1,M1)$ (See Fig. \[Fig1\]), must satisfy $\Delta {\cal L} > c t_{\rm coh}$, where $c$ is the speed of light and $t_{\rm coh}$ is the coherence time of the photons. (III) To make distinguishable those events where one photon takes $S$ and the other takes $L$, $\Delta {\cal L}$ must satisfy $\Delta {\cal L} > c \Delta t_{\rm coinc}$, where $\Delta t_{\rm coinc}$ is the duration of the coincidence window. (IV) To prevent that the local phase setting at one side can affect the outcome at the other side, the local phase settings must randomly switch ($\phi_A$ between $A_0$ and $A_1$, and $\phi_B$ between $B_0$ and $B_1$) with a frequency of the order $c/D$, where $D=d({\rm Source},BS1)$. The observers record all their data locally and then compare them. If the detectors are perfect they find that $$\begin{aligned} P(A_i=+1)=P(A_i=-1)=\frac{1}{2}, \label{Amarginal} \\ P(B_j=+1)=P(B_j=-1)=\frac{1}{2}, \label{Bmarginal}\end{aligned}$$ for $i,j \in \{0,1\}$. $P(A_0=+1)$ is the probability of detecting a photon in the detector $a=+1$ if the setting of $\phi_A$ was $A_0$. They also find $25\%$ of two-photon events in which photon $1$ is detected a time $\Delta {\cal L} /c$ before photon $2$, and $25\%$ of events in which photon $1$ is detected $\Delta {\cal L}/c$ after photon $2$. The observers reject this $50\%$ of events and keep the $50\%$ that are coincident. For these selected events, quantum mechanics predicts that $$P(A_i=a, B_j=b)=\frac{1}{4}\left[1+ab \cos(\phi_{A_i}+\phi_{B_j})\right], \label{joint}$$ where $a,b \in \{-1,+1\}$ and $\phi_{A_i}$ ($\phi_{B_j}$) is the phase setting corresponding to $A_i$ ($B_j$). The Bell-CHSH inequality is $$-2 \le \beta_{\rm CHSH} \le 2, \label{CHSH}$$ where $$\beta_{\rm CHSH} = \langle A_0 B_0 \rangle + \langle A_0 B_1 \rangle + \langle A_1 B_0 \rangle - \langle A_1 B_1 \rangle.$$ According to quantum mechanics, the maximal violation of the Bell-CHSH inequality is $\beta_{\rm CHSH} = 2 \sqrt{2}$ [@Tsirelson80], and is obtained, e.g., with $\phi_{A_0}=0$, $\phi_{A_1}=\frac{\pi}{2}$, $\phi_{B_0}=-\frac{\pi}{4}$, $\phi_{B_1}=\frac{\pi}{4}$. -------------------------------------------------------------------------------------------------------------------------------- $A_0$ $A_1$ $B_0$ $B_1$ $\langle $\langle A_0 B_1 \rangle$ $\langle A_1 $\langle A_1 B_1 \rangle$ A_0 B_0 \rangle$ B_0 \rangle$ -------- -------- -------- -------- ------------------ --------------------------- -------------- --------------------------- -- $S+$ $S+$ $S+$ $L\pm$ $+1$ rejected $+1$ rejected $L+$ $L+$ $L+$ $S\pm$ $+1$ rejected $+1$ rejected $S+$ $S-$ $L\pm$ $S+$ rejected $+1$ rejected $-1$ $L+$ $L-$ $S\pm$ $L+$ rejected $+1$ rejected $-1$ $S+$ $L\pm$ $S+$ $S+$ $+1$ $+1$ rejected rejected $L+$ $S\pm$ $L+$ $L+$ $+1$ $+1$ rejected rejected $L\pm$ $S+$ $S+$ $S-$ rejected rejected $+1$ $-1$ $S\pm$ $L+$ $L+$ $L-$ rejected rejected $+1$ $-1$ -------------------------------------------------------------------------------------------------------------------------------- : \[TableI\]$32$ sets of instructions (out of $64$) of the LHV model (the other $32$ are in Table \[TableII\]). Each row represents $4$ sets of local instructions (first $4$ entries) and their corresponding contributions for the calculation of $\beta_{\rm CHSH}$ after applying the postselection procedure of the Franson experiment (last $4$ entries). For each row, two sets (corresponding to $\pm$ signs) are explicitly written, while the other two can be obtained by changing all signs. -------------------------------------------------------------------------------------------------------------------------------- $A_0$ $A_1$ $B_0$ $B_1$ $\langle $\langle A_0 B_1 \rangle$ $\langle A_1 $\langle A_1 B_1 \rangle$ A_0 B_0 \rangle$ B_0 \rangle$ -------- -------- -------- -------- ------------------ --------------------------- -------------- --------------------------- -- $S+$ $S+$ $S-$ $L\pm$ $-1$ rejected $-1$ rejected $L+$ $L+$ $L-$ $S\pm$ $-1$ rejected $-1$ rejected $S+$ $S-$ $L\pm$ $S-$ rejected $-1$ rejected $+1$ $L+$ $L-$ $S\pm$ $L-$ rejected $-1$ rejected $+1$ $S-$ $L\pm$ $S+$ $S+$ $-1$ $-1$ rejected rejected $L-$ $S\pm$ $L+$ $L+$ $-1$ $-1$ rejected rejected $L\pm$ $S-$ $S+$ $S-$ rejected rejected $-1$ $+1$ $S\pm$ $L-$ $L+$ $L-$ rejected rejected $-1$ $+1$ -------------------------------------------------------------------------------------------------------------------------------- : \[TableII\]$32$ sets of instructions of the LHV model. [*LHV models for the Franson experiment.—*]{}A LHV theory for the Franson experiment must describe how each of the photons makes two decisions. The $+1/-1$ decision: the decision of a detection to occur at detector $+1$ or at detector $-1$, and the $S/L$ decision: the decision of a detection to occur at time $t_D=t$ or a time $t_D=t+\frac{\Delta {\cal L}}{c}$. Both decisions may be made as late as the detection time $t_D$, and may be based on events in the backward light cones of the detections. In a Franson-type setup both decisions may be based on the corresponding local phase setting at $t_D-t_I$. For a conclusive Bell test, there is no problem if photons make the $+1/-1$ decision based on the local phase setting. The problem is that the $50\%$ postselection procedure should be independent on the phase settings, otherwise the Bell-CHSH inequality (\[CHSH\]) is not valid. In the Franson experiment the phase setting at $t_D-t_I$ can causally affect the decision of a detection of the corresponding photon to occur at time $t_D=t$ or a time $t_D=t+\frac{\Delta {\cal L}}{c}$. If the $S/L$ decision can depend on the phase settings, then, after the $50\%$ postselection procedure, one can formally obtain not only the violations predicted by quantum mechanics, as proven in [@AKLZ99], but any value of $\beta_{\rm CHSH}$, even those forbidden by quantum mechanics. This is proven by constructing a family of explicit LHV models. Consider the $64$ sets of local instructions in tables \[TableI\] and \[TableII\]. For instance, if the pair of photons follows the first set of local instructions in Table \[TableI\], $(A_0=)S+$, $(A_1=)S+$, $(B_0=)S-$, $(B_1=)L+$, then, if the setting of $\phi_A$ is $A_0$ or $A_1$, photon $1$ will be detected by the detector $a=+1$ at time $t$ (corresponding to the path $S$), and if the setting of $\phi_B$ is $B_0$, photon $2$ will be detected by $b=-1$ at time $t$, but if the setting of $\phi_B$ is $B_1$, photon $2$ will be detected by $b=+1$ at time $t+\frac{\Delta {\cal L}}{c}$ (corresponding to the path $L$). If each of the $32$ sets of instructions in Table \[TableI\] occurs with probability $p/32$, and each of the $32$ sets of instructions in Table \[TableII\] with probability $(1-p)/32$, then it is easy to see that, for any value of $0 \le p \le 1$, the model gives $25\%$ of $SL$ events, $25\%$ of $LS$ events, $50\%$ of $SS$ or $LL$ events, and satisfies (\[Amarginal\]) and (\[Bmarginal\]). If $p=0$, the model gives $\beta_{\rm CHSH}=-4$. If $p=1$, the model gives $\beta_{\rm CHSH}=4$. If $0 < p < 1$, the model gives any value between $-4 < \beta_{\rm CHSH} < 4$. Specifically, a maximal quantum violation $\beta_{\rm CHSH} = 2 \sqrt{2}$, satisfying (\[joint\]), is obtained when $p=(2+\sqrt{2})/4$. The reason why this LHV model is possible is that the $50\%$ postselection procedure in Franson’s experiment allows the subensemble of selected events to depend on the phase settings. For instance, the first $8$ sets of instructions in Table \[TableI\] are rejected only when $\phi_B=B_1$. The main aim of this Letter is to introduce a similar experiment which does not have this problem. There is a previously proposed solution consisting on replacing the beam splitters $BS_1$ and $BS_2$ in Fig. \[Fig1\] by switchers synchronized with the source [@BGTZ99]. However, these active switchers are replaced in actual experiments by passive beam splitters [@TBZG00; @BGTZ99] that force a Franson-type postselection with the same problem described above. One way to avoid the problem is to make an extra assumption, namely that the decision of being detected at time $t_D=t$ or a time $t_D=t+\frac{\Delta {\cal L}}{c}$ is actually made at the first beam splitter, before having information of the local phase settings [@AKLZ99; @Franson99]. This assumption is similar to the fair sampling assumption, namely that the probability of rejection does not depend on the measurement settings. As we have seen, there are local models that do not satisfy this assumption. The experiment we propose does not require this extra assumption. [*Proposed energy-time entanglement Bell experiment.—*]{}The setup of the new Bell experiment is illustrated in Fig. \[Fig2\]. The source emits two photons, photon $1$ to the left and photon $2$ to the right. The $S$ path of photon $1$ (photon $2$) ends on the detectors $a$ on the left ($b$ on the right). The difference with Fig. \[Fig1\] is that now the $L$ path of photon $1$ (photon $2$) ends on the detectors $b$ ($a$). In this setup, the two photons end in different sides only when both are detected in coincidence. If one photon takes $S$ and the other photon takes $L$, both will end on detectors of the same side. An interferometer with this last property is described in [@RVDM08]. The data that the observers must record is the same as in Franson’s experiment. The setup must satisfy the following requirements: (I’) To have two-photon interference, the emission of the two photons must be simultaneous, the moment of emission unpredictable, and both arms of the setup identical. The phase stabilization of the entire setup of Fig. \[Fig2\] is more difficult than in Franson’s experiment. (II’) Single-photon interference is not possible in the setup of Fig. \[Fig2\]. (III’) To temporally distinguish two photons arriving at the same detector at times $t$ and $t+\frac{\Delta {\cal L}'}{c}$, where $\Delta {\cal L}'=2 [d({\rm Source},BS2)+d(BS2,M1)]$ (see Fig. \[Fig2\]), the dead time of the detectors must be smaller than $\frac{\Delta {\cal L}'}{c}$. For detectors with a dead time of $1$ ns, ${\Delta {\cal L}'} > 30$ cm. (IV’) The probability of two two-photons events in $\frac{\Delta {\cal L}'}{c}$ must be negligible. This naturally occurs when using standard non-linear crystals pumped continuously. (V’) To prevent that the local phase setting at one side can affect the outcome at the other side, the local phase settings must randomly switch ($\phi_A$ between $A_0$ and $A_1$, and $\phi_B$ between $B_0$ and $B_1$) with a frequency of the order $c/D'$, where $D'=d({\rm Source},\phi_A)\gg \Delta {\cal L}'$. There is a trade-off between the phase stabilization of the apparatus (which requires a short interferometer) and the prevention of reciprocal influences between the two local phase settings (which requires a long interferometer). By considering a random phase modulation frequency of 300 kHz, an interferometer about 1 km long would be needed. Current technology allows us to stabilize interferometers of up 4 km long (for instance, one of the interferometers of the LIGO experiment is 4 km long). With these stable interferometers, the experiment would be feasible. The predictions of quantum mechanics for the setup of Fig. \[Fig2\] are similar to those in Franson’s proposal: Eqs. (\[Amarginal\]) and (\[Bmarginal\]) hold, there is $25\%$ of events in which both photons are detected on the left at times $t$ and $t+\frac{\Delta {\cal L}'}{c}$, $25\%$ of events in which both photons are detected on the right, and $50\%$ of coincident events for which (\[joint\]) holds. The observers must keep the coincident events and reject those giving two detections on detectors of the same side. The main advantages of this setup are: (i) The rejection of events is local and does not require communication between the observers. (ii) The selection and rejection of events is independent of the local phase settings. This is the crucial difference with Franson’s experiment and deserves a detailed examination. First consider a selected event: both photons have been detected at time $t_D$, one in a detector $a$ on the left, and the other in a detector $b$ on the right. $t_I$ is the time a photon takes from $\phi_A$ ($\phi_B$) to a detector $a$ ($b$). The phase setting of $\phi_A$ ($\phi_B$) at $t_D-t_I$ is in the backward light cone of the photon detected in $a$ ($b$), but the point is, could a different value of one or both of the phase settings have caused that this selected event would become a rejected event in which both photons are detected on the same side? The answer is no. This would require a mechanism to make one detection to “wait” until the information about the setting in other side comes. However, when this information has finally arrived, the phase settings (both of them) have changed, so this information is useless to base a decision on it. Now consider a rejected event. For instance, one in which both photons are detected in the detectors $a$ on the left, one at time $t_D=t$, and the other at $t_D=t+\frac{\Delta {\cal L}'}{c}$. Then, the phase settings of $\phi_B$ at times $t_D-t_I$ are out of the backward light cones of the detected photons. The photons cannot have based their decisions on the phase settings of $\phi_B$. A different value of $\phi_A$ cannot have caused that this rejected event would become a selected event. This would require a mechanism to make one detection to wait until the information about the setting arrives to the other side, and when this information has arrived, the phase setting of $\phi_A$ has changed so this information is useless. For the proposed setup, there is no physical mechanism preserving locality which can turn a selected (rejected) event into a rejected (selected) event. The selected events are independent of the local phase settings. For the selected events, only the $+1/-1$ decision can depend on the phase settings. This is exactly the assumption under which the Bell-CHSH inequality (\[CHSH\]) is valid. Therefore, an experimental violation of (\[CHSH\]) using the setup of Fig. \[Fig2\] and the postselection procedure described before provides a conclusive (assuming perfect detectors) test of local realism using energy-time (or time-bin) entanglement. 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DO NOT EDIT. // +build 386,darwin // Code generated by cmd/cgo -godefs; DO NOT EDIT. // cgo -godefs -- -m32 _const.go package unix import "syscall" const ( AF_APPLETALK = 0x10 AF_CCITT = 0xa AF_CHAOS = 0x5 AF_CNT = 0x15 AF_COIP = 0x14 AF_DATAKIT = 0x9 AF_DECnet = 0xc AF_DLI = 0xd AF_E164 = 0x1c AF_ECMA = 0x8 AF_HYLINK = 0xf AF_IEEE80211 = 0x25 AF_IMPLINK = 0x3 AF_INET = 0x2 AF_INET6 = 0x1e AF_IPX = 0x17 AF_ISDN = 0x1c AF_ISO = 0x7 AF_LAT = 0xe AF_LINK = 0x12 AF_LOCAL = 0x1 AF_MAX = 0x28 AF_NATM = 0x1f AF_NDRV = 0x1b AF_NETBIOS = 0x21 AF_NS = 0x6 AF_OSI = 0x7 AF_PPP = 0x22 AF_PUP = 0x4 AF_RESERVED_36 = 0x24 AF_ROUTE = 0x11 AF_SIP = 0x18 AF_SNA = 0xb AF_SYSTEM = 0x20 AF_UNIX = 0x1 AF_UNSPEC = 0x0 AF_UTUN = 0x26 ALTWERASE = 0x200 ATTR_BIT_MAP_COUNT = 0x5 ATTR_CMN_ACCESSMASK = 0x20000 ATTR_CMN_ACCTIME = 0x1000 ATTR_CMN_ADDEDTIME = 0x10000000 ATTR_CMN_BKUPTIME = 0x2000 ATTR_CMN_CHGTIME = 0x800 ATTR_CMN_CRTIME = 0x200 ATTR_CMN_DATA_PROTECT_FLAGS = 0x40000000 ATTR_CMN_DEVID = 0x2 ATTR_CMN_DOCUMENT_ID = 0x100000 ATTR_CMN_ERROR = 0x20000000 ATTR_CMN_EXTENDED_SECURITY = 0x400000 ATTR_CMN_FILEID = 0x2000000 ATTR_CMN_FLAGS = 0x40000 ATTR_CMN_FNDRINFO = 0x4000 ATTR_CMN_FSID = 0x4 ATTR_CMN_FULLPATH = 0x8000000 ATTR_CMN_GEN_COUNT = 0x80000 ATTR_CMN_GRPID = 0x10000 ATTR_CMN_GRPUUID = 0x1000000 ATTR_CMN_MODTIME = 0x400 ATTR_CMN_NAME = 0x1 ATTR_CMN_NAMEDATTRCOUNT = 0x80000 ATTR_CMN_NAMEDATTRLIST = 0x100000 ATTR_CMN_OBJID = 0x20 ATTR_CMN_OBJPERMANENTID = 0x40 ATTR_CMN_OBJTAG = 0x10 ATTR_CMN_OBJTYPE = 0x8 ATTR_CMN_OWNERID = 0x8000 ATTR_CMN_PARENTID = 0x4000000 ATTR_CMN_PAROBJID = 0x80 ATTR_CMN_RETURNED_ATTRS = 0x80000000 ATTR_CMN_SCRIPT = 0x100 ATTR_CMN_SETMASK = 0x41c7ff00 ATTR_CMN_USERACCESS = 0x200000 ATTR_CMN_UUID = 0x800000 ATTR_CMN_VALIDMASK = 0xffffffff ATTR_CMN_VOLSETMASK = 0x6700 ATTR_FILE_ALLOCSIZE = 0x4 ATTR_FILE_CLUMPSIZE = 0x10 ATTR_FILE_DATAALLOCSIZE = 0x400 ATTR_FILE_DATAEXTENTS = 0x800 ATTR_FILE_DATALENGTH = 0x200 ATTR_FILE_DEVTYPE = 0x20 ATTR_FILE_FILETYPE = 0x40 ATTR_FILE_FORKCOUNT = 0x80 ATTR_FILE_FORKLIST = 0x100 ATTR_FILE_IOBLOCKSIZE = 0x8 ATTR_FILE_LINKCOUNT = 0x1 ATTR_FILE_RSRCALLOCSIZE = 0x2000 ATTR_FILE_RSRCEXTENTS = 0x4000 ATTR_FILE_RSRCLENGTH = 0x1000 ATTR_FILE_SETMASK = 0x20 ATTR_FILE_TOTALSIZE = 0x2 ATTR_FILE_VALIDMASK = 0x37ff ATTR_VOL_ALLOCATIONCLUMP = 0x40 ATTR_VOL_ATTRIBUTES = 0x40000000 ATTR_VOL_CAPABILITIES = 0x20000 ATTR_VOL_DIRCOUNT = 0x400 ATTR_VOL_ENCODINGSUSED = 0x10000 ATTR_VOL_FILECOUNT = 0x200 ATTR_VOL_FSTYPE = 0x1 ATTR_VOL_INFO = 0x80000000 ATTR_VOL_IOBLOCKSIZE = 0x80 ATTR_VOL_MAXOBJCOUNT = 0x800 ATTR_VOL_MINALLOCATION = 0x20 ATTR_VOL_MOUNTEDDEVICE = 0x8000 ATTR_VOL_MOUNTFLAGS = 0x4000 ATTR_VOL_MOUNTPOINT = 0x1000 ATTR_VOL_NAME = 0x2000 ATTR_VOL_OBJCOUNT = 0x100 ATTR_VOL_QUOTA_SIZE = 0x10000000 ATTR_VOL_RESERVED_SIZE = 0x20000000 ATTR_VOL_SETMASK = 0x80002000 ATTR_VOL_SIGNATURE = 0x2 ATTR_VOL_SIZE = 0x4 ATTR_VOL_SPACEAVAIL = 0x10 ATTR_VOL_SPACEFREE = 0x8 ATTR_VOL_UUID = 0x40000 ATTR_VOL_VALIDMASK = 0xf007ffff B0 = 0x0 B110 = 0x6e B115200 = 0x1c200 B1200 = 0x4b0 B134 = 0x86 B14400 = 0x3840 B150 = 0x96 B1800 = 0x708 B19200 = 0x4b00 B200 = 0xc8 B230400 = 0x38400 B2400 = 0x960 B28800 = 0x7080 B300 = 0x12c B38400 = 0x9600 B4800 = 0x12c0 B50 = 0x32 B57600 = 0xe100 B600 = 0x258 B7200 = 0x1c20 B75 = 0x4b B76800 = 0x12c00 B9600 = 0x2580 BIOCFLUSH = 0x20004268 BIOCGBLEN = 0x40044266 BIOCGDLT = 0x4004426a BIOCGDLTLIST = 0xc00c4279 BIOCGETIF = 0x4020426b BIOCGHDRCMPLT = 0x40044274 BIOCGRSIG = 0x40044272 BIOCGRTIMEOUT = 0x4008426e BIOCGSEESENT = 0x40044276 BIOCGSTATS = 0x4008426f BIOCIMMEDIATE = 0x80044270 BIOCPROMISC = 0x20004269 BIOCSBLEN = 0xc0044266 BIOCSDLT = 0x80044278 BIOCSETF = 0x80084267 BIOCSETFNR = 0x8008427e BIOCSETIF = 0x8020426c BIOCSHDRCMPLT = 0x80044275 BIOCSRSIG = 0x80044273 BIOCSRTIMEOUT = 0x8008426d BIOCSSEESENT = 0x80044277 BIOCVERSION = 0x40044271 BPF_A = 0x10 BPF_ABS = 0x20 BPF_ADD = 0x0 BPF_ALIGNMENT = 0x4 BPF_ALU = 0x4 BPF_AND = 0x50 BPF_B = 0x10 BPF_DIV = 0x30 BPF_H = 0x8 BPF_IMM = 0x0 BPF_IND = 0x40 BPF_JA = 0x0 BPF_JEQ = 0x10 BPF_JGE = 0x30 BPF_JGT = 0x20 BPF_JMP = 0x5 BPF_JSET = 0x40 BPF_K = 0x0 BPF_LD = 0x0 BPF_LDX = 0x1 BPF_LEN = 0x80 BPF_LSH = 0x60 BPF_MAJOR_VERSION = 0x1 BPF_MAXBUFSIZE = 0x80000 BPF_MAXINSNS = 0x200 BPF_MEM = 0x60 BPF_MEMWORDS = 0x10 BPF_MINBUFSIZE = 0x20 BPF_MINOR_VERSION = 0x1 BPF_MISC = 0x7 BPF_MSH = 0xa0 BPF_MUL = 0x20 BPF_NEG = 0x80 BPF_OR = 0x40 BPF_RELEASE = 0x30bb6 BPF_RET = 0x6 BPF_RSH = 0x70 BPF_ST = 0x2 BPF_STX = 0x3 BPF_SUB = 0x10 BPF_TAX = 0x0 BPF_TXA = 0x80 BPF_W = 0x0 BPF_X = 0x8 BRKINT = 0x2 BS0 = 0x0 BS1 = 0x8000 BSDLY = 0x8000 CFLUSH = 0xf CLOCAL = 0x8000 CLOCK_MONOTONIC = 0x6 CLOCK_MONOTONIC_RAW = 0x4 CLOCK_MONOTONIC_RAW_APPROX = 0x5 CLOCK_PROCESS_CPUTIME_ID = 0xc CLOCK_REALTIME = 0x0 CLOCK_THREAD_CPUTIME_ID = 0x10 CLOCK_UPTIME_RAW = 0x8 CLOCK_UPTIME_RAW_APPROX = 0x9 CR0 = 0x0 CR1 = 0x1000 CR2 = 0x2000 CR3 = 0x3000 CRDLY = 0x3000 CREAD = 0x800 CRTSCTS = 0x30000 CS5 = 0x0 CS6 = 0x100 CS7 = 0x200 CS8 = 0x300 CSIZE = 0x300 CSTART = 0x11 CSTATUS = 0x14 CSTOP = 0x13 CSTOPB = 0x400 CSUSP = 0x1a CTL_HW = 0x6 CTL_KERN = 0x1 CTL_MAXNAME = 0xc CTL_NET = 0x4 DLT_A429 = 0xb8 DLT_A653_ICM = 0xb9 DLT_AIRONET_HEADER = 0x78 DLT_AOS = 0xde DLT_APPLE_IP_OVER_IEEE1394 = 0x8a DLT_ARCNET = 0x7 DLT_ARCNET_LINUX = 0x81 DLT_ATM_CLIP = 0x13 DLT_ATM_RFC1483 = 0xb DLT_AURORA = 0x7e DLT_AX25 = 0x3 DLT_AX25_KISS = 0xca DLT_BACNET_MS_TP = 0xa5 DLT_BLUETOOTH_HCI_H4 = 0xbb DLT_BLUETOOTH_HCI_H4_WITH_PHDR = 0xc9 DLT_CAN20B = 0xbe DLT_CAN_SOCKETCAN = 0xe3 DLT_CHAOS = 0x5 DLT_CHDLC = 0x68 DLT_CISCO_IOS = 0x76 DLT_C_HDLC = 0x68 DLT_C_HDLC_WITH_DIR = 0xcd DLT_DBUS = 0xe7 DLT_DECT = 0xdd DLT_DOCSIS = 0x8f DLT_DVB_CI = 0xeb DLT_ECONET = 0x73 DLT_EN10MB = 0x1 DLT_EN3MB = 0x2 DLT_ENC = 0x6d DLT_ERF = 0xc5 DLT_ERF_ETH = 0xaf DLT_ERF_POS = 0xb0 DLT_FC_2 = 0xe0 DLT_FC_2_WITH_FRAME_DELIMS = 0xe1 DLT_FDDI = 0xa DLT_FLEXRAY = 0xd2 DLT_FRELAY = 0x6b DLT_FRELAY_WITH_DIR = 0xce DLT_GCOM_SERIAL = 0xad DLT_GCOM_T1E1 = 0xac DLT_GPF_F = 0xab DLT_GPF_T = 0xaa DLT_GPRS_LLC = 0xa9 DLT_GSMTAP_ABIS = 0xda DLT_GSMTAP_UM = 0xd9 DLT_HHDLC = 0x79 DLT_IBM_SN = 0x92 DLT_IBM_SP = 0x91 DLT_IEEE802 = 0x6 DLT_IEEE802_11 = 0x69 DLT_IEEE802_11_RADIO = 0x7f DLT_IEEE802_11_RADIO_AVS = 0xa3 DLT_IEEE802_15_4 = 0xc3 DLT_IEEE802_15_4_LINUX = 0xbf DLT_IEEE802_15_4_NOFCS = 0xe6 DLT_IEEE802_15_4_NONASK_PHY = 0xd7 DLT_IEEE802_16_MAC_CPS = 0xbc DLT_IEEE802_16_MAC_CPS_RADIO = 0xc1 DLT_IPFILTER = 0x74 DLT_IPMB = 0xc7 DLT_IPMB_LINUX = 0xd1 DLT_IPNET = 0xe2 DLT_IPOIB = 0xf2 DLT_IPV4 = 0xe4 DLT_IPV6 = 0xe5 DLT_IP_OVER_FC = 0x7a DLT_JUNIPER_ATM1 = 0x89 DLT_JUNIPER_ATM2 = 0x87 DLT_JUNIPER_ATM_CEMIC = 0xee DLT_JUNIPER_CHDLC = 0xb5 DLT_JUNIPER_ES = 0x84 DLT_JUNIPER_ETHER = 0xb2 DLT_JUNIPER_FIBRECHANNEL = 0xea DLT_JUNIPER_FRELAY = 0xb4 DLT_JUNIPER_GGSN = 0x85 DLT_JUNIPER_ISM = 0xc2 DLT_JUNIPER_MFR = 0x86 DLT_JUNIPER_MLFR = 0x83 DLT_JUNIPER_MLPPP = 0x82 DLT_JUNIPER_MONITOR = 0xa4 DLT_JUNIPER_PIC_PEER = 0xae DLT_JUNIPER_PPP = 0xb3 DLT_JUNIPER_PPPOE = 0xa7 DLT_JUNIPER_PPPOE_ATM = 0xa8 DLT_JUNIPER_SERVICES = 0x88 DLT_JUNIPER_SRX_E2E = 0xe9 DLT_JUNIPER_ST = 0xc8 DLT_JUNIPER_VP = 0xb7 DLT_JUNIPER_VS = 0xe8 DLT_LAPB_WITH_DIR = 0xcf DLT_LAPD = 0xcb DLT_LIN = 0xd4 DLT_LINUX_EVDEV = 0xd8 DLT_LINUX_IRDA = 0x90 DLT_LINUX_LAPD = 0xb1 DLT_LINUX_PPP_WITHDIRECTION = 0xa6 DLT_LINUX_SLL = 0x71 DLT_LOOP = 0x6c DLT_LTALK = 0x72 DLT_MATCHING_MAX = 0xf5 DLT_MATCHING_MIN = 0x68 DLT_MFR = 0xb6 DLT_MOST = 0xd3 DLT_MPEG_2_TS = 0xf3 DLT_MPLS = 0xdb DLT_MTP2 = 0x8c DLT_MTP2_WITH_PHDR = 0x8b DLT_MTP3 = 0x8d DLT_MUX27010 = 0xec DLT_NETANALYZER = 0xf0 DLT_NETANALYZER_TRANSPARENT = 0xf1 DLT_NFC_LLCP = 0xf5 DLT_NFLOG = 0xef DLT_NG40 = 0xf4 DLT_NULL = 0x0 DLT_PCI_EXP = 0x7d DLT_PFLOG = 0x75 DLT_PFSYNC = 0x12 DLT_PPI = 0xc0 DLT_PPP = 0x9 DLT_PPP_BSDOS = 0x10 DLT_PPP_ETHER = 0x33 DLT_PPP_PPPD = 0xa6 DLT_PPP_SERIAL = 0x32 DLT_PPP_WITH_DIR = 0xcc DLT_PPP_WITH_DIRECTION = 0xa6 DLT_PRISM_HEADER = 0x77 DLT_PRONET = 0x4 DLT_RAIF1 = 0xc6 DLT_RAW = 0xc DLT_RIO = 0x7c DLT_SCCP = 0x8e DLT_SITA = 0xc4 DLT_SLIP = 0x8 DLT_SLIP_BSDOS = 0xf DLT_STANAG_5066_D_PDU = 0xed DLT_SUNATM = 0x7b DLT_SYMANTEC_FIREWALL = 0x63 DLT_TZSP = 0x80 DLT_USB = 0xba DLT_USB_LINUX = 0xbd DLT_USB_LINUX_MMAPPED = 0xdc DLT_USER0 = 0x93 DLT_USER1 = 0x94 DLT_USER10 = 0x9d DLT_USER11 = 0x9e DLT_USER12 = 0x9f DLT_USER13 = 0xa0 DLT_USER14 = 0xa1 DLT_USER15 = 0xa2 DLT_USER2 = 0x95 DLT_USER3 = 0x96 DLT_USER4 = 0x97 DLT_USER5 = 0x98 DLT_USER6 = 0x99 DLT_USER7 = 0x9a DLT_USER8 = 0x9b DLT_USER9 = 0x9c DLT_WIHART = 0xdf DLT_X2E_SERIAL = 0xd5 DLT_X2E_XORAYA = 0xd6 DT_BLK = 0x6 DT_CHR = 0x2 DT_DIR = 0x4 DT_FIFO = 0x1 DT_LNK = 0xa DT_REG = 0x8 DT_SOCK = 0xc DT_UNKNOWN = 0x0 DT_WHT = 0xe ECHO = 0x8 ECHOCTL = 0x40 ECHOE = 0x2 ECHOK = 0x4 ECHOKE = 0x1 ECHONL = 0x10 ECHOPRT = 0x20 EVFILT_AIO = -0x3 EVFILT_EXCEPT = -0xf EVFILT_FS = -0x9 EVFILT_MACHPORT = -0x8 EVFILT_PROC = -0x5 EVFILT_READ = -0x1 EVFILT_SIGNAL = -0x6 EVFILT_SYSCOUNT = 0xf EVFILT_THREADMARKER = 0xf EVFILT_TIMER = -0x7 EVFILT_USER = -0xa EVFILT_VM = -0xc EVFILT_VNODE = -0x4 EVFILT_WRITE = -0x2 EV_ADD = 0x1 EV_CLEAR = 0x20 EV_DELETE = 0x2 EV_DISABLE = 0x8 EV_DISPATCH = 0x80 EV_DISPATCH2 = 0x180 EV_ENABLE = 0x4 EV_EOF = 0x8000 EV_ERROR = 0x4000 EV_FLAG0 = 0x1000 EV_FLAG1 = 0x2000 EV_ONESHOT = 0x10 EV_OOBAND = 0x2000 EV_POLL = 0x1000 EV_RECEIPT = 0x40 EV_SYSFLAGS = 0xf000 EV_UDATA_SPECIFIC = 0x100 EV_VANISHED = 0x200 EXTA = 0x4b00 EXTB = 0x9600 EXTPROC = 0x800 FD_CLOEXEC = 0x1 FD_SETSIZE = 0x400 FF0 = 0x0 FF1 = 0x4000 FFDLY = 0x4000 FLUSHO = 0x800000 FSOPT_ATTR_CMN_EXTENDED = 0x20 FSOPT_NOFOLLOW = 0x1 FSOPT_NOINMEMUPDATE = 0x2 FSOPT_PACK_INVAL_ATTRS = 0x8 FSOPT_REPORT_FULLSIZE = 0x4 F_ADDFILESIGS = 0x3d F_ADDFILESIGS_FOR_DYLD_SIM = 0x53 F_ADDFILESIGS_RETURN = 0x61 F_ADDSIGS = 0x3b F_ALLOCATEALL = 0x4 F_ALLOCATECONTIG = 0x2 F_BARRIERFSYNC = 0x55 F_CHECK_LV = 0x62 F_CHKCLEAN = 0x29 F_DUPFD = 0x0 F_DUPFD_CLOEXEC = 0x43 F_FINDSIGS = 0x4e F_FLUSH_DATA = 0x28 F_FREEZE_FS = 0x35 F_FULLFSYNC = 0x33 F_GETCODEDIR = 0x48 F_GETFD = 0x1 F_GETFL = 0x3 F_GETLK = 0x7 F_GETLKPID = 0x42 F_GETNOSIGPIPE = 0x4a F_GETOWN = 0x5 F_GETPATH = 0x32 F_GETPATH_MTMINFO = 0x47 F_GETPROTECTIONCLASS = 0x3f F_GETPROTECTIONLEVEL = 0x4d F_GLOBAL_NOCACHE = 0x37 F_LOG2PHYS = 0x31 F_LOG2PHYS_EXT = 0x41 F_NOCACHE = 0x30 F_NODIRECT = 0x3e F_OK = 0x0 F_PATHPKG_CHECK = 0x34 F_PEOFPOSMODE = 0x3 F_PREALLOCATE = 0x2a F_PUNCHHOLE = 0x63 F_RDADVISE = 0x2c F_RDAHEAD = 0x2d F_RDLCK = 0x1 F_SETBACKINGSTORE = 0x46 F_SETFD = 0x2 F_SETFL = 0x4 F_SETLK = 0x8 F_SETLKW = 0x9 F_SETLKWTIMEOUT = 0xa F_SETNOSIGPIPE = 0x49 F_SETOWN = 0x6 F_SETPROTECTIONCLASS = 0x40 F_SETSIZE = 0x2b F_SINGLE_WRITER = 0x4c F_THAW_FS = 0x36 F_TRANSCODEKEY = 0x4b F_TRIM_ACTIVE_FILE = 0x64 F_UNLCK = 0x2 F_VOLPOSMODE = 0x4 F_WRLCK = 0x3 HUPCL = 0x4000 HW_MACHINE = 0x1 ICANON = 0x100 ICMP6_FILTER = 0x12 ICRNL = 0x100 IEXTEN = 0x400 IFF_ALLMULTI = 0x200 IFF_ALTPHYS = 0x4000 IFF_BROADCAST = 0x2 IFF_DEBUG = 0x4 IFF_LINK0 = 0x1000 IFF_LINK1 = 0x2000 IFF_LINK2 = 0x4000 IFF_LOOPBACK = 0x8 IFF_MULTICAST = 0x8000 IFF_NOARP = 0x80 IFF_NOTRAILERS = 0x20 IFF_OACTIVE = 0x400 IFF_POINTOPOINT = 0x10 IFF_PROMISC = 0x100 IFF_RUNNING = 0x40 IFF_SIMPLEX = 0x800 IFF_UP = 0x1 IFNAMSIZ = 0x10 IFT_1822 = 0x2 IFT_AAL5 = 0x31 IFT_ARCNET = 0x23 IFT_ARCNETPLUS = 0x24 IFT_ATM = 0x25 IFT_BRIDGE = 0xd1 IFT_CARP = 0xf8 IFT_CELLULAR = 0xff IFT_CEPT = 0x13 IFT_DS3 = 0x1e IFT_ENC = 0xf4 IFT_EON = 0x19 IFT_ETHER = 0x6 IFT_FAITH = 0x38 IFT_FDDI = 0xf IFT_FRELAY = 0x20 IFT_FRELAYDCE = 0x2c IFT_GIF = 0x37 IFT_HDH1822 = 0x3 IFT_HIPPI = 0x2f IFT_HSSI = 0x2e IFT_HY = 0xe IFT_IEEE1394 = 0x90 IFT_IEEE8023ADLAG = 0x88 IFT_ISDNBASIC = 0x14 IFT_ISDNPRIMARY = 0x15 IFT_ISO88022LLC = 0x29 IFT_ISO88023 = 0x7 IFT_ISO88024 = 0x8 IFT_ISO88025 = 0x9 IFT_ISO88026 = 0xa IFT_L2VLAN = 0x87 IFT_LAPB = 0x10 IFT_LOCALTALK = 0x2a IFT_LOOP = 0x18 IFT_MIOX25 = 0x26 IFT_MODEM = 0x30 IFT_NSIP = 0x1b IFT_OTHER = 0x1 IFT_P10 = 0xc IFT_P80 = 0xd IFT_PARA = 0x22 IFT_PDP = 0xff IFT_PFLOG = 0xf5 IFT_PFSYNC = 0xf6 IFT_PKTAP = 0xfe IFT_PPP = 0x17 IFT_PROPMUX = 0x36 IFT_PROPVIRTUAL = 0x35 IFT_PTPSERIAL = 0x16 IFT_RS232 = 0x21 IFT_SDLC = 0x11 IFT_SIP = 0x1f IFT_SLIP = 0x1c IFT_SMDSDXI = 0x2b IFT_SMDSICIP = 0x34 IFT_SONET = 0x27 IFT_SONETPATH = 0x32 IFT_SONETVT = 0x33 IFT_STARLAN = 0xb IFT_STF = 0x39 IFT_T1 = 0x12 IFT_ULTRA = 0x1d IFT_V35 = 0x2d IFT_X25 = 0x5 IFT_X25DDN = 0x4 IFT_X25PLE = 0x28 IFT_XETHER = 0x1a IGNBRK = 0x1 IGNCR = 0x80 IGNPAR = 0x4 IMAXBEL = 0x2000 INLCR = 0x40 INPCK = 0x10 IN_CLASSA_HOST = 0xffffff IN_CLASSA_MAX = 0x80 IN_CLASSA_NET = 0xff000000 IN_CLASSA_NSHIFT = 0x18 IN_CLASSB_HOST = 0xffff IN_CLASSB_MAX = 0x10000 IN_CLASSB_NET = 0xffff0000 IN_CLASSB_NSHIFT = 0x10 IN_CLASSC_HOST = 0xff IN_CLASSC_NET = 0xffffff00 IN_CLASSC_NSHIFT = 0x8 IN_CLASSD_HOST = 0xfffffff IN_CLASSD_NET = 0xf0000000 IN_CLASSD_NSHIFT = 0x1c IN_LINKLOCALNETNUM = 0xa9fe0000 IN_LOOPBACKNET = 0x7f IPPROTO_3PC = 0x22 IPPROTO_ADFS = 0x44 IPPROTO_AH = 0x33 IPPROTO_AHIP = 0x3d IPPROTO_APES = 0x63 IPPROTO_ARGUS = 0xd IPPROTO_AX25 = 0x5d IPPROTO_BHA = 0x31 IPPROTO_BLT = 0x1e IPPROTO_BRSATMON = 0x4c IPPROTO_CFTP = 0x3e IPPROTO_CHAOS = 0x10 IPPROTO_CMTP = 0x26 IPPROTO_CPHB = 0x49 IPPROTO_CPNX = 0x48 IPPROTO_DDP = 0x25 IPPROTO_DGP = 0x56 IPPROTO_DIVERT = 0xfe IPPROTO_DONE = 0x101 IPPROTO_DSTOPTS = 0x3c IPPROTO_EGP = 0x8 IPPROTO_EMCON = 0xe IPPROTO_ENCAP = 0x62 IPPROTO_EON = 0x50 IPPROTO_ESP = 0x32 IPPROTO_ETHERIP = 0x61 IPPROTO_FRAGMENT = 0x2c IPPROTO_GGP = 0x3 IPPROTO_GMTP = 0x64 IPPROTO_GRE = 0x2f IPPROTO_HELLO = 0x3f IPPROTO_HMP = 0x14 IPPROTO_HOPOPTS = 0x0 IPPROTO_ICMP = 0x1 IPPROTO_ICMPV6 = 0x3a IPPROTO_IDP = 0x16 IPPROTO_IDPR = 0x23 IPPROTO_IDRP = 0x2d IPPROTO_IGMP = 0x2 IPPROTO_IGP = 0x55 IPPROTO_IGRP = 0x58 IPPROTO_IL = 0x28 IPPROTO_INLSP = 0x34 IPPROTO_INP = 0x20 IPPROTO_IP = 0x0 IPPROTO_IPCOMP = 0x6c IPPROTO_IPCV = 0x47 IPPROTO_IPEIP = 0x5e IPPROTO_IPIP = 0x4 IPPROTO_IPPC = 0x43 IPPROTO_IPV4 = 0x4 IPPROTO_IPV6 = 0x29 IPPROTO_IRTP = 0x1c IPPROTO_KRYPTOLAN = 0x41 IPPROTO_LARP = 0x5b IPPROTO_LEAF1 = 0x19 IPPROTO_LEAF2 = 0x1a IPPROTO_MAX = 0x100 IPPROTO_MAXID = 0x34 IPPROTO_MEAS = 0x13 IPPROTO_MHRP = 0x30 IPPROTO_MICP = 0x5f IPPROTO_MTP = 0x5c IPPROTO_MUX = 0x12 IPPROTO_ND = 0x4d IPPROTO_NHRP = 0x36 IPPROTO_NONE = 0x3b IPPROTO_NSP = 0x1f IPPROTO_NVPII = 0xb IPPROTO_OSPFIGP = 0x59 IPPROTO_PGM = 0x71 IPPROTO_PIGP = 0x9 IPPROTO_PIM = 0x67 IPPROTO_PRM = 0x15 IPPROTO_PUP = 0xc IPPROTO_PVP = 0x4b IPPROTO_RAW = 0xff IPPROTO_RCCMON = 0xa IPPROTO_RDP = 0x1b IPPROTO_ROUTING = 0x2b IPPROTO_RSVP = 0x2e IPPROTO_RVD = 0x42 IPPROTO_SATEXPAK = 0x40 IPPROTO_SATMON = 0x45 IPPROTO_SCCSP = 0x60 IPPROTO_SCTP = 0x84 IPPROTO_SDRP = 0x2a IPPROTO_SEP = 0x21 IPPROTO_SRPC = 0x5a IPPROTO_ST = 0x7 IPPROTO_SVMTP = 0x52 IPPROTO_SWIPE = 0x35 IPPROTO_TCF = 0x57 IPPROTO_TCP = 0x6 IPPROTO_TP = 0x1d IPPROTO_TPXX = 0x27 IPPROTO_TRUNK1 = 0x17 IPPROTO_TRUNK2 = 0x18 IPPROTO_TTP = 0x54 IPPROTO_UDP = 0x11 IPPROTO_VINES = 0x53 IPPROTO_VISA = 0x46 IPPROTO_VMTP = 0x51 IPPROTO_WBEXPAK = 0x4f IPPROTO_WBMON = 0x4e IPPROTO_WSN = 0x4a IPPROTO_XNET = 0xf IPPROTO_XTP = 0x24 IPV6_2292DSTOPTS = 0x17 IPV6_2292HOPLIMIT = 0x14 IPV6_2292HOPOPTS = 0x16 IPV6_2292NEXTHOP = 0x15 IPV6_2292PKTINFO = 0x13 IPV6_2292PKTOPTIONS = 0x19 IPV6_2292RTHDR = 0x18 IPV6_BINDV6ONLY = 0x1b IPV6_BOUND_IF = 0x7d IPV6_CHECKSUM = 0x1a IPV6_DEFAULT_MULTICAST_HOPS = 0x1 IPV6_DEFAULT_MULTICAST_LOOP = 0x1 IPV6_DEFHLIM = 0x40 IPV6_FAITH = 0x1d IPV6_FLOWINFO_MASK = 0xffffff0f IPV6_FLOWLABEL_MASK = 0xffff0f00 IPV6_FLOW_ECN_MASK = 0x300 IPV6_FRAGTTL = 0x3c IPV6_FW_ADD = 0x1e IPV6_FW_DEL = 0x1f IPV6_FW_FLUSH = 0x20 IPV6_FW_GET = 0x22 IPV6_FW_ZERO = 0x21 IPV6_HLIMDEC = 0x1 IPV6_IPSEC_POLICY = 0x1c IPV6_JOIN_GROUP = 0xc IPV6_LEAVE_GROUP = 0xd IPV6_MAXHLIM = 0xff IPV6_MAXOPTHDR = 0x800 IPV6_MAXPACKET = 0xffff IPV6_MAX_GROUP_SRC_FILTER = 0x200 IPV6_MAX_MEMBERSHIPS = 0xfff IPV6_MAX_SOCK_SRC_FILTER = 0x80 IPV6_MIN_MEMBERSHIPS = 0x1f IPV6_MMTU = 0x500 IPV6_MULTICAST_HOPS = 0xa IPV6_MULTICAST_IF = 0x9 IPV6_MULTICAST_LOOP = 0xb IPV6_PORTRANGE = 0xe IPV6_PORTRANGE_DEFAULT = 0x0 IPV6_PORTRANGE_HIGH = 0x1 IPV6_PORTRANGE_LOW = 0x2 IPV6_RECVTCLASS = 0x23 IPV6_RTHDR_LOOSE = 0x0 IPV6_RTHDR_STRICT = 0x1 IPV6_RTHDR_TYPE_0 = 0x0 IPV6_SOCKOPT_RESERVED1 = 0x3 IPV6_TCLASS = 0x24 IPV6_UNICAST_HOPS = 0x4 IPV6_V6ONLY = 0x1b IPV6_VERSION = 0x60 IPV6_VERSION_MASK = 0xf0 IP_ADD_MEMBERSHIP = 0xc IP_ADD_SOURCE_MEMBERSHIP = 0x46 IP_BLOCK_SOURCE = 0x48 IP_BOUND_IF = 0x19 IP_DEFAULT_MULTICAST_LOOP = 0x1 IP_DEFAULT_MULTICAST_TTL = 0x1 IP_DF = 0x4000 IP_DROP_MEMBERSHIP = 0xd IP_DROP_SOURCE_MEMBERSHIP = 0x47 IP_DUMMYNET_CONFIGURE = 0x3c IP_DUMMYNET_DEL = 0x3d IP_DUMMYNET_FLUSH = 0x3e IP_DUMMYNET_GET = 0x40 IP_FAITH = 0x16 IP_FW_ADD = 0x28 IP_FW_DEL = 0x29 IP_FW_FLUSH = 0x2a IP_FW_GET = 0x2c IP_FW_RESETLOG = 0x2d IP_FW_ZERO = 0x2b IP_HDRINCL = 0x2 IP_IPSEC_POLICY = 0x15 IP_MAXPACKET = 0xffff IP_MAX_GROUP_SRC_FILTER = 0x200 IP_MAX_MEMBERSHIPS = 0xfff IP_MAX_SOCK_MUTE_FILTER = 0x80 IP_MAX_SOCK_SRC_FILTER = 0x80 IP_MF = 0x2000 IP_MIN_MEMBERSHIPS = 0x1f IP_MSFILTER = 0x4a IP_MSS = 0x240 IP_MULTICAST_IF = 0x9 IP_MULTICAST_IFINDEX = 0x42 IP_MULTICAST_LOOP = 0xb IP_MULTICAST_TTL = 0xa IP_MULTICAST_VIF = 0xe IP_NAT__XXX = 0x37 IP_OFFMASK = 0x1fff IP_OLD_FW_ADD = 0x32 IP_OLD_FW_DEL = 0x33 IP_OLD_FW_FLUSH = 0x34 IP_OLD_FW_GET = 0x36 IP_OLD_FW_RESETLOG = 0x38 IP_OLD_FW_ZERO = 0x35 IP_OPTIONS = 0x1 IP_PKTINFO = 0x1a IP_PORTRANGE = 0x13 IP_PORTRANGE_DEFAULT = 0x0 IP_PORTRANGE_HIGH = 0x1 IP_PORTRANGE_LOW = 0x2 IP_RECVDSTADDR = 0x7 IP_RECVIF = 0x14 IP_RECVOPTS = 0x5 IP_RECVPKTINFO = 0x1a IP_RECVRETOPTS = 0x6 IP_RECVTOS = 0x1b IP_RECVTTL = 0x18 IP_RETOPTS = 0x8 IP_RF = 0x8000 IP_RSVP_OFF = 0x10 IP_RSVP_ON = 0xf IP_RSVP_VIF_OFF = 0x12 IP_RSVP_VIF_ON = 0x11 IP_STRIPHDR = 0x17 IP_TOS = 0x3 IP_TRAFFIC_MGT_BACKGROUND = 0x41 IP_TTL = 0x4 IP_UNBLOCK_SOURCE = 0x49 ISIG = 0x80 ISTRIP = 0x20 IUTF8 = 0x4000 IXANY = 0x800 IXOFF = 0x400 IXON = 0x200 KERN_HOSTNAME = 0xa KERN_OSRELEASE = 0x2 KERN_OSTYPE = 0x1 KERN_VERSION = 0x4 LOCK_EX = 0x2 LOCK_NB = 0x4 LOCK_SH = 0x1 LOCK_UN = 0x8 MADV_CAN_REUSE = 0x9 MADV_DONTNEED = 0x4 MADV_FREE = 0x5 MADV_FREE_REUSABLE = 0x7 MADV_FREE_REUSE = 0x8 MADV_NORMAL = 0x0 MADV_PAGEOUT = 0xa MADV_RANDOM = 0x1 MADV_SEQUENTIAL = 0x2 MADV_WILLNEED = 0x3 MADV_ZERO_WIRED_PAGES = 0x6 MAP_ANON = 0x1000 MAP_ANONYMOUS = 0x1000 MAP_COPY = 0x2 MAP_FILE = 0x0 MAP_FIXED = 0x10 MAP_HASSEMAPHORE = 0x200 MAP_JIT = 0x800 MAP_NOCACHE = 0x400 MAP_NOEXTEND = 0x100 MAP_NORESERVE = 0x40 MAP_PRIVATE = 0x2 MAP_RENAME = 0x20 MAP_RESERVED0080 = 0x80 MAP_RESILIENT_CODESIGN = 0x2000 MAP_RESILIENT_MEDIA = 0x4000 MAP_SHARED = 0x1 MCL_CURRENT = 0x1 MCL_FUTURE = 0x2 MNT_ASYNC = 0x40 MNT_AUTOMOUNTED = 0x400000 MNT_CMDFLAGS = 0xf0000 MNT_CPROTECT = 0x80 MNT_DEFWRITE = 0x2000000 MNT_DONTBROWSE = 0x100000 MNT_DOVOLFS = 0x8000 MNT_DWAIT = 0x4 MNT_EXPORTED = 0x100 MNT_FORCE = 0x80000 MNT_IGNORE_OWNERSHIP = 0x200000 MNT_JOURNALED = 0x800000 MNT_LOCAL = 0x1000 MNT_MULTILABEL = 0x4000000 MNT_NOATIME = 0x10000000 MNT_NOBLOCK = 0x20000 MNT_NODEV = 0x10 MNT_NOEXEC = 0x4 MNT_NOSUID = 0x8 MNT_NOUSERXATTR = 0x1000000 MNT_NOWAIT = 0x2 MNT_QUARANTINE = 0x400 MNT_QUOTA = 0x2000 MNT_RDONLY = 0x1 MNT_RELOAD = 0x40000 MNT_ROOTFS = 0x4000 MNT_SYNCHRONOUS = 0x2 MNT_UNION = 0x20 MNT_UNKNOWNPERMISSIONS = 0x200000 MNT_UPDATE = 0x10000 MNT_VISFLAGMASK = 0x17f0f5ff MNT_WAIT = 0x1 MSG_CTRUNC = 0x20 MSG_DONTROUTE = 0x4 MSG_DONTWAIT = 0x80 MSG_EOF = 0x100 MSG_EOR = 0x8 MSG_FLUSH = 0x400 MSG_HAVEMORE = 0x2000 MSG_HOLD = 0x800 MSG_NEEDSA = 0x10000 MSG_OOB = 0x1 MSG_PEEK = 0x2 MSG_RCVMORE = 0x4000 MSG_SEND = 0x1000 MSG_TRUNC = 0x10 MSG_WAITALL = 0x40 MSG_WAITSTREAM = 0x200 MS_ASYNC = 0x1 MS_DEACTIVATE = 0x8 MS_INVALIDATE = 0x2 MS_KILLPAGES = 0x4 MS_SYNC = 0x10 NAME_MAX = 0xff NET_RT_DUMP = 0x1 NET_RT_DUMP2 = 0x7 NET_RT_FLAGS = 0x2 NET_RT_IFLIST = 0x3 NET_RT_IFLIST2 = 0x6 NET_RT_MAXID = 0xa NET_RT_STAT = 0x4 NET_RT_TRASH = 0x5 NFDBITS = 0x20 NL0 = 0x0 NL1 = 0x100 NL2 = 0x200 NL3 = 0x300 NLDLY = 0x300 NOFLSH = 0x80000000 NOKERNINFO = 0x2000000 NOTE_ABSOLUTE = 0x8 NOTE_ATTRIB = 0x8 NOTE_BACKGROUND = 0x40 NOTE_CHILD = 0x4 NOTE_CRITICAL = 0x20 NOTE_DELETE = 0x1 NOTE_EXEC = 0x20000000 NOTE_EXIT = 0x80000000 NOTE_EXITSTATUS = 0x4000000 NOTE_EXIT_CSERROR = 0x40000 NOTE_EXIT_DECRYPTFAIL = 0x10000 NOTE_EXIT_DETAIL = 0x2000000 NOTE_EXIT_DETAIL_MASK = 0x70000 NOTE_EXIT_MEMORY = 0x20000 NOTE_EXIT_REPARENTED = 0x80000 NOTE_EXTEND = 0x4 NOTE_FFAND = 0x40000000 NOTE_FFCOPY = 0xc0000000 NOTE_FFCTRLMASK = 0xc0000000 NOTE_FFLAGSMASK = 0xffffff NOTE_FFNOP = 0x0 NOTE_FFOR = 0x80000000 NOTE_FORK = 0x40000000 NOTE_FUNLOCK = 0x100 NOTE_LEEWAY = 0x10 NOTE_LINK = 0x10 NOTE_LOWAT = 0x1 NOTE_MACH_CONTINUOUS_TIME = 0x80 NOTE_NONE = 0x80 NOTE_NSECONDS = 0x4 NOTE_OOB = 0x2 NOTE_PCTRLMASK = -0x100000 NOTE_PDATAMASK = 0xfffff NOTE_REAP = 0x10000000 NOTE_RENAME = 0x20 NOTE_REVOKE = 0x40 NOTE_SECONDS = 0x1 NOTE_SIGNAL = 0x8000000 NOTE_TRACK = 0x1 NOTE_TRACKERR = 0x2 NOTE_TRIGGER = 0x1000000 NOTE_USECONDS = 0x2 NOTE_VM_ERROR = 0x10000000 NOTE_VM_PRESSURE = 0x80000000 NOTE_VM_PRESSURE_SUDDEN_TERMINATE = 0x20000000 NOTE_VM_PRESSURE_TERMINATE = 0x40000000 NOTE_WRITE = 0x2 OCRNL = 0x10 OFDEL = 0x20000 OFILL = 0x80 ONLCR = 0x2 ONLRET = 0x40 ONOCR = 0x20 ONOEOT = 0x8 OPOST = 0x1 OXTABS = 0x4 O_ACCMODE = 0x3 O_ALERT = 0x20000000 O_APPEND = 0x8 O_ASYNC = 0x40 O_CLOEXEC = 0x1000000 O_CREAT = 0x200 O_DIRECTORY = 0x100000 O_DP_GETRAWENCRYPTED = 0x1 O_DP_GETRAWUNENCRYPTED = 0x2 O_DSYNC = 0x400000 O_EVTONLY = 0x8000 O_EXCL = 0x800 O_EXLOCK = 0x20 O_FSYNC = 0x80 O_NDELAY = 0x4 O_NOCTTY = 0x20000 O_NOFOLLOW = 0x100 O_NONBLOCK = 0x4 O_POPUP = 0x80000000 O_RDONLY = 0x0 O_RDWR = 0x2 O_SHLOCK = 0x10 O_SYMLINK = 0x200000 O_SYNC = 0x80 O_TRUNC = 0x400 O_WRONLY = 0x1 PARENB = 0x1000 PARMRK = 0x8 PARODD = 0x2000 PENDIN = 0x20000000 PRIO_PGRP = 0x1 PRIO_PROCESS = 0x0 PRIO_USER = 0x2 PROT_EXEC = 0x4 PROT_NONE = 0x0 PROT_READ = 0x1 PROT_WRITE = 0x2 PT_ATTACH = 0xa PT_ATTACHEXC = 0xe PT_CONTINUE = 0x7 PT_DENY_ATTACH = 0x1f PT_DETACH = 0xb PT_FIRSTMACH = 0x20 PT_FORCEQUOTA = 0x1e PT_KILL = 0x8 PT_READ_D = 0x2 PT_READ_I = 0x1 PT_READ_U = 0x3 PT_SIGEXC = 0xc PT_STEP = 0x9 PT_THUPDATE = 0xd PT_TRACE_ME = 0x0 PT_WRITE_D = 0x5 PT_WRITE_I = 0x4 PT_WRITE_U = 0x6 RLIMIT_AS = 0x5 RLIMIT_CORE = 0x4 RLIMIT_CPU = 0x0 RLIMIT_CPU_USAGE_MONITOR = 0x2 RLIMIT_DATA = 0x2 RLIMIT_FSIZE = 0x1 RLIMIT_MEMLOCK = 0x6 RLIMIT_NOFILE = 0x8 RLIMIT_NPROC = 0x7 RLIMIT_RSS = 0x5 RLIMIT_STACK = 0x3 RLIM_INFINITY = 0x7fffffffffffffff RTAX_AUTHOR = 0x6 RTAX_BRD = 0x7 RTAX_DST = 0x0 RTAX_GATEWAY = 0x1 RTAX_GENMASK = 0x3 RTAX_IFA = 0x5 RTAX_IFP = 0x4 RTAX_MAX = 0x8 RTAX_NETMASK = 0x2 RTA_AUTHOR = 0x40 RTA_BRD = 0x80 RTA_DST = 0x1 RTA_GATEWAY = 0x2 RTA_GENMASK = 0x8 RTA_IFA = 0x20 RTA_IFP = 0x10 RTA_NETMASK = 0x4 RTF_BLACKHOLE = 0x1000 RTF_BROADCAST = 0x400000 RTF_CLONING = 0x100 RTF_CONDEMNED = 0x2000000 RTF_DELCLONE = 0x80 RTF_DONE = 0x40 RTF_DYNAMIC = 0x10 RTF_GATEWAY = 0x2 RTF_HOST = 0x4 RTF_IFREF = 0x4000000 RTF_IFSCOPE = 0x1000000 RTF_LLINFO = 0x400 RTF_LOCAL = 0x200000 RTF_MODIFIED = 0x20 RTF_MULTICAST = 0x800000 RTF_NOIFREF = 0x2000 RTF_PINNED = 0x100000 RTF_PRCLONING = 0x10000 RTF_PROTO1 = 0x8000 RTF_PROTO2 = 0x4000 RTF_PROTO3 = 0x40000 RTF_PROXY = 0x8000000 RTF_REJECT = 0x8 RTF_ROUTER = 0x10000000 RTF_STATIC = 0x800 RTF_UP = 0x1 RTF_WASCLONED = 0x20000 RTF_XRESOLVE = 0x200 RTM_ADD = 0x1 RTM_CHANGE = 0x3 RTM_DELADDR = 0xd RTM_DELETE = 0x2 RTM_DELMADDR = 0x10 RTM_GET = 0x4 RTM_GET2 = 0x14 RTM_IFINFO = 0xe RTM_IFINFO2 = 0x12 RTM_LOCK = 0x8 RTM_LOSING = 0x5 RTM_MISS = 0x7 RTM_NEWADDR = 0xc RTM_NEWMADDR = 0xf RTM_NEWMADDR2 = 0x13 RTM_OLDADD = 0x9 RTM_OLDDEL = 0xa RTM_REDIRECT = 0x6 RTM_RESOLVE = 0xb RTM_RTTUNIT = 0xf4240 RTM_VERSION = 0x5 RTV_EXPIRE = 0x4 RTV_HOPCOUNT = 0x2 RTV_MTU = 0x1 RTV_RPIPE = 0x8 RTV_RTT = 0x40 RTV_RTTVAR = 0x80 RTV_SPIPE = 0x10 RTV_SSTHRESH = 0x20 RUSAGE_CHILDREN = -0x1 RUSAGE_SELF = 0x0 SCM_CREDS = 0x3 SCM_RIGHTS = 0x1 SCM_TIMESTAMP = 0x2 SCM_TIMESTAMP_MONOTONIC = 0x4 SHUT_RD = 0x0 SHUT_RDWR = 0x2 SHUT_WR = 0x1 SIOCADDMULTI = 0x80206931 SIOCAIFADDR = 0x8040691a SIOCARPIPLL = 0xc0206928 SIOCATMARK = 0x40047307 SIOCAUTOADDR = 0xc0206926 SIOCAUTONETMASK = 0x80206927 SIOCDELMULTI = 0x80206932 SIOCDIFADDR = 0x80206919 SIOCDIFPHYADDR = 0x80206941 SIOCGDRVSPEC = 0xc01c697b SIOCGETVLAN = 0xc020697f SIOCGHIWAT = 0x40047301 SIOCGIFADDR = 0xc0206921 SIOCGIFALTMTU = 0xc0206948 SIOCGIFASYNCMAP = 0xc020697c SIOCGIFBOND = 0xc0206947 SIOCGIFBRDADDR = 0xc0206923 SIOCGIFCAP = 0xc020695b SIOCGIFCONF = 0xc0086924 SIOCGIFDEVMTU = 0xc0206944 SIOCGIFDSTADDR = 0xc0206922 SIOCGIFFLAGS = 0xc0206911 SIOCGIFGENERIC = 0xc020693a SIOCGIFKPI = 0xc0206987 SIOCGIFMAC = 0xc0206982 SIOCGIFMEDIA = 0xc0286938 SIOCGIFMETRIC = 0xc0206917 SIOCGIFMTU = 0xc0206933 SIOCGIFNETMASK = 0xc0206925 SIOCGIFPDSTADDR = 0xc0206940 SIOCGIFPHYS = 0xc0206935 SIOCGIFPSRCADDR = 0xc020693f SIOCGIFSTATUS = 0xc331693d SIOCGIFVLAN = 0xc020697f SIOCGIFWAKEFLAGS = 0xc0206988 SIOCGLOWAT = 0x40047303 SIOCGPGRP = 0x40047309 SIOCIFCREATE = 0xc0206978 SIOCIFCREATE2 = 0xc020697a SIOCIFDESTROY = 0x80206979 SIOCIFGCLONERS = 0xc00c6981 SIOCRSLVMULTI = 0xc008693b SIOCSDRVSPEC = 0x801c697b SIOCSETVLAN = 0x8020697e SIOCSHIWAT = 0x80047300 SIOCSIFADDR = 0x8020690c SIOCSIFALTMTU = 0x80206945 SIOCSIFASYNCMAP = 0x8020697d SIOCSIFBOND = 0x80206946 SIOCSIFBRDADDR = 0x80206913 SIOCSIFCAP = 0x8020695a SIOCSIFDSTADDR = 0x8020690e SIOCSIFFLAGS = 0x80206910 SIOCSIFGENERIC = 0x80206939 SIOCSIFKPI = 0x80206986 SIOCSIFLLADDR = 0x8020693c SIOCSIFMAC = 0x80206983 SIOCSIFMEDIA = 0xc0206937 SIOCSIFMETRIC = 0x80206918 SIOCSIFMTU = 0x80206934 SIOCSIFNETMASK = 0x80206916 SIOCSIFPHYADDR = 0x8040693e SIOCSIFPHYS = 0x80206936 SIOCSIFVLAN = 0x8020697e SIOCSLOWAT = 0x80047302 SIOCSPGRP = 0x80047308 SOCK_DGRAM = 0x2 SOCK_MAXADDRLEN = 0xff SOCK_RAW = 0x3 SOCK_RDM = 0x4 SOCK_SEQPACKET = 0x5 SOCK_STREAM = 0x1 SOL_SOCKET = 0xffff SOMAXCONN = 0x80 SO_ACCEPTCONN = 0x2 SO_BROADCAST = 0x20 SO_DEBUG = 0x1 SO_DONTROUTE = 0x10 SO_DONTTRUNC = 0x2000 SO_ERROR = 0x1007 SO_KEEPALIVE = 0x8 SO_LABEL = 0x1010 SO_LINGER = 0x80 SO_LINGER_SEC = 0x1080 SO_NETSVC_MARKING_LEVEL = 0x1119 SO_NET_SERVICE_TYPE = 0x1116 SO_NKE = 0x1021 SO_NOADDRERR = 0x1023 SO_NOSIGPIPE = 0x1022 SO_NOTIFYCONFLICT = 0x1026 SO_NP_EXTENSIONS = 0x1083 SO_NREAD = 0x1020 SO_NUMRCVPKT = 0x1112 SO_NWRITE = 0x1024 SO_OOBINLINE = 0x100 SO_PEERLABEL = 0x1011 SO_RANDOMPORT = 0x1082 SO_RCVBUF = 0x1002 SO_RCVLOWAT = 0x1004 SO_RCVTIMEO = 0x1006 SO_REUSEADDR = 0x4 SO_REUSEPORT = 0x200 SO_REUSESHAREUID = 0x1025 SO_SNDBUF = 0x1001 SO_SNDLOWAT = 0x1003 SO_SNDTIMEO = 0x1005 SO_TIMESTAMP = 0x400 SO_TIMESTAMP_MONOTONIC = 0x800 SO_TYPE = 0x1008 SO_UPCALLCLOSEWAIT = 0x1027 SO_USELOOPBACK = 0x40 SO_WANTMORE = 0x4000 SO_WANTOOBFLAG = 0x8000 S_IEXEC = 0x40 S_IFBLK = 0x6000 S_IFCHR = 0x2000 S_IFDIR = 0x4000 S_IFIFO = 0x1000 S_IFLNK = 0xa000 S_IFMT = 0xf000 S_IFREG = 0x8000 S_IFSOCK = 0xc000 S_IFWHT = 0xe000 S_IREAD = 0x100 S_IRGRP = 0x20 S_IROTH = 0x4 S_IRUSR = 0x100 S_IRWXG = 0x38 S_IRWXO = 0x7 S_IRWXU = 0x1c0 S_ISGID = 0x400 S_ISTXT = 0x200 S_ISUID = 0x800 S_ISVTX = 0x200 S_IWGRP = 0x10 S_IWOTH = 0x2 S_IWRITE = 0x80 S_IWUSR = 0x80 S_IXGRP = 0x8 S_IXOTH = 0x1 S_IXUSR = 0x40 TAB0 = 0x0 TAB1 = 0x400 TAB2 = 0x800 TAB3 = 0x4 TABDLY = 0xc04 TCIFLUSH = 0x1 TCIOFF = 0x3 TCIOFLUSH = 0x3 TCION = 0x4 TCOFLUSH = 0x2 TCOOFF = 0x1 TCOON = 0x2 TCP_CONNECTIONTIMEOUT = 0x20 TCP_CONNECTION_INFO = 0x106 TCP_ENABLE_ECN = 0x104 TCP_FASTOPEN = 0x105 TCP_KEEPALIVE = 0x10 TCP_KEEPCNT = 0x102 TCP_KEEPINTVL = 0x101 TCP_MAXHLEN = 0x3c TCP_MAXOLEN = 0x28 TCP_MAXSEG = 0x2 TCP_MAXWIN = 0xffff TCP_MAX_SACK = 0x4 TCP_MAX_WINSHIFT = 0xe TCP_MINMSS = 0xd8 TCP_MSS = 0x200 TCP_NODELAY = 0x1 TCP_NOOPT = 0x8 TCP_NOPUSH = 0x4 TCP_NOTSENT_LOWAT = 0x201 TCP_RXT_CONNDROPTIME = 0x80 TCP_RXT_FINDROP = 0x100 TCP_SENDMOREACKS = 0x103 TCSAFLUSH = 0x2 TIOCCBRK = 0x2000747a TIOCCDTR = 0x20007478 TIOCCONS = 0x80047462 TIOCDCDTIMESTAMP = 0x40087458 TIOCDRAIN = 0x2000745e TIOCDSIMICROCODE = 0x20007455 TIOCEXCL = 0x2000740d TIOCEXT = 0x80047460 TIOCFLUSH = 0x80047410 TIOCGDRAINWAIT = 0x40047456 TIOCGETA = 0x402c7413 TIOCGETD = 0x4004741a TIOCGPGRP = 0x40047477 TIOCGWINSZ = 0x40087468 TIOCIXOFF = 0x20007480 TIOCIXON = 0x20007481 TIOCMBIC = 0x8004746b TIOCMBIS = 0x8004746c TIOCMGDTRWAIT = 0x4004745a TIOCMGET = 0x4004746a TIOCMODG = 0x40047403 TIOCMODS = 0x80047404 TIOCMSDTRWAIT = 0x8004745b TIOCMSET = 0x8004746d TIOCM_CAR = 0x40 TIOCM_CD = 0x40 TIOCM_CTS = 0x20 TIOCM_DSR = 0x100 TIOCM_DTR = 0x2 TIOCM_LE = 0x1 TIOCM_RI = 0x80 TIOCM_RNG = 0x80 TIOCM_RTS = 0x4 TIOCM_SR = 0x10 TIOCM_ST = 0x8 TIOCNOTTY = 0x20007471 TIOCNXCL = 0x2000740e TIOCOUTQ = 0x40047473 TIOCPKT = 0x80047470 TIOCPKT_DATA = 0x0 TIOCPKT_DOSTOP = 0x20 TIOCPKT_FLUSHREAD = 0x1 TIOCPKT_FLUSHWRITE = 0x2 TIOCPKT_IOCTL = 0x40 TIOCPKT_NOSTOP = 0x10 TIOCPKT_START = 0x8 TIOCPKT_STOP = 0x4 TIOCPTYGNAME = 0x40807453 TIOCPTYGRANT = 0x20007454 TIOCPTYUNLK = 0x20007452 TIOCREMOTE = 0x80047469 TIOCSBRK = 0x2000747b TIOCSCONS = 0x20007463 TIOCSCTTY = 0x20007461 TIOCSDRAINWAIT = 0x80047457 TIOCSDTR = 0x20007479 TIOCSETA = 0x802c7414 TIOCSETAF = 0x802c7416 TIOCSETAW = 0x802c7415 TIOCSETD = 0x8004741b TIOCSIG = 0x2000745f TIOCSPGRP = 0x80047476 TIOCSTART = 0x2000746e TIOCSTAT = 0x20007465 TIOCSTI = 0x80017472 TIOCSTOP = 0x2000746f TIOCSWINSZ = 0x80087467 TIOCTIMESTAMP = 0x40087459 TIOCUCNTL = 0x80047466 TOSTOP = 0x400000 VDISCARD = 0xf VDSUSP = 0xb VEOF = 0x0 VEOL = 0x1 VEOL2 = 0x2 VERASE = 0x3 VINTR = 0x8 VKILL = 0x5 VLNEXT = 0xe VMIN = 0x10 VM_LOADAVG = 0x2 VM_MACHFACTOR = 0x4 VM_MAXID = 0x6 VM_METER = 0x1 VM_SWAPUSAGE = 0x5 VQUIT = 0x9 VREPRINT = 0x6 VSTART = 0xc VSTATUS = 0x12 VSTOP = 0xd VSUSP = 0xa VT0 = 0x0 VT1 = 0x10000 VTDLY = 0x10000 VTIME = 0x11 VWERASE = 0x4 WCONTINUED = 0x10 WCOREFLAG = 0x80 WEXITED = 0x4 WNOHANG = 0x1 WNOWAIT = 0x20 WORDSIZE = 0x20 WSTOPPED = 0x8 WUNTRACED = 0x2 XATTR_CREATE = 0x2 XATTR_NODEFAULT = 0x10 XATTR_NOFOLLOW = 0x1 XATTR_NOSECURITY = 0x8 XATTR_REPLACE = 0x4 XATTR_SHOWCOMPRESSION = 0x20 ) // Errors const ( E2BIG = syscall.Errno(0x7) EACCES = syscall.Errno(0xd) EADDRINUSE = syscall.Errno(0x30) EADDRNOTAVAIL = syscall.Errno(0x31) EAFNOSUPPORT = syscall.Errno(0x2f) EAGAIN = syscall.Errno(0x23) EALREADY = syscall.Errno(0x25) EAUTH = syscall.Errno(0x50) EBADARCH = syscall.Errno(0x56) EBADEXEC = syscall.Errno(0x55) EBADF = syscall.Errno(0x9) EBADMACHO = syscall.Errno(0x58) EBADMSG = syscall.Errno(0x5e) EBADRPC = syscall.Errno(0x48) EBUSY = syscall.Errno(0x10) ECANCELED = syscall.Errno(0x59) ECHILD = syscall.Errno(0xa) ECONNABORTED = syscall.Errno(0x35) ECONNREFUSED = syscall.Errno(0x3d) ECONNRESET = syscall.Errno(0x36) EDEADLK = syscall.Errno(0xb) EDESTADDRREQ = syscall.Errno(0x27) EDEVERR = syscall.Errno(0x53) EDOM = syscall.Errno(0x21) EDQUOT = syscall.Errno(0x45) EEXIST = syscall.Errno(0x11) EFAULT = syscall.Errno(0xe) EFBIG = syscall.Errno(0x1b) EFTYPE = syscall.Errno(0x4f) EHOSTDOWN = syscall.Errno(0x40) EHOSTUNREACH = syscall.Errno(0x41) EIDRM = syscall.Errno(0x5a) EILSEQ = syscall.Errno(0x5c) EINPROGRESS = syscall.Errno(0x24) EINTR = syscall.Errno(0x4) EINVAL = syscall.Errno(0x16) EIO = syscall.Errno(0x5) EISCONN = syscall.Errno(0x38) EISDIR = syscall.Errno(0x15) ELAST = syscall.Errno(0x6a) ELOOP = syscall.Errno(0x3e) EMFILE = syscall.Errno(0x18) EMLINK = syscall.Errno(0x1f) EMSGSIZE = syscall.Errno(0x28) EMULTIHOP = syscall.Errno(0x5f) ENAMETOOLONG = syscall.Errno(0x3f) ENEEDAUTH = syscall.Errno(0x51) ENETDOWN = syscall.Errno(0x32) ENETRESET = syscall.Errno(0x34) ENETUNREACH = syscall.Errno(0x33) ENFILE = syscall.Errno(0x17) ENOATTR = syscall.Errno(0x5d) ENOBUFS = syscall.Errno(0x37) ENODATA = syscall.Errno(0x60) ENODEV = syscall.Errno(0x13) ENOENT = syscall.Errno(0x2) ENOEXEC = syscall.Errno(0x8) ENOLCK = syscall.Errno(0x4d) ENOLINK = syscall.Errno(0x61) ENOMEM = syscall.Errno(0xc) ENOMSG = syscall.Errno(0x5b) ENOPOLICY = syscall.Errno(0x67) ENOPROTOOPT = syscall.Errno(0x2a) ENOSPC = syscall.Errno(0x1c) ENOSR = syscall.Errno(0x62) ENOSTR = syscall.Errno(0x63) ENOSYS = syscall.Errno(0x4e) ENOTBLK = syscall.Errno(0xf) ENOTCONN = syscall.Errno(0x39) ENOTDIR = syscall.Errno(0x14) ENOTEMPTY = syscall.Errno(0x42) ENOTRECOVERABLE = syscall.Errno(0x68) ENOTSOCK = syscall.Errno(0x26) ENOTSUP = syscall.Errno(0x2d) ENOTTY = syscall.Errno(0x19) ENXIO = syscall.Errno(0x6) EOPNOTSUPP = syscall.Errno(0x66) EOVERFLOW = syscall.Errno(0x54) EOWNERDEAD = syscall.Errno(0x69) EPERM = syscall.Errno(0x1) EPFNOSUPPORT = syscall.Errno(0x2e) EPIPE = syscall.Errno(0x20) EPROCLIM = syscall.Errno(0x43) EPROCUNAVAIL = syscall.Errno(0x4c) EPROGMISMATCH = syscall.Errno(0x4b) EPROGUNAVAIL = syscall.Errno(0x4a) EPROTO = syscall.Errno(0x64) EPROTONOSUPPORT = syscall.Errno(0x2b) EPROTOTYPE = syscall.Errno(0x29) EPWROFF = syscall.Errno(0x52) EQFULL = syscall.Errno(0x6a) ERANGE = syscall.Errno(0x22) EREMOTE = syscall.Errno(0x47) EROFS = syscall.Errno(0x1e) ERPCMISMATCH = syscall.Errno(0x49) ESHLIBVERS = syscall.Errno(0x57) ESHUTDOWN = syscall.Errno(0x3a) ESOCKTNOSUPPORT = syscall.Errno(0x2c) ESPIPE = syscall.Errno(0x1d) ESRCH = syscall.Errno(0x3) ESTALE = syscall.Errno(0x46) ETIME = syscall.Errno(0x65) ETIMEDOUT = syscall.Errno(0x3c) ETOOMANYREFS = syscall.Errno(0x3b) ETXTBSY = syscall.Errno(0x1a) EUSERS = syscall.Errno(0x44) EWOULDBLOCK = syscall.Errno(0x23) EXDEV = syscall.Errno(0x12) ) // Signals const ( SIGABRT = syscall.Signal(0x6) SIGALRM = syscall.Signal(0xe) SIGBUS = syscall.Signal(0xa) SIGCHLD = syscall.Signal(0x14) SIGCONT = syscall.Signal(0x13) SIGEMT = syscall.Signal(0x7) SIGFPE = syscall.Signal(0x8) SIGHUP = syscall.Signal(0x1) SIGILL = syscall.Signal(0x4) SIGINFO = syscall.Signal(0x1d) SIGINT = syscall.Signal(0x2) SIGIO = syscall.Signal(0x17) SIGIOT = syscall.Signal(0x6) SIGKILL = syscall.Signal(0x9) SIGPIPE = syscall.Signal(0xd) SIGPROF = syscall.Signal(0x1b) SIGQUIT = syscall.Signal(0x3) SIGSEGV = syscall.Signal(0xb) SIGSTOP = syscall.Signal(0x11) SIGSYS = syscall.Signal(0xc) SIGTERM = syscall.Signal(0xf) SIGTRAP = syscall.Signal(0x5) SIGTSTP = syscall.Signal(0x12) SIGTTIN = syscall.Signal(0x15) SIGTTOU = syscall.Signal(0x16) SIGURG = syscall.Signal(0x10) SIGUSR1 = syscall.Signal(0x1e) SIGUSR2 = syscall.Signal(0x1f) SIGVTALRM = syscall.Signal(0x1a) SIGWINCH = syscall.Signal(0x1c) SIGXCPU = syscall.Signal(0x18) SIGXFSZ = syscall.Signal(0x19) ) // Error table var errorList = [...]struct { num syscall.Errno name string desc string }{ {1, "EPERM", "operation not permitted"}, {2, "ENOENT", "no such file or directory"}, {3, "ESRCH", "no such process"}, {4, "EINTR", "interrupted system call"}, {5, "EIO", "input/output error"}, {6, "ENXIO", "device not configured"}, {7, "E2BIG", "argument list too long"}, {8, "ENOEXEC", "exec format error"}, {9, "EBADF", "bad file descriptor"}, {10, "ECHILD", "no child processes"}, {11, "EDEADLK", "resource deadlock avoided"}, {12, "ENOMEM", "cannot allocate memory"}, {13, "EACCES", "permission denied"}, {14, "EFAULT", "bad address"}, {15, "ENOTBLK", "block device required"}, {16, "EBUSY", "resource busy"}, {17, "EEXIST", "file exists"}, {18, "EXDEV", "cross-device link"}, {19, "ENODEV", "operation not supported by device"}, {20, "ENOTDIR", "not a directory"}, {21, "EISDIR", "is a directory"}, {22, "EINVAL", "invalid argument"}, {23, "ENFILE", "too many open files in system"}, {24, "EMFILE", "too many open files"}, {25, "ENOTTY", "inappropriate ioctl for device"}, {26, "ETXTBSY", "text file busy"}, {27, "EFBIG", "file too large"}, {28, "ENOSPC", "no space left on device"}, {29, "ESPIPE", "illegal seek"}, {30, "EROFS", "read-only file system"}, {31, "EMLINK", "too many links"}, {32, "EPIPE", "broken pipe"}, {33, "EDOM", "numerical argument out of domain"}, {34, "ERANGE", "result too large"}, {35, "EAGAIN", "resource temporarily unavailable"}, {36, "EINPROGRESS", "operation now in progress"}, {37, "EALREADY", "operation already in progress"}, {38, "ENOTSOCK", "socket operation on non-socket"}, {39, "EDESTADDRREQ", "destination address required"}, {40, "EMSGSIZE", "message too long"}, {41, "EPROTOTYPE", "protocol wrong type for socket"}, {42, "ENOPROTOOPT", "protocol not available"}, {43, "EPROTONOSUPPORT", "protocol not supported"}, {44, "ESOCKTNOSUPPORT", "socket type not supported"}, {45, "ENOTSUP", "operation not supported"}, {46, "EPFNOSUPPORT", "protocol family not supported"}, {47, "EAFNOSUPPORT", "address family not supported by protocol family"}, {48, "EADDRINUSE", "address already in use"}, {49, "EADDRNOTAVAIL", "can't assign requested address"}, {50, "ENETDOWN", "network is down"}, {51, "ENETUNREACH", "network is unreachable"}, {52, "ENETRESET", "network dropped connection on reset"}, {53, "ECONNABORTED", "software caused connection abort"}, {54, "ECONNRESET", "connection reset by peer"}, {55, "ENOBUFS", "no buffer space available"}, {56, "EISCONN", "socket is already connected"}, {57, "ENOTCONN", "socket is not connected"}, {58, "ESHUTDOWN", "can't send after socket shutdown"}, {59, "ETOOMANYREFS", "too many references: can't splice"}, {60, "ETIMEDOUT", "operation timed out"}, {61, "ECONNREFUSED", "connection refused"}, {62, "ELOOP", "too many levels of symbolic links"}, {63, "ENAMETOOLONG", "file name too long"}, {64, "EHOSTDOWN", "host is down"}, {65, "EHOSTUNREACH", "no route to host"}, {66, "ENOTEMPTY", "directory not empty"}, {67, "EPROCLIM", "too many processes"}, {68, "EUSERS", "too many users"}, {69, "EDQUOT", "disc quota exceeded"}, {70, "ESTALE", "stale NFS file handle"}, {71, "EREMOTE", "too many levels of remote in path"}, {72, "EBADRPC", "RPC struct is bad"}, {73, "ERPCMISMATCH", "RPC version wrong"}, {74, "EPROGUNAVAIL", "RPC prog. not avail"}, {75, "EPROGMISMATCH", "program version wrong"}, {76, "EPROCUNAVAIL", "bad procedure for program"}, {77, "ENOLCK", "no locks available"}, {78, "ENOSYS", "function not implemented"}, {79, "EFTYPE", "inappropriate file type or format"}, {80, "EAUTH", "authentication error"}, {81, "ENEEDAUTH", "need authenticator"}, {82, "EPWROFF", "device power is off"}, {83, "EDEVERR", "device error"}, {84, "EOVERFLOW", "value too large to be stored in data type"}, {85, "EBADEXEC", "bad executable (or shared library)"}, {86, "EBADARCH", "bad CPU type in executable"}, {87, "ESHLIBVERS", "shared library version mismatch"}, {88, "EBADMACHO", "malformed Mach-o file"}, {89, "ECANCELED", "operation canceled"}, {90, "EIDRM", "identifier removed"}, {91, "ENOMSG", "no message of desired type"}, {92, "EILSEQ", "illegal byte sequence"}, {93, "ENOATTR", "attribute not found"}, {94, "EBADMSG", "bad message"}, {95, "EMULTIHOP", "EMULTIHOP (Reserved)"}, {96, "ENODATA", "no message available on STREAM"}, {97, "ENOLINK", "ENOLINK (Reserved)"}, {98, "ENOSR", "no STREAM resources"}, {99, "ENOSTR", "not a STREAM"}, {100, "EPROTO", "protocol error"}, {101, "ETIME", "STREAM ioctl timeout"}, {102, "EOPNOTSUPP", "operation not supported on socket"}, {103, "ENOPOLICY", "policy not found"}, {104, "ENOTRECOVERABLE", "state not recoverable"}, {105, "EOWNERDEAD", "previous owner died"}, {106, "EQFULL", "interface output queue is full"}, } // Signal table var signalList = [...]struct { num syscall.Signal name string desc string }{ {1, "SIGHUP", "hangup"}, {2, "SIGINT", "interrupt"}, {3, "SIGQUIT", "quit"}, {4, "SIGILL", "illegal instruction"}, {5, "SIGTRAP", "trace/BPT trap"}, {6, "SIGABRT", "abort trap"}, {7, "SIGEMT", "EMT trap"}, {8, "SIGFPE", "floating point exception"}, {9, "SIGKILL", "killed"}, {10, "SIGBUS", "bus error"}, {11, "SIGSEGV", "segmentation fault"}, {12, "SIGSYS", "bad system call"}, {13, "SIGPIPE", "broken pipe"}, {14, "SIGALRM", "alarm clock"}, {15, "SIGTERM", "terminated"}, {16, "SIGURG", "urgent I/O condition"}, {17, "SIGSTOP", "suspended (signal)"}, {18, "SIGTSTP", "suspended"}, {19, "SIGCONT", "continued"}, {20, "SIGCHLD", "child exited"}, {21, "SIGTTIN", "stopped (tty input)"}, {22, "SIGTTOU", "stopped (tty output)"}, {23, "SIGIO", "I/O possible"}, {24, "SIGXCPU", "cputime limit exceeded"}, {25, "SIGXFSZ", "filesize limit exceeded"}, {26, "SIGVTALRM", "virtual timer expired"}, {27, "SIGPROF", "profiling timer expired"}, {28, "SIGWINCH", "window size changes"}, {29, "SIGINFO", "information request"}, {30, "SIGUSR1", "user defined signal 1"}, {31, "SIGUSR2", "user defined signal 2"}, }

Love's Jazz and Art Center Love's Jazz and Art Center is located at 2510 North 24th Street in the Near North Omaha neighborhood of Omaha, Nebraska. Founded and named to honor of Omaha jazz great Preston Love, Love's highlights the African American culture of North Omaha. In addition to sponsoring a variety of events, Love's has hosted events for Native Omaha Days. See also History of North Omaha, Nebraska Music in Omaha, Nebraska Culture of Omaha, Nebraska References External links Official website Category:Music of Omaha, Nebraska Category:Museums in Omaha, Nebraska Category:African-American museums in Nebraska Category:African-American history in Omaha, Nebraska Category:Arts centers in Nebraska

1. Field of the Invention The present invention relates to an optical alignment polymer, an alignment layer using the same, and a liquid crystal display device having the alignment layer, and more particularly, to an optical alignment polymer having excellent optical alignment performance and stability against heat or impact, an alignment layer formed using the optical alignment polymer and a liquid crystal display device having the alignment layer. 2. The Related Art In general, a liquid crystal display device has upper and lower substrate, transparent electrodes and alignment layers formed on the upper and lower substrates and a liquid crystal layer between the upper and lower alignment layers. In the LCD having the aforementioned structure, according to an externally applied voltage, the arrangement of liquid crystals is changed by the electric field. According to the changed arrangement, external light introduced to the LCD is shielded or transmitted. The LCD is driven by such a property. In other words, if a voltage is applied to the transparent electrode layers, an electric field is formed in the liquid crystal layer. Thus, liquid crystals are driven in a predetermined direction. The light introduced into the liquid crystals of the LCD is shielded or transmitted according to the driving of the liquid crystals. The functions of the LCD as a display device, i.e., light transmittance, response time, view angle or contrast, are determined by the arrangement characteristic of the liquid crystal molecules. Therefore, controlling the alignment of the liquid crystal molecules uniformly is a very important factor. The uniform alignment state of the liquid crystals is difficult to accomplish by merely interposing the liquid crystals between the upper and lower substrates. Thus, it is generally known to form the alignment layers for aligning liquid crystals on the transparent electrode layers. The alignment layer is conventionally formed by a rubbing method in which a thin film made of an organic polymer material such as polyimide or polyamide is formed, cured and then rubbed with a special cloth. The rubbing method is easy to conduct and the process thereof is simple. However, minute particles or materials such as cellulose may separate from the cloth used in the rubbing treatment and contaminate the alignment layer. Further, depending on the material for forming the alignment layer, the alignment may not be accomplished smoothly. A thin film transistor may be damaged by static electricity generated during the rubbing treatment. To solve the above-described problems, an optical alignment technology has been developed in which dust, static electricity or other pollutant particles are not generated and cleanliness is maintained during the overall process. According to such a non-destructive alignment method, polarized light is irradiated onto the optical alignment layer to cause anisotropic photopolymerization. As a result, the optical alignment layer has alignment characteristic, thereby uniformly aligning the liquid crystals. The polymer for the optical alignment layer includes polyvinylcinnamate (PVCN) and polyvinylmethoxyxinnamate (PVMC). These polymer compounds have an optically aligning functional group introduced into either a main chain or a side chain thereof. If the alignment layer is formed using the optical alignment composition having such a polymer, the alignment performance by light and thermal stability becomes poor, and a pretilt angle of a liquid crystal of liquid crystal display device having the alignment layer decreases to almost 0.degree. C.

Finite-size radiation force correction for inviscid spheres in standing waves. Yosioka and Kawasima gave a widely used approximation for the acoustic radiation force on small liquid spheres surrounded by an immiscible liquid in 1955. Considering the liquids to be inviscid with negligible thermal dissipation, in their approximation the force on the sphere is proportional to the sphere's volume and the levitation position in a vertical standing wave becomes independent of the size. The analysis given here introduces a small correction term proportional to the square of the sphere's radius relative to the aforementioned small-sphere force. The significance of this term also depends on the relative density and sound velocity of the sphere. The improved approximation is supported by comparison with the exact partial-wave-series based radiation force for ideal fluid spheres in ideal fluids.

[Pulse wave velocity - a useful tool in assessing the stiffness of the arteries]. Measurement of pulse wave velocity (PWV) is a simple and noninvasive way to assess stiffness of the arteries. PWV measurement can refer to both the aorta and peripheral arterial vessels. Currently, the most clinically significant is the measurement of PWV between the carotid artery and the femoral artery, which is defined as the speed of the aortic pulse wave. Numerous studies have demonstrated the significance of prognostic PWV aortic measurement as a recognized exponent of subclinical organ damage both among the general population as well as among patients with increased cardiovascular risk, examining patients in detail with hypertension, diabetes, chronic renal failure. The prognostic value of PWV aortic measurement was reflected in the guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). In clinical trials, the repeatability and reproducibility of PWV measurements were also evaluated, both parameters being considered satisfactory. The paper presents reports from studies on the significance of pulse wave velocity results in the prognosis assessment in different disease entities as well as in age groups.

Oneida (2016) GENRE REFERENCE POINTS LINKS One of the great bands of the new millennium, Brooklyn's kings of psych and drone have been exploring propulsion and repetition for nearly twenty years, lighting the way for a generation of young Kraut-noise artists. Anchored by Kid Millions' Olympic-calibre drumming, their shows might be comprised of ethereal pulses, majestic long-form jams or pummeling squalls of feedback. Whatever they pull out of their grimy pockets, it will be a heavy trip.

Coaching Client of Tony Inman – Bernie successfully regained his sales prowess after a slump in confidence and motivation and achieved record sales. He and his wife successfully sold off the majority of their business and commenced semi-retirement. Associate of Coach Tony Inman. Read Tony’s book, ‘If Life’s Worth Doing, It’s Worth Doing Well’ and was inspired to re-think his work/life balance and to immediately set up his business in such a way that he could take more holidays. ***** David Bearsley – Business Marketing Consultant and Trainer, Owner of Superior Business Networks, Perth, Western Australia. Associate of Coach Tony Inman. Worked with Tony to co-facilitate business improvement programs. Engages Tony to host his networking groups when taking vacations. More Reviews Just in case this many coaching testimonials still haven’t reassured you of Tony’s experience, you may click here for a list of companies and/or executives with whom Coach Tony Inman has worked. If you still have questions, firstly check our FAQ page for more information. So don’t delay – Take action today. Contact Tony Inman via this website for a chat about how he can help you to move forwards in the direction of your dreams and goals! Or telephone 0419 860 382. About Tony Inman – ‘The Change Catalyst’ If you want to make changes in your life, but you're feeling stuck or overwhelmed, and you need a guide to help you get there, then you can trust in the experience and 'life-wisdom' of this Coach and Guide who walks the talk, Tony Inman. Tony is a serial entrepreneur who has set up and built around 23 small businesses in a variety of fields, experiencing many triumphs, plus his share of setbacks, along the journey. Tony Inman is also a certified and experienced Life Coach and Business Coach, a Master Practitioner and certified Trainer in NLP, certified Trainer and Assessor, workshop facilitator and presenter. Thanks to the reach of the internet, he has been assisting clients all around the world to move forwards in pursuit of happier, more successful and more fulfilling lives. He has recently co-founded 'ONE80degree Films'to help businesses, not-for-profits and individuals to share their stories via two-minute videos through to feature-length documentaries. Tony and his wife Jo also have a 'side-hustle' blog, where they provide an entertainment guide; promote local small businesses in Perth; support eco and marine-eco-friendly initiatives and generally promote helping people to live healthier and happier lives. You can follow them on Facebook at ToJo Life or via www.tojolife.com.au.

Community Services Specialized This Division is comprised of 3 specialized units. The INTENSIVE SUPERVISION / SERVICES UNIT (ISU), the DOMESTIC VIOLENCE UNIT, and the SEX OFFENDER UNIT (SOU). Caseloads assigned to the Division specialize in Mentally Ill Offenders (Behavioral Health Court- BHC); Community/ District Station Gang Offenders, Sex Offenders, Habitual Offenders, and Domestic Violence Offenders. Officers in this Division have a specific focus on cases in these areas of discipline and provide specialized attention to cases assigned to their respective caseloads. The officers in this Division generally have lower caseload sizes and provide a level of supervision which includes a significant amount of time in the community (“field”). There are some officers in this Division such as the Mental Health / BHC officers who provides some level of services for BHC clients (both probation clients and non-probation clients) as a collaborative partner in BHC process. They have certain office hours at Citywide Case Management Services in the community to facilitate the BHC services for these clients. Members of the Division attend various Community Meetings and Crime Reduction Meetings with various law enforcement agencies to provide theses service providers with input on how probation supervision efforts could be incorporated in these community activities. Certain Division assignments have collaborative process with specialized Courts such as Domestic Violence Court to provide coordinated collaborative services for probationers. These processes require staff to work closely with these community based agencies and in some cases they facilitate case conferences with these agencies to enhance these coordinated efforts. Staff in this Division used evidence based practices in the service and supervision efforts and has worked non-traditional hours to facilitate the needs of the assigned caseloads.

Daniel Talks About, Flirting, Height, Drinking Issues & Other Stuff! Written by: Chaitra Published: Wednesday, October 21, 2015, 10:27 [IST] Subscribe to Filmibeat Daniel Radcliffe, the 26 years old actor, who once played the epic role of Harry Potter, recently spoke about the much adult stuff, like flirting, girlfriend, masturbation and alcohol issues and may other things during his interview with the Playboy magazine. The 1.65 m tall British actor opened about his struggles dealing with fame, young age drinking , his inability to say 'no', and everything about his 8 Harry Potter series. He also used the platform to talk about his girlfriend Erin Darke. Daniel did a 20 Q and A with Playboy. Below are a few of the questions and Daniel's brilliant answers combined with his simple and down to earth attitude that caught our attention. We must say, the actor does have an excellent sense of humour. Daniel said: On when he drank heavily at a very young age to deal with fame .. "Anytime I'd go out to dance, camera phones would come out. That would make me very self-conscious, and what's the easiest way to escape being self-conscious? Alcohol is a quick way of doing that. So it was related in that way." He also added "A few years ago there was a TV ad that showed a lot of inventors, including a guy who invented the camera phone. He was smiling smugly into the camera, and I was just like, Fuck you. What have you wrought? Camera phones are definitely not my favorite." On whether there was time to masturbate on the sets Daniel jokingly said, "Yeah, I was like every other teenager in that sense. My favorite line about masturbation is Louis C.K.'s, something like, "I found out about it when I was 11, and I didn't skip a day." I think I started very early-before my teens. But not when I was on set." On his height issues in Hollywood .. The actor said, "I don't think so. Dustin Hoffman and Tom Cruise have very different careers, and they're both about the same height as I am. I could play a soldier. The minimum height for a marine is five feet, and I'm well above that. If you're asking, ‘Can you play a really (bleeping) tall person?' No, obviously not." On when he first met his girlfriend and flirting .. Daniel gushed about his incredibly smart and funny girlfriend. He spoke about the time he first met her on the sets in 2013 and said "That's a wonderful record of us flirting for the first time. There's no acting going on - not from my end, anyway. There's a moment when she makes me laugh, and I'm laughing as me and not as my character." From height to masturbating and gushing about his girlfriend, Daniel rocked the interview and nailed every single question he was asked. He can now look forward to seeing the Harry Potter protagonist in many other roles in the near future and add more fiction characters to our list of favorites.

The Nuiances of Mobile App Development Companies List The Nuiances of Mobile App Development Companies List The History of Mobile App Development Companies List Refuted Price should not be a determining factor when picking an app developer. Mobile applications have come to be an essential part of any business to reviews app developer com run and keep in a highlight mode. Transformative mobile applications are more than capable of altering the industry game for virtually any organization that is remarkable. If you don’t opt for the proper mobile app development company then you’ll unable to fulfill your plans. Possessing a seasoned group of professionals makes it straightforward for the firm to provide the services to the users. https://en.wikipedia.org/wiki/Software The firm is just one of the company solution for your custom made computer software development with higher excellent integration, development, security and quality assurance. Whenever there’s a constant shift in business environment and client preferences, company owners should now secure conscious of the hottest choices and trends. The choice can be quite tricky because there are a lot of important factors to contemplate. There are many app development businesses in the competition who tend to provide you with the best services. For the next two years it struggled to gain a foothold in the smartphone industry. It provides the best mobile app services to their customers. With years of experience, it builds solid feature-rich apps which are secure, reliable, and easy-to-use. Hence, below are some critical points to select the top rated iPhone app development business in India or an Android app development business in India It’s important to consult the previous projects of the organization and the revenue generated by them. It’s possible for you to find world class app developers from India with high degree of design and development wisdom and experience. Depending on the sort of your app, you might also desire a permanent tech support team to promptly find any technical issues and fix them. Finding the Best Mobile App Development Companies List The Android SDK also includes an emulated virtual device that’s fully functional to allow you to test out your work. The app will start uploading wirelessly. They run in a special virtual machine called the Dalvik VM. The simplicity of upgrading app and the total usability of the framework might prove to be a challenging experience. Rename the folder to android so that it’s going to be simple to navigate. In addition, examine the problems which you might face when building the app. The iOS Developer Center has a broad variety of tools, hints, debugging tests and guides for creating apps for practically any objective. Before development begins, you will need to detect preciselyhowyou’ll use the app. It is one of the most prospering industry worldwide that has led to the existence of more than 3 million apps. Mobile App Development Companies List – Overview It is crucial to nearly all businesses. The cost for doing the very same in america is very likely to be an order of magnitude higher. It has more than 100 employees, who have at least five years of experience in the industry. Success of any company depends upon its clients’ success. Working with Code Brew offers you a couple notable benefits. It might take a couple of minutes, particularly if it’s a huge app. The Good, the Bad and Mobile App Development Companies List QBurst is India based one of the significant mobile application development providers. Many businesses will supply the particulars of the key projects they have worked on through their sites. Consider the length of the upkeep of the enterprise app. The NineHertz development procedure is a well-planned and strategic approach to several modules. For the better experience in the area of technology and apps, individuals have to pick the very best platform wisely. There transparent app growth strategies have made them one of the greatest mobile app growth businesses. Agile development is the procedure of creating software applications which follow a disciplined approach to the project administration. Android phones are a breeze to use and navigate through its platforms. Leading app growth businesses are now investing in machinery and manpower space o technologies to maximize their marketability for business enterprises nowadays. Lies You’ve Been Told About Mobile App Development Companies List It’s also essential for customers to understand your general mobile app development procedure, which is precisely why this section is specially devoted to outlining and describing your services. Conclusion Hence bearing in mind the aforementioned factors and points, you can pick the finest mobile application development company that may fulfill every one of your requirements. A superb market penetration program should exist for a new market as everything is not yet been explored and also the present populated market can have plenty of ups and downs too. Ideally, the development team is involved at the start of the undertaking, but in case the technical men and women that are actually likely to construct your cellular app aren’t already on board, now’s the opportunity to bring them in. Take into consideration the way that you need your app to bring profit. To put it differently, set your app in the hands of a couple men and women in your intended audience.

Q: A major incident was declared A major incident was declared when winds caused two fires to merge near communication masts on Saturday. From BBC.com How should we interpret the main clause that a major incident was declared? Does it mean when winds caused fires and at that time somebody declared an incident or the major incident here is exactly the fire incident? https://www.bbc.co.uk/news/uk-england-lancashire-44676707 A: It is part of the procedure of the Fire Brigade. A small fire will be put out by the local fire brigade. But if the fire becomes more serious the local fire chief will decide to call it a "major incident" and get external help and support. In this case, there were two small fires. The winds changed and the two small fires joined up to become one large fire. This fire was near some "communication masts". The local fire chief realised that his firefighters couldn't put out the fire alone, so he called the fire a "major incident" and got help from other firefighters. As the reporter doesn't know who the fire chief is, the reporter uses the passive voice.

Since a recent Stanford study showed that students at practically all grade levels can't determine fake news from the real stuff, the push to teach media literacy has gained new momentum. The study showed that while students absorb media constantly, they often lack the critical thinking skills needed to tell fake news from the real stuff. Teachers are taking up the challenge to change that. NPR Ed put out a social media call asking how educators are teaching fake news and media literacy, and we got a lot of responses. Here's a sampling from around the country: Fake news "Simon Says" In Scott Bedley's version of Simon Says, it's not those two magic words that keep you in the game, but deciding correctly whether a news story is real or not. To start off the game, Bedley sends his fifth-graders at Plaza Vista School in Irvine, Calif., an article to read on their laptops. He gives them about three minutes to make their decision — they have to read the story carefully, examine its source and use their judgment. Those who think the article is false, stand up. The "true" believers stay in their seats. Bedley says he's been trying to teach his students for a while to look carefully at what they're reading and where it comes from. He's got a seven-point checklist his students can follow: 1. Do you know who the source is, or was it created by a common or well-known source? Example National Geographic, Discovery, etc.2. How does it compare to what you already know?3. Does the information make sense? Do you understand the information?4. Can you verify that the information agrees with three or more other sources that are also reliable?5. Have experts in the field been connected to it or authored the information?6. How current is the information?7. Does it have a copyright? Subtle changes Bedley also teamed up recently with Todd Flory at Wheatland Elementary School in Wichita, Kan., to do a fake news challenge via Skype. Flory's fourth-graders chose two real articles and wrote a fake article of their own. Then, they presented them to Bedley's class in California. The fifth-graders had four minutes to do some extra research based on the presentations, and then they decided which article out of the three were fake. Most importantly, they had to explain why they thought it was fake. Otherwise, no points. Flory says writing the fake news article was more difficult for his students than they expected because they had to make it believable. "It really hammered home the idea to them that fake news doesn't have to be too sensational," he says. "It can be a very subtle change, but that subtle change can have big consequences." Every Friday, Flory's class participates in what he calls Genius Hour. His students propose a question to answer through online research. But before they took to the Internet, Flory had to walk his students through the steps: What are reliable and trusted websites? How do you effectively search on the Internet and verify information? He uses Skype to connect his students with researchers and scientists from all over the world. He calls this "authentic research." "It's so much more powerful for them to do some of this authentic research when they're able to hear from a scientist who's seeing firsthand the effects of climate change," Flory says. This year's class got to talk to a penguin scientist. Flory says he's not only teaching his students effective media literacy skills; he is also helping them to be better citizens through global engagement and interaction. Let them eat fake (news) Remember Marie Antoinette and "Let them eat cake" — her famous line about the poor that got her in all that trouble? Thing is, it never happened. Fake news! For Diane Morey and her ninth-graders at Danvers High School in Danvers, Mass., that's a teachable moment. "The media of the day didn't have Facebook, Twitter or partisan websites," Morey says. "But they did have pamphlets." She shows her class cartoons and pamphlets from the French Revolutionary period that criticized Antoinette, and then discusses the conclusions that were made from those sources. She also includes a primary source: a letter written by Antoinette. Morey says history is rich with examples of fake news, and since source analysis is the core of her lesson plans, she doesn't need a textbook. "We don't study [history] to memorize Marie Antoinette and Louis XVI," she explains. "We're studying this because we can see this happening in the current-day political climate." Morey encourages students to bring in examples of articles from today's news that don't ring true. "Once you expose it to them," she says, "it's like a game for them, seeing, 'Hey, I'm not sure I can trust this.' " Extra layers For 13 years, Larry Ferlazzo has been teaching kids who are learning English how to read and write. Now, he's adding another layer: helping them figure out if what they're reading is true. Last month, he wrote a lesson plan on addressing fake news to English language learners (ELLs), which was published in The New York Times. He says media literacy is especially important for ELLs for two reasons. First, they're not fluent in the language they're reading, adding an extra level of difficulty in deciding what to believe. On top of that, false or exaggerated news about immigration could have a major impact on their lives. His lesson starts off with a few examples of reliable and fake news. Then, some basic journalism stuff: Students identify the different parts of the news, from the "lede" to quotations. They enter all that into a diagram on paper so they have a visual representation of what they're reading. That diagram eventually becomes a guide for students to write their own fake news lede that they can share with other classmates or post on a class blog. Media consumers and contributors In 2015, Spencer Brayton and his colleague Natasha Casey revamped a media literacy course for students at Blackburn College in Carlinville, Ill. Brayton says the key is the critical approach. "Students come in expecting that we're going to lecture," Brayton explains. "But we have them think about certain power structures in how information is produced and how it reaches them. If they're going to understand how they're going to take it in, then they have to know how the news is going to be produced." To take the class, students need a Twitter account. From the very first week, they are asked to follow five to 10 accounts on Twitter that promote media and information literacy, like Media Literacy Now or Renee Hobbs. As they follow these posts and add additional ones, the goal is that they'll start to recognize fake news and other biases or viewpoints in media. By the end of the course, Brayton says students begin to see themselves not only as creators of information, but as credible sources of information too. The Twitter assignments encourage his students to engage with social media - retweeting, following and commenting — which Brayton says helps his students see how they play a role in spreading information to other media consumers. That means they have to take what they share more seriously. "In looking at this issue, people seem to want a quick solution to fake news, but I'm not sure there is a solution (at least an easy one)," Brayton writes in an email. "Students need to recognize that these skills and ideas need to stay with them through adulthood, but that's easier said than done — we all fall into this trap."

[Treatable hereditary neuro-metabolic diseases]. Hereditary metabolic diseases may appear during adolescence or young adulthood, revealed by an apparently unexplained neurological or psychiatric disorder. Certain metabolic diseases respond to specific treatments and should be identified early, particularly in emergency situations where rapid introduction of a treatment can avoid fatal outcome or irreversible neurological damage. The main diseases leading to an acute neurological syndrome in the adult are urea cycle disorders, homocysteine metabolisms disorders and porphyria. More rarely, Wilson's disease, aminoacid diseases, organic aciduria, or pyruvate dehydrogenase deficiency, beta-oxidation disordes or biotin metabolism may be involved. Most emergency situations can be screen correctly with simple tests (serum ammonia, homocysteine, lactate, urinary prophyrines, acylcarnitine pattern, amino acid and organic acid chromatography). For chronic situations, the main treatable diseases are Wilson's disease, homocysteine, cerebrotendinous xanthomatosis, Refsum's disease, vitamin E deficiency, Gaucher's disease, Fabry's disease, and neurotransmitter metabolism disorders. We present treatable metabolic disorders as a function of the different clinical situations observed in adults.

Q: Forest trees fitting on page My forest looks like this but it does not fit on a page, this is my first time using this package. I am looking for suggestions to fit this into a page, hopefully they will not be too intensive because I plan on making an even bigger tree. \documentclass{article} \usepackage{forest} \begin{document} \begin{forest} for tree={circle,draw, l sep=20pt} [1,red [2, edge label={node[midway,left] {A}} [1,red,edge label={node[midway,left] {B}} [2,red,edge label={node[midway,right] {C}}] [2,red,edge label={node[midway,right] {D}}] ] [1,red,edge label={node[midway,right] {C}} [2,red,edge label={node[midway,right] {B}}] [2,red,edge label={node[midway,right] {D}}] ] [1,red,edge label={node[midway,right] {D}} [2,red,edge label={node[midway,right] {B}}] [2,red,edge label={node[midway,right] {C}}] ] ] [2, edge label={node[midway,left] {B}} [1,red, edge label={node[midway,left] {A}} [2,red,edge label={node[midway,right] {C}}] [2,red,edge label={node[midway,right] {D}}] ] [1,red, edge label={node[midway,right] {A}} [2,red,edge label={node[midway,right] {C}}] [2,red,edge label={node[midway,right] {D}}] ] [1,red,edge label={node[midway,right] {A}} [2,red,edge label={node[midway,right] {C}}] [2,red,edge label={node[midway,right] {D}}] ] ] [2, edge label={node[midway,left] {C}} [1,red,edge label={node[midway,left] {A}} [2,red,edge label={node[midway,right] {B}}] [2,red,edge label={node[midway,right] {D}}] ] [1,red,edge label={node[midway,right] {B}} [2,red,edge label={node[midway,right] {A}}] [2,red,edge label={node[midway,right] {D}}] ] [1,red,edge label={node[midway,right] {D}} [2,red,edge label={node[midway,right] {A}}] [2,red,edge label={node[midway,right] {B}}] ] ] [2, edge label={node[midway,left] {D}} [1,red,edge label={node[midway,left] {A}} [2,red,edge label={node[midway,right] {B}}] [2,red,edge label={node[midway,right] {C}}] ] [1,red,edge label={node[midway,right] {B}} [2,red,edge label={node[midway,right] {A}}] [2,red,edge label={node[midway,right] {C}}] ] [1,red,edge label={node[midway,right] {C}} [2,red,edge label={node[midway,right] {A}}] [2,red,edge label={node[midway,right] {B}}] ] ] ] \end{forest} \end{document} A: I would: use geometry to get more sensible margins; move some branches of the tree down to conserve space; used squared edges to avoid branches crossing things and to reduce crowding and clutter; avoid putting labels so that edges are drawn through them by repositioning them slightly for greater legibility; use a style to simplify adding the edge labels, which allows their positions to be amended more easily and determined more consistently (and saves typing) e.g. my label in the example below; consider adding colour automatically for trees where there is a pattern e.g. all final nodes are a different colour or all left-hand nodes or whatever (but this is just to save typing and clearly a matter of preference); use pdflscape for larger trees (not needed for this one). Here's an example: \documentclass{article} \usepackage{geometry} \usepackage[edges]{forest} \begin{document} \noindent \begin{forest} my label/.style={% if n=1{% edge label={node [midway,left] {#1}} }{% if n'=1{% edge label={node [midway,right] {#1}} }{% edge label={node [midway,below right] {#1}} } }, }, for tree={circle,draw, l sep=20pt}, before typesetting nodes={ where content={}{coordinate}{}, }, forked edges, [1,red [2, my label={A} [1,red,my label={B} [2,red,my label={C}] [2,red,my label={D}] ] [1,red,my label={C} [2,red,my label={B}] [2,red,my label={D}] ] [1,red,my label={D} [2,red,my label={B}] [2,red,my label={C}, tier=this] ] ] [, tier=this, my label={B} [2 [1,red, my label={A} [2,red,my label={C}] [2,red,my label={D}] ] [1,red, my label={A} [2,red,my label={C}] [2,red,my label={D}] ] [1,red,my label={A} [2,red,my label={C}] [2,red,my label={D}] ] ]] [2, my label={C} [1,red,my label={A} [2,red,my label={B}] [2,red,my label={D}] ] [1,red,my label={B} [2,red,my label={A}] [2,red,my label={D}] ] [1,red,my label={D} [2,red,my label={A}] [2,red,my label={B}, tier=this] ] ] [, tier=this, my label={D} [2 [1,red,my label={A} [2,red,my label={B}] [2,red,my label={C}] ] [1,red,my label={B} [2,red,my label={A}] [2,red,my label={C}] ] [1,red,my label={C} [2,red,my label={A}] [2,red,my label={B}] ] ]] ] \end{forest} \end{document}

"There's no doubting the footballs been shite." Exactly Harry, wtf have i been saying and getting dogs abuse from you for two seasons? You haven't been saying that for two years you've been spouting 'Trust in Jose' and trying to claim that games that have been shite have been great and that every fucker is to blame but Jose. I'm not calling for his head i'm calling for better more consistent football. Give the players a chance to be attacking, creative, brave. And stop crowing about beating average or worse teams. Jose should expect Pogba to be disiplined / capable of a variation in midfield play ,he ain't exactly asking him to play in goal or right back , he may not be as effective in that place but that's up to Jose where he gets the best out of the lad . The jury is out on where Pogba should play but that ain't Jose's , fault for me I think he should be a numb 10 behind in the present side Sanchez, but then Jose is relying to much on Matic , has Fellani injured ( and possibly in the departure lounge) Herrera not good enough but ultimately have to use him the kid who played Sat plus Carrick finished and a makeshift Blind. As for the MEN article the manager was criticised for publicly calling out players early season and when he gives them encouragement in public he gets a pelter too? "There's no doubting the footballs been shite." Exactly Harry, wtf have i been saying and getting dogs abuse from you for two seasons? You haven't been saying that for two years you've been spouting 'Trust in Jose' and trying to claim that games that have been shite have been great and that every fucker is to blame but Jose. I'm not calling for his head i'm calling for better more consistent football. Give the players a chance to be attacking, creative, brave. And stop crowing about beating average or worse teams. Belt up you big tart. What the fuck do you know about consistency. It doesn't matter how they've played you've always found time to slate Joey. End of. I saw that Jose said something about the need to work on our "attacking dynamic", or something like that, after the last game. I'm glad that he recognises that. Sanchez is a good player who improves our forward line, but it really doesn't look like it's more than the sum of its parts, it's just three (or four) individual players doing their thing. We were banging in the goals in the first month of the season, but our scoring rate has been gradually dribbling downward since then. In fact, after the first six games, which we did really well in, our record for the past 20 games is exactly the same as Liverpool's. "Despite his reputation, United manager's faith in youth has put Guardiola in the shade" It was mostly overlooked at the time, a casualty of the fanfare surrounding Alexis Sanchez's signing a few days earlier, but when Manchester United announced Jose Mourinho had signed a new contract last month, there was a line from the club's executive vice-chairman, Ed Woodward, praising the manager's commitment to blooding youth."He has embraced the club's desire to promote top quality young players to the first team," said Woodward, a pointed response to those who suggested the Portuguese would pay little more than lip service to the club's rich traditions of cultivating home-grown talent.Those suggestions had solid enough foundations. For all the success Mourinho's managerial career has brought him, there has been a perennial black splodge next to the box marked youth development and no one has been more aware of this than the man himself.It has felt very different at United, though, and while entrenched reputations can take a long time to change, certain perceptions are, for now at least, being challenged.There has been an understandable rush to measure Mourinho and United's every move against what Pep Guardiola has been doing at Manchester City. But while Guardiola has raised all sorts of bars this term, there is a certain irony that Mourinho - "the monster that kills the little kids" as he sarcastically described himself last week - has bought into the academy ethos in a way his great adversary, often heralded as a champion of youth, has yet to do with any particular conviction down the road.Tomorrow marks the 60th anniversary of the Munich air disaster, and on a weekend when United supporters honoured the memory of the Busby Babes - one of the ultimate symbols of the potency of youth - there was something rather poignant about Mourinho dropping Paul Pogba and playing academy graduate Scott McTominay in the £89million man's place against Huddersfield.Before anyone hints at an ulterior motive there, it is worth remembering that Mourinho has never been one for sentiment and that McTominay had already made more starts this season than the entirety of the five academy graduates at City who have fleetingly tasted first-team football under Guardiola since August. Note, too, that Marcus Rashford has made more appearances - 90 - than anyone since Mourinho took charge at United and another academy graduate, Jesse Lingard, who has also flourished, is fourth on that list.While Mourinho was extolling the virtues of McTominay, or the "kid" as he affectionately calls him, Guardiola was whining about not having enough players in the wake of a mounting injury list and a failed move for Riyad Mahrez, and reiterated the point with a grimly petty decision to name only six substitutes against Burnley.Such arguments really do not hold much sway when you have spent £450 million in 19 months and have an academy awash with exciting talents, any number of whom would have benefited from the experience of a match-day with the first-team squad. "If you're the academy or reserve-team manager at Manchester City, you must think, 'I'm wasting my time'," said Gary Neville, the former United defender and Sky Sports pundit. "Rather than saying in an interview, 'I haven't got the players', he could say he's brought a young player from the youth team who has been wonderful this season. It's really poor. And I can guarantee you the youth-team coach and reserve-team coach at Manchester City will feel disheartened by him having six players on the bench."It was a wretched move Mourinho's critics might have once expected him to make but the tide seems to be turning.

In this category you can find us all stand for the presentation of your cupcakes. Choose between different types of stands, in different materials and prices. Present your creations correctly and completely or Set a beautiful showcase.

Q: Are there any good tools to generate a Google Sitemap? Can you recommend any tools? Should we build our own? Should we create the sitemap manually? A: The Google Sitemap Generator for IIS generates a sitemaps based on actual HTTP requests to your server (unlike other sitemap generators that rely on a crawlable path from the homepage, Google's approach doesn't actually crawl your site). It is uniquely suited to dynamic applications, particularly those that have a deep bank of data that's surfaced through user queries alone.

Petticoat affair The Petticoat Affair (also known as the Eaton Affair), was a U.S. scandal involving members of President Andrew Jackson's Cabinet and their wives, from 1829 to 1831. Led by Floride Calhoun, wife of Vice President (VP) John C. Calhoun, these women, dubbed the "Petticoats," socially ostracized then–Secretary of War John Eaton and his wife Peggy Eaton, over disapproval of the circumstances surrounding the Eaton's marriage; what they deemed as her failure to meet the "moral standards of a Cabinet Wife". The Petticoat Affair rattled the entire Jackson Administration, and inevitably led to the resignation of all but one Cabinet member. The ordeal facilitated Martin Van Buren's rise to the presidency, and was in part responsible for VP Calhoun's transformation from a "Nationwide political figure with Presidential aspirations", into a "Sectional-leader of the Southern states". Background Margaret "Peggy" Eaton was the eldest daughter of William O'Neill, owner of The Franklin House, a boarding house and tavern located in Washington, D.C. a short distance from the White House that was a well-known social hub popular with politicians and military officials. Peggy was well-educated for a woman of that era - she studied French and was known for her ability to play the piano. William T. Barry, who later served as Postmaster General, wrote "of a charming little girl ... who very frequently plays the piano, and entertains us with agreeable songs." As a young girl, her reputation had already begun to come under scrutiny, due to being employed in a bar frequented by men as well as her casual bantering with the boarding house's clientele. In her elder years, Peggy reminisced, "While I was still in pantalettes and rolling hoops with other girls, I had the attention of men, young and old; enough to turn a girl's head." When Peggy was 15 years old, her father intervened to prevent her attempt to elope with an Army officer. In 1816, the now-17-year old married John B. Timberlake (1777-1828), a purser in the United States Navy. Timberlake, aged 39, had a reputation as a drunkard and was heavily in debt. The Timberlakes became acquainted with John Eaton in 1818. At the time, Eaton was a wealthy 28-year-old widower and newly elected U.S. Senator from Tennessee, despite not yet having reached the constitutionally-mandated minimum age of 30. He was also a long-time friend of Andrew Jackson. Once Timberlake told Eaton of his financial troubles, Eaton unsuccessfully attempted to have the Senate pass legislation that would authorize payment of the debts Timberlake had accrued during his Naval service. Eventually, Eaton paid Timberlake's debts, and procured him a lucrative posting to the U.S. Navy's Mediterranean Squadron; many rumormongers asserted that Eaton aided Timberlake as a means to remove him from Washington, in order for Eaton to socialize with Peggy. While with the Mediterranean Squadron, Timberlake died on April 2, 1828. This served to fuel new rumors throughout Washington, suggesting he had taken his own life, as the result of Eaton's supposed affair with Peggy. Medical examiners concluded Timberlake had died of pneumonia, brought on by pulmonary disease. Controversy Jackson was elected president in 1828, with his term set to begin on March 4, 1829. He was reportedly fond of Peggy Timberlake and encouraged Eaton to marry her. They were wed on January 1, 1829; only nine months after her husband's death. Customarily, it would have been considered "proper" for their marriage to have followed a longer mourning period. Historian John F. Marszalek explained his opinion on the "real reasons Washington society found Peggy unacceptable": "She did not know her place; she forthrightly spoke up about anything that came to her mind, even topics of which women were supposed to be ignorant. She thrust herself into the world in a manner inappropriate for a woman. ... Accept her, and society was in danger of disruption. Accept this uncouth, impure, forward, worldly woman, and the wall of virtue and morality would be breached and society would have no further defenses against the forces of frightening change. Margaret Eaton was not that important in herself; it was what she represented that constituted the threat. Proper women had no choice; they had to prevent her acceptance into society as part of their defense of that society's morality." When Jackson assumed the presidency, he appointed Eaton as Secretary of War. Floride Calhoun, Second Lady of the United States, led the wives of other Washington political figures, mostly those of Jackson's cabinet members in an "anti-Peggy" coalition, which served to shun the Eatons socially and publicly. The women refused to pay courtesy calls to the Eatons at their home, to receive them as visitors, and denied them invitations to parties and other social events. Emily Donelson, niece of Andrew Jackson's late wife Rachel Donelson Robards, and the wife of Jackson's confidant Andrew Jackson Donelson, served as Jackson's "surrogate First Lady". Emily Donelson chose to side with the Calhoun faction, thus leading to Jackson replacing her with his daughter-in-law Sarah Yorke Jackson, as his official hostess. Secretary of State, Martin Van Buren, was a widower, and the only unmarried member of the Cabinet; he raised himself in Jackson's esteem by aligning himself with the Eatons. Jackson's sympathy for the Eatons stemmed in part from his late wife Rachel being the subject of innuendo during the presidential campaign, when questions arose as to whether her first marriage had been legally ended before she married Jackson. Jackson believed these attacks were the cause of Rachel's death on December 22, 1828, several weeks after his election to the presidency. Eaton's entry into a high-profile cabinet post helped intensify the opposition of Mrs. Calhoun's group. In addition, Calhoun was becoming the focal point of opposition to Jackson; Calhoun's supporters opposed a second term for Jackson because they wanted Calhoun elected president. In addition, Jackson favored and Calhoun opposed the protective tariff that came to be known as the Tariff of Abominations. U.S. tariffs on imported goods generally favored northern industries by limiting competition, but southerners opposed them because the tariffs raised the price of finished goods, but not the raw materials produced in the south. The dispute over the tariff led to the Nullification Crisis of 1832, with southerners - including Calhoun - arguing that states could refuse to obey federal laws to which they objected, even to the point of secession from the Union, while Jackson vowed to prevent secession and preserve the Union at any cost. Because Calhoun was the most visible opponent of the Jackson administration, Jackson felt that Calhoun and other anti-Jackson officials were fanning the flames of the Peggy Eaton controversy in an attempt to gain political leverage. Duff Green, a Calhoun protégé and editor of the United States Telegraph, accused Eaton of secretly working to have pro-Calhoun cabinet members Samuel D. Ingham (Treasury) and John Branch (Navy) removed from their positions. Eaton took his revenge on Calhoun. In 1830, reports had emerged which accurately stated that Calhoun, while Secretary of War, had favored censuring Jackson for his 1818 invasion of Florida. These reports infuriated Jackson. Calhoun asked Eaton to approach Jackson about the possibility of Calhoun publishing his correspondence with Jackson at the time of the Seminole War. Eaton did nothing. This caused Calhoun to believe that Jackson had approved the publication of the letters. Calhoun published them in the Telegraph. Their publication gave the appearance of Calhoun trying to justify himself against a conspiracy, which further enraged the President. Resolution The dispute was finally resolved when Van Buren offered to resign, giving Jackson the opportunity to reorganize his cabinet by asking for the resignations of the anti-Eaton cabinet members. Postmaster General William T. Barry was the lone cabinet member to stay, and Eaton eventually received appointments that took him away from Washington, first as governor of Florida Territory, and then as minister to Spain. On June 17, the day before Eaton formally resigned, a text appeared in the Telegraph stating that it had been "proved" that the families of Ingham, Branch, and Attorney General John M. Berrien had refused to associate with Mr. Eaton. Eaton wrote to all three men demanding that they answer for the article. Ingham sent back a contemptuous letter stating that, while he was not the source for the article, the information was still true. On June 18, Eaton challenged Ingham to a duel through Eaton's brother in law, Dr. Philip G. Randolph, who visited Ingham twice and the second time threatened him with personal harm if he did not comply with Eaton's demands. Randolph was dismissed, and the next morning Ingham sent a note to Eaton discourteously declining the invitation, and describing his situation as one of "pity and contempt." Eaton wrote a letter back to Ingham accusing him of cowardice. Ingham was then informed that Eaton, Randolph, and others were looking to assault him. He gathered together his own bodyguard, and was not immediately molested. However, he reported that for the next two nights Eaton and his men continued to lurk about his dwelling and threaten him. He then left the city, and returned safely to his home. Ingham communicated to Jackson his version of what took place, and Jackson then asked Eaton to answer for the charge. Eaton admitted that he "passed by" the place where Ingham had been staying, "but at no point attempted to enter ... or besiege it." Aftermath In 1832, Jackson nominated Van Buren to be Minister to Great Britain. Calhoun killed the nomination with a tie-breaking vote against it, claiming his act would "...kill him, sir, kill him dead. He will never kick, sir, never kick." However, Calhoun only made Van Buren seem the victim of petty politics, which were rooted largely in the Eaton controversy. This raised Van Buren even further in Jackson's esteem. Van Buren was nominated for vice president, and was elected as Jackson's running mate when Jackson won a second term in 1832. Van Buren thus became the de facto heir to the presidency, and succeeded Jackson in 1837. Although Emily Donelson had supported Floride Calhoun, after the controversy ended Jackson asked her to return as his official hostess; she resumed these duties in conjunction with Sarah Yorke Jackson until returning to Tennessee after contracting tuberculosis, leaving Sarah Yorke Jackson to serve alone as Jackson's hostess. John Calhoun resigned as vice president shortly before the end of his term, and returned with his wife to South Carolina. Quickly elected to the U.S. Senate, he returned to Washington not as a national leader with presidential prospects, but as a regional leader who argued in favor of states' rights and the expansion of slavery. In regard to the Petticoat affair, Jackson later remarked, "I [would] rather have live vermin on my back than the tongue of one of these Washington women on my reputation." To Jackson, Peggy Eaton was just another of many wronged women who over his lifetime he had known and defended. He believed that every woman he had defended in his life, including her, had been the victim of ulterior motives, so that political enemies could bring him down. According to historian Daniel Walker Howe, the episode influenced the emergence of feminism. The Cabinet wives insisted that the interests and honor of all women were at stake. They believed a responsible woman should never accord a man sexual favors without the assurance that went with marriage. A woman who broke that code was dishonorable and unacceptable. Howe notes that this was the feminist spirit that in the next decade shaped the woman's rights movement. The aristocratic wives of European diplomats in Washington shrugged the matter off; they had their national interest to uphold, and had seen how life worked in Paris and London. Legacy Historian Robert V. Remini says that "the entire Eaton affair might be termed infamous. It ruined reputations and terminated friendships. And it was all so needless." The 1936 film The Gorgeous Hussy is a fictionalized account of the Petticoat affair. It featured Joan Crawford as Peggy O'Neal, Robert Taylor as John Timberlake, Lionel Barrymore as Andrew Jackson, and Franchot Tone as John Eaton. References Bibliography External links "Andrew Jackson and the Tavern-Keeper's Daughter", Women's History Andrew Jackson on the Web: Petticoat Affair J. Kingston Pierce, "Andrew Jackson's 'Petticoat Affair'", The History Net, June 1999 This American Life, #485 "Surrogates", Act One: Petticoats in a Twist, (January 25, 2013). Sarah Koenig talks with historian Nancy Tomes about the Petticoat Affair. Category:Political scandals in the United States Category:Political controversies in the United States Category:1831 in the United States Category:John C. Calhoun Category:Presidency of Andrew Jackson

As Erick noted earlier today, my fellow Texans have a clear, distinct choice as to who will be the Speaker of the Texas House coming up this Tuesday, January 11th. Let’s be honest. There is a clear cut difference between Joe Straus and Ken Paxton. For more on that, check this site out. In spite of all the ads he has bought on Drudge, NewsMax | Read More » As Erick noted earlier today, my fellow Texans have a clear, distinct choice as to who will be the Speaker of the Texas House coming up this Tuesday, January 11th. Let’s be honest. There is a clear cut difference between Joe Straus and Ken Paxton. For more on that, check this site out. In spite of all the ads he has bought on Drudge, NewsMax | Read More »

Q: Ng-repeat-start in angular2 - aka repeat multiple elements using NgFor I need to repeat several li-elements in a list in Angular2 for each item. In angular 1.x I used ng-repeat-start and ng-repeat-end for this. I can't find the right way to do it in Angular 2. There are some older blog posts about this, but their suggestions don't work in the newest beta of Angular2. All <li>-elements should be repeated for each category: (which I would normally do with the attribute *ngFor="#category of categories" - but I can't find where to put it... Help? <ul class="dropdown-menu" role="menu"> <li class="dropdown-header"> {{ category.title }} </li> <li> <a href="{{ '/music/' + tag.keyword }}" *ngFor="#tag of category.tags" [hidden]="tag.deleted === 1">{{ tag.tag_title_da }}</a> </li> <li class="divider"></li> <li class="dropdown-header">Alle musikstykker</li> <li><a href="/music/all">Alle musikstykker</a></li> </ul> A: If you want to repeat the contents, use the template tag, and remove the * prefix on ngFor. According to Victor Savkin on ngFor and templates: Angular treats template elements in a special way. They are used to create views, chunks of DOM you can dynamically manipulate. The * syntax is a shortcut that lets you avoid writing the whole element. <ul class="dropdown-menu" role="menu"> <template ngFor #category [ngForOf]="categories"> <li class="dropdown-header"> {{ category.title }} </li> <li> <a href="{{ '/music/' + tag.keyword }}" *ngFor="#tag of category.tags" [hidden]="tag.deleted === 1">{{ tag.tag_title_da }}</a> </li> <li class="divider"></li> <li class="dropdown-header">Alle musikstykker</li> <li><a href="/music/all">Alle musikstykker</a></li> </template> </ul> Update angular ^2.0.0 You can use ng-container and just change #var to let var. <ng-container> behaves the same as the <template> but allows to use the more common syntax. <ul class="dropdown-menu" role="menu"> <ng-container *ngFor="let category of categories"> <li class="dropdown-header"> {{ category.title }} </li> <li> <a href="{{ '/music/' + tag.keyword }}" *ngFor="let tag of category.tags" [hidden]="tag.deleted === 1">{{ tag.tag_title_da }}</a> </li> <li class="divider"></li> <li class="dropdown-header">Alle musikstykker</li> <li><a href="/music/all">Alle musikstykker</a></li> </ng-container> </ul> A: In the newer versions it works like this: <ul class="dropdown-menu" role="menu"> <template ngFor let-category [ngForOf]="categories"> <li class="dropdown-header"> {{ category.title }} </li> <li> <a href="{{ '/music/' + tag.keyword }}" *ngFor="#tag of category.tags" [hidden]="tag.deleted === 1">{{ tag.tag_title_da }}</a> </li> <li class="divider"></li> <li class="dropdown-header">Alle musikstykker</li> <li><a href="/music/all">Alle musikstykker</a></li> </template> </ul> --> let-category instead of #category

[Imagination: its definition, purposes and neurobiology]. Imagination, distinct from imagery, memory, and cognition, is a poorly understood but fascinating cognitive ability of human beings. Herein, imagination is defined as 'the cognitive process which enables the individual to manipulate intrinsically generated phenomenal information in order to create a representation perceived by the mind's senses.' This definition is expanded within the context of the neurobiology of the brain and the possible purposes the imagination fulfills in daily living, human development, and normal behavior.

Q: error rgding definition & no extension method for System.Web.Routing.RouteValueDictionary I am going through tutorial at 4GuysFromRolla website regarding Sorting and Paging a Grid of Data in ASP.NET MVC 2 by Scott Mitchell. I am receiving an error CS1061: 'System.Web.Routing.RouteValueDictionary' does not contain a definition for 'AddQueryStringParameters' and no extension method 'AddQueryStringParameters' accepting a first argument of type 'System.Web.Routing.RouteValueDictionary' could be found (are you missing a using directive or an assembly reference?). I am not sure if I need to add a dll reference or something else. Please could someone advise how to solve this thanks in advance. Also I downloaded the demo and there is no problem. error is in PagerLink.ascx file..routeData.AddQueryStringParameters(); // error pointing here RouteValueDictionaryExtensions.cs looks like this (this is the helper file)... using System.Web.Routing; namespace Web { public static class RouteValueDictionaryExtensions { public static RouteValueDictionary AddQueryStringParameters(this RouteValueDictionary dict) { var querystring = HttpContext.Current.Request.QueryString; foreach (var key in querystring.AllKeys) if (!dict.ContainsKey(key)) dict.Add(key, querystring.GetValues(key)[0]); return dict; } public static RouteValueDictionary ExceptFor(this RouteValueDictionary dict, params string[] keysToRemove) { foreach (var key in keysToRemove) if (dict.ContainsKey(key)) dict.Remove(key); return dict; } } } Global.asax.cs looks like this... enter code here namespace GridDemosMVC { // Note: For instructions on enabling IIS6 or IIS7 classic mode, // visit http://go.microsoft.com/?LinkId=9394801 public class MvcApplication : System.Web.HttpApplication { public static void RegisterRoutes(RouteCollection routes) { routes.IgnoreRoute("{resource}.axd/{*pathInfo}"); routes.MapRoute( "Default", // Route name "{controller}/{action}/{id}", // URL with parameters new { controller = "Home", action = "Index", id = UrlParameter.Optional } // Parameter defaults ); } protected void Application_Start() { AreaRegistration.RegisterAllAreas(); RegisterRoutes(RouteTable.Routes); } } } I am also using Dynamic.cs file which is available at microsoft to download. A: You need to add a using statement and <%@ Import directive for the namespace with the extension method. Alternatively, you can move the extension method into your project's namespace.

Sandrine Clet-Guet Sandrine Clet-Guet (born 1971) is a French ski mountaineer. Selected results 2002: 8th, World Championship team race (together with Laetitia Gachet) 2006: 2nd, Montée Pelluaz Pierra Menta 2002: 6th, together with Laetitia Gachet 2003: 10th, together with Laetitia Gachet References Category:Living people Category:French female ski mountaineers Category:1971 births

Balaban (instrument) Balaban, or balaman () is cylindrical-bore, double-reed wind instrument about long with eight finger holes and one thumb hole. Balaban, one of the ancient wind instruments, is played in all corners of Azerbaijan. This instrument is played in Iranian Azerbaijan and in the Republic of Azerbaijan. Balaban can be made of mulberry or other harder woods, such as walnut. The bore through the instrument is about in diameter. The double reed is made out of a single tube of cane about six cm long and pressed flat at one end. The performer uses air stored in his cheeks to keep playing the balaban while he inhales air into his lungs. This “circular” breathing technique is commonly used with all the double-reed instruments in the Middle East. Structure Balaban, which is often called also yasti (flat) balaban for flat mouthpiece and soft sound, consists of body made of apricot tree, cane, barrow and cover. Body has 8 holes on the surface and 1 on the back in the middle of 1st and 2nd holes (sound fret) on the surface. It consists of a stem, a reed, a regulator, and a cap. The stem of the balaban, or govda, is a cylindrical tube made primarily of apricot wood (sometimes also hazel, pear, mulberry, boxwood, etc.). The process of carving a balaban stem is called balaban chakma. The upper end of the stem (bash or kup) is given a round shape, whereas the lower end (ayag) is sharpened. The bore is in diameter. Eight holes or "tones" constituting a "sound tone" (sas pardasi) are made on the obverse and another one is made on the bottom side, opposite of the interval between the first and the second holes of the sas pardasi. Sometimes an additional hole called nizam pardasi is made on the lower end of the bottom side to ensure good timbre. The holes made on the stem are classified as follows: The reed (gamish, garghy or dil) made of club-rush that grows in an arid area is inserted into the upper end. It flattens and takes the shape of a double reed. It is tied to a long and wide regulator (kharak, boghazlig, boyundurug, ulama, akma) made of a willow or grape branch cut lengthways. The reed is then fixed by a collar-like regulator on one side and a pivot on the other side. The cap (qapaq, aghizlig, kip, band, etc.) made of willow, hazel, cornel or mulberry is put on the reed to prevent it from damage. It is tied to the regulator in order not to be lost. Use On solemn occasions such as weddings and holiday ceremonies, a balaban-player is accompanied by a percussionist. A traditional Azeri musical group consisting of two balaban-players and a percussionist is called balabanchilar dastasi. The short selection of Azerbaijani mugham played in balaban, national wind instrument was included on the Voyager Golden Record, attached to the Voyager spacecraft as representing world music, included among many cultural achievements of humanity. It was also used in pastoral songs and funeral music. According to Huseyngulu Sarabski, hunters played the balaban to attract quails. Certain types of the balaban are also used in ashik music. Legacy Kamil Jalilov's recording of the song with balaban was included on the Voyager Golden Record, attached to the Voyager spacecraft as representing mugham, only Azerbaijani song included among many cultural achievements of humanity. Gallery References External links Ch. Albright. BĀLĀBĀN. Iranica. Balaban, Duduk and Mey (video) Category:Single oboes with cylindrical bore Category:Azerbaijani musical instruments Category:Iranian musical instruments Category:Azerbaijani inventions Category:Azerbaijani words and phrases