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Image 1 of 5 A drawing of Peter Sagan's world champion's jersey (Image credit: Sportful) Image 2 of 5 Peter Sagan's world champion's jersey in the making (Image credit: Sportful) Image 3 of 5 The jersey design is printed (Image credit: Sportful) Image 4 of 5 Peter Sagan plays around on the podium, pretending to eat his gold medal (Image credit: Tim de Waele/TDWSport.com) Image 5 of 5 The men's road race podium of Michael Matthews (Australia), Peter Sagan (Slovakia) and Ramunas Navardauskas (Lithuania). It was the first time all three had made the podium in the elite race (Image credit: Tim de Waele/TDWSport.com) Cycling kit maker Sportful have revealed Peter Sagan's World Championship jersey design. Sportful have published a series of photos, including a drawing of the final jersey, as they begin to make the Slovakian's kit. There won't be much branding on the kit, other than the logos of the team's two main sponsors, as well as Sportful and the UCI. Each of the stripes that make up the rainbow band will be three centimetres high, making a 15-centimetre band around the jersey's chest. Rainbow stripes will adorn the sleeve cuffs and the collar. "The jersey has a very classic look even if it's a very technical Bodyfit Pro Race jersey," said Sportful Brand Communication Manager Daniel Loots. "The UCI rules on the design are pretty strict; the rainbow bands and dimensions of the sponsor logo are limited in size and position and they have to be black. There's no fluorescent anywhere and that means we have a very classic design." "Under UCI rules we can only have team issue shorts or white shorts. We haven't decided which Peter will wear yet but the rules mean he can't use black shorts." Sagan is due to debut his kit at the Abu Dhabi Tour on October 8. Download the Cyclingnews podcast on iTunes as we talk to Peter Sagan and more following his win at the World Championships.	{ "pile_set_name": "OpenWebText2" }
[PUBLISH] IN THE UNITED STATES COURT OF APPEALS FOR THE ELEVENTH CIRCUIT FILED ________________________ U.S. COURT OF APPEALS ELEVENTH CIRCUIT October 2, 2006 No. 05-11420 THOMAS K. KAHN ________________________ CLERK D. C. Docket No. 97-00238-CR-DLG UNITED STATES OF AMERICA, Plaintiff-Appellee, versus GREGORIO MACHADO, Defendant-Appellant. ________________________ Appeal from the United States District Court for the Southern District of Florida _________________________ (October 2, 2006) Before TJOFLAT and CARNES, Circuit Judges and HODGES,* District Judge. CARNES, Circuit Judge: * Honorable William Terrell Hodges, United States District Judge for the Middle District of Florida, sitting by designation. I. In March 1997 a grand jury indicted Gregorio Machado on thirteen counts of conspiracy to launder drug proceeds. The indictment included a forfeiture count pursuant to 18 U.S.C. § 982. After reaching a plea agreement with the government, Machado entered a guilty plea in May 1997. The written plea agreement contained an appeal waiver provision and a detailed forfeiture provision through which Machado pledged “to fully and unreservedly cooperate and assist the United States in the forfeiture and recovery of the forfeited assets, portions thereof, or their substitutes wherever located.” That provision included a detailed list of all the money and items that were to be forfeited. Machado says that the value of those listed items was approximately $12 million at the time of the indictment. On July 28, 1997, the district court sentenced Machado to 51 months imprisonment. At sentencing, the Assistant United States Attorney representing the government moved to dismiss eleven of the thirteen counts of the indictment in accordance with the plea agreement, and stated that “[t]he United States has not dismissed Count I or the forfeiture count at the very end.” The court responded, “Count II through XI[I] are dismissed. Count I and the forfeiture count remain in full force and effect.” The formal judgment in the case, which was entered on July 2 30, 1997, recited the numbers of the counts that had been dismissed, stated that the defendant had pleaded guilty to Count 1, and accordingly adjudged him guilty of conspiracy to launder money, and sentenced him to a term of 51 months. The only mention of forfeiture in the judgment entry is this sentence: “A separate Forfeiture order shall be entered in this cause.” On March 11, 1998, about seven months later the government filed a motion for an order of forfeiture. The following day the district court granted the motion and entered a preliminary order of forfeiture. On the government’s motion, the district court on April 24, 1998 entered an amended order to include additional property. A final order of forfeiture was entered on July 14, 1998, nearly a year after sentencing. Machado did not attempt to appeal any of those orders, including the final order of forfeiture. Instead, on September 4, 1998, about six weeks after entry of the final order, he filed a pro se motion for return of property pursuant to Fed. R. Cr. P. 41(e), requesting a return of “all documents and records seized or taken from the movant, his businesses, and residence that were used as evidence in the criminal and [forfeiture] actions.” In that motion Machado claimed that the documents he sought would reveal that some of his property had been improperly forfeited. At a hearing on January 20, 1999, the district court ordered the documents returned to 3 Machado. The government could not fully comply because some of the original documents were destroyed, but it ultimately returned others to Machado. Machado filed a pro se motion for sanctions which was ultimately denied. On April 23, 2003, three months shy of five years after entry of the final order of forfeiture, Machado filed under Rule 60(b)(4) a pro se motion for relief from that order “in light of this Circuit’s decision in United States v. Petrie, 302 F.3d 1280, 1284–85 (11th Cir. 2002).” Machado contended that because the district court had not entered the final order of forfeiture until twelve months after he was sentenced, it lacked jurisdiction to do so, and for that reason the order must be vacated. Because the district court had previously issued an order prohibiting the parties from filing any new motions until all pending motions were resolved, the district court denied that motion. Machado appealed, but we affirmed after concluding that the denial of his Rule 60(b)(4) motion on that ground was not an abuse of discretion. We never reached the merits of Machado’s claim. On May 17, 2004, Machado filed pursuant to Rule 60(b) another motion to vacate the forfeiture order. After the district court denied that motion a week later, we affirmed on November 17, 2004, explaining that Rule 60(b) cannot be used to challenge criminal forfeiture orders. Again, we did not reach the merits of Machado’s claim. 4 On December 17, 2004, which was six years and five months after the final order of forfeiture was entered, Machado filed yet another pro se motion seeking return of the forfeited property. This one asserted that he was proceeding under Fed. R. Cr. P. 41(g) and the All Writs Act, 28 U.S.C. § 1651(a). In February 2005 the district court denied the motion in a three-sentence order: “This cause came before the Court upon Defendant’s Motion for Return of Property Pursuant to Fed. R. Crim. P. Rule 41(e) . . . filed December 17, 2004. The Court having reviewed the pertinent portions of the record, and being otherwise fully advised in the premises, it is ordered and adjudged that Defendant’s Motion for Return of Property is Denied. Done and ordered in Chambers, at Miami, Florida this 7th Day of February, 2005.” Thereafter Machado filed his notice of appeal, and we appointed counsel to represent him. II. At the heart of all Machado’s arguments and efforts is his contention that the district court lacked subject matter jurisdiction to enter the final order of forfeiture nearly a full year after the judgment incorporating the sentence had been entered. Federal Rule of Criminal Procedure 32(d)(2), which was in effect when Machado was sentenced, stated that: “At sentencing, a final order of forfeiture shall be made part of the sentence and included in the judgment.” Fed. R. Cr. P. 32(d)(2) (1997). 5 Machado contends that the district court’s failure to comply with Rule 32(d)(2) when it sentenced him on July 28, 1997 means that the court lost jurisdiction to enter a forfeiture order, and did not have the power to do so when it attempted to enter the order of forfeiture on July 14, 1998. The government’s position is that Rule 32(d)(2) is not jurisdictional, and instead is a claim-processing rule that can be forfeited if the party waits too long to raise the argument, as Machado did. See United States v. Eberhart, _____ U.S. ____, ____, 126 S. Ct. 403, 405-07 (2005). We lack jurisdiction to decide the issue of whether the district court had jurisdiction to belatedly enter the final order of forfeiture. Federal Rule of Appellate Procedure 4 requires a criminal litigant who makes an appeal as of right to file a notice of appeal “within 10 days after the later of . . . the entry of either the judgment or the order being appealed . . . .” Fed. R. App. P. 4(b)(1)(A)(i). Under that rule the district court may extend that ten day period by up to thirty days if a party shows excusable neglect. Fed. R. App. P. 4(b)(4). Even if there is excusable neglect the latest a defendant may wait before appealing a final order in a criminal case is forty days after it was entered. See id. Filing a timely notice of appeal is “mandatory and jurisdictional” and if a defendant fails to do so, a court of appeals is “without jurisdiction to review the decision on the merits.” See Budinich v. Becton Dickinson and Co., 486 U.S. 196, 6 203, 108 S. Ct. 1717, 1722 (1988); accord United States v. Cartwright, 413 F.3d 1295, 1299–1300 (11th Cir. 2005) (criminal defendant’s failure to file a timely notice of appeal under Rule 4(b) requires dismissal for lack of jurisdiction); United States v. Arevalo, 408 F.3d 1233, 1236 (9th Cir. 2005) (defendant’s “failure to file a timely or effective notice of appeal renders us without jurisdiction to consider the merits of the petitioner’s claims”); United States v. Hirsch, 207 F.3d 928, 930–31 (7th Cir. 2000) (if the notice of appeal is untimely the “appeal must be dismissed for want of jurisdiction”); United States v. Rapoport, 159 F.3d 1, 2–3 (1st Cir. 1998) (same); United States v. Christunas, 126 F.3d 765, 768–69 (6th Cir. 1997) (Rule 4(b) compliance “is a jurisdictional prerequisite which this court can neither waive nor extend”); United States v. Marbley, 81 F.3d 51, 52 (7th Cir. 1996) (same); United States v. Houser, 804 F.2d 565, 568 (9th Cir. 1986) (time limits on filing a notice of appeal are “mandatory and jurisdictional”); United States v. Whitaker, 722 F.2d 1533, 1534 (11th Cir. 1984) (“Failure to file a timely notice of appeal leaves the appellate court without jurisdiction.”). The final order of forfeiture about which Machado complains was entered on July 14, 1998 and the ten days he had to file his notice of appeal ran out on July 24, 1998.1 Assuming that the district court might somehow have found excusable 1 A preliminary order of forfeiture is a final and immediately appealable order if it finally determines the defendant’s rights in the forfeited property. United States v. Gross, 213 7 neglect and granted Machado thirty more days for that reason, the last possible date for filing the notice of appeal was August 23, 1998, which was forty days after the district court entered the order. See Sanders v. United States, 113 F.3d 184, 186 (11th Cir. 1997). Machado missed that deadline. Indeed, he never filed a notice of appeal from the order which he seeks to have set aside. Even if we agreed with Machado’s suggestion at oral argument that his Rule 41(e) motion for return of documents could be construed as an appeal from the final order of forfeiture, it still came too late. The Rule 41(e) motion was filed on September 4, 1998, well after the deadline for filing his notice of appeal. And even if the deadline could have been extended under Rule 4(a)(5) for excusable neglect, the maximum extension would have been thirty days, or until August 23, 1998, and the notice of appeal came after that date. We are aware, of course, that “subject-matter jurisdiction . . . can never be forfeited or waived” and “[c]onsequently, defects in subject-matter jurisdiction require correction regardless of whether the error was raised in district court,” United States v. Cotton, 535 U.S. 625, 630, 122 S. Ct. 1781, 1785 (2002); see also F.3d 599, 600 (11th Cir. 2000). However, in this case the preliminary order was amended to include additional property and so did not finally determine Machado’s interest in all the property. Thus, Machado’s time for appeal in this case ran from the entry of the final order of forfeiture on July 14, 1998. Cf. Christunas, 126 F.3d at 768–69 (refusing to consider for lack of jurisdiction a criminal defendants’ appeal from a final order of forfeiture holding that he should have timely appealed in accordance with Rule 4(b) the preliminary order of forfeiture because it was final as to him). 8 Arbaugh v. Y& H Corp., ___ U.S. ___, ___, 126 S. Ct. 1235, 1240 (2006) (“The objection that a federal court lacks subject-matter jurisdiction . . . may be raised by a party, or by a court on its own initiative, at any stage in the litigation, even after trial and the entry of judgment.”). That principle is not, however, an exception to the requirements for appellate jurisdiction, and if those requirements are not met we cannot review whether a judgment is defective, not even where the asserted defect is that the district court lacked jurisdiction. Arbaugh does not hold or intimate that concerns about the district court’s jurisdiction to enter an order or judgment trump a lack of appellate jurisdiction to review a district court judgment. Neither Arbaugh nor any other binding decision holds that a court of appeals always has appellate jurisdiction to decide whether the district court had jurisdiction. Otherwise, an appeal could be filed months, years, or even decades late. See Des Moines Navigation & R.R. Co. v. Iowa Homestead Co., 123 U.S. 552, 8 S. Ct. 217 (1887) (upholding the res judicata effect of a prior decision in spite of the argument that the court lacked jurisdiction to render a judgment in the prior case); United States v. Valadez-Camarena, 402 F.3d 1259, 1260–61 (10th Cir. 2005) (rejecting a jurisdictional challenge to a final conviction and sentence and refusing to consider the merits because the case was no longer pending for purposes of Federal Rule of Criminal Procedure 12(b)(3)); United States v. 9 Hartwell, 448 F.3d 707, 720–21 (4th Cir. 2006) (Williams, J., concurring) (noting that when a criminal defendant failed to file a direct appeal “his conviction and sentence became insulated from jurisdictional challenge except in a collateral proceeding, such as a proceeding under 28 U.S.C.A. § 2255” and the conviction and sentence must be treated as valid for subsequent motions); III. Although we lack jurisdiction to review whether the district court had jurisdiction to enter the final order of forfeiture in July 1998, we do have jurisdiction to review whether the district court erred in denying his Rule 41(g) motion for return of property in February of 2005. The difference is that Machado did file a timely notice of appeal from the order denying that Rule 41(g) motion. We review de novo the attendant legal issues, United States v. Howell, 425 F.3d 971, 973 (11th Cir. 2005), but we review the equitable equation of the district court’s decision to deny a Rule 41(g) motion only for abuse of discretion. See id. at 974 (citing Gaudiosi v. Mellon, 269 F.2d 873, 881–82 (3d Cir.1959) (reviewing for abuse of discretion the district court’s decision to apply the equitable doctrine of unclean hands)); United States v. Bennett, 423 F.3d 271, 274 (3d Cir. 2005) (“In most Rule 41(g) cases demanding return of forfeited property, we review the District Court’s decision to exercise its equitable jurisdiction for 10 abuse of discretion.” (internal quotation marks and alteration omitted)). Rule 41(g) states: “A person aggrieved by an unlawful search and seizure of property or by the deprivation of property may move for the property’s return. The motion must be filed in the district where the property was seized.” Fed. R. Cr. P. 41(g). The district court can exercise equitable jurisdiction over a Rule 41(g) motion filed after criminal proceedings have ended. United States v. Martinez, 241 F.3d 1329, 1329 (11th Cir. 2001). “[I]n order for a district court to grant a Rule 41(g) motion, the owner of the property must have clean hands.” Howell, 425 F.3d at 974. The district court properly denied Machado’s Rule 41(g) motion, because the exercise of equitable jurisdiction in his favor would be inequitable. It would return to a criminal the fruits of his crimes, giving him an illicit multi-million dollar windfall. It would give back to him property that he voluntarily forfeited to the government as part of a valid plea agreement, an agreement which gave him ample consideration in return. Having gotten the full benefit of his bargain, it would be inequitable to allow Machado to escape the burdens. Even if Machado were not barred by equitable principles from obtaining the relief he seeks, his claim would be time barred. “When an owner invokes Rule 41(g) after the close of all criminal proceedings, the court treats the motion for 11 return of property as a civil action in equity.” Howell, 425 F.3d at 974. Civil actions filed against the government are subject to a six year statute of limitation. 28 U.S.C. § 2401(a) (“[E]very civil action commenced against the United States shall be barred unless the complaint is filed within six years after the right of action first accrues.”). Because Rule 41(g) actions filed after the close of the criminal proceedings are treated as civil actions, they are subject to the six year statute of limitation in § 2401(a). See United States v. Sims, 376 F.3d 705, 708–09 (7th Cir. 2004) (holding that § 2401(a) applies to a Rule 41(g) motion); United States v. Wright, 361 F.3d 288, 290 (5th Cir. 2004) (same); United States v. Rodriguez Aguirre, 264 F.3d 1195, 1210 (10th Cir. 2001) (same); United States v. Minor, 228 F.3d 352, 359 (4th Cir. 2000) (same); Clymore v. United States, 217 F.3d 370, 373 (5th Cir. 2000) (same). A legal claim is not like a fine wine that gets better with age. It is more like milk, which spoils after its expiration date. The six-year statute of limitations began to run when the final order of forfeiture was entered against Machado on July 14, 1998. His December 17, 2004 Rule 41(g) motion offered up a claim that had been rendered legally unpalatable by the passage of time. IV. The All Writs Act, 28 U.S.C. § 1651(a), adds nothing to Machado’s case. It 12 provides that: “The Supreme Court and all courts established by Act of Congress may issue all writs necessary or appropriate in aid of their respective jurisdictions and agreeable to the usages and principles of law.” 28 U.S.C. § 1651(a). The Supreme Court has instructed that this source of federal court power must only be used in “extraordinary circumstances.” Kerr v. U.S. Dist. Court for N. Dist. of Cal., 426 U.S. 394, 403, 96 S. Ct. 2119, 2124 (1976). As the Court has explained: “The All Writs Act is a residual source of authority to issue writs that are not otherwise covered by statute. Where a statute specifically addresses the particular issue at hand, it is that authority, and not the All Writs Act, that is controlling. Although that Act empowers federal courts to fashion extraordinary remedies when the need arises, it does not authorize them to issue ad hoc writs whenever compliance with statutory procedures appears inconvenient or less appropriate.” Pa. Bureau of Corr. v. U.S. Marshals Serv., 474 U.S. 34, 43, 106 S. Ct. 355, 361 (1985). As we put it two years ago, “[t]he Act does not create any substantive federal jurisdiction,” but instead it is only “a codification of the federal courts’ traditional, inherent power to protect the jurisdiction they already have, derived from some other source.” Klay v. United Healthgroup, Inc., 376 F.3d 1092, 1099–1100 (11th Cir. 2004). The district court did not abuse its discretion in declining to exercise 13 jurisdiction under the All Writs Act. This is not an extraordinary case that merits use of extraordinary authority. Machado had adequate remedies available to him. He could have timely appealed the final order of forfeiture in accordance with appellate Rule 4(b). Another procedure which supplies jurisdiction to determine whether this type of relief should be granted is Rule 41(g). As we have already explained, because Machado’s claim seeks relief that would not be equitable, and because he waited too late to file his Rule 41(g) motion, his claim cannot succeed under that provision. We will not use the All Writs Act as a fix all provision to plug up holes in a party’s position, holes through which any claim to relief has drained out. V. Finally, Machado asserts that the order of forfeiture violates his due process and double jeopardy rights and that we should fashion an equitable remedy to correct those violations. Machado does not have a valid due process or double jeopardy claim, and even if he did he would not have a viable procedural basis through which to assert it. The law provides appeals for the purpose of raising claims like these, and he failed to appeal. AFFIRMED. 14	{ "pile_set_name": "FreeLaw" }
Mystikal (album) Mystikal is the eponymous self-titled debut studio album by American rapper Mystikal. It was independently self-released on June 14, 1994, by Big Boy Records. The album was produced and written by Leroy "Precise" Edwards. Mystikal's re-release version of his eponymous debut album, titled Mind of Mystikal was released on October 10, 1995, by Jive Records. The re-release version added several new tracks. The re-release version debuted at number one on the US Billboard Top Heatseekers Chart. Track listing References Category:1995 debut albums Category:Mystikal albums Category:Gangsta rap albums by American artists	{ "pile_set_name": "Wikipedia (en)" }
Q: Really logging the POST request body (instead of "-") with nginx I'm trying to log POST body, and add $request_body to the log_format in http clause, but the access_log command just prints "-" as the body after I send POST request using: curl -d name=xxxx myip/my_location My log_format (in http clause): log_format client '$remote_addr - $remote_user $request_time $upstream_response_time ' '[$time_local] "$request" $status $body_bytes_sent $request_body "$http_referer" ' '"$http_user_agent" "$http_x_forwarded_for"'; My location definition(in server clause): location = /c.gif { empty_gif; access_log logs/uaa_access.log client; } How can I print the actual POST data from curl? A: Nginx doesn't parse the client request body unless it really needs to, so it usually does not fill the $request_body variable. The exceptions are when: it sends the request to a proxy, or a fastcgi server. So you really need to either add the proxy_pass or fastcgi_pass directives to your block. The easiest way is to send it to Nginx itself as a proxied server, for example with this configuration: location = /c.gif { access_log logs/uaa_access.log client; # add the proper port or IP address if Nginx is not on 127.0.0.1:80 proxy_pass http://127.0.0.1/post_gif; } location = /post_gif { # turn off logging here to avoid double logging access_log off; empty_gif; } If you only expect to receive some key-pair values, it might be a good idea to limit the request body size: client_max_body_size 1k; client_body_buffer_size 1k; client_body_in_single_buffer on; I also received "405 Not Allowed" errors when testing using empty_gif; and curl (it was ok from the browser), I switched it to return 200; to properly test with curl.	{ "pile_set_name": "StackExchange" }
5. Let b be (-105)/(-10)6/k. Let y be (-3)/1 + (-196)/b. Solve -y = 4u + 3v, -2v + 5v = -2u - 17 for u. -4 Suppose 8 = t + t. Suppose 9g - 5g = 0. Let z be g/5-1 - -2. Solve d + o = -0 - 1, zd - o - t = 0 for d. 1 Let v(r) = 2r + 7. Let o be v(-5). Let y be (-1)/(o + 10/4). Suppose -2n = ym + 2, 2n - m = 5n - 3. Solve 3g + 23 = -2w - 2w, 0 = 4g + nw + 24 for g. -5 Suppose -4l + 3h + 4 = 0, -2l + 4h = 28 - 20. Solve l = 4f - 3d, 3f - 13 - 1 = 5d for f. -2 Let v(b) = -4b + 35. Let m be v(11). Let f be (9/(-6))/(m/24). Solve -21 = k - fh, -6 = -2h + 2 for k. -5 Let w = -8 - -12. Let a be 4 - ((-1 - -3) + -2)/(-1). Suppose af = 4y + 23 + 9, 12 = -3y. Solve fx + 6 = -2h, 5 = -x + w for h. -1 Suppose 3c = 12, -2d - 5 + 29 = 5c. Suppose dy = -y + 27. Suppose k + 4 = y. Solve 12 = -2q + n, -n + 2 = -2q - kn for q. -5 Let j be (2 + 1)(-16 - -17). Solve jr + 0 = -3p + 30, 0 = p + 2r - 15 for p. 5 Let d be 2/(-11) - ((-48)/66)/4. Solve 4n - 3p + 14 = d, 4n = -3p - 29 + 3 for n. -5 Let r = -7 - -7. Let h(a) = -5a + 4. Let k be h(r). Solve -2i = -y + 4y - 19, -ky + 14 = -3i for y. 5 Let b(o) = -2o3 - 4o*2 - o + 2. Let h be b(-2). Suppose 3n = 3x, -3n + h = -x - 0n. Solve xl + 16 = 4d, -l + 13 = -2l + 3d for l. 2 Let b = 7 + -2. Let c = 2432 - 2431. Solve n + 0n + c = 2h, -10 = -bh + 4n for h. -2 Let w be (1 + 3)/1 - (127 - 125). Solve -d + 8 = wl, -4l = -4d - l + 10 for d. 4 Let h(z) = -3z - 23. Let y(w) = 8w + 68. Let o(p) = 17h(p) + 6y(p). Let m be o(-5). Suppose 8c - m = 32. Solve -3t + 5l = -0t - 12, 3l = 2t - c for t. 4 Suppose -5v + 20 = 0, j - 6 = -v - 0. Suppose w - 7 = -4n + 22, jw = -4n + 30. Suppose 0 = -2u + 4u - 16. Solve 3g + u = d, -d - ng = -3g + 6 for d. 2 Suppose 5 = -4f + 13. Solve fw - 3w - 17 = 5g, 5 = -4w + g for w. -2 Suppose 21 = 113i - 106i. Suppose -5b + 20 = -90. Solve r + b = -4r - m, -m = -i for r. -5 Suppose 24 = 2c + 4. Suppose -c = -5l - 0. Suppose -2a + 15 = 5r, -r + 16 = 5a - la. Solve -j + r = -4, 3m + 2j - 13 = 0 for m. 1 Let q be (2/(-4))/((-1)/4). Let b be -3 - ((-2)/10 - (-10302)/85). Let z = -119 - b. Solve zn - x = qx - 17, -5x = -20 for n. -1 Let d = -63 - -27. Let g be (-96)/d + 12/6. Solve 0 = c - 2c + gn - 17, -4c + 5n = 33 for c. -2 Suppose 176q + 65 = 181q. Suppose -3z - 2w = -q, -3z + 14 = z + w. Solve 0 = -3v + 5t - 34, -v + 6v - zt + 30 = 0 for v. -3 Suppose -g = p + 4, 0 = 7p - 9p - g - 4. Suppose w - 2 = 4r - 7, p = -5r + 3w + 15. Solve 0 = -b - k + 1, 3b + b - 2k - 10 = r for b. 2 Let f be 78/130 + (-4)/(-10). Solve 0 = 4p + 4i - 4, 2p - i = -11 + f for p. -3 Let g(c) = -c3 + 5c2 + c - 3. Let f(b) = -b2 + b. Let u(m) = -3f(m) - g(m). Let t be u(3). Solve 2k - r - 13 = 0, tk - 3r = 4k - 11 for k. 5 Let q(y) = y - 2. Let i be q(8). Suppose ig + 0g - 30 = 0. Solve 3h = -2x - x + 21, -23 = -2x - gh for x. 4 Suppose -3o - 18k = -22k + 8, 2k - 4 = 0. Solve 0 = -5u - 4t - 6, -u + 3t - 5 = -o for u. -2 Let w = -86 + 91. Suppose 0 = -2m + 4, 3 = -wd + m + 21. Solve -3p - 10 + 31 = -dt, 5p - 3 = -4t for t. -3 Suppose 86 = 3t - 2d, -5d - 59 = -5t + 91. Solve -4a = -2k + t, 5a + 25 + 0 = k for k. 5 Let j = -642 - -645. Solve 0s = -4y - js + 6, 2y - 8 = -4s for y. 0 Let z = -50 - -99. Let i = z + -37. Let k(m) = 3m3 + m2 - m. Let c be k(1). Solve 0 = -5x + n - c, -x + 3x = -5n - i for x. -1 Let s(b) = b*3 - 8b*2 + 9b - 4. Let i be s(7). Suppose 10 = -8j + ij. Solve 0 = -4m - 5q, -jq - 6 + 21 = m for m. -5 Let p = -1046 - -1049. Solve -3u + 5f + 24 = 0, 5u - 3f - 21 = p for u. 3 Let v = -376 - -378. Solve 0 = 2l + n - 3n + v, 4l + n = -9 for l. -2 Let w = 2602 - 2585. Solve -2r + 3 - w = -5v, 0 = -3v + 2r + 6 for v. 4 Let k(w) be the first derivative of -w*2/2 + 19w - 11. Let f be k(16). Solve 3o + t + 0t = 7, -o + 19 = -ft for o. 4 Let y = 3 - 3. Solve y = 2u + 2z - 4, -5z + 6 = 1 for u. 1 Let y = 6 - -4. Let u be (y/(-6) + 2)6. Let g(i) = 6i*2 + 8i + 8. Let p be g(-2). Solve p = -4b, -4m - ub = -3m + 4 for m. 4 Let u be ((-5427)/207)/(-9) + (-4)/(-46). Suppose 6 - 21 = -z. Solve -o + 3c - 7c - 20 = 0, o - uc = z for o. 0 Let t(y) = 2y + 21. Let g(f) = -f*2 + 7f - 11. Let k be g(6). Let z be t(k). Solve i = 2v - z, -3v = -0i - 3i - 18 for i. -1 Suppose 0 = 5l - 10. Suppose -7p = -2p - li - 19, 0 = -4p + i + 14. Suppose 0d = 3d - 12. Solve -pq - dc = -q - 14, 3c = 15 for q. -3 Let g be 4 + -19 + 8 + 28. Solve 0 = -5j - m - g, 6m - 16 = 2m for j. -5 Let h(b) = b2 - 2b - 1. Let l be h(3). Let m be ((-1)/l + 0)/(-1)4. Solve 5w = 2v - 10, -3w - 2 = -0v - mv for w. -4 Let w = 9 + -29. Suppose -4x = h - 2, 5x + 4h - 2 = 6. Let l be w/(-15)(x + 3). Solve 11 = -v - ln, -3n + 5n - 17 = -5v for v. 5 Suppose -4k - 2z + 23 - 17 = 0, -k + z - 3 = 0. Solve k = -g + 3l - 2 + 1, 6 = 2g + 2l for g. 2 Suppose 5a - 18 - 7 = d, -2d - 22 = -3a. Solve -2t + 3t - 2 = -m, at = 5m - 28 for t. -2 Suppose 101u - 95u - 12 = 0. Solve -m - 16 = 5q, -5 = 3q - um - 2m for q. -3 Let v be (2 + -1)-1 + 3. Suppose -3m + 16 = -vo, -3o + 0o + 14 = 5m. Let j be (-2 + (-16)/(-6))(-45 - -51). Solve t - j = -my - 18, -y + 4 = 4t for y. -4 Suppose z - 10 = 2i, 0 = -16z + 14z - 3i - 8. Solve f = -0j + zj - 5, j - 20 = 4f for j. 0 Let b(w) = w*3 - 9w*2 - w + 5. Let y be b(9). Let o be 83 + y + -3. Solve 9 = -3v - 2q, 0q = 4v + q + o for v. -5 Suppose -2 = -5s + 9s - 5b, -4s = 2b - 12. Solve sm - y + 4 = -0y, 2y + 4 = 0 for m. -3 Let t be 35/(-2)(-82)/287 - -12. Let s be 2/(-3(-3)/18). Solve 16 = 3b + sj, -5j = 4b - 4j - t for b. 4 Let b(o) = -5o + 2. Let x(h) = h*3 + 6h*2 - 5h + 8. Let q be x(-7). Let u be b(q). Suppose -15 = 29i - ui. Solve 0 = -2m + 3 + 3, m + 22 = ir for r. 5 Suppose 5m = 4m + 5. Suppose 67g = 64g + 57. Solve g = -l + ma, l = -4a - 0a + 8 for l. -4 Suppose -4 = 2x - 5j, -2j = -3 - 1. Solve -5h + 35 = 2b - 7b, -5h + xb = -31 for h. 5 Let j = 1991 - 1991. Solve 0 = -4f - jf - 3r + 1, 5f = -5r - 5 for f. 4 Suppose -24v = -116 - 4. Solve -3k + 3 = -4r, 5k = 3r - 4r + v for r. 0 Suppose 111 = 4u - 4v + 87, -3u - 4v = -11. Solve 12 = -t + 5b, ut - 9t = b + 6 for t. -2 Let y be 7/(0 - 5/(-75)). Let d = 105 - y. Solve -3p - 3q - 3 = d, 4p - 2p - 2 = -4q for p. -3 Let n(t) = t*2 + t + 4. Let s be n(-3). Let b(q) = 3q*3 - 35q*2 - 13q + 17. Let v be b(12). Solve 0 = 2k - 2f, k = vk + f - s for k. 2 Let o be (-4)/(-28) + (-3960)/35. Let m = o + 117. Solve 2t + 2p - m = 0, -5p + 18 = t - 0t for t. -2 Suppose -2b = 10, -3m - 5b = -3b - 29. Suppose 6v + 13 = m. Solve 2a - 15 = -a + 3c, v = a + 5c + 19 for a. 1 Let p = 331 - 329. Solve -2j = z + p + 9, -2j = 4z + 14 for j. -5 Let z be 2(-1 + (-3 - -6)). Suppose l + 3g = 2l - 5, -2g = -z. Suppose -3w - 5n = 2, -2w - 5n + 3 = l. Solve 17 = 4p + t, p - wp + 28 = -t for p. 5 Let k = -1 - -3. Let s = 2 + k. Suppose -5d + 20 = 5p, 3d - 2p - 3p = -s. Solve -4i + 16 = -4m - 0, 0 = -dm + i - 9 for m. -5 Suppose 0v - 8 = 2v. Let i be v/2 + 21/3. Solve -iq = 2p - 5p - 2, 4 = 5p - q for p. 1 Suppose 2l - 21 = -o + 23, 5l = -2o + 111. Let k = l - 7. Suppose 14y + 8 = ky. Solve -2z + 5p - 2 = 0, 0 = yz + 3p + 2 + 2 for z. -1 Let i = -120 + 123. Suppose -6 - 9 = -ib - 3n, -5n + 25 = -4b. Solve 2 = -m + 2l, m - l + 3l - 2 = b for m. 0 Suppose 19j - 93 = -17. Let z be (2/(-3))/((-10)/45). Solve zq = 2m + 10, -2q = -7q - jm - 20 for q. 0 Suppose 6m - 26 = -7m. Solve -mq - 4t = 12, 3t + t = 4q for q. -2 Let a be (-3)/(-1) + (16 - 35) + 17. Solve -3k - a = -2d, -3k - 2 = -d - 0k for d. -1 Let s = 9 + -17. Let t = 5 + s. Let x = t + 5. Solve 0 = u + 3k - 3, 5u - xk - 17 + 2 = 0 for u. 3 Suppose 141 = g - 2m + 3m, -m = 3. Let x = 147 - g. Solve 5n + 11 = -3r, -xr + 8 = -1 for n. -4 Suppose -193z + 197z - 172 = 0. Suppose -4d = -0c + 3c - z, 0 = -5c - 2d + 67. Suppose 0 = o - 5 - 0. Solve -ov = 3h + 36 - c, -13 = 5h + 2v for h. -1 Let d = -906 + 910. Let g(s) = -3*s	{ "pile_set_name": "DM Mathematics" }
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--- abstract: 'We study here properties of [free Generalized Inverse Gaussian distributions]{} (fGIG) in free probability. We show that in many cases the fGIG shares similar properties with the classical GIG distribution. In particular we prove that fGIG is freely infinitely divisible, free regular and unimodal, and moreover we determine which distributions in this class are freely selfdecomposable. In the second part of the paper we prove that for free random variables $X,Y$ where $Y$ has a free Poisson distribution one has $X\stackrel{d}{=}\frac{1}{X+Y}$ if and only if $X$ has fGIG distribution for special choice of parameters. We also point out that the free GIG distribution maximizes the same free entropy functional as the classical GIG does for the classical entropy.' author: - \| Takahiro Hasebe\ Department of Mathematics,\ Hokkaido University\ thasebe@math.sci.hokudai.ac.jp - \| Kamil Szpojankowski\ Faculty of Mathematics and Information Science\ Warsaw University of Technology\ k.szpojankowski@mini.pw.edu.pl title: On free generalized inverse gaussian distributions --- Introduction ============ Free probability was introduced by Voiculescu in [@Voi85] as a non-commutative probability theory where one defines a new notion of independence, so called freeness or free independence. Non-commutative probability is a counterpart of the classical probability theory where one allows random variables to be non-commutative objects. Instead of defining a probability space as a triplet $(\Omega,\mathcal{F},\mathbb{P})$ we switch to a pair $(\mathcal{A},\varphi)$ where $\mathcal{A}$ is an algebra of random variables and $\varphi\colon\mathcal{A}\to\mathbb{C}$ is a linear functional, in classical situation $\varphi=\mathbb{E}$. It is natural then to consider algebras $\mathcal{A}$ where random variables do not commute (for example $C^$ or $W^$–algebras). For bounded random variables independence can be equivalently understood as a rule of calculating mixed moments. It turns out that while for commuting random variables only one such rule leads to a meaningful notion of independence, the non-commutative setting is richer and one can consider several notions of independence. Free independence seems to be the one which is the most important. The precise definition of freeness is stated in Section 2 below. Free probability emerged from questions related to operator algebras however the development of this theory showed that it is surprisingly closely related with the classical probability theory. First evidence of such relations appeared with Voiculescu’s results about asymptotic freeness of random matrices. Asymptotic freeness roughly speaking states that (classically) independent, unitarily invariant random matrices, when size goes to infinity, become free.\ Another link between free and classical probability goes via infinite divisibility. With a notion of independence in hand one can consider a convolution of probability measures related to this notion. For free independence such operation is called free convolution and it is denoted by $\boxplus$. More precisely for free random variables $X,Y$ with respective distributions $\mu,\nu$ the distribution of the sum $X+Y$ is called the free convolution of $\mu$ and $\nu$ and is denoted by $\mu\boxplus\nu$. The next natural step is to ask which probability measures are infinitely divisible with respect to this convolution. We say that $\mu$ is freely infinitely divisible if for any $n \geq 1$ there exists a probability measure $\mu_n$ such that $$\mu=\underbrace{\mu_n\boxplus\ldots\boxplus\mu_n}_{\text{$n$ times}}.$$ Here we come across another striking relation between free and classical probability: there exists a bijection between classically and freely infinitely divisible probability measures, this bijection was found in [@BP99] and it is called Bercovici-Pata (BP) bijection. This bijection has number of interesting properties, for example measures in bijection have the same domains of attraction. In free probability literature it is standard approach to look for the free counterpart of a classical distribution via BP bijection. For example Wigner’s semicircle law plays the role of the Gaussian law in free analogue of Central Limit Theorem, Marchenko-Pastur distribution appears in the limit of free version of Poisson limit theorem and is often called free Poisson distribution. While BP bijection proved to be a powerful tool, it does not preserve all good properties of distributions. Consider for example Lukacs theorem which says that for classically independent random variables $X,Y$ random variables $X+Y$ and $X/(X+Y)$ are independent if and only if $X,Y$ have gamma distribution with the same scale parameter [@Luk55]. One can consider similar problem in free probability and gets the following result (see [@Szp15; @Szp16]) for free random variables $X,Y$ random variables $X+Y$ and $(X+Y)^{-1/2}X(X+Y)^{-1/2}$ are free if and only if $X,Y$ have Marchenko-Pastur (free Poisson) distribution with the same rate. From this example one can see our point - it is not the image under BP bijection of the Gamma distribution (studied in [@PAS08; @HT14]), which has the Lukacs independence property in free probability, but in this context free Poisson distribution plays the role of the classical Gamma distribution. In [@Szp17] another free independence property was studied – a free version of so called Matsumoto-Yor property (see [@MY01; @LW00]). In classical probability this property says that for independent $X,Y$ random variables $1/(X+Y)$ and $1/X-1/(X+Y)$ are independent if and only if $X$ has a Generalized Inverse Gaussian (GIG) distribution and $Y$ has a Gamma distribution. In the free version of this theorem (i.e. the theorem where one replaces classical independence assumptions by free independence) it turns out that the role of the Gamma distribution is taken again by the free Poisson distribution and the role of the GIG distribution plays a probability measure which appeared for the first time in [@Fer06]. We will refer to this measure as the free Generalized Inverse Gaussian distribution or fGIG for short. We give the definition of this distribution in Section 2. The main motivation of this paper is to study further properties of fGIG distribution. The results from [@Szp17] suggest that in some sense (but not by means of the BP bijection) this distribution is the free probability analogue of the classical GIG distribution. It is natural then to ask if fGIG distribution shares more properties with its classical counterpart. It is known that the classical GIG distribution is infinitely divisible (see [@BNH77]) and selfdecomposable (see [@Hal79; @SS79]). In [@LS83] the GIG distribution was characterized in terms of an equality in distribution, namely if we take $X,Y_1,Y_2$ independent and such that $Y_1$ and $Y_2$ have Gamma distributions with suitable parameters and we assume that $$\begin{aligned} X\stackrel{d}{=}\frac{1}{Y_2+\frac{1}{Y_1+X}}\end{aligned}$$ then $X$ necessarily has a GIG distribution. A simpler version of this theorem characterizes smaller class of fGIG distributions by equality $$\begin{aligned} \label{eq:char} X\stackrel{d}{=}\frac{1}{Y_1+X}\end{aligned}$$ for $X$ and $Y_1$ as described above. The overall result of this paper is that the two distributions GIG and fGIG indeed have many similarities. We show that fGIG distribution is freely infinitely divisible and even more that it is free regular. Moreover fGIG distribution can be characterized by the equality in distribution , where one has to replace the independence assumption by freeness and assume that $Y_1$ has free Poisson distributions. While there are only several examples of freely selfdecomposable distributions it is interesting to ask whether fGIG has this property. It turns out that selfdecomposability is the point where the symmetry between GIG and fGIG partially breaks down: not all fGIG distributions are freely selfdecomposable. We find conditions on the parameters of fGIG family for which this distributions are freely selfdecomposable. Except from the results mentioned above we prove that fGIG distribution is unimodal. We also point out that in [@Fer06] it was proved that fGIG maximizes a certain free entropy functional. An easy application of Gibbs’ inequality shows that the classical GIG maximizes the same functional of classical entropy. The paper is organized as follows: In Section 2 we shortly recall basics of free probability and next we study some properties of fGIG distributions. Section 3 is devoted to the study of free infinite divisibility, free regularity, free selfdecomposability and unimodality of the fGIG distribution. In Section 4 we show that the free counterpart of the characterization of GIG distribution by holds true, and we discuss entropy analogies between GIG and fGIG. Free GIG distributions ====================== In this section we recall the definition of free GIG distribution and study basic properties of this distribution. In particular we study in detail the $R$-transform of fGIG distribution. Some of the properties established in this section will be crucial in the subsequent sections where we study free infinite divisibility of the free GIG distribution and characterization of the free GIG distribution. The free GIG distribution appeared for the first time (not under the name free GIG) as the almost sure weak limit of empirical spectral distribution of GIG matrices (see [@Fer06]). Basics of free probability -------------------------- This paper deals mainly with properties of free GIG distribution related to free probability and in particular to free convolution. Therefore in this section we introduce notions and tools that we need in this paper. The introduction is far from being detailed, reader not familiar with free probability may find a very good introduction to the theory in [@VDN92; @NS06; @MS]. 1. A $C^$–probability space is a pair $(\mathcal{A},\varphi)$, where $\mathcal{A}$ is a unital $C^$-algebra and $\varphi$ is a linear functional $\varphi\colon\mathcal{A}\to\mathbb{C}$, such that $\varphi(\mathit{1}_\mathcal{A})=1$ and $\varphi(aa^)\geq 0$. Here by $\mathit{1}_\mathcal{A}$ we understand the unit of $\mathcal{A}$. 2. Let $I$ be an index set. A family of subalgebras $\left(\mathcal{A}_i\right)_{i\in I}$ are called free if $\varphi(X_1\cdots X_n)=0$ whenever $a_i\in \mathcal{A}_{j_i}$, $j_1\neq j_2\neq \ldots \neq j_n$ and $\varphi(X_i)=0$ for all $i=1,\ldots,n$ and $n=1,2,\ldots$. Similarly, self-adjoint random variables $X,\,Y\in\mathcal{A}$ are free (freely independent) when subalgebras generated by $(X,\,\mathit{1}_\mathcal{A})$ and $(Y,\,\mathit{1}_\mathcal{A})$ are freely independent. 3. The distribution of a self-adjoint random variable is identified via moments, that is for a random variable $X$ we say that a probability measure $\mu$ is the distribution of $X$ if $$\varphi(X^n)=\int t^n\,{{\rm d}}\mu(t),\,\mbox{for all } n=1,2,\ldots$$ Note that since we assume that our algebra $\mathcal{A}$ is a $C^$–algebra, all random variables are bounded, thus the sequence of moments indeed determines a unique probability measure. 4. The distribution of the sum $X+Y$ for free random variables $X,Y$ with respective distributions $\mu$ and $\nu$ is called the free convolution of $\mu$ and $\nu$, and is denoted by $\mu\boxplus\nu$. Free GIG distribution --------------------- In this paper we are concerned with a specific family of probability measures which we will refer to as free GIG (fGIG) distributions. The free Generalized Inverse Gaussian (fGIG) distribution is a measure $\mu=\mu(\alpha,\beta,\lambda)$, where $\lambda\in\mathbb{R}$ and $\alpha,\beta>0$ which is compactly supported on the interval $[a,b]$ with the density $$\begin{aligned} \mu({{\rm d}}x)=\frac{1}{2\pi}\sqrt{(x-a)(b-x)} \left(\frac{\alpha}{x}+\frac{\beta}{\sqrt{ab}x^2}\right){{\rm d}}x, \end{aligned}$$ where $0<a<b$ are the solution of $$\begin{aligned} \label{eq1} 1-\lambda+\alpha\sqrt{ab}-\beta\frac{a+b}{2ab}=&0\\ \label{eq2} 1+\lambda+\frac{\beta}{\sqrt{ab}}-\alpha\frac{a+b}{2}=&0. \end{aligned}$$ Observe that the system of equations for coefficients for fixed $\lambda\in \mathbb{R}$ and $\alpha,\beta>0$ has a unique solution $0<a<b$. We can easily get the following \[prop:ab\] Let $\lambda\in{\mathbb{R}}$. Given $\alpha,\beta>0$, the system of equations , has a unique solution $(a,b)$ such that $$\label{unique} 0<a<b, \qquad \|\lambda\| \left(\frac{\sqrt{a}-\sqrt{b}}{\sqrt{a}+\sqrt{b}}\right)^2<1.$$ Conversely, given $(a,b)$ satisfying , the set of equations – has a unique solution $(\alpha,\beta)$, which is given by $$\begin{aligned} &\alpha = \frac{2}{(\sqrt{a}-\sqrt{b})^2}\left( 1 + \lambda \left(\frac{\sqrt{a}-\sqrt{b}}{\sqrt{a}+\sqrt{b}}\right)^2 \right) >0, \label{eq3}\\ &\beta = \frac{2 a b}{ (\sqrt{a} - \sqrt{b})^2}\left( 1 - \lambda \left(\frac{\sqrt{a}-\sqrt{b}}{\sqrt{a}+\sqrt{b}}\right)^2 \right)>0. \label{eq4}\end{aligned}$$ Thus we may parametrize fGIG distribution using parameters $(a,b,\lambda)$ satisfying instead of $(\alpha,\beta,\lambda)$. We will make it clear whenever we will use a parametrization different than $(\alpha,\beta,\lambda)$. It is useful to introduce another parameterization to describe the distribution $\mu(\alpha,\beta,\lambda)$. Define $$\label{eq:AB} A=(\sqrt{b}-\sqrt{a})^2, \qquad B= (\sqrt{a}+\sqrt{b})^2,$$ observe that we have then $$\begin{aligned} \alpha =& \frac{2}{A}\left( 1 + \lambda \frac{A}{B} \right) >0, \qquad \beta = \frac{(B-A)^2}{8 A}\left( 1 - \lambda \frac{A}{B} \right)>0,\\ a =& \left(\frac{\sqrt{B}-\sqrt{A}}{2}\right)^2,\qquad b = \left(\frac{\sqrt{A}+\sqrt{B}}{2}\right)^2. \end{aligned}$$ The condition is equivalent to $$\label{eq:ABineq} 0<\max\{1,\|\lambda\|\}A<B.$$ Thus one can describe any measure $\mu(\alpha,\beta,\lambda)$ in terms of $\lambda,A,B$. $R$-transform of fGIG distribution {#sec:form} ---------------------------------- The $R$-transform of the measure $\mu(\alpha,\beta,\lambda)$ was calculated in [@Szp17]. Since the $R$-transform will play a crucial role in the paper we devote this section for a detailed study of its properties. We also point out some properties of fGIG distribution which are derived from properties of the $R$-transform. Before we present the $R$-transform of fGIG distribution let us briefly recall how the $R$-transform is defined and stress its importance for free probability. \[rem:Cauchy\] 1. For a probability measure $\mu$ one defines its Cauchy transform via $$G_\mu(z)=\int \frac{1}{z-x}{{\rm d}}\mu(x).$$ It is an analytic function on the upper-half plane with values in the lower half-plane. Cauchy transform determines uniquely the measure and there is an inversion formula called Stieltjes inversion formula, namely for $h_{\varepsilon}(t)=-\tfrac{1}{\pi}{\text{\normalfont Im}}\, G_\mu(t+i{\varepsilon})$ one has $${{\rm d}}\mu(t)=\lim_{{\varepsilon}\to 0^+} h_{\varepsilon}(t)\,{{\rm d}}t,$$ where the limit is taken in the weak topology. 2. For a compactly supported measure $\mu$ one can define in a neighbourhood of the origin so called $R$-transform by $$R_\mu(z)=G_\mu^{\langle -1 \rangle}(z)-\frac{1}{z},$$ where by $G_\mu^{\langle -1 \rangle}$ we denote the inverse under composition of the Cauchy transform of $\mu$.\ The relevance of the $R$-transform for free probability comes form the fact that it linearizes free convolution, that is $R_{\mu\boxplus\nu}=R_\mu+R_\nu$ in a neighbourhood of zero. The $R$-transform of fGIG distribution is given by $$\label{eq:R_F} \begin{split} r_{\alpha,\beta,\lambda}(z) &= \frac{-\alpha + (\lambda+1)z + \sqrt{f_{\alpha,\beta,\lambda}(z)}}{2z(\alpha-z)} \end{split}$$ in a neighbourhood of $0$, where the square root is the principal value, $$\label{eq:pol_fpar} f_{\alpha,\beta,\lambda}(z)=(\alpha+(\lambda-1)z)^2-4\beta z (z-\alpha)(z-\gamma),$$ and $$\begin{aligned} \gamma=\frac{\alpha^2 a b+\frac{\beta^2}{ab}-2\alpha\beta\left(\frac{a+b}{\sqrt{ab}}-1\right)-(\lambda-1)^2}{4\beta}.\end{aligned}$$ Note that $z=0$ is a removable singular point of $r_{\alpha,\beta,\lambda}$. Observe that in terms of $A,B$ defined by we have $$\begin{aligned} \gamma &= 2\frac{\lambda A^2 + A B - 2B^2}{B(B-A)^2}. \end{aligned}$$ It is straightforward to observe that implies $A (\lambda A+B)<2 A B<2B^2$, thus we have $\gamma<0$. The following remark was used in [@Szp17 Remark 2.1] without a proof. We give a proof here. \[rem:F\_lambda\_sym\] We have $f_{\alpha,\beta,\lambda}(z)=f_{\alpha,\beta,-\lambda}(z)$, where $\alpha,\beta>0,\lambda\in\mathbb{R}$. To see this one has to insert the definition of $\gamma$ into to obtain $$f_{\alpha,\beta,\lambda}(z)=\alpha z \lambda^2+\left(\left(ab\alpha^2-2\alpha\beta\frac{a+b}{\sqrt{ab}}+\frac{\beta^2}{ab}+2\alpha\beta\right)z-4 \beta z^2-\alpha\right) (z-\alpha),$$ where $a=a(\alpha,\beta,\lambda)$ and $b=b(\alpha,\beta,\lambda)$. Thus it suffices to show that the quantity $g(\alpha,\beta,\lambda):=ab\alpha^2-2\alpha\beta\frac{a+b}{\sqrt{ab}}+\frac{\beta^2}{ab}$ does not depend on the sign of $\lambda$. To see this, observe from the system of equations and that $a(\alpha,\beta,-\lambda)=\frac{\beta}{\alpha b(\alpha,\beta,\lambda)}$ and $b(\alpha,\beta,-\lambda)=\frac{\beta}{\alpha a(\alpha,\beta,\lambda)}$. It is then straightforward to check that $ g(\alpha,\beta,-\lambda) = g(\alpha,\beta,\lambda). $ The $R$-transform of the measure $\mu(\alpha,\beta,\lambda)$ can be extended to a function (still denoted by $r_{\alpha,\beta,\lambda}$) which is analytic on $\mathbb{C}^{-}$ and continuous on $({\mathbb{C}}^- \cup{\mathbb{R}})\setminus\{\alpha\}$. A direct calculation shows that using parameters $A,B$ defined by the polynomial $f_{\alpha,\beta,\lambda}$ under the square root factors as $$f_{\alpha,\beta,\lambda}(z) = \frac{(B-A)^2(B-\lambda A)}{2 A B}\left[z +\frac{2(B+\lambda A)}{B(B-A)}\right]^2 \left[ \frac{2B}{A(B-\lambda A)} - z \right].$$ Thus we can write $$\label{eq:pol_par} f_{\alpha,\beta,\lambda}(z) = 4\beta (z-\delta)^2(\eta-z),$$ where $$\begin{aligned} &\delta = - \frac{2(B+\lambda A)}{B(B-A)}<0, \label{eq5}\\ &\eta = \frac{2B}{A(B-\lambda A)} >0. \label{eq6}\end{aligned}$$ It is straightforward to verify that implies $\eta \geq \alpha$ with equality valid only when $\lambda=0$.\ Calculating $f_{\alpha,\beta,\lambda}(0)$ using first and then we get $4 \beta \eta \delta^2 = \alpha^2$, since $\eta \geq \alpha$ we see that $\delta \geq -\sqrt{\alpha/(4\beta)}$ with equality only when $\lambda=0$. Since all roots of $f_{\alpha,\beta,\lambda}$ are real, the square root $\sqrt{f_{\alpha,\beta,\lambda}(z)}$ may be defined continuously on ${\mathbb{C}}^-\cup{\mathbb{R}}$ so that $\sqrt{f_{\alpha,\beta,\lambda}(0)}=\alpha$. As noted above $\delta<0$, and continuity of $f_{\alpha,\beta,\lambda}$ implies that we have $$\label{RRR} \sqrt{f_{\alpha,\beta,\lambda}(z)} = 2(z-\delta)\sqrt{\beta(\eta-z)},$$ where we take the principal value of the square root in the expression $\sqrt{4\beta(\eta-z)}$. Thus finally we arrive at the following form of the $R$-transform $$\label{R} \begin{split} r_{\alpha,\beta,\lambda}(z) &= \frac{-\alpha + (\lambda+1)z + 2(z-\delta)\sqrt{\beta(\eta-z)}}{2z(\alpha-z)} \end{split}$$ which is analytic in ${\mathbb{C}}^-$ and continuous in $({\mathbb{C}}^- \cup{\mathbb{R}})\setminus\{\alpha\}$ as required. Next we describe the behaviour of the $R$-transform around the singular point $z=\alpha$. If $\lambda>0$ then $$\label{alpha} \begin{split} r_{\alpha,\beta,\lambda}(z) = \frac{\lambda}{\alpha-z} -\frac{1}{2\alpha} \left(1+\lambda+\frac{\sqrt{\beta}(2\eta-3\alpha+\delta)}{\sqrt{\eta-\alpha}}\right) + o(1),\qquad\mbox{as } z\to\alpha. \end{split}$$ If $\lambda<0$ then $$\label{alpha2} r_{\alpha,\beta,\lambda}(z) = - \frac{1}{2\alpha}\left(1+\lambda+\frac{\sqrt{\beta}(2\eta-3\alpha+\delta)}{\sqrt{\eta-\alpha}}\right)+ o(1), \qquad \mbox{as } z\to\alpha.$$ In the remaining case $\lambda=0$ one has $$\label{alpha3} \begin{split} r_{\alpha,\beta,0}(z) &= \frac{-\alpha + z + 2(z-\delta)\sqrt{\beta(\alpha-z)}}{2z(\alpha-z)} = -\frac{1}{2z} + \frac{\sqrt{\beta}(z-\delta)}{z\sqrt{\alpha-z}}. \end{split}$$ By the definition we have $f_{\alpha,\beta,\lambda}(\alpha) = (\lambda\alpha)^2$, substituting this in the expression we obtain that $ \alpha \|\lambda\| = 2(\alpha-\delta)\sqrt{\beta (\eta-\alpha)}. $ Taking the Taylor expansion around $z=\alpha$ for $\lambda \neq0$ we obtain $$\label{Taylor} \sqrt{f_{\alpha,\beta,\lambda}(z)}=\alpha\|\lambda\| + \frac{\sqrt{\beta}(2\eta-3\alpha+\delta)}{\sqrt{\eta-\alpha}}(z-\alpha) + o(\|z-\alpha\|),\qquad \mbox{as }z\to \alpha.$$ This implies and and so $r_{\alpha,\beta,\lambda}$ may be extended to a continued function on ${\mathbb{C}}^-\cup {\mathbb{R}}$. The case $\lambda=0$ follows from the fact that in this case we have $\eta=\alpha$. In the case $\lambda<0$ one can extend $r_{\alpha,\beta,\lambda}$ to an analytic function in ${\mathbb{C}}^-$ and continuous in ${\mathbb{C}}^- \cup{\mathbb{R}}$. Some properties of fGIG distribution ------------------------------------ We study here further properties of free GIG distribution. Some of them motivate Section 4 where we will characterize fGIG distribution in a way analogous to classical GIG distribution. The next remark recalls the definition and some basic facts about free Poisson distribution, which will play an important role in this paper. \[rem:freePoisson\] 1. Marchenko–Pastur (or free-Poisson) distribution $\nu=\nu(\gamma, \lambda)$ is defined by the formula $$\begin{aligned} \nu=\max\{0,\,1-\lambda\}\,\delta_0+\tilde{\nu}, \end{aligned}$$ where $\gamma,\lambda> 0$ and the measure $\tilde{\nu}$, supported on the interval $(\gamma(1-\sqrt{\lambda})^2,\,\gamma(1+\sqrt{\lambda})^2)$, has the density (with respect to the Lebesgue measure) $$\tilde{\nu}({{\rm d}}x)=\frac{1}{2\pi\gamma x}\,\sqrt{4\lambda\gamma^2-(x-\gamma(1+\lambda))^2}\,{{\rm d}}x.$$ 2. The $R$-transform of the free Poisson distribution $\nu(\gamma,\lambda)$ is of the form $$r_{\nu(\gamma, \lambda)}(z)=\frac{\gamma\lambda}{1-\gamma z}.$$ The next proposition was proved in [@Szp17 Remark 2.1] which is the free counterpart of a convolution property of classical Gamma and GIG distribution. The proof is a straightforward calculation of the $R$-transform with the help of Remark \[rem:F\_lambda\_sym\]. \[GIGPoissConv\] Let $X$ and $Y$ be free, $X$ free GIG distributed $\mu(\alpha,\beta,-\lambda)$ and $Y$ free Poisson distributed $\nu(1/\alpha,\lambda)$ respectively, for $\alpha,\beta,\lambda>0$. Then $X+Y$ is free GIG distributed $\mu(\alpha,\beta,\lambda)$. We also quote another result from [@Szp17 Remark 2.2] which is again the free analogue of a property of classical GIG distribution. The proof is a simple calculation of the density. \[GIGInv\] If $X$ has the free GIG distribution $\mu(\alpha,\beta,\lambda)$ then $X^{-1}$ has the free GIG distribution $\mu(\beta,\alpha,-\lambda)$. The two propositions above imply some distributional properties of fGIG distribution. In the Section 4 we will study characterization of the fGIG distribution related to these properties. \[rem:prop\] 1. Fix $\lambda,\alpha>0$. If $X$ has fGIG distribution $\mu(\alpha,\alpha,-\lambda)$ and $Y$ has the free Poisson distribution $\nu(1/\alpha,\lambda)$ and $X,Y$ are free then $X\stackrel{d}{=}(X+Y)^{-1}$. Indeed by Proposition \[GIGPoissConv\] we get that $X+Y$ has fGIG distribution $\mu(\alpha,\alpha,\lambda)$ and now Proposition \[GIGInv\] implies that $(X+Y)^{-1}$ has the distribution $\mu(\alpha,\alpha,-\lambda)$. 2. One can easily generalize the above observation. Take $\alpha,\beta,\lambda>0$, and $X,Y_1,Y_2$ free, such that $X$ has fGIG distribution $\mu(\alpha,\beta,-\lambda)$, $Y_1$ is free Poisson distributed $\nu(1/\beta,\lambda)$ and $Y_2$ is distributed $\nu(1/\alpha,\lambda)$, then $X\stackrel{d}{=}(Y_1+(Y_2+X)^{-1})^{-1}$. Similarly as before we have that $X+Y_2$ has distribution $\mu(\alpha,\beta,\lambda)$, then by Proposition \[GIGInv\] we get that $(X+Y_2)^{-1}$ has distribution $\mu(\beta,\alpha,-\lambda)$. Then we have that $Y_1+(Y_2+X)^{-1}$ has the distribution $\mu(\beta,\alpha,\lambda)$ and finally we get $(Y_1+(Y_2+X)^{-1})^{-1}$ has the desired distribution $\mu(\alpha,\beta,-\lambda)$. 3. Both identities above can be iterated finitely many times, so that one obtains that $X\stackrel{d}{=}\left(Y_1+\left(Y_2+\cdots\right)^{-1}\right)^{-1}$, where $Y_1,Y_2,\ldots$ are free, for $k$ odd $Y_k$ has the free Poisson distribution $\nu(1/\beta,\lambda)$ and for $k$ even $Y_k$ has the distribution $\nu(1/\alpha,\lambda)$. For the case described in $1^o$ one simply has to take $\alpha=\beta$. We are not sure if infinite continued fractions can be defined. Next we study limits of the fGIG measure $\mu(\alpha,\beta,\lambda)$ when $\alpha\to 0$ and $\beta\to 0$. This was stated with some mistake in [@Szp17 Remark 2.3]. As $\beta\downarrow 0$ we have the following weak limits of the fGIG distribution $$\begin{aligned} \label{eq:limits} \lim_{\beta\downarrow 0}\mu(\alpha,\beta,\lambda) = \begin{cases} \nu(1/\alpha, \lambda), & \lambda \geq1, \\ \frac{1-\lambda}{2}\delta_0 + \frac{1+\lambda}{2}\nu(\frac{1+\lambda}{2\alpha},1), & \|\lambda\|<1,\\ \delta_0, & \lambda\leq -1. \end{cases} \end{aligned}$$ Taking into account Proposition \[GIGInv\] one can also describe limits when $\alpha\downarrow 0$ for $\lambda \geq1$. This result reflects the fact that GIG matrix generalizes the Wishart matrix for $\lambda \geq1$, but not for $\lambda <1$ (see [@Fer06] for GIG matrix and [@HP00] for the Wishart matrix). We will find the limit by calculating limits of the $R$-transform, since convergence of the $R$-transform implies weak convergence. Observe that from Remark \[rem:F\_lambda\_sym\] we can consider only $\lambda\geq0$, however we decided to present all cases, as the consideration will give asymptotic behaviour of support of fGIG measure. In view of , the only non-trivial part is limits of $\beta\gamma$ when $\beta\to0$. Observe that if we define $F(a,b,\alpha,\beta,\lambda)$ by $$\begin{aligned} \left(1-\lambda+\alpha\sqrt{ab}-\beta\frac{a+b}{2ab},1+\lambda+\frac{\beta}{\sqrt{ab}}-\alpha\frac{a+b}{2}\right)^T &=\left(f(a,b,\alpha,\beta,\lambda),g((a,b,\alpha,\beta,\lambda))\right)^T\\ &=F(a,b,\alpha,\beta,\lambda). \end{aligned}$$ Then the solution to the system , are functions $(a(\alpha,\beta,\lambda),b(\alpha,\beta,\lambda))$, such that $F(a(\alpha,\beta,\lambda),b(\alpha,\beta,\lambda),\alpha,\beta,\lambda)=(0,0)$. To use Implicit Function Theorem, by calculating the Jacobian with respect to $(a,b)$, we observe that $a(\alpha,\beta,\lambda)$ and $b(\alpha,\beta,\lambda)$ are continuous (even differentiable) functions of $\alpha,\beta>0$ and $\lambda\in \mathbb{R}$. Case 1. $\lambda>1$\ Observe if we take $\beta=0$ then a real solution $0<a<b$ for the system , $$\begin{aligned} \label{Case1} 1-\lambda+\alpha\sqrt{ab}&=0\\ 1+\lambda-\alpha\frac{a+b}{2}&=0 \end{aligned}$$ still exists. Moreover, because at $\beta=0$ Jacobian is non-zero, Implicit Function Theorem says that solutions are continuous at $\beta=0$. Thus using we get $$\begin{aligned} \beta \gamma=\frac{\alpha^2 ab+\tfrac{\beta^2}{ab}-2\alpha\beta (\tfrac{a+b}{\sqrt{ab}}-1)-(\lambda-1)^2}{4}=\frac{\tfrac{\beta^2}{ab}-2\alpha\beta (\tfrac{a+b}{\sqrt{ab}}-1)}{4}. \end{aligned}$$ The above implies that $\beta\gamma\to 0$ when $\beta\to 0$ since $a,b$ have finite and non-zero limit when $\beta\to 0$, as explained above. Case 2. $\lambda<-1$\ In that case we see that setting $\beta=0$ in leads to an equation with no real solution for $(a,b)$. In this case the part $\beta\tfrac{a+b}{2ab}$ has non-zero limit when $\beta\to 0$. To be precise substitute $a=\beta a^\prime$ and $b=\beta b^\prime$ in , , and then we get $$\begin{aligned} 1-\lambda+\alpha\beta\sqrt{a^\prime b^\prime}-\frac{a^\prime+b^\prime}{2a^\prime b^\prime}=&0\\ 1+\lambda+\frac{1}{\sqrt{a^\prime b^\prime}}-\alpha\beta\frac{a^\prime+b^\prime}{2}=&0. \end{aligned}$$ The above system is equivalent to the system , with $\alpha:=\alpha\beta$ and $\beta:=1$. If we set $\beta=0$ as in Case 1 we get $$\begin{aligned} 1-\lambda-\frac{a^\prime+b^\prime}{2a^\prime b^\prime}=&0\\ \label{Case2} 1+\lambda+\frac{1}{\sqrt{a^\prime b^\prime}}=&0. \end{aligned}$$ The above system has solution $0<a^\prime<b^\prime$ for $\lambda<-1$. Calculating the Jacobian we see that it is non-zero at $\beta=0$, so Implicit Function Theorem implies that $a^\prime$ and $b^\prime$ are continuous functions at $\beta=0$ in the case $\lambda<-1$.\ This implies that in the case $\lambda<-1$ the solutions of , are $a(\beta)= \beta a^\prime+o(\beta)$ and $b(\beta)= \beta b^\prime +o(\beta)$. Thus we have $$\begin{aligned} \lim_{\beta\to 0}\beta \gamma&=\frac{\alpha^2 ab+\tfrac{\beta^2}{ab}-2\alpha\beta (\tfrac{a+b}{\sqrt{ab}}-1)-(\lambda-1)^2}{4}\\&=\frac{\tfrac{1}{a^\prime b^\prime}-(\lambda-1)^2 }{4}=\frac{(\lambda+1)^2-(\lambda-1)^2 }{4}=\lambda, \end{aligned}$$ where in the equation one before the last we used . Case 3. $\|\lambda\|< 1$\ Observe that neither nor has a real solution in the case $\|\lambda\|< 1$. This is because in this case asymptotically $a(\beta)=a^\prime \beta +o(\beta)$ and $b$ has a finite positive limit as $\beta\to0$. Similarly as in Case 2 let us substitute $a=\beta a^\prime $ in , , which gives $$\begin{aligned} 1-\lambda+\alpha\sqrt{\beta a^\prime b}-\frac{\beta a^\prime+b}{2a^\prime b}&=0\\ 1+\lambda+\frac{\sqrt{\beta}}{a^\prime b}-\alpha\frac{\beta a^\prime+b}{2}&=0. \end{aligned}$$ If we set $\beta=0$ we get $$\begin{aligned} 1-\lambda-\frac{1}{2a^\prime}&=0,\\ 1+\lambda-\alpha\frac{b}{2}&=0, \end{aligned}$$ which obviously has positive solution $(a^\prime,b)$ when $\|\lambda\|<1$. As before the Jacobian is non-zero at $\beta=0$, so $a^\prime$ and $b$ are continuous at $\beta=0$.\ Now we go back to the limit $\lim_{\beta\to 0}\beta\gamma$. We have $a(\beta)=\beta a^\prime+o(\beta)$, thus $$\begin{aligned} \lim_{\beta\to 0}\beta \gamma=\lim_{\beta\to 0}\frac{\alpha^2 ab+\tfrac{\beta^2}{ab}-2\alpha\beta (\tfrac{a+b}{\sqrt{ab}}-1)-(\lambda-1)^2}{4}=-\frac{(\lambda-1)^2}{4}. \end{aligned}$$ Case 4. $\|\lambda\|= 1$\ An analysis similar to the above cases shows that in the case $\lambda=1$ we have $a(\beta)=a^\prime \beta^{2/3}+o(\beta^{2/3})$ and $b$ has positive limit when $\beta\to 0$. In the case $\lambda=-1$ one gets $a(\beta)=a^\prime \beta+o(\beta)$ and $b(\beta)=b^\prime\beta^{1/3}+o(\beta^{1/3})$ as $\beta\to 0$. Thus we can calculate the limit of $f_{\alpha,\beta,\lambda}$ as $\beta\to 0$ , $$\lim_{\beta\downarrow0} f_{\alpha,\beta,\lambda}(z) = \begin{cases} (\alpha+(\lambda-1)z)^2, & \lambda>1, \\ \alpha^2+(\lambda^2-1)\alpha z, & \|\lambda\| \leq 1, \\ (\alpha-(\lambda+1)z)^2, & \lambda<-1. \end{cases}$$ The above allows us to calculate limiting $R$-transform and hence the Cauchy transform which implies . Considering the continuous dependence of roots on parameters shows the following asymptotic behaviour of the double root $\delta<0$ and the simple root $\eta \geq \alpha$. 1. If $\|\lambda\|>1$ then $\delta\to\alpha/(1-\|\lambda\|)$ and $\eta\to +\infty$ as $\beta \downarrow0$. 2. If $\|\lambda\|<1$ then $\delta\to-\infty$ and $\eta \to \alpha/(1-\lambda^2)$ as $\beta \downarrow0$. 3. If $\lambda=\pm1$ then $\delta\to-\infty$ and $\eta \to +\infty$ as $\beta \downarrow0$. Regularity of fGIG distribution under free convolution ====================================================== In this section we study in detail regularity properties of the fGIG distribution related to the operation of free additive convolution. In the next theorem we collect all the results proved in this section. The theorem contains several statements about free GIG distributions. Each subsection of the present section proves a part of the theorem. \[thm:sec3\] The following holds for the free GIG measure $\mu(\alpha,\beta,\lambda)$: 1. It is freely infinitely divisible for any $\alpha,\beta>0$ and $\lambda\in\mathbb{R}.$ 2. The free Levy measure is of the form $$\label{FLM} \tau_{\alpha,\beta,\lambda}({{\rm d}}x)=\max\{\lambda,0\} \delta_{1/\alpha}({{\rm d}}x) + \frac{(1-\delta x) \sqrt{\beta (1-\eta x)}}{\pi x^{3/2} (1-\alpha x)} 1_{(0,1/\eta)}(x)\, {{\rm d}}x.$$ 3. It is free regular with zero drift for all $\alpha,\beta>0$ and $\lambda\in\mathbb{R}$. 4. It is freely self-decomposable for $\lambda \leq -\frac{B^{\frac{3}{2}}}{A\sqrt{9B-8A}}.$ 5. It is unimodal. Free infinite divisibility and free Lévy measure ------------------------------------------------ As we mentioned before, having the operation of free convolution defined, it is natural to study infinite divisibility with respect to $\boxplus$. We say that $\mu$ is freely infinitely divisible if for any $n\geq 1$ there exists a probability measure $\mu_n$ such that $$\mu=\underbrace{\mu_n\boxplus\ldots\boxplus\mu_n}_{\text{$n$ times}}.$$ It turns out that free infinite divisibility of compactly supported measures can by described in terms of analytic properties of the $R$-transform. In particular it was proved in [@Voi86 Theorem 4.3] that the free infinite divisibility is equivalent to the inequality ${\text{\normalfont Im}}(r_{\alpha,\beta,\lambda}(z)) \leq0$ for all $z\in{\mathbb{C}}^-$. As in the classical case, for freely infinitely divisible probability measures, one can represent its free cumulant transform with a Lévy–Khintchine type formula. For a probability measure $\mu$ on ${\mathbb{R}}$, the free cumulant transform is defined by $${\mathcal{C}^\boxplus}_\mu(z) = z r_\mu(z).$$ Then $\mu$ is FID if and only if ${\mathcal{C}^\boxplus}_\mu$ can be analytically extended to ${\mathbb{C}}^-$ via the formula $$\label{FLK2} {\mathcal{C}^\boxplus}_{\mu}(z)=\xi z+\zeta z^2+\int_{{\mathbb{R}}}\left( \frac{1}{1-z x}-1-z x \,1_{[-1,1] }(x) \right) \tau({{\rm d}}x) ,\qquad z\in {\mathbb{C}}^-,$$ where $\xi \in {\mathbb{R}},$ $\zeta\geq 0$ and $\tau$ is a measure on ${\mathbb{R}}$ such that $$\tau (\{0\})=0,\qquad \int_{{\mathbb{R}}}\min \{1,x^2\}\tau ({{\rm d}}x) <\infty.$$ The triplet $(\xi,\zeta,\tau)$ is called the free characteristic triplet of $\mu$, and $\tau$ is called the free Lévy measure of $\mu$. The formula is called the free Lévy–Khintchine formula. The above form of free Lévy–Khintchine formula was obtained by Barndorff-Nielsen and Thorbj[ø]{}rnsen [@BNT02b] and it has a probabilistic interpretation (see [@Sat13]). Another form was obtained by Bercovici and Voiculescu [@BV93], which is more suitable for limit theorems. In order to prove that all fGIG distributions are freely infinitely divisible we will use the following lemma. \[lem:32\] Let $f\colon (\mathbb C^{-} \cup \mathbb R) \setminus \{x_0\} \to \mathbb C$ be a continuous function, where $x_0\in\mathbb{R}$. Suppose that $f$ is analytic in $\mathbb{C}^{-}$, $f(z)\to 0$ uniformly with $z\to \infty$ and ${\text{\normalfont Im}}(f(x))\leq 0$ for $x \in \mathbb R \setminus \{x_0\}$. Suppose moreover that ${\text{\normalfont Im}}(f(z))\leq 0$ for ${\text{\normalfont Im}}(z)\leq 0$ in neighbourhood of $x_0$ then ${\text{\normalfont Im}}(f(z))\leq 0$ for all $z\in \mathbb{C}^{-}$. Since $f$ is analytic the function ${\text{\normalfont Im}}f$ is harmonic and thus satisfies the maximum principle. Fix ${\varepsilon}>0$. Since $f(z)\to 0$ uniformly with $z\to \infty,$ let $R>0$ be such that ${\text{\normalfont Im}}f(z)<{\varepsilon}$. Consider a domain $D_{\varepsilon}$ with the boundary $$\partial D_{\varepsilon}=[-R,x_0-{\varepsilon}] \cup \{x_0+{\varepsilon}e^{{{\rm i}}\theta}: \theta \in[-\pi,0]\} \cup[x_0+{\varepsilon},R]\cup\{R e^{{{\rm i}}\theta}: \theta \in[-\pi,0]\}$$ Observe that on $\partial D_{\varepsilon}$ ${\text{\normalfont Im}}f(z)<{\varepsilon}$ by assumptions, and hence by the maximum principle we have ${\text{\normalfont Im}}f(z)<{\varepsilon}$ on whole $D_{\varepsilon}$. Letting ${\varepsilon}\to 0$ we get that ${\text{\normalfont Im}}f(z) \leq 0$ on $\mathbb{C}^{-}$. Next we proceed with the proof of free infinite divisibility of fGIG distributions. $ $ [Case 1.]{} $\lambda<1$. Observe that we have $$\label{hypo} {\text{\normalfont Im}}(r_{\alpha,\beta,\lambda}(x)) \leq 0, \qquad x\in{\mathbb{R}}\setminus\{\alpha\}.$$ From we see that ${\text{\normalfont Im}}(r_{\alpha,\beta,\lambda}(x))=0$ for $x \in(-\infty,\alpha) \cup (\alpha,\eta]$, and $$\label{r} {\text{\normalfont Im}}(r_{\alpha,\beta,\lambda}(x)) = \frac{(x-\delta)\sqrt{\beta (x-\eta)}}{x (\alpha-x)}<0,\qquad x>\eta$$ since $\eta>\alpha>0>\delta$.\ Moreover observe that by for ${\varepsilon}>0$ small enough we have ${\text{\normalfont Im}}(r_{\alpha,\beta,\lambda}(\alpha+{\varepsilon}e^{i \theta}))<0$, for $\theta\in[-\pi,0]$. Now Lemma \[lem:32\] implies that free GIG distribution if freely ID in the case $\lambda>0$. [Case 2]{} $\lambda>0$. In this case similar argument shows that $\mu(\alpha,\beta,\lambda)$ is FID. Moreover by $\eqref{alpha2}$ point $z=\alpha$ is a removable singularity and $r_{\alpha,\beta,\lambda}$ extends to a continuous function on ${\mathbb{C}}^-\cup{\mathbb{R}}$. Thus one does not need to take care of the behaviour around $z=\alpha$. [Case 3]{} $\lambda=0$. For $\lambda=0$ one can adopt a similar argumentation using . It also follows from the fact that free GIG family $\mu(\alpha,\beta,\lambda)$ is weakly continuous with respect to $\lambda$. Since free infinite divisibility is preserved by weak limits, then the case $\lambda=0$ may be deduced from the previous two cases. Next we will determine the free Lévy measure of free GIG distribution $\mu(\alpha,\beta,\lambda)$. Let $(\xi_{\alpha,\beta,\lambda}, \zeta_{\alpha,\beta,\lambda},\tau_{\alpha,\beta,\lambda})$ be the free characteristic triplet of the free GIG distribution $\mu(\alpha,\beta,\lambda)$. By the Stieltjes inversion formula mentioned in Remark \[rem:Cauchy\], the absolutely continuous part of the free Lévy measure has the density $$-\lim_{{\varepsilon}\to0}\frac{1}{\pi x^2}{\text{\normalfont Im}}(r_{\alpha,\beta,\lambda}(x^{-1}+{{\rm i}}{\varepsilon})), \qquad x \neq 0,$$ atoms are at points $1/p~(p\neq0)$, such that the weight is given by $$\tau_{\alpha,\beta,\lambda}(\{1/p\})=\lim_{z\to p} (p - z) r_{\alpha,\beta,\lambda}(z),$$ is non-zero, where $z$ tends to $p$ non-tangentially from ${\mathbb{C}}^-$. In our case the free Lévy measure does not have a singular continuous part since $r_{\alpha,\beta,\lambda}$ is continuous on ${\mathbb{C}}^-\cup{\mathbb{R}}\setminus\{\alpha\}$. Considering – and we obtain the free Lévy measure $$\tau_{\alpha,\beta,\lambda}({{\rm d}}x)=\max\{\lambda,0\} \delta_{1/\alpha}({{\rm d}}x) + \frac{(1-\delta x) \sqrt{\beta (1-\eta x)}}{\pi x^{3/2} (1-\alpha x)} 1_{(0,1/\eta)}(x)\, {{\rm d}}x.$$ Recall that $\eta \geq \alpha >0>\delta$ holds, and $\eta=\alpha$ if and only if $\lambda=0$. The other two parameters $\xi_{\alpha,\beta,\lambda}$ and $\zeta_{\alpha,\beta,\lambda}$ in the free characteristic triplet will determined in Section \[sec:FR\]. Free regularity {#sec:FR} --------------- In this subsection we will deal with a property stronger than free infinite divisibility, so called free regularity.\ Let $\mu$ be a FID distribution with the free characteristic triplet $(\xi,\zeta,\tau)$. When the semicircular part $\zeta$ is zero and the free Lévy measure $\tau$ satisfies a stronger integrability property $\int_{{\mathbb{R}}}\min\{1,\|x\|\}\tau({{\rm d}}x) < \infty$, then the free Lévy-Khintchine representation reduces to $$\label{FR} {\mathcal{C}^\boxplus}_\mu(z)=\xi' z+\int_{{\mathbb{R}}}\left( \frac{1}{1-z x}-1\right) \tau({{\rm d}}x) ,\qquad z\in {\mathbb{C}}^-,$$ where $\xi' =\xi -\int_{[-1,1]}x \,\tau({{\rm d}}x) \in {\mathbb{R}}$ is called a drift. The distribution $\mu$ is said to be free regular [@PAS12] if $\xi'\geq0$ and $\tau$ is supported on $(0,\infty)$. A probability measure $\mu$ on ${\mathbb{R}}$ is free regular if and only if the free convolution power $\mu^{\boxplus t}$ is supported on $[0,\infty)$ for every $t>0$, see [@AHS13]. Examples of free regular distributions include positive free stable distributions, free Poisson distributions and powers of free Poisson distributions [@Has16]. A general criterion in [@AHS13 Theorem 4.6] shows that some boolean stable distributions [@AH14] and many probability distributions [@AHS13; @Has14; @AH16] are free regular. A recent result of Ejsmont and Lehner [@EL Proposition 4.13] provides a wide class of examples: given a nonnegative definite complex matrix $\{a_{ij}\}_{i,j=1}^n$ and free selfadjoint elements $X_1,\dots, X_n$ which have symmetric FID distributions, the polynomial $\sum_{i,j=1}^n a_{ij} X_i X_j$ has a free regular distribution with zero drift. For the free GIG distributions, the semicircular part can be found by $\displaystyle\zeta_{\alpha,\beta,\lambda}= \lim_{z\to \infty} z^{-1} r_{\alpha,\beta,\lambda}(z)=0$. The free Lévy measure satisfies $${{\rm supp}}(\tau_{\alpha,\beta,\lambda}) \subset (0,\infty), \qquad \int_0^\infty \min\{1,x\} \tau_{\alpha,\beta,\lambda}({{\rm d}}x)<\infty$$ and so we have the reduced formula . The drift is given by $\displaystyle \xi_{\alpha,\beta,\lambda}'=\lim_{u \to -\infty} r_{\alpha,\beta,\lambda}(u)=0$. Free selfdecomposability ------------------------ Classical GIG distribution is selfdecomposable [@Hal79; @SS79] (more strongly, hyperbolically completely monotone [@Bon92 p. 74]), and hence it is natural to ask whether free GIG distribution is freely selfdecomposable.\ A distribution $\mu$ is said to be freely selfdecomposable (FSD) [@BNT02a] if for any $c\in(0,1)$ there exists a probability measure $\mu_c$ such that $\mu= (D_c\mu) \boxplus \mu_c $, where $D_c\mu$ is the dilation of $\mu$, namely $(D_c\mu)(B)=\mu(c^{-1}B)$ for Borel sets $B \subset {\mathbb{R}}$. A distribution is FSD if and only if it is FID and its free Lévy measure is of the form $$\label{SD Levy} \frac{k(x)}{\|x\|}\, {{\rm d}}x,$$ where $k\colon {\mathbb{R}}\to [0,\infty)$ is non-decreasing on $(-\infty,0)$ and non-increasing on $(0,\infty)$. Unlike the free regular distributions, there are only a few known examples of FSD distributions: the free stable distributions, some free Meixner distributions, the classical normal distributions and a few other distributions (see [@HST Example 1.2, Corollary 3.4]). The free Poisson distribution is not FSD. In view of , the free GIG distribution $\mu(\alpha,\beta,\lambda)$ is not FSD if $\lambda > 0$. Suppose $\lambda\leq0$, then $\mu(\alpha,\beta,\lambda)$ is FSD if and only if the function $$k_{\alpha,\beta,\lambda}(x)=\frac{(1-\delta x) \sqrt{\beta (1-\eta x)}}{\pi \sqrt{x} (1-\alpha x)}$$ is non-increasing on $(0,1/\eta)$. The derivative is $$k_{\alpha,\beta,\lambda}'(x) = - \frac{\sqrt{\beta} [1+(\delta-3\alpha)x +(2 \alpha \eta -2\eta\delta + \alpha \delta )x^2]}{2\pi x^{3/2} (1-\alpha x)^2 \sqrt{1-\eta x}}.$$ Hence FSD is equivalent to $$g(x):=1+(\delta-3\alpha)x +(2 \alpha \eta -2\eta\delta + \alpha \delta )x^2 \geq 0,\qquad 0\leq x \leq 1/\eta.$$ Using $\eta \geq\alpha >0>\delta$, one can show that $2 \alpha \eta -2\eta\delta + \alpha \delta >0$, a straightforward calculation shows that the function $g$ takes a minimum at a point in $(0,1/\eta)$. Thus FSD is equivalent to $$D:=(\delta-3\alpha)^2 - 4 (2 \alpha \eta -2\eta\delta + \alpha \delta ) \leq 0.$$ In order to determine when the above inequality holds, it is convenient to switch to parameters $A,B$ defined by . Using formulas derived in Section \[sec:form\] we obtain $$D= \frac{4(B+\lambda A)(8\lambda^2 A^3 -9\lambda^2 A^2 B +B^3)}{A^2 B (A-B)^2 (B-\lambda A)}.$$ Calculating $\lambda$ for which $D$ is non-positive we obtain that $$\lambda\leq-\frac{B^{\frac{3}{2}}}{A\sqrt{9B-8A}}.$$ One can easily find that the maximum of the function $-\frac{B^{\frac{3}{2}}}{A\sqrt{9B-8A}}$ over $A,B\geq 0$ equals $-\frac{4}{9}\sqrt{3}$. Thus the set of parameters $(A,B)$ that give FSD distributions is nonempty if and only if $\lambda \leq -\frac{4}{9}\sqrt{3}$. In the critical case $\lambda = -\frac{4}{9}\sqrt{3}$ only the pairs $(A, \frac{4}{3}A), A>0$ give FSD distributions. If one puts $A=12 t, B= 16 t$ then $a=(2-\sqrt{3})^2t,b=(2+\sqrt{3})^2t$, $\alpha = \frac{3-\sqrt{3}}{18 t}$, $\beta = \frac{3+\sqrt{3}}{18}t, \delta= -\frac{3-\sqrt{3}}{6t}=- 2\eta$. One can easily show that $\mu(\alpha,\beta,-1)$ is FSD if and only if $(0<A<)~B\leq \frac{-1+\sqrt{33}}{2} A$. Finally note that the above result is in contrast to the fact that classical GIG distributions are all selfdecomposable. Unimodality ----------- Since relations of free infinite divisibility and free self decomposability were studied in the literature, we decided to determine whether measures from the free GIG family are unimodal. A measure $\mu$ is said to be unimodal if for some $c\in{\mathbb{R}}$ $$\label{UM} \mu({{\rm d}}x)=\mu(\{c\})\delta_c({{\rm d}}x)+f(x)\, {{\rm d}}x,$$ where $f\colon{\mathbb{R}}\to[0,\infty)$ is non-decreasing on $(-\infty,c)$ and non-increasing on $(c,\infty)$. In this case $c$ is called the mode. Hasebe and Thorbj[ø]{}rnsen [@HT16] proved that FSD distributions are unimodal. Since some free GIG distributions are not FSD, the result from [@HT16] does not apply. However it turns out that free GIG measures are unimodal. Calculating the derivative of the density of $\mu(\alpha,\beta,\lambda)$ one obtains $$\frac{ x (a + b - 2 x)(x \alpha + \tfrac{\beta}{\sqrt{a b}}) - 2 (b - x) (x-a) (x \alpha + \tfrac{2 \beta}{\sqrt{ a b}})}{2 x^3 \sqrt{(b - x) (x-a)}}$$ Denoting by $f(x)$ the quadratic polynomial in the numerator, one can easily see from the shape of the density that $f(a)>0>f(b)$ and hence the derivative vanishes at a unique point in $(a,b)$ (since $f$ is quadratic). Characterizations the free GIG distribution =========================================== In this section we show that the fGIG distribution can be characterized similarly as classical GIG distribution. In [@Szp17] fGIG was characterized in terms of free independence property, the classical probability analogue of this result characterizes classical GIG distribution. In this section we find two more instances where such analogy holds true, one is a characterization by some distributional properties related with continued fractions, the other is maximization of free entropy. Continued fraction characterization ----------------------------------- In this section we study a characterization of fGIG distribution which is analogous to the characterization of GIG distribution proved in [@LS83]. Our strategy is different from the one used in [@LS83]. We will not deal with continued fractions, but we will take advantage of subordination for free convolutions, which allows us to prove the simpler version of ”continued fraction” characterization of fGIG distribution. \[thm:char\] Let $Y$ have the free Poisson distribution $\nu(1/\alpha,\lambda)$ and let $X$ be free from $Y$, where $\alpha,\lambda>0$ and $X>0$, then we have $$\begin{aligned} \label{eq:distr_char} X\stackrel{d}{=}\left(X+Y\right)^{-1}\end{aligned}$$ if and only if $X$ has free GIG distribution $\mu(\alpha,\alpha,-\lambda)$. Observe that the “if” part of the above theorems is contained in the remark \[rem:prop\]. We only have to show that if $\eqref{eq:distr_char}$ holds where $Y$ has free Poisson distribution $\nu(1/\alpha,\lambda)$, then $X$ has free GIG distribution. As mentioned above our proof of the above theorem uses subordination of free convolution. This property of free convolution was first observed by Voiculescu [@Voi93] and then generalized by Biane [@Bia98]. Let us shortly recall what we mean by subordination of free additive convolution. Subordination of free convolution states that for probability measures $\mu,\nu$, there exists an analytic function defined on $\mathbb{C}\setminus\mathbb{R}$ with the property $F(\overline{z})=\overline{F(z)}$ such that for $z\in\mathbb{C}^+$ we have ${\text{\normalfont Im}}F(z)>{\text{\normalfont Im}}z$ and $$G_{\mu\boxplus\nu}(z)=G_\mu(\omega(z)).$$ Now if we denote by $\omega_1$ and $\omega_2$ subordination functions such that $G_{\mu\boxplus\nu}=G_\mu(\omega_1)$ and $G_{\mu\boxplus\nu}=G_\nu(\omega_2)$, then $\omega_1(z)+\omega_2(z)=1/G_{\mu\boxplus\nu}(z)+z$. Next we proceed with the proof of Theorem \[thm:char\] which is the main result of this section. First note that is equivalent to $$\frac{1}{X}\stackrel{d}{=}X+Y,$$ Which may be equivalently stated in terms of Cauchy transforms of both sides as $$\begin{aligned} \label{eqn:CharCauch} G_{X^{-1}}(z)=G_{X+Y}(z). \end{aligned}$$ Subordination allows as to write the Cauchy transform of $X+Y$ in two ways $$\begin{aligned} \label{Sub1} G_{X+Y}(z)&=G_X(\omega_X(z)),\\ \label{Sub2} G_{X+Y}(z)&=G_Y(\omega_Y(z)). \end{aligned}$$ Moreover $\omega_X$ and $\omega_Y$ satisfy $$\begin{aligned} \omega_X(z)+\omega_Y(z)=1/G_{X+Y}(z)+z. \end{aligned}$$ From the above we get $$\begin{aligned} \label{subrel} \omega_X(z)=1/G_{X+Y}(z)+z-\omega_Y(z), \end{aligned}$$ this together with and gives $$\begin{aligned} G_{X^{-1}}(z)&=G_X\left(\frac{1}{G_{X^{-1}}}(z)+z-\omega_Y(z)\right). \end{aligned}$$ Since we know that $Y$ has free Poisson distribution $\nu(\lambda,1/\alpha)$ we can calculate $\omega_Y$ in terms of $G_{X^{-1}}$ using . To do this one has to use the identity $G_Z^{\langle -1\rangle}(z)=r_Z(z)+1/z$ for any self-adjoint random variable $Z$ and the form of the $R$-transform of free Poisson distribution recalled in Remark \[rem:freePoisson\]. $$\begin{aligned} \label{omegax} \omega_Y(z)=\frac{\lambda }{\alpha-G_{X^{-1}}(z) }+\frac{1}{G_{X^{-1}}(z)} \end{aligned}$$ Now we can use , where we substitute $G_{X+Y}(z)=G_{X^{-1}}(z)$ to obtain $$\begin{aligned} \label{FE} G_{X^{-1}}(z)=G_{X}\left(\frac{\lambda }{G_{X^{-1}}(z)-\alpha }+z\right). \end{aligned}$$ Next we observe that we have $$\begin{aligned} \label{CauchInv} G_{X^{-1}}(z)=\frac{1}{z}\left(-\frac{1}{z}G_X\left(\frac{1}{z}\right)+1\right), \end{aligned}$$ which allows to transform to an equation for $G_X$. It is enough to show that this equation has a unique solution. Indeed from Remark \[rem:prop\] we know that free GIG distribution $\mu(\alpha,\alpha,\lambda)$ has the desired property, which in particular means that for $X$ distributed $\mu(\alpha,\alpha,\lambda)$ equation is satisfied. Thus if there is a unique solution it has to be the Cauchy transform of the free GIG distribution. To prove uniqueness of the Cauchy transform of $X$, we will prove that coefficients of the expansion of $G_X$ at a special “good” point, are uniquely determined by $\alpha$ and $\lambda$. First we will determine the point at which we will expand the function. Observe that with our assumptions $G_{X^{-1}}$ is well defined on the negative half-line, moreover $G_{X^{-1}}(x)<0$ for any $x<0$, and we have $G_{X^{-1}}(x)\to0$ with $x\to-\infty$. On the other hand the function $f(x)=1/x-x$ is decreasing on the negative half-line, and negative for $x\in(-1,0)$. Thus there exist a unique point $c\in(-1,0)$ such that $$\label{key eq} \frac{1}{c} = \frac{\lambda}{G_{X^{-1}}(c)-\alpha}+c.$$ Let us denote $$M(z):= G_X\left(\frac{1}{z}\right)$$ and $$\label{eqn:funcN} N(z):=\left(\frac{\lambda}{G_{X^{-1}}(z)-\alpha}+z\right)^{-1} = \frac{-z+ \alpha z^2 +M(z)}{-(1+\lambda)z^2 +\alpha z^3 + z M(z)},$$ where the last equality follows from .\ One has $N(c)=c$, and our functional equation may be rewritten (with the help of ) as $$\label{FE2} -M(z) +z = z^2 M(N(z)).$$ Functions $M$ and $N$ are analytic around any $x<0$. Consider the expansions $$\begin{aligned} M(z) &= \sum_{n=0}^\infty \alpha_n (z-c)^n, \\ N(z) &= \sum_{n=0}^\infty \beta_n (z-c)^n. \end{aligned}$$ Observe that $\beta_0=c$ since $N(c)=c$. Differentiating we observe that any $\beta_n,\, n\geq1$ is a rational function of $\alpha, \lambda, c, \alpha_0,\alpha_1,\dots, \alpha_n$. Moreover any $\beta_n,\,n\geq 1 $ is a degree one polynomial in $\alpha_n$. We have $$\begin{aligned} \beta_n = \frac{-\lambda}{[\alpha_0 -(1+\lambda)c+\alpha c^2]^2} \alpha_n + R_n, \end{aligned}$$ where $R_n$ is a rational function of $n+3$ variables evaluated at $(\alpha,\lambda,c,\alpha_0,\alpha_1,\dots, \alpha_{n-1})$, which does not depend on the distribution of $X$. For example $\beta_1$ is given by $$\label{eq:beta1} \begin{split} \beta_1 &=N'(c) =\left. \left(\frac{-z+ \alpha z^2 +M(z)}{-(1+\lambda)z^2 +\alpha z^3 + z M(z)}\right)' \right\|_{z=c} \\ &=\frac{-\lambda c^2 \alpha_1 + c^2(-1-\lambda +2\alpha c -\alpha^2 c^2)+2c(1+\lambda-\alpha c)\alpha_0- \alpha_0^2 }{c^2[\alpha_0-(1+\lambda)c+\alpha c^2]^2}. \end{split}$$ Next we investigate some properties of $c, \alpha_0$ and $\alpha_1$. Evaluating both sides of at $z=c$ yields $$-M(c)+c = c^2 M(N(c)) = c^2M(c),$$ since $M(c)=\alpha_0$ we get $$\label{eq1c} \alpha_0=\frac{c}{1+c^2}.$$ Observe that $\alpha_0= M(c) = G_X(1/c)$ and $\alpha_1=M'(c)=-c^{-2} G_X'(1/c)$ hence we have $$\frac{1}{1+c^2}= \int_{0}^\infty \frac{1}{1-c x} {{\rm d}}\mu_X( x), \qquad \alpha_1 = \int_{0}^\infty \frac{1}{(1-c x)^2} {{\rm d}}\mu_X( x),$$ where $\mu_X$ is the distribution of $X$. Using the Schwarz inequality for the first estimate and a simple observation that $0\leq1/(1-cx) \leq1$ for $x>0$, for the latter estimate we obtain $$\label{eq:alpha1} \frac{1}{(1+c^2)^{2}}=\left(\int_{0}^\infty \frac{1}{1-c x} \mu_X({{\rm d}}x)\right)^2 \leq \int_{0}^\infty \frac{1}{(1-c x)^2} \mu_X({{\rm d}}x)= \alpha_1 \leq \frac{1}{1+c^2}.$$ The equation together with gives $$\label{eq2c} \frac{1}{c} = \frac{\lambda c^2}{-\alpha_0 + c - \alpha c^2} +c.$$ Substituting to after simple calculations we get $$\label{eq:c} \alpha c^4 - (1+\lambda)c^3+(1-\lambda)c -\alpha = 0.$$ We start by showing that $\alpha_0$ is determined only by $\alpha$ and $\lambda$. We will show that $c$, which we showed before is a unique number, depends only on $\alpha$ and $\lambda$ and thus shows that $\alpha_0$ is determined by $\alpha$ and $\lambda$. Since the polynomial $c^4 - (1+\lambda)c^3$ is non-negative for $c<0$ and has a root at $c=0$, and the polynomial $(\lambda-1)c +\alpha$ equals $\alpha>0$ at $c=0$ it follows that there is only one negative $c$, such that the two polynomials are equal and thus the number $c$ is uniquely determined by $(\alpha,\lambda)$. From we see that $\alpha_0$ is also uniquely determined by $(\alpha,\lambda)$. Next we will prove that $\alpha_1$ only depends on $\alpha$ and $\lambda$. Differentiating and evaluating at $z=c$ we obtain $$\label{eq3c} 1-\alpha_1 = 2 c \alpha_0 + c^2 \alpha_1 \beta_1.$$ Substituting $\alpha_0$ and $\lambda$ from the equations and we simplify and we get $$\beta_1 = \frac{(1-c^4)\alpha_1 -1+2c^2-\alpha c^3 -\alpha c^5}{c(\alpha-c+\alpha c^2)}$$ and then equation may be expressed in the form $$\label{eq:alpha2} c(1+c^2)^2 \alpha_1^2 + (\alpha(1+c^2)^2-2c )(1+c^2)\alpha_1 -(\alpha-c + \alpha c^2) =0.$$ The above is a degree 2 polynomial in $\alpha_1$, denote this polynomial by $f$, we have then $$f(0) <0,\qquad f\left(\frac{1}{1+c^2}\right) = \alpha c^2 (1+c^2)>0.$$ Where the first inequality follows from the fact that $c<0$. Since the coefficient $c(1+c^2)^2$ is negative we conclude that $f$ has one root in the interval $(0,1/(1+c^2))$ and the other in $(1/(1+c^2),\infty)$. The inequality implies that $\alpha_1$ is the smaller root of $f$, which is a function of $ \alpha$ and $c$ and hence of $\alpha$ and $\lambda$. In order to prove that $\alpha_n$ depends only on $(\alpha,\lambda)$ for $n\geq2$, first we estimate $\beta_1$. Note that and imply that $$\label{eq4c} \beta_1 = \frac{1-c^2}{\alpha_1 c^2(1+c^2)} -\frac{1}{c^2}.$$ Combining this with the inequality we easily get that $$\label{eq:beta} -1 \leq \beta_1 \leq -c^2.$$ Now we prove by induction on $n$ that $\alpha_n$ only depends on $\alpha$ and $\lambda$. For $n\geq2$ differentiating $n$-times and evaluating at $z=c$ we arrive at $$\label{eq5c} -\alpha_n = c^2(\alpha_n \beta_1^n + \alpha_1 \beta_n) + Q_n,$$ where $Q_n$ is a universal polynomial (which means that the polynomial does not depend on the distribution of $X$) in $2n+1$ variables evaluated at $(\alpha,\lambda,c,\alpha_1,\dots, \alpha_{n-1}, \beta_1,\cdots, \beta_{n-1})$. According to the inductive hypothesis, the polynomials $R_n$ and $Q_n$ depend only on $\alpha$ and $\lambda$. We also have that $\beta_n=p \alpha_n + R_n$, where $$p := \frac{-\lambda}{[\alpha_0 -(1+\lambda)c+\alpha c^2]^2} = \frac{1-c^4}{c(\alpha-c+\alpha c^2)}.$$ The last formula is obtained by substituting $\alpha_0$ and $\lambda$ from and . The equation then becomes $$(1+c^2\beta_1^n + c^2 p \alpha_1)\alpha_n + c^2 \alpha_1 R_n + Q_n=0.$$ The inequalities and show that $$\begin{split} 1+c^2\beta_1^n + c^2 p \alpha_1 &\geq 1-c^2 +\frac{c^2(1-c^4)}{c(\alpha-c+\alpha c^2) (1+c^2)} =\frac{\alpha(1-c^4)}{\alpha-c+\alpha c^2}>0, \end{split}$$ thus $1+c^2\beta_1^n + c^2 p \alpha_1$ is non-zero. Therefore, the number $\alpha_n$ is uniquely determined by $\alpha$ and $\lambda$. Thus we have shown that, if a random variable $X>0$ satisfies the functional equation for fixed $\alpha>0$ and $\lambda>0$, then the point $c$ and all the coefficients $\alpha_0,\alpha_1,\alpha_2,\dots$ of the series expansion of $M(z)$ at $z=c$ are determined only by $\alpha$ and $\lambda$. By analytic continuation, the Cauchy transform $G_X$ is determined uniquely by $\alpha$ and $\lambda$, so there is only one distribution of $X$ for which this equation is satisfied. Remarks on free entropy characterization ---------------------------------------- Féral [@Fer06] proved that fGIG $\mu(\alpha,\beta,\lambda)$ is a unique probability measure which maximizes the following free entropy functional with potential $$\begin{aligned} I_{\alpha,\beta,\lambda}(\mu)=\int\!\!\!\int \log\|x-y\|\, {{\rm d}}\mu(x) {{\rm d}}\mu(y)-\int V_{\alpha,\beta,\lambda}(x)\, {{\rm d}}\mu(x), \end{aligned}$$ among all the compactly supported probability measures $\mu$ on $(0,\infty)$, where $\alpha, \beta>0$ and $\lambda \in {\mathbb{R}}$ are fixed constants, and $$V_{\alpha,\beta,\lambda}(x)=(1-\lambda) \log x+\alpha x+\frac{\beta}{x}.$$ Here we point out the classical analogue. The (classical) GIG distribution is the probability measure on $(0,\infty)$ with the density $$\label{C-GIG} \frac{(\alpha/\beta)^{\lambda/2}}{2K_\lambda(2\sqrt{\alpha\beta})} x^{\lambda-1} e^{-(\alpha x + \beta /x)}, \qquad \alpha,\beta>0, \lambda\in{\mathbb{R}},$$ where $K_\lambda$ is the modified Bessel function of the second kind. Note that this density is proportional to $\exp(-V_{\alpha,\beta,\lambda}(x))$. Kawamura and Iwase [@KI03] proved that the GIG distribution is a unique probability measure which maximizes the classical entropy with the same potential $$H_{\alpha,\beta,\lambda}(p) = - \int p(x) \log p(x)\, {{\rm d}}x -\int V_{\alpha,\beta,\lambda}(x)p(x)\, {{\rm d}}x$$ among all the probability density functions $p$ on $(0,\infty)$. This statement is slightly different from the original one [@KI03 Theorem 2], and for the reader’s convenience a short proof is given below. The proof is a straightforward application of the Gibbs’ inequality $$\label{Gibbs} -\int p(x)\log p(x)\,{{\rm d}}x \leq -\int p(x)\log q(x)\,{{\rm d}}x,$$ for all probability density functions $p$ and $q$, say on $(0,\infty)$. Taking $q$ to be the density of the classical GIG distribution and computing $\log q(x)$, we obtain the inequality $$\label{C-entropy} H_{\alpha,\beta,\lambda}(p) \leq -\log \frac{(\alpha/\beta)^{\lambda/2}}{2K_\lambda(2\sqrt{\alpha\beta})}.$$ Since the Gibbs inequality becomes equality if and only if $p=q$, the equality in holds if and only if $p=q$, as well. From the above observation, it is tempting to investigate the map $$C e^{-V(x)}\, {{\rm d}}x \mapsto \text{~the maximizer $\mu_V$ of the free entropy functional $I_V$ with potential $V$},$$ where $C>0$ is a normalizing constant. Under some assumption on $V$, the free entropy functional $I_V$ is known to have a unique maximizer (see [@ST97]) and so the above map is well defined. 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Hyperolius ferrugineus Hyperolius ferrugineus is a species of frog in the family Hyperoliidae. It is endemic to Democratic Republic of the Congo. Its natural habitats are subtropical or tropical moist lowland forests, swamps, freshwater marshes, and intermittent freshwater marshes. References Schiøtz, A. 2004. Hyperolius ferrugineus. 2006 IUCN Red List of Threatened Species. Downloaded on 22 July 2007. ferrugineus Category:Endemic fauna of the Democratic Republic of the Congo Category:Amphibians described in 1943 Category:Taxonomy articles created by Polbot	{ "pile_set_name": "Wikipedia (en)" }
1. Introduction {#s0005} =============== Tarlov cysts are perineural fluid-filled sacs that are usually found in the lumbosacral spine around the junction of peripheral nerve roots and the respective dorsal root ganglia. The cysts are extradural meningeal cysts with collections of cerebrospinal fluid (CSF) within the nerve root sheath \[[@bb0005]\]. Tarlov cysts are found in roughly 1%--5% of the general population. \[[@bb0010],[@bb0015]\]. Interestingly, some studies have demonstrated that women account for 59%--70% of cases \[[@bb0010],[@bb0020]\]. Symptomatic Tarlov cysts are rare but can sometimes grow in size and compress adjacent nerve root structures, leading to localized or radicular pain, bowel and bladder symptoms, or other neurological sequelae. The most common presenting symptoms are back pain, pelvic pain, perineal pain, lumbar radiculopathy, or bowel/bladder symptoms. These are generally exacerbated by maneuvers that raise the CSF pressure such as standing, coughing, sneezing, or straining to void or defecate. Diagnosis is generally done with imaging and magnetic resonance imaging (MRI) is the modality of choice. Tarlov cysts were first described by Tarlov in 1938 as an incidental finding during an autopsy \[[@bb0025]\]. Since then a variety of surgical and non-surgical interventions have been described for the treatment of Tarlov cysts. Unfortunately, there is a high rate of complications associated with surgical treatment of these cysts including hemorrhage, neurological deficit, CSF leak, infection, chronic pain, and cyst recurrence. A systematic review of surgical and non-surgical management of Tarlov cysts demonstrated a 21% and 12.47% complication rate respectively. There was a higher rate of transient sciatica, CSF-related complications, and bladder/bowel complications. Interestingly, both groups reported symptomatic improvement in 83.5% of patients. Transient exacerbation of symptoms and cyst recurrence was noted to be higher in non-surgically managed groups, suggesting surgical management is associated with higher postprocedural complication rates but better long-term efficacy for symptoms and cyst resolution \[[@bb0030]\]. Given the rarity of the condition and the high complication rates associated with surgical management, there is currently no consensus regarding the best treatment for patients who are symptomatic. We describe a patient who had a longstanding history of chronic pelvic pain secondary to multiple sacral Tarlov cysts. She underwent surgery for her condition, but it worsened her symptoms and the patient ultimately obtained relief with the use of a high-frequency spinal cord stimulator (SCS). 2. Case Description {#s0010} =================== The patient was a 66-year-old woman with a longstanding history of chronic pelvic pain secondary to multiple large Tarlov cysts affecting the S1-S4 nerve roots. She had attempted medication management with acetaminophen, NSAIDs, and neuropathic pain medications. She had also undergone a series of epidural steroid injections and a trial of superior hypogastric plexus blocks but obtain minimal relief with these. She ultimately had surgery for the removal of the Tarlov cysts as well as sacral lamina reconstruction ([Fig. 1](#f0005){ref-type="fig"}). However, the patient\'s surgery resulted in worsening of her chronic pelvic pain, and also produced new-onset back pain and lumbar radiculopathy down both legs. The patient reported constant debilitating back and pelvic pain with intermittent stabbing and burning pain in her legs. Her worsening symptoms were uncontrolled with continued medication management as well as a repeat series of epidural steroid injections.Fig. 1Lumbosacral MRI demonstrating post-surgical changes after the patient\'s initial surgery.Fig. 1 Given that the patient\'s worsening symptoms were unrelieved with both medication management and interventional pain procedures, we tried high-frequency spinal cord stimulation for her worsening pain and new-onset radiculopathy. The patient was counseled regarding the risks and benefits of the procedure and elected to proceed. A spinal cord stimulator lead was introduced into the epidural space and advanced to the superior endplate of T8. A second lead was placed at the superior endplate of T9 ([Fig. 2](#f0010){ref-type="fig"}).Fig. 2Fluoroscopic imaging demonstrating SCS lead placement in the posterior epidural space at the superior levels of T8 and T9.Fig. 2 The patient presented for follow-up after the procedure and reported significant improvement in her symptoms. She noted that the use of SCS had resulted in a 90% improvement of her back pain, a 95% improvement in her pelvic pain, and \>50% improvement in her radiculopathy. Additionally, she reported she was much more active and was able to decrease her medication use with the pain relief she obtained from spinal cord stimulation. 3. Discussion {#s0015} ============= Tarlov cysts can be a challenging condition to recognize and diagnose given the rarity of the condition. Although these cysts most commonly affect the sacral nerve roots, they have been found in lumbar, thoracic, and cervical regions as well. The condition is generally asymptomatic. However, a small percentage of patients may demonstrate symptoms related to nerve root compression. Tarlov cysts tend to expand over time and can cause nerve root irritation, leading to pain or other neurological disturbances. There is no consensus on the optimal management of symptomatic Tarlov cysts. Percutaneous cyst drainage is a nonsurgical intervention has been used to treat this condition \[[@bb0015]\]. This treatment is only temporary though, as cysts tend to gradually reform and symptoms recur. In addition to percutaneous drainage, one study has demonstrated that cyst aspiration with the placement of fibrin glue can prevent recurrence of the cysts. However, these patients are also at significant risk for postprocedural aseptic meningitis \[[@bb0035]\]. Surgical treatment of symptomatic cysts varies and can involve complete cyst removal with excision of the affected posterior root and ganglion, decompressive laminectomy, cyst wall resection, and cyst fenestration \[[@bb0040], [@bb0045], [@bb0050], [@bb0055]\]. The success and complication rates vary greatly by procedure. Again, there is no consensus regarding when surgical management for Tarlov cysts is warranted, though one study suggested that cysts larger than 1.5 cm with associated radicular pain or bowel/bladder dysfunction may benefit the most from surgical intervention \[[@bb0050]\]. We recommend that patients presenting with symptomatic Tarlov cysts diagnosed by imaging should initially undergo conservative management with medication management, including acetaminophen, nonsteroidal anti-inflammatory drugs, and neuropathic pain medications such as gabapentin. Additionally, patients may respond to interventional pain procedures such as epidural steroid injections. Surgery should be reserved for patients who fail conservative management, given the high complication rates. We would also like to comment on the success of spinal cord stimulation in this patient. SCS has been proven to be effective for treating intractable neuropathic pain such as lumbar radiculopathy and post-laminectomy syndrome \[[@bb0060], [@bb0065], [@bb0070]\]. There is also growing evidence that SCS can even be helpful for treating debilitating chronic visceral pelvic pain \[[@bb0075]\]. We believe this case is of importance as it describes the complicated management of patients with symptomatic Tarlov cysts who ultimately fail to respond to conservative therapy. We also describe the use of SCS in this patient and the benefit it can provide for patients who are suffering from severe radiculopathy after surgery as well as those with chronic pelvic pain ([Fig. 3](#f0015){ref-type="fig"}).Fig. 3An example of an implantable high-frequency spinal cord stimulator system showing the percutaneous leads and implantable pulse generator.Fig. 3 4. Conclusion {#s0020} ============= Tarlov cysts are an uncommon condition that present more often in women. This condition rarely becomes symptomatic, producing a variety of neurologic symptoms and painful conditions. Given the rarity of the condition and the high complication rates associated with surgery, there is no clear treatment algorithm for symptomatic patients. These cysts can be managed conservatively or surgically; surgical management has higher complication rates but better long-term results for symptom and cyst resolution. Patients who develop new or worsening pain after Tarlov cyst surgery may benefit from spinal cord stimulation. This case may provide guidance for physicians managing patients suffering from symptomatic Tarlov cysts, or worsening pain symptoms after surgical management of these cysts. Contributors {#s0025} ============ Jamal Hasoon contributed to the drafting, literature review, and critical revision of the article. Amnon A. Berger contributed to the drafting, literature review, and critical revision of the article. Ivan Urits contributed to review and critical revision of the article. Vwaire Orhurhu contributed to review and critical revision of the article. Omar Viswanath contributed to review and critical revision of the article. Musa Aner provided supervision, and contributed to review and critical revision of the article. Conflict of Interest {#s0030} ==================== The authors declare that they have no conflict of interest regarding the publication of this case report. Funding {#s0035} ======= No funding from an external source supported the publication of this case report. Patient Consent {#s0040} =============== Obtained. Provenance and Peer Review {#s0045} ========================== This case report was peer reviewed.	{ "pile_set_name": "PubMed Central" }
(countable, textiles) A wedge-shaped piece of cloth taken out of a garment (such as the waist of a dress) to diminish its circumference. (electronics) a voltage or current applied for example to a transistor electrode (statistics) the difference between the expectation of the sample estimator and the true population value, which reduces the representativeness of the estimator by systematically distorting it (sports) In the game of crown green bowls: a weight added to one side of a bowl so that as it rolls, it will follow a curved rather than a straight path; the oblique line followed by such a bowl; the lopsided shape or structure of such a bowl. The translations below need to be checked and inserted above into the appropriate translation tables, removing any numbers. Numbers do not necessarily match those in definitions. See instructions at Help:How to check translations.	{ "pile_set_name": "Pile-CC" }
Sunday, July 27, 2008 Hi Everyone. I hope you have all had nice weekends. Not much excitement happening around here. Just got home from dad's bbq and watching the Nascar race. Let me tell you, what a boring race. Tire troubles all day long. So disappointing and not much fun. If all the races were like that I'd give up watching it entirely. Can you believe it will be August on Friday? Wow, time has sure flown by this year. Only two more months and it will be Halloween. Tomorrow is just another reminder that I'm getting old so I will forgo talking about it. LOL I really don't have much to say at the moment. Everything is fine here, but not much excitement. I guess I need a little more of that in my life. Rene is working as usual but he will be quitting in about a month to start attending school. He is finally using his GI bill which is good. He is getting so very tired of retail and he is so intelligent that he is wasting away with it as well. He belongs in a professional career and that is what he aims to do. It will take several years and lots of hard work but he has my full support and I know he has the skill and dedication it takes. On Myspace I am playing this silly game called Mobsters. I'm doing ok I guess but I don't have many people in my "family" and people are whacking me left and right lately. LOL Those gangsters can be so awnry and not very nice, knocking off an innocent angel like me! Well, that is about all for now. Hope your week will be happy ones and any negativity wont be part of your lives. Luv ya! TTFN Your Life Path Number is 8 Your purpose in life is to help others succeed You are both a natural leader and a natural success. You are also a great judge of character.You have a head for business and finance. You know how to make money.A great visionary, you can see gold where other people see nothing. In love, you are very generous - with gifts, time, and guidance. You love to inspire people, but it can be frustrating when they don't understand your vision.Great success comes easily for you. But so does great failure, as you are very reckless.You are confident, and sometimes this confidence borders on arrogance. Sunday, July 20, 2008 Today I want to acknowledge my sweet husband. We have been married for two years now. It seems like just two days ago that we were exchanging our vows to one another. I thought I'd get a head start tonight . . . well it is our anniversary in some parts of the country already LOL. Baby, You make time fly for me, never a dull moment. You are my sunshine. You are the light in my life when darkness sets in. You mean so very much to me and I cherish every moment I spend with you and all the good times we have had and will have together. I'm so proud to be your wife. Happy Anniversary honey. Saturday, July 19, 2008 Hi everyone! I hope you all had good weeks and now that the weekend is here I hope that you will be enjoying some fun! I am going out in a little while with my friends Heather and Valerie. Along with doing our mall shopping, we are planning on going to see The Dark Knight, the latest installment of the Batman series. Heather has this gold pass that will get us in to just about any theatre for any showing of this movie or any other movie. She is so spoiled, and by me being her friend I am as well. So it should be a fun day. I'm sure we will go out to dinner. Poor Rene is working today, but he is planning on doing some guy things with his friends tonight so all is good. The weather here hasn't been too bad. In the mid to upper eighties mostly with low clouds in the morning. I can't believe that it is July 19th already. Our anniversary is Monday and my birthday is next Sunday. Jeez, I'm getting old, this will be my last birthday celebration in my twenties. (Update, this shows you how old I'm getting, I added an extra year to my age, I am only going to be 28 not 29, what a ditz huh? LOL) Nothing more to report on from here. I haven't gotten any Dear Ally requests from anyone . I'm guessing that all of you out there are doing wonderful and have no need for Ally's advice, which I guess is a good thing. But just in case email Ally atCuteallison1980@aol.comand visitDear Ally . Have a happy weekend everyone. Luv ya! TTFN Your Bedroom Personality: Healthy In the bedroom, you are open, honest, and giving.You are the ideal partner in many ways! Anyone is lucky to be with you. You see physical intimacy as an opportunity to grow and connect.You are up for experimentation, but you don't require it. Thursday, July 10, 2008 I thought I'd stop by and say hi. It's been almost a week since I've been in this particular journal. I've been bad and neglected it. Here's a plug . . . Don't forget to stop by Dear Ally and leave a comment or send me an email at Cuteallison1980@aol.com with your question or request for advice from Ally. Me and her are tight so I know she will get it and be reading it. Let's see, how has this week gone. It has been long and a bit on the warm side but that is to be expected since it is Summer. Nothing out of the ordinary has happened. My friend Heather is off for the Summer this year, she usually goes to school, but she wanted a little time out and what miss Princess wants miss Princess gets! LMAO Valerie and her have been spending a lot of time together, which is understandable since Val is staying with her since moving from Texas. If any of you are on myspace, be sure to join my reality show group if you haven't already, and if you have then be sure to go there and participate pretty please. It was nice to see DeAnna so happy on Monday night as she chose Jesse of Jason to be her pick on the Bachelorette. She seems so sweet and I hope they make it work. Hell's Kitchen came to an end on Tuesday night and Christina was chosen by Chef Ramsey as his new executive chef in his restaurant in West Hollywood called London LA. I may have to go there and check it out sometime. The big reality news coming up is that Big Brother 10 starts on Sunday night. I can't wait!! That show is my fave!! Well that is about all for now. I hope you will all have happy Fridays and your weekends will be super special. Luv ya! TTFN You Are Bold When it Counts You don't make a big fuss about getting what you want... unless it's really important to you.Then you're as bold as you want to be. You just go for it! You're often up for a little excitement and adventure. Well, as long as the cost isn't too great.You enjoy risk, but not for it's own sake. Let's just say you've learned a few lessons about risk in your life. Friday, July 4, 2008 Hi Everyone! I just wanted to stop by and Wish you all a Wonderful and Happy . . . Safe and Sane Fourth of July! Happy Birthday America!! Land of the Free and Home of the Brave! Those words should never be taken lightly since many nations don't allow their citizens to be free and where they may have courage, our country has been filled with so many Brave people throughout our history. Enjoy your day, your family, the fireworks and remember that you live in the greatest nation on the face of the Earth. God Bless the United States of America! Thank you to Emmi and Donna for the wonderful tags provided in this entry, you two are truly talented and loved! Remember that I do have another journal that is just waiting for anyone that would life advice whether it be for something important or maybe even something rather silly. Please visit Dear Ally and email me with your questions at Cuteallison1980@aol.com What Your These Fireworks Say About You You are focused, single minded, and intense. You don't let others see your intensity often, and when they do, they are quite surprised. You burn brightly, but you also burn steadily.You have the endurance to get the one thing you desire most. Hug I got the nicest compliment from the sister of a friend and I thought I'd share it with you. It is simple but sweet."God my sister is so smart she told me just the other day that talking to you is like a big friendly hug, she's so right, it is."That is all I have ever wanted to be reckognized as, a sweet caring person that is happy to be there for people. Thank you so much Kacey and Deb! Carrie Underwood (Click to go to her official website) My Fave, Love her, love her, love her! A Little About Me My name is Allison, no duh huh, I am sure you figured that out already. LOL I'm 28 years old, and I live in California. I enjoy being here in what I call Bloggerville. It was sad to see AOL Journals leave but I think this place is better suited for our wonderful community. I hope you enjoy your stay here and I look forward to visiting your blogs as well. If I haven't been by lately please let me know. Have a happy day everyday. Luv ya!	{ "pile_set_name": "Pile-CC" }
General condition biomarkers in relation to contaminant burden in European flounder (Platichthys flesus). In respect to the differences found for vitellogenin (VTG) expression in male and immature flounder, general biological aspects and a set of chemical residues in the liver were compared between flounder from the Mersey and Dee estuaries (UK). Except for alpha-HCH, all pollutant chemicals analysed in flounder liver differed highly significantly between Mersey and Dee fish. Overall, the higher liver contaminant concentrations were found in VTG-induced Mersey flounder. The biomarkers studied were not found to indicate significant differences between Mersey and Dee fish. However, when all of the minor differences are taken into consideration, it appears that the slightly lower growth rates after age 2 in Mersey flounder, lower gonadosomatic index in both mature male and female animals, less precise seasonal patterns of condition factor (CF), hepatosomatic index and gonadosomatic index, and lower CF in immature Mersey fish may well be signs of a contaminant-affected Mersey population.	{ "pile_set_name": "PubMed Abstracts" }
Additional InformationDriving license: category B, CWillingness to travel: YesReferences and links: produce on demandKey skills and achievements:Trained, highly motivated (because of this self-understood in many industrial processes).Sociability, mobility, responsibility, analytical mind.I have experience in automation, not only by design but also understand the actuator.Classes in the spare time I conduct an active way of life, play tennis, no bad habits. A short list of projects:FSUE “NIISK” project pilot plant 3,4-polyisoprene (3,4-PI) and isoprene-styrene copolymer (TPE-IS). Distributed Control System (DCS and ESD), is based on the software and hardware complex Siemens Simatic (S7-300). LLC “Kraft Foods Rus”, St. PetersburgThe automated system of technical registration of electricity (ASTUE). The system is based on software and hardware company Siemens (multifunctional measuring instruments Sentron PAC3200, Simatic WinCC, Simatic WinCC Powerrate Add-On). JSC “Confectionery Factory Krupskaya”, St. PetersburgAutomated feeding system of the masses in the casting bath stations. The system is based on software and hardware complex Siemens Simatic (S7-1200). JSC “Russian Railways”, railcar depot St. Petersburg-Moscow (PM-10) PCS boiler with 3 boilers, designed for maintenance of buildings territory railcar depot Metallostroy JSC “Russian Railways”. The system is built on the basis of program-technical complex PTK “Kontarev” production of “MZTA.”JSC “Rosengineering” Sochi Combined complex for competitions in cross-country skiing and biathlon, mountain Olympic village (1100 seats). The fourth stage of construction. Development of the project of automation of individual heating units. LLC “NTFF” POLYSAN “, Leningrad RegionDevelopment of the project of automation of the processing of industrial waste water of the second start-up complex of the enterprise for the production of drugs. JSC “Flotenk”, St. PetersburgThe TNC winder with horizontal bed. The system is based on software and hardware complex Siemens Simatic (S7-200). JSC “Ust-Luga” in Kingisepp, Leningrad region“Development of Commercial Sea Port of Ust-Luga. The base provides fleet in Ust-Luga “sections:– Heating and ventilation of buildings and structures– Automation and control of engineering systems– Refueling point. JSC “OMZ” (Izhora Plants) KolpinoProject development of the automated process control system in a thermal electric SDS-90.140.80 / 10,5-500l1. The system is based on software and hardware complex Siemens Simatic (S7-300).Ltd. “KINEF”, Leningrad RegionDevelopment of the project of automation systems engineering central laboratory and many other projects.	{ "pile_set_name": "Pile-CC" }
Hatamabad, Markazi Hatamabad (, also Romanized as Ḩātamābād) is a village in Farmahin Rural District, in the Central District of Farahan County, Markazi Province, Iran. At the 2006 census, its population was 39, in 20 families. References Category:Populated places in Farahan County	{ "pile_set_name": "Wikipedia (en)" }
<?php defined('BX_DOL') or die('hack attempt'); /** * Copyright (c) UNA, Inc - https://una.io * MIT License - https://opensource.org/licenses/MIT * * @defgroup UnaCore UNA Core * @{ / class BxDolModuleQuery extends BxDolDb implements iBxDolSingleton { protected function __construct() { if (isset($GLOBALS['bxDolClasses'][get_class($this)])) trigger_error ('Multiple instances are not allowed for the class: ' . get_class($this), E_USER_ERROR); parent::__construct(); } /* * Prevent cloning the instance / public function __clone() { if (isset($GLOBALS['bxDolClasses'][get_class($this)])) trigger_error('Clone is not allowed for the class: ' . get_class($this), E_USER_ERROR); } /* * Get singleton instance of the class / public static function getInstance() { $sClass = __CLASS__; if(!isset($GLOBALS['bxDolClasses'][__CLASS__])) $GLOBALS['bxDolClasses'][__CLASS__] = new $sClass(); return $GLOBALS['bxDolClasses'][__CLASS__]; } function getModuleById($iId, $bFromCache = true) { $sSql = $this->prepare("SELECT FROM `sys_modules` WHERE `id`=? LIMIT 1", $iId); return $bFromCache ? $this->fromMemory('sys_modules_' . $iId, 'getRow', $sSql) : $this->getRow($sSql); } function getModuleByName($sName, $bFromCache = true) { $sSql = $this->prepare("SELECT * FROM `sys_modules` WHERE `name`=? LIMIT 1", $sName); return $bFromCache ? $this->fromMemory('sys_modules_' . $sName, 'getRow', $sSql) : $this->getRow($sSql); } function getModuleByUri($sUri, $bFromCache = true) { $sSql = $this->prepare("SELECT * FROM `sys_modules` WHERE `uri`=? LIMIT 1", $sUri); return $bFromCache ? $this->fromMemory('sys_modules_' . $sUri, 'getRow', $sSql) : $this->getRow($sSql); } function enableModuleByUri($sUri) { $sSql = $this->prepare("UPDATE `sys_modules` SET `enabled`='1' WHERE `uri`=? LIMIT 1", $sUri); return (int)$this->query($sSql) > 0; } function disableModuleByUri($sUri) { $sSql = $this->prepare("UPDATE `sys_modules` SET `enabled`='0' WHERE `uri`=? LIMIT 1", $sUri); return (int)$this->query($sSql) > 0; } function setModulePendingUninstall($sUri, $bPendingUninstall) { $sSql = $this->prepare("UPDATE `sys_modules` SET `pending_uninstall` = ? WHERE `uri` = ? LIMIT 1", $bPendingUninstall ? 1 : 0, $sUri); return $this->query($sSql); } function isModule($sUri) { $sSql = $this->prepare("SELECT `id` FROM `sys_modules` WHERE `uri`=? LIMIT 1", $sUri); return (int)$this->getOne($sSql) > 0; } function isModuleByName($sName) { $sSql = $this->prepare("SELECT `id` FROM `sys_modules` WHERE `name`=? LIMIT 1", $sName); return (int)$this->getOne($sSql) > 0; } function isModuleParamsUsed($sUri, $sPath, $sPrefixDb, $sPrefixClass) { $sSql = "SELECT `id` FROM `sys_modules` WHERE `uri`='" . $sUri . "' \|\| `path`='" . $sPath . "' \|\| `db_prefix`='" . $sPrefixDb . "' \|\| `class_prefix`='" . $sPrefixClass . "' LIMIT 1"; return (int)$this->getOne($sSql) > 0; } function isEnabled($sUri) { $sSql = $this->prepare("SELECT `id` FROM `sys_modules` WHERE `uri`=? AND `enabled`='1' LIMIT 1", $sUri); return (int)$this->getOne($sSql) > 0; } function isEnabledByName($sName) { $sSql = $this->prepare("SELECT `id` FROM `sys_modules` WHERE `name`=? AND `enabled`='1' LIMIT 1", $sName); return (int)$this->getOne($sSql) > 0; } function getModules() { $sSql = "SELECT * FROM `sys_modules` ORDER BY `title`"; return $this->fromMemory('sys_modules', 'getAll', $sSql); } function getModulesBy($aParams = array(), $bFromCache = true) { $aMethod = array('name' => 'getAll', 'params' => array(0 => 'query')); $sPostfix = $sWhereClause = $sOrderByClause = ""; $aBindings = array(); switch($aParams['type']) { case 'type': if(!is_array($aParams['value'])) $aParams['value'] = array($aParams['value']); $sPostfix .= '_type_' . implode('_', $aParams['value']); $sWhereClause .= " AND `type` IN (" . $this->implode_escape($aParams['value']) . ")"; break; case 'modules': $sPostfix .= '_modules'; $aBindings['type'] = BX_DOL_MODULE_TYPE_MODULE; $sWhereClause .= " AND `type`=:type"; break; case 'languages': $sPostfix .= '_languages'; $aBindings['type'] = BX_DOL_MODULE_TYPE_LANGUAGE; $sWhereClause .= " AND `type`=:type"; break; case 'templates': $sPostfix .= '_templates'; $aBindings['type'] = BX_DOL_MODULE_TYPE_TEMPLATE; $sWhereClause .= " AND `type`=:type"; break; case 'path_and_uri': $sPostfix .= '_path_and_uri_' . $aParams['path'] . '_' . $aParams['uri']; $aMethod['name'] = 'getRow'; $aBindings = array_merge($aBindings, array( 'path' => $aParams['path'], 'uri' => $aParams['uri'] )); $sWhereClause .= " AND `path`=:path AND `uri`=:uri"; break; case 'all_pairs_name_uri': $sPostfix .= 'all_pairs_name_uri'; $aMethod['name'] = 'getPairs'; $aMethod['params'][1] = 'name'; $aMethod['params'][2] = 'uri'; break; case 'all': break; } if(isset($aParams['active'])) { $sPostfix .= "_active"; $aBindings['enabled'] = (int)$aParams['active']; $sWhereClause .= " AND `enabled`=:enabled"; } $sOrderByClause = " ORDER BY " . (isset($aParams['order_by']) ? $aParams['order_by'] : '`title`'); $aMethod['params'][0] = "SELECT `id`, `type`, `name`, `title`, `vendor`, `version`, `help_url`, `path`, `uri`, `class_prefix`, `db_prefix`, `lang_category`, `date`, `enabled` FROM `sys_modules` WHERE 1 " . $sWhereClause . $sOrderByClause; $aMethod['params'][] = $aBindings; if(!$bFromCache \|\| empty($sPostfix)) return call_user_func_array(array($this, $aMethod['name']), $aMethod['params']); return call_user_func_array(array($this, 'fromMemory'), array_merge(array('sys_modules' . $sPostfix, $aMethod['name']), $aMethod['params'])); } function getModulesUri() { return $this->fromMemory('sys_modules_uri', 'getColumn', 'SELECT `uri` FROM `sys_modules` ORDER BY `uri`'); } function getDependent($sName, $sUri) { return $this->getAll("SELECT `id`, `title`, `enabled` FROM `sys_modules` WHERE (`dependencies` LIKE " . $this->escape('%' . $sName . '%') . " OR `dependencies` LIKE " . $this->escape('%' . $sUri . '%') . ") AND `enabled`='1'"); } public function updateModule($aParamsSet, $aParamsWhere = array()) { if(empty($aParamsSet)) return false; $sWhereClause = !empty($aParamsWhere) ? $this->arrayToSQL($aParamsWhere, " AND ") : "1"; $sSql = "UPDATE `sys_modules` SET " . $this->arrayToSQL($aParamsSet) . " WHERE " . $sWhereClause; return $this->query($sSql); } } /** @} */	{ "pile_set_name": "Github" }
Human airway epithelia function in barrier formation, defense against pathogens, and mucociliary clearance ([@b11-ehp-119-784]). They represent the first barrier against airborne environmental pollutants, and they coordinate recruitment of pivotal inflammatory cells in several pathologies, including chronic obstructive pulmonary disease (COPD) ([@b14-ehp-119-784]; [@b17-ehp-119-784]; [@b30-ehp-119-784]). The inhalation of diesel exhaust particles (DEP), produced by vehicular traffic contributing to urban smog, leads to serious respiratory diseases (e.g., COPD, emphysema, bronchial cancer, chronic asthma) ([@b28-ehp-119-784]). The particles' carbonaceous cores are coated with thousands of organics and heavy metals. Because large numbers of hazardous chemicals are present on DEP, its pathological effects on human airways are pleiotropic. We and others have found that DEP evokes the secretion of matrix metalloproteinase-1 (MMP-1) from human bronchial epithelia ([@b3-ehp-119-784]; [@b14-ehp-119-784]). Matrix metalloproteinase-1 (MMP-1) plays a role in tissue remodeling during development, inflammation, migration of inflammatory and malignant cells, and COPD and emphysema pathogenesis ([@b22-ehp-119-784]). It also has neurotropic effects, possibly enhancing sensitization of airway-innervating sensory neurons, contributing to airway hypersensitization and chronic cough ([@b6-ehp-119-784]). We recently identified a novel pathway that results in DEP-induced MMP-1 activation and entails activation of RAS-RAF-MEK-extracellular signal--regulated kinase (ERK) signaling, dependent on β-arrestins ([@b14-ehp-119-784]). From a global health perspective, one important finding was that the human MMP-1 polymorphism at position −1607(1G/2G) of the MMP-1 promoter yielded, after DEP exposure, either a diminutive (1G) or large (2G) response. The 2G polymorphism is found in 75% of humans. Against this background, we sought to identify critical elements upstream of RAS in human airways in response to DEP. The pathogenic component of DEP that activates MMP-1 is primarily retained in its organic extract (OE), such that DEP carbonaceous core particles shuttle water-insoluble OE to the ciliary plasma membrane. The DEP/OE initially activates proteinase-activated receptor 2 (PAR-2), which, via G~i/o~ G-protein, phospholipase-Cβ3 (PLCβ3), and phosphatidylinositol 3 kinase (PI3-K), activates Ca^2+^-permeable TRPV4 (transient receptor potential vanilloid, family member 4) ion channels ([@b15-ehp-119-784]; [@b16-ehp-119-784]; [@b25-ehp-119-784]; [@b26-ehp-119-784]). A uniquely protracted Ca^2+^ influx through TRPV4 follows, which is critical for mitogen-activated protein kinase (MAPK)--mediated MMP-1 activation. Localization studies show that PAR-2, PLCβ3, and TRPV4 colocalize to cilia of human differentiated airway epithelia. DEP exposure greatly enhances protein--protein complex formation between these signaling molecules and calmodulin. Importantly, we observed that TRPV4~P19S~, a human genetic polymorphism previously identified as a COPD susceptibility locus ([@b32-ehp-119-784]), increases MMP-1 activation via increased Ca^2+^ influx, providing a mechanistic link between human airway epithelia signaling, airway disease, and air pollution. Materials and Methods ===================== DEP --- Particles were generated at the U.S. Environmental Protection Agency (EPA; Research Triangle Park, NC) from a Deutz four-cylinder diesel engine, running at three defined engine loads before collection, as described previously ([@b14-ehp-119-784]). For experiments, we used DEP at 100 μg/mL. DEP organic extract (OE) was prepared by washing organic chemicals off of DEP using methylene chloride, followed by solvent exchange with dimethyl sulfoxide (DMSO). In experiments, we used 20 μg/mL OE, which is equivalent to the organic compounds contained in 100 μg DEP. We used Degussa Printex 90 carbon nanospheres (P90; provided by W. Moeller, GSF, Munich, Germany) as controls. Chemicals --------- We used the following compounds: pertussis toxin (G~i/o~ inhibitor; Sigma Chemical Co., St. Louis, MO), U73122 (PLC inhibitor; Tocris, Ellisville, MO), LY294002 and PI828 (PI3-K inhibitors; Tocris), 4α-phorbol 12,13 didecanoate (4α-PDD; TRPV4 activator; Tocris), GSK205 \[TRPV4 blocker ([@b19-ehp-119-784])\], ruthenium red \[TRP(V) blocker; Tocris\], gadolinium(III) chloride \[GdCl~3~ (Sigma); inhibitor of store-operated calcium entry (SOCE) at 5 μM ([@b4-ehp-119-784])\], thapsigargin (Ca^2+^-store depletion; Tocris), GM1489 and Z-PDLDA-NHOH (pan-MMP inhibitors; Endogen, Rockford, IL), and W-7 (calmodulin blocker at 10 μM; Sigma). Cell culture ------------ BEAS-2B cells were obtained from ATCC (Rockville, MD), maintained as previously described ([@b14-ehp-119-784]), and used for stimulation with DEP or OE and for all DNA and small interfering RNA (siRNA) transfection experiments. Primary human bronchial epithelial (HBE) cells were tracheobronchial cells derived from healthy, nonsmoking adult volunteers. We obtained institutional review board approval for this study from the participating institutions, and volunteer donors provided informed consent for use of the cells in research. Additional details on cell culture are available in Supplemental Material (doi:10.1289/ehp.1002807). MMP-1 reporter gene assays were conducted as described previously ([@b14-ehp-119-784]). A set of MMP-1 promoters of different lengths was available for both human polymorphisms, −1607G and −1607GG. siRNA was transfected into BEAS-2B cells following previously published methods ([@b14-ehp-119-784]). siRNA was directed against PAR-2, PAR-1, β-arrestins 1 and 2, and TRPV4. Scrambled controls were used as provided by the manufacturer (Dharmacon, Lafayette, CO). siRNA efficiency was confirmed by quantitative reverse-transcriptase polymerase chain reaction (PCR) and Western blotting. TRPV3 and TRPV4 dominant-negative (DN) isoforms were generated by isolating a truncated form of each channel, from 10 amino- acids N-terminal to the fifth transmembrane domain to 10 amino-acids C-terminal to the sixth transmembrane domain. In addition, two point mutations were generated as M680K and D682K for TRPV4 and as L619K and D621K for TRPV3 in order to render the channel fragments Ca^2+^ impermeable. Both of these constructs were C-terminally fused to monomeric red fluorescent protein (RFP). Dominant-negative isoforms of STIM1 and ORAI1, -2 and -3 were provided by L. Birnbaumer and S. Muallem. These cDNAs were driven by CMV promoters in eukaryotic expression plasmids, the coding region fused to eGFP. DN-STIM1 and DN-ORAI1-3 have been shown to specifically interfere with function of their cognate wildtype isoforms and inhibit them. Enzyme-linked immunosorbent assays (ELISAs) for MMP-1, RANTES (regulated on activation, normal T-expressed and secreted), and IP-10 (interferon-γ--induced protein 10 kDa, CXCL10) were conducted using commercially available kits. For MMP-1 secretion, we previously demonstrated its correlation to the specific proteolytic activity of MMP-1 ([@b14-ehp-119-784]). Ca^2+^ imaging of BEAS-2B cells was conducted using 2 μM fura-2 acetoxymethyl ester for loading and following a protocol for ratiometric Ca^2+^ imaging using 340/380 nm blue light for dual excitation, recording emissions with specific filter sets. Ratios of the emissions were acquired every 5 sec. ΔR/R~0~ is the fraction of the increase of a given ratio over the baseline ratio, divided by baseline ratio. For stimulation of cells with DEP, we used particles at 100 μg/mL and analyzed only cells with microscopically verified contact with particles. For stimulation with OE, all cells were analyzed. To stimulate TRPV4, hypotonicity was used at 260 mOsmol/L, and 4α-PDD at 10 μM; Ca^2+^ stimulation was accomplished by switching from 0 to 2 mM. Ca^2+^ imaging of primary HBE cells was conducted by excising the air--liquid interface matrix with a scalpel and affixing it to the opening of a glass-bottom dish, with other procedures as for BEAS-2B cells. Electrophysiological recordings ------------------------------- Extracellular Ca^2+^ was precipitated by addition of EGTA. We conducted PI3-K Förster resonance energy transfer (FRET) imaging based on FRET of membrane-targeted enhanced green fluorescent protein (eGFP; donor) and the pleckstrin homology domain of Bruton's tyrosine kinase, fused to mCherry fluorescent protein (acceptor). With low phosphatidylinositol (3,4,5)-trisphosphate (PIP3) levels, the mCherry is cytoplasmic; with increased PIP3 levels, it translocates to the membrane leading to FRET, which we quantified using two-photon fluorescence lifetime imaging. Additional details for electrophysiological recordings are given in Supplemental Material (doi:10.1289/ehp.1002807). The phosphorylated ERK (phospho-ERK) trafficking assay was performed as described previously ([@b14-ehp-119-784]). Briefly, BEAS-2B cells were stimulated either with DEP or with OE and fixed (4% paraformaldehyde) at 5-, 10-, 20-, and 30-min time points. Phospho-ERK~1/2~ was verified by fluorescent immunodetection and quantified densitometrically (≥ 75 cells/time point), corrected for background, in the nuclear area using ImageJ software (version 1.42q; [@b20-ehp-119-784]). Confocal imaging was conducted after immunocytochemical staining for acetylated α-tubulin, PLCβ3, TRPV4, and PAR-2. Fluorescently labeled sections were visualized using a Zeiss LSM710 confocal imaging suite with lasers tuned to the emission spectra of the secondary fluorescent antibodies. Coimmunoprecipitation studies were conducted using 10^6^ BEAS-2B cells per experiment; cells were harvested in lysis buffer (1% NP40 detergent). Exactly 100 μg protein was incubated with rabbit anti--PLC-β3, rabbit anti-TRPV4, or mouse monoclonal anti--PAR-2 overnight at 4°C, and then solutions were exposed to 15 μL protein-A/G-Sepharose for 4 hr (4°C). After stringency washing, complexes were investigated by Western blotting using antibodies specific for TRPV4, PAR-2, or calmodulin. Normal rabbit or mouse isotype antibodies were used as controls. Western blotting was performed following standard methodology with chemoluminescence detection. Statistical analysis -------------------- We compared mean and SE of quantified outcome parameters after stimulation with their respective controls. Group comparisons were performed using Student's t-test or analysis of variance with post hoc Scheffe test for multigroup comparison, applying the statistics program StatPlus:mac (AnalystSoft, Vancouver, British Columbia, Canada). Minimum significance was set at p \< 0.05. Results ======= The OE of DEP contains the active component to activate MMP-1 --------------------------------------------------------------- To understand which component(s) of DEP activate MMP-1, we investigated effects of DEP and its OE in human BEAS-2B and primary HBE cells, the latter exposed at air--liquid interface \[see Supplemental Material, Figure 1 (doi:10.1289/ehp.1002807)\]. Our findings suggest that the carbonaceous core of DEP, by size a carbon nanoparticle, acts as a vehicle carrier for delivery of the highly active, water-insoluble organic fraction to the plasma membrane of human airway epithelia to elicit MMP-1 activation. Extracellular Ca^2+^ influx is necessary for activation of MMP-1 ------------------------------------------------------------------ Previous studies in lung cells and neurons have shown that particulate matter evokes Ca^2+^ transients ([@b1-ehp-119-784]); other studies have shown that Ca^2+^ increases activated RAS ([@b13-ehp-119-784]) and that DEP activates RAS ([@b14-ehp-119-784]). Therefore, we examined whether DEP and/or OE causes Ca^2+^ influx and whether this can activate MMP-1. We found that DEP and OE evoke extracellular Ca^2+^ influx ([Figure 1A--D](#f1-ehp-119-784){ref-type="fig"}), as indicated by curtailing of the response by addition of EGTA ([Figure 1C,D](#f1-ehp-119-784){ref-type="fig"}). P90 control carbon nanoparticles had no effect on Ca^2+^ ([Figure 1B](#f1-ehp-119-784){ref-type="fig"}), whereas DEP activated a uniquely protracted and monotonically increasing response with a peak at approximately 60 min that gradually declined (data not shown). In comparison, the response to OE increased more rapidly, reaching a maximum at approximately 20 min and decreasing to baseline in the next 10 min ([Figure 1B](#f1-ehp-119-784){ref-type="fig"}), indicating that the particle core retarded Ca^2+^ influx by slowing delivery of the organic fraction to the plasma membrane. To determine whether DEP-induced Ca^2+^ influx was necessary for transcriptional activation of MMP-1, we exposed cells to DEP in the presence and absence of extracellular Ca^2+^ and measured MMP-1 transcriptional activation at 2 and 24 hr and the appearance of nuclear phospho-ERK at 30 min ([Figure 1E--I](#f1-ehp-119-784){ref-type="fig"}). These experiments indicated that extracellular Ca^2+^ was necessary for both nuclear translocation of phospho-ERK and MMP-1 activation in response to DEP or OE. In primary HBE cells, EGTA eliminated MMP-1 secretion in response to DEP or OE ([Figure 1H](#f1-ehp-119-784){ref-type="fig"}), thus confirming the validity of this mechanism. We were unable to demonstrate functionality of SOCE in DEP/OE--evoked Ca^2+^ influx \[see Supplemental Material, Figure 2A--C (doi:10.1289/ehp.1002807)\]. Preincubation with 5 μM thapsigargin or 5 μM GdCl~3~ ([@b4-ehp-119-784]) did not markedly change DEP-evoked Ca^2+^ increase. Furthermore, cotransfection of STIM1-DN and ORAI1-3--DN, both known to function in SOCE, did not significantly alter Ca^2+^ responses evoked by DEP or OE. Finally, we found that DEP and OE also caused the Ca^2+^-dependent secretion of proinflammatory mediators RANTES ([@b12-ehp-119-784]) and IP-10 ([@b29-ehp-119-784]) \[see Supplemental Material, Figure 2D,E (doi:10.1289/ehp.1002807)\]. Thus, in human lung cells, Ca^2+^ influx is necessary for DEP/OE--evoked activation of MMP-1, IP-10, and RANTES. PAR-2 is a DEP-sensitive G-protein--coupled receptor (GPCR) that activates G~i/o~, PLCβ3, and PI3-K --------------------------------------------------------------------------------------------------- We focused on PAR-2 because an earlier low-throughput proteomics screen revealed that, compared with DEP alone, DEP plus PAR-2--activating peptide (PAR-2-AP) increased MMP-1 secretion (data not shown). We first conducted experiments in BEAS-2B cells by siRNA-mediated knockdown of PAR-2. PAR-2 mRNA was significantly reduced by PAR-2 siRNA but not by the scrambled control \[see Supplemental Material, Figure 3A (doi:10.1289/ehp.1002807)\]. Cells treated with PAR-2 siRNA exhibited significantly reduced Ca^2+^ influx, MMP-1 reporter gene activation, and MMP-1 secretion ([Figure 2A](#f2-ehp-119-784){ref-type="fig"}; see also Supplemental Material, Figure 3B,C). This demonstrates that PAR-2 functions upstream of Ca^2+^-mediated MMP-1 activation. In addition to scrambled siRNA controls, PAR-1--specific siRNA had no effect on MMP-1 activation (data not shown). Costimulation of BEAS-2B and primary HBE cells with DEP or OE and PAR-2-AP potentiated MMP-1 activation \[[Figure 2B](#f2-ehp-119-784){ref-type="fig"}; see also Supplemental Material, Figure 3D,E (doi:10.1289/ehp.1002807)\]. To boost its moderate expression level in BEAS-2B cells, we overexpressed PAR-2. This led to increased baseline and DEP-evoked MMP-1 activation, indicating that PAR-2 overexpression is sufficient to increase MMP-1 expression and to render the cell more responsive to DEP (see Supplemental Material, Figure 3F). Thus, specific activation and inhibition of PAR-2 imply that this receptor is critical in DEP-mediated Ca^2+^ influx that leads to MMP-1 activation. We next investigated whether secreted MMP-1 activates PAR-2 proteolytically, as it does for PAR-1 ([@b5-ehp-119-784]), which might explain the protracted Ca^2+^ influx in response to DEP. This was not the case, because MMP inhibitors accelerated MMP-1 reporter gene activity in response to DEP \[see Supplemental Material, Figure 3G (doi:10.1289/ehp.1002807)\]. We addressed whether β-arrestins are necessary for PAR-2--mediated Ca^2+^ influx in response to DEP or OE ([@b7-ehp-119-784]). This was not the case in view of Ca^2+^ increase in the absence of β-arrestins 1 and 2 \[siRNA-mediated knockdown; see Supplemental Material, Figure 3H (doi:10.1289/ehp.1002807)\]. We previously verified elimination of MMP-1 activation by siRNA-mediated β-arrestin knockdown ([@b14-ehp-119-784]). Together, these results implicate β-arrestins as MAPK scaffolds necessary for the DEP--MMP-1 response yet dispensable for PAR-2--mediated Ca^2+^ influx in response to DEP or OE. We examined G~i/o~ signaling because of PAR-2's known signal transduction mechanisms via this G-protein ([@b18-ehp-119-784]). We found that the DEP--MMP-1 response, namely, Ca^2+^ influx, MMP-1 transcription, and MMP-1 secretion, depends on G~i/o~, which we targeted specifically with pertussis toxin in both BEAS-2B and primary HBE cells \[[Figure 2A,B](#f2-ehp-119-784){ref-type="fig"}; see also Supplemental Material, Figure 4A (doi:10.1289/ehp.1002807)\]. Because G~i/o~ is known to activate PLC ([@b8-ehp-119-784]), we next treated cells with PLC-selective inhibitor, U73122, which led to a marked DEP--MMP-1 response ([Figure 2A,B](#f2-ehp-119-784){ref-type="fig"}; see also Supplemental Material, Figure 4B). PLC has several isoforms; we investigated the β-isoforms because of PLCβ's link to GPCRs, specifically PLCβ3, in view of its previously established link to G~i/o~ ([@b23-ehp-119-784]). When we immunolabeled for PLCβ1--4, we found the most robust expression for PLCβ3 in primary HBE cells (data not shown). Interestingly, using a phospho-specific antibody against PLCβ3, we documented phospho-PLCβ3 up-regulation within 30 min after DEP application ([Figure 2C](#f2-ehp-119-784){ref-type="fig"}). This finding can help explain the protracted Ca^2+^ influx because PLCβ3, being upstream of extracellular Ca^2+^ influx, was previously demonstrated to be attenuated by phosphorylation ([@b31-ehp-119-784]). Another phospholipid-metabolizing enzyme that signals downstream of G~i/o~ and upstream of TRP channel Ca^2+^ conductances is PI3-K ([@b33-ehp-119-784]). We identified its critical role in response to DEP or OE using the PI3-K inhibitor LY294002 by documenting significant reduction of Ca^2+^ influx and subsequent MMP-1 activation in both BEAS-2B and primary HBE cells \[[Figure 2D](#f2-ehp-119-784){ref-type="fig"}; see also Supplemental Material, Figure 4C (doi:10.1289/ehp.1002807)\], suggesting the signaling position of PI3-K upstream of Ca^2+^ influx. Moreover, using a novel FRET-based assay, we could visualize the enzymatic activity of PI3-K (change in PIP3) in BEAS-2B cells in response to DEP or OE, which indicated PI3-K activity as an early signaling event ([Figure 2D](#f2-ehp-119-784){ref-type="fig"}). Furthermore, in addition to time-scale resolution after DEP or OE exposure, this method illustrates the confinement of PI3-K signaling to the plasma membrane. TRPV4 forms a DEP-sensitive Ca^2+^ pathway downstream of PI3-K/PLC-β3 --------------------------------------------------------------------- PAR-2 has been shown to sensitize TRP channels, including TRPV1, TRPV4, and TRPA1 ([@b2-ehp-119-784]; [@b9-ehp-119-784]; [@b10-ehp-119-784]). Because TRPV4 is expressed in tracheobronchial epithelia ([@b16-ehp-119-784]), we addressed whether it functions downstream of the above signaling cascade, initially by inhibiting its function in BEAS-2B cells expressing TRPV4-DN \[see Supplemental Material, Figure 5A--C (doi:10.1289/ehp.1002807)\], which produced strong reduction of Ca^2+^ influx in response to DEP yet no reduction for TRPV3-DN ([Figure 3A](#f3-ehp-119-784){ref-type="fig"}). We also knocked down TRPV4 using specific siRNA, which effectively down-regulated TRPV4 mRNA and protein (see Supplemental Material, Figure 5B,C). Compared with the scrambled control, the siRNA-TRPV4 knockdown reduced Ca^2+^ influx in response to DEP or OE ([Figure 3B](#f3-ehp-119-784){ref-type="fig"}). Thus, TRPV4 is necessary for DEP-evoked Ca^2+^ influx. Next we addressed whether DEP-evoked, TRPV4-mediated Ca^2+^ influx activates MMP-1. Using MMP-1 reporter assays, we found that TRPV4-specific siRNA decreased MMP-1 transcriptional activation, thus implying that TRPV4 is critical for DEP/OE--evoked Ca^2+^ influx, which then activates MMP-1 \[see Supplemental Material, Figure 5D (doi:10.1289/ehp.1002807)\]. Based on these results, we used the MMP-1 reporter platform to determine that TRPV4 functions downstream of PAR-2 because siRNA-mediated TRPV4 knockdown virtually eliminated potentiated MMP-1 activation by DEP or OE plus PAR-2-AP (see Supplemental Material, Figure 5E). This effect of TRPV4-specific siRNA was recapitulated for DEP-evoked MMP-1 secretion in BEAS-2B cells ([Figure 3C](#f3-ehp-119-784){ref-type="fig"}). Finally, we found that ruthenium red, an unspecific TRP(V) blocker, decreased MMP-1 activation (see Supplemental Material, Figure 5F). TRPV4 activation by 4α-PDD or hypotonicity strongly increased MMP-1 secretion, indicating that in airway epithelia, TRPV4 activation is sufficient to up-regulate MMP-1 ([Figure 3D](#f3-ehp-119-784){ref-type="fig"}). Furthermore, TRPV4 transfection in BEAS-2B cells increased MMP-1 reporter activation. Because these findings were obtained in the BEAS-2B cell line, we also tested TRPV4 function in primary HBE cells. First, we were able to significantly attenuate the DEP-evoked Ca^2+^ response by GSK205, a specific small-molecule TRPV4 inhibitor ([@b19-ehp-119-784]), in a dose-dependent manner ([Figure 3E](#f3-ehp-119-784){ref-type="fig"}). In addition, secreted MMP-1 in response to DEP was significantly reduced by two concentrations of GSK205 ([Figure 3F](#f3-ehp-119-784){ref-type="fig"}). Thus, the cornerstones of TRPV4's involvement in the DEP--MMP-1 response, namely, dependence of the Ca^2+^ response and MMP-1 secretion on TRPV4, were recapitulated in primary HBE cells. Whenever possible, we performed the same experiment in human primary HBE cells as in permanent human BEAS-2B cells. Taken together, these findings point toward critical functioning of TRPV4 in Ca^2+^ influx into human airway epithelia evoked by DEP, a globally relevant air pollutant. TRPV4 signaling complex is located on motile cilia of primary human airway epithelia ------------------------------------------------------------------------------------ Because TRPV4 channels have been found in primary motile cilia of mouse tracheal epithelia ([@b16-ehp-119-784]), we determined TRPV4's subcellular location in human ciliated airway epithelia. Primary HBE cells were differentiated in culture until they became ciliated. They showed ciliary location of TRPV4, PAR-2, and PLCβ3 ([Figure 4](#f4-ehp-119-784){ref-type="fig"}). Thus, critical DEP-responsive membrane-bound components all localize to motile cilia of primary human HBE cells. DEP-facilitated recruitment to a membrane-associated receptor-signaling multicomplex ------------------------------------------------------------------------------------ Given the ciliary localization of the DEP-evoked transduction cascade, we asked whether these membrane-associated signaling molecules coaggregate in response to DEP or OE ([Figure 5](#f5-ehp-119-784){ref-type="fig"}). In aggregate, DEP-responsive membrane-bound signaling is characterized by a nonincremental interaction between PLCβ3 and TRPV4, with subsequent recruitment of PAR-2 and calmodulin caused by DEP exposure. Calmodulin's response to DEP is inhibitory, because specific inhibition of calmodulin with W-7 increased Ca^2+^ signaling and MMP-1 activation ([Figure 5B,C](#f5-ehp-119-784){ref-type="fig"}). This suggests as explanatory mechanism(s) an increase in intracellular Ca^2+^ concentration (\[Ca^2+^\]~i~) via disinhibited TRPV4 and/or activation of PLCβ3, both of which have previously been shown to bind calmodulin. COPD-associated TRPV4~P19S~ increases MMP-1 activation in response to DEP or OE --------------------------------------------------------------------------------- For human TRPV4, a number of genetic polymorphisms enhance susceptibility for COPD; one of them, P19S, is located in the coding region ([@b32-ehp-119-784]). In another study, TRPV4~P19S~ was reported as a DN channel in transfected HEK cells in response to weak but not strong hypotonicity ([@b27-ehp-119-784]). Because our finding that DEP-evoked Ca^2+^ influx via TRPV4 causes MMP-1 activation rationalizes airway injury by MMP-1 as caused by TRPV4 channel activity, not by DN channels, we attempted to resolve these seemingly contradictory concepts. Compared with wild-type TRPV4 (TRPV4~wt~), TRPV4~P19S~ exhibited gain-of-function effects in Ca^2+^ influx, patch clamp, MMP-1 reporter gene activation, and MMP-1 secretion \[[Figure 6](#f6-ehp-119-784){ref-type="fig"}; see also Supplemental Material, Figure 6 (doi:10.1289/ehp.1002807)\]. For MMP-1 transcriptional activation, TRPV4~P19S~ gain-of-function effects were strictly dependent on Ca^2+^ influx. This was evidenced by inhibitory effects of TRPV4~P19S/M680K~, where the selectivity-filter-- blocking M680K mutation causes Ca^2+^ impermeability, leading to elimination of gain of function ([Figure 6D](#f6-ehp-119-784){ref-type="fig"}). Furthermore, Ca^2+^ influx in response to changes in Ca^2+^ concentration and to DEP or OE were significantly increased in TRPV4~P19S~ versus TRPV4~wt~, as was nonstimulated \[Ca^2+^\]~i~ \[extracellular Ca^2+^ concentration, 2 mM) ([Figure 6A--C](#f6-ehp-119-784){ref-type="fig"}; see also Supplemental Material, Figure 6). Thus, in a human airway epithelium--derived cell line with robust similarity to primary HBE cells, TRPV4~P19S~ functions as Ca^2+^-permeable gain-of-function channel to hyperactivate the pathogenic mediator gene MMP-1 in response to the common air pollutant DEP. Discussion ========== We identified a novel DEP-activated signaling pathway in human airway epithelia that consists of a GPCR (PAR-2) signaling to a TRP channel (TRPV4). Specific activation of PAR-2 by OE leads to Ca^2+^ influx mediated by TRPV4 channels, via membrane phospholipid signaling involving PLCβ3 and PI3-K. This pathway can be used to develop effective medical therapy for human airway injury caused by airborne particulate pollution, a well-recognized global health problem that contributes to development of COPD and other respiratory illnesses. Regarding COPD, we identified a molecular, cellular, and subcellular mechanism for how the COPD-predisposing nonsynonymous genetic polymorphism TRPV4~P19S~ may potentiate DEP-evoked Ca^2+^ influx and activation of airway-pathogenic MMP-1. A schematic of our findings is presented [Figure 7](#f7-ehp-119-784){ref-type="fig"}. In the context of our results, three qualifiers should be mentioned. First, TRPV4 may not be the only critical Ca^2+^ conductance that is activated. Second, regarding generation of phospholipid molecules with modulatory activity on TRPV4 (e.g., by PI3-K and PLCβ3), we speculate that ratios of active small molecules in the immediate vicinity of the channel are critical for channel function. These two aspects deserve further study. Third, mice do not have an MMP-1--orthologous gene, thus restricting the direct translatability of our findings into a rodent model that is amenable to genetic engineering. The critical participants of the DEP response, PAR-2, PLCβ3, and TRPV4, were localized to motile cilia of differentiated primary human respiratory epithelia. Motile cilia represent a cellular extension that enhances transfer of DEP organics to ciliary membranes via aerogenic exposure, given the enormous increase in cellular surface ([Figure 7A](#f7-ehp-119-784){ref-type="fig"}). This delivery mechanism can be viewed as "slow-release" delivery of organic chemicals from coated particles to lipid membranes. We also intend to address the question of how this novel signaling pathway has been shaped by evolution. PAR-2 signaling, as yet another variant of sensory signaling ([@b21-ehp-119-784]), has evolved in respiratory cilia likely as a sentinel for activation by microbial proteases, such as granzyme and chitinase. PAR-2 signaling thus would have conferred survival benefits in host defenses of airway integrity yet has subsequently been hijacked by man-made air pollution, a detrimental turn that occurred very recently, during the last milliseconds of the evolutionary clock. A recently published landmark report showed that bitter taste receptors and PLCβ2 localized to motile cilia of human primary airway epithelia ([@b24-ehp-119-784]); however, we found a different isoform, PLCβ3, that localized to respiratory cilia. Whether bitter taste receptor--mediated Ca^2+^ increase will trigger a different set of responses compared with PAR-2/TRPV4--mediated Ca^2+^ influx remains to be established. Our results in the present study suggest that TRPV4-mediated Ca^2+^ influx in response to DEP or OE leads to maladaptive, propathogenic reprogramming of gene-regulatory mechanisms in human airway epithelia. In the novel signaling mechanism in human airway epithelia described here, Ca^2+^ influx is characterized by uniquely slow kinetics. Two possible causes for the slow kinetics are a) DEP-dependent PLCβ3 phosphorylation, and b) DEP-enhanced calmodulin binding to a receptor-signaling multiplex containing TRPV4 and PLCβ3 ([Figures 5](#f5-ehp-119-784){ref-type="fig"}, [7](#f7-ehp-119-784){ref-type="fig"}), both of which attenuate signaling via known properties of the modified phospholipase or channel. The attractive hypothesis of proteolytic activation of PAR-2 by MMP-1 has not been not corroborated. This study is relevant for global human health because of the global presence of DEP. However, we also discovered a possibly novel mechanism of airway injury that is caused by DEP yet enhanced by the human COPD-susceptibility polymorphism TRPV4~P19S~. Our identification of TRPV4~P19S~ as a gain-of-function Ca^2+^-permeable channel in a human respiratory epithelial cell line, in response to DEP, links COPD pathogenesis to pathologically increased Ca^2+^ influx into human airway epithelia elicited by a globally relevant air pollutant. Furthermore, our results imply that two human genetic polymorphisms are linked to respiratory health, TRPV4~P19S~ and MMP-1 (−1607G/GG), thus highlighting the concept of disease susceptibility as a function of genetic "makeup" combined with environmental insults. Finally, we note yet another translational medical implication: The novel pathway described here can be targeted by inhalation of compounds that can specifically inhibit critical signaling molecules. In other words, although DEP injures respiratory epithelia via a luminal--apical unloading mechanism of DEP organics delivered by carbonaceous nanoparticles, this very same route could become the avenue for safe and effective therapy now that key participants are known. Supplemental Material is available online (doi:10.1289/ehp.1002807 via <http://dx.doi.org/>). R. Lefkowitz (Duke University) provided invaluable discussions and suggestions regarding signaling and β-arrestin--related reagents, and J. Putney \[National Institute of Environmental Health Sciences (NIEHS)\] provided enlightened discourse on Ca^2+^ entry mechanisms and their pharmacology. The following reagents were kindly supplied by the following colleagues: P90 carbon particles, W. Moeller (GSF, Munich, Germany); MMP-1 reporter gene constructs, C.E. Brinckerhoff (Dartmouth University); dominant-negative ORAI constructs, L. Birnbaumer (NIEHS); and dominant-negative STIM1 construct, S. Muallem (University of Texas Southwestern Medical Center. This research was supported by startup funds from Duke University and financial support from R.J. Reynolds, Inc., to W.L.; by a grant from Philip Morris USA Inc. and Philip Morris International to S.A.S.; and by U.S. Environmental Protection Agency (EPA) internal funds to A.G. Fellowship support for J.L. (Duke University Integrated Toxicology and Environmental Health Program, Leon-Goldberg Fellowship) and S.H.C. (Research Participation Program in U.S. EPA administered by the Oak Ridge Institute for Science and Education) is acknowledged. S.A.S. and W.L. received funding from Philip Morris USA and Philip Morris International, and W.L. received funding from R.J. Reynolds. The other authors declare they have no actual or potential competing financial interests. ![Ca^2+^ influx is required for DEP or OE to evoke MMP-1 secretion. (A) Fura-2 Ca^2+^ imaging in BEAS-2B cells exposed to 100 μg/mL DEP at 0, 30, and 60 min (bar = 20 μm). (B) Ca^2+^ response (ΔR/R~0~ vs. time) to DEP (n = 43), OE (n = 62), and P90 control particles (n = 48 in BEAS-2B cells). Note the protracted time course of the Ca^2+^ signal, in particular with DEP versus OE. (C) Rapid reduction in DEP-induced Ca^2+^ signal in BEAS-2B cells, after the extracellular addition of the Ca^2+^ chelator EGTA (2 mM) (n = 32). (D) In BEAS-2B cells, response to DEP in the absence or presence of extracellular Ca^2+^; note the rapid increase in fluorescence upon addition of 2 mM CaCl~2~ (n = 19). (E) Detection of nuclear phospho-ERK~1/2~ in response to DEP and OE depends on presence of extracellular Ca^2+^ (indicated by the lack of response after OE + EGTA treatment in BEAS-2B cells). Note the statistically significant levels of increase for DEP and OE compared with controls (n ≥ 75 cells for each condition; 30-min time point); two representative micrographs are depicted as insets. (F and G) In BEAS-2B cells, DEP-induced transcriptional activation of MMP-1 depends on external Ca^2+^, as detetermined using 1G and 2G polymorphisms in the firefly luciferase reporter assay (fLUC) at 2-hr (F) and 24-hr (G) time points; note the statistically significant reduction at the 2-hr time point (F) for the --1607GG (2G) polymorphism compared with the --1607G (1G) polymorphism. (H) In BEAS-2B cells, DEP-induced secretion of MMP-1 is eliminated in the presence of 2 mM EGTA. (I) In HBE cells, DEP-induced secretion of MMP-1 is eliminated in the presence of 2 mM EGTA. Note the different y-axis scale in H and I.\ \\p \< 0.01, and ^\#^p \< 0.001.](ehp-119-784f1){#f1-ehp-119-784} ![Signal transduction in response to DEP or OE involves PAR-2, G~i/o~, and PLCβ3. (A) In BEAS-2B cells, Ca^2+^ response (ΔR/R~0~ vs. time) to OE is significantly attenuated with PAR-2 siRNA \[for proof of efficiency, see Supplemental Material, Figure 3A (doi:10.1289/ehp.1002807)\], pertussis toxin (PTX; G~i/o~ inhibitor), the PLC inhibitor U73122, and the PI3-K inhibitor LY294002 (n ≥ 50 cells per condition). (B) In primary HBE cells, modulation of these pathways affects MMP-1 secretion; PAR-2 gain of function potentiates the response, whereas inhibition of G~i/o~, PLC, and PI3-K significantly attenuates/eliminates it. For results in BEAS-2B cells, including PAR-2 gain and loss of function (siRNA), plus all other pathways, see Supplemental Material, Figures 3 and 4 (doi:10.1289/ehp.1002807). (C) Increase in phospho-PLCβ3 in response to DEP shown by representative confocal micrographs of immunolabeled primary HBE cells (top; bar = 5 μm) and densitometry (bottom; n ≥ 50 cells per time point). Results show the phospho-PLCβ3 increase peaking at 30 min and decreasing at 60 min. (D) PI3-K activity in live transfected BEAS-2B cells shown by real-time imaging in response to OE using a novel FRET-based methodology. FRET measurements are shown in micrographs (top; bar = 4 μm), reiterating that PI3-K activity resides in the plasma membrane. The time course of PIP3 generation (bottom) shows that FRET generated by membrane-targeted eGFP and mCherry-tagged pleckstrin homology domain of Bruton's tyrosine kinase increases robustly after application of OE and became significantly attenuated in response to subsequent application of the specific PI3-K inhibitor LY294002 (10 μM). The graph (bottom) shows the time course of the change in PIP3 evoked by OE (quantified at the membrane) and its attenuation by preincubation with another specific PI3-K inhibitor, PI828 (50 μM).\ \*p \< 0.05, and ^\#^p \< 0.001 compared with the 0-min time point.](ehp-119-784f2){#f2-ehp-119-784} ![TRPV4 channels are critical for DEP-evoked MMP-1 activation and function downstream of PAR-2. Abbreviations: +, with; −, without. (A) The DEP-evoked Ca^2+^ response in BEAS-2B cells was significantly and specifically attenuated by inhibition of TRPV4 upon transfection of cells with RFP-tagged TRPV4-DN (n = 33) and unaffected by transfection with TRPV3-DN \[n = 44; see also Supplemental Material, Figure 4A (doi:10.1289/ehp.1002807)\]. (B) TRPV4 loss of function is illustrated by robust inhibition of OE-evoked Ca^2+^ responses in BEAS-2B cells transfected with TRPV4 siRNA compared with transfection with scrambled control siRNA; for proof of efficiency of TRPV4 siRNA, see Supplemental Material, Figure 5B,C. (C) siRNA-mediated TRPV4 knockdown in BEAS-2B cells virtually eliminated MMP-1 activation, thus confirming that TRPV4 functions downstream of PAR-2; note the elimination of MMP-1 secretion in response to DEP or DEP plus PAR-2-AP when TRPV4 is knocked down with TRPV4 siRNA. (D) TRPV4 activation is sufficient to activate MMP-1 hypotonicity (HYPO; 260 mosmol/L) and the specific TRPV4 activator 4α-PDD (10 μM) induced MMP-1 secretion from BEAS-2B cells. (E) Specific inhibition of TRPV4 with GSK205 led to dose-dependent reduction of DEP-evoked Ca^2+^ responses in primary HBE cells. (F) Specific inhibition of TRPV4 with GSK205 led to a significant reduction of DEP-evoked MMP-1 secretion in primary HBE cells; note the increasing effect with increasing dose.\ \*p \< 0.05, \\p \< 0.01, and ^\#^p \< 0.001.](ehp-119-784f3){#f3-ehp-119-784} ![Colocalization of ciliary marker acetylated (Ac) α-tubulin with PLCβ3 (A) or TRPV4 (B), and colocalization of PAR-2 with PLCβ3 (C) or TRPV4 (D) in cilia of primary HBE cells. Columns are as follows: green channel, anti-mouse; red channel, anti-rabbit; the merged image; and the the XZ-series reconstruction. Confocal micrographs are top view for the first three columns, and the XZ-series (fourth column) depicts a schematic rendering of an enlarged lateralized section. Bars = 10 μm. Primary HBE cells in D were not fully differentiated, showing "budding" cilia at the time of immunolabeling. More elongated cilia were present in C, PAR-2 colabeled for PLCβ3, and in A, Ac α-tubulin colabeled for PLCβ3. Nevertheless, A--C suggest that PAR-2 and TRPV4 colocalize to cilia of primary HBE cells.](ehp-119-784f4){#f4-ehp-119-784} ![In BEAS-2 cells, protein--protein complex formation after exposure to DEP involves PAR-2, PLCβ3, TRPV4, and calmodulin (which is functional in DEP-evoked Ca^2+^ influx). (A) Representative Western blots of immunoprecipitation (IP) experiments performed preexposure (Pre) and 30 and 120 min after DEP exposure; for controls, a control antibody was used for IP. With PLCβ3 IP (top three panels), complexes formed containing TRPV4, PAR-2, and calmodulin; after exposure to DEP, the protein--protein interaction increased for PAR-2 and calmodulin. Under Pre conditions, the PLCβ3--calmodulin and PLCβ3--TRPV4 complexes were present and appreciable. With TRPV4 IP, complexes formed containing calmodulin; after DEP exposure both interactions clearly increase. PAR-2 IP shows that PAR-2 forms a protein--protein complex with calmodulin and that this interaction increased after DEP exposure. Potentiating effect of the specific calmodulin inhibitor W-7 on DEP-evoked Ca^2+^ influx (B) and MMP-1 secretion (C). The arrow in B indicates the time of DEP exposure.\ ^\#^p \< 0.001 for W-7 DEP compared with control DEP and for W-7 control compared with control control.](ehp-119-784f5){#f5-ehp-119-784} ![In BEAS-2B cells, TRPV4~P19S~ functions as a gain-of-function channel in response to DEP, causing increased MMP-1 activation via influx of Ca^2+^. (A) Time course showing increased Ca^2+^-facilitated activation of TRPV4~P19S~ compared with TRPV4~wt~ (n ≥ 24 cells per group). (B) Time course showing OE-evoked Ca^2+^ influx in Ca^2+^-free buffer (note the presence of Ca^2+^ in OE) followed by the addition of external Ca^2+^ (2 mM), which leads to accelerated Ca^2+^ influx for TRPV4~P19S~ versus TRPV4~wt~. The signal of TRPV4~wt~ declined after the peak, whereas TRPV4~P19S~-transfected cells did not desensitize; the signal remained high at least during this observation period. Arrows in A and B indicate the time of Ca^2+^ or OE exposure. (C) Internal \[Ca^2+^\]~i~ was significantly elevated in TRPV4~P19S~-expressing BEAS-2B cells cultured in external media containing Ca^2+^. (D) In keeping with Ca^2+^ responses shown in B, TRPV4~P19S~ increased MMP-1 transcriptional activation. First, transfection of TRPV4~wt~ increased MMP-1 reporter gene activation in response to OE by approximately 2-fold. Second, transfection of TRPV4~P19S~ strikingly increased baseline MMP-1 reporter gene activation in response to OE by a factor of approximately 4--5 versus control-transfected cells and by a factor of \> 2 versus TRPV4~wt~. TRPV4~wt~- and TRPV4~P19S~-mediated increases were virtually eliminated with a second point mutation, M680K (selectivity-filter block). This finding indicates that the effects of TRPV4~wt~ and TRPV4~P19S~ are mediated by an influx of external Ca^2+^ through the channel's pore. (E) Validity of results and conclusions for MMP-1 secretion by transfected BEAS-2B cells.\ \*p \< 0.05, and \\p \< 0.01.](ehp-119-784f6){#f6-ehp-119-784} ![Schematic overview showing effects of DEP on signaling in human ciliated airway epithelia leading to TRPV4-mediated Ca^2+^ influx. Abbreviations: β, G-protein β; γ, G-protein γ; C, C-terminus of TRPV4; N, N-terminus of PAR-2; P, position 19 of TRPV4 ion channel protein proline (wild-type); S, position 19 of TRPV4 ion channel protein proline serine (P19S polymorphism). (A) Overview of respiratory epithelia exposed to airborne DEP. (Left) Apical DEP with attached OE approaching the ciliary brush, basement membrane, and innervating nerve endings (blue). (Right) Detailed view of cilia showing DEP core particles contacting cilia and delivering organic chemicals (OE; light green circles) to the plasma membrane (ciliary colocalization is shown in [Figure 4](#f4-ehp-119-784){ref-type="fig"}). (B) The signaling cascade begins with activation of PAR-2 (green); this ultimately leads to the influx of Ca^2+^ (dark green circles) via TRPV4 (blue) by GPCR signaling encompassing G~i/o~, which in turn leads to activation of PLCβ3 and PI3-K. PLCβ3 is phosphorylated (Phos) in response to DEP, partially accounting for the protracted Ca^2+^ response. PLCβ3 and PI3-K then regulate Ca^2+^ influx through TRPV4, which binds calmodulin (CaM), which is enhanced by DEP exposure; the increased CaM also protracts Ca^2+^ influx. (C) TRPV4-mediated Ca^2+^ entry activates RAS-RAF-MEK MAPK signaling ([@b14-ehp-119-784]), resulting in reprogramming of transcriptional mechanisms that orchestrate remodeling of the extracellular matrix via activation of MMP-1. The COPD-susceptibility polymorphism TRPV4~P19S~ functions as a gain-of-function channel for additional Ca^2+^ influx and MMP-1 activation, thus being relevant to human health.](ehp-119-784f7){#f7-ehp-119-784} [^1]: These authors contributed equally to this work. [^2]: Deceased.	{ "pile_set_name": "PubMed Central" }
i'm not a fan of killing people. i never have been. however, i suppose this particular person had it coming for quite a while now. still, i will never really get used to people cheering when other people die. whether it's in the streets of palestine the day after 9/11, or right now in washington. yes i know it is understandable, but that doesn't make it right. i do think i'm hearing the word closure a little too much. of course i understand the great big sigh of relief, but please let us not pretend this is all over now. I was just talking to my mom about this. I'm especially concerned about the message that people are sending to their children, to future generations, by this partying in the streets because someone was killed. I think I can see why people are treating this like a sporting event. The information people get to hear is very basic, good and bad, us and them - So people take to the streets to celebrate. Understandable, I guess. After a series of draws and losses we just won a very big game. As long as we remember the season is not over yet.	{ "pile_set_name": "Pile-CC" }
Stand-alone electronic cash registers including payment card readers and receipt printers have been used for years in stores, retail outlets and service outlets to facilitate the completion of cash, cheque, credit card or debit card transactions for the purchase of goods and/or services. With the advent of sophisticated and inexpensive computing equipment, input devices and secure communication networks, point-of-sale (POS) stations have, for the most part, replaced such stand-alone electronic cash registers. POS stations typically include a host device and a plurality of peripherals connected to the host device. The host device is commonly in the form of a personal computer that executes a POS application. The peripherals often include a keyboard, a display screen, a cash drawer, a printing device, a payment card reader and a barcode reader. In some cases, a touch-sensitive display screen is used instead of separate keyboard and display screen peripherals. The POS application communicates with the peripherals via application program interfaces (APIs) to allow product and/or service transactions to be completed. When payment is effected using a debit or credit card, the host device establishes a connection to the appropriate financial institution over an information network so that approval for the transaction may be obtained. Upon completion of any transaction, the host device signals the printing device causing the printing device to generate a transaction receipt and possibly a signing receipt, if payment is made using a credit card. In larger stores, retail outlets and service outlets, POS stations are typically linked via a local area network and communicate with a backend computing device that maintains a database for transaction, inventory, accounting, sales, tax, etc. information. Transaction data received by each of the POS stations is conveyed to the backend computing device for storage in the database allowing all transaction data to be stored in a common location. Collectively storing all transaction data in one common location allows retailers to track, account for and maintain inventory, collected taxes and pricing information. Also, by linking the POS stations, updates relating to sales on products and/or services, tax, etc. can be communicated to each POS station over the local area network avoiding the need to update the POS stations one at a time. Two initiatives to standardize the development of POS stations based on the UnifiedPOS standard have been developed, namely object linking and embedding POS (“OPOS”) and Java for Retail POS (“JavaPOS”). Java and all Java-based marks are a trademark or registered trademark of Oracle Corporation. These standards have enabled peripherals to be readily interchanged and easily integrated into POS stations allowing POS stations to be configured to meet changing needs. This of course has been a leading factor to POS station acceptance. In JavaPOS environments, information relating to the configuration of peripherals is stored in one or more files, typically in XML format, that is separate from POS application run by the host device. Each configuration XML file contains information for all peripherals connected in a given configuration. The configuration XML file associated with the desired configuration is selected for use. To link the POS application and the configuration XML files, the POS application comprises a compressed Java archive (JAR) file that embodies a properties file storing pointers to the configuration XML files. When a configuration XML file is deployed, i.e the selected configuration XML file is saved to a new location or a new configuration XML file that is to be used is saved, in order to update the pointer associated with the deployed configuration XML file, it has been necessary for a user to extract manually the compressed JAR file, locate and access the properties file therein and then update the appropriate pointer entry so that the pointer entry correctly points to the deployed configuration XML file. As will be appreciated, updating the pointer entry in this manner is cumbersome and time consuming. Methods for enhancing the use of Java archive files and Java implemented applications, and improving file management are well documented in the art. For example, U.S. Pat. No. 6,571,389 to Spyker et al. discloses a method, system, and computer-readable code for improving the manageability and usability of a Java environment. A technique that combines the advantages of applets and applications while avoiding particular disadvantages of both is employed whereby all Java programs are executed without relying on the use of a browser to provide a run-time environment. Dependencies are specified in a manner that enables the Java programs to be dynamically located and installed, and in a manner that enables sharing dependent modules (including run-time environments) among applications. The dependency specification technique ensures that all dependent code will be automatically available at run-time, without requiring a user to perform manual installation. The run-time environment required for an application is specified, and a technique is provided for dynamically changing the run-time that will be used (including the ability to change run-times on a per-program basis), without requiring user intervention. U.S. Patent Application Publication No. 2003/0225795 to Abdallah et al. discloses a mechanism for extending a Java archive file to include additional information that describes the contents of the archive file as update information. The mechanism comprises a program for determining differences between an initial file system tree and a final file system tree and for encoding the differences into entries in a Java archive file. An extractor class is included in the Java archive file and named as the main class. The Java archive file may be transported to a site that needs a file system update. The Java archive file may be executed in a Java runtime environment to update a target file system. The extractor class is executed to decode and effectuate the difference entries in the Java archive file. U.S. Patent Application Publication No. 2004/0123285 to Berg et al. discloses application configurations, including applications themselves, application components, and modules associated with applications, which are installed on an application-server machine and stored in system-determined locations. The system-determined locations, or absolute paths, are then stored in a “loose configuration”. As new versions of applications, application components, and/or modules are installed, they are placed in unique locations and given unique version numbers. Records of each application configuration version are stored and are referred to as “snapshots”. These snapshots provide a record of, and pointers to, the various elements that make up the various application configuration versions, so that at any time, a current version of an application configuration can be “rolled back” to a previous version of an application configuration. The methodology can be utilized to provide a self-healing configuration, whereby a faulty version of an application configuration can be rolled back to a previous version automatically. U.S. Patent Application Publication No. 2005/0021688 to Felts et al. discloses a system and method of configuring a domain. The method comprises providing a first user interface operable to configure the domain and a second user interface operable to configure a cluster. Configuration of the domain is based on a domain template. U.S. Patent Application Publication No. 2005/0234987 to Cyphers discloses a method for updating values within the contents of a Java archive (JAR) file without altering the JAR file structure. A smart archive program (SAP) creates a temporary directory in memory and stores the JAR file structure in the memory. The SAP then extracts the JAR file content into the temporary directory and allows the user to update the field values within the JAR file content. When the user has finished updating the field values in the JAR file content, the SAP archives the JAR file content into a new JAR file according to the JAR file structure stored in the memory. Consequently, field values within the JAR file content can be updated without altering the JAR file structure. U.S. Patent Application Publication No. 2005/0240902 to Bunker et al. discloses a system and method for an extendable application framework, comprising a user interface, at least one service, and at least one extension. At least one of the extensions provides access to functionality in the user interface and at least one of the services provides access to functionality in at least one of the extensions. U.S. Patent Application Publication No. 2005/0278280 to Semerdzhiev et al. discloses a system for updating files in a computer system. The update system downloads files from a centralized database during a start up process. The start up process completes loading of all services and applications to be provided by the computer system and then initiates an update process. During the update process, open archive files are closed and may be replaced by downloaded files. File replacement is handled by an updated module without requiring the generation of scripts or code to be executed during a subsequent start up process in order to complete the update. As will be appreciated, although the above references disclose Java management techniques, there exists a need for an improved method of dealing with POS peripheral configuration updates. It is therefore an object of the present invention to provide a novel configuration tool and method of updating an archive file property relating to at least one point-of-sale (POS) peripheral.	{ "pile_set_name": "USPTO Backgrounds" }
What do we really know about dark energy? In this paper, we discuss what we truly know about dark energy. I shall argue that, to date, our single indication for the existence of dark energy comes from distance measurements and their relation to redshift. Supernovae, cosmic microwave background anisotropies and observations of baryon acoustic oscillations simply tell us that the observed distance to a given redshift z is larger than the one expected from a Friedmann-Lemaître universe with matter only and the locally measured Hubble parameter.	{ "pile_set_name": "PubMed Abstracts" }
No wonder the state department tried to stop Marie Yovanovitch from talking. The former ambassador’s written testimony to Congress expresses clearly and in the most solemn of settings, what growing numbers American diplomats have been feeling: that their institution is being left to rot. It is too soon to say whether her evisceration of the state department delivered behind closed doors, will mark a turning point in Donald Trump’s struggle to hold on to his office. There will without doubt be a counter-attack. But Yovanovitch’s decision to ignore the state department gag and appear before the House committees – without having to be subpoenaed – has already cracked the wall of silence. On Monday, the national security council’s British-born former senior director for Europe and Russia, Fiona Hill, is due to give her account. Hill, not a Trump loyalist but an expert on Russia and Vladimir Putin, resigned from her post in August. So she was in her job at the time of the infamous 25 July telephone conversation between Trump and the newly elected Ukrainian president, Volodymyr Zelenskiy. In that call, Trump sought to persuade the comedian-turned-leader to investigate the company that had employed Hunter Biden, the son of the former vice-president and Democratic presidential contender. At the time, his aides were conditionally offering a White House visit, and Trump had put a hold on military aid the new government in Kyiv desperately needed. On Thursday, it will be the turn of the US ambassador to the European Union, Gordon Sondland, who announced through his lawyer on Friday that he would be giving a deposition – again in defiance of state department instructions. Sondland got his job after donating $1m to the Trump inauguration fund, but he is not a loyalist. He backed other Republican contenders for the 2016 nomination and only leapt onboard the Trump wagon when it was past the finish line. In WhatsApp messages released by Congress, Sondland is revealed have led the effort to persuade Ukraine to launch the politically motivated investigations, bragging that he was acting on presidential authority, only to deny there was any quid pro quo when it became clear an investigation was in the pipeline. It will be hard to stick to that story when confronted by his own words next Thursday. Which way Sondland chooses to jump could have an important bearing on perceptions of the impeachment process among Republicans. Polls now show that half the electorate already support it. As Yovanovitch was arriving on Capitol Hill on Friday, there were reports that more whistleblowers may be coming forward, and it seems probable that the ambassador’s words will inspire others to break ranks. “Her quiet dignity stands in sharp contrast to the corruption of the president and many of his associates,” Nicholas Burns, former under secretary of state for political affairs, said. “Her open defiance may well encourage other career officials to come forward to tell the truth about Trump’s Ukraine policy.” She gave a compelling account of her life: born to escapees from both Nazism and communism, an immigrant who rose to the top of US diplomacy and was appointed ambassador three times. After more than three decades as a diplomat, under six presidents, she expressed her “deep disappointment and dismay” about what had happened to her faith that “we enjoyed a sacred trust with our government”. “That basic understanding no longer holds true,” she said. “Today, we see the state department attacked and hollowed out from within.” The harm would not just come from the exodus of talent, Yovanovitch said. “The harm will come when private interests circumvent professional diplomats for their own gain, not the public good,” she went on. “The harm will come when bad actors in countries beyond Ukraine see how easy it is to use fiction and innuendo to manipulate our system. In such circumstances, the only interests that will be served are those of our strategic adversaries, like Russia, that spread chaos and attack the institutions and norms that the US helped create and which we have benefited from for the last 75 years.” When Yovanovitch talked about private interests, it was clear what she was talking about. She had already speculated that it was private interests that were driving a quest led by Trump’s personal lawyer, Rudy Giuliani, to have her ousted from her position because of the embassy’s anti-corruption campaign. The week’s dramatic news provided a vivid split-screen illustration of what private interests entailed. On one side a veteran diplomat walking purposefully through the halls of Congress on her way to testify; on the other, mugshots of Giuliani’s two associates, Lev Parnas and Igor Fruman, who had worked with Trump’s lawyer to look for dirt on the Bidens, and who had boasted they had helped get rid of Yovanovitch. Booking photos for Igor Fruman and Lev Parnas. Photograph: Alexandria Sheriff/Handout/EPA The pair are charged with funneling foreign cash into the Trump campaign and into the coffers other Republican candidates, as well as seeking to buy politicians to grant a licence for a recreational marijuana farm. In their wake they have left a trail of fraud accusations, and failed ventures including a movie that was to be called Anatomy of an Assassin, which collapsed when investors’ money evaporated. This was the gang that was running a parallel foreign policy in Ukraine, sidelining Yovanovitch and other career diplomats. The longer they stay in the news, the greater insight the public will have into the corruption of US diplomacy that has been under way beneath the surface for nearly three years. Kurt Volker, the former special envoy on the Ukraine tried to work with Trump’s shadow diplomacy, reasoning that it was the most effective way to reach US policy objectives. If Giuliani and Trump were placated, US-Ukraine ties would be strengthened in the face of the threat from Russia. But when his gung-ho texts became public he simply appeared complicit. No one who knew him doubted that he was a dedicated public servant, but very few if any who think they can handle this president come away untarnished. He resigned from his envoy position, and lost his prestigious academic post as well. Others still in the administration are likely to learn the lessons from Yanovanitch and Volker’s stories, and decide that now is the time to make a clean break.	{ "pile_set_name": "OpenWebText2" }
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# 练习 1：文本编辑器，vim > 原文：[Exercise 1. Text Editor, The: vim](https://archive.fo/5vf0X) > 译者：[飞龙](https://github.com/wizardforcel) > 协议：[CC BY-NC-SA 4.0](http://creativecommons.org/licenses/by-nc-sa/4.0/) > 自豪地采用[谷歌翻译](https://translate.google.cn/) 在 Linux 中，就像任何类 Unix 操作系统，一切都只是文件。而 Unix 哲学指出，配置文件必须是人类可读和可编辑的。在几乎所有的情况下，它们只是纯文本。所以，首先，你必须学习如何编辑文本文件。为此，我强烈建议你学习 vim 的基础知识，这是在 Linux 中处理文本的最强大的工具之一。Vim 是由 Bill Joy 于 1976 年编写的，[vi](http://en.wikipedia.org/wiki/Vi) 的重新实现。vi 实现了一个非常成功的概念，甚至 Microsoft Visual Studio 2012 有一个[插件](http://visualstudiogallery.msdn.microsoft.com/59ca71b3-a4a3-46ca-8fe1-0e90e3f79329/)，它提供了一个模式，与这个超过 35 岁的编辑器兼容。你可以在这里玩转它（[这是在浏览器中运行的真正的 Linux](https://bellard.org/jslinux/vm.html?url=https://bellard.org/jslinux/buildroot-x86.cfg)）。完成之后，最后获取我的虚拟机。如果我还没成功说服你，你可以了解 [nano](http://www.howtogeek.com/howto/42980/the-beginners-guide-to-nano-the-linux-command-line-text-editor/)来代替。但至少要试试。现在，登入`vm1`，之后键入： ``` vim hello.txt ``` 你应该看到： ``` Hello, brave adventurer! ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ "hello.txt" [New File] 0,0-1 All ``` 有一个笑话说，vim有两种模式 - “反复哔哔”和“破坏一切”。那么，如果你不知道如何使用 vim，这是非常真实的，因为 vim 是模态的文本编辑器。模式是： + 普通模式：移动光标并执行删除，复制和粘贴等文本操作。 + 插入模式：输入文本。 > 译者注：还有一个命令模式，用于生成真 · 随机字符串（笑）。这十分使新手头疼，因为他们试图尽可能地避免普通模式。那么这是错误的，所以现在我将给你正确的大纲来使用 vim ： ``` start vim while editing is not finished, repeat navigate to desired position in NORMAL mode enter INSERT mode by pressing i type text exit INSERT mode by pressing <ESCAPE> when editing is finished, type :wq ``` 最重要的是，几乎任何时候都呆在普通模式，短时间内进入插入模式，然后立即退出。以这种方式，vim 只有一种模式，而这种模式是普通模式。现在让我们试试吧。记住，按`i`进入插入模式，以及`<ESCAPE>` 返回到普通模式。键入以下内容（在每行末尾按`<ENTER>`）： ``` iRoses are red Linux is scary <ESCAPE> ``` 这是你应该看到的： ``` Roses are red Linux is scary ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 4,17 All ``` 现在我给你命令列表，在普通模式下移动光标： + `h` - 向左移动 + `j` - 向下移动 + `k` - 向上移动 + `l` - 右移 + `i` - 进入插入模式 + `o` - 在光标下插入一行并进入插入模式 + `<ESCAPE>` - 退出插入模式 + `x` - 删除光标下的符号 + `dd` - 删除一行 + `:wq` - 将更改写入文件并退出。是的，没错，这是一个冒号，后面跟着`wq`和`<ENTER>`。 + `:q!` - 不要对文件进行更改并退出。那就够了。现在，将光标放在第一行并输入： ``` oViolets are blue<ESCAPE> ``` 之后，将光标放在`Linux is scary`那一行，并输入： ``` oBut I'm scary too<ESCAPE> ``` 你应该看到： ``` Roses are red Violets are blue Linux is scary But I'm scary too ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 4,17 All ``` 现在键入`:wq`保存文件，并退出。你应该看到： ``` Violets are blue Linux is scary But I'm scary too ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ "hello.txt" 4L, 64C written user1@vm1:~$ ``` 好的。你做到它了。你刚刚在 vim 中编辑了文本文件，很好很强大！ ## 附加题 + 通过键入键入`vim hello.txt`再次启动 vim，并尝试我给你的一些命令。 + 玩这个游戏，它会让你更熟悉 vim：<http://vim-adventures.com/>	{ "pile_set_name": "Github" }
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/* Copyright (C) 2011 Mark Chandler (Desura Net Pty Ltd) Copyright (C) 2014 Bad Juju Games, Inc. This program is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA. Contact us at legal@badjuju.com. / #ifndef DESURA_SCRIPTCOREINTERNAL_H #define DESURA_SCRIPTCOREINTERNAL_H #ifdef _WIN32 #pragma once #endif #include "v8.h" class ScriptCoreInternal { public: void init(); void del(); void runScript(const char file, const char* buff, uint32 size); void runString(const char* string); protected: void doRunScript(v8::Handle<v8::Script> script); gcString reportException(v8::TryCatch* try_catch); private: friend bool IsV8Init(); static std::mutex s_InitLock; static bool s_IsInit; static bool s_Disabled; static void OnFatalError(const char* location, const char* message); v8::Persistent<v8::Context> m_v8Context; }; #endif //DESURA_SCRIPTCOREINTERNAL_H	{ "pile_set_name": "Github" }
Q: Axios returns promise pending i want this function to return either true or false, instead I get /** * Sends request to the backend to check if jwt is valid * @returns {boolean} */ const isAuthenticated = () => { const token = localStorage.getItem('jwt'); if(!token) return false; const config = {headers : {'x-auth-token' : token}}; const response = axios.get('http://localhost:8000/user' , config) .then(res => res.status === 200 ? true : false) .catch(err => false); return response; } export default isAuthenticated; I tried separating them and using async/await : const isAuthenticated = async () => { const response = await makeRequest(); return response; } const makeRequest = async () => { const token = localStorage.getItem('jwt'); const config = {headers : {'x-auth-token' : token}}; const response = await axios.get('http://localhost:8000/user' , config) .then(res => res.status === 200 ? true : false) .catch(err => false); return response; } And still the same.. After some suggestions : const isAuthenticated = () => { const response = makeRequest(); return response; } const makeRequest = async () => { try { const token = localStorage.getItem('jwt'); const config = {headers : {'x-auth-token' : token}}; const response = await axios.get('http://localhost:8000/user', config); if (response.status === 200) { // response - object, eg { status: 200, message: 'OK' } console.log('success stuff'); return true; } return false; } catch (err) { console.error(err) return false; } } export default isAuthenticated; A: First of all if. If you are using the default promise then & catch, then the success action should be handled within the 'then' function. axios.get('http://localhost:8000/user', config) .then(res => console.log('succesfull stuff to be done here') .catch(err => console.error(err)); // promise if you want to use the async/await syntactic sugar, which I personally like it's const makeRequest = async () => { try { const token = localStorage.getItem('jwt'); const config = {headers : {'x-auth-token' : token}}; const response = await axios.get('http://localhost:8000/user', config); if (response.status === 200) { // response - object, eg { status: 200, message: 'OK' } console.log('success stuff'); return true; } return false; } catch (err) { console.error(err) return false; } }	{ "pile_set_name": "StackExchange" }
1. Introduction {#sec1-ijerph-17-01164} =============== Diabetes represents a clustering of heterogeneous risk factors that affects all aspects of quality of life due to the lifetime demands of diabetes care \[[@B1-ijerph-17-01164]\]. Health-related quality of life (HRQoL) refers to a multi-dimensional concept of quality of life, which can be affected by illnesses or treatments. Thus, assessment of HRQoL is an important outcome measure to evaluate overall disease management for patients with diabetes, including disease course, early detection of complications, and effectiveness and efficacy of interventions \[[@B2-ijerph-17-01164]\]. Comorbidity is defined as the presence of chronic conditions existing concurrently with a primary disease \[[@B3-ijerph-17-01164]\]. Patients with diabetes often have multiple comorbidities, including hypertension, overweight or obesity, hyperlipidemia, chronic kidney disease, and cardiovascular disease, all of which can impact the patient's HRQoL \[[@B4-ijerph-17-01164],[@B5-ijerph-17-01164]\]. Consequently, the management of chronic conditions in patients with diabetes will benefit from a focus on HRQoL. Cardiorespiratory fitness (CRF), which is defined as the minimum volume of oxygen consumption during a maximal exercise test, has been found to protect against chronic diseases and premature death from those diseases \[[@B6-ijerph-17-01164],[@B7-ijerph-17-01164]\]. For example, higher CRF is associated with lower risks of morbidity and mortality in younger and older adults \[[@B8-ijerph-17-01164]\]. Some studies have examined the association between physical activity and HRQoL in healthy persons, as well as those with chronic diseases, reporting positive relationships for both groups \[[@B9-ijerph-17-01164],[@B10-ijerph-17-01164]\]. Unlike physical activity (PA), less attention has been paid to the relationship between CRF and HRQoL. Although research in this area is limited, the current evidence suggests a positive relationship between CRF and HRQoL in patients with chronic and metabolic diseases \[[@B11-ijerph-17-01164]\]. In older persons, however, objectively measuring CRF can be difficult due to the requirements related to its measurement, such as specialized equipment; trained personnel; amount of time, volitional exertion; and mobility. Importantly, studies have found that CRF can be estimated with acceptable accuracy from routinely obtained health indicators \[[@B12-ijerph-17-01164],[@B13-ijerph-17-01164]\]. We have previously shown that non-exercise-based estimation of cardiorespiratory fitness (eCRF) can serve as a prognostic tool for estimating the risk of mortality from all and specific causes in older Korean adults \[[@B14-ijerph-17-01164]\]. Nationwide data in South Korea revealed that a majority of patients with diabetes have one or more comorbidities which can affect HRQoL, including obesity, hypertension, hypercholesterolemia, and others \[[@B15-ijerph-17-01164]\]. Health behaviors, including PA and CRF, likely mediate the impact of comorbidities on HRQoL among these patients. To the best of our knowledge, however, no previous studies have examined the mediating effect of CRF on the relationships between comorbidities and HRQoL in patients with diabetes in South Korea. Therefore, we investigated whether eCRF mediates the impact of comorbidities on HRQoL in older Korean adults with type-2 diabetes. 2. Materials and Methods {#sec2-ijerph-17-01164} ======================== 2.1. Study Design and Participants {#sec2dot1-ijerph-17-01164} ---------------------------------- The cross-sectional data used for this study were drawn from the Korea National Health and Nutrition Examination Surveys (KNHANES) IV and V, which are nationwide surveys that were conducted from 2008 until 2011 in South Korea. A detailed description of the survey sampling method is available elsewhere \[[@B16-ijerph-17-01164],[@B17-ijerph-17-01164]\]. For the current study, we initially selected a total of 2757 adults aged 60 years and older from those who participated in the 2008--2011 KNHANES IV and V. We then excluded 1386 individuals because no baseline data were available regarding body composition (n = 352), resting heart rate (n = 799), PA (n = 17), and HRQoL (n = 218). Consequently, a total of 1371 older adults with diabetes (604 men; 767 women) were included in the final data analyses. The presence of diabetes was determined with a self-reported questionnaire that asked whether the participants had ever received a diagnosis of diabetes from a physician. The institutional review board of human study reviewed and approved the study protocol participants (SKKU 2017-06-009). Informed consent was obtained from all participants in the study. 2.2. Study Variables {#sec2dot2-ijerph-17-01164} -------------------- ### 2.2.1. Assessment of HRQoL (Dependent Variable, Y) {#sec2dot2dot1-ijerph-17-01164} HRQoL was assessed with the EuroQoL group, which consists of a health-status descriptive system (EQ-5D) and a visual analogue scale (EQ-VAS). The EQ-5D records the level of self-reported problems in five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression \[[@B18-ijerph-17-01164],[@B19-ijerph-17-01164]\]. Each of the dimensions is assessed based on a single question with three response levels (no problems, some problems, and extreme problems). Scores on the EQ-5D index range from −0.171 to 1, where 1 indicates no problems in any of the five dimensions, zero indicates death, and negative values indicate a health status worse than death. Next, patients report their health status with the EQ-VAS, which involves a VAS ranging from 0 (worst imaginable health) to 100 (best imaginable health) \[[@B18-ijerph-17-01164]\]. ### 2.2.2. Assessment of Comorbidities (Independent Variable, X) {#sec2dot2dot2-ijerph-17-01164} Participants were asked if they had ever been diagnosed by a physician with any of the following medical condition(s): malignancy, hypertension, heart disease (acute myocardial infarction or angina), stroke, arthritis, and/or chronic renal disease. ### 2.2.3. Estimation of Cardiorespiratory Fitness (Mediator, M) {#sec2dot2dot3-ijerph-17-01164} Non-exercise-based eCRF was calculated as one-minute peak volume of oxygen consumption (VO~2peak~) in units of metabolic equivalents (METs), in accordance with previously reported procedures \[[@B13-ijerph-17-01164]\]: Once the algorithms were implemented, participants were classified into low (lowest 25%), middle (middle 50%), and high (highest 25%) categories on the basis of sex-specific tertiles of the estimated peak VO~2~ distributions. ### 2.2.4. Covariates {#sec2dot2dot4-ijerph-17-01164} Measured covariates included age, sex, household income, education level (lower than elementary school, middle/high school, or college or higher), marital status (yes or no), current smoker (never or past/current), frequency of alcohol consumption (more or less than twice per week), and regular exercise (yes or no). 2.3. Statistical Analyses {#sec2dot3-ijerph-17-01164} ------------------------- All variables were checked for normality, both visually and through the Kolmogorov--Smirnov test, and subjected to an appropriate transformation, if necessary, prior to statistical analyses. Descriptive statistics are presented as means and standard deviations for continuous variables and as frequencies and percentages for categorical variables. Analysis of variance (ANOVA) was used to test linear trends in outcome variables according to number of comorbidities and eCRF categories. We examined the relationships between number of comorbidities, eCRF, and HRQoL using parametric and non-parametric statistics. Then, the impact of comorbidities on HRQoL through eCRF was tested based on four criteria for the mediation paths proposed by Baron and Kenny \[[@B20-ijerph-17-01164]\], as illustrated in [Figure 1](#ijerph-17-01164-f001){ref-type="fig"}: (1) the coefficient of path "a" is significant in identifying the effect of the independent variable (IV) on the mediating variable (MV); (2) the MV is significantly related to the dependent variable (DV) of the IV (path b); (3) a significant direct association (path c) between the IV and DV is confirmed; and (4) the association between the IV and DV is weakened when the MV is controlled (path c′). The PROCESS macro in SPSS-PC (version 23.0, IBM Corporation, Armonk, NY, USA) was used to carry out the mediation analyses. No covariates were included in Model 1, demographics and socio-economic status (SES) variables were included in Model 2, and variables of health behaviors were added to Model 3. The possible mediating effect of eCRF on the impact of comorbidities on HRQoL was identified using the Sobel mediation test with a bootstrapping process, which overcomes the assumption of a normal distribution of the classical Sobel mediation test. The robustness of p-values was confirmed via the bootstrapping process. An α level of 0.05 was used for all statistical analyses. 3. Results {#sec3-ijerph-17-01164} ========== [Table 1](#ijerph-17-01164-t001){ref-type="table"} summarizes descriptive statistics of participants. Overall, male participants were older (p \< 0.001), heavier (p \< 0.001), more educated (p \< 0.001), and less likely to be alone (p \< 0.001) than female participants. Men had higher values for smoking (p \< 0.001) and alcohol intake (p \< 0.001), but lower values for resting heart rate (p = 0.023) and number of comorbidities (p \< 0.001) than women. Men were less physically active (p \< 0.001) but had higher values on the EQ-5D index (p \< 0.001) and EQ-VAS (p \< 0.001) than women. We found no significant differences in marital status or income between older men and women. [Table 2](#ijerph-17-01164-t002){ref-type="table"} compares the measured parameters in relation to number of comorbidities. Significantly, positive, linear trends in mean age (p \< 0.001), solitary status (p = 0.022), and smoking status (p \< 0.001) and significant, negative linear trends in education (p = 0.001), alcohol consumption (p = 0.004), EQ-5D index (p \< 0.001), and EQ-VAS score (p = 0.002) were found in relation to the number of comorbidities. In general, patients with one or more comorbidities were older, more likely to live alone, less likely to smoke, consumed alcohol less frequently, and had worse HRQoL than patients with no comorbidities. [Table 3](#ijerph-17-01164-t003){ref-type="table"} compares the measured parameters according to eCRF category. Significantly, negative linear trends in mean age (p \< 0.001), solitary status (p = 0.003), physical activity (p \< 0.001), and number of comorbidities (p = 0.008) and significant, positive linear trends in education (p = 0.002), alcohol consumption (p = 0.034), EQ-5D index (p \< 0.001), and EQ-VAS score (p \< 0.001) were found in relation to increased eCRF (from low to high). Patients who were physically fit were younger, less likely to live alone, less physically active, had more education, consumed alcohol more frequently, had fewer comorbidities, and had higher values on the EQ-5D index and EQ-VAS than patients who were less physically fit. No significant linear trends in sex, marital status, income, or smoking were found in relation to eCRF category. [Table 4](#ijerph-17-01164-t004){ref-type="table"} represents the impact of eCRF on the associations between comorbidities and HRQoL. Mediation analysis showed that number of comorbidities had a direct effect on HRQoL independent of eCRF (β~c'~ = −1.913, p \< 0.005; c' path). However, the number of comorbidities also indirectly affected HRQoL through its effect on eCRF. The number of comorbidities was negatively associated with eCRF (βa = −0.528, p \< 0.001; a path), and eCRF was positively associated with HRQoL (β~b~ = 1.434, p \< 0.001; b path). Both comorbidity and eCRF remained significant predictors of HRQoL even after adjusting for demographics and SES (i.e., age, marital status, living condition, and education in Model 2 (β~c'~ = −2.327, p \< 0.001; c' path; β~b~ = 0.996, p \< 0.001; b path, respectively), as well as health behaviors (i.e., smoking, alcohol consumption, and regular exercise) in Model 3 (β~c'~ = −2.039, p \< 0.005; c' path and β~b~ = 1.153, p \< 0.005; b path, respectively). The mediating effect of eCRF on the impact of comorbidities on HRQoL was further tested using the Sobel mediation test with a bootstrapping procedure ([Table 4](#ijerph-17-01164-t004){ref-type="table"} and [Figure 1](#ijerph-17-01164-f001){ref-type="fig"}). The Sobel mediation test showed a significant indirect effect of eCRF on the impact of comorbidities on HRQoL (Z = −4.632, p \< 0.001). The results of the bootstrap procedure corroborated those of the Sobel test: the 95% bias-corrected confidence interval (95% CI −1.104 to −0.453) was non-zero, indicating that eCRF mediated the relationship between comorbidities and HRQoL (Model 1) and accounted for 28.4% of the total effect on HRQoL. The Sobel mediation effect of eCRF on the relationship between comorbidities and HRQoL remained significant even after adjusting for demographics and SES in Model 2 (Z = −3.004, p = 0.001), with 16.1% of the total effect being explained. Likewise, this relationship remained significant after adjustments for Model 2 plus inclusion of parameters for health behaviors in Model 3 (Z = −2.753, p = 0.005), with 12.1% of the total effect explained. 4. Discussion {#sec4-ijerph-17-01164} ============= In this study, we examined the mediating effect of eCRF on the relationships between comorbidities and HRQoL in older Korean adults with diabetes. Our findings show that both comorbidities and eCRF are important predictors of HRQoL among older Korean patients. This is the first study to report that eCRF mediates the impact of comorbidities on HRQoL partially and independently among patients with diabetes. The current findings agree with previous studies reporting an inverse relationship between comorbidities and HRQoL in patients with diabetes. For example, Wexler et al. \[[@B21-ijerph-17-01164]\] examined the impacts of medical comorbidities and depression on HRQoL in a large primary care cohort of patients with type 2 diabetes and showed that treatment of depression and prevention of complications were important determinants of HRQoL. By analyzing the treatment options for type 2 diabetes in adolescents and youth (TODAY) study data, Larkin et al. \[[@B22-ijerph-17-01164]\] showed that HRQoL was negatively associated with depressive symptoms and number of comorbidities in youth with type 2 diabetes. This inverse relationship between HRQoL and comorbidities has also been observed in patients with chronic conditions \[[@B23-ijerph-17-01164]\], dementia \[[@B24-ijerph-17-01164]\], psoriatic arthritis \[[@B25-ijerph-17-01164]\], and survivors of breast \[[@B26-ijerph-17-01164]\] and colorectal cancer \[[@B27-ijerph-17-01164]\]. Likewise, the current findings are consistent with previous studies reporting a positive relationship between CRF and HRQoL in patients with type 2 diabetes \[[@B28-ijerph-17-01164]\], pediatric patients with type 1 diabetes \[[@B29-ijerph-17-01164]\], and women at risk of gestational diabetes \[[@B30-ijerph-17-01164]\]. Using patient records from the 2002 to 2012 Calidad de Vida Center, Clennin et al. \[[@B11-ijerph-17-01164]\] examined the relationship between CRF and HRQoL in a Uruguayan cohort at risk for developing cardiovascular disease (CVD) and found positive associations between CRF and several dimensions of HRQoL (women: vitality, physical health, physical role, bodily pain, and general health; men: physical health). In children and adolescents with type 1 diabetes, Lukács et al. \[[@B31-ijerph-17-01164]\] examined associations among HRQoL, clinical profiles, anthropometric measures, and physical activity and CRF and found that good CRF was significantly associated with better HRQoL and favorable metabolic control among the youth. Similarly, this positive association between CRF and HRQoL was observed in community-dwelling older adults \[[@B32-ijerph-17-01164]\] and workers \[[@B33-ijerph-17-01164]\], as well as in patients with CVD \[[@B11-ijerph-17-01164]\], McArdle disease \[[@B34-ijerph-17-01164]\], severe mental illness \[[@B35-ijerph-17-01164]\], and survivors of cancer \[[@B36-ijerph-17-01164]\]. Our study is the first to extend these findings to show that CRF may mediate the impact of comorbidities on HRQoL in patients with diabetes. The mediating effect of eCRF on the relationship between comorbidities and HRQoL was independent of potential covariates, including demographics (age, sex, marital status), SES (income and education), health behaviors (smoking, alcohol consumption, and regular exercise) and depressive symptoms. In support of the current findings, the findings of the FIT study involving 46,979 patients showed that achieving ≥12 METs reduced the incidence of diabetes compared to achieving \<6 METs in both non-obese (hazard ratio = 0.73; 95% CI = 0.59−0.91; p \< 0.001) and obese individuals (hazard ratio = 0.56; 95% CI 0.42−0.73; p \< 0.001) \[[@B37-ijerph-17-01164],[@B38-ijerph-17-01164]\]. In that study \[[@B37-ijerph-17-01164]\], the protective effect of achieving high CRF was found to be independent of a number of confounders, including age, sex, race, BMI, history of hypertension, hypertension medication use, ACE inhibitor use, angiotensin II receptor blocker use, b-blocker use, diuretic use, history of hyperlipidemia, lipid lowering medication use, statin use, history of obesity, family history of coronary heart disease, current smoking status, sedentary lifestyle, treated pulmonary disease, depression medication use, and indication for stress testing. Taken together, those findings suggest that high CRF may alleviate the impact of comorbidities on HRQoL in patients with diabetes. Thus, promotion of CRF in conjunction with management of comorbidities targeted at increasing HRQoL should be a key component of the overall management of such patients. HRQoL worsens as the number of diabetes-related comorbidities increases \[[@B21-ijerph-17-01164]\]. Thus, information regarding determinants and/or mediators of HRQoL is essential for development and implementation of an effective care program to promote physical and mental well-being for older patients with diabetes. Higher levels of physical activity and fitness are associated with lower risks of morbidity and mortality in healthy adults and patients with chronic diseases. Higher CRF is also associated with better HRQoL in healthy adults and in patients with chronic disease. The current study has some limitations. First, the cross-sectional study design does not allow causal inference regarding the relationships among comorbidities, eCRF, and HRQoL. A randomized controlled trial on exercise training would be necessary to confirm the mediating effect of CRF on the relationship between comorbidities and HRQoL in a cause-and-effect manner. Second, several potential mediators such as sex, SES, depression, and social networking were identified in previous studies \[[@B29-ijerph-17-01164]\]. A more complex mediation model or examination of a larger number of mediation variables should help elucidate the roles of mediator(s) in determining the relationships between exposure and outcomes. Third, the questionnaire of the survey used in this study was not designed to identify the type of diabetes, which should be addressed in a future study. Lastly, a further study will be necessary to investigate the mechanism(s) through which CRF mediates the relationship between comorbidities and HRQoL in diabetes. 5. Conclusions {#sec5-ijerph-17-01164} ============== In summary, our findings indicate the mediating effect of eCRF on the relationship between comorbidities and HRQoL in older Korean adults with diabetes. Assessment of eCRF should be considered an important measure for evaluating the overall management of diabetes. From a public health perspective, these findings could help guide public agencies when developing future healthcare policies to promote health equality for geriatric patients with diabetes in South Korea. The authors thank to Kelly O'Keefe (English editor) and anonymous Reviewers who allowed us to improve the manuscript. Conceptualization, I.L. and H.K.; Methodology, I.L., S.K. and H.K.; Formal Analysis, I.L., S.K. and H.K.; Investigation, I.L., S.K. and H.K.; Writing-Original Draft Preparation, I.L. and H.K.; Writing-Review & Editing, I.L. and H.K.; Funding Acquisition, National Research Foundation (NRF), S.K. All authors have read and agreed to the published version of the manuscript. This study was supported by the National Research Foundation Grant funded by the Korean Government (NRF-2017R1A2B4010684). The authors declare no conflict of interest. ![Mediation analysis. Path coefficients of comorbidities on health-related quality of life (HRQoL) through non-exercise based estimation of cardiorespiratory fitness (eCRF). \\ indicates statistical significance at p \< 0.001 for all the paths.](ijerph-17-01164-g001){#ijerph-17-01164-f001} ijerph-17-01164-t001_Table 1 ###### Descriptive statistics of study participants (Mean ± SD). ---------------------------------------------------------------------------------------------- Variables All\ Men\ Women\ p-Value (n = 1371) (n = 604) (n = 767) ---------------------------------- --------------- --------------- --------------- ----------- Demographics Age (years) 69.1 ± 6.1 68.3 ± 5.9 69.8 ± 6.2 \<0.001 Marital status, n (%) 0.606 Yes 1360 (99.2) 600 (99.3) 760 (99.1) No 11 (0.8) 4 (0.7) 7 (0.9) Living condition, n (%) \<0.001 Live someone 1176 (85.8) 564 (93.4) 612 (79.8) Alone 195 (14.2) 40 (6.6) 155 (20.2) Socioeconomic Status Income (10,000 won/month) 228.1 ± 113.0 217.1 ± 319.9 236.8 ± 148.6 0.752 Education, n (%) \<0.001 Lower than elementary school 558 (40.7) 122 (20.2) 436 (56.8) Middle/high school 597 (43.5) 304 (50.3) 293 (38.2) Over than college 216 (15.8) 178 (29.5) 38 (5.0) Health Behavior Factors \<0.001 Smoking, n (%) Never 769 (56.1) 87 (14.4) 682 (88.9) Past/current 602 (43.9) 517 (85.6) 85 (11.1) Weekly alcohol intake, n (%) \<0.001 \<2 1137 (82.9) 394 (65.2) 743 (96.9) ≥2 234 (17.1) 210 (34.8) 24 (3.1) Regular exercise, n (%) \<0.001 Yes 430 (31.4) 243 (40.2) 187 (24.4) No 941 (68.6) 361 (59.8) 580 (75.6) Number of Comorbidity, n (%) \<0.001 0 220 (16.0) 133 (22.0) 87 (11.3) 1 567 (41.4) 286 (47.4) 281 (36.6) ≥2 584 (42.6) 185 (30.6) 399 (52.1) eCRF Variables eCRF (METs) 7.1 ± 2.3 9.1 ± 1.6 5.6 ± 1.5 \<0.001 BMI (kg/m^2^) 24.7 ± 3.3 24.0 ± 3.0 25.3 ± 3.5 \<0.001 RHR (beats/min) 73.0 ± 10.2 72.3 ± 10.5 73.5 ± 9.8 0.023 Physical activity score, n (%) \<0.001 Level 1 224 (16.3) 66 (10.9) 158 (20.6) Level 2 642 (46.9) 283 (46.9) 359 (46.8) Level 3 23 (1.7) 8 (1.3) 15 (2.0) Level 4 95 (6.9) 40 (6.6) 55 (7.2) Level 5 387 (28.2) 207 (34.3) 180 (23.4) Health-Related Quality of Life EQ-5D problems Mobility, n (%) 621 (45.3) 189 (31.3) 432 (56.3) \<0.001 Self-care, n (%) 205 (15.0) 55 (9.1) 150 (19.6) \<0.001 Usual activities, n (%) 409 (29.8) 121 (20.0) 288 (37.5) \<0.001 Pain/discomfort, n (%) 585 (42.7) 189 (31.3) 396 (51.6) \<0.001 Anxiety/depression, n (%) 260 (19.0) 79 (13.1) 181 (23.6) \<0.001 EQ-5D index 0.85 ± 0.18 0.90 ± 0.15 0.81 ± 0.19 \<0.001 EQ-VAS score 67.0 ± 22.1 70.1 ± 19.0 64.6 ± 24.0 \<0.001 ---------------------------------------------------------------------------------------------- SD---standard deviation; eCRF---estimated cardiorespiratory fitness; MET---metabolic equivalents; BMI---body mass index; RHR---resting heart rate; EQ-5D---euroqol-5 dimension; EQ-VAS---euroqol-visual analogue scale. ijerph-17-01164-t002_Table 2 ###### Comparison of measurement variables according to number of comorbidity (Mean ± SD). Variables Number of Comorbidity p for Linear Trend -------------------------------- ----------------------- ---------------------- --------------- --------- Socio-Demographic Status Age (years) 67.6 ± 6.0 69.3 ± 6.3 69.6 ± 5.9 \<0.001 Marital status, n (%) 0.194 Yes 219 (99.5) 564 (99.5) 577 (98.8) No 1 (0.5) 3 (0.5) 7 (1.2) Living condition, n (%) 0.022 Live someone 197 (89.5) 491 (86.6) 488 (83.6) Alone 23 (10.5) 76 (13.4) 96 (16.4) Socio-Economic Status Income (10,000 won/month) 236.5 ± 386.3 268.0 ± 172.2 186.8 ± 289.2 0.583 Education, n (%) 0.001 Lower than elementary school 71 (32.3) 234 (41.3) 253 (43.3) Middle/high school 106 (48.2) 234 (41.3) 257 (44.0) Over than college 43 (19.5) 99 (17.4) 74 (12.7) Health Behavior Factor Smoking, n (%) \<0.001 Never 102 (46.4) 285 (50.3) 382 (65.4) Past/current 118 (53.6) 282 (49.7) 202 (34.6) Weekly alcohol intake, n (%) 0.004 \<2 181 (82.3) 444 (78.3) 512 (87.7) ≥2 39 (17.7) 123 (21.7) 72 (12.3) Regular exercise, n (%) 0.251 Yes 79 (35.9) 172 (30.3) 179 (30.7) No 141 (64.1) 395 (69.7) 405 (69.3) HRQoL EQ-5D problems Mobility, n (%) 69 (31.4) 221 (39.0) 331 (56.7) \<0.001 Self-care, n (%) 24 (10.9) 58 (10.2) 123 (21.1) \<0.001 Usual activities, n (%) 41 (18.6) 136 (24.0) 232 (39.7) \<0.001 Pain/discomfort, n (%) 73 (33.2) 209 (36.9) 303 (51.9) \<0.001 Anxiety/depression, n (%) 33 (15.0) 93 (16.4) 134 (22.9) \<0.001 EQ-5D index 0.90 ± 0.14 0.87 ± 0.16 0.81 ± 0.20 \<0.001 EQ-VAS score 69.2 ± 22.7 69.4 ± 20.9 63.9 ± 22.5 0.002 ijerph-17-01164-t003_Table 3 ###### Descriptive statistics of measured parameters according to eCRF categories (Mean ± SD). Variables eCRF Categories p for Linear Trend ---------------------------------- ----------------- ---------------------- --------------- --------- eCRF (METs) 5.3 ± 1.8 7.0 ± 1.9 9.3 ± 1.8 \<0.001 Demographics Age (years) 74.3 ± 5.5 67.9 ± 5.3 66.5 ± 5.2 \<0.001 Marital status, n (%) 0.198 Yes 339 (99.1) 678 (98.8) 343 (100.0) No 3 (0.9) 8 (1.2) 0 (0.0) Living condition, n (%) 0.003 Live someone 274 (80.1) 600 (87.5) 302 (88.0) Alone 68 (19.9) 86 (12.5) 41 (12.0) Socioeconomic Status Income (10,000 won/month) 291.4 ± 220.3 191.7 ± 253.6 238.0 ± 418.4 0.547 Education, n (%) 0.002 Lower than elementary school 155 (45.3) 288 (42.0) 115 (33.5) Middle/high school 144 (42.1) 284 (41.4) 169 (49.3) Over than college 43 (12.6) 114 (16.6) 59 (17.2) Health Behavior Factors Smoking, n (%) 0.676 Never 186 (54.4) 391 (57.0) 192 (56.0) Past/current 156 (45.6) 295 (43.0) 151 (44.0) Weekly alcohol intake, n (%) 0.034 \<2 301 (88.0) 555 (80.9) 1.9) ≥2 41 (12.0) 131 (19.1) 62 (18.1) Regular exercise, n (%) \<0.001 Yes 83 (24.3) 216 (31.5) 131 (38.2) No 259 (75.7) 470 (68.5) 212 (61.8) Number of Comorbidity, n (%) 0.008 0 36 (10.5) 115 (16.8) 69 (20.1) 1 156 (45.6) 270 (39.4) 1.1) ≥2 150 (43.9) 301 (43.8) 133 (38.8) Health-Related Quality of Life EQ-5D problems Mobility, n (%) 206 (60.2) 288 (42.0) (37.0) 127 \<0.001 Self-care, n (%) 85 (24.9) 85 (12.4) 35 (10.2) \<0.001 Usual activities, n (%) 141 (41.2) 178 (25.9) 90 (26.2) \<0.001 Pain/discomfort, n (%) 170 (49.7) 271 (39.5) 144 (42.0) 0.041 Anxiety/depression, n (%) 64 (18.7) 140 (20.4) 56 (16.3) 0.425 EQ-5D index 0.80 ± 0.22 0.87 ± 0.16 0.87 ± 0.16 \<0.001 EQ-VAS score 62.9 ± 24.9 67.3 ± 20.9 70.6 ± 20.7 \<0.001 ijerph-17-01164-t004_Table 4 ###### The association between comorbidity and health related quality of life, mediated by eCRF, in diabetes. Path Model 1 Model 2 Model 3 ------------------------------------------------ --------------------- ------------------ --------------------- ------------------ --------------------- ------------------ Comorbidity → eCRF, a −0.528 (0.063) \\ −0.652 to −0.404 −0.388 (0.055) \\ −0.495 to −0.281 −0.244 (0.046) \\ −0.335 to −0.154 eCRF → Quality of life, b 1.434 (0.258) \\ 0.928 to 1.940 0.996 (0.300) \\ 0.407 to 1.586 1.153 (0.358) \* 0.452 to 1.855 Total effect, c −2.670 (0.611) \\ −3.868 to −1.472 −2.327 (0.609) \\ −3.522 to −1.133 −2.321 (0.613) \\ −3.522 to −1.119 Direct effect, c′ −1.913 (0.619) \* −3.128 to −0.698 −1.941 (0.618) \* −3.153 to −0.729 −2.039 (0.617) \* −3.249 to −0.829 Indirect effect, ab −0.757 (0.168) −1.104 to −0.453 −0.387 (0.135) −0.672 to −0.145 −0.282 (0.107) −0.517 to −0.095 Ratio of indirect to total effect mediated (%) 28.4 16.1 12.1 Sobel test −4.632 \\ −3.004 \\ −2.753 \\ Model 1 was non-adjusted. Model 2 was adjusted for age, marital status, living condition, and education. Model 3 was adjusted for Model 2 + smoking, weekly alcohol consumption, and regular exercise. Number of bootstrap samples for bias-corrected bootstrap confidence intervals: 5000. eCRF---non-exercise-based estimation of cardiorespiratory fitness; CI---confidence interval; SE---standard error. \* p \< 0.005, \\ p \< 0.001.	{ "pile_set_name": "PubMed Central" }
In the past, coating compositions were commonly prepared by dissolving or dispersing film forming organic polymers in volatile organic compounds. Environmental and health concerns associated with applications involving large-scale vapor emissions have led to research in the development of coating compositions wherein the emission of volatile organic compounds is minimized. Among the various methods of reducing the vapor emissions of coating compositions, the use of reactive diluents to replace all or part of the volatile organic solvent component of a coating composition is of particular interest. As used herein, the term "reactive diluent" refers to non volatile or nearly non volatile organic solvents or dispersants having as an integral part of their structures functional groups which are reactive with a film forming polymer and/or cross linking agent. In addition to providing a low level of volatile emissions, a coating composition should have a sufficiently low viscosity to permit easy handling and application. Other desirable properties in a coating composition are sufficient stability to ensure a commercially acceptable shelf life and the ability to provide a cured coating having suitable properties such as toughness, adhesion, gloss, uniformity, impact resistance, abrasion resistance, scratch resistance, weatherability, and resistance to attack by solvents, acids, bases and other chemicals. Coating compositions wherein all or a portion of the volatile organic solvent component thereof is replaced by a reactive diluent are illustrated by the following patents: U.S. Pat. No. 4,417,022, to Chang et al. discloses coating compositions, the vehicle portion of which consists essentially of from about 60 percent to about 97 percent of a curable film-forming component and from about 3 percent to about 40 percent of an organic reactive diluent capable of chemically combining with the curable film forming component. Disclosed as reactive diluents are ethers having less than five ether groups, amides, esters, urethanes, ureas, sulfur containing compounds, and mixtures thereof which have one primary or secondary hydroxyl group. The reactive diluents disclosed by Chang et al. are further characterized as having a retained solids value of greater than about 80 percent, a hydroxyl equivalent of from about 180 to about 800, and a liguid viscosity of less than about 10 poise at 60.degree. C. Preferred reactive diluents disclosed by Chang et al. are ester containing reactive diluents, with ester containing reactive diluents having allyl side chains being most preferred. Coating compositions having ester-containing reactive diluents to produce cured coatings which lack desirable adhesion, hardness and/or weatherability. As a further example, U.S. Pat. No. 4,520,167 to Blank et al. discloses a coating compsition comprising (a) a hydroxyalkyl carbamate of the formula: ##STR1## wherein n=0 or 1, R is a C.sub.1 to C.sub.20 organic moiety which may contain one or more constituents selected from the class consisting of hetero-atoms and hydroxyl groups, and each of R.sub.1, R.sub.2, and R.sub.3 is independently H or CH.sub.3 ; (b) an aminoplast cross-linker; and (c) a polymer containing active sites which at elevated temperature are reactive with the amide-aldehyde cross-linker (b). Blank et al. exemplifying as suitable reactive diluents compounds of the formula: ##STR2## Cured coatings formed from the coating compositions containing the reactive diluents exemplified by Blank et al. are, within a range of environmentally acceptable formulations, widely variable as regards the surface properties possessed by same. Among the compounds which have been offered for use as reactive diluents in coating compositions are dicyclopentenyl oxyethyl ethyl methacrylates, modified caprolactones, and unsaturated melamines. In general, these compounds are poor solvents, have relatively high viscosities and/or produce cured coatings having undesirable chemical and/or physical properties. A cured coating's toughness, adhesion, impact resistance, abrasion resistance, scratch resistance, weatherability and resistance to chemical attack depend to a large extent upon the film-forming polymer and reactive diluent components of the composition used to produce same. As disclosed in U.S. patent application Ser. No. 759,172 filed on July 26, 1985, and U.S. patent application Ser. No. 807,738 filed on Dec. 11, 1985, both in the name of K. L. Hoy, et al., coating compositions containing carbamate and urea derivatives as reactive diluents are found to provide cured coatings having desirable toughness and adhesion. The ability of a coating composition to form a defect-free film depends in part on (a) the ability of a composition to cover or "wet" a substrate and (b) the rheology of composition flow during coating application and cure. A coating composition's ability to "wet" a substrate is related to the degree of surface energy which exists between the coating composition and the substrate surface. As the industry has moved to higher solid content compositions to satisfy ecological considerations, the molecular weight, functionality and geometry of the coating polymers have been lowered, increased and altered, respectively, to minimize the viscosity of the polymer which is reguired for application of the composition contents. In doing so, the wetting of the substrate by the coating compositions has been degraded to the point where many coatings have marginal film forming properties. Indeed, molecules having a higher reactive polar functionality content (increased cohesive character) tend to associate with themselves rather than orient towards the substrate surface. In doing so they tend to pull away from the substrate surface, especially at points of substrate imperfection. The tendency of a coating to shrink away from a substrate surface results in various types of coating defects, a more severe form of which is termed "cratering". Cratering refers to a surface defect caused by a coating composition covering patches of a substrate surface very thinly and other areas of the substrate more thickly, giving rise to the appearance of gullies or "craters" in the finished coating. In order to reduce the severity of surface defects caused by the inability of a composition to properly wet a surface, common practice is to provide a coating composition with one or more anti-cratering additives which, typically, are surfactants. Owing to its biphilic nature, a surfactant additive is effective in reducing the surface energy at coating substrate interfaces of high chemical potential, thereby improving the ability of the coating to wet a substrate surface. These materials, however, tend to exude and migrate to the substrate and surface of the coating during curing. In the extreme, they can cause loss of adhesion, film haze (loss of gloss), and loss of corrosion protection, all of which are serious defects in a coating system. Flow properties of a coating composition depend to some extent on the composition's viscosity. Compositions having higher viscosities generally flow onto substrate surfaces less evenly than compositions having lower viscosities. Coating compositions having poor flow ability tend to produce cured coatings having uneven or irregular surfaces. Among the imperfections attributed to poor composition flow is a surface appearance which, as a result of its resemblance to the rind of an orange, is termed "orange peel". For several applications (e.g., automotive and appliance finishes), the loss of surface uniformity and gloss resulting from orange peel is deemed a commercially unacceptable surface defect. Coatings art teaches that the addition of a high boiling but volatile "reflow" or "tail" solvent will circumvent many of these undesirable flow properties. This formulation strategy provides for the applied coating to flow and level during the early part of a curing cycle before chain extension and cross linking reactions can take place. This practice does, however, contribute to the volatile emissions and in the case of polymer systems designed for high solids finishes, results in the surface defects previously decribed. The optimum viscosity for a given coating application depends in part on the method by which the coating is applied. For example, low pressure spray applications may reguire the use of lower viscosity compositions than high pressure spray applications. As previously noted, reactive diluents oftentimes increase the viscosities of the coating compositions into which they are incorporated. Undesirably high composition viscosities are commonly reduced by volatile organic compound addition. Owing to the environmental constraints on volatile organic compound emission levels, reactive diluent containing compositions typically have relatively narrow formulation ranges. Accordingly, it is an object of this invention to provide a high solids coating composition suitable for use in the production of cured coatings having commercially acceptable chemical and physical properties. It is a further object of this invention to provide a high solids coating composition capable of providing cured coatings having optimum surface appearance. Additionally, it is an object of this invention to provide a high solids coating composition which may be formulated over a relatively broad compositional range.	{ "pile_set_name": "USPTO Backgrounds" }
Microbial communities inhabiting the fairy ring of Floccularia luteovirens and isolation of potential mycorrhiza helper bacteria. Floccularia luteovirens, an important edible mushroom widely distributed in the Qinghai-Tibet plateau, is ecologically important as an ectomycorrhizal fungus and can form the fairy ring. To explore the influence of F. luteovirens fairy ring on soil microbial communities, we compared the soil microbial communities in three different fairy ring zones (inside the fairy ring (IN); beneath the fairy ring (ON); and outside the fairy ring (OUT)). A total of 1.77 million bacterial reads and 1.59 million fungal reads were obtained. Moreover, sequence clustering yielded 519,613 (57,735 per sample) bacterial OTUs, and 513,204 (57,023 per sample) fungal OTUs representing. Microbial diversity was lower in samples from the ON zone compared with the other two zones. Mycorrhiza helper bacteria (MHB) such as Bradyrhizobium and Paenibacillus were more common in the ON zone, and we isolated four potential MHB from rhizosphere soil. Canonical correspondence analysis showed that the soil nutritional condition and physical changes caused by F. luteovirens shaped the microbial communities in the ON zone. This is the first report on the study of soil microbial diversity influenced by fairy ring F. luteovirens, and further studies need to be conducted to study the ecological function influenced by this species.	{ "pile_set_name": "PubMed Abstracts" }
Throughout the Syrian Civil War, Turkey has sought to ease the costs of absorbing millions of civilian refugees by establishing a “safe zone” in Syrian territory, along their mutual border, which could house the refugees instead. Turkey has often tried to sell this to the US with an idea that it would also house Western-backed rebels, giving them meaningful territory. With their invasion of Syria two weeks ago, Turkey has effectively occupied a good chunk of this proposed zone militarily already, but despite trying to present this as having already done the heavy lifting, there is still little international support for the plan. Much of the international community wasn’t thrilled with Turkey just up and invading Syria, and even if they weren’t exactly surprised, it seems that there is a substantial uphill battle to sell anyone else on the idea of funding and defending this safe zone. Ironically, while Turkey seemingly hoped the invasion would force the issue on a plan that has long been debated but never fully endorsed, the fact that they are already there, and already defending the zone, may convince even potential supporters of the idea that they don’t need to stick their necks out at all. Turkey is already there, and that makes it Turkey’s problem. How does a supposedly “antiwar” publication avoid mentioning the obvious fact that Turkey is committing a blatant violation of the UN Charter and international law, by militarily attacking, invading and occupying territory unquestionably belonging to another sovereign nation? You folks are a sick joke.	{ "pile_set_name": "Pile-CC" }
A subsidiary energy company that would deliver natural gas to LNG Canada’s Kitimat plant has filed an application for an injunction against the Unist’ot’en Camp, south of Houston, B.C. Coastal GasLink, a subsidiary of TransCanada Pipelines Ltd., filed an application for an injunction on Friday to gain access to the Morice River Bridge, which it claims is being blockaded by the Unist’ot’en Camp and stalling construction on the project. The Coastal GasLink pipeline would deliver natural gas, starting in an area close to Dawson Creek, all the way to the proposed LNG Canada facility in Kitimat. The Unist’ot’en Camp was constructed in 2010 to assert and “reoccupy” the land of the Wet’suwet’en people, on which several proposed pipelines would be constructed. The Unist’ot’en are a clan of the Wet’suwet’en people. In the application, Coastal GasLink’s proposed injunction would prohibit anyone from “physically preventing, impeding or restricting or in any way physically interfering” with access to the Morice River Bridge or the Morice West Forest Service Road, or coming within 10 metres of Coastal GasLink’s employees or vehicles in the area. The application would also give police authority to arrest people breaching the injunction. In a statement posted on its website, Coastal GasLink said that “this decision was not taken lightly” and is “a last resort and a necessary action in our efforts to safely gain access to the area.” Coastal GasLink named Freda Huson and Warner Naziel, and referenced “others” involved in the bridge blockade, alleging that they were “preventing access” to the area. If the blockade stalled the project, the company claimed, there would be a “significant risk” that the project will miss the date of completion under the contract with LNG, which it claims added up to $24 million in contracts. Karla Tait, an Unist’ot’en house group member, said in a statement that the two people named in the application were not hereditary chiefs and that the injunction ignored the group’s jurisdiction over the land, on which it operates a holistic healing lodge. “The fact that this company can make a civil suit thinking that Freda Huson and Warner Naziel are the only ones standing in the way of their project is utterly ignorant and out of touch with all that we stand for as Unist’ot’en and as Indigenous people,” she said in the statement. StarMetro Vancouver [SOURCE]	{ "pile_set_name": "OpenWebText2" }
New evidence of red blood cell rheological disorders in beta-thalassaemia minor. Haemorheological parameters, such as red blood cell deformability, membrane elastic modulus and membrane surface viscosity in twenty one thalassaemia heterozygous patients (14 beta0/beta and 7 beta+/beta) were compared with normal individuals (n = 15). Parameters were measured applying a laser diffractometric method (ektacytometry). Thalassaemia erythrocytes showed statistically significant lower deformability and higher elastic modulus. Surface viscosity showed no significant differences in thalassaemia. Creep and recovery curves were registered by diffractometry. The normal recovery curve was fitted by a first order exponential decay function, expressing the fitting degree by the chi2 coefficient. The shape of the recovery curve in beta-thalassaemia patients (beta0/beta or beta+/beta) was significantly different from the control group. The possible mechanism of red blood cells abnormal rheological behaviour in beta-thalassaemia minor could be explained by a surface charge reduction. Our results enable us to conclude that the shape of the recovery curve (chi2 coefficient) could be considered as a marker that might be useful in beta-thalassaemia diagnosis.	{ "pile_set_name": "PubMed Abstracts" }
The company is seeking to remove six activists from the Polar Pioneer oil drilling rig, which is travelling to the Chukchi Sea. MOSCOW, April 8 (Sputnik) — Lawyers for the Dutch oil giant Shell have filed a lawsuit with a US federal court against Greenpeace after its activists illegally boarded an Arctic drilling rig, media reports said Wednesday. "Greenpeace has a demonstrated pattern of conducting direct actions against Arctic oil and gas operations that violate the rights of others and create dangerous situations for their targets, law enforcement, and their own members," the lawsuit asserts, as quoted by CBC. The company is seeking to remove the six activists from the Polar Pioneer oil drilling rig, which is travelling to the Chukchi Sea, off the Alaskan coast, aboard a heavy-lift ship called the Blue Marlin. According to the complaint, Greenpeace's ship Esperanza has been stalking the oil platform. The vessel is now trailing the rig at a safe distance after depositing the protesters. Shell has been absent from the Chukchi Sea for three years after its oil rig ran aground there in 2012. Last week, the US Interior Department reapproved Shell's 2008 lease, prompting a relocation of its drilling equipment to the region. Shell will be drilling in dangerous proximity to Wrangel Island reserve off the Russian Far East coast. The United Nations has classified it as a World Heritage Site due to the island's exceptional biodiversity.	{ "pile_set_name": "OpenWebText2" }
Introduction {#Sec1} ============ Major depressive disorder (MDD) is a disease affecting around 16% of people over the age of 13 in the US^[@CR1]^. This prevalent mood disorder greatly impacts a patient's quality of life and is the leading cause of disability around the world^[@CR2]^. Experiencing stressful events throughout one's life, particularly childhood trauma, further increases the likelihood of being diagnosed with MDD^[@CR3]^. These stresses often exacerbate chronic medical issues, such as heart disease, diabetes and other inflammatory disorders^[@CR4]--[@CR6]^. To quantify biological stress, studies have used measured levels of cortisol, a stress hormone, as well as Interleukin (IL-6) and C-reactive protein (CRP), two markers of inflammation. Increased levels of all three of these measures have been linked to both early life stress and MDD^[@CR7]--[@CR9]^. Psychological stress and MDD have also been reported to affect brain anatomy, with numerous brain regions shown to have decreased volumes in patients^[@CR10]^. Indeed, the hippocampus, a subcortical structure critically involved in memory and cognition, has been shown to be sensitive to stress and smaller hippocampal volumes are characteristic of various mood disorders, including MDD^[@CR11]--[@CR13]^. Although global hippocampal volume may differ between populations, the hippocampus is in fact made up of anatomically and functionally distinct subfields that may be differentially sensitive to stressors and play varying roles in mood disorder pathophysiology^[@CR14]^. Therefore, investigating whether specific subfields are linked to MDD may serve to provide greater clarity as to the mechanisms behind the disease^[@CR15]^. There have been several studies published on hippocampal subfields in MDD, some of which have reported volume decreases in the cornu ammonis (CA) and dentate gyrus, while others have found no significant differences between MDD subjects and healthy controls (HCs)^[@CR16]--[@CR18]^. More recent studies have conducted their analyses using the automated segmentation algorithm released in Freesufer 6.0. This algorithm was developed using an atlas based on ex vivo brain tissue, which was scanned under ultra-high field strength. It has been shown to result in more accurate segmentation of the hippocampus, and it is able to label the molecular layer (ML) and granule cell layer (GCL), both which were not available in previous segmentation algorithms^[@CR19]^. Yet, there are relatively few studies published that use the novel algorithm, and conflicting results as to whether differences between the subfields of MDDs and HCs are significant^[@CR20]--[@CR23]^. Only one of these studies used high-field 7T scanners to acquire their hippocampal neuroimaging data. Due to its complex structure and distinct subfields, the hippocampus can particularly benefit from the enhanced resolution and contrast acquired by a 7T scan. Indeed, a study comparing 7T images with ex vivo anatomy found 7T images to provide excellent anatomic detail of the hippocampus^[@CR24]^. Recent developments in ultra-high-field (UHF ≥ 7T) imaging allow for enhanced exploration of both structure and function of the brain. Due to increased signal-to-noise (SNR), spatial resolution, and contrast-to-noise (CNR) ratios, finer details and difficult to scan structures can be better visualised^[@CR25]^. UHF imaging simultaneously poses a number of challenges, such as non-uniform radiofrequency fields, enhanced susceptibility artifacts and higher radiofrequency energy deposition in the tissue creating a higher likelihood of focal RF heating and tissue damage. These issues, however, can be solved at the level of hardware (such as coils), software (such as using particular scanning parameters) and post-scanning data processing (such as bias correction)^[@CR26]^. UHF imaging may also induce transient physiological effects such as nausea, dizziness, metallic taste, magnetophosphenes and increased blood pressure in some subjects. However, these effects are temporary, pose minimal risk to the subject, and do not create major obstacles to scanning^[@CR26]^. Therefore, given the great potential for more accurate and reliable hippocampal segmentations, using 7T imaging data to study the hippocampal subfields of MDD patients may provide more definitive conclusions about the neurobiology of the hippocampus in MDD. This study aimed to explore the brain anatomical and biological stress signatures of MDD and how early exposure to psychological trauma may affect the presentation of the illness using 7T MRI scans. We hypothesised that our MDD subjects would have higher levels of biological stress measures, specifically cortisol, IL-6 and CRP. Despite the hippocampal subfield literature being mixed, we hypothesised that we would find smaller global hippocampal volumes and reductions in the dentate gyrus and cornu ammonis in the MDD group. Methods {#Sec2} ======= Subjects {#Sec3} -------- Adult volunteers between the ages of 18 and 65 were recruited for this study. Patients meeting DSM-IV diagnosis of MDD without other Axis 1 conditions, such as bipolar disorder, psychosis, or substance dependence (determined using the Standard Clinical Interview for Diagnostic and Statistical Manual for Mental Health Disorders---Fourth Edition)^[@CR27]^ were included. Patients with a clinically significant risk of suicidal behaviour, or a need for urgent drug treatment were excluded. Healthy controls without a current or past history of Axis I disorders on DSM-IV were included. Any potential subject with contraindications to magnetic resonance (MR) imaging, who was pregnant or breastfeeding, or was involved in a research project during the month preceding the study was excluded from the study sample as well. Mood ratings were measured using the Hamilton Rating Scale for Depression (HAM-D)^[@CR28]^ and the Beck Depression Inventory (BDI)^[@CR29]^, while anxiety ratings were scored using the Spielberger State Anxiety Inventory (STAI)^[@CR30]^. We also measured anhedonia with the Snaith--Hamilton Pleasure Scale (SHAPS)^[@CR31]^ and fatigue with the Chalder Fatigue Scale (CFS)^[@CR31],[@CR32]^. Collectively, these scores were used to capture illness severity of a given subject. Childhood trauma was measured using the Childhood Trauma Questionnaire (CTQ)^[@CR33]^. All subjects included in this study gave informed written consent, and this study was approved by the National Research Ethics Service Committee (NRES), South-Central Oxford B. Biological stress measures {#Sec4} -------------------------- Venous blood samples were taken at the time of scanning. Five millilitres were assayed on the same day for high sensitivity C-Reactive Protein (hsCRP), using a standard immunoturbidimetric method on an Abbott c 16 000 automatic chemistry analyzer (Abbott Diagnostics, Maidenhead, UK). Another 5 mL were collected into an EDTA tube, centrifuged for 10 min at 1250×g within 30 min to separate plasma, which was then stored at −30 °C until assay. On study completion, the plasma samples were transferred in a single batch, in unlinked anonymized form, for Human IL-6 Immunoassay using a Quantikine® HS (high sensitivity) ELISA kit (R&D Systems, Abingdon, UK). The assay was performed in duplicates. Salivary cortisol was assayed in duplicate using a commercial, ELISA-based method according to manufacturer's instructions (Salimetrics). Imaging {#Sec5} ------- All participants were scanned at the Functional Magnetic Resonance Imaging of the Brain (FMRIB) Centre in Oxford using a 7T Siemens MAGNETOM scanner (Siemens, Erlangen, Germany) with a Nova Medical 32 channel receive array head coil. The whole-brain 1 mm isotropic T1-MPRAGE image was obtained (MPRAGE: repetition time = 8.60 ms, echo time = 4.00 ms, flip angle = 7°, field of view = 192 mm, GRAPPA factor = 4). All MRI scans were visually inspected for anatomical abnormalities before being processed. Due to greater intensity inhomogeneity in 7T scans compared to 3T, images were bias corrected in SPM12 before processing as per the Freesurfer recommendations, with FWHM set at 18 mm, sampling distance at 2 mm, and bias regularisation at 0.001 (<https://surfer.nmr.mgh.harvard.edu/fswiki/>). All other parameters remained at default. Freesurfer 6.0 was then used for motion correction, intensity normalisation, automated topology corrections and fully automatic segmentation of cortical and subcortical regions^[@CR34]--[@CR36]^. Segmentation of the hippocampal subfields was conducted using the automated segmentation method developed by Iglesias et al, which, as shown in Fig. [1](#Fig1){ref-type="fig"}, results in the parcellation of 12 hippocampal subfields^[@CR19]^. All segmentations were visually assessed by taking the segmented image and superimposing it on the corresponding structural T1-weighted image. Only one subject was excluded from analysis due to poor subfield segmentation.Fig. 1A sample segmentation of the left hippocampal subfields of a healthy subject.CA cornu ammonis. In order to optimise the power of our study, we selected eight hippocampal subfields to include in our analysis based on prior findings in the literature^[@CR20],[@CR37],[@CR38]^. The following subfields were included in our analysis: CA1, CA2 and CA3 (noted as CA3 due to the indistinguishable MR contrast between CA2 and CA3), CA4, Granule cell layer, molecular layer, presubiculum, subiculum and the hippocampal tail. Statistical analysis {#Sec6} -------------------- All statistics were performed in RStudio 3.5.0. Chi-square and independent, two-sample t-tests, and Mann--Whitney tests were used to test for demographic differences between groups. Due to the visibly skewed nature of the mood scores and biological stress measure data, shapiro tests of normality were used to evaluate whether parametric testing would be appropriate to evaluate group differences. Mann--Whitney tests were used in lieu of independent two-sample t-tests if the measures were not normally distributed. As an exploratory investigation into biological stress, for each of the biological stress measures, we used the average level across all subjects to divide MDD subjects into 'low' and 'high' level groups and tested whether the groups differed in subfield volume, CTQ scores, illness duration, and illness severity using Mann--Whitney tests. General linear models were conducted to assess the effect of diagnostic group on hippocampal subfield volumes. We also tested whether MDD subjects in the 'high' biological stress measure groups had different subfield volumes than HCs. In order to fully explore gender effects, we also divided the data into male and female datasets and repeated the general linear model analysis to investigate hippocampal subfield differences between MDDs and HCs. In addition, partial correlations were used to examine the relationship between subfield volumes, biological stress markers, mood scores, and illness duration for MDD subjects. FDR corrections were used to adjust for multiple comparisons for all the general linear models and partial correlations. General linear models and partial correlations also controlled for age, gender and total intracranial volume. Significance threshold was set at p \< 0.05. Results {#Sec7} ======= Biological stress measures {#Sec8} -------------------------- Demographic, mood, and biological stress data are summarised in Table [1](#Tab1){ref-type="table"}. There were significant group differences in IL-6 levels, while CRP differences trended towards significance (W = 770.5, p = 0.02; W = 829.5, p = 0.08). There was a positive correlation between IL-6 and CRP levels. Cortisol, however, did not differ significantly between groups and did not have a significant relationship with the other stress measures collected. In addition, there were no significant relationships between any biological stress measures and CTQ or illness duration. We used the average level of each of the biological stress markers to subdivide the MDD subjects into 'low' and 'high' groups; these averages were: cortisol, 0.209 μg/dL; IL-6, 1.27 pg/mL; CRP, 0.88 mg/L. Mann--Whitney tests analysing hippocampal subfield differences between "low" and 'high' groups were not significant for any of the biological stress measures. We also tested for differences in illness duration and mood rating scale scores. There was a trend that indicated subjects with higher CRP scores having higher SHAS scores (low: m = 32.69 ± 5.98; high: m = 35.94 ± 7.84; W = 243.5, p = 0.066). No other differences were significant or approached significance.Table 1Demographic information of study participants.HC (46)MDD (71)tWX^2^pAge (years)31.5 ± 10.531.6 ± 10.20.070.94Gender\<0.0011.00 Male45.7% (21)45.1% (32) Female54.3% (25)54.9% (39)Cortisol (μg/dL)0.2 ± 0.20.2 ± 0.11118.50.89CRP (mg/L)0.5 ± 0.51.1 ± 1.6829.50.08IL-6 (pg/mL)1.2 ± 1.31.4 ± 1.1770.50.02CTQ Emotional abuse6.6 ± 2.412.6 ± 5.7455.5\<0.001 Physical abuse5.3 ± 1.07.7 ± 3.8781.5\<0.001 Sexual abuse5.2 ± 0.76.6 ± 3.91127\<0.001 Emotional neglect8.1 ± 3.514.1 ± 5.0501.5\<0.001 Physical neglect6.0 ± 2.18.5 ± 3.8781.5\<0.001 Denial0.5 ± 1.00.2 ± 0.61662.50.07Currently on medication--22.5% (16)Illness duration (years)--10.9 ± 11.0BDI2.1 ± 4.730.8 ± 8.626.5\<0.001HAM-D0.6 ± 2.422.1 ± 5.510\<0.001STAI26.4 ± 7.152.9 ± 12.0100\<0.001CFS10.1 ± 3.223.2 ± 4.823\<0.001SHAS19.2 ± 5.533.4 ± 6.6165.5\<0.001HC healthy controls, MDD major depressive disorder, BDI beck depression inventory, HAM-D Hamilton Rating Scale for depression, STAI Spielberger state anxiety inventory, CFS Chalder Fatigue Scale, SHAPS Snaith--Hamilton Pleasure Scale. Hippocampal subfields {#Sec9} --------------------- There were no significant group differences in any of the hippocampal subfields examined (Fig. [2](#Fig2){ref-type="fig"}). Global hippocampal volume differences were also not significantly different. Although we found IL-6 levels to increase along with right CA3 volumes (t = 2.751, p = 0.007), this did not survive multiple comparison correction. There were also no hippocampal subfield differences between MDD subjects with high levels of our biological stress measures and MDDs with normal levels. There were no significant relationships between any subfield and any other biological stress measure, CTQ score, illness duration, or mood rating scale. We separated males and females and repeated the hippocampal subfield analysis on both datasets and found no differences between MDDs and HCs. We also compared the hippocampal subfield volumes of our MDD subjects who had high cortisol, IL-6, and CRP levels relative to the rest of the study sample to our HC group. We found the right CA 1 to be smaller in high cortisol MDD patients compared to controls \[MDD high cortisol- M = 567.6 ± 47.2 mm^3^, HC- M = 597.4 ± 61.9 mm^3^, F(1,66) = 5.0, p = 0.03\]. This, however, did not survive FDR correction for multiple comparisons across subfields. The hippocampal subfield volumes of MDD subjects who had high levels of IL-6 and CRP did not differ significantly than those of HCs.Fig. 2Hippocampal subfield volumes of all subjects (mm^3^).Subfield volumes MDDs and HCs were compared using general linear models that were then FDR corrected for multiple comparisons. No subfield differences were found between subject groups. HC Health Controls, MDD Major Depressive disorder, F Female, M Male, CA Cornu Ammonis, GCL Granule Cell Layer, HT Hippocampal Tail, ML Molecular Layer. Discussion {#Sec10} ========== Our study sought to investigate how stress and trauma affect the pathophysiology and symptomatology of MDD. Our MDD cohort had higher levels of trauma than our HC's in all CTQ domains except for denial. Furthermore, MDD subjects were shown to have higher levels of IL-6 and CRP, two common markers of biological stress that we also found to be correlated with one another. Our biological stress measures did not have significant relationships with childhood trauma and did not appear to be related to hippocampal subfield volumes. Although we expected to find hippocampal subfield volume differences between MDD and HC subjects and those with low versus high CTQ scores, our data did not show these trends. As aforementioned, due to the lack of consistent findings regarding hippocampal subfields in MDD, more studies are needed for a clearer characterisation of the role of the hippocampus in the pathophysiology of MDD^[@CR20]--[@CR23]^. In addition, these discrepancies in the literature may be due to the heterogeneity of inherent to mood disorders, and future work emphasising computational approaches to classifying subjects has the potential to better explore MDD and other mood disorders^[@CR39]^. Additionally, a power analysis based on the effect size of 0.35 reported in a meta-analysis on the hippocampus in MDD indicated that our study had a power statistic of 0.38^[@CR11]^. Regarding the association between CTQ scores and hippocampal volumes, studies have reported subjects with higher scores having smaller global hippocampal volume as well as deficits in certain subfields, specifically the CA3, subiculum, and the dentate gyrus^[@CR40],[@CR41]^. However, a meta-analysis examining the effects of childhood maltreatment on global hippocampal volume found an effect size of just 0.08^[@CR42]^. Such a small effect size, in turn, leaves our study with a power statistic equal to 0.07. Therefore, despite having a relatively large sample when compared to published hippocampal subfield studies, the power of our analysis remains limited due to the small effect sizes characteristic of hippocampal abnormalities. Future studies with even larger cohorts and multi-site datasets will have greater power and may provide a clearer picture on the role of hippocampal subfields in MDD. Our findings did, however, imply greater illness severity in MDD subjects with CRP levels above the calculated threshold compared to MDDs in the lower range. As this pattern trended, a more balanced sample of MDD subjects with and without high CRP levels will serve to further elucidate the role of CRP in MDD symptomology. Moreover, when examining the distribution of CRP and IL-6 levels in our sample, we noted that our subjects had lower levels than those reported in studies showing associations between these two biological stress measures and grey matter volumes, which may also factor into our null findings^[@CR43],[@CR44]^. Ultimately our study reports on the intersection between trauma, stress, and hippocampal structure. Due to the rarity of our imaging data being acquired using high-field 7T scanner and the relatively large size sample, we believe that our lack of significant findings regarding the impact that childhood trauma and MDD have on hippocampal subfields remains a useful contribution to a mixed body of literature in need of further investigation. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. These authors contributed equally: Jonika Tannous, Beata R. Godlewska, Phil J. Cowen, Sudhakar Selvaraj This work was supported by an MRC program grant to P.J.C. (MR/K022202/1) and the Oxford Health NIHR Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR or the Department of Health. We thank all the participants, as well as Jon Campbell, David Parker, Michael Sanders and Caroline Young for expert radiographic assistance, and care of the participants during scanning. Anonymized individual subject data are available at the Open Source Framework: osf.io/2cwya/ S.S. has received speaking honoraria from Global Medical Education and honoraria from British Medical Journal Publishing Group; own shares at Flow Med Tech; Research support from Compass pathways. P.J.C has no conflicting interests during the last 3 years. B.R.G. has received travel expenses from Janssen UK. P.J.C. has no conflict of interest. J.C.S. has received grants/research support from BMS, Forrest, J&J, Merck, Compass pathways, Stanley Medical Research Institute, NIH and has been a speaker for Pfizer and Abbott. J.T. has no conflict of interest.	{ "pile_set_name": "PubMed Central" }
#ifndef _NRF_DELAY_H #define _NRF_DELAY_H // #include "nrf.h" /lint --e{438, 522} "Variable not used" "Function lacks side-effects" / #if defined ( __CC_ARM ) static __ASM void __INLINE nrf_delay_us(uint32_t volatile number_of_us) { loop SUBS R0, R0, #1 NOP NOP NOP NOP NOP NOP NOP NOP NOP NOP NOP NOP BNE loop BX LR } #elif defined ( __ICCARM__ ) static void __INLINE nrf_delay_us(uint32_t volatile number_of_us) { __ASM ( "loop:\n\t" " SUBS R0, R0, #1\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " NOP\n\t" " BNE loop\n\t"); } #elif defined ( __GNUC__ ) __INLINE static void nrf_delay_us(uint32_t volatile number_of_us) { do { __ASM volatile ( "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" "NOP\n\t" ); } while (--number_of_us); } #endif void nrf_delay_ms(uint32_t volatile number_of_ms); #endif	{ "pile_set_name": "Github" }
A number of pneumatically or hydraulically operated impact tools have been designed for driving nails into metal/metal or metal/concrete workpieces, with the fasteners being fed from a spring-loaded magazine. As used herein, the term "nail" is intended to include various type of fastening pins that are designed to be driven into a workpiece. The term "workpiece" denotes a multi-layered arrangement of separate members that are to be fastened together by fastening pins, e.g., a corrugated steel decking plate overlying a framework (substrate) formed of interconnected beams, e.g., I-shaped or H-shaped beams or bar joists (2 L-shaped angle irons secured back to back). Such impact tools, often called "powered drivers" or "powered nail drivers" and exemplified by U.S. Pat. Nos. 4,253,598 4,227,637, 4,196,833, 4,040,554, 3,952,398, 3,711,008, 3,638,532 and 3278103 and the prior art cited therein, generally comprise a housing having a hammer guide track in the form of a bore along which a fastening pin driver element (also known as a "hammer") is reciprocated rapidly on command, and a side opening intersecting the guide track which functions as a fastening pin feed port, whereby a fastening pin may be introduced from a magazine into the guide track in the path of the driver element immediately after the driver element has completed a cycle of operation consisting of a drive stroke and a return stroke. While it is possible to load the magazine with loose fastening pins on a one by one basis, loading is facilitated if the fastening pins are pre-assembled in a plastic strip so as to form a clip which can be easily and rapidly inserted into the magazine, and the magazine is provided with a spring biased pusher element for advancing the clip along a guideway in the magazine through the fastening pin feed port into the hammer guide track. Examples of clips of fasteners that have been used in powered nail-driving tools are disclosed in U.S. Pat. No. 3954176, issued on May 4, 1976 to Harry M. Haytayan, U.S. Pat. Nos. 4106618 and 4106619, both issued on Aug. 15, 1978 to Harry M. Haytayan; and U.S. Pat. No. 4106819, issued on Aug. 16, 1978 to Harry M. Haytayan; and the prior art cited in the aforementioned patents. Prior to this invention, the preferred form of nail clip was one that comprised a plastic strip in the form of a row of interconnected sleeves, with a nail extending through and gripped by portions of each sleeve. Such plastic strips are arranged so that the leading sleeve may be sheared off from the remainder of the strip when the nail carried by that sleeve is driven by the hammer of the driver. However, providing strips of nail-supporting sleeves that can be sheared off as intended without jamming the tool has presented problems. It is essential that the plastic strip be designed so as to avoid or minimize any tendency of the leading nail to tilt as it is introduced into the hammer guide track or while it is in the hammer guide track, since whenever a nail is not aligned with the axis of the guide track, there is an increased likelihood that such nail will jam the tool when the hammer commences its drive stroke. Accordingly it is known that each sleeve should be sized so as to make a close sliding fit in the hammer guide track. Typically the guide track is a bore of circular cross-section and the sleeves have a generally cylindrical shape with a maximum outer diameter ("o.d.") about 0,010" less than the diameter of the hammer guide track. This requirement is particularly acute for nail clips where the plastic sleeves do not surround the nail shanks for their full lengths and are spaced from one another by interconnecting web sections. Another known design technique for reducing the likelihood of jamming is to connect them with web sections that minimize the spacing or gap between adjacent sleeves but extend for substantially the full height of the sleeves, whereby the web sections are better able to keep the sleeves perpendicular to the longitudinal axis of the nail strip. Also the web sections are made thin to minimize the shear force required to separate the leading nail sleeve from the next nail sleeve. Typically the web sections have a length measured along the length of the strip of about 0.015 to 0.020" and a width (thickness) of about 0.035". Another design guide rule to prevent tilting of the nail disposed in the hammer guide track is to make the strip of a relatively high density plastic. As used herein the term "high density plastic", e.g., high density polyethylene, means a material with a durometer value of at least 70 on the A scale. A strip of the type described made of a 70-80 durometer plastic provides a stiffness adequate to keep the leading nail straight in the hammer guide bore, thus minimizing jamming of the tool. However, using a high density plastic nail strip suffers from the handicap that the plastic sleeves do not squash as readily as they would if made of a low density material, so that often a substantial portion of the squashed sleeve will be trapped between the workpiece and the driven nail. The stiffness of the nail strip is more critical in steel decking applications where metal deck fastening pins (nails) are required to penetrate a relatively thin steel decking, such as a 0.029" thick (22 gage) corrugated steel sheet, and anchor it to a steel substrate, e.g., to the flange of a bar joist as previously described, such flange typically having a thickness of 0,125" . If a plastic sleeve holding the decking pins is made of a relatively stiff material such as an 80 durometer polyethylene, when a decking pin is driven into the steel decking, the plastic sleeve surrounding that pin tends to act as a piston, deforming the decking and thereby transmitting a force that causes the substrate (bar joist) to (a) separate from the decking so as to leave a gap therebetween and/or (b) deform the substrate by bending and twisting the leg portion of the angle rods that make up the bar joists, and/or (c) preventing the pin from being driven fully into the substrate. In that particular circumstance, the plastic sleeve surrounding the driven nail may or may not completely disintegrate or squeeze out from between the nail head and the steel decking; but regardless of what happens to the squashed sleeve, the holding power of the pin is diminished, frequently enough to require application of another pin to assure that the decking is adequately secured to the substrate. In order to achieve maximum holding force, and thus transmit maximum shear strength to the deck complex, it is essential that the underside of the head of the pin (nail) be in full contact with the steel deck when the steel deck is fastened to the bar joist. Making the strips of a relatively low density polyethylene, e.g., a 40-60 durometer polyethylene, allows the decking pins to be driven so as to achieve maximum holding power. However, the softer low density strips are plagued by the aforementioned tendency of the leading nail to tilt in the hammer guide bore, thereby increasing the likelihood of jamming. This tendency is increased when the tool is used outdoors in hot weather, since a thermoplastic material such as polyethylene will soften with increasing temperature, thereby decreasing the stiffness of the nail strip. In connection with the concern about softening of the nail strip due to increasing temperature, it is important to appreciate that the pushing force exerted on the nail clip by the clip pusher member of the magazine of a tool such as is shown in U.S. Pat. No. 4253598 tends to compress and hence deform the leading sleeve that is disposed in the hammer guide track, and, depending on the ambient temperature and how long the tool lays idle in the sun, the deformation can be sufficient to cause the nail carried by the leading sleeve to be misaligned in the hammer guide track bore, with the result that the tool will jam the next time it is operated.	{ "pile_set_name": "USPTO Backgrounds" }
11 Shares 0 11 0 German spy agency the BND, said that Saudi Arabia was becoming more “impulsive” in its foreign policy, a claim rebuffed on Thursday by the German government. The agency was in particular critical of Saudi’s defense minister, Mohammad bin Salman Al Saud. A government spokesman said "The published assessment does not reflect the position of the German government.” The spokesman added a reaffirmation of Germany’s position that sees Saudi Arabia as an essential partner "in a crisis-ridden world," adding that the relationship is important "especially on the way to peace in Syria.” He made it clear that Germany holds the Saudis in esteem, but from a more practical perspective, as a regional solution and effective fight against the ISIS is precedented on Saudi cooperation, according to the spokesman. The BND briefing that caused the stir was first published in German media. It alleges that changes in Saudi foreign policy have been exaggerated since King Salman came to power in January, and was particularly critical of Saudi’s increasing military intervention in Yemen. Saudi Arabia has led a coalition of nine Arab states carrying out airstrikes and a naval blockade on Yemen since March 2015 to influence the outcome of the country’s civil war. Since the Saudi-led coalition began its airstrike campaign, 78% or 20 million Yemenis have been under attack, in desperate need of food, water and medical aid. The situation has been called a “humanitarian disaster” by human rights groups. The BND further mentioned Saudi Arabia’s decision to back Syrian rebels and Saudi policies in Bahrain, Lebanon and Iraq. The briefing warned against the new leadership in Saudi Arabia saying "What was previously a cautious diplomatic stance of the elder leaders in the royal family is being replaced by an impulsive policy of intervention," further claiming that the Saudis were losing faith in the US’ ability to support their same sides of power. As recently as July, the German Foreign Minister Frank-Walter Steinmeier, speaking with Al Arabiya News praised among other things, the Saudi role in aiming for stability in the region and fighting against Iran’s proxy fighters like Lebanon’s Hizbollah. “Germany and Saudi Arabia have been partners for many years. We know each other well and trust each other. We both hold a leading position in our respective regions. We are both members of the G20. Our governments are firmly committed to working closely together, be it on crisis management in the Middle East or on topics such as energy and climate protection. There is mutual respect between our two governments,” the Foreign Minister said.	{ "pile_set_name": "OpenWebText2" }
You will learn when you start to do pick-up and seduction that “good girl” and “nice girl” are not the same thing. Good girls will test you and they will do it tough. Remember anyway that there is one main thing good girls test for primarily: safety. Realize that all the women you will meet in the course of your pick-up will try to have you become subservient to them. This is deep in our culture and it is also hardwired in woman’s biology. Thousands of years of evolution are at work. Good girls will test you early on and try to have you become subservient to them just like any other kind of woman. It is absolutely not true basing on my field experience that all the women will respond with sexual submission to men who do not supplicate. Instead there are two groups with different behavioral response in regard to supplication. The best women you will meet in the course of your pick-ups will actively try to have you supplicate in a way or another and will be extremely aroused sexually and attracted to you if you don’t. They will test you hard for that, believe me, early on! These are the best women and you want to go for them! On the contrary the women who are trouble will do all what they can to have you supplicate and will become even more resistant to your pick-up and seduction if you don’t. They will have a reaction to your response not easily recognized in the pick-up and seduction community: they will dump you if you don’t supplicate! In this group there are the women to absolutely avoid! For a good girl to be really such she has to be able to live with the fact that a man will not give up his pride, masculinity and sense of honor for a woman. The women in this “try hard” group in regard to supplication are usually: Women in provider-seeking mode who are not able to accept male leadership. You want to be the one to decide are you going to be a provider to a woman or not. You don’t want to start so that she chooses you for that role by having you supplicate. Drop these ones early on! They mean trouble. Women who are unable to have a healthy relationship with a man – for example man haters or women with psychological issues. Women with an agenda. They want you to supplicate to get some advantage out of you. These ones will try to have you supplicate and will become resistant to your seduction if you don’t because they are either scared of the feminine side in their personality or have an agenda. The agenda could be at the simplest: getting married with you! They try to have you supplicate with the purpose of controlling themselves. They can control their own horniness if the guy supplicates to them. On the contrary the women of the first group – the one you want to choose for a relationship – want to feel the joy connected with their own horniness and the joy of being under a strong male’s leadership. These are the women you want to screen in and seduce! The good girls this about is about! During the process of pick-up it is important to quickly distinguish between these two groups. If you invest too much time in the women of the second group you basically get in trouble, get a lot of negative feelings and waste your own time. To avoid subservient behavior and screen out the “bad girls” you need to do a few things: Ask from yourself at any step when she does a move is she trying to have you supplicate. If the answer is yes then you need to ask from yourself the following question: if I do not supplicate is her reaction an increased horniness and emotional submissiveness? Of course to ask from you this question you need to be good enough to not supplicate. If you answer is that she is not reacting with increased horniness and emotional submissiveness to your non subservient behavior then you have to consider these options: 1. Your game was not good enough. In this case learn from the experience. 2. She is trying to control herself for a reason. In the case you feel she is trying to control herself for a reason (usually too much fear or an agenda) simply eject the girl. She is not a good girl by definition! She either has psychological problems or is trying to put you into the subservient frame for a reason. If you are interested in getting to know better bad girls just go for it. If your goal is to find good girls at this stage you can already drop her. At this stage you already know that she is not a good girl: she is controlling herself for a reason! The reason is either big psychological problems or she has an agenda. We will continue this conversation in the next article so stay tuned!	{ "pile_set_name": "OpenWebText2" }
[Cleaniness and hygiene from infancy to adolescence in Karabuk, Safranbolu, Eflani and Eskipazar]. This paper on cleanliness and hygiene from infancy to adolescence is obtained from knowledge collected by means of an interview with women and men informed on the subject. This research is consisted of four main chapters: 1. Environmental and physical hygiene; 2. Baby and child care; 3. Beliefs regarding menstruation; it is commonly called regl - of French origin - in Turkish, which is called "colored" (renkli) days in this area, due to the similarity in the sound of the two words; 4. Beliefs and practices concerning circumcision. This essay deals in washing clothes with usual cleaning agents or using ash alone and ashed water without scrubbing. The practice of hair removal among women and girls is described. Swadding clothes, cradles, pots called havruz and subek for urination of babies in the district, are dealt with in detail. The customs and practices regarding menstruation are described and classified. Before the use of bikini underpants, pads and the menstruation cloth was one of the most important items of a girl's dowry. The techniques used in circumcision in this region were carefuly studied and the beliefs regarding circumcision were put down. This research was completed in fifty one weeks. Various objects obtained during the research have been handed over to the Medical History Museum of Cerrahpasa Medical School.	{ "pile_set_name": "PubMed Abstracts" }
Q: How to say "I look" as in "I look stupid" in French? How do you say "I look" as in "I look pretty/stupid/etc"? Do you use ressemble? Also, out of topic: how do you say "you seem adjective", and how do you express "pretty" as in "That's pretty dumb"? A: "To look" + adjective in French can be said a couple different ways. "Avoir l'air______", e.g. "J'ai l'air ridicule." "Paraître______" e.g. "Elle paraît fatiguée." "Sembler______" e.g. "Ça semble intéressant !" "pretty" can be said a few different ways as well, depending on the context. "Plutôt" "Assez" are the most commonly used. For your examples, you could say: "J'ai l'air plutôt ridicule." "Elle paraît assez fatiguée." "Ça semble plutôt/assez intéressant !"	{ "pile_set_name": "StackExchange" }
Groupon Guide When most people hear the word opera these days, they don’t think of a grand, enthralling tradition that stretches back to 16th-century Italy. Maybe they think of Pagliaccio getting maced with cherry Binaca on a certain episode of Seinfeld, or maybe they think of Bugs Bunny in full valkyrie regalia, but the fact remains that most people have never actually seen an opera for themselves. It’s a powerful experience, and one that’s about much more than viking helmets and guys dressed like sad clowns.	{ "pile_set_name": "Pile-CC" }
Q: How to replace nested functions with class call I need to replace a nested function with a class call. Here is the original code. import numpy as np from variables_3 import vars def kinetics(y,t,b1,b2): v = vars(y) def dydt(v): return [ (b1 v.n) + (b2 * v.c1), (b1 * v.n) - (v.c1), (b1 * v.n) - (v.c2) ] dydt=dydt(v) return dydt In this code, variables3.py contains: class vars: def __init__(self, args): (self.n, self.c1, self.c2)= args I would like my final code to look something like this: import numpy as np from variables_3 import vars from equations_3 import eqns def kinetics(y,t,b1,b2): v = vars(y) dydt=eqns.dydt(v) return dydt What could the file equations_3.py possibly look like to do this? I have tried: from variables_3 import vars class eqns: def dydt(b1,b2,v): return [ (b1 * v.n) + (b2 * v.c1), (b1 * v.n) - (v.c1), (b1 * v.n) - (v.c2)] But that code does not work. Thanks in advance! A: When passing dydt=eqns.dydt(v) in def kinetics(y,t,b1,b2):, make sure to pass b1 and b2 in your function call. Your dydt() function call should look like this: dydt=eqns.dydt(b1, b2, v)	{ "pile_set_name": "StackExchange" }
Q: HTML5 video loading time I am trying to calculate the measure time of html 5 video. I use javascript to listen to html5 video event loadstart and canplaythrough using: media.addEventListener('loadstart'getStartTime(){ startTime = new Date().getTime();}, false) and similar for endTime with event set as canplaythrough to listen. However I could not get any data. Can someone please guide me how to measure video load time using javascript. Thank you for your response, but the solution is I believe using jQuery. however, i was wondering if it is possible from javascript. I have attached a copy of my codes: function loadVideo(){ var timeNow = Date.now(), timeStartLoad, timeFinishLoad; myVideos = new Array(); myVideos[0] = "trailer.mp4"; myVideos[1] = "trailer.ogg"; myVideos[2] = "trailer.m4v"; var videoId = document.getElementById('idForVideo'); var video = document.createElement('video'); for(var i=0; i } however i get undefined for both timestartLoad adn timeFinishLoad. my html body has onload method link to this function. A: Your code has some (copy & paste) syntax problems. var timeInit = Date.now(), timeLoad, timeCanPlay; $("movie").addEventListener('loadstart', function(){ timeLoad = Date.now(); $("t1").innerHTML = "load: " + (timeLoad - timeInit) + " msecs"; }); $("movie").addEventListener('canplaythrough', function(){ timeCanPlay = Date.now(); $("t2").innerHTML = "canplay: " + (timeCanPlay - timeLoad) + " msecs"; }); $("movie").src = "http://ia600208.us.archive.org/12/items/FarSpeak1935/FarSpeak1935_512kb.mp4"; $("movie").play(); Try out: http://jsfiddle.net/noiv/98xZP/:	{ "pile_set_name": "StackExchange" }
The present invention relates to catalyst components for the polymerization of olefins, to the catalysts obtained therefrom and to the use of said catalysts in the polymerization of olefins CH2xe2x95x90CHR in which R is hydrogen or a hydrocarbyl radical with 1-12 carbon atoms. In particular the present invention relates to catalyst components, suitable for the stereospecific polymerization of olefins, comprising Ti, Mg, halogen and an electron donor compound selected from heteroatom containing esters of malonic acids (heteroatom containing malonates). Said catalyst components when used in the polymerization of olefins, and ill particular of propylene, are capable to give polymers in high yields and with high isotactic index expressed in terms of high xylene insolubility. The use of some esters of malonic acid as internal electron donors in catalysts for the polymerization of propylene is already known in the art. In EP-A-45977 is disclosed the use of an ester of malonic acid (diethyl 2,2-diisobutylmalonate) as internal donor of a catalyst for the polymerization of olefins. EP-A-86473 discloses a catalyst for the polymerization of olefins comprising (a) an Al-alkyl compound, (b) an electron donor compound having certain reactivity features towards MgCl2 and (c) a solid catalyst component comprising, supported on MgCl2 a Ti halide and an electron donor selected from many classes of ester compounds including malonates. None of the above-cited applications discloses malonates containing heteroatoms. The same applies to EP-A-86644 that discloses the use of diethyl 2-n-butyl malonate and diethyl 2-isopropylmalonate as internal donors in Mg-supported catalysts for the polymerization of propylene. It is apparent from the analysis of the polymerization results reported in the above-mentioned applications that a common drawback experienced in the use of the mentioned malonates was represented by a still unsatisfactory polymerization yield and/or a not suitable isotactic index of the final polymer. This is confirmed also by the disclosure of JP-08157521. This application relates to a process for preparing a solid catalyst component for polymerization of olefins which is characterized by contacting a solid catalyst component produced by the reaction among a magnesium compound, a titanium compound and an halogen compound, with one or more electron donating compounds represented by the general formula: wherein Rc and Rd are, the same or different, a straight-chain or branched-chain hydrocarbon group having 1-10 carbon atoms, and Ra and Rb are the same or different, a saturated or cyclic saturated hydrocarbon group containing one or more secondary or tertiary carbons and having 3-20 carbon atoms. Although an improvement in terms of yields and isotactic index over the previously cited documents is obtained, the results are still not satisfactory for an economical use of the catalyst components disclosed therein. It has now surprisingly been found that the polymerization yields and the isotactic index of the polymer can be improved by using catalyst components comprising heteroatom containing malonates as internal donors. It is therefore an object of the present invention to provide a solid catalyst component for the polymerization of olefins CH2xe2x95x90CHR in which R is hydrogen or a hydrocarbon radical with 1-12 carbon atoms, comprising Mg, Ti, halogen and an heteroatom containing malonate. The term heteroatom means any atom, different from C and H, in addition to the oxygen atoms deriving from the malonic acid. In particular, the electron donor compounds can be selected from esters of malonic acids of formula (I): wherein R1 and R2 equal to or different from each other, are H or a C1-C20 linear or branched alkyl, alkenyl, cycloalkyl, aryl, arylalkyl or alkylaryl group and said R1 and R2 can also be joined to form a cyclic group; R3 and R4 are independently selected from C1-C20 linear or branched alkyl, alkenyl, cycloalkyl, aryl, arylalkyl or alkylaryl group and R3 and R4 can also be joined to form a cyclic group; with the proviso that at least one of the R1 to R4 groups contains at least one heteroatom selected from the group consisting of halogens, N, O, Si, Ge, P, and S. The heteroatoms, are preferably selected from the group consisting of F, Cl, Br, and Si, and, in a preferred embodiment, they are contained in the R1 or R2 groups. Preferably, R3 and R4 are primary alkyl, arylalkyl or alkylaryl groups having from 2 to 8 carbon atoms which may contain heteroatoms. More preferably, they are primary branched alkyl groups optionally containing heteroatoms. Examples of suitable R3 and R4 groups not containing heteroatoms are methyl, ethyl, n-propyl, n-butyl, isobutyl, neopentyl, 2-ethylhexyl. Examples of suitable R3 and R4 groups containing heteroatoms are 2-chloroethyl, 1-trifluoromethylethyl, 2-trifluoromethylpropyl 2-trimethylsilylethyl, 2-bromoethyl, 2-trifluoromethylpropyl, 4-chlorobenzyl, 2-fluoroethyl, 3-trimethylsilylallyl. R2 is preferably, and particularly when R1 is H, a linear or branched C3-C20 alkyl, cycloalkyl, arylalkyl group; more preferably R2 is a C3-C20 secondary alkyl, cycloalkyl, or arylalkyl. Particularly preferred are also compounds of formula (I) in which R1 is H and R2 is a C5-C20 primary linear or branched alkyl, a C5-C20 cycloalkyl, a C7-C20 arylalkyl or alkylaryl group. Preferably R2 contains at least one heteroatom. Specific examples of suitable monosubstituted malonate compounds are diethyl 2-(1-trifluoromethylethyl)malonate, diethyl 2-(1-trifluoromethylethylidene)malonate, bis(2-chloroethyl) 2-isopropylmalonate, diethyl 2-(trimethylsilylmethyl)malonate, diethyl 2-p-chlorobenzylmalonate, diethyl 2-piperidyl malonate, diethyl 2-(2-ethylpiperidyl)malonate, diethyl 2-(1-trifluoromethyl-1-methylethyl)malonate, diethyl 2-xcex1-phenyl-p-(trifluoromethyl)benzyl malonate, bis(2-fluoroethyl) 2-isopropylmalonate, bis(2-fluoroethyl) 2-ethylmalonate. Among disubstituted malonates preferred compounds are those in which at least one of R1 and R2 is a primary C3-C20 alkyl, cycloalkyl, arylalkyl group. Specific examples of suitable disubstituted malonate compounds are: diethyl-2(1-trifluoromethylethyl)-2-benzylmalonate, diethyl 2-(1-trifluoromethylethyl)-2-methylmalonate, diethyl 2-methyltrimethylsilyl-2-methylmalonate, diethyl 2-p-chlorobenzyl-2-isopropylmalonate, diethyl 2-piperidyl-2-methylmalonate, diethyl 2-(1-trifluoromethyl-1-methylethyl)-2-methylmalonate, bis(2-trimethylsilylethyl) 2-isopropyl-2-isobutylmalonate bis(p-chlorobenzyl) 2-cyclohexyl-2-methylmalonate. It has been surprisingly found that catalyst components in which the internal donor is a heteroatom containing malonate perform better, in term of yields and isotactic index, than catalyst components comprising analogous malonates not containing heteroatoms. As explained above, catalyst components according to the invention comprise, in addition to the above electron donor, Ti, Mg and halogen. In particular, the catalyst component comprises a titanium compound, having at least a Ti-halogen bond and the above mentioned electron donor compound supported on a Mg halide. The magnesium halide is preferably MgCl2 in active form which is widely known from the patent literature as a support for Ziegler-Natta catalysts. Patents U.S. Pat. No. 4,295,718 and U.S. Pat. No. 4,495,3,538 were the first to describe the use of these compounds in Ziegler-Natta catalysis. It is known from these patents that the magnesium dihalides in active form used as support or co-support in components of catalysts for the polymerization of olefins are characterized by X-ray spectra in which the most intense diffraction line that appears in the spectrum of the non-active halide is diminished in intensity and is replaced by a halo whose maximum intensity is displaced towards lower angles relative to that of the more intense line. The preferred titanium compounds used in the catalyst component of the present invention are TiCl4 and TiCl3; furthermore, also Ti-haloalcoholates of formula Ti(OR)nxe2x88x92yXy, where n is the valence of titanium and y is a number between 1 and n, can be used. The preparation of the solid catalyst component can be carried out according to several methods. According to one of these methods, the magnesium dichloride in an anhydrous state and the heteroatom containing malonate are milled together under conditions in which activation of the magnesium dichloride occurs. The so obtained product can be treated one or more times with an excess of TiCl4 at a temperature between 80 and 135xc2x0 C. This treatment is followed by washings with hydrocarbon solvents until chloride ions disappear. According to a further method, the product obtained by co-milling the magnesium chloride in an anhydrous state, the titanium compound and the heteroatom containing malonate is treated with halogenated hydrocarbons such as 1,2-dichloroethane, chlorobenzene, dichloromethane etc. The treatment is carried out for a time between 1 and 4 hours and at temperature of from 40xc2x0 C. to the boiling point of the halogenated hydrocarbon. The product obtained is then generally washed with inert hydrocarbon solvents such as hexane. According to another method, magnesium dichloride is preactivated according to well known methods and then treated with an excess of TiCl4 at a temperature of about 80 to 135xc2x0 C. which contains, in solution, a heteroatom containing malonate. The treatment with TiCl4 is repeated and the solid is washed with hexane in order to eliminate any non-reacted TiCl4. A further method comprises the reaction between magnesium alcoholates or chloroalcoholates (in particular chloroalcoholatcs prepared according to U.S. Pat. No. 4,220,554) and an excess of TiCl4 comprising the heteroatom containing malonate in solution at a temperature of about 80 to 120xc2x0 C. According to a preferred method, the solid catalyst component can be prepared by reacting a titanium compound of formula Ti(OR)nxe2x88x92yXy, where n is the valence of titanium and y is a number between 1 and n, preferably TiCl4, with a magnesium chloride deriving from an adduct of formula MgCl2. pROH, where p is a number between 0.1 and 6 and R is a hydrocarbon radical having 1-18 carbon atoms. The adduct can be suitably prepared in spherical form by mixing alcohol and magnesium chloride in the presence of an inert hydrocarbon immiscible with the adduct, operating under stirring conditions at the melting temperature of the adduct (100-130xc2x0 C.). Then, the emulsion is quickly quenched, thereby causing the solidification of the adduct in form of spherical particles. Examples of spherical adducts prepared according to this procedure are described in U.S. Pat. No. 4,399,054 and U.S. Pat. No. 4,469,648. The so obtained adduct can be directly reacted with the Ti compound or it can be previously subjected to thermal controlled dealcoholation (80-130xc2x0 C.) so as to obtain an adduct in which the number of moles of alcohol is generally lower than 3 preferably between 0.1 and 2.5. The reaction with the Ti compound can be carried out by suspending the adduct (dealcoholated or as such) in cold TiCl4 (generally 0xc2x0 C.); the mixture is heated up to 80-130xc2x0 C. and kept at this temperature for 5-2 hours. The treatment with TiCl4 can be carried out one or more times. The heteroatom containing malonate can be added during the treatment with TiCl4. The treatment with the electron donor compound can be repeated one or more times. The preparation of catalyst components in spherical form is described for example in European Patent Applications EP-A-395083, EP-A-553805, EP-A-553806, EP-A-601525 and WO98/44001. The solid catalyst components obtained according to the above method show a surface area (by B.E.T. method) generally between 20 and 500 m2/g and preferably between 50 and 400 m2/g, and a total porosity (by B.E.T. method) higher than 0.2 cm3/g preferably between 0.2 and 0.6 cm3/g. The porosity (Hg method) due to pores with radius up to 10.000 xc3x85 generally ranges from 0.3 to 1.5 cm3/g, preferably from 0.45 to 1 cm3/g. A further method to prepare the solid catalyst component of the invention comprises halogenating magnesium dihydrocarbyloxide compounds, such as magnesium dialkoxide or diaryloxide, with solution of TiCl4 in aromatic hydrocarbon (such as toluene, xylene etc.) at temperatures between 80 and 130xc2x0 C. The treatment with TiCl4 in aromatic hydrocarbon solution can be repeated one or more times, and the heteroatom containing malonate is added during one or more of these treatments. In any of these preparation methods the desired heteroatom containing malonate can be added as such or, in an alternative way, it can be obtained in situ by using an appropriate precursor capable to be transformed in the desired electron donor compound by means, for example, of known chemical reactions such as esterification, transesterification etc. Generally, the heteroatom containing malonate is used in molar ratio with respect to the MgCl2 of from 0.01 to 1 preferably from 0.05 to 0.5. The solid catalyst component according to the present invention are converted into catalysts for the polymerization of olefins by reacting them with organoaluminum compounds according to known methods. In particular, it is an object of the present invention a catalyst for the polymerization of olefins CH2xe2x95x90CHR, in which R is hydrogen or a hydrocarbyl radical with 1-12 carbon atoms, comprising the product of the reaction between: (a) a solid catalyst component comprising a Mg, Ti and halogen as essential elements and an heteroatom containing ester of malonic acids; (b) an alkylaluminum compound and, optionally, (c) one or more electron-donor compounds (external donor). The alkyl-Al compound (b) is preferably selected from the trialkyl aluminum compounds such as for example triethylaluminum, triisobutylaluminum, tri-n-butylaluminum, tri-n-hexylaluminum, tri-n-octylaluminum. It is also possible to use mixtures of trialkylaluminum""s with alkylaluminum halides, alkylaluminum hydrides or alkylaluminum sesquichlorides such as AlEt2Cl and Al2Et3Cl3. The external donor (c) can be of the same type or it can be different from the heteroatom containing malonate. Suitable external electron-donor compounds include silicon compounds, ethers, esters such as ethyl 4-ethoxybenzoate, amines, heterocyclic compounds and particularly 2,2,6,6-tetramethyl piperidine, ketones and the 1,3-diethers of the general formula (II): wherein RI, RII, RIII, RIV, RV and RVI equal or different to each other, are hydrogen or hydrocarbon radicals having from 1 to 18 carbon atoms, and RVII and RVIII, equal or different from each other, have the same meaning of RI-RVI except that they cannot be hydrogen; one or more of the RI-RVIII groups can be linked to form a cyclic group. Particularly preferred are the 1,3-diethers in which RVII and RVIII are selected from C1-C4 alkyl radicals. Another class of preferred external donor compounds is that of silicon compounds of formula Ra5Rb6Si(OR7)c, where a and b are integer from 0 to 2, c is an integer from 1 to 3 and the sum (a+b+c) is 4; R5, R6, and R7, are alkyl, cycloalkyl or aryl radicals with 1-18 carbon atoms optionally containing heteroatoms. Particularly preferred are the silicon compounds in which a is 1, b is 1, c is 2, at least one of R5 and R6 is selected from branched alkyl, cycloalkyl or aryl groups with 3-10 carbon atoms optionally containing heteroatoms and R7 is a C1-C10 alkyl group, in particular methyl. Examples of such preferred silicon compounds are methylcyclohexyldimethoxysilane, diphenyldimethoxysilane, methyl-t-butyldimethoxysilane, dicyclopentyldimethoxysilane, 2-ethylpiperidinyl-2-t-butyldimethoxysilane and 1,1,1, trifluoropropyl-2-ethylpiperidinyl-dimethoxysilane. Moreover, are also preferred the silicon compounds in which a is 0, c is 3, R6 is a branched alkyl or cycloalkyl group, optionally containing heteroatoms, and R7 is methyl. Examples of such preferred silicon compounds are cyclohexyltrimethoxysilane, t-butyltrimethoxysilane and thexyltrimethoxysilane. The electron donor compound (c) is used in such an amount to give a molar ratio between the organoaluminum compound and said electron donor compound (c) of from 0.1 to 500, preferably from 1 to 300 and more preferably from 3 to 100. As previously indicated, when used in the (co)polymerization of olefins, and in particular of propylene, the catalysts of the invention allow to obtain, with high yields, polymers having a high isotactic index (expressed by hitch xylene insolubility X.I.), thus showing an excellent balance of properties. This is particularly surprising in view of the fact that, as it can be seen from the comparative examples here below reported, the use as internal electron donors of malonate compounds not containing heteroatoms gives worse results in term of yields and/or xylene insolubility. Therefore, it constitutes a further object of the present invention a process for the (co)polymerization of olefins CH2xe2x95x90CHR, in which R is hydrogen or a hydrocarbyl radical with 1-12 carbon atoms, carried out in the presence of a catalyst comprising the product of the reaction between: (a) a solid catalyst component comprising a Mg, Ti, halogen arid a heteroatom containing malonate, (b) an alkylaluminum compound and, optionally, (c) one or more electron-donor compounds (external donor). Said polymerization process can be carried out according to known techniques for example slurry polymerization using as diluent an inert hydrocarbon solvent, or bulk polymerization using the liquid monomer (for example propylene) as a reaction medium. Moreover, it is possible to carry out the polymerization process in the gas-phase operating in one or more fluidized or mechanically agitated bed reactors. The polymerization is generally carried out at temperature of from 20 to 120xc2x0 C., preferably of from 40 to 80xc2x0 C. When the polymerization is carried out in the gas-phase the operating pressure is generally between 0.5 and 10 MPa, preferably between 1 and 5 MPa. In the bulk polymerization the operating pressure is generally between 1 and 6 MPa preferably between 1.5 and 4 MPa. Hydrogen or other compounds capable to act as chain transfer agents can be used to control the molecular weight of polymer.	{ "pile_set_name": "USPTO Backgrounds" }
1. Introduction {#sec1-ijerph-17-01067} =============== Nasolacrimal duct obstruction (NLDO) is the most common cause of childhood epiphora \[[@B1-ijerph-17-01067]\]. Failed canalisation of the distal nasolacrimal duct, associated with a membranous obstruction at the level of Hasner's valve, is the main cause of congenital NLDO; acquired causes of NLDO include infections and traumatic obstructions \[[@B2-ijerph-17-01067]\]. Congenital NLDO is managed conservatively in the first year of life, usually resolving spontaneously, coincident with elongation and volume expansion of the nasolacrimal duct \[[@B3-ijerph-17-01067],[@B4-ijerph-17-01067],[@B5-ijerph-17-01067]\]. Epiphora which persists after the age of one year old may require surgical intervention, as the success rates of conservative treatment decline with increasing age \[[@B6-ijerph-17-01067]\]. The surgical treatment of NLDO in children is classically based on a stepwise paradigm, with probing as the primary procedure, followed by balloon catheter dilation \[[@B7-ijerph-17-01067]\]. Intubation has traditionally been reserved for congenital NLDO refractory to other measures \[[@B7-ijerph-17-01067],[@B8-ijerph-17-01067],[@B9-ijerph-17-01067]\]. Intubation involves the placement of a stent within the nasolacrimal duct to prevent re-closure of the membranous obstruction. With the advent of technologically superior instrumentation and surgical skills, lacrimal intubation is not only an increasingly popular alternative to dacryocystorhinostomy (DCR) for cases which fail conservative management and probing, but also serves as an adjunct during balloon dacryoplasty \[[@B9-ijerph-17-01067]\] and DCR \[[@B10-ijerph-17-01067],[@B11-ijerph-17-01067]\]. This systematic review aims to present the current role of intubation in the management of children with NLDO requiring surgical intervention. 2. Materials and Methods {#sec2-ijerph-17-01067} ======================== 2.1. Search Strategies {#sec2dot1-ijerph-17-01067} ---------------------- The search was conducted over a period of 5 months (November 2018 to March 2019) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines \[[@B12-ijerph-17-01067]\] and the Cochrane Handbook \[[@B13-ijerph-17-01067]\] when appropriate. The literature search was conducted by searching for English-language articles from the electronic databases PubMed, SCOPUS, and the COCHRANE library. The following keywords were used either individually or in combination to aid in retrieving the articles: stents, children, lacrimal intubation, endoscopic DCR (EDCR), external DCR (extDCR), NLDO, dacryocystitis, congenital, acquired. Literature for inclusion in the review was restricted to the period of 1997 to 2019 in order to keep the information as relevant and up to date as possible. 2.2. Eligibility Criteria {#sec2dot2-ijerph-17-01067} ------------------------- Articles were included in the systematic review if they fulfilled the following eligibility criteria: (1) prospective comparative design (e.g., randomised and non-randomised controlled trials (RCT), cohort study), retrospective with comparative group design (e.g., case-control, cross-sectional), retrospective or prospective non-comparative design (e.g., case series, before and after study); (2) included participants were less than 18 years of age; (3) intubation was part of the management of NLDO. Articles were excluded if they were (1) case reports; (2) abstract only studies; (3) published in a language other than English. 2.3. Study Outcomes {#sec2dot3-ijerph-17-01067} ------------------- The primary outcome was defined as the success of the intervention, determined by the resolution of symptoms and the patency of the lacrimal anatomy confirmed by the fluorescein dye disappearance test, syringing or irrigation of the nasolacrimal duct. The secondary outcome was the presence of complications. 2.4. Screening and Data Extraction {#sec2dot4-ijerph-17-01067} ---------------------------------- The authors selected the studies according to the predetermined inclusion and exclusion criteria for this systematic review. This was done by reading the abstracts and/or the full articles. A standardised data extraction form was developed by the authors and used in the present study. The variables extracted from the studies included study location (country), number of patients, age, gender, intervention procedure, duration of tube removal, duration of follow up, overall successful outcome, and post-operative complications. Data extraction from the included studies was done by two authors independently. Any discrepancy between the two authors with respect to the data extracted were discussed. When disagreements remained, a third author was consulted for his/her opinion and decision. 2.5. Quality Assessment {#sec2dot5-ijerph-17-01067} ----------------------- The quality assessment of the included studies was conducted by using the Effective Public Health Practice Project (EPHPP) checklist \[[@B14-ijerph-17-01067]\]. The EPHPP has been widely used in assessing the quality of public health intervention studies of varying study designs \[[@B15-ijerph-17-01067],[@B16-ijerph-17-01067],[@B17-ijerph-17-01067]\]. The EPHPP checklist has six components of assessment of study methodology; selection bias, study design, confounders, blinding, data collection methods, withdrawal and dropouts. These components were scored as either weak, moderate, or strong. The overall quality rating for each included study was also scored as either weak, moderate, or strong. An overall quality rating of 'strong' was assigned when there were no weak ratings, 'moderate' was assigned when there was one weak rating, and 'weak' was assigned when there were two or more weak ratings on the components of EPHPP. The quality assessment was conducted by two authors. Any discrepancy of scoring was discussed to reach consensus. Some components of EPHPP were labelled as not applicable for some studies. For example, the component of withdrawals and dropouts were not applicable for studies with retrospective study design, while that of blinding was not applicable for non-comparative studies, case series, or studies with a single group. 3. Results {#sec3-ijerph-17-01067} ========== 3.1. Literature Search {#sec3dot1-ijerph-17-01067} ---------------------- A total of 144 articles were identified from the electronic databases. One hundred and twenty- eight articles remained after duplicates were removed. Seventy-nine articles were excluded after screening the titles and abstract as they did not meet the review criteria. Of the remaining 49 articles, data extraction was done by two authors independently; 14 articles that included adult samples and did not report subgroup analysis result for children samples below 16 years old were excluded. A total of 35 studies which fulfilled the selection criteria were included in the review (see [Figure 1](#ijerph-17-01067-f001){ref-type="fig"}). From the included studies, several types of study designs were used by the authors. These were randomised controlled trials (5 studies), non-randomised controlled trials (5 studies), retrospective with comparative groups (4 studies), non-comparative or single group (20 studies), and retrospective record review with descriptive study (1 study). 3.2. Description of the Studies {#sec3dot2-ijerph-17-01067} ------------------------------- A total of 2953 patients were pooled. The total number of patients for each study ranged from 4 to 635 patients. The mean age of patients ranged from 15 months to 11 years old. All studies involved the use of silicone stents. The majority of the included studies involved lacrimal intubation (85.7%, 30 studies), with or without a comparative group; followed by intubation as an adjunctive procedure to extDCR (2 studies), EDCR (1 study), both extDCR and EDCR (1 study), and balloon dacryoplasty (1 study). The duration of the stent placements varied, while the average follow-up after removal of stent ranged from 9 weeks to 40 months. [Table 1](#ijerph-17-01067-t001){ref-type="table"} summarises the studies included in this systematic review. 3.3. Outcomes {#sec3dot3-ijerph-17-01067} ------------- A meta-analysis was not performed due to the heterogeneity of all the included studies. Hence, meaningful interpretation of the study outcomes in the included studies required expert discussion and clinical judgement. The two main outcomes, percentage of success and presence of complications, are narratively described in [Table 2](#ijerph-17-01067-t002){ref-type="table"}. The overall success outcome of the studies' interventions ranged from 41.1% to 100%. Post-operative complications were reported in 23 studies, while nine studies reported no complications. Three studies did not report the complication rate. 3.4. Quality Assessment {#sec3dot4-ijerph-17-01067} ----------------------- Using the EPHPP global rating decision tool, four studies were assessed as being of moderate quality and 31 of weak quality (see [Table 3](#ijerph-17-01067-t003){ref-type="table"}). Most of the studies were considered weak due to the study design and non-control of confounding factors. However, based on individual methodology component assessment, all studies were assessed as being of strong quality in terms of selection bias. All eligible patients in the included studies were from hospital-based samples. As clinical cases of children with nasolacrimal duct obstruction requiring surgical intervention were limited in nature, probability sampling methods such as the random sampling method were considered infeasible. Therefore, the authors considered that the studies assessed had included samples that were representative of their target population and were thus of strong quality in terms of selection bias. Five studies were rated as strong quality in terms of study design because the authors used randomised controlled trials in their intervention study. Four studies were rated as strong quality in terms of controlling for confounding variables (e.g., age, gender), as confounders were either balanced at baseline, or controlled for during the analysis. Data collection methods were considered strong for all studies because the authors used a standard assessment criteria of success, such as complete resolution of epiphora and the dye disappearance test. 4. Discussion {#sec4-ijerph-17-01067} ============= The management of children with epiphora is challenging, not only because of the miniaturized and variable anatomy of the lacrimal drainage pathways, but also because of the lack of high quality evidence regarding the optimal treatment of NLDO in children. Probing, which involves pushing a metal wire through the punctum, canaliculi, lacrimal sac, and nasolacrimal duct into the nose, is the standard of care for congenital NLDO. Although probing is successful in uncomplicated obstructions of the distal nasolacrimal duct \[[@B50-ijerph-17-01067]\], which comprise the majority of cases in children \[[@B51-ijerph-17-01067]\], NLDO due to anatomical variations or scarred tissue, such as in Down syndrome, trauma or craniofacial malformations, is more difficult to manage \[[@B28-ijerph-17-01067],[@B52-ijerph-17-01067],[@B53-ijerph-17-01067],[@B54-ijerph-17-01067],[@B55-ijerph-17-01067]\]. In cases which fail primary probing, treatment options include repeat probing, lacrimal intubation or balloon dacryoplasty, before resorting to DCR as a last measure \[[@B6-ijerph-17-01067],[@B56-ijerph-17-01067]\]. The role of stenting in the management of children with NLDO is poorly defined. Unlike in adults with acquired NLDO, where trials have shown no benefit of intubation on the 12-month success rate of endonasal DCR \[[@B57-ijerph-17-01067],[@B58-ijerph-17-01067]\], the value of stenting in cases of paediatric NLDO requires further elucidation. Most of the studies reviewed involved only lacrimal intubation, which generally had high success rates. Two RCTs compared stenting with other interventions for NLDO in children. Elsawaby et al. found no statistically significant difference in success rates between stenting and probing as a primary treatment for patients with congenital NLDO aged 6 months to 36 months \[[@B21-ijerph-17-01067]\]. Unfortunately, the lack of blinding or controlling for confounders resulted in a weak overall global rating for this study. Other non-randomized studies comparing stenting to probing as a primary procedure were likewise rated weak; Eshraghi et al. found a significantly higher success rate (73.3% vs. 48.9%) in the Masterka stent group compared with the probing group in children older than 18 months \[[@B27-ijerph-17-01067]\], while Al-Faky et al. noted a success rate of 88% for stenting and 80.3% for probing \[[@B28-ijerph-17-01067]\]. In general, intubation has been found to have an advantage over probing alone in certain groups, such as those with bilateral congenital NLDO, Down syndrome, history of acute dacryocystitis, and other causes of complex NLDO \[[@B28-ijerph-17-01067],[@B59-ijerph-17-01067],[@B60-ijerph-17-01067]\]. Unfortunately, beyond a certain age, the success rate of intubation as a primary or secondary procedure after failed probing appears to decline \[[@B32-ijerph-17-01067],[@B55-ijerph-17-01067]\]. A RCT by Ceylan et al. observed that intubation was inferior to balloon dilation for the primary surgical treatment of congenital NLDO in children older than three years of age \[[@B20-ijerph-17-01067]\]. Two types of intubation were evaluated in the studies assessed; intubation using monocanalicular versus bicanalicular stents. The monocanalicular stent passes through a single canaliculus to the lacrimal sac and NLD, whereas the bicanalicular stent courses through both canaliculi into the sac and nasal cavity, after which the ends are tied in a loop inside the nasal cavity. Using a monocanalicular or bicanalicular stent had no statistically significant effect on outcome \[[@B18-ijerph-17-01067],[@B23-ijerph-17-01067]\], although some authors prefer monocanalicular intubation for its ease of insertion and tube removal as well as a lower incidence of canalicular slit \[[@B25-ijerph-17-01067],[@B26-ijerph-17-01067]\]. The duration of stenting ranged from three weeks to six months. In most studies, stents were removed after three months. It may be important to note that retention of stents for longer than 12 months has been associated with a significantly lower success rate \[[@B61-ijerph-17-01067]\]. On the contrary, early stent removal (at approximately two months) has not been shown to affect the success rate among younger children, particularly those less than two years of age \[[@B22-ijerph-17-01067],[@B37-ijerph-17-01067],[@B62-ijerph-17-01067]\]. In older children, higher reoperation rates are associated with stent removal prior to 4--6 weeks \[[@B37-ijerph-17-01067],[@B62-ijerph-17-01067]\]. The rationale for intubation is that the stent may maintain patency of the newly-created lacrimal drainage passage by preventing the formation of granulation-related obstruction \[[@B63-ijerph-17-01067]\]. The latter may be a particular problem in children due to their anatomically narrower nasolacrimal ducts \[[@B64-ijerph-17-01067]\], elevated inflammatory tendencies, and unpredictable remodeling in response to probing-induced trauma \[[@B65-ijerph-17-01067]\], all of which may contribute to a greater risk of restenosis and failure after probing. When used as adjunctive treatment in DCR, intubation has been associated with a significantly lower incidence of operative revision \[[@B41-ijerph-17-01067]\]. Although there is a paucity of histopathological evidence of the effect of stenting in children, comparison of lacrimal sac biopsies in adults with and without silicone stents has not demonstrated any significant differences in mucosal histopathology \[[@B66-ijerph-17-01067]\]. The duration of stenting in the aforementioned study was approximately three months. A study of tear inflammatory cytokines after endoscopic endonasal DCR observed that levels of interleukin (IL)-1β, IL-2, IL-6, vascular endothelial growth factor and fibroblast growth factor-2 were higher in patients post DCR than in the control group, but rapidly returned to control group levels after stent removal \[[@B67-ijerph-17-01067]\]. This may explain the lower success rates associated with prolonged stent retention, as persistently elevated cytokines may cause sustained inflammation and fibrosis \[[@B61-ijerph-17-01067]\]. Another downside of intubation is that stent-related complications are not uncommon \[[@B68-ijerph-17-01067]\]. The most common of these is early stent dislodgement or loss, occurring in up to 50% of cases \[[@B22-ijerph-17-01067],[@B23-ijerph-17-01067],[@B25-ijerph-17-01067],[@B26-ijerph-17-01067],[@B30-ijerph-17-01067],[@B38-ijerph-17-01067],[@B68-ijerph-17-01067]\]. The prognostic value of this complication depends on age and the timing of tube displacement; the risk of reoperation is higher in children older than two years with stent retention of less than two months \[[@B36-ijerph-17-01067],[@B62-ijerph-17-01067]\]. Stent displacement may also cause corneal abrasions \[[@B10-ijerph-17-01067],[@B26-ijerph-17-01067],[@B55-ijerph-17-01067]\] and ulceration \[[@B21-ijerph-17-01067],[@B38-ijerph-17-01067]\]. Minor complications include those related to the lacrimal passages, such as punctal or canalicular slitting due to cheese-wiring \[[@B25-ijerph-17-01067],[@B26-ijerph-17-01067],[@B30-ijerph-17-01067],[@B37-ijerph-17-01067],[@B43-ijerph-17-01067]\] and granuloma formation \[[@B26-ijerph-17-01067],[@B37-ijerph-17-01067],[@B45-ijerph-17-01067]\]. This systematic review observed that lacrimal intubation is most commonly performed as a primary procedure in children with congenital NLDO, with good outcome. It is preferred over probing alone in complex NLDO \[[@B28-ijerph-17-01067],[@B59-ijerph-17-01067],[@B60-ijerph-17-01067]\]. Up to approximately ten years old, age is not predictive of intubation failure \[[@B32-ijerph-17-01067],[@B61-ijerph-17-01067]\]. The optimal timing of stent removal is two months post insertion, although children more than two years old may require a longer duration of stenting. The main complication is stent dislodgement. Considering the technical ease of stent manipulation and high success rates, it seems reasonable to perform primary intubation in children undergoing initial probing. However, well-designed, adequately powered RCTs are required to define the role of intubation as a primary or adjunctive procedure in the surgical management of children with NLDO. 5. Conclusions {#sec5-ijerph-17-01067} ============== This systematic review identified only two RCTs evaluating the benefit of stenting over other surgical modalities in the management of children with NLDO. In the absence of high-quality evidence, the decision of whether to perform lacrimal intubation in children with NLDO requiring surgical intervention depends on clinical judgement and other low-level evidence, such as observational non-randomised trials. The authors would like to express their gratitude and heartfelt thanks to the librarian in Universiti Sains Malaysia for providing articles needed in the present review. Conceptualisation, B.A., E.L.M.T., and Y.C.K.; Methodology, B.A., E.L.M.T., and Y.C.K.; Validation, B.A., E.L.M.T., and Y.C.K; Formal analysis, B.A., E.L.M.T., and Y.C.K.; Resources, B.A., E.L.M.T., and Y.C.K.; Writing---Original Draft Preparation, B.A., E.L.M.T., and Y.C.K.; Writing---Review and Editing, B.A., E.L.M.T., and Y.C.K. All authors have read and agreed to the published version of the manuscript. This research received no external funding. The authors declare no conflicts of interest. ![Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart.](ijerph-17-01067-g001){#ijerph-17-01067-f001} ijerph-17-01067-t001_Table 1 ###### Characteristics of the studies reviewed. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Study Design First Author, Year Country Procedure Number of Patients\\|Number of Eyes Mean Age in mo/yr\ Gender in % (male) Timing of Postoperative Stent Removal in d/wk/mo Mean Follow--up in wk/mo (min--max) (min--max) -------------------------------------------------------------------------------- ------------------------------------------------ ------------------- ------------------------------------------------------------- ------------------------------------ -------------------- --------------------------- -------------------------------------------------- ------------------------------------- Randomised controlled trials Andalib, 2010 \[[@B18-ijerph-17-01067]\] Iran LI 57\\|70 MCI: 34.9mo NR 3mo NR (13--71mo) BCI: 38.7mo (14--84mo) Andalib, 2014 \[[@B19-ijerph-17-01067]\] Iran LI 49\\|53 MCI: 26.25mo NR 3mo NR (13--49mo) PMCI: 26.85mo (16--68mo) Ceylan, 2007 \[[@B20-ijerph-17-01067]\] Turkey LI 20\\|24 (BCI) 50.8mo (36--120mo) NR Average 6.2 mo NR (12mo--NR) Elsawaby, 2016 \* \[[@B21-ijerph-17-01067]\] Egypt LI 27\\|30 14.85mo 50 At least 3wk 16wk (NR) (7--30mo) Kominek, 2010 \[[@B22-ijerph-17-01067]\] Czech Republic LI 83\\| 95 (Group 1: 42\\|48; Group 2:41\\|47) NR (15--30mo) NR Group 1: 2mo NR (NR--6mo) Group 2: 5mo Non--randomised controlled trials Eshraghi, 2017a \[[@B23-ijerph-17-01067]\] Iran LI 99\\|99 (MCI:52\\|52; BCI:47\\|47) 3.56yr 57.6 3mo NR (NR--12mo) (1.3--10yr) Fayet, 2011 ^\#^ \[[@B24-ijerph-17-01067]\] France LI 68\\|68 (Group 2:6\\|6; Group 3:62\\|62) Group 2: NR NR Group 2: 39d Group 3: 29d Group 2: 14wk (3--30wk) (1--9yr) Group 3: NR Group 3: 16wk (3--74wk) (1--6yr) Lee, 2012 \[[@B25-ijerph-17-01067]\] South Korea LI 46\\|60 (BCI:22\\|30; MCI:24\\|30) BCI:23.3mo 52.2 BCI: 5--22wk BCI: 16.4 wk (NR) (9--52mo) MCI: 23.1mo MCI:5--15wk MCI: 11.6 wk (NR) (8--62mo) Kominek, 2011 \[[@B26-ijerph-17-01067]\] Czech Republic LI 53\\|70 (BCI:24\\|35; MCI:29\\|35) NR (10--36mo) 44.3 3--4mo NR (NR--6mo) Eshraghi, 2017b \[[@B27-ijerph-17-01067]\] Iran LI 45\\|45 (LI only, study compared LI and probing) 28mo (NR) NR Average 9.2 wk NR (1wk--6mo) Retrospective with comparative groups Al--Faky, 2012 ^\$^ \[[@B28-ijerph-17-01067]\] Iran LI 350\\|454 32.6mo 46 3mo 15.3mo (12--132mo) (3--108mo) Kaufman, 1998 ^&^ \[[@B29-ijerph-17-01067]\] United States LI 64\\|73 (Prospective:39\\|48 31.8mo NR 4--6mo NR (3--12wk) Retrospective:25\\|25) (12--87mo) Rajabi, 2016 \[[@B30-ijerph-17-01067]\] Iran LI 338\\|338 (Crawford:248\\|248; Monoka:52\\|52; Masteka:38\\|38) NR 56.1 3mo Schedule follow up 3mo (1--4yr) Khatib, 2017 \[[@B31-ijerph-17-01067]\] United States LI 53\\|72 (complex; simple) 22mo NR 2--3mo 14mo (5--65mo) (6--29mo) Retrospective/prospective with single group/non--comparative/consecutive cases Okumus, 2016 \[[@B32-ijerph-17-01067]\] Turkey LI 30\\|30 10.7yr 60 Average 4.6mo 8.8mo (7--15yr) (6--16mo) Orhan, 1997 \[[@B33-ijerph-17-01067]\] Turkey LI 16\\|18 25mo 43.8 4--7mo 12mo (18--48mo) (4--24mo) Eshraghi, 2014 \[[@B34-ijerph-17-01067]\] Iran LI 44\\|44 3.2yr (NR) 45.5 2mo 9mo (6.5--13mo) Ali, 2013 \[[@B35-ijerph-17-01067]\] India ExtDCR 10\\|11 9.4yr 30 12--16wk NR (3--6mo) (6--15yr) Engel, 2007 \[[@B10-ijerph-17-01067]\] United States LI 635\\|803 18mo 45 Median of 8wk Median of 12wk (6.5--103.8mo) Dotan, 2015 \[[@B36-ijerph-17-01067]\] Israel LI 46\\|54 37.6mo (NR) 52.2 4--6mo NR El--Essawy, 2013 \[[@B37-ijerph-17-01067]\] Egypt LI 192\\|236 21.2mo 51 3--6mo 5mo (3--16mo) (8--48mo) Fayet, 2012 \[[@B38-ijerph-17-01067]\] France LI 88\\|110 2.4yr NR 3wk 33.7wk (4--139wk) (1--8yr) Casady, 2006 \[[@B7-ijerph-17-01067]\] United States LI NR\\|7 NR NR 3--3.5mo NR (4--6wk) (12--18mo) Eloy, 2009 \[[@B39-ijerph-17-01067]\] Belgium EDCR 8\\|10 4.3yr 87.5 1--3mo 10.5mo (8mo--9yr) (6--15wk) Han, 2015 \[[@B40-ijerph-17-01067]\] South Korea LI 56\\|77 29.8mo 53.6 2--3mo NR (6mo--12yr) Nemet, 2008 \[[@B41-ijerph-17-01067]\] Australia ExtDCR/ EDCR 82\\|104 6.6yr (NR) 51.2 6mo 1.44yr (6mo--8yr) Napier, 2016 \[[@B42-ijerph-17-01067]\] United Kingdom LI 177\\|246 2.1yr (0--9.8yr) 50.4 At least 12wk NR (6--12wk) Yazici, 2006 \[[@B43-ijerph-17-01067]\] Turkey LI 42\\|50 37.3mo 47.6 3mo 18.1mo (9mo--7yr) (3--48mo) Pelit, 2009 \[[@B44-ijerph-17-01067]\] Turkey LI 30\\|34 5yr (2--10yr) 53.3 6mo 40.32mo (12--96mo) Yalaz, 2004 \[[@B45-ijerph-17-01067]\] Turkey LI 26\\|29 4.85yr (2--12yr) 46.2 6mo 8.3mo (6--25mo) Fayet, 2010a \[[@B46-ijerph-17-01067]\] France LI 14\\|18 26.2mo (14--46mo) NR Average of 34d 8.7wk (3--26wk) Pe, 1998 \[[@B47-ijerph-17-01067]\] United States LI 28\\|34 19.5mo (5mo--5yr 3mo) 39.3 2--6mo NR (NR) Fayet, 2010b \[[@B48-ijerph-17-01067]\] France LI 4\\|6 33mo (30--37mo) NR 3wk NR (2--3mo) Huang 2009 \[[@B9-ijerph-17-01067]\] Taiwan Balloon dacryocystoplasty and LI (MCI) 25\\|33 3.5yr 60 4--6mo 6mo Five year record review (descriptive study) Abdu, 2014 \[[@B49-ijerph-17-01067]\] Nigeria ExtDCR 17\\|NA NR (NR--15yr) 52.9 6wk Up to 1yr -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Notes. \* refer to group B, the intubation group; ^\#^ Group 1 was excluded (aged over 16 years); ^\$^ comparison based on age groups; ^&^ comparison based on two different cohorts (prospective and retrospective groups had monocanalicular and bicanalicular silastic tube intubation respectively); MCI, monocanalicular; BCI, bicanalicular; PMCI, pushed monocanalicular; NR, not reported; d, day; wk, week; mo, month; yr, year; min, minimum; max, maximum; %, percentage; LI, lacrimal intubation; EDCR, endoscopic dacryocystorhinostomy; ExtDCR, external dacryocystorhinostomy. ijerph-17-01067-t002_Table 2 ###### Summary of reported outcomes. First Author, Year Criteria for Successful Outcome Overall Successful Outcome % Post--Operative Complication --------------------------------------------- ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- -------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------ Andalib, 2010 \[[@B18-ijerph-17-01067]\] Munk score of 0 or 1 at 3 months after tube removal MCI: 86.2 None BCI: 89 Andalib, 2014 \[[@B19-ijerph-17-01067]\] Complete resolution of epihora at 3 months after tube removal MCI: 90 Slit punctum in PMCI PMCI: 50 Ceylan, 2007 \[[@B20-ijerph-17-01067]\] Complete remission of epiphora at 12 months, maintained for 4 months 62.5 Ocular irritation, false lumen in the inferior meatus, iatrogenic punctal laceration Elsawaby, 2016 \[[@B21-ijerph-17-01067]\] Munk's score 0 or 1 after 3 months from surgery 83.3 \* Corneal ulcer, epistaxis Kominek, 2010 \[[@B22-ijerph-17-01067]\] Fluorescein dye disappearance grade 0--1, corresponding to complete resolution of previous symptoms Group 1(removal at 2 mo): 89.6 None Group 2 (removal at 6 mo): 91.5 Eshraghi, 2017 \[[@B23-ijerph-17-01067]\] Dye disappearance test grade 0--1 & complete resolution of symptom at 12 months' follow up MCI: 59.6 Loss of tubes BCI: 74.4 Fayet, 2011 ^&^ \[[@B24-ijerph-17-01067]\] Absence of epiphora, absence of mucous discharge Group 2 (age 1--9 years): 100 Group 2: none Group 3 (age 1--6 years): 88.3 Group 3: Loss of tube, keratitis Lee, 2012 \[[@B25-ijerph-17-01067]\] Complete disappearance of symptoms BCI: 93.3 Tube prolapse, punctal slitting MCI: 90 Kominek, 2011 \[[@B26-ijerph-17-01067]\] Fluorescein dye disappearance test grade 0--1 = complete resolution from symptoms BCI: 82.86 Dislodging of tube, premature removal, loss of tube, slitting of punctum and canaliculi, granuloma pyogenicum, corneal erosion MCI: 88.57 Eshraghi, 2017b \[[@B27-ijerph-17-01067]\] Complete absence of clinical signs and symptoms of congenital nasolacrimal duct obstruction at 6 months after the procedure 73.3 Epiphora with tubes in place Al--Faky, 2012 \[[@B28-ijerph-17-01067]\] Normal dye disappearance test, positive Jones primary dye test 88 NR Kaufman, 1998 \[[@B29-ijerph-17-01067]\] Negative dye disappearance test 79 Bilateral preseptal cellulitis, migration of punctal anchor into canaliculus, corneal abrasion, corneal ulcer, premature removal of tube Rajabi, 2016 \[[@B30-ijerph-17-01067]\] No sign and symptom of tearing or discharge BCI:80.2 Tube dislodging, spontaneous extrusion, corneal abrasion, punctual slitting due to cheese wiring, punctal plug migration to canaliculus MCI:41.1 Khatib, 2017 \[[@B31-ijerph-17-01067]\] Complete resolution of symptoms, negative dye disappearance test 75 Early tube loss Okumus, 2016 \[[@B32-ijerph-17-01067]\] Complete resolution of previous signs and symptoms and DDT grade 0--1 73.3 None Orhan, 1997 \[[@B33-ijerph-17-01067]\] Resolution of symptoms and previous signs 100 Epiphora with tubes in place Eshraghi, 2014 \[[@B34-ijerph-17-01067]\] Complete resolution or partial improvement 82.6 None Ali, 2013 \[[@B35-ijerph-17-01067]\] Resolution of symptoms 91 NR Engel, 2007 \[[@B10-ijerph-17-01067]\] Good clearance of fluorescein dye and/or absence of symptomatic testing 96 Conjunctival--corneal abrasion Dotan, 2015 \[[@B36-ijerph-17-01067]\] Complete resolution of all preoperative CNLDO symptoms and signs 85 Spontaneous tube loss El--Essawy, 2013 \[[@B37-ijerph-17-01067]\] Complete resolution of symptoms, no epiphora, no discharge, no increase tear lake 82.2 Cheesewiring of canaliculi, late postoperative granuloma formation Fayet, 2012 \[[@B38-ijerph-17-01067]\] Absence of symptoms after stent removal or loss 85 Keratitis, tube loss, epiphora with tubes in place Casady, 2006 \[[@B7-ijerph-17-01067]\] Complete resolution of symptoms 100 None Eloy, 2009 \[[@B39-ijerph-17-01067]\] Complete resolution of symptoms 90 Transient slight epiphora Han, 2015 \[[@B40-ijerph-17-01067]\] Disappearance of epiphora symptoms by a minimum of 2 months 89.6 Tube prolapse, tube loss Nemet, 2008 \[[@B41-ijerph-17-01067]\] Objective confirmation of free fluorescein flow to the nose 95.2 Jones tube placement Napier, 2016 \[[@B42-ijerph-17-01067]\] Complete resolution of symptoms and signs 91.7 NR Yazici, 2006 \[[@B43-ijerph-17-01067]\] Resolution of lacrimal symptoms and signs, normal tear meniscus, and in cooperative patients, normal dye disappearance test and/or patent nasolacrimal duct on irrigation at the last examination. 86 Slit punctum Pelit, 2009 \[[@B44-ijerph-17-01067]\] Complete resolution of previous lacrimal symptoms and signs 100 None Yalaz, 2004 \[[@B45-ijerph-17-01067]\] Relief from symptom and/or positive results in fluorescein dye disappearance test 93.2 (initial intubation); Granuloma 100 (reintubation) Fayet, 2010a \[[@B46-ijerph-17-01067]\] Absence of epiphora, absence of mucous discharge 88 Mildly watery eye Pe, 1998 \[[@B47-ijerph-17-01067]\] Easy, uncomplicated retrieval of the Prolene guide thread during intubation; complete resolution of previous signs and symptoms and a normal result of the dye disappearance test 97 None Fayet, 2010b \[[@B48-ijerph-17-01067]\] Residual epiphora after ablation 100 None Huang 2009 \[[@B9-ijerph-17-01067]\] Complete resolution of symptoms and normal dye disappearance test 97 None Abdu, 2014 \[[@B49-ijerph-17-01067]\] Patent nasolacrimal duct 1 year after surgery 88 Extrusion of the tube, infection Notes. NNR, not reported; MCI, monocanalicular; BCI, bicanalicular; PMCI, pushed monocanalicular; \* study consisted of probing and stent groups, the value refers to stent group; ^&^ study consisted of three groups; group 1 aged 44--77 years was excluded. ijerph-17-01067-t003_Table 3 ###### EPHPP quality assessment tool rating for individual studies. First Author, Year Selection Bias Study Design Confounders Blinding Data Collection Methods Withdrawals and Dropouts Global Rating -------------------------------------------- ---------------- -------------- ------------- ---------- ------------------------- -------------------------- --------------- Andalib, 2010 \[[@B18-ijerph-17-01067]\] S S S W S S M Andalib, 2014 \[[@B19-ijerph-17-01067]\] S S S W S M M Ceylan, 2007 \[[@B20-ijerph-17-01067]\] S S W W S S W Elsawaby, 2016 \[[@B21-ijerph-17-01067]\] S S W W S S W Kominek, 2010 \[[@B22-ijerph-17-01067]\] S S W W S S W Eshraghi, 2017 \[[@B23-ijerph-17-01067]\] S M W W S S W Fayet, 2011 \[[@B24-ijerph-17-01067]\] S M W W S S W Lee, 2012 \[[@B25-ijerph-17-01067]\] S M S W S S M Kominek, 2011 \[[@B26-ijerph-17-01067]\] S M W W S S W Eshraghi, 2017b \[[@B27-ijerph-17-01067]\] S M W W S S W Al-Faky, 2012 \[[@B28-ijerph-17-01067]\] S M W W S NA W Kaufman, 1998 \[[@B29-ijerph-17-01067]\] S M W W S S W Rajabi, 2016 \[[@B30-ijerph-17-01067]\] S M W W S NA W Khatib, 2017 \[[@B31-ijerph-17-01067]\] S M W W S NA W Okumus, 2016 \[[@B32-ijerph-17-01067]\] S W W NA S S W Orhan, 1997 \[[@B33-ijerph-17-01067]\] S W W NA S S W Eshraghi, 2014 \[[@B34-ijerph-17-01067]\] S W S NA S S M Ali, 2013 \[[@B35-ijerph-17-01067]\] S W W NA S S W Engel, 2007 \[[@B10-ijerph-17-01067]\] S W W NA S NA W Dotan, 2015 \[[@B36-ijerph-17-01067]\] S W W NA S NA W El-Essawy, 2013 \[[@B37-ijerph-17-01067]\] S W W NA S NA W Fayet, 2012 \[[@B38-ijerph-17-01067]\] S W W NA S NA W Casady, 2006 \[[@B7-ijerph-17-01067]\] S W W NA S NA W Eloy, 2009 \[[@B39-ijerph-17-01067]\] S W W NA S NA W Han, 2015 \[[@B40-ijerph-17-01067]\] S W W NA S NA W Nemet, 2008 \[[@B41-ijerph-17-01067]\] S W W NA S NA W Napier, 2016 \[[@B42-ijerph-17-01067]\] S W W NA S NA W Yazici, 2006 \[[@B43-ijerph-17-01067]\] S W W NA S NA W Pelit, 2009 \[[@B44-ijerph-17-01067]\] S W W NA S NA W Yalaz, 2004 \[[@B45-ijerph-17-01067]\] S W W NA S NA W Fayet, 2010a \[[@B46-ijerph-17-01067]\] S W W NA S NA W Pe, 1998 \[[@B47-ijerph-17-01067]\] S W W NA S NA W Fayet, 2010b \[[@B48-ijerph-17-01067]\] S W W NA S NA W Huang 2009 \[[@B9-ijerph-17-01067]\] S W W NA S NA W Abdu, 2014 \[[@B49-ijerph-17-01067]\] S W W NA S NA W Notes. EPHPP: Effective Public Health Practice Project; S: strong; M: medium; W: weak; NA: not applicable.	{ "pile_set_name": "PubMed Central" }
By Casey Peacock: PNT Staff Writer Continuing to feel the outpouring of support from the community, Mike and Cindy Mitchell stepped into the sale ring at Portales Livestock for a $136,375 check. The check was the result of a benefit sale sponsored by Portales Livestock owner Randy Bouldin to help the couple. The Mitchell’s business, […] PNT Staff Report After defeating St. Mike’s 5-4 in the morning, the Portales Lady Rams were handed their own tournament championship late Saturday night after the Lady Horsemen played all day for the rematch before forfeiting the title game. According to Portales coach Michelle Wallis the St. Mike’s girls were upset about having to play […] By Dave Wagner: Freedom Newspapers ALBUQUERQUE — The butterflies in Tara Johnson’s stomach belied her confident approach. Johnson made two free throws with 15.9 seconds remaining, leading Portales into the girls Class 3A championship game for the seventh straight year as the Rams beat St. Michael’s 32-31 in the semifinals Thursday. “I was so nervous. […] By Mickey Winfield, PNT Staff Writer SANTA FE — The Portales Rams unexpected ride through the Class 3A playoffs continues, all the way to the state championship game. Down by a point late in the fourth quarter in Saturday’s semifinals, junior quarterback Chris Mosier led Portales on a 12-play, 71-yard drive capped by an Eric […] Kyle Joe Musick Services: 10 a.m. Wednesday at 21st Street Church of Christ. Mr. Kyle Joe Musick, 46, of Albuquerque, died Wednesday, May 24, 2006, at his home. He was born Nov. 22, 1959, in Farmington to William Charles and Naomia Jean Justus Musick. He graduated from Grants High in 1977. He graduated from Lubbock […] By Eric Butler: PNT Correspondent A trip back to the states for one of Eastern New Mexico University’s all-time greats gave ENMU cross country coach Joel McMullen the chance to tie the past to the present. And that he did through a 40-year celebration of Eastern’s program Saturday night at Cannon AFB’s The Landing. While […] Mr. Dennis “Chris” Christensen The annual Christmas Tournament, the “Grand Finale” golf event of the 2005 golf season, attracted 64 golfers. The tournament kicked off with an 8 a.m. champagne breakfast followed by shotgun start tee times at 9 a.m. on Dec. 3 at the Whispering Winds Golf Course. The format for the tournament was […] Darlene Superville: The Associated Press WASHINGTON — Mike Brown, the subject of blistering criticism after Hurricane Katrina battered the Gulf Coast and overwhelmed the government’s response, quit Monday as director of the Federal Emergency Management Agency. The White House moved quickly to replace him, installing a top agency official with three decades of firefighting experience […] By Kevin Wilson: PNT Managing Editor Two conversations, 15 years apart, start the same way. “What do you think about Tyson losing Saturday?” Two different reactions ensued, and by all indications we have said an uncomfortable goodbye to boxer Mike Tyson, a man for whom the star label seemed less comfortable with each passing day. […] By Mike Linn By Mike Linn Freedom Newspapers Mike_Linn@link.freedom.com In his first public comments as head football coach of Eastern New Mexico University, Mark Ribaudo said he will work to continue the program’s success in graduating players and winning games. His only change: Win more games. Ribaudo, defensive coordinator for the Greyhounds the past eight […] By Kevin Wilson Eastern New Mexico University’s new head football coach is already on staff, but officials on Tuesday would not be more specific about who will replace Bud Elliott. The university has scheduled a press conference for 1:30 p.m. today at Greyhound Arena to announce the successor to Elliott, who guided the Greyhounds for […] By David Irvin They’re the trendiest wheels on the road. But yes, you do need a license to operate a pocket bike on local streets. And at least one retail store owner said last week the mini-motorcycles are not safe in city traffic. Mary Ortiz said pocket bikes are just too small to be seen […] By Dave Wagner After a standout football career at Portales High, Jeff Howard found himself struggling to decide where he wanted to play in college. His father, Eastern New Mexico University offensive coordinator Mike Howard, wasn’t much help. After all, he and the rest of coach Bud Elliott’s staff at ENMU figured Jeff would end […] By Tony Parra Give Ted Allen Clark a fiddle and he’d spin a delightful tune. Give him seven children and he’d share with them the importance of work ethic and education. Clark had seven children, was a member of the Old Time Fiddler’s Hall of Fame and a former Roosevelt County resident. He died on […] In the old days, I resigned myself that bad luck came in threes, i.e., three flat tires, three smashed fingers or three social faux pas. It’s comforting to know that good ol’ Dakota Mike is still proving my theory. And, I’m not even counting the initial injury that resulted in a swollen right knee, which […] By Mike Linn A Roswell truck driver suspected of vehicular homicide in connection with the death of a 2-week-old boy will face a Roosevelt County grand jury on Thursday afternoon. Brian Moshier, 40, is accused of slamming his tractor-trailer rig into a compact car while driving drunk on U.S. Highway 70 near Elida in the […] By Kevin Wilson As an unwritten rule, workers in the Portales editorial department need to have a certain cinematic IQ to get along with me. Obscure movie references and disturbingly accurate scene reprisals make up a percentage of my conversation that I’m embarrassed to admit. So it was right down my alley when I read […]	{ "pile_set_name": "Pile-CC" }
All Wesleyan undergraduates received an email this morning announcing the cancellation of October classes. There was no one reason for the decision, says President Michael Roth, but the largest contributing factor was that the Wesleyan administration hasn’t been “feeling it.” “This semester’s been kind of a wash,” said Dean Louise Brown. “Some people feel okay about school. They read and write what professors tell them to. But many students feel aimless. They don’t care about their classes and sometimes they don’t want to go to them.” After talking about her October plans to have a few dinner parties and spend more time with her dog, Brown added, “Everyone could use some time to figure stuff out.” Both professors and students have welcomed the change. “My syllabuses have been kind of a slog,” said Professor Timothy Nelson of the Government Department. “All September we’ve been going over ethical justification of war and its application to Balkan conflicts, and I can’t help but think, ugghhh.” Physics Professor Natasha Bethem agreed, saying, “I wish I were in bed. My feet were so cold this morning.” The sudden hiatus presents a problem to upperclassmen with research projects, particularly in the sciences. But that’s not a big deal. Henry Wu ’11 said, “So my bacteria die. What does that really matter, long-term? There’ll be more bacteria. Better to go home, see some people, catch up on Mad Men. I haven’t been to the doctor in a while.” The prevailing attitude seems to be that there’s more to life thanWesleyan, and that’s all too easy to forget. The administration stresses that things will be better than ever when we come back. Some class material will be sacrificed, but only the unimportant stuff. “This won’t happen every year,” Roth said. “The University just thinks, having felt it out, that we should press the reset button, so to speak. Take a nap. Have you seen the foliage this autumn? Have you woken up in an orchard and eaten an apple straight off the bough? Now you have time. We all have time.” Last Monday, College of Letters major and well-liked Hewitt resident Emily Bristol ’13 excitedly announced her plans to begin blogging while abroad next semester. Bristol plans to spend the spring semester in Bordeaux, France, which she expects will be “basically pretty chill.” “I just figured, you know, why not try something different while I’m abroad?” Bristol explained to close friends and family. “Why not create a venue through which I can share thoughtful multicultural insights, like how hot my host brother looks without a shirt, or how low the sinks are in France?” Bristol’s familiarity with French culture is already “pretty much magnifique,” she says, as evidenced by her enthused participation in last semester’s “Tour de Franzia” night. The 19-year-old Boston native has not yet settled on a name for her blog, though brainstorming has yielded some promising contenders. “My top choice right now is Bitch in Bordeaux,” she revealed. “It’s sort of ironic, `cause I’m not actually a bitch, haha. But I kind of like the idea of A Broad Abroad, because, like, I’m going abroad and also I am a broad.” “Or at least my uncle says I am. But he also eats Cream of Wheat with a fork and knife. So whatever.” Bristol admits that her blogging experience is a bit thin, but says frequent contributions WesBreasts have given her a solid familiarity with Tumblr. “I haven’t had my own blog since, like, eighth grade,” Bristol recalled wistfully. “And that was just a Xanga site where I posted my favorite Evanescence lyrics.” “I’ll try not to post Evanescence lyrics on this one,” she added, grinning. “But no promises.” Several audience members at Thursday night’s benefit performance of Destiny Africa Children’s Choir expressed great outrage upon learning that the concert was not, in fact, a reunion of Destiny’s Child, the R&B group from the late 1990s. The concert, which took place at the Memorial Chapel on High Street, asked for an optional donation to the Kampala Children’s Centre, a Ugandan orphanage. Once it became apparent that Beyoncé and her cohorts would not perform, people began to ask for their money back. “When I heard Destiny’s Child would be playing a concert in September, I was even more psyched to come to Wesleyan,” said Keelin Ryan ’14, during the show. “But what a let-down.” Joan Cooper Burnett, the designated Protestant Chaplain at the university, said that at the beginning of the concert she had been hopeful. “Even an hour before the concert began, people were lined up all the way down High Street in order to get seats; I thought, finally, something we’re doing, it’s getting people’s attention. But,” she added mournfully, “after two songs, people just started leaving.” “The Chapel is simply not large enough to house the number of people who planned to attend the concert,” Mother Burnett said, “but as dissatisfied customers started to leave, more room opened up inside the hall. And yet, almost as soon as the new people entered, they left. So what ultimately happened was this rip tide effect with the people going out saying ‘It’s not Destiny’s Child, don’t go in there,’ and the people coming in just too eager and not listening and trampling over everyone else. It was utter pandemonium.” Once it dawned upon the large crowd outside that they would not get to see a revival performance of “Say My Name” or “Bootylicious,” people began to riot. One unidentifiable junior shouted, “I came to see Destiny’s Child, not orphans!” A small group of sophomores wearing DC apparel — including shirts, headbands, and sweatpants — were weeping in a huddle. Inside the concert hall, the pandemonium was even greater. In the middle of the second song, students started hurling tomatoes and apples at the orphans who were dancing on stage and the performance eventually had to be cut short. After the concert was halted, one child testified to a university reporter: “This is even worse than Uganda.” Another child replied, “No, it’s not.	{ "pile_set_name": "Pile-CC" }
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Highwire Daze named “Under the Influence”one of the top Rock albums of 2016! “Under The Influenceis the 17th mammoth recording by the legendary rock and blues band Foghat, and it shows a collective still at the very height of their creative blues rocking energy. From the tasty lead guitar licks and powerhouse vocals…”	{ "pile_set_name": "Pile-CC" }
In manufacturing semiconductor devices such as LSI and super-LSI or in manufacturing a liquid crystal display board or the like, a pattern is made by irradiating a light to a semiconductor wafer or an original plate for liquid crystal, but if a dust particle is attached to a photo mask or a reticle (hereinafter collectively referred to as “photo mask” for simplicity) which is used during the irradiation operation, the dust particle would block off or reflect the light so that the resulting pattern would have roughened edges or black stains on the base, which would lead to problems such as damaged dimensions, poor quality, and deformed external appearance. Thus, these works are usually performed in a cleanroom, but it is still not easy to keep the photo mask clean all the time; therefore, a pellicle is attached to a surface of the photo mask as a dust-fender before light exposure is carried out. Under such circumstances, dust particles do not directly adhere to the surface of the photo mask but adhere only to the pellicle film, and since this film is sufficiently remote from the photo mask surface if the photo focus is set on a lithography pattern on the photo mask, the foreign particles on the pellicle film fail to transfer their shadows on the photo mask and thus no longer become a cause for problems to the image transfer performance. In general, a pellicle is made by adhering a transparent pellicle film, which is made of a highly light transmitting material such as cellulose nitrate, cellulose acetate, fluorine-containing polymer and the like, to an upper annular end face of a pellicle frame made of aluminum, stainless steel, polyethylene or the like, using as the glue either a solvent capable of dissolving the pellicle film, which is applied to said upper annular end face (hereinafter this face is called “upper end face”) and then air-dried before receiving the film (ref. IP Publication 1), or an adhesive such as acrylic resin, epoxy resin or the like (ref. IP Publication 2). Further the other annular end face (hereinafter called “lower end face”) of the pellicle frame is covered with an agglutinant layer made of polybutene resin, polyvinyl acetate resin, acrylic resin, silicone resin or the like for attaching the pellicle frame to the photo mask, and over this agglutinant layer is laid a release liner (separator) to protect the agglutinant layer. Now, in recent years, the semiconductor devices and the liquid display board have undergone further improvement in integration and densification. Currently, a technology of forming a fine pattern having a resolution level of 32 nm on a photo resist film is on the verge of realization. Such patterning can be effectively achieved by improved technologies such as the immersion exposure method, wherein the space between the semiconductor wafer or the original plate for liquid crystal on one hand and the projection lenses on the other is filled with a liquid such as super pure water and the photo resist film is exposed to an argon fluoride (ArF) eximer laser, or the double exposure method, which uses a conventional argon fluoride (ArF) eximer lasar, to which the photo resist film is exposed. However, the next-generation semiconductor devices and the liquid display board are called on to have even denser patterning of a level of 10 nm or smaller, and there is scarce room for the conventional exposure technology depending on excimer laser to improve to answer such high demand of making a dense pattern of the level of 10 nm or smaller. Now, as a most promising method for forming a pattern of a density of 10 nm or smaller, an EUV exposure technology which uses an EUV light of a dominant wavelength of 13.5 mm is in the spotlight. In order to achieve a pattern formation on the density level of as high as 10 nm or smaller on the photo resist film, it is necessary to solve the technical problems with regard to the choices of light source, photo mask, pellicle, etc., and in respect of light source and photo mask there have been considerable progress and various porposals have been made. With respect to the pellicle that could improve yields of semiconductor device products or liquid crystal displays, IP Publication 3, for example, discloses a silicon film of a thickness of 0.1-2.0 micrometers to act as the pellcile film for EUV lithography which is transparent and does not give rise to optical distortion; however there remain unsolved problems in this film, which have prevented realization of the EUV light exposure technology.	{ "pile_set_name": "USPTO Backgrounds" }
My secret Santa did amazing with providing myself, my wife and our bunny with gifts! Little Dusty BunnBunn received lots of treats and things to chew on! It was so adorable for them to think about him like that! As for my wife and I, we received a $100 gift card to a local restaurant that we love going to for our anniversary and any other special occasions. Appealing to the military shenanigans, they gave us What Do You Meme card game/ party game for adults! They also gave us (myself more over) a $100 Sony PlayStation gift card! Thank you so much for the amazing gifts guys! Happy Holidays!	{ "pile_set_name": "OpenWebText2" }
“Flipping” an asset loosely means buying and swiftly reselling it to make a quick profit. You can flip stocks, trading them within 24 hours. If you want to flip houses, you can buy them, fix them up, put them back on the market, and—if you’re lucky—get your own hit HGTV show In the art world, however, flipping is a dirty word. “It’s disgusting,” said art adviser Lisa Schiff, noting how speculative buying practices can harm young artists’ careers. Speaking more subtly, Dr. Elizabeth Pergam, who teaches at Sotheby’s Institute of Art, noted that rapid run-ups in auction prices lead to a widely-held idea that flipping is “not healthy for the market.” Regardless of the data, art flipping carries a significant stigma in an industry that runs on relationships and reputations. Who flipping really hurts Most artworks, unlike stocks and houses, are made by working artists who rely on sales to support their creative practices. Artists often work with gallerists, who sell their artworks to institutions and collectors and give them a large portion of the proceeds. Such private exchanges are considered primary market sales. Once a collector decides to put an artwork up for auction, it enters the secondary market. Artists don’t benefit from any of these sales, except in the few jurisdictions with resale royalty laws ; most of the money goes to the consignors and auction houses. Heather Bhandari, an independent curator and educator who previously worked as a director at the Chelsea gallery Mixed Greens (which closed in 2015), believes that the art world frowns upon flipping in part “because the buyer rarely does anything to help increase the value of the work—they profit from artists’ continued hard work without paying anything to the artists.” Christina Quarles Kerry James Marshall Gerhard Richter For Pergam, buying and selling a single work of art within 5 to 10 years is a rapid turnover, and constitutes flipping. Schiff prefers a you-know-it-when-you-see-it definition. “It’s always obvious,” she said. It happens when “this artist is too young to be at auction.” From Schiff’s perspective, a painting by, who’s in her mid-thirties, doesn’t have any place sharing an auction catalog with canvases byor. The latter artists are far more established, with roughly 30 and 50 additional years of artmaking to their names. They’ve had adequate time to develop their work, without facing the pressures of the art market. Jeff Koons Takashi Murakami Jean-Michel Basquiat No one’s too concerned about flipping if the artist is well-established or dead—nobody is bothered on behalf of, or. But if an artist is just gaining traction in the art world, flipping can lead to spiking prices and ultimately destroy a career. Lucien Smith Anselm Reyle Christian Rosa The trajectories of artists including, andillustrate the dangers of flipping. Smith’s work began appearing at auction in 2013, when he was in his early 20s. Artnet’s price database lists 116 results since then. Smith’s first canvas to go to auction, Hobbes, The Rain Man, and My Friend Barney / Under the Sycamore Tree (2011), sold for $389,000—well over twice its high estimate of $150,000. In recent years, however, Smith’s works have increasingly been “bought in” (not sold) or gone for prices in the $5,000–$20,000 range. In a 2015 article for Bloomberg , James Tarmy tracked a similar downfall for Reyle’s market. In 2007, before the artist turned 40, a work of his fetched $634,000 despite its high estimate of $51,000. “In one year, Reyle’s record at auction had increased by more than 1,000 percent,” Tarmy wrote. After the financial crisis hit in 2008, however, Reyle’s market toppled. That year, a third of his work, according to Tarmy, sold below its estimate or not at all. “The bottom line: A work by the once-hot artist Anselm Reyle sold last year for about $66,000, $30,000 less than it fetched four years ago,” Tarmy concluded. Unable to sustain his studio costs, Reyle had to temporarily retire from painting. What are flipping’s macro repercussions? While most agree that flipping hurts young artists, it’s less clear how the practice impacts the market as a whole. Doomsayers assert that today’s flipping is a new, ramped-up phenomenon—indicative of a vulgar, fad-obsessed class of collectors—which is bad news for the art market as a whole. Yet in an article for the New York Times, Lorne Manley and Robin Pogrebin found that the pace for turning over art in 2013 “was only slightly faster than it was in the mid-1990s, signaling that the reselling may be just the latest iteration of a historical cycle, not a lasting change.” New ways of tracking who’s hot and who’s not, however, are making flipping a more in-your-face phenomenon. ArtRank , which started as an art fund’s algorithm back in 2012, ranks artists by their investment potentials. Categories include “Buy Under $10,000,” “Buy Under $30,000,” “Sell/Peaking,” and “Undervalued Blue Chip.” Not a single image of an artwork adorns the site’s welcome page, suggesting that aesthetics, creativity, ingenuity, and self-expression—values that draw many people to art in the first place—have been totally superseded by quantitative concerns. A cure for flipping? Flipping isn’t good for galleries, which play a key role in nurturing artists’ careers. While they can put clauses in contracts, restricting collectors’ terms of resale, Pergam noted that “lawyers say those clauses are unenforceable.” Yet “if you buy art from respected galleries and they know you’ve sold it within 5, 10 years, they’re not going to sell you another one.” Auctions place no such restrictions on buyers. If you’re the highest bidder, you win the work—no matter your art world reputation. Peter Doig It’s not just young, greedy collectors, new to the market, who flip, either. According to the New York Times article, artistaccused Charles Saatchi of flipping. Collector Stefan Simchowitz has even advocated the practice. Both men have amassed extremely influential collections. Galleries aren’t going to stop selling to them over infractions that make up a small piece of their larger portfolios. Schiff asserted that art advisers must be vigilant, too. She said speculative buyers—“fake people”—try to hire her and her peers “as beards for bad behavior.” The art world itself weeds out art advisers whose clients speculate: If her clients flipped, Schiff noted, “I wouldn’t have any clients or be an adviser. I would get cut off from every gallery.” Schiff added that she “loves the art world and artists” and has “no desire to destroy careers.” A client’s profit in the short term could diminish her livelihood, an artist’s, and that of the gallerist who sold the client the flipped work. According to artnet News , to guard against the practice David Zwirner has imposed financial penalties on salespeople who sell work that ends up on the auction block too quickly. Both Schiff and Bhandari believe the onus is on auction houses to curb flipping. Schiff doesn’t think auctions should be sourcing and selling art by artists who haven’t reached a certain stage in their careers. Bhandari, on the other hand, advocates resale royalties. “Regardless of when the secondary market sale happens, artists should share in the profit,” she said. “It is a way to bring more equity to the market. In other creative industries, royalties are a necessary income stream.” In the music industry, if someone wants to use your song for an advertisement, you often make money. Scholar Amy Whitaker believes that using blockchain to track an artwork could be a viable solution. For her part, Pergam thinks the media and celebrity culture have helped feed the booming interest in contemporary art, which has led to flipping. “A lot can be attributed to the success of Art Basel in Miami [Beach] and that culture that’s sort of about glitziness,” she said. If rappers and movie stars are snapping up major works and going to art parties, perhaps bad actors will be encouraged to get in on the art-buying action—and turn a quick profit to further their exploits. That genie, however, doesn’t seem to be going back in the bottle anytime soon.	{ "pile_set_name": "OpenWebText2" }
Saturday, December 28, 2013 This week's edition of "The 3" includes the story of violence on Christmas Day in nation of Iraq. Also, there was some good news for "Duck Dynasty" fans and Christians who were alarmed when family father and grandfather Phil Robertson was suspended by the cable network carrying the show for his comments on homosexuality. And, the top story: the celebration of Christmas and the timeless message of God's love for humanity that has been proclaimed to a greater degree throughout the last few weeks. 3 - Churches in Baghdad come under attack on Christmas Day Tragedy struck in Baghdad, the capital city of Iraq, on Christmas Day, where militants killed almost three dozen people – most of them Christians – in two bomb attacks, according to BBC News, cited by Open Doors USA. One bomb exploded outside of the St. John’s Catholic Church while worshippers were leaving a Christmas Day service, killing at least 24. Another bomb ripped through an outside market in a Christian neighborhood, killing at least 11 (information updated from BBC website). There were an estimated 60 wounded in the two bombings. Pastor Tariq (not his real name) told Open Doors recently that “churches are targets for terrorists, especially on Christmas Day. Many Christians stay home because they are too afraid.” An Open Doors field worker said in an earlier report: “We received documents and threats stating that the aim of Islamist insurgents is to make Iraq a ‘Muslim only’ country. They want Christians out.” Iraq is No. 4 on the 2013 Open Doors World Watch List, which ranks countries that are the worst persecutors of Christians. In the early 1990's, there were an estimated 1.2 million Christians in the nation, and that number has diminished to an estimated 330,000 Christians left in that nation, as many have fled the country due to violence and persecution. Dr. David Curry, president/CEO of Open Doors USA, stated that, “There is a concerted effort by extremists to drive Christians out of the Middle East...Iraq not only is a hostile, volatile environment in general, but often the violence is directed specifically towards Christians... “Only the power of prayer is going to improve the conditions for believers in Iraq and countries such as Syria and Iran. Pray that the families of the victims will feel the embrace of Jesus. Pray that the government of Iraq will do more to protect people of all faiths. And pray that in 2014 Christians will be able to worship the Lord in peace and freedom.” Curry adds that attacks on Christians during Christmas and New Year’s Eve is a “very disturbing trend.” He cited the bombing of the Two Saints Coptic Church in Alexandria, Egypt on New Year’s Eve and attacks on Christians in Nigeria on Christmas Eve the last three years. 2 - Phil Robertson reinstated to "Duck Dynasty" by A&E Friday afternoon, the A&E cable network lifted its suspension of Phil Robertson, the patriarch of the family featured in the reality show, "Duck Dynasty" In a statement which was quoted by The Hollywood Reporter website, the network said that, regarding comments made about homosexuality which were consistent with the teachings of the Bible: While Phil's comments made in the interview reflect his personal views based on his own beliefs and his own personal journey, he and his family have publicly stated they regret the "coarse language" he used and the misinterpretation of his core beliefs based only on the article. He also made it clear he would "never incite or encourage hate." We at A+E Networks expressed our disappointment with his statements in the article and reiterate that they are not views we hold. But Duck Dynasty is not a show about one man's views. It resonates with a large audience because it is a show about family … a family that America has come to love. As you might have seen in many episodes, they come together to reflect and pray for unity, tolerance and forgiveness. These are three values that we at A+E Networks also feel strongly about. The channel reportedly had discussions with the Robertson family and consulted with "numerous advocacy groups" prior to their decision to lift what was announced to be an "indefinite" suspension. A&E also said they would launch a public service campaign promoting unity, tolerance and acceptance among all people, "a message that supports our core values as a company and the values found in Duck Dynasty." The attacks on Phil Robertson revealed to the American people that the push to redefine marriage is less about the marriage altar than it is fundamentally altering America's moral, political and cultural landscape. A&E Network's reversal in the face of backlash is quite telling to the American people who are growing tired of GLAAD and cultural elites who want to silence people and remove God and His word from every aspect of public life. He went on to say: We've also seen these intimidation tactics used against wedding florists, bakers, photographers who have been hauled into court, fined and even ordered to violate their religious beliefs by participating in same-sex weddings. Where is the fairness there? Where's the tolerance? There is none. This is why hundreds of thousands of Americans had enough and took a stand by signing petitions in support of Phil Robertson and the right of Christians to quote the Bible". The Hollywood Reporter article also quotes Chris Stone of Faith Driven Consumer, which started the IStandWithPhil.com website, which had generated over 200,000 signatures. He said: "Despite our celebration, we remain uncertain of A&E's true intent. Today, in the network’s statement of their core values – centered on ‘creativity, inclusion, and mutual respect’ - Faith Driven Consumers are left wondering whether A&E considers us to be a part of America's rich rainbow of diversity...Do they also now embrace the biblically based values and worldview held by the Robertson family and millions of Faith Driven Consumers?" Perkins and Stone both pose good questions. Unfortunately, in the name of "tolerance", the views of Christians based on the teachings of the Scriptures have been marginalized and denigrated. Could this represent a tipping point, where the voices of people of faith may actually be included in the conversations and our views tolerated? Do we still have the freedom of religion in America to be able to express Biblical views without being chastised? People will disagree with one another about a variety of issues, and it is important that we have that freedom to express different views without the threat of being silenced. 1 - Christians celebrate our Savior's birth Throughout the world, Christians set aside this past Wednesday and the days leading up to it as a time to celebrate our Savior's birth. And, even though a new Pew study shows that about a third of Americans see Christmas as a cultural holiday, over half of those survey (51%) still see Christmas as a religious holiday. 96% of Christians say they celebrate Christmas, and two-thirds of Christians see it as a religious holiday. And, the indications from this polling data show that over half of Americans attended some sort of Christmas service recently. While about seven-in-ten Americans said they typically attended Christmas Eve or Christmas Day religious services when they were children, 54% said they planned to attend Christmas services this year. Pew also reports significant generational differences in the way Americans planned to celebrate Christmas this year, with younger adults less likely than older adults to incorporate religious elements into their holiday celebrations. Adults under age 30 are far less likely than older Americans to say they see Christmas as more of a religious than a cultural holiday, they are less likely to attend Christmas religious services, and to believe in the virgin birth. This is consistent with other research showing that younger Americans are helping to drive the growth of the religiously unaffiliated population within the U.S. But the report on the Pew survey points out that even among Christians, young people are more likely than older adults to view Christmas as more of a cultural than a religious holiday. It is clear that people are celebrating Christmas differently - there was a difference in the number of people putting up a Christmas tree, in contrast to their childhood. Belief in Santa Claus and the participation in caroling? Respondents indicated a sharp decline over what they did during their childhood years. But, even though methods and degrees of celebration have changed, the message of Christmas has not changed - God sent his Son, Jesus, into the world, so that the world might receive His love and come into a right relationship with God through salvation in Christ. And, when you consider that even 8-in-10 non-Christians in America still celebrate Christmas, that tells me that there is at least a sensitivity to something special during the season, even though they may not acknowledge the real meaning of it. So, our mission as Christians during the Christmas season is to shine the light of Christ, to recognize that the holiday was established to be centered on the birth of our Savior, and to find ways to communicate that incredible truth to a world that so desperately needs to hear it. Sunday, December 22, 2013 This week in my week-in-review feature, "The 3": What's being described as an early Christmas gift was extended to 180 ministries who receive health benefits from a organization of the Southern Baptist Convention - temporary relief from having to comply with the HHS contraception mandate. Also, same-sex marriage had 2 positive court rulings this week - one from the New Mexico Supreme Court, another from a Federal court judge in Utah. And, of course, the top story involves comments made by Duck Dynasty patriarch Phil Robertson about homosexuality and the Biblical view of it. 3 - Judge gives relief to 180 evangelical ministries from HHS mandate There continues to be news about the progress of lawsuits involving the mandate from the Department of Health and Human Services requiring that employers provide free contraception and abortion-inducing drugs as part of their health care plans. Christianity Today reports a positive outcome, albeit temporary, in one of two class-action lawsuits filed against the mandate, as The Becket Fund for Religious Liberty announced that an Oklahoma judge granted GuideStone Financial Resources a temporary injunction against the Affordable Care Act requirement. CT cited a Baptist Press piece that reported that GuideStone had sued on behalf of 180 evangelical ministries affiliated with the Southern Baptist Convention. Becket writes: These evangelical organizations only object to four out of twenty FDA-approved contraceptives—those like the "morning after pill" and the "week after pill" that may cause early abortions. The court's order is an early Christmas gift that came just days before the January 1, 2014 deadline that would have forced the ministries to choose between following their religious beliefs about the sanctity of life and paying thousands of dollars a day in fines. Becket had said that the class, represented by Reaching Souls International and Truett-McConnell College, includes over 100 ministries that currently receive conscience-compliant health benefits through GuideStone. None of the ministries that comprise the class qualify for HHS' narrow "religious employer" exemption, and they all face enormous fines if they do not comply with the government's mandate by January 1, 2014. "The very purpose of the GuideStone plan is to provide ministry organizations with employee health benefits according to Biblical principles," said O.S. Hawkins, GuideStone's President and Chief Executive Officer. "The government shouldn't prohibit us from continuing in that ministry." This week, the New Mexico Supreme Court ruled in favor of same-sex marriage in the state. According to a CitizenLink report, state marriage laws, enacted in 1961, do not clearly define the institution. There are sections for a “male” and “female” on its marriage applications. It also includes the words “husband” and “wife.” Activists claim the ambiguous laws open the door for same-sex marriage. Many attorneys and legal analysts disagree. Earlier this year, the ACLU sued the state, claiming that because the state Constitution does not exclude same-sex marriage, that it should, therefore, issue marriage licenses to same-sex couples. This summer, six of the state’s 33 county clerks began issuing marriage licenses to same-sex couples. Shortly after, a judge ordered a Santa Fe clerk to issue the licenses. State Attorney General Gary King refused to take any action against the clerks. Jim Campbell of the Alliance Defending Freedom (ADF) responded to the ruling, saying, “The New Mexico Supreme Court ignored that time-tested understanding of marriage and replaced it with the recently conceived notion that marriage means special government recognition for close relationships.” And, this week, a Utah Federal judge, Robert Shelby ruled that the state's voter-approved constitutional amendment defining marriage as one man and one woman, was unconstitutional. Byron Babione of ADF said, “The government’s purpose for recognizing marriage is to bring together one man and one woman as husband and wife to be a father and a mother to any children their union may produce. The ruling in this case ignores that time-tested and rational understanding of marriage--affirmed by 66 percent of Utah voters--and replaces it with the recently conceived notion that marriage means special government recognition for close relationships. A court should not impose this shortsighted, novel view of marriage on the people of Utah. We encourage the state to appeal this decision.” This comes just days after another Federal judge in Utah ruled that a portion of the law banning polygamy in the state was unconstitutional. A CitizenLink story relates that judge, Clark Waddoups, found in favor of the family of Kody Brown of the TLC reality series, Sister Wives. Judge Waddoups claims the part of the law making cohabitation illegal violates the Constitution. 1 - Duck Commander comments unleash controversy This week, an article was published on the website for GQ, which featured Phil Robertson, the patriarch of the Robertson family featured in the A&E hit television series, Duck Dynasty. His comments on sin, and specifically homosexuality, resulted in a predictable reaction by groups such as the Gay and Lesbian Alliance Against Defamation (GLAAD). Basically, Robertson took the traditional teaching of the Bible and the church and enhanced it in his own unique way. “Everything is blurred on what’s right and what’s wrong... Sin becomes fine,” he said. “Start with homosexual behavior and just morph out from there. Bestiality, sleeping around with this woman and that woman and that woman and those men.” Paraphrasing [1st] Corinthians he added: “Don’t be deceived. Neither the adulterers, the idolaters, the male prostitutes, the homosexual offenders, the greedy, the drunkards, the slanderers, the swindlers—they won’t inherit the kingdom of God. Don’t deceive yourself. It’s not right.” Wilson Cruz of GLAAD stated: "Phil and his family claim to be Christian, but Phil's lies about an entire community fly in the face of what true Christians believe...He clearly knows nothing about gay people or the majority of Louisianans – and Americans - who support legal recognition for loving and committed gay and lesbian couples. Phil's decision to push vile and extreme stereotypes is a stain on A&E and his sponsors who now need to reexamine their ties to someone with such public disdain for LGBT people and families." Robertson responded firmly to the critics, releasing a statement that said: “I myself am a product of the 60s; I centered my life around sex, drugs and rock and roll until I hit rock bottom and accepted Jesus as my Savior. “My mission today is to go forth and tell people about why I follow Christ and also what the bible teaches, and part of that teaching is that women and men are meant to be together. "However, I would never treat anyone with disrespect just because they are different from me. We are all created by the Almighty and like Him, I love all of humanity. We would all be better off if we loved God and loved each other.” Well, in less than a day, A&E took action. FOX411 quotes a statement from the network: "We are extremely disappointed to have read Phil Robertson's comments in GQ, which are based on his own personal beliefs and are not reflected in the series Duck Dynasty...His personal views in no way reflect those of A&E Networks, who have always been strong supporters and champions of the LGBT community. The network has placed Phil under hiatus from filming indefinitely." Who knows what that means, but the family was none too pleased at the reaction of the network, for whom they have made a large sum of money. And, the family released a statement on Thursday and posted it on its website: We want to thank all of you for your prayers and support. The family has spent much time in prayer since learning of A&E's decision. We want you to know that first and foremost we are a family rooted in our faith in God and our belief that the Bible is His word. While some of Phil’s unfiltered comments to the reporter were coarse, his beliefs are grounded in the teachings of the Bible. Phil is a Godly man who follows what the Bible says are the greatest commandments: “Love the Lord your God with all your heart” and “Love your neighbor as yourself.” Phil would never incite or encourage hate. We are disappointed that Phil has been placed on hiatus for expressing his faith, which is his constitutionally protected right. We have had a successful working relationship with A&E but, as a family, we cannot imagine the show going forward without our patriarch at the helm. We are in discussions with A&E to see what that means for the future of Duck Dynasty. Again, thank you for your continued support of our family. And, Todd Starnes of FOX reported that Cracker Barrel announced the removal of some Duck Dynasty merchandise from its store shelves. The chain of stores released this statement on its Facebook page: “Cracker Barrel’s mission is Pleasing People. We operate within the ideals of fairness, mutual respect and equal treatment of all people. These ideals are the core of our corporate culture. We continue to offer Duck Commander products in our stores. We removed selected products which we were concerned might offend some of our guests while we evaluate the situation. We continually evaluate the products we offer and will continue to do so.” Starnes said that Cracker Barrel's statement led to confusion among some customers who wondered if the restaurant was removing Duck Dynasty products owned by A&E or products owned by the Robertson family's Duck Commander business. Well, Sunday morning, Cracker Barrel posted on its Facebook page that it was reversing that decision: "When we made the decision to remove and evaluate certain Duck Dynasty items, we offended many of our loyal customers. Our intent was to avoid offending, but that's just what we've done. You told us we made a mistake. And, you weren't shy about it. You wrote, you called and you took to social media to express your thoughts and feelings. You flat out told us we were wrong. We listened. Today, we are putting all our Duck Dynasty products back in our stores. And, we apologize for offending you. We respect all individuals' right to express their beliefs. We certainly did not mean to have anyone think different. We sincerely hope you will continue to be part of our Cracker Barrel family." And, this illustrates a point that has been regularly made in areas of religious liberty and freedom of expression of Christian values: in an attempt to appease certain segments of the population that do not embrace Biblical principles or respect Christian values, who do you end up offending? The Christians! At least Cracker Barrel admitted they were wrong and apologized for offending their customers. What's next? Who know - I believe A&E made this "suspension" to buy time and let things die down. It's still disturbing that they felt the need to capitulate to GLAAD and similar groups, which represent a small percentage of the population. A new season is about to launch after the first of the year, and I just have a hunch they won't be editing all (if any) of Phil's appearances out. Sunday, December 15, 2013 On this edition of my week-in-review feature, "The 3", an update on the efforts being made by the wife of an Iranian-American pastor, who is currently being held in prison in Iran, to set him free. Also, a judge has ruled that a long-standing veteran's memorial in California that features a large cross must be taken down. And, the top story involves the ongoing confusion over the proper, constitutional expressions of Christmas in public schools.3 - Imprisoned Iranian-American pastor's wife testifies before Congress As Christmas approaches, believers continue to be reminded about the plight of Saeed Abedini, a pastor and an American citizen who was born in Iran and returned there to do ministry over a year ago. He was arrested and has been placed in notorious prisons in the nation, including Evin prison and now the Rajai Shahr prison, where his plight is said to be worsening. His wife, Naghmeh, testified before a House subcommittee on foreign affairs on Thursday. According to a story on the ReligionToday.com website, quoting Charisma News, she said that, "Each day that [Saeed Abedini] remains in that dreadful place could mean a death sentence; any day could be execution day." Jordan Sekulow of the American Center for Law and Justice (ACLJ) joined Abedini before Congress. He related that, "The Obama Administration and the U.S. State Department had a historic opportunity to demand Pastor Saeed’s release, along with that of all wrongly detained Americans in Iran, as a precondition to the nuclear negotiations...As Dr. Katrins Lantos Sweet, Vice Chair of the United States Commission on International Religious Freedom, testified, this would have been an easy ask. Yet, the Obama Administration intentionally chose not to even ask for his release as a precondition to the negotiations, leaving Pastor Saeed behind – malnourished, in increasing pain, and without medication.” Naghmeh is quoted as saying that, “As Christmas quickly approaches, it is just another painful reminder of life without Saeed for our family. When I ask my children what they want for Christmas, their answer is simple. It’s the same thing they wanted for their birthdays this year. It’s the same thing they want every day. They just want Daddy. They want Daddy home..." At the website, BeHeardProject.com, which you can access by typing in SaveSaeed.com, you can add your name to an online petition calling for his release. Over 161,000 people have done that thus far. The section of the website dealing with Pastor Saeed mentions the nuclear "deal" with Iran, so you might assume that this number has been acquired since that deal, because, previously, over 610,000 signatures were reported to have been collected. Also, over 193,000 people have written to the President of Iran asking him to release Pastor Saeed. 2 - Mount Soledad cross ordered to be removed Since 1954, a large cross has stood on Mount Soledad, overlooking the city of San Diego, as a memorial to the sacrifices of veterans. It is surrounded by 3,000 plaques to memorialize America’s war heroes from the Revolutionary War forward. CitizenLink reports that a Federal judge has ruled that the Mt. Soledad Veterans Memorial Cross must be removed from the San Diego site. Liberty Institute vows to appeal the decision all the way to the U.S. Supreme Court — if necessary. Hiram Sasser, Director of Litigation for Liberty Institute says that, “The judge reluctantly agreed with a previous ruling by 9th U.S. Circuit Court of Appeals that this hallowed veterans memorial must be removed." The appeals court had ruled in 2011 that the cross was unconstitutional. Sasser said he’s confident that the memorial will win on appeal. The legal proceedings started in 1989 when the ACLU and other groups filed suit saying the 43-foot-tall cross violated the Establishment Clause of the First Amendment. Since then many attempts have been made to save the cross. Congress passed a law in 2004 making the city-owned display a national memorial. Bruce Bailey, president of the Mt. Soledad Memorial Association, told Fox News: “It is unfortunate that the 9th Circuit left the judge no choice but to order the tearing down of the Mt. Soledad Veterans Memorial Cross." He added that he’s grateful the judge chose to allow the memorial to remain in place while the court challenge continues. 1 - Christmas clashes occur throughout America The top story of the week is actually an amalgamation of a number of different stories, all centered around the same issue - the rights of students to have freedom of expression as it pertains to the celebration of Christmas. We have seen instances throughout the years of school districts who have placed restrictions on the acknowledgement and celebration of this holiday, which is a Federal holiday, and the state of Texas earlier this year attempted to codify the rights of students regarding Christmas by passing the "Merry Christmas" Bill, which was introduced by Texas State Rep. Dwayne Bohac, who says he just wants to inject a little common sense back into the holiday season, according to the website, YourHoustonNews.com. The bill amended the education code to allow Texas public school administrators, teachers, students and parents to discuss, use traditional greetings of and display symbols and scenes of “traditional winter celebrations,” generally Christmas and Hannukkah, without proselytizing. Bohac held a press conference this week in an attempt to remind school districts about this legislation. In a release announcing the conference, Bohac uses an example given by Rep. Pat Fallon, who said that before Thanksgiving a PTA email distributed through Frisco ISD outlined a list of “winter party rules” that included no references to any religious holiday, no use of red and green colors, and no Christmas trees would be allowed. Fallon contacted the PTA and informed it of the new law. Bohac said, “With Christmas around the corner, our goal is to educate the public on this new law so that our teachers and students are able to celebrate the upcoming holiday season without fear of retribution or punishment...We also hope by raising awareness this legislation will become a model for others states around the country.” Religion Today also reports that Missouri overrode a governor's veto to pass a similar law. CitizenLink ran a story this week on 3 Montana high schools, who faced threats from the ACLU and the Freedom from Religion Foundation (FFRF), demanding that choir students not participate in a community Christmas festival at a local church. These schools represented students from 2 districts, who both agreed the show should go on as scheduled. Student choirs are allowed to voluntarily participate in Christmas events. The Alliance Defending Freedom wrote to the district superintendents, saying, “We write to commend you for rejecting the ACLU’s and FFRF’s unfounded demands that school choirs be excluded from the community Christmas festival. Such participation fully complies with applicable law...Your school districts were also right to be concerned that only disallowing choir students from singing at community events sponsored by churches would violate the First Amendment.” Religion Today reported on a recent Rasmussen poll, showing that 75% of American adults believe Christmas should be celebrated in public schools. The pollsters note, “Despite school administrators’ concerns nationwide, Americans strongly believe that Christmas should be a part of public schools. They feel just as strongly that religious symbols should be allowed on public property.” Widespread public support, however, has not squelched threatened litigation and school policy fights. Periodically at Faith Radio, we receive calls or e-mails from listeners who relate to us instances where they feel that students' rights of religious expression are being inhibited. Sometimes, people ask us to whom they could turn to find legal relief. Earlier in this story, I had mentioned the Alliance Defending Freedom. They have published a Christmas Memo, outlining the legal ways in which Christmas can be commemorated in a public school setting. They also have a Fact Sheet about this issue. Recently, ADF wrote a letter to over 13,000 school districts across the nation about the constitutional celebration of Christmas on school grounds. This letter was intended, according to ADF, "to explain constitutional protections for religious Christmas carols that some districts have censored due to misinterpretations of the First Amendment. The letter also backs up the legitimacy of schools participating in community service projects sponsored by religious organizations and offers free legal assistance to districts that need help." Other legal advocacy organizations that are involved in defending the religious rights of students include Liberty Institute (www.libertyinstitute.org), which defended to so-called "Candy Cane Case", out of Plano, TX, where a student had been prohibited from handing out candy cane pens to his classmates because there was a message attached regarding the legend of the candy cane, which points to Jesus. That case is still being litigated, apparently. Liberty Counsel (www.lc.org) is another organization that has actively defended students whose religious expression rights have been limited. The American Center for Law and Justice (www.aclj.org) is also involved in defending students' rights. Sunday, December 08, 2013 It's time for another edition of my weekly listing of top stories impacting the Christian community, including information, links, and commentary. I call it "The 3", including 3 stories of relevance. This week, one item involves action before the U.S. Supreme Court regarding health care - the justices decided not to hear an appeal in a case involving Liberty University and the employer mandate in the health care law, along with other issues. Another story involves two high-profile pastors and their large-scale book releases this week. And, the top story spotlights opportunities for charities, including ministry organizations, to shine and to raise funding. 3 - Supreme Court rejects Liberty University challenge to Affordable Care Act The day that President Obama signed the Affordable Care Act into law - March 23, 2010 - a lawsuit was filed on behalf of Liberty University and two private individuals. They are represented by Liberty Counsel, which stated that the case challenged (1) the entire employer mandate, (2) the forced funding of abortion drugs and devices under the law and as implemented by the federal Department of Health and Human Services (HHS), and (3) the forced funding of abortion by individuals under the individual mandate. The Liberty University case first reached the U.S. Supreme Court in 2011, and the issue raised by the case, the Anti-Injunction Act, became the subject of the first day of the three-day oral argument in 2012. In November 2012, the High Court ordered the federal court of appeals to rehear the remaining unresolved issues, including the employer mandate. After the three-judge panel (two of whom were appointed by President Obama) upheld the law, the case again went back to the Supreme Court. This week, the high court decided not to hear Liberty's appeal in the case. Mat Staver, Founder and Chairman of Liberty Counsel, said, “The High Court has decided to take up the HHS contraception and abortion drug mandate, but it is not ready yet to tackle the entire employer mandate. That challenge will wait for another day...The Liberty University case would make strong arguments that the employer mandate could not be upheld as a tax because the penalties are exorbitantly high and punitive. Deciding the case would have highlighted the absurdity of the Supreme Court’s convoluted decision upholding the individual mandate as a tax. Apparently the Court was not willing right now to venture back into that morass.” 2 - Major pastors Jeremiah, Warren announce new releases This past week marked the release of 2 major works by 2 of America's highest-profile pastors. The Christian Post reports that in New York City's Madison Square Garden, an crowd packed the 5,500-seat venue to celebrate the release of Dr. David Jeremiah's new Jeremiah Study Bible. The 72-year-old pastor told his family, friends and ministry supporters, "Tonight, we are celebrating the completion and publication of the Jeremiah Study Bible. This is the culmination of a lifetime of teaching and studying the Word of God...Over these many years I have watched this book and the savior it presents permanently change the lives of people. And it is my prayer that the study Bible introduced on this night, will encourage you to make the study of God's Word a priority in your life." [sic] The Jeremiah Study Bible: What It Says. What It Means. What It Means for You is in the New King James Version and includes over 8,000 study notes, hundreds of sidebars and more than 60 articles on "Essentials of the Christian Faith." Dr. Jeremiah is speaker on Turning Point radio and television and Senior Pastor of the Shadow Mountain Community Church in San Diego, had a number of musical guests on hand to mark the release of the Bible: Marshall Hall, Gordon Mote, The Brooklyn Tabernacle Singers, Kari Jobe, and MercyMe. Also, this week, the Senior Pastor of Saddleback Community Church in Lake Forest, California, Rick Warren, took to the airwaves to discuss his new book, The Daniel Plan: 40 Days to a Healthier Life, co-written with Dr. Daniel Amen and Dr. Mark Hymen. Media appearances included Piers Morgan Liveand CBS This Morning. According to a story on The Christian Post website, Pastor Warren and members of the church have undergone life-changing weight-loss experiences after collectively realizing three years ago that many of them needed to lose weight. About half of the church reportedly participated in the challenge, resulting in a collective weight loss of more than 250,000 pounds after the first year. Now, Warren aims to go beyond his own congregation and spread the word about living healthy with his new book. Warren, in an interview with Parade Magazine, said that, "There's a verse in the Bible that says Jesus went into every village preaching, teaching, and healing. I say that preaching is evangelism; teaching is education; and healing is health care." He added, "Jesus didn't only care about getting people into heaven. He cared about spirit, mind, and body. To me, health care isn't simply helping the sick get well, but helping the well not get sick." Warren stated that, "People say they want to work on their marriages, their careers, or get their finances in shape. If you can get your energy level up by living healthier, then you can say, 'now I can start working on my marriage, then I can work on my finances or my career or my parenting.' We're really starting at a base level." He says the Daniel Plan is about spiritual motivation. There are 5 components: faith, food, fitness, focus, and friends. 1 - Churches, charities use Giving Tuesday to motivate This past Tuesday marked the second annual Giving Tuesday event, involving thousands of non-profit organizations, including a variety of ministry-related groups. The Nonprofit Quarterly website reports that according to online donation company Blackbaud, they processed donations worth $19.2 million, an increase of 90 percent over last year. (On Giving Tuesday 2012, the company processed $10.1 million in donations.) This year there was a dramatic increase both in promotion of the event and in the numbers of nonprofits taking part. Not only were there more social media and email campaigns, there was also much more coverage in print and television. According to Crain’s New York Business, 10,000 nonprofits participated this year, as compared to 2,500 in 2012. There was much more infrastructure this year. On the #GivingTuesday webpage, there is a playbook for kickstarting a Giving Tuesday campaign and an article on measuring success. A new word/hashtag combination was coined: “#unselfies.” An unselfie is a picture of someone marking the act of giving back. A Christian denomination became involved in the #GivingTuesday concept this year. According to a report on the Newsday website, the United Methodist church General Board of Global Ministries announced that the first-ever UMC #GivingTuesday generated a record $6.5 million online on December 3. Nearly 11,000 donors in 34 countries gave more than 16,300 gifts through The Advance to mission and ministries they believe in. Global Ministries matched the first $500,000 received. The Advance is The United Methodist Church’s giving channel which ensures that 100 percent of each gift supports the project designated by the donor; it is a link that connects the church in mission. The Advance encompasses more than 850 Methodist-related projects and more than 300 missionaries, all of them reviewed and monitored by Global Ministries staff. In the wake of #Giving Tuesday, the Evangelical Council for Financial Accountability released some financial giving statistics. Christianity Today reports that the ECFA revealed that charitable giving to more than 1,600 of its accredited organizations increased 6.4 percent last year. Donations reached $11 billion in 2012, compared to $10.3 billion in 2011. The organization reports that giving to evangelical churches and ministries outpaced giving to secular charities in 2012. The Chronicle of Philanthropy's recently released giving data for the largest 400 charities in America reflected a giving increase of 4 percent for 2012, compared with 2011. This data most closely correlates with giving to ECFA members with $25 million or more in revenue, which showed a 7.5 percent increase. Sunday, December 01, 2013 This week's edition of "The 3", which is my week-in-review feature, begins with a story about a court ruling from the previous Friday which has been producing responses since then, as news spread last week. Also, a major announcement this past week came from the U.S. Supreme Court regarding the mandate forcing employers to provide contraception and abortion-inducing drugs in their health care plans. And, the top story - giving thanks! A ruling issued on Friday, November 22nd has brought response from a number of Christian organizations. According to Religion News Service, U.S. District Court Judge Barbara Crabb ruled that an Internal Revenue Service exemption that allows a clergy housing exemption, in order to reduce their Federal tax burden, is unconstitutional. The exemption applies to an estimated 44,000 ministers, priests, rabbis, imams and others. If the ruling stands, some clergy members could experience an estimated 5 to 10 percent cut in take-home pay. The suit was filed by the Wisconsin-based Freedom from Religion Foundation on grounds that the housing allowance violates the separation of church and state and the constitutional guarantee of equal protection. The group’s founders have said that if tax-exempt religious groups are allowed a housing subsidy, other tax-exempt groups, such as FFRF, should get one, too. CitizenLink quotes Dan Busby, President of the Evangelical Council for Financial Accountability, as saying that, “We find the Freedom from Religion Foundation’s argument to be disingenuous...They indicate that they are harmed by the inability to claim the clergy housing exclusion for their leaders, when they actually never attempted to claim this exclusion.” ECFA says on its website that, "The district court’s decision on the clergy housing exclusion may be appealed to the Seventh Circuit. Since the case was filed over two years ago, attorneys for the federal government have defended the constitutionality of the clergy housing exclusion and have argued that FFRF lacked legal standing to bring the challenge in the first place." According to RNS, the Southern Baptist Convention’s Ethics and Religious Liberty Commission and Southern Baptist-affiliated GuideStone Financial Resources plan to fight for the exemption. ERLC President Russell Moore says, “The clergy housing allowance isn’t a government establishment of religion, but just the reverse...The allowance is neutral to all religions. Without it, clergy in small congregations of all sorts would be penalized and harmed.” 2 - U.S. Supreme Court to consider HHS contraception mandate The U.S. Supreme Court announced Tuesday that it would hear Hobby Lobby's challenge to the government mandate requiring potential abortion-inducing drugs in employee health plans. The arts-and-crafts chain, owned by evangelical Christians, filed suit against the Obama administration last year. CitizenLink reports that in July, a federal court granted Hobby Lobby temporary relief from the mandate. This followed an appeals court order favoring such a reprieve. The administration then asked the high court to hear the case. Also, the high court will take a case involving a Mennonite-owned business in Lancaster County, PA, Conestoga Wood Specialties, owned by the Hahn family. The lower courts ruled against the family. The Obama administration required for-profit businesses to comply with the Health and Human Services (HHS) mandate by August 2012. Nonprofits - many of which are faith-based - have a so-called safe harbor until January. More than 80 suits are in play. According to CitizenLink, as of last Tuesday, courts have granted 32 injunctions, halting the mandate for for-profit businesses; six of these requests have been denied. 1 - Christians celebrate Thanksgiving, ministries demonstrate love of Christ This past Thursday, people from a variety of faith backgrounds, even those without a faith perspective, participated in the celebration of Thanksgiving. And, for a believer in Jesus Christ, we have plenty for which to be thankful, and Christians have a large opportunity to show our appreciation for what God has done in our lives by putting His love on display. A report earlier last week highlighted the work of rescue missions across America, partnering with people in their local communities to reach out to those less fortunate. A release from the Association of Gospel Rescue Missions (AGRM), the oldest and largest network of independent, faith-based crisis shelters and rehabilitation centers, estimated that its member-ministries served about 50 million meals annually, with the year-end holidays being one of the busiest times. John Ashmen, president of AGRM, is quoted in a press release from the Association, posted on the Christian Newswire website: "All are saying the same thing: Volunteers and donations are consistent with that of past years, but the number of people in need seems to have increased substantially." He also said that, "On behalf of every one of the rescue missions out there, I am extremely thankful for all of the volunteered hours and donated dollars...These gift are making the holidays -- starting with Thanksgiving -- meaningful to so many. But we all must remember that hunger and homelessness are not reserved for November and December. The problem is year-round." And, in Houston, a number of area churches turned Black Friday into "Bless Friday". According to its website, since 2010, Houston area churches have provided an alternative to frenzied Christmas shopping on the day after Thanksgiving. Continuing this tradition, an assortment of churches scheduled community service projects on Friday, November 29. These churches ask families and individuals to celebrate Bless Friday as an alternative to Black Friday. Chuck Fox, founder of Bless Friday, states, “People get our message that when we focus too much on buying things, we lose sight of the real reason for Christmas – remembering and honoring Christ. We want to begin our Christmas celebration by serving others just as Jesus did.” Also, best-selling author Karen Kingsbury teamed up with the large Christian retail chain Family Christian Stores to help provide relief for children in Haiti. According to a Christianity Today piece, Kingsbury, who has adopted three of her five sons from Haiti, said in a recent FCS press release, "Haiti is still recovering from the 2010 earthquake that ravaged the already-destitute nation. As in any crisis, many of those most gravely affected were the most vulnerable—infants and children...This Thanksgiving weekend, Family Christian and its customers will be telling these children that they are not forgotten, they are not abandoned and they are not without hope." The chain said that it would donate 100 percent of its profits from customer purchases over the three-day holiday weekend to build a neonatal orphanage in Haiti. Furthermore, it would match any donations made during the period. And, the Christian Defense Coalition was asking Americans to leave an empty place at their Thanksgiving dinners as a sign of solidarity with Pastor Saeed Abedini and the persecuted church worldwide, according to ChristianToday.com. Pastor Abedini, an Iranian and US citizen, has been imprisoned in Iran for over a year as a result of his Christian faith. He is serving an eight-year sentence in one of the most notorious prisons in the world, Tehran's Evin prison.	{ "pile_set_name": "Pile-CC" }
Q: How to get the OSM file to generate width of the streets? I'm attempting to load osm data into a database and i've used both osm2p0 and osm2pgrouting and kept realizing I wasnt seeing anything that referenced the width of the streets. This is important for me as I am writing a program to perform search and rescue where the size of the street is important as it can limit which vehicles can use which roads. So I started looking in the osm.xml file and I havent see anything that references width of streets. http://wiki.openstreetmap.org/wiki/Key:width. It says the key should be width. The key width describes the actual width of a way or other feature. Am I missing something or is width not actually provided within the OSM. A: Well, if you look at the OSM tags in use, you will discover the width=* tag, that can be used for highways, too. There are also some more tags that indicate the width of a road/way: maxwidth, lanes. All of this tags are optional and you don't should expect an global coverage... I guess most important criteria (as present for every road) is the road classification itself. But you need to take the country specific defaults into account, which is tricky and will take a lot of research. You might want to use TrafficMining to create a custom routing profile that takes the road width into account to move your HGV vehicles. Maybe the Humaniterian OSM Team has already some experience on such technologies to assist desaster and emergency response.	{ "pile_set_name": "StackExchange" }
Control of neuronal gene expression. Some 30,000 genes are expressed exclusively in the rat brain, many of which contain a genetic element called an identifier sequence located in at least one of their introns. The identifier sequences are transcribed by RNA polymerase III exclusively in neurons to produce two RNA species, BC1 and BC2, of 160 and 100 to 110 nucleotides. This transcriptional event may define regions of chromatin that contain neuronal-specific genes and may poise these genes for transcription by polymerase II by rendering the gene promoters accessible to soluble trans-acting molecules.	{ "pile_set_name": "PubMed Abstracts" }
Q: Renaming items in export menu in highcharts Can someone please suggest if there is anyway we can rename the items in the export menu in highcharts. Currently it has entries like: Download PNG image Download JPEG image ... I want to remove word "image". Moreover want to control the complete styling. A: There are lots of options for this. Some can be done in Javascript, and I'm sure more can be done in CSS. Here is a JSFiddle example showing the desired text changes and some style changes. You can read the details on this in the API under lang and navigation. The text is changed with: lang: { printChart: 'Print chart', downloadPNG: 'Download PNG', downloadJPEG: 'Download JPEG', downloadPDF: 'Download PDF', downloadSVG: 'Download SVG', contextButtonTitle: 'Context menu' } And the style of the button and menu with: navigation: { menuStyle: { border: '1px solid #A0A0A0', background: '#FFFFFF', padding: '5px 0' }, menuItemStyle: { padding: '0 10px', background: null, color: '#303030', fontSize: '11px' }, menuItemHoverStyle: { background: '#4572A5', color: '#FFFFFF' }, buttonOptions: { symbolFill: '#E0E0E0', symbolSize: 14, symbolStroke: '#666', symbolStrokeWidth: 3, symbolX: 12.5, symbolY: 10.5, align: 'right', buttonSpacing: 3, height: 22, // text: null, theme: { fill: 'white', // capture hover stroke: 'none' }, verticalAlign: 'top', width: 24 } } You can get the default values from the source code, almost at the very top. Some of the defaults use variables that you won't have though, so you may need to change them. And as mentioned, CSS may get you the extra distance.	{ "pile_set_name": "StackExchange" }
Promising strategies for obesity pharmacotherapy: melanocortin-4 (MC-4) receptor agonists and melanin concentrating hormone (MCH) receptor-1 antagonists. Despite remarkable progress in the elucidation of energy balance and regulation, the development of new anti-obesity drugs is still at the stage of infancy. Herein we briefly reviewed several investigational anti-obesity agents currently under development, consisting of agents controlling appetite, modulating nutrient absorption and lipid metabolism, sensing and regulating nutrient status, stimulating energy expenditure, and reducing adiposity. In particular, two promising targets such as melanocortin-4 (MC-4) receptor and melanin concentrating hormone (MCH)-1 receptor will be highlighted in this review covering major medicinal chemistry efforts and biological aspects of the compounds synthesized. Considering the enthusiastic efforts to develop efficacious and safe anti-obesity drugs, a range of novel medications treating obesity more effectively than is currently managed by pharmacotherapy will be available in near future.	{ "pile_set_name": "PubMed Abstracts" }
LinkedIn Builds Social Media Bridge Between Teens and Higher Education In making its online professional networking platform relevant to a new audience, social media giant LinkedIn is set to lower the age for participation from 18 to 14 next month with the aim of providing the means by which colleges and universities can reach potential students. The initiative kicked off Monday with LinkedIn announcing University Pages, a new platform feature that includes extensive institutional profiles at which LinkedIn users can connect with school staff members and alumni. More than 200 schools have developed University Pages profiles and have begun to use them as LinkedIn prepares to open its platform for younger users. Schools with University Pages profiles include New York University, University of California San Diego, University of Michigan, Villanova University, Rochester Institute of Technology, University of Illinois and Albion College. Over the next several weeks, hundreds of additional schools will debut their University Pages profiles, according to LinkedIn. Christina Allen, LinkedIn’s director of product management, described the University Pages feature as “one cornerstone of our strategy to help students at every critical milestone from campus to fulfilling, successful careers.” “We believe University Pages will be especially valuable for students making their first big decision about where to attend college. Therefore, beginning on September 12, we will be making LinkedIn available to high school students who can use LinkedIn to explore schools worldwide, greatly expand their understanding of the careers available, and get a head start on building a network of family and friends to help guide them at every milestone,” Allen wrote in a Linkedin blog. Users of University Pages will be able to get updates on school news, learn how many of the school’s alumni are on LinkedIn and explore the organizations where the graduates are working. In a section called “Explore Careers,” students can find out about individuals who have attended a particular school and what those individuals have done after graduation. Julie Inouye, a LinkedIn spokesperson, says LinkedIn stands out from other social media platforms, such as Facebook, due to the alumni database it has developed from its traditional users, who are typically working professionals. “We have all of this great insight and data because of the LinkedIn members that have gone to these schools,” Inouye told The Huffington Post. David Lawrence, the associate director of digital media strategy at Albion College, said the Albion, Mich.-based college is one of the 200 institutions that were invited to get an early start on its University Pages profile. That recently completed page has already provided more than 8,000 alumni automated Albion College news and information updates, adding to the extensive outreach efforts the college already conducts with its alumni, according to Lawrence. “The alumni outreach has been going pretty strong, but our next step is to build the [University Pages] platform for current students,” he explained. “We expect to do more outreach and training and tutorials on how current students can use LinkedIn to promote themselves.” Lawrence is cautious about speculating on how popular Linkedin will become among the 14- to 17-year-olds who will be able to use the service next month. “I think LinkedIn has to do some cultural shifting in convincing teenagers that this is an important thing to do and promote this as a college research tool. That’s an uphill battle, and I wish them lots of luck,” he said. One of the many schools now completing a University Pages profile is Morehouse College, a historically Black private college based in Atlanta. Morehouse communications staff members are working with LinkedIn officials to build out the school’s page, which is expected to be more extensive than its current LinkedIn organizational profile. While it remains to be seen just how much high school students will utilize the Morehouse page, school officials expect that alumni and other constituencies will readily benefit from the profile page features and tools. Professor Apologizes for Fiery Response to Muslim Student CINCINNATI — A University of Cincinnati music teacher has apologized for his fiery online responses to a Muslim student who was critical of Donald Trump’s presidency and talked about celebrating freedom and diversity. College-Conservatory of Music...	{ "pile_set_name": "Pile-CC" }
Miami-Dade Judge Maxine Cohen Lando has yet to file a written order from the Feb. 11 hearing and the affidavit appears to be an explanation of the steps Ben-Ezra & Katz took to improve its foreclosure practices as business ramped up. Ben-Ezra made several attempts during the Feb. 11 hearing to do just that, but Lando shut him down each time as the following exchange shows: Mr. Ben-Ezra: I’m prepared to tell you about some of the things that we’re doing. The Court: You better be prepared to tell me about this case because this is the case that you’re here for contempt of court. In the April 1 affidavit filed in the case _ Central Mortgage Company v. Eduardo Gonzalez Del Real _ Ben-Ezra said the firm has gone to great lengths to ensure attorneys and staff follow proper procedure. That includes creating a program called “BEKPA U” (Ben-Ezra & Katz, P.A. University?) to “further the foreclosure-related education of our attorneys. “We have invested well in excess of $1 million in case management software in the course of the last year alone,” Ben-Ezra said in the affidavit. “Partners have had numerous meetings reinforcing the message that at BEKPA we do things right. We do not cut corners.” Ben-Ezra & Katz lost its foreclosure business from Fannie Mae in February after the federal mortgage backer said it found problems with “execution issues.” The firm has also tangled with Chase Home Finance, which cut ties with it March 9 and then sued to get its files back. Ben-Ezra & Katz says it is owed $6.2 million in legal fees. A ruling last week said Chase will have to pay a $4 million surety bond to get its files back. But the loss of business has affected the firm’s finances. Late last month, the firm filed notice with the state that it planned to lay off 54 employees in May. That follows a staff cut of 236 employees in February.	{ "pile_set_name": "Pile-CC" }
Rock out to the softcover edition of 'Votes for Women: The Battle for the 19th Amendment' as well as the digital edition. Free shipping to the U.S.! Includes: Print edition E-book Your name in the book Less	{ "pile_set_name": "OpenWebText2" }
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Q: Q about [42000] and passed by reference I have two errors in my php script, the only weard thing is this is the exact code as my other scripts. thats the reason that i can't find the solutions. Can you help me to find the solution? Strict Standards: Only variables should be passed by reference in /home/joshua/domains/*******/public_html/panel/settings.php on line 130 Fatal error: Uncaught exception 'PDOException' with message 'SQLSTATE[42000]: Syntax error or access violation: 1064 You have an error in your SQL syntax; check the manual that corresponds to your MySQL server version for the right syntax to use near 'insert = NULL, lastname = 'Hiwat', password = '$2a$13$nAJT6kLx8N5Hd0G8zQ4yheEOad' at line 1' in /home/joshua/domains/*****/public_html/panel/settings.php:216 Stack trace: #0 /home/joshua/domains/******/public_html/panel/settings.php(216): PDOStatement->execute() #1 {main} thrown in /home/joshua/domains/tubecreators.com/public_html/panel/settings.php on line 216 And here my code... <?php if($_SERVER['REQUEST_METHOD'] == 'POST') { $errors = Array(); if(isset($_POST['name'])) { if(trim($_POST['name']) != '') { if(strlen(trim($_POST['name'])) < 2) { $errors[] = 'De voornaam is te kort (2).'; } }else{ $errors[] = 'De voornaam is leeg gelaten.'; } }else{ $errors[] = 'Er is geen voornaam meegestuurd.'; } if(isset($_POST['password'])) { if(trim($_POST['password']) != '' && strlen(trim($_POST['password'])) < 6) { $errors[] = 'Het wachtwoord moet minimum 6 karakters bevatten. Kies zorgvuldig een veilig wachtwoord met (hoofd)letters, cijfers en eventueel symbolen. Indien je je wachtwoord verliest kan je contact opnemen met de ICT manager.'; } }else{ $errors[] = 'Er is geen wachtwoord meegestuurd.'; } if(isset($_POST['passwordrepeat'])) { if(trim($_POST['passwordrepeat']) != trim($_POST['password'])) { $errors[] = 'De opgegeven wachtwoorden zijn niet hetzelfde.'; } }else{ $errors[] = 'Er is geen herhaald wachtwoord meegestuurd.'; } if(isset($_POST['lastname'])) { if(trim($_POST['lastname']) != '') { if(strlen(trim($_POST['lastname'])) < 2) { $errors[] = 'De achternaam is te kort (2).'; } }else{ $errors[] = 'De achternaam is leeg gelaten.'; } }else{ $errors[] = 'Er is geen achternaam meegestuurd.'; } if(isset($_POST['birth'])) { if(trim($_POST['birth']) != '') { if(strlen(trim($_POST['birth'])) < 2) { $errors[] = 'De de geboortedatum is ongeldig (2).'; } }else{ $errors[] = 'De geboortedatum is leeg gelaten.'; } }else{ $errors[] = 'Er is geen geboortedatum meegestuurd.'; } if(isset($_POST['city'])) { if(trim($_POST['city']) != '') { if(strlen(trim($_POST['city'])) < 1) { $errors[] = 'De stadsnaam is te kort (2).'; } }else{ $errors[] = 'De stadsnaam is leeg gelaten.'; } }else{ $errors[] = 'Er is geen stadsnaam meegestuurd.'; } if(isset($_POST['mail'])) { if(trim($_POST['mail']) != '') { if(filter_var(trim($_POST['mail']), FILTER_VALIDATE_EMAIL)) { $checkexist = $dbh->prepare('SELECT COUNT(id) FROM users WHERE mail = :mail AND NOT id = :id'); $checkexist->bindParam(':mail', trim($_POST['mail']), PDO::PARAM_STR); $checkexist->bindParam(':id', $user['id'], PDO::PARAM_INT); $checkexist->execute(); if($checkexist->fetchColumn() > 0) { $errors[] = 'Er is al een account met dit mailadres.'; } }else{ $errors[] = 'De e-mail is ongeldig.'; } }else{ $errors[] = 'De e-mail is leeg gelaten.'; } }else{ $errors[] = 'Er is geen e-mail meegestuurd.'; } if(isset($_POST['youtube'])) { if(trim($_POST['youtube']) != '') { if(strlen(trim($_POST['youtube'])) < 6) { $errors[] = 'De Youtube gebruikersnaam is te kort (6).'; } }else{ $errors[] = 'De Youtube gebruikersnaam is leeg gelaten.'; } }else{ $errors[] = 'Er is geen Youtube gebruikersnaam meegestuurd.'; } if(isset($_POST['about'])) { if(trim($_POST['about']) != '') { if(strlen(trim($_POST['about'])) < 20) { $errors[] = 'Het stukje over jezelf is te kort (2).'; } }else{ $errors[] = 'Het stukje over jezelf is leeg gelaten.'; } }else{ $errors[] = 'Er is geen stukje over jezelf meegestuurd.'; } if(isset($_POST['category'])) { if(trim($_POST['category']) != '') { if(strlen(trim($_POST['category'])) < 1) { $errors[] = 'De Youtube categorie is te kort (2).'; } }else{ $errors[] = 'De Youtube categorie is leeg gelaten.'; } }else{ $errors[] = 'Er is geen Youtube categorie meegestuurd.'; } if(count($errors) == 0) { $name = trim($_POST['name']); $password = trim($_POST['password']); if($password != '') { $bcrypt = new Bcrypt($config['security']['passwordsafety']); $passwordHashed = $bcrypt->hash($password); } $lastname = trim($_POST['lastname']); $birth = trim($_POST['birth']); $city = trim($_POST['city']); $mail = trim($_POST['mail']); $youtube = trim($_POST['youtube']); $about = trim($_POST['about']); $category = trim($_POST['category']); $update = $dbh->prepare('UPDATE users SET name = :name, insert = :insert, lastname = :lastname, ' . (($password != '') ? 'password = :password, ' : '') . 'birth = :birth, country = :country, city = :city, mail = :mail, facebook = :facebook, twitter = :twitter, google = :google, instagram = :instagram, youtube = :youtube, pinterest = :pinterest, about = :about, category = :category WHERE id = :id'); $update->bindParam(':name', $name, PDO::PARAM_STR); $update->bindParam(':insert', $insert, PDO::PARAM_STR); $update->bindParam(':lastname', $lastname, PDO::PARAM_STR); if($password != '') { $update->bindParam(':password', $passwordHashed, PDO::PARAM_STR); } $update->bindParam(':birth', $birth, PDO::PARAM_STR); $update->bindParam(':country', $country, PDO::PARAM_STR); $update->bindParam(':city', $city, PDO::PARAM_STR); $update->bindParam(':mail', $mail, PDO::PARAM_STR); $update->bindParam(':facebook', $facebook, PDO::PARAM_STR); $update->bindParam(':twitter', $twitter, PDO::PARAM_STR); $update->bindParam(':google', $google, PDO::PARAM_STR); $update->bindParam(':instagram', $instagram, PDO::PARAM_STR); $update->bindParam(':youtube', $youtube, PDO::PARAM_STR); $update->bindParam(':pinterest', $pinterest, PDO::PARAM_STR); $update->bindParam(':about', $about, PDO::PARAM_STR); $update->bindParam(':category', $category, PDO::PARAM_STR); $update->bindParam(':id', $user['id'], PDO::PARAM_INT); $update->execute(); addlog('Account gewijzigd', $user['id']); echo '<font color="gree">De gebruiker is succesvol gewijzigd.</font><meta http-equiv="refresh" content="1;url=http://panel.tubecreators.com/instellingen">'; $edited = true; }else{ echo '<font color="red">Er ging wat mis. De volgende dingen gingen fout:<ul><li>' . join('</li><li>', $errors) . '</li></ul>De gebruiker is nniet gewijzigd.</font>'; } } if(!isset($edited)) { ?> A: insert is a reserved MySQL keyword. You need to quote it in backticks like `insert`. You should get used to doing this for all table and column names. Only variables should be passed by reference means exactly what it says. It is expecting a reference, therefore a variable must be passed to it. I can update this once you point me to line 130 of panel/settings.php. My assumption is the error is generated by bind_param which requires a reference. The one line of code I see that would certainly generate this warning is: $checkexist->bindParam(':mail', trim($_POST['mail']), PDO::PARAM_STR); Here you are passing a return value instead of a variable. You could do this: $trimMail = trim($_POST['mail']) $checkexist->bindParam(':mail', $trimMail, PDO::PARAM_STR);	{ "pile_set_name": "StackExchange" }
In English-----------Hail holy queen, mother of mercy,Hail our life, our sweetness and our hope.To you do we cry poor banished children of Eve,To you do we send up our sighs, mourning and weeping in this valley of tears.Turn then, most gracious advocateyour eyes of mercy toward us.And after this, our exile,Show us the fruit of your womb, Jesus.O clement, O loving, O sweet Virgin Mary. All gifts, virtues, and graces of the Holy Spirit are administered by the hands of the Blessed Virgin Mary to whomsoever she desires, when she desires, and in the manner she desires, and to whatever degree she desires.	{ "pile_set_name": "Pile-CC" }
Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy. Unfractionated heparin is the most commonly used anticoagulant in continuous renal replacement therapy (CRRT), but it can increase the risk of bleeding. Citrate is a promising substitute. Our study was to assess the efficacy and safety of citrate versus unfractionated heparin in CRRT. We searched the MEDLINE, the EMBASE, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure Database until up to November 2011 for randomized controlled trials comparing citrate with unfractionated heparin in adult patients with acute kidney injury prescribed CRRT. The primary outcome was mortality and the secondary outcomes included circuit survival, control of uremia, risk of bleeding, transfusion rates, acid-base statuses, and disturbance of sodium and calcium homeostasis. Four trials met the inclusion criteria. Meta-analysis found no significant difference between two anticoagulants on mortality. Less bleeding and more hypocalcemic episodes were with citrate. Citrate was superior or comparable to unfractionated heparin in circuit life. Citrate anticoagulation in CRRT seems to be superior in reducing bleeding risk and with a longer or similar circuit life, although there is more metabolic derangement. Mortality superiority has not been approved.	{ "pile_set_name": "PubMed Abstracts" }
Prevention of and treatment for hepatitis B virus infection after liver transplantation in the nucleoside analogues era. Post-transplant prophylaxis with hepatitis B immune globulin (HBIG) has significantly reduced hepatitis B virus (HBV) recurrence rates, but it is rather ineffective in patients with pretransplant viremia. Moreover, long-term HBIG administration is very expensive and may be associated with emergence of escape HBV mutants. Lamivudine has been widely used in the management of HBV transplant patients. Pretransplant lamivudine lowers HBV viremia, decreasing the risk of post-transplant HBV recurrence, but to try and minimize development of resistant HBV strains, it should start within the last 6 months of the anticipated transplantation timing. Preemptive post-transplant lamivudine monotherapy is associated with progressively increasing HBV recurrence rates, but combined therapy with lamivudine and HBIG at relatively low dosage is currently the most effective approach in this setting, even in HBV-DNA-positive patients, who also receive lamivudine in the pretransplant period. The most frequent therapy for post-transplant HBV recurrence is lamivudine, but the increasing resistance rates represent a rather challenging problem. Adefovir dipivoxil and entecavir are currently the most promising agents for lamivudine-resistant HBV strains. All these advances in anti-HBV therapy have made HBV liver disease an indication for liver transplantation irrespective of viral replication status, a complete turn around from 10 years ago.	{ "pile_set_name": "PubMed Abstracts" }
The access gateway allows particularly equipment or devices located on a customer site to access a wide area communication network WAN (for “wide area network”), such as the Internet network. These devices are also called CPEs, for “customer premises equipment”. For a local area network, they are particularly the access gateway, a TV decoder “set-top box” and a mobile terminal. Within the context of a home automation network, they are also household appliances, alarm systems and sensors. In order to guarantee quality services, it is preferable for an operator of the wide area communication network to be able to manage such devices remotely. Remote management of the devices particularly requires: detection and knowledge of the devices that are present in the local area network, for example their serial numbers, their hardware and software versions; supervision of these devices, for example by obtaining supervision information and performance indicators. Remote management of the devices of a local area network is reliant on a technical report drafted by the Broadband Forum, TR-069 “CPE WAN Management Protocol”. This technical report defines a CWMP protocol, allowing communication between a piece of administrative equipment, called remote auto-configuration equipment ACS (for “auto-configuration server”), and a device of the local area network. The CWMP protocol defines a mechanism that allows, in particular, secure auto-configuration of the equipment of the local area network and other functions for managing these devices. It is particularly possible for the operator of the network to make remote interventions, such as: updating the software or the firmware of a device when the software version or the firmware needs to move on; making a diagnosis when a device has a malfunction; dynamically installing and configuring new services; monitoring the state and the performance of a device. The CWMP protocol is reliant on the Internet protocol, more precisely on TCP/IP (for “transmission control protocol”). The data allowing remote management of the devices of the network, for example data for assisting in diagnosis, are transmitted by each device to the administrative equipment by means of the CWMP protocol. When access to the wide area communication network WAN is no longer possible via the access gateway, it is then impossible to make contact with the administrative equipment in order to transmit data for assisting in diagnosis to it. Consequently, it is impossible for a customer support advisor of the operator to automatically retrieve the data for assisting in diagnosis when the access gateway no longer allows access to the wide area communication network. The advisor therefore has to question the customer orally in order to be able to establish a technical diagnosis, making this work difficult and not very reliable.	{ "pile_set_name": "USPTO Backgrounds" }
--- abstract: 'We describe the first-principles design and subsequent synthesis of a new material with the specific functionalities required for a solid-state-based search for the permanent electric dipole moment of the electron. We show computationally that perovskite-structure europium barium titanate should exhibit the required large and pressure-dependent ferroelectric polarization, local magnetic moments, and absence of magnetic ordering at liquid helium temperature. Subsequent synthesis and characterization of Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ ceramics confirm the predicted desirable properties.' author: - 'K. Z. Rushchanskii' - 'S. Kamba' - 'V. Goian' - 'P. Vaněk' - 'M. Savinov' - 'J. Prokleška' - 'D. Nuzhnyy' - 'K. Knížek' - 'F. Laufek' - 'S. Eckel' - 'S. K. Lamoreaux' - 'A. O. Sushkov' - 'M. Ležaić' - 'N. A. Spaldin' title: 'First-principles design and subsequent synthesis of a material to search for the permanent electric dipole moment of the electron' --- \ The Standard Model of particle physics incorporates the breaking of the discrete symmetries of parity ($P$) and the combined charge conjugation and parity ($CP$). It is thought however, that the $CP$-violation within the framework of the Standard Model is insufficient to explain the observed matter-antimatter asymmetry of the Universe [@Trodden1999], therefore a so far unknown source of $CP$-violation likely exists in nature. The existence of a non-zero permanent electric dipole moment (EDM) of a particle, such as an electron, neutron, or atom, would violate time reversal ($T$) symmetry (Fig. \[PT\_cartoon\]) and therefore imply $CP$-violation through the $CPT$ theorem [@Khriplovich1997]. In the Standard Model these EDMs are strongly suppressed, the theoretical predictions lying many orders of magnitude below the current experimental limits. However, many theories beyond the Standard Model, such as supersymmetry, contain a number of $CP$-violating phases that lead to EDM predictions within experimental reach [@Bernreuther1991]. Searching for EDMs therefore constitutes a background-free method of probing the $CP$-violating physics beyond the Standard Model. A number of experimental EDM searches are currently under way or are being developed – systems studied in these experiments include diatomic molecules [@Hudson2002; @Kawall2004], diamagnetic atoms [@Griffith2009; @Guest2007; @Tardiff2007], molecular ions [@Stutz2004], cold atoms [@Weiss2003], neutrons [@Baker2006], liquids [@Ledbetter2005], and solids [@Heidenreich2005; @Bouchard2008] – with one of the most promising novel techniques being electric-field-correlated magnetization measurements in solids [@Shapiro1968; @Lamoreaux2002; @Budker2006]. This technique rests on the fact that, since spin is the only intrinsic vector associated with the electron, a non-vanishing electron EDM is either parallel or antiparallel to its spin and hence its magnetic moment. As a result, when an electric field, which lifts the degeneracy between electrons with EDMs parallel and antiparallel to it, is applied to a sample, the associated imbalance of electron populations generates a magnetization (Fig. \[Zeeman\]). The orientation of the magnetization is reversed when the electric field direction is switched; in our proposed experiment we will monitor this change in sample magnetization using a SQUID magnetometer [@Sushkov2009; @Sushkov2010]. Such [magnetoelectric responses]{} in materials with permanent [macroscopic]{} magnetizations and polarizations are of great current interest in the materials science community because of their potential for enabling novel devices that tune and control magnetism using electric fields[@Spaldin/Ramesh:2008]. \ Since the experiment aims to detect the intrinsic magnetoelectric response associated with the tiny electric dipole moment of the electron, the design constraints on the material are stringent. First, the solid must contain magnetic ions with unpaired spins, since the equal and opposite spins of paired electrons have corresponding equal and opposite EDMs and contribute no effect. Second, it must be engineered such that the [conventional]{} linear magnetoelectric tensor is zero; our approach to achieving this is to use a paramagnet in which the conventional effect is forbidden by time-reversal symmetry[@Fiebig:2005]. To reach the required sensitivity, a high atomic density of magnetic ions ($n\approx 10^{22}$ cm$^{-3}$) is needed, and these magnetic ions must reside at sites with broken inversion symmetry. The energy splitting $\Delta$ shown in Fig. \[Zeeman\] is proportional to the product of the effective electric field experienced by the electron, $E^$, and its electric dipole moment, $d_e$. The effective electric field, which is equal to the electric field one would have to apply to a free electron to obtain the same energy splitting, is in turn determined by the displacement of the magnetic ion from the center of its coordination polyhedron; for a detailed derivation see Ref. [@Mukhamedjanov2003]. For example, in Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ ceramics (see below) with $\sim$1 $\mu$C/cm$^2$ remanent polarization, the mean displacement of the Eu$^{2+}$ ion with respect to its oxygen cage is 0.01 Å and this results in an effective electric field of $\sim$10 MV/cm, even when no external electric field is applied. We choose a ferroelectric so that it is possible to reverse the direction of the ionic displacements, and hence of the effective electric field, with a moderate applied electric field. Finally, the experiment will be performed inside liquid helium, so the material properties described above must persist at low temperature. A detailed derivation of the dependence of the sensitivity on the material parameters is given in Ref. [@Sushkov2010]. Note that conventional impurities such as defects or domain walls are not detrimental to the experiment since they do not violate time-reversal symmetry. In summary, the following material specifications will allow a sensitive EDM search to be mounted: (i) The material should be ferroelectric, with a large electric polarization, and switchable at liquid He temperature. (ii) There should be a high concentration of ions with local magnetic moments that remain paramagnetic at liquid He temperature; both long-range order and freezing into a glassy state must be avoided. (iii) The local environment at each magnetic ion should be strongly modified by the ferroelectric switching, and (iv) the sample should be macroscopic. With these material properties, and optimal SQUID noise levels, the projected experimental sensitivity is 10$^{-28}$ e.cm after ten days of averaging[@Sushkov2010]. No known materials meet all the requirements. Indeed the contra-indication between ferroelectricity and magnetism has been studied extensively over the last decade in the context of multiferroics [@Hill:2000], where the goal has been to achieve simultaneous ferroelectric and ferromagnetic ordering at high temperature. In spite of extensive efforts, a room temperature multiferroic with large and robust ferroelectricity and magnetization at room temperature remains elusive. While the low temperature constraints imposed here seem at first sight more straightforward, avoiding any magnetic ordering at low temperature, while retaining a high concentration of magnetic ions poses a similarly demanding challenge. In addition the problem of ferroelectric switchability at low temperature is challenging, since coercivities tend to increase as temperature is lowered [@Merz:1951]. We proceed by proposing a trial compound and calculating its properties using density functional theory to determine whether an experimental synthesis should be motivated. We choose an alloy of europium titanate, EuTiO$_3$ and barium titanate, BaTiO$_3$, with motivation as follows: To incorporate magnetism we require unfilled orbital manifolds of localized electrons; to avoid magnetic ordering the exchange interactions should be small. Therefore the tightly bound $4f$ electrons are likely to be the best choice. For conventional ferroelectricity we require transition metal ions with empty $d$ orbitals to allow for good hybridization with coordinating anions on off-centering [@Rondinelli/Eidelson/Spaldin:2009]. (Note that while here we use a conventional ferroelectric mechanism, many alternative routes to ferroelectricity that are compatible with magnetism – and which could form a basis for future explorations – have been recently identified; for a review see Ref. ). Both EuTiO$_3$ and BaTiO$_3$ form in the ABO$_3$ perovskite structure, with divalent Eu$^{2+}$ or Ba$^{2+}$ on the A site, and formally $d^0$ Ti$^{4+}$ on the B site. BaTiO$_3$ is a prototypical ferroelectric with a large room temperature polarization of 25 $\mu$C/cm$^2$.[@Wemple:1968] In the cubic paraelectric phase its lattice constant is 3.996 Å [@Miyake/Ueda:1947]. The Ba$^{2+}$ ion has an inert gas electron configuration and hence zero magnetic moment. The lattice parameter of EuTiO$_3$ is 3.905 Å [@Katsufuji/Takagi:2001], notably smaller than that of BaTiO$_3$. It is not ferroelectric, but has a large dielectric constant ($\epsilon \approx 400$) at low temperature, indicative of proximity to a ferroelectric phase transition; indeed it has recently been reported to be a quantum paraelectric[@Katsufuji/Takagi:2001; @kamba:2007]. First-principles electronic structure calculations have shown that ferroelectricity should be induced along the elongation direction by either compressive or tensile strain [@Fennie/Rabe:2006]. The Eu$^{2+}$ ion has seven unpaired localized $4f$ electrons resulting in a large spin magnetization of 7 $\mu_B$, and EuTiO$_3$ is an antiferromagnet with $G$-type ordering at a low Néel temperature of $\sim$5.3K [@McGuire_et_al:1966; @Chien/DeBenedetti/Barros:1974]. (Independently of the study presented here, EuTiO$_3$ is of considerable current interest because its dielectric response is strongly affected by the magnetic ordering [@Katsufuji/Takagi:2001; @kamba:2007] and because of its unusual third order magnetoelectric response [@Shvartsman_et_al:2010]. These behaviors indicate coupling between the magnetic and dielectric orders caused by sensitivity of the polar soft mode to the magnetic ordering [@Fennie/Rabe:2006; @Goian:2009].) Our hypothesis is that by alloying Ba on the A-site of EuTiO$_3$, the magnetic ordering temperature will be suppressed through dilution, and the tendency to ferroelectricity will be increased through the expansion of the lattice constant. Our hope is to identify an alloying range in which the magnetic ordering temperature is sufficiently low while the ferroelectric polarization and the concentration of magnetic ions remain sufficiently large. In addition, we expect that the polarization will be sensitive to the lattice constant, allowing its magnitude and consequently the coercivity, to be reduced with pressure. First-Principles Calculations ============================= Taking the 50/50 (Eu,Ba)TiO$_3$ ordered alloy as our starting point (Fig. \[th\_phonons\] inset), we next calculate its properties using first-principles. For details of the computations see the Methods section. We began by calculating the phonon dispersion for the high symmetry, cubic perovskite reference structure at a lattice constant of 3.95 Å (chosen, somewhat arbitrarily, for this first step because it is the average of the experimental BaTiO$_3$ and EuTiO$_3$ lattice constants), with the magnetic spins aligned ferromagnetically; our results are shown in Fig. \[th\_phonons\], plotted along the high symmetry lines of the Brillouin zone. Importantly we find a polar $\Gamma$-point instability with an imaginary frequency of 103$i$ cm$^{-1}$ which is dominated by relative oxygen – Ti/Eu displacements (the eigenmode displacements for Eu, Ba, Ti, O$_{\parallel}$ and O$_{\perp}$ are 0.234, -0.059, 0.394, -0.360 and -0.303 respectively); such polar instabilities are indicative of a tendency to ferroelectricity. The zone boundary rotational instabilities that often occur in perovskite oxides and lead to non-polar, antiferrodistortive ground states are notably absent (in fact the flat bands at $\sim$60 cm$^{-1}$ are stable rotational vibrations). Interestingly we find that the Eu ions have a significant amplitude in the soft-mode eigenvector, in contrast to the Ba ions both here and in the parent BaTiO$_3$. Next we performed a structural optimization of both the unit cell shape and the ionic positions of our Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ alloy with the total volume constrained to that of the ideal cubic structure studied above (3.95$^3$ Å$^3$ per formula unit). Our main finding is that the Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ alloy is polar with large relative displacements of oxygen and both Ti and Eu relative to the high symmetry reference structure. Using the Berry phase method we obtain a ferroelectric polarization value of $P = 23$ $\mu$C/cm$^2$. Our calculated ground state is orthorhombic with the polarization oriented along a \[011\] direction and lattice parameters $a=3.94$ Å, $b=5.60$ Å and $c=5.59$ Å. As expected from our analysis of the soft mode, the calculated ground state is characterized by large oxygen – Ti/Eu displacements, and the absence of rotations or tilts of the oxygen octahedra. Importantly, the large Eu amplitude in the soft mode manifests as a large off-centering of the Eu from the center of its oxygen coordination polyhedron in the ground state structure. The origin of the large Eu displacement lies in its small ionic radius compared with that of divalent Ba$^{2+}$: The large coordination cage around the Eu ion which is imposed by the large lattice constant of the alloy results in under-bonding of the Eu that can be relieved by off-centering. Indeed, we find that in calculations for fully relaxed single phase EuTiO$_3$, the oxygen octahedra tilt to reduce the volume of the A site in a similar manner to those known to occur in SrTiO$_3$, in which the A cation size is almost identical. This Eu off-centering is desirable for the EDM experiment because the change in local environment at the magnetic ions on ferroelectric switching determines the sensitivity of the EDM measurement. P ($\mu$C/cm$^2$) ------- ------------------- ---- 61.63 (constrained) 23 62.30 (experimental) 28 64.63 (relaxed) 44 : Calculated ferroelectric polarizations, P, of Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ at three different volumes.[]{data-label="PversusV"} We note that the magnitude of the polarization is strongly dependent on the volume used in the calculation (Table \[PversusV\]). At the experimental volume (reported in the next section), which is only slightly larger than our constrained volume of $3.95^3$ Å$^3$, we obtain a polarization of 28 $\mu$C/cm$^2$. At full relaxation, where we find a larger volume close to that of BaTiO$_3$, we obtain a polarization of 44 $\mu$C/cm$^2$, almost certainly a substantial over-estimate. This volume dependence suggests that the use of pressure to reduce the lattice parameters and suppress the ferroelectric polarization could be a viable tool for reducing the coercivity at low temperatures. Indeed our computations show that, at a pressure corresponding to 2.8 GPa applied to the experimental volume the theoretical structure is cubic, with both the polarization and coercive field reduced to zero. Finally, to investigate the likelihood of magnetic ordering, we calculated the relative energies of the ferromagnetic state discussed above and of two antiferromagnetic arrangements: planes of ferromagnetically ordered spins coupled antiferromagnetically along either the pseudo-cubic $z$ axis or the $x$ or $y$ axes. (Note that these are degenerate in the high-symmetry cubic structure). For each magnetic arrangement we re-relaxed the lattice parameters and atomic positions. As expected for the highly localized Eu $4f$ electrons on their diluted sublattice, the energy differences between the different configurations are small – around 1 meV per 40 atom supercell – suggesting an absence of magnetic ordering down to low temperatures. While our calculations find the ferromagnetic state to be the lowest energy, this is likely a consequence of our A-site ordering and should not lead us to anticipate ferromagnetism at low temperature (Note that, after completing our study, we found a report of an early effort to synthesize (Eu,Ba)TiO$_3$[@Janes/Bodnar/Taylor:1978] in which a large magnetization, attributed to A-site ordering and ferromagnetism, was reported. A-site ordering is now known to be difficult to achieve in perovskite-structure oxides, however, and we find no evidence of it in our samples. Moreover the earlier work determined a tetragonal crystal structure in contrast to our refined orthorhombic structure.) In summary, our predicted properties of the (Eu,Ba)TiO$_3$ alloy – large ferroelectric polarization, reducible with pressure, with large Eu displacements, and strongly suppressed magnetic ordering – meet the criteria for the electron electric dipole moment search and motivate the synthesis and characterization of the compound, described next. Synthesis ========= Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ was synthesized by solid-state reaction using mechanochemical activation before calcination. For details see the Methods section. The density of the sintered pellets was 86-88% of the theoretical density. X-ray diffraction at room temperature revealed the cubic perovskite $Pm\bar{3}m$ structure with a=3.9642(1)Å. At 100K we obtain an orthorhombic ground state with space group $Amm2$, in agreement with the GGA$+U$ prediction, and lattice parameters 3.9563(1), 5.6069(2) and 5.5998(2) Å. Characterization ================ The final step in our study is the characterization of the samples, to check that the measured properties are indeed the same as those that we predicted and desired. Figure \[Fig3\] shows the temperature dependence of the complex permittivity between 1Hz and 1MHz, measured using an impedance analyzer ALPHA-AN (Novocontrol). The low-frequency data below 100kHz are affected above 150[$\,\mbox{K}$]{} by a small defect-induced conductivity and related Maxwell-Wagner polarization; the high-frequency data clearly show a maximum in the permittivity near $T_c$=213[$\,\mbox{K}$]{} indicating the ferroelectric phase transition. Two regions of dielectric dispersion – near 100[$\,\mbox{K}$]{} and below 75[$\,\mbox{K}$]{} – are seen in tan$\delta(T)$; these could originate from oxygen defects or from ferroelectric domain wall motion. Measurement of the polarization was adversely affected by the sample conductivity above 150[$\,\mbox{K}$]{}, but at lower temperatures good quality ferroelectric hysteresis loops were obtained (Fig. \[Fig3\], inset). At 135[$\,\mbox{K}$]{} we obtain a saturation polarization of $\sim$8 $\mu$C/cm$^2$. The deviation from the predicted value could be the result of incomplete saturation as well as the strong volume dependence of the polarization combined with the well-known inaccuracies in GGA$+U$ volumes. As expected, at lower temperatures the coercive field strongly increases, and only partial polarization switching was possible even with an applied electric field of 18kV/cm (at higher electric field dielectric breakdown was imminent). The partial switching is responsible for the apparent decrease in saturation polarization below 40K. Time-domain THz transmission and infrared reflectivity spectra (not shown here) reveal a softening of the polar phonon from $\sim$40[$\,\mbox{cm}^{-1}$]{} at 300[$\,\mbox{K}$]{} to $\sim$15[$\,\mbox{cm}^{-1}$]{} at $T_c$, and then its splitting into two components in the ferroelectric phase. Both components harden on cooling below $T_c$, with the lower frequency component remaining below 20[$\,\mbox{cm}^{-1}$]{} down to 10[$\,\mbox{K}$]{}, and the higher-frequency branch saturating near 70[$\,\mbox{cm}^{-1}$]{} at 10[$\,\mbox{K}$]{}. This behavior is reminiscent of the soft-mode behavior in BaTiO$_{3}$[@Hlinka:2008]. However, when we extract the contribution to the static permittivity that comes from the polar phonon, we find that it is considerably smaller than our measured value (Fig. \[Fig3\]) indicating an additional contribution to the dielectric relaxation. Our observations suggest that the phase transition is primarily soft-mode driven, but also exhibits some order-disorder character. Finally, we measured the magnetic susceptibility $\chi$ at various static magnetic fields as a function of temperature down to 0.4K. (For details see the Methods section.) Our results are shown in Fig. \[Fig4\]. $\chi(T)$ peaks at $T\sim$1.9K indicating an absence of magnetic ordering above this temperature. The $\chi(T)$ data up to 300K show Curie-Weiss behavior $\chi(T)=\frac{C}{T+\theta}$ with $\theta$=-1.63K and $C = 0.017$ emuK/(gOe). The peak in susceptibility at 1.9K is frequency independent and not influenced by zero field heating measurements after field cooling, confirming antiferromagnetic order below $T_N = 1.9$K. As in pure EuTiO$_3$, the $\chi(T)$ peak is suppressed by a static external magnetic field, indicating stabilization of the paramagnetic phase [@Katsufuji/Takagi:2001]. Magnetization curves (Fig. \[Fig4\] inset) show saturation above $2\times10^4$ Oe at temperatures below $T_{N}$ and slower saturation at 5K. No open magnetic hysteresis loops were observed. In summary, we have designed a new material – Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ – with the properties required to enable a measurement of the EDM to a higher accuracy than can currently be realized. Subsequent synthesis of Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ ceramics confirmed their desirable ferroelectric polarization and absence of magnetic ordering above 1.9K. The search for the permanent dipole moment of the electron using Eu$_{0.5}$Ba$_{0.5}$TiO$_3$ is now underway. Initial measurements have already achieved an EDM upper limit of 5 $\times 10^{-23}$ e.cm, which is within a factor of 10 of the current record with a solid-state-based EDM search [@Heidenreich2005]. We are currently studying a number of systematic effects that may mask the EDM signal. The primary error originates from ferroelectric hysteresis-induced heating of the samples during polarization reversal. This heating gives rise to a change in magnetic susceptibility, which, in a non-zero external magnetic field, leads to an undesirable sample magnetization response. We are working to control the absolute magnetic field at the location of the samples to the 0.1 $\mu$G level. Our projected sensitivity of 10$^{-28}$ e.cm should then be achievable. Acknowledgments =============== This work was supported by the US National Science Foundation under award number DMR-0940420 (NAS), by Yale University, by the Czech Science Foundation (Project Nos. 202/09/0682 and AVOZ10100520) and the Young Investigators Group Programme of Helmholtz Association, Germany, contract VH-NG-409. We thank O. Pacherova, R. Krupkova and G. Urbanova for technical assistance and Oleg Sushkov for invaluable discussions. Author contributions ===================== SKL supervised the EDM measurement effort at Yale. AOS and SE performed the analysis and made preliminary measurements, showing that these materials could be useful in an EDM experiment. ML and NAS selected (Eu,Ba)TiO$_3$ as the candidate material according to the experimental requirements and supervised the ab-initio calculations. KZR performed the ab-initio calculations. ML, NAS and KZR analysed the ab-initio results and wrote the theoretical component of the paper. Ceramics were prepared by PV. Crystal structure was determined by KK and FL. Dielectric measurements were performed by MS. JP investigated magnetic properties of ceramics. VG performed infrared reflectivity studies. DN investigated THz spectra. SK coordinated all experimental studies and wrote the synthesis and characterization part of manuscript. NAS coordinated the preparation of the manuscript. Methods ======= Computational details --------------------- We performed first-principles density-functional calculations within the spin-polarized generalized gradient approximation (GGA) [@PBE:1996]. The strong on-site correlations of the Eu $4f$ electrons were treated using the GGA+$U$ method [@Anisimov/Aryasetiawan/Liechtenstein:1997] with the double counting treated within the Dudarev approach [@Dudarev_et_al:1998] and parameters $U=5.7$ eV and $J=1.0$ eV. For structural relaxation and lattice dynamics we used the Vienna Ab Initio* Simulation Package (VASP) [@VASP_Kresse:1996] with the default projector augmented-wave (PAW) potentials [@Bloechl:1994] (valence-electron configurations Eu: $5s^2 5p^6 4f^{7}6s^{2}$, Ba: $5s^{2}5p^{6}6s^{2}$, Ti: $3s^{2}3p^{6}3d^{2}4s^{2}$ and O: $2s^{2}2p^{4}$.) Spin-orbit interaction was not included. The 50/50 (Eu,Ba)TiO$_3$ alloy was represented by an ordered A-site structure with the Eu and Ba ions alternating in a checkerboard pattern (Fig. \[th\_phonons\], inset). Structural relaxations and total energy calculations were performed for a 40-atom supercell (consisting of two 5-atom perovskite unit cells in each cartesian direction) using a $4\times4\times4$ $\Gamma$-centered $k$-point mesh and a plane-wave cutoff of 500 eV. Ferroelectric polarizations and Born effective charges were calculated using the Berry phase method [@King-Smith:1993]. Lattice instabilities were investigated in the frozen-phonon scheme [@Kunc:1982; @Alfe:2009] for an 80 atom supercell using a $\Gamma$-centered $2\times2\times2$ $k$-point mesh and 0.0056 Å atomic displacements to extract the Hellman-Feynman forces. Synthesis --------- Eu$_2$O$_3$, TiO$_2$ (anatase) and BaTiO$_3$ powders (all from Sigma-Aldrich) were mixed in stoichiometric ratio then milled intensively in a planetary ball micro mill Fritsch Pulverisette 7 for 120min. in a dry environment followed by 20 min. in suspension with n-heptane. ZrO$_2$ grinding bowls (25ml) and balls (12mm diameter, acceleration 14g) were used. The suspension was dried under an IR lamp and the dried powder was pressed in a uniaxial press (330MPa, 3min.) into 13mm diameter pellets. The pellets were calcined in pure H$_2$ atmosphere at 1200[$\,{}^\circ$C]{} for 24hr (to reduce Eu$^{3+}$ to Eu$^{2+}$), then milled and pressed by the same procedure as above and sintered at 1300[$\,{}^\circ$C]{} for 24hr in Ar+10%H$_2$ atmosphere. Note that pure H$_2$ can not be used for sintering without adversely increasing the conductivity of the sample. Characterization ---------------- Magnetic susceptibility was measured using a Quantum Design PPMS9 and a He$^3$ insert equipped with a home-made induction coil that allows measurement of ac magnetic susceptibility, $\chi$ from 0.1 to 214Hz. [10]{} url \#1[`#1`]{}urlprefix\[2\][\#2]{} \[2\]\[\][[\#2](#2)]{} . , (). & (, , ). & . , (). , , & . **, (). , , , & . ***, (). et al.* . *, (). et al.* . *, (). et al.* . , (). & . **, (). , & . ***, (). et al.* . , (). , & . ***, (). et al.* . , (). , , , & . **, (). . **, (). . **, (). , , & . **, (). , & . **, (). , & **, (). & . **, (). . **, (). , & . **, (). **, (). . **, (). , & . **, (). & . **, (). , & . **, (). & . **, (). & . ***, (). et al.* . , (). & . **, (). , , , & . **, (). , & . **, (). , , , & . ***, (). et al.* . , (). , & . ***, (). et al.* . , (). , & . **, (). , & . **, (). , , , & . **, (). & . **, (). . **, (). & . **, (). & . **, (). . ****, ().	{ "pile_set_name": "ArXiv" }
Coffeehouse Post Single Post Permalink Yes, but that's missing my point. If you wanted a folder sync-ed from your local machine then either drop it in the skydrive folder, or create a link or junction while we wait to see if they will add "Sync this folder"	{ "pile_set_name": "Pile-CC" }
Van Mensvoort Artist and philosopher. The discovery of Next Nature has been the most profound experience in my life so far. It is my aim to better understand our co-evolutionary relationship with technology and help set out a track towards a future that is rewarding for both humankind and the planet at large. Tags Share Rather than growing whole steaks in bio-reactors, Knitted Meat assumes that it is more feasible to create thin threads of protein. Supermarkets sell balls of meat fiber seasoned with various spices and vegetable flavors. New kitchen appliances enable consumers to weave meat according to preset preferences. Texture, taste and tenderness can be controlled to create a personal, multisensory eating experience. Groups of diners can even knit their own sections of a protein scarf, enabling multiple people to share a unique moment. Tags Share Here’s a video for the tiny niche of Dutch-speaking-long-attention-span-visitors of this website. Some months ago the Rotterdam Think Café organized a Next Nature night featuring your dearest long-standing nextnature connoisseur. Rather than a lecture, the event was an improvised conversation on next nature in response to images selected by the organizers. Slow video alert! Tags Share Today, shoes have been naturalized to the extend that we hardly can imagine life without them. Yet, shoes didn’t exist in old nature, hence there must have been a day when footwear was a radical new technology people had to get attuned to. At that time, some ten-thousand of years ago, one had to decide whether to embrace or decline the emerging footwear technology, similar to mobile technology in our time. Over the years, footwear moved from being an unfamiliar to an accepted phenomenon, from a second nature to a first nature. Like the mobile phones we carry only more recently, we can still decide to take off our shoes and experience life without them today. Indeed almost no one ever does that for a longer period, but at least we can. The unidentified wearer of the Converse Sneaker Tattoo apparently decided he didn’t want to experience any shoe-less moments in life anymore? Or he just wanted to get his feet on a blog? In any case, he got what he wanted. Peculiar image of the week. Via BoingBong. Tags Share Here’s one for the retro-trendwatchers. This 24-minute self-directed film was made in 1996 by artist-writer Douglas Coupland as a portrait of postmodern culture. Soon after it was abandoned and forgotten, yet if you watch it now it is striking how the film anticipates contemporary phenomena like social media and self-branding. You may want to spend 24-minutes on this Close Personal Friend. Tags Share The Kitchen Meat Incubator does for home cooking what the electronic synthesizer did for the home musician. It provides its users with a set of pre-programmed samples that can be remixed and combined to their liking. Besides the preparation of traditional styles like steak, sausage or meatballs, consumers can bring their own imagination to the meat preparation process. The handy sliders on the device control size, shape and texture. More expensive models of the Kitchen Meat Incubator also come with a wireless link that allows you to download meat recipes from the internet or share them with friends. Tags Share Another step in the fusion of the made & the born: Biological physicist Gabor Forgacs envisions to “print” new organs for use in clinical trials. Similar to an inkjet printer, Forgacs and his team use bio-ink particles to print living cells that sequentially organize themselves into a more complex tissue structures. Since the organ is printed from your own cells, chances of rejection should be minimal. Tags Share Magic Meatballs are designed to playfully familiarize children with lab-grown meat. Young people are more prone to overconsumption of proteins and fats, and are more sensitive to the hormones and antibiotics used in conventional meat production. Luckily, lab-grown Magic Meatballs can be tailored precisely to a child’s individual needs. The basic meat consists solely of animal protein, and the combination of fats, omega-3s and vitamins is completely customizable. Colors and flavors can also be added to the neutral base to make the meat change color or crackle in your mouth. Magic Meatballs actively involve kids with the meat they eat, so that future generations will more readily accept protein grown in labs. Tags Share As the planet’s population speeds towards 9 billion, it’s becomes impossible to continue consuming meat like we do today. Will we all be eating rice and beans? Grasshoppers perhaps? Scientists hope to keep us eating vertebrate protein with in vitro meat. Grown in bioreactors from animal cells, in vitro meat could be a sustainable and humane alternative to raising a whole animal from birth to slaughter. The first lab-grown hamburger is expected within the next few months. But why should lab-grown meat look like the meat we consume today? Growing protein in bioreactors could lead to entirely new forms of meat with radically different aesthetics, materials and eating rituals. While these new products might seem unfamiliar and artificial, much of the meat we already consume is divorced from the animal’s natural form: Ground beef, smoked sausages, and chicken nuggets. A selection of these future in-vitro meat scenarios is currently shown at the highly recommended Food Culture: Eating by Design exhibition at the Design Huis in Eindhoven (NL). As you might not happen to be in the neighborhood, we will also publish them online over the next few weeks. The projects were coached by Menno Stoffelsen, Koert van Mensvoort, Cor van der Weele, Daisy van der Schaft and Ronald van Tienhoven. Illustration by K. Cheng. Do you want to know more about the future of meat? We are writing a speculative cookbook of in-vitro meat dishes, join us on www.bistro-invitro.com. Tags Share Unsure whether this tank escaped from an 8-bit videogame or the general that ordered the pixelated camouflage pattern didn’t quite quite understand what digital warfare is all about. Anyhow, it is our peculiar image of the week. Tags Share Design by planning vs design by doing. Desire paths are unplanned paths grown by the erosion of its use. They emerge as shortcuts where constructed pathways take a circuitous route. Perhaps one day, all our roads will be desire paths. Tags Share Imagine what you could do if you had one million Twitter followers. You would be so rich! Now seriously: Are followers becoming an alternative currency? Perhaps, although we are still awaiting the day that you can walk into a bakery and routinely buy a loaf of bread with your Twitter following. Scratch to win. Or if you don’t believe in lotteries, you can simply buy one million twitter followers for only $8295. Tags Share As advances in nanotechnology bring us increasingly energy efficient products, plant life such as algae could become attractive sources for tapping energy. The Latro lamp by designer Mike Thompson is a speculative product responding to this potential future market. It utilizes living algae as its power source. The idea was inspired by a scientific breakthrough by scientists from Yansei and Stanford University that allows a small electrical current to be drawn from algae during photosynthesis. Placing the lamp outside in the daylight, the algae use sunlight to synthesize foods from CO2 and water. According to the ingredients list the drink does indeed contains both strawberry and dragonfruit substrates. The bats are missing, however, they’re merely added to the marketing mix to metaphorically enforce the association with night live. Bacardi furthermore recommends to enjoy the drink with ginger ale for a quadruple biomimicmarketing mix of Dragons, Berries, Bats, Ginger and Headaches. Image consumption in the overdrive. Cheers folks! Tags Share After being denied permission to reproduce the famed Little Mermaid statue from Copenhagen, the authorities of the modern town Vancouver (Canada) decided to go for something more realistic. The “Girl in a Wetsuit” was created by Elek Imredy. Tags Share ‘Everything is an event on the skin,’ wrote 19th-century scientist and philosopher Hermann von Helmholtz. This quote inspired body-architect & powershow speakerLucy McRae to create Morphē, a vibrant short film exploring the human body as a point of rendezvous for the made & the born.	{ "pile_set_name": "Pile-CC" }
Shock absorbers are used in conjunction with automotive suspension systems and other suspension systems to absorb unwanted vibrations which occur during movement of the suspension system. In order to absorb these unwanted vibrations, automotive shock absorbers are generally connected between the sprung (body) and the unsprung (suspension/chassis) masses of the vehicle. The most common type of shock absorbers for automobiles is the dashpot type which can be either a mono-tube design or a dual-tube design. In the mono-tube design, a piston is located within a pressure tube and is connected to the spring mass of the vehicle through a piston rod. The pressure tube is connected to the unsprung mass of the vehicle. The piston divides the pressure tube into an upper working chamber and a lower working chamber. The piston includes compression valving which limits the flow of damping fluid from the lower working chamber during a compression stroke and rebound valving which limits the flow of damping fluid from the upper working chamber to the lower working chamber during a rebound or extension stroke. Because the compression valving and the rebound valving have the ability to limit the flow of damping fluid, the shock absorber is able to produce a damping force which counteracts the vibrations which would otherwise be transmitted from the unsprung mass to the sprung mass. In a dual-tube shock absorber, a fluid reservoir is defined between the pressure tube and a reservoir tube which is positioned around the pressure tube. A base valve assembly is located between the lower working chamber and the fluid reservoir to control the flow of dampening fluid. The compression valving of the piston is moved to the base valve assembly and is replaced by a compression check valve assembly. In addition to the compression valving, the base valve assembly includes a rebound check valve assembly. The compression valving of the base valve assembly produces the damping force during a compression stroke, and the rebound valving of the piston produces the damping force during a rebound or extension stroke. Both the compression and rebound check valve assemblies permit fluid flow in one direction, but prohibit fluid flow in an opposite direction; however, they are designed such that they do not generate a damping force. In applications where a low level of flow restriction is a priority for the check valve assemblies, the working surface for lifting the check valve disc must be maximized. In addition, this low flow restriction level also calls for a very lightweight disc. When first reviewing the design for the check valve assembly, it may seem logical to utilize a valve spring, which has a low stiffness. This design choice is overruled by the need for a fast closing check valve assembly, as well as the need to avoid “chuckle” noise when the shock absorber is mounted on the vehicle. As the check valve disc becomes lighter and thinner, and the area of the check valve disc which is acted upon by fluid pressure becomes greater, the check valve disc becomes very sensitive to the high fluid pressure which urges the check valve assembly into its closed position. The continued development of check valve assemblies has been directed towards reducing the level of flow restriction without compromising the sensitivity of the check valve assembly to the high pressure fluid which urges the check valve assembly into its closed position.	{ "pile_set_name": "USPTO Backgrounds" }
Spoilers for Mass Effect and Dragon Age ahead! You've been warned! Recently on Reddit I saw a few posts regarding Dragon Age: Inquisition. While the majority of people were praising the game, the ending came under particular scrutiny, with one user saying "Dear Bioware, when designing endgame sequences, ask yourself: 'is this enough like Mass Effect 2's endgame? The answer is always No". While I certainly got a chuckle out of it, it makes a good point on the state of player choice. BioWare got it right with Mass Effect 2. Depending if you're a Hammerhead or Mako fan or whether you preferred the heavier RPG elements of the original you might have some issues with the gameplay but in my opinion the story was nearly perfect. It was simple but compelling, well paced but allowed for freedom and most importantly, every choice you made had impact, particularly during the Suicide Mission ending. If you didn't make sure your companions were loyal, they would die; if you didn't make sure your ship was ready, people would die; if you delayed when you were clearly told time was of the essence, people would die. It was perfect because every consequence was avoidable by player choice and nearly every choice had direct impact on the way the story ended. If you made terrible choices you could kill your entire team and die yourself; kind of a bummer sure, but it meant your decisions mattered. Nobody was going to Deus Ex Machina you out of the Collector Base. This is also why people had a problem with the Mass Effect 3 ending; because the choices you made, the alliances forged had little or no effect on the ending at all. Choice was seen as an illusion in that game when the potential result was limited to different coloured explosions. In my opinion, Inquisition suffers from the same issue. Now let me be clear, I love Inquisition. I am currently in the 60th hour of my second playthrough and I'm planning a 3rd; I have a stack of games I haven't played yet because I've been swallowed whole by this game. The only issue I have (besides illusive schematics, I mean seriously where is the Tier 3 Rogue stuff!?) is the final encounter. I spent 90 hours building my Inquisition, I recruited the Mages, redeemed the Grey Wardens, saved the Empress of Orlais and did countless war table missions and side quests to bolster my forces and it had exactly zero effect on my final confrontation. I fought Corypheus with my regular party and beat him and everything was fine forever. Yes, I know my forces were far away and could not march back fast enough but I think we all saw this for what it was; a cheap cop out to avoid having to include them in the final battle. That could have been fine, but nothing factored into the final battle. You only bring 3 of the 9 companions you spent 90 hours getting to know, the other 6 deciding you can probably handle it until the aftermath. Yes it's a 3 companion party system, but what were the other 6 doing, just chilling at Skyhold playing Wicked Grace? I missed a few companion quests by chance in my first playthrough, nothing happened as a result. No other Inquisition soldiers appear; what, we didn't leave a few guards back at Skyhold to mind the gate? Not even Cullen or Leliana pick up a sword, despite them both being well-established as extremely capable fighters. Its this dissonance between the story I created and the ending I experienced which has made me look back at my favorite game of the year with such a critical eye. Feels a bit lonely up here... Oddly, the Adamant siege in the games second act conveys the weight of the Inquisition handily. Maybe the story team got their cutscenes mixed up but it certainly feels strange to have the epic scale confrontation come at the 40 hour mark of a 100 hour experience. I want to reiterate that I love this game, I was just disappointed in how little my choices, my game impacted the conclusion. BioWare is the "Player Choice" company, their RPGs are based around the idea of the player authoring their own story where every decision is supposed to have weight. When Mass Effect 3 was pitched as having dramatically different endings, gamers were so incensed they approached the Better Business Bureau with claims of false advertising. It seems BioWare recognized the issue this time because Inquisition came with its Extended Cut DLC built in, a slideshow with a voiceover to address results of your actions; which I would bet is BioWare's effort to avoid another Mass Effect 3 debacle. Seeing similar issues appear not 3 years later from the same company nonetheless makes me worry the industry isn't learning from its mistakes. The reason I don't feel bad or whiney or entitled for asking for more from BioWare is because I know they're capable of it. They had choice, stakes and consequence down pat in 2010, I don't think it's unreasonable to ask them to cut a Hinterlands quest or two to spend a little while longer on the ending. So for Mass Effect 4 or the next Dragon Age I'd just say one thing; "Is it enough like Mass Effect 2?"	{ "pile_set_name": "OpenWebText2" }
Unravelling early events in the Taphrina deformans-Prunus persica interaction: an insight into the differential responses in resistant and susceptible genotypes. Leaf peach curl is a devastating disease affecting leaves, flowers and fruits, caused by the dimorphic fungus Taphrina deformans. To gain insight into the mechanisms of fungus pathogenesis and plant responses, leaves of a resistant and two susceptible Prunus persica genotypes were inoculated with blastospores (yeast), and the infection was monitored during 120 h post inoculation (h.p.i.). Fungal dimorphism to the filamentous form and induction of reactive oxygen species (ROS), callose synthesis, cell death and defence compound production were observed independently of the genotype. Fungal load significantly decreased after 120 h.p.i. in the resistant genotype, while the pathogen tended to grow in the susceptible genotypes. Metabolic profiling revealed a biphasic re-programming of plant tissue in susceptible genotypes, with an initial stage co-incident with the yeast form of the fungus and a second when the hypha is developed. Transcriptional analysis of PRs and plant hormone-related genes indicated that pathogenesis-related (PR) proteins are involved in P. persica defence responses against T. deformans and that salicylic acid is induced in the resistant genotype. Conducted experiments allowed the elucidation of common and differential responses in susceptible versus resistant genotypes and thus allow us to construct a picture of early events during T. deformans infection.	{ "pile_set_name": "PubMed Abstracts" }
For those of you who didn’t attend the recent American Gear Manufacturers Association (AGMA) annual meeting, you missed a great opportunity to network and hear about a number of issues that are and will affect the gear industry here and around the world. One of other major takeaways from the meeting was that many of the gear manufacturers are buying equipment — mostly new — to modernize their shops and help them compete for work. I’m sure that some of you are thinking, “ I can’t afford to buy a new or even used machine.” Well, I contend the opposite. You can’t afford not to. New and used gear equipment is some of the most expensive on the machine tool market. A new, basic, entry-level CNC hobber can cost $350,000. Adding options and additional capabilities like skiving, loaders, high-precision or high-speed hob heads, 90-degree hob heads, etc., can add on tens of thousands of dollars quickly. Add in the work holding and cutting tooling and well, the sky is truly the limit. However, these machines can be very productive and make higher quality parts than machines made even 10–15 years ago. As an example of what new machines are capable of, when my company purchased it’s first CNC shaper from Fellows, we had some jobs that we were cutting approximately five to eight pieces-per-hour. In addition, tool life was bad — only five pieces-per-grind due to excessive rubbing. After purchasing the new shaper, we were cutting nearly 25 pieces-per-hour and tool life was about 35 pieces-per-sharpening. What were the benefits you ask? Obviously, lower costs that allowed us lower the price to customer and still make more money per hour. The cutters lasted longer allowing us to ship parts quicker (fewer shutdowns for sharpening) and clearly the increase in piece rate helped as well. The first machine purchase helped us pay for the second. Another key thought here is that while you can “gamble” and get a machine that has some features that you don’t currently have on other machines, you must have at least a base book of business to support the machine. While trite, machines only make money when the spindles are turning (or going up and down). With the prices of machines at the levels they are, they must run the maximum amount possible. You cannot afford to buy a machine on a “build it and they will come” basis. Now that I’ve got you convinced to modernize your shop, do you buy new or used equipment? This decision depends on what the use is going to be and what you can afford. If your backlog of work for this machine is thin, or if your quality requirements are not super high, used machines may get the job done. On the other hand, if you need high quality and have a ton of work, a new machine with a loader might be the ticket. New or used, your best bet is to deal with reputable OEMs and used machine dealers. Just make sure you get the right machine sized for your work. Tooling and initial setups should also be discussed. New machines normally carry a warranty of a year of parts and labor. Used machines are generally as sold as-is with no warranties expressed or implied. This is where dealing with a used machine dealer with a history in the gear industry is the only sure way to get maximum value. There is another alternative to buying new or used. You can contract with manufacturers who specialize in re-building or re-manufacturing machines. You can send them one of your machines to put through the process, buy a used machine yourself and send to them, or just buy the machine completely done from the manufacturer. A good re-manufacturer will completely strip the machine to the casting and start there to replace wear items and add additional components such as CNC, loaders etc. The approximate cost for this process is about 60-70 percent of a new machine, but you are getting a warranty and a lot more functionality. Now, here comes the hard part — how to pay for the machine. Obviously, if you’ve got the cash, you may want to consider paying for it out right. Talk to your accountant about this as they may suggest you take out a loan or lease the machine instead. According to David Bolt of SBG Capital in Chandler, Arizona, there is really no difference in the amount of the payment between a lease and a loan. Leases normally carry a one -dollar buyout at the end, but the monthly check is the same. Most leases and loans are for five years and companies with stronger credit will receive the best terms and rates. And, just so you know, all banks and other lenders will put liens on the machines to protect the asset until it is paid off. Used equipment as well as re-building and re-manufacturing costs can also be leased or put on a loan. Again, talk to a well-established bank or machine finance company to avoid any problems. In all cases, make sure your accounting firm is in the loop to help you make the right choice and also to insure how they will treat your purchase on your financial statements. As I indicated earlier, you’ve got to stay current with your machine and process technology. If you don’t, your competition surely will. is the president of TopGun Consulting, a manufacturing consultancy with a focus on helping companies improve their practices and processes to increase the profitability and satisfaction of the owners of those companies. David has over 30 years of experience in manufacturing, more specifically in the gear industry. Using his experience, David is able to quickly assess difficulties and recommend simple, yet effective, solutions to those issues. For more information, contact David Senkfor at david@topgunconsulting.net or (602) 510-5998, or visit Top Gun’s website at www.topgunconsulting.com. Gear Solutions is designed to shine a spotlight on the multi-faceted gear industry. Through editorial contributions from industry experts, we explore elements of the gear production process, including raw materials, design, costs, heat treat, quality control, workflow, and more.	{ "pile_set_name": "Pile-CC" }
A study by Italian academics has tracked references to the militant group Isis in Arabic language social media posts and news articles from July to October. The analysis attempts to differentiate between positive and negative mentions of the group	{ "pile_set_name": "OpenWebText2" }
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Brampton is set to receive more than $11 million in funding from the Ontario government to help fuel transit system expansion. In an announcement on Tuesday (Dec. 19) at the city’s transit facility on Sandalwood Parkway, Minister of Transportation Steven Del Duca announced the provincial funding breakdown. He was joined by mayor of Brampton Linda Jeffery and Harinder Malhi, the MPP for Brampton-Springdale. The funding is up from the $10 million Brampton received for the 2016-2017 year. Brampton is among 105 municipal transit systems servicing 142 communities the Ontario government is supporting across the province with the Gas Tax Fund. First started in 2004, the fund has been working toward providing $3.7 billion to municipalities in Ontario to finance various transit projects that will ease congestion and lower air pollution. This year a total of $357 million was given in funding in Ontario. This is expected to grow to $642 million by 2021-2022. “Brampton Transit is growing quickly and we have experienced extremely high ridership growth,” said Jeffery in a media release. Jeffery went onto say that an increase in demand in the city has made this investment into the transit system a necessity. Brampton’s rapidly growing population has been a part of the demand increase Jeffrey spoke of. In Canada’s latest census, it was revealed that Brampton’s population grew 13.3 per cent to 593,638 in 2016 from the 2011 census results that recorded the population at 523,906. In previous years, Brampton used the funding to purchase new buses, improve service on existing lines and help fund the Brampton Rapid Transit service on Steeles Avenue. The new funding will be focused on improving the existing transit system in Brampton after a council vote in 2015 shot down plans to extend the proposed Hurontario LRT through city’s downtown area. This time around, the funding could mean more new buses, longer hours of service and more routes in Brampton. Mississauga will also be receiving funding for public transit in the amount of $18 million, which is up from the $16 million that was released for the 2016-2017 year.	{ "pile_set_name": "OpenWebText2" }
A TEENAGER'S penis was "degloved" and his scrotum inverted after a horror bike crash. The 14-year-old had been cycling along a pavement one-handed while holding a drink when he smashed into a parked car and his handlebars impaled his groin. 1 A 14-year-old boy suffered a horror groin injury after cycling along one-handed Credit: Getty - Contributor He was taken to A&E at John Radcliffe Hospital, Oxford, in a pelvic binder and the wound packed, according to an article published in BMJ Case Reports. When he arrived, doctors found the handlebars had sliced through his pubic area leaving a 14cm-long wound across and a 10cm cut down into his perineum. This had inverted his left scrotum and partially degloved the penis - meaning the skin and tissue is ripped away, exposing muscle or bone. He was put under general anaesthetic so the wound could be washed out and the damaged tissue removed. Post-op They noted that some of the deeper layers of tissue that protect the penis and testicles had been exposed but were able to close the wound up after inspecting the area for foreign bodies and neurovascular damage. At his post-operation follow up four weeks later, doctors said the boy had no significant vascular damage and normal sensation. They were unable to say what impact the injury would have on his sexual function in the future. He was discharged the next day with a course of antibiotics and support dressings. Unusual case Dr Hannah Thompson, professor of Paediatric Surgery, University of Oxford and John Radcliffe Hospital, said: "This case is unusual in both mechanism and resulting injury. "Handlebar injuries causing blunt abdominal trauma are well described in the literature, however, reports of impalement or degloving injuries are spars. This unusual case demonstrates the potential damage resulting from handlebar injuries even at low velocity Dr Hannah Thompson "Most bicycle-associated injuries are skin abrasions, however, extensive morbidity has been described in association with bicycle injuries, especially handlebar injuries, due to the low surface area of the bare metal end of the handlebar." MORE ON HEALTH Exclusive WINTER IS COMING Dr Alex warns people not to forget flu amid double threat from Covid WATER WARNING Disaster declared after brain-eating amoeba found in Texas water supply SLAUGHTER IN THE SEAS Half a million sharks face slaughter to make new Covid vaccines OFF THE HOOK NHS 111 calls 'rise 200% as staff unsure they're giving correct Covid advice' SAVE OUR SON Family of toddler denied medical cannabis on NHS ask Matt Hancock for help Warning SKINCREDIBLE Woman plagued by horrific skin condition 'cures' it with £10 'miracle' cream Dr Thompson continued: "It is important to note that impalement, as well as severe blunt intra-abdominal injuries may occur due to the small surface area at the edges of handlebars acting in a spear-like fashion. "A prospective study of 813 bicycle-related injuries in children found 21 handlebar injuries, 10 of whom had life-threatening intra-abdominal trauma. In all 10, the bicycle handlebars had no plastic covering on the end of the handle." She added: "This unusual case demonstrates the potential forces involved, and potential damage resulting from handlebar injuries even at low velocity."	{ "pile_set_name": "OpenWebText2" }
Is LARC for Everyone? A Qualitative Study of Sociocultural Perceptions of Family Planning and Contraception Among Refugees in Ethiopia. Objective Ethiopia is home to an increasingly large refugee population. Reproductive health care is a critical issue for these groups because refugee women are at high risk for unmet family planning needs. Efforts to expand contraceptive use, particularly long acting reversible contraceptive (LARC) methods are currently underway in several Ethiopian refugee camps. Despite availability of LARC methods, few refugee women opt to use them. The purpose of this study was to explore how culture influences contraceptive attitudes and behaviors, particularly towards LARC methods, among Ethiopia's refugee populations. Methods Focus group discussions and individual interviews were conducted with Eritrean and Somali refugees living in Ethiopia. The qualitative data was analyzed to identify important themes highlighting the relationship between cultural values and contraceptive attitudes and behaviors. Results Childbearing was highly valued among participants in both study groups. Eritreans reported desire to limit family size and attributed this to constraints related to refugee status. Somalis used cultural and religious faith to deal with economic scarcity and were less likely to feel the need to adapt contraceptive behaviors to reduce family size. Participants held overall positive views of the contraceptive implant. Attitudes toward the intrauterine device (IUD) were overwhelmingly negative due to its long-acting nature. Conclusions Culture, religion and refugee status form a complex interplay with family planning attitudes and behaviors among Eritrean and Somali refugees. For these populations, the three-year implant appears to be a more acceptable contraceptive method than the longer-acting IUD because it is in line with their reproductive plans.	{ "pile_set_name": "PubMed Abstracts" }
Q: Can't connect to web socket react-native-meteor iOS I'm using react-native-meteor, and am having trouble connecting to the web socket with iOS only. My application works just fine when running on the android simulator, but just doesn't work in iOS simulator or device. This is my code: Meteor.connect('ws://app.mysite.com/websocket'); And the logs: [info][tid:main][RCTBatchedBridge.m:72] Initializing <RCTBatchedBridge: 0x7fe23b23d4c0> (parent: <RCTBridge: 0x7fe239d65090>, executor: RCTJSCExecutor) [warn][tid:main][RCTEventEmitter.m:54] Sending `websocketFailed` with no listeners registered. Disconnected from DDP server. Any idea why I can't connect on iOS only? I have already disabled App Transport Security, and downloaded a non-https webpage, so I know that's not the problem A: Well I figured it out. I think I had incorrectly configured the app transport security exception. To fix it, I connected to the secure web socket like this (note the extra s): Meteor.connect('wss://app.mysite.com/websocket');	{ "pile_set_name": "StackExchange" }
Is the living of life an axiom? (Part Two) Is the living of life an axiom? (Part Two) Life is an axiom, as established in Part One of this post. It concluded by showing ‘when law courts falsely assert citizenship to be the ruling axiom, all attempts are futile to assert the superiority of life .’ Here’s a reminder concerning axioms— An axiom is a proposition that defeats its opponents by the fact that they have to accept it and use it in the process of any attempt to deny it. —Ayn Rand; Galt’s Speech, For the New Intellectual, 155 Exposing the flaw It is the attempt by authoritarian governments to make citizenship axiomatic that necessitates ‘citizen status’ must be used in law courts to refute life’s legitimacy. Did you spot the oxymoron? It is the attempt to render life as useless when every voice and action in law courts depends on life. Life must be used in every attempt to deny it, whereby every denial is self-cancelled. Q would say ‘these people are stupid,’ but such stupidity is much worse; it’s tragic A monarchy is a system in which one person is supposed to be the ruling principle or first cause of every legal action, every other person being no more than an obedient subject of the monarch. In an oligarchy a few persons (the oligarchs), acting in concert but without a fixed hierarchy among them, are thought to be the source of all legal actions. In the modern system of parliamentary sovereignty, for example, the members of parliament constitute an oligarchy. All members have equal standing within the parliament. However, the results of their deliberations and decisions are supposed to bind all people who, because of their citizenship or residence, are assumed to be subject to the authority of the state. —Frank van Dun False Assumptions That assumption must be challenged, and ‘life’ is the only tool that can do that — not life in general, not human life, but the life of every individual. Anna Von Reitz has her finger on the pulse— You will note that the exact verbiage of the Maxim is– “Truth in commerce is established in the form of an Affidavit”. Thus, when you wish to act in the capacity of a Living Man in a commercial court, you do not offer an Affidavit — because in the current scenario that allows them to ignore every word you say or write. Instead, you offer “Living Testimony in the Form of an Affidavit”. — Anna Von Reitz Life prevails Do you see the difference? Life is the first word uttered by your testimony. You follow the “form” of an affidavit which is to swear or affirm for the Public and Private Record and from without the United States that your testimony is true, correct, and not misleading – and then you enumerate your facts: 1, 2, 3, 4… This allows the Court to hear your facts and gives de facto rebuttal to the presumption that you are acting in the capacity of a corporate franchise. And since your opponent is a corporation, it has no ability to answer your ‘Living Testimony in the Form of an Affidavit’ with any countering Affidavit – and your facts stand as Truth in Commerce by default. — Anna Von Reitz “Inasmuch as every government is an artificial person, an abstraction, and a creature of the MIND ONLY with other artificial persons. The imaginary, having neither actuality nor substance, is foreclosed from creating and attaining parity with the tangible. The legal manifestation of this is that NO government, as well as any law agency, aspect, court, etc., can concern itself with anything other than Corporate, Artificial Persons and the Contracts between them.” — Anna Von Reitz Life is preeminent It dispossesses all contrary. There is no parity between living and artificial beings, nor can there ever be. Moreover, since your life as an independent being began, nothing having your life and given names existed to which an artificial entity could be attached. Until you gained independent life nothing could claim it; no claim possible thereafter. The distinctive characteristic of a kritarchy is therefore that it is a political system without the institution of political rule. If one thinks of it as ‘the rule of judges’, one should remember that these judges enjoy no particular privileges or special powers. It is ‘the rule of law’, not the rule of legislators, judges or any other category of privileged officials. —Frank van Dun That difference needs to be fully understood if we are to establish society as Creator intended. Individual life is the key element. The notion that citizenship is to be prized above life itself is abhorrent in the extreme, the source of the greatest and most tragic fraud in human history. If you want more, then study of Conscious Dynamics and natural law must go on your ‘to-do’ list.	{ "pile_set_name": "Pile-CC" }
Q: JQuery Autocomplete trouble I'm trying to recreate JQUery autocomplete example from its website: http://jqueryui.com/autocomplete/#multiple-remote The only thing I change is I changes the source property from : source: function( request, response ) { $.getJSON( "search.php", { term: extractLast( request.term ) }, response ); }, To: source: function (request, response) { $.ajax({ type: "POST", url: "/UIClientsWebService.asmx/SearchCRMUsers", data: "{term:'" + extractLast(request.term) + "'}", contentType: "application/json; charset=utf-8", dataType: "json", success: function (result) { $("#commentBody").autocomplete("option", "source", result.d); } }, response); }, Now the problem is autocomplete just work for first ',' . When I choose my first item, then when I want to search and choose second item, nothing happen. There is no error in my firebug. I can see search method call but source does not change and also nothing shown as my autocomplete items. I can see my search term change correctly but actually no search happen. A: try add the option multiple: true to your script $(document).ready(function() { src = '/UIClientsWebService.asmx/SearchCRMUsers'; $("#yourSelector").autocomplete({ source: function(request, response) { $.ajax({ url: src, dataType: "json", data: "{term:'" + extractLast(request.term) + "'}", success: function(data) { response(data); } }); }, min_length: 3, delay: 300, multipleSeparator:",", multiple: true, }); });	{ "pile_set_name": "StackExchange" }
Hi, I'm Saša Jurić, a software developer with 10+ years of professional experience in programming of web and desktop applications using various languages, such as Elixir, Erlang, Ruby, JavaScript, C# and C++. I'm also the author of the Elixir in Action book. In this blog you can read about Elixir, Erlang, and other programming related topics. You can subscribe to the feed, follow me on Twitter or fork me on GitHub. Phoenix is modular 2016-02-22 A few days ago I saw this question on #elixir-lang channel: Have any of you had the initial cringe at the number of moving parts Phoenix needs to get you to just “Hello World” ? Coincidentally, on that same day I received a mail where a developer briefly touched on Phoenix: I really like Elixir, but can’t seem to find happiness with Phoenix. Too much magic happening there and lots of DSL syntax, diverts from the simplicity of Elixir while not really giving a clear picture of how things work under the hood. For instance, they have endpoints, routers, pipelines, controllers. Can we not simplify endpoints, pipelines and controllers into one thing - say controllers… I can sympathize with such sentiments. When I first looked at Phoenix, I was myself overwhelmed by the amount of concepts one needs to grasp. But after spending some time with the framework, it started making sense to me, and I began to see the purpose of all these concepts. I quickly became convinced that Phoenix provides reasonable building blocks which should satisfy most typical needs. Furthermore, I’ve learned that Phoenix is actually quite modular. This is nice because we can trim it down to our own preferences (though in my opinion that’s usually not needed). In fact, it is possible to run a Phoenix powered server without a router, controller, view, and template. In this article I’ll show you how, and then I’ll provide some tips on learning Phoenix. But first, I’ll briefly touch on the relationship between Phoenix and Plug. Phoenix and Plug Phoenix owes its modularity to Plug. Many Phoenix abstractions, such as endpoint, router, or controller, are implemented as plugs, so let’s quickly recap the idea of Plug. When a request arrives, the Plug library will create a Plug.Conn struct (aka conn). This struct bundles various fields describing the request (e.g. the IP address of the client, the path, headers, cookies) together with the fields describing the response (e.g. status, body, headers). Once the conn struct is initialized, Plug will call our function to handle the request. The task of our code is to take the conn struct and return the transformed version of it with populated output fields. The Plug library then uses the underlying HTTP library (for example Cowboy) to return the response. There are some fine-print variations to this concept, but they’re not relevant for this discussion. So essentially, our request handler is a function that takes a conn and transforms it. In particular, each function that takes two arguments (a conn and arbitrary options) is called a plug. Additionally, a plug can be a module that implements two functions init/1 which provides the options, and call/2 which takes a conn and options, and returns the transformed conn. Request handlers can be implemented as a chain of such plugs, with the help of Plug.Builder. Since a plug is basically a function, your request handler boils down to a chain of functions threading the conn struct. Each function takes a conn, does it’s own processing, and produces a transformed version of it. Then the next function in the chain is invoked to do its job. Each plug in the chain can do various tasks, such as logging (Plug.Logger), converting the input (for example Plug.Head which transforms a HEAD request into GET), or producing the output (e.g. Plug.Static which serves files from the disk). It is also easy to write your own plugs, for example to authenticate users, or to perform some other custom action. For example, for this site I implemented a plug which counts visits, measures the processing time, and sends stats to graphite. Typically, the last function in the chain will be the “core” handler which performs some request-specific processing, such as data manipulation, or some computation, and produces the response. When it comes to Phoenix, endpoint, router, and controllers are all plugs. Your request arrives to the endpoint which specifies some common plugs (e.g. serving of static files, logging, session handling). By default, the last plug listed in the endpoint is the router where request path is mapped to some controller, which is itself yet another plug in the chain. Trimming down Phoenix Since all the pieces in Phoenix are plugs, and plugs are basically functions, nothing stops you from removing any part out of the chain. The only thing you need for a basic Phoenix web app is the endpoint. Let’s see an example. I’ll create a simple “Hello World” web server based on Phoenix. This server won’t rely on router, controllers, views, and templates. First, I need to generate a new Phoenix project with mix phoenix.new simple_server --no-ecto --no-brunch --no-html. The options specify I want to omit Ecto, Brunch, and HTML views from the generated project. This already makes the generated code thinner than the default version. There are still some pieces that can be removed, and I’ve done that in this commit. The most important change is that I’ve purged all the plugs from the endpoint, reducing it to: defmodule SimpleServer.Endpoint do use Phoenix.Endpoint, otp_app: :simple_server end All requests will end up in an endpoint which does nothing, so every request will result in a 500 error. This is a consequence of removing all the default stuff. There are no routers, controllers, views, or templates anymore, and there’s no default behaviour. The “magic” has disappeared and it’s up to us to recreate it manually. And that’s it! The output is now rendered through a precompiled EEx template. And still, no router, controller, or Phoenix view has been used. You can find the complete solution here. It’s worth noting that by throwing most of the default stuff out, we also lost many benefits of Phoenix. This simple server doesn’t serve static files, log requests, handle sessions, or parse the request body. Live reload also won’t work. You can of course reintroduce these features if you need them. What’s the point? To be honest, I usually wouldn’t recommend this fully sliced-down approach. My impression is that the default code generated with mix phoenix.new is a sensible start for most web projects. Sure, you have to spend some time understanding the flow of a request, and roles of endpoint, router, view, and template, but I think it will be worth the effort. At the end of the day, as Chris frequently said, Phoenix aims to provide the “batteries included” experience, so the framework is bound to have some inherent complexity. I wouldn’t say it’s super complex though. You need to take some time to let it sink in, and you’re good to go. It’s a one off investment, and not a very expensive one. That being said, if you have simpler needs, or you’re overwhelmed by many different Phoenix concepts, throwing some stuff out might help. Hopefully it’s now obvious that Phoenix is quite tunable. Once you understand Plug it’s fairly easy to grasp how a request is handled in Phoenix. Tweaking the server to your own needs is just a matter of removing the plugs you don’t want. In my opinion, this is the evidence of a good and flexible design. All the steps are spelled out for you in your project’s code, so everything is explicit and you can tweak it as you please. Learning tips Learning Phoenix is still not a small task, especially if you’re new to Elixir and OTP. If your Elixir journey starts with Phoenix, you’ll need to learn the new language, adapt to functional programming, understand BEAM concurrency, become familiar with OTP, and learn Plug, Phoenix, and probably Ecto. While none of these tasks is a “rocket science”, there’s obviously quite a lot of ground to cover. Taking so many new things at once can overwhelm even the best of us. So what can be done about it? One possible approach is a full “bottom-up”, where you focus first on Elixir, learn its building blocks and familiarize yourself with functional programming. Then you can move to vanilla processes, then to OTP behaviours (most notably GenServer and Supervisor), and finally OTP applications. Once you gain some confidence there, you “only” need to understand Plug and Phoenix specifics, which should be easier if you built solid foundations. I’m not suggesting you need to fully master one phase before moving to the next one. But I do think that building some solid understanding of basic concepts will make it easier to focus on the next stage. The benefit of this approach is that you get a steady incremental progress. Understanding concurrency is easier if you don’t have to wrestle with the language. Grasping Phoenix is easier if you’re already confident with Elixir, OTP, and Plug. The downside is that you’ll reach the final goal at the very end. You’re probably interested in Phoenix because you want to build scalable, distributed, real-time web servers, but you’ll spend a lot of time transforming lists with plain recursion, or passing messages between processes, before you’re even able to handle a basic request. It takes some commitment to endure this first period. If you prefer to see some tangible results immediately, you could consider a “two-pass bottom-up” approach. In this version, you could first go through excellent official getting started guides on Elixir and Phoenix sites. These should get you up to speed more swiftly than reading a few hundred pages book(s), though you won’t get as much depth. On the plus side, you’ll be able to experiment and prototype much earlier in the learning process. Then you can start refining your knowledge in the second pass, perhaps by reading some books, watching videos, or reading the official docs. There are of course many other strategies you can take, so it’s up to you to choose what works best for you. Whichever way you choose, don’t be overwhelmed by the amount of material. Try to somehow split the learning path into smaller steps, and take new topics gradually. It’s hard if not impossible to learn everything at once. It’s a process that takes some time, but in my opinion, the effort is definitely worth the gain. I’m a very happy customer of Erlang/OTP/Elixir/Phoenix, and I don’t think any other stack can give me the same benefits. Where is the comments section? Until I figure out the GDPR implications, the comments are disabled. In the meantime, if you have some questions, you can find me at the Elixir Forum. Either tag me in a public post, or send me a DM, and I'll do my best to respond in a timely manner :-)	{ "pile_set_name": "Pile-CC" }
Childhood is the most important stage in human development, since exactly during this period the foundation for a healthy, successful and happy life is laid. Supporting child development is the strategic goal of society. There are 5,623,387 children in Kazakhstan aged from 0 to 17 years, which is about 31% of the population. Since 2008, when the country switched to international criteria for live birth, Kazakhstan has made significant progress in reducing infant mortality. Neonatal mortality rates have been reduced by more than 50%. However, despite a significant decline, infant mortality in Kazakhstan is still relevant. In the regions, programs for perinatal and neonatal care and care for sick newborns are not working effectively. UNICEF provides technical assistance to improve the skills and qualifications of health workers to support early childhood development.	{ "pile_set_name": "OpenWebText2" }
Padern Padern (Languedocien: Padèrn) is a commune in the Aude department in southern France. Population Monuments The Château de Padern is a ruined castle that stands on a hill overlooking the village. See also Corbières AOC Communes of the Aude department References INSEE Category:Communes of Aude Category:Aude communes articles needing translation from French Wikipedia	{ "pile_set_name": "Wikipedia (en)" }
1. Field of the Invention The invention relates to an operator control unit, in particular for operating a multimedia system in a motor vehicle, having an operator control element which can be rotated about an axis and displaced along this axis and can be latched in a position on this axis. Such an operator control element is known from U.S. Pat. No. 5,270,689.There, by rotating a rotary switch about an axis, a specific function is selected from a menu represented on a screen, and confirmed by pressing the switch. Inadvertent confirmation can be rescinded by pulling the switch. As a result of the confirmation, the unit is changed over into another menu in which a selection is possible in the same way.	{ "pile_set_name": "USPTO Backgrounds" }
This article features the history of the placement of the milestones along the long road from Calcutta to Benares in the late 1820s. It inquires into the practices of measurement in early colonial India and attempts to understand how the numbers were produced as fixed and final entities of measurement practices. It exposes the confusion, recalcitrance, guesswork and reckoning behind the emergence of this numerate culture. The confusion over distance measurement was often attributed to the inauthenticity or absence of instruments, to the variation of routes followed by the surveyors. But in spite of all practical difficulties, the administration demanded precise distance charts to fix the payments of the postal runners. The officers had no options but to choose from a multiple number of distance charts and finalise the numbers inscribed on the milestones. This was the way “scientific” measurements were done and “exact” numbers were produced. Subscribers please login to access full text of the article. New 3 Month Subscription to Digital Archives at ₹826for India $50for overseas users Get instant access to the complete EPW archives Subscribe now	{ "pile_set_name": "OpenWebText2" }
Some of the country's leading veterinarians say pets could potentially be receiving better medical care than their owners. In the prosthetics world in particular, veterinary surgeries are making huge strides and, in some cases, human surgeries could be falling behind. Dr Ignacio Calvo, senior lecturer in small animal orthopaedics at the Royal Veterinary College, says it is "easier to make the jump into clinical trials when you are dealing with an animal rather than a person". The reason for increased innovation in animal medicine can be put down to the fact that all pet care is private and, unlike the NHS, fairly well-funded per patient. Dr Calvo said it could also be down to the patients themselves. "We are gathering quite a bit of information regarding endoprosthesis as an alternative to full amputation in legs," he said. "And, now that we have clinical experience, we know what happens when the animal is actually walking." There are now calls for doctors and vets to work more closely to learn from one another. Orthopaedic surgeon Dr Viquar Quarashi from Russel Hall Hospital told Sky News that innovations in the pet world can translate to new treatments from humans. "A few of these prosthetic ideas have definitely come from vets," he said. "There is always innovation because there is nothing stopping them going to whatever limit they want. Yes, we should start learning from them, there's no hesitation about it." However, there are some in the industry who are less keen on the explosion of innovation in veterinary science. Jasper Gale, from Kirks Vets, does not "think it's the job of a vet GP to have a go and see what they can achieve just by trying it out". He added: "I don't think we should or have in recent years been experimenting on people's pets just to push new techniques and push the boundaries."	{ "pile_set_name": "Pile-CC" }
--------------- Custom Commands --------------- ``xse trip`` show last Trip value ``xse recu up`` ``xse recu down`` set Rekuperation up or down. Works only if Rekuperation is enabled in car ``xse charge`` set charge and leave Time. Example: ``xse charge 7 15 off`` set Time at 7:15 clock with pre climate off ``xse charge 9 55 on`` set Time at 9:55 clock with pre climate on	{ "pile_set_name": "Github" }
Q: Can I display a message in MySQL? I have a question related to SQL. Can I display a custom message in MySQL phpMyAdmin, something like this: SELECT * FROM table_name PRINT 'The message that I want to write!'; I tried to do it with PRINT syntax, because I found something like that, but it doesn't work. Do you have some ideas? A: Put the text in the SELECT statement SELECT , 'PRINT' FROM foo; If you're wanting to print a long message, and want a different column name, simply use an alias by using AS. SELECT , 'The message i want to print' AS msg FROM foo;	{ "pile_set_name": "StackExchange" }
/* * Copyright 2019 The Error Prone Authors. * * Licensed under the Apache License, Version 2.0 (the "License"); * you may not use this file except in compliance with the License. * You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. / package com.google.errorprone.bugpatterns; import static com.google.errorprone.BugPattern.SeverityLevel.ERROR; import static com.google.errorprone.matchers.Description.NO_MATCH; import static com.google.errorprone.matchers.JUnitMatchers.hasJUnit4TestRunner; import static com.google.errorprone.util.ASTHelpers.getAnnotationWithSimpleName; import static com.google.errorprone.util.ASTHelpers.hasAnnotation; import com.google.errorprone.BugPattern; import com.google.errorprone.VisitorState; import com.google.errorprone.bugpatterns.BugChecker.ClassTreeMatcher; import com.google.errorprone.fixes.SuggestedFix; import com.google.errorprone.fixes.SuggestedFixes; import com.google.errorprone.matchers.Description; import com.sun.source.tree.AnnotationTree; import com.sun.source.tree.ClassTree; /* Flags uses of parameters in non-parameterized tests. */ @BugPattern( name = "ParametersButNotParameterized", summary = "This test has @Parameters but is using the default JUnit4 runner. The parameters will" + " have no effect.", severity = ERROR) public final class ParametersButNotParameterized extends BugChecker implements ClassTreeMatcher { private static final String PARAMETERIZED = "org.junit.runners.Parameterized"; private static final String PARAMETER = "org.junit.runners.Parameterized.Parameter"; private static final String PARAMETERS = "org.junit.runners.Parameterized.Parameters"; @Override public Description matchClass(ClassTree tree, VisitorState state) { if (!hasJUnit4TestRunner.matches(tree, state)) { return NO_MATCH; } if (tree.getMembers().stream() .noneMatch( m -> hasAnnotation(m, PARAMETER, state) \|\| hasAnnotation(m, PARAMETERS, state))) { return NO_MATCH; } AnnotationTree annotation = getAnnotationWithSimpleName(tree.getModifiers().getAnnotations(), "RunWith"); SuggestedFix.Builder fix = SuggestedFix.builder(); fix.replace( annotation, String.format("@RunWith(%s.class)", SuggestedFixes.qualifyType(state, fix, PARAMETERIZED))); return describeMatch(tree, fix.build()); } }	{ "pile_set_name": "Github" }
206 Ga. 477 (1950) 57 S.E.2d 578 CAPITOL DISTRIBUTING COMPANY et al v. REDWINE, Revenue Commissioner; et vice versa. 16887, 16901. Supreme Court of Georgia. January 12, 1950. Rehearing Denied February 17, 24, 1950. 483 MacDougald, Troutman, Sams & Schroder, and Dan MacDougald Jr., for plaintiffs. Eugene Cook, Attorney-General, and M. H. Blackshear Jr., Assistant Attorney-General, for defendant. CANDLER, Justice. (After stating the foregoing facts.) 1. There is set out above a copy of the enrolled act as attached to and made a part of the petition as amended. As enrolled the act shows on its face that taxation on wines is included in the title and in the body. The plaintiffs in error contend that there were irregularities during the process of the legislation such as to controvert any valid reference to wines in the title. A portion of the petition as amended alleges in substance that the words, "to increase the excise taxes upon domestic wines, foreign wines, and domestic and foreign fortified wines," were neither read before nor voted on by the legislature nor did they appear in the title when the bill was before the legislature. Instead, it is contended that those words were composed and inserted by some agency or method other than the joint action of the two houses after the bill was voted on and passed. Further, it is contended that the words, "and that the caption be amended accordingly," were written underneath the body of the amendment, but that the same were not constitutionally sufficient to authorize the first above-quoted words which were written into the title. The petition as amended attempts to show the facts relied on by photostatic copies of the bill, its amendment during process of passage, and Legislative Journal entries. Involved in these contentions there are several provisions of the 484 State Constitution, alleged to be violated, as follows: article III, section 1, paragraph 1 (Code, Ann. § 2-1301), reading: "The legislative power of the State shall be vested in a General Assembly which shall consist of a Senate and House of Representatives," the contention being that the alleged new matter inserted in the manner alleged constitutes an unlawful delegation of legislative authority in violation thereof; article III, section VII, paragraph VII (Code, Ann. § 2-1907), reading: "Every bill, before it shall pass, shall be read three times, and on three separate days, in each House, unless in cases of actual invasion, or insurrection, but the first and second reading of each local bill, shall consist of the reading of the title only, unless said bill is ordered to be engrossed," it being contended that, the entire act not being read, this clause was violated; article III, section VII, paragraph VII (Code, Ann. § 2-1908), reading: "No law shall pass which refers to more than one subject matter, or contains matter different from what is expressed in the title thereof," the contention in this connection being that the act having made reference in the body to wines, without having reference to the same in the title, is in violation of this provision; and article I, section I, paragraph III (Code, Ann. § 2-103), reading: "No person shall be deprived of life, liberty, or property, except by due process of law," it being contended that the legislature undertook to have the caption changed after the act passed and did so in terms so vague, uncertain, and indefinite as not to apprise anyone thereof. Before a determination of the questions above presented, it is obvious that consideration must be given to the effect thereon of the decisions of this court on the principle commonly known as the conclusive presumption of an enrolled act. In Atlantic Coast Line R. Co. v. State, 135 Ga. 545 (69 S. E. 725), it was held: "A duly enrolled act properly authenticated by the regular presiding officers of both houses of the General Assembly, approved by the Governor, and deposited with the Secretary of State as an existing law, will be conclusively presumed to have been enacted in accordance with the constitutional requirements; and it is not permissible to show, by the legislative journals or other records, that it did not receive on its passage a majority vote of all the members elected to each house, or that there was 485 any irregularity in its enactment." See also DeLoach v. Newton, 134 Ga. 739 (68 S. E. 708), and Williams v. MacFeeley, 186 Ga. 145 (197 S. E. 225). A case cited and relied on by the plaintiffs in error is Solomon v. Commissioners of Cartersville, 41 Ga. 157. It held that an act of the General Assembly signed by Rufus B. Bullock, Governor, May 26, 1869, was invalid because it was not signed within the time prescribed by the Constitution. The Solomon case, supra, was cited in DeLoach v. Newton, supra, and the court, after discussing the possible uses of the legislative journals, said: "A possible use for them might arise on the construction of an act. In Solomon v. Commissioners of Cartersville, 41 Ga. 157, the journals of the General Assembly were consulted to ascertain when the legislature adjourned. In Gormley v. Taylor, 44 Ga. 76, a query was put on this subject." Evidently the court in DeLoach v. Newton, supra, did not consider the case of Solomon v. Commissioners of Cartersville, supra, any obstacle to reaching its decision. Neither do we, in this case, find anything in it to prevent us from following DeLoach v. Newton, Atlantic Coast Line R. Co. v. State, and Williams v. MacFeeley (supra), in circumstances where, as in the present case, the attempt is to impeach a legislative act in reference to matters alleged to have transpired before the signing of the bill by the Governor, and where the issue is not whether or not the Governor did actually sign the bill within the time required by the Constitution. The plaintiffs in error argue that the decided cases in this State on the question of conclusive presumption of an enrolled act do not, as to any of them, embrace a situation exactly like that presented by the facts in the instant case. If not in exact detail with the facts here involved, the principles in the cited cases upholding the conclusive presumption doctrine are sufficiently controlling for us to adhere to the same rule in this case. Thus, we reach the conclusion that where, as in this case, a copy of an enrolled act purporting to contain the signatures of the Speaker of the House, Clerk of the House, President of the Senate, Secretary of the Senate, and the Governor, is set out and made a part of the amended petition, which seeks to show invalidity upon the contention that a portion of the title was composed and inserted by some method or agency in an irregular manner during the process of its passage, neither the 486 legislative journals nor photostatic copies of the bill are permissible to impeach the act, because of the conclusive presumption against any irregularity in its enactment; and, accordingly, this court cannot consider violations of the State Constitution that are dependent on being so shown. 2. The act is assailed as being in violation of article III, section VII, paragraph VIII of the State Constitution (Code, Ann. § 2-1908), particularly the portion thereof reading, "No law shall pass which refers to more than one subject matter," because, as the plaintiffs in error contend, it embraces legislation on "malt beverages" and "wines." Specifically it is contended that the regulation, control, and taxation of malt beverages is a separate subject-matter from that of wines. Seeking to illustrate, it is insisted that they have been dealt with as a separate series of legislation; that in certain court decisions the term "malt beverages" has been held not to include "wines"; that legislative declarations in the wine act of 1935, to the effect that the same was to promote temperance and prosperity of the people of Georgia and foster the growing of grapes, fruits, and berries on Georgia farms, indicate that wines are recognized by the legislature as being in a different subject-matter category from that of malt beverages; and that executive and administrative treatment has recognized them as separate. The "subject" of an act, within the meaning of the constitutional provision that no act shall contain more than one subject, is regarded as the matter or thing forming the groundwork of the act. Lloyd v. Richardson, 158 Ga. 633 (124 S. E. 37); 50 Am. Jr. 172, § 191; Mayes v. Daniel, 186 Ga. 345, 353 (198 S. E. 535). In Whitley v. State, 134 Ga. 758 (68 S. E. 716), involving an act of 1907 to prohibit the manufacture, sale, and other things relating to various named forms of alcoholic liquors or drinks, the dual subject-matter provision of the State Constitution was invoked and held not to be applicable, it being pointed out that "all these things were germane to and formed a part of the general purpose of the act. They were not so entirely distinct and different as to constitute different subject-matters within the meaning of the paragraph of the constitution." See also Carroll v. Wright, 131 Ga. 728 (63 S. E. 260). Looking to the language of the act in the instant case, the general purpose is illustrated by words and figures 487 that unmistakably stand out as indicating that an increase in excise taxes is the thing chiefly sought. Whatever may have been the reasons prompting the legislature in the year 1935 to deal separately with malt beverages (Ga. L. 1935, pp. 73-81) and wines (Ga. L. 1935, pp. 492-4), or amending the same separately afterwards, it does not appear to us that the terms, "malt beverages" and "wines" are so incongruous per se that they could not be dealt with in a single act for a purpose that was applicable. Although the original wine act of 1935 legalized the making of domestic wines and exempted from taxation wine made from Georgia grapes, fruits, and berries, the tax-free provision was eliminated by an act approved March 30, 1937 (Ga. L. 1937, p. 851), and a tax was prescribed to be levied and collected on domestic wines and foreign wines graduated on alcoholic content. Since that time the amended act has contained levies of taxes upon wines of all classes, and the original theory of tax exemption on wine made from Georgia grapes, fruits, and berries has no longer obtained. It is true that the levies against wines made from Georgia products have been at a lower rate than other wines. Rationally, however, the declarations in the original wine act of 1935, to the effect that promotion of temperance and prosperity for Georgia people and to foster and encourage the growing of grapes, fruits, and berries in Georgia, were more in harmony with the act when it first legalized domestic wines with a limited alcoholic content, without taxes, than now apply since the amendments letting in foreign as well as domestic wines and permitting an increased alcoholic content. The question in McKown v. Atlanta, 184 Ga. 221 (190 S. E. 571), and McCaffrey v. State, 183 Ga. 827 (189 S. E. 825), was whether a law or ordinance pertaining to "malt beverages" comprehended "wines" within that term. No such issue is involved here, and those cases are not applicable. In view of the foregoing, the act now under consideration does not contain a dual subject-matter within the meaning of the constitutional provision that no act shall contain more than one subject. 3. The plaintiffs in error contend that section 2-a of the act unconstitutionally discriminates against them, in that a tax of $1 per gallon is levied on wine manufactured in Georgia from out-of-State grapes as against a ten-cents-per-gallon levy on 488 wine of the same class manufactured from Georgia raw materials. The constitutional provisions alleged to be violated are as follows: denial of due process and equal protection as guaranteed by the Fourteenth Amendment to the Constitution of the United States, especially that portion thereof reading, "nor shall any State deprive any person of life, liberty or property without due process of law"; nor deny any person within its jurisdiction the equal protection of the laws"; and burdening interstate commerce, as forbidden by article 1, section 8, paragraph 3, especially the portion reading: "The Congress shall have Power . . . To regulate commerce . . among the several States." It is insisted that the definition of foreign wines, making applicable the taxation, illustrates the unconstitutionality claimed. The definition reads: "Foreign wines are hereby defined and declared to be wines which are imported in whole or in part in the State of Georgia or manufactured in the State of Georgia from products imported in whole or in part from without the State and produced by natural fermentation." The United States Supreme Court has held in State Board of Equalization v. Young's Market Co., 299 U. S. 57 (57 Sup. Ct. 77, 81 L. ed. 38), Mahoney v. Joseph Triner Corp., 304 U. S. 401 (58 Sup. Ct. 952, 82 L. ed. 1424), and Indianapolis Brewing Co. v. Liquor Control Commission of the State of Michigan, 305 U. S. 391 (59 Sup. Ct. 254, 83 L. ed. 243), that the Twenty-first Amendment to the Constitution of the United States renders inoperative asserted violations of such provisions as due process, equal protection, and interstate commerce, where State action within the subject-matter of the Twenty-first Amendment is involved. Beer and beer dealers were involved in the alleged discrimination in the Indianapolis Brewing Co. case, supra. Upon the basis of the Twenty-first Amendment to the Constitution of the United States, this court in Scott v. State, 187 Ga. 702 (2 S. E. 2d, 65), held that a statute imposing a tax on distilled spirits imported into the State and making it a misdemeanor to possess unstamped liquor did not violate the commerce clause of the Federal Constitution on the ground that it prohibited purchase of distilled spirits outside of the State for the purchaser's own use. The plaintiffs in error cite U. S. v. Frankfort Distilleries, 324 U. S. 293 (65 Sup. Ct. 661, 89 L. ed. 951), 489 and Jatros v. Bowles, 143 Fed. 2d, 453, and claim the same as authority for their contention that the Twenty-first Amendment does not immunize the portion of the act involved from the effect of the commerce clause. The Frankfort Distilleries case, supra, involved an alleged conspiracy in fixing prices in violation of the Sherman Act, and it was pointed out that it was not being enforced in that case in such manner as to conflict with the law of Colorado. Jatros v. Bowles, supra, involved Emergency War Price controls which rested under the war powers. Neither of the two last-mentioned cases conflicts with the right of the State's authority to determine conditions upon which liquor can come into its territory and what will be done with it after it gets there. Therefore, they are not applicable to the question here. Mason v. State, 1 Ga. App. 534 (5) (58 S. E. 139), holds that "wine" is included in the definition of the term "intoxicating liquors." The Twenty-first Amendment embraces "wine" such as is the subject-matter dealt with in the portion of the act under attack in this case. If the portion of the act is discriminatory, it is outside the pale of protection of the due-process and equal-protection clauses of the Fourteenth Amendment and the commerce clause of the Federal Constitution by reason of the Twenty-first Amendment thereof. Therefore, we cannot consider the grounds of discrimination and unconstitutionality which are raised by the plaintiffs in error and discussed in this division of the opinion. (a) Likewise, there is no merit in the contention here made that section 2-a of the act of 1949 (Ga. L. 1949, Ex. Sess. p. 5) offends article 1, section 1, paragraph 2 of the Constitution of 1945 (Code, Ann., § 2-102), which declares "Protection to person and property is the paramount duty of government, and shall be impartial and complete." 4. In view of the above rulings, there was no error in sustaining the general demurrers, which attacked the petition as amended on grounds that no cause of action was set out, nor did the allegations warrant the granting of the equitable relief prayed. Because of said rulings on these general demurrers, it becomes unnecessary to pass on the special demurrers brought up by the cross-bill of exceptions. Judgment affirmed on the main bill of exceptions. All the 490 Justices concur, except Wyatt and Head, JJ., who dissent from division 2 of the opinion and the judgment of affirmance, Duckworth, C. J., and Almand J., concur specially. Cross-bill of exceptions dismissed. All the Justices concur. ALMAND, Justice. I concur in the ruling in division 1 of the opinion only because of prior unanimous decisions of this court, cited in the opinion. I think that these previous decisions are wrong and should be overruled, but since a sufficient number of members of the present court to overrule these cases do not agree with me, I am bound by these prior rulings. I am authorized to say that Chief Justice Duckworth concurs in this special concurrence.	{ "pile_set_name": "FreeLaw" }
1. Field The present invention relates to communication of data, and more particularly, to sending messages from a wireless device in a multiple communication modes environment. 2. Background Various communication systems operating according to different communication protocols provide for communication of messages. Generally, communication of messages is provided through different message services. One of the message services is the short message service (SMS.) The SMS is a wireless message service for providing a medium for communication of alphanumeric messages of limited size. The communication of SMS messages may be between mobile devices, or a mobile device and a wireless network. The SMS may be used for a variety of communication services such as electronic mail, paging, facsimile, voice mail, or Internet access. The SMS is available in communication systems operating in accordance with the Global System for Mobile Communications (GSM) standard, and code division multiple access (CDMA) standards, such as CDMA1X, CDMA2000, and WCDMA. The standards may include a specific set of protocols for communication of data. Such specific protocols include the General Packet Radio Service (GPRS) and the Universal Mobile Telecommunications Service (UMTS). Another type of message service is known as Enhanced Messaging Service (EMS.) The EMS allows users of EMS-compliant mobile devices to send and receive text, melodies, pictures, and simple sounds and animations, or a combination thereof. The EMS is also supported by a number of communication standards. A mobile device having multiple communication modes may support the operations of communicating data in accordance with more than one standard. Therefore, the mobile device may be a multi-mode wireless device (MWD.) The MWD allows a user to send and receive voice and data over multiple wireless networks, each operating in accordance with a communication standard. The communication modes include, without limitation, operations in CDMA or GSM based systems, or GSM-based derivatives such as GPRS or UMTS. Other CDMA-based systems are also included, such as CDMA1X, CDMA2000, etc. The MWDs are generally compatible with the SMS and EMS for sending and receiving messages. Most communication modes provide at least one message service. Each message service, however, has distinct formats, interfaces, and protocols for generating, sending, and receiving messages. In the past, mobile service providers required users to choose a single wireless system for their service. Thus, a wireless device had to support only one set of message services. The proliferation of MWDs, however, requires the ability to support multiple message services for corresponding multiple communication modes, as well as each message service's unique standards. Currently, a user of an MWD must determine which wireless communication mode or modes is available for use, and must manually select an appropriate corresponding message service. Further, the MWD may employ a different application for each message service, and each application includes a distinct interface and set of procedures for sending a message. There is therefore a need in the art for a method and apparatus for sending a message in which a wireless communication mode and a message service can be automatically selected.	{ "pile_set_name": "USPTO Backgrounds" }
Only Eight People Have 50% Of The World’s Wealth, But I Might Be One Of Those Eight Someday So I Don’t Think We Should Do Anything About It Wealth distribution across the world is highly unequal and the fact that only eight people hold on to 50% of the world’s money is shocking. Your knee-jerk reaction may be that we have to do something to balance the scales, but then again, one day I might be one of those eight people so let’s just leave things as they are, shall we? Sure the odds are 8 in about 7.6 billion but you never know! Genetics, upbringing, socioeconomic status, and location all make it so you barely even have a chance to be even in the top 10% of wealthiest people. But then again, what if one of them is me? How about you walk a mile in my hypothetical Tramezza Leather Medallion-Toe Oxfords? I don’t think you want the government to take away your ability to own five houses or a Ferrari Segway, do you? Especially when I’m potentially days away from a billion dollar idea or winning the lottery even though I don’t buy tickets. Do you want to have to pay taxes to support people who are as poor as me at this moment? Well, I certainly don’t. You can say I’m voting against my own interests but I’m only interested in the vast wealth I plan to accumulate through… whatever, I dunno how yet but it’s on my vision board so, yeah. I may never use the acreage on the moon I will most certainly buy but I’ll be damned if the government tries to take away my money so I can’t afford it. And I know I don’t need a crystal iPhone dock or a Faberge Egg collection, but if the poor want to expense eggs then they should try to be more like me. So call me a bootlicker if you must, because someday the boots I’ll be licking will be my very own Tramezza Leather Medallion-Toe Oxfords. You’re probably wondering why I wouldn’t hire my own personal bootlicker, but that would be a ridiculously frivolous and I don’t want to be greedy or anything.	{ "pile_set_name": "OpenWebText2" }
[Expression of CD117, MITF and NAT10 and their prognostic values in sinonasal mucosal melanoma]. Objective: To investigate the correlation between the expression of CD117, MITF, NAT10 and clinical parameters in sinonasal mucosal melanoma (SNMM). Methods: Formalin-fixed paraffin-embedded tumor specimens of 80 cases of SNMM at the Eye, Ear, Nose and Throat Hospital, Fudan University, from December 1999 to November 2013 were analyzed for CD117, MITF and NAT10 expression by immunohistochemistry. Results: There were 40 men and 40 women. The median age was 61 years, age 26 to 85 years. There was no correlation of the expression of CD117, MITF and NAT10 with the patients' age, gender, tumor site, stage, therapy method and brain metastases (P>0.05). The expression of MITF and NAT10 was associated with lymph node metastasis and the tumors were more likely to metastasize when MITF and NAT10 were positive. However, expression of CD117 had no correlation with lymph node metastasis. Log-rank test revealed that the expression of CD117 was correlated with both three-year and five survival rate (P=0.012, P=0.023; respectively) and patients with tumor having low expression of CD117 had the worse outcome. COX test revealed that low CD117 expression, advanced age and lymph node metastasis were independent risk factors (P<0.05). No significant association was found between the expression of CD117, MITF and NAT10 with disease free survival (P>0.05). Conclusions: Patients with SNMM expressing low level of CD117 have decreased survival rate. Tumors with high level of MITF and NAT10 expression are more likely to metastasize. The expression level of CD117 can be used as an important indicator for the patient survival, and the expression of MITF and NAT10 can be used as a predictor of tumor metastasis.	{ "pile_set_name": "PubMed Abstracts" }
The adult dentate gyrus continuously generates granule cells (DGCs) that are needed for specific learning and memory tasks, but the precise contribution of new neurons to information processing in the hippocampal circuitry remains unknown. In the past, we have demonstrated that key developmental processes occurring in the perinatal brain such as maturation of excitability, afferent synaptogenesis and function are all recapitulated during adult neurogenesis. We now propose the central hypothesis that newly born cells establish functional outputs as they develop, and the population of postsynaptic target cells contacted by young neurons is predominantly inhibitory, therefore different from the mixed excitatory/inhibitory network activated by mature granule cells. Thus, there would be a time window in which young DGCs primarily activate feedforward and/or feedback inhibitory circuits without exciting pyramidal cells, exerting a tight inhibitory control over the dentate gyrus output. In Aim 1 we will build a spatio-temporal map of target activation by young developing neurons of the adult dentate gyrus. We will use retroviral transduction to express the light- activated cation channel Channelrhodopsin-2 in newborn DGCs of young-adult female mice (C57Bl6/J). We will sacrifice the animals at different times and prepare acute brain slices to carry out electrophysiological recordings. By stimulating the whole hippocampal slice with brief light pulses, all retrovirally transduced neurons will spike. We will search randomly for active postsynaptic target cells throughout the hilus and CA3 regions, and identify and characterize responsive neurons by combining loose patch and whole-cell recordings. In Aim 2 we will investigate the functional maturation of new mossy fiber synapses made onto GABAergic and glutamatergic targets. We plan to utilize whole-cell recordings to test whether synapses forming onto GABAergic interneuron targets mature faster than those made onto pyramidal cells, as suggested by our previous structural studies. We will also study presynaptic mechanisms of short- and long-term plasticity that will shape both activity-dependent competition and activation of postsynaptic circuits. This project will address fundamental questions about connectivity and activation (spiking) of newborn cells that will contribute to understanding the precise impact of adult neurogenesis in the preexisting hippocampal network and the rules of neuronal connectivity in the adult brain. Identifying the rules by which neurons integrate in the existing network in a manner that is both safe and functionally relevant is also crucial for developing future brain repair therapies. Novel retroviral tools will be developed in collaboration with the Gage lab to enhance Channelrhodopsin-2 expression, thus improving the capability of light activation of newborn cells. In turn, experimental data obtained here will be used to feed into the theoretical model being developed by the Gage lab on the role of immature neurons in signal processing. The success of the proposed project relies on strengthening the close interaction between the Schinder laboratory at the Leloir Institute (Buenos Aires) and the Gage laboratory at the Salk Institute of La Jolla. Members of the Schinder lab will have the opportunity to train at Salk on the generation and characterization of novel retroviral vectors, improving the capabilities to develop advanced molecular tools at the foreign institution. We anticipate that capacity building leading to the design, generation and use of novel retroviral tools at the Leloir Institute will have an enormous impact on the local scientific community. This collaborative effort will therefore serve as a driving force to increase the critical mass of Argentine investigators that incorporate competitive technologies for the study of neurodegenerative disorders within their research focus. An increase in the number of laboratories carrying out regeneration- related projects will certainly enhance awareness to these and related problems to our community.	{ "pile_set_name": "NIH ExPorter" }
Q: Rails nested form, attributes not getting passed So I have a Conversation model, which has_many messages. I'm trying to create a new message when I create a conversation. Here's my ConversationsController: class ConversationsController < ApplicationController before_filter :authenticate_user! def new recipient = User.find(params[:user]) @conversation = Conversation.new(from: current_user, to: recipient) @conversation.messages.build(from: current_user, to: recipient) end def create @conversation = Conversation.create(params[:conversation]) redirect_to @conversation end end And here's my form (conversations/new.html.erb): <%= form_for @conversation do \|f\| %> <%= f.fields_for :messages do \|g\| %> <%= g.label :subject %> <%= g.text_field :subject %> <%= g.label :content %> <%= g.text_field :content %> <% end %> <%= f.submit "Send" %> <% end %> The problem: when I submit the form, the conversation's message gets saved, but the to and from fields that I specified as parameters in build are not saved (they are nil). However, the subject and content fields filled out in this form are saved just fine. I've done a little bit of digging... if I do a puts on @conversation.messages in the new action, or in the new.html.erb, the message seems to have to and from. It's only when the message reaches the create action do those fields disappear. A: UPDATED: class ConversationsController < ApplicationController before_filter :authenticate_user! def new recipient = User.find(params[:user]) @conversation = Conversation.new(to: recipient) @conversation.messages.build end def create @conversation = current_user.conversations.build(params[:conversation]) # Set all the attributes for conversation and messages which # should not be left up to the user. @conversation.to = current_user @conversation.messages.each do \|message\| message.to = @conversation.to message.from = @conversation.from end redirect_to @conversation end end <%= form_for @conversation do \|f\| %> <%= f.hidden_field :recipient %> <%= f.fields_for :messages do \|g\| %> <%= g.label :subject %> <%= g.text_field :subject %> <%= g.label :content %> <%= g.text_field :content %> <% end %> <%= f.submit "Send" %> <% end %> You may still want to validate the recipient in your Conversation model.	{ "pile_set_name": "StackExchange" }
Bondi Digital Publishing Bondi Digital Publishing is a privately held New York City-based digital media company that specializes in publishing complete digital archives of major consumer magazines. Founded by David Anthony and Murat Aktar in 2004, Bondi Digital Publishing began by developing the technology that allowed The New Yorker to publish The Complete New Yorker in September 2005, a digital archive of its entire print archive on 8 DVD-ROMs. In 2006, The New Yorker used Bondi's technology again when they released their digital archive on a portable hard drive. In 2007, Bondi launched its publishing division when it partnered with Rolling Stone and Playboy magazines to publish both companies' entire print archives in searchable digital archives on DVD-ROM. First published in the fall of 2007, Rolling Stone Cover To Cover, the First 40 Years () and Playboy Cover to Cover, the 50s () were part of the company's Cover to Cover Series of digital archive box sets. The company marketed the series through national book and media retailers. In a September 2007 interview, Anthony stated "By the holiday 2008 season, we hope to have six - eight Cover To Cover titles in the line.". However, as of March, 2009, the only public release other than the aforementioned Rolling Stone and Playboy sets was a rerelease of the Rolling Stone set without the extras included in the original. A Playboy Cover to Cover, the 60s set was mentioned in the interview, but it, along with subsequent sets, is now being released exclusively through the website http://playboyarchive.com/ In March 2009, Bondi announced that using its technology, select digital back issues of Playboy would be available for free viewing at http://playboyarchive.com. It also announced that https://web.archive.org/web/20111006215634/http://covertocover.com/ would be changing in the Summer of 2009 to allow users to browse, search and purchase digital back issues from the entire print runs of Playboy and Rolling Stone using Bondi's online magazine application, but as of May 2011, this has not occurred. Instead, in April 2010, Rolling Stone'''s website began offering subscribers access to their digital archive. In November 2010, Bondi released a portable hard drive for Playboy, this time containing every issue from 1953 to 2010. In January 2011, it was announced that a Playboy'' iPad app would be available in March. References External links Bondi Digital Publishing's website Bondi's consumer site Bondi's site for digital back issues of Playboy Category:Media companies of the United States Category:Companies based in New York City	{ "pile_set_name": "Wikipedia (en)" }
Riyadh, Saudi Arabia -- U.S. Secretary of State Mike Pompeo said Monday that President Donald Trump's threat to devastate NATO ally Turkey's economy if it attacks U.S.-backed Kurdish fighters in Syria underscores America's commitment to its partners. Pompeo said he had yet to speak with Turkish officials or Mr. Trump about the president's Sunday afternoon threat, and that he assumed the president was referring to the imposition of sanctions should Turkey take military action against the Kurds in Syria, vital U.S. allies in the fight against ISIS. On Sunday, Trump tweeted that the U.S. would "attack again from existing nearby base if it (ISIS) reforms. Will devastate Turkey economically if they hit Kurds." Starting the long overdue pullout from Syria while hitting the little remaining ISIS territorial caliphate hard, and from many directions. Will attack again from existing nearby base if it reforms. Will devastate Turkey economically if they hit Kurds. Create 20 mile safe zone.... — Donald J. Trump (@realDonaldTrump) January 13, 2019 Mr. Trump's decision to leave Syria, which he initially said would be rapid but later slowed down, shocked U.S. allies and angered the Syrian Kurds. A U.S. official told CBS News last week it was expected to take between 90 and 120 days. Get Breaking News Delivered to Your Inbox Pompeo said the U.S. message on the Kurds had been straightforward and unchanged since Mr. Trump made the decision to withdraw U.S. troops from Syria last month. "The administration has been very consistent with respect to our requirement that the Turks not go after the Kurds in ways that are inappropriate," Pompeo said. "If they are terrorists, we're all about taking down extremists wherever we find them. I think the president's comments this morning are consistent with that." On Sunday, CBS News "Face the Nation" moderator Margaret Brennan asked Pompeo directly whether Turkish President Recep Tayyip Erdogan had agreed not to attack America's allies in Syria. "Yeah, look when President Erdogan and President Trump spoke, they talked about this issue. The Turks have made clear that they understand that there are folks down in Syria that have their rights," Pompeo told Brennan. "We also want to make sure that those in Syria aren't attacking -- terrorists aren't attacking Turkey from Syria. We're fully engaged. Ambassador Jeffrey is fully engaged in conversations with the Turks as well as with the SDF (Kurdish-led fighters) in Syria to make sure that we accomplish all of those missions. We can -- we can do each of those things." Asked specifically about what Mr. Trump meant by devastating Turkey's economy if the country does attack the Kurds, Pompeo said Monday: "We apply sanctions in many places around the world. I assume he's speaking about those kinds of things but you would have to ask him." Turkey lashes out over tweeted threat Mr. Trump's tweet drew a sharp response from Ankara and the Turkish lira lost some 0.84 percent of its value against the dollar on Monday following the U.S. president's threat. President Recep Tayyip Erdogan's spokesman responded to Mr. Trump on Twitter by saying that Turkey "fights against terrorists, not Kurds" as a people. "Terrorists can't be your partners & allies," the spokesman, Ibrahim Kalin, said. He said in Ankara's view there is "no difference" between the Kurdish YPG militia, which has led the U.S.-backed opposition Syrian Democratic Forces (SDF), and ISIS, and that Turkey would "continue to fight against them all." Mr @realDonaldTrump Terrorists can’t be your partners & allies. Turkey expects the US to honor our strategic partnership and doesn’t want it to be shadowed by terrorist propaganda. There is no difference between DAESH, PKK, PYD and YPG. We will continue to fight against them all. https://t.co/Yyzgyp9RQ4 — Ibrahim Kalin (@ikalin1) January 13, 2019 Turkish Foreign Minister Mevlut Cavusoglu also rebuked Mr. Trump, saying that strategic partners do not speak to each other through social media and stressing that Turkey is "not afraid of any threat. You cannot achieve anything with economic threats." "We would do whatever is necessary to eliminate threat to our security," Cavusoglu added. Mutual interest in Syria buffer zone Pompeo said Mr. Trump's call for a 20-mile safe zone between Turkish forces and the Kurds was consistent with what the U.S. is trying to achieve in talks with the Turks. But, he said it remained a work in progress. "We want to make sure that the folks who fought with us to take down the caliphate and ISIS have security and also that terrorists ... (in) Syria aren't able to attack Turkey, those are our twin aims," he told reporters in Riyadh after talks with Saudi officials. "If we can get a space, call it a buffer zone ... if we can get the space and the security arrangements right, this will be a good thing for everyone in the region," Pompeo added. For his part, Cavusoglu welcomed Mr. Trump's proposal for a 20-mile safe zone, saying Turkey had long advocated such a zone in northern Syria. "They bandied this idea after they saw Turkey's determination," Cavusoglu said during a news conference. "We are not against it."	{ "pile_set_name": "OpenWebText2" }
We consider a pencil-shaped active medium consisting of two- level initially excited atoms and described by 1D Maxwell- Bloch equations. With the help of these equations solution without slowly varying envelope approximation we shown, that internal field reflections from the ends of the sample transform the so-called 'lethargic' regime of super-radiance (SR) pulse amplification to the amplification regime similar to usual exponential law. iT can lead to the pulse development acceleration and counter-propagating waves synchronization. A simple formula for SR pulse delay time evaluation is presented. The criterion of the counter- propagating waves synchronization is discussed.	{ "pile_set_name": "Pile-CC" }
Iron-catalysed transformation of molecular dinitrogen into silylamine under ambient conditions. Although stoichiometric transformations using transition metal-N(2) complexes have been well investigated towards the goal of nitrogen fixation under mild reaction conditions, only a few examples of the catalytic transformations of N(2) using transition metal-N(2) complexes as catalysts have been reported. In almost all the catalytic systems, the use of Mo is essential to realize the catalytic transformation of N(2), where Mo-N(2) complexes are considered to work as effective catalysts. Here we show the first successful example of the Fe-catalysed transformation of N(2) into N(SiMe(3))(3) under ambient conditions, in which iron complexes such as iron pentacarbonyl [Fe(CO)(5)] and ferrocenes have been found to work as effective catalysts. A plausible reaction pathway is proposed, where Fe(II)-N(2) complex bearing two Me(3)Si groups as ancillary ligands has an important role as a key reactive intermediate, with the aid of density-functional-theory calculations.	{ "pile_set_name": "PubMed Abstracts" }
The hazard of the unrestrained occupant. A review of 208 cases involving injuries sustained by vehicle occupants was extracted from the computer storage at the Highway Safety Research Institute, University of Michigan, Ann Arbor. In addition, 157 new car crashes investigated by the authors were separately analyzed. Data analysis indicates injuries are sustained by direct occupant-to-occupant contact and by one occupant forcing another into or against one or more interior car structures. All body areas can be involved in this previously unreported injury mechanism, with the upper portion of the body more susceptibel to injury. Case histories from field accident investigations document a variety of these injury mechanisms.	{ "pile_set_name": "PubMed Abstracts" }

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