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Challenging heteronormativity in the consultation: a focus group study among general practitioners. To reflect on and further understand mechanisms of heteronormativity in the consultation, with special focus on the relative invisibility of lesbian women. Tape-recorded focus group interviews transcribed verbatim and analysed using qualitative methods. General practitioners (GPs) from the city of Göteborg, Sweden, who had formerly answered a postal questionnaire about lesbian women in the consultation, were invited to take part in subsequent focus groups. Ten GPs from the questionnaire who accepted the invitation and volunteered to participate in focus groups. A discourse analytical approach using interaction regarding consensus and disagreement between informants in creating major and minor themes. Consultation skills were forwarded as a major tool in receiving optimal information from patients. However, traditional concepts of family and sexuality restricted information and hampered an accepting attitude. Bringing up issues of sexual identity/orientation was left to the lesbian patient and strongly related to her reason for attending. Consultation skills are a useful but not sufficient means of making lesbian women visible in the doctor-patient relationship. Doctors also need to transcend traditional concepts of family and sexuality and reflect on what is a relevant issue from the patient's perspective.
From the founder of Big E Toys. "The Future of Board Games" is as you might expect, an exploration of the future of board games. In what direction are we headed and why? What will we be playing? How will we interact? What will games look like in the future? Two men were chatting outside the Minneapolis public library the other day, discussing the upside of unemployment. “I’m spending more time with my family, and we’re just hanging out —doing old-fashioned stuff like playing board games and cards.” His unmarried friend was incredulous. “Well, you don’t need a ruined economy to do that!” But it seemed to me the bachelor was missing the point, and the family man was reading my mind: “Losing my job made me rewrite my whole budget, which made me realize that working hard in order to spend hard meant a lot of sacrifices. For what? Less time, more junk, deeper debt.” The bachelor thought a moment, and then said, “Dude, it’s people like you who are making the recession longer and harder for everyone.” The bachelor might have been correct from a macroeconomic point of view — economists call it the paradox of thrift: The less consumers spend, the longer the recovery. But who could blame the family man for looking out for number one? Consumers of every income level are realizing that getting tougher on the budget has a lot of upside. They get their finances in order, build on a more solid economic foundation for the future and, yes, recommit to core beliefs without the distractions of debt-driven consumerism. Will that delay recovery? Yes. But when recovery comes, we’ll not likely see another Great Recession in our lifetimes.
- 3*t**2 + 6*t**2 - 2*t - 1. Let r be f(-1). Suppose 0 = -3*m + 8*m - r. Sort -3, m, 0 in descending order. m, 0, -3 Suppose 0 = 2*p + p + 6. Let o be p + 1 - (-2)/3. Put 0, o, -4 in ascending order. -4, o, 0 Let v = 8 + -3. Let u(f) = -f**3 + 6*f**2 - 5*f - 2. Let a be u(v). Sort -1, a, 0 in descending order. 0, -1, a Let g = 3 - 9. Put g, -5, 1 in increasing order. g, -5, 1 Let n = -4 - -3. Let l = -1.1 - n. Let h = l - 0. Sort 2/5, -5, h. -5, h, 2/5 Let a = 77.9 - 74. Let s = -4 + a. Put -3, s, -4/5 in decreasing order. s, -4/5, -3 Suppose 0 = p + 3 - 0. Sort -1, p, 0 in descending order. 0, -1, p Let u(t) = -t**2 - t - 1. Let o be u(-1). Suppose 4*b = 5*d - 23, -2*d + 29*b + 12 = 26*b. Sort d, -2, o. -2, o, d Let t be 1 + -3 - 50/(-2). Sort 1, -1, t in descending order. t, 1, -1 Let m(j) = -j**2 + 2*j - 3. Let g be m(3). Suppose -3*c - c = 5*v - 26, c - 4 = 0. Let k = g + v. Put k, 2, -3 in decreasing order. 2, -3, k Suppose -4*s = -3*y - y + 16, -4*y + 12 = 0. Put 5, s, 2, -2 in descending order. 5, 2, s, -2 Suppose -2*r - 20 = 2*r. Sort 5, 3, r in ascending order. r, 3, 5 Let h = 42.5 - 31. Let b = h - 12. Sort 3, 4, b in increasing order. b, 3, 4 Suppose 5*z + 6 = 31. Sort -3, -1, z in descending order. z, -1, -3 Let a = 0.04 + -2.04. Suppose q + 6 = -5*n, 2*q - 4 = -2*n + 8. Let l be (-58)/(-18) - 2/q. Put l, -5, a in increasing order. -5, a, l Let p = -3.06 - -0.06. Let w = 0 - -1. Let o be (-8)/56*(1 - 0). Sort p, w, o in descending order. w, o, p Let h = -20863/259 - 228/37. Let u = h + 87. Let r = -0.8 - 0.2. Sort u, -5, r in ascending order. -5, r, u Let j = 65/187 - 9/17. Put j, -5, 3/2 in increasing order. -5, j, 3/2 Let m be -5 + 102/8 + -2 - 5. Let l = 2 - 3.3. Sort 2/7, m, l in decreasing order. m, 2/7, l Suppose 0 = -5*v + 6 + 9. Sort 0, v, 4 in increasing order. 0, v, 4 Suppose -11 = -2*z + 3*c, c = -z - c + 2. Put -0.2, 1, z in increasing order. -0.2, 1, z Let u(z) = -15*z - 40. Let c be u(-3). Put c, -5, -3, 2 in ascending order. -5, -3, 2, c Let i = -38.2 - -38. Sort -0.05, i, -3 in descending order. -0.05, i, -3 Let r = -5 + 2. Suppose 2*n + 3 = -1, -5*n - 13 = -h. Sort h, r, 1. r, 1, h Let y = -0.12 + -14.88. Let g = 20 + y. Put 0.4, g, 1 in ascending order. 0.4, 1, g Let w be 9/6*8/3. Suppose 3*s - d - 38 = 0, 2*s + w*d - d - 40 = 0. Suppose 0 = 5*q - 4 + s. Put 2, q, -3 in increasing order. -3, q, 2 Suppose q - 4*f = -20, -5*f = -2 - 18. Let a = 8 + q. Suppose 5 = -a*o - 5*k, 2*k = o + k + 8. Put -3, -4, o in ascending order. o, -4, -3 Let t = 0.26 - -0.14. Sort -5/2, 2, t in descending order. 2, t, -5/2 Let j be (4/(-10))/((-3)/90). Suppose 2*m - 8 = -2*m - 2*n, 5*m + 3*n = j. Suppose -1 = y - 2. Sort 2, y, m in descending order. 2, y, m Let n = -0.033 - -0.333. Sort n, -2/11, 77. -2/11, n, 77 Let j = -41 - -40.67. Let m = 0.13 + j. Put 1, m, -0.1 in descending order. 1, -0.1, m Let j = -3 + 5. Let c be (1 - 2)*(10 + -8). Let v be (c - -1)/((-1)/(-1)). Sort v, 3, j in descending order. 3, j, v Let p = -21 + 20. Sort -2/13, -2, p. -2, p, -2/13 Let l = -55.06 - -55. Sort l, 4, 1. l, 1, 4 Let j = 23.1 + -22. Let w = 43 + -42.3. Let l = w - j. Sort 2/9, -1, l. -1, l, 2/9 Suppose 4*a - a = -0*a. Let x(n) = n**2 - n. Let r be x(0). Let c = r + -1. Put a, c, 2 in descending order. 2, a, c Let w = -4 - -8. Suppose 0 = 5*i - 3*u + 29, 16 = -w*i + 3*i + 4*u. Let q be i/(-22) - (-43)/(-55). Sort -0.3, q, -5. -5, q, -0.3 Let s(t) = -t + t + 1 - t. Let u be s(-4). Suppose 0 = -2*o + 7 - u. Sort -5, 5, o. -5, o, 5 Suppose 2*u + 2 = 4*a - 0*a, -2*u + 12 = 3*a. Suppose a + 18 = 5*m. Sort m, -5, 0. -5, 0, m Let v = -3 - -2. Let i(s) = s**2 - 7*s - 12. Let z be i(9). Let c = z + v. Put c, 1, 3 in descending order. c, 3, 1 Let l(g) = -2*g + 6. Let h be l(8). Sort -3, -4, h in increasing order. h, -4, -3 Let o = -17.5 + 18. Sort -1, o, 8. -1, o, 8 Let t be -2*4/20*(-6)/(-4). Sort t, -5, 3 in ascending order. -5, t, 3 Let q(h) = -4*h - 2. Let z be q(5). Let j be ((-3)/12)/(15/(-1300)). Let f = z + j. Put f, -2/3, 2/13 in ascending order. -2/3, f, 2/13 Let g = 0.8 + -0.4. Let r = -5 + 8. Let h = r - 3.2. Put h, g, 0 in ascending order. h, 0, g Let q be (6/4)/(57/(-152)). Put 3, -5, -7, q in descending order. 3, q, -5, -7 Let z = 2.03 - 2. Let d = -1.08 - -1.51. Let o = d - z. Sort o, 1, 0.1 in increasing order. 0.1, o, 1 Let m be (18/3 + -2)/2. Suppose -10 = 3*w + 2*s + 15, -m*w = -3*s - 5. Let v be (-2)/15*(-15)/(-12). Sort w, 0.3, v in decreasing order. 0.3, v, w Let y(h) = -2*h**2 + 7*h - 6. Let u be y(3). Suppose 0 = -4*x + x. Sort x, 2, u. u, x, 2 Let i(r) = -r - 14. Let k be i(-9). Sort -3, 3/2, 0.3, k. k, -3, 0.3, 3/2 Suppose 4*f + 2*h - 24 = 0, -f + 5*h = -3*f + 4. Let b = f - 6. Let l be ((-5)/45)/(b/2). Sort 2, l, -0.2. l, -0.2, 2 Let w = -2 - -8. Let o = -1 + -1. Let g be 21/(-9) - o/w. Put g, 5, 4 in descending order. 5, 4, g Let s(j) = -j**2 - 9*j - 5. Let h be s(-8). Sort 0.4, h, 4, 5 in ascending order. 0.4, h, 4, 5 Let u(t) = t - 1. Let c be u(-3). Let o = -19 - -16. Put 5, c, o in decreasing order. 5, o, c Suppose 3*w = 1 - 10. Let h be (-5)/2*(-4)/5. Let p be h + ((-38)/8 - -2). Sort 0.1, p, w in descending order. 0.1, p, w Let y be -1*(0/1 + -3). Let m(a) = a + 1. Let g be m(4). Suppose -2*q = 10 - 2. Sort y, q, g in descending order. g, y, q Let o be (-6)/14 - 45/(-7). Sort 1, o, 5 in descending order. o, 5, 1 Let k = -6 - -24. Let j = 14 - k. Sort 0.1, j, 1/3 in descending order. 1/3, 0.1, j Let l(v) = v**3 + v**2 - 4*v + 1. Let g be l(-3). Sort 0, g, 6, -1. g, -1, 0, 6 Let m = 2.018 + -0.018. Sort -4, m, -0.5, -5 in descending order. m, -0.5, -4, -5 Suppose -3*x = -0*x - 4*j + 27, 4*x - 2*j + 26 = 0. Suppose -l - 3*l + 19 = -t, -2*t + 3*l = 18. Sort x, -1, t. x, t, -1 Suppose 3*w - 4*r - 3 - 4 = 0, -w + 4*r + 13 = 0. Sort 3, 0, w in decreasing order. 3, 0, w Suppose -t + 2*b = -10, -4*t - 5*b + 1 = -0*b. Suppose -16 = t*w + 4. Let h = 0.115 + 0.885. Put 0.3, h, w in decreasing order. h, 0.3, w Let m = 2 - 1. Let f = 0.7 - m. Suppose -17*z = -35 + 69. Put z, f, 4 in descending order. 4, f, z Suppose -9 = -8*y - 97. Sort -5, 2, 1, y in decreasing order. 2, 1, -5, y Let g be (2 - -6)*(-2)/4. Let h(f) = f**3 + 4*f**2 + 4*f + 3. Let a be h(-3). Sort g, 3, a in decreasing order. 3, a, g Let w(s) = 9*s**2 - s. Let h be w(1). Let k(u) = u - 3. Let o be k(h). Suppose 3*n + 2*l = -l + 15, 0 = -5*n - l + o. Put -1, n, 3 in decreasing order. 3, n, -1 Suppose 2*m - 8 = -2*x + x, m + 14 = 4*x. Suppose x*b + b = -20. Sort -3, b, -5 in ascending order. -5, b, -3 Suppose -3*v + 5*q + 53 = 0, 3*v - 30 = v - 2*q. Let b be (-2)/(-8) - 1060/v. Let s be (-3)/(b/(-8)*2). Sort s, 4, 3 in descending order. 4, 3, s Let k = 9 + -6. Suppose 30 = -k*y + t - 0*t, 2*y + 15 = -t. Let q be 1/(-2) - y/162. Sort -0.2, -0.3, q in decreasing order. -0.2, -0.3, q Suppose 10*b - 5*b - 10 = 0. Put b, -4, -5 in descending order. b, -4, -5 Suppose -w + 0 = -3. Suppose 0 = 2*j + j + 12. Sort j, -5, w. -5, j, w Let h = -33/2 + 17. Let g = 8/11 + -97/88. Sort 3/2, h, g in descending order. 3/2, h, g Let j = 24 - 23.89. Let y = j - 4.11. Sort y, -2/7, -0.3. y, -0.3, -2/7 Let o be -5 - ((-1 - -1) + -2). Let u(i) = -i**3 + 16*i**2 - 15*i - 6. Let x be u(15). Sort 4, x, o in decreasing order. 4, o, x Let p be -4*(-2 + 1)/18. Sort 3, -2, p in descending order. 3, p, -2 Suppose 3*r = -5*m + 29, 5*r - 38 = -2*m + 4*m. Let n be 2/8 - 26/r. Let u(f) = -2*f**3 + 13*f**2 + 7*f + 5. Let z be u(7). Sort 4, z, n in decreasing order. z, 4, n Let g(z) = 62*z**2 - 3*z. Let p be g(-1). Sort -5, -2, -3, p in ascending order. -5, -3, -2, p Suppose -3*q = -1 - 14. Suppose -q = k, -2*a + 2 = -k - 1. Suppose -5*x - 10 = -10*x. Put a, 1, x in decreasing order. x, 1, a Let z be (-15)/10*4/45. Put -3, z, 3/7 in increasing order. -3, z, 3/7 Let a = 11 + -13. Let p = 3 + a. Sort p, -3, -5 in increasing order. -5, -3, p Suppose m = -5*y + 23, 2*m = -5*y - 12 + 33. Let v be ((-6)/(-10))/((-2)/(-10)). Put m, v, -4 in descending order. v, m, -4 Let s = 188 + -191. Suppose 3*y - 3 + 0 = 0. Sort y, 4, s in increasing order. s, y, 4 Let l be -6 + 1 + -2 + 2. Let y = -7 - -7. Sort -2, l, y in descending order. y, -2, l Let l = -265/4 - -65. Let i = -83/4 + 21. Put i, l, 2/5 in descending or
Game Review – Monster Hunter Stories (3DS) Slipping under everyone’s radar, comes this little JRPG that turn out to be one of the best games I’ve played this year. I know everyone is going crazy over the newest Pokemon, but Monster Hunter Stories may be just as good, or maybe even better! 4 responses to “Game Review – Monster Hunter Stories (3DS)” This was a great review! It points out just how great Monster Hunter Stories really is, and I’m still hoping Capcom and Nintendo will do something to ensure this one gets launched in the West (due to the anime being licensed by Funimation here). It really looks like the sort of JRPG that we’ve been missing for so long now since the Vita launched a whole new wave of more fanservicey JRPGs. And while I have nothing against those games (a few are sitting as titles I’m eager to get my hands on when they release here next year), it’s nice to see something that just oozes what made JRPGs appealing for me as a child (and an adult) so present in such a nice package – and bonus points for it not being a remake of a classic title.
// // PLSettingsView.h // PLMediaStreamingKitDemo // // Created by 冯文秀 on 2020/6/9. // Copyright © 2020 Pili. All rights reserved. // #import <UIKit/UIKit.h> NS_ASSUME_NONNULL_BEGIN typedef enum { PLStreamTypeAll = 0, // 音视频 PLStreamTypeAudioOnly = 1, // 纯音频 PLStreamTypeImport = 2, // 外部导入 PLStreamTypeScreen = 3, // 录屏 } PLStreamType; @class PLSettingsView; @protocol PLSettingsViewDelegate <NSObject> @optional - (void)settingsView:(PLSettingsView *)settingsView didChangedSession:(PLMediaStreamingSession *)mediaSession streamSession:(PLStreamingSession *)streamSession ; @end @interface PLSettingsView : UIView @property (nonatomic, assign) id<PLSettingsViewDelegate> delegate; // URL 输入框 @property (nonatomic, strong) UITextField *urlTextField; // 流类型 @property (nonatomic, assign) PLStreamType streamType; // 列表 view 的父视图 @property (nonatomic, strong) UIView *listSuperView; - (id)initWithFrame:(CGRect)frame mediaSession:(PLMediaStreamingSession *)mediaSession streamSession:(PLStreamingSession *)streamSession pushURL:(NSString *)pushURL; @end NS_ASSUME_NONNULL_END
package com.baidu.dsp.common.constant; /** * @author liaoqiqi * @version 2013-12-2 */ public enum ModuleCode { OTHER(0, "Other"), REMOTE(3, "Remote"), EXCEPTION(5, "EXCEPTION"), FILE(6, "FILEUPLOAD"); ; private int code = 0; private String modelName = null; private ModuleCode(int code, String modelName) { this.code = code; this.modelName = modelName; } public int getCode() { return code; } public String getModelName() { return modelName; } }
The Possible Role of Nitric Oxide Pathway in Pentylenetetrazole Preconditioning Against Seizure in Mice. Preconditioning is defined as an induction of adaptive response in organs against lethal stimulation provoked by subsequent mild sublethal stress. Several chemical agents have been demonstrated to cause brain tolerance through preconditioning. The aim of the present study is to test the hypothesis that preconditioning with pentylenetetrazole (PTZ) may have protective effect against seizure induced by i.v. infusion of PTZ. Mice were preconditioned by low-dose administration of PTZ (25 mg/kg) for 5 consecutive days, and the threshold of seizure elicited by i.v. infusion of PTZ was measured. To investigate the possible role of nitric oxide, NOS inhibitor enzymes, including L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) (10 mg/kg), aminoguanidine (AG) (50 mg/kg), 7-nitroindazole (7-NI) (15 mg/kg), and L-arginine (L-arg) (60 mg/kg), were administered concomitantly with PTZ in both acute and chronic phases. Determination of seizure threshold revealed significant enhancement after preconditioning with low dose of PTZ. While the protective effect of PTZ preconditioning was enhanced after the administration of L-arg, it was reversed following administration of L-NAME and 7NI, suggesting the involvement of nitric oxide pathway as an underlying mechanism of PTZ-induced preconditioning. Preconditioning with PTZ led to brain tolerance and adaptive response in animal model of PTZ-induced seizure. This effect is in part due to the involvement of nitric oxide pathway.
Challenges of developing a bioanalytical method for a macrolide immunosuppressant compound by LC-MS/MS. The quantification of tacrolimus in human whole blood was developed by LC-MS/MS for a range of 50.0 to 50,000.0 pg/ml. Different challenges were faced during method development due to ion-suppression, lack of sensitivity and low recovery. The optimization of the extraction procedure played a crucial role as tacrolimus had to be isolated from red blood cells, to which it is strongly bound. Another particular challenge arose from the freeze-thaw stability where the extracted samples from fresh blood always showed a lower recovery. Finally, matrix effect was observed in some matrices over time, which resulted in a failed long-term stability in whole blood. In order to resolve the matrix effect issue, the sample procedure had to be improved. The final assay showed good recovery, low matrix effect, linearity, blood stability and good precision and accuracy.
USING: accessors assocs globs io.pathnames kernel memoize namespaces regexp sequences sorting splitting strings unicode xml xml.data xml.syntax xml.traversal xmode.loader xmode.rules xmode.utilities ; IN: xmode.catalog TUPLE: mode file file-name-glob first-line-glob ; TAGS: parse-mode-tag ( modes tag -- ) TAG: MODE parse-mode-tag dup "NAME" attr [ mode new { { "FILE" f file<< } { "FILE_NAME_GLOB" f file-name-glob<< } { "FIRST_LINE_GLOB" f first-line-glob<< } } init-from-tag [ [ >case-fold <glob> ] [ f ] if* ] change-file-name-glob [ [ >case-fold <glob> ] [ f ] if* ] change-first-line-glob ] dip rot set-at ; : parse-modes-tag ( tag -- modes ) H{ } clone [ swap children-tags [ parse-mode-tag ] with each ] keep ; MEMO: modes ( -- modes ) "vocab:xmode/modes/catalog" file>xml parse-modes-tag ; MEMO: mode-names ( -- modes ) modes keys natural-sort ; : reset-catalog ( -- ) \ modes reset-memoized ; MEMO: (load-mode) ( name -- rule-sets ) modes at [ file>> "vocab:xmode/modes/" prepend parse-mode ] [ "text" (load-mode) ] if* ; SYMBOL: rule-sets : no-such-rule-set ( name -- * ) "No such rule set: " prepend throw ; : get-rule-set ( name -- rule-sets rules ) dup "::" split1 [ swap (load-mode) ] [ rule-sets get ] if* [ at* [ nip ] [ drop no-such-rule-set ] if ] keep swap ; DEFER: finalize-rule-set : resolve-delegate ( rule -- ) dup delegate>> dup string? [ get-rule-set dup rule-set? [ "not a rule set" throw ] unless swap rule-sets [ dup finalize-rule-set ] with-variable >>delegate drop ] [ 2drop ] if ; : each-rule ( rule-set quot -- ) [ rules>> values concat ] dip each ; inline : resolve-delegates ( ruleset -- ) [ resolve-delegate ] each-rule ; : ?update ( keyword-map/f keyword-map -- keyword-map ) over [ assoc-union! ] [ nip clone ] if ; : import-keywords ( parent child -- ) over [ [ keywords>> ] bi@ ?update ] dip keywords<< ; : import-rules ( parent child -- ) swap [ add-rule ] curry each-rule ; : resolve-imports ( ruleset -- ) dup imports>> [ get-rule-set swap rule-sets [ [ nip resolve-delegates ] [ import-keywords ] [ import-rules ] 2tri ] with-variable ] with each ; : finalize-rule-set ( ruleset -- ) dup finalized?>> [ drop ] [ t >>finalized? [ resolve-imports ] [ resolve-delegates ] bi ] if ; : finalize-mode ( rulesets -- ) dup rule-sets [ [ nip finalize-rule-set ] assoc-each ] with-variable ; : load-mode ( name -- rule-sets ) (load-mode) dup finalize-mode ; : reset-modes ( -- ) \ (load-mode) reset-memoized ; : ?matches ( string glob/f -- ? ) [ >case-fold ] dip dup [ matches? ] [ 2drop f ] if ; : suitable-mode? ( file-name first-line mode -- ? ) [ nip ] 2keep first-line-glob>> ?matches [ 2drop t ] [ file-name-glob>> ?matches ] if ; : ?find-mode ( file-name first-line -- mode/f ) [ file-name ] dip modes [ nip [ 2dup ] dip suitable-mode? ] assoc-find 2drop 2nip ; : find-mode ( file-name first-line -- mode ) ?find-mode "text" or ; inline
Revised standards for sterilisation: the changes. The standards for the three main methods of sterilising medical devices, ethylene oxide, radiation and moist heat, have been revised. This article discusses the major changes in the requirements, which will need to be addressed to demonstrate compliance with the revised standards.
Yana Novikova Yana Novikova is an actor from Belarus who stars in the critically-acclaimed Ukranian film The Tribe, which won the 2014 International Critics’ Week Award at Cannes. The Tribe boasts a cast of deaf actors, most newcomers to film like Novikova.
145 Ill. App.3d 1070 (1986) 496 N.E.2d 755 LINDA BRANDON, Ex'r of the Estate of Faye Caisse, Deceased, Plaintiff-Appellee, v. ARMAND ROBERT CAISSE, Defendant-Appellant. No. 85-0468. Illinois Appellate Court — Second District. Opinion filed August 11, 1986. George P. Lindner and Jon Yambert, both of Lindner, Speers & Reuland, P.C., of Aurora, for appellant. Richard H. Balog, of St. Charles, for appellee. Judgment reversed. JUSTICE STROUSE delivered the opinion of the court: This action was brought by Faye Caisse to dissolve her marriage to Armand Caisse. At the close of the evidence and before final judgment, Faye died. Thereafter, Linda Brandon, executor of Faye's estate, *1071 was substituted for her. Armand motioned to dismiss on the basis that the proceedings abated since a judgment of dissolution had not been entered. The motion was denied, and approximately two months after Faye's death, the trial judge entered a judgment of dissolution of marriage and distribution of property. Faye and Armand were married on September 12, 1970, and had two children: Dustin Daniel and Autumn. The children were ages 5 and 12, respectively, at the time Faye filed a petition for dissolution of marriage on July 1, 1983. The dissolution hearing was held on March 23, 1984. Following the proof, the trial judge asked Armand, "[A]lthough you may not agree with those grounds, is it true you are not contesting the grounds issue? You are not contesting the grounds for dissolution? * * * Mental cruelty." Armand answered, "I'm not contesting." The trial judge then stated: "Alright. I'll find that the testimony is sufficient to establish the grounds of mental cruelty." A formal written order finding as a fact that grounds for dissolution were proved was entered. However, no minute order, docket entry, or order of dissolution was entered before trial on the remaining issues. Trial on the remaining issues covered four days of testimony: August 30, 1984, September 19, 1984, September 25, 1984, and September 26, 1984. Final arguments were made on October 1 and 5, 1984. Faye died on October 8, 1984. Armand filed a motion to dismiss because the proceedings abated before judgment for dissolution had been entered. A hearing on Armand's motion was held on October 29, 1984. The trial judge agreed that a judgment had not yet been entered. The judge, however, denied the motion based on In re Marriage of Davies (1983), 95 Ill.2d 474. The trial judge determined that his previous finding that grounds existed would be construed as a judgment. A judgment for dissolution was thereafter entered on December 17, 1984, along with the distribution of property. The trial judge awarded Faye's estate all personal property that had been in her possession, including the household furnishings, without fixing a value to these items. Fixed assets awarded to the estate included the marital residence, the car, all bank accounts, loans receivable and retirement plans with the exception of $1,392.59. The trial judge awarded all business-related assets, the motorcycle, the pickup truck, and the worker's compensation award of $18,600 to Armand. The custody of the children was awarded to Armand. Armand's post-trial motion was denied, and this appeal followed. Armand contends on appeal that since a judgment of dissolution *1072 had not been entered before Faye's death, the proceedings for dissolution abated. The estate maintains, citing Tunnell v. Edwardsville Intelligencer, Inc. (1969), 43 Ill.2d 239, and In re Marriage of Davies (1983), 95 Ill.2d 474, that although there was never a formal judgment of dissolution entered the litigation was ripe for judgment. • 1 Generally, death of a party during the course of a divorce proceeding has been held to abate the action. (In re Marriage of Davies (1983), 95 Ill.2d 474, 478; In re Estate of Chandler (1980), 90 Ill. App.3d 674, 677.) The supreme court has held, however, that there is no abatement upon the prejudgment death of a party to a nonsurviving action if the litigation is ripe for judgment. In re Marriage of Davies (1983), 95 Ill.2d 474, 480; Tunnell v. Edwardsville Intelligencer, Inc. (1969), 43 Ill.2d 239, 242-43. In Tunnell, the supreme court held that where the trial court, in a libel action, set aside the jury's award of punitive damages, and plaintiff died subsequent to filing a notice of appeal, the case was ripe for judgment when plaintiff died. (Tunnell v. Edwardsville Intelligencer, Inc. (1969), 43 Ill.2d 239, 243-44.) The court stated that even as to actions which do not survive there is no abatement upon the death of a party if the litigation has progressed to a point at which the merits of plaintiff's allegations have been affirmatively determined. (43 Ill.2d 239, 242.) The court noted that a case becomes ripe for judgment following the return of a verdict. 43 Ill.2d 239, 242. In Davies, the trial court, which elected to proceed in a bifurcated marriage dissolution action, entered a judgment dissolving the marriage and expressly providing that marital-property rights and related matters would be resolved after a separate hearing. After conducting a hearing, the trial court issued an opinion letter dividing the marital property and directing plaintiff's attorney to prepare a judgment order conforming with the terms. Before the order was entered, plaintiff died. (In re Marriage of Davies (1983), 95 Ill.2d 474, 475-76.) The supreme court held that if a jury verdict is a sufficiently final resolution of the factual questions to preclude abatement of the action upon the death of a party, a judge's opinion letter must be given the same effect. Accordingly, the litigation was considered ripe for judgment. 95 Ill.2d 474, 480. Following the Davies decision, the legislature amended section 401(3), effective September 9, 1983, to provide that the death of a party following a bifurcated judgment of dissolution but before remaining issues are resolved does not abate the proceedings. (Ill. Rev. Stat. 1983, ch. 40, par. 401(3).) Section 401(3) of the Illinois Marriage and Dissolution of Marriage Act (Act) provides, in relevant part: *1073 "The death of a party subsequent to entry of a judgment for dissolution but before judgment on reserved issues shall not abate the proceedings." (Emphasis added.) Ill. Rev. Stat. 1983, ch. 40, par. 401(3). • 2 In construing a statute, it is fundamental that the judicial role is to ascertain the intent of the legislature and give it effect. (City of Springfield v. Board of Election Commissioners (1985), 105 Ill.2d 336, 340-41.) In ascertaining the intent of the legislature, it is proper for the court not only to consider the language employed by the legislature, but also to look to the reason and necessity for the law, the evils to be remedied, and the objects and purposes to be obtained. People v. Steppan (1985), 105 Ill.2d 310, 316. • 3 It is presumed that the legislature acted with full knowledge of the judicial decisions concerning prior and existing law and legislation. (Kozak v. Retirement Board (1981), 99 Ill. App.3d 1015, 1018.) It is also presumed that where the statute was enacted after judicial opinions on the matter, the legislature acted with knowledge of the prevailing case law. (People v. Jones (1985), 134 Ill. App.3d 1048, 1052.) Despite the language of the court in Davies, the legislature used the words "entry of a judgment for dissolution" rather than "ripe for judgment of dissolution." We interpret our legislature's failure to do so as an indication that a judgment for dissolution must be entered. Further, Supreme Court Rule 272 defines when a judgment is entered. (87 Ill.2d R. 272.) If a judgment is announced orally but requires a written order, it is entered as a judgment only when the signed order is filed, if it is an oral pronouncement, it is entered when the clerk makes the docket entry of record. In this case no judgment of dissolution was entered until two months after Faye's death. • 4 Considering the narrow holding of both Tunnell and Davies, the legislature's intent in amending the Act, and Rule 272, which defines entry of a judgment, we hold that in this case, the cause of action abated on Faye's death. The judgment of the trial court is, therefore, reversed. Reversed. NASH, P.J., and LINDBERG, J., concur.
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--- abstract: 'We investigate the competition between superconductivity and nematic order in $d$-wave high-$T_c$ superconductor. Apart from the competitive interaction with superconducting order, the nematic order also couples strongly to gapless nodal quasiparticles. The interplay of these two interactions is analyzed by means of renormalization group method. An interesting consequence of ordering competition is the appearance of runaway behavior for some specific parameters, which implies an instability of first order transition. We show that the ratio between gap velocity and Fermi velocity, $\kappa = v_\Delta/v_F$, of nodal quasiparticles plays a crucial role in determining the fixed point of the system. As $\kappa$ decreases, the possibility of first order transition is enhanced. At the nematic critical point where $\kappa \rightarrow 0$ driven by the critical nematic fluctuation, no stable fixed point exists and first order transition becomes inevitable. Our results indicate that gapless fermionic degrees of freedom should be taken into account in the theoretical description of competing orders.' author: - Jing Wang - 'Guo-Zhu Liu' title: 'Competition between superconductivity and nematic order in high-$T_c$ superconductor' --- Introduction ============ Unconventional superconductors usually refer to the superconductors those can not be understood within the conventional Bardeen-Cooper-Schrieffer (BCS) theory. Notable examples of unconventional superconductors include high-$T_c$ cuprate superconductor, heavy fermion superconductor, and iron-based superconductor. Unlike BCS superconductors, unconventional superconductivity is generally driven by electron-electron interactions, and often has a magnetic origin. Another interesting property of unconventional superconductor is that its ground state is not unique. In addition to the defining superconducting state, unconventional superconductors also exhibit a variety of other symmetry-broken ground states, including antiferromagnetc, nematic, and stripe states, upon tuning such parameters as doping and pressure [@Kivelson03; @Vojta; @Fradkin; @heavyfermion; @Flouquet]. A widely recognized notion is that the long-range superconducting order competes, and under certain circumstances coexists, with other long-range orders. The competition and possible coexistence between different orders can give rise to rich properties, and hence have attracted intense theoretical and experimental interest in the past years. The successful microscopic theory of competing orders has not yet been established to date, primarily because the pairing mechanism in most unconventional superconductors is still undetermined. A realistic and commonly used strategy is to build low-energy effective field theory on phenomenological grounds. One can first write down the Ginzburg-Landau (GL) actions for two bosonic order parameters and then introduce certain coupling terms between these two scalar fields. Such generalized GL model has recently been applied to describe competing orders in a number of unconventional superconductors [@Arovas; @Kivelson02; @Demler; @Moon; @Zaanen; @Nussinov; @Millis10; @Chubukov; @Chowdhury; @Schmalian]. An early success of such theoretical investigation is the prediction of field-induced antiferromagnetic core in the supercondcuting vortices of high-$T_c$ superconductors [@Arovas]. This prediction was subsequently confirmed in experiments [@Lake1; @Lake2]. Interestingly, experiments further found that the antiferromagnetic order not only exists in the vortex cores, but also extends into the superconducting region [@Lake1] and exhibits nontrivial spatial modulation [@Lake2; @Hoffman]. A phenomenological field theory that contains a simple quadratic-quadratic coupling term between superconducting and antiferromagnetic order parameters was put forward to understand these new findings [@Demler; @Kivelson02]. Recently, the issue of competing orders has attracted revived interest. It is found that the competitive interaction between distinct orders can drive an instability, which gives rise to a general tendency of first order transition [@Zaanen; @Millis10]. This phenomenon may account for the first order transition observed in some unconventional superconductors [@heavyfermion]. In addition, nonuniform glassy electronic phases and Brazovskii type transitions are predicted to emerge due to competition between two long-range orders [@Nussinov]. Another interesting observation is that the competition between superconducting and antiferromagnetic orders can help to judge the gap symmetry of iron-based superconductors [@Chubukov; @Schmalian]. Furthermore, the competition between superconducting and nematic orders might be responsible for [@Chowdhury] the electronic anisotropy observed in the vortex state of FeSe superconductor [@Xue]. The effective field theory adopted in previous analysis of competing orders normally contains only two bosonic order parameters. The fermionic degrees of freedom are usually completely integrated out in the spirit of Hertz-Millis-Moriya (HMM) theory [@Hertz; @Millis; @Moriya]. This integration procedure is expected to be applicable in systems that do not contain gapless fermionic excitations. For instance, the iron-based superconductors seem to have a $s$-wave energy gap, so the electronic excitations are fully gapped and can be safely integrated out [@Chubukov; @Schmalian]. However, such integration manipulation is not always valid. Indeed, its validity has recently been questioned in several itinerant electron systems [@Belitz; @Abanov; @Rech; @Metzner]. In the systems that exhibit gapless fermionic excitations, integrating out fermions may lead to singularities, especially in the vicinity of quantum critical point (QCP). Actually, infrared singularities have been found on the border of several quantum phase transitions [@Belitz; @Rech; @Abanov; @Metzner]. In order to properly describe the quantum critical behavior in these systems, it is more appropriate to maintain both bosonic order parameter and gapless fermions in the effective theory. When a long-range order competing with superconductivity also couples to gapless fermions, it would be interesting to go beyond HMM theory and examine the role of gapless fermions. Recent analysis presented in Refs. [@Moon; @Liu] did suggest nontrivial roles played by gapless fermions. ![Schematic phase diagram on $(x,T)$-plane of high-$T_c$ superconductors. $x$ represents doping concentration. $x_1$ and $x_2$ are QCPs of superconducting and nematic phase transitions, repectively.[]{data-label="Fig_coexist"}](coexist.eps){width="3in"} In various superconductors, superconductivity compete with several possible orders. To examine the role of fermions, we wish to study a prototypical model which describes competition between two distinct long-range orders, contains gapless fermions, and in the meantime is technically controllable. In this paper, we choose to consider competition between superconductivity and nematic order in the contexts of high-$T_c$ superconductors. In recent years, there has been increasing experimental evidence pointing towards the existence of an electronic nematic phase in some high-$T_c$ superconductors [@Kivelson03; @Fradkin; @Vojta; @Ando; @Hinkov; @Daou; @Lawler], especially YBa$_2$Cu$_3$O$_{6+\delta}$ and Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$. According to these experiments, a nematic order is predicted to compete and coexist with superconductivity, which is schematically plotted in Fig. 1. The nematic phase transition and the coupling of nematic fluctuation with fermionic degrees of freedom have stimulated intense research efforts [@Kivelson03; @Fradkin; @Vojta; @Kivelson; @VojtaSachdev; @Metznernematic; @Oganesyan; @Kim; @Huh; @Xu; @Fritz; @Lawler2; @WLK; @Liu]. From a field-theoretic viewpoint, the nematic order parameter is a simple real scalar field and does not carry finite wave vector, which substantially simplifies theoretical calculations. It is known that high-$T_c$ superconductor has a $d_{x^2 - y^2}$ energy gap, which vanishes at four nodes, $\left(\pm\frac{\pi}{2}, \pm\frac{\pi}{2}\right)$. Therefore, gapless nodal quasiparticles (qps) are present even at the lowest energy in the superconducting phase. These nodal qps are believed to be responsible for many anomalous low-temperature properties of the superconducting dome. When a nematic QCP exists somewhere in the superconducting dome, as shown in Fig. 1, the fluctuation of nematic order parameter will couple to these nodal qps. Such coupling can generate non-Fermi liquid behaviors and other unusual phenomena in the vicinity of nematic QCP [@Kim; @Huh; @Fritz; @Xu; @Lawler2; @WLK; @Liu]. It may also have significant effects on the interplay between superconductivity and nematic order, which is the topic of this paper. In the following, we first write down an effective field theory that describes both the competitive interaction between superconducting and nematic order parameters and the coupling between nematic order and nodal qps. We then perform a detailed renormalization group (RG) analysis [@Shankar94] within such effective theory. In particular, we drive and solve the RG flow equations of all the physical parameters in order to determine the possible stable fixed points. We show that the competitive interaction between superconducting and nematic order parameters still lead to first order transition after including gapless nodal qps. However, the nodal qps do have important impacts on the fixed-point structure. In particular, the velocity ratio $\kappa$ between gap velocity $v_{\Delta}$ and Fermi velocity $v_F$ of nodal qps turns out to be a crucial controlling parameter. The region that exhibits runaway behavior is greatly enlarged as $\kappa$ decreases, implying an enhanced possibility of first order transition. At the nematic QCP where $\kappa \rightarrow 0$ driven by the critical nematic fluctuation, the system does not have any stable fixed point, so first order transition occurs inevitably. These results clearly indicate the importance of including gapless fermions in the effective field theory of competing orders. In Sec. \[sec\_model\], we write down the effective action which contains two bosonic order parameters and gapless nodal qps. In Sec. \[sec\_RG\_analysis\], we make RG calculations and derive the flow equations for all parameters in the effective action. In Sec. \[sec\_numerical\_discussion\], we present numerical solutions of the flow equations and discuss the physical implications. The paper is ended in Sec. \[sec\_summary\] with summary and conclusion. Effective field theory of competing orders {#sec_model} ========================================== We first need to write down an effective field theory to describe the competition between superconducting and nematic orders. This will be done largely on phenomenological grounds. In the phase diagram presented in Fig. \[Fig\_coexist\], the horizonal axe is doping concentration $x$. The QCP of superconducting transition is $x_1$, which is roughly $x_1 \approx 0.05$ in many high-$T_c$ superconductors. The anticipated QCP for nematic transition is represented by $x_2$. So far, the precise value, and even the very existence, of $x_2$ have not yet been unambiguously determined. Here, we assume that $x_2$ is larger than $x_1$, which implies a bulk coexistence of superconducting and nematic orders. In the present system, there are three types of degrees of freedom: superconducting order parameter $\psi$, nematic order parameter $\phi$, and gapless nodal qps $\Psi$. The competition between superconducting and nematic orders can be described by a repulsive quadratic-quadratic coupling term, $\propto \psi^2 \phi^2$, which is widely adopted in the description of competing orders. In addition to this competitive interaction, the nematic order parameter $\phi$ also interacts with gapless nodal qps $\Psi$, which is usually described by a Yukawa-type coupling term. There is, however, no direct coupling between the superconducting order parameter and nodal qps. First, the nodal qps are excited from the $d_{x^2 - y^2}$ gap nodes where superconducting order parameter vanishes. Moreover, these qps are known to have a sharp peak and a very long lifetime in the superconducting dome in the absence of competing orders [@Orenstein00], so their coupling to $\psi$ must be quite weak. On the basis of the above qualitative analysis, we can write down the following partition function $$\begin{aligned} Z&=&\int \mathcal{D}\psi\mathcal{D}\phi \mathcal{D}\bar{\Psi} \mathcal{D}\Psi e^{S},\end{aligned}$$ where the effective action is $$\begin{aligned} S &=& S_{\psi} + S_{\phi} + S_{\Psi} + S_{\psi\phi} + S_{\Psi\phi},\label{Eq_action_total} \\ S_{\psi} &=& \frac{1}{2}\int \frac{d^3q}{(2\pi)^3}(-2\alpha+q^2) \psi^2 + \frac{\beta}{2} \int d^2\mathbf{r}d\tau\psi^{4}, \\ S_{\phi} &=& \frac{1}{2}\int \frac{d^3q}{(2\pi)^3}\left(-2r + q^2 \right)\phi^2 + \frac{u}{2} \int d^2\mathbf{r}d\tau\phi^{4},\label{Eq_S_phi}\\ S_{\Psi} &=& \int \frac{d^3k}{(2\pi)^3} [\Psi^{\dagger}_{1i}(-i\omega + v_{F}k_{x}\tau^{z} + v_{\Delta}k_{y}\tau^x)\Psi_{1i} \nonumber \\ && + \Psi^{\dagger}_{2i}(-i\omega + v_{F}k_{y}\tau^{z} + v_{\Delta}k_{x}\tau^{x})\Psi_{2i}], \\ S_{\psi\phi} &=& \gamma \int d^2xd\tau \psi^2 \phi^2,\\ S_{\Psi\phi} &=& \int d^2xd\tau [\lambda_0 \phi(\Psi^{\dagger}_{1 i} \tau^{x}\Psi_{1 i} + \Psi^{\dagger}_{2i} \tau^{x}\Psi_{2i})],\label{Eq_S_Psi_phi}\end{aligned}$$ where $\tau^{x,y,z}$ are Pauli matrices and the flavor index $i$ sums up $1$ to $N$. $\Psi^{\dagger}_{1}$ represents nodal QPs excited from $(\frac{\pi}{2},\frac{\pi}{2})$ and $(-\frac{\pi}{2},-\frac{\pi}{2})$ points, and $\Psi^{\dagger}_{2}$ the other two. The physical flavor of nodal qps, $N = 2$. Here, $r$ is tuning parameter for nematic transition with $r = 0$ at $x_2$. $v_{F,\Delta}$ are the Fermi velocity and gap velocity of nodal qps, respectively. The competitive interaction term $\psi^2 \phi^2$ has a positive coefficient, $\gamma > 0$. The propagators are shown in Fig. (\[propagators\]). In order to simplify calculations, it proves convenient to make two transformations [@Huh]: $\phi \rightarrow \phi/\lambda_0$, and $r\rightarrow \lambda_0^2 r$. It is now easy to rewrite Eq. (\[Eq\_S\_Psi\_phi\]) as $$\begin{aligned} S_{\Psi\phi} &=& \int d^2xd\tau \phi(\Psi^{\dagger}_{1 i}\tau^{x}\Psi_{1 i} + \Psi^{\dagger}_{2i} \tau^{x}\Psi_{2i}).\end{aligned}$$ ![(a): Free propagator of superconducting field $\psi$; (b): Free propagator of nematic field $\phi$; (c): Free propagator of nodal qps $\Psi$.[]{data-label="propagators"}](propagators.eps){width="3in"} The effective action represented by Eq. (2) was studied recently in Ref. [@Liu]. It was demonstrated that both superfluid density and critical temperature $T_c$ are significantly suppressed at nematic QCP $x_2$. However, the superconducting order parameter $\psi$ was assumed in Ref. [@Liu] to be classical, which is valid only when $x_2$ is not close to $x_1$. In this paper, we go beyond such approximation and consider the quantum fluctuations of both superconducting and nematic order parameters. As emphasized in Ref. [@Liu], the gapless nodal qps can have important impacts on the competition between superconductivity and nematic order. The simplest way to include the fermionic degrees of freedom is to introduce the polarization function $\Pi(q)$ due to nodal qps into the effective action of nematic order, $S_{\phi}$. To the leading order of $1/N$-expansion, the polarization function $\Pi(q)$ is represented by the one-loop Feynman diagram shown in Fig. \[Fig\_Pi\_Sigma\](a) and formally given by [@Huh; @WLK] $$\begin{aligned} \Pi(\epsilon,\mathbf{q}) = N\int\frac{d\omega d^{2}\mathbf{k}}{(2\pi)^3} \mathrm{Tr}[\tau^{x}G_{0}(\omega,\mathbf{k})\tau^{x} G_{0}(\omega+\epsilon,\mathbf{k+q})], \nonumber\end{aligned}$$ where $$\begin{aligned} G_0(\omega,\mathbf{k}) = \frac{1}{-i\omega + v_{F}k_x \tau^{z} + v_{\Delta}k_y \tau^{x}} \nonumber\end{aligned}$$ is the free propagator for nodal QPs $\Psi_1$ (free propagator for nodal QPs $\Psi_2$ can be similarly written down). The polarization function $\Pi(\epsilon,\mathbf{q})$ has already been calculated previously [@Huh; @Liu], and is known to have the form $$\begin{aligned} \Pi(\epsilon,\mathbf{q}) \!=\! \frac{N}{16v_F v_\Delta}\!\!\left[\!\frac{\epsilon^2 + v_F^2 q_x^2}{(\epsilon^2 + v_F^2 q_x^2 + v_{\Delta}^2 q_y^2)^{1/2}} \!+\! (q_x \!\leftrightarrow\! q_y)\!\right]\!\!.\end{aligned}$$ After including this term, the quadratic part of $S_{\phi}$ becomes $$\begin{aligned} \left(-2r+q^2\right)\phi^2 \rightarrow \left[-2r+ q^2 + \Pi(q) \right]\phi^2.\end{aligned}$$ From the expression of polarization $\Pi(q)$, it is easy to see that inclusion of $\Pi(q)$ does not change the dynamical exponent $z = 1$ of $\phi$. However, $\Pi(q) \propto q$, so it dominates over the kinetic term $q^2$ in the low energy regime. More importantly, the polarization $\Pi(q)$ introduces two important quantities, nodal qps’ Fermi velocity $v_F$ and gap velocity $v_{\Delta}$, into the effective action of $\phi$. Although the polarization $\Pi(q)$ represents the influence of nodal qps, we can not completely integrate the nodal qps out and drop them from the effective theory. These gapless nodal qps should be maintained for several reasons. First, according to the general spirit of RG, one can safely integrate out high-energy modes at low energies. However, the nodal qps are gapless and hence exist even at the lowest energy. Integrating out gapless fermions completely may lead to unphysical singularities. Second, the coupling of gapless fermions with order parameter fluctuation can lead to non-Fermi liquid behavior in observable quantities. In the specific case of nematic transition, the critical nematic fluctuation causes unusual fermion velocity renormalization and extreme anisotropy, which would be overlooked if gapless fermions are fully integrated out. As will be shown below, the velocity ratio $\kappa = v_{\Delta}/v_{F}$ play nontrivial roles. The effective field theory contains seven parameters: $\alpha, r, \beta, u, \gamma, v_F, v_\Delta$. They are all subjected to renormalizations due to the mutual interactions among three field operators: $\psi$, $\phi$, and $\Psi$. We will study the flow of these seven parameters under scaling transformations and eventually obtain seven RG equations. Since we study the $\psi$-$\phi$ interaction and $\Psi$-$\phi$ interaction on equal footings, these seven RG equations are self-consistently coupled to each other. The low-energy behaviors of these parameters and the possible fixed points of the effective field theory can be determined by solving these coupled RG equations. Renormalization group calculations {#sec_RG_analysis} ================================== In this section, we make a RG analysis and obtain the flow equations of all the aforementioned parameters. In order to examine the impacts of gapless nodal qps, we go beyond the HMM theory and maintain nodal qps throughout our calculations. We first analyze the coupling between nematic order and nodal qps, and derive the RG equations for fermion velocities, $v_{F,\Delta}$. We then consider the competitive interaction between superconducting and nematic order parameters, and obtain the RG equations for the rest five parameters, $(\alpha,r,\beta,u,\gamma)$, which depend on the fermion velocities, $v_{F,\Delta}$. These seven equations are self-consistently coupled to each other since $v_{F,\Delta}$ appearing in equations of $(\alpha,r,\beta,u,\gamma)$ flow according to their own equations. ![(a): Polarization function for nematic field $\phi$; (b): Fermion self-energy correction due to nematic fluctuation.[]{data-label="Fig_Pi_Sigma"}](Pi_Sigma.eps){width="3in"} Flow equations of $v_{F}$ and $v_{\Delta}$ ------------------------------------------ The Yukawa-type interaction between nematic order and gapless nodal qps has been recently investigated in several papers [@Kim; @Huh; @Xu; @Lawler2; @Fritz; @WLK; @Liu]. It is well-known that the Fermi velocity of nodal qps is not equal to the gap velocity, i.e., $v_{F} \neq v_{\Delta}$. Experiments [@Chiao; @Orenstein00] have determined that the velocity ratio $\kappa = v_{\Delta}/v_F \approx 0.1$. This ratio is a very important parameter since it enters into a number of observable quantities of high-$T_c$ superconductors, including electric conductivity [@Lee93; @Durst], thermal conductivity [@Durst], superfluid density [@Durst; @Lee97], and $T_c$ [@Lee97]. An interesting property revealed and discussed in Refs. [@Kim; @Huh; @Xu; @Lawler2; @Fritz; @WLK; @Liu] is that the velocity anisotropy is significantly enhanced by the nematic fluctuation. The calculation of nodal qps self-energy function and the derivation of flow equations have already been presented in previous publications [@Huh; @WLK], and therefore are not shown here. It is only necessary to summarize the basic calculations as well as the relevant results. To the leading order, the fermion self-energy is represented by the diagram Fig. \[Fig\_Pi\_Sigma\](b), and has the form $$\begin{aligned} \Sigma(\omega,\mathbf{k}) = \int \frac{d\epsilon d^2\mathbf{q}}{(2\pi)^3} G_0(\omega+\epsilon,\mathbf{k}+\mathbf{q})\frac{1}{q^2 + \Pi(q)}.\end{aligned}$$ As shown in Ref. [@Huh], it can be written as $$\begin{aligned} \frac{d\Sigma(\mathbf{k},\omega)}{d\ln\Lambda} = C_1(-i\omega) + C_2 v_F k_x \tau^z + C_3 v_{\Delta} k_y \tau^x,\end{aligned}$$ where $$\begin{aligned} C_1 &=& \frac{2(v_\Delta/v_F)}{N \pi^3}\int^{\infty}_{-\infty}dx \int^{2\pi}_{0} d \theta \mathcal {G}(x,\theta)\nonumber \\ &&\times\frac{x^2-\cos^2\theta-(v_\Delta/v_F)^2 \sin^2\theta}{(x^2+\cos^2\theta+(v_\Delta/v_F)^2 \sin^2\theta)^2}, \\ C_2 &=& \frac{2(v_\Delta/v_F)}{N \pi^3}\int^{\infty}_{-\infty}dx \int^{2\pi}_{0} d \theta \mathcal{G}(x,\theta) \nonumber \\ &&\times\frac{\cos^2\theta-x^2-(v_\Delta/v_F)^2 \sin^2\theta}{(x^2+\cos^2\theta+(v_\Delta/v_F)^2 \sin^2\theta)^2}, \\ C_3 &=& \frac{2(v_\Delta/v_F)}{N \pi^3}\int^{\infty}_{-\infty}dx \int^{2\pi}_{0} d \theta \mathcal{G}(x,\theta) \nonumber \\ &&\times\frac{x^2+\cos^2\theta-(v_\Delta/v_F)^2 \sin^2\theta}{(x^2+\cos^2\theta+(v_\Delta/v_F)^2 \sin^2\theta)^2}, \\ \mathcal{G}^{-1} &=& \frac{x^2+\cos^2\theta}{\sqrt {x^2+\cos^2\theta+(v_\Delta/v_F)^2 \sin^2\theta}} \nonumber \\ && + \frac{x^2+\sin^2\theta}{\sqrt{x^2 + \sin^2\theta+(v_\Delta/v_F)^2\cos^2\theta}},\end{aligned}$$ Using Dyson equation, it is easy to get a renormalized fermion propagator $$\begin{aligned} G^{-1}_{\psi}(\mathbf{k},\omega) = -i\omega + v_F k_x\tau^z + v_{\Delta} k_{y}\tau^{x} -\Sigma(\mathbf{k},\omega),\end{aligned}$$ which leads to the following RG equations, $$\begin{aligned} \frac{d v_F}{dl}&=&(C_1 - C_2)v_F,\label{Eq_RG_v_F}\\ \frac{d v_\Delta}{dl}&=&(C_1 - C_3)v_\Delta,\label{Eq_RG_v_D}\\ \frac{d(v_{\Delta}/v_{F})}{dl} &=& (C_{2}-C_{3})(v_{\Delta}/v_{F}),\label{Eq_RG_v_D_v_F}\end{aligned}$$ where $l>0$ is running scale. A straightforward analysis showed that the ratio $v_{\Delta}/v_F$ flows to zero at the lowest energy, giving rise to a novel fixed point of extreme velocity anisotropy [@Huh]. Such fixed point in turn leads to a number of nontrivial consequences, such as unusual broadening of spectral function [@Kim], non-Fermi liquid behavior [@Xu], enhancement of dc thermal conductivity [@Fritz], and suppression of superconductivity [@Liu]. To analyze the influence of velocity renormalization and especially the extreme anisotropy manifested at nematic QCP on the nature of superconducting transition, we require that the constant fermion velocities appearing in the polarization $\Pi(q)$ to flow with running scale $l$ according to Eqs. (\[Eq\_RG\_v\_F\]) and (\[Eq\_RG\_v\_D\]). ![One-loop corrections to mass parameters $\alpha$ in (a) and $r$ in (b), respectively.[]{data-label="Fig_alpha_r"}](alpha_r.eps){width="3in"} The extreme velocity anisotropy is a special feature of the nematic QCP, where $r = 0$ and the nematic fluctuation is critical. Away from nematic QCP, $r \neq 0$, so the nematic fluctuation leads only to relatively unimportant renormalization of fermion velocities. For $r \neq 0$, $v_{F,\Delta}$ and therefore their ratio $v_{\Delta}/v_F$ remain finite. Flow equations of $\alpha$, $r$, $\beta$, $u$, and $\gamma$ ----------------------------------------------------------- We next consider the competitive interaction between nematic and superconducting order parameters. Our analysis follows closely the scheme presented in a recent work of She *et al.* [@Zaanen]. It was assumed in Ref. [@Zaanen] that all the fermionic degrees of freedom can be integrated out and their effects can be represented by the dynamical exponent $z$. Compared with Ref. [@Zaanen], the main difference here is the inclusion of polarization $\Pi(q)$ in the effective action of nematic order $\phi$, which is supposed to reflect the influence of nodal qps. The corresponding (sub)action that describes ordering competition is $$\begin{aligned} S_{\mathrm{com}}=S_{\psi}+S_{\phi}+S_{\psi\phi},\label{Eq_action_eff}\end{aligned}$$ where $$\begin{aligned} S_\psi &=& \frac{1}{2}\int \frac{d^2\mathbf{k}d\omega}{(2\pi)^3} \left(-2\alpha+\mathbf{k}^2+\omega^2\right)\psi^2\nonumber\\ && + \frac{\beta}{2}\int \prod^4_{m=1}\frac{d^2\mathbf{k}_md\omega_m} {(2\pi)^3}\delta^2\left(\sum\mathbf{k}_m\right) \delta\left(\sum\omega_m\right)\psi^4,\nonumber\\ S_\phi &=& \int \frac{d^2\mathbf{q}d\epsilon}{(2\pi)^3} \frac{1}{2}\left[-2r+\mathbf{q}^2+\epsilon^2+\Pi(q)\right]\phi^2\nonumber\\ &&+\frac{u}{2} \int \prod^4_{m=1}\frac{d^2\mathbf{q}_md\epsilon_m} {(2\pi)^3}\delta^2\left(\sum\mathbf{q}_m\right) \delta\left(\sum\epsilon_m\right)\phi^4,\nonumber\\ S_{\psi\phi} &=& \gamma\int \prod_{i=1,2} \frac{d^2\mathbf{k}_id\omega_id^2\mathbf{q}_id\epsilon_i} {(2\pi)^6}\psi(\mathbf{k}_i,\omega_i) \phi(\mathbf{q}_i,\epsilon_i)\nonumber\\ &&\times \delta^2\left(\mathbf{k}_1+\mathbf{k}_2+ \mathbf{q}_1 + \mathbf{q}_2\right) \delta\left(\omega_1+\omega_2+\epsilon_1 +\epsilon_2\right).\nonumber\end{aligned}$$ Before performing a standard RG analysis within this action, it is convenient to rescale momenta and energy by $\Lambda$, i.e, $\mathbf{k}\rightarrow \mathbf{k}/\Lambda$, $\omega \rightarrow \omega/\Lambda$. According to the sprit of RG theory [@Shankar94; @Huh; @WLK; @Liu; @Zaanen], we employ the following scaling transformations: $$\begin{aligned} &&k_i=k'_ie^{-l},\\ &&\omega=\omega' e^{-l},\\ &&\psi(\mathbf{k},\omega)=\psi'(\mathbf{k'},\omega')e^{5l/2};\\ &&q_i=q'_ie^{-l},\\ &&\epsilon=\epsilon' e^{-l},\\ &&\phi(\mathbf{q},\epsilon)=\phi'(\mathbf{q'},\epsilon')e^{5l/2};\end{aligned}$$ where $i=x,y$. Applying these RG transformations, we will be able to derive the RG flow equations for the parameters $\alpha$, $\beta$, $r$, $u$, and $\gamma$. Each field operator can be separated into slow mode and fast mode, i.e., $$\begin{aligned} \psi &=& \psi_s + \psi_f, \\ \phi &=& \phi_s + \phi_f.\end{aligned}$$ After introducing an UV cutoff $\Lambda$, we can define the slow mode of superconducting order parameter as $\psi_s = \psi(k)$ with $0 < k < e^{-l}\Lambda$ and the fast mode as $\psi_f = \psi(k)$ with $e^{-l}\Lambda < k < \Lambda$, using the formalism of Ref. [@Shankar94]. Based on such modes separation, the effective action (\[Eq\_action\_eff\]) is decomposed into three parts: $S^{s}$ that contains only slow modes, $S^{f}$ that contains only fast modes, and $S^{sf}$ that contains both slow and fast modes. More concretely, we have $$\begin{aligned} S_{\mathrm{com}} &=&S^{s}+S^{f}+S^{sf}\nonumber\\ &=&\left(S^{s}_\psi+S^{s}_\phi+S^{s}_{\psi\phi}\right) +\left(S^{f}_\psi+S^{f}_\phi\right) + S^{sf},\label{Eq_action_eff_s_f}\end{aligned}$$ where $$\begin{aligned} S^{s}_{\psi} &=& \frac{1}{2}\int \frac{d^2\mathbf{k}d\omega}{(2\pi)^3} \left(-2\alpha+\mathbf{k}^2 + \omega^2\right)\psi_s^2 \nonumber\\ && + \frac{\beta}{2}\int \prod^4_{m=1} \frac{d^2\mathbf{k}_md\omega_m}{(2\pi)^3} \delta^2\left(\sum\mathbf{k}_m\right) \delta\left(\sum\omega_m\right)\psi_s^4,\nonumber\\ S^{s}_{\phi} &=& \frac{1}{2}\int \frac{d^2\mathbf{q}d\epsilon}{(2\pi)^3} \left[-2r+\mathbf{q}^2+\epsilon^2+\Pi(q)\right]\phi_s^2 \nonumber\\ && + \frac{u}{2}\int \prod^4_{m=1}\frac{d^2\mathbf{q}_md\epsilon_m} {(2\pi)^3}\delta^2\left(\sum\mathbf{q}_m\right) \delta\left(\sum\epsilon_m\right)\phi_s^4,\nonumber\\ S^{s}_{\psi\phi} &=& \gamma\int \prod_{i=1,2} \frac{d^2\mathbf{k}_id\omega_id^2\mathbf{q}_id\epsilon_i} {(2\pi)^6}\psi(\mathbf{k}_i,\omega_i) \phi(\mathbf{q}_i,\epsilon_i)\nonumber\\ && \times \delta^2 \left(\mathbf{k}_1+\mathbf{k}_2+ \mathbf{q}_1+\mathbf{q}_2\right)\delta\left(\omega_1+\omega_2+\epsilon_1 +\epsilon_2\right);\nonumber\\ S^{f}_{\psi} &=& \frac{1}{2}\int \frac{d^2\mathbf{k}d\omega}{(2\pi)^3} \left(-2\alpha+\mathbf{k}^2+\omega^2\right)\psi_f^2\nonumber\\ &&+\frac{\beta}{2}\int \prod^4_{m=1}\frac{d^2\mathbf{k}_md\omega_m} {(2\pi)^3}\delta^2\left(\sum\mathbf{k}_m\right) \delta\left(\sum\omega_m\right)\psi_f^4,\nonumber\\ S^{f}_{\phi} &=& \frac{1}{2} \int \frac{d^2\mathbf{q}d\epsilon}{(2\pi)^3} \left[-2r+\mathbf{q}^2+\epsilon^2+\Pi(q)\right]\phi_f^2\nonumber\\ &&+\frac{u}{2}\int \prod^4_{m=1}\frac{d^2\mathbf{q}_md\epsilon_m} {(2\pi)^3}\delta^2\left(\sum\mathbf{q}_m\right) \delta\left(\sum\epsilon_m\right)\phi_f^4,\nonumber\\ S^{sf} &=& \int \frac{d^2\mathbf{k}d\omega}{(2\pi)^3} \frac{3}{2} \left(\beta\psi_f \psi_f \psi_s \psi_s + u\phi_f \phi_f \phi_s \phi_s\right) \nonumber\\ && + \int \prod_{i=1,2}\frac{d^2\mathbf{k}_i d\omega_i d^2\mathbf{q}_id\epsilon_i}{(2\pi)^6} \delta^2 \left(\mathbf{k}_1+\mathbf{k}_2+\mathbf{q}_1+\mathbf{q}_2\right)\nonumber\\ && \times \delta\left(\omega_1+\omega_2+\epsilon_1+\epsilon_2\right) \left(\gamma\psi_s\psi_s\phi_f\phi_f\right.\nonumber\\ &&\left.+\gamma\psi_f\psi_f\phi_s\phi_s+ 4\gamma\psi_f\psi_s\phi_f\phi_s\right).\nonumber\end{aligned}$$ After this decomposition, now the partition function can be rearranged in the following way, $$\begin{aligned} Z&=&\int \mathcal{D}\psi_s\mathcal{D}\phi_s \mathcal{D}\bar{\Psi} \mathcal{D}\Psi \int \mathcal{D}\psi_f\mathcal{D}\phi_f\nonumber\\ &&\times\exp\left[{\left(S^{s}_\psi+S^{s}_\phi+S^{s}_{\psi\phi}\right) +\left(S^{f}_\psi+S^{f}_\phi\right) +S^{sf}}\right]\nonumber\\ &=&\int \mathcal{D}\psi_s\mathcal{D}\phi_s \mathcal{D}\bar{\Psi} \mathcal{D}\Psi \exp{\left(S^{s}_\psi+S^{s}_\phi+S^{s}_{\psi\phi}\right)}\nonumber\\ &&\times \int \mathcal{D}\psi_f\mathcal{D}\phi_f \exp\left[{\left(S^{f}_\psi+S^{f}_\phi\right) +S^{sf}}\right] \nonumber\\ &=&\int \mathcal{D}\psi_s\mathcal{D}\phi_s \mathcal{D}\bar{\Psi} \mathcal{D}\Psi \exp{\left(S'^{s}_\psi+S'^{s}_\phi + S'^{s}_{\psi\phi}\right)}\nonumber\\ &\equiv&\int \mathcal{D}\psi_s\mathcal{D}\phi_s \mathcal{D}\bar{\Psi} \mathcal{D}\Psi\exp{\left(S'_{\mathrm{eff}}\right)}.\end{aligned}$$ The next step is to integrate over all the fast modes, and obtain an effective action of slow modes. The functional integration can be performed using the standard diagrammatic techniques. The propagators for the superconducting order $\psi$ and the nematic order $\phi$, shown in Fig. (\[propagators\]), are $$\begin{aligned} G_\psi(\mathbf{k},\omega) &=& \frac{1}{-2\alpha+\mathbf{k}^2+\omega^2},\\ G_\phi(\mathbf{q},\epsilon) &=& \frac{1}{-2r+\mathbf{q}^2+\epsilon^2+\Pi(q)}.\end{aligned}$$ The polarization appearing in $G_\phi(\mathbf{q},\epsilon)$ reflects the presence of gapless nodal qps. As already pointed out, $\Pi(q)$ dominates over the kinetic term $q^2$ in the low-energy regime. In order to further simplify the nematic propagator, we consider the close vicinity of nematic QCP where $r$ is very small. In this case, we are allowed to approximate the nematic propagator by $$\begin{aligned} G_\phi(\mathbf{q},\epsilon) &\approx& \frac{1}{-2r + \Pi(q)} \nonumber \\ &\approx& \frac{1}{\Pi(q)\left(1 - \frac{2r}{\Pi(q)}\right)} \nonumber \\ &\approx&\frac{1}{\Pi(q)}+\frac{2r}{\Pi^2(q)}.\end{aligned}$$ This expansion is apparently inappropriate when $r$ is not small. For large $r$, it is better to consider $\Pi(q)/r$ as small expanding parameter, which will be discussed later. ![One-loop corrections to quartic coefficients $\beta$ in (a) and $u$ in (b), respectively.[]{data-label="Fig_beta_u"}](beta_u.eps){width="3in"} Now let us work in the spherical coordinates. We first define $\epsilon \equiv vq_0 = vq\cos\theta$, $q_1 = q\sin\theta\cos\varphi$, and $q_2 = q\sin\theta\sin\varphi$, with $v$ being the velocity of nematic order parameter $\phi$. For convenience, we could extract constant $v$ from the energy $\omega$ of superconducting order parameter $\psi$. Accordingly, the velocities of nodal qps, $v_F$ and $v_\Delta$, can be divided by $v$. After this manipulation, $v_F$ and $v_\Delta$ become dimensionless. Now the polarization function can be written in the form, $$\begin{aligned} \Pi(q,\theta,\varphi) = q D(\theta,\varphi),\label{Eq_Pi_D}\end{aligned}$$ where the function $$\begin{aligned} \label{Eq_D_theta_varphi} &&D(\theta,\varphi) = \frac{1}{16v_F v_{\Delta}} \nonumber \\ && \times \left(\frac{\cos^2\theta + v_F^2 \sin^2\theta\cos^2\varphi} {\sqrt{\cos^2\theta + v_F^2 \sin^2\theta\cos^2\varphi + v_{\Delta}^2 \sin^2\theta\sin^2\varphi}}\right. \nonumber\\ && +\left.\frac{\cos^2\theta + v_F^2\sin^2\theta\sin^2\varphi} {\sqrt{\cos^2\theta + v_F^2\sin^2\theta\sin^2\varphi + v_{\Delta}^2\sin^2\theta\cos^2\varphi}}\right)\nonumber\end{aligned}$$ is dimensionless. Before proceeding with the next calculations, it is helpful to define $$\begin{aligned} F_1 &\equiv& F_1(v_F,v_\Delta)= \int^\pi_0\!\!d\theta\int^{2\pi}_0\!\!d\varphi \frac{\sin\theta}{(2\pi)^{3} D(\theta,\varphi)},\label{Eq_F_1} \\ F_2 &\equiv& F_2(v_F,v_\Delta)= \int^\pi_0\!\!d\theta\int^{2\pi}_0\!\!d\varphi \frac{\sin\theta}{(2\pi)^{3}D^2(\theta,\varphi)},\label{Eq_F_2}\\ F_3 &\equiv& F_3(v_F,v_\Delta)= \int^\pi_0\!\!d\theta\int^{2\pi}_0\!\!d\varphi \frac{\sin\theta}{(2\pi)^{3} D^3(\theta,\varphi)}.\label{Eq_F_3}\end{aligned}$$ With these arrangements, we can now turn to calculate the one-loop contribution to the RG equations of all parameters. $\alpha,r$ ----------- The diagrams contributing to $\alpha$ to leading order are shown in Fig. \[Fig\_alpha\_r\](a). We perform the following calculations, $$\begin{aligned} S[\alpha] &=&\int^{b}\frac{d^{3}q}{(2\pi)^{3}} \psi_s(q)\psi_s(-q)\left[-2\alpha+3\beta\int^1_{b} \frac{d^{3}q'}{(2\pi)^{3}} G^f_\psi\right.\nonumber\\ &&+\left.\gamma\int^1_b\frac{d^{3}q'}{(2\pi)^{3}} G^f_\phi\right]\nonumber\\ &\approx&\int^{b}\frac{d^{3}q}{(2\pi)^{3}} \psi_s(q)\psi_s(-q)(-2\alpha)\nonumber\\ &&\times\exp\left\{-\frac{l}{2\alpha}\left[\frac{3\beta}{2\pi^2} \left(1+2\alpha\right) + \gamma\left(F_1 + 2rF_2\right)\right]\right\}\nonumber\\ &=&\int^{1}\frac{d^{3}q}{(2\pi)^{3}}e^{-3l} \psi_s(q)\psi_s(-q)e^{5l/2}e^{5l/2}(-2\alpha)\nonumber\\ &&\times\exp\left\{-\frac{l}{2\alpha}\left[\frac{3\beta}{2\pi^2} \left(1+2\alpha\right) + \gamma(F_1+2rF_2)\right]\right\}\nonumber\\ &\equiv&\int^{1}\frac{d^{3}q}{(2\pi)^{3}} \psi_s(q)\psi_s(-q) (-2\alpha'),\label{Eq_S_alpha}\end{aligned}$$ where $$\begin{aligned} \alpha' = \alpha \exp\left\{2l-\frac{l}{2\alpha}\left[\frac{3\beta}{2\pi^2}\left( 1+2\alpha\right)+\gamma (F_1+2rF_2)\right]\right\}.\nonumber\end{aligned}$$ Its derivative with respect to running scale $l$ is $$\begin{aligned} \frac{d\alpha}{dl} = 2\alpha-\left[\frac{3\beta}{4\pi^2} \left( 1+2\alpha\right) + \frac{\gamma}{2} (F_1+2rF_2)\right].\end{aligned}$$ By calculating the diagrams shown in Fig. \[Fig\_alpha\_r\](b), the flow equation for parameter $r$ can be obtained similarly, $$\begin{aligned} \frac{dr}{dl}=2r-\left[\frac{3u}{2}(F_1+2rF_2) +\frac{\gamma}{4\pi^2}\left( 1+2\alpha\right)\right].\end{aligned}$$ In the absence of fermionic degrees of freedom, $F_1 = F_2 = \frac{1}{2\pi^2}$, then the flow equation of $\alpha$ is identical to that of $r$ [@Zaanen]. Such an “exchange symmetry" is certainly broken by gapless nodal qps via the polarization $\Pi(q)$ appearing in the effective action of nematic order $\phi$. $\beta,u$ ---------- The one-loop corrections to $\beta$ are depicted in Fig. \[Fig\_beta\_u\](a). By paralleling the steps performed in Eq. (\[Eq\_S\_alpha\]), we can similarly obtain $$\begin{aligned} S[\beta]&\equiv&\int^{1} \prod^4_{m=1} \frac{d^2\mathbf{k}_md\omega_m} {(2\pi)^3}\delta^2\left(\sum\mathbf{k}_m\right) \delta\left(\sum\omega_m\right) \frac{\beta'}{2}|\psi_s|^4,\nonumber\end{aligned}$$ where $$\begin{aligned} \beta'=\beta \exp{\left\{1-\frac{2}{\beta} \left[\frac{9\beta^2}{2\pi^2} +\gamma^2(F_2+4rF_3)\right]\right\}l}.\nonumber\end{aligned}$$ It leads to $$\begin{aligned} \frac{d\beta}{dl} = \beta- \left[\frac{9\beta^2}{\pi^2} + 2\gamma^2(F_2 + 4rF_3)\right].\end{aligned}$$ By calculating diagrams shown in Fig. \[Fig\_beta\_u\](b), the RG equation for $u$ is found to be $$\begin{aligned} \frac{du}{dl}=u-\left[\frac{\gamma^2}{\pi^2} +18u^2(F_2+4rF_3)\right].\end{aligned}$$ Once again, the influence of gapless nodal qps is reflected in the functions $F_{2,3}$. $\gamma$ --------- ![One-loop corrections to coupling constant $\gamma$.[]{data-label="Fig_gamma"}](gamma.eps){width="3.4in"} Now we consider the flow of $\gamma$, which characterizes the strength of competitive interaction. The one-loop corrections to the term $\gamma \psi^2 \phi^2$ has three diagrams, presented in Fig. (\[Fig\_gamma\]). Following similar procedure, we eventually obtain $$\begin{aligned} S[\gamma]\!&\equiv&\!\!\int^{1}\!\! \prod^4_{m=1}\frac{d^2\mathbf{k}_m} {(2\pi)^2}\frac{d\omega_m}{2\pi}\delta^2 \left(\sum\mathbf{k}_m\right) \delta\left(\sum\omega_m\right) \gamma'\psi^2_s\phi^2_s,\nonumber\end{aligned}$$ where $$\begin{aligned} \gamma'&=&\gamma\exp\Bigl\{l-\Bigl[\frac{3\beta}{\pi^2}+6u(F_2+4rF_3).\nonumber\\ &&+8\gamma\left(F_1+F_22r+F_12\alpha\right)\Bigr]l\Bigr\}.\nonumber\end{aligned}$$ The flow equation of $\gamma$ is therefore given by $$\begin{aligned} \frac{d \gamma}{dl}&=&\gamma\Bigl\{1-\Bigl[\frac{3\beta}{\pi^2} +6u(F_2+4rF_3)\nonumber\\ &&+8\gamma\left(F_1+F_22r+F_12\alpha\right)\Bigr]\Bigr\}.\end{aligned}$$ Numerical results and physical implications {#sec_numerical_discussion} =========================================== In order to specify the possible fixed point of the system under consideration, we need to solve the RG equations. For later reference, it is useful to list all the RG equations obtained in the previous section, $$\begin{aligned} \frac{d\alpha}{dl} &=&2\alpha-\left[\frac{3\beta} {4\pi^2}\left(1+2\alpha\right) +\frac{\gamma}{2}(F_1+2rF_2)\right],\label{Eq_alpha_RGEq}\\ \frac{dr}{dl}&=&2r-\left[\frac{3u}{2}(F_1+2rF_2) +\frac{\gamma}{4\pi^2}\left( 1+2\alpha\right)\right],\label{Eq_r_RGEq}\\ \frac{d\beta}{dl}&=&\beta-\left[\frac{9\beta^2}{\pi^2} +2\gamma^2(F_2+4rF_3)\right],\label{Eq_beta_RGEq}\\ \frac{du}{dl}&=&u-\left[\frac{\gamma^2}{\pi^2} +18u^2(F_2+4rF_3)\right],\label{Eq_u_RGEq}\\ \frac{d\gamma}{dl} &=& \gamma\Bigl\{1-\Bigl[\frac{3\beta}{\pi^2}+ 6u(F_2 + 4rF_3)\nonumber\\ &&+8\gamma\left(F_1 + F_2 2r + F_1 2\alpha\right)\Bigr]\Bigr\},\label{Eq_gamma_RGEq}\\ \frac{d v_F}{dl} &=& (C_1 - C_2)v_F,\\ \frac{d v_\Delta}{dl} &=& (C_1 - C_3)v_{\Delta}.\end{aligned}$$ Compared with the case in which the action contains only two bosonic order parameters, the gapless nodal qps show their existence through the three functions $F_{1,2,3}$, which are determined by fermion velocities, $v_{F,\Delta}$. We now address how the velocity ratio affects the fixed point structure of the interacting system. As already pointed out, extreme velocity anisotropy with $\kappa \rightarrow 0$ is a special property of nematic QCP with $r = 0$. For finite $r$, the velocities receive only unimportant renormalizations, and the ratio $\kappa$ remains finite. To make our analysis simpler, we first consider the case of finite $r$ and solve the above RG equations by assuming two representative constant values of $\kappa$. From the solutions, we will know qualitatively how the fixed point evolves as $\kappa$ decreases. We then consider nematic QCP with $r = 0$, and solve the flow equations (\[Eq\_alpha\_RGEq\], \[Eq\_r\_RGEq\], \[Eq\_beta\_RGEq\], \[Eq\_u\_RGEq\], \[Eq\_gamma\_RGEq\]) self-consistently after taking into account the extreme anisotropy limit, $\kappa \rightarrow 0$. $v_\Delta/v_F=0.1$ ------------------ First, we consider a constant $v_\Delta/v_F = 0.1$, which is an appropriate value for the velocity ratio in some realistic high-$T_c$ superconductors [@VojtaSachdev; @Orenstein00; @Chiao]. In the presence case, the dimensionless velocity is set to $v_F = 1$ [@Vojta], and therefore $v_\Delta = 0.1$. Substituting them into Eq. (\[Eq\_D\_theta\_varphi\]), we have $$\begin{aligned} D(\theta,\varphi) &=&\frac{5}{8}\left(\frac{\cos^2\theta + \sin^2\theta\cos^2\varphi} {\sqrt{\cos^2\theta + \sin\theta^2\cos^2\varphi + 0.01 \sin\theta^2\sin^2\varphi}}\right.\nonumber\\ &&+\left.\frac{\cos^2\theta +\sin^2\theta\sin^2\varphi} {\sqrt{\cos^2\theta + \sin^2\theta\sin^2\varphi + 0.01\sin^2\theta\cos^2\varphi}}\right),\nonumber\end{aligned}$$ and $$\begin{aligned} F_1&=& \int^\pi_0d\theta\int^{2\pi}_0d\varphi \frac{\sin\theta}{(2\pi)^{3} D(\theta,\varphi)} \approx0.053,\\ F_2&=& \int^\pi_0d\theta\int^{2\pi}_0d\varphi \frac{\sin\theta}{(2\pi)^{3} D^2(\theta,\varphi)} \approx0.057,\\ F_3&=& \int^\pi_0d\theta\int^{2\pi}_0d\varphi \frac{\sin\theta}{(2\pi)^{3} D^3(\theta,\varphi)} \approx 0.062.\end{aligned}$$ Now the RG equations (\[Eq\_alpha\_RGEq\], \[Eq\_r\_RGEq\], \[Eq\_beta\_RGEq\], \[Eq\_u\_RGEq\], \[Eq\_gamma\_RGEq\]) can be approximated as $$\begin{aligned} \frac{d\alpha}{dl}\!\!&=&\!\!2\alpha\!-\!\left[\frac{3\beta}{4\pi^2} \left( 1+2\alpha\right)\!+\!\frac{\gamma}{2}(0.053+0.114r)\right]\!,\\ \frac{dr}{dl}\!\!&=&\!\!2r\!-\!\left[\frac{3u}{2}(0.053+0.114r) \!+\!\frac{\gamma}{4\pi^2}\left( 1+2\alpha\right)\right]\!,\\ \frac{d\beta}{dl}\!\!&=&\!\!\beta\!-\!\left[\frac{9\beta^2}{\pi^2} +2\gamma^2(0.057+0.248r)\right]\!,\\ \frac{du}{dl}\!\!&=&\!\!u\!-\!\left[\frac{\gamma^2}{\pi^2} \!+\!18u^2(0.057+0.248r)\right]\!,\\ \frac{d\gamma}{dl}\!\!&=&\!\!\gamma\Bigl\{1-\Bigl[\frac{3\beta} {\pi^2}+6u(0.057+0.248r)\nonumber\\ &&+8\gamma\left(0.053+0.114r +0.106\alpha\right)\Bigr]\Bigr\}\!.\end{aligned}$$ By setting all these derivatives to zero, the fixed points could be determined. After numerical calculations, we find the following solutions (unphysical ones have been discarded): 1\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.034935,0.041791,0.377768,0.540608,1.355735)$, 2\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.040467,0.035673,0.487222,0.374853,1.433849)$, 3\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.050708,0.030099,0.757159,0.266773,1.348298)$, 4\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.053547,0.043491,1.013065,0.757126,0.754569)$. We need to find out the stable fixed point from these four solutions. By fixing $\alpha=\alpha^*,r=r^*,\gamma=\gamma^*$, and making numerical analysis, we find that $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx(0.053547,0.043491,1.013065,0.757126,0.754569)$ corresponds to the stable fixed point. In fact, we only need to address the physical properties in the vicinity of the stable fixed point. At $\alpha=\alpha^*,r=r^*,\gamma=\gamma^*$, it appears that the flow trajectories of $\beta$ and $u$ show runaway behavior when the initial values of $\beta$ and $u$ are below the critical values $\beta_c \approx 0.0835$ and/or $u_c \approx 0.0625$, which are shown in Fig. (\[plot\_v\_D\_v\_F\_0.1\]). As extensively discussed previously [@Millis10; @Zaanen; @Halperin; @Fisher; @Cardy1996], such runaway behavior implies a first-order phase transition. $v_\Delta/v_F=0.01$ ------------------- We then assume that $v_\Delta/v_F = 0.01$, and examine how the fixed point structure is modified as the ratio $v_\Delta/v_F$ decreases. In the present case, we have $$\begin{aligned} D(\theta,\varphi) &=& \frac{25}{4}\left(\frac{\cos^2\theta + \sin^2\theta\cos^2\varphi}{\sqrt{\cos^2\theta+\sin^2\theta\cos^2\varphi + 0.0001 \sin^2\theta\sin^2\varphi}}\right.\nonumber\\ &&+\left.\frac{\cos^2\theta +\sin^2\theta\sin^2\varphi} {\sqrt{\cos^2\theta + \sin^2\theta\sin^2\varphi + 0.0001\sin^2\theta\cos^2\varphi}}\right);\nonumber\end{aligned}$$ and then $$\begin{aligned} F_1 &=& \int^{\pi}_{0} d\theta \int^{2\pi}_0 d\varphi \frac{\sin\theta}{(2\pi)^{3} D(\theta,\varphi)} \approx 0.005274,\\ F_2 &=& \int^{\pi}_{0}d\theta \int^{2\pi}_0 d\varphi \frac{\sin\theta}{(2\pi)^{3} D^2(\theta,\varphi)} \approx 0.000561,\\ F_3 &=& \int^{\pi}_{0} d\theta \int^{2\pi}_0 d\varphi \frac{\sin\theta}{(2\pi)^{3} D^3(\theta,\varphi)} \approx 0.000062.\end{aligned}$$ Hence, the set of RG equations (\[Eq\_alpha\_RGEq\], \[Eq\_r\_RGEq\], \[Eq\_beta\_RGEq\], \[Eq\_u\_RGEq\], \[Eq\_gamma\_RGEq\]) approximately becomes $$\begin{aligned} \frac{d\alpha}{dl}\!\!&=&\!\!2\alpha\!-\!\!\left[\!\frac{3\beta}{4\pi^2} \left( 1\!+\!2\alpha\right)\!+\!\frac{\gamma}{2} (0.00527\!+\!0.00112r)\!\right]\!,\\ \frac{dr}{dl}\!\!&=&\!\!2r\!-\!\!\left[\!\frac{3u}{2}(0.00527\!+\!0.00112r) \!+\!\frac{\gamma}{4\pi^2}\!\left( 1\!+\!2\alpha\right)\!\right]\!,\\ \frac{d\beta}{dl}\!\!&=&\!\!\beta\!-\!\left[\!\frac{9\beta^2}{\pi^2} \!+\!2\gamma^2(0.00056+0.00025r)\!\right]\!,\\ \frac{du}{dl}\!\!&=&\!\!u\!-\!\left[\!\frac{\gamma^2}{\pi^2} \!+\!18u^2(0.00056+0.00025r)\!\right]\!,\\ \frac{d\gamma}{dl}\!\!&=&\!\!\gamma\Bigl\{1-\Bigl[\frac{3\beta} {\pi^2}+6u(0.00056+0.00025r)\nonumber\\ &&+8\gamma\left(0.00527+0.00112r +0.01055\alpha\right)\Bigr]\Bigr\}\!.\end{aligned}$$ By applying the same methods used in the case of $v_\Delta/v_F = 0.1$, we also find four solutions: 1\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.053548,0.437666,1.013124,76.671917, 7.590670)$, 2\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.034916,0.420692,0.377357,54.780339, 13.639865)$, 3\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.040451,0.358983,0.486613,37.941187,14.432612)$, 4\) $(\alpha^*,r^*,\beta^*,u^*,\gamma^*) \approx\\(0.050767,0.302544,0.758586,26.941770,13.562402)$. Among these points, only the first is stable. The corresponding critical values of $\beta, u$ are $\beta_c \approx 0.0833$ and $u_c \approx 6.32$, which are shown in Fig. (\[plot\_v\_D\_v\_F\_0.01\]). Compared with the results obtained at $v_\Delta/v_F = 0.1$, we find that the probability of first-order transition rapidly rises as velocity ratio $\kappa$ decreases, because the region of runaway behavior is significantly enhanced. It is nature to speculate that first-order transition may be inevitable when the velocity ratio $\kappa$ vanishes. In order to judge this speculation, we finally consider the nematic QCP where $r = 0$. $r=0$ ----- At nematic QCP with $r = 0$, the velocity is no longer finite: it becomes scale-dependent, and vanishes at the lowest energy. In this case, we should study the fixed point by self-consistently solving the following equations, $$\begin{aligned} \frac{d\alpha}{dl} \!\!&=&\!\! 2\alpha\!-\!\left[\frac{3\beta}{4\pi^2} \left( 1+2\alpha\right) \!+\! \frac{\gamma }{2}F_1\right]\!\!=\!0,\\ \frac{d\beta}{dl} \!\!&=&\!\! \beta\!-\!\left[\frac{9\beta^2}{\pi^2} \!+\!2\gamma^2F_2\right]\!\!=\!0,\\ \frac{du}{dl}\!\!&=&\!\!u\!-\!\left[\frac{\gamma^2}{\pi^2} \!+\!18u^2F_2\right]\!\!=\!0,\\ \frac{d\gamma}{dl}\!\!&=&\!\!\gamma\left\{\!1\!-\!\left[\!\frac{3\beta} {\pi^2}\!+\!6uF_2\!+\!8\gamma\left(F_1 +F_12\alpha\right)\!\right]\!\right\}\!\!=\!0,\\ \frac{d v_F}{dl}\!\!&=&\!\!(C_1 - C_2)v_F\!=0,\\ \frac{d v_\Delta}{dl}\!\!&=&\!\!(C_1 - C_3)v_\Delta\!\!=\!0,\end{aligned}$$ which are obtained at the nematic QCP $r = 0$. Since the equations of $v_F,v_\Delta$ are relatively independent of other parameters, they could be first solved. It is easy to get $v_F^*=0, v_\Delta^*=0$, which implies that $F_1 = F_2 = F_3 = 0$. The rest equations now become $$\begin{aligned} \frac{d\alpha}{dl}&=&2\alpha-\frac{3\beta}{4\pi^2} \left( 1+2\alpha\right)=0,\\ \frac{d\beta}{dl}&=&\beta-\frac{9\beta^2}{\pi^2}=0,\\ \frac{du}{dl}&=&u-\frac{\gamma^2}{\pi^2}=0,\\ \frac{d\gamma}{dl}&=&\gamma\left(1-\frac{3\beta} {\pi^2}\right)=0,\end{aligned}$$ which have two solutions: 1) $r^*=u^*=\gamma^*=0$, $\beta^*=\alpha^*=0$; 2) $r^*=u^*=\gamma^*=0$, $\beta^*=\frac{\pi^2}{9}, \alpha^*=\frac{1}{22}$. One can check that both of these two solutions are unstable. Hence, there is no stale fixed point at all at nematic QCP where the velocity ratio $v_\Delta/v_F$ vanishes due to critical nematic fluctuation. The corresponding schematic flow diagram is shown in Fig. (\[plot\_r\_eq\_0\]). The runaway behavior is present in the whole region spanned by $(\beta,u)$, indicating that first-order phase transition always takes place. Now let us discuss a little more about the role of nodal qps. Within the HMM theory, the fermionic degrees of freedom can be fully integrated out. If we do so in our case, then we would obtain an effective action that consists of solely two bosonic order parameters, $\psi$ and $\phi$. The influence of gapless nodal qps is only reflected by the polarization $\Pi(q)$ which contributes a term $\Pi(q)\phi^2$ to the effective Lagrangian. The fermion velocities, $v_{F,\Delta}$, have to take their bare values and can not be renormalized, because the coupling between nematic order and nodal qps is neglected once the nodal qps are completely integrated out. It is therefore not possible to incorporate the extreme velocity anisotropy driven by the critical nematic fluctuation into the theoretical analysis. However, as shown in the above calculations, such extreme velocity anisotropy does have significant effects on the RG trajectories (please compare Fig. 9 with Fig. 7). Apparently, an important indication of results is that gapless nodal qps do play an essential role and therefore should be taken into account in the effective theory of competing orders. Relatively large $r$ -------------------- In the above calculations, we have simplified the effective propagator of nematic order parameter, $G_{\phi}(q)$, in terms of small quantity $r/\Pi(q)$. This expansion is appropriate in the close vicinity of nematic QCP with small $r$. When $r$ is relatively large, we consider $\Pi(q)/r$ as small parameter and expand $G_{\phi}(q)$ as $$\begin{aligned} G_\phi(\mathbf{q},\epsilon) &\approx& \frac{1}{-2r + \Pi(q)} \nonumber \\ &\approx& \frac{1}{-2r\left(1 - \frac{\Pi(q)}{2r}\right)} \nonumber \\ &\approx& -\frac{1}{2r} + \frac{\Pi(q)}{4r^2}.\end{aligned}$$ We have performed RG calculations using this propagator for relatively large $r$, and found that our qualitative conclusion reached above does not change. Summary and discussion {#sec_summary} ====================== In summary, we have performed a RG analysis within an effective field theory of the competition between superconductivity and nematic order in the context of $d$-wave high-$T_c$ superconductors. Our results confirm the qualitative conclusion of Refs. [@Millis; @Zaanen] that ordering competition can generically give rise to first order transition. Different from previous treatments, we go beyond the HMM framework and incorporate gapless nodal qps explicitly in our calculations. It is found that the ratio $\kappa$ between gap velocity $v_{\Delta}$ and Fermi velocity $v_F$ of nodal qps plays a crucial important role in determining the RG flow diagram of the system. As $\kappa$ decreases from its bare value, the possibility of first order transition is enhanced. When $\kappa$ approaches zero at the nematic QCP due to the critical nematic fluctuation, first order transition become inevitable because the system exhibits runaway behavior in the whole space spanned by parameters $u$ and $\beta$, the quartic coefficients of superconducting and nematic order parameters respectively. These results indicates that gapless fermionic degrees of freedom can neither be ignored nor fully integrate out. The competition between superconductivity and nematic order is merely a very simple example of ordering competition. It is more interesting to study the competition between superconductivity and antiferromagnetism, which is a fundamental issue in high-$T_c$ superconductor, heavy fermion superconductor, and iron-based superconductor. Compared with the case of competing nematic order, the interplay between superconductivity and antiferromagnetism is more complicated and exhibits richer properties. 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Q: Is it practical to record table creation/modificaion events in a separate table? I'm about to begin designing a database for an MVC web app and am considering using a table called 'changes' or 'events' to keep track of all changes made to the database. It would have a field for the table name, record id, user making the change, the timestamp and whether it was a creation or modification event. My question is whether this is a poor design practice compared to having 'created by', 'created on', 'modified by', 'modified on' fields in each table. I was thinking that in the parent Model class, I would use a before-save function recorded every change. I can see a pitfall might be if many records were updated at once, it might be difficult to get the function to save the changes properly. A: This is a matter of weighing up the benefit of having the granular info against the overhead of writing to this table every time something in the database changes and the additional storage required. If you are concerned about using a function on the model class then an alternative would be database triggers. This would be quite robust, but would be more work to set up as you would need to define triggers for each table unless the database you are using has a facility to log DML changes generically. Finally, I would also advise considering archiving as this table has the potential to get very big very quickly.
// Copyright 2012 The Go Authors. All rights reserved. // Use of this source code is governed by a BSD-style // license that can be found in the LICENSE file. #include <unistd.h> #include "runtime.h" #include "defs.h" int32 getproccount(void) { int32 n; n = (int32)sysconf(_SC_NPROC_ONLN); return n > 1 ? n : 1; }
/* * Copyright 2016 Facebook, Inc. * * 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. */ #include <folly/Array.h> #include <folly/portability/GTest.h> #include <string> using namespace std; using folly::make_array; TEST(make_array, base_case) { auto arr = make_array<int>(); static_assert( is_same<typename decltype(arr)::value_type, int>::value, "Wrong array type"); EXPECT_EQ(arr.size(), 0); } TEST(make_array, deduce_size_primitive) { auto arr = make_array<int>(1, 2, 3, 4, 5); static_assert( is_same<typename decltype(arr)::value_type, int>::value, "Wrong array type"); EXPECT_EQ(arr.size(), 5); } TEST(make_array, deduce_size_class) { auto arr = make_array<string>(string{"foo"}, string{"bar"}); static_assert( is_same<typename decltype(arr)::value_type, std::string>::value, "Wrong array type"); EXPECT_EQ(arr.size(), 2); EXPECT_EQ(arr[1], "bar"); } TEST(make_array, deduce_everything) { auto arr = make_array(string{"foo"}, string{"bar"}); static_assert( is_same<typename decltype(arr)::value_type, std::string>::value, "Wrong array type"); EXPECT_EQ(arr.size(), 2); EXPECT_EQ(arr[1], "bar"); } TEST(make_array, fixed_common_type) { auto arr = make_array<double>(1.0, 2.5f, 3, 4, 5); static_assert( is_same<typename decltype(arr)::value_type, double>::value, "Wrong array type"); EXPECT_EQ(arr.size(), 5); } TEST(make_array, deduced_common_type) { auto arr = make_array(1.0, 2.5f, 3, 4, 5); static_assert( is_same<typename decltype(arr)::value_type, double>::value, "Wrong array type"); EXPECT_EQ(arr.size(), 5); }
Sustainability in 2017- Are We at a Tipping Point to Become Mainstream? As we are nearing the end of the year, we’d like to reflect on how sustainability initiatives have progressed in 2016. What is the state of the art in sustainability for business? And what can we look forward to in sustainability in 2017? The group of companies that is taking sustainability seriously is still growing. And that’s good news. These companies acknowledge that they have to become more sustainable, not only to manage their reputation and risk and to increase their efficiency – including that of their supply chain – but most of all to ensure new revenue streams in the future, with sustainable products. 2016 – A Year of Scaling up Sustainability Initiatives In the past year, we’ve seen many initiatives and concrete examples, like Adidas using plastic waste from the oceans and Patagonia’s Repair & Care Guides. On a political level, the EU has put a lot of effort into the PEFCR/OEFSR pilots to create a level playing field for measuring the impact of products. From this initiative, so called ‘shadow PEFs’ are starting to arise, where companies are already working with the Product Environmental Footprint rules as they stand so far to get used to the process and reap the early benefits. The scale and impact of these initiatives is growing. Overall, there’s a lot of energy and drive to make the strategy and the results happen. Don’t Get Hit by a Boomerang, Measure the Impacts of Your Sustainability Programme However, this drive and growing impact comes with an obligation: when it comes to sustainability programmes, we must not only think or feel that we’re doing the right thing, we must know for sure. This conviction is in PRé’s DNA, but unfortunately, it’s not in everybody’s. Recently, I visited a meeting evaluating government sustainability programmes, and there was no upfront measurement of the environmental impact to assess whether these programmes make sense or not. That’s a serious threat to all this positive energy. If it turns out that these programmes have only a limited positive impact – or even worse, a negative impact – that can hit you in the back like a boomerang. Not knowing how to measure progress can lead to situations where everyone is focusing on the same driver, like recycling in a circular economy, while in practice there are many more, and potentially more important, hotspots. Quality Data and The Need for Fact-based Decisions The need for datato fuel these insights has only become bigger. Robust methods and tools are needed, more than ever, to turn data into meaningful insights. Sector initiatives, like The Sustainability Consortium and the Sustainable Apparel Coalition, are putting a lot of effort in providing data, tools and methods so their members use the right facts to make strategic decisions about risk, reputation, cost savings and innovation. Government initiatives like the European Commission’s PEFCR/OEFSR pilots and UNEP’s GLAD initiative to create a global LCI Database platform are also paving the way forward. These life-cycle-thinking-based approaches help companies to assess their environmental and social impact. Sustainability Needs to be Carried by the Users We are proud that we can contribute to making these sustainability initiatives more fact-based. These projects also taught us not only to focus on the metrics itself but on the context they’re used in. It’s important to have the metrics right, but it’s really the purpose they’re used for that makes them valuable and impactful. This is a lesson worth repeating to ourselves. In the end, users will ask themselves how these metrics help them to achieve their goals. Making sustainability more fact-based is a good and much-needed development to make the business case for sustainability. We believe that if companies invest in understanding the impact of what they do, they can use it for multiple purposes….and that many of the insights to do this are often already available. That’s why we try to activate our ecosystem of SimaPro users, consultancy clients and partners to share data and models that will help others to get started. The PEF models can have the same impact in the future, as people don’t have to start from scratch and don’t need to invest heavily in knowledge and experience. A Switch in Mindset – From Compliance to Innovation Once you have built the model of the life cycle or value chain for your product, service or organisation, you can use it not only to report on the current status, but also to create scenarios for more sustainable products and monitor the performance of your operations and supply chain. That will help to move away from an approach driven by risk and reputation management to one of eco-efficiency and value creation. The business case for sustainability is made through insights into the current situation, performance improvement and identifying opportunities for innovation and value creation. Once we realise how we can get the facts right to make this business case , we can reap the benefits from a more sustainable approach: risk and reputation management, cost savings, but most of all generating new revenues with sustainable products and services. Using insights from the entire life cycle opens up opportunities for new collaboration and partnerships: internally across departments, but also with suppliers and customers. Personally, I believe that extending the scope of your view and working with others is the biggest value of a more sustainable approach. Metrics can play a very important role in getting the right focus and creating momentum for these partnerships. As we’ve seen from the many examples, sustainability in business is on the brink of becoming mainstream. Let’s Make it Happen for Sustainability in 2017! Contact the author ‘Sustainability is all about impact. Positive impact makes you meaningful. But first you have to know where you are having an impact and where you can create shared value. That’s where PRé comes in. Pinpointing your impact is an essential starting point for taking joint action with people and organizations in your ecosystem. The combination of sustainability and social business can make a real change in the way we do business.’ For the Sustainable Apparel Coalition, a global alliance of apparel, footwear and home textile companies, PRé developed three tools for sustainable product development. The tools focus on material sustainability, ecodesign and data gathering.
“The Demographic Consequences of Sex-Selection Technology” Juan Pantano, The University of Chicago Over the last several years highly accurate methods of sex selection before conception have been developed. Given that strong preferences for sex variety in offspring have been documented for the U.S., we move beyond bioethical and moral considerations and ask what the demographic consequences of sex-selection technology could be. Lacking variation across space and time in access to this technology, we estimate a dynamic programming model of fertility decisions with microdata on fertility histories from the National Survey of Family Growth. We leverage the quasi-experimental variation inherent in the random determination of sex at conception to identify the key structural parameter characterizing preferences for sex variety in offspring. After recovering these preferences, we simulate the introduction of this technology. While this technology can reduce fertility by allowing parents efficiently reach their preferred sex mix, it could also increase fertility. This is because without this technology, many parents may opt not to have another baby given the uncertainty about its sex. Results suggest that these two effects operate simultaneously, but on net, sex selection technology ends up increasing the average family size among married women by about 2.5 percent in the steady state.
Tips for Parents of Teen Drivers A parent rightfully feels a mix of conflicting emotions when a teenager earns a driver’s license and begins driving alone. On the one hand it’s great that teens can get themselves around, giving them access to work opportunities and social events without needing their parents’ help. On the other hand, teenaged drivers are much more likely than older drivers to get into an accident, and car accidents are still a leading cause of serious injury and death among teenagers. Parents can take steps to improve their teenaged children’s safety on the road. Talk to your kids about safe driving habits. Perhaps the most important thing parents can do to keep their kids safe is to talk about the importance of following safety rules. Reminding your teen that he or she is still learning how to drive well may induce an eye roll or two, but it may also spur second thoughts about making aggressive moves that cross the line into recklessness. Teaching kids about the importance of seat belt use should start well before they learn to drive, but as drivers it’s important to emphasize that both they and their passengers need to buckle up. Teenagers also need to be told about how to deal with fatigue and how to respond calmly to other aggressive drivers on the road. Establish and enforce ground rules. Establishing rules and enforcing them can be effective ways to discourage bad behavior. Some rules should be applied to every teen driver. Drinking or using drugs and then driving is a serious mistake that increases the danger of accidents and puts the driver’s license at risk. Parents should go a step further and take steps to address what may be an early stage of a longer-term problem. Other rules may need to be tailored to a specific teen’s personality. For example, it’s often a good idea to prohibit a teenaged driver from carrying passengers for a period of time, to reduce distractions and potential peer pressure to do something foolish. Some teens may need to be limited in terms of the hours during which they are allowed to drive. Talk about costs. Being up-front about the cost of driving—everything from the cost of cars and gas to the price of insurance and how it can change—can give teenagers an appreciation for the financial risks of accidents. Even if parents will pay some of these costs, teenagers should be asked to bear them in mind. The mechanics of insurance can be especially useful. Perhaps parents can only afford to pay premiums that are set when the teenager has a clean accident record. A teenager who knows this might be more careful about avoiding accidents than one who doesn’t connect his or her behavior with costs. Be prepared to take away driving privileges. Although taking away a teenager’s driving privileges can be a hard step for parents as well as their affected kids, it can be a powerful way to send a message. Even if the law doesn’t step in to stop a teenager from making mistakes, parents should protect themselves and their children by taking away the keys when the teenager has shown a lack of respect for the risks involved in driving. GGRM is a Las Vegas personal injury law firm The law firm of Greenman Goldberg Raby Martinez has represented accident clients in the Las Vegas area for over 45 years. If you have questions about how to manage your teenager’s risks behind the wheel, please give us a call today at 702-388-4476. We can also be reached through our contacts page.
Moderately elevated body mass index is associated with metabolic variables and cardiovascular risk factors in Swedish children. To evaluate associations between anthropometrics and metabolic variables as well as cardiovascular risk factors among children. Subjects were recruited from a cohort of 274 healthy children in Umeå, Sweden. Anthropometric measures, blood pressure and venous blood samples were collected at age 10 years and simultaneously from parents. Altogether 144 children (53%), 142 mothers and 123 fathers participated. The prevalence of overweight and obesity among the children was 18 and 2%, respectively. Overweight children (above age- and sex-specific cut offs corresponding adult BMI ≥ 25 kg/m(2) ), compared to normal weight children, had significantly higher BMI already during infancy and higher S-insulin and Homeostatic Model Assessment (HOMA) index at 10 years. The children's BMI was positively associated with waist (boys' r = 0.67, girls' r = 0.81), hip (r = 0.68), waist/hip ratio (girls' r = 0.37), waist/height ratio (boys' r = 0.59, girls' r = 0.80), sagittal abdominal diameter (r = 0.75), S-insulin (r = 0.45), HOMA index (r = 0.49), systolic blood pressure (r = 0.24), mothers' BMI (girls' r = 0.42) and mothers' waist (girls' r = 0.42). Children at 10 years of age with moderately elevated BMI had higher levels of some metabolic variables and cardiovascular risk factors than did normal weight children, and there was a correlation between BMI and some metabolic variables as well as cardiovascular risk factors.
The world is increasingly complex, instrumented and virtual. There’s vast amounts of information about consumers and the factors that influence their behavior that simply didn’t exist in the data warehouse era. Here, we take a closer look at how all this data will affect retail when it comes together with recent technology trends. We’ve gotten used to emphasizing the divide between digital and physical, but it’s quickly disappearing: when digital data about the physical world is comprehensive, real-time and freely available, the physical and digital augment each other. When testing innovations, it’s risky to ask consumers to compare a new concept against an actual product that they currently purchase. This unbalances the entire evaluation by setting up an unfair comparison. FMCG success today is now dependent on quality product images, solid SEO and prominent placement on e-tailer websites—far more so than simply having an abundant quantity or variety on the shelf at the local store. Unbeknownst to most consumers, tremendous thought goes into developing even the most commonplace products. As a result, product development in the FMCG industry is anything but fast-moving. But what if algorithms could help streamline the process and the outcomes? The variety and increasing scale of data, as well as the scope of activity it is meant to inform, demands a solution that goes well beyond a simple enterprise data warehouse. So what might that more robust solution look like? How many things can you say for certain that you're paying attention to, or even seeing, at any given moment? Our brains just aren’t good at recalling the kinds of details marketers need to evaluate their efforts in a complex world. That’s where the right neuroscience tools can help. The premium sector is growing globally, and as it turns out, it isn’t ritzy categories like diamonds and champagne that are topping the charts. Rather, global consumers are most often willing to trade up for everyday consumables. In the coming decades, machine learning will transform work as we know it. And unlike previous revolutions, which primarily affected blue-collar workers, the smart machine revolution has white-collar workers in its sights. Most new product launches are “small” or “sustaining” innovations, which include the many, many brand extensions that large companies launch year after year. These launches are absolutely essential for growing existing brands and defending shelf space. Most of the customer data companies gather about innovation is structured to show correlations rather than causations. Yet after decades of watching great companies do poorly at innovation, we’ve come to the conclusion that the focus on correlation is taking firms in the wrong direction. Brands armed with new products have always rushed to be first to market, as first movers often establish a stronghold that can be difficult for later entrants to break into. But being “first mover” at the expense of being “best mover” can often lead brands to competitive disadvantage. Growing a brand isn’t easy, especially for those in in crowded categories. But even the most established categories change over time, and even categories that appear stable may be one critical innovation away from awarding one brand a significant long-term advantage. Marketers often think of “earned” media as asymmetric marketing opportunities—they’re cheap and fast, which make them quite easy for smaller brands to exploit. But the power of earned media as an asymmetric strategy is more appearance than reality. Typically, small teams build concepts, get qualitative or quantitative feedback, refine concepts, collect another round of feedback, and so on, until they arrive at a “winning” concept. This technique works well, but it suffers from one major drawback: It often produces ideas that are good enough but not the best. VOD services are undoubtedly transforming the way audiences consume video, so it’s important to tune in to what’s driving engagement around the world. Our recent online global survey found that while several strong motivating factors will support continued growth, there are a few barriers to be mindful of, too. As the media landscape evolves, so too do the sources consumers use to find out about new products. Globally, shoppers' reliance on earned media is growing while their attention toward some paid media sources are declining. Globally, more than six-in-10 respondents (63%) say they like when manufacturers offer new products. But while consumers across the globe are enthusiastic about new products, their purchasing patterns vary widely. Brand building can be costly and time consuming, so the ability to grow via line extensions—the use of an established product brand for a new item in the same category–can be extremely advantageous. In fact, line extensions are approximately three to four times more common than “new manufacturer” and “new brand” launches combined. Innovation matters. In the consumer product realm, it can drive profitability and growth, and it can help companies succeed—even during tough economic times. On the opposite side of the sales counter, consumers have a strong appetite for innovation, but they’re increasingly demanding and expect more choice than ever before. All established companies must address a key challenge: How to find the next disruptive innovation while reacting to the disruptive innovations of others. To use the language of this year's TIBCO conference, how can one “ride the disruption wave”? Mitch Barns explores three things he's found that can play a big role. Successful companies in the private sector have gained deep insight into consumer psychology and individual and collective decision-making. Public policy leaders and program managers can make use of these insights to improve significantly the likelihood of success in achieving their policy goals. Earlier this week, I had the honor of participating in a panel at the Aspen Ideas Festival. The topic—“Global trends that will affect us all”—hit on the key issues that will shape our economies and cultures for the next 20 years. Year after year, thousands of products across brands and organizations hit the retail shelves. Some succeed, whereas most fail. But every once in a while, comes along a product that changes the rules of the game and witnesses unprecedented success. This miniscule percentage falls within the realm of what we call ‘breakthrough innovation’. Scaling this summit is not easy but there are some fundamentals that can help you achieve this. The 'Breakthrough Innovation Report' is a deep dive into the competitive world of innovation in the fast-moving consumer goods space.
BRAF, KIT and NRAS mutations and expression of c-KIT, phosphorylated extracellular signal-regulated kinase and phosphorylated AKT in Japanese melanoma patients. To clarify the status of gene mutation and activation of growth signal in melanoma of Japanese patients in vivo, we analyzed the mutation of BRAF exon 15, NRAS exon 2, and KIT exons 9, 11, 13, 17 and 18 in melanoma cells obtained by laser capture microdissection, and performed direct sequencing in 20 cases of acral lentiginous melanoma (ALM) and 17 cases of superficial spreading melanoma (SSM). In the study of the mutation of BRAF, pyrosequencing was also done. To examine the cell proliferation signaling, immunohistochemistry for phosphorylated extracellular signal-regulated kinase (pERK), phosphorylated AKT (phosphorylated AKT) and c-KIT was done. The mutation of BRAF p.V600E was detected in 13 cases of ALM (65.0%) and 12 cases of SSM (70.6%). No NRAS mutation was found in all cases. The mutation in exons 9, 11, and 18 of KIT was detected in nine cases. The mutation of BRAF and KIT showed no correlation with clinical stage, lymph node metastasis, tumor thickness, ulceration and histology. pERK and pAKT was observed in small population of melanoma cells and there was no correlation with gene mutation. Our results indicate that the mutations of BRAF and KIT exist in Japanese melanoma patients, however, the cell growth signaling may be regulated by not only these mutated genes, but by other unknown regulatory factors, which may affect the prognosis of melanoma.
Hops in the mash. Hops in the empty kettle. Hops in the full kettle. Hops at flame out. Hops in the whirlpool. Hops with the yeast. Hops after fermentation. Hops before cold crashing. There were alot of hop additions in this beer and every single Columbus addition has added a layer of that stereotypical west coast flavour. Enjoy fresh. Enjoy often.
import os import collections import torch import numpy as np import scipy.misc as m import matplotlib.pyplot as plt from torch.utils import data from ptsemseg.augmentations import Compose, RandomHorizontallyFlip, RandomRotate class camvidLoader(data.Dataset): def __init__( self, root, split="train", is_transform=False, img_size=None, augmentations=None, img_norm=True, test_mode=False, ): self.root = root self.split = split self.img_size = [360, 480] self.is_transform = is_transform self.augmentations = augmentations self.img_norm = img_norm self.test_mode = test_mode self.mean = np.array([104.00699, 116.66877, 122.67892]) self.n_classes = 12 self.files = collections.defaultdict(list) if not self.test_mode: for split in ["train", "test", "val"]: file_list = os.listdir(root + "/" + split) self.files[split] = file_list def __len__(self): return len(self.files[self.split]) def __getitem__(self, index): img_name = self.files[self.split][index] img_path = self.root + "/" + self.split + "/" + img_name lbl_path = self.root + "/" + self.split + "annot/" + img_name img = m.imread(img_path) img = np.array(img, dtype=np.uint8) lbl = m.imread(lbl_path) lbl = np.array(lbl, dtype=np.int8) if self.augmentations is not None: img, lbl = self.augmentations(img, lbl) if self.is_transform: img, lbl = self.transform(img, lbl) return img, lbl def transform(self, img, lbl): img = m.imresize(img, (self.img_size[0], self.img_size[1])) # uint8 with RGB mode img = img[:, :, ::-1] # RGB -> BGR img = img.astype(np.float64) img -= self.mean if self.img_norm: # Resize scales images from 0 to 255, thus we need # to divide by 255.0 img = img.astype(float) / 255.0 # NHWC -> NCHW img = img.transpose(2, 0, 1) img = torch.from_numpy(img).float() lbl = torch.from_numpy(lbl).long() return img, lbl def decode_segmap(self, temp, plot=False): Sky = [128, 128, 128] Building = [128, 0, 0] Pole = [192, 192, 128] Road = [128, 64, 128] Pavement = [60, 40, 222] Tree = [128, 128, 0] SignSymbol = [192, 128, 128] Fence = [64, 64, 128] Car = [64, 0, 128] Pedestrian = [64, 64, 0] Bicyclist = [0, 128, 192] Unlabelled = [0, 0, 0] label_colours = np.array( [ Sky, Building, Pole, Road, Pavement, Tree, SignSymbol, Fence, Car, Pedestrian, Bicyclist, Unlabelled, ] ) r = temp.copy() g = temp.copy() b = temp.copy() for l in range(0, self.n_classes): r[temp == l] = label_colours[l, 0] g[temp == l] = label_colours[l, 1] b[temp == l] = label_colours[l, 2] rgb = np.zeros((temp.shape[0], temp.shape[1], 3)) rgb[:, :, 0] = r / 255.0 rgb[:, :, 1] = g / 255.0 rgb[:, :, 2] = b / 255.0 return rgb if __name__ == "__main__": local_path = "/home/meetshah1995/datasets/segnet/CamVid" augmentations = Compose([RandomRotate(10), RandomHorizontallyFlip()]) dst = camvidLoader(local_path, is_transform=True, augmentations=augmentations) bs = 4 trainloader = data.DataLoader(dst, batch_size=bs) for i, data_samples in enumerate(trainloader): imgs, labels = data_samples imgs = imgs.numpy()[:, ::-1, :, :] imgs = np.transpose(imgs, [0, 2, 3, 1]) f, axarr = plt.subplots(bs, 2) for j in range(bs): axarr[j][0].imshow(imgs[j]) axarr[j][1].imshow(dst.decode_segmap(labels.numpy()[j])) plt.show() a = input() if a == "ex": break else: plt.close()
For male or female, this product is effective for us in reducing sudden urges to urinate. One a day is effective dose. This got me through some issues associated with side effects of some medication. Now, I use it only sporadically when needed. My system responds to it quickly.
A display device includes a display panel and a backlight disposed on a rear surface side of the display panel. The display device includes a lower frame accommodating a light source and an optical plate, which constitutes a backlight, a frame-like middle frame (also referred to as a mold frame) that is fixed to the lower frame with screws while holding a display panel, and a frame-like upper frame that is fixed to the lower frame or middle frame with screws while covering the display panel from a display surface side. Recently, in the display device, there is known a problem in that a warp occurs due to heat generation associated with increase in size and high luminance and the display panel is brought into contact with another component. For example, WO 2010/073804 discloses a technique for solving the problem. In the technique of WO 2010/073804, a spacer is provided between a peripheral portion of the display panel and a peripheral portion of an optical member to separate the display panel from the optical member.
The SEGA Saturn was something of a black sheep in SEGA’s family of consoles. It divorced itself from many of its predecessor’s most well-known franchises, and instead focused on a slew of original IPs. Even Sonic Team would take a big break from Sonic, instead focusing on NiGHTS into Dreams and Burning Rangers, the former becoming the Saturn’s mascot. This would lead to the Saturn becoming the one and only SEGA console to not feature a wholly original Sonic platforming game. Instead, the Saturn merely saw a trio of spin offs, in the form of Sonic 3D Blast, Sonic R and the subject of today’s review, Sonic Jam. The first two were fairly mediocre spin offs created by Traveler’s Tales for the purpose of filling the cap by the canned Sonic X-Treme game. Sonic Jam was easily the best Sonic game on the Saturn, though largely because it capitalized so heavily on the past: it was a compilation of the best Sonic titles ever made. Firstly, let’s talk about the quality of the ports: I am happy to say that there was clear effort put into bringing these games to the Saturn. These are not simple emulations, but rather ports recoding the games for the Saturn hardware. As a result, many bugs from the originals have been removed, including the infamous spike death glitch from Sonic 1. Additions have also been made to all the games, including the addition of a spin dash in Sonic 1, as well as alternate difficulty modes that change or remove stages to reduce the challenge, and a time attack mode. On top of the improvements made to the original games, Sonic Jam also adds some all new content in the form of “Sonic World”, a small three dimensional level that the player can run around in. This world is the closest we ever come to playing a true 3D Sonic adventure game on the Saturn, and it is indeed a glorious experience for any Saturn fan who’s had to endure the myth that the Saturn can’t handle three dimensional graphics. Sonic World is both a testament to Saturn’s technical capabilities, and a fun little area to run around in. The world gives you a series of trials to complete, such as collection rings, hitting goal posts, and rescuing tales. The world also serves as a hub for the game’s special features. You can listen to music, watch Japanese commercials and rarely seen cartoons, and look at art for the games, all through the world’s various museums. Graphically, Sonic Jam is a top notch affair through and through. The frame rate is often better than the Genesis originals, ironing out some of the stuttering that occurred in the originals. Sonic Jam also runs well, and is easily one of the best examples of three dimensional graphics on the Saturn. It’s amazing what Sonic Team has been able to do here, especially when compared with many of the third party efforts on the Saturn. The world serves as playable proof of Sonic Team’s deep understanding of the machine. Sonic Jam’s audio is also top notch. The Sonic series is renowned for its soundtrack, and newcomers will be able to see why here. The Sonic series’ music is a mix of jazzy tunes, 16 bit rock, and all sorts of other melodies. Sky Sanctuary is a particularly favorite of mine. It has a sweeping, epic track that makes some of the best use of the Genesis’ musical capabilities out of any game I’ve experienced. I’ve frequently come back to this level largely because of its music. The music in Sonic Jam’s Sonic World also certainly fits in with the audio tracks from the Genesis games, though it’s not quite as catchy. Sonic Jam still stands as an exceptional compilation, even today. It’s head and shoulders above a recent release. (link to Sonic Classic Collection) It doesn’t have as many games as Sonic Mega Collection or Sonic Gems collection, but I would say it’s still better then these other compilations. No one wants to play Sonic Spinball, or the Genesis version of Sonic 3D Blast, or Sonic R. While SMC and SGM just take a bunch of roms and slap them on a disc, Sonic Jam has the definitive versions of core Sonic games people actually care about and want to play. Sonic Jam isn’t as cool as it was when it came out. The art, music, and movies in the game’s museums are now all readily available on the internet. SMC and SGM also have some pretty cool games that Sonic Jam lacks, like Ristar and Sonic Triple Trouble. There really is no definitive Sonic compilation. For those who just want to play the core Sonic Genesis games Sonic Jam is still easily the best choice. At least, until SEGA finally decides to stop screwing around and just throw a rom of Sonic Jam onto Xbox Live. Positives Definitive versions of Sonic’s best games Loads of videos, music, and concept art Sonic World is a neat little example of 3D Sonic on the Saturn Negatives
Dysplastic nevi of the scalp and forehead in children. To determine if there is a significant difference in the relative frequency and degree of atypia of sporadic dysplastic nevi from the scalp, face, and neck area in children as compared with nevi from the rest of the body, we reviewed 99 consecutive biopsy specimens of melanocytic nevi from the scalp, face, and neck areas in children less than 18 years of age and compared them with 95 consecutive cases of nevi from other areas of the body in children of the same age. Large numbers of the nevi biopsied from the scalp (13 of 31; 41.93%) and forehead (2 of 10; 20%) were dysplastic. The number of dysplastic nevi from the neck (1 of 58; 1.72%) was not assessed as very different from the incidence found in other regions of the body, where 7 dysplastic nevi (7.36%) from a total of 95 nevi were found. Of the 13 dysplastic nevi from the scalp, 9 showed minimal atypia and 4 showed moderate atypia. No nevi with severe atypia were found. Many pigmented nevi from the scalp and forehead in children in this study were dysplastic. This finding points out the importance of examining the scalp of children for the presence of dysplastic nevi. The majority of nevi from the neck were common nevi.
This paper investigates the income effects of the South African Social Pension. Using data from three waves of the the Labour Force Survey, we find that there appears to be a significant negative association between labour ... We use longitudinal tax data linked to immigrant landing records to study the effect of selective attrition on the estimated earnings assimilation of immigrants to Canada. Contrary to findings in the existing international ... We use panel data collected in metropolitan Cape Town to document the role played by aging parents in caring for the children of children who die. In addition, we quantify the probabilities that older adults and the older ... The rapid growth in imports from China over the past decade is seen as a key factor contributing towards the relatively slow growth in output and the decline in employment in South African manufacturing during this period. ... This paper proposes a model that can be used to predict the likely impacts of tobacco tax increases and harmonisation in the East African Community. The model has five sections, one for each EAC country. These sections ... Mussa, R.(Southern Africa Labour and Development Research Unit, 2010-09) The paper uses data from the Second Malawi Integrated Household Survey (IHS2) to investigate the impact of fertility on poverty in rural Malawi. We use two measures of poverty; the objective and the subjective. After ... This paper examines the impact of health status on poverty status, accounting for the endogeneity of health status. Using exogenous measures of health status from the South African Integrated Health Survey, we instrument ... The HIV/AIDS pandemic continues to have a devastating impact, particularly on the lives of sub‐ Saharan African children. In addition to reversing the downward secular trend in infant and child mortality, HIV/AIDS has ... The use of small-scale off-grid renewable energy for rural electrification is now seen as part of the sustainable energy solutions. The expectation from such small-scale investment is that it can meet the basic energy needs ... We analyse longitudinal data from a demographic surveillance area (DSA) in KwaZulu-Natal, to examine the impact of parental death on children's outcomes. We find significant differences in the impact of mothers' and fathers' ... Post-apartheid education funding is designed to redress past inequalities in funding and, in doing so, work towards providing all learners with high quality education (Schools Act, 1996). In August 2006, new National Norms ... Cash transfer programs are used as new policies to increase nutrition and human capital of children from poor families. We evaluate South Africa's unconditional Child Support Grant (CSG) in which cash grants are made to ... The introduction of combination antiretroviral therapy (ART) has been one of the great public health success stories of the past 40 years. ART has led to increased survival in people living with HIV, and subsequently to ... South Africa is distinguished from other countries by its history of Apartheid, in which race-based policies resulted in vastly inferior education and labour market opportunities for African, Coloured and Asian/Indian ... This paper investigates changes in and patterns of income inequality in South Africa during the post-apartheid period 1994 to 2004. While findings show a rapidly growing high-income African population (a trend that began ...
Many students take out loans during their studies, only to realize it's not so easy to pay back that money after the fact. The U.S. Federal Reserve reports that the average monthly student loan payment is $393 (not including borrowers whose payments are in deferment). That's a lot of money to fork over on a regular basis, and it partly explains why such a large number of borrowers have already failed to keep up with their student loan payments. As of early 2019, there are 5.2 million borrowers in default on their federal student loans, according to our Student Loan Debt Statistics for 2019. And those same borrowers face a host of consequences as a result. The trouble with defaulting Federal student loans are considered to be in default once a borrower goes 270 days without making a payment. But as soon as you reach default status, you face a host of unsavory repercussions. For one thing, your credit score is pretty much guaranteed to tank. That's a problem if you want to borrow money in the form of a personal loan, auto loan, or credit card. And, in some industries, poor credit can actually prevent you from getting a job. But credit score implications aside, defaulting on student loans can also result in a scenario where some of your wages are garnished. And needless to say, if you're already struggling financially, that'll only make your situation worse. As such, it pays to do everything in your power to avoid defaulting on your student loans -- because your finances can't afford that kind of hit. Avoiding default The good thing about federal student loans is that they come with a number of borrower protections designed to help you avoid that dreaded default scenario. First, if you're spending a large chunk of your income on loan payments and can no longer afford to keep doing so, you can apply for an income-driven repayment plan. Under one of these plans, your monthly loan payments will be recalculated based on a reasonable percentage of your income -- and for the most part, that percentage is capped at 10%. Another thing you can do if you've fallen behind on your loans, or are at risk of falling behind, is to reach out to your loan servicer and see if it's possible to hit the pause button on your payments. You have two options in this regard -- forbearance and deferment. With the former, interest continues to accrue on your student loans during the period in which you're not making payments. With the latter, you don't accrue interest. To qualify for either option, however, you'll need to demonstrate a legitimate financial hardship, such as being unemployed. As such, you might have better luck getting on an income-driven repayment plan. Keep in mind that forbearance and deferment are only on the table if you haven’t defaulted on your debt. Once you reach default status, you lose these protections. It's unfortunate that more than 5 million federal loan borrowers have defaulted on their student debt, but you don't need to join their ranks. Do your best to manage your loans by staying on a tight budget, and pursue the above remedies if you start to fall behind on your payments. Remember, default doesn't kick in right away, so if you miss a loan payment or two, there's plenty of opportunity to recover before your finances truly take a long-term turn for the worse.
1. Field of the Invention The present invention relates to chemical oxygen iodine laser's (COIL) and more particularly to a coil gain generator which provides enhanced efficiency, flow capacity and pressure recovery. 2. Description of the Related Art COIL (Chemical Oxygen Iodine Laser) devices produce laser optical energy from energy stored in a form of oxygen known as singlet delta oxygen, (O.sub.2 (.sup.1 .DELTA.)). The O.sub.2 (.sup.1 .DELTA.) is typically produced in a gas liquid contact reactor (see e.g., U.S. Pat. No. 5,658,535, U.S. Pat. No. 5,624,654 and U.S. Pat. No. 5,516,502) from gaseous chlorine (Cl.sub.2) and liquid basic hydrogen peroxide (BHP). The BHP is a mixture of hydrogen peroxide and a strong base such as KOH. The gaseous Cl.sub.2 is absorbed into the BHP and reacts to form the highly energetic O.sub.2 (.sup.1 .DELTA.) which diffuses out of the BHP into the gaseous phase. The O.sub.2 (.sup.1 .DELTA.) has a strong tendency to be quenched by pooling the energy of two O.sub.2 (.sup.1 .DELTA.) molecules to form an even more energetic specie known as oxygen singlet sigma, (O.sub.2 (.sup.1 .SIGMA.)). The O.sub.2 (.sup.1 .SIGMA.) quickly returns to the O.sub.2 (.sup.1 .DELTA.) state, with the overall process resulting in a net loss of the equivalent stored energy of one O.sub.2 (.sup.1 .DELTA.) molecule. As a consequence of this pooling loss process, the reactors producing O.sub.2 (.sup.1 .DELTA.) must be operated at low O.sub.2 (.sup.1 .DELTA.) pressure and short gas residence time to avoid excessive losses. The need for short residence time encourages the designer to use fast gas velocity in the reactor, but carryover of liquid with the O.sub.2 (.sup.1 .DELTA.) product gas sets a limit on the maximum gas velocity which can be used. The need for low O.sub.2 (.sup.1 .DELTA.) pressure encourages the designer to employ low pressure reactors. However, a vacuum system is needed to exhaust all laser exhaust. The lower the reactor pressure, the lower the vacuum pressure must be, leading to a larger and more costly vacuum system. Typically, the Cl.sub.2 reactant is mixed with a diluent to raise the overall pressure of the reactor while keeping the O.sub.2 (.sup.1 .DELTA.) pressure low. To minimize gas density in the reactor, a low molecular weight diluent is selected, and it is most often helium. Downstream of the reactor producing O.sub.2 (.sup.1 .DELTA.), iodine is mixed into the oxygen (see e.g., U.S. Pat. No. 4,653,062). Usually the iodine is in the form of diatomic molecules, (I.sub.2). The iodine is quickly dissociated into iodine atoms by a process involving O.sub.2 (.sup.1 .DELTA.). Iodine atoms have an elevated energy level very near to the difference in energy levels of O.sub.2 (.sup.1 .DELTA.) and ground state oxygen (O.sub.2.sup.3 .SIGMA.). The energy of O.sub.2 (.sup.1 .DELTA.) is quickly interchanged back and forth with the iodine atoms in a process which is near to equilibrium. The excited iodine atoms, often designated as I*, are the lasing specie used to extract energy from the mixed gases. The equilibrium fraction of iodine atoms in the I* state increases as the gas temperature is lowered. The I* specie is unfortunately quenched to the ground state very quickly, with conversion of the energy to heat, by several species, the specie of most concern being water vapor (from the BHP) which accompanies O.sub.2 (.sup.1 .DELTA.) effluent from the reactor. The I* quenching issue is most important in the region between the I.sub.2 injection location and the start of the laser cavity (the "dissociation zone"), Consequently, the length of the dissociation zone is kept as small as practical by the COIL designer to minimize the losses due to I* quenching. The issue is less pronounced in the laser cavity because the lasing process reduces fraction of I* and hence the rate of quenching is reduced. Because the equilibrium toward I* is more pronounced at low temperature, there is a power extraction efficiency advantage to running the laser cavity at low temperature. This is typically achieved by accelerating the gases to supersonic Mach numbers. As higher Mach numbers are selected, the pressure in the cavity must be lowered (rather than increasing the gas source pressure), since the available O.sub.2 (.sup.1 .DELTA.) pressure is limited by the need to keep the reactor producing O.sub.2 (.sup.1 .DELTA.) at low pressure as discussed above. The major disadvantage of higher Mach numbers is the impact on the vacuum system needed to operate the laser. Generally after laser energy extraction the high Mach number gases are passed into a diffuser where pressure is recovered from the high Mach number momentum. The typical COIL operates at a supersonic cavity Mach number of about 2, which is a compromise between higher laser power extraction at low temperatures corresponding to higher Mach numbers, and less pressure recovery at higher Mach numbers, and lower cavity pressure which leads to less pressure recovery at higher Mach numbers. Oftentimes, the iodine injection/mixing/dissociation function and the nozzle for accelerating the gas to Mach 2 are combined in the same piece of hardware, since the dissociation zone is best kept small. The three most difficult issues related to COIL devices are (1) the avoidance of liquid BHP carryover (which scatters laser light and produces deleterious water vapor) with the reactor effluent, (2) the low pressure recovery which results in a large exhaust vacuum system, and (3) achievement of high overall efficiency (defined in terms of the ratio of laser power output to Cl.sub.2 gas input). Direct substitution of nitrogen diluent for the usual helium diluent in a COIL device reactor producing singlet delta oxygen generator results in a low flow capacity due to the effects of higher gas density leading to carryover of the liquid basic hydrogen peroxide into the laser cavity. As a consequence, it is necessary to significantly reduce the throughput of the laser device. Furthermore, the high gas density requires a lower gas flow velocity to avoid liquid carryover. The low velocity leads to decay of the singlet delta oxygen before it reaches the laser cavity. The net result is reduction by almost 50% in total flow capacity, and a further reduction of approximately 50% in laser efficiency. The same device, thus produces only about 1/4th the total laser power.
Inverness CT 3-1 Coventry City Coventry City capped off their pre-season tour of Scotland with a 3-1 defeat to Inverness Caledonian Thistle at the Tulloch Caledonian Stadium. Richie Foran converted a spot kick after 19 minutes to put the hosts ahead and Bill McKay made it two four minutes after the break. Shaun Jeffers grabbed one back for City five minutes later nly for Cally substitute Jason Oswell to notch a third for the hosts late on. City had their best opportunity of the first half to open the scoring in the first three minutes when a through ball from Shaun Jeffers found Gary McSheffrey who was brought down by Graeme Shinnie for a penalty. John Fleck, who converted twice from the spot in City's friendly with Brora on Tuesday, stepped up to take the penalty but struck the post. Jordan Clarke fizzed an effort just wide of the far post after 12 minutes and McSheffrey also had a chance to put City ahead after a superb through ball from Fleck set him free, his first time effort saved by Ryan Esson. Inverness then got themselves infront with their own spot kick on 19 minutes. Andrew Shinnie broke free and played through Billy McKay. City defender William Edjenguele slid in top put the stoppers on the striker but handles on the follow through, referee Iain Brines pointing to the spot where Foran converted. Carl Baker then almost carved out a goal for City on the half hour with a great cross for Jeffers who glanced his header just wide from six yards out. City's second half started on a sour note when after 49 minutes Cally increased their lead. Andrew Shinnie's long range effort was parried by Joe Murphy but only as far as McKay who fired home the loose ball from six yards. It was game on again though five minutes later when a superbly crafted move allowed the Sky Blues to pull one back through Jeffers, Baker rushing through the midfield and playing a short ball to McSheffrey whose first time chip over the defence fell into the path of Jeffers who cooly slotted home from a narrow angle. The second half though descended into a midfield battle after a blistering opening ten minutes as both sides fought to take control of the game. Aaron Doran forced a fingertip save out of Murphy on 76 minutes, the City keeper tipping the shot around his post. McSheffrey then looked like he was going to get another back for the Sky Blues with seven minutes left when he dribbled into a scoring position just inside the edge of the area only to take one touch too many and see the opportunity pass by as his eventual shot was blocked by a stray leg. Substitute Jason Oswell finished off the game though with his late goal, a cutback from Doran finding him unmarked as he ghosted into the area before firing a measured finish past Murphy
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11 Wn. App. 42 (1974) 521 P.2d 233 ELMER MARTINSON et al., Respondents, v. PUBLISHERS FOREST PRODUCTS COMPANY, Appellant. No. 1825-1. The Court of Appeals of Washington, Division One. April 22, 1974. Lenihan, Ivers, Jensen & McAteer and Carl P. Jensen, for appellant. John Ward, for respondents. CALLOW, J. The plaintiffs Elmer and Cleon Martinson, who did business as Martinson Brothers Logging Company, brought an action to recover funds retained by the defendant, Publishers Forest Products Company, as a cash bond to guarantee the performance of a logging contract and other funds retained to assure construction of a spur road on the logging location. The plaintiffs claimed they partly performed the contract and then ceased performance at the request of the defendant. The defendant cross claimed alleging that the plaintiffs failed to construct roads pursuant to the contract, that the defendant never requested the plaintiffs to stop logging and that because of the plaintiffs' breach of the contract, the defendant was damaged substantially. Judgment was entered for the plaintiffs for the return of the withheld funds, and the cross claim of the defendant was dismissed. The defendant has appealed claiming the trial court erred in the entry of certain findings of fact and conclusions of law, in dismissing the defendant's cross claim and in denying the motion to dismiss the plaintiffs' case on the ground that the plaintiffs were contractors and were not licensed under RCW 18.27. The pertinent terms of the contract which had an effective date of May 1, 1970, read as follows: 1. Logging Operations: The Contractor shall log and deliver to the Company all of the merchantable and otherwise usable timber ... designated for logging by a representative of the Company (hereinafter called "Forester") on the below described land, containing approximately *44 _______ acres and approximately 5000 M board feed of timber: Including Pulp ... 2. Term: The term of this contract shall be from the date hereof to and including December 31, 1970. ... 5. Time of Performance: Time is the essence of this contract, and the Contractor will promptly perform each and every obligation, as hereinafter provided, and will commence active logging on said lands as soon as possible after the execution of this Contract and will carry on a continuous operation to the end that the logs to be produced hereunder will be logged and delivered within the term of this Contract. ... 10. Roads and Rights-of-Way: Unless otherwise stated under "Special Conditions," Paragraph 23 hereof, the Company will permit the Contractor to use at his own risk such existing roads and rights-of-way on its property as may be required, ... All additional roads required shall be constructed by the Contractor at his sole expense, to specifications of location, grade, alignment and construction as may be approved by the Company.... ... The Company may withhold from amounts owing by it to the Contractor, as a cash bond to guarantee full and faithful performance of this contract, the sum of $ ____ per 1000 lbs. or $2.00 per M board feet of logs delivered until the amount retained equals the sum of $8,000.00. Said cash bond, or so much thereof as has not otherwise been applied, shall be paid to the Contractor upon completion of this Contract satisfactory to the Company in accordance with its terms. ... CONTRACTOR WILL PAY COST OF ALL SPUR ROAD CONSTRUCTION, ROAD REPAIR OF CLEARWATER ROAD, AND HIS PRORATA SHARE OF CLEARWATER ROAD MAINTENANCE, AND ORDINARY MAINTENANCE OF U.S. FOREST SERVICE MIDDLE FORK ROAD. COMPANY WILL PAY THE COST OF CRUSHED ROCK REPLACEMENT ON FOREST SERVICE ROAD. COMPANY SHALL WITHHOLD $5.00 PER M. ON ALL LOGS DELIVERED UNTIL SPUR ROAD CONSTRUCTION ON LOCATION APPROVED BY PUBLISHERS HAS BEEN COMPLETED. *45 SAID LOCATION HAS BEEN SHOWN APPROXIMATELY ON EXHIBIT "A". The findings of the trial court reflected that the plaintiffs were not licensed or registered as contractors under RCW 18.27. The findings further indicated that the parties entered into a written contract which required the plaintiffs to furnish all labor, material, machinery, and equipment to log, remove and deliver approximately 5 million board feet of timber from land owned by the defendant. This contract also required the plaintiffs to do such repair work on the access road to said premises as was necessary to accomplish this logging and to construct such spur roads as were necessary to log said land. The contract provided that the defendant might retain out of sums due under the contract the sum of $2 per thousand board feet until a total sum of $8,000 was accumulated, in lieu of a performance bond. The defendant accumulated $3,394.08 under this provision. The contract further provided that the defendant was authorized to withhold $5 per thousand board feet on all logs delivered until the spur road construction had been completed. Eight thousand four hundred and eighty-five dollars and twenty cents had been retained by the defendant under this provision in the contract. The logging operation was to be supervised by Douglas Mavor, the defendant's logging manager. Ron Smith, the defendant's forestry engineer, was to lay out the spur roads to be built for access to the timber. The defendant acted through Mavor and Smith at all relevant times. The findings also showed that the plaintiffs had inspected the road which was the access to the premises to be logged and those premises prior to the execution of the written contract. The plaintiffs repaired this access road as required by the contract. The plaintiffs commenced the required road construction in May 1970. Thereafter, logging was begun and was carried out along the access road and not along spur roads. *46 The trial judge found that in August or September of 1970 it became apparent to both parties that the plaintiffs could not complete the logging of the timber by December 31, 1970. Both parties testified that of the approximately 5 million board feet of timber to be logged and delivered by plaintiffs that they only logged and delivered 1.7 million board feet. It is further the undisputed testimony of the parties that the plaintiffs did not construct all of the spur roads required in order to accomplish the logging of this tract. The finding is that Mavor had casual contact with the plaintiffs but did not complain about their logging production or road construction. It was found that during September 1970, Mavor indicated to the plaintiffs that the defendant did not want any more timber. The forestry engineer, Smith, voiced similar statements, and his assistant told plaintiffs that the defendant company did not want any more logs delivered to LaConner. The plaintiffs continued to log and deliver logs until November 24, 1970. Continuing, the findings were that during the fall of 1970 Mavor negotiated with the plaintiffs to the effect that the plaintiffs were to commence cutting cedar poles in an area at lower elevation, and the plaintiffs were thereafter advised that they could start cutting cedar poles when they wanted to. The defendant through its forester secured a permit from the State Department of Natural Resources in early November 1970, which permit had an expiration date of December 31, 1970. The next activity with respect to the May 1970 contract was on June 4, 1971, when the attorney for the plaintiffs wrote demanding payment of the retained sums under the contract, in the total amount of $11,879.28. The defendant replied on June 7, 1971, advising that as far as the defendant knew, the plaintiffs intended to complete the contract. On July 6, 1971, the defendant wrote to the plaintiffs purporting to extend the contract to December 31, 1971. Finally, the court found that the defendant had negotiated with other loggers to complete the logging of the tract. *47 The assignments of error raise the following issues: (1) whether loggers are prohibited by RCW 18.27 from bringing a suit based upon a logging and road construction contract, (2) whether the dismissal of the cross claim was proper, and (3) whether the contract was mutually abandoned. [1] The plaintiffs were not required to be licensed as contractors under RCW 18.27. The purpose of the act as discussed in Stewart v. Hammond, 78 Wn.2d 216, 219, 471 P.2d 90 (1970), has been reaffirmed often. There the court said: RCW 18.27, et seq., was designed to prevent the victimizing of a defenseless public by unreliable, fraudulent and incompetent contractors, many of whom operated a transient business from the relative safety of neighboring states. Public protection was sought by the registration and bonding of contractors. RCW 18.27.020-.040 inclusive. Noncompliance was discouraged by providing a criminal penalty, RCW 18.27.020, and by denying offenders access to the courts for collection of compensation for performance of work or for breach of contract. RCW 18.27.080. See also H.O. Meyer Drilling Co. v. Alton V. Phillips Co., 79 Wn.2d 431, 486 P.2d 1071 (1971); Murphy v. Campbell Inv. Co., 79 Wn.2d 417, 486 P.2d 1080 (1971). It was pointed out in Jeanneret v. Rees, 82 Wn.2d 404, 511 P.2d 60 (1973), that a contractor could not maintain an action for compensation for the performance of any work or for the breach of any contract without alleging and proving he was duly registered and had a current valid certificate of registration unless (a) he had substantially complied with RCW 18.27 or (b) registration was not required because of one of the specific exceptions set forth in the act. We do not find a substantial compliance with the act. The primary requirements of compliance with the act are the filing of a surety bond and registration. RCW 18.27. The chapter contains specific directives as prerequisites to registration. While the owner and the contractor secured a permit to cut timber from the supervisor of forestry (RCW 76.08.030) *48 and the contract provided for the withholding of sums to provide a cash bond to guarantee performance of the contract, these two circumstances are not an adequate replacement for the purposes of registration and the posting of a bond with the state under RCW 18.27. Each case must rest on its own facts and the statutory language of the registration act involved. Northwest Cascade Constr. Inc. v. Custom Component Structures, Inc., 83 Wn.2d 453, 519 P.2d 1 (1974); Stewart v. Hammond, supra. The circumstances present do not call for an inquiry into the authorities of other states, but see Fray v. Rogers, 272 Cal. App.2d 858, 77 Cal Rptr. 776 (1969); Annot., 19 A.L.R.3d 1407 (1968). The deeds of the plaintiff were insufficient substitutes for actual registration to enfold the activity in the cloak of substantial performance. [2] RCW 18.27.010 defines a contractor as any firm who or which "in the pursuit of an independent business undertakes to, ... construct, alter, repair, ... for another, any ... road,..." The plaintiff was not required to register, however, under the exception provided by RCW 18.27.090(10) which exempts from the provisions of RCW 18.27 any construction or operation incidental to clearing or other work upon land in rural districts for fire protection purposes. The logging contract which the parties entered into on May 1, 1970, provided that the contractor agreed to comply with all laws and regulations relating to fire hazard in the conduct of these logging operations. The contract also provided that the contractor (a) agree to build all fire trails specified by the forester at his own expense, (b) construct tractor skid roads only with prior approval of the forester, (c) keep road ditching and culverts cleaned and free of obstructions, (d) perform the maintenance or repair of roads by and at the expense of the contractor to the satisfaction of the forester and to leave the roads as improved, in good condition and repair. The logging engineer for the defendant testified that the purpose of the spur roads and of the logging roads once the *49 logging was completed was for fire protection and management of the new stand. He further testified that some of the spur roads would be kept open for 4-wheel vehicles for fire protection after the spur roads were no longer used for logging. The primary purpose of the construction of the roads was for logging access, but an important incidental purpose was fire prevention. The plaintiff was not required to register under RCW 18.27. RCW 18.27.090(10); Jeanneret v. Rees, supra. The trial court, in addition to the findings previously recited, also found: The duties and obligations imposed by the contract between the parties were mutually abandoned by both parties. [3, 4] The determination that a contract has been abandoned was treated as a finding of fact in Monroe v. Fetzer, 56 Wn.2d 39, 42, 350 P.2d 1012 (1960), which said: The finding of the trial court that the parties mutually abandoned the contract is supported by substantial evidence, and is in harmony with the rule that a contract will be treated as abandoned where the acts of one party inconsistent with its existence are acquiesced in by the other. Ferris v. Blumhardt, 48 Wn. (2d) 395, 293 P. (2d) 935 (1956); Wiegardt v. Becken, 21 Wn. (2d) 59, 149 P. (2d) 929 (1944). See also Sauder v. Dittmar, 118 F.2d 524 (10th Cir.1941); In re Estate of Lyman, 7 Wn. App. 945, 503 P.2d 1127 (1972). Whether a contract has been abandoned by the mutual consent of the parties is a finding to be made by the trial court based upon the facts and circumstances surrounding the transaction. The inquiry of the trial court is to determine what, if any, new aim and purpose the parties had in mind. As In re Estate of Wittman, 58 Wn.2d 841, 844, 365 P.2d 17 (1961), declared: An agreement of rescission must itself be a valid agreement. 12 Am. Jur. 1011, § 431. Thus, all parties to the contract must assent to its rescission and there must be a meeting of their minds. 17 C.J.S. 881, § 389. Morango v. Phillips, 33 Wn. (2d) 351, 205 P. (2d) 892. *50 The existence of abandonment depends upon intent and may be implied from the acts of the parties. Lohn v. Fletcher Oil Co., 38 Cal. App.2d 26, 100 P.2d 505 (1940); Warren v. Gray, 90 Ga. App. 398, 83 S.E.2d 86 (1954); Moore v. Hayter, 153 Kan. 1, 108 P.2d 495 (1940). Conceptual difficulties arise from the terms employed to describe the action taken by the parties to terminate performance under a contract. The occurrence of the action is described as the occurrence of a fact; yet the finding of abandonment gives rise to a legal conclusion and result. The classification of abandonment as a finding of fact or a conclusion of law has little impact, but realizing the existence of mutual intent to discontinue performance is dispositive. Likewise, abandonment and rescission often are alluded to as synonymous. Jakober v. E.M. Loew's Capitol Theatre, Inc., 107 R.I. 104, 265 A.2d 429 (1970), held that whether a contract has been abandoned is a question of fact and then defined the terms as follows at page 111: In 2 Black, Rescission of Contracts (2d ed.) § 532, at 1306-1307, the author points out that, where a party distinctly and completely abandons all rights and obligations under a contract, the other party may assent to such an abandonment and thereby effect a rescission of the contract; or he may refuse to accept the abandonment and sue for damages because of the other party's repudiation; or he can await for the time of performance and hold the other party responsible for all the consequences of his nonperformance including a bill for specific performance.... rescission is something more than the termination of a contractual obligation. It seeks to create a situation as if no contract existed.... rescission differs from a breach of a contract by abandonment or repudiation in that to have a rescission there must be a mutuality expressed or implied. Likewise, rescission is defined in 5A Corbin, Contracts, § 1236, at 533, as a mutual agreement by the parties to an existing contract to discharge and terminate their duties thereunder. ... if one of the contracting parties assents to the abandonment of the contract by the other party, there has been a rescission of the contract. Both parties are then *51 restored to the status they occupied prior to the contract, and neither can sue the other on the contract.... Abandonment, ... is a unilateral act. Rescission is a bilateral action. With these precepts set forth, we must determine if the record supports abandonment as a fact with substantial evidence. It had become apparent to both parties in the late summer of 1970 that the logging on the premises described in the contract could not be completed by December 31, 1970. The agents of the defendant told the plaintiffs they did not want any more timber. By their statements and acts, the parties concurred that logging would cease in that area; and the plaintiffs phased out the logging operations under way. In the fall of 1970, Mavor negotiated with the plaintiffs to commence cutting cedar poles in an area at a lower elevation, and a permit was secured to cut timber in the new area from whence the cedar poles were to be taken. The plaintiffs transferred their operations to the new area. The securing of the first and second permit is entirely consistent with the mutual abandonment and rescission of the May 1970 agreement in November and the undertaking of the new project at that time. The trial court could interpret the evidence thusly and hold the contract abandoned. The action of the parties in negotiating and concluding a separate agreement whereby plaintiffs were to cut cedar poles in a different location during a time period covered by the original contract, in addition to their other conduct, was inconsistent with the continued existence of the original contract. The evidence of an agreement to extend the contract is inconclusive and consists primarily of evidence that similar contracts had been extended in the past and that certain equipment had been left at the contract site. The finder of the fact could find the intent of the parties to be to mutually rescind and *52 abandon the contract. The cross claim for damages must fall in view of this result. The judgment is affirmed. SWANSON, C.J., and WILLIAMS, J., concur. Petition for rehearing denied July 22, 1974. Review denied by Supreme Court October 11, 1974.
531 F.3d 474 (2008) Teresa HANCOCK, Plaintiff-Appellant, v. John E. POTTER, Postmaster General of the United States Postal Service, Defendant-Appellee. No. 07-1589. United States Court of Appeals, Seventh Circuit. Argued April 3, 2008. Decided June 24, 2008. *475 Armand L. Andry (argued), Chicago, IL, for Plaintiff-Appellant. Monica Mallory (argued), Office of the United States Attorney, Rockford, IL, for Defendant-Appellee. Before FLAUM, MANION, and TINDER, Circuit Judges. FLAUM, Circuit Judge. Teresa Hancock worked for the U.S. Postal Service and suffered a lumbar strain while on the job. After going through a series of examinations designed to assess her ability to perform certain physical tasks on the job, she was given a *476 new set of duties. She had disagreements with her supervisors regarding whether her new tasks ran afoul of her physical restrictions. These disagreements ultimately formed the basis of her complaint in the district court alleging gender discrimination, disability discrimination, retaliation, and a hostile work environment. The district court dismissed Hancock's claims on summary judgment in large part because she did not suffer an adverse employment action and she could not identify a similarly situated employee. Because we find no error in the district court's analysis, we affirm. I. Background From 1992 to 2001, Hancock was employed with the U.S. Postal Service in Rockford, Illinois as a "flat sorter." The job involved utilizing and maintaining a flat sorting machine that would organize and separate pieces of mail larger than letter-size, such as magazines, newspapers, and manila envelopes. The first several years of her employment with the Postal Service were uneventful, save for an award she received early on for discharging her duties in a safe manner. Hancock's troubles began in March 1998, when she filed a grievance alleging that her supervisor, Leon Woods, yelled at her and was disrespectful towards her. A month later, this grievance was settled. Then, on June 18, 1999, Hancock suffered a job-related back injury, namely a lumbar strain. This injury limited her ability to bend, stoop, and twist. Consistent with Department of Labor requirements, she was given a limited duty job assignment that modified the nature of her work. Soon after working this modified job, she told a supervisor that it did not comport with restrictions set out in her limited duty assignment.[1] Supervisors examined her restrictions and disagreed; they told her to keep working. In response, Hancock asked for a union representative, and was given one within four hours. She utilized the union assistance to document her injury, but she did not request medical treatment. Hancock then made an appointment to see her own physician. At the same time, the Postal Service had her attend a fitness-for-duty examination to determine her ability to work, and to clarify the extent of her restrictions. The Postal Service physician completed a new duty status report which delineated Hancock's restrictions. She was given a corresponding new job offer that involved working on a different piece of equipment — the meter belt. Hancock refused to accept the new assignment on the grounds that, in her view, it would trigger her injury. The Postal Service physician assessed the information a second time and confirmed that she could perform this new job in a manner that was consistent with her restrictions. But Hancock still refused. She then received a note from her personal physician excusing her from work for a few days until he had the chance to examine her. When she returned to work, she came with a note from her physician directing that she not work the meter belt. Because her injury had worsened since June, she was given a new, more stringent set of restrictions that also called for her to refrain from working on the meter belt. As a result, Hancock was given a job offer for a different shift, because there as no work available on her shift that also met her restrictions.[2] *477 While she was on her restrictions, Hancock requested to work in an area known as the Registry Cage. This is a secure section on the workroom floor where a single employee works. Her request was denied for two reasons. First, the Postal Service determined that additional staffing for this position was only needed on Hancock's regular day off. Second, despite Hancock's contrary belief, the Postal Service concluded that the work requirements of the Registry Cage were outside her restrictions. For instance, the duties included lifting up to 70 pound bags of coin, which was clearly beyond Hancock's restrictions. Hancock also wanted to participate in the Associate Supervisor Program (a management trainee program) but was ultimately denied. This was due, in large measure, to an unfavorable evaluation issued by the Manager of Distribution Operations, Linda Medearis, on August 4, 1999. Hancock claims that she received this negative evaluation because she had filed grievances and had complained about management and her supervisors. Critically, none of these grievances was the subject of an Equal Employment Opportunity ("EEO") complaint that took place prior to August 4, 1999. Indeed, Medearis claims that she did not select Hancock for the program because a number of co-workers had indicated that she was not doing her job. This is consistent with prior events: Medearis also did not recommend Hancock for this program in the March 1999 cycle, before the injury and accompanying work restrictions, and before she started filing administrative complaints. Contemporaneous with these events, Hancock filed an injury compensation claim with the Office of Workers Compensation ("OWCP"). All of the documentation received by the Postal Service Injury Compensation Specialist concerning Hancock's injury was forwarded to OWCP. Then, on October 18, 1999, OWCP notified Hancock that her claim was denied due to insufficient medical documentation.[3] She was subsequently reclassified from a "limited duty" status (which is for employees who are injured on the job) to a "light duty" status (which is for employees who are injured outside of their job duties). This meant that her workload was reduced to 20 hours per week and that her availability to be assigned beyond these hours depended on available work that was within her restrictions. Later, on February 11, 2000, OWCP reversed its decision because it located a treatment note from Hancock's physician. This took her from light duty back to limited duty, which meant that her full time work hours were restored. From August 1999 to April 2000, Hancock filed several complaints with the Equal Employment Opportunity Commission ("EEOC") alleging discrimination based on sex, physical disability, age, and retaliation for prior EEO activity. In the context of these complaints, she made the following six claims: (1) her limited duty job restrictions were violated; (2) her request to be trained in the Registry Cage was not honored in order to harass her and deny her an accommodation for her disability; (3) she was harassed and denied *478 accommodations when presented with job offers; (4) her work hours were reduced; (5) she was given an unfavorable evaluation for the Associate Supervisor Program; and (6) injury compensation personnel withheld medical information in her worker's compensation cases. After exhausting her administrative remedies, Hancock filed a complaint with the district court consistent with this set of claims in October 2002. Specifically, she alleged that the Postal Service discriminated against her on the basis of gender in violation of Title VII of the Civil Rights Act of 1964, 42 U.S.C. § 2000e, et seq., on the basis of disability in violation of the Americans with Disabilities Act ("ADA"),[4] on the basis of age in violation of the Age Discrimination in Employment Act ("AEDA"), and that the Postal Service retaliated against her for speaking out against a practice that Title VII forbids. After an answer was filed, the Postal Service moved for summary judgment on February 1, 2006. The district court granted this motion in favor of the Postal Service. This appeal followed. II. Discussion Hancock raises four issues before this Court. She argues that the district court erred in denying her gender discrimination, disability discrimination, retaliation, and hostile work environment claims. We analyze each issue in turn, bearing in mind that we review a district court's grant of summary judgment de novo and view the evidence in the light most favorable to the appellant. Hoffman v. MCA, Inc., 144 F.3d 1117, 1121 (7th Cir.1998). Because Hancock did not provide any direct or circumstantial evidence of gender discrimination, in order to make a colorable claim, she had to prove that (1) she was a member of a protected class; (2) she was meeting her employer's legitimate business expectations; (3) she suffered an adverse employment action; and (4) the employer treated a similarly situated employee outside of the class more favorably. Kampmier v. Emeritus Corp., 472 F.3d 930, 939 (7th Cir.2007). Upon establishing these elements, the burden shifts to the employer to produce "evidence which, taken as true, would permit the conclusion that there was a nondiscriminatory reason for the adverse action." St. Mary's Honor Center v. Hicks, 509 U.S. 502, 509, 113 S.Ct. 2742, 125 L.Ed.2d 407 (1993). If the employer succeeds here, then the burden shifts back to the employee to prove that these reasons were merely a pretext for discrimination. E.E.O.C. v. Our Lady of the Resurrection Medical Center, 77 F.3d 145 (7th Cir.1996). Hancock's gender discrimination claim fails at the outset because she did not suffer an adverse employment action and because she could not point to a single similarly situated employee outside the class who was treated more favorably. An adverse employment action is one that significantly alters the terms and conditions of the employee's job. Griffin v. Potter, 356 F.3d 824, 829 (7th Cir.2004). General hostility, unless it was severe and pervasive, does not meet the mark. Id. The action must be more disruptive than a mere inconvenience or an alteration of job responsibilities. Rabinovitz v. Pena, 89 F.3d 482, 488 (7th Cir.1996). Given this framework, it is clear that Hancock cannot meet her burden. Nearly all of the so-called adverse employment actions that Hancock raises were merely attempts by the Postal Service to ensure that she provided *479 it with work but did not work beyond her personal restrictions. This is certainly true of her supervisor's decision to subject her to fitness-for-duty examinations (which is required) and subsequent disagreements regarding whether work on the meter belt violated her restrictions. Also, Hancock protests that her work hours were reduced, but this was simply due to the fact that there was a lack of available work that fell within her very limiting restrictions. We could exhaustively critique each of Hancock's complaints in this way, but we need not do so because there is an even more clear-cut flaw in her case: she has not provided this Court, or the district court, with a single similarly situated employee. There is no evidence in the record that indicates that Hancock's supervisor acted differently when faced with a disagreement from any other employee about whether an assignment was within their restrictions, nor is there evidence that Postal Service supervisors acted differently when assessing what productive work was available for Hancock. Hancock provides conclusory affidavits from co-workers that state that other employees were given better treatment, but not a single actual name is provided. For all of these reasons, Hancock falls well short of making her prima facie case of gender discrimination. Hancock's disability discrimination claim fares no better, because she was not disabled as that term is defined in the ADA. In order to establish her case here, Hancock had to show that (1) she has a physical or mental impairment which substantially limits one or more of her major life activities; (2) she has a record of such impairment; or (3) she is regarded as having such impairment by her employer. Peters v. City of Mauston, 311 F.3d 835, 842 (7th Cir.2002). What undermines Hancock's claim here is that she has not adduced any evidence that any of her major life activities were affected by her injury. See 29 C.F.R. § 1630(i) (noting that caring for one's self, performing manual tasks, seeing, walking, speaking, hearing, breathing, leaning, and possibly working, are major life activities). Hancock merely had a work-related back injury that temporarily limited her ability to perform certain job duties and short-term absences. But even if Hancock could somehow establish that she was disabled under the ADA, her claim would still fail on the grounds that she cannot point to a single similarly situated employee outside the protected class who was treated more favorably. In order to prevail on her retaliation claim, Hancock had to prove that the Postal Service took an adverse action against her because she opposed a practice that Title VII forbids. Kampmier, 472 F.3d at 939. Here, Medearis did make written and oral comments in March and August 1999 that one of the reasons she did not recommend Hancock for the Associate Supervisor Program, in addition to statements made by co-workers that she was not doing her job, was the fact that she had "filed grievances claiming harassment from [management]." Hancock magnifies this comment and argues that within one month of complaining about discriminatory treatment, Medearis acted to deny her an appointment to the program. This statement is not consistent with the facts. Hancock did in fact complain to Medearis in August 1999 about the treatment she was receiving from her supervisor Leon Woods, and Medearis did in fact give Hancock a negative evaluation for the program later that month. However, Medearis also gave Hancock a similarly negative evaluation for the program five months earlier, in March. This was before Hancock lodged any complaints and, more importantly, before she engaged in any EEO-related activity.[5]*480 Moreover, Medearis's statements did not mention that Hancock complained of discrimination — she generally referred to "grievances," and her statement was made in the context of describing Hancock's "very negative attitude" towards management. Hancock's only real response here is an attempt to recharacterize her March 1998 grievance against her supervisor (for raising his voice at her) as prior EEO activity. She contends that it was this grievance that formed the basis of Medearis's negative evaluation. This rereading of the events in this case is not persuasive. First, Hancock did not base any of her five EEO complaints (starting in August 1999) on an allegation that this March 1998 grievance was prior EEO activity for which she was retaliated against. Second, and consistent with this view, her district court complaint also only refers to prior EEO activity in 1999. There is no mention of EEO activity that occurred in 1998. Third, and most significantly, Hancock filed this grievance because her supervisor was "disrespectful towards her." There was no evidence, or even an allegation, that this disrespect was fueled by a discriminatory animus. In the alternative, Hancock tries to establish her claim of retaliation by utilizing the burden-shifting approach articulated above. She was required to show "that (1) after lodging a complaint about discrimination, (2) only [she], and not otherwise similarly situated employees who did not complain, was (3) subjected to an adverse employment action even though (4)[she] was performing [her] job in a satisfactory manner." Id. at 642. Like her gender and disability discrimination claims, Hancock's attempt to make out a prima facie case falls short because she has not identified a similarly situated non-complaining employee, much less presented convincing evidence that such an employee was treated more favorably. As a part of her hostile work environment claim, Hancock had to demonstrate that the conduct complained of was "sufficiently severe or pervasive to alter the conditions of employment and create an abusive working environment." Ezell v. Potter, 400 F.3d 1041, 1047 (7th Cir.2005). In Hancock's case, she had to show that she was subjected to unwelcome harassment based upon either her gender or disability. Beamon v. Marshall & Ilsley Trust Co., 411 F.3d 854, 863 (7th Cir.2005). We decline to reach the substance of Hancock's hostile work environment claim because she never alleged such a claim in her district court complaint. It was raised for the first time in her opposition to the Postal Service's motion for summary judgment, and so it is not properly before this Court. See Shanahan v. City of Chicago, 82 F.3d 776, 781 (7th Cir.1996). We acknowledge that plaintiff's working environment was not the most supportive. Her supervisor criticized her, she complained, and her manager viewed her as an employee who, among other things, was not a "team player." However, at every step of the way, Hancock was not able to shore up any bit of evidence that indicated that she was discriminated against on the basis of her gender or disability or that she was retaliated against because she complained of discrimination. She was injured and inconvenienced. She was treated somewhat unkindly. But there is a significant gap between such conduct, which was fundamentally personal, and discrimination. *481 III. Conclusion For the foregoing reasons, we AFFIRM the district court's judgment. NOTES [1] These restrictions were as follows: lifting and carrying limited to 50 pounds, twisting limited to no more than 12 tubs per 15 minutes, and no pushing greater than 475 pounds. [2] Postal Service Regulations require that if adequate duties are not available within the employee's work limitation tolerances, in the craft and work facility to which the employee is regularly assigned, and within her regular house of duty, other work may be assigned within the facility. [3] The Federal Employees Compensation Act, 5 U.S.C. § 8101, et seq., holds the employee responsible for: (1) establishing that the injury occurred while on the job, (2) proving that the medical condition is causally related to the injury, and (3) submitting a medical report from an attending physician. [4] The term "employer" under the ADA specifically excludes the United States and its agencies from its definition, 42 U.S.C. § 12111(5)(B), and so Hancock should have actually sued under the Rehabilitation Act, 29 U.S.C. § 794. [5] Hancock began filing complaints with the EEOC in August 1999.
I'm a little confused with translations. in the game, they're called "Dhrellers" and in the show they seem to be called "Phorrors" and I'm trying to figure out why the name change?? Also in the game the sheeps are called Gobballs but I think in the show they're called "Bouftons?" And somehow "Tristepin" translates to "Saddlygrove????" halp plz so confusedand also ahhh Xavier Sir your art is always so inspiring to me *_*!
Q: How to get the Package-List of a debian/ubuntu package? It's possible to view the Package-List of a debian/ubuntu package, using the package management tools like apt, aptitude or dpkg? I need to list the packages provided by a package, the list is visible in the dsc file: Example: http://archive.ubuntu.com/ubuntu/pool/main/l/lxc/lxc_1.0.0~beta3-0ubuntu1.dsc Section Package-List. A: You can use apt-cache showsrc and use awk (or similar tools) to get the output you want: $ apt-cache showsrc lxc | awk '/Package-List/{a=1;next}/^[^ ]/{a=0}a{print $1}' lxc lxc-dbg lxc-dev
Heredity in dementia of the Alzheimer type. Family, twin and linkage studies in Alzheimer's disease are reviewed. Several of these studies appear to be burdened with sources of error, mainly related to sampling and clinical diagnoses. It was previously thought that early-onset cases of Alzheimer's disease were heavily genetically influenced, whereas late-onset cases were sporadic. The author questions whether this difference is mainly due to methodological error.
Gold nanoparticle-aluminum oxide adsorbent for efficient removal of mercury species from natural waters. We report a new adsorbent for removal of mercury species. By mixing Au nanoparticles (NPs) 13 nm in diameter with aluminum oxide (Al(2)O(3)) particles 50-200 μm in diameter, Au NP-Al(2)O(3) adsorbents are easily prepared. Three adsorbents, Al(2)O(3), Au NPs, and Au NP-Al(2)O(3), were tested for removal of mercury species [Hg(2+), methylmercury (MeHg(+)), ethylmercury (EtHg(+)), and phenylmercury (PhHg(+))]. The Au NP adsorbent has a higher binding affinity (dissociation constant; K(d) = 0.3 nM) for Hg(2+) ions than the Al(2)O(3) adsorbent (K(d) = 52.9 nM). The Au NP-Al(2)O(3) adsorbent has a higher affinity for mercury species and other tested metal ions than the Al(2)O(3) and Au NP adsorbents. The Au NP-Al(2)O(3) adsorbent provides a synergic effect and, thus, is effective for removal of most tested metal ions and organic mercury species. After preconcentration of mercury ions by an Au NP-Al(2)O(3) adsorbent, analysis of mercury ions down to the subppq level in aqueous solution was performed by inductively coupled plasma mass spectrometry (ICP-MS). The Au NP-Al(2)O(3) adsorbent allows effective removal of mercury species spiked in lake water, groundwater, and seawater with efficiencies greater than 97%. We also used Al(2)O(3) and Au NP-Al(2)O(3) adsorbents sequentially for selectively removing Hg(2+) and MeHg(+) ions from water. The low-cost, effective, and stable Au NP-Al(2)O(3) adsorbent shows great potential for economical removal of various mercury species.
Please select a resort, then choose a date and click on a time to submit a request. Your Wedding. Your Style. Weddings at the resorts made for love. When it comes to destination weddings, Sandals has what you need for an elegant and fun celebration. We know you want an experience that is stress-free and filled with personalized details that reflect your style. A Sandals WeddingMoon marries the wedding and the honeymoon, so after you've exchanged your vows, you can begin your happily ever after. Romance abounds at the resorts made for love, and you'll find endless ways to enjoy your time together, from suites so exotic and romantic, we named them "Love Nests Dream Suites", to intimate dining beneath the moonlit sky, hand-in-hand strolls along the beach, and every land and water sport under the sun.
Louisiana State University entomologist Rodrigo Diaz said researchers only recently discovered the foreign family of insects to which the invasive species belongs, called Aclerdidae, which is native to Japan and China. But the lab tests that identified it couldn’t reveal how it arrived — on a ship, attached to a migrating bird or even on the wind. What’s certain is that last year a team of surveyors checking the cane, which comes in various shades of green, found stalks bent in water, brown and dead in the mouth of the Mississippi River. That’s when they began to notice significant die-offs of four varieties of cane and more open water in the hundreds of acres the cane once occupied. Two to three years before, there was a thick, unrelenting wall of marsh. AD AD “They are feeding on it,” said J. Andrew Nyman, a professor at the School of Renewable Natural Resources at LSU. “The bugs suck the sap out. The leaves are trying to send sugar to the roots, and they suck out so much that the plant can’t function. It dies.” Nyman said he picked up a stalk one day, and the bugs covered it. In an online seminar about the invasion, Diaz displayed a graph that said six feet of cane can have nearly 200 insects almost invisible to the naked eye, and 700 in extreme cases. He described them as translucent, extremely small but highly mobile, and moving in dense populations. The mealy bug, as it’s also known, adds to the many invasive insects that have made their way to the United States from Asia and Europe. Animals that have ruined plants and crops, and even invaded homes, include the brown marmorated stink bug, the kudzu bug, the emerald ash borer, and aphids that are threatening Florida’s citrus industry by destroying orange groves and wreaking havoc on Christmas tree pines from West Virginia to North Carolina along the Appalachian Mountains. AD AD The Louisiana cane is crucial to staving off land loss. It builds soil in an area that lost 250 square miles of coast to erosion and sinking land over about a half century. Roseau cane also has a checkered history. At least one variety, the European, is itself invasive. The delta Roseau cane from North Africa and the greeny variety from Europe were introduced. Scientists aren’t sure whether a fourth variety, the Gulf Roseau cane, is invasive or introduced. But on a coast beaten down by harsh weather and erosion, even the exotic species turned out to be a godsend for stabilizing the land. In other areas of Louisiana and other states, they are a nuisance, which is why some people, Diaz said, want to transport the parasite to those areas to destroy the cane. Bad idea, he said. Who knows where the bugs will go after the cane is gone. They could wander to native plants, even farm crops, and develop a taste for those. But the insects don’t wait for human transport. Even now they hop aboard grackles and red-winged blackbirds that flock into the reedy cane, hoping for a ride to another healthy batch of cane to get a meal and lay eggs. They’re also known to hop into air boats piloted by fishermen. Scientists have pleaded with the owners to wash them down. Diaz said experts are weighing options to fight the threat. An idea for a controlled burn is derived from China, where blazes are set in marshes to get rid of the swarm. But fire can spread, and the Louisiana coast has a network of oil and gas wells that could explode in flames. AD AD Planting a plague-resistant strain of cane has come up, but no one knows whether such a thing exists. Insecticide is another consideration, but that could get expensive because of the vast area that needs spraying and would require environmental assessments. Another concern is the inadvertent contamination of speckled trout, redfish, shrimp and oysters — not to mention the birds that feed on them. Maybe the parasite’s natural predator, a tiny wasp from Asia, can be employed. They have been considered as a solution to the stink bug problem as well, but it takes years of study before a new species can be released, for fear that the wasp might turn on native animals and start killing them, too. Or maybe, just maybe, the insect is its own worst enemy. It might eat itself out of house and home before anything else can be done. “What you could end up with in 10 years is the bugs will die back,” Nyman said, after killing all the cane. “They’ll become a smaller part of the landscape, both the bug and the plant.”
<node> <interface name='org.gtk.Application'> <method name='Activate'> <arg type='a{sv}' name='platform_data' direction='in'/> </method> <method name='Open'> <arg type='as' name='uris' direction='in'/> <arg type='s' name='hint' direction='in'/> <arg type='a{sv}' name='platform_data' direction='in'/> </method> <method name='CommandLine'> <arg type='o' name='path' direction='in'/> <arg type='aay' name='arguments' direction='in'/> <arg type='a{sv}' name='platform_data' direction='in'/> <arg type='i' name='exit_status' direction='out'/> </method> <property name='Busy' type='b' access='read'/> </interface> </node>
The present invention relates to a gas turbine engine and, more particularly, to a nozzle for a miniature gas turbine engine. Miniature gas turbine or turbojet engines (typically of 150 lbf thrust and smaller) are often utilized in single usage applications such as reconnaissance drones, cruise missiles, decoy and other weapon applications, including air-launched and ground-launched weapon systems. The use of such an engine greatly extends the range of the weapon in comparison to the more conventional solid fuel rocket engine. To achieve economically feasible extended range expendable propulsion sources for such applications, it is necessary that the miniature gas turbine engines be manufactured relatively inexpensively yet provide the highest degree of starting and operational reliability when launched from air or ground systems.
Fetal megacystis: prediction of spontaneous resolution and outcome. To investigate the natural history of fetal megacystis from diagnosis in utero to postnatal outcome, and to identify prognostic indicators of spontaneous resolution and postnatal outcome after resolution. This was a national retrospective cohort study. Fetal megacystis was defined in the first trimester as a longitudinal bladder diameter (LBD) ≥ 7 mm, and in the second and third trimesters as an enlarged bladder failing to empty during the entire extended ultrasound examination. LBD and gestational age (GA) at resolution were investigated with respect to likelihood of resolution and postnatal outcome, respectively. Sensitivity, specificity and area under the receiver-operating characteristics curve (AUC) were calculated. In total, 284 cases of fetal megacystis (93 early megacystis, identified before the 18th week, and 191 late megacystis, identified at or after the 18th week) were available for analysis. Spontaneous resolution occurred before birth in 58 (20%) cases. In cases with early megacystis, LBD was predictive of the likelihood of spontaneous resolution (sensitivity, 80%; specificity, 79%; AUC, 0.84), and, in the whole population, GA at regression was predictive of postnatal outcome, with an optimal cut-off at 23 weeks (sensitivity, 100%; specificity, 82%; AUC, 0.91). In the group with early megacystis, the outcome was invariably good when resolution occurred before the 23rd week of gestation, whereas urological sequelae requiring postnatal surgery were diagnosed in 3/8 (38%) cases with resolution after 23 weeks. In the group with late megacystis, spontaneous resolution was associated with urological complications after birth, ranging from mild postnatal hydronephrosis in infants with resolution before 23 weeks, to more severe urological anomalies requiring postnatal surgery in those with resolution later in pregnancy. This supports the hypothesis that an early resolution of megacystis is often related to a paraphysiological bladder enlargement that resolves early in pregnancy without consequences, while antenatal resolution occurring later in pregnancy (after the 23rd week of gestation) should suggest a pathological condition with urological sequelae. In fetal megacystis, LBD and GA at regression can be used as predictors of resolution and outcome, respectively. These parameters could help in fine-tuning the prognosis and optimizing the frequency of follow-up scans. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
--- abstract: 'Remote attestation schemes have been utilized for assuring the integrity of a network node to a remote verifier. In recent years, a number of remote attestation schemes have been proposed for various contexts such as cloud computing, Internet of Things (IoTs) and critical network infrastructures. These attestation schemes provide a different perspective in terms of security objectives, scalability and efficiency. In this report, we focus on remote attestation schemes that use a hardware device and cryptographic primitives to assist with the attestation of nodes in a network infrastructure. We also point towards the open research challenges that await the research community and propose possible avenues of addressing these challenges.' author: - Ioannis Sfyrakis - 'Thomas Gro[ß]{}' bibliography: - 'bibliography.bib' title: A Survey on Hardware Approaches for Remote Attestation in Network Infrastructures --- \ Introduction {#sec:intro} ============ Network Infrastructures (NIs) exist in companies, industry and critical infrastructure sectors. In the context of companies, the network infrastructure is considered as the backbone of the operation and offering services to customers. For instance, in cloud computing used by many of today’s companies, cloud network infrastructures provide the base service model to realize cloud services. Another area where we can find network infrastructures is in any of the 16 critical infrastructures sectors [@cisa:2020] such as energy and financial services. Both application areas of network infrastructures depend on the integrity of their nodes to provide a trustworthy service to clients. Compromising the integrity of nodes in a network infrastructure such as virtual network devices in Infrastructure-as-a-Service (IaaS) clouds [@bays:2015] or even sensor nodes in an energy smart grid [@enisa:smart_grid:2012; @sakhini:iot_smartgrid:2019] can have tremendous effect in the trustworthiness of these systems. Attacks performed in these network infrastructures [@chasaki:attacks_networkinfra:2011] can have a devastating effect, which can affect industry and society [@cisa:alert:2018]. Current network infrastructures in cloud computing and critical infrastructure systems have a large number of nodes which makes attestation not feasible when attesting only one node at a time. Remote attestation schemes traditionally focus on attesting the integrity of a single node and providing evidence for its current state to a remote verifier. There are proposals that attempt to tackle the issue of attesting more than one node especially in the realm of wireless sensor networks [@steiner:2016]. The security objectives and assumptions in these remote attestation schemes are different where a number of attestation schemes provide protection from software-based attacks and/or physical attacks. Other attestation schemes protect from Denial of Service (DoS) attacks [@rasmussen2016DAC]. **Our contribution:** In this paper, we offer an overview on the current state of the art regarding hardware-based architectures for attestation and their related attestation schemes in network infrastructures that use cryptography. We focus on attestation schemes that rely on hardware to prove that the software of a network node was not tampered with. In addition, we review attestation schemes that depend on cryptographic primitives and protocols to prove that the network node is in a legitimate state. Architectures and attestation schemes that do not meet these criteria are not included in this paper. Outline {#subsec:outline} ------- In section \[sec:background\] we discuss background information regarding network infrastructures and remote attestation. Section \[sec:arch-ra\] provides an overview of the main hardware based architectures that can realize remote attestation schemes. Section \[sec:hw-ra\] continues with a discussion on the hardware-based attestation schemes. Section \[sec:hy-ra\] focuses on the remote attestation schemes that are categorized as hybrid attestation schemes. Section \[sec:open-res\] discusses the open research problems and possible ways of resolving them. Term Description --------------- -------------------------- $V$ Verifier $P$ Prover $n_V$ Challenge nonce from $V$ $\sigma$ Signature of attestation $s$ Internal state $k$ Security parameter $\mathcal{S}$ Sign operation $\mathcal{H}$ Hash operation : Notation Summary[]{data-label="tab:notation-summary"} Background {#sec:background} ========== Network Infrastructures ----------------------- Network Infrastructures (NI) provide the telecommunication backbone for a variety of contexts such as cloud computing, enterprise networks and critical infrastructures. NIs consist of a connected group of computer systems linked with a number of network hardware components. As seen in Figure \[fig:net-infra\] the main hardware components are routers, wireless access points, switches and firewalls. Each hardware component employs a software layer that is managed by network administrators. The software layer can be as simple as firmware used in routers or switches to full blown operating systems to manage cloud infrastructure networking. NIs are categorized as either open or closed. Open NIs means that the infrastructure employs an open architecture such as the Internet. In a closed NI the network is confined to a certain boundaries. For instance, an enterprise intranet is considered a closed NI. Another categorization of NIs is the method the nodes in the network use to communicate with their peers. The nodes in the network can either communicate via wired network connection or a wireless one or even a combination of the two methods. In recent years there has been many research works regarding NIs to create higher-level abstractions. One method is to decouple the network functions from network devices using virtualization, which is called network function virtualization (NFV) [@mijumbi:nfv_survey:2015]. For instance a network function such as a firewall can be deployed as virtual network function in software which enhances its programmability. Another method is by using Software Defined Networking (SDN) [@kreutz:sdn_survey:2014]. SDN separates the network control from the actual network devices. This means that the network control becomes programmable via open interfaces such as OpenFlow [@lara:openflow_survey:2014]. In this setting the network devices become forwarding devices and a centralized controller implements the control logic. As we have seen so far there is a variety of technologies that are created on top of NIs. Even though the network devices are used in a different way depending on which method is selected, we still require that the devices are protected from malicious users. This can be achieved by using remote attestation schemes for NIs to ensure that nodes are authenticated and have not been compromised by a malicious user. ![Network infrastructures deployed in various contexts such as cloud computing, enterprise networks, mobile networks and backbone networks[]{data-label="fig:net-infra"}](figures/network-infrastructure.pdf) Remote Attestation {#sec:remote} ------------------ Remote attestation is a mechanism that enables a remote verifier to ascertain the integrity of a host that it is in a known state. This mechanism follows a challenge-response protocol and the main entities in this protocol are the *Prover*($P$) and the *Verifier*($V$). The goal of an honest, non-compromised prover is to construct a response such that it can convince a *Verifier* that the prover is in an acceptable state for the time the attestation was requested. There are three main types of remote attestation according to the taxonomy by Steiner and Lupu [@steiner:2016]: 1. *software-based attestation* where the attestation mechanism relies on strict time measurements to convince a verifier that the prover is in a legitimate state. 2. *hardware-based attestation* where a tamper-resistant hardware component is used to execute the attestation routines in a secure environment. 3. *hybrid attestation* where the attestation method uses hardware/software co-design to offer attestation services but does not require complex hardware components. In hybrid attestation the main requirements are minimal hardware components such as Read Only Memory (ROM) and a Memory Protection Unit (MPU) that a device with limited capabilities can include in its design. ![Taxonomy of state-of-the-art hardware approaches for remote attestation[]{data-label="fig:tax-hw"}](figures/mindmap) In this study, we aim to review the state-of-the-art remote attestation approaches that are either based on hardware components or they offer a software/hardware co-design architecture that realizes the attestation scheme. In addition, we focus on remote attestation schemes that utilize cryptographic primitives as part of their attestation protocol. We further categorize the remote attestation schemes in terms of the number of attesting nodes in a network infrastructure. The first category attests one node each time while the second category the attestation happens in groups of nodes. Strong security is of paramount importance in today’s environment where attackers are able to launch attacks to network infrastructures. Therefore, cryptography can be used in a way that benefits the attestation of nodes in a network infrastructure. Figure \[fig:tax-hw\] depicts the taxonomy of the hardware approaches for remote attestation in network infrastructures. We structure this report around the taxonomy and discuss each category for the remote attestation schemes. In addition we compare the research works in each category in terms of how the attestation works in network infrastructures and the number of attested nodes the method supports. The cryptographic primitives used in each attestation research works are compared and discuss the reasoning for adding them to each attestation scheme. We acknowledge previous works in remote attestation that provide a generic protocol view for attestation schemes  [@francillon2014minimalist; @coker:principles_ra:2011; @datta:logic_trustedcomputing:2009; @armknecht:software_attestation:2013; @li:framework_softwareattestation:2014] and we adopt that the attestation involves three main stages: (1) `Challenge`, (2) `Attest` and (3) `Verify`. Figure \[tab:genattprot\] illustrates a concise overview of a generic remote attestation protocol that uses cryptography. The attestation protocol is similar to the ones in [@francillon2014minimalist; @coker:principles_ra:2011; @datta:logic_trustedcomputing:2009]. In this generic protocol view of remote attestation we assume that both the *Verifier* and the *Prover* have generated key pairs according to a parameter $k$. The *Prover* initiates the protocol by sending a message to the *Verifier* requesting for an attestation to be performed in her platform. Then the *Verifier* responds by first generating a nonce that is used a challenge nonce and sending the nonce back to the *Prover*. The *Prover* upon receiving the challenge nonce fro the *Verifier* then she performs the attestation process `Attest` and generating the appropriate attestation data as evidence for the *Verifier* to prove. For instance, in the TPM one might use as attestation evidence the current contents of the Platform Configuration Registers (PCRs) which demonstrate the current state of the platform. After the attestation data has been collected then the *Prover* signs the attestation data and the challenge nonce using a signature scheme. The signature $\sigma$ is then communicated to the *Verifier*. In this instance, the *Verifier* is starting the authentication process `AuthProver(P)` to authenticate that the *Verifier* is talking to the right *Prover*. The next step in the remote attestation protocol is to verify the signature received from the *Prover* using the `Verify(k,\sigma,P)` process. The outcome of the verification process is either true or false. Hardware-based Architectures for Remote Attestation {#sec:arch-ra} =================================================== In this section, we review the main architectures based on hardware device or component for realizing remote attestation schemes. Table \[tab:hardware-attestation-summary\] provides an overview of all the architectures that are used for realizing remote attestation schemes. TPM --- One of the most prevalent examples of a discrete tamper-resistant hardware component for remote attestation is the Trusted Platform Module (TPM). This device is added in motherboards as a way to provide trusted computing facilities to the platform. Currently there are two versions of the TPM. The first version of the TPM v1.2  [@tpm1.2] is based on RSA cryptography and the second version TPM v2.0 is based on elliptic curve cryptography [@brickell2004direct; @tcg:tpm2]. The TPM works as coprocessor and is able to store keys and realize remote attestation. The Platform Configuration Registers (PCRs) in the TPM hold hashes of code or data that are used in remote attestation. The published specification for TPM v1.2 outlines the functionality and cryptographic primitives that are required for the hardware component. Generating random data in a TPM is supported using a Randomness Number Generator (RNG). The main cryptographic primitive that is supported is RSA key generation and signature schemes. For calculating the hashes the TPM uses the SHA-1 hash algorithm, which is now considered vulnerable to attacks. The first key enclosed in the TPM is the Endorsement Key (EK) and is generated during the manufacturing process. This key is used in almost all key related operations in the TPM. Other keys that can be generated are the Attestation Identity Keys (AIK) used in digital signature operations and the storage keys used in encryption and decryption of data. The first approach for supporting remote attestation in TPM v1.2 used a Trusted Third Party (TTP) called Privacy-CA [@chen:priv_ca:2010] that raised privacy concerns. Another remote attestation scheme was added that provides privacy-preserving remote attestation based on a group signature scheme [@brickell2004direct] based on RSA called Direct Anonymous Attestation (DAA). The TPM specification was updated to version 2.0 [@tcg:tpm2:architecture] provides a number of new features for the trusted hardware component. First, the TPM v2.0 supports a larger variety of cryptographic algorithms, and especially for privacy-preserving attestation the implementation is less rigid giving room for realizing different flavors of DAA-like schemes. Second, this version of the TPM supports multiple banks of PCRs and three key hierarchies. One of the main disadvantages of using TPMs in network infrastructures is that they support high-power hardware. They are used in hardware platforms that have enough processing power to assist with the computation of attestation schemes. Another disadvantage that exists in TPMs is that they privacy-preserving attestation schemes are considered complex and they are difficult to deploy in large network infrastructures. Intel SGX --------- Intel Software Guard Extensions (SGX) [@mckeen:intel_sgxra:2013] is a trusted execution environment that was first announced in 2013 and supports both local and remote attestation. Applications can support Intel SGX by partitioning the application in two parts the untrusted and trusted part. We create an enclave with the trusted part of the application. Intel SGX assures the confidentiality and integrity of code and data that reside in an enclave. In addition, there is no other software such as OS or a hypervisor that can access the memory region that the enclave resides. The enclave pages reside in a memory region called Processor Reserved Memory (PRM). This region includes two structures for the enclaves, the Enclave Page Cache (EPC) and Enclave Page Cache Map (EPCM). The EPC store the code and data of the enclave while the EPCM holds state information for the enclave. Untrusted software create and initialize the enclave and the hardware assures that the enclave can only be modified before it is initialized. During the initialization phase all the contents of the enclave such as its code and data are measured and this measurement can become the basis for future local and remote attestations. One feature of Intel SGX is that an enclave can attest to another that it has been loaded correctly by producing a report which includes information about the author of the enclave or the enclave measurement. This process consists the method for local attestation. Intel SGX uses a specific enclave called quoting enclave that wraps the report into a quote. More precisely the quote is signed using an asymmetric attestation key. This process is part of the Enhanced Privacy Identifier (EPID) [@brickell2007enhanced] signature scheme provided by Intel, which is an extension of the DAA scheme used in TPMs. A remote verifier can then receive the quote and start the verification process with a corresponding verification key that is provided by Intel. The attestation in Intel SGX requires specific CPUs and provides a closed ecosystem for realizing attestation schemes that are totally controlled by Intel. There are efforts that attempt to create third party attestation services [@scarlata:sgx_attest_prim:2018] using Intel SGX but it is still required to use an Intel provided enclave named Provisioning Certification Enclave (PCE) that acts as a local certificate authority. SMART ----- SMART [@defrawy:2012] is a reference hardware architecture that supports attestation in low-powered devices. The main features of this architecture is that it includes immutable attestation code stored in a Read-only Memory (ROM) that guarantees that the code is not changed after it is placed there. In addition, SMART supports secure key storage and atomic execution of operations. The design principles behind this architecture propose that changes to hardware components and interfaces should be kept to a minimum. As the attestation code is immutable SMART architecture can support only one attestation scheme instance. TrustLite --------- The TrustLite [@koeberl:trustlite:2014] hardware architecture is a flexible and efficient software isolation platform for low-powered devices. This architecture introduces trustlets, which are trusted tasks developed to realize an application. The goal of trustlets is to isolate the enclosed software components and protect the confidentiality and integrity of their code and data. The memory protection scheme in this architecture involves the Execution-Aware Memory Protection Unit (EA-MPU). The EA-MPU can be programmed in software and offers a flexible allocation of memory across memory and I/O components. Another feature of the architecture is the Secure Loader, which loads the selected trustlets alongside their data into memory. Another goal of the Secure Loader is to program the Memory Protection Unit (MPU) to protect its own code and the memory regions of all trustlets. The Secure Loader also start the chain of trust process for remote attestation. One of the advantages of this architecture is that it enables the local attestation between multiple trustlets. Trusted communication between trustlets happens using a simple handshake protocol between a Trustlet A and Trustlet B. Trustlet A is the initiator that verifies the platform configuration and the security policy of the MPU for Trustlet B who is the responder. The initiator can also verify the cryptographic hash of the responder’s internal state so that it can be assured that is not modified. Then the responder can also perform a local attestation on the initiator using the same attestation process as the initiator. A cryptographic hash over the identifiers of the trustlets and their corresponding nonces comprise the cryptographic session token. The token can be used to authenticate bidirectional messages between the two trustlets. Another advantage of TrustLite is that its security extensions do not depend on the CPU instruction set and can be adjusted using software. Thus all the related software such as the Secure Loader and security policies can be updated. This is in contrast with the SMART architecture where the attestation code and key are not updateable. One of the main disadvantages of this security architecture is that it only support the local attestation of trustlets that remain on the same system. Another disadvantage is that TrustLite requires a custom built software in order to support the memory protection scheme and the user tasks. In terms of cryptography support it only uses a cryptographic hash for the attestation process. Of course the architecture could be extended with additional cryptographic components such as cryptographic accelerators. The default configuration is to just enable a cryptographic hash for measuring the state of a trustlet. In addition, the static software configuration does not enable to change the software configuration dynamically during runtime. Tytan ----- Tytan  [@braser:tytan:2015] is a hardware security architecture for low-powered devices. The system architecture of Tytan consists of ten different components. Tasks represent the applications in embedded systems and there are two types of tasks. The first type is the normal tasks that are isolated from other tasks but not from the OS. The second type is the secure tasks that are isolated from all the other software. In addition, each task has a unique identifier. The Execution-aware Memory Protection Unit (EA-MPU) hardware component enforces memory access control and makes sure that each task can only access the memory it has been allocated. The hardware component is also coupled with a driver that enables the dynamic handling of tasks and the loading or unloading of a secure task. Tytan is assigned a platform key that the EA-MPU enforces the access to the key. Tytan architecture includes a real time OS to provide a real-time scheduling. The main features of this architecture include the strong isolation of dynamically configured software components using dynamic root of trust and real time guarantees. Another feature of Tytan is the local and remote attestation. Tytan also supports secure inter-process communication (IPC) between two parties using authentication. Attestation in Tytan is realized by executing the Root of Trust of Measurement (RTM) task. This task is executed to prove the integrity of a either a local or a remote by computing a cryptographic hash over the binary code of each attested task. In order to prove authenticity to a local verifier the task identifier is used. For remote attestation the a Message Authentication Code (MAC) is computed alongside an attestation key. In terms of disadvantages this architecture does not support the updating of tasks during runtime and only supports a cryptographic hash method for the attestation process. Sanctum ------- Sanctum [@costan:sanctum:2016; @lebedev:sanctum_ra:2018] is an architecture that depends on minimal and minimal invasive changes to the hardware. It uses a trusted software component called security monitor to yield security properties similar to Intel SGX. The architecture relies on a hardware/software co-design to isolate and protect the integrity of applications. The authors make slight adjustments to well understood building blocks and mechanisms. The CPU building blocks do not require any adjustments as Sanctum only makes changes to the interfaces of these building blocks. Thus, the integration of Sanctum to other hardware platforms is easier to achieve in comparison to Intel SGX which requires specific CPUs in order to function. Sanctum relies on a select set of trusted software components to drive similar security mechanisms with those in Intel SGX. For instance both systems support a method to locally attest the integrity of software. Sanctum provides an open-source implementation of the security monitor which is portable to different CPU architectures and amenable to rigorous security analysis. In contrast, the Intel SGX relies on microcode which its source code is not openly available and is specific to the CPU models. The trusted software components replace the microcode that Intel SGX uses. There are three software components that are part of the Sanctum architecture. The first component is the measurement root that is burned in an on-chip ROM. The goal of the measurement root is to execute successfully three tasks: compute a cryptographic hash from the security monitor which is added as input to both generate a monitor attestation key pair and attestation certificate. The second component is the security monitor which takes over when the measurement root has managed to construct the attestation measurement chain. The security monitor offers an API that focuses on managing enclaves and allocating memory regions. The API can be invoked both from the OS and the enclaves. Timing attacks can deployed in such a setting for the API. For this reason the security monitor is prohibited from accessing any enclave data and from accessing any memory regions related to the attestation key. In addition, the security monitor is not allowed to perform any cryptographic operations that use attestation keys. Thus, computing attestation signatures is deferred to the signing enclave. The third component is the signing enclave which executes the signing algorithm. The reasoning behind this design decision is to avoid any timing attacks and remove the dependency on the security monitor to compute the signatures for attestation. The signing enclave is executed inside the security monitor as an enclave isolated from other software. The security monitor evaluates any calls to the signing enclave by checking the known measurement of the signing enclave. If the call is successfully evaluated, then it proceeds to the singing enclave. For instance, the first call that the signing enclave receives is the monitor’s private attestation key which is then copied to the enclave’s memory. The signing enclave can authenticate another enclave and uses a mechanism similar to the Intel SGX’s reporting mechanism called mailbox. Mailboxes are part of the enclave’s metadata and are specified during construction. This is a synchronous messaging mechanism that requires both sending and receiving enclave to run simultaneously and exist in memory so that they can communicate. The receiving enclave uses an API call that includes the mailbox that will receive the message and the sending enclave’s identity. The sending enclave which want to be authenticated sends an API call to the receiving enclave with the identity of the receiving enclave and the mailbox inside the receiving enclave. Then the receiving enclave issues a read API call to request the contents of the message to be moved from the mailbox to the enclave’s memory. The receiving enclave is assured of the sending enclave’s identity when the API call to read is successful. Hardware-based attestation {#sec:hw-ra} ========================== In this section we focus on the attestation methods that use a tamper-resistant hardware component to drive the attestation process. We separate the methods used in two categories depending on if the methods support attesting only one node each time or a group of nodes. We also discuss two variations of the hardware-based approach. First, a discrete tamper-resistant hardware component embedded in a motherboard provides the required attestation services such as generating and storing cryptographic keys, signing attested data. Second, there are co-processor hardware components that assist the attestation process and collaborate with other hardware components. Single Platform Attestation --------------------------- In this subsection, we focus on approaches that attest one node at a time in a network infrastructure. ### Trusted Platform Module (TPM) Attesting the integrity of a single platform is the focus of most attestation schemes developed during the last 20 years of research. It is a popular problem domain, which has been thoroughly researched and especially for trusted computing. In the following paragraphs we discuss the main schemes that have been developed. The protocol in the Trusted Computing Group (TCG) specification for the TPM v1.2 is based on the third party *Privacy Certificate Authority (CA)* [@tcg:2005] to complete the attestation of the platform identify. When a user purchases a trusted computing platform it does not have an identity. In order for the platform to gain an identity the TPM owner requests a certificate from a trusted third-party Privacy CA. The output of this process is the Attestation Identity Key (AIK) certificate that the platform can use to attest the integrity of the platform. The main disadvantage of this process is that the Privacy CA knows the identity of the platform. If the verifier colludes with the Privacy CA then the integrity of the platform cannot be assured. Another disadvantage of this approach is that the Privacy-CA is a single point of failure and it can become a performance bottleneck if the verifier queries the Privacy-CA for each verification request. Paired dictate this is very good approach regarding this at the station skin skin scheme. The next idea that is included in this report discusses the main aspects off the security and privacy issues what are eyes doing the execution off the other stations game receipt ### Direct Anonymous Attestation The *Direct Anonymous Attestation* (DAA) [@brickell2004direct] scheme uses zero-knowledge proofs and CL-signatures to enable the attestation of a platform without compromising the identity of the platform. The DAA scheme includes three entities: platform, issuer and verifier. The role of the issuer is to generate and issue credentials to platforms and consult a revocation list to revoke platforms that are considered compromised. The platform entity in the DAA scheme consists of a host computer and a TPM device. Both components in the platform contribute to create signatures that prove to a verifier that the platform which created the signature was indeed issued a credential by the issuer. As a result the verifier checks the proofs and is not able to identify the platform that created the signature. The initial version proposed is based on RSA and is considered inefficient and forms part of the TCG specification for TPM v1.2. Subsequent works extend the DAA scheme and use Elliptic Curve Cryptography (ECC) and bilinear maps [@brickell:2008] to further improve efficiency of the scheme. This scheme includes three main entities: issuer, prover and verifier. DAA uses group signatures and zero-knowledge proofs to attest that the remote attestation originates from an authentic TPM without disclosing to the verifier the exact identity of the TPM. The issuer in DAA is provided with an anonymous credential instead of an identity for the TPM. Then the TPM proves its identity to the verifier using zero-knowledge proofs and its pseudonym. There has been a large body of research over the DAA scheme with improvements suggested and new schemes developed that aim to improve the efficiency of the scheme or integrate DAA in other platforms such as ARM TrustZone. In addition, there is research that manage to extend DAA scheme to encode attributes which can bind multiple TPMs to an anonymous credential. A recent research thread for direct anonymous attestation is to leverage lattices for creating DAA schemes [@kassem2019daalat] that are post-quantum safe. ### Binary remote attestation is used to attest the platform integrity. In this scheme the TPM signs the PCR values representing the integrity of the platform. The TPM subsequently sends the TPM signature and the measurement log to the remote verifier. Then the remote verifier is able to attest the current state of the platform. Realization of this scheme is the IBM Integrity Measurement Architecture (IMA) [@Sailer:2004wa] and the trusted linux client (TLC) system [@safford2005trusted]. One of the disadvantages of this scheme is that it discloses the software and hardware configuration of the platform to the remote verifier, which makes the platform vulnerable to malicious attacks. In addition, there is a great variety of software and their configurations and when the system needs to be updated it makes it difficult to evaluate the configuration integrity of the platform. ### Property-based Attestation (PBA) Another scheme used for remote attestation that attempts to overcome the shortcomings of the binary remote attestation is the *Property-based Attestation (PBA)* [@Sadeghi:2004:PAC:1065907.1066038; @chen:2008] scheme. In this scheme the platform configurations are mapped to properties which are attested in order to avoid the disclosure of the platform configurations. ### Physical Unclonable Functions (PUFs) Another type of hardware component to be used in remote attestation schemes is the Physical Unclonable Functions (PUFs) [@sadeghi2011short; @kong:pufatt_ra:2014]. The PUF is a hardware-based security primitive first introduced by Gassend et.al. [@gassend:puf:2002] The authors propose that architecting the construction of the hardware component in a secure way it can protect the attestation process and provide a secure basis for the attestation computations. Hybrid attestation {#sec:hy-ra} ================== This attestation method includes a hardware component for the attestation process, but also integrates with the software each network node uses. A type of hybrid attestation that is related to our research area is *swarm attestation* or *collective attestation* [@carpent:lisa_ra:2017; @asokan2015seda; @meng2018dynamic; @rabbani2019shela]. The main premise of this hybrid attestation method is the ability to attest a large number of nodes across a network with various interaction patterns. The main focus is to offer attestation services to remote embedded devices that have limited processing power. Even though collective attestation schemes focus on embedded devices and devices with limited processing power they still have a hardware component that they can rely on to fulfill or assist with the attestation process. Multiple Platform Attestation ----------------------------- *Swarm attestation* or *collective attestation* [@asokan2015seda; @ambrosin2016sana; @ibrahim:seed:2017; @carpent:lisa_ra:2017; @ibrahim2016darpa; @kohnhauser2018salad; @wedaj2019dads] focuses on remote attestation of multiple platforms at a large scale. This type of attestation is considered a hybrid attestation scheme since it utilizes a software/hardware co-design since the computing platforms are embedded devices with limited capabilities and processing power. In this context a TPM component could not be added to the device. If a TPM component was added to a small embedded device, it would increase production costs and the price of the device. Collective attestation works by distributing the attestation process across all devices in a network. A spanning tree is created during attestation over the network topology. The root of the spanning tree is the verifier who also initiates the attestation. During the process of the attestation each device validates their child devices and propagate in the spanning tree an aggregate attestation report to their parent devices. The first research work to propose a collective attestation scheme was *Scalable Embedded Device Attestation (SEDA)* [@asokan2015seda]. This attestation scheme works by using groups of many provers. SEDA includes an off-line phase where an operator $OP$ initializes the devices in the swarm with a particular software configuration and certificate and an online phase for the attestation process. This attestation scheme requires devices which includes minimal security features and without any complex security hardware such as a TPM. A central verifier $V$ generates attestation requests that are propagated to all nodes of the network topology using a flooding protocol as seen in Figure \[fig:seda-attestation\]. Then the verifier accepts the aggregate attestation reports of the devices in the network. ![SEDA collective attestation in a swarm of 8 devices [@asokan2015seda][]{data-label="fig:seda-attestation"}](figures/seda-attestation.pdf){width="0.8\linewidth"} The *Secure Collective Attestation Scheme (SANA)* [@ambrosin2016sana] is a collective attestation scheme for dynamic embedded devices network that employs signature scheme called Optimistic Aggregate Signature scheme (OAS). This scheme integrates aggregate and multi-signatures in which $n$ signers sign messages $m_1, \ldots, m_n$. The majority of the signers sign the default message $M$. Each signature is aggregated into an aggregate signature, which is shorter than signing $n$ different signatures. The main parties of this attestation scheme are: prover ($P$), aggregator ($A$), owner ($O$) and verifier ($V$). A prover $P_i$ constructs the proof of integrity of its software configuration to be sent to the verifier. An aggregator $A_i$ relays the messages between different parties, collects and aggregates the responses from other provers or aggregators. The network owner $O$ is responsible to deploy and maintain the embedded devices that act as provers. A remote verifier $V$ is assured of the software integrity of all provers that are part of the network during the attestation process. SANA also considers the possibility of compromised devices, which do not affect the integrity of the attestation process. *SeED* [@ibrahim:seed:2017] is another attestation scheme for multiple embedded devices which introduces a non-interactive attestation protocol. The attestation process is executed at random times which is known between the verifier and prover. This way the messages exchanged between an $V$ and $P$ are kept to a minimum. The $P$ creates an attestation response which is sent to the $V$. The $V$ accepts the response only if it is inside the time period for this attestation execution. If that is true then the $V$ checks for authenticity, freshness, and trustworthiness of software measurements corresponding to an accepted software state. This protocol mitigates Denial of Service (DoS) attacks while exhibiting low communication overhead and low network congestion. *Lightweight Swarm Attestation (LISA)* [@carpent:lisa_ra:2017] aims at investigating methods of attesting a possibly mobile group of provers. A new metric is introduced called Quality of Swarm Attestation (QoSA) that measures the information offered by different collective attestation schemes. LISA provides two practical variations of the collective attestation scheme presented in Figure \[fig:seda-attestation\]. LISA’s main focus is the construction of the spanning tree. The first variation includes a synchronous mechanism to aggregate the attestation reports. The second variation uses an asynchronous protocol that forwards the attestation reports directly to the verifier without any previous aggregation. *Device Attestation Resilient to Physical Attacks (DARPA)* [@ibrahim2016darpa] is a collective attestation scheme that can detect both software-based and physical attacks. The authors propose a heartbeat protocol that is executed at regular time intervals. The heartbeat is propagated throughout the network topology and it proves the presence of neighbouring devices that are members in a network topology. This way an adversary that compromises a device can be detected, under the premise that the adversary needs to take the device offline to attack it. A verifier can then detect if any devices are missing when collecting the heartbeat logs. In addition, this work is can be integrated with other collective attestation schemes such as SEDA or LISA to protect the network topology from an adversary with physical access. *Secure and Lightweight Attestation of Highly Dynamic and Disruptive Networks (SALAD)* [@kohnhauser2018salad] is a collective attestation scheme for highly dynamic networks. The main difference of this scheme is that instead of creating a spanning tree of the network topology during attestation with the root node being the verifier, the attestation process uses a distributed approach. The idea is to have devices that communicating with other nearby devices to attest the software integrity of each other. Then they exchange the attestation proofs, which also include accumulated attestation proofs of other nearby devices. SALAD protects against DoS attacks when some of the devices prevent an attestation of other devices in the network. In addition, the verifier can receive the attestation result from any participating device, without the need to hold the communication with a particular network device. *Decentralized Attestation for Device Swarms (DADS)* [@wedaj2019dads] is another scheme that proposes a decentralized collective attestation scheme that is scalable to a large number of embedded devices and supports high mobility networks with a dynamic topology. In this scheme each member device in the network is attested by a device in its vicinity. Each attested device is then assigned to verify other devices. Thus, there is only a need for a central verifier during the initial stages of the attestation process and makes this scheme resilient to single point failures. In addition, DADS offers a local attestation process where a node can locally attest the software integrity of its modules. In case there are any compromised nodes DADS provides a means of graph restructuring the network topology of the attested nodes. *Scalable Heterogeneous Layered Attestation (SHeLa)* [@rabbani2019shela] is a collective attestation scheme that adds an additional edge layer in between the root verifier and the swarm devices present in the infrastructure network. The edge layer consists of the edge verifier and the swarm nodes present in this layer, which take the role of the prover in this locality. This scheme uses a distributed method of attestation where the verifier can obtain the attestation result from any node in the swarm. Even though this solution is scalable, there are privacy concerns since each edge verifier keeps a log of related information and the root verifier stores information regarding all the layers of the infrastructure. *Practical Attestation for Highly Dynamic Swarm Topologies (PADS)* [@ambrosin2018pads] discusses a non-interactive attestation scheme for dynamic and unstructured swarm networks. The main feature of this scheme is the reduction of the collective attestation problem to a minimum consensus problem. The provers attest themselves and add their attestation result into an aggregate attestation by sharing their knowledge to adjacent provers that reside in the swarm network. *Efficient Remote Attestation via Self-Measurement for Unattended Settings (ERASMUS)* [@carpent2018erasmusa; @carpent:self_measurement_ra:2019] is a remote attestation scheme that is based on the notion of self-measuring the software code of provers in timed intervals and storing them locally. A verifier can request the measurement history and discern if there is any mobile malicious code present that has tampered with the measurements. The authors discuss the advantages of ERASMUS in comparison with on-demand attestation and how this scheme can be used in the context of collective attestation by integrating with an on-demand attestation scheme such as LISA. ERASMUS can operate both according to a schedule and on-demand when receiving a query from a verifier. The authors claim that ERASMUS is well suited for collective attestation since it supports high mobility of the devices. Even though, this scheme minimizes the prover computations it still uses LISA for the collective attestation inheriting the shortcomings of the scheme. In all above schemes, the main issue is that the verifiers learn about the structure of the network topology that is being attested. However, there are cases where we would want to keep the structure of the network confidential and provide other means of attesting the nodes in a network. One such case is when a tenant verifier asks a cloud provider that software integrity of her virtualized host is not compromised. The cloud provider would not want to publicize the blueprint of her infrastructure. Therefore, we require to create novel privacy-preserving attestation schemes that can scale to large networks and be resilient in software and physical attacks. ------------------------------------------------------------------- ------------------- ----------------------- ----------------------- ------------------------- -------------------------------------------- -- -- -- Interaction Software Physical Attestation Cryptographic Pattern Attacks Attacks Method Primitives SEDA [@asokan2015seda] $1-N$ $\CIRCLE$ $\CIRCLE$ Centralized ECDSA, SHA-1 \[-2pt\][SANA [@ambrosin2016sana]]{} \[-2pt\][$1-N$]{} \[-2pt\][$\CIRCLE$]{} \[-2pt\][$\CIRCLE$]{} \[-2pt\][Centralized]{} \[-2pt\][Optimistic Aggregate Signature]{} DARPA [@ibrahim2016darpa] $1-N$ $\CIRCLE$ $\CIRCLE$ Centralized MAC \[-2pt\][SeED [@ibrahim:seed:2017]]{} \[-2pt\][$1-N$]{} \[-2pt\][$\CIRCLE$]{} \[-2pt\][$\Circle$]{} \[-2pt\][Centralized]{} \[-2pt\][HMAC-DRBG]{} LISA [@carpent:lisa_ra:2017] $1-N$ $\CIRCLE$ $\Circle$ Centralized ECDSA-256, SHA-256 \[-2pt\][SALAD [@kohnhauser2018salad]]{} \[-2pt\][$1-N$]{} \[-2pt\][$\CIRCLE$]{} \[-2pt\][$\CIRCLE$]{} \[-2pt\][Distributed]{} \[-2pt\][ECDH, SHA-256, HMAC, EdDSA]{} DADS [@wedaj2019dads] $M-N$ $\CIRCLE$ $\Circle$ Decentralized ECDSA, HMAC SHeLa [@rabbani2019shela] $1-N$ $\CIRCLE$ $\Circle$ Distributed SHA-256 PADS [@ambrosin2018pads] $1-N$ $\CIRCLE$ $\Circle$ Distributed HMAC ERASMUS [@carpent2018erasmusa; @carpent:self_measurement_ra:2019] $1-N$ $\CIRCLE$ $\Circle$ Centralized HMAC ------------------------------------------------------------------- ------------------- ----------------------- ----------------------- ------------------------- -------------------------------------------- -- -- -- : Comparison of collective attestation schemes focusing on security aspects \ \[tab:sec-comp\] Open Research Problems {#sec:open-res} ====================== The current remote attestation solutions have issues that give room for improvement. In this section, we discuss open research problems and provide avenues of further research in remote attestation schemes. The main focus of this section is about the privacy and confidentiality issues that arise when using remote attestation schemes and possible ways of addressing those issues. Privacy Issues -------------- In hardware-based approaches discussed in this report exhibit a number of privacy issues in terms of how the attestation is executed and the amount of information that that the $V$ learns about the structure of the network infrastructure that is attesting. An issue that arises mainly when attesting nodes in a network is the information that the intermediary nodes learn about the attestation result of adjacent nodes and how resilient is the attestation scheme when the node attested is a malicious one and tries to add its own bogus information to relay to other adjacent nodes in the network. In the attestation schemes that adjacent nodes learn the attestation result of the previous nodes this can be an issue in terms of relaying reliable information to the other nodes and finally the $V$ will receive attestation results that will not be correct in case that a malicious node injects its own attestation results. Therefore, a method to relay attestation results without the intermediary network nodes to know is beneficial to improve the privacy of an attestation scheme. A number of approaches could be selected to achieve the required privacy level. One such approach involves cryptographic primitives that are privacy-preserving and hide information from potential adversaries. Anonymous credential schemes provide a way to construct privacy-preserving attestation schemes for nodes in a network. DAA is one of the most prevalent cryptographic scheme based on anonymous credentials and group signatures. When we attest multiple platforms in compound proof statements in a network infrastructure, a cryptographic scheme based on anonymous credentials would be a step forward for protecting the privacy of intermediary attestation results which include the software configuration of the device. Confidentiality Issues ---------------------- Apart from the privacy issues mentioned above there are a number of issues regarding the confidentiality of attestation schemes in network infrastructures. In collective attestation schemes a malicious prover that is adjacent to a number of other nodes in a network can discover the structure of the network using the attestation results of other nodes that it is collecting. In order to keep the structure of the network secret, there needs to be a method of protecting the blueprint of the network without disclosing its structure. One way is to use signature schemes and zero knowledge proof of knowledge protocols to convince adjacent provers that the structure of the network is known but the actual structure is not disclosed to other provers. Then the verifier can be assured that the structure of the network has been protected. This method make sure that the verifier also does not get to know the structure of the network from the attestation results collected from the network nodes. Conclusions =========== Attesting network infrastructures is an important avenue for ensuring that nodes in a network are in a legitimate state and are authenticated. There are a number of hardware architectures that have been proposed to further support attestation schemes. A number of these hardware architectures support higher-end hardware and cryptographic primitives for attestation schemes, while other architectures exhibit a more minimal approach supporting lower-end hardware and lightweight cryptographic primitives. We presented a categorization of attestation schemes depending on the type of the attestation each research work used and the cryptographic primitives employed to realize the schemes. This allowed us to compare and contrast the attestation schemes that focus on different aspects on how to create attestation schemes for network infrastructures. We also identified open research issues in terms of confidentiality and privacy. Finally, we presented possible avenues of resolving the issues in attestation schemes. This paper shows that there are many works related to attestation architectures and schemes. However, there is still room for improvement in terms of scalability, privacy and confidentiality issues for attestation. We hope this survey acts as a starting point to future research on attestation.
Introduction {#S0001} ============ According to the World Health Organization (WHO) global tuberculosis (TB) report in 2018, TB is the number one infectious killer globally \[[1](#CIT0001)\]. Different species of mycobacteria have been shown to elicit different immune responses \[[2](#CIT0002)\]. Pathogenic mycobacteria are known to survive inside the host by arresting phagosome maturation \[[3](#CIT0003)--[5](#CIT0005)\]. The pathogen survives inside the optimal environment of the phagosome and the mechanism responsible for its growth and survival inside the host is still unknown \[[6](#CIT0006)--[8](#CIT0008)\]. The enigma of the host response to effectively counter nonpathogenic bacteria but being unable to destroy pathogenic bacteria may be deciphered by comparing the host immune response toward these pathogenic and nonpathogenic infections. One of the most widely used approaches for evaluating the host response to *M. tuberculosis (M. tb)* infection is transcriptome analysis using RNA sequencing \[[9](#CIT0009) [10](#CIT0010),\]. In the present study, we used an AmpliSeq^TM^, which is reported to be cost-effective, highly sensitive and reproducible for the detection of differentially expressed transcripts \[[11](#CIT0011)\]. We also used Luminex technology as a multiplex immunoassay platform to study the levels of cytokines post-infection. Previous studies have also used multiplex ELISA for comparing the host immune response to infection at the protein level \[[12](#CIT0012) [13](#CIT0013),\]. The present study is a follow-up to our earlier work studying the initial host response to hyper-virulent *M. tb* infection in murine bone marrow-derived macrophages (BMDMs) \[[9](#CIT0009)\]. The way in which the host cell responds to pathogenic (e.g. R179) and nonpathogenic mycobacteria (*M.smegmatis*) is believed to be largely different due to genomic and biochemical variability of mycobacteria \[[14](#CIT0014)\]. In the present study, we used R179 *M. tb*, a known multi drug-resistant clinical isolate (Beijing genotype strain R220) prevalent in the Western Cape of South Africa \[[15](#CIT0015)\]. We also used avirulent sub-strain of *M bovis* BCG (Tokyo 172) a mycobacterial species known for causing disease in both animals and humans \[[16](#CIT0016)\]. We used *M. smegmatis* as nonpathogenic mycobacterial species which is known to be killed within 48 h of *in vitro* infection \[[17](#CIT0017) [18](#CIT0018),\]. The host can control *M. smegmatis* infection, although the factors behind this is understudied. We hypothesized that identifying these factors can help in developing interventions against pathogenic mycobacterial infection as well. Therefore, we compared the *in-vitro* host immune response from hMDMs toward mycobacteria of different pathogenicities using Ampliseq, qRT-PCR and multiplex ELISA, to elucidate the potential factors involved in countering the nonpathogenic mycobacteria (*M. smegmatis*). Materials and methods {#S0002} ===================== Enrollment of study participants {#S0002-S2001} -------------------------------- Healthy participants were screened for any symptoms of TB. Participants with cavities on chest X-ray, night sweats, recent unexplained weight loss, persistent cough, and fever were excluded. Additional exclusion criteria included: use of any medication, major surgery in the recent past, pregnancy, anemia, and insomnia. Additionally, we aimed to select equal representation of gender and ethnicity. We screened 26 individuals, out of which 14 were excluded ([Figure 1](#F0001)). Twelve healthy participants (6 males and 6 females) with no history of TB were enrolled ([Table 1](#T0001)).10.1080/21505594.2020.1726561-F0001Figure 1.Study outline.Abbreviations: CFUs = colony-forming units, ELISA = enzyme-linked immunosorbent assay, PBMCs = peripheral blood mononuclear cells, DEGs = differentially expressed genes, MOI = multiplicity of infection, qRT-PCR = quantitative reverse transcriptase-polymerase chain reaction. Ethical approval for the study was obtained from the Health Research Ethics Committee (HREC), Stellenbosch University, Tygerberg campus, Cape Town (HREC Reference \#S17/10/211). Cell isolation and culture medium {#S0002-S2002} --------------------------------- Blood (80 ml) was collected into Heparin Vacutainer (Lasec, South Africa, Cat No. VGRV455051R) by phlebotomy. The buffy coat was obtained by centrifugation and macrophage-like cells were isolated under culture conditions that allow differentiation of monocytes into macrophages, i.e. by culturing in Teflon-coated culture flasks using RPMI-1640 medium supplemented with 20% heparinized plasma and incubated at 37^°^C and 5% CO~2~ for 5 days. After 5 days of culture, the cells were washed with phosphate buffer saline (PBS) and incubated in 12-well culture plates for 2 h at 37°C in a 5% CO~2~ incubator for adherence of hMDMs (otherwise lymphocytes will be difficult to remove) \[[19](#CIT0019)\]. For infection experiments, human macrophage cells were seeded in 12-well plates with 0.7 × 10^6^ cells per well. Infection with mycobacteria {#S0002-S2003} --------------------------- Pathogenic (R179), and nonpathogenic (*M. smegmatis* and *M. bovis* BCG) species of mycobacteria were used for infection. All three mycobacterial species were cultured in detergent-free media for infection. Mycobacteria were cultured in 7H9 media (Sigma Aldrich, USA) supplemented with 10% Oleic Albumin Dextrose Catalase (OADC) (Sigma Aldrich, USA) and 0.5% glycerol without Tween-80. We avoided use of Tween, since Tween is known to affect the rate at which macrophages ingest *M. tb* and form phagosomes as well as the subsequent immune response to *M. tb* \[[20](#CIT0020)\]. A syringe-settle-filtrate (SSF) method was performed in order to disaggregate the detergent-free grown mycobacterial species, hence preparing the infecting doses equivalent for each strain. Stock cultures of mycobacteria stored at −80°C were thawed and disaggregated by pipetting 10 times with a 1-ml tip. Subsequently, the solution was passed through a 25-gauge needle 20 times \[[21](#CIT0021)\] and any remaining aggregate was allowed to settle for up to 1 min \[[22](#CIT0022)\]. The settling time was different for each species (*M.smegmatis *= 30 s, BCG = 1 min, R179 = 1 min). The top 750 µl of the solution was collected and added to 4.25 ml of RPMI-glutamine media. This 5 ml bacterial suspension was then immediately filtered through 5.0 µm pore size filter (Merck Millipore, Germany) to which 10% human serum (Celtic, Cat No. S4190) was added as a final concentration. This method was performed in our laboratory earlier to determine the effect of culturing the mycobacteria in the absence of a detergent as compared to its presence \[[20](#CIT0020)\]. hMDMs were infected separately with each mycobacterial strain at multiplicity of infection (MOI) = 1. After 4 h of infection, cells were washed three times with PBS to remove any extracellular mycobacteria. Cells were then incubated for another 8 h in 5% CO~2~ incubator at 37°C. Uninfected hMDMs served as a control. Cells were then plated for colony-forming units (CFUs) and processed for RNA extraction. Culture supernatants were collected for measurement of cytokine levels using the Luminex platform (Biocom, USA, Cat. No. PPX-12). Determination of bacterial uptake {#S0002-S2004} --------------------------------- CFUs were determined in hMDMs infected with *M. smegmatis, M. bovis* BCG and R179 mycobacterial species. Infected cells were lysed using 0.1% Triton X-100 (Sigma Aldrich, Cat No. T8787). Bacterial uptake was determined by serial dilution (10^−1^ -- 10^−4^) and plating out of mycobacteria onto 7H11 agar plates. Mycobacterial uptake was measured at 4 h and the mycobacteria survival within the infected cells was monitored at 12- and 24-h post infection. The percent uptake was calculated by dividing the number of bacteria taken up per milliliter by number of macrophages in each well. Cytotoxicity analysis {#S0002-S2005} --------------------- Cell cytotoxicity was tested with Roche WST-1 Cell Cytotoxicity Reagent (Roche, USA) in 1:10 dilution of WST-1 reagent to RPMI complete media. Since the hMDMs do not proliferate in a 4-day culture, cells at different time points (12- and 24-h post infection) were processed here. Cells were incubated for 1 h at 37° C in a 5% CO~2~ incubator. Absorbance was measured at two different wavelengths for correction (450 and 630 nm). RNA extraction {#S0002-S2006} -------------- Total RNA from human macrophages was extracted using a kit (RNeasy Plus Mini Kit) per the manufacturer's instructions. The extraction was performed immediately following the 12-h infection period. Genomic DNA was removed by column filtration "gDNA eliminator" column included in the kit. For each experiment, RNA quantity and quality was assessed using an Agilent 2100 Bioanalyzer. Only RNA samples with an RNA integrity number (RIN) ≥ 9 were used for amplicon-based RNA sequencing and qRT-PCR experiments. Total RNA was extracted and frozen immediately at −80°C until needed. Amplicon-based RNA sequencing {#S0002-S2007} ----------------------------- Transcriptome sequencing was performed at Central Analytical Facility (CAF) at Stellenbosch University, South Africa using the Ion AmpliSeq™ Transcriptome Human Gene Expression Kit (Thermo Fisher Scientific) according to the manufacturer's protocol (protocol MAN0010742 Rv B.0). Total RNA (100 ng) was reverse-transcribed using the SuperScript® VILO™ cDNA Kit to generate cDNA. The 20.802 RefSeq genes were amplified for 10 reaction cycles using the Human Gene Expression Core Panel. After partial digestion, barcode adaptors (from the IonCde Adapters Kit) were ligated and the libraries were purified with Agencourt ™ AMPure™ XP reagent and eluted in low TE buffer. The concentrations of the RNA library were determined using the Ion Library TaqMan Quantitation Kit according to the protocol (MAN0015802 Rev A.0) and all libraries were diluted to a target concentration of 60 pM. To avert potential bias during sequencing or emulsion PCR, the 84 libraries were mixed before emulsion PCR, enrichment and chip loading on the Ion CHEF using the Ion PI™ Hi‑Q™ Chef Reagents, Solutions and Supplies according to the protocol (MAN0010967 Rev B.0). To limit the effect of run-to-run variation, all libraries were pooled and sequenced on multiple Ion P1™ v3 Chips on the Ion Proton™ according to the manufacturer's protocol (MAN0010967 RevB.0). Sequence data were analyzed using Torrent Suite Version 5.4.0 Software Partek Flow. All the reads were mapped by the TMAP module (as implemented in Torrent Suite). These mapped reads were exported as binary alignment and mapping (BAM) files (.bam extension) into the Partek Flow Software tool where the various data files for each sample were combined to create one dataset for each sample. After alignment, the QC module of Partek Flow was used to visualize the average base quality score per-position and per-alignment mapping. These mapped reads were quantitated using a separate set of software (RefSeq transcripts) annotation for quantification using the Partek E/M method. Differential expression analyses was performed using "edgeR" version 3.4.1. Statistical analyses were carried out by the Division of Statistics at Stellenbosch University. We used edgeR to model a negative binomial distribution of count data and estimated dispersion parameters. Subsequently, we determined differential expression using one-way repeated measures ANOVA using Limma \[[23](#CIT0023)\]. We used Benjamini-Hochberg false discovery rate to correct for multiple testing \[[24](#CIT0024)\]. The edgeR statistical method was used to select DEGs. The DEG list was filtered using a combination of stringent gene filtering measures which included log counts per million (CPM), FDR \<0.001 and fold changes (\>1.5). qRT-PCR {#S0002-S2008} ------- Good quality RNA (RIN\>9, 0.8 µg) was converted to cDNA using Quantitect® Reverse Transcription Kit. To ensure the removal of genomic DNA, "gDNA wipe-out buffer" was used. qRT-PCR amplification was run on a LightCycler® 96 system (Roche, Germany). LightCycler® 480 SYBR Green I Master and QuantiTect® primer assays were used. Hs-GAPDH and Hs-UBC were selected as reference genes conferring to stable expression levels from amplicon-based RNA sequencing data and validated through qRT-PCR. The amplification process involved 45 cycles of 95°C for 10 s followed by 60°C for 10 s and finally 72°C for 10 s. Gene expression fold-changes were computed for pathogenic infected and nonpathogenic infected macrophages using calibrated, normalized relative quantities using the equation N = N~0~ × 2^Cp^. All qRT-PCRs were performed on RNA extracted from three separate experiments. All biological replicates, a positive control and a non-reverse transcription control were run in triplicate (along with calibrator) as per the MIQE Guidelines \[[25](#CIT0025)\]. Ingenuity Pathway Analysis (IPA®) {#S0002-S2009} --------------------------------- IPA® was performed using IPA Gene View Software (version 01--13). Statistical measures reflecting dataset genes interacting with each other (p-value) and activation (z-score) were based on the known direction of up- and down-regulated genes. For detailed pathway evaluation differentially expressed genes (DEGs) with fold changes \>1.5 and adjusted p-value ≤ 0.05 were used in the analysis. These data was also used to generate lists of top Canonical Pathways, top upstream regulators and top regulator effect networks in hMDMs after infection with mycobacteria with respect to potential DEGs which were selected based on the stringent gene filtering measures. Multiplex ELISA {#S0002-S2010} --------------- A panel of 7 cytokines was selected from the list of 19 DEGs. This panel included IDO-1, five interleukins (IL-1β, IL-6, IL-8, IL-12-β \[IL-12p40, IL-12p70\] and IL-23) and type-II interferon (IFN-γ) which was designed for studying their host response upon infection with mycobacteria at different time points using the Luminex platform. Cytokine concentrations were evaluated using on the Bioplex platform (BioRad Laboratories, Hercules, CA, USA) using Procarta Luminex kits -- ThermoFisher (Cat No. PPX-12) according to the manufacturer's protocol. The coefficient of variation for duplicate runs was \<20% for all samples (range, 5.2--19.6%) and the concentrations of all analytes in the quality control reagents were within their expected ranges. The standard curve for all samples ranged from 3.6 to 10,000 pg/ml. Bioplex Manager Software version 1 (BoiRad, south Africa) was used for analysis of median fluorescent intensities. Statistical analysis {#S0003} ==================== The qRT-PCR data were analyzed using Light Cycler 96 SW 1.1 Software and Graph-pad Prism Version 7. Relative Expression which measures target transcript in a treatment group to that of untreated group was measured through the software in response to the calibrator and non-transcription control. The significance of the effect of strain was determined by one-way ANOVA using GraphPad Prism (Graph-Pad Software Version 7, San Diego California, USA) and Tukey's honest significant difference test to correct for multiple testing. The reads were quality trimmed on the 3ʹ end using a 30-bp sliding window. When the average base quality value was below 16, the last 15 bases were trimmed, and the evaluation was performed for the next window of 30 bases. The qRT-PCR data in the study is presented as mean ± SD from 12 healthy participants. Cytotoxicity graphs and CFUs were plotted with an average of the technical triplicates leading to the mean of all the biological replicates. Statistical analysis was performed through Graph-pad Prism V7 software where the percentage of every expressing cell was generated, and p-value was calculated using two-way ANOVA with Tukey's correction. Luminex data were analyzed by two-way ANOVA with Tukey's correction using Graph-Pad Prism. Results and discussion {#S0004} ====================== The pathogenicity of different species of mycobacteria can be attributed, in part, to components of the bacterial cell wall, genome and metabolome that differ between species \[[26](#CIT0026)\]. It is challenging to characterize host response-related factors, especially those that can control, or alter, pathogenicity of the mycobacteria. Recent publications used Ampliseq and RNAseq to compare the host response from alveolar macrophages and hMDMs against H37Rv, and found key genes (*TREM1* and *IL10*) involved in pathogenesis of TB \[[11](#CIT0011) [27](#CIT0027),\]. The biological factors that contribute to pathogenicity in mycobacteria remain poorly understood. In the present study, we examined differential gene expression during the infection of hMDMs with pathogenic (*M. tb* R179; drug resistant Beijing genotype strain R220) and nonpathogenic (*M. smegmatis*) species of mycobacteria along with *M. bovis* BCG (BCG Tokyo 172 strain) \[[15](#CIT0015) [28](#CIT0028) [29](#CIT0029),,\]. Ampliseq analysis of RNA derived from hMDMs before and after infection across three mycobacterial species identified overlapped 274 DEGs at 12-h post infection. Out of which, 229 are upregulated and 45 are downregulated (Accession no. GSE 122,619). Out of 274 DEGs, we selected 19 DEGS of potentially higher importance after applying stringent filtering parameters using edgeR statistical method. A similar viability was observed at 12 and 24 h for hMDMs infected with all three species (Figure S3). We examined the process of intracellular killing at 12-h post *M. smegmatis* infection \[[17](#CIT0017) [18](#CIT0018),\]. Importantly, we used detergent-free mycobacterial cultures for the *in vitro* infection experiments, since detergents (Tween) are used to prevent cellular clumping of *M. tb*, but are known to alter bacterial uptake by macrophages and alter the subsequent innate immune response \[[30](#CIT0030) [31](#CIT0031),\]. In the present study, the bacterial uptake by macrophages for *M. smegmatis, M. bovis* BCG and *R179* were confirmed to be similar ([Figure 2(a](#F0002))) and host-cell viability remained high (Figure S2). We confirmed intracellular killing of all three species using intracellular CFU counts at 12- and 24-h post infection. We observed a dramatic decrease in CFUs of *M. smegmatis* at 24 h compared to 12 h (p \< 0.001), which was not observed for *M. bovis* BCG (p = 0.060) and *M. tb* R179 (p = 0.193) ([Figure 2(b](#F0002))). Also, CFUs of hMDMs infected with *M. bovis* BCG and *M. tb* R179 at 48-, 72- and 96-h post infection were found to significantly higher compared to 12-h post-infection (Figure S1). CFUs of hMDMs infected with *M. smegmatis* could not be determined beyond 24-h post-infection, as it is known to be killed within 48 h \[[17](#CIT0017) [18](#CIT0018),\]. This indicates that host can control *M. smegmatis* infection, although the reason behind this is understudied. We therefore present the host transcriptome at 12-h post-infection in response to pathogenic and nonpathogenic mycobacteria in an attempt to unravel the genes that are involved during this crucial time. In the present study, we have performed Ampliseq at only 12-h post-infection indicating higher expressions of DEGs in hMDMs infected with *M. smegmatis*, it is however highly likely that these genes continue to overexpress at 24-h post-infection to facilitate killing of mycobacteria. Results of amplicon-based RNA sequencing show the DEGs from hMDMs infected with three mycobacterial species compared to uninfected hMDMs ([Figure 2(c](#F0002))). Similar to a previous study \[[32](#CIT0032)\], we found hMDMs infected with *M. smegmatis* had higher expression of DEGs when compared to *M. bovis* BCG and R179.10.1080/21505594.2020.1726561-F0002Figure 2.Uptake, CFUs and global transcriptome profile of hMDMs infected with mycobacteria. (a) Percent uptake of *M. smegmatis, M. bovis* BCG and *M. tb* R179 by hMDMs at 4 h, the percent uptake was calculated by dividing the number of bacteria taken up per milliliter by number of macrophages in each well., (b) CFUs of mycobacteria with multiplicity of infection (MOI) of 1 at 12- and 24-h post infection, and (c) heatmap of differentially expressed transcripts analyzed by AmpliSeq where hMDMs infected with *M. smegmatis, M. bovis* BCG or *M. tb* R179 were compared to uninfected hMDMs. The level of expression of each gene in each sample in comparison to the level of expression of uninfected sample is depicted with a color scale with red as maximum and blue as the minimum expression. *M. smegmatis* having the maximum red indicates stronger host response as compared to other two strains. Dendrogram indicates sample clustering.Abbreviations: BCG = Bacillus Calmette--Guerin, CFUs = colony-forming units, hMDMs = human monocyte derived macrophages, *M. tb = Mycobacterium tuberculosis*. Ampliseq found 19 DEGs across the three mycobacterial species based on lowest false discovery rate (FDR\<0.001). Out of these, 17 DEGs were upregulated and two downregulated upon *M. smegmatis* infection ([Table 2](#T0002)). The heat map noticeably delineates 17 up-regulated and 2 down-regulated genes comprising largely interleukin (IL-1β, IL-6, IL-8, IL-12β and IL-23A) and interferon (IFN-γ, *IFI44, IFI44L, IFIT1, IFIT2, IFIT3, MX2* and *ISG15*) families ([Figure 3](#F0003)).10.1080/21505594.2020.1726561-T0001Table 1.Demographic characteristics of study participants.VariablesStudy participants (n = 12)Age (Years)27Median (IQR)(26--28.5)**Gender (%)** Female6 (50%)Male6 (50%)**BMI (kg/m^2^)**\ (Mean ± SD)\ 23.59 ± 2.32**Ethnicity (%)** Black6 (50%)White6 (50%)[^2] 10.1080/21505594.2020.1726561-F0003Figure 3.Differential expression of host gene transcripts in infected hMDMs. Heatmap of 19 differentially expressed transcripts with lowest false-discovery-rate analyzed by Ampliseq, hMDMs infected with *M. smegmatis, M. bovis* BCG or *M. tb* R179 were compared to uninfected hMDMs. The level of expression of each gene in each sample in comparison to the level of expression of uninfected sample is depicted with a color scale with red as minimum and white as the maximum expression. Dendrogram indicates sample clustering.Abbreviations: BCG = Bacillus Calmette--Guerin, hMDMs = human monocyte derived macrophages, *M. tb = Mycobacterium tuberculosis*10.1080/21505594.2020.1726561-T0002Table 2.Differentially expressed genes selected from AmpliSeq analysis of hMDMs 12-h post infection with pathogenic (*M. bovis* BCG, *M. tb* R179) and nonpathogenic (*M. smegmatis*) mycobacteria. *M. smegmatisM. bovis* BCG*M. tb* R179Gene nameFold changep valueFDRFold changep valueFDRFold changep valueFDR*IFIT1*6.33.36E-192.02E-151.61.16E-184.64E-151.86.09E-181.83E-14*IFIT2*42.27E-111.01E-081.62.5E-111.07E-081.83.76E-111.56E-08*IFIT3*6.92.53E-094.75E-072.82.95E-095.46E-072.53.87E-076.99E-07*MX1*4.66.05E-112.27E-081.66.51E-112.37E-081.76.7E-112.39E-08*MX2*3.41.85E-173.18E-141.91.45E-162.06E-131.81.54E-162.06E-12*IFI44*42.19E-083.29E-061.62.42E-083.59E-061.62.58E-083.78E-06*IFI44L*97.49E-112.58E-082.31.1E-103.69E-081.71.49E-104.7E-08*ISG15*3.57.23E-101.64E-071.78.71E-101.94E-071.91.08E-092.36E-07*IL12B*178.11.11E-138.38E-1157.31.55E-131.1E-1029.72.58E-131.73E-10*IL23A*9.16.86E-101.62E-073.27.03E-101.63E-071.75.92E-101.43E-07*IL6*12.45.64E-050.000296.55.89E-050.000234.66.07E-050.00023*IL8*8.72.45E-060.000217.22.46E-060.000215.92.83E-060.000238*RSAD2*7.95.62E-075.64E-053.16.75E-076.71E-052.66.8E-086.71E-05*TRIB3*−7.53.12E-070.00031−74.4E-070.00041−1.95.23E-070.00051*MT1A*−321.42E-050.00053−411.42E-050.00041−1.81.52E-050.00053*IDO1*12.61.79E-050.000156.61.8E-050.0001151.81E-050.00014*EIF2AK2*2.34.11E-344.94E-301.68.47E-181.91E-141.69.51E-181.91E-14*IFN-γ*14.47.08E-076.93E-053.97.29E-077.08E-053.47.53E-077.25E-05[^3] There are some mechanisms through which the macrophage host immune response controls the growth of *M. smegmatis*. A previous study showed that phagocytosis of *M. smegmatis* induces reactive oxygen species (ROS), resulting in the production of proinflammatory cytokines. ROS induced during phagocytosis is associated with the *M. smegmatis*-mediated endoplasmic reticulum (ER) stress response in macrophages \[[33](#CIT0033)\]. Another study showed that *M. smegmatis* harboring unique multigenic PE_PGRS41 protein boosted the survival within macrophage accompanied with enhanced cytotoxic cell death through inhibiting autophagy and cell apoptosis \[[34](#CIT0034)\]. In the present study, biological network analysis found primary up-regulated pathways of interferon and interleukins family involved in the killing of *M. smegmatis* (Figure S4). The increase or decrease in the downstream functional outcomes are caused by the activated or inhibited upstream regulators, hence termed as regulator effect network. For each regulator effect network, a consistency score was calculated, where higher scores are given to networks with consistent directions \[[35](#CIT0035)\]. In the present study, top regulator effect networks of the 19 DEGs demonstrated an important role in cell activation (Figure S4), DNA binding and viral replication. With a higher consistency score predicting a unidirectional consistent gene finding directed us toward DNA activation and cellular binding ([Tables 3](#T0003)--[5](#T0005)). Infection with *M. tb* is known to affect DNA binding activity through IFN-γ activation \[[36](#CIT0036)\]. It is noteworthy that the amplicon-based RNA-sequencing results were validated through qRT-PCR hence confirming the similar trend of up-regulatory and down-regulated genes. The cytokines profile of IFN-γ, IL-12p40, IL-12p70 and IL-23 as assessed through multiplex ELISA was found to be significantly higher (p \< 0.001) in *M. smegmatis* infection as compared to *M. bovis* BCG or R179. The levels of IL-1β and IL-6 was found to be similar across all three mycobacterial species ([Figure 4(a--f](#F0004))). mRNA expression level of these 19 DEGs measured by qRT-PCR confirms the Ampliseq results ([Figure 5(a](#F0005),[b](#F0005))). Upon *M. smegmatis* infection as compared to *M. bovis* BCG and R179 multiplex ELISA of eight pro-inflammatory cytokines (of 19 DEGs) showed a similar trend as observed in amplicon-based RNA sequencing and qRT-PCR results (Table S1). This included IDO-1, IFN-γ and six interleukins \[IL-1β, IL-6, IL-8, IL-12p40, IL-12p70 and IL-23\]. Multiplex ELISA ([Figure 4(a--f](#F0004))) results found four key cytokines, i.e. IL-12p40, IL-12p70, IL-23 and IFN-γ with higher expression in hMDMs infected with *M. smegmatis* (p \< 0.001) as compared to *M. bovis* BCG and *M. tb* R179. 10.1080/21505594.2020.1726561-T0004Table 4.Top upstream regulators activated in hMDMs after infection with mycobacteria with respect to 19 potential DEGs.Upstream regulatorp-Value of overlapPredicted activationIFNL14.33E-26ActivatedTLR35.86E-25ActivatedIFN-β1.56E-23ActivatedTLR94.68E-23ActivatedTLR74.81E-23Activated[^4] 10.1080/21505594.2020.1726561-F0004Figure 4.Cytokines levels after infection of hMDMs with *M. smegmatis, M. bovis* BCG or *M. tb* R179 compared to uninfected hMDMs measured through multiplex ELISA. (a) INF-γ, (b) IL-1β, (c) IL-12p40, (d) IL-12p70, (e) IL-6, and (f) IL-23. Detailed comparison of multiplex ELISA results are in Table S1.Abbreviations: BCG = Bacillus Calmette--Guerin, hMDMs = human monocyte derived macrophages, IDO-1 = indoleamine 2,3-dioxygenase-1, IFN = interferon, IL = interleukin, *M. tb = Mycobacterium tuberculosis*.10.1080/21505594.2020.1726561-F0005Figure 5.Expression analysis using qRT-PCR of twelve key transcriptomes (a) and seven key cytokines (b) in hMDMs of 12 healthy participants infected with *M. smegmatis, M. bovis* BCG or *M. tb* R179 as compared to uninfected hMDMs. (\*) depicts significant (p \< 0.05) expression.Abbreviations: BCG = Bacillus Calmette--Guerin, hMDMs = human monocyte-derived macrophages, *IFIT1 *= interferon-induced protein with tetracopeptide, *MX *= interferon-induced GTP binding protein, *IFI *= interferon-induced protein, *ISG *= interferon-stimulated gene, *RSAD *= radical s-adenosyl methionine domain-containing protein, *EIF2AK2 *= eukaryotic translation initiation factor 2 alpha kinase 2, *TRIB3 *= trible homolog, *MTA *= metastasis-associated protein.10.1080/21505594.2020.1726561-T0003Table 3.Top canonical pathways activated in hMDMs after infection with mycobacteria with respect to 19 potential DEGs.RegulatorsDisease and functionsConsistency scoreAPP, CHUK, CSF2, EIF2AK2, IFNAR, IL-10, IL1β, MYD88, RELActivation of cell, binding of DNA119.05IFN, IFNA/IFNA13, IFNA4, JAK1/2Replication of viral replicon8.05IRF3Immune response of cells4.899IRF3Infection of Mammalia4.899[^5]10.1080/21505594.2020.1726561-T0005Table 5.Top regulator effect networks in hMDMs after infection with mycobacteria with respect to 19 potential DEGs.Pathwayp-ValueOverlap (%)Interferon signaling9.51E-0811.1%Cytokines mediated communication between immune cells8.03E-087.4%Pattern Recognition Receptors in recognition of bacteria and viruses3.43E-072.9%Hypercytokinemia/hyperchemokinemia in the Pathogenesis4.87E-067%Hematopoiesis from pluripotent stem cells6.08E-056.2%[^6] IFN-γ is primarily responsible for activation of macrophages and bactericidal activity \[[37](#CIT0037)\]. It plays a key role in apoptotic induction through a nitric-oxide dependent pathway in macrophages infected with mycobacteria \[[38](#CIT0038) [39](#CIT0039),\]. We observed an increase in IL-12p40 and IL-12p70, which are the key members of IL-12 family and are primarily secreted by antigen-presenting cells and macrophages \[[40](#CIT0040) [41](#CIT0041),\]. IL-12 is known to enhance the synthesis of IFN-γ during infection \[[42](#CIT0042)\]. Further, IL-12 and IL-23 have been demonstrated to confer protective cellular responses and promote host survival against *M. tb* \[[43](#CIT0043)\]. Table S1 provides a detailed comparison of multiplex ELISA results measured at 12-h post-infection. Importantly, IDO-1, IL-1β and IL-8 expression (at the transcript level) was found to be increased in hMDMs infected with *M. smegmatis* compared to the other two species in amplicon-based RNA sequencing and qRT-PCR. We found no significant difference between protein levels of IDO-1, IL-1β or IL-8 across the three mycobacterial species compared to uninfected hMDMs (Figure S2). Previous studies also demonstrated that *M. tb* up-regulates host IL-6 production to inhibit type I interferon \[[44](#CIT0044)\]. Additionally, IL-8 has been shown to play an instrumental role in cell recruitment since IL-8 is the major chemokine responsible for recruiting neutrophils \[[45](#CIT0045)\]. IDO-1 has been shown to be increased in a murine model of TB in previous studies \[[46](#CIT0046)\]. Interestingly, in our exploration using amplicon-based RNA sequencing (and confirmed by qRT-PCR), we found metastasis-associated protein-1A (*MT1A*) and trible homolog (*TRIB3*) exhibiting significantly different expression levels in hMDMs infected with *M. smegmatis* compared to *M. bovis* BCG and *M. tb* R179 ([Figures 3](#F0003) and [5](#F0005)). *TRIB3* is a protein kinase that negatively regulate NF-kB and sensitize cells to TNF- and TRAIL-induced apoptosis \[[47](#CIT0047)\]. Also, *TRIB 3* can negatively regulate the AKT 1 (serine/threonine-protein kinase B) altering cell survival \[[48](#CIT0048)\]. Another DEG, *MT1A* gene is *a* member of the metallothionein family and act as anti-oxidants, protect against free radicals of hydroxyl, and help in detoxification of heavy metals \[[49](#CIT0049) [50](#CIT0050),\]. The third DEG, *EIF2AK2* is a dsRNA-dependent serine/threonine-protein kinase induced by IFN, which plays an important role in the innate immune response against viral infection and is found to be involved in the regulation of apoptosis, signal transduction, cell proliferation and differentiation. *EIF2AK2* inhibits viral replication by targeting alpha subunit of eukaryotic initiation factor 2 (EIF2S1) via phosphorylation, which impairs the recycling of EIF2S1 leading to inhibition of translation which subsequently results in cessation of cellular and viral protein synthesis \[[51](#CIT0051)\]. Notably, the downregulated DEGs *TRIB-3* and *MT1A* were found to be similarly expressed by macrophages infected with *M. smegmatis* and *M. bovis* species, which were significantly lower compared to macrophages infected with pathogenic *M. tb* R179. Previous studies have observed an increased level of *TRIB3* in patients with colorectal cancer and its expression suggests poor overall survival \[[52](#CIT0052)\]. Also, its expression is found to have poor prognosis in patients with non-small cell lung cancer and breast cancer \[[53](#CIT0053) [54](#CIT0054),\]. The *MT1A* gene was found to be linked to oxidative stress, carcinogenesis, and obesity \[[55](#CIT0055)--[57](#CIT0057)\]. Genes *TRIB3* and *MT1A* are understudied in TB and are downregulated in *M. smegmatis* as compared to other two species, knocking-down these genes in pathogenic *M. tb* infected cells could yield lower CFUs indicating a potential immune-therapeutic candidate. *EIF2AK2* expression was found to be increased only in *M. smegmatis* infection when compared to the other two species. Previous gene profiling meta-analysis found *EIF2AK2* as a shared gene between TB and rheumatoid arthritis \[[58](#CIT0058)\]. *EIF2AK2* has previously been studied in viral infection and found to block translation of viral mRNA and promote cellular apoptosis \[[59](#CIT0059)\]. This upregulated gene is not well studied in TB and certainly warrants further investigations. The limitations of the present study include: 1) we selected only three mycobacterial species (pathogenic and nonpathogenic) to study the host response. The future studies can increase number and types of species in order to study a broader response of the host toward the mycobacteria. 2) We studied only one time point for amplicon-based RNA-sequencing analysis. 3) We have not performed any experiments to determine the role of any of the 19 DEGs (including *EIF2AK2, MT1A*, and *TRIB3*) in intracellular mycobacterial killing/survival. We have planned functional gene knock-down (using siRNA) and gene knock-up (using vector-derived overexpression) experiments for follow-up study. In conclusion, we found 19 differentially expressed genes against mycobacteria, in hMDMs infected with *M. smegmatis* as compared to *M. bovis* BCG and *M. tb* R179. Out of which three are unique (*EIF2AK2, MT1A*, and *TRIB3*) DEGs. These unique targets should be studied for their functional properties (using knock-down/knock-up approach) to access their role in the intracellular killing of pathogenic mycobacteria. Authors Contributions {#S0005} ===================== AM and BB designed the experiments. AM, HM, NNC, RDP performed the experiments. AM, HM, CJVH and GT analysed the data. AM, HM, GL, GT and BB wrote and edited the manuscript. Disclosure statement {#S0006} ==================== No potential conflict of interest was reported by the authors. Data Availability Statement {#S0007} =========================== AmpliSeq^TM^ data have been deposited in the NCBI Gene Expression Omnibus (GEO) database with experiment series accession number \[GSE122619\]. <https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122619> Supplementary material {#S0008} ====================== Supplemental data for this article can be accessed [here](https://doi.org/10.1080/21505594.2020.1726561). ###### Supplemental Material [^1]: Joint first authors [^2]: **Abbreviations**: IQR = interquartile range, SD = standard deviation. [^3]: Abbreviations: BCG, Bacillus Calmette--Guerin; EIF2AK2, eukaryotic translation initiation factor 2 alpha kinase 2; FDR, false discovery rate; IDO, indoleamine 2,3-dioxygenase; hMDMs, human monocyte-derived macrophages; IFI, interferon-induced protein; IFIT, interferon-induced protein with tetratricopeptide; IFN, interferon gamma; IL, interleukin; ISG, interferon-stimulated gene; MTA, metastasis-associated protein; MX, interferon-induced GTP binding protein; RSAD, radical S-adenosyl methionine domain-containing protein 2; TRIB, trible homolog; UBC, polyubiquitin-C. [Figure 3](#F0003) is the pictorial heat-map of these results. [^4]: Abbreviations: hMDMs, human monocyte derived macrophages; DEGs, differentially expressed genes; IFNL, interferon ligand; TLR, toll like receptor. The data were analyzed through the use of IPA (QIAGEN Inc., <https://www.qiagenbioinformatics.com/products/ingenuitypathway-analysis>). [^5]: Abbreviations: APP, amyloid precursor protein; CHUK, helix-loop-helix ubiquitous kinase; CSF2, colony-stimulating factor 2; DEGs, differentially expressed genes; EF2AK2, eukaryotic translation initiation factor 2-alpha kinase 2; hMDMs, human monocyte derived macrophages; IFNAR, type I interferon (IFN) receptor; IL-10, interleukin-10; IL-1β, interleukin-β; MYD88, myeloid differentiation primary response 88; REL, proto-oncogene c-rel; IFN, interferon; JAK, Janus kinases; IRF, Interferon regulatory factor 1. The data were analyzed through the use of IPA (QIAGEN Inc., <https://www.qiagenbioinformatics.com/products/ingenuitypathway-analysis>). [^6]: Abbreviations: hMDMs, human monocyte derived macrophages; DEGs, differentially expressed gene. The data were analyzed through the use of IPA (QIAGEN Inc., <https://www.qiagenbioinformatics.com/products/ingenuitypathway-analysis>).
New Super Mario Bros. Wii is also the first Nintendo game to feature a dynamic help system, which allows you to access a mode showing how a level can be completed if you are stuck. The best thing about this mode is that you are free to jump into the action you’re watching on screen at any time! So, instead of the game beating a level while you grab a snack, it shows you what moves to make and you can mimic what happens on the screen. A few of us here stated that was the case all along. I’m assuming there’s two actions upon using this feature: 1. Start where you left off yourself (as in unpause the game if Demo play is via pause screen) 2. Jump in where you stop the video I don’t mind it, though I still don’t think this game needs it unless it really is harder than the DS game. Guest wow implementing this would make the game too easy and boring. no thanks. the thing is that if people start liking this help thing, they might put this crap on mario galaxy2. people need to die and gameover on games to adapt and improve. It wouldn’t be easy and boring if you don’t use it. It’s optional. It’s the gamer’s own fault if they cannot enjoy it because they overuse the feature. They way Nintendo did it is a bit much but hey, hopefully the don’t pull punches with difficulty but I doubt it. Ereek This is true. When I was much younger playing certain NES Mario levels I simply got frustrated and had to turn the console off. The same can be said of Sonic and, later on, Rocket Knight. I think something like this might help the younger players get more out of their games. They love the games and want to continue, but they simply might be too frustrated. Joanna I had the same experiences. The frustration actually drove me away from games. I stopped playing for a good couple of years until I was 12 and discovered pokemon. I think these tutorials are a good idea. I’m with Kuronoa, I always assumed and believed it would be a tutorial without the game actually doing anything for you. I don’t understand the amount of backlash this gets. If you don’t like it, don’t use it. But let other more inexperienced players have the option of this additional help. malek86 Modern Nintendo games don’t really need this kind of walkthrough anyway. Also: “The best thing about this mode is that you are free to jump into the action you’re watching on screen at any time!” What if i jump in at the very end, so the level is basically complete and I don’t have to do anything else? Joanna I understood this as meaning you can stop the tutorial at any time (so you don’t have to view the whole thing) and jump back into the action (as in playing again). Of course I see what you are worried about, the way the sentence is worded can imply something else, but taking the interview as a whole, I think my interpretation makes more sense. malek86 “Worried” is not the right word here. I mean, it’s not like they are forcing me to use it. I’m just curios to see how exactly this will work. This is how I read it too. After watching the tutorial you can jump back into the game or perhaps watch a tutorial player (ghost?) on screen and play along with it, attempting to mimic the tutorial ghost moves. After writing this people seem to have been reading the quote in a different way, like you can jump in at the end of a level. I think this is a misread of NOE’s ad copy. It’s definitely not clear from the language that you can’t simply pick up from wherever Demo Play leaves off. Given that we can’t tell for sure, I’m inclined to believe that Miyamoto knew what he was talking about. Video game stories from other sites on the web. These links leave Siliconera.
UNPUBLISHED UNITED STATES COURT OF APPEALS FOR THE FOURTH CIRCUIT No. 08-5079 UNITED STATES OF AMERICA, Plaintiff - Appellee, v. JASON YOUNG, Defendant - Appellant. Appeal from the United States District Court for the Eastern District of Virginia, at Alexandria. Liam O’Grady, District Judge. (1:08-cr-00240-LO-6) Submitted: January 7, 2010 Decided: March 22, 2010 No. 08-5111 UNITED STATES OF AMERICA, Plaintiff - Appellee, v. FARES ABULABAN, a/k/a Sameh, Defendant - Appellant. Appeal from the United States District Court for the Eastern District of Virginia, at Alexandria. Liam O’Grady, District Judge. (1:08-cr-00101-JCC-1; 1:08-cr-00240-LO-1) Argued: January 27, 2010 Decided: March 22, 2010 Before TRAXLER, Chief Judge, AGEE, Circuit Judge, and Catherine C. BLAKE, United States District Judge for the District of Maryland, sitting by designation. Affirmed by unpublished opinion. Judge Blake wrote the opinion, in which Chief Judge Traxler and Judge Agee joined. ARGUED: Marvin David Miller, Alexandria, Virginia, for Appellant Fares Abulaban. David Brian Goodhand, OFFICE OF THE UNITED STATES ATTORNEY, Alexandria, Virginia, for Appellee. ON BRIEF: Kevin M. Schad, SCHAD & SCHAD, Lebanon, Ohio; Heather Golias, LAW OFFICE OF MARVIN D. MILLER, Alexandria, Virginia, for Appellants. Dana Boente, United States Attorney, Lawrence J. Leiser, Assistant United States Attorney, OFFICE OF THE UNITED STATES ATTORNEY, Alexandria, Virginia, for Appellee. Unpublished opinions are not binding precedent in this circuit. 2 BLAKE, District Judge: Fares Abulaban and Jason Young pled guilty to drug conspiracy and related gun charges and were sentenced to total terms of imprisonment of 232 months for Abulaban and 270 months for Young. Both appeal aspects of their sentencing; Abulaban also appeals the denial of his motion to suppress a firearm seized during a warrantless search of the automobile in which he drove to the site of the supposed cocaine transaction. In fact it was a “reverse sting” operation. For the reasons that follow, we affirm the rulings of the district court. I. A. In February 2008, agents of the Immigration and Customs Enforcement (“ICE”) Division of the Department of Homeland Security planned a “reverse sting” operation in which ICE undercover agent Tony Rodriguez played the role of a drug dealer with cocaine connections in Columbia. Defendant Abulaban agreed to find purchasers for 20 kilograms of cocaine which Agent Rodriguez was to have available for sale on February 15, 2008 in Morgantown, West Virginia. Defendant Young was to be one of the buyers. Several meetings took place among Abulaban, Rodriguez, and other co-conspirators or undercover agents prior to February 15, 3 2008. On February 7, 2008, Abulaban met with Rodriguez and others to discuss arrangements for buyers to purchase the 20 kilograms of cocaine. It was agreed that Abulaban would receive some fee or percentage of the purchase price for his work, and there was discussion about using vehicles, including his, to pick up money or drugs. Abulaban left that meeting in a silver BMW he had apparently recently purchased (“the BMW”). On February 14, 2008, Abulaban met with Agent Rodriguez and others again, driving them in his BMW to Club Envy, the site of the next day’s planned transaction, where he gave the agents a tour of the Club including its entrances and exits before driving the agents back to the lot where their car was parked. On February 15, 2008, Abulaban initially picked up the agents in a different car to drive around and discuss the deal, including Abulaban’s intention to take two of the kilos himself to sell. In the course of the discussion, Abulaban asked Agent Rodriguez if he had his gun with him or had a gun. After parking in front of the Morgantown Hotel, Abulaban entered the hotel and later exited carrying a paper bag, which he handed to Agent Rodriguez. The bag contained approximately $40,000 in banded cash. Abulaban then drove the agents, with the money, to Club Envy in his silver BMW. Other conspirators arrived, also with money, and eventually another undercover agent brought the purported 20 kilograms of cocaine to the Club. Once the “drugs” 4 were placed in view, the conspirators were arrested. Abulaban and defendant Jason Young, one of the buyers, were among those arrested. While Abulaban did not have a gun on his person, weapons were recovered from other persons arrested at the Club. Following the arrests, agents searched Abulaban’s BMW and found a loaded .380 caliber semi-automatic handgun in the driver’s side map compartment. B. On March 13, 2008, a federal grand jury in Alexandria, Virginia, returned an indictment (08-CR-101) charging Abulaban, Young, and others with conspiracy to distribute and possess with intent to distribute both cocaine and ecstasy in violation of 21 U.S.C. §§ 841(a)(1) and 846. A single-count superseding indictment returned June 19, 2008, narrowed the scope of the conspiracy and did not name Young. A separate indictment returned June 12, 2008 (08-CR-240), charged Abulaban, Young, and others with conspiracy to possess with intent to distribute five kilograms or more of cocaine, in violation of 21 U.S.C. §§ 841(a)(1), 846, and 860 (Count One); charged Abulaban with possessing a firearm (the .380 caliber semi-automatic found in his BMW) on February 15, 2008 in furtherance of a drug trafficking offense, in violation of 18 U.S.C. § 924(c) (Count Two); and charged Young with using and carrying a firearm (a .38 caliber Taurus revolver) on February 15, 2008 during and in 5 relation to a drug trafficking offense, also in violation of 18 U.S.C. § 924(c) (Count Three). Prior to trial Abulaban moved to suppress the handgun seized from his BMW, claiming that the warrantless search violated the Fourth Amendment. After an evidentiary hearing, the district court found the search lawful, concluding that “the officers had probable cause to search the BMW, as it was an instrumentality of the drug conspiracy and thereby falls within the vehicle exception to the warrant requirement.” J.A. 300. Secondarily, the court concluded that the officers had probable cause to believe the BMW was subject to forfeiture and that it could be seized without a warrant. Accordingly, the motion to suppress was denied. 1 On July 12, 2008, Abulaban pled guilty to Counts One and Two of the indictment in 08-CR-240 arising from the February 15, 2008 transaction (conspiracy to possess with intent to distribute cocaine and possession of a firearm in furtherance of a drug-trafficking offense); Young pled guilty to Counts One and Three of the same indictment (the cocaine conspiracy and using and carrying a firearm). Neither had a written plea agreement, 1 This ruling was made by Judge James C. Cacheris in connection with the 08-CR-101 indictment. The § 924(c) charge involving the handgun later became part of the 08-CR-240 indictment, assigned to Judge Liam O’Grady. Judge O’Grady adopted Judge Cacheris’s ruling. J.A. 353. 6 although Abulaban and the government agreed he had reserved the right to appeal the denial of his suppression motion. Abulaban also pled guilty, with a written agreement, to Count One of the superseding indictment in 08-CR-101, which charged a conspiracy to possess with intent to distribute ecstasy based on a meeting with co-conspirator Mohammed Alazzam and an undercover agent in March 2007 to plan the acquisition and sale to the agent of 2500 ecstasy pills at a price of $10 per tablet. Abulaban was to be paid as a broker for this sale, but it was never carried out. On October 10, 2008, the district court sentenced Young to 210 months’ incarceration on Count One and 60 months consecutive on Count Three. On October 30, 2008, the court sentenced Abulaban to 172 months’ incarceration on Count One of both 08-CR-101 and 08-CR-240, to run concurrently, and 60 months consecutive on Count Two of 08-CR-240. This appeal followed. 2 II. A. We first consider whether the district court erred in denying Abulaban’s motion to suppress the gun found in his BMW. 2 Both Abulaban and Young filed notices of appeal and briefed their respective issues. Their appeals were consolidated. Prior to oral argument, however, because of a change in counsel for Young, the appeals were deconsolidated. Young’s claims will be resolved on the briefs. 7 We review the court’s findings of fact for clear error and its conclusions of law de novo. United States v. Kelly, 592 F.3d 586, 589 (4th Cir. 2010). Abulaban argues that for the automobile exception to apply the vehicle must be “readily mobile” and there must be “probable cause to believe it contains contraband,” citing Maryland v. Dyson, 527 U.S. 465, 467 (1999). This is of course consistent with precedent. To the extent he suggests, however, that the car was no longer “mobile” because the agents had seized the keys and arrested Abulaban, and therefore the automobile exception no longer applied, this suggestion has been rejected, for reasons thoroughly and recently explained in Kelly, 592 F.3d at 591. The inherent mobility of the car, combined with the lesser expectation of privacy in an automobile as compared to a home or office, justify application of the exception even if the police have control over the automobile at the time of the warrantless search. Id. at 590-91; see also United States v. Brookins, 345 F.3d 231, 237-38 (4th Cir. 2003). Abulaban also argues that the agents lacked probable cause to believe the BMW contained contraband, relying on testimony from agents that they were not aware of any contraband in the BMW after the bag of money was removed, and that they had not seen Abulaban with a pistol. There was ample evidence to conclude, however, that Abulaban planned to receive a fee from 8 the transaction and to take a portion of the drugs; it is simple logic to find, as the district court did, that Abulaban intended to use the BMW to transport his share of the money and the cocaine away from Club Envy. Nor is there any dispute that he had used the car to transport drug purchase money to the Club. As the district court concluded, this case falls well within the parameters set forth in United States v. Dickey-Bey, 393 F.3d 449, 457 (4th Cir. 2004), permitting the search of the car as an instrumentality of the crime. In addition, as the government argues, examining the facts from the standpoint of an objectively reasonable police officer, there was probable cause to believe Abulaban was concealing a gun in the BMW and perhaps other evidence of the conspiracy. His question about whether the agent had a gun, combined with the value of the purported drugs and the fact that other co-conspirators had weapons, supported a fair probability that Abulaban, who had no weapon on his person, had concealed a weapon in his BMW. See Brookins, 345 F.3d at 235 (internal citation omitted). Further, the BMW admittedly had been used to transport both participants and money before the transaction at the Club. Thus, to the extent the question is distinct from whether the BMW was an “instrumentality” of the drug conspiracy, we conclude the search was also justified by probable cause to believe the BMW 9 contained evidence of the crime or contraband, including a weapon. 3 B. We now turn to Abulaban’s challenge to his within Guidelines sentence. As recently explained, now that the Guidelines are effectively advisory, district courts must first correctly calculate the defendant’s Guidelines range and then “allow the parties to argue for what they believe to be an appropriate sentence and consider those arguments in light of the factors set forth in 18 U.S.C.A. § 3553(a).” United States v. Engle, 592 F.3d 495, 500 (4th Cir. 2010). The district court must explain its reasons for the sentence it imposes; the appellate court then reviews that sentence for reasonableness, including both a procedural and a substantive component. First, the appellate court must ensure that the district court committed no significant procedural error, such as failing to calculate (or improperly calculating) the Guidelines range, treating the Guidelines as mandatory, failing to consider the § 3553(a) factors, selecting a sentence based on clearly erroneous facts, or failing to adequately explain the chosen sentence – including an explanation for any deviation from the Guidelines range. 3 In light of this conclusion, we need not reach the applicability of the forfeiture statute as a basis to seize the BMW. 10 Id., quoting Gall v. United States, 552 U.S. 38, 51 (2007). The second step considers the substantive reasonableness of the sentence, taking into account the totality of the circumstances and applying an abuse of discretion standard. Id. The appellate court, though not the district court, may accord a presumption of reasonableness to a sentence that falls within a properly calculated Guidelines range. United States v. Smith, 566 F.3d 410, 414 (4th Cir. 2009); United States v. Brewer, 520 F.3d 367, 372 (4th Cir. 2008). Abulaban essentially raises a procedural challenge, alleging the Guidelines were not correctly calculated because, in his view, the court sentenced him on the basis of unrelated conspiracies in North and South Carolina and on the basis of an additional 1000-pill ecstasy sale in New York. He characterizes this (1) as a violation of Fed. R. Crim. P. 32(i)(3)(B) based on his objection to the fact that the presentence report (“PSR”) included the names of other alleged coconspirators and (2) as a Fifth and Sixth Amendment violation on the theory that he was sentenced for offenses to which he did not plead guilty and in which he was not involved. 4 4 Abulaban’s argument that he had not waived his right to appeal the sentence was mooted by the government’s response that it did not seek to enforce any such waiver. 11 Regardless of the underlying theory, a fair reading of the sentencing transcript makes it clear that Abulaban was sentenced only on the two drug conspiracies to which he pled guilty, and on the related firearms charge. The conspiracy in 08-CR-240 involved 20 kilograms; Abulaban brokered the entire deal. The ecstasy conspiracy in 08-CR-101 involved a planned distribution of 2,500 tablets in March or April 2007 in Virginia. Abulaban admitted to both these conspiracies on July 15, 2008 before Judge O’Grady. J.A. 363-65, 368-71, 391-93. On October 30,2008, he was sentenced by Judge O’Grady, who added a 4-level role enhancement to the PSR’s 34 levels, which was based on 20 kilograms of cocaine and 1,015 tablets of ecstasy. J.A. 496. 5 The judge declined to find obstruction of justice, deducted three levels for acceptance of responsibility, and noted an advisory Guidelines range of 168 to 210 months at level 35 Criminal History Category I. J.A. 486-87, 496. In listening to arguments about the appropriate sentence, Judge O’Grady said “I am going to sentence him based on what he did in two different drug conspiracies and the possession of a firearm.” J.A. 503. He later referred to Abulaban putting together the 20-kilogram deal and being the leader of the drug organization for the deal 5 If anything, therefore, the quantity of ecstasy was understated. 12 at Club Envy. J.A. 515. While he misspoke by referring to methamphetamine as one of the “multiple” conspiracies, he quickly accepted counsel’s correction. J.A. 516. Considering the seriousness of the offense, the need for deterrence and punishment, as well as Abulaban’s age, medical condition, and limited criminal record, he imposed a sentence close to the bottom of the Guidelines range. To suggest that Judge O’Grady relied on criminal conduct for which Abulaban’s guilt was not firmly established borders on the frivolous. The sentence was reasonable and did not violate any provision of the Constitution. C. Defendant Young also challenges his sentence in several respects: first, the court’s attribution of the entire 20 kilograms to him for purposes of sentencing; second, the four- level enhancement for use of body armor; third, the alleged reliance of the court on evidence from a proceeding where Young was not present; and fourth, that the 270-month term of incarceration was substantively unreasonable. These will be addressed in turn. First, the record before the trial court amply supports a finding that the full 20 kilograms of cocaine not only were foreseeable to Young but also were within the scope of his particular agreement. Young knew that he was part of “a big, 20 13 kilogram, cocaine deal.” J.A. 576. As the PSR noted, there was evidence that when it appeared the purchasers would fall short, Young agreed to take his initial five kilos and quickly sell enough to return to Club Envy later that evening to buy two more kilos. J.A. 549, 574. 6 While the PSR attributed only seven kilograms to Young, the government contended that Young should be accountable for all 20 kilos. Reviewing the facts that showed Young’s knowledge of and participation in a specific 20- kilogram transaction, the trial court correctly concluded that the entire 20 kilograms was reasonably foreseeable to Young “within the scope of the criminal activity that he jointly undertook.” J.A. 466-67. See U.S.S.G. § 1B1.3(a)(1)(A) & (B) and app. Note 2. Second and third, the district judge correctly enhanced Young’s sentence for use of body armor based primarily on Young’s own admission to law enforcement agents that he had a gun and body armor that night, although he took off the body armor when he ran to the back of the Club. J.A. 460-61, 467. Reference to trial evidence as consistent with Young’s own statements did not undercut the independent basis for the 6 Young admitted he had been asked to take more than his five kilos, but denied agreeing to do so. J.A. 577. 14 court’s finding at sentencing nor did it violate Young’s due process rights. Finally, Young has not persuaded us that the sentence, at the low end of the advisory Guidelines range, was substantively unreasonable. The district judge emphasized the seriousness of the offense, as reflected by the quantity of cocaine and the possession of both a weapon and body armor, 7 but he also considered Young’s individual history, as noted by the court’s downward departure from Criminal History Category III to Category II when calculating the Guidelines. Considering the totality of the circumstances, we cannot say that the district judge abused his substantial discretion in sentencing Young to the low end of the Guidelines on the cocaine conspiracy, followed by the mandatory minimum consecutive 60 months on the firearms charge. III. Accordingly, for the reasons explained above, the suppression ruling and the Judgment and Commitment orders entered by the district court as to Fares Abulaban and Jason Young are AFFIRMED. 7 Possession of body armor also contributed to Young’s sentence being longer than other co-conspirators. 15
Synovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints which possess cavities, known as synovial joints. The condition is usually painful, particularly when the joint is moved. The joint usually swells due to synovial fluid collection. In principal, changes of the synovial membrane can be inflammatory or non-inflammatory. To the latter group belong some benign tumors, such as tenosynovial giant cell tumor, lipoma or synovial chondromatosis. Rare non-inflammatory changes are the group of storage diseases. Inflammatory synovial diseases can be differentiated into crystal-induced arthropathy, such as gout and pseudogout, granulomatous diseases, such as tuberculosis, sarcoidosis and foreign body reactions and into the large group of non-granulomatous synovitis. This last group is by far the most common and often causes difficulties in assigning the histopathological findings to a definite diagnosis. Hence, synovitis may occur in association with arthritis as well as lupus, gout, and other conditions. Synovitis is more pronounced in rheumatoid arthritis than in other forms of arthritis, and can thus serve as a distinguishing factor, although it is also present in many joints affected with osteoarthritis (OA). Visco-supplementation is the process of injecting a gel-like substance into the joint. The substance is thought of as an additive to the joint fluid, thus lubricating the cartilage, and improving joint flexibility. This method of treatment, however, requires ongoing injections, as benefits are only temporary, because the currently used substances are degradable within weeks to months. Substances used in visco-supplementation include hyaluronic acid, or HA (Legend®, Hylartin® and Synacid®, Synvisc, Euflexxa, Supartz etc) and poly-sulfated glycosaminoglycans (PSGAGS) such as Adequan®. Polyacrylamide hydrogel (PAAG) is known for its ability to support cellular growth in vitro and allow in-growth of host tissue cells in vivo. This has been documented in the soft subcutaneous tissues of mice, rats, rabbits, pigs and humans. The tissue integration begins immediately after PAAG injection as a sort of foreign body reaction to the PAAG. Host macrophages and foreign-body giant cells initially surround the PAAG and then invade it. In the process these cells are gradually transformed into fibroblasts and endothelial cells, which eventually form a thin vessel-bearing fibrous network inside the PAAG. However, the integration of PAAG in these tissues was not associated with any luminal surfaces and the PAAG contained macrophages and giant cells up until 14 months post injection. WO 02/16453 discloses the use of a polyacrylamide hydrogel (PAAG) for treating e.g. arthritis. where the treatment is considered to be based on a lubricating and cushioning effect of the hydrogel. WO 2012/123385 discloses use of PAAG in the treatment and/or prevention of joint swelling and/or bone oedema in a mammal suffering from arthritis. Neither WO 02/16453 nor WO 2012/123385 discloses prevention and/or treatment of synovitis in a mammal. Christensen and Daugaard (J Arthritis 5: 217; Sep. 16, 2016) provide a case report on the histological appearance of the synovial membrane after treatment of knee osteoarthritis with polyacrylamide gel injections. The common symptoms for all types of synotivis in mammals include varied levels of pain in mammals. Synovitis symptoms can be treated with anti-inflammatory drugs such as NSAIDs. Another possibility is injection of steroids directly into the affected joint. Specific treatment depends on the underlying cause of the synovitis. Common to the various types of existing treatment is that they all have their disadvantages, e.g. short term treatment, toxicity and side-effects. Hence, there is a need for an alternative or improved way to prevent and/or treat synovitis in a mammal. Also, there is a need for an alternative or improved way to prevent and/or treat synovitis pain in a mammal. Surprisingly, the present inventors have found that polyacrylamide hydrogel (PAAG) is useful in the prevention and/or treatment of synovitis. Without being bound by a particular theory, the analgesic effect on synovitis is considered caused by a stable, long-lasting sub-synovial layer of PAAG traversed with thin strands of connective tissue and changes to synovial cell composition or cytokine production. Accordingly, the present invention surprisingly demonstrated the formation of a novel synovial lining layer after integration of the PAAG into mammal joints that persisted for at least 24 months.
Kangarock {Ben 10 fan alien} By Ashlynnii Watch 13 Favourites 2 Comments 630 Views Another fan alien! I wonder why there hasn't been a kangaroo alien yet, hm... made a boxing kangaroo! Name: Kangarock (Kangaroo + rock) Species: Pugilisian (from "pugilist," the term for a professional boxer) Planet: Cusso Aringo (from "concussion," a type of head trauma from blunt force, and a combination of "arena" and "ring") Omnitix location: Forehead Abilities: Fast, close-combat specialist, powerful kicks and punches, powerful tail, "hyperspace" pouch, natural blades on elbows and ankles, natural "brass knuckles." Weaknesses: can only move through jumping (sneaking is hard), can have pouch taken if not careful, "glass cannon" Notes: - speaks with an Australian accent - Since he is male, his pouch is artifical; Gwen 10 Kangarock would have a natural pouch due to being female, negating the "pouch can be taken" weakness. - His ears and black marks are supposed to look like a face covering - The colors of his lower arms and his blades are based on the "golden gloves" award for experienced and professional boxers I hope you like it! IMAGE DETAILS Image size 3000x3000px 1.01 MB Show More Published : Apr 9, 2018
<?php /** * @link http://github.com/zendframework/zend-servicemanager for the canonical source repository * @copyright Copyright (c) 2005-2016 Zend Technologies USA Inc. (http://www.zend.com) * @license http://framework.zend.com/license/new-bsd New BSD License */ namespace ZendTest\ServiceManager; use PHPUnit\Framework\TestCase; use ProxyManager\Autoloader\AutoloaderInterface; use RecursiveDirectoryIterator; use RecursiveIteratorIterator; use RecursiveRegexIterator; use RegexIterator; use stdClass; use Zend\ServiceManager\Exception\ServiceNotCreatedException; use Zend\ServiceManager\Exception\ServiceNotFoundException; use Zend\ServiceManager\Factory\InvokableFactory; use Zend\ServiceManager\Proxy\LazyServiceFactory; use Zend\ServiceManager\ServiceManager; use ZendTest\ServiceManager\TestAsset\InvokableObject; /** * @covers \Zend\ServiceManager\ServiceManager */ class LazyServiceIntegrationTest extends TestCase { public $proxyDir; public function setUp() { $this->proxyDir = sys_get_temp_dir() . '/zend-servicemanager-proxy'; if (! is_dir($this->proxyDir)) { mkdir($this->proxyDir); } } public function tearDown() { if (! is_dir($this->proxyDir)) { return; } $this->removeDir($this->proxyDir); foreach ($this->getRegisteredProxyAutoloadFunctions() as $autoloader) { spl_autoload_unregister($autoloader); } } public function removeDir($directory) { $handle = opendir($directory); while (false !== ($item = readdir($handle))) { if ('.' === $item || '..' === $item) { continue; } $path = $directory . '/' . $item; if (is_dir($path)) { $this->removeDir($path); continue; } if (is_file($path)) { unlink($path); continue; } } closedir($handle); rmdir($directory); } public function listProxyFiles() { $rdi = new RecursiveDirectoryIterator($this->proxyDir); $rii = new RecursiveIteratorIterator($rdi); return new RegexIterator($rii, '/^.+\.php$/i', RecursiveRegexIterator::GET_MATCH); } public function assertProxyDirEmpty($message = '') { $message = $message ?: 'Expected empty proxy directory; found files'; // AssertEquals instead AssertEmpty because the first one prints the list of files. $this->assertEquals([], iterator_to_array($this->listProxyFiles()), $message); } public function assertProxyFileWritten($message = '') { $message = $message ?: 'Expected ProxyManager to write at least one class file; none found'; // AssertNotEquals instead AssertNotEmpty because the first one prints the list of files. $this->assertNotEquals([], iterator_to_array($this->listProxyFiles()), $message); } /** * @covers \Zend\ServiceManager\ServiceManager::createLazyServiceDelegatorFactory */ public function testCanUseLazyServiceFactoryFactoryToCreateLazyServiceFactoryToActAsDelegatorToCreateLazyService() { $config = [ 'lazy_services' => [ 'class_map' => [ InvokableObject::class => InvokableObject::class, ], 'proxies_namespace' => 'TestAssetProxy', 'proxies_target_dir' => $this->proxyDir, 'write_proxy_files' => true, ], 'factories' => [ InvokableObject::class => InvokableFactory::class, ], 'delegators' => [ InvokableObject::class => [LazyServiceFactory::class], ], ]; $this->assertProxyDirEmpty(); $container = new ServiceManager($config); $instance = $container->build(InvokableObject::class, ['foo' => 'bar']); $this->assertProxyFileWritten(); // Test we got a usable proxy $this->assertInstanceOf( InvokableObject::class, $instance, 'Service returned does not extend ' . InvokableObject::class ); $this->assertContains( 'TestAssetProxy', get_class($instance), 'Service returned does not contain expected namespace' ); // Test proxying works as expected $options = $instance->getOptions(); $this->assertInternalType( 'array', $options, 'Expected an array of options' ); $this->assertEquals(['foo' => 'bar'], $options, 'Options returned do not match configuration'); $proxyAutoloadFunctions = $this->getRegisteredProxyAutoloadFunctions(); $this->assertCount(1, $proxyAutoloadFunctions, 'Only 1 proxy autoloader should be registered'); } /** * @covers \Zend\ServiceManager\ServiceManager::createLazyServiceDelegatorFactory */ public function testMissingClassMapRaisesExceptionOnAttemptToRetrieveLazyService() { $config = [ 'lazy_services' => [ ], 'factories' => [ InvokableObject::class => InvokableFactory::class, ], 'delegators' => [ InvokableObject::class => [LazyServiceFactory::class], ], ]; $container = new ServiceManager($config); $this->expectException(ServiceNotCreatedException::class); $this->expectExceptionMessage('class_map'); $container->get(InvokableObject::class); } /** * @covers \Zend\ServiceManager\ServiceManager::createLazyServiceDelegatorFactory */ public function testWillNotGenerateProxyClassFilesByDefault() { $config = [ 'lazy_services' => [ 'class_map' => [ InvokableObject::class => InvokableObject::class, ], 'proxies_namespace' => 'TestAssetProxy', ], 'factories' => [ InvokableObject::class => InvokableFactory::class, ], 'delegators' => [ InvokableObject::class => [LazyServiceFactory::class], ], ]; $this->assertProxyDirEmpty(); $container = new ServiceManager($config); $instance = $container->build(InvokableObject::class, ['foo' => 'bar']); // This is the important test $this->assertProxyDirEmpty('Expected proxy directory to remain empty when write_proxy_files disabled'); // Test we got a usable proxy $this->assertInstanceOf( InvokableObject::class, $instance, 'Service returned does not extend ' . InvokableObject::class ); $this->assertContains( 'TestAssetProxy', get_class($instance), 'Service returned does not contain expected namespace' ); // Test proxying works as expected $options = $instance->getOptions(); $this->assertInternalType( 'array', $options, 'Expected an array of options' ); $this->assertEquals(['foo' => 'bar'], $options, 'Options returned do not match configuration'); $proxyAutoloadFunctions = $this->getRegisteredProxyAutoloadFunctions(); $this->assertCount(1, $proxyAutoloadFunctions, 'Only 1 proxy autoloader should be registered'); } public function testOnlyOneProxyAutoloaderItsRegisteredOnSubsequentCalls() { $config = [ 'lazy_services' => [ 'class_map' => [ InvokableObject::class => InvokableObject::class, stdClass::class => stdClass::class, ], 'proxies_namespace' => 'TestAssetProxy', ], 'factories' => [ InvokableObject::class => InvokableFactory::class, ], 'delegators' => [ InvokableObject::class => [LazyServiceFactory::class], stdClass::class => [LazyServiceFactory::class], ], ]; $container = new ServiceManager($config); $instance = $container->build(InvokableObject::class, ['foo' => 'bar']); $this->assertInstanceOf( InvokableObject::class, $instance, 'Service returned does not extend ' . InvokableObject::class ); $instance = $container->build(stdClass::class, ['foo' => 'bar']); $this->assertInstanceOf( stdClass::class, $instance, 'Service returned does not extend ' . stdClass::class ); $proxyAutoloadFunctions = $this->getRegisteredProxyAutoloadFunctions(); $this->assertCount(1, $proxyAutoloadFunctions, 'Only 1 proxy autoloader should be registered'); } public function testRaisesServiceNotFoundExceptionIfRequestedLazyServiceIsNotInClassMap() { $config = [ 'lazy_services' => [ 'class_map' => [ stdClass::class => stdClass::class, ], 'proxies_namespace' => 'TestAssetProxy', ], 'factories' => [ InvokableObject::class => InvokableFactory::class, ], 'delegators' => [ InvokableObject::class => [LazyServiceFactory::class], ], ]; $this->assertProxyDirEmpty(); $container = new ServiceManager($config); $this->expectException(ServiceNotFoundException::class); $this->expectExceptionMessage('not found in the provided services map'); $container->build(InvokableObject::class, ['foo' => 'bar']); } /** * @return AutoloaderInterface[] */ protected function getRegisteredProxyAutoloadFunctions() { $filter = function ($autoload) { return ($autoload instanceof AutoloaderInterface); }; return array_filter(spl_autoload_functions(), $filter); } }
A Review Of social app Menu A Review Of social app A company continuity approach (BCP) can be a document that includes the significant information a company requires to continue ... On the list of crucial factors of SMM is social media optimization (SMO). Like seo (SEO), SMO is a method for drawing new and unique website visitors to a web site. Parental ignorance of Kik will make the application especially desirable to young people. ''Youngsters are transferring from open Fb updates given that they know their moms and dads are viewing them, and they are shifting on to Kik,'' cyber security guide Martine Oglethorpe claimed. YouTube was the only real social media platform that shown an General beneficial influence on youngsters's mental health and fitness from the study. This kind of guidelines contain directives for when an worker need to discover himself for a agent of the corporation with a social networking website, as well as rules for what kinds of information may be shared. Well known Asian messaging applications like WeChat, KakaoTalk, and LINE have taken the direct to find revolutionary means to help keep users engaged. They’ve also built productive methods for monetizing their providers. Regardless of this simple fact, lots of Iranians have a peek here nonetheless use VPNs given that they are usually not versed in Web protection, but pretty nicely versed in bypassing censorship," she explained. Google+ (pronounced Google as well as) is Google's social networking job, intended to duplicate how men and women interact offline far more carefully than is the situation in other social networking providers. The challenge’s slogan is “Serious-lifestyle sharing rethought for the online.” The teens ended up proven "neutral" pictures demonstrating things such as foods and friends, and "dangerous" photographs depicting cigarettes and alcohol, pictured. The analyze located that teens were being additional prone to "like" popular pics, regardless of the type of graphic. "There are times in the event the Iranian government places them (VPNs) out in the marketplace to crack down on activists and people vocal in opposition to the establishment. To address this, the Modern society has also suggested the introduction of the pop-up warning to notify customers which they are on the internet for too very long. A cloud storage assistance is a business that maintains and manages its consumers' data and helps make that facts obtainable more than a ... Favored social networks to observe superstars according to teen and younger Grownup Snapchat buyers in The us as of February 2016U.S. youth Snapchat buyers subsequent famous people on social media 2016 Cloud internet hosting is the process of outsourcing a corporation's computing and storage resources into a company provider that provides ... All this information is likewise accessible though your smartphone is offline. The app is available in twenty five languages with simple choice to switch from a person language to another.
1. Introduction {#sec1-nutrients-12-02325} =============== Low-grade chronic inflammation is characterized by chronically (two to three-fold) increased concentrations of several cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, as well as other pro-inflammatory substances such as C-reactive protein (CRP) \[[@B1-nutrients-12-02325]\]. Fat accumulation has been suggested to be the main reason for increased levels of these pro-inflammatory markers \[[@B2-nutrients-12-02325],[@B3-nutrients-12-02325]\]. Many chronic diseases such as arthritis, type-2 diabetes or cancer, and pathological conditions such as insulin resistance or atherosclerosis have been found to be associated with low-grade systemic inflammation \[[@B2-nutrients-12-02325],[@B3-nutrients-12-02325],[@B4-nutrients-12-02325]\]. Physical inactivity has also been linked to low-grade systemic inflammation and subsequent increased risk for the development of chronic diseases \[[@B5-nutrients-12-02325]\]. On the other hand, regular exercise has been associated with an anti-inflammatory status, characterized by higher levels of anti-inflammatory markers such as IL-10 and adiponectin, and lower levels of pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β \[[@B2-nutrients-12-02325],[@B4-nutrients-12-02325]\]. It has been pointed out that exercise-induced anti-inflammatory effects could be produced by reduced fat accumulation \[[@B2-nutrients-12-02325]\]. Interestingly, sedentary behavior, commonly defined as any sitting activity with a low energy expenditure, has been also linked to low-grade inflammation, independently of physical activity levels or adiposity \[[@B6-nutrients-12-02325],[@B7-nutrients-12-02325],[@B8-nutrients-12-02325],[@B9-nutrients-12-02325]\]. Caffeine, due to its widespread presence in foods such as coffee, tea, and chocolate, and its stimulant effects, is highly consumed around the world. In vitro studies have suggested an anti-inflammatory role for caffeine, mainly inhibiting TNF-α production \[[@B10-nutrients-12-02325]\]. Regarding in vivo studies, only a few have addressed the effects of caffeine supplementation on blood inflammatory markers in humans \[[@B11-nutrients-12-02325]\]. These studies used a single dose of caffeine or used coffee as supplement when longer interventions were tested, reporting slight anti-inflammatory effects from the supplementation \[[@B12-nutrients-12-02325],[@B13-nutrients-12-02325]\]. However, when coffee is used, many more components than caffeine alone are included in the supplement, as coffee is rich in bioactive compounds with antioxidant and anti-inflammatory properties, mainly chlorogenic acids \[[@B14-nutrients-12-02325],[@B15-nutrients-12-02325]\]. In a similar way, when effects of habitual caffeine intake are analyzed it is impossible not to consider coffee consumption and the contribution of other coffee components, because in most countries, including Spain, coffee has been reported to be the main dietary source of caffeine \[[@B16-nutrients-12-02325]\]. In this regard, it has been shown that regular coffee intake is associated with reduced risk of type 2 diabetes \[[@B17-nutrients-12-02325],[@B18-nutrients-12-02325]\] and metabolic syndrome \[[@B19-nutrients-12-02325]\] among other clinical conditions where low-grade inflammation and oxidative stress is involved in their development \[[@B11-nutrients-12-02325]\]. Furthermore, studies have shown anti-inflammatory effects of regular coffee consumption \[[@B20-nutrients-12-02325],[@B21-nutrients-12-02325],[@B22-nutrients-12-02325],[@B23-nutrients-12-02325]\]. To our knowledge the effect of habitual caffeine intake on the inflammatory status of people performing different levels of physical activity, while taking into consideration the amount of sitting time, in a healthy young population has not yet been determined. Therefore, the aim of the present study was to determine the effect of regular caffeine intake, physical activity levels and sedentary behavior on the inflammatory status in healthy participants. Because physical activity and also caffeine, or coffee, have been suggested to induce anti-inflammatory effects, it could be expected that physically active participants consuming caffeine could present a more anti-inflammatory profile. 2. Materials and Methods {#sec2-nutrients-12-02325} ======================== 2.1. Study Design and Participants {#sec2dot1-nutrients-12-02325} ---------------------------------- Two hundred and forty-four participants (112 men and 132 women) volunteered to participate in this descriptive cross-sectional study. Participants were recruited among healthy students, workers, researchers and lecturers from the University of the Balearic Islands. All the participants were informed of the purpose and demands of the study before giving their written consent to participate. The protocol was in accordance with the Declaration of Helsinki for research of human participants and was approved by the Balearic Islands Clinical Investigation Ethics Committee (IB 2399/14 PI). Participants were enrolled after fulfilling all inclusion criteria and presenting none of the exclusion criteria. Participants could be included if they were currently healthy, aged between 18 and 55 years and to have maintained constant physical activity levels (regardless of how high or low the level of activity) and sedentary behavior within the previous two months. Exclusion criteria were: smokers, professional, elite and those athletes with a habitual participation in endurance and ultra-endurance events, significant body weight fluctuations within the previous two months (±2 kg), regular alcohol or drugs consumption, and habitual consumption, or consumption within the 2 weeks preceding the study, of anti-inflammatory medication. Two hundred and forty-eight participants were recruited, but blood samples could not be obtained from four, leading to the final number of participants indicated above. 2.2. Laboratory Visit {#sec2dot2-nutrients-12-02325} --------------------- Participants arrived at the laboratory between 08:00 and 10:00 h following an overnight fast of approximately 12 h. They had been previously informed about the study demands and about the inclusion and exclusion criteria. They had also been instructed to abstain from any moderate-vigorous intensity exercise during the 24 h before coming to the laboratory. Information about the study was given again to the participants, they completed an inclusion/exclusion criteria questionnaire and they then signed an informed consent form. Each participant was asked to empty their bladder before body mass, height and body composition were recorded. Participants then sat quietly for 10 min and completed questionnaires to determine physical activity levels, caffeine intake and adherence to the Mediterranean diet, before a blood sample was taken. The women were also asked about the date of their last menstruation. Seated venous blood samples were collected in suitable vacutainers with ethylenediaminetetraacetic acid (EDTA). Plasma was obtained from the blood samples within 30 min after blood collection by centrifugation (15 min, 1000× *g*, 4 °C). Plasma aliquots were stored at −70 °C until measurements were performed. 2.3. Anthropometrical Measurements {#sec2dot3-nutrients-12-02325} ---------------------------------- Height was measured to the nearest 0.5 cm using a stadiometer (Seca 220 (CM) Telescopic Height Rod for Column Scales, Seca gmbh, Hamburg). Body weight, percentage of body fat mass, and rating of visceral fat were measured using a Body Composition Analyzer (Bioelectrical Impedance Analysis, TANITA MC-780MA, TANITA Europe BV, Amsterdam, The Netherlands). Body weight was measured to the nearest 0.1 kg. The visceral fat measurement using this methodology provides a rating from 1 to 59, with values from 1 to 12 considered healthy (arbitrary units and information provided by the manufacturer, <https://tanita.eu/help-guides/products-manuals/>). Body mass index (BMI) was calculated as weight (kg) divided by height (m) squared (kg·m^−2^). 2.4. Questionnaires {#sec2dot4-nutrients-12-02325} ------------------- Physical activity levels were determined using the standard short form of the validated International Physical Activity Questionnaire (IPAQ), thus providing quantitative information on physical activity levels in metabolic equivalents (MET)-h·week^−1^. Total weekly physical activity time and daily sitting time were also determined. Diet quality was measured as the Adherence to the Mediterranean diet using a simplified assessment of adherence to the Mediterranean Diet (14-item questionnaire), previously developed and validated for the Spanish population \[[@B24-nutrients-12-02325]\]. Each item was scored as 0 or 1. A global score of 9 or higher indicates a good adherence to the Mediterranean Diet. Habitual caffeine intake was measured using a self-reported questionnaire previously developed and used by our group \[[@B25-nutrients-12-02325],[@B26-nutrients-12-02325]\]. The frequency intake of common products containing caffeine was ascertained, and caffeine daily consumption determined by using the caffeine content of each product \[[@B16-nutrients-12-02325]\]. Products included in the questionnaire were coffee preparations, including decaffeinated coffee, instant coffee (as cups or spoons), tea, chocolate, cola drinks, energy or stimulant beverages, and pharmaceutical caffeine supplements. Coffee intake was estimated from the intake of each coffee preparation contained in the questionnaire. The most common preparations in Spain were considered: espresso, "cortado" (espresso coffee, one serving, with a shot of milk), and "café con leche" (white coffee, or espresso coffee, one serving, with the remaining half of a cup filled with milk or steamed milk). Because a dose-response plasma appearance of the chlorogenic and phenolic acids contained in coffee has been shown after instant coffee ingestion \[[@B27-nutrients-12-02325]\], and because of its caffeine content, instant coffee was also considered as a coffee preparation. When applicable, the number of instant coffee servings was determined considering the number of spoons indicated by participants and that each serving contained 3.4 g of instant coffee \[[@B27-nutrients-12-02325]\]. Therefore, the total coffee intake, in number of servings, was determined considering all preparations indicated above. 2.5. Measurement of Inflammatory Markers {#sec2dot5-nutrients-12-02325} ---------------------------------------- Plasma IL-10, IL-6, IL-1β, TNF-α, adiponectin, and CRP concentrations were determined to describe the inflammatory status of participants. These inflammatory markers were measured using commercially available solid-phase sandwich enzyme-linked immunosorbent assays and performed according to the manufacturers' instructions. Concentrations of IL-10, IL-6, and TNF-α were measured using Invitrogen high sensitivity kits (ThermoFisher SCIENTIFIC, Waltham, MA, USA). IL-10 was measured using the "IL-10 Human ELISA Kit, High Sensitivity" (BMS215HS); IL-6 was measured using the "IL-6 Human ELISA Kit, High Sensitivity" (BMS213HS); and TNF-α was measured using the "TNF alpha Human ELISA Kit, High Sensitivity" (BMS223HS). IL-1β, adiponectin and CRP were measured using RayBio^®^ kits (RayBiotech, Norcross, GA, USA). IL-1β was measured using the "Human IL-1 beta ELISA" (ELH-IL1b); Adiponectin was measured using the "Human Adiponectin (Acrp30) ELISA" (ELH-Adiponectin); and CRP was measured using the "Human CRP ELISA" (ELH-CRP). All kits were exclusive for human samples (plasma, serum, and culture supernatants), and micro-plates were supplied with wells pre-coated with the specific antibody. For all assays, the absorbance was measured spectrophotometrically on a microplate reader (PowerWavei; BioTek, Winooski, VT, USA), and the concentration of each cytokine was calculated by comparison with a calculation curve established in the same measurement. 2.6. Statistical Analysis {#sec2dot6-nutrients-12-02325} ------------------------- Statistical analysis was carried out using IBM SPSS Statistics 22.0 software (SPSS/IBM, Chicago, IL, USA). All the data were tested for their normal distribution (Kolmogorov--Smirnov test). The results are expressed as means and standard deviations (SD), or median and interquartile ranges as specified. Percentages were also used when required. Student's t-test for unpaired data or the Mann-Whitney U test were used to evaluate differences between sexes. Kruskal-Wallis one-way ANOVA was used to determine the effect of the menstrual cycle on cytokine, adiponectin and CRP concentrations in women. Because no effect of menstrual cycle was observed (results not shown), this variable was not included in the following main analysis. The existence of significant bivariate correlations between the main variables was ascertained by determining Pearson correlation coefficients. These correlations were determined for the whole sample and for male and female participants separately. Multiple linear regression analysis, using the stepwise procedure, was applied to determine the relation between each dependent variable (logarithmic transformed IL-10, IL-6, IL-1β, TNF-α, adiponectin, and CRP concentrations) and independent and control variables. Habitual caffeine intake, IPAQ score and sitting time were included in the analysis as independent variables. Sex, body fat percentage, visceral fat rating, and diet quality, measured as the Adherence to the Mediterranean diet, were included in the analysis as control variables. Kruskal-Wallis one-way ANOVA was used to analyze IL-10 and TNF-α values depending on sitting time categorized in tertiles. A post-hoc power analysis calculation was performed (G\*Power 3.1.9.4. Universität Kiel, Germany) for the regression analysis (*n* = 244, eight predictors, α = 0.05). The power statistical calculation reported values higher than 90% for all significant regression reported. Statistical significance was accepted at *p* \< 0.05. 3. Results {#sec3-nutrients-12-02325} ========== 3.1. General Characteristics of Participants in the Study {#sec3dot1-nutrients-12-02325} --------------------------------------------------------- [Table 1](#nutrients-12-02325-t001){ref-type="table"} shows the general characteristics of participants in the study stratified per sex. The study population was, on average, young, with a BMI value within the normal weight range, a Mediterranean diet score slightly under the threshold for a good adherence, and with a higher number of women. Regarding anthropometrical characteristics, 20.5% of participants were overweight (BMI between 25 and 30 kg·m^−2^), and 3.7% were obese (BMI higher than 30 kg·m^−2^). On the other hand, 2.2% of participants showed an unhealthy visceral fat rating. Regarding caffeine intake, 4.9% of participants did not take caffeine, and 17% of participants took more than 400 mg per day (which is considered the higher-end value for a throughout the day, not in a single dose, safe consumption in healthy people \[[@B16-nutrients-12-02325]\]). Regarding coffee intake, 22.1% of participants reported no coffee intake, and 7% of participants reported an intake greater than 3 servings. Men reported non-significantly higher physical activity levels, both when expressed in METs and in hours. No significant differences between sexes were observed in the sitting time. 3.2. Sources of Caffeine Consumption {#sec3dot2-nutrients-12-02325} ------------------------------------ Among caffeine consumers, coffee was the main caffeine source for participants in the study ([Table 2](#nutrients-12-02325-t002){ref-type="table"}). No significant differences were found between male and female participants. 3.3. Concentration of Inflammatory Markers {#sec3dot3-nutrients-12-02325} ------------------------------------------ [Table 3](#nutrients-12-02325-t003){ref-type="table"} shows cytokine concentrations of all participants and categorized by sex. Significant differences were observed for IL-6, TNF-α, CRP, and adiponectin, with higher values in men for IL-6 (*p* = 0.003) and TNF-α (*p* = 0.005), and higher values in women for CRP (*p* \< 0.001) and adiponectin (*p* \< 0.001). 3.4. Bivariate Correlations between Dependent and Independent Variables {#sec3dot4-nutrients-12-02325} ----------------------------------------------------------------------- [Table 4](#nutrients-12-02325-t004){ref-type="table"} shows bivariate correlations between all dependent and independent (continuous) variables. Positive correlations were found for IL-6 (*p* = 0.001) and TNF-α (*p* = 0.014) with age. However, IL-10 was inversely correlated with age (*p* = 0.032). Caffeine intake was inversely correlated with CRP levels (*p* = 0.044). Physical activity levels were correlated with IL-10 (*p* = 0.002). Sitting time showed a positive correlation with TNF-α (*p* \< 0.001) and an inverse correlation with IL-10 levels (*p* \< 0.001). Percentage of body fat was correlated with CRP (*p* \< 0.001), while it was inversely correlated with IL-10 (*p* = 0.001) and adiponectin (*p* \< 0.001). An inverse correlation was found between visceral fat rating and IL-10 (*p* = 0.013). However, visceral fat showed positive correlations with IL-6 (*p* \< 0.001) and TNF-α (*p* \< 0.001). IL-1β levels were correlated with the adherence to the Mediterranean diet (*p* = 0.039). [Table 5](#nutrients-12-02325-t005){ref-type="table"} shows bivariate correlations between all dependent and independent variables in female participants. An inverse correlation was found between IL-10 and age (*p* = 0.020). However, a positive correlation was found for IL-6 with age (*p* = 0.023). Physical activity levels were correlated with IL-10 (*p* = 0.033). Sitting time showed a positive correlation with TNF-α (*p* = 0.001) and an inverse correlation with IL-10 levels (*p* = 0.001). Percentage of body fat showed a positive correlation with CRP (*p* \< 0.001). Positive correlations were found for IL-6 (*p* = 0.037) and TNF-α (*p* = 0.049) with visceral fat. No correlation was found for adherence to the Mediterranean diet or caffeine intake with any of the dependent variables. [Table 6](#nutrients-12-02325-t006){ref-type="table"} shows bivariate correlation between all dependent and independent variables in male participants. A positive correlation was found between TNF-α and age (*p* = 0.042). Physical activity levels were positively correlated with IL-10 (*p* = 0.010) and inversely correlated with TNF-α (*p* = 0.005). Sitting time showed a positive correlation with TNF-α (*p* = 0.047) and an inverse correlation with IL-10 levels (*p* \< 0.001). Percentage of body fat was correlated with IL-6 (*p* = 0.001), TNF-α (*p* \< 0.001), and CRP (*p* \< 0.001), while it was inversely correlated with adiponectin (*p* \< 0.001) and IL-10 (*p* = 0.002). Visceral fat was correlated with IL-6 (*p* = 0.002), TNF-α (*p* \< 0.001), and CRP (*p* \< 0.001), and it was inversely correlated with IL-10 (*p* = 0.008). No correlation was found for adherence to the Mediterranean diet or caffeine intake with any of the dependent variables. 3.5. Multivariable Linear Regression Analysis {#sec3dot5-nutrients-12-02325} --------------------------------------------- [Table 7](#nutrients-12-02325-t007){ref-type="table"} shows the results of the regression analysis for IL-10. Regression analysis revealed that sitting time (*p* \< 0.001) and the percentage of fat (*p* = 0.001) were negative predictors for IL-10 levels, while physical activity was a positive predictor (*p* = 0.028). Sitting time was found to be the main predictor (change in R^2^ 0.106 vs. 0.040 for fat mass and 0.017 for physical activity). [Table 8](#nutrients-12-02325-t008){ref-type="table"} shows de-regression analysis results for adiponectin. Sex was revealed as the main predictor for adiponectin (change in R^2^ 0.097, *p* \< 0.001), with higher values for females, as has been indicated above. Percentage of fat mass was inversely associated with adiponectin (change in R^2^ 0.017, *p* = 0.032). [Table 9](#nutrients-12-02325-t009){ref-type="table"} shows the results of the regression analysis for IL-6. Visceral fat was revealed as the only significant predictor for IL-6 (*p* \< 0.001), with a positive association. Sitting time (change in R^2^ 0.044, *p* \< 0.001,) and visceral fat rating (change in R^2^ 0.112, *p* \< 0.001) were found as positive predictors for TNF-α concentrations, with visceral fat as the main predictor ([Table 10](#nutrients-12-02325-t010){ref-type="table"}). [Table 11](#nutrients-12-02325-t011){ref-type="table"} shows the results of the regression analysis for CRP. Percentage of fat mass was found as the main predictor for CRP (change in R^2^ 0.182, *p* \< 0.001), showing a positive association. Caffeine intake was shown to be a negative predictor for CRP (change in R^2^ 0.037, *p* = 0.001). The regression analysis did not report any significant predictor for IL-1β. 3.6. Effects of Sitting Time on IL-10 and Tumor Necrosis Factor (TNF) -a Concentrations {#sec3dot6-nutrients-12-02325} --------------------------------------------------------------------------------------- [Figure 1](#nutrients-12-02325-f001){ref-type="fig"} shows values of IL-10 (a) and TNF-α (b) categorized by sitting time tertiles. A significant effect of sitting time was found for both IL-10 (*p* = 0.001) and TNF-α (*p* \< 0.001). IL-10 values in the third tertile (longer sitting time, 9 to 15 h) were significantly lower (*p* = 0.001) than in the first tertile (shortest sitting time, 1 to 5 h). TNF-α values in the third tertile were significantly higher than in the second tertile (*p* = 0.004) and in the first tertile (*p* \< 0.001). 4. Discussion {#sec4-nutrients-12-02325} ============= The main finding of the present study was that in a healthy population, low caffeine intake could exert a slight anti-inflammatory effect characterized by lower CRP plasma levels. Body fat, both total and visceral, and sedentary behavior have been shown to be important and independent inflammatory predictors, inducing higher levels of pro-inflammatory markers, but also decreased levels of anti-inflammatory markers. Participants in the study population were, on average, young and with a higher number of women. These characteristics reflect properly the university population, with higher figures for young female students. Caffeine intake observed in the present study was similar to previous studies in Spain, and similar, or slightly lower to the average value, when participants of a similar age from most occidental countries were considered \[[@B16-nutrients-12-02325],[@B28-nutrients-12-02325],[@B29-nutrients-12-02325],[@B30-nutrients-12-02325]\]. Concerning this consumption, coffee remains the main source for caffeine intake, a common finding in most European countries, except for the UK and Ireland \[[@B16-nutrients-12-02325]\]. As coffee preparations in Spain are quite different from the ones in other countries, it becomes difficult to compare coffee intake observed in the present study with the habitual intake of other countries. For these reasons, caffeine intake, rather than coffee intake, has been used as the main variable for the analysis, and also as an indicator of coffee consumption. Previous studies, both observational and clinical trials, have reported that coffee intake increases adiponectin levels \[[@B13-nutrients-12-02325],[@B20-nutrients-12-02325]\]. The mechanism involved seems to be the stimulatory effect of caffeine on the expression of the peroxisome proliferator activated receptor γ (PPARγ), which positively elevates the adiponectin concentration \[[@B31-nutrients-12-02325]\]. In fact, a previous study reported increased levels of adiponectin after a supplementation with caffeinated coffee but no effect with decaffeinated coffee \[[@B13-nutrients-12-02325]\]. However, a higher daily intake of coffee (four cups, or more than 600 mg of caffeine) than that observed in the present study, seems to be required to increase adiponectin levels \[[@B20-nutrients-12-02325]\]. Therefore, and as suggested, low amounts of coffee or caffeine consumption may be the reason for not observing a significant effect of caffeine intake on adiponectin \[[@B32-nutrients-12-02325]\] but also on IL-10, TNF-α, and IL-6 concentrations in the present study. It should also be considered that some studies reporting positive effects of regular coffee consumption on adiponectin levels were performed in overweight participants \[[@B13-nutrients-12-02325]\], while in the present study only \~24% of participants were overweight or obese; or in older populations \[[@B20-nutrients-12-02325]\]. Therefore, it is possible that the protective effect of coffee was emphasized in such conditions. The association between CRP, which is considered an appropriate marker for low grade systemic inflammation \[[@B33-nutrients-12-02325]\], and coffee intake has been recently reviewed \[[@B34-nutrients-12-02325]\]. Despite this review suggesting that on average, coffee consumption is not associated with CRP levels, some studies have reported a protective healthy effect because decreased levels of CRP have been observed in participants ingesting at least a daily cup of coffee \[[@B20-nutrients-12-02325],[@B21-nutrients-12-02325],[@B22-nutrients-12-02325],[@B23-nutrients-12-02325]\]. Results of the present study are in agreement with this observation as it was observed that caffeine consumption is inversely associated with CRP levels. Therefore, it seems that in contrast with the other inflammatory markers analyzed, low regular coffee intake could be enough to prevent higher CRP levels. It is worth noting however, that decaffeinated coffee seems to also be effective in decreasing CRP levels, therefore other components of coffee rather than caffeine itself, could contribute to this effect \[[@B22-nutrients-12-02325]\]. It has been suggested that chlorogenic acid, the main phenolic acid in coffee with antioxidant and anti-inflammatory properties \[[@B14-nutrients-12-02325]\], can play an important role in the reduction of inflammatory factors such as CRP \[[@B35-nutrients-12-02325]\]. The low, on average, BMI of participants in the present study could have been an important factor that influenced the inverse association between coffee intake and CRP, as all studies reporting the protective anti-inflammatory effect of coffee consumption were performed in populations with low BMIs \[[@B20-nutrients-12-02325],[@B21-nutrients-12-02325],[@B22-nutrients-12-02325],[@B23-nutrients-12-02325]\]. In fact, it has been suggested that the different BMI of populations considered in previous studies could be a key factor for the inconsistent results found regarding this association \[[@B34-nutrients-12-02325]\]. Interestingly, in the present study, and in agreement with previous reports \[[@B36-nutrients-12-02325],[@B37-nutrients-12-02325]\], a positive association was found between body fat mass and CRP. Therefore, our data indicates that, in the context of an average low BMI, caffeine consumption, probably as a coffee consumption marker, presents an inverse association with CRP, inducing the opposite effect of body fat mass accumulation. Inverse associations were found between percentage of body fat and anti-inflammatory markers such as adiponectin and IL-10. Adiponectin is an anti-inflammatory adipokine secreted almost exclusively from adipose tissue \[[@B38-nutrients-12-02325]\], and low adiponectin levels have been associated with body fat accumulation and obesity, leading to increased risk of inflammation \[[@B3-nutrients-12-02325]\]. It is striking that in the present study this potential negative effect was observed in young and healthy participants, with an incidence of obesity as low as 3.7%. In addition, and despite the fact women present a relatively greater percentage body fat, adiponectin levels were found to be higher in women, which is in agreement with previous results, mainly when lean populations have been considered \[[@B39-nutrients-12-02325]\]. The anti-inflammatory IL-10 has not been commonly measured when associations between fat mass and inflammation have been investigated. In the present study, and in the same line of results indicated above, IL-10 was inversely associated with body fat mass. It has been reported that fat accumulation is accompanied by adipose tissue infiltration by pro-inflammatory immune cells (T2), increased release of pro-inflammatory markers such as TNF-α, decreased production of anti-inflammatory markers, such as IL-10, and the development of the low-grade systemic inflammatory state described above \[[@B3-nutrients-12-02325]\]. Within this picture, and regarding adipose tissue, visceral fat has been suggested to play an important role \[[@B2-nutrients-12-02325]\]. In the present study positive associations were found between visceral fat and TNF-α and also between visceral fat and IL-6. Previous studies, using different approaches to measure visceral fat, have shown similar associations \[[@B40-nutrients-12-02325],[@B41-nutrients-12-02325],[@B42-nutrients-12-02325]\]. Whether TNF-α and IL-6 levels are more dependent on total body fat or visceral fat remains to be elucidated, because some studies have reported associations with both parameters \[[@B37-nutrients-12-02325],[@B42-nutrients-12-02325],[@B43-nutrients-12-02325]\]. However, taken together, the opposite associations found for IL-10 and, on the other hand, TNF-α and IL-6 with regard to fat content, total or visceral, could reflect the predominant anti-inflammatory production when fat content is low as well as the predominant pro-inflammatory release when fat is accumulated. In the present study only a small effect of physical activity levels on the IL-10 concentrations were observed. However, more strong associations were found for sedentary time: a positive association with TNF-α and an inverse association with IL-10, which, together, define a pro-inflammatory picture induced by sedentary behavior and independent of physical activity levels. It is possible that the average moderate levels reported could limit the effects of physical activity. However, previous studies showed that sedentary behavior was linked to low-grade inflammation, independently of physical activity levels or adiposity \[[@B6-nutrients-12-02325],[@B7-nutrients-12-02325],[@B8-nutrients-12-02325],[@B9-nutrients-12-02325]\]. This observation is in agreement with results obtained in the present study and suggests an independent link between sitting time and low-grade inflammation \[[@B7-nutrients-12-02325]\]. To our knowledge, the association between sedentary time and IL-10 has not been reported, as previous studies focused on the pro-inflammatory markers. This novel result could indicate that sedentary behavior, independent of fat mass and physical activity, influences levels of both pro-inflammatory and anti-inflammatory compounds. This study presents some limitations that should be acknowledged. In addition to the limitations due to the observational nature, the current study was limited to cross-sectional data from a single university population. However, the patterns of physical activity and sedentary behavior observed in the present study could be applied to other populations, even outside the university. Both sedentary time and physical activity levels, two of the main variables of the study, were self-reported. However, the IPAQ, which is a widely used and validated questionnaire, was utilized to collect these data, as has been done in previous studies using the same or similar questionnaires \[[@B6-nutrients-12-02325],[@B9-nutrients-12-02325]\]. Regarding sedentary time, an important limitation was that the number, duration, and frequency of sedentary breaks were not recorded. In this regard, it has been reported that these breaks could modify to some extent associations between sedentary time and inflammatory markers \[[@B8-nutrients-12-02325]\], at least when sitting time is not too long \[[@B7-nutrients-12-02325]\]. Furthermore, methodology used to determine both percentage of fat mass and visceral fat rating has been reported to present some limitations \[[@B44-nutrients-12-02325]\]. Finally, despite the statistical power analysis revealed high power for most of the associations found, these associations could be considered weak. However, there is a concordance between most of them, highlighting the pro-inflammatory role of sedentary behavior and fat mass accumulation. 5. Conclusions {#sec5-nutrients-12-02325} ============== The limited effects of caffeine or coffee intake observed in the present study could be explained by relatively low caffeine and coffee intakes. However, this relatively low caffeine or coffee consumption could slightly prevent CRP increases induced by increased fat mass. Sedentary behavior and body fat accumulation, even within the young, healthy and, on average, normal weight participants in the present study induced pro-inflammatory effects. However, only slight effects of physical activity levels were observed. Interestingly, both sedentary behavior and fat accumulation induced lower levels of the essential anti-inflammatory cytokine IL-10. Future studies should be performed to determine coffee intake needed to observe greater health effects and, also, to determine the mechanism linking sedentary behavior to inflammation. The authors would like to thank all the participants in the study. Conceptualization, P.T. and S.M.; Methodology, P.T., S.M., A.R.-S. and L.R.; Formal Analysis, P.T. and A.A.; Investigation, L.R., S.M., A.R.-S., A.A. and P.T.; Writing-Original Draft Preparation, L.R.; Writing-Review and Editing, P.T., A.R.-S., A.A. and S.M.; Visualization, L.R.; Supervision, P.T. and S.M.; Project Administration, P.T. and S.M.; Funding Acquisition, P.T. All authors have read and agreed to the published version of the manuscript. This research was funded by the Ministerio de Economía, Industria y Competitividad (MINECO), the Agencia Estatal de Investigación (AEI) and the European Regional Development Funds (ERDF), project DEP2013-45966-P (MINECO/AEI/ERDF, EU). The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. ![IL-10 (**a**) and TNF-α (**b**) plasma concentrations categorized by sitting time tertiles. Median, 25th, 75th percentile, and lowest and highest values are shown for IL-10 and TNF-α values. \# indicates significant differences to first tertile. & indicates significant differences to second tertile. IL: interleukin; TNF: tumor necrosis factor.](nutrients-12-02325-g001){#nutrients-12-02325-f001} nutrients-12-02325-t001_Table 1 ###### General characteristics of participants in the study. ------------------------------------------------------------------------------------------------------------------ All\ Men\ Women\ *p* Value (*n* = 244) (*n* = 112) (*n* = 132) ------------------------------------------------- --------------- --------------- --------------- ---------------- Age (years) 32.1 ± 10.8 33.4 ± 10.8 31.1 ± 10.8 0.098 Weight (kg) 66.9 ± 13.3 76.3 ± 11.4 58.9 ± 8.7 **\<0.001** \* Height (cm) 170.0 ± 9.0 177.0 ± 6.5 164.0 ± 6.0 **\<0.001** \* BMI (kg·m^−2^) 23.0 ± 3.4 24.3 ± 3.3 22.0 ± 3.2 **\<0.001** \* Fat mass (%) 23.3 ± 7.9 18.3 ± 6.3 27.6 ± 6.5 **\<0.001** \* Visceral fat rating 4.01 ± 3.30 5.66 ± 3.68 2.63 ± 2.12 **\<0.001** \* Mediterranean diet score 8.18 ± 1.91 8.22 ± 1.93 8.15 ± 1.91 0.771 Caffeine intake (mg·day^−1^) 164.3 ± 143.4 174.7 ± 152.4 155.5 ± 135.3 0.298 Caffeine intake (mg·kg body weight^−1^·day^−1^) 2.48 ± 2.18 2.33 ± 2.18 2.60 ± 2.18 0.346 Coffee intake (servings·day^−1^) 1.32 ± 1.35 1.41 ± 1.47 1.24 ± 1.25 0.311 Physical activity levels (METs-hour·week^−1^) 43.8 ± 36.1 48.7 ± 33.7 39.7 ± 37.5 0.054 Physical activity (hours·week^−1^) 9.18 ± 8.50 9.90 ± 7.36 8.57 ± 9.35 0.224 Sitting time (hours·day^−1^) 6.96 ± 2.77 7.20 ± 3.09 6.77 ± 2.46 0.235 ------------------------------------------------------------------------------------------------------------------ Values are expressed as means ± standard deviations. \* indicates significant differences between sexes (with *p* significant values also in bold) (*p* \< 0.05), Student's t-test for unpaired data. BMI: body mass index. nutrients-12-02325-t002_Table 2 ###### Sources of caffeine intake among those participants consuming caffeine. ---------------------------------------------------------------------------- Source All\ Men\ Women\ *p* Value (*n* = 228) (*n* = 105) (*n* = 123) ---------------------- ------------- ------------- ------------- ----------- Coffee (%) 67.5 ± 37.1 69.6 ± 37.4 66.0 ± 36.9 0.538 Tea (%) 10.1 ± 19.8 8.9 ± 19.4 11.0 ± 20.1 0.425 Cola drinks (%) 12.8 ± 24.7 14.0 ± 26.8 11.8 ± 22.9 0.506 Chocolate (%) 7.9 ± 20.4 5.2 ± 14.1 10.2 ± 24.2 0.054 Energetic drinks (%) 1.6 ± 7.6 2.2 ± 9.0 1.0 ± 6.1 0.241 Sport products (%) 0.1 ± 0.7 0.1 ± 1.0 n.d. 0.175 ---------------------------------------------------------------------------- Values are expressed as means ± standard deviations and represent the caffeine contribution in percentage of each source with respect to total caffeine intake. No differences between men and women were found, Student's t-test for unpaired data. n.d.: non detected (no consumption reported). nutrients-12-02325-t003_Table 3 ###### Cytokine concentrations of participants in the study. ------------------------------------------------------------------------------------------------------ Inflammatory Marker All\ Men\ Women\ *p* Value (*n* = 244) (*n* = 112) (*n* = 132) ------------------------- ------------------- ------------------- ------------------- ---------------- IL-10 (μg·mL^−1^) 0.65 (0.54, 0.77) 0.65 (0.55, 0.83) 0.66 (0.54, 0.74) 0.333 IL-6 (μg·mL^−1^) 2.17 (1.44, 3.04) 2.38 (1.84, 3.12) 1.89 (1.14, 2.99) **0.003** \* IL-1β (pg·mL^−1^) 3.84 (2.66, 6.29) 4.02 (2.88, 6.40) 3.58 (2.43, 6.00) 0.205 TNF-α (pg·mL^−1^) 1.98 (1.52, 2.68) 2.11 (1.64, 3.04) 1.76 (1.49, 2.51) **0.005** \* CRP (μg·mL^−1^) 3.50 (1.81, 5.67) 2.46 (1.58, 4.28) 4.26 (2.42, 6.34) **\<0.001** \* Adiponectin (μg·mL^−1^) 5.78 (3.62, 7.96) 4.59 (3.12, 6.22) 6.72 (4.77, 8,78) **\<0.001** \* ------------------------------------------------------------------------------------------------------ Values are expressed as median (25th, 75th percentile). \* indicates significant differences between men and women (with *p* values in bold) (*p* \< 0.05), Mann Whitney U test. IL: interleukin; TNF: tumor necrosis factor; CRP: C-reactive protein. nutrients-12-02325-t004_Table 4 ###### Bivariate correlations between dependent and independent variables (all participants). ------------------------------------------------------------------------------------------------------------------------------------------ Age %Fat Vis Fat MD Caffeine PA Sit ------------- ---------------- ------------------ ------------------ ---------------- ---------------- ---------------- ------------------ IL-10 −0.138\ −0.219\ −0.159\ −0.083\ −0.094\ 0.195\ −0.325\ (**0.032** \*) (**0.001** \*) (**0.013** \*) (0.197) (0.142) (**0.002** \*) (**\<0.001**\*) IL-6 0.205\ 0.063\ 0.290\ −0.032\ 0.089\ −0.037\ 0.003\ (**0.001** \*) (0.329) (**\<0.001** \*) (0.615) (0.164) (0.561) (0.957) IL-1β 0.006\ 0.071\ 0.052\ 0.132\ −0.006\ −0.009\ −0.030\ (0.932) (0.267) (0.417) (**0.039** \*) (0.930) (0.889) (0.639) TNF-α 0.157\ 0.086\ 0.335\ −0.023\ 0.067\ −0.081\ 0.249\ (**0.014** \*) (0.180) (**\<0.001** \*) (0.717) (0.299) (0.208) (**\<0.001** \*) CRP 0.009\ 0.427\ 0.115\ −0.109\ −0.129\ −0.037\ −0.039\ (0.889) (**\<0.001** \*) (0.074) (0.088) (**0.044** \*) (0.563) (0.549) Adiponectin −0.107\ −0.222\ −0.117\ −0.012\ −0.087\ −0.041\ −0.003\ (0.095) (**\<0.001** \*) (0.072) (0.429) (0.182) (0.520) (0.963) ------------------------------------------------------------------------------------------------------------------------------------------ Pearson correlation coefficient and (*p* value) is shown (*n* = 244). \* indicates significant correlations (with *p* values in bold) (*p* \< 0.05). % Fat: percentage of total body fat; Vis fat: visceral fat rating; MD: adherence to the Mediterranean diet; Caffeine: caffeine intake; PA: physical activity levels. Sit: sitting daily time. Logarithmic transformations of dependent variables were used. IL: interleukin; CRP: C-reactive protein; TNF: tumor necrosis factor. nutrients-12-02325-t005_Table 5 ###### Bivariate correlations between dependent and independent variables in females. ------------------------------------------------------------------------------------------------------------------------- Age %Fat Vis Fat MD Caffeine PA Sit ------------- ---------------- ------------------ ---------------- --------- ---------- ---------------- ---------------- IL-10 −0.203\ −0.133\ −0.170\ −0.045\ −0.098\ 0.185\ −0.281\ (**0.020** \*) (0.128) (0.052) (0.605) (0.265) (**0.033** \*) (**0.001** \*) IL-6 0.198\ 0.162\ 0.182\ −0.046\ 0.054\ −0.100\ 0.017\ (**0.023** \*) (0.064) (**0.037** \*) (0.597) (0.539) (0.254) (0.844) IL-1β −0.005\ −0.011\ 0.048\ 0.157\ −0.016\ −0.028\ −0.091\ (0.959) (0.902) (0.588) (0.072) (0.854) (0.754) (0.300) TNF-α 0.096\ 0.164\ 0.172\ −0.062\ −0.034\ −0.016\ 0.297\ (0.274) (0.060) (**0.049** \*) (0.479) (0.699) (0.856) (**0.001** \*) CRP −0.066\ 0.330\ 0.158\ −0.097\ −0.155\ 0.030\ 0.048\ (0.455) (**\<0.001** \*) (0.070) (0.267) (0.077) (0.729) (0.582) Adiponectin −0.111\ 0.063\ −0.053\ 0.152\ −0.027\ −0.106\ −0.062\ (0.243) (0.510) (0.579) (0.109) (0.773) (0.268) (0.513) ------------------------------------------------------------------------------------------------------------------------- Pearson correlation coefficient and (*p* value) is shown (*n* = 132). \* indicates significant correlations (with *p* values in bold) (*p* \< 0.05). % Fat: percentage of total body fat; Vis fat: visceral fat rating; MD: adherence to the Mediterranean diet; Caffeine: caffeine intake; PA: physical activity levels. Sit: sitting daily time. Logarithmic transformations of dependent variables were used. IL: interleukin; CRP: C-reactive protein; TNF: tumor necrosis factor. nutrients-12-02325-t006_Table 6 ###### Bivariate correlations between dependent and independent variables in males. ----------------------------------------------------------------------------------------------------------------------------- Age %Fat Vis Fat MD Caffeine PA Sit ------------- ---------------- ------------------ ------------------ --------- ---------- ---------------- ------------------ IL-10 −0.100\ −0.295\ −0.249\ −0.120\ −0.102\ 0.242\ −0.369\ (0.296) (**0.002** \*) (**0.008** \*) (0.207) (0.286) (**0.010** \*) (**\<0.001** \*) IL-6 0.180\ 0.300\ 0.293\ −0.024\ 0.130\ −0.023\ −0.042\ (0.058) (**0.001** \*) (**0.002** \*) (0.803) (0.164) (0.806) (0.662) IL-1β −0.002\ −0.054\ −0.011\ 0.094\ −0.006\ 0.004\ 0.026\ (0.980) (0.577) (0.913) (0.323) (0.953) (0.953) (0.784) TNF-α 0.193\ 0.353\ 0.378\ 0.115\ 0.148\ −0.262\ 0.188\ (**0.042** \*) (**\<0.001** \*) (**\<0.001** \*) (0.226) (0.118) (**0.005** \*) (**0.047** \*) CRP 0.166\ 0.366\ 0.381\ −0.122\ −0.074\ −0.051\ 0.076\ (0.079) (**\<0.001** \*) (**\<0.001** \*) (0.200) (0.440) (0.594) (0.424) Adiponectin −0.107\ −0.222\ −0.117\ −0.012\ −0.087\ −0.041\ −0.003\ (0.095) (**\<0.001** \*) (0.072) (0.429) (0.182) (0.520) (0.963) ----------------------------------------------------------------------------------------------------------------------------- Pearson correlation coefficient and (*p* value) is shown (*n* = 112). \* indicates significant correlations (with *p* values in bold) (*p* \< 0.05). % Fat: percentage of total body fat; Vis fat: visceral fat rating; MD: adherence to the Mediterranean diet; Caffeine: caffeine intake; PA: physical activity levels. Sit: sitting daily time. Logarithmic transformations of dependent variables were used. IL: interleukin; CRP: C-reactive protein; TNF: tumor necrosis factor. nutrients-12-02325-t007_Table 7 ###### Multiple linear regression for IL-10. Variable B 95% CI β t *p* Value --------------------- -------- ------------------ -------- -------- ---------------- Age −0.002 (−0.006, 0.002) −0.104 −1.706 0.089 Sex 0.010 (−0.060, 0.080) 0.042 0568 0.570 Fat mass −0.003 (−0.005, −0.001) −0.189 −3.171 **0.002** \* Visceral fat rating −0.002 (−0.014, 0.010) −0.066 −1.346 0.180 Adherence to MD −0.005 (−0.013, 0.003) −0.078 −1.324 0.187 Caffeine intake 0.000 (−0.001, 0.000) −0.080 −1.336 0.183 Physical activity 0.000 (0.000, 0.001) 0.136 2.218 **0.028** \* Sitting time −0.012 (−0.017, −0.007) −0.281 −4.607 **\<0.001** \* Model: R: 0.405; R^2^ 0.164; Adjusted R^2^ 0.153; *p* \< 0.001; \* indicates significant predictors (with *p* values in bold) (*p* \< 0.05). IL: interleukin; MD: Mediterranean diet; CI: confidence intervals. nutrients-12-02325-t008_Table 8 ###### Multiple linear regression for adiponectin. Variable B 95% CI β t *p* Value --------------------- -------- ------------------ -------- -------- ---------------- Age 0.000 (−0.004, 0.004) −0.019 −0.285 0.776 Sex 0.194 (0.124−0.265) 0.407 5.426 **\<0.001** \* Fat mass −0.005 (−0.009, −0.001) −0.162 −2.156 **0.032** \* Visceral fat rating 0.004 (−0.004−0.012) 0.050 0.443 0.658 Adherence to MD 0.008 (−0.006, 0.022) 0.065 1.075 0.283 Caffeine intake 0.000 (−0.001, 0.000) −0.068 −1.092 0.276 Physical activity 0.000 (−0.001, 0.000) −0.012 0.010 0.846 Sitting time 0.003 (−0.007, 0.013) 0.039 0.637 0.585 Model: R^2^ 0.115; Adjusted R^2^ 0.107; *p* \< 0.001; \* indicates significant predictors (with *p* values in bold) (*p* \< 0.05). MD: Mediterranean diet; CI: confidence intervals. nutrients-12-02325-t009_Table 9 ###### Regression analysis for IL-6. Variable B 95% CI β t *p* Value --------------------- -------- ----------------- -------- -------- ---------------- Age 0.001 (−0.003, 0.005) 0.013 0.151 0.880 Sex −0.035 (−0.075, 0.005) −0.073 −1.055 0.292 Fat mass −0.001 (−0.003, 0.001) −0.028 −0.439 0.661 Visceral fat rating 0.021 (0.012, 0.030) 0.290 4.701 **\<0.001** \* Adherence to MD −0.005 (−0.017, 0.007) −0.044 −0.706 0.481 Caffeine intake 0.000 (0.000, 0.001) 0.039 0.579 0.563 Physical activity −0.001 (−0.002, 0.001) −0.059 −0.948 0.344 Sitting time −0.003 (−0.011, 0.005) −0.033 −0.532 0.595 Model: R^2^ 0.084; Adjusted R^2^ 0.080; *p* \< 0.001; \* indicates significant predictors (with *p* values in bold) (*p* \< 0.05). IL: interleukin; MD: Mediterranean diet; CI: confidence intervals. nutrients-12-02325-t010_Table 10 ###### Multiple linear regression for tumor necrosis factor (TNF) -α. Variable B 95% CI β t *p* Value --------------------- -------- ----------------- -------- -------- ---------------- Age −0.002 (−0.005, 0.001) −0.108 −1.327 0.186 Sex −0.014 (−0.128, 0.100) −0.041 −0.608 0.544 Fat mass −0.001 (−0.011, 0.010) −0.023 −0.367 0.714 Visceral fat rating 0.016 (0.010, 0.022) 0.309 5.166 **\<0.001** \* Adherence to MD 0.001 (−0.009, 0.012) 0.007 0.119 0.905 Caffeine intake 0.000 (−0.001, 0.000) −0.060 −0.936 0.350 Physical activity 0.000 (−0.001, 0.000) −0.025 −0.984 0.326 Sitting time 0.013 (0.004, 0.019) 0.211 3.538 **\<0.001** \* Model: R^2^ 0.156; Adjusted R^2^ 0.149; *p* \< 0.001; \* indicates significant predictors (with *p* values in bold) (*p* \< 0.05). TNF: tumor necrosis factor; MD: Mediterranean diet; CI: confidence intervals. nutrients-12-02325-t011_Table 11 ###### Multiple linear regression for C-reactive protein (CRP). Variable B 95% CI β t *p* Value --------------------- -------- ------------------ -------- -------- ---------------- Age −0.002 (−0.010, 0.006) −0.039 −0.601 0.549 Sex −0.016 (−0.082, 0.050) −0.021 −0.288 0.774 Fat mass 0.018 (0.013, 0.022) 0.454 7.885 **\<0.001** \* Visceral fat rating 0.006 (−0.022, 0.034) 0.063 0.980 0.328 Adherence to MD −0.011 (−0.029, 0.007) −0.070 −1.219 0.224 Caffeine intake −0.002 (−0.003, −0.001) −0.195 −3.379 **0.001** \* Physical activity 0.000 (−0.004, 0.004) 0.023 0.407 0.684 Sitting time 0.000 (−0.013, 0.013) 0.011 0.187 0.852 Model: R^2^ 0.219; Adjusted R^2^ 0.213; *p* \< 0.001; \* indicates significant predictors (with *p* values in bold) (*p* \< 0.05). CRP: C-reactive protein; MD: Mediterranean diet; CI: confidence intervals.
Establishment of Cellular Polarity in Sequential Stages of Cortical Development {#s1} =============================================================================== Neural Stem Cell Polarity {#s1-1} ------------------------- The mammalian cerebral cortex emerges from the neuroectoderm. At the end of neurulation and neural tube closure, occurring from embryonic day (E) 7 to E9 in mice, the early neuroepithelium is composed of neuroepithelial stem cells (NESCs) from which all subsequent neural progenitor cells and their neuron lineages derive (Figure [1](#F1){ref-type="fig"}). NESCs are highly polarized and their nuclei exhibit interkinetic nuclear migration whereby they translocate from the ventricular (apical) side to the more basal side in concert with the cell cycle (Lee and Norden, [@B90]). NESC polarity correlates with the asymmetric distribution of cell fate determinants which are thought to control the fine balance between symmetric and asymmetric progenitor divisions (Shitamukai and Matsuzaki, [@B154]). Such balance is critical for the generation of the correct number of radial glia progenitor cells (RGPCs), which are not only lineally related to NESCs but exhibit even more polarized cellular morphology with an extended basal process (Taverna et al., [@B163]). In the initial stages of neurogenesis, NESCs arrange the mitotic spindle in parallel (division plane perpendicular) to the ventricular zone (VZ) and divide mostly symmetrically, thereby expanding the progenitor pool (Postiglione and Hippenmeyer, [@B134]; Taverna et al., [@B163]). The disruption of the mitotic spindle, anchored to the lateral walls of NESCs, results in the precocious generation of neurons and apoptosis (Yingling et al., [@B189]). Thus the correct cellular polarization of the earliest neural progenitor cells in the developing cerebral cortex is absolutely essential for the correct lineage progression and eventual neuron production. While it has been well established that components of the planar cell polarity signaling pathway play critical roles in establishing and maintaining progenitor polarity (Knoblich, [@B83]; Homem et al., [@B66]), the signaling cues and molecular mechanisms that instruct polarization and the break of symmetry in NESCs are not well understood *in vivo*. ![Establishment of cell polarity in cerebral cortex development. **(A)** The early neuroepithelium is composed of highly polarized neuroepithelial stem cells (NESCs, apical-basal polarity is indicated). NESCs give rise to radial glia progenitor stem cells (RGPCs) which exhibit even more polarized cellular morphology with an extended basal process. During neurogenesis symmetric radial glia progenitor (RGP) divisions may generate two RGPs but asymmetric divisions produce a renewing RGP and a neuron or an intermediate progenitor (IP). IPs further divide symmetrically in the subventricular zone (SVZ) to produce neurons. The basal processes of RGPs serve as a scaffold for nascent post-mitotic neurons, which migrate in a step-wise fashion coupled with changes in cell polarity, from the ventricular zone (VZ)/SVZ through the intermediate zone (IZ) in order to reach the cortical plate (CP). After nascent cortical projection neurons have delaminated from the neuroepithelium at the ventricular surface they move radially away to the SVZ exhibiting bipolar (BP) morphology. Within the SVZ/IZ, neurons "sojourn" for about 24 h or longer and most adopt a multipolar (MP) morphology, extending and retracting processes in all directions. At one point fundamental cellular polarization events take place that predetermine the future axon of the neuron before the neuron again adopts a bipolar morphology and starts locomoting along the radial glial fiber through the IZ. Once reaching the subplate (SP), neurons enter the CP and migrate towards the marginal zone (MZ) where they detach from the radial glial fiber. Finally, neurons settle in their appropriate position in the CP and the leading process will eventually become the dendrite. **(B)** This panel depicts the migrating neuron from panel **(A)** in higher detail with the leading and trailing processes which eventually become the dendrite and axon, respectively.](fncel-11-00176-g0001){#F1} Radial glia progenitors (RGPs) have been demonstrated to be the major neural progenitors in the developing cortex responsible for producing the vast majority of cortical excitatory neurons (Malatesta et al., [@B97]; Noctor et al., [@B120]; Anthony et al., [@B3]; Lui et al., [@B96]; Franco and Muller, [@B40]; Borrell and Götz, [@B12]; Taverna et al., [@B163]). The RGP division patterns and dynamics determine the number of neurons in the mature cortex. RGP cell division during mitosis occurs at the surface of the embryonic VZ and can be either symmetric or asymmetric, which is defined by the fate of the two daughter cells (Lui et al., [@B96]; Gao et al., [@B42]; Taverna et al., [@B163]; Homem et al., [@B66]). The extrinsic and intracellular signaling cues that instruct the mode of cell division are not well understood. The directional segregation of cell fate determinants such as Notch, components of the planar cell polarity signaling module, or entire centrosomes (i.e., duplicated centrioles) in dividing neural stem cells indicates however that polarized secretion and/or trafficking is a key mechanism (Wang et al., [@B176]; Lui et al., [@B96]; Paridaen et al., [@B126]; Taverna et al., [@B163]). Symmetric RGP divisions generate two RGPs to amplify the progenitor pool or two postmitotic neurons. In contrast, asymmetric divisions produce a renewing RGP and a neuron or an intermediate progenitor (IP). IPs can further divide symmetrically in the subventricular zone (SVZ) to produce neurons (Noctor et al., [@B121]; Kowalczyk et al., [@B85]). Interestingly, IPs adopt a multipolar morphology (Noctor et al., [@B121]; Kowalczyk et al., [@B85]) and it is currently not known whether the transition from bipolar (RGP) to multipolar (IP) state could correlate with, or even be instructive, for the neurogenic potential in dividing IPs. RGPs may also produce other types of transient amplifying progenitors, such as short neural precursors (SNPs; Stancik et al., [@B157]) and outer SVZ radial glial progenitors (oRGs aka basal RGs or bRGs; Fietz et al., [@B36]; Hansen et al., [@B57]; Shitamukai et al., [@B155]; Wang X. et al., [@B177]; Kelava et al., [@B80]; Betizeau et al., [@B11]; Florio et al., [@B38]; Johnson et al., [@B77]; Pollen et al., [@B132]). Although oRGs like RGPs are bipolar, they have been shown to adopt different morphological states and thus likely exhibit distinct cellular polarity since they lack apical attachment at the ventricle. Distinct oRG morphologies may reflect distinct competence states with respect to the number and types of neurons which are generated (Betizeau et al., [@B11]). Although the above studies provide a framework of stem cell polarity and lineage progression at the cellular level (Figure [1](#F1){ref-type="fig"}), the underlying molecular and biochemical mechanisms of progenitor cell polarization are still poorly defined. Polarity in Nascent Postmitotic Neurons---Implications for Neuronal Migration {#s1-2} ----------------------------------------------------------------------------- The basal processes of RGPs serve as a scaffold for nascent cortical neurons, which migrate from the VZ/SVZ through the intermediate zone (IZ), in order to reach the cortical plate (CP; Rakic, [@B135]; Evsyukova et al., [@B34]). Cortical layering occurs in an "inside-out" fashion whereby earlier born neurons populate deep layers and later born neurons occupy progressively upper layers (Angevine and Sidman, [@B2]; Rakic, [@B136]). Newly-born cortical neurons migrate, in a step-wise fashion coupled with changes in cell polarity, from the VZ/SVZ through IZ zone in order to reach the CP where they position themselves at their final location (Figure [1](#F1){ref-type="fig"}; Rakic, [@B135]; Nadarajah and Parnavelas, [@B108]; Noctor et al., [@B121]; Tsai et al., [@B169]; Marín et al., [@B99]; Hippenmeyer, [@B61]). Timelapse and videomicroscopy approaches (Tabata and Nakajima, [@B161]; Noctor, [@B119]; Tsai and Vallee, [@B168]) with the goal to trace the migration paths of individual cortical projection neurons have impressively revealed that: (1) radially migrating neurons proceed though several distinct migratory phases; (2) change their morphology and polarize along the way; and (3) adjust their mode of migration while transiting through the different zones along the radial migratory path (Nadarajah et al., [@B109]; Tabata and Nakajima, [@B160]; Noctor et al., [@B121]; Tsai et al., [@B169]; Sekine et al., [@B147]; Figure [1](#F1){ref-type="fig"}). From these observations through live-imaging, it is evident that nascent migrating neurons undergo a series of morphological changes including the depolarization and repolarization within the SVZ/IZ. The molecular mechanisms controlling these morphological transitions are poorly defined but if they are perturbed or delayed, the development of the cortical cytoarchitecture may be compromised. This is in particular relevant in humans that suffer from e.g., Lissencephaly (a severe cortical malformation disorder) where the loss of *LIS1* activity results in a defect to repolarize migrating neurons which in turn accumulate in ectopic positions instead of properly migrating into the developing CP (Tsai et al., [@B169]; Wynshaw-Boris et al., [@B184]). LIS1 is only one of many molecules which are involved in more than one cellular polarization process. As such LIS1 plays a role in neural progenitor polarization and in the establishment of polarity in postmitotic neurons. It will thus be important to precisely dissect the sequential and/or distinct functions of proteins orchestrating cellular polarity during development. Establishment of Axon and Dendrite Compartments in Cortical Projection Neurons {#s1-3} ------------------------------------------------------------------------------ After nascent cortical projection neurons, exhibiting bipolar (BP) morphology, have delaminated from the neuroepithelium at the ventricular surface they move radially away to the SVZ. Within the SVZ neurons "sojourn" for about 24 h or longer and most adopt a multipolar (MP) morphology, extending and retracting processes in all directions (Tabata and Nakajima, [@B160]; Noctor et al., [@B121]). While this stage is critical for the progression of the sequential migration program it is also essential for establishing the cellular compartments that later transform into axonal and dendritic processes. During this phase, multipolar (MP) neurons tend to migrate tangentially in an apparent random fashion (Noctor et al., [@B121]; Jossin and Cooper, [@B79]). At one point however, fundamental cellular polarization events take place that predetermine the future axon of the neuron (Barnes and Polleux, [@B7]) before the neuron again adopts a bipolar morphology (Figure [1](#F1){ref-type="fig"}). In the remainder of this review we synthesize a framework of neuronal polarization based upon *in vitro* biochemical, cell culture and genetic loss of function experiments *in vivo*. We reflect upon the relative contribution of extrinsic cues and cell-intrinsic molecular and biochemical signaling modules that dictate the break in symmetry and control polarization of cortical projection neurons. Extracellular Cues Controlling Projection Neuron Polarity in Cortex Development {#s2} =============================================================================== Developing cortical neurons can break symmetry in the absence of external cues suggesting that the role of the extracellular signals in the *in vivo* context is solely to activate/trigger an intrinsic symmetry-breaking pathway. The intrinsic signaling pathways on the other hand are dependent on the internal biochemical state of the cell (Figures [2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"} and see below for detailed discussion). Albeit cell intrinsic mechanisms have received much more attention than extracellular regulatory cues it is clear that in the developing cortex, cell-to-cell interactions, the local microenvironment and long-range signaling constitute essential factors for the establishment of projection neuron polarity *in vivo*. ![Molecular signaling pathways controlling neuronal polarization. **(A)** A simplified illustration of the biochemical network of axon determination. Only interactions localized to the nascent axon are shown. **(B)** Positive feedback loops in the process of axon determination. **(C)** Probing PIP~3~ localization and accumulation in polarizing neurons with Akt-pleckstrin-homology (PH)-GFP as a probe for PIP~3~.](fncel-11-00176-g0002){#F2} ![Table of key polarity proteins in *C. elegans* and their neuronal homologs. The localization of the nematode proteins is illustrated according to their anterior or posterior domain affiliation. In neurons the respective localization is classified according to the indicated patterns (A--C). A supernumerary axon phenotype is indicated by a plus sign, while 0 represents the absence of an axon upon overexpression or downregulation of the respective polarity protein. References describing neuronal protein systems are marked with an asterisk.](fncel-11-00176-g0003){#F3} Cell-Cell Interactions {#s2-1} ---------------------- Nascent projection neurons are embedded in a heterogeneous environment and cell-cell interactions are likely to play an important role in neuronal polarization (Jossin, [@B78]; Gartner et al., [@B43]; Namba et al., [@B113]). It has been suggested that the radial glial scaffold, on which neurons perform locomotion in the IZ, could be involved in the MP-to-BP transition. Experiments inhibiting the cell-adhesion molecule N-cadherin have shown that newly-born neurons expressing a dominant-negative form of N-cadherin establish abnormal leading processes (Gartner et al., [@B44], [@B43]). These experiments have also indicated that radial glial-neuron interactions mediated by N-cadherin play an essential role in the initial radial alignment of nascent neurons and thus possibly (albeit in an indirect manner) in the subsequent MP-to-BP transition. Interestingly, polarized N-cadherin localization has been shown to occur in a single neurite during MP-to-BP transition and thus likely represents one of the earliest consequences of the symmetry-break (Gartner et al., [@B44]). In such context, it has been proposed that the interaction of multipolar cells and RGPs mediated by N-cadherin leads to the establishment of axon-dendrite polarity through polarized distribution of active RhoA in the neurite contacting the RGC and active Rac1 on the opposite side where the axon is formed (Xu et al., [@B185]). Physical interactions between pioneering axons from earlier generated neurons and the dynamic neurites from newly born neurons have been shown to contribute to polarization in MP neurons (Namba et al., [@B114], [@B113]). These interactions involve the cell adhesion molecule transient axonal glycoprotein 1 (TAG-1). The highest expression of TAG-1 has been observed in the lower IZ (Namba et al., [@B114]), exactly where nascent neurons switch from MP-to-BP morphology. Current models propose that TAG-1 is expressed in both MP cells and pioneering axons and thus could mediate homophilic cell-cell contacts. Indeed, shRNA-mediated knockdown of TAG-1 results in the disruption of the MP-to-BP transition and axon specification. The underlying mechanism of TAG-1 action in polarization may involve: (1) an increase in physical tension in the immature neurite leading to axon induction and formation; and (2) contact-mediated activation of signaling molecules that instruct axon specification (Namba et al., [@B113]). Interestingly, N-cadherin is mainly expressed in the upper IZ (Xu et al., [@B185]) but TAG-1 in the lower IZ (Namba et al., [@B114]). Thus N-cadherin and TAG-1 could act as two separate polarity inducing cues which might work complementary in axon-dendrite formation as proposed by the Kaibuchi laboratory (Xu et al., [@B185]). Whether the induction of cellular polarization within these two distinct zones correlates with a certain neuron type (e.g., derived from either RGCs or IPs) remains to be determined. Secreted Factors {#s2-2} ---------------- ### Reelin {#s2-2-1} Newly born cortical projection neurons migrate from the VZ to the CP in order to reach their final target area (Marín et al., [@B99]; Hippenmeyer, [@B61]). A key regulatory module controlling neuronal migration includes the Reelin pathway (Honda et al., [@B67]). The function of Reelin in neuronal migration has been studied extensively for decades and several hypotheses concerning the mechanism of Reelin action have been put forward (Honda et al., [@B67]). However, it has also become clear recently that Reelin fulfills an important role in the polarization of nascent projection neurons (Jossin and Cooper, [@B79]; Jossin, [@B78]). Reelin is mainly expressed by Cajal-Retzius cells in the marginal one (MZ) in the developing cortex (Ogawa et al., [@B122]). The Reelin protein primarily binds to its two cognate receptors, very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2/LRP8; D'Arcangelo et al., [@B27]), which are mainly expressed in RGPs and nascent migrating neurons (Perez-Garcia et al., [@B128]). Binding of Reelin to its receptors triggers the activation of a Src family kinase (SFK) called Fyn which in turn phosphorylates the adaptor protein disabled-1 (DAB1; Howell et al., [@B69], [@B70]). Phosphorylated DAB1 functions as a hub for several downstream intracellular signals and has been shown to activate the effectors CRK, C3G and PI3K which in turn regulate the activity of Limk1, Akt and Rap1 to eventually modulate the dynamic cytoskeleton (Honda et al., [@B67]; Sekine et al., [@B148]). Thus the Reelin-DAB1 pathway translates extracellular cues into cytoskeletal changes in migrating neurons (Frotscher, [@B41]; Forster et al., [@B39]). How Reelin might regulate dynamic polarization events in nascent cortical projection neurons is less well understood. Interestingly however, it has been shown that while VLDLR is mainly localized on the leading processes of migrating neurons in the MZ, ApoER2 is primarily localized to neuronal processes and the cell membranes of multipolar neurons in the SVZ and lower IZ. In addition to strong expression of Reelin in the MZ, it was also demonstrated that Reelin is also expressed in the IZ at early developmental stages (Hirota et al., [@B63]). *Ex vivo* experiments where exogenous Reelin was added to cultured brain slices have shown an effect on the morphology and dynamic behavior of nascent neurons in the IZ (Britto et al., [@B14]). Thus, based on the expression pattern of Reelin and its cognate receptors it is conceivable that Reelin could play a prominent role during the polarization process of nascent cortical projection neurons. Indeed, Jossin and Cooper propose a three step model (Jossin and Cooper, [@B79]) how Reelin controls the radial orientation of multipolar neurons in SVZ/IZ. First, multipolar neurons migrate tangentially in a stochastic manner in the SVZ/IZ until they encounter Reelin which leads to the activation of the small GTPase RAP1, likely via pDAB1-CRK/CRKL-C3G signaling (Ballif et al., [@B6]; Voss et al., [@B172]). Next, active RAP1 triggers an increase of the surface level of N-Cadherin in multipolar neurons. These increased cell surface levels of N-Cadherin could then allow the multipolar neurons to sample local microenvironmental cues which then could initiate the break in symmetry and induce polarization. The cortical projection neurons then progressively exit the multipolar stage and adopt a bipolar morphology (Jossin, [@B78]; Jossin and Cooper, [@B79]). Altogether, the above data and model indicates that Reelin acts as a critical cue for the directional movement of nascent migrating cortical projection neurons and could serve as a critical extracellular cue for modulating polarization of nascent migrating cortical projection neurons. It will be intriguing to decipher the precise intracellular and biochemical signaling pathways controlling RAP1-dependent N-Cadherin trafficking and how N-Cadherin-dependent signaling triggers the break in symmetry. ### Neurotrophins {#s2-2-2} Brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are highly expressed in the developing brain and have been shown to stimulate axon specification and elongation (Morfini et al., [@B105]; Nakamuta et al., [@B112]). Both, BDNF and NT-3 as extracellular regulators of neuronal polarity are of special interest since they act in an autocrine and/or paracrine manner in cell-culture (Nakamuta et al., [@B112]). This feature indicates that neurons are able to produce extracellular stimuli (in form of secreted neurotrophins) that activate the intrinsic machinery for axon-dendrite specification in a cell-autonomous and non-cell-autonomous manner. BDNF and NT-3 bind to tropomyosin related kinases receptors (TRK), TRK-B and TRK-C respectively (Chao, [@B17]). Upon TRK receptor binding, the small GTPase Ras and PI3K are activated. This leads to the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP~3~) and the activation of its downstream signaling pathways (Reichardt, [@B137]). Neurotrophin signaling through TRK receptors also leads to increased levels of inositol triphosphate (IP3)-induced calcium release which in turn activates the calmodulin-dependent protein kinase kinase (CaMKK) and calmodulin-dependent protein kinase I (CamKI; Nakamuta et al., [@B112]). The activation of CaMKK and CamKI triggers the phosphorylation of microtubule affinity regulating kinase 2 (MARK2). This leads to the phosphorylation of downstream microtubule associated proteins (MAPs) MAP2/4, Tau and DCX which reduces microtubule stability (Drewes et al., [@B31]; Schaar et al., [@B144]; Nakamuta et al., [@B112]). Interestingly, acute knockdown of MARK2 has been shown to stall MP-to-BP transition in the IZ in mice (Sapir et al., [@B140]). Thus, proper regulation of MARK2 appears to be essential for neuronal polarization *in vivo*. BDNF signaling via TrkB has been demonstrated in culture experiments to lead to the activation of LKB1 (liver kinase b1 in mammals and PAR-4 in *C. elegans* (Figures [2](#F2){ref-type="fig"}, [3](#F3){ref-type="fig"}; Shelly et al., [@B150]). Loss of function of LKB1 either by genetic knockout or knockdown by shRNA in nascent cortical projection neurons results in striking phenotypes: axon specification is completely abolished while the dendrite appears to still be specified (Barnes et al., [@B8]; Shelly et al., [@B150]). In contrast, overexpression of LKB1 in neural progenitors and postmitotic neurons lead to formation of multiple axons. In a biochemical pathway downstream of BDNF/TrkB, LKB1 is phosphorylated by protein kinase A (PKA) or ribosomal S6 kinase (p90RSK) at Serine 431 (Collins et al., [@B24]; Sapkota et al., [@B141]). Phosphorylated LKB1 leads to downstream activation of MARK2 (Shelly et al., [@B150]) and the SAD kinases which in turn phosphorylate Tau-1 (Kishi et al., [@B82]; Barnes et al., [@B8]). Remarkably, SAD-A/B double knockout precisely mimic the LKB1 loss of function phenotype with complete absence of the axon (Kishi et al., [@B82]). In summary, the above studies established a model whereby BDNF signaling via TrkB results in the activation of LKB1 which is translated into an intracellular symmetry break in multipolar cortical projection neurons while sojourning in the SVZ/IZ. Phosphorylated LKB1 localizes into the nascent axon and is required for axon extension and development. It will be interesting to determine the extent of specificity and functional redundancy of individual downstream components along the BDNF/TrkB-LKB1-SAD-A/B signaling module while executing the break in symmetry. ### Semaphorins {#s2-2-3} Semaphorins consist of a large family of membrane bound or secreted proteins (Nakamura et al., [@B110]). The secreted semaphorin, Sema3A have been shown to act as a chemotactic factor for migrating cortical projection neurons (Polleux et al., [@B133]; Chen et al., [@B19]). Sema3A expression is highest near the pial surface in the developing cortex and the Sema3A expression domain establishes a descending gradient across the emerging cortical layers (Polleux et al., [@B133]; Chen et al., [@B19]). Sema3A binds its co-receptors Plexin and Neuropilin (Negishi et al., [@B115]) and it has been suggested that Sema3A may actively control the process of symmetry breaking and cellular polarization. Sema3A activates a number of downstream cascades resulting in the tuning of relative levels of cGMP and cyclic adenosine 3′,5′-monophosphate (cAMP) which negatively affects axon formation by downregulation of PKA-dependent phosphorylation of LKB1 (Shelly et al., [@B151]). Interestingly, exposure of undifferentiated neurites to local sources of Sema3A in hippocampal neuron cell culture leads to the suppression of axon-formation but promotion of dendrite formation in culture conditions (Shelly et al., [@B151]). Strikingly, *in vivo* knockdown of the Sema3A receptor neuropilin-1 in rat embryonic cortical progenitors results in severe polarization defects. Furthermore, Sema4D inactivates Ras (Oinuma et al., [@B124]) while it activates RhoA (Swiercz et al., [@B159]) which prevents axon formation and/or outgrowth via reduced actin dynamics and actin contraction. Thus, Sema3A acting via the neuropilin-1 receptor and semaphorins in general are critically involved in the symmetry break and polarization of nascent projection neurons in the developing cortex (Shelly et al., [@B151]). ### TGF-β {#s2-2-4} The transforming growth factor β (TGF-β) has been reported to play an important role in the polarization of nascent cortical projection neurons in the developing cerebral cortex (Yi et al., [@B188]). Upon binding of one of the three TGF-β ligands (TGF-β1-3) to the type II TGF-β receptor (TβR2), this receptor is recruited to the type I TGF-β receptor (TβR1) to form a complex which triggers the phosphorylation of the two receptors by the serine/threonine kinase domain (Shi and Massagué, [@B153]). The TβR2-TβR1 receptor complex has been shown to phosphorylate Par-6 which in turn regulates Cdc42/Rac1 activity by recruiting the ubiquitin ligase Smurf1 which promotes proteasomal degradation of the RhoA GTPase. This results in reduced activity of RhoA in the nascent axon thereby stimulating its outgrowth (Gonzalez-Billault et al., [@B51]). Thus, RhoA activity can be precisely regulated in response to TGF-β signaling thereby controlling the dynamics of the local actin organization which is essential for axon specification and thus cellular polarization (Yi et al., [@B188]). Interestingly, TGF-β2-3 is highly expressed near the VZ/SVZ. Thus nascent developing neurons could be exposed to a gradient which delivers a uniform stimuli for axon specification (Yi et al., [@B188]). However, the majority of MP neurons extend their axons tangentially (Hatanaka and Yamauchi, [@B59]) rather than towards the ventricular side. It is thus conceivable that TGF-β might only act as a stimulus for axon specification rather than an axon guidance cue (Yi et al., [@B188]). Bone morphogenic protein (BMP), also a member of the TGF-β superfamily appears to play important functions in the MP-to-BP transition as well. BMPs are known to signal via the intracellular downstream mediator SMAD which leads to the suppression of collapsin response mediator protein 2 (CRMP2), a transcription factor known to promote microtubule assembly (Shi and Massagué, [@B153]; Sun et al., [@B158]). Strikingly, upon suppression of CRMP2 or overexpression of dominant negative forms of CRMP2 multipolar cells accumulate in the SVZ/IZ in the developing cortex. While these findings suggest that a BMP-SMAD signaling pathway, via CRMP2, regulates the polarization of cortical projection neurons the precise molecular and biochemical mechanisms remain to be determined (Sun et al., [@B158]). Altogether, different members of the TFG-β superfamily play important roles in multipolar cortical neurons and direct neuronal polarization through distinct signaling pathways. Intrinsic Biochemical Networks That Mediate Neuronal Polarity {#s3} ============================================================= While the above sections illustrated the role of extracellular cues for triggering and/or execution of neuronal polarization, the intrinsic molecular mechanisms involved in symmetry breaking will be discussed in the sections below with a focus on *in vitro* and cell culture experiments. Isolated neurons in cell culture form one axon and several dendrites. External chemical or physical cues of instructive or antagonistic nature that determine axon formation have been identified (Lamoureux et al., [@B88]; Gomez et al., [@B49]; Shelly et al., [@B151]). However, cultured neuronal cells are able to polarize even in the absence of any external cue (Dotti et al., [@B30]) suggesting that cells have intrinsic ability to break symmetry, which is solely activated externally. What are the functional cell-intrinsic networks that underlie cell polarization and determine the biochemical state of the cell? Based on Turing's idea of a reaction-diffusion mechanism to explain how spatial order during embryogenesis may arise (Turing, [@B170]), Gierer and Meinhardt developed a conceptual framework for pattern formation, which is based on the local activation in the form of self-enhancing feedback, which amplifies and reinforces spatially asymmetric distributions of molecules, coupled to long-range inhibitory processes (Meinhardt and Gierer, [@B100]). While this concept was originally developed to explain spatial patterning during morphogenesis, it also provides a framework to understand cell polarity. Accordingly, cell polarization is seen as a self-organized process (Wennekamp et al., [@B180]), which involves local symmetry breaking, signal amplification and long-range inhibition (Wang, [@B173]; Chau et al., [@B18]). Previous work was able to identify many molecular players involved in the processes that allow a neuron to choose the one neurite to become an axon (Barnes and Polleux, [@B7]). While cell polarization can theoretically arise from a single molecular species that features a positive feedback (Altschuler et al., [@B1]), symmetry breaking in neurons likely reflects interactions among multiple, partially redundant pathways with crosstalk among them (Namba et al., [@B113]). This network can be subdivided into several, partially overlapping modules, each of which comprises a subset of molecular players that encode for specific cellular functions. To a rough approximation, the output of one module can serve as the input for a module downstream. Here, we want to illustrate how these functional modules orchestrate neuronal polarization and how they are embedded in a more complex biochemical network giving rise to axon specification. Importantly, individual modules are often evolutionarily conserved among species and pathways that regulate cell polarization in seemingly distinct tissues and contexts are remarkably similar. Accordingly we can to some degree take advantage of known cell polarization concepts in yeast, *C. elegans* and migrating cells (Iden and Collard, [@B71]), with the goal to anticipate a better understanding of the molecular processes that underlie axon specification. PIP/PI~3~K Module {#s3-1} ----------------- Molecules involved in the initial symmetry breaking event are commonly localized to the plasma membrane, where not only integral membrane proteins receive extracellular signals, but where also peripherally binding membrane proteins bind reversibly to the membrane (Cho and Stahelin, [@B23]). This restricts the diffusion of these proteins, increases the efficiency of protein-protein interactions and/or modulates their catalytic activity (Vaz et al., [@B171]; Leonard and Hurley, [@B92]; Ebner et al., [@B32]). As a result, the membrane can be interpreted as a computational platform where transient protein clusters integrate, interpret and amplify incoming biochemical signals (Groves and Kuriyan, [@B53]). One component of membrane-based signaling pathways that was found to be essential for the establishment of intracellular organization include phosphoinositides (PIPs). Even though they represent only about 1% of membrane phospholipids (Di Paolo and De Camilli, [@B29]), the associated signaling pathways control cell growth, division, survival and differentiation, and allow to generate highly polarized neuronal morphologies such as growth cones and synapses (Sasaki et al., [@B143]). Cells use a precisely defined spatiotemporal distribution of PIPs to control the activity of intracellular signaling pathways. For cell polarity, it is the asymmetry of phosphatidylinositol-3,4,5-phosphate (PI(3,4,5)P~3~ = PIP~3~) at the plasma membrane that is used to establish a polarity axis in the cell. The intramembranous PIP~3~ concentration is controlled by activation of the phosphoinositide-3-kinase (PI3K; Whitman et al., [@B181]) as well as phosphatases such as phosphatase and tensin homolog (PTEN; Lee et al., [@B91]) that directly antagonize PI3K by dephosphorylating PIP~3~ to PI(4,5)P~2~ (PIP~2~) (Carracedo and Pandolfi, [@B16]). Overexpression of PTEN or inhibition of the PI3K were both found to abolish cell polarization and axon specification (Shi et al., [@B152]; Jiang et al., [@B74]). In contrast, reduction of PTEN expression results in neurons with multiple axons (Jiang et al., [@B74]). Together, these results demonstrate that the activities of these enzymes need to be tightly balanced to produce one and only one axon. Since polarization is a dynamic spatiotemporal process, not only the total amount of phosphoinositides but also their distribution in space and time needs to be precisely regulated. In cells, the intracellular distribution of PIP~3~ can be visualized using a fluorescent reporter protein that specifically binds to PIP~3~; e.g., GFP fused to the Pleckstrin-homology (PH) domain of the serine/threonine kinase Akt (Gray et al., [@B52]). This probe visualized PIP~3~ accumulation at the tip of a neurite contributing to neuronal polarity and axon specification (Ménager et al., [@B101]). In contrast, EGFP-PLCd1-PH, which binds to PI(4, 5)P2 or IP3 showed a homogeneous distribution in cultured neuronal cells (Ménager et al., [@B101]). The localized accumulation of PIP~3~ likely represents the first spatial landmark that establishes the polarity axes of the cell. *In vivo*, activity of PI3K and PIP~3~ production is most likely regulated by asymmetric distribution of extracellular factors (Namba et al., [@B113]), still, neurons polarize in cell culture without obvious asymmetries in their environment (Dotti et al., [@B30]). This suggest that starting from a homogeneous distribution of signaling molecules, dedicated biochemical circuits are able to amplify small fluctuations of signaling lipids in the plasma membrane. These interactions eventually break the symmetry of the cell and control cell morphogenesis (Wennekamp et al., [@B180]). The biochemical network underlying phosphoinositide polarity was studied in detail in other model systems. For example, *Dictyostelium discoideum* cells (Malchow et al., [@B98]), leukocytes and neutrophils (Trepat et al., [@B167]) polarize in response to a gradient of the chemoattractant cAMP or a variety of chemokines respectively by establishing domains of different phosphoinositides: PIP~3~ at the leading edge of the cell and PIP~2~ at its tail (Petrie et al., [@B129]). Importantly, and similar to neurons, the ability to break symmetry is independent from directional sensing, as cells that are placed in a uniform distribution of chemoattractant are still able to polarize (Petrie et al., [@B129]). Again, this illustrates the intrinsic ability of biochemical networks to polarize the cell in the absence of exogenous spatial signals (Wedlich-Soldner and Li, [@B179]). While phosphoinositide signaling was found to spatially organize the actin cytoskeleton, the initial symmetry breaking event itself does not depend on actin filaments. Fluorescently-labeled PH~Akt~ and PTEN, which acted as probes for PIP~3~ and PIP~2~ respectively, were found to self-organize into traveling waves in *Dictyostelium discoideum* cells even in the presence of the actin polymerization inhibitor latrunculin A (Gerisch et al., [@B46]). Importantly, this finding indicates that the ability to break symmetry in the membrane is established upstream and independent of the cytoskeleton. Instead, a PIP~3~-dependent negative regulation of PTEN recruitment to the membrane was suggested to allow PIP~3~ to accumulate. In addition, PTEN localization and activity has been found to be dependent on the small GTPase RhoA, which was found to restrict PTEN to the rear of chemotaxing leukocytes (Li et al., [@B93]) and *Dictyostelium* cells. Arai et al. ([@B4]) further suggest a Ras-dependent positive feedback of PI3K activity to stabilize the polarized state of the cell. In addition, negative regulation of PTEN activity downstream of the PIP~3~ activated AKT kinase has been reported, which constitutes a parallel mechanism to maintain and stabilize polarity (Papakonstanti et al., [@B125]). While phosphoinositides are the most important lipid species for cellular signaling there are also other lipid species involved in neuronal polarization: plasma membrane ganglioside sialidase (PMGS), which controls the ganglioside content in the plasma membrane of neurons was also found to show an asymmetric distribution of its activity: it is enriched in one of the stage 2 neurites and facilitates axon outgrowth by enhancing Rac and PI3K activity (Da Silva et al., [@B26]). Thus, the asymmetric distribution of two different kinds of lipid species appears to control the polarity of the cell. GEFs and Small GTPases {#s3-2} ---------------------- Which biochemical circuits underlie signal amplification in neurons? By now, the identity of several PI3K-dependent GTPases involved in neuronal polarization is known, such as H-Ras (Yoshimura et al., [@B191]), Cdc42 (Garvalov et al., [@B45]) or Rap1B (Schwamborn and Püschel, [@B146]; Nakamura et al., [@B111]). Similar to PI3K (Shi et al., [@B152]) their overexpression results in supernumerary axons (see Figure [3](#F3){ref-type="fig"}), while their knock down prevents axon formation (Schwamborn and Püschel, [@B146]; Yoshimura et al., [@B191]; Garvalov et al., [@B45]; Nakamura et al., [@B111]), however, these proteins do not interact with PIP~3~ themselves. Instead, the phosphorylation state of phosphoinositides in the plasma membrane is recognized by soluble guanine nucleotide exchange factors (GEFs) that contain PIP3 binding domains, such as GEFs of the Dbl and DOCK180 families (Rossman et al., [@B139]; Laurin and Côté, [@B89]). These protein families in turn activate GTPases while recruiting them to the membrane (Cherfils and Zeghouf, [@B22]). Though a systematic characterization of GEFs that directly interact with PIP~3~ and control cell polarization is not complete yet, candidate proteins include SOS and RasGFR, both members of the Dbl family of GEFs that contain a canonical DH-PH domain structure (Zheng, [@B193]). The PH (Pleckstrin homology) domain binds to phosphoinositides and thereby controls localization and the DH (Dbl homology) domain is responsible for catalyzing nucleotide exchange (Zheng, [@B193]). Dock7, a Dock180 related protein that catalyzes the nucleotide exchange of Rac1 (Watabe-Uchida et al., [@B178]), was found to specifically bind PIP~3~ via its DHR-1 domain (Kobayashi et al., [@B84]; Cote et al., [@B25]). Importantly, Dock7 is enriched in one of the stage 2 neurites---potentially the designated axon---supposedly controlling polarization and morphogenesis of the neuron (Watabe-Uchida et al., [@B178]). Controlled by these regulators, small GTPases can show phosphoinositide dependent activity patterns and a characteristic spatial distribution in the cell. However, direct evidence that GEF enrichment is a direct consequence of elevated PIP~3~ levels in a stage 2 neurite is largely missing. Accordingly, the spatial distribution of GEFs could also depend on another PIP~3~ binding protein which is recruited to and initiates a nascent axon. As a result of their activation, GTP-bound GTPases engage in specific protein-protein interactions. By recruiting so-called effector proteins to the plasma membrane small GTPases determining the spatiotemporal activation pattern of other protein systems in the cell (Cherfils and Zeghouf, [@B22]). Effector proteins can be categorized in two classes: first, they can control cell morphology by directly acting on regulators of the actin or microtubule cytoskeleton, namely by increasing actin dynamicity and microtubule stabilization in the axon while stabilizing actin filaments in dendrites (Neukirchen and Bradke, [@B117]). For example, activation of Rac1 leads to a stabilization of axon microtubules via the stathmin pathway (Watabe-Uchida et al., [@B178]) while triggering actin remodeling (Hall et al., [@B56]; Gonzalez-Billault et al., [@B51]). In contrast, active RhoA promotes actin stabilization and contraction in dendrites as revealed by fluorescent activity sensors (Gonzalez-Billault et al., [@B51]). Second, effector proteins can be involved in the regulation of other small GTPases (DerMardirossian et al., [@B28]) or constituents of supramolecular complexes with various functions (Joberty et al., [@B75]; Lin et al., [@B94]). For example, they can act as coincidence detector for multiple binding partners (Carlton and Cullen, [@B15]) or signal to additional levels of regulation. For example, a common theme for the activation of small GTPases is that they comprise positive feedback loops. These self-amplifying circuits may not only lead to a local enrichment of GTPases on the membrane, but can also lead to collective, switch-like activation of proteins (Mizuno-Yamasaki et al., [@B103]). Accordingly, these kind of interactions can give rise to nonlinear signaling circuits with emergent properties, which can be crucial for breaking the symmetry and spatially organizing the cell (Yoshimura et al., [@B190]). The importance of positive feedback regulation for the symmetry breaking is probably best characterized in single-cell organisms such as yeast (Johnson et al., [@B76]). Despite the much lower complexity of this model organism, the general architecture of the biochemical network leading to cell polarization is most probably similar. In yeast, Cdc42 is the main spatial organizer of the cell as it regulates asymmetric cell division. Active, GTP-bound Cdc42 binds to the plasma membrane via its prenylated C-terminus, while GDP-bound Cdc42 is kept soluble in the cytoplasm via its interaction with its Guanosine nucleotide dissociation inhibitor (GDI) Rdi1. Cdc42-GTP is thought to form a locally confined protein cluster on the membrane by a local amplification of spontaneous asymmetries. The positive feedback is thought to arise from an effector-GEF complex, where the activated GTPase recruits an effector protein that in turn interacts with its activator. In yeast, a small, transient patch of Cdc42-GTP would recruit the scaffolding protein Bem-1 to the membrane, which interacts with the Cdc42 GEF Cdc24. Bem-1 not only binds to Cdc24 but also boosts its GEF activity. Thus Bem-1 efficiently catalyzes proximal Cdc42-GDP to exchange their nucleotide to Cdc42-GTP which again is able to recruit more Bem-1-Cdc24 complex (Nern and Arkowitz, [@B116]; Gulli et al., [@B54]; Johnson et al., [@B76]). Effector-GEF interactions have been found to be involved for the regulation of many different small GTPases (Mizuno-Yamasaki et al., [@B103]) and might be generally required for collective, switch-like activation of GTPases. These kind of decisive signaling reactions are of crucial importance for the cell, as they not only lead to cell polarization, but also regulate other fundamental processes such as membrane trafficking and the dynamic properties of the actin and microtubule cytoskeletons, thereby controlling the morphogenesis of the cell. While the role of many proteins involved in neuronal polarity has been studied in neuronal cell culture, the function of Cdc42 has also been studied *in vivo* (Garvalov et al., [@B45]). Only about 30% of neurons derived from Cdc42 null mice were able to form a Tau-1 positive axon and the activity levels of the actin regulator cofilin were disturbed. However, when axon formation in Cdc42 null cells was initiated by cytochalasin, axons formed even if the drug was washed away. This indicates that Cdc42 is needed for the initial steps of axon specification but is dispensable for axon outgrowth (Garvalov et al., [@B45]). The PAR System {#s3-3} -------------- During cell polarization, the asymmetric distribution of phosphoinositides provides an initial signal to a number of protein systems that together control cell morphogenesis. One of those protein systems is the PAR system, which is recruited downstream of activated Cdc42 (Etienne-Manneville and Hall, [@B33]; Yamanaka et al., [@B186]; Nishimura et al., [@B118]). The PAR system is a set of highly conserved proteins that organize cell polarity in all metazoan cells. In neurons, it was found that the PAR system is required for axon dendrite polarity (Shi et al., [@B152]; Chen et al., [@B21]), migration (Sapir et al., [@B140]) and dendrite development (Terabayashi et al., [@B164]). However, a complete mechanistic characterization of how these proteins regulate axon formation is missing. The PAR system is probably best studied in the nematode *Caenorhabditis elegans*, where it controls the first division. In a single cell embryo, the PAR proteins self-organize into two non-overlapping domains (anterior and posterior domain) to govern asymmetric spindle positioning and ultimately the generation of daughter cells with different fate (Kemphues et al., [@B81]; Gönczy and Rose, [@B50]). The PAR proteins have been categorized in anterior PARs (aPARs; PAR-3, PAR-6, PKC-3, cdc42) and posterior PARs (pPARs; PAR-2, PAR-1, LGL-1), all of which are peripheral membrane proteins. Their mutual exclusion is thought to arise from cross-phosphorylation by the two kinases PKC-3 and PAR-1, which leads to membrane detachment, controls oligomerization state and hence their diffusivity (Feng et al., [@B35]; Hoege and Hyman, [@B64]; Arata et al., [@B5]). PKC-3 can phosphorylate all posterior PARs (Hao et al., [@B58]; Hoege et al., [@B65]), in return, PAR-1 phosphorylates PAR-3 (Guo and Kemphues, [@B55]; Benton and St Johnston, [@B10]; Motegi et al., [@B107]). A network of regulatory biochemical interactions between aPARs and pPARs is thought to finely tune the activity of these kinases, leading to two dynamically stable cellular domains that govern a plethora of downstream events (Goehring, [@B47]). Apart from PAR-2, the PAR system is conserved among most multicellular organisms and defines polarity via mutual exclusion in different contexts such as anterior-posterior polarity in *Drosophila* oocytes and apical-basal polarity in epithelial tissues (Morton et al., [@B106]; Goldstein and Macara, [@B48]; Thompson, [@B165]). The overall importance of the PAR system for axon dendrite polarity was firmly established in dissociated hippocampal cell culture system and enrichment of anterior PARs at the tip of the outgrowing axon has been observed (Shi et al., [@B152]). Subsequent knock down or overexpression studies of several PAR members showed that genetic manipulation of the PAR system either results in no or supernumerary axons (Figure [3](#F3){ref-type="fig"}). If mutual exclusion among aPARs and pPARs is a universal feature of the PAR system one would expect the posterior PAR-1 homolog MARK2 to be absent from the tip of the axon. Surprisingly, fluorescence sensors to measure MARK2 activity in the developing axon of cortical neurons showed highest kinase activity in the growing axon tip (Moravcevic et al., [@B104]; Timm et al., [@B166]). This indicates that both active PAR-1 kinases and aPARs are co-localizing at tip of the outgrowing axon and mutual exclusion of the "opposing" PAR complexes is not a requirement for axon dendrite polarity establishment. On a functional level, antagonism between MARK2 and the aPAR complex has been suggested (Chen et al., [@B21]). Analog to the *C. elegans* system, aPKC phosphorylates MARK2, which results in membrane detachment and most likely in reduced activity. Overexpression of MARK2 in hippocampal neurons prevented axon formation while knock down caused multiple axons (Chen et al., [@B21]; Wu et al., [@B183]). The opposite was seen for aPKC overexpression, which resulted in multiple axons (Figure [3](#F3){ref-type="fig"}; Parker et al., [@B127]). The overexpression phenotype of MARK2 was rescued by simultaneous overexpression of aPARs. No rescue was observed with a non phosphorylatable MARK2, indicating that direct inhibition of MARK2 by aPKC is responsible for the observed rescue. In a simple view, this could mean that MARK2 is a negative regulator of axon formation which is specifically inhibited by axon enriched aPARs via aPKC phosphorylation. However, *in vivo* knock out of the other PAR-1 homologs (SAD-kinases) also inhibited axon formation (see also above), indicating that a fine balance between these activities is needed (Kishi et al., [@B82]). Both, MARK2 and SAD kinases have to be activated by LKB1/PAR-4 (Lizcano et al., [@B95]; Shelly and Poo, [@B149]), which itself is downstream of cAMP/PKA signaling (Shelly et al., [@B150]). Thus, the PAR system not only translates PIP~3~ dependent signaling into altered cytoskeleton dynamics but also integrates the input of heterotrimeric G protein receptor ligands. Interestingly and in contrast to *C. elegans*, LKB1/PAR-4 is enriched in the axon (Shelly et al., [@B150]) while it is homogenously distributed in the *C. elegans* zygote (Goehring, [@B47]). Knockdown of LGL-1 prevents axon formation but the precise role of LGL-1 in axon development is still poorly understood (Plant et al., [@B131]; Wang T. et al., [@B175]). Another fundamental difference between the neuronal and nematode PAR system is their dependence on a previous symmetry breaking event. In *C. elegans*, the sperm entry marks a single symmetry breaking event that starts actomyosin based flows and facilitates PAR domain establishment whereas no asymmetries of PIP~3~ have been reported. The PAR system in neurons is clearly downstream of regulators that directly control or are controlled by PIP~3~, such as PI3K or ATK/GSK3b, Cdc42 and Rap1B (Insolera et al., [@B72]), whereas initial polarity formation in *C. elegans* does not depend on these PIP~3~ controlled proteins (Schlesinger et al., [@B145]; Insolera et al., [@B72]). A possible explanation for this difference could be that neurons have to screen their environment during development (open systems) to remain a certain degree of plasticity while communication with the extracellular space is less important in the early stages of worm development. Thus, the PAR system is integrated into a more complex signaling network in neurons while it constitutes a rather autonomous polarity system in *C. elegans*. Since many PAR system intrinsic reactions (like phosphorylation events) seem to be conserved, it is still not clear how these reactions have to occur in space and time in neurons for faithful axon dendrite polarity establishment. Super resolution microscopy and higher temporal resolution of simultaneous activity monitoring of PARs and PIP~3~ may be required to solve the question of how PARs fulfil their functions during neuronal development. Closing the Loop {#s3-4} ---------------- So far, we have only considered biochemical reactions downstream of an initial asymmetry of PIP~3~. For robust symmetry breaking, a self-enforcing loop is required, which would give rise to a local accumulation of PIP~3~ despite its rapid diffusion in the plasma membrane and the proteins in the cytoplasm. One possible functional network could originate from PIP~3~ and at the same time further increase its local concentration on the membrane. Therefore, the described functional modules need to talk to each other and eventually feed back to the activity of PI3K. The molecular players involved for this regulatory network could for example be GTPases or their GEFs and effector proteins, which would not only translate local PIP~3~ enrichment into altered cytoskeleton dynamics and transport, but themselves further enhance the activity of PI3K. For example, Ras-GTP (Sasaki et al., [@B142]) and Rac1-GTP (Srinivasan et al., [@B156]) in combination with actin polymerization (Peyrollier et al., [@B130]; Wang et al., [@B174]) or via additional players like the Par6/Par3 aPKC complex where found to activate PI3K (Motegi et al., [@B107]; Laurin and Côté, [@B89]). Indeed, these proteins were all found to be required for axon formation (Shi et al., [@B152]; Yoshimura et al., [@B191]; Tahirovic et al., [@B162]). H-Ras is a direct activator of PI3K and is also activated downstream of PI3K (Rodriguez-Viciana et al., [@B138]; Yang et al., [@B187]). Interestingly, this feedback loop results in H-Ras translocation via vesicle based transport into the future axon, which depletes H-RAS from the other neurites, presumably leading to reduced PI3K activity in other neurites and subsequently to inhibition of their outgrowth (Fivaz et al., [@B37]). While the idea of this amplifying circuit is at least partially based on experimentally verified protein-protein interactions, the emergent properties of this network have not been tested yet. For example, the role of PTEN localization and activity for phosphoinositide polarization in neurons is not yet clear (Kreis et al., [@B86]) and there might be functional networks that involve either less or a different set of molecular players. Furthermore, the connectivity of those circuits could even change with time, different extracellular inputs or in different subcellular locations. Another layer of regulation can also be performed on the level of GDP dissociation inhibitors (GDIs), whose main function is to maintain their target, lipid-modified GTPases in an inactive, soluble state (Cherfils and Zeghouf, [@B22]). There is evidence that the affinity of RhoGDIs for different GTPases can be modulated by phosphorylation. For example, the kinase PAK1 is an effector protein of Rac1 that was found to phosphorylate RhoGDIs (DerMardirossian et al., [@B28]). Phosphorylation of these GDIs can enhance the dissociation of Rac1 from the GDI complex, thereby increasing the rate of Rac1 activation. As this leads to further stimulation of PAK1 activity such interaction may give rise to another positive feedback and symmetry breaking in neurons (Figure [2B](#F2){ref-type="fig"}). Finally, and in addition to molecular processes that depend on locally confined phosphorylation and dephosphorylation of PIPs, PIP~3~ can also accumulate in the outgrowing axon with the help of directed microtubule-based transport. For example, the plus-end directed kinesin-like motor Gakin transports PIP~3~-containing vesicles through the interaction with the adaptor protein α-centaurin (Horiguchi et al., [@B68]). MARK2, a homolog of PAR-1, inhibits this transport by phosphorylating Gakin thereby preventing the development of axons (Yoshimura et al., [@B192]). MARK2 itself is deactivated by the PIP~3~-regulated kinase aPKC (Chen et al., [@B21]; Ivey et al., [@B73]). Thus a high local PIP~3~ concentration could inhibit MARK2 in the axon shaft, further enhancing directed transport of PIP~3~-containing vesicles to the growth cone. Accordingly, this could result in a self-perpetuating feedback loop supporting axon outgrowth (Yoshimura et al., [@B192]). Collectively, these feedback loops stabilize polarity that can arise from short-lived local concentration fluctuations of external signals, temporal fluctuations in the output signal strength of receptors (Ladbury and Arold, [@B87]) or subtle heterogeneities on a coverslip. These small differences then lead to high and persistent activity of modulators that favor actin dynamicity and microtubule stability in the designated axon. Studies using drugs that either stabilized microtubules (Witte et al., [@B182]) or destabilized actin filaments (Bradke and Dotti, [@B13]) are sufficient to induce the formation of multiple axons, consistent with the view that the effects of the above mentioned circuits are transmitted via selective modulation of the cytoskeleton. In particular, these are the MARK2/SAD target and microtubule stabilizing tau proteins, microtubule destabilizers such as stathmin, actin dynamics modulators cofilin and WAVE and/ or inactivation of regulators that prevent axon outgrowth such as the RhoA/Rock module. This ultimately gives rise to a permanent molecular difference between axon and dendrites that will later on be manifested in a functional/electrophysiological difference of the two compartments, axon and dendrites. How this compartmentalization is maintained is not well understood and probably also relies on long range inhibitory signals, but future research will be needed to entangle the exact communications of these compartments during neuronal development. Conclusion and Perspectives {#s4} =========================== The phenomenon of neuronal polarization has been extensively studied in the last decades. Many of the analyses used the elegant cell culture system developed by Dotti et al. ([@B30]). Thus the current model of neuronal polarization is to a large extent based on single hippocampal cells in an isolated system. Still, these extensive *in vitro* biochemical and cell biological analyses have provided a solid understanding of the general principles of cell polarization. A key question however remains: what are the cell-intrinsic biophysical and molecular mechanisms that induce the initial break in symmetry in cortical progenitor cells and developing cortical projection neurons *in vivo*? In order to address this question it will be essential to establish tools that allow the visualization and/or manipulation of the precise localization of molecular markers at high resolution in an *in situ* tissue context. The CRISPR-Cas9-dependent SLENDR method promises a high-throughput platform to visualize the endogenous localization of candidate proteins at high micro- to nanometer resolution (Mikuni et al., [@B102]). Given that a number of "polarity signaling systems" seem quite sensitive to perturbation and not particularly resilient, the precise determination of "polarity gene" function at distinct stages in development represents a current challenge in the field. In order to probe the function of genes encoding regulators of neuronal polarity *in vivo*, the genetic mosaic analysis with double markers (MADM) technology (Zong et al., [@B194]; Hippenmeyer et al., [@B62]; Hippenmeyer, [@B60]) offers an experimental opportunity. By exploiting MADM, one can induce sparse genetic mosaics with wild-type and mutant cells labeled in two distinct colors at high resolution. In combination with live-imaging such an experimental MADM paradigm enables: (1) the dissection of the cell-autonomous gene function; and (2) determination of the relative contribution of non-cell-autonomous effects *in situ* at the global tissue level (Beattie et al., [@B9]). Altogether, the experimental platforms above promise a robust approach to determine the so far unknown functions of regulators implicated in the polarization process of progenitor cells and nascent cortical projection neurons. A key open question in a functional context is: what is the level of redundancy and specificity in extracellular cues and intracellular amplification mechanisms? Interestingly, the process of MP-to-BP transition appears to involve not only dynamic cytoskeletal-associated processes but also regulation at the transcriptional level (Hippenmeyer, [@B61]; Ohtaka-Maruyama and Okado, [@B123]). It will be important to analyze transcriptional responses at high temporal resolution and evaluate the influence on the general biochemical cell state. In future experiments it will be also important to establish biochemical and biophysical methods and assays that should allow the precise analysis of the break in symmetry at high molecular and/or structural resolution. In a broader context it will be important to address the question whether cell-type diversity may imply the necessity for adaptation in the mechanisms controlling polarization? In other words, how conserved is the process of symmetry break and polarization in distinct classes of neurons with different morphologies? The future analysis of the core signaling modules controlling cell polarity in a variety of brain areas and at high cellular and molecular resolution promises great conceptual advance. Author Contributions {#s5} ==================== AHH, CD, CM, ML and SH contributed equally to the writing of the initial draft. All authors revised the manuscript. Conflict of Interest Statement {#s6} ============================== The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This work was supported by IST Austria institutional funds; the European Union (FP7-CIG618444 to SH) and a program grant from the Human Frontiers Science Program (RGP0053/2014 to SH). CD was supported by a postdoctoral ISTFELLOW fellowship and CM was a postdoctoral fellow of the FWF Herta Firnberg programme. [^1]: Edited by: Annette Gaertner, Evotec (Germany), Germany [^2]: Reviewed by: Anthony Paul Barnes, Oregon Health & Science University, United States; Yves Jossin, Université catholique de Louvain, Belgium [^3]: ^†^These authors have contributed equally to this work.
1. Field of the Invention The present invention relates to a dispenser pump of a novel type for dispensing liquid products which may be very fluid (alcohol), of creamy consistency or more or less viscous (liquid soap, shaving cream, and so on). 2. Description of the Prior Art Dispenser pumps of this type are already known but are subject to various drawbacks in all cases. In the first place, they often have a complex structure which entails high production cost. It is consequently necessary to make provision for re-use of these pumps with a number of successive refills of the product to be dispensed. This gives rise to problems of asepsis when it is desired to employ them, for example, in the operating theater of a hospital. It should further be mentioned that the majority of known pumps allow external air to flow upwards into the product after each use. These pumps consequently have a tendency to clog as a result of drying of the product. In addition, admissions of air again present a problem of asepsis for medical uses.
HONG KONG—Hong Kong’s oldest television broadcaster, once a cultural mainstay, is on the verge of collapse after battling financial woes and a growing disconnect with local viewers for years. For the second time in three months, Asia Television Ltd. held back paying salaries to its over 700 employees, and on Tuesday paid just half their November wages. The station, better known as ATV, promised to pay the balance soon, but said that the payout of December salaries was uncertain. The government has threatened to take legal action against ATV for violating labor laws while some of its news department staff plan to walk off their jobs on Jan. 1 if they aren’t paid. This could potentially disrupt news programming at ATV and violate its broadcast license. ATV, launched in 1957 as Rediffusion Television, is one of Hong Kong’s two free-to-air TV stations. It brought international programming to the city, and launched the careers of several famous actors. Yet there are no sympathetic calls among the city’s public to help save the local institution, which in recent years has lost most of its programming power and cultural cache, as it instead targets mainland Chinese viewers. ATV’s signal reaches many parts of neighboring Guangdong Province. Variety shows and advertising in Mandarin Chinese for products unavailable in Hong Kong lead many to believe ATV has grown steadily out of touch with local viewers. ATV mainly broadcasts in Cantonese, which is Hong Kong’s main Chinese dialect, as well as English. Protesters rally against the government's decision to not award a free-to-air broadcast license to Hong Kong Television in 2013. The refusal to grant HKTV a license intensified the public's dissatisfaction over Asia Television, which is on the verge of collapse. Reuters “We can see talk shows on ATV narrating viewpoints that are definitely not those of the local people,” says Anthony Fung, professor of journalism and communications at the Chinese University of Hong Kong. “The last time I felt ATV was a part of popular culture was maybe 15 years ago,” he said. The frustration over Hong Kong’s airwaves comes on the heels of the recent pro-democracy protests, which highlighted deep dissatisfaction with increased mainland Chinese presence and Beijing’s reach into the city. Rather than produce new shows, ATV mostly airs reruns of decades-old dramas. In 2011, it inaccurately reported the death of former Chinese President Jiang Zemin, incurring a 300,000 Hong Kong dollar (US$38,600) fine by Hong Kong authorities for the error. Some of the public’s dissatisfaction over ATV intensified after the government’s refusal last year to grant a broadcast license to upstart Hong Kong Television Network Ltd. , a move seen by some analysts to protect incumbents like ATV, which toes a more pro-Beijing line in its news and other programming. HKTV’s slick programming, in contrast to ATV’s, targets younger viewers. HKTV, which launched in November as an Internet streaming service, produces shows that tackle more controversial social and political topics the mainstream stations generally avoid. At the heart of ATV’s problems is a dispute among shareholders, as well as criticisms of mismanagement of the station, which led the Hong Kong Communications Authority to advise the government against renewing ATV’s free-to-air license when it expires in 2015. The station is now seeking buyers to rescue the company. “We are still talking to a number of potential investors that have expressed intense interest,” ATV Executive Director Ip Ka-po said Tuesday. “I believe ATV, with its free-to-air license, is very attractive,” he said. Ownership of ATV changed hands numerous times as the privately held station struggled to boost viewership and profits even as its ratings have been eclipsed for decades by dominant broadcaster Television Broadcasts Ltd. ATV sought innovative ways to boost ratings, such as producing a local version of the highly popular program “Who Wants to Be a Millionaire” in 2001, as well as focusing on lower-budget infotainment programming.
Q: How to develop a custom sculpt tool? Blender comes with a bunch of sculpting tools: I am wanting to create a custom sculpting tool but I am not sure where to begin. How would I go about creating a custom sculpting tool with several extra properties in the properties area: As an aside, when looking at the contents of a .blend file I noticed that all of the sculpting tools are inside there; so I basically want to add a new custom one into there somehow... What I am looking to create The tool that I want to create would basically have three properties "Source Mesh Min", "Source Mesh Max" and "Direction". Both of the source meshes would have the exact same topology as the actual mesh that is being sculpted. The sculpting tool would then essentially lerp the current mesh towards one of the two source meshes depending upon the selected direction. A: Sculting is a very calculation intensive task. For speed reasons it has been developed in the core of blender using the C language. Implementing the tools you describe in sculpting is possible, but not using the python API. Gladly Blender is OpenSource so you will be able to get the sourcecode and change it to your likings. Python Alternative: As in your description the topology must be the same it sounds like sculpting is more the UI/workflow and not the tool (using sculpting the topology does not have to be the same (Dynamic topology). Implementing such a feature inside the 3d editor using python seems to be an good alternative. You could even store the values in a Weightmap and use this data to calculate the new mesh. Getter the interactivity will be the challenge.
--- abstract: 'Crystal and magnetic structures of the mineral centennialite CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O are investigated by means of synchrotron x-ray diffraction and neutron diffraction measurements complemented by density functional theory (DFT) and pseudofermion functional renormalization group (PFFRG) calculations. CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O crystallizes in the $P\bar{3}m1$ space group and Cu$^{2+}$ ions form a geometrically perfect kagome network with antiferromagnetic $J_1$. No intersite disorder between Cu$^{2+}$ and Ca$^{2+}$ ions is detected. CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O enters a magnetic long-range ordered state below $T_\text{N}=7.2$ K, and the $\mathbf{q}=\mathbf{0}$ magnetic structure with negative vector spin chirality is obtained. The ordered moment at 0.3 K is suppressed to $0.58(2)\mu_\text{B}$. Our DFT calculations indicate the presence of antiferromagnetic $J_2$ and ferromagnetic $J_d$ superexchange couplings of a strength which places the system at the crossroads of three magnetic orders (at the classical level) and a spin-$\frac{1}{2}$ PFFRG analysis shows a dominance of $\mathbf{q}=\mathbf{0}$ type magnetic correlations, consistent with and indicating proximity to the observed $\mathbf{q}=\mathbf{0}$ spin structure. The results suggest that this material is located close to a quantum critical point and is a good realization of a $J_1$-$J_2$-$J_d$ kagome antiferromagnet.' author: - 'K. Iida' - 'H. K. Yoshida' - 'A. Nakao' - 'H. O. Jeschke' - 'Y. Iqbal' - 'K. Nakajima' - 'S. Ohira-Kawamura' - 'K. Munakata' - 'Y. Inamura' - 'N. Murai' - 'M. Ishikado' - 'R. Kumai' - 'T. Okada' - 'M. Oda' - 'K. Kakurai' - 'M. Matsuda' title: '$\mathbf{q}=\mathbf{0}$ long-range magnetic order in centennialite CaCu$_3$(OD)$_6$Cl$_2$$\cdot$0.6D$_2$O: A spin-1/2 perfect kagome antiferromagnet with $J_1$-$J_2$-$J_d$' --- The search for quantum spin liquid (QSL) has been pursued intensively after the initial idea of a resonating valence bond was proposed [@RVB]. The spin-1/2 kagome lattice with the nearest neighbor antiferromagnetic $J_1$ is the prime candidate for hosting QSLs [@Review1; @Review2]. Several types have been proposed theoretically, but consensus for example concerning gapless or gapped excitations has yet to be reached. Herbertsmithite, ZnCu$_3$(OH)$_6$Cl$_2$, is the most investigated material in this context [@ZnHerber_Shores_2005; @ZnHerber_Mendels_2010; @ZnHerber_Norman_2016] and shows QSL behavior down to $50$ mK [@ZnHerber_Mendels_2007; @ZnHerber_Han_2012]. There is nonnegligible intersite disorder between Cu$^{2+}$ and Zn$^{2+}$, which may hinder the true ground state [@ZnHerber_Lee_2007; @ZnHerber_Olariu_2008]. On the other hand, YCu$_3$(OH)$_6$Cl$_2$ [@YCu3_Zorko_uSR_2019; @YCu3_Zorko_2019; @YCu3_Barthelemy_2019] and CdCu$_3$(OH)$_6$(NO$_3$)$_2\cdot$H$_2$O [@Cdkagome_Okuma_2017] are disorder free spin-1/2 perfect kagome lattice antiferromagnets and exhibit $\mathbf{q}=\mathbf{0}$ long-range magnetic order owing to the Dzyaloshinskii-Moriya (DM) interaction [@DM_Cepas_2008]. There is an alternative attempt to search for a QSL state in kagome compounds, in which competing interactions such as $J_2$ and $J_d$ across the hexagon (see Fig. \[Fig:Structure\]) are introduced. Kapellasite, which is a polymorph of herbertsmithite, is the prototype compound of the $J_1$-$J_2$-$J_d$ kagome lattice magnet [@Kapellasite_Janson_2008; @ZnKape_Colman_2008; @ZnKape_Fak_2012; @ZnKape_Kermarrec_2014]. Zn$^{2+}$ in herbertsmithite is located between the kagome planes, whereas Zn$^{2+}$ in kapellasite is located at the center of a hexagon of a kagome layer, resulting in the finite strength of $J_2$ and $J_d$ [@Kapellasite_Janson_2008]. Eventually, the kapellasite family $A$Cu$_3$(OH)$_6$Cl$_2$ where $A$ is Zn or Mg provides a rich phase diagram as a function of $J_2$ and $J_d$ [@ClassicalEnergy; @HTSE; @CdKapellasite_Iqbal_2015]. Both ZnCu$_3$(OH)$_6$Cl$_2$ and MgCu$_3$(OH)$_6$Cl$_2$ (known as haydeeite) possess ferromagnetic $J_1$ [@ZnKape_Fak_2012; @MgKape_Boldrin_2015]. Haydeeite undergoes ferromagnetic order below $T_\text{C}=4.2$ K [@MgKape_Boldrin_2015], while kapellasite shows QSL behavior down to 20 mK [@ZnKape_Fak_2012]. Meanwhile, both ZnCu$_3$(OH)$_6$Cl$_2$ and MgCu$_3$(OH)$_6$Cl$_2$ have intersite disorder between $A^{2+}$ and Cu$^{2+}$ [@ZnKape_Kermarrec_2014; @MgKape_Colman_2010]. CdCu$_3$(OH)$_6$Cl$_2$ was theoretically proposed to carry antiferromagnetic $J_1$ [@CdKapellasite_Iqbal_2015] but it has not been synthesized yet. Instead, CdCu$_3$(OH)$_6$(NO$_3$)$_2\cdot$H$_2$O (Cd kapellasite) is reported to exhibit antiferromagnetic $J_1$ but is discussed in terms of $J_1$ and DM interactions [@Cdkagome_Okuma_2017]. Recently, CaCu(OH)$_6$Cl$_2\cdot0.6$H$_2$O (centennialite), a sister mineral of kapellasite and haydeeite, was discovered [@CaCu3_2014; @CaCu3_Crichton_2017; @CaCu3_Sun_2016]. Centennialite has an ideal kagome network and Ca$^{2+}$ ion is located at the center of the hexagon as described in Fig. \[Fig:Structure\]. Remarkably, large single crystals are available for centennialite [@CaCu3_Yoshida_2017]. The magnetic susceptibilities exhibit negative Curie-Weiss temperature ($\Theta_\text{CW}$), indicating that the dominant interaction is antiferromagnetic $J_1$ [@CaCu3_Yoshida_2017]. Furthermore, the high temperature series expansion (HTSE) reveals the existence of $J_2$ and $J_d$ as in kapellasite [@ZnKape_Fak_2012] and haydeeite [@MgKape_Boldrin_2015]. Since kapellasite and haydeeite have ferromagnetic $J_1$ [@ZnKape_Fak_2012; @MgKape_Boldrin_2015], centennialite is considered to be an ideal compound for investigating the $J_1$-$J_2$-$J_d$ kagome lattice with antiferromagnetic $J_1$ [@CaCu3_Yoshida_2017]. The heat capacity [@CaCu3_Yoshida_2017] and nuclear magnetic resonance [@CaCu3_Ihara_2017] measurements show that centennialite undergoes long-range magnetic ordering below $T_\text{N}=7.2$ K. However, detailed crystal and magnetic structures of centennialite have not been reported yet by diffraction techniques. In this paper, we investigated in detail the crystal and magnetic structures by synchrotron x-ray and neutron diffraction measurements using single crystals. In addition, we also performed density functional theory (DFT) calculations to theoretically evaluate the exchange couplings in centennialite, and subsequently employed the pseudofermion functional renormalization group (PFFRG) method [@Reuther-2010] to reveal the momentum resolved magnetic susceptibility profile for the DFT Hamiltonian. We demonstrate that CaCu(OH)$_6$Cl$_2\cdot0.6$H$_2$O is the first $J_1$-$J_2$-$J_d$ kagome lattice antiferromagnet and hence offer the new playground for geometrical frustration. ![ Crystal structure of CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O. The exchange couplings $J_1$, $J_2$, $J_3$, and $J_d$ are also illustrated. Dotted lines represent the structural unit cell.[]{data-label="Fig:Structure"}](Fig1.eps){width="\linewidth"} Single crystals of centennialite and deuterated centennialite were grown by a hydrothermal reaction [@CaCu3_Yoshida_2017]. Precise crystal structure determination of centennialite was performed using the imagingplate x-ray diffractometer BL-8A installed at Photon Factory (PF). Incident x-ray energy of 18 keV was used. Neutron diffraction measurements on deuterated single crystals of centennialite were carried out using the time-of-flight (TOF) chopper spectrometers AMATERAS [@AMATERAS; @Utsusemi] and 4SEASONS [@Utsusemi; @4SEASONS_1; @4SEASONS_2; @SM], and the TOF neutron diffractometer SENJU [@SENJU] installed at Materials and Life Science Experimental Facility (MLF), Japan Proton Accelerator Research Complex (J-PARC). The incident energy of neutrons $E_i=5.24$ meV with the energy resolution of 0.16 meV (full width at half maximum) at the elastic channel was used at AMATERAS. A neutron wavelength of $0.4\sim4.4$ $\text{\AA}$ was used at SENJU. We perform density functional theory calculations based on the all electron full potential local orbital (FPLO) basis [@Koepernik1999] with generalized gradient approximation (GGA) exchange correlation functional [@Perdew1996]. We use a GGA$+U$ correction [@Liechtenstein1995] to account for the strong electron correlations on the Cu$^{2+}$ $3d$ orbitals. We deal with the small disorder of the Ca and water molecule positions by fixing Ca in the Cu plane and by simplifying to 1/2 water molecules per formula unit. We apply the energy mapping technique [@Guterding2016; @Iqbal2017] to extract the Heisenberg Hamiltonian parameters of centennialite [@SM]. To gain insight into the magnetic behavior of CaCu(OH)$_6$Cl$_2\cdot0.6$H$_2$O, we employ the theoretical framework of PFFRG [@Reuther-2010] to compute the real part of the static and momentum-resolved spin susceptibility expected from this set of interactions. Synchrotron x-ray diffraction measurements on single-crystal CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O are performed to determine the crystal structure below and above $T_\text{N}$, and the refined crystal structure parameters are summarized in the Supplemental Material [@SM]. As kapellasite [@ZnKape_Colman_2008] and haydeeite [@MgKape_Colman_2010], CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O crystallizes in the $P\bar{3}m1$ space group, which persists below $T_\text{N}$. The Cu$^{2+}$ sites form a structurally perfect kagome lattice (Fig. \[Fig:Structure\]), separated by $5.74$ $\text{\AA}$ along the $c$ axis, giving rise to good two dimensionality. The mixing amount between Cu$^{2+}$ and Ca$^{2+}$ ions is zero within errors because of the large difference of their ionic radii [@CaCu3_Sun_2016; @CaCu3_Yoshida_2017]. The large ionic radius induces disorder of the Ca site along the $c$ axis, and the average position is the center of the hexagon of the kagome plane. ![ (a, b) Reciprocal-space neutron scattering intensity maps of CaCu$_3$(OD)$_6$Cl$_2\cdot0.6$D$_2$O at (a) 40 K and (b) 0.3 K measured at AMATERAS. Energy transfer ($\hbar\omega$) is averaged over $[-0.15, 0.15]$ meV. Solid lines represent the two-dimensional structural Brillouin zones. Pink and blue circles in panel (b) represent, respectively, the magnetic reflections at $\mathbf{Q}=(1,0,0.5)$ and $(1,1,0.5)$ with their equivalent positions. Single crystals are fixed by the hydrogen-free grease which gives the ring-shape background at $Q=1.3$ $\text{\AA}^{-1}$ \[yellow arrow in panel (a)\] as described in detail in the Supplemental Material [@SM]. (c) Temperature dependence of the neutron scattering intensity at $\mathbf{Q}=(1,0,0.5)$ measured at SENJU. The dotted line represents $T_\text{N}=7.2$ K determined by the heat capacity measurements [@CaCu3_Yoshida_2017]. []{data-label="Fig:Diffraction"}](Fig2.eps){width="\linewidth"} To understand the magnetic ground state of CaCu$_3$(OD)$_6$Cl$_2\cdot0.6$D$_2$O, elastic neutron scattering measurements were performed at AMATERAS. Figures \[Fig:Diffraction\](a) and \[Fig:Diffraction\](b) depict the reciprocal-space neutron scattering intensity maps of CaCu$_3$(OD)$_6$Cl$_2\cdot0.6$D$_2$O at $T=40$ and 0.3 K in the $(HK0.5)$ plane. Evolution of several peaks of $10\frac{1}{2}$ and $11\frac{1}{2}$ with their equivalent positions can be seen at 0.3 K \[see circles in Fig. \[Fig:Diffraction\](b)\]. The peak at $\mathbf{Q}=\left(0,1,\frac{1}{2}\right)$ has the resolution-limited peak width [@SM], indicative of the long-range magnetic order. The temperature dependence of the neutron scattering intensity at $\mathbf{Q}=(1,0,0.5)$ momentum transfer is shown in Fig. \[Fig:Diffraction\](c). Clearly, the peak at $\mathbf{Q}=(1,0,0.5)$ develops below $T_\text{N}$, revealing the magnetic origin. In addition, magnetic reflections are also observed at higher $\mathbf{Q}$ [@SM]. The observed magnetic reflections are located at the center of the two-dimensional structural Brillouin zones \[Fig. \[Fig:Diffraction\](b)\]. This result indicates the $\mathbf{q}=\mathbf{0}$ magnetic structure, and the corresponding magnetic propagation vector is $\mathbf{k}=(0,0,0.5)$. There are, however, several possibilities of the spin textures for the magnetic propagation vector [@YCu3_Zorko_2019; @Cdkagome_Okuma_2017], some of which are shown in the insets of Fig. \[Fig:Fitting\]. ![ Observed and calculated magnetic structure factors of CaCu$_3$(OD)$_6$Cl$_2\cdot0.6$D$_2$O. Experimental data are measured at 0.3 K using SENJU [@SM]. Magnetic structures with (a, b) positive vector spin chirality and (c, d) negative vector spin chirality are refined. []{data-label="Fig:Fitting"}](Fig3.eps){width="\linewidth"} For unambiguous determination of the magnetic structure of CaCu$_3$(OD)$_6$Cl$_2\cdot0.6$D$_2$O, we further perform detailed neutron diffraction measurements at SENJU using a deuterated single crystal with the dimensions of $1.2\times1.2\times0.3$ mm$^3$. Magnetic structure analysis was performed using the JANA2006 software [@JANA]. Considering the crystal symmetry $P\bar{3}m1$ with the magnetic propagation vector of $\mathbf{k}=(0,0,0.5)$, the candidates for the magnetic space group of CaCu$_3$(OD)$_6$Cl$_2\cdot0.6$D$_2$O are $P_{2c}\bar{3}m'1$, $P_{2c}\bar{3}m1$, $C_{2c}12/m'1$, $C_{2c}12/m1$, $P\bar{1}$, and $P1$. We refined the neutron diffraction data using trigonal and monoclinic symmetries among them. For the $C$-monoclinic models with the $2a\times(a+b)\times c$ unit cell, the 120$^\circ$ spin structure with the same moment sizes for two independent Cu sites \[see the insets of Fig. \[Fig:Fitting\](c) and \[Fig:Fitting\](d)\] and three twinned domains owing to a trigonal-to-monoclinic modulation are considered. In all models, we assumed that the magnetic moments lie in the kagome plane. We refined the four models using the 36 magnetic reflections \[$I>3\sigma(I)$\]. Refinement results and the reliability factors are described in Fig. \[Fig:Fitting\]. Apparently, the magnetic structures belonging to $C_{2c}12/m'1$ and $C_{2c}12/m1$ with the negative vector spin chirality are favored over $P_{2c}\bar{3}m'1$ and $P_{2c}\bar{3}m1$ with the positive vector spin chirality. On the other hand, the present data set cannot distinguish the $C_{2c}12/m'1$ and $C_{2c}12/m1$ models because of the domain contributions. The above assumption that the magnetic moments lie in the kagome plane is justified by the discussion in Refs. \[\]; the $\mathbf{q}=\mathbf{0}$ spin structure with the negative vector spin chirality energetically favors the coplanar spin structure over the noncoplanar canted spin structure within the realistic magnetic anisotropy in contrast to the case with the positive vector spin chirality as realized in the iron jarosite [@jarosite]. In addition, the spin correlations with the negative spin chirality is consistent with the recent nuclear magnetic resonance measurements on single-crystal CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O [@CaCu3_Ihara_2020]. Therefore, the $\mathbf{q}=\mathbf{0}$ spin texture with the negative vector spin chirality is realized in CaCu$_3$(OD)$_6$Cl$_2\cdot0.6$D$_2$O as in YCu$_3$(OH)$_6$Cl$_2$ [@YCu3_Zorko_2019] and CdCu$_3$(OH)$_6$(NO$_3$)$_2\cdot$H$_2$O [@Cdkagome_Okuma_2017]. The obtained ordered moment of centennialite at 0.3 K is $0.58(2)\mu_\text{B}$ which is reduced about $40\%$ from the ideal value for the spin-1/2 system. The ordered moment in the $J_1$-only perfect kagome lattice antiferromagnet YCu$_3$(OH)$_6$Cl$_2$ is $0.42(2)\mu_\text{B}$ (reduced about $60\%$) [@YCu3_Zorko_2019]. Thus, $J_2$ and $J_d$ in centennialite suppress the quantum fluctuations compared to YCu$_3$(OH)$_6$Cl$_2$. On the other hand, the frustration parameter $\left|\Theta_\text{CW}\right|/T_\text{N}$ in CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O is 7.8 [@CaCu3_Yoshida_2017] which is higher than 6.6 for YCu$_3$(OH)$_6$Cl$_2$ [@YCu3_Zorko_2019; @YCu3_Sun_2016]. This result indicates that the geometrical frustration owing to the kagome network persists in CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O even in the presence of finite $J_2$ and $J_d$. $U$ (eV)    $J_1$ (K)     $J_2$ (K)     $J_{3}$ (K)    $J_{d}$ (K)       $\Theta_\text{CW}$ (K) ------------ ---------------- --------------- ---------------- ------------------- ------------------------ 6.0  74(2) 3.4(1.9) 0.0(2.2) $-2.3$(3.7) $-76.3$ 7.0  64(2) 2.8(1.6) 0.0(1.8) $-2.0$(3.1) $-65.8$ 8.0  55(2) 2.2(1.3) 0.0(1.5) $-1.7$(2.5) $-56.4$ : Exchange interactions of CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O calculated within GGA$+U$. See Fig. \[Fig:Structure\] for the definition of $J_1$, $J_2$, $J_3$, and $J_d$. The Curie-Weiss temperature is calculated by the equation $\Theta_\text{CW}=-\frac{2}{3}S (S + 1) \big(2 J_1 + 2 J_2 + 2 J_3 + J_d\big)$ [@SM]. []{data-label="Tab:DFT"} We now proceed to determine the in-plane exchange couplings for CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O by mapping the energies for selected spin configurations on the Heisenberg Hamiltonian. In Table \[Tab:DFT\], we list the $J_i$ for several values of the on-site interaction $U$, calculated for the $T=213$ K structure reported in Ref. \[\]. Interestingly, the $T=5$ K structure yields almost identical Heisenberg Hamiltonian parameters; this is surprising as exchange interactions can be quite temperature dependent even without change of space group symmetry. The Curie-Weiss temperature for $J$s with $U=8$ eV is in good agreement with the in-plane Curie-Weiss temperature $\Theta_\text{CW}=-56.5$ K determined by the magnetic susceptibility measurements [@CaCu3_Yoshida_2017]. The magnetic susceptibilities are calculated by using the $J$s obtained by our DFT calculations, which are compared to the experimental results as shown in Fig. \[Fig:PhaseDiagram\](a). The set of $J$s for $U=8.0$ eV excellently reproduce the magnetic susceptibilities of CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O, confirming the validity of our DFT calculations. We also fit the magnetic susceptibilities by HTSE using the DFT results as the initial parameters, yielding $J_1=52.6$ K, $J_2=13.7$ K, and $J_d=-1.29$ K [@SM]. Both DFT calculations and the HTSE fitting [@CaCu3_Yoshida_2017; @SM] indicate the presence of sizable antiferromagnetic $J_2$ and ferromagnetic $J_d$. Therefore, our results demonstrate that centennialite is the first $J_1$-$J_2$-$J_d$ kagome lattice antiferromagnet and provide the fertile playground for geometrical frustration. ![ (a) Temperature dependencies of the magnetic susceptibilities of CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O under the external magnetic field $B=1$ T. Solid lines are the HTSE results [@HTSE] using $J_1$, $J_2$, and $J_d$ obtained by the GGA$+U$ calculations in Table \[Tab:DFT\]. The experimental data is taken from Ref. \[\]. (b) Classical phase diagram of the $J_1$-$J_2$-$J_d$ kagome-lattice magnet for antiferromagnetic $J_1$ [@ClassicalEnergy; @HTSE]. The cuboc1 state is the twelve sublattice noncoplanar spin structures [@cuboc]. Purple and yellow solid squares represent the GGA$+U$ result and the HTSE fitting result [@SM] for CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O. (c) Momentum resolved spin susceptibility (in units of $1/J_{1}$) profile obtained using PFFRG evaluated at the lowest simulated temperature $T=J_{1}/100$ [@footnote]. The solid (dashed) hexagons depict the first (extended) Brillouin zones of the kagome lattice. The momenta $(k_{x},k_{y})$ are expressed in units where the edge length of the kagome triangles is set to unity. []{data-label="Fig:PhaseDiagram"}](Fig4.eps){width="\linewidth"} The classical phase diagram of the $J_1$-$J_2$-$J_d$ kagome-lattice magnet with antiferromagnetic $J_1$ [@ClassicalEnergy; @HTSE] is illustrated in Fig. \[Fig:PhaseDiagram\](b). Both sets of $J$s in CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O determined by our DFT calculations and the HTSE fitting are located in the $\mathbf{q}=\mathbf{0}$ phase of the classical phase diagram, however, given the spin-$\frac{1}{2}$ nature of the system and its proximity to a tricritical point, one expects amplified quantum fluctuations with the low-energy physics being governed by a subtle interplay of quantum corrections to the different magnetic orders. Indeed, our PFFRG analysis for the DFT interaction parameters reveals the presence of a quantum paramagnetic phase which displays magnetic fluctuation tendencies towards $\mathbf{q}=\mathbf{0}$ order as confirmed by the presence of soft maxima at the expected location \[$\mathbf{q}=(0,2\pi/\sqrt{3}$) and symmetry related positions, i.e., the center of the sides of the extended Brillouin zone\] of the incipient Bragg peaks \[see Fig. \[Fig:PhaseDiagram\](c)\] seen in neutron diffraction measurements \[Fig. \[Fig:Diffraction\](b)\]. Ultimately, the onset of $\mathbf{q}=\mathbf{0}$ order is triggered by a nonnegligible out-of-plane DM interaction ($D_{z}>0$) whose magnitude in centennialite, as reported by thermal conductivity measurements [@CaCu3_Doki_2018], is estimated to be $D_{z}/J_{1}\sim0.1$. Given the fact, that in the $J_{1}$ only model the kagome spin liquid gives way to $\mathbf{q}=\mathbf{0}$ order for $D_{z}/J_{1}\sim0.1$ [@DM_Cepas_2008; @Hering-2017; @Buessen-2019], one may expect that owing to the presence of small antiferromagnetic $J_{2}$ ($4\%$ of $J_{1}$) and ferromagnetic $J_{d}$ ($\sim2\%$ of $J_{1}$) both of which favor $\mathbf{q}=\mathbf{0}$ spin pattern [@Suttner-2014; @Iqbal-2015], that a slightly smaller value $D_{z}$ might suffice to drive the system out of the quantum paramagnetic phase and induce $\mathbf{q}=\mathbf{0}$ long-range magnetic order, as seen in experiments. These results indicate that while centennialite is located in the $\mathbf{q}=\mathbf{0}$ ordered phase, it is not immersed deep inside it, but rather precariously placed in the vicinity of a quantum critical point. This also explains the reduced magnetic moment in centennialite. In fact, low temperature heat capacity measurements revealed the existence of the $T$ linear term in addition to the spin wave term [@CaCu3_Yoshida_2017]. The $T$ linear term suggests that the continuum excitations exist even below $T_\text{N}$. On the other hand, spinon like behavior is also observed above $T_\text{N}$ in thermal conductivity measurements of centennialite [@CaCu3_Doki_2018]. In summary, we investigate in detail the crystal and magnetic structures of CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O. Cu$^{2+}$ ions form a perfect kagome lattice without intersite disorder between Cu$^{2+}$ and Ca$^{2+}$. Magnetic diffraction measurements determine the $\mathbf{q}=\mathbf{0}$ magnetic structure with the negative vector spin chirality. The magnetic propagation vector is $\mathbf{k}=(0,0,0.5)$ and the ordered moment at 0.3 K is suppressed to be $0.58(2)\mu_\text{B}$. Exchange couplings of CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O are estimated by a DFT calculations to be $J_1=55$ K, $J_2=2.2$ K, and $J_d=-1.7$ K, and a spin-$\frac{1}{2}$ PFFRG analysis of the same shows the presence of magnetic fluctuation tendencies towards $\mathbf{q}=\mathbf{0}$ magnetic structure. The estimated DM interaction of $D_{z}\sim0.10$ in centennialite likely places the system on the edge of a phase transition but in the $\mathbf{q}=\mathbf{0}$ ordered phase. The present results demonstrate that CaCu$_3$(OH)$_6$Cl$_2\cdot0.6$H$_2$O is a first realization of a $J_1$-$J_2$-$J_d$ kagome-lattice magnet with antiferromagnetic $J_1$ and is located in the vicinity of a quantum critical point. [*Acknowledgments*]{}. We thank Yoshihiko Ihara and Minoru Yamashita for helpful discussions. We also thank for technical support from the MLF sample environment team. Single crystals were checked at the CROSS user laboratories. Synchrotron x-ray diffraction at PF was carried out under the proposal number 2017S2-001. Neutron experiments at MLF were conducted under the user program with the proposal numbers 2017A0013 and 2017BU1401 for AMATERAS, 2017I0001 for 4SEASONS, and 2018A0009 and 2018B0008 for SENJU. Present work was supported by JSPS KAKENHI Grant Number JP18K03529 and the Cooperative Research Program of “Network Joint Research Center for Materials and Devices” (20181072). Y.I. acknowledges the Science and Engineering Research Board (SERB), DST, India for support through Startup Research Grant No. SRG/2019/000056 and MATRICS project No. MTR/2019/001042. 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Contextual information is changing the world. We have more data available to us than ever before, and much of it is being generated and consumed by the mobile devices in our pockets. Right now, businesses are creating systems and apps that will enable us to act on that data to automate our lives. Apple and Google, as the two most important entities in the mobile industry, are leading the way and opening up new, exciting possibilities for app creators. But questions have recently been raised about what the future holds for custom apps, as mobile operating systems become more intelligent. Google Now, Siri and Artificial Intelligence An important upgrade to Google’s digital assistant, Google Now, was recently announced at Google I/O 2015. One of the most prominent changes is Google Now on Tap, which enables users to immediately be directed to relevant contextual information, simply by tapping the home button when within an app. Combined with its enhanced contextual understanding of your activities, calendar, contacts, and location, Google Now is beginning to feel like the personal assistant that really knows us. With more than 100 services that currently tie into Google Now, there is already a broad pool of data for it to draw from, and as it grows, many more services are certain to integrate with it. When I first saw the demo, I immediately thought of The Knowledge Navigator, a vision presented by John Sculley in 1987, then CEO of Apple, and contextual “Data Detectors” that we were working on in the 90s when I was at Apple. At WWDC 2015, Apple followed suit by showing off a smarter Siri, which added predictive intelligence that can learn a user’s preferences, which it uses to automate how it presents information. With its new “proactive” features, Siri is beginning to catch up to Google Now in its ability to use artificial intelligence to better understand users. But in contrast to Google’s strategy, Apple is focused on privacy, and promised to keep user data anonymous. So, Siri can’t really understand what you’re looking at on the screen at that moment, although a “Siri, remember this” promises to return you to whatever you were doing at a future point in time. With more artificial intelligence being built into operating systems and their greater ability to find and present relevant data, some have predicted contextual information may eventually push users off of third-party apps. In fact, WIRED’s John Pavlus recently envisioned the future of mobile as an appless Cold War between the two ecosystems: “Instead of Apple and Google behaving like singular superpowers in an app-driven arms race, iOS and Android ecosystems will be more like NATO and the Warsaw Pact: parallel dominions competing for influence in post-app ‘proxy wars’ like wearable tech, connected homes, and automated transportation.” Although the recent announcements have reignited the debate, the point of view that Google Now and Siri could be the death of apps isn’t new. Tom Simonite, MIT Technology Review’s San Francisco Bureau Chief, wrote in February 2013 that “virtual helpers conceived [to be general purpose tools] could transform how people get stuff done with a smartphone, and remove the need for them to interact with the apps and websites they must turn to today… It may be that the era of apps being the main thing about mobile devices is ending.” After all, why open an app if the data within it is easily accessible through Google Now or Siri? Because the user experience still matters. Arguments about the virtual assistant layer making app design and the existence of anything more than the data behind the app irrelevant are intrinsically flawed. Here are three reasons why: Apps Will Be More Connected One of the improvements Google made at I/O was to improve deep linking between apps and web pages. Developers are now able to tell the Android operating system which app to open automatically, rather than requiring the user to choose. The connectivity between apps and the web continues to improve and the transition between them is constantly becoming less noticeable. Google Now and Siri have a place in this, too, as they will surface a combination of Web and app content based on your context. By tying into the new Google Now and Siri “app content” APIs, apps can also provide custom search results. This enables Google Now and Siri to help you prioritize app content, as they should, because if you have taken the time to download an app, you probably value its content more than what you might find on a website. However, information from the Internet is also valuable to supplement app data to provide additional information that might not reside in your existing apps. The increased connectivity between apps and the Web will enhance the user experience by offering the right data, from the right source, at the right time. Glance-able Information Will Complement Deeper Experiences Consumers appreciate glance-able information – little bits of relevant information presented at the most needed time – but deeper, engaging experiences are necessary as well. Virtual assistants will actually help increase engagement with applications due to their ability to bring notifications front-and-center and leverage increasingly connected information sources. In most apps, glanceable moments are one piece of the experience. Both Google Now and Siri will allow deep linking to take the user from those instant notifications into additional rich content of the apps they’re connected to. But other apps don’t serve an informational purpose at all, such as games. The experience of playing Minecraft or Angry Birds will stay the same, regardless of upgrades to Google Now or Siri. App categories like media, e-reader or social media apps might have discoverable information, but the actual consumption of content and engagement with it will still primarily take place within the apps. Take Facebook, for example: Someday soon you might find out a friend is nearby when Google Now alerts you. You might then open the Facebook app to find out your friend’s recent updates, and after that, glance over to your feed and get sucked in for hours. Apps deliver a deeper level of engagement and a richer experience, which is why they will continue to dominate mobile phone usage (some estimates put that number at over 80 percent of time spent). Virtual Assistants and Notifications Will Encourage App Usage Virtual assistants and their associated notifications will provide an additional point of entry that will lead to more frequent interactions with apps. In fact, among developers, one of the biggest complaints about Siri was the lack of third-party support. However, Apple announced at WWDC that it plans to open up custom search results to developers, so third-party app results will soon appear in Siri and Spotlight Search, which significantly expands the platform’s potential. Both Google Now and Siri offer users a snapshot of contextually relevant info from an app, and embedded links will encourage people to open the app. What we’re seeing is an evolution of notifications. And notifications actually significantly increase app usage. So will virtual assistants. Apps will continually evolve. Mobile platforms will become more intelligent, and the mobile experience of the future will be vastly improved because of apps’ greater connectedness and smarter use of data. Google Now and Siri will not be the death of apps, they just might be ushering in a new era. Read Next: Google ‘Now on Tap’ makes it easy to get contextual answers from anywhere in Android Image credit: Shutterstock Read next: Here's the real story of a fake logo in HBO's 'Silicon Valley'
Document Type Article Publication Date Spring 2001 Publication Title State and Local Government Review Publisher Carl Vinson Institute Volume 21 Issue 33 Abstract There is growing recognition of the importance of executive tenure and turnover for the performance of organizations in both the private and public sector. Because turnover can affect service delivery and fiscal management, understanding the reasons why managers exit their positions has import for both practitioners and scholars. In this article, turnover of municipal administrators is examined as a function of political uncertainty, conflict with elected officials, fiscal conditions, and population growth. A random-effects logit analysis of data from a pooled cross-sectional panel of U.S. cities reveals that mayoral turnover is associated with turnover of administrators in mayor-council cities but not in council-manager cities. Growth in per capita personal income results in a decreased likelihood of turnover of city administrators in both mayor-council and council-manager cities. One important "non-finding" is that growth in property tax revenue apparently has no significant effect on the tenure of administrators-that is, increases in this unpopular tax do not seem to influence whether administrators stay in their positions or leave them. Keywords City managers; County government; County officials and employees; County services; Labor turnover – Economic aspects; Leadership; Local government; Municipal government by city manager; United States Disciplines Public Administration | Public Affairs, Public Policy and Public Administration
Subscribe to our Newsletter The Family Of Girl In R. Kelly's Alleged Sex Cult Is Demanding Proof Her Relationship With The Singer Is Consensual Share facebook twitter whatsapp tumblr pinterest email The Family Of Girl In R. Kelly's Alleged Sex Cult Is Demanding Proof Her Relationship With The Singer Is Consensual They aren't believing she's there on her own free will. Published January 12th The family of Joycelyn Savage, a girl supposedly being held against her will in R. Kelly’s alleged sex cult, is demanding that the singer provide proof that the relationship between her and him is consensual. According to The Blast, Savage’s father’s lawyer told the publication, “It should be respectfully stated that we requested two of R. Kelly’s previous managers and two of R. Kelly’s previous attorneys for the Savage family to see Joycelyn,” said Gerald Griggs. Griggs’ request comes after Steven Greenberg, Kelly’s attorney, did an interview with CBS, in which he described Lifetime’s six-part documentary series “Surviving R. Kelly” “trash TV.” Furthermore, Greenberg believes that no criminal conduct has ever taken place between his client and the women accusing him of sexual wrongdoing. “I think Mr. Kelly should live his life however he wants to live his life,” he said. “He’s not breaking any laws. He’s not doing anything illegal. He’s not taking advantage of anybody.” The family’s response? “If you want to show that this is a consensual relationship, allow Joycelyn to see her parents,” they said, according to The Blast. They believe if they’re able to speak with Joycelyn it “will remove all doubt whether the relationship is consensual or not.” An investigation has been launched into R. Kelly’s background and current living situation in both Georgia and Illinois. He’s maintained he is innocent of any misconduct ever. Written by BET Staff Photo: Tim Mosenfelder/Getty Images COMMENTS Get the latest from BET in your inbox! Sign up now for the latest in celebrity, sports, news and style from BET. By clicking submit, I consent to receiving BET Newsletters and other marketing emails. BET Newsletters are subject to our Privacy Policy and Terms of Use. Users can unsubscribe at anytime. BET Newsletters are sent by BET Networks, 1540 Broadway, New York, NY 10036. www.bet.com OR JOIN US ON Subscribe to our Newsletter By clicking submit, I consent to receiving BET Newsletters and other marketing emails. BET Newsletters are subject to our Privacy Policy and Terms of Use. Users can unsubscribe at anytime. BET Newsletters are sent by BET Networks, 1540 Broadway, New York, NY 10036. www.bet.com
Build with modern libraries like Tensorflow, Theano, Keras, PyTorch, CNTK, MXNet. Train faster with GPU on AWS. In this course you will learn about batch and stochastic gradient descent, two commonly used techniques that allow you to train on just a small sample of the data at each iteration, greatly speeding up training time. You will also learn about momentum, which can be helpful for carrying you through local minima and prevent you from having to be too conservative with your learning rate. You will also learn about adaptive learning rate techniques like AdaGrad, RMSprop, and Adam which can also help speed up your training. Complete guide on deriving and implementing word2vec, GLoVe, word embeddings, and sentiment analysis with recursive nets In this course you are going to look at advanced NLP. It will show you exactly how word2vec works, from theory to implementation, and you’ll see that it’s merely the application of skills you already know. nWord2vec is interesting because it magically maps words to a vector space where you can find analogies, like:king — man = queen — woman, France — Paris = England — London, December — Novemeber = July — June. You are also going to look at the GLoVe method, which also finds word vectors, but uses a technique called matrix factorization, which is a popular algorithm for recommender systems. Amazingly, the word vectors produced by GLoVe are just as good as the ones produced by word2vec, and it’s way easier to train. You will also look at some classical NLP problems, like parts-of-speech tagging and named entity recognition, and use recurrent neural networks to solve them. You’ll see that just about any problem can be solved using neural networks, but you’ll also learn the dangers of having too much complexity. Lastly, you’ll learn about recursive neural networks, which finally help us solve the problem of negation in sentiment analysis. Recursive neural networks exploit the fact that sentences have a tree structure, and we can finally get away from naively using bag-of-words. Complete guide to artificial intelligence and machine learning, prep for deep reinforcement learning When people talk about artificial intelligence, they usually don’t mean supervised and unsupervised machine learning. These tasks are pretty trivial compared to what we think of AIs doing — playing chess and Go, driving cars, and beating video games at a superhuman level. Reinforcement learning has recently become popular for doing all of that and more.And yet reinforcement learning opens up a whole new world. As you’ll learn in this course, the reinforcement learning paradigm is more different from supervised and unsupervised learning than they are from each other. It’s led to new and amazing insights both in behavioral psychology and neuroscience. In this course, there are many analogous processes when it comes to teaching an agent and teaching an animal or even a human. It’s the closest thing we have so far to a true general artificial intelligence. Go hands-on with the latest neural network, artificial intelligence, and data science techniques employers are seeking. If you’ve got some programming or scripting experience, this course will teach you the techniques used by real data scientists and machine learning practitioners in the tech industry — and prepare you for a move into this hot career path. Each concept is introduced in plain English, avoiding confusing mathematical notation and jargon. It’s then demonstrated using Python code you can experiment with and build upon, along with notes you can keep for future reference. You won’t find academic, deeply mathematical coverage of these algorithms in this course — the focus is on practical understanding and application of them. At the end, you’ll be given a final project to apply what you’ve learned. The topics in this course come from an analysis of real requirements in data scientist job listings from the biggest tech employers. It’ll cover the machine learning and data mining techniques real employers are looking for, including: Deep Learning / Neural Networks (MLP’s, CNN’s, RNN’s), Regression analysis, K-Means Clustering, Principal Component Analysis, Train/Test and cross validation, Bayesian Methods, Decision Trees and Random Forests, Multivariate Regression, Multi-Level Models, Support Vector Machines, Reinforcement Learning, Collaborative Filtering, K-Nearest Neighbor, Bias/Variance Trade off, Ensemble Learning, Term Frequency / Inverse Document Frequency, Experimental Design and A/B Tests and much more. In this course, we will start from the very scratch. This is a very applied course, so we will immediately start coding even without installation! You will see a brief bit of absolutely essential theory and then we will get into the environment setup and explain almost all concepts through code. You will be using Keras — one of the easiest and most powerful machine learning tools out there. You will start with a basic model of how machines learn and then move on to higher models such as: Convolutional Neural Networks Residual Connections Inception Module All with only a few lines of code. All the examples used in the course comes with starter code which will get you started and remove the grunt effort. The course also includes finished codes for the examples run in the videos so that you can see the end product should you ever get stuck. This course is divided into days, but of course you can learn at your own pace. In Day 2 we teach you all the fundamentals of the Python programming language. If you already have experience coding in this popular language, brushing up on the fundamentals and fixing bad coding habits is a great exercise. If you are a beginner this section ensures you do not get lost with the rest of the crowd. At Day 3 we dive into machine learning and neural networks. You also get an introduction to convolutions. These are hot topics that are in high demand in the market. If you can use this new technology to your advantage you are pretty much guaranteed a job! Everyone is desperate for employees with these skills. In Day 4 we go headfirst into Keras and understanding the API and Syntax. You also get to know TensorFlow, the open source machine learning framework for everyone. At Day 5 we explore the CIFAR-10 image dataset. Then we are ready to build our very own image classifier model from scratch. You will learn how to classify images by training a model.
A couple of weeks ago, we had Clint Scoles give us a preview of the Royals draft and now that the picks are all in, he joined us again to talk about the results. It’s an unexpected set of picks, but there’s talent there. Clint covers the big names, the approach, and what it means for the Royals future. We also discussed Brad Keller, Danny Duffy, a putrid Royals offense, and – unexpectedly – a Jon Jay trade that broke while we were recording.
Atoka, Oklahoma updated Wed. March 14, 2018 19, 1930 in Atoka, Okla. He worked as an auto mechanic at Chrysler for many years. He enjoyed painting, hunting, fishing, being outdoors, singing and playing the guitar. He was preceded in death by sister, Joann. Surviving relatives include his wife, Shirley Christensen of Alpine; sons, David Christensen ... Healdton isn't the first Oklahoma district to introduce bulletproof shelters into its classrooms, either. In June 2017, KFOR-TV reported that a school board in Atoka, Oklahoma, voted to install six bulletproof safety rooms on the Atoka Elementary School campus. While parents, teachers, and students seemed ... Let's copy Atoka, Oklahoma's, idea. For its elementary school, Atoka purchased six bulletproof safety rooms, which were placed throughout the school in places like the gym, hallways and the library in case of emergency. Once inside the room, the students can see what is going on throughout the school via ... Born to Wilson Mathew "Rick" Weaver and Renie Delpha (Fleming) Weaver on May 18, 1930 in Paris, Texas. The family relocated to Atoka, Oklahoma in 1935 and moved back to Paris, Texas in 1945 where Clemmie Faye "Lady", "as she was fondly known by her family and friends", excelled academically ... Several students at McCall Junior High School in Atoka were suspended for using hand sanitizer in class. (KTEN). ATOKA, Okla. -- Some students were suspended at a Texoma School after using hand sanitizer in a classroom. Atoka Public Schools said the students at McCall Junior High "colluded" with ... ATOKA, Okla. - An Oklahoma man is fighting for his life after being diagnosed with the flu. The family of 48-year-old Michael Keeler says he was perfectly healthy before being diagnosed. "There was just nothing we could do, he was just one of the unlucky people this season," said Shuana Keeler, Michael's ... ATOKA, Okla. (KXII) -- An Atoka father who caught the flu is now fighting for his life in the hospital. "There was just nothing we could do, he was just one of the unlucky people this season," Shuana Keeler said. Michael Keeler's family said he was a perfectly healthy 48-year-old man. He and his daughters ... "From Atoka, Oklahoma, it's the Granger family," Family Feud host Steve Harvey said. Meet the family of Mike and Cheri Granger: their son Kyle and his wife Heather, their son Zac and his wife Stephanie and their four grandkids. The family owns a pawn shop and pest control company in Atoka, and all live ... ATOKA, Okla. (KXII) - Kelvin Rayford has been a performing mixed martial arts for the past six years, and he's been training for a few weeks for his next fight. "I'm ready," Rayford said. Saturday night Rayford will headline an MMA competition that's being held in Atoka County for the first time, and it's all ... Executives from major pipeline companies say environmental activists have become more intense, coordinated and sophisticated in their campaigns against energy infrastructure. The industry needs to anticipate challenges from activists and leave no room for projects to be appealed in courts or in the halls ... ... up on that evening," Hudson said. The shelters can hold up to 35 students and two teachers. The bulletproof storm shelters in Healdton are the first to be installed in the country. Shelter-In-Place officials said they have since installed shelters in Atoka, Oklahoma, and are in talks with other school districts. The bulletproof storm shelters in Healdton are the first to be installed in the country. Shelter-In-Place officials said they have since installed shelters in Atoka, Oklahoma, and are in talks with other school districts. Healdton schools use bulletproof storm shelters to keep students safe. Loading more articles. Atoka, Okla. (The Baptist Messenger) -- Tierra Caliente, otherwise known as "the Hot Lands" is a region in Guerrero, Mexico, a city where the Baptist General Convention of Oklahoma (BGCO) has a partnership mission connection. Atoka-Coal Association has made it their mission to help church plants in ... The bulletproof storm shelters in Healdton are the first to be installed in the country. Shelter-In-Place officials said they have since installed shelters in Atoka, Oklahoma, and are in talks with other school districts. Healdton schools use bulletproof storm shelters to keep students safe. Loading more articles. Born to Wilson Mathew "Rick" Weaver and Renie Delpha (Fleming) Weaver on May 18, 1930 in Paris, Texas. The family relocated to Atoka, Oklahoma in 1935 and moved back to Paris, Texas in 1945 where Clemmie Faye "Lady", "as she was fondly known by her family and friends", excelled academically ... Several students at McCall Junior high school in Atoka were suspended for using hand sanitizer in class. (KTEN). Atoka, Okla. -- Some students were suspended at a Texoma school after using hand sanitizer in a classroom. Atoka public schools said the students at McCall Junior High "colluded" with ... Atoka, Okla. - An Oklahoma man is fighting for his life after being diagnosed with the flu. The family of 48-year-old Michael Keeler says he was perfectly healthy before being diagnosed. "There was just nothing we could do, he was just one of the unlucky people this season," said Shuana Keeler, Michael's ... Atoka, Okla. (KXII) -- An Atoka father who caught the flu is now fighting for his life in the hospital. "There was just nothing we could do, he was just one of the unlucky people this season," Shuana Keeler said. Michael Keeler's family said he was a perfectly healthy 48-year-old man. He and his daughters ... Or, perhaps you live in or around Atoka, OK and still haven't tasted all the best meals around town. Let our top list be your guide to great eats around. From Mexican to Vietnamese, to Italian, to Sushi - our list includes a taste from around the world right here in or near Atoka, OK. The United States has ... Atoka, Okla. -- An Atoka man has been charged with the shooting death of his father last Thursday. In a statement, the Oklahoma State Bureau of Investigation said Wyatt Arp, 20, initially told agents that he had dropped a gun and it discharged, killing 55-year-old Douglas Arp at a residence in the 500 ... Atoka, Okla. (AP) -- The Oklahoma State Bureau of Investigation has arrested a 20-year-old man following the death of his 55-year-old father from a rifle wound. OSBI investigators say Wyatt Arp was arrested Monday on a complaint of first-degree murder in connection with the death of his father, Douglas ... Atoka, Okla. (KXII) -- An Atoka woman and her 13-year-old nephew are without a place to live after a fire Monday night destroyed their home, car and belongings. The woman is now recovering in the hospital, but her family said if it weren't for the help of some strangers, it could have been much worse. "From Atoka, Oklahoma, it's the Granger family," Family Feud host Steve Harvey said. Meet the family of Mike and Cheri Granger: their son Kyle and his wife Heather, their son Zac and his wife Stephanie and their four grandkids. The family owns a pawn shop and pest control company in Atoka, and all live ... Atoka, Okla. (KXII) - Kelvin Rayford has been a performing mixed martial arts for the past six years, and he's been training for a few weeks for his next fight. "I'm ready," Rayford said. Saturday night Rayford will headline an MMA competition that's being held in Atoka County for the first time, and it's all ... Atoka, Okla. (KXII) -- Atoka County deputies said two Arkansans were arrested after a search revealed they had more than $10,000 worth of methamphetamine. On Monday, officers tried to stop Joshua Kinnard and Roger Willis for a traffic violation on U.S. Highway 69. Deputies said that before the car ... Atoka, Okla. (KXII) -- Family and friends are remembering the life of a 17-year-old Atoka student who drowned at Coalgate Lake Tuesday. A friend to all, a talented drummer and a young man with an energetic spirit, those are the phrases used to describe Atoka high school student DeMarcus Colbert. Atoka, Okla. (KXII) -- Two Atoka men are headed to prison after pleading guilty to second degree murder charges. James Moore, 45, his nephew, Christopher Maxey, 27, and Maxey's brother Cody Maxey were arrested in connection with Kathern Moore's death. Deputies said she was shot in the head ... Atoka, Okla. (KXII) -- An Atoka woman is recovering after police said she was assaulted by a male co-worker last week. Craig Allen Viefhaus, 41, is charged with aggravated assault and battery. A police report states Veifhaus went to talk to FirstBank President Mark Burrage about his employment status ... Atoka, Okla. (KXII) -- A local family will soon have the chance to win big bucks on a popular TV game show. Out of thousands who auditioned, an Atoka family said they think their tight-knit bond helped them get selected to be one of the next contestants on Family Feud. Now the family is hoping that bond ... Atoka, Okla. (KXII) -- The Oklahoma medical examiner said the baby who died in Atoka last August was beaten to death. Thirteen-month-old Seminole Nieto was found dead at his home on Kentucky Avenue in Atoka. "It's just a shock, it's just a shock to the whole community," McKinley Cheadle said, whose ... An Atoka County man has been charged with poaching an alligator in late December, while hunting deer in a rural area near Atoka. The Oklahoma Department of Wildlife says Randy Littleton, 50, confessed to the incident. A game warden told KXII, the CBS affiliate in Sherman, Texas, Littleton was deer ... DEQ, working in tandem with ORWA leak specialists like Mr. Deshazo, often has a tough sell when it talks with community water systems in need of repairs. In the case of Atoka, Okla., the water manager didn't even want their help, says Michelle Smith, who was the bookkeeper at the time. "He wasn't happy ... He married Mary Ruth Davis in 1946, at Atoka, Okla. Coley attended Durwood schools. He was a member of Durwood Missionary Baptist Church all his life and served as Deacon. He was preceded in death by his parents and wife, Mary Ruth Davis. Coley is survived by numerous nieces and nephews. Atoka, OK is a great place to pass through when you're looking to find a great meal. Let our top list of places to eat in Atoka, OK be your guide the next time you're in town. Your appetite will be satisfied with the top eateries located in Atoka, OK. Whether you're looking for a romantic bistro or pizza joint, Atoka ... Atoka, Okla. (KOKH) -- An Atoka man has been arrested in connection to the fatal shooting of his father. The Oklahoma State Bureau of Investigation reports that Wyatt Arp, 20, has been arrested on a complaint of murder in the first degree. On Nov. 30, authorities were called to a home at 522 S. Bentley ... Atoka, Okla. -- An Atoka man has been charged with the shooting death of his father last Thursday. In a statement, the Oklahoma State Bureau of Investigation said Wyatt Arp, 20, initially told agents that he had dropped a gun and it discharged, killing 55-year-old Douglas Arp at a residence in the 500 ... Hello! Thank you for visiting TDTNews.com, the online home of the Temple Daily Telegram. 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2.22.2010 i want, i need...i want! so Anthropologie has these so unbelievably cute coin purse necklaces and I am, to say the least OBSESSED!! I want one of these necklaces so bad, but I'm a little thrown off by the $228 price. I am, as I type trying to come up with a DIY project to make one of my own, if I have any success with this idea I will be sure to post!! meanwhile check out the fabulousness that is below!! ;) 1 comment: Anonymous said... it is natalie! i wore this necklace around work for an hour the other day, after this old lady brought it to my attention in the case. then! another old lady tried to convince me it was a necessary purchase that i just needed to make. thank goodness i was practicing self control that day. but it was a close call. if you can recreate the loveliness that is this necklace i would love you forever and ever. (not like i don't already, but...you know what i mean!)
$cell vectors 1.0 8.7534958811126096 0.0000000000000000 0.0000000000000000 -0.0192362783949727 5.0120607273357765 0.0000000000000000 0.0000000000000000 0.0000000000000000 8.2140961349228423 8 16 Direct 0.1755000000000003 0.5534000000000000 0.6844999999999998 # Si1 0.1596999999999998 0.4489999999999998 0.3085999999999998 # Si2 0.6754999999999995 0.0534000000000000 0.6844999999999998 # Si3 0.6596999999999997 0.9489999999999996 0.3085999999999998 # Si4 0.8244999999999997 0.4465999999999999 0.1844999999999998 # Si5 0.8403000000000002 0.5510000000000000 0.8085999999999998 # Si6 0.3245000000000003 0.9465999999999999 0.1844999999999998 # Si7 0.3403000000000002 0.0510000000000001 0.8085999999999998 # Si8 0.3336000000000000 0.0003000000000005 0.9969999999999998 # O1 0.9879999999999999 0.4265000000000000 0.2852999999999996 # O2 0.2669999999999998 0.3304999999999996 0.7728000000000000 # O3 0.2409999999999997 0.6714000000000003 0.2105999999999999 # O4 0.8335999999999999 0.5003000000000005 0.9969999999999998 # O5 0.4879999999999999 0.9265000000000001 0.2852999999999996 # O6 0.7669999999999998 0.8304999999999996 0.7728000000000000 # O7 0.7409999999999997 0.1714000000000004 0.2105999999999999 # O8 0.6664000000000000 0.9997000000000003 0.4969999999999999 # O9 0.0120000000000000 0.5734999999999998 0.7852999999999997 # O10 0.7330000000000001 0.6695000000000002 0.2728000000000000 # O11 0.7589999999999997 0.3286000000000006 0.7105999999999999 # O12 0.1664000000000000 0.4997000000000005 0.4969999999999999 # O13 0.5119999999999999 0.0734999999999998 0.7852999999999997 # O14 0.2330000000000002 0.1695000000000003 0.2728000000000000 # O15 0.2590000000000003 0.8286000000000004 0.7105999999999999 # O16
Age, testing at preferred or nonpreferred times (testing optimality), and false memory. Two experiments investigated whether age and testing at preferred (optimal) times of day or nonpreferred (nonoptimal) times affected the ability to select relevant from irrelevant but thematically related alternatives in a verbal false memory paradigm. A 3rd experiment pursued the same issues with a visual false memory paradigm. In all 3 experiments, younger adults (n = 195) correctly recalled studied items more often than older adults (n = 121), whereas the 2 age groups correctly recognized about the same numbers of previously studied items. In all 3 experiments, nonoptimally tested older adults had more difficulty excluding nonstudied but thematically related items than the other groups; thus, they showed the greatest evidence of false memory, although all groups did so to a significant extent. The results suggest that optimality and its circadian determinants need to be considered with some tasks for the elderly. Various models and mechanisms are discussed.
Introduction ============ Over the last 15 years, Italy has experienced a great increase of separations and divorces. From 1995 to 2011, separations increased by 68.8% and the rate of divorces nearly doubled. Official statistics show that in 2012 the separations were 88,288 and 51,319 divorces and that the children involved were 112.253 in separations and 53.553 in divorces. Slightly less than half (48.7%) of separations and one--third (33.1%) of divorces involve marriages with at least one child less than 18 years ([@B22]). The prevalence and consequences of marital instability and divorce in Italy have stimulated a large interest from a host of public and private sectors, including policy makers, scholars and practitioners, women's and fatherhood associations. In the Italian courts always more frequently separations and divorces are characterized by high and persistent conflicts. Individual problems and psychological distress during marital dissolution may interfere with parenting practices and affect the parent--child relationship. Mothers in high conflict marriages are reported to be less warm, more rejecting, and use harsher discipline, and fathers withdraw more and engage in more intrusive interactions with their children compared with parents in low-conflict marriages ([@B19]; [@B28]). Divorce has several direct and indirect economic consequences that are absorbed not only by individuals, but also by communities and governments. Health professionals and social workers offer notable support to families who are in high conflict to achieve agreement between parents and to decrease the effect of disruption on the quality of parent--child relationships during marital dissolution. Moreover, following separation or divorce, in some instances of parental conflict, the child may be asked or expected to take action (as opposed to being a passive recipient of one parent's negative view of the other parent) and may respond by aligning with one parent, sometimes referred to as triangulation in the family systems literature ([@B32]). Research on family postdivorce shows that high and persistent conflict is more likely to be destructive when parents use their children to express their anger and are verbally and physically aggressive ([@B24]; [@B23]). Parents put their children in the middle by asking children to carry hostile messages, by denigrating the other parent in front of the child, or by prohibiting mention of the other parent in their presence. Parental alienation (PA) is the term used to describe a range of parental behaviors that are likely to foster a child's unreasonable and unwarranted rejection of the other parent, referred to as the "targeted parent." From the studies, 17 specific behaviors have become known as the primary PA behaviors ([@B5]; [@B8]), such as "limiting contact between the child and the targeted parent," "withholding love and affection from the child when the child is affectionate or positive toward the targeted parent," "forcing the child to reject the targeted parent, telling the child that the targeted parent does not love him/her." PA behaviors produce conflict between the child and targeted parent and create a psychological cohesion between the child and the parent engaging in these behaviors. In some cases, the child becomes so affected by these PA behaviors that s/he will cut off all contact with the targeted parent. In this context of court-mandated, reunification efforts attempted by mental health professionals and social workers often have a high failure rate. While the targeted parent is highly motivated to treatment, the alienating parent--child dyad is highly motivated to see treatment fail. This is because for them, the rejection of the targeted parent is not the problem, rather it is the solution to the problem ([@B16]). The psychological base of PA -- lack of empathy and the inability to tolerate the child's separate needs and perception ([@B5]; [@B6]) -- could be also the expression of a specific parenting style characterized by low care and high overprotection. Parents who engage in alienating behaviors can be cold, rejecting, disengaged as well as intrusive and psychologically controlling. What are the negative outcomes of these dysfunctional parental behaviors? The literature on the impact of divorce on young adults shows that divorce, and inter-parental conflict can negatively affect children throughout their lifespan. Studies demonstrate that even when parents initiate a divorce when their offspring are over the age of 18, the impact can be substantial ([@B1]). Some of these relational patterns remain during young adulthood and may interfere with the individual's ability to separate and become self-sufficient ([@B33]; [@B3]; [@B2]). Children of divorce who feel caught between their parents' conflict have been found to have a more problematic adjustment and internalizing problems than those who do not feel caught ([@B12]). According to [@B2] youth who are involved in their parents' conflict can feel caught between their parents and hence experience stressful loyalty conflicts and cognitive dissonance. Although such an alliance can resolve the child's immediate feeling of being caught in the middle ([@B16]), it can entail its own set of problems. For example, [@B2] suggest that when children become turned against one parent, they lose the support and guidance of the now rejected parent, and they may experience feelings of guilt and shame for rejecting and betraying the other parent. Several studies have shown significant associations between recall of exposure to parental loyalty conflicts behaviors and negative outcomes in adulthood as a low autonomy, low cooperativeness, low self-esteem, depressive symptoms, and psychological distress ([@B6]; [@B10]; [@B42]; [@B11]). Therefore is not simply the degree of parental conflict that seems to affect youth detrimentally following the divorce of their parents, but rather the degree to which they are drawn into their parents' conflict (and hence likely to be exposed to PA behaviors). Parental bonding is considered as a main developmental task that is critical for adequate functioning. Comfortable bonding with caregivers is assumed to provide the psychological foundation for healthy functioning in adulthood. Many studies have found associations of parental care and overprotection with domains of adult functioning ([@B21]; [@B44]) and with development of psychiatric disorders ([@B31]; [@B17]). Living with competent parents is a protective factor associated with positive outcome in children ([@B19]; [@B25]; [@B41]). When parents provide warmth, emotional support, adequate monitoring, authoritarian discipline, and maintain age-appropriate expectations, children and adolescents experience positive adjustment compared with children whose divorced parents are inattentive, less supportive, and use coercive discipline ([@B19]; [@B28]; [@B29]). The long term outcomes of children are dependent on many factors, among them the quality of parenting they received before and after divorce, and the encapsulation in the conflict between parents that they experienced during the marriage and after divorce. Many authors have emphasized the role of early relationships with parents in determining the way in which the children develop their beliefs about their worth as a separate, unique person and where they stand in relation to others ([@B40]). Self-esteem is a significant psychological construct and a central component of individuals' daily experience. It refers to how individuals feel about themselves and reflects and affects their transactions with the environment and the people they encounter ([@B38]; [@B27]). Self-esteem was found to be positively related to mother and father care and negatively related to parental overprotection for people with Anglo and Vietnamese cultural backgrounds ([@B20]). Other studies found that family environment, especially the problematic parental relationship, is a predictor of self-esteem ([@B30]). Moreover, research on the relations between self-esteem and psychopathological symptoms, both in children and adolescents and in adults, show inverse relationships between these constructs ([@B45]; [@B18]). Another important issue is that the negative outcomes of divorce on children do not depend only on family processes, such as family dysfunction and parental conflict. Literature has demonstrated that children and adolescents vary as to their vulnerability to the effects of marital conflict ([@B19]; [@B26]). Negative life events -- in which we might include also separation/divorce with high conflict -- may trigger psychological stress which can also be influenced by individual factors, including self-esteem ([@B35]). Therefore, an important question is to explore whether certain children are more or less vulnerable due to their own personal qualities. The study of these individual qualities may provide information on potential protective factors to help them even in at-risk contexts ([@B13]) and to direct intervention programs aimed to disrupt the intergenerational cycle of dysfunctional relationships. In the Italian context, international psychological literature is frequently used because there is a lack of national researches on some crucial issues that may have significant implications for what is in the best interest of children in divorced families who are in legal conflicts. To date, no researcher has attempted to examine how the associations between parental functioning -- in terms of parental bonding and PA -- and self-esteem could affect psychological distress in adults whose parents are separated/divorced. Since individual protective factors are a meaningful variables for psychological adjustment, we are interested to know the extent to which family variables (i.e., parental bonding and PA) and an individual variable (self-esteem) could predict psychological distress in adulthood. The specific questions in the current study included: (1) What is the prevalence of recall of childhood exposure to parental loyalty conflict behaviors in an Italian population of adults whose parents had separated or divorced?; (2) What kind of parental bonding perceived adults whose parents had separated or divorced?; (3) Did recall of exposure to parental loyalty conflict behaviors vary by parental bonding?; (4) Were reports of parental bonding and recall of exposure to parental loyalty conflict behaviors associated with self-esteem?; (5) Was psychological distress predicted by parental functioning and individual self-esteem? Material and Methods ==================== Participants and Procedure -------------------------- Between April and December of 2013, flyers were delivered to a variety of employment, recreational, and university settings in the southern region of Italy as well as distributed to friends and colleagues who were encouraged to forward it to others. The flyers stated that a researcher in the Clinical Psychology Laboratory at University of Chieti was "Seeking adults whose parents are separated/divorced." Interested individuals were invited to contact the researcher via telephone or e-mail. Once individuals came to the Laboratory were asked for their willingness to take part in a research study related to parental relationships. Those who were interested were informed of the voluntary nature of their participation and they right to withdraw at any time. All participants received and signed an informant consent. Individuals who provided consent were escorted to a private area where they could sit and complete the questionnaire packet. The packet contained two demographic questions that would provide certain information about participants regarding specific inclusion/exclusion criteria. Specifically, only those individuals were selected for the final sample who experienced parental separation/divorce and who had both parents alive until the age of at least 12 years. A non-random convenience sample of 497 participants was recruited. Nineteen cases were eliminated due to incomplete data, and an additional eight participants were excluded because they only had one parent. Thus, the final sample was made up of 470 adults whose parents are separated/divorced residing in southern Italy. Mean age of participants was 25.4 (*SD* = 6.13), and 55.5% were female; 76.4% of the participants had a high school degree or less, 41% had a job, and 40% were students. Mean age at first parental separation was 12.7 (*SD* = 6.10). The protocol was realized according to the ethical guidelines of the Italian Association of Psychology (AIP) and was approved by the local ethics committee. Measures -------- The paper and pencil measures consisted of a series of demographic questions (age, age at first parental separation/divorce, gender, level of education, and employment) and a series of standardized questionnaires, four of which were examined for this study. Baker Strategy Questionnaire (BSQ; [@B7]). The BSQ is a 20-item measure comprised of a list of 19 specific behaviors and one general behavior that parents might engage in to induce loyalty conflict in their child. The respondents answered separately for mother and father on a five- point scale from never (0) to always (4). Total scores could range from 0 to 80 for each parent. For the mother total scores ranged from 0 to 80 (Mean = 13.5, *SD* = 14.7) and for the father total scores ranged from 0 to 66 (Mean = 10.6, *SD* = 12.4). In the present study, the measure demonstrated high internal consistency for the mother and for father (α = 0.94). Scores across parents were also combined to create a "total exposure to PA measure" which could range from 0 to 160 and did range from 0 to 122 (Mean = 23.8, *SD* = 23.7). Parental Bonding Instrument (PBI; [@B34]; [@B39]). The quality of the parent--child relationship was measured with the Parental Bonding Instrument, a widely used research tool for assessing adult retrospective accounts of two dimensions of the parent--child relationship: care (12 items) and over-protectiveness (13 items). Respondents completed the scale twice, once for mother, once for father. The Care scale consists of items tapping warmth, understanding, and acceptance (e.g., "Enjoys talking things over with me," "Makes me feel better when I'm upset"). The Overprotection scale measures control, intrusiveness, and encouragement of dependence (e.g., "Tries to control everything I do," "Invades my privacy"). Total scale scores could range from 0 to 36 (Care scale) and from 0 to 39 (Overprotection scale). The mean scores in this sample were: mother care = 25.22, *SD* = 7.7, mother overprotection = 13.81, *SD* = 6.7, father care = 20.53, *SD* = 8.4, father overprotection = 12.10, SD = 6.6. Cronbach's alpha for the four scales were: mother care = 0.93, mother overprotection = 0.85, father care = 0.92, father overprotection = 0.83. Additionally, scores can be assigned to four quadrants reflecting variations in care and control: (1) high care/low control = optimal parenting, (2) high care/high control = affectionate constraint, (3) high control/low care = affectionless control and (4) low care/low control = neglectful. Assignment to 'high' and 'low' categories is based on the following cut-off scores: mothers, 27 for care and 14 for protection; fathers, 24 for care and 13 for protection ([@B34]). Overprotection and Care scales were created for each parent and then summed to create an overall Overprotection and Care index. Rosenberg Self-Esteem Scale (RSES; [@B38]; [@B36]). Self-esteem was assessed with the 10-item self-report Rosenberg Self-Esteem Scale in which each item was rated on a four-point Likert scale from strongly disagree (0) to strongly agree (4). Total scores were created by summing the 10 items after reverse coding. In this study the summary score ranged from 16 to 40 (Mean = 29.4, *SD* = 4.8) and had an internal consistency coefficient of 0.82. Symptom Checklist-90-Revised (SCL-90-R; [@B14]; [@B37]). This is a self-report questionnaire applied as a psychiatric case-finding instrument, as a measure of symptom severity, and as a descriptive measure of psychopathology in different patient populations. The SCL-90 is intended to measure symptom intensity on nine different subscales and three global indexes of distress. The 90 items of the questionnaire are scored on a five-point Likert scale from none (0) to extreme (4), indicating the rate of occurrence of the symptom during the time period in question. The instrument's Global Severity Index (GSI) is created as the mean value of all of the items and ranges from 0 to 4. The GSI is the most often used SCL-90-R global index when a single measure of psychological distress is warranted \[40\]. In the current study only the GSI was used as a measure of global psychological distress. In this sample the GSI ranged from 0 to 3.26 (Mean = 0.74, *SD* = 0.58), with a Cronbach's alpha of 0.98. Results ======= All data were checked for invalid values, out-of-range data, and counting of missing values. Missing items were replaced with the individual's mean item score of the completed items as recommended by [@B15]. In addition, the scores were checked for normality, and parametric tests were then applied. Descriptive statistics were calculated for the sample. Preliminary analyses were conducted to test whether any of the demographic variables (age, age at first parental separation, gender, and educational level) were significantly associated with the dependent measure. Only participant's age was significantly associated with GSI score; consequently it was included in subsequent analyses. What is the Prevalence of Recall of Childhood Exposure to Parental Loyalty Conflict Behaviors in an Italian Population of Adults Whose Parents Separated or Divorced? --------------------------------------------------------------------------------------------------------------------------------------------------------------------- To address the first research question about the prevalence of childhood exposure to parental loyalty conflict behaviors, the proportion of respondents who endorsed each of the 20 behaviors was calculated with frequency distributions (see **Table [1](#T1){ref-type="table"}**). ###### Frequency distribution of endorsement of 20 specific loyalty conflict behaviors. Behavior *N* \% ---------------------------------------------- ----- ------ Made negative comments 378 81.4 Discomfort at other parent 288 62.1 Confided in child 277 59.7 Encouraged reliance on him/herself 255 55.5 Upset at child's affection with other parent 244 53.4 Required favoritism of child 247 53.3 Tried to turn against other parent 216 46.1 Asked child to keep secrets 208 44.7 Made child choose 189 40.7 Limited contact 184 39.8 Fostered anger/hurt at other parent 167 35.8 Encouraged disregard of other parent 162 35.2 Asked child to spy 159 34.4 Said parent was unloving 152 32.9 Said parent was unsafe 135 29.1 Hard to be with extended family 134 29.0 Made communication difficult 124 26.6 Called other parent by first name 82 17.8 Withheld or blocked messages 71 15.3 Referred to new spouse mom/dad 46 9.9 As can be seen, all 20 behaviors were endorsed by at least some participants. Looking at the proportion of endorsers of each behavior, it can be seen that 19 of the 20 items were endorsed by at least 10% of the sample. Two items were endorsed by over 60% of the sample (made negative comments, indicated discomfort about other parent). Seven of the behaviors were endorsed by between 40 and 60% of the respondents (made child choose, asked child to keep secrets, tried to turn against other parent, required favoritism of child, upset child affectionate with other parent, encouraged reliance on himself or herself, confided in child). Eight of the PA behaviors were endorsed by 20 and 40% of the respondents (made communication difficult, hard to be with extended family, said parent was unsafe, said parent was unloving, asked child to spy, encouraged disregard of other parent, made it fostered anger/hurt with other parent, limited contact with other parent). Three behaviors were endorsed by under 20% of the respondents (called other parent by first name, withheld or blocked messages, and referred to the new spouse as Mom or Dad). What Kind of Parental Bonding have Perceived Adults Whose Parents had Separated or Divorced? -------------------------------------------------------------------------------------------- To address the second research question we examined the parental Care and Overprotection data. The distribution of cases across the four possible parenting types revealed that for mothers 151 (35%) of the sample were in the "optimal parenting" quadrant, 83 (19.2%) were in the "affectionate constraint" quadrant; 113 (26.2%) were in the affectionless control quadrant, and 85 (19.7%) were in the neglectful parenting quadrant. For fathers, the percentages were 29.4% for optimal parenting, 14.5% for affectionate constraint, 28.5% for affectionless control, and 26.4% were in the neglectful parenting quadrant. Did Recall of Exposure to Parental Loyalty Conflict Behaviors Vary by Parental Bonding? --------------------------------------------------------------------------------------- In order to examine the relationship between exposure to parental loyalty conflict behaviors and parental bonding, we examined mean differences in BSQ scores by PBI quadrants (optimal parenting, affectionate constraint, affectionless control, neglectful parenting). One-way ANOVA's were conducted to test the hypothesis that perceived lack of care and overprotection during childhood would be associated with exposure to parental loyalty conflict behavior by mothers and by fathers. Mean scale scores are presented in **Table [2](#T2){ref-type="table"}**. ###### Means of parental alienation behaviors by PBI bonding quadrants of parents. By Mother By Father --------------- ----------- ------------- -------------- ----- ------------- -------------- Optimal 151 8.4 (10.5) 6.75, 10.13 127 6.9 (8.1) 5.53, 8.37 Affectionate 83 8.4 (9.7) 6.24, 10.49 63 6.4 (7.6) 4.47, 8.32 Affectionless 113 22.7 (17.8) 19.39, 26.04 123 18.2 (16.4) 15.25, 21.10 Neglectful 85 15.0 (14.7) 11.87, 18.20 114 8.9 (9.9) 7.02, 10.73 CI, confidence interval. Optimal (parenting); affectionate (constraint); affectionless (control); neglectful (parenting). The results indicated significant differences across PBI quadrants (mother) for exposure to maternal loyalty conflict behaviors \[*F*(3,431) = 28.975, *p* \< 0.001\]. *Post hoc* test Bonferroni revealed that, compared to individuals who reported optimal parenting and affectionate constraint, individuals who experienced affectionless control reported significantly higher exposure to maternal loyalty conflict behaviors. Moreover, individuals who reported neglectful parenting had significantly higher recall of exposure to maternal loyalty conflict behaviors compared to participants who reported optimal parenting and affectionate constraint, and lower recall compared to adults who experienced maternal affectionless control. For paternal parenting, differences across PBI quadrants (father) on measures of exposure to paternal loyalty conflict behaviors were significant \[*F*(3,426) = 25.702, *p* \< 0.001\]. *Post hoc* test Bonferroni revealed that, compared to individuals who reported optimal parenting, affectionate constraint, and neglectful parenting, individuals who experienced affectionless control reported significantly higher recall of exposure to paternal loyalty conflict behaviors. Were Reports of Parental Bonding and Recall of Exposure to Parental Loyalty Conflict Behaviors Associated with Self-esteem? --------------------------------------------------------------------------------------------------------------------------- Pearson correlations were conducted between RSES score and both the PBI and BSQ overall indexes. These data are presented in **Table [3](#T3){ref-type="table"}**. As can be seen parental care, parental overprotection, and recall of exposure to parental loyalty conflict behaviors were statistically significantly associated with self-esteem. Higher care scores, lower overprotection scores, and lower recall of exposure to parental loyalty conflict behaviors were all associated with higher self-esteem scores. ###### Bivariate correlations for study variables. 1 2 3 4 5 6 ----------------------------------------- --- ----------- ------------ ------------ ------------ ------------ \(1\) SCL-90-R -- global severity index 1 -0.114^∗^ -0.244^∗∗^ 0.193^∗∗^ 0.239^∗∗^ -0.537^∗∗^ \(2\) Age 1 -0.203^∗∗^ 0.144^∗∗^ 0.042 0.132^∗∗^ \(3\) PBI -- parental care 1 -0.313^∗∗^ -0.410^∗∗^ 0.273^∗∗^ \(4\) PBI -- parental overprotection 1 0.251^∗∗^ -0.230^∗∗^ \(5\) BSQ -- parental alienation 1 -0.232^∗∗^ \(6\) RSES -- self-esteem 1 SCL-90-R, Symptom Checklist-90-Revised; PBI, Parental Bonding Instrument; BSQ, Baker Strategy Questionnaire; RSES, Rosenberg Self-Esteem Scale. ∗ p \< 0.05. ∗∗ p \< 0.01. Was Psychological Distress Predicted by Parental Functioning and Individual Self-esteem? ---------------------------------------------------------------------------------------- To address the last research question we began with Pearson correlations between age, PBI and BSQ overall indexes, RSES and GSI scores. Results revealed that GSI score was statistically positively associated with parental overprotection (*r* = 0.193, *p* \< 0.01) and recall of exposure to parental loyalty conflict behaviors (*r* = 0.239, *p* \< 0.01), and was statistically negatively associated with age (*r* = -0.114, *p* \< 0.05), parental care (*r* = -0.244, *p* \< 0.01), and self-esteem (*r* = -0.537, *p* \< 0.01). All of these variables were entered into hierarchical regression to test whether psychological distress was predicted by parental functioning (in terms of care, overprotection and exposure to parental loyalty conflict behaviors) and by self-esteem. In regression a GSI score was the dependent variable and parental care, parental overprotection, and age were entered as a first block, recall of exposure to parental loyalty conflict behaviors was added in the second block followed by self-esteem in the third block. The data are presented in **Table [4](#T4){ref-type="table"}**. ###### Hierarchical regression analysis predicting global severity index (GSI) from familiar and individual variables. Predictor Δ *R^2^* β -------------------------------- ----------- ------------- Step 1 7.8^∗∗∗^ PBI -- parental care -0.220^∗∗∗^ PBI -- parental overprotection 0.114^∗^ Age -0.150^∗∗^ Step 2 1.9^∗∗^ PBI -- parental care -0.161^∗∗^ PBI -- parental overprotection 0.090 Age -0.139^∗∗^ BSQ -- parental alienation 0.155^∗∗^ Step 3 19.4^∗∗∗^ PBI -- parental care -0.056 PBI -- parental overprotection 0.022 Age -0.046 BSQ -- parental alienation 0.101^∗^ RSES -- self-esteem -0.474^∗∗∗^ Total *R*^2^ 29.1^∗∗∗^ *n* = 423 PBI, Parental Bonding Instrument; BSQ, Baker Strategy Questionnaire; RSES, Rosenberg Self-Esteem Scale. ∗ p \< 0.05, ∗∗ p \< 0.01, ∗∗∗ p \< 0.001. The hierarchical regression revealed that at Block 1 all of the variables contributed significantly to the regression model, *F*(3,419) = 11.77, *p* \< 0.001 and accounted for 7.8% of the variation in global psychological distress. Introducing parental loyalty conflict behaviors (Block 2) explained an additional 1.9% of variation in global psychological distress and this change in *R*^2^ was significant, *F*(4,418) = 11.23, *p* \< 0.001. Each of the variables entered in Block 1, with the exception of parental overprotection, remained significant predictors once parental loyalty conflict behaviors were added to the model. The addition of self-esteem to the regression model (Block 3) explained an additional 19.7% of the variation in global psychological distress. The change in *R*^2^ for self-esteem was statistically significantly associated, *F*(5,417) = 34.30, *p* \< 0.001, with global psychological distress over and above the effects of age, parental care, and parental overprotection, (29.1% of the variance in global psychological distress). Discussion ========== This study investigated the prevalence of recall of childhood exposure to parental loyalty conflict behaviors, the kind of parental bonding perceived by adults whose parents had separated or divorced, and the link between parental functioning, individual self-esteem and psychological distress. The current study extends our empirical knowledge of the childhood exposure to dysfunctional parenting in families postdivorce. A number of important findings were shown in the data. First, 46% of the sample endorsed the item "one parent tried to me against the other parent," a similar proportion than in [@B42] for the subsample of participants whose parents divorced or separated, indicating the high prevalence of this problem for children of divorce. Results revealed that all behaviors measured by BSQ were endorsed by at least some participants. Rates of endorsement for the specific types of parental behaviors assessed ranged from about 10% (referring to a stepparent as "Mom" or "Dad") to about 81% (made negative and untrue statements about the other parent to the child). Behaviors endorsed at a particularly high rate included making negative comments about the other parent, indicating discomfort when the child speaks or asks about other parent, confiding in child, and encouraging the child's reliance. These data are consistent with what is known about the prevalence and the quality of PA within divorcing families ([@B7]). Second, a significant finding is that about 65--70% of the participants has perceived by both parents a dysfunctional parenting characterized by low care and high overprotection (affectionless control) or by high care and high overprotection (affectionate constraint) or low care and low overprotection (neglectful parenting). This finding is consistent with specialized literature reporting how separated or divorced parents are less effective in monitoring their children and more emotionally detached from their role as parents ([@B19]; [@B28]; [@B43]; [@B29]). Third, the recall of exposure to parental loyalty conflict behaviors varied by parental bonding perceived. Interestingly, parents perceived as less caring and more controlling are also described as more engaged in PA behaviors. This was true for ratings of mothers as well as fathers. This finding provides the empirical confirmation of the theoretical definition of the PA behaviors as a lack of empathy and inability to tolerate the child separate needs and perceptions ([@B5]; [@B6]). Encouraging disobedience in the children and blaming behavior on the other parent, or disparaging the children's image of the other parent, or sharing excessive information with the child and promoting parentification are all behaviors that involve low care and high psychological control. Likewise, these data contribute to the growing body of knowledge about how rapidly identify parents at risk to engage in alienating behaviors. Fourth, the results revealed that self-esteem was associated positively with parental care and negatively with parental overprotection and PA. That is, Italian adults' perception of comfortable bonding with caregivers defined by affection, emotional warmth, empathy, closeness, and promotion of independence and autonomy is associated with a positive self-concept. These results confirm findings from previous studies ([@B20]; [@B9]) and extend the evidence into Italian adults whose parents are separated or divorced. The final significant finding was that high exposure to parental loyalty conflict behaviors and low self-esteem were associated with psychological distress even after controlling for quality of the parent--child relationship. Therefore, the current data demonstrate that exposure to parental loyalty conflict behaviors and low self-esteem can also increase an adult's risk of psychological distress. These data are consistent with literature regarding negative consequences of exposure to PA in adulthood ([@B6]; [@B10]; [@B11]). The results also support the role of self-esteem as an individual factor to cope with psychological distress ([@B42]) after experiencing negative life events as parental separation/divorce. One possible reason is that low self-esteem could bring a person to perceive only negative aspects of situations or to have a poor perception of one's capacity to cope with stressing environments. Limitations ----------- There are a number of limitations in this study that should be taken into account. The first is the cross-sectional nature of the design. Although this is a common design in studies of PA, we emphasize the need for prospective studies for establishing causal pathways. The second limitation is the retrospective nature of data collected through self-report measures. Data did not necessarily reflect the full complement of parental loyalty conflict behaviors to which the person had been exposed. Nevertheless, [@B4] reported some overlap between retrospective and independent measures of parental behaviors noting that the perception of the parental relationship is more important than the actual parental relationship. The third is the limited generalizability due to the convenience nature of the sample. The findings should be replicated in other settings and in other samples of various ages, backgrounds, and life experiences. Despite these limitations, the current study also had several strengths. All of the measures have been used in prior research and most are standardized measures with established reliability and validity. Also, there are methodological advantages of a large community sample used in this study. Furthermore, this was the first study conducted on a general sample of adults whose parents are separated/divorced in Italy highlighting the importance of subsequent research on the causal linkages between dysfunctional parenting and individual resilience and psychological distress. Future research with varied ages and diverse populations as well as other individual variables will complete these findings on how familiar and individual factors affect the adjustment in adulthood following parental divorce. Implications ------------ In this study there was strong support for a link between crucial variables to the psychological climate of the divorced families (e.g., parental loyalty conflict, low caring in terms of emotional coldness, indifference, neglect, and high control in terms of overprotection, intrusion, excessive contact, infantilization, and prevention of independent behavior), self-esteem and well-being in adulthood. The results of the present research bring to light several important implications for policymakers and practitioners working with divorced families and suggest the need for interventions based on a greater knowledge of the dysfunctional family processes. Clinicians and forensic psychologists should be aware that improve parenting practices and promote self-esteem in children or adolescents after marital dissolution may prevent the development of negative outcomes. As can be seen in literature there are many variables (biological, psychological, familiar, interpersonal, etc.) to be considered in the prevention and treatment of psychological distress, but our results about the offspring of divorced parents corroborate the evidence that exposure to PA and individual self-esteem significantly affect their well-being in adulthood. Prevention programs could be directed to reinforcing health and social services to support divorcing and high conflict families. Health professionals and social workers should receive training specifically about the PA strategies that parents can engage in, dysfunctional parenting practices, and specific negative outcomes for children. Other prevention programs directed at high risk parents (those divorcing or involved in high conflict) could involve mandatory training for high conflict parents. Psycho-educational programs should focus on interventions for enhancing parenting skills and appropriate child rearing and co-parenting practices. Psychological interventions for children of divorce exposed to dysfunctional parenting could also be carried out to increase coping strategies and resilience in order to protect them from the long-term damage to their sense of self. Given the potential detrimental impact of parental loyalty conflict behaviors on the well-being of children, it is critical to develop interventions to address this phenomenon. Despite a recent awareness of this problem, very few health and social services use adequate strategies for the management of their clients. Therefore, policy changes in health and social care to promote training on this issue could aid in disseminating of professional training in this area. Practitioners should receive training specifically about how: (a) to create a buffer zone to facilitate crossing the co-parental boundary, (b) to help the child separate from the enmeshment with the alienating parent, (c) to block intrusions from the alienating parent, (d) to strengthen the bond with the targeted parent, and (e) to weaken the coalition around the alienating parent--child dyad ([@B16]). Finally, this information about family dysfunctions in marital dissolution should be widespread to the family court judges in order to decide an arrangement that will promote the best interest of the child. Conflict of Interest Statement ============================== The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. [^1]: Edited by: *Gianluca Castelnuovo, Università Cattolica del Sacro Cuore, Italy* [^2]: Reviewed by: *Suzie Xu Wang, Leeds Beckett University, UK; Jimmy Thomas Efird, Brody School of Medicine, USA* [^3]: This article was submitted to Psychology for Clinical Settings, a section of the journal Frontiers in Psychology
simon cowell During this weeks semi-final competition on NBC's America's Got Talent, the State of Wyoming was prominently featured during a magic act! Jon Dorenbos is a professional football player and is entering his 14th season in the NFL and is getting ready for this year with the Philadelphia Eagle… Are you a solo singer? A girl group? duo? boy band? or a vocal group? Maybe you and your friends have always wanted to form a group or maybe you gave up on your dream of being a singer years ago? Well, now IS your time - it’s never too late to follow your dreams...
In nitration processes to produce nitrated aromatic products, nitro-phenolic species and other oxidative decomposition compounds are formed as by-products. For example, nitration of benzene produces nitrophenols, nitration of toluene produces nitrocresols, and nitration of xylene produces nitroxylenols. The crude nitrated aromatic product requires purification to remove these by-products before it is suitable as a feedstock to downstream hydrogenation processes, where these impurities are believed to adversely affect the catalyst performance. The purification of nitrated aromatic products is commonly practiced industrially by contacting the crude nitrated organic with an alkaline water stream in a multi-stage counter-current washing system. The nitro-phenolics and other oxidation compounds, which are organic acids, are neutralized into their respective organic salt form and extracted into the alkaline water phase to produce a water effluent stream rich in nitro-phenolics and other oxidation species. This process is well known, and is described in the patent literature: U.S. Pat. No. 6,288,289 (Boyd et al.); U.S. Pat. No. 4,604,214 (Carr et al.); U.S. Pat. No. 6,506,948 (Sawicki); US 2007/0088183 (Hermann et al.); and WO 2012/156095 (Polmann et al.). The generated effluent stream is commonly known as strong effluent or red water, due to its high nitro-phenolic concentration and its strong characteristic color. The treatment of this effluent stream is particularly challenging since some nitro-phenolics are highly bio-toxic, such that biological wastewater treatment plants can only tolerate very low concentrations. Therefore, this effluent stream usually requires pre-treatment to reduce its toxicity before it can be discharged to a biological treatment facility. There are several effluent treatment technologies currently in use to treat this strong effluent stream. These include: thermal destruction (U.S. Pat. No. 4,230,567), wet oxidation (U.S. Pat. No. 5,250,193, U.S. Pat. No. 8,801,932), solvent extraction (U.S. Pat. No. 4,597,567 and U.S. Pat. No. 4,925,565), ozonation (U.S. Pat. No. 4,604,214) and incineration/thermal oxidation (U.S. Pat. No. 6,288,289). The optimum treatment technology is dependent on many factors, including local site conditions, economics and operator preference. In addition, the selected treatment technology is dependent on the type of base used to provide alkalinity in the nitrated product purification system. In most industrial plants, caustic soda (sodium hydroxide) is used as the washing base to provide the required alkalinity for the nitrated product purification process; however, aqueous ammonia is used in a small fraction of industrial nitration processes. The reason for caustic soda being favored is that it is a stronger base than ammonia, and as such, results in superior washing efficiency and leads to higher product quality, with lower nitro-phenolic and oxidation species in the final washed nitrated aromatic product. Ammonia, being a weaker base, is not able to effectively neutralize and thereby extract some of the weaker organic acid by-products (i.e., those which have higher pKa values). In addition, caustic is non-volatile whereas ammonia exerts a significant vapor pressure and may deposit unstable ammonium nitrite salts formed by reacting ammonia with NOx present in the nitration plant vent. However, ammonia may be the preferred washing base if incineration/thermal oxidation is chosen as the strong effluent treatment option. In general, inorganic salts produce ash in the incinerator which can attack the refractory lining and require the installation of a slag collection system; whereas, ammonia is reduced to nitrogen in a thermal oxidizer so there are no ash deposits to deal with. Operating costs of incineration can be fairly high due to the large amount of water that has to be vaporized. However, in some circumstances incineration may be an attractive option as it has the benefit of not requiring further treatment, such as a biological treatment, and can reduce total capital investment costs of a project. It can also achieve competitive operating costs where there is a low cost of energy or alternatively where the effluent stream can be used to offset water already used in an incineration process. In summary, selecting caustic soda as the washing base results in improved product quality but requires additional treatment processes to treat the generated strong effluent. Alternatively, selecting ammonia allows for incineration/thermal oxidation which can eliminate the requirement for further treatment processes but results in reduced product quality, which may negatively affect the downstream processes.
Vitals 8-week placebo-controlled trial of oxytocin for treatment of in children with autism City: Chapel Hill State/Province: NC State/Province Full: North Carolina Country: United States Oxytocin is a brain peptide that appears critically important in normal prosocial behaviors. Oxytocin system changes in mice lead to some autistic-like behaviors. Several different types of genetic evidence suggest that the oxytocin receptor gene is involved in autism. Multiple studies show that oxytocin can enhance social judgment and prosocial behaviors in people with autism or typical development. Two small studies in people with schizophrenia suggest brief oxytocin treatment is safe. The first goal of this study is to obtain preliminary data necessary to inform the design of a large conclusive study of the benefits of oxytocin in autism. Other goals are to see if 1) recently discovered non-inherited differences in DNA around the oxytocin receptor in autism have functional effects on oxytocin receptors and 2)if measurements of oxytocin system molecules appear related to severity of social problems or benefits in autism. The investigators will treat 24 youth 3-17 year old who have autism and any level of cognitive functioning with oxytocin or saline nasal spray 2x/D for 2 months. Neither the practitioner nor the participants will know who gets oxytocin and who gets saline. Afterwards, everyone will receive oxytocin for 2 months. The researchers will determine how many participants would need to be in a larger study to get a clear answer about whether oxytocin is beneficial and how best to measure improvements due to oxytocin. DNA changes will be examined to see if they control the number of oxytocin receptors and if they relate to symptoms or oxytocin response. It is expected that oxytocin will be beneficial and that DNA changes will correlate with the amount of oxytocin receptor made. Measurement of oxytocin system molecules will identify a distinct group of people with social disabilities in autism and will predict who will respond to oxytocin treatment. This is one of the first potential treatments for autism that is based on information about biologic processes that may cause core autistic symptoms. The results will inform the design of a conclusive study that gives a clear answer about whether oxytocin has benefit in autism. This pilot study may also help develop a blood test that would tell us who is most likely to respond to oxytocin treatment. Finally, the data will increase understanding about how non-inherited changes in the DNA around the oxytocin receptor affect people with autism.
Involvement of MRE11A and XPA gene polymorphisms in the modulation of DNA double-strand break repair activity: a genotype-phenotype correlation study. DNA double-strand breaks (DSB) are the most lethal form of ionizing radiation-induced DNA damage, and failure to repair them results in cell death. In order to see if any associations exist between DNA repair gene polymorphisms and phenotypic profiles of DSB repair (DSBR) we performed a genotype-phenotype correlation study in 118 young healthy subjects (mean age 25.8±6.7years). Subjects were genotyped for 768 single nucleotide polymorphisms (SNPs) with a custom Illumina Golden Gate Assay, and an H2AX histone phosphorylation assay was done to test DSBR capacity. We found that H2AX phosphorylation at 1h was significantly lower in subjects heterozygous (no variant homozygotes were observed) for the XPA gene SNP rs3176683 (p-value=0.005), while dephosphorylation was significantly higher in subjects carrying the variant allele in three MRE11A gene SNPs: rs1014666, rs476137 and rs2508784 (p-value=0.003, 0.003 and 0.008, respectively). An additive effect of low-activity DNA repair alleles was associated with altered DSBR activity, as demonstrated by both H2AX phosphorylation at 1 h (p-trend <0.0001) and γH2AX dephosphorylation at 3h (p-trend <0.0001). Our study revealed that in addition to SNPs of genes that are well-established players in DSBR, non-DSBR genes, such as the XPA gene that is mainly involved in the nucleotide excision repair pathway, can also influence DSBR in healthy subjects. This suggests that successful DSBR may require both DSBR and non-DSBR mechanisms.
Premises Liability The state of Florida is a property owner's paradise. Beautiful weather, countless tourists and consumer driven residents make the Sunshine State a prominent shopping and business environment. When individuals enter their property, the owners and proprietors have an obligation to provide a safe and secure environment for them. When they fail to do so, those in their care can be subject to serious dangers. Premises liability is the legal term for the responsibility of property owners or proprietors for the issues that develop on their land. Apartment, office and shop owners are all required to abide by safe practices. When they are unable to keep those around them safe, the injured individual has the right to file suit in the form of personal injury litigation. If you or a loved one has been injured due to the negligent actions (or inaction) of a property owner, it is vital that you work with a capable attorney who can effectively navigate through the complex legal waters towards a favorable solution that compensates you for the related costs. Melbourne Premises Liability Attorney When tragedy strikes, a quick response is paramount. With qualified representation, a premises liability case can be undertaken in a professional and productive manner. Our attorney is well versed in these cases and have years of proven experience helping residents and visitors of Central Florida. Focused on providing comprehensive representation, we take control of every element of your premises liability case, from gathering evidence and interviewing witnesses, to technical analysis of the scene and evaluating the cost of your injuries. Personal injury litigation must be undertaken by those who understand the risks involved, and our firm is ready to fight for your rights against the selfish interests of those who are looking to protect themselves and their bottom line. As a Melbourne based legal practice, our firm is a convenient option for individuals and families throughout Brevard County, Florida, including Palm Bay, Satellite Beach, Palm Shores, Cocoa, Cape Canaveral, and Rockledge. We are also committed to a quick response and timely representation, so we will immediately begin your case following an initial consultation. To schedule a time to meet with an attorney and go over your premises liability case, please call (321) 586-9944 or send an online message today. These instances of premises liability will be used to start developing a list of damages to pursue. Damages are the costs related to the injuries and include monetary and nonmonetary elements. The most common of these damages include: Anguish Loss of wages Medical bills Disfigurement Loss of companionship and society Mental or emotional pain and suffering Physical impairment and/or Physical pain and suffering Premises Liability and Criminal Acts There is a possibility that an injury incurred on private or commercial property was the result of criminal activity. Just like in any other situation, it is the obligation of the proprietor to provide a safe environment. There are limits to this liability, though. According to §768.0705 or the Florida Statutes, the owner or operator of a business that takes certain measures against criminal activity may be limited in their potential liability. The statute lists the following factors needed to keep from being held fully liable for an injury: A security camera system capable of recording and retrieving an image to assist in offender identification and apprehension. A drop safe or cash management device for restricted access to cash receipts. A lighted parking lot illuminated at an intensity of at least 2 foot-candles per square foot at 18 inches above the surface. A conspicuous notice at the entrance, which states that the cash register contains $50 or less. Window signage that allows a clear and unobstructed view from outside the building, and in a normal line of sight of the cash register and sales transaction area. Height markers at the entrance of the convenience business which display height measures. A cash management policy to limit the cash on hand at all times after 11 p.m. A convenience business shall not have window tinting that reduces exterior or interior view in a normal line of sight. §812.174 goes on to state that the owner or principal operator of a convenience business or convenience businesses shall provide proper robbery deterrence and safety training by an approved curriculum to its retail employees within 60 days of employment. Proving Negligence in Premises Liability In order to prove liability in a personal injury case, there are four elements that need to be analyzed. These elements are duty, breach, causation and damages. In simple terms, the following must be proven so that you can proceed with a premises liability case: The injured party must be able to prove a condition existed on the premises that posed an unreasonable risk of harm to anyone present on the premises. The person in possession of the premises knew or should have known the condition on the premises posed an unreasonable risk of harm. The owner or landlord should have reasonable knowledge that a guest on the property would not have been able to discover the danger or they would not be able to protect themselves from the danger. The landlord or owner was negligent when the condition was created, or they knew about the condition and failed to correct it. The guest on the premises must have been injured. The dangerous condition on the premises must have caused the injury. Another factor that needs to be taken into account is the status of the injured individual. A premises liability claim could hinge on the details of whether you were invited onto the property or not. Simply put, there are three types of designations in premises liability: Invitee (invited by owner), Licensee (permission to enter property, but without invitation) and Trespasser (no permission, no invitation). From these three, it can be assumed that a trespasser will have a very difficult time proving negligence, considering the fact that he or she was unlawfully on the property. Premises Liability Resources Premises Liability Statutes – To proceed in a premises liability case, it is vital that you know the precise legal wording as provided in the Florida Statutes. This link will send you to the section of the statutes related to negligence and the limitation on premises liability. Brevard County Civil Court – If you are considering litigation, it is also important to have a strong understanding of the legal and court process. This links you to the Brevard County Clerk of the Court website. You can find information on case searches, frequently asked questions, forms, reports and the civil side of Florida law. Florida Building Codes - The building code within the state can allow you and your attorney to immediately identify structural problems, which can help prove negligence. This link sends you to a page that contains many of the various Florida commercial building codes, including structural, plumbing, mechanical, electrical and fire. The Law Offices of James B. Coulter | Brevard County Premises Liability Lawyer As a customer or visitor, your safety should be on the forefront of the owner or proprietors mind. When they fail in their duties, serious injuries can occur. When this happens, having a qualified and experienced attorney at your side can help you regain the money lost due to the various costs, while also holding the responsible party accountable and liable for their actions. We prepare meticulously for the possibility of trial in each case because it gives our clients leverage in negotiations and the best chance for success. Through a firm resolve and aggressive trial advocacy, we have helped many clients protect their rights, freedom, and future. The Law Offices of James B. Coulter is a Melbourne-based legal practice, making us a convenient option for individuals and families throughout Central Florida, including the cities of Satellite Beach, Indialantic, West Melbourne, Melbourne Beach, Indian Harbour Beach, and Malabar among many others. Schedule your free initial consultation with James Coulter of The Law Offices of James B. Coulter to go over the details of your case, contact us at (321) 586-9944 or send an online message. The information provided on this website is for general information purposes only. The legal information you obtain at this website is not, nor is it intended to be, legal advice. You should consult a criminal defense lawyer in Orlando, FL, for advice regarding your own individual situation. We invite you to contact us and welcome your calls, letters and electronic mail. Contacting us, however, does not create an attorney-client relationship. Please do not send any confidential information to us until after an attorney-client relationship has been established.
--- author: - ZEUS Collaboration date: September 2006 title: 'Measurement of open beauty production at HERA in the $D^*\mu$ final state' --- [ The ZEUS Collaboration ]{} S. Chekanov$^{ 1}$, M. Derrick, S. Magill, S. Miglioranzi$^{ 2}$, B. Musgrave, D. Nicholass$^{ 2}$, , R. Yoshida\ [*Argonne National Laboratory, Argonne, Illinois 60439-4815*]{}, USA $^{n}$ M.C.K. Mattingly\ [*Andrews University, Berrien Springs, Michigan 49104-0380*]{}, USA N. Pavel $^{\dagger}$, A.G. Yagües Molina\ [*Institut für Physik der Humboldt-Universität zu Berlin, Berlin, Germany*]{} S. Antonelli, P. Antonioli, G. Bari, M. Basile, L. Bellagamba, M. Bindi, D. Boscherini, A. Bruni, G. Bruni, , F. Cindolo, A. Contin, M. Corradi$^{ 3}$, S. De Pasquale, G. Iacobucci, , R. Nania, A. Polini, L. Rinaldi, G. Sartorelli, A. Zichichi\ [*University and INFN Bologna, Bologna, Italy*]{} $^{e}$ G. Aghuzumtsyan$^{ 4}$, D. Bartsch, I. Brock, S. Goers, H. Hartmann, E. Hilger, H.-P. Jakob, M. Jüngst, O.M. Kind, E. Paul$^{ 5}$, J. Rautenberg$^{ 6}$, R. Renner, U. Samson$^{ 7}$, V. Schönberg, M. Wang, M. Wlasenko\ [*Physikalisches Institut der Universität Bonn, Bonn, Germany*]{} $^{b}$ N.H. Brook, G.P. Heath, J.D. Morris, T. Namsoo\ [*H.H. Wills Physics Laboratory, University of Bristol, Bristol, United Kingdom*]{} $^{m}$ M. Capua, S. Fazio, A. Mastroberardino, M. Schioppa, G. Susinno, E. Tassi\ [*Calabria University, Physics Department and INFN, Cosenza, Italy*]{} $^{e}$ J.Y. Kim$^{ 8}$, K.J. Ma$^{ 9}$\ [*Chonnam National University, Kwangju, South Korea*]{} $^{g}$ Z.A. Ibrahim, B. Kamaluddin, W.A.T. Wan Abdullah\ [*Jabatan Fizik, Universiti Malaya, 50603 Kuala Lumpur, Malaysia*]{} $^{r}$ Y. Ning, Z. Ren, F. Sciulli\ [*Nevis Laboratories, Columbia University, Irvington on Hudson, New York 10027*]{} $^{o}$ J. Chwastowski, A. Eskreys, J. Figiel, A. Galas, M. Gil, K. Olkiewicz, P. Stopa, L. Zawiejski\ [*The Henryk Niewodniczanski Institute of Nuclear Physics, Polish Academy of Sciences, Cracow, Poland*]{} $^{i}$ L. Adamczyk, T. Bołd, I. Grabowska-Bołd, D. Kisielewska, J. Łukasik, , L. Suszycki\ [*Faculty of Physics and Applied Computer Science, AGH-University of Science and Technology, Cracow, Poland*]{} $^{p}$ A. Kotański$^{ 10}$, W. S[ł]{}omiński\ [*Department of Physics, Jagellonian University, Cracow, Poland*]{} V. Adler, U. Behrens, I. Bloch, A. Bonato, K. Borras, N. Coppola, J. Fourletova, A. Geiser, D. Gladkov, P. Göttlicher$^{ 11}$, I. Gregor, T. Haas, W. Hain, C. Horn, B. Kahle, U. Kötz, H. Kowalski, E. Lobodzinska, B. Löhr, R. Mankel, I.-A. Melzer-Pellmann, A. Montanari, D. Notz, A.E. Nuncio-Quiroz, R. Santamarta, , A. Spiridonov$^{ 12}$, H. Stadie, U. Stösslein, D. Szuba$^{ 13}$, J. Szuba$^{ 14}$, T. Theedt, G. Wolf, K. Wrona, C. Youngman,\ [*Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany*]{} \ [*Deutsches Elektronen-Synchrotron DESY, Zeuthen, Germany*]{} G. Barbagli, E. Gallo, P. G. Pelfer\ [*University and INFN, Florence, Italy*]{} $^{e}$ A. Bamberger, D. Dobur, F. Karstens, N.N. Vlasov$^{ 15}$\ [*Fakultät für Physik der Universität Freiburg i.Br., Freiburg i.Br., Germany*]{} $^{b}$ P.J. Bussey, A.T. Doyle, W. Dunne, J. Ferrando, D.H. Saxon, I.O. Skillicorn\ [*Department of Physics and Astronomy, University of Glasgow, Glasgow, United Kingdom*]{} $^{m}$ I. Gialas$^{ 16}$\ [*Department of Engineering in Management and Finance, Univ. of Aegean, Greece*]{} T. Gosau, U. Holm, R. Klanner, E. Lohrmann, H. Salehi, P. Schleper, , J. Sztuk, K. Wichmann, K. Wick\ [*Hamburg University, Institute of Exp. Physics, Hamburg, Germany*]{} $^{b}$ C. Foudas, C. Fry, K.R. Long, A.D. Tapper\ [*Imperial College London, High Energy Nuclear Physics Group, London, United Kingdom*]{} $^{m}$ M. Kataoka$^{ 17}$, T. Matsumoto, K. Nagano, K. Tokushuku$^{ 18}$, S. Yamada, Y. Yamazaki\ [*Institute of Particle and Nuclear Studies, KEK, Tsukuba, Japan*]{} $^{f}$ A.N. Barakbaev, E.G. Boos, A. Dossanov, N.S. Pokrovskiy, B.O. Zhautykov\ [*Institute of Physics and Technology of Ministry of Education and Science of Kazakhstan, Almaty,* ]{} D. Son\ [*Kyungpook National University, Center for High Energy Physics, Daegu, South Korea*]{} $^{g}$ J. de Favereau, K. Piotrzkowski\ [*Institut de Physique Nucléaire, Université Catholique de Louvain, Louvain-la-Neuve, Belgium*]{} $^{q}$ F. Barreiro, C. Glasman$^{ 19}$, M. Jimenez, L. Labarga, J. del Peso, E. Ron, J. Terrón, M. Zambrana\ [*Departamento de Física Teórica, Universidad Autónoma de Madrid, Madrid, Spain*]{} $^{l}$ F. Corriveau, C. Liu, R. Walsh, C. Zhou\ [*Department of Physics, McGill University, Montréal, Québec, Canada H3A 2T8*]{} $^{a}$ T. Tsurugai\ [*Meiji Gakuin University, Faculty of General Education, Yokohama, Japan*]{} $^{f}$ A. Antonov, B.A. Dolgoshein, I. Rubinsky, V. Sosnovtsev, A. Stifutkin, S. Suchkov\ [*Moscow Engineering Physics Institute, Moscow, Russia*]{} $^{j}$ R.K. Dementiev, P.F. Ermolov, L.K. Gladilin, I.I. Katkov, L.A. Khein, I.A. Korzhavina, V.A. Kuzmin, B.B. Levchenko$^{ 20}$, O.Yu. Lukina, A.S. Proskuryakov, L.M. Shcheglova, D.S. Zotkin, S.A. Zotkin\ [*Moscow State University, Institute of Nuclear Physics, Moscow, Russia*]{} $^{k}$ I. Abt, C. Büttner, A. Caldwell, D. Kollar, W.B. Schmidke, J. Sutiak\ [*Max-Planck-Institut für Physik, München, Germany*]{} G. Grigorescu, A. Keramidas, E. Koffeman, P. Kooijman, A. Pellegrino, H. Tiecke, M. Vázquez$^{ 17}$,\ [*NIKHEF and University of Amsterdam, Amsterdam, Netherlands*]{} $^{h}$ N. Brümmer, B. Bylsma, L.S. Durkin, A. Lee, T.Y. Ling\ [*Physics Department, Ohio State University, Columbus, Ohio 43210*]{} $^{n}$ P.D. Allfrey, M.A. Bell, A.M. Cooper-Sarkar, A. Cottrell, R.C.E. Devenish, B. Foster, K. Korcsak-Gorzo, S. Patel, V. Roberfroid$^{ 21}$, A. Robertson, P.B. Straub, C. Uribe-Estrada, R. Walczak\ [*Department of Physics, University of Oxford, Oxford United Kingdom*]{} $^{m}$ P. Bellan, A. Bertolin, R. Brugnera, R. Carlin, R. Ciesielski, F. Dal Corso, S. Dusini, A. Garfagnini, S. Limentani, A. Longhin, L. Stanco, M. Turcato\ [*Dipartimento di Fisica dell’ Università and INFN, Padova, Italy*]{} $^{e}$ B.Y. Oh, A. Raval, J. Ukleja$^{ 22}$, J.J. Whitmore\ [*Department of Physics, Pennsylvania State University, University Park, Pennsylvania 16802*]{} $^{o}$ Y. Iga\ [*Polytechnic University, Sagamihara, Japan*]{} $^{f}$ G. D’Agostini, G. Marini, A. Nigro\ [*Dipartimento di Fisica, Università ’La Sapienza’ and INFN, Rome, Italy*]{} $^{e}~$ J.E. Cole, J.C. Hart\ [*Rutherford Appleton Laboratory, Chilton, Didcot, Oxon, United Kingdom*]{} $^{m}$ H. Abramowicz$^{ 23}$, A. Gabareen, R. Ingbir, S. Kananov, A. Levy\ [*Raymond and Beverly Sackler Faculty of Exact Sciences, School of Physics, Tel-Aviv University, Tel-Aviv, Israel*]{} $^{d}$ M. Kuze\ [*Department of Physics, Tokyo Institute of Technology, Tokyo, Japan*]{} $^{f}$ R. Hori, S. Kagawa$^{ 24}$, N. Okazaki, S. Shimizu, T. Tawara\ [*Department of Physics, University of Tokyo, Tokyo, Japan*]{} $^{f}$ R. Hamatsu, H. Kaji$^{ 25}$, S. Kitamura$^{ 26}$, O. Ota, Y.D. Ri\ [*Tokyo Metropolitan University, Department of Physics, Tokyo, Japan*]{} $^{f}$ M.I. Ferrero, V. Monaco, R. Sacchi, A. Solano\ [*Università di Torino and INFN, Torino, Italy*]{} $^{e}$ M. Arneodo, M. Ruspa\ [*Università del Piemonte Orientale, Novara, and INFN, Torino, Italy*]{} $^{e}$ S. Fourletov, J.F. Martin\ [*Department of Physics, University of Toronto, Toronto, Ontario, Canada M5S 1A7*]{} $^{a}$ S.K. Boutle$^{ 16}$, J.M. Butterworth, C. Gwenlan$^{ 27}$, T.W. Jones, J.H. Loizides, M.R. Sutton$^{ 27}$, C. Targett-Adams, M. Wing\ [*Physics and Astronomy Department, University College London, London, United Kingdom*]{} $^{m}$ B. Brzozowska, J. Ciborowski$^{ 28}$, G. Grzelak, P. Kulinski, P. [Ł]{}użniak$^{ 29}$, J. Malka$^{ 29}$, R.J. Nowak, J.M. Pawlak, A. Ukleja$^{ 30}$, A.F. Żarnecki\ [*Warsaw University, Institute of Experimental Physics, Warsaw, Poland*]{} M. Adamus, P. Plucinski$^{ 31}$\ [*Institute for Nuclear Studies, Warsaw, Poland*]{} Y. Eisenberg, I. Giller, D. Hochman, U. Karshon, M. Rosin\ [*Department of Particle Physics, Weizmann Institute, Rehovot, Israel*]{} $^{c}$ E. Brownson, T. Danielson, A. Everett, D. Kçira, D.D. Reeder, P. Ryan, A.A. Savin, W.H. Smith, H. Wolfe\ [*Department of Physics, University of Wisconsin, Madison, Wisconsin 53706*]{}, USA $^{n}$ S. Bhadra, C.D. Catterall, Y. Cui, G. Hartner, S. Menary, U. Noor, M. Soares, J. Standage, J. Whyte\ [*Department of Physics, York University, Ontario, Canada M3J 1P3*]{} $^{a}$ $^{\ 1}$ supported by DESY, Germany\ $^{\ 2}$ also affiliated with University College London, UK\ $^{\ 3}$ also at University of Hamburg, Germany, Alexander von Humboldt Fellow\ $^{\ 4}$ self-employed\ $^{\ 5}$ retired\ $^{\ 6}$ now at Univ. of Wuppertal, Germany\ $^{\ 7}$ formerly U. Meyer\ $^{\ 8}$ supported by Chonnam National University in 2005\ $^{\ 9}$ supported by a scholarship of the World Laboratory Björn Wiik Research Project\ $^{ 10}$ supported by the research grant no. 1 P03B 04529 (2005-2008)\ $^{ 11}$ now at DESY group FEB, Hamburg, Germany\ $^{ 12}$ also at Institut of Theoretical and Experimental Physics, Moscow, Russia\ $^{ 13}$ also at INP, Cracow, Poland\ $^{ 14}$ on leave of absence from FPACS, AGH-UST, Cracow, Poland\ $^{ 15}$ partly supported by Moscow State University, Russia\ $^{ 16}$ also affiliated with DESY\ $^{ 17}$ now at CERN, Geneva, Switzerland\ $^{ 18}$ also at University of Tokyo, Japan\ $^{ 19}$ Ram[ó]{}n y Cajal Fellow\ $^{ 20}$ partly supported by Russian Foundation for Basic Research grant no. 05-02-39028-NSFC-a\ $^{ 21}$ EU Marie Curie Fellow\ $^{ 22}$ partially supported by Warsaw University, Poland\ $^{ 23}$ also at Max Planck Institute, Munich, Germany, Alexander von Humboldt Research Award\ $^{ 24}$ now at KEK, Tsukuba, Japan\ $^{ 25}$ now at Nagoya University, Japan\ $^{ 26}$ Department of Radiological Science\ $^{ 27}$ PPARC Advanced fellow\ $^{ 28}$ also at Łódź University, Poland\ $^{ 29}$ Łódź University, Poland\ $^{ 30}$ supported by the Polish Ministry for Education and Science grant no. 1 P03B 12629\ $^{ 31}$ supported by the Polish Ministry for Education and Science grant no. 1 P03B 14129\ \ $^{\dagger}$ deceased\ -------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- $^{a}$ supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) $^{b}$ supported by the German Federal Ministry for Education and Research (BMBF), under contract numbers HZ1GUA 2, HZ1GUB 0, HZ1PDA 5, HZ1VFA 5 $^{c}$ supported in part by the MINERVA Gesellschaft für Forschung GmbH, the Israel Science Foundation (grant no. 293/02-11.2) and the U.S.-Israel Binational Science Foundation $^{d}$ supported by the German-Israeli Foundation and the Israel Science Foundation $^{e}$ supported by the Italian National Institute for Nuclear Physics (INFN) $^{f}$ supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) and its grants for Scientific Research $^{g}$ supported by the Korean Ministry of Education and Korea Science and Engineering Foundation $^{h}$ supported by the Netherlands Foundation for Research on Matter (FOM) $^{i}$ supported by the Polish State Committee for Scientific Research, grant no. 620/E-77/SPB/DESY/P-03/DZ 117/2003-2005 and grant no. 1P03B07427/2004-2006 $^{j}$ partially supported by the German Federal Ministry for Education and Research (BMBF) $^{k}$ supported by RF Presidential grant N 1685.2003.2 for the leading scientific schools and by the Russian Ministry of Education and Science through its grant for Scientific Research on High Energy Physics $^{l}$ supported by the Spanish Ministry of Education and Science through funds provided by CICYT $^{m}$ supported by the Particle Physics and Astronomy Research Council, UK $^{n}$ supported by the US Department of Energy $^{o}$ supported by the US National Science Foundation $^{p}$ supported by the Polish Ministry of Science and Higher Education $^{q}$ supported by FNRS and its associated funds (IISN and FRIA) and by an Inter-University Attraction Poles Programme subsidised by the Belgian Federal Science Policy Office $^{r}$ supported by the Malaysian Ministry of Science, Technology and Innovation/Akademi Sains Malaysia grant SAGA 66-02-03-0048 -------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Introduction {#sec-int} ============ The production of beauty quarks in $ep$ collisions at HERA is a stringent test for perturbative Quantum Chromodynamics (QCD) since the large $b$-quark mass ($m_b \sim 5 \gev$) provides a hard scale that should ensure reliable predictions. For $b$-quark transverse momenta comparable to the $b$-quark mass, next-to-leading-order (NLO) QCD calculations in which the $b$ quarks are generated dynamically are expected to provide accurate predictions [@np:b412:225; @*np:b454:3-24; @*frixione3; @np:b452:109; @*pl:b353:535; @*pr:d57:2806]. The beauty-production cross section has been measured in $p\bar{p}$ collisions at the S$p\pbar$S [@beautyUA10; @*pl:b256:121-128; @*zfp:c61:41-52] and Tevatron colliders [@beautyCDF1; @*beautyCDF2; @*beautyCDF3; @*beautyCDF4; @*beautyCDF5; @*beautyCDF6_pap; @*beautyD00; @*beautyD01; @*beautyD02; @*beautyD03], in $\gamma \gamma$ interactions at LEP [@beautyLEP0; @*beautyLEP1], in fixed-target $\pi N$ [@WA78; @*E706] and $pN$ [@E771; @*E789; @*HERAB] experiments, and in $ep$ collisions at HERA [@pl:b467:156; @*epj:c18:625; @epj:c40:349; @*epj:c41:453; @*Aktas:2005iw; @*H1phjets; @pr:d70:012008; @pl:b599:173; @pl:b621:56-71]. While most results, including recent results from the Tevatron, are in agreement with QCD predictions, some, in particular those from LEP, show large discrepancies. This paper reports a measurement of beauty production via the reaction $e p \to e b \bar{b} X \to e D^* \mu X^\prime$ using the ZEUS detector at HERA. This reaction offers the advantage of providing a data sample enriched in $b$ quarks and with strongly suppressed backgrounds from other processes, which allows low-$p_T$ threshold cuts to be applied. This analysis therefore yields a measurement of beauty production closer to the production threshold than previous HERA measurements based on leptons and/or jets with high transverse momentum [@pl:b467:156; @*epj:c18:625; @epj:c40:349; @*epj:c41:453; @*Aktas:2005iw; @*H1phjets; @pr:d70:012008; @pl:b599:173]. A similar measurement has been performed by the H1 collaboration [@pl:b621:56-71]. Of particular interest are events in which the muon and $D^*$ originate from the same parent $B$ meson (Fig. \[fig\_topol\]a), e.g. $B^0 \to D^{*-}\mu^+\nu_\mu$. These yield unlike-sign $D^*$-muon pairs produced in the same detector hemisphere. Due to the partial reconstruction (e.g. missing neutrino) the invariant mass is constrained to lie below the $B$-meson mass. Another important contribution arises from charm-pair production, where one charm quark fragments into a $D^*$ and the other decays into a muon (Fig. \[fig\_topol\]b). This again yields unlike-sign $D^*$-muon pairs, but with the $D^*$ and the muon produced predominantly in opposite hemispheres. In addition, beauty-pair production in which the $D^*$ and muon originate from different beauty quarks can yield both like- and unlike-sign $D^*$-muon combinations, depending on whether the muon is from the decay of the primary beauty quark (Fig. \[fig\_topol\]c), or from a secondary charm quark (Fig. \[fig\_topol\]d), and whether $B^0$-$\bar{B^0}$ mixing has occured. Background contributions to both like- and unlike-sign combinations include events with either fake $D^*$ mesons, originating from combinatorial background, or fake muons. In this analysis, the signal is extracted from the unlike-sign sample, while the like-sign sample is used as a cross check. Cross sections are extracted separately for the photoproduction ($\gamma p$, photon virtuality $Q^2 \lesssim 1$ GeV$^2$), and deep inelastic scattering (DIS, $Q^2 \gtrsim 1$ GeV$^2$) regimes, as well as for the entire range in $Q^2$, which includes the kinematic region in which these two event classes cannot easily be distinguished. Experimental set-up {#sec-exp} =================== The data sample used in this analysis corresponds to an integrated luminosity ${\cal L}=114.1 \pm 2.3 ~\rm{pb}^{-1}$, collected by the ZEUS detector in the years 1996-2000. During the 1996-97 data taking, HERA provided collisions between an electron[^1] beam of $E_e=27.5 \gev$ and a proton beam of $E_p=820\gev$, corresponding to a centre-of-mass energy $\sqrt s=300\gev$ (${{\cal L}_{300}}=38.0\pm 0.6~ \rm{pb}^{-1}$). In the years 1998-2000, the proton-beam energy was $E_p=920\gev$, corresponding to $\sqrt s=318\gev$ (${{\cal L}_{318}}=76.1\pm 1.7~\rm{pb}^{-1}$). A detailed description of the ZEUS detector can be found elsewhere [@zeus:1993:bluebook]. A brief outline of the components that are most relevant for this analysis is given below. The high-resolution uranium-scintillator calorimeter (CAL) consists of three parts: the forward (FCAL), the barrel (BCAL) and the rear (RCAL) calorimeters. Each part is subdivided transversely into towers and longitudinally into one electromagnetic section and either one (in RCAL) or two (in BCAL and FCAL) hadronic sections. The smallest subdivision of the calorimeter is called a cell. The CAL energy resolutions, as measured under test-beam conditions, are $\sigma(E)/E=0.18/\sqrt{E}$ for electrons and $\sigma(E)/E=0.35/\sqrt{E}$ for hadrons, with $E$ in $\Gev$. The position of electrons scattered at small angles to the electron beam direction was measured using the small-angle rear tracking detector (SRTD) [@nim:a401:63; @epj:c21:443]. The SRTD is attached to the front face of the RCAL and consists of two planes of scintillator strips, arranged orthogonally. The strips are 1 cm wide and 0.5 cm thick. The muon system consists of rear, barrel (R/BMUON) [@nim:a333:342] and forward (FMUON) [@zeus:1993:bluebook] tracking detectors. The B/RMUON consists of limited-streamer tube chambers placed behind the BCAL (RCAL), inside and outside a magnetized iron yoke surrounding the CAL. These chambers cover polar angles from $34^{\rm o}$ to $135^{\rm o}$ and from $135^{\rm o}$ to $171^{\rm o}$, respectively. The luminosity was measured using the bremsstrahlung process $ep \to e p \gamma$. The resulting small-angle energetic photons were measured by the luminosity monitor [@Desy-92-066; @*zfp:c63:391; @*acpp:b32:2025], a lead-scintillator calorimeter placed in the HERA tunnel at $Z = -107$ m. Data Selection {#data_sel} ============== The data were selected online via a three-level trigger system through a combination of three different trigger chains: - a muon reaching the inner B/RMUON chambers and matched to a minimum ionizing energy deposit in the CAL or any muon reaching the outer B/RMUON chambers or - a $D^*$ candidate [@np:b729:492-525] or - a scattered-electron candidate in the CAL [@pl:b599:173]. In part of the data taking, the cuts on the electron candidate were relaxed if a muon in the inner B/RMUON chambers was detected. Due to this redundancy, the trigger efficiency for beauty events was high, $94 \pm 3$% for the inclusive study, and $98 \pm 2$% for the DIS selection. Muons were reconstructed offline using the following procedure: a track was found in the inner B/RMUON chambers, then a match in position and angle to a CTD track was required. In the bottom region of the detector, where there are no inner chambers, the outer chambers were used instead. If a match was found to both inner and outer chambers, a momentum-matching criterion was added. The angular coverage of the B/RMUON and of the track requirements in the CTD restrict the muon acceptance to the pseudorapidity region $$\label{mu:eta} -1.75<\eta^{\mu}<1.3 \ .$$ A cut on the muon transverse momentum $$\label{mu:pt} p_{T}^{\mu}>1.4\gev$$ was applied, reflecting the requirement that the muon reaches the inner muon chambers in the barrel region. In order to have uniform kinematic acceptance, this cut was also applied in the rear region. $D^*$ candidates were reconstructed in the $D^{*+} \to D^0(\to K^- \pi^+)\pi_s^+$ decay channel (+c.c.) making use of the $\Delta M$ ($\equiv M(K\pi\pi_s)-M(K\pi)$) technique described in previous publications [@np:b729:492-525] with the following cuts: $$\begin{aligned} \label{e:dscuts} D^0~\textrm{mass} && 1.81 < M(K\pi) < 1.92\gev; \nonumber \\ D^*-D^0~\textrm{mass difference} && 0.1435 < \Delta M < 0.1475\gev; \nonumber \\ D^*~\textrm{transverse momentum} && p_T^{D^*} > 1.9\gev; \\ D^*~\textrm{pseudorapidity} && \vert\eta^{D^*}\vert<1.5; \nonumber \\ K,\pi~\textrm{transverse momentum} && p_T^{K,\pi} > 0.5\gev; \nonumber \\ \textrm{slow pion} && p_T^{\pi_s} > 0.125\gev. \nonumber\end{aligned}$$ To allow the background to the $D^*$ signal to be determined, $D^0$ candidates with wrong-charge combinations, in which both tracks forming the $D^0$ candidates have the same charge and the third track has the opposite charge, were also retained. The hadronic system was reconstructed from the calorimeter information and the reconstructed vertex. A four-momentum $(p_X^i,p_Y^i,p_Z^i,E^i)$ was assigned to each calorimeter cell. Global hadronic variables were reconstructed by summing over these cells. In the case of identified DIS events (see below), the scattered electron candidates were excluded from this sum. The inelasticity $y$ was reconstructed from the Jacquet-Blondel estimator $y_{\rm JB}=(E-P_Z)/2E_e$ [@proc:epfacility:1979:391], where and the sum runs over all cells. In the case of DIS events, the alternative value $y_e=1-\frac{E_e^\prime}{2E_e} (1-\cos \theta_{e})$ as well as the photon virtuality $Q^2$ were obtained from the energy $E_e^\prime$ and scattering angle $\theta_e$ of the final-state electron candidate [@pl:b599:173]. A sample of events with one muon and one $D^*$ candidate was selected by requiring: - $\ge 1$ muon in the muon chamber regions defined by Eq. (\[mu:eta\]) and Eq. (\[mu:pt\]); - $\ge 1$ $D^*$ candidate in the $D^*$ acceptance region defined by Eq. (\[e:dscuts\]); - the muon candidate track is not one of the three $D^*$ candidate tracks, eliminating backgrounds from semileptonic $D^0$ decays; - the $D^*\mu$  system carries a significant fraction of the total transverse energy of the event, $p_T^{D^*\mu}/E_T>0.14$, where $E_T$ is the transverse energy measured by the CAL outside a cone of 10$^\circ$ around the proton beam direction to exclude the proton remnant, and $p_T^{D^*\mu}$ is the transverse momentum of the $D^*\mu$ system, reducing combinatorial $D^*$ background; - a reconstructed vertex compatible with the nominal interaction point, suppressing non-$ep$ background. After this selection, a sample of 232 events remained. The resulting $\Delta M$ distributions for the like and unlike $D^*\mu$ charge combinations, before the $\Delta M$ cut, are shown in Figs. \[fig1\]a and \[fig1\]b. A subsample of photoproduction events was selected by requiring: - no scattered-electron candidate found in the CAL; - $E-P_Z < 34 \gev$; retaining 81% of the inclusive sample. After the unfolding of the detector response, these cuts correspond to an effective cut $Q^2<1\gev^2$ and $0.05<y<0.85$. The lower limit on $y$ arises from the interplay between the $b$-quark mass and the acceptance in rapidity. Alternatively, a clean DIS sample was obtained by applying the following additional conditions [@pl:b599:173]: - a reconstructed electron with energy $E_e^\prime >$10 GeV; - $Q^2 > 2$ GeV$^2$; - inelasticity $y_{\rm{JB}}>0.05$ and $y_{e} < 0.7$; - $40< E-P_Z < 60 \gev$; - the electron hits the rear calorimeter outside a rectangle of $|X|<13$ cm and $|Y|<7$ cm. These cuts correspond to an effective cut $Q^2>2\gev^2$ and $0.05<y<0.7$. For this sample, which contains less combinatorial background, the $D^*$ cuts were relaxed to $$\begin{aligned} \label{e:dsDIS} p_T^{D^*} &>& 1.5\gev; \nonumber \\ p_T^{K,\pi} &>& 0.4\gev; \\ p_T^{\pi_s} &>& 0.12\gev; \nonumber\end{aligned}$$ and the cut on $p_T^{D^*\mu}/E_T$ was dropped. All other cuts on the $D^*$ and the muon remained unchanged. A sample of 44 events was obtained. The resulting $\Delta M$ distributions for the like and unlike $D^*\mu$ charge combinations are shown in Figs. \[fig1\]c and \[fig1\]d. Backgrounds and event simulation ================================ Several contributions to the selected data sample were evaluated: - the signal from beauty decays; - the background from fake $D^*$ combinations; - the $D^*\mu$ background from charm decays; - the background from fake or non-prompt muons with a real $D^*$ from charm. For the signal from beauty and charm production, Monte Carlo (MC) simulations were performed using the [Pythia]{} [@cpc:82:74], [Rapgap]{} [@cpc:86:147] and [Herwig]{} [@cpc:67:465] generators. These simulations are based on leading-order matrix elements complemented by parton showers to obtain higher-order topologies. The direct photon-gluon fusion process ($\gamma g \to Q \bar Q$, $Q=b,c$), flavour excitation in the resolved photon and proton (e.g. $Q g \to Q g$, $\gamma Q \to Q g$), and hadron-like resolved photon processes ($g g \to Q \bar{Q}$) were included. Gluon splitting into heavy flavours ($g\to Q\bar Q$) in events with only light quarks in the hard scattering was not included in the simulations; this contribution is, however, expected to be small [@thesis:longhin:2004]. For all generated events, the ZEUS detector response was simulated in detail using a programme based on GEANT 3.21 [@GEANT]. The number of background events under the $D^*$ mass peaks (fake $D^*$) was estimated using the wrong-charge $K\pi$ combinations combining the like- and unlike-sign samples. This was found to minimize the bias due to charge correlations [@thesis:longhin:2004]. Wrong-charge combinations were normalised to the data outside the $D^*$ peak in the side-band $0.15 < \Delta M < 0.17\gev$, separately for the like-sign and unlike-sign $D^*\mu$ sample, as shown in Fig. \[fig1\]. Dedicated studies [@thesis:longhin:2004] performed by selecting data on the $D^*$ side-band showed that this procedure correctly reproduces shape and normalisation of the fake-$D^*$ background for the relevant variables used in the analysis. Fake muons can be produced by hadron showers leaking from the back of the calorimeter or by charged hadrons traversing the entire calorimeter without interaction. In addition, low-momentum muons can originate from in-flight decays of pions and kaons. It is also possible for tracks reconstructed in the central tracker to be wrongly associated to a signal from a real muon in the muon chambers. A dedicated study [@thesis:longhin:2004] based on pions from $K^0$ decays, protons from $\Lambda$ decays, and kaons from $\phi$ and $D^*$ decays, showed that the detector simulation reproduced these backgrounds reasonably well. The fake muon probability for the $K^0\to\pi^+\pi^-$ sample is about 0.2%. Most fake muons are associated with fake $D^*$ candidates, and therefore accounted for in the fake-$D^*$ background estimated directly from the data. Fake muons associated with a real $D^*$ are included in the charm and beauty MC samples. Distributions of variables used in the event selection or relevant for the event kinematics, for the unlike-sign inclusive sample, are compared to the expectations from these simulations in Fig. \[fig:controlplots\], separately for the beauty- and charm-enriched regions defined in Section \[sect:signal\]. Agreement with expectations is obtained, apart from some possible deviations in the $p_T^{D^*\mu}$ and $p_T^{D^*\mu}/E_T$ distributions in the beauty-enriched region, which are accounted for in the systematic uncertainties (Section \[sect:syst\]). Signal extraction {#sect:signal} ================= In this section, the signal-extraction procedure is described for the inclusive sample. The $\gamma p$ subsample and the DIS sample were treated in an analogous way. Figures \[fig2\]a and \[fig2\]b show the distribution of the angular difference $\Delta R = \sqrt{\Delta \phi^2 + \Delta \eta^2}$ between the $D^*$ and the muon, where $\phi$ is the azimuthal angle, for events passing all selections, including the $\Delta M$ cut. The distributions are shown separately for like- and unlike-sign $D^*\mu$ events. The expected signal and background distributions, normalised to the fractions determined later in the analysis and described below, are also indicated. For unlike-sign events, the region $\Delta R > 2$, which mainly corresponds to the back-to-back configuration, is clearly dominated by events from charm. Indications that the simulated distribution might be more sharply peaked than the data turned out to have little influence on the determination of the beauty fraction. In contrast, the region $\Delta R < 2$ is enriched in beauty events, in which the $D^*$ and muon originate mainly from decays of the same parent $B$ hadron. This is illustrated further in the $D^*\mu$ invariant-mass distribution (Figs. \[fig2\]c and \[fig2\]d) for events in the beauty-enriched region ($\Delta R < 2$). A peak with an upper edge close to 5 GeV, which can be attributed to the partial reconstruction of the decaying $B$ meson, is clearly visible. A comparison with the like-sign sample shows that the low-mass edge of this peak is dominated by background. An invariant-mass cut of $3~{\rm GeV} < M(D^*\mu) <5~{\rm GeV}$ was therefore applied to the $\Delta R < 2$ subsample. After this additional cut, and after statistical subtraction of the fake-$D^*$ background, the contributions of charm and beauty were determined by a two-component fit to the $\Delta R$ or $\Delta \phi$ distributions, shown in Figs. \[fig3\]a and \[fig3\]c. The fake-muon background with a real $D^*$ from charm, which is treated as part of the charm component, is shown separately. The small fraction of fake muons from beauty was included in the beauty component. The fit result for the fraction of beauty events in the final inclusive sample shown in Figs. \[fig3\]a and \[fig3\]c, using the shapes predicted by [Pythia]{}, is: - $f_b = 0.307 \pm 0.064{\rm (stat.)}~{\rm for~the}~\Delta R$ and - $f_b = 0.290 \pm 0.062{\rm (stat.)}~{\rm for~the}~\Delta \phi$ distribution. The $\Delta R$ result was chosen as the reference, and the $\Delta \phi$ result used as a systematic check. With these fitted fractions, the breakdown into the corresponding number of beauty, charm, and fake-muon candidates in each subsample is given in Table \[tab\_evts\]. In the unlike-sign part, the beauty and charm contributions are well separated, with only small cross-contaminations. The normalisation of the beauty and charm contributions in Fig. \[fig2\] already reflects these fitted fractions. Agreement is seen, also in the like-sign part, which was not included in the fit. The results from the application of the same procedure to the $\gamma p$ subsample are also shown in Table \[tab\_evts\]. The analogous results for the DIS sample are shown in Figs. \[fig3\]b and \[fig3\]d. The $\Delta \phi$ distribution gives less discrimination in this case, due to the transverse boost from the exchanged virtual photon. Therefore, the $M(D^*\mu)$ distribution was used. The fitted beauty fractions in the DIS sample, using the shapes predicted by [ Rapgap]{}, are - $f_b = 0.55 \pm 0.25\rm{(stat.)}$ for the $\Delta R$ and - $f_b = 0.43 \pm 0.30\rm{(stat.)}$ for the $M(D^*\mu)$ distribution. Again, the $\Delta R$ result is chosen as the reference, and the other as a cross check. The breakdown into different event categories is shown in Table \[tab\_evts\]. The acceptance corrections for the cross sections which will be presented in Section \[sec:results\] were evaluated using [Pythia]{} for $Q^2<1\gev ^2$, [Rapgap]{} for $Q^2>1\gev ^2$, and [Herwig]{} as a systematic check. Theoretical predictions and uncertainties ========================================= For direct comparisons with QCD, next-to-leading-order predictions were used. Calculations in which $b$ quarks are treated as massless particles [@bmassless1; @*bmassless2; @*bmassless3] are not applicable in this kinematic range, while calculations based on alternative parton-evolution schemes [@bkt1; @*bkt2; @*jung1; @*jung2] do not yet exist with full NLO implementation. Fixed-order NLO calculations with massive $b$ quarks should yield accurate predictions. Different types of such predictions were evaluated. The FMNR program [@np:b412:225] evaluates cross sections for next-to-leading-order beauty production in $\gamma p$ collisions in the fixed-order massive approach, for both point-like and hadron-like photon coupling to the heavy quarks. The parton-density functions used were CTEQ5M [@epj:c12:375] for the proton and GRV-G-HO [@pr:d46:1973-1979] for the photon. The renormalisation and factorisation scales $\mu$ were chosen to be equal and parametrised by $\mu_0 = \sqrt{p_{T}^2+m_b^2}$, where $p_T^2$ is the average of the squared transverse momentum of the two emerging $b$ quarks and $m_b=4.75$ GeV. An estimate of the theoretical uncertainty was obtained by simultaneously varying $4.5 < m_b < 5.0$ GeV and $\mu_0/2 < \mu < 2\mu_0$ such that the uncertainty was maximised. Typical uncertainties resulting from this procedure (e.g. for the $b\bar b$ total cross section) are +40% and -25%. Variations of the parton densities led to uncertainties which were much smaller than the uncertainties related to mass and scale variations. They were therefore neglected. Predictions at the level of visible $D^*\mu$ final states are needed in addition to those at parton level. The FMNR program provides a framework to fragment $b$ quarks into $B$ hadrons, and simulate the decay of these hadrons by interfacing them to appropriately chosen decay spectra. However, decays to complex final states, such as a $D^*$ and $\mu$ from the same $B$ hadron with cuts on both particles, cannot be easily implemented in this scheme. A straightforward interface of the parton-level events produced by FMNR to MC-like fragmentation and decay chains is also impracticable, since these events have positive and negative weights spanning more than 8 orders of magnitude, making such an approach extremely inefficient. These difficulties were overcome in a two-step process. In the first step, two or more FMNR parton-level events with large positive and negative weights and similar topology were combined into events with much smaller weights by averaging the parton momentum vectors [@LizDIS]. Events were considered to have similar topology if the differences in transverse momentum, rapidity and azimuthal angle of the $b$ quarks were less than user cut values that reflect the detector resolution. Furthermore, events with small weights were sampled with a probability proportional to their weight. In this way, the weight range was reduced to about two orders of magnitude. It was explicitly checked that this procedure preserves the NLO accuracy for the relevant cross sections at parton level (e.g. $b$ quark $p_T$ and angular distributions). In the second step, these parton-level events were interfaced to the [Pythia/Jetset]{} [@hep-ph-0108264] fragmentation and decay chain, making use of the full decay tables and decay kinematics implemented in [Pythia 6.2]{}. Therefore, non-dominant complex decays, such as $B \to D^* D$ followed by $D \to \mu X$, or muons produced through intermediate $J/\psi$ or $\tau$ states, were automatically included. The initial-state partons were allowed to have intrinsic $k_T$ (typically $\sim 300$ MeV) as implemented in [ Pythia]{}. This has a negligible effect on the resulting cross sections ($\sim 1$%). Parton showering was not included in order to avoid double counting of higher-order contributions[^2]. Fragmentation of $b$ quarks close to production threshold is non-trivial. The details of the threshold treatment were found to be much more important than the choice of a particular fragmentation function. The Peterson formula [@pr:d27:105] with $\epsilon = 0.0035$ was used. Three approaches were considered: - independent fragmentation as implemented in [Pythia]{} [@hep-ph-0108264]. The use of this quite old model was motivated by the fact that FMNR does not provide colour connections on an event-by-event basis; - fragmentation in the Lund string model [@zfp:c20:317; @*np:b238:492; @*cpc:39:347], again as implemented in [Pythia]{}. For this purpose, reasonable colour connections were assigned to each event; - the independent fragmentation scheme provided within the FMNR framework, rescaling the $B$-hadron momentum to a fraction of the $b$-quark momentum according to the Peterson formula, which is a somewhat crude approximation at threshold. The second option was used for all central predictions. The first option was used to obtain the lower systematic error (typically -5%). The third option could not be applied directly, since it does not provide cross-section predictions for correlated final states from the same $b$ quark, as needed here. Instead, it was applied to a cross section in which the final-state correlations originate from different $b$ quarks only, which is more easily calculable in this scheme. The results were used to evaluate a generic upper systematic error of +15% on the fragmentation procedure close to $b$ production threshold. The effect of a variation of the Peterson parameter $\epsilon$ in the range 0.0023 to 0.0045 was found to yield uncertainties that were much smaller than the uncertainties due to the different fragmentation procedures. It was therefore neglected. The branching fractions were corrected to correspond to those obtained from the Particle Data Group [@pl:b592:1], as listed in Table \[tab:branchings\]. Branching fraction uncertainties resulted in uncertainties on the $D^*\mu$ cross section of typically $\pm 12\%$. In principle, FMNR predictions are only valid for the photoproduction regime. The Weizsäcker-Williams approximation with an effective $Q^2_{\rm max}$ cutoff of 25 GeV$^2$ ($\sim m_b^2$) [@zfp:88:612; @*pr:45:729; @*pl:b319:339-345] was used to include the $\sim$15% DIS contribution to the combined cross section. Alternatively, the DIS part can be calculated using the NLO predictions from HVQDIS [@np:b452:109; @*pl:b353:535; @*pr:d57:2806]. Only point-like contributions are included in this prediction. The parton density function used was CTEQ5F4 [@epj:c12:375]. The renormalisation and factorisation scales $\mu$ were chosen to be equal and parametrised by $\mu_0 = \sqrt{Q^2+m_b^2}$. Mass and scales were varied as for FMNR. A scheme for the calculation of visible cross sections for correlated final states, corresponding to the FMNR$\otimes$[Pythia]{} interface described above, was not available. Therefore, cross-section comparisons in DIS are limited to the parton level. Systematic uncertainties {#sect:syst} ======================== The main experimental uncertainties are described below, in order of importance. Numbers in parentheses are quoted for the inclusive selection. Uncertainties for the $\gamma p$ results are also quoted when they differ significantly from the inclusive results. For the DIS sample, the statistics were often too small to derive meaningful systematic errors. The errors from the inclusive sample were used instead. - [**Simulation of $\bf {p_T^{D^*\mu}}$**]{}. The largest error arises from the observation that the muon and $D^*$ $p_T$ spectra in the $b$ signal region of the data ($\Delta R(D^*\mu) < 2$, $3<M(D^*\mu)<5$ GeV) appear to be somewhat softer than predicted by the Monte Carlo simulations (Fig. \[fig:controlplots\]). The differences are concentrated at small values of $p_T^{D^*\mu}/E_T$. Since the corresponding spectra are well reproduced in the charm region with larger statistics, this cannot be attributed to problems with the muon or $D^*$ reconstruction. There are several ways to interpret these differences: - they are statistical fluctuations. This assumption leads to the central result reported; - the signal distribution is significantly softer than predicted by QCD. Due to the rising efficiency as a function of $p_T^b$, this would change the efficiency calculation for the measurement of the visible cross section. To evaluate this possibility, the MC $p_T^{D^*\mu}$ (true level) distribution in the signal region was reweighted to be compatible at the 1 $\sigma$ level with the measured $p_T^{D^*\mu}$ spectrum of the inclusive sample (Fig. \[fig:controlplots\]) (+14%); - there is an additional unknown background contribution at low $p_T$, which occurs only in the beauty-enriched region. There is no indication that this is the case. Nevertheless, to account for this possibility, the $p_T^{D^*\mu}/E_T$ cut was tightened from 0.14 to 0.2, which removes most of the differences (Fig. \[fig:controlplots\]) (-33% for inclusive, -18% for $\gamma p$ selection). - [**Branching fractions**]{}. The beauty-enriched region, which dominates the fit result, is mainly populated by events in which the $D^*$ and $\mu$ originate from the same $b$. The rate of these events depends on different branching fractions from those relevant to the charm-enriched region, in which the $D^*$ and $\mu$ originate from different $b$ quarks. A variation of these branching fractions, within the uncertainties quoted in Table \[tab:branchings\], therefore affects the shape of the beauty contribution and the fitted beauty fraction ($\pm 8$%). - [**Fragmentation and parton showering**]{}. The [Herwig]{} MC uses a different fragmentation model from that of [Pythia]{} and [Rapgap]{}. It also yields different $b\bar{b}$ correlations from direct/resolved contributions and parton showering. This leads to differences in the acceptance, and in the fitted beauty fraction (+5/-8%). - [**Signal-extraction procedure**]{}. In addition to statistical fluctuations, different ways to fit the data can yield systematic differences due to binning effects and different systematics for different variables, e.g. imperfections in the shape of the MC distributions. To check the error from this effect, the cross sections were evaluated using different procedures: fits to $\Delta R(D^*\mu)$, $\Delta \phi(D^*\mu)$, $M(D^*\mu)$, and simple event counting. In all cases the differences were well within the quoted errors. To avoid double counting of statistical and systematic errors, these were used as cross checks only. - [**Uncertainty on the estimation of the muon chamber efficiency**]{}. Corrections to the MC muon chamber reconstruction efficiency were obtained from independent data samples and varied within their uncertainties ($\pm 5\%$). - [**Fake muon background**]{}. The background from fake muons has been extensively studied [@thesis:longhin:2004] and is further constrained by the like-sign distribution of Fig. \[fig2\]b, which is dominated by this background. Accordingly, it was varied by a factor 1.5 (-4%). - [**Luminosity measurement**]{}. The uncertainty associated with the luminosity measurement for the 1996-00 data taking periods used for this analysis was included ($\pm$2%). - [**Tracking**]{}. All tracking-based cuts ($p_T$ and mass cuts) were varied by their respective uncertainties. To avoid double counting of statistical uncertainties, the $D^*$-related systematics were taken from previous ZEUS DIS [@pr:d69:012004] and $\gamma p$ [@pl:b590:143] analyses employing similar cuts but with larger event samples. The cut on $p_T^\mu$ was varied by $\pm$40 MeV. This yielded a combined error of +6% and -4%. - [**Trigger acceptance**]{}. The error on the trigger acceptance was evaluated by comparing the efficiencies of the different trigger chains in the data with each other and with the MC ($\pm$3%). - [**$B^0$-$\bar{B^0}$ mixing**]{}. The possible systematic effect due to the variation of the mixing rate was found to be negligible. The total systematic uncertainty was obtained by adding the above contributions in quadrature. Results {#sec:results} ======= To present results from the combined data sets, the measurements from the 1996-97 run at $\sqrt{s} = 300 \gev$ have been corrected using the predicted cross section ratio [@np:b412:225] of 1.06, to correspond to the higher center-of-mass energy of 318 GeV. All cross sections are therefore quoted for $\sqrt{s}$ = 318 GeV. Visible cross sections ---------------------- The first step is the extraction of visible cross sections for the $D^*\mu$ final state from beauty. The acceptance for the $D^* \to D^0\pi_s \to (K\pi)\pi_s$ decay chain was unfolded using a branching fraction of $2.57\pm 0.06$% [@pl:b592:1]. The effective $b$ branching fractions used in the different MC generators were corrected to those listed in Table \[tab:branchings\] in order to account for their influence on the overall acceptance, and on the shape of the predicted beauty contributions. The measured beauty fraction in the inclusive sample, corrected for detector acceptance and branching fractions, was used to obtain the cross section for the process $ep \to e b \bar{b} X \to e D^{*\pm}\mu X$ in the visible kinematic range $p_T^{D^*} > 1.9$ GeV, $-1.5 < \eta^{D^*} < 1.5$, $p_T^{\mu} > 1.4$ GeV and $-1.75 < \eta^{\mu} < 1.3$ as: $$\label{sig:tot} \sigma_{\rm vis}(ep \to e b \bar{b} X \to e D^{*\pm}\mu X) = 160 \pm 37 \rm{(stat.)}^{+ 30}_{- 57}\rm{(syst.)}~\rm{pb}.$$ This includes both unlike- and like-sign $D^*\mu$ combinations. The leading-order cross sections predicted by [Pythia]{} and [ Herwig]{} in the same kinematic range are $\sigma_{\rm vis}(ep \to e b \bar{b} X \to e D^*\mu X) =$ 80 and 38 pb, respectively. The measured cross section is larger than, but compatible with, the FMNR$\otimes$[Pythia]{} NLO prediction $$\sigma_{\rm vis}^{\rm NLO}(ep \to e b \bar{b} X \to e D^{*\pm}\mu X) = 67^{+20}_{-11} \rm{(NLO)}^{+ 13}_{- 9}\rm{(frag. \oplus br.)}~\rm{pb},$$ where the first error refers to the uncertainties of the FMNR parton-level calculation, and the second error refers to the uncertainties related to fragmentation and decay. For the photoproduction subsample, a visible cross section in the kinematic range $Q^2 < 1$ GeV$^2$ and $0.05 < y < 0.85$ was obtained: $$\label{sig:PHP} \sigma_{{\rm vis},\gamma p}(ep \to e b \bar{b} X \to e D^{*\pm}\mu X) = 115 \pm 29 \rm{(stat.)}^{+21}_{-27}\rm{(syst.)}~\rm{pb}.$$ This can be compared to the NLO prediction from FMNR$\otimes$[Pythia]{}, $$\sigma_{{\rm vis},\gamma p}^{\rm NLO}(ep \to e b \bar{b} X \to e D^{*\pm}\mu X) = 54^{+15}_{-10} \rm{(NLO)} ^{+10}_{-7}\rm{(frag. \oplus br.)}~\rm{pb}.$$ As in the inclusive case, the NLO prediction underestimates the measured cross section by about a factor of 2, but is compatible with the measurement (Table \[tab:cross\]). From the DIS sample, a visible cross section in the kinematic range $Q^2 > 2$ GeV$^2$, $0.05 < y < 0.7$ and $p_T^{D^*} > 1.5$ GeV (other $D^*$ and muon cuts as for Eq. (\[sig:tot\])) of $$\label{sig:DIS} \sigma_{\rm vis,DIS}(ep \to e b \bar{b} X \to e D^*\mu X) = 58 \pm 29 \rm{(stat.)}^{+11}_{-20}\rm{(syst.)} ~\rm{pb}$$ was obtained. Again, the cross sections obtained from [Rapgap]{} (used to compute acceptance corrections for the central signal extraction) and [Herwig]{} (used for systematic checks, particularly with regard to differences in the $b\bar{b}$ correlations) in the same kinematic regime are considerably lower, $\sigma(ep \to e b \bar{b} X \to e D^*\mu X) =$ 26 and 10 pb, respectively. An NLO prediction is not available for this kinematic region. Comparison to H1 results ------------------------ A photoproduction cross section similar to Eq. (\[sig:PHP\]) in a slightly different kinematic range, $p_T^{D^*} > 1.5$ GeV, $|\eta^{D^*}| < 1.5$, $p^{\mu} > 2.0$ GeV, $|\eta^{\mu}| < 1.735$, $Q^2 < 1$ GeV$^2$ and $0.05 < y < 0.75$ has been obtained by the H1 collaboration [@pl:b621:56-71] $$\sigma_{{\rm vis},\gamma p}^{\rm H1}(ep \to e b \bar{b} X \to e D^{*\pm}\mu X;\rm{H1}) = 206 \pm 53 \rm{(stat.)} \pm {35} \rm{(syst.)}~\rm{pb}.$$ The ZEUS cross section of Eq. (\[sig:PHP\]) extrapolated to the same kinematic range as the H1 measurement using FMNR$\otimes$[Pythia]{} is $$\sigma_{{\rm vis},\gamma p}(ep \to e b \bar{b} X \to e D^{*\pm}\mu X;\rm{H1}) = 135 \pm 33 \rm{(stat.)}^{+ 24}_{- 31}\rm{(syst.)}~\rm{pb},$$ which is somewhat smaller, but in agreement within errors. The corresponding FMNR$\otimes$[Pythia]{} NLO prediction is $$\sigma_{{\rm vis},\gamma p}^{\rm NLO}(ep \to e b \bar{b} X \to e D^{*\pm}\mu X ; \rm{H1}) = 61^{+17}_{-12} \rm{(NLO)} ^{+12}_{-8}\rm{(frag. \oplus br.)}~\rm{pb}.$$ This is larger than the NLO cross section evaluated by H1 [@pl:b621:56-71] due to the inclusion of the hadron-like photon contribution, the inclusion of secondary-muon branching fractions for $D^*$ and $\mu$ from the same $b$ quark (Table \[tab:branchings\]), and a detailed simulation of the kinematics of the $b \to B \to D^*$ chain rather than direct collinear fragmentation of $b$ quarks into $D^*$ mesons. The data to NLO ratio is consistent with the results in the ZEUS kinematic range. Cross sections for $D^*\mu$ from the same $b$ quark --------------------------------------------------- In all the cross sections evaluated above, a significant part of the systematic error arises from the fraction of the beauty contribution in the charm enriched or like-sign regions, where it cannot be well measured ($\Delta R > 2$ region in Fig. \[fig2\]a; Figs. \[fig2\]b and \[fig2\]d). This fraction depends on details of the description of $b\bar b$ correlations in the MC used for the signal extraction. In the beauty-enriched low-$\Delta R$ unlike-sign region, which dominates the fit of the beauty fraction, about 95% of the $D^*\mu$ pairs are produced from the same parent $b$ quark. The systematic error can thus be reduced by reinterpreting the measurements in terms of cross sections for this subprocess only. The corresponding cross section for photoproduction of a $D^*$ and $\mu$ from the same $b$ quark (always unlike sign, same kinematic cuts as for Eq. (\[sig:PHP\])) is $$\label{sig:PHPsame} \sigma_{{\rm vis},\gamma p}(ep \to e b (\bar{b}) X, b (\bar{b}) \to e D^*\mu X) = 52 \pm 13 \rm{(stat.)}^{+9}_{-11}\rm{(syst.)} ~\rm{pb}$$ where $b (\bar{b})$ stands for the sum of $b$ and $\bar b$ cross sections, and all other cuts remain the same. This can be compared with the NLO prediction $$\sigma_{{\rm vis},\gamma p}^{\rm NLO}(ep \to e b (\bar{b}) X, b (\bar{b}) \to e D^*\mu X) = 29^{+8}_{-5} \rm{(NLO)}^{+5}_{-4}\rm{(frag. \oplus br.)}~\rm{pb}.$$ For the DIS kinematic range (same as Eq. (\[sig:DIS\])) $$\label{sig:DISsame} \sigma_{\rm vis,DIS}(ep \to e b (\bar{b}) X, b (\bar{b}) \to e D^*\mu X) = 28 \pm 14 \rm{(stat.)}^{+5}_{-10}\rm{(syst.)} ~\rm{pb}$$ is obtained. Parton-level cross sections --------------------------- For a direct comparison with the NLO parton-level predictions, the measured visible cross sections were extrapolated to $b$-quark level. In order to minimize the systematic error, the $b$-level cross section is quoted for individual $b$ (or $\bar{b}$) production rather than for correlated $b\bar{b}$-pair production, i.e. using the cross sections displayed in Eqs. (\[sig:PHPsame\]) and (\[sig:DISsame\]). A significant fraction of the parent $b$ quarks of the selected events is expected to have very low $p_T^b$ values [@thesis:longhin:2004]. Therefore, cross sections with no cut on $p_T^b$ have been measured. Furthermore, there is a strong correlation between the pseudorapidity of the $D^*\mu$ system and the rapidity of the parent $b$ quark, $\zeta^b = \frac{1}{2}\ln\frac{E_b+p_{z,b}}{E_b-p_{z,b}}$. In order to reflect the limited angular acceptance of the detector for both the $D^*$ and the muon, the cross-section measurement was restricted to $\zeta^b < 1$. In this range, restricted to photoproduction, the $p_T^b$ and $\zeta^b$ distributions of [Pythia]{} (after parton showering) agree with the central NLO $b$-quark spectra from FMNR to within $\pm15$% [@thesis:longhin:2004]. Therefore, [Pythia]{} was used to extrapolate the visible cross section for the photoproduction region. Similarly, the corresponding [Rapgap]{} spectra for the DIS case agree [@thesis:longhin:2004] with the central NLO predictions from HVQDIS. The acceptance for $b$ quarks due to the kinematic cuts on the fragmentation and decay products ranges from $\sim$ 4% at $p_T^b=0$ GeV to $\sim$ 55% at $p_T^b=10$ GeV. The remaining part of the extrapolation is due to the relevant branching ratios. The extrapolation implies additional systematic uncertainties from the $b$-quark fragmentation (+5/-15%) and decay ($\pm 9$%) and the details of the shape of the $p_T^b$ spectrum ($\pm 5$%). The extrapolation was calculated assuming the validity of the NLO $p_T^b$ shape and is therefore valid only in the context of this theoretical framework; the uncertainty for the visible cross section corresponding to a potential deviation from this shape, namely the reweighting of the $p_T^{D^*\mu}$ spectrum, is removed. The result for the extrapolated cross section for $\zeta^b<1,\ Q^2<1~{\rm GeV}^2,\ 0.05<y<0.85$ and $m_b = 4.75$ GeV was $$\label{sig:PHPext} \sigma_{\gamma p}(ep\to b (\bar{b})X)= 11.9 \pm 2.9\rm{(stat.)}^{+1.8}_{-3.3}\rm{(syst.)}~\rm{nb}.$$ The corresponding result for the extrapolated cross section for $\zeta^b<1,\ Q^2>2~{\rm GeV}^2,\ 0.05<y<0.7$ and $m_b = 4.75$ GeV was $$\label{sig:DISext} \sigma_{DIS}(ep\to b (\bar{b})X)= 3.6 \pm 1.8\rm{(stat.)}^{+0.5}_{-1.4}\rm{(syst.)}~\rm{nb}.$$ These cross sections are to be compared to the NLO prediction for the same kinematic range using the FMNR calculation of $$\sigma_{\gamma p}^{NLO}(ep\to b (\bar{b)}X) = 5.8^{+ 2.1}_{-1.3}{\rm ~nb},$$ and to the NLO HVQDIS prediction of $$\sigma_{DIS}^{NLO}(ep\to b (\bar{b)}X) = 0.87^{+ 0.28}_{-0.16}{\rm ~nb}.$$ These cross sections are presented in Fig. \[fig7\]. The ratio of measured to predicted cross sections in the photoproduction region remains the same as the ones obtained from the comparison at visible level (Table \[tab:cross\]). This confirms the self-consistency of the extrapolation procedure used. Comparison to previous ZEUS measurements ---------------------------------------- In order to compare the photoproduction cross section to previous ZEUS results [@pl:b467:156; @*epj:c18:625; @pr:d70:012008], the cross sections Eq. (\[sig:PHPsame\]) or equivalently Eq. (\[sig:PHPext\]), already referring to the production of a single $b$ quark, need to be translated into a differential cross section, $\frac{d\sigma}{dp_{T}^b}$, in the pseudorapidity range $|\eta^b| < 2$[@pr:d70:012008]. The median $p_{T}^b$ value for events satisfying the cuts for Eq. (\[sig:PHPsame\]) is 6.5 GeV [@thesis:longhin:2004]. The measured cross section, Eq. (\[sig:PHPsame\]), is therefore extrapolated to this value using FMNR$\otimes$[Pythia]{}, yielding $$\label{sig:PHPdiff} \frac{d\sigma}{dp_{T}^{b}}(p_{T}^b = 6.5 {\rm ~GeV}, |\eta^b| < 2) = 0.30 \pm 0.07\rm{(stat.)}^{+0.05}_{-0.06}\rm{(syst.)}~\rm{nb}.$$ This result is compared to theory and previous measurements in Fig. \[fig9\]. It is higher than, but consistent with, these measurements. Conclusions =========== Cross sections for beauty production in $ep$ collisions at HERA have been measured in both the photoproduction and DIS regimes using an analysis technique based on the detection of a muon and $D^*$. Agreement is obtained with the corresponding H1 result. Since the analysis is sensitive to $b$-quark production near the kinematic threshold, the measured visible cross sections were extrapolated to $b$-quark cross sections without an explicit cut on $p_T^b$. Both at visible and at quark level, the measured cross sections exceed the NLO QCD predictions, but are compatible within the errors. The data to NLO ratio is also larger than, but compatible with, previous ZEUS measurements of the $b$ production cross section at higher $p_T^b$. Acknowledgements {#acknowledgements .unnumbered} ================ We thank the DESY Directorate for their strong support and encouragement. The remarkable achievements of the HERA machine group were essential for the successful completion of this work and are greatly appreciated. We are grateful for the support of the DESY computing and network services. The design, construction and installation of the ZEUS detector have been made possible owing to the ingenuity and effort of many people who are not listed as authors. It is also a pleasure to thank S. 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[**B 590**]{}, 143 (2004) --- ----------------------------- ---- ------ -------------- ------------ ------ prompt $\mu$ fake $\mu$ $\Delta R < 2$, $3<M<5$ GeV 41 28.8 3.6 2.5 11.2   $\Delta R > 2$ 93 6.5 56.5 18.4 6.4 $\Delta R < 2$, $3<M<5$ GeV 18 1.6 0.7 1.3 9.2   $\Delta R > 2$ 36 11.1 2.0 21.2 5.2 $\Delta R < 2$, $3<M<5$ GeV 31 23.6 1.2 1.6 8.3   $\Delta R > 2$ 79 6.2 48.8 14.0 6.2 $\Delta R < 2$, $3<M<5$ GeV 14 1.5 0.6 0.4 6.9   $\Delta R > 2$ 28 9.1 1.9 17.1 5.2 $\Delta R < 2$, $3<M<5$ GeV 11 8.1 1.6 0.5 1.0   $\Delta R > 2$ 14 3.2 6.1 1.2 3.9 $\Delta R < 2$, $3<M<5$ GeV 3 1.2 0.1 0.5 0.3   $\Delta R > 2$ 10 5.0 0.2 2.6 1.2 --- ----------------------------- ---- ------ -------------- ------------ ------ : Composition of the final $D^*\mu$ event samples (number of events) as determined from the fit to the $\Delta R$ distribution.[]{data-label="tab_evts"} channel branching fraction w/o $B^0$-$\bar B^0$ mixing --------------------------------------------------- ------------------------------------------------ $17.3 \pm 2.0$ % $86\pm3$ % $D^{*+}$, $14\pm3$ % $D^{*-}$ $b \to \mu^-$ direct $10.95 \pm 0.27$ % $b \to \mu^{+}$ indirect $8.27 \pm 0.40$ % $b \to \mu^{-}$ indirect $2.21 \pm 0.50$ % all $b \to \mu^{\pm} $ $21.43 \pm 0.70$ % $ b \bar b \to D^{*\pm} \mu^{\pm} $ (diff. $b$’s) $4.34 \pm 0.92$ % $ b \bar b \to D^{*\pm} \mu^{\mp} $ (diff. $b$’s) $3.08 \pm 0.60$ % $b \to D^{*+} \mu^- $ direct $2.75 \pm 0.19$ % $b \to D^{*\pm} \mu^{\mp} $ indirect $1.09 \pm 0.27$ % all $b \to D^{*\pm} \mu^{\mp} $ $3.84 \pm 0.33$ % : Branching fractions assumed for cross-section determinations. The indirect contributions include cascade decays into muons via charm, anticharm, $\tau^\pm$ and $J/\psi$. The values in the Table are given before the inclusion of the effect of $B^0$-$\bar B^0$ mixing (mixing parameter $\chi = 0.1257 \pm 0.0042$) [@pl:b592:1].[]{data-label="tab:branchings"} cross section measured NLO QCD ratio ---------------------------------------------------- ----------------------------------------------- ------------------------------------- --------------------- inclusive, visible, Eq.(\[sig:tot\]) $160 \pm 37 ^{+ 30}_{- 57}~\rm{pb}$ $67^{+24}_{-14}~\rm{pb}$ $2.4^{+0.9}_{-1.3}$ $\gamma p$, visible, Eq.(\[sig:PHP\]) $115 \pm 29 ^{+21}_{-27}~\rm{pb}$ $54^{+18}_{-12}~\rm{pb}$ $2.1^{+0.8}_{-1.0}$ DIS, visible, Eq.(\[sig:DIS\]) $ 58 \pm 29 ^{+11}_{-20}~\rm{pb}$ - - $\gamma p $, vis. same $b$, Eq.(\[sig:PHPsame\]) $ 52 \pm 13 ^{+9}_{-11}~\rm{pb}$ $ 29^{+9}_{-6}~\rm{pb}$ $1.8^{+0.7}_{-0.8}$ DIS, vis. same $b$, Eq.(\[sig:DISsame\]) $28 \pm 14 ^{+5}_{-10}~\rm{pb}$ - - $\gamma p$, $b$ quark, Eq.(\[sig:PHPext\]) $11.9 \pm 2.9 ^{+1.8}_{-3.3}~\rm{nb}$ $5.8^{+2.1}_{-1.3}~{\rm nb}$ $2.0^{+0.8}_{-1.1}$ DIS, $b$ quark, Eq.(\[sig:DISext\]) $3.6 \pm 1.8 ^{+0.5}_{-1.4}~\rm{nb}$ $0.87^{+0.28}_{-0.16}~{\rm nb}$ $4.2^{+2.3}_{-2.9}$ $\gamma p$, $b$ differential, Eq.(\[sig:PHPdiff\]) $0.30 \pm 0.07 ^{+0.05}_{-0.06}~\rm{nb/GeV} $ $0.16^{+0.04}_{-0.02}~{\rm nb/GeV}$ $1.8^{+0.7}_{-0.8}$ : Comparison of measured and predicted cross sections. For the measured cross sections, the first error is statistical, and the second systematic. For the QCD prediction, the error is due to the parton-level NLO calculation convoluted with the uncertainties of fragmentation and decay to the visible final state. The number in parentheses refers to the corresponding equation for each cross section, see text. For the definition of the kinematic range of each cross section see text.[]{data-label="tab:cross"} (150,140) (0,70) (80,70) (0,0) (80,0) (5,120)[(a)]{} (85,120)[(b)]{} (5,50)[(c)]{} (85,50)[(d)]{} ![Distribution of $\Delta M$ for data (full circles) and combinatorial background (hatched histogram) for (a) inclusive unlike-sign (b) inclusive like-sign (c) DIS unlike-sign and (d) DIS like-sign muon-$D^*$ combinations. The $D^*$ signal region is indicated by the shaded area.[]{data-label="fig1"}](DESY-06-166_2.eps) ![Distributions of variables used in the event selection or relevant for the event kinematics, for the unlike-sign inclusive sample after all cuts. All variables are defined in the text except $n_{trks}$ (total number of tracks) and $\zeta^{D^*\mu}$ (rapidity of the $D^*\mu$ system). The distributions are shown separately for the beauty- and charm-enriched regions as defined in Section \[sect:signal\]. The beauty, charm, fake-muon and wrong-charge $K\pi$ background distributions are indicated by different shading styles, and normalized to the fractions determined later in the analysis.[]{data-label="fig:controlplots"}](DESY-06-166_3.eps) ![Distribution of (a),(b) $\Delta R(D^*\mu)$ and (c),(d) $M(D^*\mu)$ for inclusive data (full circles), beauty and charm signal, fake-$\mu$ and fake-$D^*$ backgrounds. The latter are distinguished by different shading styles. Unlike-sign and like-sign $D^*\mu$ combinations are shown separately. Cuts described in the text are indicated by the arrows. The relative contributions of charm and beauty are determined by the fit to the $\Delta R$ distribution. []{data-label="fig2"}](DESY-06-166_4.eps) ![Distributions of (a) $\Delta R(D^*\mu)$, (c) $\Delta \phi(D^*\mu)$ for unlike-sign events in the inclusive sample, (b) $\Delta R(D^*\mu)$ and (d) $M(D^*\mu)$ for unlike-sign events in the DIS sample after subtraction of the fake-$D^*$ background. Data points (full circles) are shown together with the contributions from beauty and charm, as determined in the fit. The fake-muon contribution from charm is shown separately, but fitted together with the charm contribution.[]{data-label="fig3"}](DESY-06-166_5.eps) ![Cross section for single $b$ or $\bar b$-quark production in the rapidity range $\zeta^b < 1$ for photoproduction (left) and DIS (right), compared to NLO QCD predictions from FMNR (left) and HVQDIS (right). The $\gamma p$ cross section is for $0.05 < y < 0.85$, $Q^2<1 \gev^2$ and the DIS cross section for $0.05 < y < 0.7$, $Q^2 > 2 \gev^2$. The cross sections are integrated over the $Q^2$ ranges, and over the full $p_T^b$ range.[]{data-label="fig7"}](DESY-06-166_6.eps) ![Differential cross-section $\frac{d\sigma}{dp_T^b}$ of this analysis (filled square) compared to measurements from previous ZEUS analyses, after rescaling to the kinematic range indicated in the Figure.[]{data-label="fig9"}](DESY-06-166_7.eps) [^1]: Electrons and positrons are not distinguished in this paper and are both referred to as electrons. [^2]: The [ MC@NLO]{} approach [@jhep:06:029; @*jhep:08:007], which allows the combination of NLO matrix elements with parton showers, is not yet available for $ep$ interactions.
Hundreds of thousands of believers from Hungary, Transylvania and other places around the world, make the pilgrimage to Csíksomlyó (Sumuleu Ciuc) at Pentecost. We collected the best pictures: President highlights message of reconciliation in pilgrimage homily Hungarian President János Áder stressed the message of reconciliation in a homily delivered at a pilgrimage in Sumuleu Ciuc (Csíksomlyó), Romania, on Saturday. “Peace was the central message of Bishop András Veres’s homily,” Áder told journalists after the celebration of the mass. “We must make peace with ourselves as well as create peace within our families, communities, cities and countries. It would be welcome if this message was heard by as many people as possible,” he added. Photo: MTI Áder noted that he was participating in the annual pilgrimage for the fifth time since taking the office of president. Photo: MTI Source: MTI TAGS Related Posts Hundreds of thousands observed All Saints Day on Sunday in cemeteries throughout Hungary, tending the graves of deceased loved ones. (See gallery.) Heavy traffic was reported near Budapest cemeteries. Photo:…
The results confirm that voters have not elected their caste or tribe but their Hindu-ness. | Photo Credit: BCCL Narendra Modi will be the first non-Congress politician to serve two full consecutive terms as Prime Minister in a majority government. His victory is certain to have convulsive consequences. Apart from the obvious implications for the Congress and some other regional political parties who might now have to fight to stay relevant, the triumph spells a major crisis of credibility for the so-called ‘’Khan Market Consensus”: An entitled clique who purport to have crafted the ideological bedrock of Indian democracy. The results confirm that voters have not elected their caste or tribe but their Hindu-ness. Where the Mandir failed, the “Khan Market Consensus” has succeeded in awakening the Hindu. Ever since the rise of Modi, virtually from the first day he assumed office, the “Khan Market Consensus” has droned on about his allegedly corrosive impact on the secular fabric of the nation. Its rasping excoriation of Modi’s RSS background and its simplistic hyphenation with a mean-spirited Hindu chauvinism meant that all his supporters were branded as bigots. Indeed, as the vanguard of a new kind of “bhakti” movement the difference being that this avatar was not syncretic but Semitic. A Klu-Klux-Klan governed by a code and hooded by blinding hatred towards Muslims, Dalits, LGBTQI, Liberals, democrats and everything that stood in the way of a Hindu Rashtra. Sorry, but it’s a jaundiced, illiberal conflation of the type that cost Hillary Clinton the elections in 2016. Remember, when she shamed Trump supporters by branding them all as “deplorables". Being so dismissive taught her a lesson. Today, Indian voters have taught Rahul Gandhi, Mamata and several other satraps who were the political ‘sutradhars’ of this ‘’Khan Market’’ construct a lesson. Just like not every liberal is an Urban Naxal, not every Modi supporter is a bigot, prejudiced, sicko. On the contrary, most Modi’s supporters recognise he has made some mistakes. They have been anguished when he has given a podium to the faces of an uncompromising anti-Muslim component, they have felt their stomach churn when abominable crimes were visited upon Muslims in the name of Gau-raksha, they have been disappointed when he has been reticent to embrace progressive social order where same-sex love is not stigmatised. In fact, they have even been grateful when the courts have stepped in to remind Modi of his omissions and Constitutional obligations. Had the “Khan Market Consensus” not been so busy snootily looking down their patrician noses they would have read the results of Assembly elections and Lok-Sabha by-elections over the last 18 months for what they were: A sense of disaffection with Modi for some of his mistakes. But instead of embarking on an agenda that would have provided Modi supporters a genuine reason to vote for another manifesto, they continued to shame them. In fact, not content with labelling, they went further by insidiously pursuing a policy of dividing Hindus. If the results of the Lok Sabha elections tell us something it is this: Modi supporters don’t want to be divided by self-serving politics but want to be united by hope. The hope that they too will someday wear without guilt a “suit-boot” accessorised by perhaps even a “tilak”. The hope that they won’t have to flash their caste certificate to apply for the next job or scheme. The hope that saying “Bharat Mata Ki Jai” would not be construed as an indignity but as a privilege available to anyone who decides to delight in the pageantry of patriotism. The views expressed by the author are personal and do not in any way represent those of Times Network.
Home / Section: Comic strips Dear Editor: Bring Back Non Sequitur The number of newspapers dropping Non Sequitur over a lapse in judgment is approaching double digit dozens. Now fans and readers of Wiley‘s comic are expressing disappointment in the newspapers’ actions and requesting the return of one of their favorite cartoonists. Halltoons by Ed Hall I hope you will reconsider! Non Sequitur is probably one of the most enjoyable comics in the newspaper…The artist who produces Non Sequitur is innovative, unique and totally interesting. He has apologized and said it would not happen again. I guess his word is not enough for those “people who know who they are” out there who can’t stand anything different or thought provoking Please do not discontinue “Non Sequitur.” It is the best comic strip on the page. Good grief! Is everything offensive? What kind of sheltered life are we leaving to the poor snowflakes among us? Be bold! Resume publishing Non Sequitur and add Mallard Fillmore! Many of the responses mentioned Mallard Fillmore and Doonesbury, though not in the positive manner as the reader above. Others suggested a temporary, not permanent, punishment. Non Sequitur is humor, fantasy, parables Some are replying with their pocketbooks. To be sure there were those who agreed with the decision made by newspapers. Those who disagreed. And those who demanded the drop before the paper officially did so. While some understood but will miss Non Sequitur all the same. Last weekend the comic artist Wiley Miller made the mistake of actually writing out what he was thinking and the N&R has responded both quickly and appropriately…“Non Sequitur” outstripped other comics by being both well-drafted and able to pull the veil off many of our current absurdities. Just going to have to rely on “Doonesbury” until it, too, gets axed for crossing some other PC line. above: today some newspaper subscribers missed the beautiful art of Wiley. More than a few compared the comic to the very public tweets and statements of President Trump: Wiley speaks Truth to Power. Some accuse the newspapers of unnecessary censorship and cowardice. The N&O has reached a new journalistic low in self-censorship with its decision to drop “Non Sequitur” from its comic pages…But you can’t stop there — Dennis the Menace has some very troubling themes concerning corporal punishment of children, and Blondie indulges in blatant and dated stereotypes of women. The N&O has got a lot of work ahead of it to make its comic pages inoffensive to its readers! After careful rereading of my favorite comic strip in the Bangor Daily News, I find the BDN’s censorship offensive. What happened to freedom of speech and protection of satire and humorous expression of political differences? It does seem rather spineless and petty that The Sun would remove one of the smarter and more insightful cartoons from its publication. For some fans it’s the editors’ lack of knowing the good comics from the bad. Bless your heart, I know you can’t help not having much of a sense of humor. You need to leave the comics alone — quit changing them — and do not remove “Non-Sequitur.” I need to see how the bears will again try to trap the humans. The Dallas News published a quintet of letters damning, praising, and suggesting replacements. The San Diego Union-Tribune also published a number of letters both pro and con. Daytona Beach News-Journal letters run the gamut from dismay to approval to a paper wimping out. But, by far, most of the letters bemoaned the loss of an excellent comic and supported Wiley. Like this: Like Loading...
Ultraviolet A1 phototherapy: One center's experience. Ultraviolet A1(UVA1) phototherapy is increasingly being used in the treatment of morphea, atopic dermatitis, lupus and some other recalcitrant dermatoses. We present a retrospective review of our experience with this modality. To evaluate the treatment response rates for various dermatoses and adverse effects of UVA1 phototherapy. We reviewed phototherapy notes along with electronic and/or paper case records for all patients treated with UVA1 phototherapy from October 1996 to December 2008. A total of 269 patients (outcomes available for 247) had 361 treatment courses (treatment data available for 317 courses) over this period. We found phototherapy to be beneficial in 28 (53%) of 53 patients with atopic dermatitis and 19 (51%) of 37 patients with morphea. A beneficial outcome was recorded in all six (100%) cases of urticaria and six (85.7%) of seven patients treated for a polymorphic light eruption. Benefit was also recorded in systemic lupus erythematosus (8 (44.4%) of 18), lichen sclerosus (6 (42.9%) of 14), mastocytosis (2 (33.3%) of 6), necrobiosis lipoidica (4 (30.8%) of 13), granuloma annulare (2 (25%) of 8), scleroderma (2 (22.2%) of 9) and keloids (1 (7.7%) of 13). Overall, treatment was well tolerated with no patients having to stop treatment due to adverse effects. This is a retrospective study with no control group. Subjective/recall bias is quite possible as a number of patients were followed up over the phone. Our data suggest that ultraviolet A1 can be considered for the treatment of selected dermatoses. However, long-term malignancy risk is as yet unknown.
Q: A king in a fort with two doors with two buttons A king wants to go outside. He comes to the end of the fort. There are two doors there, and two buttons. These buttons do opposite things - if you push button 1, the king will come out of door 2 and vice versa. If you press both at once, you don't know through which door the king will come out (or whether he will be divided into two pieces). What is the king's name? This was asked by a stranger during a train ride. Though I couldn't ask him the answer. So I won't be able to provide hints. A few things if they can help: That person didn't read Science after 5th grade. So, physics and chemistry related answers are not possible. It might be a reference to a product. But if it does, then it should be the one available in India. He did give emphasis on the button part. Therefore, the answer must satisfy that clue too. Update: So, I met this person again, and I asked for hint instead of giving any answer. That hint was: It's a bad thing that you wouldn't wanna keep. After getting this hint, I gave the answer provided by Keelhaul, which was correct. A: It might be Sir Booger Indeed If you press your left nostril while blowing your nose, the mucus will go out from the right nostril, and vice versa. However, if you press both your nostrils, well... we don't really know what will happen, do we? You can pop your ears or the "King" will come out forcibly from the left or right nostril, or both as several "pieces". A: Maybe it's an allegory of Double-slit experiment, made by Thomas Young pushing the button open opposite door, so he come from the other door pushing both open both doors, and we don't know if it will come from one random door, or both as for the king name maybe as this experiment show how light behave, I suppose it's Louis XIV, A.K.A. the Sun King A: We are talking about A roll of King peppermint The buttons are simply the sides of the rolls; push on the left side and your peppermint comes out on the right and vice versa. Pushing both buttons might break your peppermint due to the pressure exerted on it
The news comes from st. from one of the brokerage firm based in NOIDA . Due to this current agitation/ protest/ movement by Farmers all the projects will get delay by 1 year.Builder will take undue advantage of this tension irrespective of the property falls in litigation or not. Really bad news for all of us. Dec-2012 will be dream now for PAN A, B,C & D towers. The quality of construction of the structure is far better than the quality I see in a few soceities in Indirapuram.Patel construction group is doing a good job.Te structure have no signes of honey combing.This shows that there is good workmanship. Seems like PAN Oasis going to be one the best project in term of structure quality. Work is going on at high speed and tower A-D possession is less than 12 months as structure is almost complete with brick work also done. And just to add-on for Tower A-D they even started White-wash, : road facing towers. Its again shows the imp of road facing towers are always in adv. as for new customers this is what they see, related to progress of project and this is true for almost all the projects in Noida. I guess apart for Tower A-D, all other towers will be delayed by at least 18 months ( I am talking about Phase-1 Tower A-J).So now the question is how many of us will get the Penalty? I know few of the guys posted in Amarpali Platinum Thread that they are getting penalty from Builder. Other very important point for Phase-1 buyers, they have different possession dates, for instance in my FBA it says July-2012 +- 3 months ( mine is under co-operate booking Tower-H) wherein i know people from Tower H, in their FBA it says 36 months from the date of singing the FBA , which comes at around mid of 2013. And i believe majority of the people are with 36 months clause. Lets see what PAN will do. I guess apart for Tower A-D, all other towers will be delayed by at least 18 months ( I am talking about Phase-1 Tower A-J).So now the question is how many of us will get the Penalty? I know few of the guys posted in Amarpali Platinum Thread that they are getting penalty from Builder. Other very important point for Phase-1 buyers, they have different possession dates, for instance in my FBA it says July-2012 +- 3 months ( mine is under co-operate booking Tower-H) wherein i know people from Tower H, in their FBA it says 36 months from the date of singing the FBA , which comes at around mid of 2013. And i believe majority of the people are with 36 months clause. Lets see what PAN will do. Lately I have seen construction work picking up for towers other then A-D. Towers like E,F,L,M,N have reached till 5 floor and work is picking up for other towers too in last 2-3 months. I have heard that builder is using additional manforce and machinary from NE(where work has stopped) in PAN oasis. So I hope it will bring some speed to the construction.Regarding the late delivery panelty I think many corporate buyers have flats in towers from E-J and all corporate buyer have late penalty starting from Oct-12. Infact for retails buyer who signed BBA in Feb,Mar-10 late penalty starts at Mar-13. So lets hope that we will get late panelty atleast for coporate buyers from Oct-12.Regarding delay by 18 months, I think if work picks up, then builder can deliver alteast Phase-1 by Oct-13 i.e a delay of 1 year atleast. I guess apart for Tower A-D, all other towers will be delayed by at least 18 months ( I am talking about Phase-1 Tower A-J).So now the question is how many of us will get the Penalty? I know few of the guys posted in Amarpali Platinum Thread that they are getting penalty from Builder. Other very important point for Phase-1 buyers, they have different possession dates, for instance in my FBA it says July-2012 +- 3 months ( mine is under co-operate booking Tower-H) wherein i know people from Tower H, in their FBA it says 36 months from the date of singing the FBA , which comes at around mid of 2013. And i believe majority of the people are with 36 months clause. Lets see what PAN will do. I signed my BBA in March 2010 and it says 36 month + 3 month grace period.Meaning NO penalty till June 2013. I have already paid 80% of BSP +Floor PLC. Another 10% coming by this month end.I am expecting tower D to be delivered by Oct 2012. But might go till Dec 2012. Booked in Nov 09 and if I get it by Dec 2012 then still I will feel lucky..Although I am not in INDIA and can not be in India for another 3-4 years as when I want to move in my home I should feel it's my home not bank's home. I signed my BBA in March 2010 and it says 36 month + 3 month grace period.Meaning NO penalty till June 2013. I have already paid 80% of BSP +Floor PLC. Another 10% coming by this month end.I am expecting tower D to be delivered by Oct 2012. But might go till Dec 2012. Booked in Nov 09 and if I get it by Dec 2012 then still I will feel lucky..Although I am not in INDIA and can not be in India for another 3-4 years as when I want to move in my home I should feel it's my home not bank's home. I also agree that PAN have one of the best payment plan in NCR. Most of the people in the project till date have paid around 40% and 5th floor is ready for most of the towers. For people who have paid more then that line in tower A-D strucuture is almost complete and plastering and other work have started.Advantage of same is that people who have paid less and if there is some delay in delivery they will save some money due to the payment plan and another better thing is that the plan itself gives option to people to pay from their own pocket rather than depending on bank. Best thing is that PAN charges 10% after completion of 5 floor,10 floor,15 floor so on.Infact at the begining they charged 10% and remaining 30% was charged when they started with BBA and construction. Bhuwan, BSP of people who booked in Corporate was 2400 (2900- other charges).So far a tower below 5 floor constructed they only paid 40% of BSP.And if allowed can easliy sell for 4000 BSP in CLP today meaning 66% profit in 2 years on a 1385 sqft on which a corporate buyer has paid only 13.86 lakh in 2 years. Not a single project in NOIDA when a 1385 sqft flat owner has paid only 13.8 lakh in Flexi in 2 years what ever be the construction stage. As per builder due to Noida extention issue, all resources from NE has been used for PAN Oasis then NE issue should streach another 6 months, PAN Oasis complete ho jayega..(funny comment not serious):) What is your gut feel guys will tower A-D will be delivered by Oct 2012 ?If delivered then will it be livable ? Other builders asking for interior /color etc is PAN asking like anything ?
In known types of manually operated silk screen printing apparatus, a hand-held squeegee is used to distribute ink across the screen and to force the ink through the screen onto the item to be printed in the pattern dictated by an intelligence pattern formed on the screen. While hand-held squeegees are inexpensive, even experienced printers, particularly when tired or distracted, sometimes fail to maintain a uniform pressure across the length of the squeegee blade during the printing stroke, resulting in an uneven print quality. Further, with hand-held squeegees, it is difficult to duplicate exactly the squeegee print action from one print to the next so that occasionally even consecutively-made prints may be non-uniform in quality. This is particularly noticeable in moderately long production runs of large-sized jobs. Currently, manual silk screen printing units have been developed in which the squeegee blade is mounted on an elongated lever arm that is pivotally mounted at one end and that extends across the screen. The other end of the lever arm is a free or handle end that allows upward or downward movement of a squeegee carried on the lever arm to engage or disengage the screen. The squeegee is mounted on a carriage slideable along the lever arm when pushed and pulled by the operator through a print and flood stroke across the screen. Typically, the squeegee is pivoted on the carriage and the operator grasps the top of the squeegee with a hand on opposite sides of the lever arm and the carriage. The operator balances the amount of downward force exerted by each hand on the top of the squeegee to maintain the squeegee level and to try to exert uniform pressure on opposite halves of the squeegee blade onto the screen. The operator also adjusts the angle of incidence of the squeegee manually and tries to maintain a relatively uniform angle during an entire printing or flood stroke. The operator is free to adjust this angle during the stroke or between strokes and often inadvertantly makes such adjustments. That is, the operator is free to swing the squeegee to any angle of incidence with the screen, with the higher, more vertical angles for the squeegee exerting more force onto the screen to push the ink through the screen than when the squeegee is swung more toward the horizontal. The operator flips the squeegee between its print and flood strokes to an inclined angle of incidence between the flood and print stokes. In a typical, multi-arm, manual textile printer illustrated herein, the operator prints with the squeegee's lower end tilted away from the operator at the end of the level arm. At the end of the print stroke the operator turns the squeegee to an opposite inclination, with the lower end of the squeegee closer to the operator who is pushing the squeegee radially inwardly along the lever arm. Operators often have problems adjusting and maintaining this angle of incidence. Manual operated silk screen printers are low in cost compared to automatic motor driven printers and any changes therein to produce better quality of printing or higher rates of production must be cost competitive to be commercially successful. Production from a manual silk screen printing press can be increased with the present invention by reducing the number of failures to achieve the quality of print needed and by reducing operator fatigue. Accordingly, it is the primary object of the present invention to provide an improved, manual screen printing apparatus of the foregoing kind. More particularly, it is an object to provide such an apparatus which is compact in size so as to be readily usable for printing small areas. It is a further object to provide a manual screen printing apparatus that provides smooth, even and repeatable squeegee action across the screen which reduces operator fatigue and increases production from the apparatus. Other objects and advantages will become apparent upon reference to the drawing and the detailed description of the preferred embodiment.
from unittest.mock import patch, Mock, call from django.db import IntegrityError, transaction from federation.entities import base from federation.entities.activitypub.entities import ActivitypubComment from federation.tests.factories import entities from federation.types import UserType, ReceiverVariant from socialhome.content.enums import ContentType from socialhome.content.models import Content from socialhome.content.tests.factories import ContentFactory, LocalContentFactory, PublicContentFactory from socialhome.enums import Visibility from socialhome.federate.tasks import forward_entity # noinspection PyProtectedMember from socialhome.federate.utils.tasks import ( process_entities, get_sender_profile, process_entity_post, process_entity_retraction, sender_key_fetcher, process_entity_comment, process_entity_follow, process_entity_share, _process_mentions) from socialhome.federate.utils import make_federable_profile from socialhome.federate.utils.entities import make_federable_content, make_federable_retraction from socialhome.notifications.tasks import send_follow_notification from socialhome.tests.utils import SocialhomeTestCase, SocialhomeTransactionTestCase from socialhome.users.models import Profile from socialhome.users.tests.factories import ( ProfileFactory, UserFactory, BaseProfileFactory, BaseShareFactory, PublicProfileFactory, SelfUserFactory) class TestProcessEntities(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.post = entities.PostFactory() cls.comment = base.Comment() cls.retraction = base.Retraction() cls.follow = base.Follow() cls.profile = BaseProfileFactory() cls.share = BaseShareFactory() cls.receiving_user = UserFactory() cls.receiving_profile = cls.receiving_user.profile @patch("socialhome.federate.utils.tasks.process_entity_post") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_post_is_called(self, mock_sender, mock_process): process_entities([self.post]) mock_process.assert_called_once_with(self.post, "profile") @patch("socialhome.federate.utils.tasks.process_entity_post") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_post_is_called__with_receiving_profile(self, mock_sender, mock_process): process_entities([self.post]) mock_process.assert_called_once_with(self.post, "profile") @patch("socialhome.federate.utils.tasks.process_entity_retraction") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_retraction_is_called(self, mock_sender, mock_process): process_entities([self.retraction]) mock_process.assert_called_once_with(self.retraction, "profile") @patch("socialhome.federate.utils.tasks.process_entity_comment") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_comment_is_called(self, mock_sender, mock_process): process_entities([self.comment]) mock_process.assert_called_once_with(self.comment, "profile") @patch("socialhome.federate.utils.tasks.process_entity_comment") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_comment_is_called__with_receiving_profile(self, mock_sender, mock_process): process_entities([self.comment]) mock_process.assert_called_once_with(self.comment, "profile") @patch("socialhome.federate.utils.tasks.process_entity_follow") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_follow_is_called(self, mock_sender, mock_process): process_entities([self.follow]) mock_process.assert_called_once_with(self.follow, "profile") @patch("socialhome.federate.utils.tasks.Profile.from_remote_profile") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_profile_is_called(self, mock_sender, mock_from): process_entities([self.profile]) mock_from.assert_called_once_with(self.profile) @patch("socialhome.federate.utils.tasks.process_entity_share") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_process_entity_share_is_called(self, mock_sender, mock_process): process_entities([self.share]) mock_process.assert_called_once_with(self.share, "profile") @patch("socialhome.federate.utils.tasks.process_entity_post", side_effect=Exception) @patch("socialhome.federate.utils.tasks.logger.exception") @patch("socialhome.federate.utils.tasks.get_sender_profile", return_value="profile") def test_logger_is_called_on_process_exception(self, mock_sender, mock_process, mock_logger): process_entities([self.post]) self.assertEqual(mock_logger.called, 1) class TestProcessMentions(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.create_local_and_remote_user() cls.entity = entities.PostFactory() cls.content = ContentFactory() cls.profile2 = ProfileFactory() cls.content.mentions.add(cls.profile2) def test_addition_happens(self): self.entity._mentions = { self.profile.fid, self.profile2.fid, } _process_mentions(self.content, self.entity) self.assertEqual( set(self.content.mentions.all()), {self.profile, self.profile2}, ) def test_removal_happens(self): self.entity._mentions = {} _process_mentions(self.content, self.entity) self.assertEqual( set(self.content.mentions.all()), set(), ) class TestProcessEntityPost(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.local_content = LocalContentFactory() cls.profile = ProfileFactory() cls.receiving_user = UserFactory() cls.receiving_profile = cls.receiving_user.profile cls.local_user = UserFactory() cls.local_user2 = UserFactory() cls.profile.followers.add(cls.local_user.profile, cls.local_user2.profile) def test_post_is_created_from_entity(self): entity = entities.PostFactory() process_entity_post(entity, ProfileFactory()) content = Content.objects.get(fid=entity.id) self.assertEqual(content.limited_visibilities.count(), 0) def test_visibility_is_added_to_receiving_followers(self): entity = entities.PostFactory(actor_id=self.profile.fid) entity._receivers = [UserType(id=entity.actor_id, receiver_variant=ReceiverVariant.FOLLOWERS)] process_entity_post(entity, self.profile) content = Content.objects.get(fid=entity.id) self.assertEqual( set(content.limited_visibilities.all()), {self.local_user.profile, self.local_user2.profile}, ) def test_visibility_is_added_to_receiving_profile(self): entity = entities.PostFactory() entity._receivers = [UserType(id=self.receiving_profile.fid, receiver_variant=ReceiverVariant.ACTOR)] process_entity_post(entity, ProfileFactory()) content = Content.objects.get(fid=entity.id) self.assertEqual( set(content.limited_visibilities.all()), {self.receiving_profile}, ) def test_visibility_is_not_added_to_public_content(self): entity = entities.PostFactory(public=True) entity._receivers = [UserType(id=self.receiving_profile.fid, receiver_variant=ReceiverVariant.ACTOR)] process_entity_post(entity, ProfileFactory()) content = Content.objects.get(fid=entity.id) self.assertEqual(content.limited_visibilities.count(), 0) def test_entity_images_are_prefixed_to_post_text(self): entity = entities.PostFactory( _children=[ base.Image(url="foobar"), base.Image(url="zoodee", name="foo"), ], ) process_entity_post(entity, ProfileFactory()) content = Content.objects.get(fid=entity.id) assert content.text.index("![](foobar) ![foo](zoodee) \n\n%s" % entity.raw_content) == 0 def test_post_is_updated_from_entity(self): entity = entities.PostFactory() author = ProfileFactory(fid=entity.actor_id) ContentFactory(fid=entity.id, author=author) process_entity_post(entity, author) content = Content.objects.get(fid=entity.id) self.assertEqual(content.text, entity.raw_content) # Don't allow updating if the author is different invalid_entity = entities.PostFactory(id=entity.id) process_entity_post(invalid_entity, ProfileFactory(fid=invalid_entity.actor_id)) content.refresh_from_db() self.assertEqual(content.text, entity.raw_content) self.assertEqual(content.author, author) def test_post_text_fields_are_cleaned(self): entity = entities.PostFactory( raw_content="<script>alert('yup');</script>", provider_display_name="<script>alert('yup');</script>", id="https://example.com/foobar", ) process_entity_post(entity, ProfileFactory()) content = Content.objects.get(fid="https://example.com/foobar") assert content.text == "&lt;script&gt;alert('yup');&lt;/script&gt;" assert content.service_label == "alert('yup');" @patch("socialhome.federate.utils.tasks.Content.objects.update_or_create", return_value=(None, None), autospec=True) def test_local_content_is_skipped(self, mock_update): entity = entities.PostFactory(id=self.local_content.fid) process_entity_post(entity, ProfileFactory()) self.assertFalse(mock_update.called) class TestProcessEntityComment(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.content = ContentFactory(visibility=Visibility.LIMITED) cls.public_content = ContentFactory(visibility=Visibility.PUBLIC) cls.receiving_user = UserFactory() cls.receiving_profile = cls.receiving_user.profile cls.profile = ProfileFactory() cls.local_user = UserFactory() cls.local_user2 = UserFactory() cls.profile.followers.add(cls.local_user.profile, cls.local_user2.profile) def setUp(self): super().setUp() self.comment = base.Comment( id="https://example.com/comment", target_id=self.content.fid, raw_content="foobar", actor_id="https://example.com/profile", ) def test_mentions_are_linked(self): self.comment._mentions = {self.profile.fid} process_entity_comment(self.comment, ProfileFactory()) content = Content.objects.get(fid=self.comment.id) self.assertEqual( set(content.mentions.all()), {self.profile}, ) def test_reply_is_created_from_entity(self): process_entity_comment(self.comment, ProfileFactory()) content = Content.objects.get(fid=self.comment.id, parent=self.content) self.assertEqual(content.limited_visibilities.count(), 0) def test_visibility__added_to_receiving_followers(self): self.comment.actor_id = self.profile.fid self.comment._receivers = [UserType(id=self.comment.actor_id, receiver_variant=ReceiverVariant.FOLLOWERS)] process_entity_comment(self.comment, self.profile) content = Content.objects.get(fid=self.comment.id) self.assertEqual( set(content.limited_visibilities.all()), {self.local_user.profile, self.local_user2.profile}, ) def test_visibility__added_to_receiving_profile(self): self.comment._receivers = [UserType(id=self.receiving_profile.fid, receiver_variant=ReceiverVariant.ACTOR)] process_entity_comment(self.comment, ProfileFactory()) content = Content.objects.get(fid=self.comment.id, parent=self.content) self.assertEqual( set(content.limited_visibilities.all()), {self.receiving_profile}, ) def test_visibility__not_added_if_public_parent_content_if_no_visibility_on_comment(self): comment = base.Comment( id="https://example.com/comment2", target_id=self.public_content.fid, raw_content="foobar", actor_id="https://example.com/profile2", ) comment._receivers = [UserType(id=self.receiving_profile.fid, receiver_variant=ReceiverVariant.ACTOR)] process_entity_comment(comment, ProfileFactory()) content = Content.objects.get(fid=comment.id, parent=self.public_content) self.assertEqual(content.limited_visibilities.count(), 0) def test_visibility__added_if_public_parent_content_if_visibility_on_comment__non_public_comment(self): comment = ActivitypubComment( id="https://example.com/comment2", target_id=self.public_content.fid, raw_content="foobar", actor_id="https://example.com/profile2", public=False, ) comment._receivers = [UserType(id=self.receiving_profile.fid, receiver_variant=ReceiverVariant.ACTOR)] process_entity_comment(comment, ProfileFactory()) content = Content.objects.get(fid=comment.id, parent=self.public_content) self.assertEqual( set(content.limited_visibilities.all()), {self.receiving_profile}, ) def test_visibility__not_added_if_public_parent_content_if_visibility_on_comment__public_comment(self): comment = ActivitypubComment( id="https://example.com/comment2", target_id=self.public_content.fid, raw_content="foobar", actor_id="https://example.com/profile2", public=True, ) comment._receivers = [UserType(id=self.receiving_profile.fid, receiver_variant=ReceiverVariant.ACTOR)] process_entity_comment(comment, ProfileFactory()) content = Content.objects.get(fid=comment.id, parent=self.public_content) self.assertEqual(content.limited_visibilities.count(), 0) def test_entity_images_are_prefixed_to_post_text(self): self.comment._children = [ base.Image(url="foobar"), base.Image(url="zoodee", name="foo"), ] process_entity_comment(self.comment, ProfileFactory()) content = Content.objects.get(fid=self.comment.id, parent=self.content) print(content.text) self.assertEqual(content.text.index("![](foobar) ![foo](zoodee) \n\n%s" % self.comment.raw_content), 0) def test_reply_is_updated_from_entity(self): author = ProfileFactory(fid=self.comment.actor_id) ContentFactory(fid=self.comment.id, author=author) process_entity_comment(self.comment, author) content = Content.objects.get(fid=self.comment.id, parent=self.content) self.assertEqual(content.text, self.comment.raw_content) # Don't allow updating if the author is different invalid_entity = base.Comment( id=self.comment.id, raw_content="barfoo", actor_id="https://example.com/notthesameperson", target_id=self.content.fid, ) process_entity_comment(invalid_entity, ProfileFactory(fid=invalid_entity.actor_id)) content.refresh_from_db() self.assertEqual(content.text, self.comment.raw_content) self.assertEqual(content.author, author) # Don't allow changing parent invalid_entity = base.Comment( id=self.comment.id, raw_content="barfoo", actor_id="https://example.com/notthesameperson", target_id=ContentFactory().fid, ) process_entity_comment(invalid_entity, author) content.refresh_from_db() self.assertEqual(content.text, self.comment.raw_content) self.assertEqual(content.author, author) def test_reply_text_fields_are_cleaned(self): self.comment.raw_content = "<script>alert('yup');</script>" process_entity_comment(self.comment, ProfileFactory()) content = Content.objects.get(fid=self.comment.id, parent=self.content) self.assertEqual(content.text, "&lt;script&gt;alert('yup');&lt;/script&gt;") @patch("socialhome.federate.utils.tasks.django_rq.enqueue") def test_does_not_forward_relayable_if_not_local_content(self, mock_rq): process_entity_comment(self.comment, ProfileFactory()) Content.objects.get(fid=self.comment.id, parent=self.content) self.assertFalse(mock_rq.called) @patch("socialhome.federate.utils.tasks.django_rq.enqueue", autospec=True) def test_forwards_relayable_if_local_content(self, mock_rq): user = UserFactory() self.content.author = user.profile self.content.save() self.content.refresh_from_db() mock_rq.reset_mock() process_entity_comment(self.comment, ProfileFactory()) Content.objects.get(fid=self.comment.id, parent=self.content) call_args = [ call(forward_entity, self.comment, self.content.id), ] self.assertEqual(mock_rq.call_args_list, call_args) @patch("socialhome.federate.utils.tasks.Content.objects.update_or_create", return_value=(None, None), autospec=True) def test_local_reply_is_skipped(self, mock_update): user = UserFactory() ContentFactory(fid=self.comment.id, author=user.profile) process_entity_comment(self.comment, ProfileFactory()) self.assertFalse(mock_update.called) class TestProcessEntityRetraction(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.content = ContentFactory() cls.local_content = LocalContentFactory() cls.create_local_and_remote_user() cls.reply = PublicContentFactory( author=cls.content.author, content_type=ContentType.REPLY, parent=cls.content, ) cls.share = PublicContentFactory( author=cls.content.author, content_type=ContentType.SHARE, share_of=cls.content, ) def setUp(self): super().setUp() self.content.refresh_from_db() @patch("socialhome.federate.utils.tasks.logger.debug", autospec=True) def test_non_post_entity_types_are_skipped(self, mock_logger): process_entity_retraction(Mock(entity_type="foo"), Mock()) mock_logger.assert_called_with("Ignoring retraction of entity_type %s", "foo") @patch("socialhome.federate.utils.tasks.logger.warning", autospec=True) def test_does_nothing_if_content_doesnt_exist(self, mock_logger): process_entity_retraction(Mock(entity_type="Post", target_id="https://example.com/notfound"), Mock()) mock_logger.assert_called_with("Retracted remote content %s cannot be found", "https://example.com/notfound") @patch("socialhome.federate.utils.tasks.logger.warning", autospec=True) def test_does_nothing_if_content_is_not_local(self, mock_logger): process_entity_retraction(Mock(entity_type="Post", target_id=self.local_content.fid), Mock()) mock_logger.assert_called_with( "Retracted remote content %s cannot be found", self.local_content.fid, ) @patch("socialhome.federate.utils.tasks.logger.warning", autospec=True) def test_does_nothing_if_content_author_is_not_same_as_remote_profile(self, mock_logger): remote_profile = Mock() process_entity_retraction(Mock(entity_type="Post", target_id=self.content.fid), remote_profile) mock_logger.assert_called_with( "Content %s is not owned by remote retraction profile %s", self.content, remote_profile ) def test_deletes_content__content(self): process_entity_retraction( Mock(entity_type="Post", target_id=self.content.fid, actor_id=self.content.author.fid), self.content.author ) with self.assertRaises(Content.DoesNotExist): Content.objects.get(id=self.content.id) def test_deletes_content__object(self): process_entity_retraction( Mock(entity_type="Object", target_id=self.content.fid, actor_id=self.content.author.fid), self.content.author ) with self.assertRaises(Content.DoesNotExist): Content.objects.get(id=self.content.id) def test_deletes_content__reply(self): process_entity_retraction( Mock(entity_type="Comment", target_id=self.reply.fid, actor_id=self.reply.author.fid), self.reply.author ) with self.assertRaises(Content.DoesNotExist): Content.objects.get(id=self.reply.id) def test_deletes_content__share(self): process_entity_retraction( Mock(entity_type="Share", target_id=self.share.fid, actor_id=self.share.author.fid), self.share.author ) with self.assertRaises(Content.DoesNotExist): Content.objects.get(id=self.share.id) class TestProcessEntityFollow(SocialhomeTransactionTestCase): def setUp(self): super().setUp() self.create_local_and_remote_user() def test_follower_added_on_following_true(self): process_entity_follow(base.Follow(target_id=self.profile.fid, following=True), self.remote_profile) self.assertEqual(self.remote_profile.following.count(), 1) self.assertEqual(self.remote_profile.following.first().fid, self.profile.fid) def test_follower_removed_on_following_false(self): self.remote_profile.following.add(self.profile) process_entity_follow(base.Follow(target_id=self.profile.fid, following=False), self.remote_profile) self.assertEqual(self.remote_profile.following.count(), 0) @patch("socialhome.users.signals.django_rq.enqueue", autospec=True) def test_follower_added_sends_a_notification(self, mock_enqueue): process_entity_follow(base.Follow(target_id=self.profile.fid, following=True), self.remote_profile) mock_enqueue.assert_called_once_with(send_follow_notification, self.remote_profile.id, self.profile.id) class TestProcessEntityShare(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.create_local_and_remote_user() cls.local_content = LocalContentFactory() cls.local_content2 = LocalContentFactory() cls.remote_content = PublicContentFactory() cls.remote_profile2 = PublicProfileFactory() @patch("socialhome.federate.utils.tasks.django_rq.enqueue", autospec=True) def test_does_not_forward_share_if_not_local_content(self, mock_rq): entity = base.Share( id="https://example.com/share", actor_id=self.remote_profile.fid, target_id=self.remote_content.fid, public=True, ) process_entity_share(entity, self.remote_profile) self.assertFalse(mock_rq.called) @patch("socialhome.federate.utils.tasks.django_rq.enqueue", autospec=True) def test_forwards_share_if_local_content(self, mock_rq): entity = base.Share( id="https://example.com/share", actor_id=self.remote_profile.fid, target_id=self.local_content.fid, public=True, ) process_entity_share(entity, self.remote_profile) mock_rq.assert_called_once_with(forward_entity, entity, self.local_content.id) def test_share_is_created(self): entity = base.Share( id="https://example.com/share", actor_id=self.remote_profile.fid, target_id=self.local_content.fid, public=True, ) process_entity_share(entity, self.remote_profile) share = Content.objects.fed(entity.id, share_of=self.local_content).get() self.assertEqual(share.text, "") self.assertEqual(share.author, self.remote_profile) self.assertEqual(share.visibility, Visibility.PUBLIC) self.assertEqual(share.service_label, "") self.assertEqual(share.fid, entity.id) # Update entity.raw_content = "now we have text" process_entity_share(entity, self.remote_profile) share.refresh_from_db() self.assertEqual(share.text, "now we have text") @patch("socialhome.federate.utils.tasks.retrieve_remote_content", autospec=True, return_value=None) def test_share_is_not_created_if_no_target_found(self, mock_retrieve): entity = base.Share( id="https://example.com/share", actor_id=self.remote_profile.fid, target_id="https://example.com/doesnotexistatall", public=True, ) process_entity_share(entity, self.remote_profile) self.assertFalse(Content.objects.filter(fid=entity.id, share_of=self.local_content).exists()) def test_share_cant_hijack_local_content(self): entity = base.Share( id=self.local_content2.fid, actor_id=self.local_content2.author.fid, target_id=self.local_content.fid, public=True, raw_content="this should never get saved", ) current_text = self.local_content2.text with self.assertRaises(IntegrityError): with transaction.atomic(): process_entity_share(entity, self.remote_profile) self.local_content2.refresh_from_db() self.assertIsNone(self.local_content2.share_of) self.assertEqual(self.local_content2.text, current_text) @patch("socialhome.federate.utils.tasks.retrieve_remote_content", autospec=True) def test_share_target_is_fetched_if_no_target_found(self, mock_retrieve): entity = base.Share( id="https://example.com/share", actor_id=self.remote_profile.fid, target_id="https://example.com/notexistingatallll", public=True, ) mock_retrieve.return_value = entities.PostFactory( id=entity.target_id, actor_id=self.remote_profile2.fid, public=True, ) process_entity_share(entity, self.remote_profile) mock_retrieve.assert_called_once_with( entity.target_id, guid=entity.target_guid, handle=entity.target_handle, entity_type="Post", sender_key_fetcher=sender_key_fetcher, ) self.assertTrue(Content.objects.fed(entity.target_id, content_type=ContentType.CONTENT).exists()) self.assertTrue( Content.objects.fed( entity.id, share_of__fid=entity.target_id, content_type=ContentType.SHARE ).exists() ) class TestGetSenderProfile(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.create_local_and_remote_user() def test_returns_existing_profile(self): self.assertEqual(get_sender_profile(self.remote_profile.fid), self.remote_profile) def test_returns_none_on_existing_local_profile(self): self.assertIsNone(get_sender_profile(self.profile.fid)) @patch("socialhome.federate.utils.tasks.retrieve_remote_profile", autospec=True) def test_fetches_remote_profile_if_not_found(self, mock_retrieve): mock_retrieve.return_value = entities.ProfileFactory( name="foobar", raw_content="barfoo", public_key="xyz", id="https:/example.com/foo/bar", ) sender_profile = get_sender_profile("https:/example.com/foo/bar") assert isinstance(sender_profile, Profile) assert sender_profile.name == "foobar" assert sender_profile.visibility == Visibility.PUBLIC assert sender_profile.rsa_public_key == "xyz" assert not sender_profile.rsa_private_key @patch("socialhome.federate.utils.tasks.retrieve_remote_profile") def test_returns_none_if_no_remote_profile_found(self, mock_retrieve): mock_retrieve.return_value = None assert not get_sender_profile("https:/example.com/foo/bar") @patch("socialhome.federate.utils.tasks.retrieve_remote_profile") def test_cleans_text_fields_in_profile(self, mock_retrieve): mock_retrieve.return_value = entities.ProfileFactory( name="<script>alert('yup');</script>", raw_content="<script>alert('yup');</script>", public_key="<script>alert('yup');</script>", id="https:/example.com/foo/bar", image_urls={ "small": "<script>alert('yup');</script>", "medium": "<script>alert('yup');</script>", "large": "<script>alert('yup');</script>", }, location="<script>alert('yup');</script>", ) sender_profile = get_sender_profile("https:/example.com/foo/bar") assert isinstance(sender_profile, Profile) assert sender_profile.name == "alert('yup');" assert sender_profile.rsa_public_key == "alert('yup');" assert sender_profile.image_url_small == "alert('yup');" assert sender_profile.image_url_medium == "alert('yup');" assert sender_profile.image_url_large == "alert('yup');" assert sender_profile.location == "alert('yup');" class TestMakeFederableContent(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.content = ContentFactory(visibility=Visibility.PUBLIC) cls.reply = ContentFactory(parent=cls.content, visibility=Visibility.PUBLIC) cls.share = ContentFactory(share_of=cls.content, visibility=Visibility.PUBLIC) def test_content_returns_entity(self): entity = make_federable_content(self.content) self.assertTrue(isinstance(entity, base.Post)) self.assertEqual(entity.raw_content, self.content.text) self.assertEqual(entity.id, self.content.fid) self.assertEqual(entity.actor_id, self.content.author.fid) self.assertEqual(entity.public, True) self.assertEqual(entity.provider_display_name, "Socialhome") self.assertEqual(entity.created_at, self.content.effective_modified) self.content.visibility = Visibility.LIMITED entity = make_federable_content(self.content) self.assertEqual(entity.public, False) self.content.visibility = Visibility.SELF entity = make_federable_content(self.content) self.assertEqual(entity.public, False) self.content.visibility = Visibility.SITE entity = make_federable_content(self.content) self.assertEqual(entity.public, False) def test_reply_returns_entity(self): entity = make_federable_content(self.reply) self.assertTrue(isinstance(entity, base.Comment)) self.assertEqual(entity.raw_content, self.reply.text) self.assertEqual(entity.id, self.reply.fid) self.assertEqual(entity.target_id, self.reply.parent.fid) self.assertEqual(entity.actor_id, self.reply.author.fid) self.assertEqual(entity.created_at, self.reply.effective_modified) def test_share_returns_entity(self): entity = make_federable_content(self.share) self.assertTrue(isinstance(entity, base.Share)) self.assertEqual(entity.raw_content, self.share.text) self.assertEqual(entity.id, self.share.fid) self.assertEqual(entity.target_id, self.share.share_of.fid) self.assertEqual(entity.actor_id, self.share.author.fid) self.assertEqual(entity.public, True) self.assertEqual(entity.provider_display_name, "Socialhome") self.assertEqual(entity.created_at, self.share.effective_modified) self.content.visibility = Visibility.LIMITED entity = make_federable_content(self.content) self.assertEqual(entity.public, False) self.content.visibility = Visibility.SELF entity = make_federable_content(self.content) self.assertEqual(entity.public, False) self.content.visibility = Visibility.SITE entity = make_federable_content(self.content) self.assertEqual(entity.public, False) @patch("socialhome.federate.utils.tasks.base.Post", side_effect=Exception) def test_returns_none_on_exception(self, mock_post): mock_post = Mock() mock_post.parent = False entity = make_federable_content(mock_post) self.assertIsNone(entity) class TestMakeFederableRetraction(SocialhomeTestCase): def test_returns_entity(self): content = ContentFactory() entity = make_federable_retraction(content, content.author) self.assertEqual(entity.entity_type, "Post") self.assertEqual(entity.target_id, content.fid) self.assertEqual(entity.actor_id, content.author.fid) @patch("socialhome.federate.utils.tasks.base.Retraction", side_effect=Exception) def test_returns_none_on_exception(self, mock_post): entity = make_federable_retraction(Mock(), Mock()) self.assertIsNone(entity) class TestMakeFederableProfile(SocialhomeTestCase): def test_make_federable_profile(self): user = SelfUserFactory() profile = user.profile entity = make_federable_profile(profile) self.assertTrue(isinstance(entity, base.Profile)) self.assertEqual(entity.id, profile.fid) self.assertEqual(entity.raw_content, "") self.assertEqual(entity.public, True) self.assertEqual(entity.name, profile.name_or_handle) self.assertEqual(entity.public_key, profile.rsa_public_key) self.assertEqual(entity.image_urls, { "small": profile.safer_image_url_small, "medium": profile.safer_image_url_medium, "large": profile.safer_image_url_large, }) class TestSenderKeyFetcher(SocialhomeTestCase): @classmethod def setUpTestData(cls): super().setUpTestData() cls.create_local_and_remote_user() def test_existing_remote_profile_public_key_is_returned(self): self.assertEqual(sender_key_fetcher(self.remote_profile.fid), self.remote_profile.rsa_public_key) def test_local_profile_is_skipped(self): self.assertIsNone(sender_key_fetcher(self.profile.fid), self.profile.rsa_public_key) @patch("socialhome.federate.utils.tasks.retrieve_remote_profile") @patch("socialhome.federate.utils.tasks.Profile.from_remote_profile") def test_remote_profile_public_key_is_returned(self, mock_from_remote, mock_retrieve): remote_profile = Mock(rsa_public_key="foo") mock_retrieve.return_value = mock_from_remote.return_value = remote_profile self.assertEqual(sender_key_fetcher("https://example.com/foo"), "foo") mock_retrieve.assert_called_once_with("https://example.com/foo") mock_from_remote.assert_called_once_with(remote_profile) @patch("socialhome.federate.utils.tasks.retrieve_remote_profile", return_value=None) @patch("socialhome.federate.utils.tasks.logger.warning") def test_nonexisting_remote_profile_is_logged(self, mock_logger, mock_retrieve): self.assertEqual(sender_key_fetcher("https://example.com/foo"), None) mock_logger.assert_called_once_with("get_sender_profile - Remote profile %s not found locally " "or remotely.", "https://example.com/foo")
At 14:00 JST (06:00 GMT) on Wednesday, September 26, HobbyLink Japan will be installing system upgrades and our services will be unavailable for 90-120 minutes.Please complete your transactions before that time to avoid potential interruptions. Product Description The SD Gundam Cross Silhouette series allows you to choose between two different inner frames that will change the proportions of your kits. You can choose between the cuter look of the SD (Super Deformed) frame, or the taller and more action-packed look of the CS (Cross Silhouette) frame! The SD Cross Silhouette Unicorn Gundam 03 Phenex (Destroy Mode) features a generous amount of clear parts throughout its body to reproduce its distinctive color! It comes with its Beam Magnum, Beam Saber, and Armed Armor DE, and by assembling it to the Cross Silhouette Frame (sold separately), you can give it a less super-deformed, more realistic appearance. The SD Frame in gray is included. Get yours today!
Q: What is the simplest & shortest way to access outer this from inside callback in javascript? I know the following code can access outer this. var o = function() { var that = this; this.a = 1; $('html').click(function() { alert(that.a); }); } new o(); But I don't wanna use two variable names(for example, this and that) for the same one object. And I don't wanna repeatedly write var that = this on every class. I think the following code which uses _this instead of that is a little bit simpler. var o = function() { var _this = this; this.a = 1; $('html').click(function() { alert(_this.a); }); } new o(); But are there other simpler and shorter ways? A: here is some similar code but I believe it is 'safer' than your example, if you create more than 1 instance of 'o' each instance could update the 'a' property var bar = function() { var that = {}; that.a = 1; that.showA = function () { $('html').click(function() { alert(that.a); }); }; return that; } var instanceOfBar = bar(); instanceOfBar.showA(); I might be off base here, have not had my hands in javascript for a few months, so rusty at the moment
NIH researchers have recently announced the isolation of a human B-lymphotropic virus (HBLV) from six individuals with various lymphoproliferative and immune disorders. HBLV appears to belong to the group of human herpes viruses and may be associated with B-lymphoproliferative disorders. Serological tests using indirect immunofluorescence methods revealed that only 4 of 220 random healthy blood donors were seropositive for HBLV antibodies. An ELISA-based assay for HBLV antibody detection would facilitate further study of the prevalence of infection with this virus and the relation of infection to human disease. So far, however, HBLV has not been seen to be infectious for any cells other than fresh B-lymphocytes. In this proposal, the investigators present their plan for using HBLV cultured in B-lymphocytes obtained from umbilical cords to demonstrate the feasibility of developing an ELISA-based test kit for HBLV antibody detection. They also discuss their plans for establishing a cell culture system other than fresh B-lymphocytes for virus proliferation, so that tests can be produced on a commercial scale.
''We can't have a system - and G20 leaders have made that clear here - we can't have a system where some of those institutions that are pushing back on this are still reliant ultimately on the state and are getting a massive subsidy from the taxpayer.'' Australia's banking regulator, John Laker, last week also hit back at bank lobbying for softer capital rules, arguing against ''turning back the clock on regulatory reform''. A former executive at Goldman Sachs in London, Tokyo, New York and Toronto, Mr Carney moved to the top job at the Bank of England last July direct from his post at the top of the Bank of Canada. He is the first non-Briton to lead the bank that governs the City of London, a transition Britain's Chancellor of the Exchequer joked would be made easier by the fact that as a Canadian he was already subject to the Queen. ''Let's put in some context,'' he said, returning to mutterings about his ideas being too tough. ''If you look at a major mining company in Australia or around the world they will run with let's say 50 per cent equity to total capital. It depends slightly on the industry, slightly on where they are in the cycle, but let's say the average leverage ratio is two to one. The leverage ratio for banks, this 'big blunt horrible blunt instrument', is 33 to one.'' But requiring more capital is just the start, because it could never be enough. The governor wants the world's biggest banks to be backed not just by shareholders funds but by ''bail-in-able bonds''. ''Then the bondholders would know - not depositors, but the bondholders - that, if one of these banks made mistakes and needed to be recapitalised, the bondholders would become equity holders,'' Mr Carney said. ''It has two advantages. One is it is more efficient and builds buffers in the banks. Secondly, it means the bondholders actually pay attention to what the banks are doing. Into the crisis and quite frankly throughout the crisis, the lesson has been that the bondholders have a free ride, because basically they own government debt.'' Mr Carney's aim is to protect depositors and governments to the greatest extent possible. The exact size of the bail-in-able bond requirement would be decided by the Financial Stability Board, most likely at the next G20 meeting in Brisbane. It would not apply to Australian banks, only to the 29 ''globally systemic'' banks whose failure would have worldwide consequences. But he is keen to commend the idea to his Australian counterpart, Glenn Stevens, himself once touted for the job at the Bank of England that Mr Carney got. As governor, the 48-year-old Canadian is also in charge of the more public side of the Bank of England, the one that manages the economy and sets interest rates. And he has become a victim of his own success. In a bid to end five years of stagnation, he gave an undertaking. He would keep interest rates low for as long as it took to cut Britain's unemployment rate from 7.8 per cent to 7 per cent. ''I met over 700 businesses and the message went through loud and clear: it made them more keen to hire, and more keen to invest. We are now the fastest-growing major economy, we have the fastest employment growth on record, inflation back at target, and inflation expectations well anchored. ''It's hard to find a criteria by which you would not judge it successful.'' But unemployment is now down to 7.1 per cent and businesses are getting nervous about the implicitly promised rate rise. ''We've made it through the easy phase of guidance, which is to say what we would not do,'' Mr Carney emphasises. ''Now it becomes a question of what will we do and how and under what criteria as the economy continues to recover. ''By necessity that's a more complex set of judgments. We are trying to provide assurance that: (a) we will not take risks with the recovery; and (b) we are going to set the path of monetary policy in a way that ensures that we see sustainable growth in jobs and incomes and in spending.'' Loading Mr Carney agrees that it won't be easy. But he makes even that sound easy. He ran 10 kilometres from Bondi Beach to Clovelly and back on Saturday morning. He made that, too, sound easy, and he said Sydney was beautiful. With Clancy Yeates
Towards evidence based emergency medicine: best BETs fromthe Manchester Royal Infirmary. BET 1: BCG scar changes in Kawasaki's disease. A short cut review was carried out to establish whether BGC scar changes can aid in the diagnosis of Kawasaki's disease. 24 unique relevant papers were found using the reported searches, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. It is concluded that BCG scar changes may help in suggesting that diagnosis of Kawasaki's disease should be considered.
/* Base styles and content styles */ @import 'variables.css'; html { font-family: "Open Sans", sans-serif; color: var(--fg); background-color: var(--bg); text-size-adjust: none; } body { margin: 0; font-size: 1rem; overflow-x: hidden; } code { font-family: "Source Code Pro", Consolas, "Ubuntu Mono", Menlo, "DejaVu Sans Mono", monospace, monospace; font-size: 0.875em; /* please adjust the ace font size accordingly in editor.js */ } .left { float: left; } .right { float: right; } .hidden { display: none; } .play-button.hidden { display: none; } h2, h3 { margin-top: 2.5em; } h4, h5 { margin-top: 2em; } .header + .header h3, .header + .header h4, .header + .header h5 { margin-top: 1em; } h1 a.header:target::before, h2 a.header:target::before, h3 a.header:target::before, h4 a.header:target::before { display: inline-block; content: "»"; margin-left: -30px; width: 30px; } .page { outline: 0; padding: 0 var(--page-padding); } .page-wrapper { box-sizing: border-box; } .js:not(.sidebar-resizing) .page-wrapper { transition: margin-left 0.3s ease, transform 0.3s ease; /* Animation: slide away */ } .content { overflow-y: auto; padding: 0 15px; padding-bottom: 50px; } .content main { margin-left: auto; margin-right: auto; max-width: var(--content-max-width); } .content a { text-decoration: none; } .content a:hover { text-decoration: underline; } .content img { max-width: 100%; } .content .header:link, .content .header:visited { color: var(--fg); } .content .header:link, .content .header:visited:hover { text-decoration: none; } table { margin: 0 auto; border-collapse: collapse; } table td { padding: 3px 20px; border: 1px var(--table-border-color) solid; } table thead { background: var(--table-header-bg); } table thead td { font-weight: 700; border: none; } table thead tr { border: 1px var(--table-header-bg) solid; } /* Alternate background colors for rows */ table tbody tr:nth-child(2n) { background: var(--table-alternate-bg); } blockquote { margin: 20px 0; padding: 0 20px; color: var(--fg); background-color: var(--quote-bg); border-top: .1em solid var(--quote-border); border-bottom: .1em solid var(--quote-border); } :not(.footnote-definition) + .footnote-definition, .footnote-definition + :not(.footnote-definition) { margin-top: 2em; } .footnote-definition { font-size: 0.9em; margin: 0.5em 0; } .footnote-definition p { display: inline; } .tooltiptext { position: absolute; visibility: hidden; color: #fff; background-color: #333; transform: translateX(-50%); /* Center by moving tooltip 50% of its width left */ left: -8px; /* Half of the width of the icon */ top: -35px; font-size: 0.8em; text-align: center; border-radius: 6px; padding: 5px 8px; margin: 5px; z-index: 1000; } .tooltipped .tooltiptext { visibility: visible; }
ALIAGA (Turkey) (AFP) - A Turkish court ruled Monday to keep an American Christian pastor in custody, deeming him to be a flight risk, after his trial opened in a case that has raised tensions with Washington. Andrew Brunson, who ran a Protestant church in the western city of Izmir, has been detained by Turkish authorities since October 2016. If convicted, he risks up to 35 years in jail. Brunson -- wearing a black suit, speaking fluent Turkish and sometimes bursting into tears -- emphatically rejected all the charges against him at the first court hearing in the town of Aliaga north of Izmir. He is accused of engaging in activities on behalf of the group led by exiled Muslim preacher Fethullah Gulen -- who Ankara says is behind a failed 2016 coup -- and the Kurdistan Workers' Party (PKK). Both the Gulen movement and the PKK are banned by Turkey as terror groups. Brunson is also accused of espionage for political or military purposes. The judge ordered Brunson to stay in jail, setting the next hearing for May 7. The ruling was based on evidence given by witnesses in the case and the risk that Brunson might flee. The United States expressed concern. "We have seen no credible evidence that Mr Brunson is guilty of a crime and are convinced that he is innocent," State Department spokeswoman Heather Nauert said. "We hope that the judicial system in Turkey will resolve his case in a timely, fair and transparent manner." In an indication of the importance of the case for Washington, the hearing was attended by Sam Brownback, the US ambassador at large for religious freedom, and Senator Thom Tillis from Brunson's home state of North Carolina. "We are very disappointed. If anything, I think the information that has been presented today creates a more compelling reason why he is innocent," Tillis told reporters after the ruling. Brunson reacted with emotion, telling his wife Norine in English: "I am going crazy. I love you." He had earlier told the judge tearfully: "I want to return my home. For 16 months, I have been separated from my wife." Story continues - 'Reject all accusations' - "I want the whole truth to be revealed. I reject all the accusations in the indictment. I haven't been involved in any illegal activity," Brunson told the court. "I haven't done anything against Turkey. On the contrary, I love Turkey. I have been praying for Turkey for 25 years." He moved to the country in 1993 and opened his Izmir church in 2010. The Brunson case has further hiked tensions between NATO allies Turkey and the United States, with US President Donald Trump raising the issue in talks with Turkish counterpart Recep Tayyip Erdogan. Relations are already strained over American backing for a Kurdish militia in Syria despised by Ankara and the jailing of two employees at American missions in Turkey. "That relationship is going to have difficulty in moving forward as long as Andrew Brunson is incarcerated," Brownback told reporters at the courthouse. In September, Erdogan suggested that Turkey could free Brunson if Washington handed over Gulen, who lives in self-imposed exile in Pennsylvania. Washington brushed off the offer but has been working intensely to secure the release of Brunson, one of several American nationals caught up in the crackdown after the failed coup against Erdogan in July 2016. In February, NASA scientist Serkan Golge, a dual national, was jailed for 7.5 years for being a member of Gulen's movement in a conviction denounced by Washington. Senator Tillis said there was "no deal," adding: "This is about what we believe is an innocent man who has been in prison for a year and a half." In his statement to the court, Brunson rejected the accusations of links to Gulen's group, saying: "That would be an insult to my religion. I am a Christian. I would not join an Islamic movement." Gulen denies any role in the failed coup and says his Hizmet (Service) movement promotes a peaceful form of Islam. Numbering just several thousand, the Protestant community in overwhelmingly Sunni Muslim Turkey largely comprises converts from Islam, expatriates and refugees. The Turkish Association of Protestant Churches said in a report that 2017 was marked by continued hate crimes and physical attacks. Brownback described the trial as a "religious freedom case." "Turkey, in its history, has been very open, so that's one of the things that's really troubling about this," he said.
We use cookies to enhance your experience on our website. By continuing to use our website, you are agreeing to our use of cookies. You can change your cookie settings at any time.ContinueFind out more In numbers after 30 the conjunction y is used between the tens and the units, but not between the hundreds and the tens: 46 = cuarenta y seis 432 = cuatrocientos treinta y dos millón requires the use of de: a million people = un millón de personas three million votes = tres millones de votos Numbers over one million 1 000 000 000 = mil millones or un millardo (one billion) 1 000 000 000 000 = un billón, un millón de millones (one trillion) 1015 = mil billones (one quadrillion) 1018 = un trillón (one quintillion) The examples above show Spanish usage as recommended by the RAE. However, billón and trillón are increasingly being used as the equivalents of the English billion and trillion respectively. This usage is not sanctioned by the RAE. It should be noted that the Real Academia Española (RAE) recommends the International Standardization Office's ruling on the treatment of thousands. This states that spaces should be used to separate groups of three digits. This has been followed in the list above. However, in practice it will be found that spaces, points, and commas are used as separators. In most Spanish-speaking countries a point is used for writing figures over one thousand: 1,000 (one thousand)= 1.000 (mil) 1,000,000 (one million)= 1.000.000 (un millón) Some Latin American countries, however, use the comma as in English: 1,000 (one thousand)= 1,000 (mil) 1,000,000 (one million)= 1,000,000 (un millón) Gender and agreement Numbers in Spanish are masculine when used as nouns, and require an article:
Q: C# XML XDocument I am coding a media player in C# so I saved playlists in an XML as below : So I want to get attributes of playlist "name" and attribute of media "path". I am able to get both using this code : var xdoc = XDocument.Load(@"mypath"); var names = from i in xdoc.Descendants("playlist") select new { Path = (string)i.Attribute("name") }; var paths = from i in xdoc.Descendants("media") select new { Path = (string)i.Attribute("path") }; foreach (var name in names) { System.Diagnostics.Debug.WriteLine(name.Path); foreach (var path in paths) System.Diagnostics.Debug.WriteLine(path.Path); } So I get this : Films E:\Projets\CS - MyWindowsMediaPlayer\Example Medias\Music1.mp3 E:\Projets\CS - MyWindowsMediaPlayer\Example Medias\MusicInfos1.mp3 E:\Projets\CS - MyWindowsMediaPlayer\Example Medias\Video2.mp4 E:\Projets\CS - MyWindowsMediaPlayer\Example Medias\Video1.mp4 E:\Projets\CS - MyWindowsMediaPlayer\Example Medias\Video3.mp4 But I want to sort by categories, for example getting only links that corresponds with films. A: Lets use a combination with SelectMany and GroupBy. The SelectMany will create a single list, with a tuple containing the playlist name and the media path, then we use GroupBy to group this list by playlist name, and finally we can use the Where to filter only the playlist with a given name, in this case, Films. var xdoc = XDocument.Load(@"mypath"); var paths = xdoc.Descendants("playlist") .SelectMany(x => x.Descendants("media"), (pl, media) => Tuple.Create(pl.Attribute("name").Value, media.Attribute("path").Value)) .GroupBy(x => x.Item1) .ToList(); foreach (var name in paths.Where(x => x.Key == "Films")) { Console.WriteLine(name.Key); foreach (var tuple in name) { Console.WriteLine(tuple.Item2); } }
Welcome to D3's blog. We are a class of fantastic Year 4 students at Papatoetoe East Primary School. We are excited to share our learning through this blog. We hope you will enjoy D3's learning journey this year. Thursday, April 7, 2016 Relating to Others Relating to others is getting to know people and what they think and feel, including people and being honest in a kind way. I relate to others by showing great leadership, respect and treating others how they want to be treated. It is important for me to relate to others because you need to interact with a group of friends or a friend so you can get to know people or new students in school. By Hunter Relating to others being honest in a kind way and learning about what others think and feel. I relate to others by telling the truth and making them happy by being kind and friendly.
Schumacher avoids any further action after alleged blocking Formula 1 Betting Formula 1 Betting Bet with Sky Bet Mark Webber has been handed a reprimand by U.S. GP stewards for failing to enter the weighbridge for a random check during qualifying. According to Rule 26.1 of Formula 1's regulations "cars taking part in Q1 and Q2 will be selected at random to undergo the weighing procedure...When signaled to do so the driver will proceed directly to the FIA garage and stop his engine." However, Webber missed the light at the end of the pit-lane alerting him to the check and proceeded straight to the Red Bull garage - an oversight Sky Sports F1's Anthony Davidson could understand. "The light is on the right hand side as you come in, but Red Bull is the first garage on the left and that is where Mark will have been looking so it is easy to miss," the former Super Augri driver said. The stewards could have handed the Australian a grid penalty, or excluded him from Sunday's race, but in the hours after the end of qualifying the FIA confirmed that only a reprimand would be issued against the driver. "Driver failed to proceed directly to the FIA garage for weighing when signalled to do so. However upon realising the error, the team brought the car back to the FIA garage immediately," the stewards' reasoning read. Watch the U.S. GP exclusively live on Sky Sports F1 Can Fernando Alonso stop Sebastian Vettel winning a third consecutive title this weekend? Watch the U.S. GP exclusively live only on Sky Sports F1 to find out. Sky TV customers, upgrade to Sky Sports today to get £5 off your first bill. Find out more at sky.com The outcome is therefore a relief to Red Bull as they go in search of a third straight Constructors' Championship in Sunday's race. Webber will start from the head of the second row directly behind pole-sitting team-mate Sebastian Vettel. Michael Schumacher was also called to face the stewards after qualifying in Austin after Ferrari complained he had obstructed Fernando Alonso during Q2, but escaped sanction. The German was very slow on the apex of turn 15 as he created a gap ahead of him before attempting a flying lap - forcing Alonso to abandon a timed lap of his own. The Ferrari driver gesticulated from the cockpit at the rear of the Mercedes whilst shouting "unbelievable Michael, unbelievable Michael" on the radio to the pit-wall. However, with both drivers progressing to the final part of qualifying the stewards decided the seven-time World Champion had not made any indiscretion and no further action was taken.
--- abstract: 'We present microlensing events in the 2015 Korea Microlensing Telescope Network (KMTNet) data and our procedure for identifying these events. In particular, candidates were detected with a novel “completed event” microlensing event-finder algorithm. The algorithm works by making linear fits to a $(t_0,t_\eff,u_0)$ grid of point-lens microlensing models. This approach is rendered computationally efficient by restricting $u_0$ to just two values (0 and 1), which we show is quite adequate. The implementation presented here is specifically tailored to the commission-year character of the 2015 data, but the algorithm is quite general and has already been applied to a completely different (non-KMTNet) data set. We outline expected improvements for 2016 and future KMTNet data. The light curves of the 660 “clear microlensing” and 182 “possible microlensing” events that were found in 2015 are presented along with our policy for their public release.' author: - | <span style="font-variant:small-caps;">D.-J. Kim$^{1}$, H.-W. Kim$^{1}$, K.-H. Hwang$^{1}$\ and\ M. D. Albrow$^{2}$, S.-J.Chung$^{1}$, A. Gould$^{1,3,4}$, C. Han$^{5}$, Y. K. Jung$^{6}$, Y.-H. Ryu$^{1}$, I.-G. Shin$^{6}$, J. C. Yee$^{6}$, W. Zhu$^{4}$, S.-M. Cha$^{1}$, S.-L. Kim$^{1}$, C.-U. Lee$^{1}$, D.-J. Lee$^{1}$, Y. Lee$^{1}$, B.-G. Park$^{1}$, R. W. Pogge$^{4}$\ (The KMTNet Collaboration)\ </span> title: 'Korea Microlensing Telescope Network Microlensing Events from 2015: Event-Finding Algorithm, Vetting, and Photometry' --- [Introduction]{} \[sec:intro\] ============================== @gouldloeb originally advocated a two-step approach for finding planets by gravitational microlensing. In the first step, a wide area survey would monitor 10s or 100s of million of stars roughly once per night using a wide-angle camera in order to find microlensing events. Then, in the second step, individual events found in the first step would be monitored at high cadence from several longitudes using narrow angle cameras. That is, the cadence of each survey would be matched to the timescale of the effects being sought: a few dozen points during the roughly month-long microlensing events from the first survey and a few dozen points over the day-long (or shorter) planetary perturbations from the second survey. As @gouldloeb specifically pointed out, this approach required “microlensing alerts”, i.e., the recognition and public notification of microlensing events while they were still in progress, and preferably before they peaked. This approach was in fact adopted by the microlensing community and led to the detection of several dozen planets. Right from the beginning, however, (including the very first microlensing planet OGLE-2003-BLG-235, @ob03235) planets were detected by the surveys themselves, without any “second step” follow-up observations. As the surveys went through several generations of improvements, such survey-only detections became more common, e.g., @ob120406. Nevertheless, given that many of the planets found do require a second step, the same “microlensing alert” mode of event detection, pioneered by the Optical Gravitational Lensing Experiment (OGLE) group [@ews1; @ews2], remained the main practical method by which events were discovered. Although the “microlensing alert” system is the main path to event detection, the alternate approach of finding “completed events” in the data set has been present from the birth of the field. Both the MACHO and EROS collaborations developed algorithms for searching through archival data to find microlensing events [@alcock97; @eros2; @eros2_2], and in particular, the very first microlensing event MACHO-LMC-1 was found this way [@lmc1]. One important advantage of this approach is that it has relatively little reliance on human input and therefore can (mostly) be modeled as an objective algorithm, which then permits objective estimates of microlensing event rates (or planet rates). Such algorithms have been used to measure the microlensing optical depth in the LMC and SMC [@wyr09; @wyr10; @wyr11a; @wyr11b]. @wyr15 specifically applied this approach to OGLE-III observations of the Galactic bulge, which is the main (so far, only) field where microlensing planets are discovered. Directly opposite the @gouldloeb observing regime would be a very high-cadence survey with multiple sites allowing continuous monitoring of the Galactic bulge without the need for any followup observations. The first survey of this type was a collaboration between the OGLE, MOA, and Wise observatories [@shvartzvald12; @shvartzvald14]. As originally conceived, the Korea Microlensing Telescope Network (KMTNet, @kmtnet) would also lie in this regime. KMTNet consists of three 1.6m telescopes, each equipped with $4\,{\rm deg}^2$ cameras, and located on three southern continents, CTIO (KMTC, South America), SAAO (KMTS, Africa), and SSO (KMTA, Australia). According to the original plan, which was basically implemented in 2015, it would observe four fields ($16\,{\rm deg}^2$) continuously with a cadence of $\Gamma=6\,{\rm hr}^{-1}$. Hence, there would be virtually no point in follow-up observations, and therefore no point in microlensing alerts. This in turn implied that KMTNet should focus on finding completed events, both because it is easier than finding events in real time and because (as noted above) of the potential of such an event-finding algorithm for measuring rates. In fact, the above paragraph notwithstanding, there would be many potential applications for KMTNet alerts. Most of these stem from the fact that KMTNet has abandoned its original strategy as implemented in 2015, in favor of the layered approach pioneered by the OGLE group. Currently, (3,7,11,3) fields are observed at cadences $\Gamma=(4,1,0.4,0.2)\,{\rm hr}^{-1}$. In all but the highest cadence fields, high-magnification events could be profitably followed-up at substantially higher cadence. Moreover, if anomalies could be alerted in real time in these fields, then detected planets could be characterized much better. Actually, alerts for the highest cadences fields would be exceptionally important for the next few years due to the emergence of [*Spitzer*]{} microlensing, which was not at all anticipated at the time KMTNet was conceived in 2004. Because [ *Spitzer*]{} is in solar orbit, synoptic [*Spitzer*]{} observations can yield “microlens parallaxes”, which are critical for characterizing the microlens and any planets it may have [@ob140124; @yee15; @prop2013; @prop2014; @prop2015a; @prop2015b; @prop2016]. However, in order for [*Spitzer*]{} to take useful observations, it must be alerted to the microlens target before the event ends, and usually before peak. Hence, in sharp contrast to the situation envisaged a decade ago, both a “completed-event” finder and alert capability are important for KMTNet. Ideally, therefore, both forms of event-finder would have been basically ready when the first KMTNet data began arriving from the telescope in early 2015, or certainly by early 2016 following the first year of commissioning data. Unfortunately, work on event-finders did not begin until mid-2016. By the time the event finder was first tested, it was late 2016, meaning that two full years of data were already taken. This fact alone implied that much higher priority had to be given to constructing an event finder that worked on completed events than to developing alert capability. Combined with the facts that the original core of KMTNet science was built around a pure-survey detection strategy, and that fine-tuning and operating a completed-event finder is much easier and less time-consuming than an alert system, this made the completed-event finder the obvious first choice for development. In this paper, we present the first microlensing events detected directly from the KMTNet survey data. In Sections \[sec:algo\] and \[sec:robust\], we present the basic algorithm for identifying microlensing event candidates and discuss its robustness. In Section \[sec:2015data\], we detail the specific procedure for applying this algorithm to the 2015 KMTNet data starting with the photometric pipeline and proceeding through the application of this algorithm and the vetting of the event candidates. We also assess the efficacy of the event-finding process by comparison to OGLE-IV EWS alerts and by checking the detectability of binaries with our algorithm. A summary of the detected events is given in Section \[sec:esum\]. Information on accessing the final sample of events is given in Section \[sec:policy\] along with our data policy. We discuss some potential improvements to the algorithm in Section \[sec:improve\] and summarize our findings in Section \[sec:discuss\]. The Basic Algorithm {#sec:algo} =================== The main challenge of an event-finder is that it must be both quick and robust. “Quick” here has two senses. First, it must sift though $10^{12}$ photometric observations each year, spread over $3\times 10^8$ light curves, in a reasonable amount of computer time. Second, it must show a restricted subsample to an operator who can vet these candidates in a reasonable amount of time. And it must find all candidates that might plausibly harbor a planetary signal. By far, the fastest method of evaluating light curves is a linear fit, which applies a simple deterministic formula twice: once to determine the parameters and the second time to evaluate $\chi^2$. Unfortunately, microlensing events are described by five parameters, only two of which are linear: $$F(t) = f_s A[u(t;t_0,u_0,t_\e)] + f_b; \qquad u(t) = \sqrt{{(t-t_0)^2\over t_\e^2} + u_0^2}; \qquad A(u) = {u^2 + 2\over u\sqrt{u^2+4}}. \label{eqn:foft}$$ Here $F$ is the observed flux, $A$ is the magnification, $t_0$ is the time of maximum magnification, $u_0$ is the impact parameter (normalized to the Einstein radius $\theta_\e$), $t_\e$ is the Einstein timescale, $f_s$ is the source flux, and $f_b$ is any blended flux that does not participate in the event. Hence, if one wishes to use a linear fit, one must work on a 3-dimensional (3D) grid of $(t_0,u_0,t_\e)$, which is prohibitive. We therefore begin with the insight of @gould96 that in the high-magnification limit, microlensing events can be described by just two non-linear parameters $$F(t) = {f_\max \over \sqrt{1 + (t - t_0)^2/t_\eff^2}} + f_b \label{eqn:highmag}$$ where $t_\eff \rightarrow u_0 t_\e$ and $f_\max \rightarrow f_s/u_0$. This formula is approximately valid only for $u\la 0.5$, and so cannot be applied to the entire light curve, but only to a segment around peak. @gould96 therefore advocated a search for high magnification events based on a 2D grid and Equation (\[eqn:highmag\]), with each trial restricted to a few effective timescales $t_\eff$ around its peak time $t_0$. @gould96 was only concerned with high-magnification events because that was all he thought could be detected in M31, the subject of his paper. Whether or not this is true of M31, it is certainly not true of the Galactic bulge, where we expect to detect many low magnification events as well. Therefore, we augment the @gould96 approach by considering also a representative low magnification event, namely Equation (\[eqn:foft\]) with $u_0=1$. That is, we consider $$F(t) = f_1 A_j[Q(t;t_0,t_\eff)] + f_0; \quad Q(t;t_0,t_\eff)\equiv 1 + \biggl({t-t_0\over t_\eff}\biggr)^2; \quad (j=1,2) \label{eqn:general}$$ where $$A_{j=1}(Q) = Q^{-1/2}; \qquad A_{j=2}(Q) = {Q + 2\over \sqrt{Q(Q+4)}} = [1 - (Q/2 +1)^{-2}]^{-1/2} \label{eqn:ajoftau}$$ Note that we no longer call the two flux parameters $(f_s,f_b)$, but rather $(f_0,f_1)$. This is because no physical meaning can be ascribed to these parameters. In the high-magnification limit, $f_1\rightarrow f_\max$ and at $u_0=1$, $(f_1,f_0)\rightarrow (f_s,f_b)$, but in the general case, these flux parameters are not identifiable with any specific physical quantities. The set of $t_{\eff,k}$ are a geometric series $$t_{\eff,k+1} = (1+\delta_{t_\eff})t_{\eff,k} \label{eqn:teffseries}$$ and for each $t_{\eff,k}$, we choose an arithmetic series for $t_{0,k,l}$ $$t_{0,k,l+1} = t_{0,k,l} +\delta_{t_0}t_{\eff,k}. \label{eqn:t0series}$$ We adopt $$\delta_{t_0} = \delta_{t_{\eff}} = 1/3, \label{eqn:deltavals}$$ which we show below to be quite conservative. We set $t_{\eff,3}=1\,$day (so $t_{\eff,1}\simeq 0.56\,$day), with a maximum $t_\eff\simeq 99\,$days. It is not possible to reliably detect events that are substantially longer than this upper limit in a single season. The lower limit is also conditioned by the characteristics of the first season’s data. We discuss extending these limits in Section \[sec:improve\]. We consider values of $t_0$ from $\delta_{t_0}$ before the first epoch of the 2015 season until $\delta_{t_0}$ after the last epoch. We restrict the fits to data within $t_0\pm Z t_\eff$ where $Z=5$. We require that this interval contain at least $N_\min= 50$ points. For 2015 data, we consider only data taken at CTIO in the initial, automated phase of the search. We discuss expanding the search to include other observatories in Section \[sec:improve\]. There are therefore about $2\Delta T/(\delta_{t_0}t_{\eff,k})$ trial fits for each value of $t_{\eff,k}$ and these trials will contain a total of $4ZN/\delta_{t_0} = 240,000$ data points (with repeats). Here $\Delta T\sim 250\,$days is the duration of the 2015 season and $N\sim 4000$ is the total number of data points taken. Since the computation time is basically proportional to the number of data points, this means that each $t_\eff$ trial takes about the same amount of time. The total number of trials is roughly $2(1+\delta_{t_\eff}^{-1})\Delta T/(\delta_{t_0}t_{\eff,\min})\sim 10,000$. Analytic Characterization of Robustness {#sec:robust} ======================================= Since we are sampling a continuous function of three variables $(t_0,t_\eff,u_0)$ on a discrete grid, the $\Delta\chi^2$ of the fit (relative to a flat light-curve model) will inevitably be smaller than for the optimal values of $(t_0, t_\eff, u_0)$. This is not in itself of any concern because the only purpose of these fits is to find which of the light curves have sufficient deviation to warrant showing them to the operator. If, for example, the discrete-model $\Delta\chi^2$ could be as much as 10% smaller than the true (continuous model) $\Delta\chi^2$, then one simply has to set the $\Delta\chi^2$ threshold 10% lower than the level that one wishes to investigate. Here we show how the discretization of the parameter space impacts the fits. We would expect the largest $\Delta\chi^2$ deviation from the most coarsely sampled parameter $u_0$. As outlined in Section \[sec:algo\], $u_0$ is represented by just two discrete values: “high-mag” ($u_0\ll 1$, in effect, “$u_0=0$”) and $u_0=1$. To test the robustness of this approach, we consider light curves with $u_0=4,2,1,1/2,1/4,1/8$ and fit each of them to each of these two forms, i.e., by adjusting $(t_0,t_\eff)$ to get the best fit. Figure \[fig:hm\] shows that for $u_0=1/4$, the high-magnification formula $A_1(Q)=Q^{-1/2}$ already works extremely well, while at $u_0=1/8$, the input curve is almost indistinguishable from the model. On the other hand, Figure \[fig:lm\] shows that the $u_0=2$ and $u_0=4$ inputs are quite well fit by the $u_0=1$ (i.e., $A_2$) model. Note that $u_0=4$ ($A_\max\sim 1.006$) is already at, or somewhat beyond, the practical limits of microlensing detection. The most difficult case is $u_0=2$. This differs from both model curves by a noticeable amount, but these differences are still quite small. Since these are purely theoretical investigations, the conclusion that one of $A_1$ or $A_2$ will fit the data acceptably regardless of the true $u_0$ is independent of the magnitude of the event. Next, we ask how $\Delta\chi^2$ is affected if the true value of $t_0$ differs from the model $t_0$ by $\epsilon t_\eff$. Note that, by construction, $\epsilon\leq\delta_{t_0}/2$. We can quantify the offset between the grid-based and true-model light curves by $\delta\chi^2/\chi^2$, where $\delta\chi^2$ is the difference between the best $\Delta\chi^2$ and the one that is obtained from a fit forced to $u_0=0$ (or $u_0=1$), while $\chi^2\equiv\sum_i [f_s(A_i-1)/\sigma_i]^2$. Note that (because the algorithm compares the observed lightcurve to its mean – rather than a true baseline) $\Delta\chi^2\sim\chi^2/3$. Assuming uniform cadence and below-sky errors, one finds that for high-magnification light curves $A_1(Q)=Q^{-1/2}$, $${\delta\chi^2\over \chi^2}\simeq 1 - {\int_{-\infty}^\infty dx [(1 + (x-\epsilon/2)^2)(1 + (x+\epsilon/2)^2 )]^{-1/2} \over\int_{-\infty}^\infty dx (1 + x^2)^{-1}} \rightarrow {\epsilon^2\over 8}. \label{eqn:dchi2}$$ Since, as mentioned above, $\epsilon\leq\delta_{t_0}/2=1/6$, this ratio is negligibly small. The $\Delta\chi^2$ deficit due to discretely chosen $t_\eff$ leads to a similar calculation with the result: $\delta\chi^2/\chi^2=\epsilon^2/32$. The calculations of this section show that our discretization choices are, if anything, too conservative. That is, we could afford to use a coarser grid. We discuss in Section \[sec:binary\] why such conservative choices are appropriate at this stage and why they may possibly be relaxed in future years. Implementation for the KMTNet 2015 Data {#sec:2015data} ======================================= In addition to introducing the algorithm itself, this paper has two main goals. The first, addressed in this section, is to identify the strengths and weaknesses of the algorithm by applying it to a real data set. The second is to make available the results of the event search to the general microlensing community, which we will address further in Section \[sec:policy\]. Both of these goals require that the algorithm be specifically applied to our data set through a series of concrete choices. One choice, for example, is whether to search for events in the data from a single observatory or whether to conduct the search by simultaneously fitting data from all three (or perhaps just two) observatories. Another choice is whether to initially vet for variable stars and artifacts by some sort of algorithm or whether to reject these totally in the operator stage “by eye”. The actual choices made for the 2015 data were strongly conditioned by the operational environment, including both the nature of the 2015 data and the operational pressures affecting the reduction and analysis of these data. It is therefore necessary to summarize these operational constraints to understand both the empirical evaluation of the algorithm conducted below and the data products, as well as to develop ideas on how to improve application of the algorithm in the future. The last point is discussed in Section \[sec:improve\]. Operational Constraints {#sec:operations} ----------------------- Much of the 2015 data is of very high scientific quality, and they have already been the basis of many published and submitted scientific papers [@ob151285; @ob151212; @isolated1; @ob150954; @ob150768; @ob150051; @galdist1; @ob151482] However, 2015 was the commissioning year and as such it was heavily impacted by engineering tests as well as physical problems, refinements, and repairs. For example, the electronics of the KMTC camera were changed substantially on HJD$^\prime\equiv {\rm HJD}-2450000=7129$ and 7192, leading to discontinuities in the photometric scale in some (but far from all) light curves at those dates. There were further experiments on the KMTC detector electronics that sometimes resulted in quite noisy data. For most of 2015, KMTS was impacted by condensation on one of the cooling lines, which triggered a short in a wallboard (before the problem was recognized) and so impacted photometry until it was replaced. And while KMTC and KMTS observations began very close to the beginning of the season (HJD$^\prime\sim 7050$), KMTA began only on HJD$^\prime=7180$. There were many other issues as well, including problems with the polar alignment and pointing model. Problems of this order are completely normal for the commissioning of relatively complex systems, but they also imply that algorithmic ideas that are designed for basically homogeneous data must be significantly adjusted if they are to function in this environment. The first step was to write a pipeline to extract photometry from the images. This pipeline construction impacted the event-finder in several ways, both direct and indirect. This will be discussed in the next several subsections. However, from the present standpoint the main impact was to delay the development and testing of the event-finder. It required about 8 months to develop and test the pipeline and another 3 months, using all available computer resources, to extract light curves just for KMTC. Testing of the event-finder could proceed in parallel with light curve extraction, but full implementation could only be carried out after the light curves were extracted. Hence, event finding for 2015 did not begin in earnest until the end of the 2016 season. The combined effect of these considerations was to drive us toward event-finding procedures that could be implemented quickly and would be robust in the face of inhomogeneous data. Work on more sophisticated versions was deferred, although this was subsequently initiated. See Section \[sec:improve\] for a discussion of the progress on a more advanced version. Catalog Construction and Pipeline {#sec:pipeline} --------------------------------- The most straightforward way to extract light curves is to measure photometry at the positions of known stars. This requires a catalog of stars matched to the detector coordinate system. The original approach that had been taken was to carry out point-spread-function (PSF) photometry using the DoPhot package [@dophot], which extracts a catalog directly from the images themselves. Then, those DoPhot light curves would be searched for events, and finally difference image analysis (DIA, @alard98) re-reductions using the @albrow09 pySIS package would be used for events of particular interest. This plan was well-matched to the available computer resources but suffered from what turned out to be a fatal flaw: the DoPhot-based catalogs contained a factor $\sim 5$ times fewer entries than the number of potential source stars that give rise to usable microlensing events. If not corrected, this would reduce the potential power of the experiment by roughly a factor three[^1]. A new pipeline was written based on publicly available DIA code from @wozniak2000. The central problem remained, however, of constructing a deep input catalog. While various packages were tried, it proved impossible to even come close to matching the depth of the existing OGLE-III [@oiiicat] catalog. The reasons for this are not completely clear. No doubt, this is partly explained by the fact that OGLE pixels are much smaller than KMTNet pixels ($0.26^{\prime\prime}$ versus $0.4^{\prime\prime}$), but it is difficult to believe that this is the full explanation. Probably the biggest factor is just greater photometric experience. The OGLE-III catalog provides stellar positions in RA and Dec, so it was astrometrically matched to the template frame, i.e., the image coordinates, by cross-matching with the DoPhot catalog. The pipeline uses the OGLE-III catalog stars and photometric scale whenever possible. However, the OGLE-III catalog does not cover the full extent of the 2015 KMTNet fields. Some KMTNet fields cover fairly broad continuous regions that are not covered by the OGLE-III survey. In addition, the OGLE-III catalog has non-trivial topology, due to gaps of various sizes and shapes between OGLE-III fields. Approximately 10.3% of the area covered by the four prime KMTNet fields is not covered by OGLE-III (see Section \[sec:artifacts\]). In these regions, the input catalog is derived from DoPhot templates and the photometric scale is calibrated by cross-matching with the OGLE-III catalog in nearby regions. In total, our OGLE-III + DoPhot catalog consists of 71,555,640 stars. Automated Light Curve Search {#sec:autosearch} ---------------------------- Once the light curves for all catalog stars are extracted, they must be searched for microlensing events. Note that for 2015 data, only KMTC light curves were used to search for events (as indeed these were the only data reduced). The basic algorithm for searching for the best microlensing model was described in Section \[sec:algo\]. Its basic features were to perform linear fits to the data on a grid of $(t_0, t_\eff, u_0)$ and to fit only those data from the interval ($t_0-5\,t_\eff<t<t_0+5\,t_\eff$). In practice, those linear fits were performed in four phases. First, all the points were included in the fits to evaluate the best-fit parameters, $(f_0,f_1)$. Then, the exact procedure was repeated to determine the naive $\chi^2$ of each data point, using the $(f_0,f_1)$ from the previous step. Then the 10% worst-$\chi^2$ points were eliminated, and the data were refitted to redetermine $(f_0,f_1)$. Finally, these $(f_0,f_1)$ were used to determine the overall $\chi^2_{\rm \mu lens}$. To determine the significance of the microlensing signal, the final sample of points (i.e., with 10% points removed) was then fitted to a flat line, i.e., a constant flux level. Nominally, this would imply a single parameter, i.e., the mean flux during the interval probed ($t_0-5\,t_\eff<t<t_0+5\,t_\eff$). In fact, however, to allow for breaks in the light curve due to firmware adjustments at KMTC, each of the three intervals described in Section \[sec:operations\] was permitted a separate mean flux level. Hence, there could be one, two, or three such parameters depending on how many of these three intervals were included in ($t_0-5\,t_\eff<t<t_0+5\,t_\eff$). This procedure yields $\chi^2_{\rm flat}$. Finally, the renormalized $\Delta\chi^2$ was derived, $$\Delta\chi^2 \equiv \biggl({\chi^2_{\rm \mu lens}\over\chi^2_{\rm flat}} -1\biggr)N_{\rm data}$$ where $N_{\rm data}$ is the number of data points remaining after rejecting the worst 10%. Automated Light Curve Grouping {#sec:autogroup} ------------------------------ Several catalog stars can yield very similar light curves, i.e., with similar $t_0$ and $t_\eff$. If these are produced by stars in close proximity, it may be assumed that there is only one true variable (whether microlensing or otherwise), and the other variations are simply echos of the real one. For example, there can be two catalog stars within $1^{\prime\prime}$. If one undergoes a microlensing event then when DIA is applied to the other (with $1^{\prime\prime}$ displacement of its tapered aperture), it will also generate a microlensing-like light curve. In this case, we would like to examine only the better curve, i.e., the one with higher $\Delta\chi^2$. We find that in the case of bright variables (or, very occasionally, bright microlensing events) these echo light curves can extend over many tens of pixels. We therefore develop a friends-of-friends algorithm to apply to candidates found in the above search. A “friend” is defined as a light curve from another star within 10 pixels ($4^{\prime\prime}$) and with $|t_{0,1} - t_{0,2}|< 0.4(t_{\eff,1} + t_{\eff,2})$. Then friends of friends are grouped and only the highest $\Delta\chi^2$ member of the group is shown to the operator. While most groups are small, it is not uncommon to have groups of several dozens, or even more than 100. Manual Light Curve Review {#sec:manureview} ------------------------- If $\Delta\chi^2>500$ then the candidate “event” is shown to the operator in a four-panel display, together with some auxiliary information (Figures \[fig:BLG01K0734.0458.jpg\]–\[BLG01K0734.0458\_all.jpg\] and Figure \[fig:BLG02N2215.1660.jpg\]). Each panel contains all the data (not just the data surviving the 10% rejection). One reason to show all of the data is that caustic crossings in binaries are likely to be removed by the 10% rejection cut as “outliers” from the point lens fit. The bottom two panels show the whole season of data, while the top two show only the $10\,t_\eff$ that were fitted to the model. The left two panels are restricted to the flux range predicted by the model (plus small border regions at top and bottom), while the right two panels show the full range of data values within the temporal range of the diagram. These four displays allow the operator to rapidly determine whether this is plausibly a microlensing event. For example, the upper left panel gives a very clear impression of whether the event is reasonably well fit by point lens microlensing over the $10\,t_\eff$ range that is being fit (see Figure \[fig:BLG01K0734.0458.jpg\]). If, on the other hand, the event has pronounced binary structure (e.g., a pronounced caustic near the peak of the event), then this structure will mostly not be visible on this plot, and the light curve may appear to deviate from point-lens microlensing in an unfamiliar way. However, this caustic structure will appear clearly on the upper right panel, even if the main part of the microlensing event (easily visible on the upper left) now is so small that it is barely visible (see Figure \[fig:BLG02M1119.3178.jpg\]). This approach also permits rapid rejection of variables. The algorithm itself quite easily fits wide classes of variables to microlensing light curves because it “censors” data from outside the $10\,t_\eff$ fitting interval. However, this is readily apparent from the two full-season light curve panels (see Figure \[fig:BLG01T0401.0003.jpg\]). Above the upper-right panel are displayed four numbers $(\Delta\chi^2, I_{\rm cat}, {\rm RMS(mag)},{\rm RMS(flux)})$. Here $I_{\rm cat}$ is the magnitude of the catalog star, RMS(mag) is the amplitude of scatter of this star derived from the OGLE-III catalog, and RMS(flux) $\equiv {\rm RMS(mag)}\times 10^{0.4(28-I_{\rm cat})}$. The last number then gives the expected variability in flux units. For OGLE-III stars, $I_{\rm cat}$ is derived from the OGLE-III catalog. For non-OGLE-III stars, it is derived by calibrating the DoPhot photometry based on the overlap with OGLE-III areas. In this case, there is no information on variability, so the final two numbers are set to arbitrary negative numbers, meaning “ignore”. The operator then classifies the candidate into one of four categories: “clear microlensing”, “possible microlensing”, “variable”, and “artifact”. Three-Observatory Confirmation {#sec:confirm} ------------------------------ All “clear” or “possible” microlensing events are then further evaluated using KMTS and KMTA data. As mentioned above, for 2015, only the KMTC data were reduced en masse. For candidate events, KMTS and KMTA light curves were extracted from individual $(256\times 256)$ patches cut from each image taken by these two observatories, which were then analyzed using DIA to produce light curves. These light curves are then sent through exactly the same “event-finder”, except with a threshold $\Delta\chi^2>0$ (instead of $\Delta\chi^2>500$) so that some result will be reported regardless of the quality of the fit. The operator then views all three individual displays (each with four panels) and a display with the combined data to make a final decision, again choosing from the same four categories (see Figure \[BLG01K0734.0458\_all.jpg\]). For genuine microlensing events, the most usual situation is that the other two observatories (or, for events before the onset of KMTA, one) have independently observed the same event and the event-finder has “found” this event and appropriately displayed it. In a few cases, the event-finder will find a “better candidate” in one of the data sets that is actually an artifact. Still it is relatively easy to check from the two full-season displays and the combined plot that the real event is present in the data. In these cases, the event can be fully confirmed as “clear” even though its KMTC-only classification is “possible microlensing”. There are some instances in which the other two observatories lack data during the candidate event’s time of significant magnification, in which case the classification must be based on KMTC data alone. We note, however, that even when there are data from several sites, these do not constitute absolutely fool-proof security against false positives. First, eruptions by cataclysmic variables (CVs) can mimic microlensing events. Having data from several sites can help guard against these, particularly because CVs usually rise faster than microlensing events (for the same fall time) and sometimes these rises are not present in KMTC data but are present in KMTS or KMTA. However, in other cases, it can remain difficult to distinguish, either because there are few/no rising data or because the CV rises unusually slowly. One of the biggest problems in identifying microlensing events from a single year of data is that there are no “out of year” baseline data with which to reject variables. For short events, this is not much of a problem because there are “in year” baseline data. However, there is no unambiguous way to distinguish full-season microlensing events from long-period variables. In some cases, particularly for the catalog stars derived from OGLE-III (the overwhelming majority), the variables can be vetted using “RMS(flux)”. However, this is not completely secure, since variables can remain dormant for several years or vary more in a given year than in several previous years. For the cases for which there is no obvious reason to reject the microlensing explanation, these are called “possible microlensing”. Vetting for Artifacts by Image Inspection {#sec:artifacts} ----------------------------------------- A less obvious path to “false positive confirmation” comes from artifacts. Based on the commissioning issues described in Section \[sec:operations\], one can well imagine that there are a large number of artifacts in KMTC data that trigger the event finder. In the overwhelming majority of cases, these are easily recognized as such (or perhaps “misclassified” as variables) and so do not make it to the stage of vetting by KMTS and KMTA comparisons. In many of the remaining cases, these artifacts are easily removed because they are not duplicated in data from one or both of the other observatories. However, a large fraction of candidates initially classified as “possible microlensing” and a handful of those initially classified as “clear microlensing”, turn out to be examples of one of two types artifacts: “bleeding columns” and “displaced variables”. We developed simple procedures for identifying these. For each of the events that was classified as either “clear” or “possible” microlensing, we display side-by-side the finding chart and a difference image from near the peak of the “event”. Below these are the set of light-curve displays described in Section \[sec:confirm\], and below these panels are a set of four difference images: the two nearest the peak, and two other good seeing images relatively near peak. We place cross-hairs at the catalog position of the source in all images. From the top-level difference image, one can easily see whether or not the cross hairs are at the position of the variation. If variation is not at the catalog (cross hair) position, this is not in itself a problem: many microlensing events occur on stars that are too faint to be cataloged, and are recognized by the flux variations that they induce at the position of a neighboring catalog star due to the finite width of the PSF. However, if the finding chart contains a bright star at the position corresponding to the flux variation on the difference image, then the “event” is almost certainly an artifact, i.e., an echo of variations in this bright star. Of course, a given bright star might actually undergo a microlensing event, and this event would likewise be “echoed” at the positions of neighboring cataloged stars. But in this case we would expect that the bright star would itself be cataloged and would yield a microlensing light curve with higher $\Delta\chi^2$. For variable sources, however, the “cleaner” light curve from the variable is much more easily excluded as a “variable” than is the “echo”, so only the echo winds up in the list of candidates. Moreover, it is almost always the case that these echos last for most or all of the season, simply because repeating variations would have been recognized as variables, even in their echos. In the course of this vetting, we noted a handful (2–3) cases for which the source position was offset and coincident with a bright star, but the event was nevertheless short and well contained within the season. We accepted these as microlensing events and assumed that either the catalog or the event finder had failed to function properly in these cases. This means that there were probably also a few long microlensing events with similar characteristics that we misclassified as variables, but this problem cannot be addressed with only a single year of data. Another quite common artifact that easily shows up in the difference images are fake events due to bleeding columns. In fact, the level of bleeding is far too low to be noticed directly in the images, and can only be perceived in difference images, which permit a much stronger “stretch”. Time variable bleeds can be generated by variable stars, in which case they are typically either long-timescale or repeating. However, they can also be generated by shorter-period irregular variables that only rise above the bleed threshold for a relatively short period, once in a season. In addition, they can be caused by changes in seeing and background. The former is not likely to be correlated among observatories, but the latter is, i.e., if it is due to lunar phase. In any case, as mentioned above, such bleeding columns are easily recognized by examining the four images that we routinely display. The event finder yielded 955,659 candidates, which were automatically grouped into 385,565 groups to be shown to the operator. Of these, 148,010 were classified as “variables”, and 236,698 as “artifacts”. Our final catalog of events consists of 673 “clear microlensing” and 184 “possible microlensing” events (with some duplicates). See Figure \[fig:geom\]. Section \[sec:esum\] summarizes the properties of our final sample. It is interesting to compare this map of detections with a map of the underlying catalog (Figure \[fig:fldmap\]). Note in particular that BLG02N has a density only about 1.35 times higher than BLG04N but has an order of magnitude more “clear microlensing” events. This is broadly consistent with our expectations based on @poleski16, which shows that the microlensing event rate should be highest near the center of BLG02N. Comparison to OGLE-IV EWS Detections {#sec:comp} ------------------------------------ The best external check on the event-detection procedures described above is to compare with OGLE-IV. Since OGLE operates from a very nearby site in Chile, it has very similar field visibility and weather to KMTC, i.e., the KMTNet site used for the initial selections. In fact, the visibility is not identical because OGLE observes to greater hour angle than KMTC and also longer into austral spring. On the other hand, KMTNet observes during all lunar phases, while OGLE typically halts observations when the Moon is in the Galactic Bulge. Similarly, KMTNet observes in all atmospheric conditions, provided that these do not endanger the telescope and provided that the sky is not opaque. Further, for about a quarter of the KMTNet prime area, OGLE-IV observes with cadence $\Gamma=3\,{\rm hr}^{-1}$, which is not qualitatively different from the KMTNet cadence. And, for most of the remaining area, OGLE-IV observes with cadence $\Gamma=1\,{\rm hr}^{-1}$, which still should be sufficient to detect a substantial majority of microlensing events that are accessible to KMTNet. For this comparison, we use the set of OGLE-IV events announced by their Early Warning System [EWS @ews2]. These events are identified in real-time based on only a partial light curve rather than a full microlensing fit to a completed event. As such, this comparison sample may not be complete and it may also contain some false positives. However, it represents the most complete, publicly available, independent list of microlensing discoveries for the 2015 season. ### [OGLE-IV Events Not found by KMTNet ]{} 428 OGLE-IV events (after eliminating duplicates) in the KMTNet field were not recovered by our event finding procedure, neither as “clear” nor “possible” microlensing events. These represent potential false negatives and may indicate problems with our procedure. We first assess the fraction of the OGLE-IV alerts discovered as a function of brightness. We define $I_{\rm peak} = 18 - 2.5*\log [f_{\rm S}(A_{\rm max} - 1) ]$, where $f_{\rm S}$ and $A_{\rm max}$ are determined from the OGLE EWS table. For the following ranges of $I_{\rm peak}$, we find the recovery percentages are $I_{\rm peak} (< 14\, $mag$\, = 63\%$, $[14$–$15] = 91\%$, $[15$–$16] = 76\%$, $[16$–$17] = 72\%$, $[17$–$18] = 72\%$, $[18$–$19] = 61\%$, $[19$–$20] = 43\%$, and $>20 = 16\%$), i.e., the events missed by our procedure tend to be biased toward the faint end. To explore this in more detail, we examined one out of each 20 OGLE-IV events in the KMTNet fields that were not found by the procedures outlined above. This test was conducted after selection based on KMTC data, and before vetting based on KMTS and KMTA data, in order to provide the closest basis of comparison. One result of this test was that we found that three of the 22 tested events lay in image patches that had not been processed by the event-finder due to a failure in the computer architecture (and so having nothing to do with the event finder itself). These computer problems were fixed and these patches were re-run. We report only on the remaining 19 tested events. Of these 19 “missing events”, three were clear failures, three were judged to be “marginally acceptable” false negatives, and remaining 13 were “acceptable” false negatives. Two of the clear failures (OGLE-2015-BLG-0693 and OGLE-2015-BLG-1589) were due to operator error. The first was mislabeled as “CV”, and the second should have been called “possible microlensing” (and then further investigated using KMTS and KMTA data). The third failure (OGLE-2015-BLG-1015) lay in a thin band between two patches. Each $1\,{\rm deg}^2$ chip of the 2015 data was analyzed in a ($40\times 40$) grid of “overlapping” ($256\times 256$) patches, but in a few cases (given the “dead zone” boundaries imposed by the DIA software) the patches did not actually overlap. This issue is resolved for 2016+ data by going to much larger patches with much larger boundaries. Two of the three “marginally acceptable” cases (OGLE-2015-BLG-0870 and OGLE-2015-BLG-1138) were missed because the operator judged the data to be too noisy for reliable microlensing detection. In hindsight (and knowing that there is a real event there), these might have been classified as “possible” and further investigated using KMTS and KMTA data. However, these events were quite near the threshold at which “letting in” additional events would have led to vast increase in “investigations” of pure noise and variables. The third marginal case (OGLE-2015-BLG-1589) was not shown to the operator because $\Delta\chi^2=436$. If it had been shown, it probably would have been classified as “possible microlensing”. Rectification of this “problem” would require setting the threshold lower and so greatly increasing the already large number of events to be vetted. To better understand the issues involved in possibly setting a lower threshold, we show in Figure \[fig:cum\] cumulative distributions by $\Delta\chi^2$ of i) all event groups, ii) “clear microlensing” events, and iii) “possible microlensing” events. Of particular note: while 64% of all (385,565) event groups had $500<\Delta\chi^2<1000$, only 6.2% of “clear microlensing” events lay in this range. The remaining 13 event non-detections were all judged to be “acceptable” false negatives. For two of these, (OGLE-2015-BLG-0059 and OGLE-2015-BLG-0960) the nearest stars in the catalog were $1.2^{\prime\prime}$ and $2.4^{\prime\prime}$, which led to very weak and no signal respectively. Neither passed the $\Delta\chi^2=500$ threshold, but if they had, neither would have been chosen by the operator. Both events lie in regions not covered by the OGLE-III catalog, and for which we are dependent on the much shallower DoPhot catalogs. One event peaked midway between 2014 and 2015 seasons, and so was not recognizable based on 2015 data. Two were long events that were (correctly) judged by the operator to be consistent with being variables based on 2015 data. Two events were affected by artifacts in the 2015 data. The remaining eight had low S/N and so were not shown to the operator, but if they had been they would have been judged as too noisy for reasonable identification as microlensing events. (One of these, OGLE-2015-BLG-1835, may be a CV.) In brief, this test shows that of order $3\times 20=60$ genuine microlensing events that could have been detected in this region were not. These failures are mostly due to “operator fatigue” from reviewing hundreds of thousands of light curves. In future years, this may be ameliorated by eliminating most variables in advance and by reduction in the number of artifacts now that commissioning is complete. ### Events in KMTNet Not Found by OGLE-IV {#sec:notOGLE} For “clear microlensing" events found by KMTNet but not found by the OGLE-IV EWS, we would like to try to understand why they were not detected by OGLE-IV. For these events there are three possibilities: OGLE could not detect (or would have extreme difficulty detecting) the event due to insufficient data, OGLE excluded the event as a false positive, or the OGLE EWS missed the event. Since OGLE has a different camera, a different site, and different observing protocols, the data on a particular event might be insufficient due to the location of chip gaps or observability gaps. The OGLE survey has also been in operation for many years and so can identify (and exclude) false positives due to long-timescale, sporadic variables. We examine a representative sample of the KMTNet events not found by the OGLE EWS in greater detail to assess whether or not we expect OGLE to have detected them. If it appears that OGLE ought to have detected an event, then that event is a candidate for being a false positive, i.e. it is possible OGLE did not alert the event because they had reason to believe it was a variable star rather than microlensing. At the same time, the absence of an alert is not conclusive evidence of a false positive; the event could simply have been missed. On the other hand, if the synoptic observing information suggests that OGLE would have difficulty detecting an event, than the absence of an alert does not provide any information about whether or not an event is a false positive or real microlensing. An unpublished study by Gould & Udalski has already determined that events detected by MOA but not by OGLE are overwhelmingly undetectable by OGLE because they are in chip gaps, outside the OGLE fields, during gaps in the data, etc. A few are variable stars that have been masked from the OGLE catalog (in this case, two of 40, P. Mróz, 2017, private communication). Thus, if an event is detected by MOA but not by OGLE, we do not investigate it further because there is likely a plausible explanation as to why it was not alerted. We then reviewed a random 10% (i.e., 18) of the 177 remaining events to assess whether or not there was sufficient data for OGLE to alert them. We find that four of these randomly chosen 18 could not plausibly have been detected by OGLE since they were either in chip gaps or would have had very few magnified points (BLG01N.3928.2251, BLG02M.0326.3862, BLG02T.0123.2655, BLG03M.0939.0577). Four additional events were very likely missed either because they lay very near a chip edge (though formally within the chip) or because they would have had only 3 or 4 significantly magnified points. (BLG01T.2412.0089, BLG02N.2218.3192, BLG03K.3511.3254, BLG04N.3638 2631). Thus, it is not possible to draw conclusions based the absence of an OGLE alert for these $4+4=8$ events. There were four other events that appeared to us to be probably detectable, but because they contained only 6–8 magnified points, could have plausibly been missed, perhaps due to mildly adverse conditions (BLG02T.2218.3029, BLG03N.2123.2010, BLG04K.2626.3153, BLG04T.2822.2817). Here we should keep in mind that by selecting non-OGLE events, we are biased toward such adverse circumstances. Finally, there were six events that we thought should clearly have been detected by OGLE (BLG01K.0126.0793, BLG01M.1125.1711, BLG01N.0633.3015, BLG02N.0726.2197, BLG02N.3209.0444, BLG03T.1911.1388). Five of these six lie in OGLE fields BLG505, BLG506, or BLG512, which had OGLE cadences of $\Gamma=3\,{\rm hr}^{-1}$ in 2015. If there are false positives in our sample, these should be good candidates. In reviewing these events, we find that all look plausibly like microlensing. In all cases the $t_\eff<10\,$days and the remainder of the light curve is consistent with being flat. In all cases, all three data sets basically agree on the form of the light curve (except for the first, for which there are no KMTA data). In one case (BLG01M.1125.1711) the variation is offset from the catalog star and at the position of another resolved star, which we would generally regard as a warning sign that the resolved star is a variable and the “event” is an echo. However, as discussed in Section \[sec:artifacts\], we override this concern when the event is of short duration and the remainder of the season is flat. This is particularly true in the present case, for which the star that is varying is relatively faint. Hence, while any of these candidates could in principle be false positives, there is no evidence that this is the case. Subsequent to the posting of this paper on arXiv, P. Mróz (2017, private communication) kindly provided a list of all events in OGLE high cadence fields that were recognized as variables by OGLE. This list contained one of the four we thought “likely missed" by OGLE, two of the four events that we considered “probably" should have been detected, but none of the six events that we considered should “definitely" have been detected. Binary Detection {#sec:binary} ---------------- We expect that our approach will be efficient at detecting planetary events simply because these typically look similar to point-lens events but with relatively brief anomalies. One might be concerned that these anomalies could reduce $\Delta\chi^2$ and so prevent their being shown to the operator. However, recall that the 10% “worst outliers” to the point-lens-like fit are eliminated from the comparison with a flat light curve. Hence, we actually do not expect this to be an issue. The situation is, however, quite different for binary events, many of which look nothing like point-lens events. When we devised the event-finder, we had no definite expectation of how well it would perform on binaries. We conducted a test to evaluate this performance after the fact. We manually examined all OGLE events lying in the KMTNet fields to find those that either were, or plausibly could be binaries. We found 57 binary events announced by the OGLE EWS that lie in the KMTNet fields. Thirty-four are included in our list of microlensing events (all of them are classified as “clear". Of the 23 that were missed, only one of these both plausibly looks like microlensing in KMTC data and failed to be shown to the operator (i.e., had $\Delta\chi^2<500$). This was OGLE-2015-BLG-0390, which shows a sharply rising caustic exit in KMTC data but has $\Delta\chi^2=265$. The reason for this low $\Delta\chi^2$ is that the “effective time scale” of this rise is much shorter than the 0.56 day minimum of the current search. This limit was in turn set by the large number of artifact-driven “events” that would be found in the 2015 data, which would have greatly multiplied the work of the operator. Of the other 22 that were missed, three were due to operator error: one (OGLE-2015-BLG-0095) should have been classified as “clear” microlensing and two (OGLE-2015-BLG-1346 and OGLE-2015-BLG-2017) as “possible microlensing”. For the remaining 19, the signal in the data (whether shown to the operator or not) was not sufficient to count them as plausible microlensing events. From the perspective of understanding the algorithm, the key point is that only one known binary was missed because the algorithm itself failed to detect it. We consider it somewhat surprising that the algorithm is working as well as it is on binaries, given that it is specifically tailored to find point-lens events. One reason for this is that the algorithm will detect pretty much any sort of bump provided that it is sufficiently pronounced and not too sharp, as illustrated by Figure \[fig:BLG02N2215.1660.jpg\]. We suspect that the good binary sensitivity then derives from the sampling density of the 3-parameter point-lens grid described in Section \[sec:robust\]. While this sampling density is overly conservative for detecting point lens events, it likely permits matching with sharp caustic features, allowing the detection of microlensing binaries. This conjecture can be tested in the context of the improved event finder (Section \[sec:improve\]) by repeating the fitting procedure on known binaries with a progressively less dense grid. However, because the event finding procedure is significantly less computationally intensive than the photometry pipeline, there is no strong driver to scale back the sampling density. If the computational situation changes, this test should be performed before scaling back the sampling density. Summary of Detected Events {#sec:esum} -------------------------- In total, this procedure for identifying microlensing events from the 2015 KMTNet commissioning data resulted in 857 microlensing event candidates; 15 of which are duplicates leaving 842 event candidates. Of these, we classify 660 as “clear" microlensing events and 182 as “possible" microlensing. Based on @mroz15 and P. Mróz (2017, private communication), we find that 40 of the “clear" microlensing events and 54 of the “possible" microlensing events were classified as variables by the OGLE collaboration. Of the remaining events, 483 “clear" events and 38 “possible" events were detected by either the OGLE EWS or the MOA alert system (or both). Thus, KMTNet has detected 137 “clear" microlensing events and 90 “possible" events not found by any other survey. Based on our investigation described in Section \[sec:notOGLE\] and P. Mróz (2017, private communication), there is no evidence indicating these are false positives. The distributions of $t_{\rm eff}$ and $I_{\rm base}$ for these events are shown in Figure \[fig:hist\]. The reader should bear in mind that $t_{\rm eff}$ is discretely defined as described in Section \[sec:algo\] and therefore is not a perfect representation of the event timescale. Data Policy and Data Releases {#sec:policy} ============================= KMTNet data policy is framed by several goals, which are basically compatible but are subject to some mutual tension. First, we seek to give adequate time for the KMTNet team to publish results based on the huge amount of work required to obtain and process these data. Second, we want the KMTNet data to be exploited to the maximum extent possible, whether by KMTNet team members or others. Third, we want to promote the microlensing field by making data available to as many workers as possible. Fourth, we want to avoid overworking our team on tasks that are auxiliary to the team’s own effort to publish our results. Finally, we want to avoiding infringing on the data rights of others, whether explicitly or implicitly. KMTNet Website {#sec:website} -------------- KMTNet data are available at http://kmtnet.kasi.re.kr/$\sim$ulens/event/2015/ . The main page is ordered by KMT event number in the form KMT-2015-BLG-\[NNNN\]. These numbers are in turn sorted by field BLG\[NN\] (01, 02, 03, 04), chip (K,M,N,T), patch, and star number. The “clear microlensing” events are listed first, so that all entries $\leq 0673$ are “clear” and all events $\geq 0674$ are “possible”. Each line contains the best fit event-finder parameters $(t_0,t_\eff,u_0)$ (Equations (\[eqn:general\]) and (\[eqn:ajoftau\])), the baseline flux, and the RA and Dec. There are also cross references to OGLE and MOA discoveries. By clicking on the event name, one can see the finding chart as well as the same 16 panels of light curve displays shown to the operator. These pages also contain links to the light curve data. 2015 Policy and Releases {#sec:policy2015} ------------------------ Guided by the above principles, we have formulated the following policies for KMTNet data for 2015. We then outline issues that are under consideration for future years in the next section. 1\) All 2015 KMTNet data remain proprietary until the acceptance for publication of this paper and all papers based on 2015 KMTNet data that are explicitly mentioned in Section \[sec:operations\]. 2\) Beginning immediately (i.e., before the end of the proprietary period), all light curves that are posted together with this paper (see below) can be used by anyone to prepare future papers for publication. However, during the proprietary period (see (1)), they cannot be submitted for publication, nor posted on arXiv. 3\) Once the priority period ends (see (1)), papers can be submitted based on the released data. We welcome collaboration with the KMTNet team, but do not require it as a condition for publication. For the cases that we collaborate, the KMTNet team does not demand any “editorial control”, but rather simply reserves the right to withdraw from papers with which we disagree strongly enough to warrant such withdrawal. 4\) If additional data processing is needed, we will either provide re-reduced light curves in exchange for co-authorship or we will provide flat-fielded “stamps” surrounding the event, provided that sufficient evidence is given to us that there is substantive progress toward publication of a paper. 5\) No data will be given out for events discovered by other teams but not independently discovered by KMTNet using the algorithm presented here, unless there is explicit agreement with those teams. The data that will be made available are 1\) All the data used by the event finder for all events that were determined to be either “clear microlensing” or “possible microlensing”. Recall that these data are based on @wozniak2000 DIA using input positions derived from a pre-constructed catalog. Hence, they are not usually of the highest quality, although sometimes they are in fact close to optimal. 2\) Automated @albrow09 pySIS reductions of all light curves[^2]. In roughly half of all cases, these reductions are better or substantially better than the reductions from (1). Unfortunately, in the other half of cases, these automated reductions either basically fail or totally fail. This means that, for a substantial fraction of events, obtaining very good or excellent light curves requires additional, by hand, reductions. No effort will be made to rectify these or any other residual problems for the 2015 data release as a whole. As discussed in Section \[sec:operations\], the 2015 data have intrinsic problems that are not likely to propagate into future years, and our main data reduction efforts will be applied to those future-year data. 2016+ Policy and Releases {#sec:policy2016} ------------------------- Future data policy and releases will be governed by the same principles, but will be modified based both on the experience of the 2015 release and the improved quality of 2016+ data. For 2015, we are posting light curves about 18 months after the close of the 2015 season. We hope that this time lag will be substantially improved for 2016 and further improved for 2017. Since we do not know exactly what problems we will encounter, we cannot guarantee it. However, at this point we believe that a 6-month delay is a plausible target for 2017+ data because if a paper cannot be drafted within 6 months of time the data are taken, it is likely to fall down the list of priorities as the next season of data start to become available. For 2016, we hope to have an earlier release of the events in the [*Kepler*]{} K2 C9 field. (See @henderson16 for a description of the K2 C9 project.) For KMTNet-discovered events, these data will have no proprietary period. We will also have a public release of KMTNet data on events discovered by other teams but not discovered by KMTNet. However, for these data, we will require that prospective authors obtain permission from the other teams before using the KMTNet data for publications. Future Improvements {#sec:improve} =================== Following the work reported here creating and implementing the 2015 event-finder algorithm, and based on this experience, numerous improvements are already being implemented for the 2016, 2017 and 2018 versions of this algorithm. They will be described more fully in the 2016 (and subsequent data release paper(s). The first improvement is simultaneous fitting to data from all three observatories. This is straightforward in principle because all three observatories have identical input star catalogs, so one can easily cross-identify light curves of the same physical “star” (really “catalog star”, which very frequently is actually a multi-star asterism). The second is simultaneous fitting of overlapping fields. This was completely unnecessary in 2015 because there were no overlapping fields. However, in 2016, each of the three “prime fields” BLG01, BLG02, BLG03, was also observed, slightly shifted, as BLG41, BLG42, BLG43, in order to cover the gaps between chips. Further, fields BLG02 and BLG03 are now somewhat overlapping in order to obtain a very high cadence on a small area $\Gamma=8\,{\rm hr}^{-1}$. Hence, there can be as many as four overlapping fields (see Figure \[fig:penny\]). And this also means (taken together with the previous paragraph) that there can be as many as 12 light curves that might be combined. In order to reliably cross-identify stars, however, this improvement will only be implemented for OGLE-III catalog stars. In 2015, we did not consider events with $t_\eff>99\,$days because we had no out-of-year baseline data. This will remain so in 2016 because the fields have been changed between 2015 and 2016, but also because the artifacts in the 2015 data make them unsuitable as a baseline of comparison. Such longer events can only be investigated beginning 2017. On the other hand, it should be possible to extend the search to much shorter timescales than the 2015 limit, $t_\eff\geq 0.56\,$days. In 2015, such a search was not possible because of the large number of short timescale artifacts. It is likely that in 2016, the search will be conducted independently in the $t_\eff\geq 1\,$day and $t_\eff< 1\,$day domains, to guard against long timescale events being “killed” by remaining short timescale artifacts. Finally, we note that these short timescale searches should resolve the problem found in 2015 searches of missing binary events characterized primarily by very fast rising caustics. Experience with the 2015 data shows that it is quite difficult to reliably identify microlensing events based on the current threshold $(\Delta\chi^2>500)$. In 2015, we tentatively identified events from KMTC data only based on this threshold, but then relied on data from other observatories to confirm them, so the true $\Delta\chi^2$ was significantly higher. For 2016+, we are already using all available data for 1) OGLE-III catalog stars in all fields and 2) all stars outside of the six fields mentioned in the previous paragraph. For these, we will therefore demand $(\Delta\chi^2>1000)$. For the remainder (i.e., non-OGLE-III stars in BLG01, 02, 03, 41, 42, 43), we will continue to demand $(\Delta\chi^2>500)$. In addition, the process of visual inspection of 2015 light curve was quite laborious. For 2016, we added automated rejection of published variables, as well as variables that were detected by KMTNet in 2015. This will remove most variables from the prime fields. For the new fields (of which there are 19), as well as the non-OGLE-III catalog stars in the prime fields, we will have to flag the variables in 2016, but then will be able to automatically censor them in future years. In 2017, we extended the rejection of cataloged KMTNet variables to all fields and added (after suitable testing) a rejection of previously found “artifacts” as well. We also introduced a new algorithm to eliminate a broad class of periodic variables, which is not a periodogram, but whose details will be described elsewhere. And we introduced a new algorithm to remove short timescale artifacts that masqueraded as short microlensing events. Again, this will be described elsewhere. Finally, for 2018, we are introducing injection of fake microlensing events into the process in order to measure the efficiency as a function of event characteristics of the entire selection process, both machine and human. See for example, @gould06. [Summary]{} {#sec:discuss} =========== We have presented a new algorithm for finding “completed” microlensing events and described its specific application to the four, primary 2015 commissioning fields of the KMTNet microlensing survey. We find 660 “clear microlensing” events and 182 “possible microlensing” events discovered and assessed by our method. The light curves of these events will be made publicly available on our website (see Section \[sec:website\]) according to the data policy described in Section \[sec:policy2015\]. In Section \[sec:policy\], we have presented our general approach to KMTNet data releases, in addition to the specific implementation of this approach for 2015 data. Feedback on the data products, data policy, etc., based on the use of these data will be helpful in preparing future releases. Our procedure for vetting microlensing candidates still relies heavily on human inspection of the microlensing candidates. Thus, we also discuss potential modifications for future years when we expect the data to be substantially cleaner. In fact, work is currently underway to improve this algorithm for the 2016 data. Finally, we note that although the procedure for eliminating false positives will remain dependent on the specific characteristics of the data, the algorithm itself as presented in Section \[sec:algo\] is completely general and could be applied to diverse microlensing data sets. Indeed, @ukirt16 have already applied this algorithm to find the first infrared-only microlensing events from their UKIRT survey of heavily extincted bulge regions. We thank the OGLE collaboration for making available full information about their 2015 event detections via their website http://ogle.astrouw.edu.pl/, which enabled systematic checks of our event-finder. Work by YKJ, WZ and AG was supported by AST-1516842 from the US NSF. Work by IGS and AG was supported by JPL grant 1500811. This research has made use of the KMTNet system operated by the Korea Astronomy and Space Science Institute (KASI) and the data were obtained at three host sites of CTIO in Chile, SAAO in South Africa, and SSO in Australia. [99]{} Afonso, C., Albert, J. N., Alard, C., et al. 2003, , 404, 145 Alcock, C., Akerlof, C.W., Alssman, R.A., et al. 1993, Nature, 365, 621 Alcock, C., Allsman, R. A., Alves, D., et al. 1997, , 479, 119 Alard, C. & Lupton, R.H.,1998, , 503, 325 Albrow, M. D., Horne, K., Bramich, D. M., et al. 2009, , 397, 2099 Bond, I.A., Udalski, A., Jaroszyński, M. et al. 2004, , 606, L155 Bozza, V., Shvartzvald, Y., Udalski, A., et al. 2016, , 820, 79 Chung, S.-J., Zhu, W., Udalski, A., et al. 2017, , in press Gould, A. 1996, , 470, 201 Gould, A. & Loeb, A. 1992, , 396, 104 Gould, A., Dorsher, S., Gaudi, B. S., Udalski, A., 2006, Acta Astron., 56, 1 Gould, A., Carey, S., & Yee, J. 2013, 2013spitz.prop.10036 Gould, A., Carey, S., & Yee, J. 2014, 2014spitz.prop.11006 Gould, A., Yee, J., & Carey, S., 2015a, 2015spitz.prop.12013 Gould, A., Yee, J., & Carey, S., 2015b, 2015spitz.prop.12015 Gould, A., Yee, J., & Carey, S., 2016, 2016spitz.prop.13005 Hamadache, C., Le Guillou, L., Tisserand, et al. 2006, , 454, 185 Han, C., Udalski, A., Lee, C.-U., et al. 2016a, , 827, 11 Han, C., Udalski, A., Gould, A., et al. 2016b, , 152, 95 Henderson, C.B., Poleski, R., Penny, M. et al. 2016 128, 124401 Kim, S.-L., Lee, C.-U., Park, B.-G., et al. 2016, JKAS, 49, 37 Mróz, P., Udalski, A., Poleski, R., et al. 2015, Acta Astron., 65, 313 Poleski, R., Udalski, A., Dong, S. et al. 2014, , 782, 47 Poleski, R., 2016, , 455, 3656 Schechter, P.L., Mateo, M., & Saha, A. 1993, , 105, 1342 Shin, I.-G., Ryu, Y.H, Udalski, A. et al. 2016, JKAS, 49, 73 Shvartzvald, Y., Maoz, D. 2012, , 419, 3631 Shvartzvald, Y., Maoz, D., Kaspi, S., et al. 2014, , 439, 604 Shvartzvald, Y., Udalski, A., Gould, A. et al. 2015, , 814, 111 Shvartzvald, Y., Bryden, G., Gould, A. et al. 2017, , 153, 61 Szymański, M.K., Udalski, A., Soszyński, I., et al. 2011, Acta Astron., 61, 83 Udalski, A. 2003, Acta Astron., 53, 291 Udalski, A., Szymanski, M., Kaluzny, J., Kubiak, M., Mateo, M., Krzeminski, W., & Paczyński, B. 1994, Acta Astron., 44, 317 Udalski, A., Yee, J.C., Gould, A., et al. 2015, , 799, 237 Woźniak, P. R. 2000, Acta Astron., 50, 421 Wyrzykowski, Ł., Kozłowski, S., Skowron, J., et al. 2009, , 397, 1228 Wyrzykowski, Ł., Kozłowski, S., Skowron, J., et al. 2010, , 407, 189 Wyrzykowski, Ł., Kozłowski, S., Skowron, J., et al. 2011, , 413, 493 Wyrzykowski, L., Skowron, J., Kozłowski, et al. 2011, , 416, 2949 Wyrzykowski, Ł., Rynkiewicz, A.E., Skowron, J., et al. 2015, , 216, 12 Yee, J.C., Gould, A., Beichman, C., 2015, , 810, 155 Zhu, Wei; Calchi Novati, S.; Gould, A. et al., 2016, , 825, 60 Zhu, W., Udalski, A., Calchi Novati, S, et al. 2017, , in press, arXiv:1701.05191 [^1]: This factor is less than the naive “five” because, for identical event geometries, brighter sources have smaller magnitude errors, making it is easier to detect and measure subtle anomalies. [^2]: Note that as of the time of submission, these reductions are not yet complete, but will be uploaded to the website as they are completed.
If any one wants to make a stupid comment to me about me joining the Gym today, save it cause I don't have the patience to deal with your sarcastic and flirty comments on how I should keep my ass tight. When I've wanting to get back in to yoga and now find out I have a hereditary disease that affects my ability... Read More I'll be happy when my town goes back to Normal, once the Bikers leave the Rally today, I take pride in where I grew up. But it gets old with all the Old biker dudes taking over the town. I wasn't planning on making a appearance, but my cousin insisted we go and try and meet Chibs and Bobby Elvis from Sons Of... Read More My fourth of July weekend started out with me deciding to play hookie from work because I needed to spend some therapy time with my dogs and clear my head. The fourth of July has not had the same meaning for me the last few years because I haven't really been happy with my surroundings or the path I'm walking,been depending on to many other people for my happiness and it's gotten me knowhere,so I've decided that it's time to move on not look back and if I burn bridges then so be it. I got my hands on the new Holly Madison book " down the rabbit hole," I'll read a few pages but save most of it for when I go to the beach with my cousin so she can read it to at the same time, since she wants to borrow after I finish. I really need something juicy to read in my spare time. In... Read More Going to San Francisco on Valentines Day, was so worth it except that I pulled a muscle in my left leg, and was limping like an old lady up and down Haight street.... I was expecting the weather to be shitty, so I wore a few too many layers to stay warm, but the day was beautiful and sunny. I finally got my SF tattoo... Read More
'Primitive' White House technology lost more than 1M emails over 1,000 days, former employee says Nick Juliano Published: Wednesday February 27, 2008 | Print This Email This Questions remain over Cheney's missing Plame e-mails The internal workings of the White House that caused it to lose perhaps millions of internal e-mails over several years is becoming clearer, but with that sharper focus comes diminishing hopes among Democrats and open-government activists that history will ever get the full picture of how the Bush administration operated. At a Capitol Hill hearing yesterday, a former White House computer technician outlined the administration's shortcomings in implementing a "primitive" e-mail archiving system that created a high risk the information would be lost. Steven McDevitt, who worked for the administration from 2002 to 2006, also doubled previously reported estimates of the number of days of missing e-mails. Investigators for the House Oversight and Government Reform Committee previously said e-mails were missing for 473 days; McDevit said in written testimony to the committee that the number was closer to 1,000 days. He also said at least 1 million e-mails were believed to have gone missing; activists have estimated the number of missing e-mails is closer to 10 million. The exact number of missing e-mails is unknown, but several days on which e-mails were not archived covered key dates in a Justice Department inquiry into the roles of Vice President Dick Cheney and his aides in leaking the identity of covert CIA agent Valerie Plame Wilson. As RAW STORY previously reported, no e-mails were archived on the very day the probe was announced and White House officials were ordered to maintain anything that could become evidence in the investigation that ended the conviction of I. Lewis "Scooter" Libby, Cheney's former chief of staff, on perjury and obstruction of justice charges. As The Associated Press reports, Tuesday's hearing shed some light on what happened to e-mails from the Vice President's office, but many questions remain unanswered. For the first time, a former White House computer technician went public with the details. Steven McDevitt revealed in written statements submitted to Congress how a plan was developed to try to recover the missing e-mail for [Special Prosecutor Patrick] Fitzgerald. Ultimately, 250 pages of electronic messages were retrieved from the personal e-mail accounts of officials in Cheney's office, but whether that amounted to all the relevant e-mail is a question that may never be answered. McDevitt made clear that it was a sensitive issue inside the White House. "I worked with ... White House Counsel on efforts to provide an explanation to the special prosecutor," McDevitt wrote. "This included providing a briefing to the special prosecutor's staff on this subject." Rep. Henry Waxman, the committee's chairman, also said during Tuesday's hearing that the Republican National Committee, which had hosted e-mail addresses used for official business by White House adviser Karl Rove and others, "has no intention of trying to restore the missing White House e-mails." The Washington Post provides some background: Administration officials have acknowledged that Rove and many other White House officials routinely used RNC accounts for government business, despite rules requiring that they conduct such business through official communications channels. The RNC deleted all e-mails until 2004, when it exempted White House officials from its e-mail purging policy. About 80 White House aides used RNC accounts for official government business, committee staff members said. Rove, for example, sent or received 140,000 e-mails on RNC servers from 2002 to 2007, and more than half involved official ".gov" accounts, the panel has said. The RNC dispute is part of a broader debate over whether the Bush administration has complied with long-standing statutory requirements to preserve official White House records -- including those reflecting potentially sensitive policy discussions -- for history and in case of future legal demands. Whether historians will ever get a full picture of internal deliberations remains to be seen. But Tuesday's hearing went a long way toward exposing problems with the White House and RNC. McDevitt, according to the Associated Press, also revealed that: _The White House had no complete inventory of e-mail files. _Until mid-2005 the e-mail system had serious security flaws, in which "everyone" on the White House computer network had access to e-mail. McDevitt wrote that the "potential impact" of the security flaw was that there was no way to verify that retained data had not been modified. _There was no automatic system to ensure that e-mails were archived and preserved. The National Security Archive, which is suing the White House over its poor record keeping, said Tuesday that the hearing revealed incompetence on the part of the White House, which also ignored warnings that its e-mails were not being archived in accordance with legal requirements. "The White House's witnesses disclaimed knowledge and responsibility for the e-mail problem," said Meredith Fuchs, the group's general counsel, in a statement. "The [National Archives] witnesses said that they are waiting for the White House to take action. But no one is doing anything and time is running out."
As the 2012 race in Colorado’s always hotly contested 4th congressional district officially kicked off this week, Republicans in Larimer County, the most populous county in the district, are suffering through another humiliating chapter in the unfolding history of incompetence and corruption that plagued the county party under the recent direction of Larry Carillo. Police issued a felony theft arrest warrant for the former party chairman Tuesday, accusing him of stealing more than $17,000 to pay bills and gambling debts. Carillo is alleged to have unwittingly set up payments to a company created by the Department of Homeland Security to fight online gambling and money laundering. Carillo paid more than $27,000 in online gambling debts while he was party chairman. Mounting evidence suggests Carillo was struggling personally and part hapless and part opportunist as party chair from February 2009 to February 2011. He failed repeatedly to file campaign finance reports, racking up roughly $65,000 in state fines. State Senate President Brandon Shaffer, a Longmont Democrat, announced Monday he was running to unseat CD4 Republican freshman Congressman Cory Gardner in 2012. The race is sure to be hard fought. Shaffer has eyed the seat for some time, running briefly to represent CD4 in 2008, before withdrawing to make room for Democrat Betsy Markey, who that year unseated Republican social conservative Marilyn Musgrave. Carillo was replaced as Larimer GOP chairman by Tom Lucero, one-time CU regent and Republican CD4 2010 candidate. Lucero told Bob Moore at the Fort Collins Coloradoan that the warrant for Carillo’s arrest represents a big step forward out of the swamp of mismanagement and bad news that has dogged the local party for months. “We’re finally able to bring closure to this and we’re able to move on to the final step, which is our [campaign finance fine] appeals process with the secretary of state and we’ll be able to very soon put this chapter behind us and close the book on it.” Carillo on Tuesday afternoon told Moore he was planning to surrender to Fort Collins police. The Coloradoan has owned the story of the struggling Larimer County GOP. Read Bob Moore’s story posted today for rich detail. [ Via Fort Collins Coloradoan ]
Ovarian hormones regulate expression of the focal adhesion proteins, talin and paxillin, in rat uterine luminal but not glandular epithelial cells. During early pregnancy in the rat, focal adhesions disassemble in uterine luminal epithelial cells at the time of implantation to facilitate their removal so that the implanting blastocyst can invade into the underlying endometrial decidual cells. This study investigated the effect of ovarian hormones on the distribution and protein expression of two focal adhesion proteins, talin and paxillin, in rat uterine luminal and glandular epithelial cells under various hormone regimes. Talin and paxillin showed a major distributional change between different hormone regimes. Talin and paxillin were highly concentrated along the basal cell surface of uterine luminal epithelial cells in response to oestrogen treatment. However, this prominent staining of talin and paxillin was absent and also a corresponding reduction of paxillin expression was demonstrated in response to progesterone alone or progesterone in combination with oestrogen, which is also observed at the time of implantation. In contrast, the distribution of talin and paxillin in uterine glandular epithelial cells was localised on the basal cell surface and remained unchanged in all hormone regimes. Thus, not all focal adhesions are hormonally dependent in the rat uterus; however, the dynamics of focal adhesion in uterine luminal epithelial cells is tightly regulated by ovarian hormones. In particular, focal adhesion disassembly in uterine luminal epithelial cells, a key component to establish successful implantation, is predominantly under the influence of progesterone.
Janitorial service providers commonly collect trash, dust, sweep, and perform light washing and kitchen clean-up. These providers employ specialized tools and products in providing these services. A commonly used tool is a commercial trash barrel. Such a trash barrel is available in a standard 44-gallon size and has the approximate shape of a tapered cylinder. Typical dimensions of the trash barrel are 20-inch diameter at its base, 24-inch diameter at its top and a height of 32 inches. The trash barrel accepts a flexible plastic trash barrel liner that keeps the trash barrel clean and facilitates removal of trash. The trash barrel has a screw fitting protruding from its base. The screw fitting protrudes approximately ¾-inch and has a diameter of approximately 11 inches. The screw fitting mates with a corresponding fitting on a wheeled dolly. The trash barrel mounted on the wheeled dolly can be moved and maneuvered much more easily than a trash barrel not mounted on a wheeled dolly. In addition to the trash barrel/wheeled dolly combination, the service provider carries an assortment of tools and cleaning supplies useful in performing assigned tasks. Such tools may include brooms, brushes and cleaning cloths, and such supplies may include spray cleaners, soaps and polishes. Oftentimes a service provider carries tools and supplies in a makeshift fashion by hanging them from the trash barrel or placing them inside the trash barrel. A makeshift approach can leave the provider's tools and supplies disorganized, unsecured, difficult to access and hard to keep track of. In addition, the tools and supplies may interfere with removal and replacement of the flexible plastic trash barrel liner. It is desirable to carry such tools and supplies organized and secure in a tool caddy attached to the trash barrel in a manner that does not interfere with removal and replacement of the flexible plastic trash barrel liner. A tool caddy that protrudes outward from a trash barrel reduces the maneuverability of the trash barrel. A compromise exists between designing a tool caddy large enough to provide adequate storage space, but not so large as to substantially reduce the maneuverability of the trash barrel. When full of trash the trash barrel is quite heavy. The ergonomically preferred method of emptying a trash barrel is to lay the barrel on its side and remove the trash by extracting the flexible plastic trash barrel liner that contains the trash. One deficiency of the trash barrel is that its circular shape makes it prone to uncontrolled rolling when laid on its side. The rolling instability of the barrel makes removal of the trash more difficult. A device that stabilizes a trash barrel lain on its side would facilitate removal of the flexible plastic trash barrel liner filled with trash. One deficiency of a trash barrel mounted on a dolly is that it has high center of gravity when filled with trash. This high center of gravity makes the trash barrel susceptible to accidental tipping. A tool caddy attached at or near the top of a trash barrel further raises the center of gravity and aggravates the tipping problem. The top diameter of a trash barrel is typically greater than the bottom diameter. Additionally, a narrow lip protrudes outward from the top edge and continues around the entire circumference. The protruding upper lip is generally the outermost point of a trash barrel. As a service provider maneuvers a trash barrel through a cleaning area, the upper lip often bumps or rubs against walls and other objects in the cleaning area. A common deficiency of a trash barrel is its tendency to mar surfaces, particularly painted walls, when the top lip bumps or rubs against them.