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Expression, regulation and biological actions of growth hormone (GH) and ghrelin in the immune system. Immune and neuroendocrine systems have bidirectional communications. Growth hormone (GH) and an orexigenic hormone ghrelin are expressed in various immune cells such as T lymphocytes, B lymphocytes, monocytes and neutrophils. These immune cells also bear receptors for hormones: growth hormone receptor (GHR) for GH and growth hormone secretagogue receptor (GHS-R) for ghrelin. The expression of GH in immune cells is stimulated by ghrelin as in anterior pituitary cells, whereas the regulation of GH secretion in the immune system by other peptides seems to be different from that in the anterior pituitary gland. Cytokines and mitogens enhance GH secretion from immune cells. GH has several biological actions in the immune system: enhancing thymopoiesis and T cell development, modulating cytokine production, enhancing B cell development and antibody production, priming neutrophils and monocytes for superoxide anion secretion, enhancing neutrophil adhesion and monocyte migration and anti-apoptotic action. Biological actions of ghrelin include attenuation of septic shock and anti-inflammatory actions, modulating phagocytosis, and enhancing thymopoiesis. The effect of ghrelin may be direct or through GH production, and that of GH may be direct or through insulin like growth factor-I (IGF-I) production. Elucidation of the roles of GH and ghrelin in the immune system may shed light on the treatment and prevention of immunological disorders such as AIDS and organ damages due to obesity/ageing-related chronic inflammation.
{ "pile_set_name": "PubMed Abstracts" }
*((c*c**(5/4)*c)/(c*c**(-12)/c))**(-11) assuming c is positive. c**(-7577/28) Simplify (v/v**0)**(-1/6)/(v**(-1/4))**(34/5)*v*(v/((v**(1/5)*v*v*v)/v))/v*v*(v/(v/(v**(2/13)/v)))/v*v**(-8)/((v*v**6*v)/v*v*v*v) assuming v is positive. v**(-722/39) Simplify ((z*z*z**(-2/7))**(-28))**(-5/2)*(z**0)**39*(z/(z/((z/(z*z**(-3/2)*z*z*z)*z*z*z)/z))*z)/z*z/(z*z**(-1/2)*z) assuming z is positive. z**120 Simplify ((v**(-1/4)/(v*v**(2/13)))/(v**(-6)/v*v**(1/7)))/((v/(v/(v/(v**3/v))))/v*v**(3/7))**(-1/36) assuming v is positive. v**(8861/1638) Simplify ((c*(c**(-6/5)*c)/c*c)/c*c*((c**22*c)/c)/c*c**26*c**(-26))**(-1/15) assuming c is positive. c**(-109/75) Simplify (h**9/(h**(-2/3)*h)*h**(-1)/(h/(h/(h*h**(-7/3)*h*h*h))))**(-37) assuming h is positive. h**(-222) Simplify ((k/((k**(-1/3)*k*k)/k)*k)/(k/(k*k/k**(-3)*k*k)))**(-30)*(k/(k**0*k))**(-16/7)/((k/k**3)/k**3) assuming k is positive. k**(-215) Simplify ((((t/(t*t/(t*(t/(t**(10/17)/t))/t)*t))/t*t/(t*t**(1/45)*t)*t*t*t*t)**(-3/10))**(-42/11))**(1/22) assuming t is positive. t**(7441/102850) Simplify (q*q/q**45)/q**40*q/(q*((q**(-31)/q)/q)/q)*q**(-2/83) assuming q is positive. q**(-4069/83) Simplify (i*i/i**(-2/3)*(i*i**(-2)*i)/i*i)/(i**(-5)*i**(-2/5))*((i**(-2)*i)**(-30))**20 assuming i is positive. i**(9121/15) Simplify ((v/v**(7/5))/(v/v**(5/3)*v))**45/((v*v**1/v)**41*(v*(v/(v**(2/21)*v))/v)/((v*v*v/(v/(v**(4/5)/v)))/v)) assuming v is positive. v**(-7676/105) Simplify ((k**(-21)*k*k**17)/(k/(k*k**(-1/8)/k))**21)**42 assuming k is positive. k**(-4473/4) Simplify ((i**2/i)/i**(-1/31)*(i*i**(-2/39))/i**(-13))**(-1/3) assuming i is positive. i**(-18112/3627) Simplify (j*j*j**3*j/((j**(-2)*j)/j)*j*j)**42*(j**(-6)/(j*j*j/(j*(j*j**(-2))/j*j)))**49 assuming j is positive. j**(-21) Simplify ((x**0/x)**(2/9)/((x**(-1/12)*x*x)/x**(-3)))/(x/x**(-3/8)*x/x**(-1)*x**(-7)/(x*x/x**(2/9))) assuming x is positive. x**(19/72) Simplify (((m**(-1)*m*m)**(42/13)*(m*m**1/m)**7)**39)**(-3/16) assuming m is positive. m**(-1197/16) Simplify ((y**35/(y*(y/(y**16/y))/y))/((y*y/y**(1/11))/((y**7*y)/y)))**11 assuming y is positive. y**595 Simplify d*d**(-4)*d*d*d**(-1/4)*(d*d**(-1/4))/d**(-1)*(d**(-1)/d**(-2/11))/((d/(d*d**(-2)/d))/(d**4/d)) assuming d is positive. d**(-7/22) Simplify (y/y**(-2))/y*y*y**(-1/5)*(y/y**0*y)/y**(-2/7)*(y**5/y*y/y**(-4)*y)/(y/(y**0/y)*y*y)**(-49) assuming y is positive. y**(7388/35) Simplify ((d**(-1))**(-5/2))**(-15)/(((d*d**(4/7)/d)/(d**0/d*d))/((d**(-2/11)/d)/d**(5/6))) assuming d is positive. d**(-9260/231) Simplify (l**(2/17)/l**2)/(l**(-1/2)/l)**8*(l**(-3)/(l*l**(-1/13)))/(l**(-1/5)*l**8) assuming l is positive. l**(-1774/1105) Simplify (y**3*y**(-2/15))**(1/9)*(y/y**(-2))**34/(y**5/y*y*y*y**(-1/15)) assuming y is positive. y**(13012/135) Simplify ((((z/z**(1/7))/z*z)/z*z)/z**(-2/5)*z**1/z**(-6))/(z**(-4)/z**(-5)*z/z**(6/7)*z**(-5)) assuming z is positive. z**(424/35) Simplify (l**(4/7)*l**(1/4)*(l/(l/(l*l/l**3*l)*l*l))/l**(-2/9))/((l**(4/5)*l**(1/10))/(l**(2/9)*l**(-1)*l*l)) assuming l is positive. l**(-799/1260) Simplify ((z**(-1/68))**(-2/93)*(z*z**13)**(-31))**(2/39) assuming z is positive. z**(-1372307/61659) Simplify ((f*f*f**17*f)**(-11/4)/((f*(f*f**(1/22)*f*f)/f)/(f**24/f)))**(-12/13) assuming f is positive. f**(4626/143) Simplify ((s/s**1)/(s**(-1/3)*s*s))**(21/5)*s/(s/(s/s**4))*((s*s/(s*s**(2/7)))/s)/s*(s**(-2/5))**(-31) assuming s is positive. s**(39/35) Simplify (((h**(-5)/h)/h)**(-6)/(h**(-1/9)/(h/h**(-2/15)*h)))**(-32) assuming h is positive. h**(-63712/45) Simplify ((r*(r/(r/((r/r**(-1))/r))*r)/r)**25)**(-28)/(((r*r/((r**(-1/4)*r)/r)*r*r)/r**7)/(r**2/r**(-3))) assuming r is positive. r**(-5569/4) Simplify ((s**(-2/69)*s/s**(-1/27))/((s/((s/s**(2/51))/s))/(s/(s**(-1/8)/s))))**(1/38) assuming s is positive. s**(176837/3209328) Simplify ((l*l**29*l)/l)/((l/((l*l**(-27)*l)/l))/l)*(l**(-4/3)*l*l)/l**(-34) assuming l is positive. l**(116/3) Simplify (c/(c**(-8)*c)*c**(4/9)*c**8/c*c**(-4))/((c*c/(c*c**0))/c**(3/11)*c*c**5/c*c*c**5) assuming c is positive. c**(-28/99) Simplify ((x**(6/7)/(((x/x**18*x)/x)/x))/(x/(x**7/x)*x**3))**(-11/2) assuming x is positive. x**(-803/7) Simplify ((o/o**(1/15))/o**(-7))**(16/9)/(o/(o/(o/(o**(-3)/o)))*o**4/o*o/(o*o**2)*o*o**(-4)) assuming o is positive. o**(1499/135) Simplify (r**5/(r/(r/(r/(r/r**(-2/15)))))*(r**(-2/5)*r)**(-7))/(r**(-1/3)*r**(-2/5)*((r*r**(1/2)*r)/r*r)**(-36)) assuming r is positive. r**(275/3) Simplify (o*o**14*o/o**5*o*o)**(17/5)*((o**2*o*o*o)/o**(2/23))/((o/(o**(-2/21)/o))/(o*o*o**(-2)*o)) assuming o is positive. o**(115963/2415) Simplify ((m**(1/17)/m**(2/21))/(m**(1/17)/(m/(m**(2/33)/m))))**41 assuming m is positive. m**(5822/77) Simplify (m**11/(m**2/m*m))**(2/47)*m*m**1*m**(-1/4)*((m*m**(-2/7)*m)/m)**(-2/131) assuming m is positive. m**(365837/172396) Simplify s/s**(-5)*s*s*s**(-1)/s*s*s*s*s/s**(-1/10)*s*s**(-4)/s*(s/s**(1/2)*(s*(s*s*s*s**(-10)*s)/s*s)/s)**(-10/11) assuming s is positive. s**(111/10) Simplify ((q**(3/5)*q*q*(q/((q*(q/(q/(q*q**(-9))))/q)/q*q))/q)/(q**(-1/7)/q**(3/7)))**(-44) assuming q is positive. q**(-17204/35) Simplify (w/w**6)/(w**(-1/2)*w*w)*(w/w**(-8))/w**(-2/3)*((w*w**(1/3)*w)/w)/w**2*(w/(((w*w**5*w)/w)/w))/w**(-3) assuming w is positive. w**(3/2) Simplify ((((o**(-2/13))**19)**19)**34)**40 assuming o is positive. o**(-981920/13) Simplify ((d/d**8)/(d*d**(-2/13)*d)*(d**(-1/2)/d)**(14/11))/(d**(-1/16)/(d/(d*d*d**(-13)*d*d)))**44 assuming d is positive. d**(247101/572) Simplify ((n**(2/9)/(n/(n/(n*n**10))*n))/(n*n*n**(-2)*n*n/((n/(n**(10/7)/n*n))/n)*n))**(-2/37) assuming n is positive. n**(2042/2331) Simplify ((a**(-1/4)/a)**34*a**(-2/13)/a*a**(-1/3)/a)/(a*a**(-1/6)*a/(a**(3/4)/a)*a*a**(1/13)/(a*a**(-1)/a)) assuming a is positive. a**(-7667/156) Simplify (z**(2/7)*z*z**(-2/7))**(-35)/(((z/(z/((z**(-3)*z*z)/z)))/(z*(z/(z**(-4)*z*z))/z*z))/(z/z**(-2/9)*z*z**(-1/3))) assuming z is positive. z**(-244/9) Simplify ((k/(k**(-1)*k)*k*k)**(-44))**(-5/3)*(k**(2/9))**(-3/29)/(k**(2/5)/k**(2/17)) assuming k is positive. k**(1624642/7395) Simplify ((l*l/(l*l*l*l**(2/5)*l*l))/l*l**12/l*l**(6/17)*l/((l/(l*l*l**(-4)*l))/l))**31 assuming l is positive. l**(18321/85) Simplify (a*a**(-2/79)*a*a*a/(a/a**(-16))*(a/(a**16*a))**(-1/3))**(-28) assuming a is positive. a**(51044/237) Simplify ((v**0*v)**(-1/13)/(v**(-26/7)*v*v**32))**(1/6) assuming v is positive. v**(-1336/273) Simplify (((q**(-15/8)*q)/(q/q**20))**37)**(-10) assuming q is positive. q**(-26825/4) Simplify (m/m**2*m**(4/9)*m*m)**4/(m**7*(m*(m/(m*m**3)*m)/m*m*m*m)/m*m)**(1/24) assuming m is positive. m**(49/9) Simplify ((w**(1/4))**(-23/5)*w**(-2/7)*w*w*w**(-5/3)/w)/(((w*w**(1/7)/w)/(w*w/w**(-2)*w))/(w**1)**(1/10)) assuming w is positive. w**(1199/420) Simplify ((v**31*v)/v**(11/5))/(v**(-9/8)*v*v**(7/3)*v) assuming v is positive. v**(3191/120) Simplify ((d**(-15))**(5/12)*d*d**19*d*(d/(d/(d/(d/d**(-38)*d))))/d)**(-18) assuming d is positive. d**(909/2) Simplify u/u**(1/8)*(u*u**(-3/20)/u)/u*u*u**(8/7)*u**(-42) assuming u is positive. u**(-11237/280) Simplify ((c**(7/3)/c*c)/(c/c**(-2/9)))**27/(c**(-3/2)*c*c**2*c*c*((c*(c/(c*c**(-2/9)))/c*c)/c)/(c**(-2/13)/c)) assuming c is positive. c**(5879/234) Simplify (j**(-10)*j/((j/(j*j**(3/11)))/j)*j)**(-9)/(j**(-2/21)/j**(-2/13))**(-4/5) assuming j is positive. j**(909794/15015) Simplify j**(-2)/(j/(j*(j*j*j**(-1/2)/j)/j*j))*((j*j*j**(5/4)*j)/j)/j**(1/7)*(j/(j**(-1)*j))**(11/8)*j*j**(-6)*j*(j*j**(-1/4)*j)/j assuming j is positive. j**(-15/56) Simplify ((r**(-3/22)/(r/(r*r*r**(-21)/r)))/(r**(-11)*r*r**(1/24)))**44 assuming r is positive. r**(-2951/6) Simplify ((h**11*h)/h*h)**(-2/7)/(((h**(5/9)/h)/h*h*h)/h**(3/34)) assuming h is positive. h**(-8345/2142) Simplify ((l**(-1))**(-9/7))**11/((((l/((l**(2/5)/l)/l))/l)/l)**(-11/2)*(l**(-1/3))**(-18)) assuming l is positive. l**(801/70) Simplify ((c*c**(-1)*c)**(-25))**(1/27)/(c**10*(c/c**4)/c)**(-13/3) assuming c is positive. c**(677/27) Simplify ((l*l**(-6))/l**(-5)*((l*(l/(l/(l*l**6*l)))/l*l)/l*l)/l**2)/((l**(-1/4))**(-5/8))**(2/5) assuming l is positive. l**(111/16) Simplify ((d*d**(3/4)/d)/(d*d*d**(3/8)))**28*(d*d**(-5)*d**(-2))/(d**4*d*d**4/d) assuming d is positive. d**(-119/2) Simplify ((z*z/(z**(1/18)/z))**10/((z/(z/z**10))/z)**(5/21))**1 assuming z is positive. z**(1720/63) Simplif
{ "pile_set_name": "DM Mathematics" }
/** * Copyright (c) 2016-present, Facebook, Inc. * All rights reserved. * * This source code is licensed under the BSD-style license found in the * LICENSE file in the root directory of this source tree. An additional grant * of patent rights can be found in the PATENTS file in the same directory. */ #import <XCTest/XCTest.h> #import <IGListKit/IGListKit.h> #import "IGListDebugger.h" #import "IGListAdapterUpdaterInternal.h" #import "IGListTestAdapterDataSource.h" #import "IGListMoveIndexInternal.h" #import "IGListMoveIndexPathInternal.h" @interface IGListDebuggerTests : XCTestCase @end @implementation IGListDebuggerTests - (void)test_whenSearchingAdapterInstances_thatCorrectCountReturned { UIViewController *controller = [UIViewController new]; UICollectionView *collectionView = [[UICollectionView alloc] initWithFrame:CGRectZero collectionViewLayout:[UICollectionViewFlowLayout new]]; IGListAdapterUpdater *updater = [IGListAdapterUpdater new]; NSIndexPath *path = [NSIndexPath indexPathForItem:0 inSection:0]; updater.applyingUpdateData = [[IGListBatchUpdateData alloc] initWithInsertSections:[NSIndexSet indexSetWithIndex:1] deleteSections:[NSIndexSet indexSetWithIndex:2] moveSections:[NSSet setWithObject:[[IGListMoveIndex alloc] initWithFrom:3 to:4]] insertIndexPaths:@[path] deleteIndexPaths:@[path] moveIndexPaths:@[[[IGListMoveIndexPath alloc] initWithFrom:path to:path]]]; IGListTestAdapterDataSource *dataSource = [IGListTestAdapterDataSource new]; dataSource.objects = @[@1, @2, @3]; IGListAdapter *adapter1 = [[IGListAdapter alloc] initWithUpdater:[IGListAdapterUpdater new] viewController:nil workingRangeSize:0]; adapter1.collectionView = collectionView; adapter1.dataSource = dataSource; IGListAdapter *adapter2 = [[IGListAdapter alloc] initWithUpdater:[IGListAdapterUpdater new] viewController:controller workingRangeSize:2]; adapter2.collectionView = collectionView; IGListAdapter *adapter3 = [[IGListAdapter alloc] initWithUpdater:[IGListAdapterUpdater new] viewController:controller workingRangeSize:2]; adapter3.collectionView = collectionView; NSArray *descriptions = [IGListDebugger adapterDescriptions]; XCTAssertEqual(descriptions.count, 4); } @end
{ "pile_set_name": "Github" }
Q: Are there any tutorials on version 10 notebook templating and report generation? Are there missing docs? Bug introduced in 10.0 and persisting through 10.2 or later I am trying to understand the new templating in version 10. While there is a general documentation page with links to docs for each new function, so far I am unable to find any report generation worked examples of what a user may do after they open File > New > Template Notebook. Additionally when I press the help button on the template notebook it seems there is documentation missing: When you type "ReportGeneration" in the docs this is what you get: Templates were first introduced in the Finance Platform -- which is essentially a version of Mathematica with a few other functions. Rather than have report generation functions without any coherent description of how a user can start from scratch and make a template and an automated report, the Finance Platform has a wealth of material, including a tour: ...detailed extensive documentation: ...a specific palette that contains links to the tour, the extensive documentation and a video: All of this stuff is missing from my OS X version 10. Is it present in Windows? A: Confirmed bug by WRI tech support A: John Fultz gave a great talk about the templating system at the European Wolfram Technology Conference in 2014 - http://www.wolfram.com/events/technology-conference-eu/2014/presentations/Fultz_ReportGeneration.nb As requested, here's a video of John doing madlibs http://www.wolfram.com/broadcast/video.php?sx=Report%20Generation&v=1096 A: Maybe they renamed it. You should search the help for "AutomatedReports" this will bring you to guide/AutomatedReports. Or on the web: AutomatedReports. Some small examples and more details are presented at Automated Report Generation and the links therein.
{ "pile_set_name": "StackExchange" }
Friday, June 18, 2010 Camy here: If you haven't read anything by Robin Lee Hatcher yet, you need to go out right now and buy this book! I have to admit that I enjoy her historical novels more than her contemporaries. (I hope that doesn't make her upset. :) You can read excerpts of all her books on her website in case you don't believe me when I tell you she's a fabulous writer! Robin Lee Hatcher discovered her vocation as a novelist after many years of reading everything she could put her hands on, including the backs of cereal boxes and ketchup bottles. The winner of the Christy Award for Excellence in Christian Fiction (Whispers from Yesterday), the RITA Award for Best Inspirational Romance (Patterns of Love and The Shepherd's Voice), two RT Career Achievement Awards (Americana Romance and Inspirational Fiction), and the RWA Lifetime Achievement Award, Robin is the author of over 50 novels, including Catching Katie, named one of the Best Books of 2004 by the Library Journal. Robin enjoys being with her family, spending time in the beautiful Idaho outdoors, reading books that make her cry, and watching romantic movies. She is passionate about the theater, and several nights every summer, she can be found at the outdoor amphitheater of the Idaho Shakespeare Festival, enjoying Shakespeare under the stars. She makes her home outside of Boise, sharing it with Poppet the high-maintenance Papillon ABOUT THE BOOK It's 1918, and Daphne McKinley, heiress to a small fortune, has found contentment in the town of Bethlehem Springs, Idaho. But Daphne has a secret. A series of dime novels loosely based on local lore and featuring a nefarious villain known as Rawhide Rick has enjoyed modest popularity among readers. Nobody in Bethlehem Springs knows the man behind the stories ... except Daphne. When newspaperman Joshua Crawford comes to town searching for the man who sullied the good name of his grandfather, Daphne finds herself at a crossroads, reassessing the power of her words, re-thinking how best to honor her gifts, and reconsidering what she wants out of life. Propelled by a white hot fury, Joshua Crawford pushed open the door to Gregory Halifax’s office so hard it hit the wall with a loud wham. Startled, Gregory looked up a split second before Joshua slapped the newspaper onto the desk. “What is this garbage?” Joshua demanded. Gregory’s expression changed from one of surprise to a smirk. “So you read it.” “Of course I read it, and I’m here to demand a retraction.” “A retraction? For what?” “For what you wrote about my grandfather.” Gregory laughed softly. “You must be joking. The article is about dime novelists. The part about Richard Terrell was the words of the author, not mine.” “But you made what Mr. Morgan wrote in his novels sound as if it was fact rather than fiction. It’s not.” “How do you know it’s not? Tell me. What do you know about your grandfather before he settled in St. Louis? Nothing, that’s what. You’ve said so yourself.” “Did you contact anyone in Idaho to try to confirm that the character in Morgan’s books is based on the real Richard Terrell?” “I didn’t need to. I interviewed the publishers for my story. And again, the focus of my article is the men who write dime novels, not on the characters found in their books.” “But in the process you’ve dragged my grandfather’s good name through the mud. I want a retraction.” Gregory pushed back his chair and stood, the smile gone from his face. “When you prove anything I wrote is in error, then come see me again, and we’ll have this discussion. Until then, get out.” For one moment, Joshua thought he might be able to control his temper. For one very brief moment — just before he caught Gregory’s jaw with a right hook followed by a left jab to the gut. Gregory flew backward into the wall. The glass in the office door rattled again. Joshua readied himself for the other man to fight back. To his dissatisfaction, it didn’t happen. Gregory’s eyes were still unfocused when more men poured into the office and grabbed Joshua by the arms, hauling him away. One of the men was Joshua’s boss, Langston Lee. “You’re fired, Crawford. Collect your things and get out. I won’t have my reporters brawling. You hear me. Get out or I’ll call the police.” Joshua longed to turn his rage onto his boss, to give Langston Lee a little of what he’d already given Gregory Halifax. But he had enough good sense left to resist the urge. He was already out of a job. He didn’t want to spend time in a jail cell besides. But so help him, he would get a retraction out of this newspaper. He would prove Gregory Halifax was a shoddy reporter and see that he was fired. He would hear Langston Lee apologize. And he would make certain D. B. Morgan never again maligned his grandfather in print. This wasn’t over yet. Chapter 1 October 1918 Maybe it was time to kill Rawhide Rick. He’d served his purpose, the old rascal. He’d hunted buffalo and fought Indians and stolen gold from hardworking miners and sent men to the gallows. Now might be the time for him to meet his Maker. The trick was deciding how to kill him. Daphne McKinley rose from her desk and walked into the parlor, where she pushed aside the curtains at the window. A golden haze blanketed Bethlehem Springs. It had been a beautiful autumn. The prettiest one yet in her three years in this serene Idaho mountain town. The trees had been the brightest of golds, the most fiery of reds, the deepest of greens. Daphne had spent many a mild afternoon walking trails through the forest, enjoying the colors and the smells. If Rawhide Rick — who by this point in the series of books had become the infamous Judge Richard Terrell — was dead, what would become of the dashing Bill McFarland, hero of The McFarland Chronicles? Without his arch enemy, his life might become rather dull. Or perhaps it was Daphne who would find life dull without Rawhide Rick. Wicked he was, but he certainly kept things interesting whenever he was around. She rubbed her eyelids with the tips of her fingers, and when she pulled them away, she noticed ink stains on her right hand. Her fountain pen was leaking. Perhaps it was time to buy a typewriter. But would writing on a machine feel the same? Daphne turned from the window, her gaze sweeping the parlor. She’d come to love this small house on Wallula Street. Since moving into it soon after Gwen — its previous owner — married Daphne’s brother, she’d delighted in making it her home, decorating and furnishing it in ways that pleased her. Daphne’s childhood homes had been large and filled with servants waiting to attend to her slightest wish. But she had often been forced to live by the timetables of others. Now she could do as she willed, when she willed. The freedom she enjoyed was intoxicating. The best part was when she wanted to be with family, she got into her motorcar — her very own, quite wonderful McLaughlin- Buick — and drove to her brother’s home to play with her young nephew and infant niece. She was completely dotty over the two of them. She loved to crawl around on the floor with Andy — he would turn two at the end of November — the both of them squealing and giggling. And there was nothing like cuddling three-month-old Ellie. Daphne thought the baby girl smelled like sunshine. A sigh escaped her. She hadn’t time for daydreaming about Morgan’s and Gwen’s darling children. She must decide what to do. If she was going to kill the judge, she needed to notify Elwood Shriver at once. Wavering in indecisiveness served no good purpose. She returned to her small office. The floor around her desk was littered with wadded sheets of paper. It was always thus when words frustrated her. “So wasteful,” she scolded softly. of the war half a world away was splashed across the front page. More than a million American men — just boys, many of them — were now fighting in Europe alongside the Allied Powers. The end was near, some said. She prayed to God they were right. Too many had died already. Others, like Woody Statham, would wear the scars from their war wounds for the remainder of their lives — if not on their bodies then in their souls. She flipped through several more pages of the newspaper, but nothing she read captured her imagination or sparked her creativity. Besides, she’d read every article before, some of them several times. Maybe her problem wasn’t with Rawhide Rick. Maybe the problem was Bill McFarland. Maybe she was tired of him. Maybe he should die. “Maybe the whole lot of them should perish,” she muttered as she laid the newspaper aside. She spun her chair toward the bookcase beneath the office window. There, on the bottom row, were copies of The McFarland Chronicles by D. B. Morgan, all ten volumes. And if she didn’t decide soon what to do about Rawhide Rick, ten volumes would be all there were. There was no question that Daphne loved writing stories of adventure and danger in the West of forty and fifty years ago. And while she would concede that her books were not great literature, they were entertaining, for readers and for herself. But there were days like today when she was tempted to contact her editor in New York City and tell him that she (D. B. McKinley, whom Elwood Shriver thought to be a man) was retiring and thus so must D. B. Morgan (the pseudonym used on her books). However, she knew she would miss the storytelling were she to give it up. After all, it didn’t take much effort to clean her small house or cook the As she sat down, she took up the five-day-old newspaper. News occasional meal. Without her writing pursuits, what would she do with her time? It would be nice if she could discuss her feelings with someone, but there wasn’t another person, in Bethlehem Springs or elsewhere, who knew she was the author of dime novels. She wasn’t sure her brother would believe her if she told him. The only soul who might suspect anything was Dedrik Finster, the Bethlehem Springs postmaster, because of the mail she sent and received, but his English wasn’t the best and he probably had no idea that Shriver & Sons was a publishing company. Why would he? Maybe what she needed more than anything was a drive out to the Arlington ranch and a long visit with Griff Arlington, Gwen and Cleo’s father. That man had given her more story ideas in the last three years than she could ever hope to put on paper. It was Griff who had told her about the escapades of the real-life Richard Terrell, every bit as much a scoundrel as her fictional character, although perhaps in different ways. Yes, a visit with Griff was just what the doctor ordered. Her mind made up, she rose and went in search of hat, gloves, and coat. **** Joshua stepped from the passenger car onto the platform and looked about him. A large family — father, mother, and six children — were being escorted into the railroad station by a young man in a blue uniform. They were on their way to a hot springs resort located north of Bethlehem Springs. He knew this because they had spoken of little else during the journey, and Joshua couldn’t have helped but overhear their conversation as they’d been a rather boisterous group. He, on the other hand, was headed into the town that appeared to be about a quarter mile or so up a dirt road that passed between two low-slung hills. Switching his valise to the opposite hand, he set off in that direction. The first building he saw upon entering Bethlehem Springs was a church. All Saints Presbyterian, according to the sign out front. Catty-corner from All Saints was the Daily Herald, his destination. He crossed the street and entered the newspaper office. Familiar smells — newsprint, ink, dust — filled his nostrils. An attractive but pale-looking woman, dressed in black, came out of the back room, hesitated when she saw him, then moved forward, stopping on the opposite side of a raised counter. “May I help you, sir?” “Yes.” He set down his valise and removed his hat. “My name is Joshua Crawford. I’m here to see Nathan Patterson.” “I’m sorry, Mr. Crawford.” Her voice broke, and it took her a moment to continue. “Mr. Patterson passed away.” She drew a long breath and released it. “I’m his widow. Perhaps I can assist you.” Either Nathan Patterson had been much older than his wife or he had died tragically young, for Joshua guessed the woman to be no more than in her early thirties. Joshua had counted on this job. Without it, he couldn’t afford to stay in Idaho. He would barely have enough money for train fare back to St. Louis, as long as he didn’t spend a night in the hotel, and even then he wouldn’t have much left over to buy food. He would be extremely hungry before he reached Missouri. Not to mention that he wouldn’t have a job waiting for him when he got there — unless he was successful here first. “I’m glad you’ve come, Mr. Crawford. My husband would be heartbroken to see this newspaper fail. I assume you can do more than report?” “Ma’am?” “You are qualified to manage the paper, I trust.” Manage it? That was more than he’d expected. But if it worked out . . . “Yes, I am qualified,” he answered — with more confidence than he felt. “Good. Nathan’s final instruction was for me to offer you the job as managing editor of the Daily Herald. If you’re interested, that is.” He hadn’t thought to be in Idaho more than a month or two. Surely he could discover the information he needed, take care of matters, and return to Missouri before Christmas. On the other hand, success as a managing editor would look good on his résumé, would give him many more opportunities than simply working as a reporter for a small paper. “Are you interested, Mr. Crawford?” He had few other options. None, actually. Not if he wanted to honor his grandfather’s memory. Not if he wanted to restore his own good name and get back his old job. Taking the job as managing editor didn’t mean he would be here forever. He could keep the newspaper running until Mrs. Patterson found his replacement. It was the least he could do for the man who had paid his train fare from Missouri to Idaho. “Yes, Mrs. Patterson. I’m interested.” “The pay will be ninety-five dollars a month to start. I know it isn’t the sort of salary you must have received at a large newspaper, but you’ll have a place to live for free.” She pointed at the ceiling. “There’s an apartment above the office with a kitchen and bath. It hasn’t been used for several years, but with a bit of elbow grease, it should clean up well and prove adequate for a bachelor such as yourself.” Ninety-five a month. Not quite twelve hundred a year. Less than Langston Lee had paid him back in St. Louis, but more than the sum Nathan Patterson had offered when he’d applied for the job with the Daily Herald. With a place to live thrown in, the salary would allow him to put money aside for when he returned to Missouri. “That sounds fine,” he answered. Mrs. Patterson gave him a fleeting smile. “Good. Now let me show you to your quarters. I’m sure you must be weary from your journey. We can begin work in the morning.” **** Daphne was invited by Griff Arlington to have supper with the family and to spend the night at the ranch as she occasionally did, but she declined. Griff ’s storytelling about his early days in Idaho had done just what she’d hoped. Ideas were rolling around in her head, and she was desperate to get them on paper before they disappeared like a puff of smoke in the wind. As soon as she walked into her house, she tossed her coat over the nearest chair, dropped her hat on the table, and hurried into her office, where she lit the lamp and began scribbling as fast as she could. It seemed she barely drew a breath for the next hour. When she looked up at last, she saw that night had fallen over Bethlehem Springs. Her stomach growled, reminding her that she’d missed supper. Still, she had little desire to cook. This seemed like a good evening to pay a visit to one of the town’s restaurants. Daphne had three choices — the Gold Mountain, which served the most wonderful breakfasts; the restaurant inside the Washington Hotel where she liked to dine before an evening at the Opera House; and the South Fork, famous for their pies and home-style fare. She decided on the latter. As she walked briskly along Wallula Street toward Main, her way was lit by street lamps, one of many improvements made during Mayor Gwen McKinley’s term of office, which had ended almost ten months earlier. Daphne thought it unfortunate for the town that her sister-in-law had retired from public service. She hoped that, when her nephew and niece were older, Gwen would run for office again. As Daphne neared the office of the Daily Herald, she noticed light spilling through the windows of the apartment above it, something she’d never seen before. Was the newly widowed Christina Patterson up there, perhaps sorting through memorabilia from her marriage? Should Daphne postpone her evening meal another hour and see if she could offer the woman any comfort or assistance? Nathan Patterson’s death had been a shock to the town. A man of thirty-seven years, he’d looked in the pink of health. To have him weaken and die so suddenly had taken everyone, especially his wife, by surprise. And even while they grieved the loss of a friend, many wondered about the future of the Daily Herald. It had been almost a week since the last edition. What would become of the newspaper without Nathan at its helm? A shadow fell across the nearest window, and Daphne stopped on the sidewalk, still pondering what she should do. Would Christina welcome a visit from her or had she gone up there to escape intrusion? Daphne remembered all too well how difficult the death of a loved one could be. She’d been a girl of sixteen when her beloved father died, a young woman of twenty when she’d lost her mother. Even now, all these years later, she felt a painful sting in her chest, knowing she wouldn’t see either of them again this side of heaven. She also remembered that sometimes she’d wanted to be alone with her memories, alone to cry and mourn. And so she decided not to disturb the new widow and instead moved on, rounding the corner onto Main Street and entering the South Fork Restaurant a few moments later. Delicious scents filled the dining room, making her stomach grumble once again. It was late enough that the dinner crowd had come and gone. There were customers at only two tables — Mabel and Roscoe Finch, who worked for her brother and sister-in-law, and Ashley Thurber, the elementary school teacher. Daphne greeted each one of them before sitting at a table in the corner, her back to the wall. Whenever she dined out, she preferred similar seating. It allowed her to study others without being too obvious. She loved to watch and listen to people. She’d learned a great deal from the habit, and much of what she’d learned had made it into her stories at one time or another. Sara Henley — a shy, plain girl of eighteen — approached Daphne, a pad in her hand and a smile on her face. “Evening, Miss McKinley.” “Wonderful.” Sara lowered her voice. “My dad’s agreed I can study art. I won’t leave for school until spring, and I have to save every cent I earn to help cover my expenses. But all winter I can look forward to going.” Daphne touched the back of Sara’s hand with her fingertips. “I’m glad for you. You have a wonderful talent. You must promise that you’ll write and tell me all about the school and its instructors once you’re there.” “’Course I will. If it wasn’t for your encouragement, I never would’ve had the nerve to ask my dad to let me go.” Daphne had done little besides tell Sara that she shouldn’t give up on her dreams, no matter how long it took, that God could open doors in surprising ways if she would simply trust Him. But she was glad Sara had found her words to be helpful and even more glad that Sara’s father had consented. “I believe art school will be the making of you. Wait and see if I’m not right.” As Sara disappeared into the restaurant kitchen, the front door opened, letting in the cool night air along with a man Daphne had never seen before. He was tall, at least six feet, perhaps a little more. He had brown hair that was shaggy near his collar, and unless the poor light in the restaurant deceived her, there was the shadow of a beard under the skin of his jaw and upper lip. Who was he? Not a cowboy nor a miner. That was clear by the clothes he wore. His suit appeared of good quality, but even from where she sat she could tell it had seen its share of wear. A man of trade perhaps or a salesman. Definitely not a guest of her brother’s spa, for he looked neither wealthy nor in poor health. At that moment, the stranger turned his head and his gaze met hers. She swallowed a gasp of surprise. Good heavens! He had the most astonishing eyes. What color were they? She wished she could tell. So pale. Perhaps blue. Or maybe a silvery-gray. No, they were blue. She was sure of it. And she seemed unable to look away, even when she knew she should. Thankfully, he broke the connection and moved to a table, sitting in a chair with his right side toward her. Daphne drew a hungry breath into her lungs. Until that moment she hadn’t known she’d held it. Could I capture his eyes with words? What a character he would make. He could be Bill’s friend. Perhaps he could ride with him for the next few adventures. What name should I give him? She pulled a small notebook and the stub of a pencil from her pocket and made a few notes to herself. In Daphne’s fourth, fifth, and sixth novels, her hero, Bill McFarland, had courted a woman in Idaho City, but she’d grown tired of waiting for him to propose and had married someone else. Perhaps this new friend with his magnetic eyes could help Bill find the right woman, one who wouldn’t object to his adventurous spirit. Then again, Bill would have to watch out or his new friend might steal the right woman for himself. The thought caused her to glance up from her notebook — only to discover he was looking in her direction. Her breath caught for a second time and a blush warmed her face as she dropped her gaze again. Oh, yes. Mr. Blue Eyes would definitely make things interesting for the readers of The McFarland Chronicles. She hoped her dinner would arrive soon. Another late-night writing session was looming. **** December 5, 1871 There comes a time in a man’s life when it seems prudent that he look hard at his past, to remember from whence he came, to learn to be grateful for God’s mercy, perhaps even for the purpose of becoming a cautionary tale for others. And so I have decided to write an account of my life, from beginning to the present, knowing all the while that the future will be significantly different from those years that have gone before. In truth, I already know that my life will soon change for the better. I know this because, at the age of fifty, I am about to take a wife. No former associate of mine could be more surprised at this news than I am. I never believed I was the marrying kind. Nor would I have believed a woman as fine as my Annie would agree to be my wife, especially after she learned of my less than pristine past. But I am getting ahead of myself. A record of my life should begin at the beginning. And so it shall. **** I was born on a small farm in Missouri in the winter of 1821, the youngest of five children, all boys. My parents came to the region after the War of 1812, along with many other settlers. Like most everyone they knew, my parents were poor. They eked out a living the only way they knew how, through hard work and sweat and tears. They weren’t educated, and they yearned for something quite different for their children. It amazes me, as I look back, that my mother managed to teach her sons so much when she never attended school a day in her life. Not that I appreciated her efforts back then. All I wanted when I was a lad was to go fishing or hunting or even just to lie on my back on a hot summer day and watch the clouds drift by. Still, despite my lack of enthusiasm, I learned to read and write and do arithmetic. I even came to appreciate, albeit many years later, the wisdom and enjoyment that could be found in books. My parents were god-fearing people, but since there was no church within easy distance of our farm, it fell to my father and mother to see that their sons came to know the Bible and to embrace the tenants of the Christian faith. In this regard, I was even less enthusiastic. Rebellion resided in my stubborn heart, and it did not matter if my father took a strap to me or my mother sweetly entreated me. I would not yield. Perhaps, given enough time, I might have come to know the God my parents believed in. But there wasn’t enough time. They died of the fever when I was eight years old, along with two of my brothers. Moses was ten and Oliver was nine. That was in the winter of 1829. February, I believe. There was deep snow on the ground and the temperatures were frigid. My surviving two brothers could manage no more than shallow graves as the ground was frozen hard. I have never confessed this to a living soul, but I cried myself to sleep at night more often than not in the months that followed. My two oldest brothers, Jefferson and Lyman, took over running the farm and raising me. They did the best they were able, them being just boys themselves, Jefferson not yet eighteen, Lyman only sixteen. I wish now that I had appreciated them more. After I stopped crying myself to sleep at night, anger took the place of tears. I was angry with everyone, and my temper got me into plenty of trouble. I was fourteen the year I hit Lyman so hard I broke his nose. Of course, he gave me back in kind. A few weeks later, I struck out on my own. I never knew what happened to my brothers. By the time I got to an age and a place where I wanted to get in touch with them, where I would have liked to see them again, they were gone. I was told they sold the farm and nobody knew where they went from there. I have often wondered if they are still alive. I wonder if they think of me and wonder the same. Get info on my latest Regency romance novel. I only send out an email when I have a new release or a sale on one of my books. (My contemporary romance and romantic suspense newsletter signup is below.)
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983 F.Supp. 977 (1997) SITHON MARITIME COMPANY, Plaintiff, v. HOLIDAY MANSION, a Division of Mohawk, Inc., and Mercury Marine, a Division of Brunswick Corporation, Defendants. No. CIV. A. 96-2262-EEO. United States District Court, D. Kansas. October 22, 1997. *978 *979 *980 *981 Lee M. Smithyman, Smithyman & Zakoura, Chtd., Overland Park, KS, Michael G. Chalos, Richard M. Ziccardi, George J. Tsimis, New York City, for Plaintiff Sithon Maritime Co. Norman R. Kelly, Norton, Wasserman, Jones & Kelly, Salina, KS, Anthony M. DeMarea, Shughart, Thompson & Kilroy, Overland Park, KS, for Defendant Holiday Mansion. Heather Suzanne Woodson, Stinson, Mag & Fizzell, P.C., Overland Park, KS, John C. Aisenbrey, Stinson, Mag & Fizzell, P.C., Kansas City, MO, Alex B. Marconi, Patrick X. Fowler, Snell & Wilmer L.L.P., Phoenix, AZ, for Defendant Mercury Marine. MEMORANDUM AND ORDER EARL E. O'CONNOR, District Judge. This matter is before the court on the motion for summary judgment of defendant Mercury Marine ("Mercury") on plaintiff's complaint (Doc. # 73), and defendant Mercury's motion for summary judgment on defendant Holiday Mansion's cross-claim (Doc. # 124). After careful consideration of the parties' briefs and evidentiary materials, the court is prepared to rule. For the reasons stated below, Mercury's motion on plaintiff's complaint is granted as to counts I, II, V, VIII, and IX, granted in part and denied in part as to counts IV and VII, and denied as to counts III and VI. Mercury's motion is granted as to all counts on defendant Holiday Mansion's cross-claim. Summary Judgment Standards Summary judgment is appropriate "if the pleadings, depositions, answers to interrogatories, and admissions on file, together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law." Fed.R.Civ.P. 56(c); accord Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 247, 106 S.Ct. 2505, 2510, 91 L.Ed.2d 202 (1986); Vitkus v. Beatrice Co., 11 F.3d 1535, 1538-39 (10th Cir.1993). A factual dispute is "material" only if it "might affect the outcome of the suit under the governing law." Anderson, 477 U.S. at 248, 106 S.Ct. at 2510. The moving party bears the initial burden of showing that there is an absence of any genuine issue of material fact. Celotex Corp. v. Catrett, 477 U.S. 317, 323, 106 S.Ct. 2548, 2552-53, 91 L.Ed.2d 265 (1986); Hicks v. City of Watonga, 942 F.2d 737, 743 (10th Cir.1991). Essentially, the inquiry as to whether an issue is genuine is "whether the evidence presents a sufficient disagreement to require submission to the jury or whether it is so one-sided that one party must prevail as a matter of law." Anderson, 477 U.S. at 251-52, 106 S.Ct. at 2511. An issue of fact is genuine if the evidence is sufficient for a reasonable jury to return a verdict for the nonmoving party. Id. at 248, 106 S.Ct. at 2510. This inquiry necessarily implicates the substantive evidentiary standard of proof that would apply at trial. Id. at 252, 106 S.Ct. at 2511-12. Once the moving party meets its burden, the burden shifts to the nonmoving party to demonstrate that genuine issues remain for trial "as to those dispositive matters for which it carries the burden of proof." Applied Genetics Int'l, Inc. v. First Affiliated Sec., Inc., 912 F.2d 1238, 1241 (10th Cir. 1990); see also Matsushita Elec. Indus. Co. v. Zenith Radio Corp., 475 U.S. 574, 586-87, 106 S.Ct. 1348, 1355-56, 89 L.Ed.2d 538 (1986); Bacchus Indus., Inc. v. Arvin Indus., Inc., 939 F.2d 887, 891 (10th Cir.1991). The nonmoving party may not rest on his pleadings but must set forth specific facts. Applied Genetics, 912 F.2d at 1241. "[W]e must view the record in the light most favorable to the parties opposing the motion for summary judgment." Deepwater Invs., Ltd. v. Jackson Hole Ski Corp., 938 F.2d 1105, 1110 (10th Cir.1991). "In a response to a motion for summary judgment, a party cannot rely on ignorance of facts, on speculation, or on suspicion, and may not escape summary judgment in the mere hope that something will turn up at trial." Conaway v. Smith, 853 F.2d 789, 793 (10th Cir. 1988). The mere existence of some alleged factual dispute between the parties will not defeat an otherwise properly supported motion for summary judgment. Anderson, 477 U.S. at 256, 106 S.Ct. at 2514. Where the nonmoving party fails to properly respond to the motion for summary judgment, the facts *982 as set forth by the moving party are deemed admitted for purposes of the summary judgment motion. D.Kan.Rule 56.1. In this diversity case, we ascertain and apply Kansas law with the objective that the result obtained in federal court should be the same result as in a Kansas court. See Adams-Arapahoe School Dist. No.28-J v. GAF Corp., 959 F.2d 868, 870 (10th Cir.1992). With respect to plaintiff's fraud claims under Kansas law, federal law standards for granting summary judgment apply. See Fed.R.Civ.P. 56. In Anderson v. Liberty Lobby, 477 U.S. at 252, 255, 106 S.Ct. at 2512, 2513-14, the United States Supreme Court held: we are convinced that the inquiry involved in a ruling on a motion for summary judgment or for a directed verdict necessarily implicates the substantive evidentiary standard of proof that would apply at the trial on the merits.... Consequently, where the ... "clear and convincing" evidence requirement applies, the trial judge's summary judgment inquiry as to whether a genuine issue exists will be whether the evidence presented is such that the jury applying that evidentiary standard could reasonably find for either the plaintiff or the defendant. Allegations of fraud must be proven by clear and convincing evidence. See Rajala v. Allied Corp., 919 F.2d 610, 626 (10th Cir.1990), cert. denied, 500 U.S. 905, 111 S.Ct. 1685, 114 L.Ed.2d 80 (1991); Sipes v. Crum, 204 Kan. 591, 464 P.2d 1, 6 (1970). Thus, plaintiff as the nonmoving party carrying the burden of proof at trial must present sufficient evidence of a clear and convincing nature to withstand summary judgment on its fraud claims. See Ramirez v. IBP, Inc., 913 F.Supp. 1421, 1430 (D.Kan.1995); Sprague v. Peoples State Bank, Colby, Kan., 844 F.Supp. 662, 667 (D.Kan.1994); All West Pet Supply Co. v. Hill's Pet Prods. Div., Colgate-Palmolive Co., 840 F.Supp. 1426, 1431 (D.Kan.1993). Analysis I. Mercury's Motion For Summary Judgment On Plaintiff's Complaint. A. Factual Background. For purposes of defendant's motion, the following is a brief summary of the material facts that are uncontroverted, deemed admitted, or where controverted viewed in the light most favorable to the non-movant, pursuant to Federal Rule of Civil Procedure 56 and District of Kansas Rule 56.1. Plaintiff Sithon Maritime Company ("Sithon") was organized in December 1994 for the purpose of obtaining exclusive government issued permits to operate a high speed ferry boat service to shuttle passengers between two of three peninsulas in Northern Greece. In late 1994, Mr. Vagianos, who later became president of Sithon, began negotiating with defendant Holiday Mansion for the possible purchase of four 50-passenger ferry boats. Mr. Vagianos advised Holiday Mansion that the boats needed to achieve a cruising speed of at least 24 knots for the anticipated ferry service and that the ferry boats would run 24 hours a day. Holiday Mansion advised Mr. Vagianos that the ferries could be powered by either two Mercury 7.3L diesel engines and Bravo III stern drives or by two Volvo diesel engines and stern drives. Mr. Byquist of Holiday Mansion advised Mr. Vagianos that the Mercury engines had more horsepower and would allow the boats to go faster than boats equipped with the Volvo engines. Mr. Byquist told Mr. Vagianos that he would contact Mercury to confirm that Mercury's engines would meet Mr. Vagianos' speed requirements. Mr. Vagianos testified that Mr. Byquist told Mr. Vagianos that he received assurances from Mercury personnel that its propulsion system would enable the Holiday Mansion ferry boats to attain a cruising speed of 24 knots and a maximum speed of 28 knots. Mr. Byquist denies making this statement to Mr. Vagianos. Mr. Byquist testified that (1) no one at Mercury told anyone at Holiday Mansion that the boats sold to Sithon would travel 24 knots cruising speed or 28 knots maximum speed when equipped with the Mercury stern drive engines; (2) no one at Mercury endorsed using the Mercury stern drive engines with the boats sold to Sithon; and (3) no one at Mercury told Holiday Mansion that the boats sold to Sithon would be a proper application for the Mercury stern drive engines. *983 Before purchasing the boats, Sithon requested and received from Mr. Brown of Holiday Mansion a letter representing that the boats equipped with Mercury engines would have a cruising speed of 24 knots and a maximum speed of 28 knots. Mr. Brown testified that he had no factual basis for making the representation and that he did not consult with anyone at Holiday Mansion or Mercury before making the representation. Holiday Mansion asked Alan Fila of Mercury for the proper gear drive ratio and propeller pitch for the boats. After consulting with various Mercury employees, Mr. Fila recommended to Holiday Mansion a gear drive ratio of 1.65 to 1 with 20-pitch propellers. On or about January 5, 1995, Sithon agreed to purchase the four passenger ferry boats from Holiday Mansion. In manufacturing the boats, Holiday Mansion set the gear ratios and purchased propellers in accordance with Mr. Fila's recommendations. A Mercury field engineer visited the Holiday Mansion factory and inspected the installation of the Mercury engines and stern drives into one of the four boats. In February 1995, Mr. Vagianos of Sithon received a copy of a Mercruiser/Mercury operation and service manual from Holiday Mansion. Warranty information is contained in the manual starting at the top of page 84. The actual "Warranty Policy" is on pages 86 and 87 and contains eleven numbered paragraphs. Paragraph 10 of the warranty policy provides: WARRANTIES OF MERCHANTABILITY AND FITNESS ARE EXCLUDED FROM THIS WARRANTY. IMPLIED WARRANTIES ARE LIMITED TO THE LIFE OF THIS WARRANTY. SOME STATES OR COUNTRIES DO NOT ALLOW LIMITATIONS ON HOW LONG AN IMPLIED WARRANTY LASTS OR THE EXCLUSION OR LIMITATION OF INCIDENTAL OR CONSEQUENTIAL DAMAGES, SO THE ABOVE LIMITATION OR EXCLUSIONS MAY NOT APPLY TO YOU. Sithon received the four ferry boats from Holiday Mansion in April. On May 19, 1995, Sithon commenced its ferry boat operations in Northern Greece. Within days, the propulsion systems of all four boats began to experience various mechanical problems during operation. The four boats could reach speeds of only 16 knots when empty and approximately 12 to 13 knots when full. On June 1, Holiday Mansion advised Mercury that the Mercury propulsion systems installed on Sithon's boats were not working properly. On June 5, Jim Puddy of Mercury's International Service Department concluded that the boats required a 2 to 1 gear drive ratio and that the Bravo III stern drives should be replaced with Bravo II stern drives. Mercury implemented these changes on the boats in June 1995. On or about July 6, the propulsion systems on the Sithon ferries continued to malfunction. In particular, the hard rubber hubs of the new propellers on the Bravo II stern drives melted during operation. As a result of the propeller and other mechanical problems, Sithon was forced to take three of its four boats out of service. On July 10, another Mercury representative advised Holiday Mansion that the 2 to 1 gear drive ratio would over-torque the engines and cause propeller hubs to be more susceptible to failing. In mid-July, Mercury concluded that the passenger boats were too heavy for the Mercury engines. On at least two occasions in July 1995, a Sithon boat lost all propulsion power. On one occasion, a Sithon boat filled with passengers broke down at sea in the middle of the night. The passengers were stranded until another boat could be located to pick up the passengers. In early August 1995, Mercury replaced two of the 7.3L diesel engines in one of Sithon's boats with two new engines. The two new engines had lower horsepower than the original engines in an attempt to address the problems of overheating and wear. A Mercury representative observed the installation of these two new engines and conducted various tests on the boat. Mercury subsequently sent six additional engines for installation into Sithon's boats. Four of the six engines were installed. Sithon's boats *984 continued to experience many of the same mechanical problems in 1996. B. Breach Of Contract (Count VIII). Sithon alleges that Mercury breached its contract with Sithon for the sale of the four ferry boats. Sithon claims that the following evidence establishes that a contract existed between Mercury and Sithon: (1) Mercury provided Holiday Mansion with information regarding the speed performance of the boats, (2) Mercury recommended to Holiday Mansion the gear ratio and propeller pitch size for the propulsion systems to be used on the boats, and (3) a Mercury field engineer inspected and approved the installation of the Mercury propulsion systems in Sithon's passenger boats. Sithon has failed to present sufficient evidence to raise an issue of material fact as to whether a contract for sale of the boats existed between Sithon and Mercury. The Kansas Supreme Court has held repeatedly that "[i]n order to form a binding contract, there must be a meeting of the minds on all essential terms." Albers v. Nelson, 248 Kan. 575, 580, 809 P.2d 1194, 1198 (1991); see Sidwell Oil & Gas Co., Inc. v. Loyd, 230 Kan. 77, 79, 630 P.2d 1107, 1110 (1981). "To constitute a meeting of the minds there must be a fair understanding between the parties which normally accompanies mutual consent and the evidence must show with reasonable definiteness that the minds of the parties met upon the same matter and agreed upon the terms of the contract." Sidwell, 230 Kan. at 84, 630 P.2d at 1113 (quoting Steele v. Harrison, 220 Kan. 422, 428, 552 P.2d 957, 962 (1976)). Sithon has not offered any evidence which tends to establish a meeting of the minds between Mercury and Sithon regarding the terms for sale of the four ferry boats. Although Sithon contracted with Holiday Mansion, Mercury was not a party to the contract. Sithon also has failed to come forward with any evidence of the alleged terms of the sales contract between Mercury and Sithon. Mercury is not liable on the contract between Holiday Mansion and Sithon by supplying Holiday Mansion with various parts or even by recommending specific actions to be taken on Sithon's boats. Accordingly, the court will grant summary judgment in favor of defendant Mercury on count VIII of Sithon's complaint. C. Express Warranty Regarding Speed (Count I). Sithon alleges that Mercury breached its express warranty that the passenger boats, if equipped with the Mercury propulsion systems, would attain a cruising speed of at least 24 knots. Sithon's claim is based on section 2-313 of the Kansas Uniform Commercial Code ("UCC"). See Kan.Stat.Ann. § 84-2-313(1)(a) ("[a]ny affirmation of fact or promise made by the seller to the buyer which relates to the goods and becomes part of the basis of the bargain creates an express warranty that the goods shall conform to the affirmation or promise."). "Express warranties are those for which the buyer bargained; they go to the essence of the bargain, being a part of its basis, and are contractual, having been created during the bargaining process." Corral v. Rollins Protective Services Co., 240 Kan. 678, 685, 732 P.2d 1260, 1266 (1987) (quoting 67A Am.Jur.2d, Sales § 690). "It is clear that for there to be an express warranty there must be an explicit statement, written or oral, by the party to be bound prior to or contemporaneous with the execution of the contract." Id. To prevail on its claim, Sithon must prove that Mercury made an express warranty to Sithon regarding what speed the boats could achieve if equipped with the Mercury engines and that Sithon relied upon the warranty. See Owens-Corning Fiberglas Corp. v. Sonic Development Corp., 546 F.Supp. 533, 541 (D.Kan.1982). Mercury contends that it never made any express warranty to Sithon regarding the speed of the ferry boats. Sithon's only evidence on this point consists of the testimony of Mr. Vagianos of Sithon. Mr. Vagianos testified that Mr. Byquist of Holiday Mansion told him that an unnamed Mercury representative told Mr. Byquist that the boats equipped with Mercury engines could attain a cruising speed of 24 knots and a maximum speed of 28 knots. Mr. Byquist specifically denies making this statement to Mr. Vagianos. Mr. Vagianos' testimony regarding *985 what Mercury represented to Mr. Byquist constitutes inadmissible hearsay. Mr. Vagianos was not present when the Mercury representative allegedly made the statement to Mr. Byquist. Sithon offers the statement of the unnamed Mercury representative for the truth of the matter asserted. The statement, however, does not fall within any of the exceptions to the hearsay rule. Even if the court considers Mr. Vagianos' testimony, Sithon has not produced sufficient evidence to show that Mercury ever made any explicit statements to Sithon regarding the speed of the boats as required for an express warranty claim. In this case, the absence of a direct relationship between Mercury and Sithon is fatal to Sithon's express warranty claim regarding speed of the boats. See Wight v. Agristor Leasing, 652 F.Supp. 1000, 1011 (D.Kan.1987); AgriStor Leasing v. Meuli, 634 F.Supp. 1208, 1219 (D.Kan.1986). Although an express warranty claim can be premised on an indirect relationship between the buyer and manufacturer, as when the buyer relies on a manufacturer's advertisement before purchasing the product from a third party, no such facts are present in this case. See, e.g., Cricket Alley Corp. v. Data Terminal Sys., Inc., 240 Kan. 661, 665, 732 P.2d 719, 723 (1987) (citing comment to Kan.Stat.Ann. § 84-2-313). Moreover, Sithon has not alleged or presented any evidence to establish that Holiday Mansion was in any way acting as Mercury's agent with respect to the alleged representations of boat speeds made by Holiday Mansion. Sithon argues that a disputed issue of fact exists because there is some evidence which indicates that Mercury made representations as to expected speed of boats to two other customers. Sithon argues that this evidence is contrary to Mercury's position that it does not discuss with its customers expected speeds of boats equipped with Mercury engines. Although Sithon's evidence raises a disputed issue as to whether Mercury has made representations regarding the speed of boats to some of its customers, the evidence does not create a disputed factual issue as to whether Mercury made any representations to Sithon regarding the speed of the boats it purchased from Holiday Mansion. For the above reasons, the court will grant summary judgment in favor of defendant Mercury on count I of Sithon's complaint. D. Breach Of Contract (Count IX). Sithon alleges that Mercury breached its contract with Sithon to repair and correct the mechanical problems with the propulsion systems. Mercury first maintains that Sithon has failed to establish that a binding contract existed between the parties. As noted above, to form a binding contract, "there must be a meeting of the minds on all essential terms." Albers, 248 Kan. at 580, 809 P.2d at 1198. "To constitute a meeting of the minds there must be a fair understanding between the parties which normally accompanies mutual consent and the evidence must show with reasonable definiteness that the minds of the parties met upon the same matter and agreed upon the terms of the contract." Sidwell, 230 Kan. at 84, 630 P.2d at 1113 (internal quotation omitted). Sithon claims that there is sufficient evidence for the trier of facts to find that a binding contract existed between Sithon and Mercury. The court has sifted through plaintiff's reference to 53 statements of fact and underlying documentation, which allegedly support its breach of contract claim. Only two of the statements of fact are even arguably relevant to the issue of whether a contract to correct and repair the propulsion systems existed. At most, plaintiff has presented evidence that (1) on June 5, 1995, Holiday Mansion sent Mercury a letter stating that Sithon is ready to go to the American Embassy and their lawyers regarding the problems with the boats, (2) a Mercury representative stated in a June 5, 1995 internal memorandum that Mercury is willing to do a customer relations repair on the boats at no cost to Sithon or Holiday Mansion, and (3) Mercury representatives told a Sithon representative in July 1995 that the new Bravo II engines would allow the engines to work at the correct RPM. Based on the record evidence, no reasonable juror could find the necessary "meeting of the minds" between Sithon and Mercury. There is no *986 evidence to show with reasonable certainty that the minds of the parties met upon the same matter and agreed upon the terms of the contract. See Sidwell, 230 Kan. at 84, 630 P.2d at 1113. Therefore, the court will grant summary judgment in favor of defendant Mercury on count IX of plaintiff's complaint. E. Express Warranty Regarding Repairs (Count II). Sithon alleges that Mercury expressly warranted that it would correct all of the mechanical problems connected to the propulsion systems on Sithon's boats. Mercury argues that Sithon's claim fails because express warranties cannot arise unless there is a contract for sale. Express warranties, however, are not limited to contracts for sale and may be present in any type of contract. See Corral, 240 Kan. at 684, 732 P.2d at 1265. As noted above, "for there to be an express warranty there must be an explicit statement, written or oral, by the party to be bound prior to or contemporaneous with the execution of the contract." Id. In addition, plaintiff must establish that he relied upon the express warranty made by the defendant. See Owens-Corning, 546 F.Supp. at 541. Sithon's express warranty claim regarding repairs fails for several reasons. First, Sithon has not presented any evidence of an explicit oral or written statement by Mercury of a warranty regarding repairs. Moreover, Sithon has not presented sufficient evidence to establish that Sithon and Mercury ever executed a contract. Although Kansas courts do not require a direct buyer-seller relationship as a predicate for an express warranty claim, there must be some contract. See Corral, 240 Kan. at 685, 732 P.2d at 1266 (contract required); Professional Lens Plan, Inc. v. Polaris Leasing Corp., 234 Kan. 742, 751, 675 P.2d 887, 895 (1984) ("[T]he law permits a non-privity buyer to recover for direct economic loss if the remote seller has breached an express warranty."); Fullerton Aircraft Sales & Rentals, Inc. v. Beech Aircraft Corp., 842 F.2d 717 (4th Cir. 1988) (applying Kansas law, privity of contract not required). Here, Sithon does not present evidence of any contract executed subsequent or contemporaneous with the alleged express warranty to correct and repair the propulsion systems. With no contract, there are no express warranties. Finally, Sithon has not established that it took any actions in reliance on the alleged representations made by Mercury. The vague statement made by a Holiday Mansion representative that Sithon may go to its attorneys is insufficient to show that Sithon relied on any alleged warranty regarding repairs made by Mercury. Accordingly, defendant Mercury is entitled to summary judgment on count II of Sithon's complaint. F. Covenant Of Good Faith And Fair Dealing (Count V). Sithon alleges that Mercury breached the covenant of good faith and fair dealing under section 1-203 of the Uniform Commercial Code. See Kan.Stat.Ann. § 84-1-203 ("Every contract or duty within this act imposes an obligation of good faith in its performance or enforcement."). Sithon argues that such a duty exists in this case because of the alleged contracts between Sithon and Mercury for the sale of the boats and for repair of the propulsion systems. As noted above, Sithon has not presented sufficient evidence to establish that either contract exists. Therefore, the court will grant summary judgment in favor of defendant on count V of plaintiff's complaint. G. Implied Warranty Of Merchantability (Count III) And Fitness For A Particular Purpose (Count IV). Sithon alleges that Mercury breached an implied warranty of merchantability because the Mercury propulsion systems were not fit for the ordinary purpose of being used in passenger ferry boats. See Pl's Compl. ¶ 85. Sithon also alleges Mercury breached an implied warranty of fitness for a particular purpose because (1) Mercury knew at the time it installed the engines that an express requirement of the sales contract between Sithon and Holiday Mansion was that the ferry boats could travel at 24 knots cruising speed and 28 knots maximum speed and (2) Mercury knew at the time it repaired the engines in the Summer of 1995 that Sithon *987 required that the ferry boats could travel at 24 knots cruising speed and 28 knots maximum speed. See Pl's Compl. ¶¶ 95-97. Mercury argues that all of Sithon's claims for implied warranties fail because Mercury disclaimed such warranties and there was no privity of contract between Sithon and Mercury. In addition, Mercury argues that Sithon failed to present sufficient evidence in support of its implied warranty of fitness claims because there is no evidence that Mercury knew of Sithon's speed requirements. The court will separately address each of Mercury's arguments. 1. Disclaimer Of Implied Warranties. Mercury argues that all of Sithon's claims for implied warranties fail because Mercury properly excluded the implied warranties of merchantability and fitness pursuant to the Kansas UCC. See Kan.Stat.Ann. § 84-2-316(2). Mercury argues that no Kansas case has addressed the issue of how a remote manufacturer can exclude implied warranties. Mercury concludes that no "basis of the bargain" requirement can logically be imposed where there was no bargain between Sithon and Mercury. We agree that a basis of the bargain requirement seems inapplicable to disclaimers of implied warranties by remote manufacturers. The other requirements of the Kansas UCC, however, are relevant. To exclude the implied warranty of merchantability, a party must mention the word "merchantability" in the exclusion and, if the exclusion is in writing, it must be conspicuous. See id. To exclude the implied warranty of fitness, the exclusion must be in writing and conspicuous. See id. Mercury's disclaimer is contained on page 87 of its operation and service manual. There is a title "Warranty Information" at the top of page 84 of the manual. The actual "Warranty Policy" is on pages 86 and 87 and contains eleven numbered paragraphs. The disclaimer at issue appears in the tenth paragraph. The disclaimer provides: WARRANTIES OF MERCHANTABILITY AND FITNESS ARE EXCLUDED FROM THIS WARRANTY. IMPLIED WARRANTIES ARE LIMITED TO THE LIFE OF THIS WARRANTY. SOME STATES OR COUNTRIES DO NOT ALLOW LIMITATIONS ON HOW LONG AN IMPLIED WARRANTY LASTS OR THE EXCLUSION OR LIMITATION OF INCIDENTAL OR CONSEQUENTIAL DAMAGES, SO THE ABOVE LIMITATION OR EXCLUSIONS MAY NOT APPLY TO YOU. Mercury certainly meets the requirements of mentioning the word "merchantability" and having the exclusion in writing. The critical issue, however, is whether Mercury's disclaimer is conspicuous. The Kansas Uniform Commercial Code provides: A term or clause is conspicuous when it is so written that a reasonable person against whom it is to operate ought to have noticed it. A printed heading in capitals (as: NON-NEGOTIABLE BILL OF LADING) is conspicuous. Language in the body of a form is "conspicuous" if it is in larger or other contrasting type or color.... Whether a term or clause is "conspicuous" or not is for decision by the court. Kan.Stat.Ann. § 84-1-201(10). "In determining conspicuousness of a disclaimer, the court must consider the entire document." Kelley Metal Trading Co. v. Al-Jon/United, Inc., 812 F.Supp. 185, 189 (D.Kan.1993) (citing J & W Equipment, Inc. v. Weingartner, 5 Kan.App.2d 466, 618 P.2d 862, 866 (1980)). "Contrasting type, ink color, and type size are relevant factors in the determination, but they are not the sole arbiters." Kelley, 812 F.Supp. at 189 (citing J & W Equipment). Although the disclaimer in the instant action is in capital letters, the court finds that the disclaimer is not conspicuous when viewed in light of the entire document. In particular, the exclusion appears on page 87 of an operation and maintenance manual, a document neither party signed and a document Sithon did not receive until after it agreed to purchase the Holiday Mansion boats equipped with Mercury engines. In addition, the disclaimer appears near the end of the warranty policy and is not set off from the text around it except by capital letters. We note that other parts of the manual have been set off with more distinctive features. *988 For the above reasons, the court finds that Mercury's disclaimers did not exclude the implied warranties of merchantability and fitness as to Sithon. 2. Privity Of Contract. Mercury also argues that all of Sithon's implied warranty claims are barred because there is no privity of contract between Mercury and Sithon. "[I]mplied warranties are imposed by operation of law in Kansas on public policy grounds and without regard to whether the parties to the implied warranty are in `privity' or whether the loss suffered is purely economic when the product is such that it would be inherently dangerous if defectively manufactured." Fullerton, 842 F.2d at 721 (4th Cir.) (applying Kansas law) (citing Professional Lens, 234 Kan. 742, 755, 675 P.2d 887, 898-99 (1984)); see Boehm v. Fox, 473 F.2d 445, 449 (10th Cir.1973) ("An implied warranty will be imposed by operation of law on the basis of public policy and privity of contract is not essential.") (citing Evangelist v. Bellern Research Corp., 199 Kan. 638, 433 P.2d 380 (1967)). As noted previously, there is no contractual privity between Sithon and Mercury. In addition, Sithon seeks economic losses in this action. Therefore, to withstand summary judgment on its implied warranty claims, Sithon must establish that engines used for passenger boats can be inherently dangerous if defectively manufactured. In Professional Lens, the alleged defective product was a computer and its hard disc component part, which the court found were not inherently dangerous products. 234 Kan. at 755, 675 P.2d at 898. In other cases, however, courts have held that an aircraft and an automobile tire are inherently dangerous products. See Fullerton, 842 F.2d at 718, 720-22 (alleged defect was "abnormal vibrations" on an aircraft); B.F. Goodrich Co. v. Hammond, 269 F.2d 501, 506 (10th Cir.1959) (tire allegedly did not protect against blow outs). Although no court apparently has decided this precise issue under Kansas law, we conclude that engines for passenger boats fall into the category of inherently dangerous products if defectively manufactured. Indeed, on at least two occasions, Sithon's boats equipped with Mercury engines lost all propulsion power while at sea. The passengers on the boats were stranded and subject to the threat of personal injury. Although privity of contract is not required in this case, Sithon has not provided any authority for the proposition that an implied warranty can arise without any contract at all. Under Kansas law, there must be some contract before an implied warranty of fitness for a particular purpose can arise. See Corral, 240 Kan. at 678, 732 P.2d at 1261, Syl. ¶ 6 (purpose of implied warranties is to protect party from loss where the subject matter of the contract fails to conform to the normal commercial standard or meet the party's known particular purpose). Indeed, section 315 of the Uniform Commercial Code provides that the implied warranty of fitness arises only "[w]here the seller at the time of contracting has reason to know any particular purpose for which the goods are required." Kan.Stat.Ann. § 84-2-315 (emphasis added). Applying the above principles, the court finds that privity of contract is not required for Sithon to maintain its implied warranty of merchantability claim or its implied warranty of fitness claim at the time the engines were installed in the ferry boats. The existence of a sales contract between Sithon and Holiday Mansion may be sufficient to create implied warranties running from Mercury to Sithon. On the other hand, Sithon's claim that an implied warranty of fitness arose when Mercury repaired the propulsion systems in the Summer of 1995 is barred. The court determined previously that Sithon did not present sufficient evidence of a contract to repair between Sithon and Mercury. Without any contract in the Summer of 1995, no implied warranty of fitness could arise. The court also finds that Sithon has failed to present sufficient evidence in support of such a claim. See infra, section 3, Evidence Of Implied Warranty Of Fitness Regarding Speed Of The Ferry Boats. For the above reasons, the court will grant summary judgment in favor of defendant Mercury on Sithon's implied warranty of fitness claim with respect to Mercury's *989 repair of the propulsion systems in the Summer of 1995. 3. Evidence Of Implied Warranty Of Fitness Regarding Speed Of The Ferry Boats. As noted above, Sithon alleges that an implied warranty of fitness from Mercury arose, both at the time the engines were installed and when they were subsequently repaired, that the ferry boats could travel at 24 knots cruising speed and 28 knots maximum speed. With respect to both of these claims, Sithon has failed to present sufficient evidence to establish either (1) Mercury had reason to know that Sithon required water craft that could travel 24 knots cruising speed and 28 knots maximum speed or (2) Mercury had reason to know that Sithon was relying on Mercury to select engines which would enable the water craft to achieve these specified speeds. See Kan.Stat.Ann. § 84-2-315. Accordingly, the court will grant summary judgment in favor of defendant Mercury on both of these claims. Although the court finds in favor of defendant Mercury on the two specific claims for implied warranties of fitness regarding speed of the ferry boats, the court will not grant summary judgment in favor of defendant Mercury on count IV in its entirety. Liberally construing Sithon's complaint, the court finds that Sithon's claim under count III that Mercury breached an implied warranty of merchantability, i.e., the propulsion systems were not fit for the ordinary purpose of being used in passenger ferries also may be pled as a claim under count IV that Mercury breached an implied warranty of fitness, i.e., the propulsion systems were not fit for the particular purpose of being used in passenger ferries. The parties did not specifically address in their briefs whether use of the Mercury propulsion systems in passenger ferry boats is an ordinary or particular use of the systems. Therefore, the court will not dismiss count IV in its entirety at this time. For all of the above reasons, the court will deny Mercury's motion for summary judgment on counts III and IV with respect to Sithon's claim of an implied warranty that the Mercury propulsion systems were not fit for the purpose of being used in passenger ferries. The court will grant summary judgment in favor of Mercury on count IV of Sithon's complaint with respect to Sithon's claim of implied warranties of fitness, both at the time the engines were installed and when they were subsequently repaired, that the water craft would achieve a cruising speed of 24 knots and a maximum speed of 28 knots. H. Fraud (Count VII). Sithon alleges in its complaint that Mercury failed to inform Sithon, both at the time Mercury originally installed the propulsion systems and when it subsequently repaired the propulsion systems, that the boats sold could not reach speeds of 24 knots cruising speed and 28 knots maximum speed. See Pl's Compl. ¶¶ 126-27, 129-30. These two related fraud claims are based on the legal theory of fraud through silence. To prevail on a claim of fraud through silence, plaintiff must show by clear and convincing evidence: (1) defendant had knowledge of material facts which plaintiff did not have and which plaintiff could not have discovered by the exercise of reasonable diligence; (2) defendant was under an obligation to communicate the material facts to the plaintiff; (3) defendant intentionally failed to communicate to plaintiff the material facts; (4) plaintiff justifiably relied on defendant to communicate the material facts to plaintiff; and (5) plaintiff sustained damages as a result of defendant's failure to communicate the material facts to the plaintiff. [citation omitted.] OMI Holdings, Inc. v. Howell, 260 Kan. 305, 344-45, 918 P.2d 1274, 1299 (1996) (quoting Lesser v. Neosho County Community College, 741 F.Supp. 854, 863 (D.Kan.1990)). The court will analyze the above elements separately with respect to each fraud claim. *990 1. Disclosure Of Speeds At Time Of Engine Installation. Sithon first argues that Mercury failed to inform Sithon at the time Mercury installed the engines that the boats equipped with the Mercury propulsion systems could not reach speeds of 24 knots cruising speed and 28 knots maximum speed. Mercury argues that none of the evidence presented by Sithon in its opposition memorandum is relevant to this claim. The court agrees. Sithon has failed to present clear and convincing evidence in support of its fraud claim. First, Sithon has not presented any evidence that Mercury knew at the time the engines were installed what speeds the boats could achieve if equipped with the Mercury propulsion systems. Sithon also has not established that it could not have discovered this information by the exercise of reasonable diligence. Sithon likewise has failed to present any evidence in support of the other elements of a fraudulent omission claim. In particular, Sithon has failed to present any evidence that Mercury intentionally withheld any speed estimates of the boats from Sithon at the time of engine installation or that Sithon justifiably relied on Mercury to communicate this information. In light of the lack of evidence presented by Sithon, the court will grant summary judgment in favor of defendant Mercury on Sithon's claim that Mercury failed to disclose at the time Mercury installed the engines that the boats could not achieve a cruising speed of 24 knots and a maximum speed of 28 knots. See Pl's Compl. ¶¶ 126-27. 2. Disclosure Of Speeds At Time Of Repair. Sithon also contends that Mercury failed to inform Sithon at the time of repair in the Summer of 1995 that the boats equipped with the repaired Mercury propulsion systems could not reach speeds of 24 knots cruising speed and 28 knots maximum speed. Sithon has presented some evidence in support of this claim in its opposition memorandum. Sithon has presented evidence that (1) Mercury knew what speed the boats could achieve after repair and replacement of the propulsion systems, (2) Mercury knew that some of the repairs and changes would reduce the cruising speed of the boats, and (3) Mercury failed to advise Sithon of this information. In their voluminous briefs, neither party specifically discussed this claim factually or with respect to the legal elements of a fraudulent omission claim. Therefore, the court will deny defendant Mercury's motion for summary judgment on this claim. Although the court will not grant summary judgment on Sithon's second fraud claim, the court doubts that the record evidence would be sufficient to withstand a properly supported motion for judgment as a matter of law. In particular, there does not appear to be any record evidence which establishes that (1) Sithon could not have discovered the information regarding speed of the boats by the exercise of reasonable diligence or (2) Sithon justifiably relied on Mercury to communicate such information. Mercury argues in the alternative that Sithon should be required to replead its fraud claim with particularity. The court finds that Sithon's complaint provides Mercury sufficient notice of the particular fraud allegation. The requirement that fraud shall be stated with particularity primarily is to allow the defendant to prepare an adequate responsive pleading. See Todaro v. Orbit Int'l Travel, Ltd., 755 F.Supp. 1229, 1234 (S.D.N.Y.1991); United Nat'l Records, Inc. v. MCA, Inc., 609 F.Supp. 33, 38 (N.D.Ill. 1984). By analogy to the time requirements for pleading defenses under rule 12, a rule 9(b) objection is waived unless made as a separate motion prior to or concurrent with the filing of a responsive pleading. See Todaro, 755 F.Supp. at 1234; MCA, 609 F.Supp. at 38-39. Here, Mercury was on sufficient notice of Sithon's fraud allegations to prepare a detailed answer. Although Mercury raised a general objection under rule 9(b) in its answer, there is no evidence to suggest that Mercury was precluded from drafting an adequate responsive pleading because of the lack of particularity in Sithon's fraud claims. Of course, Sithon may be required to state its fraud claim with more particularity in the pretrial order. *991 3. Sithon's New Fraud Theories. Sithon alleges numerous new fraud theories in its opposition brief and its surreply memorandum. In sum, Sithon argues that Mercury withheld information of the shortcomings of the propulsion systems, knew that it could never repair or improve the performance of the propulsion systems, and nevertheless assured Sithon that it would correct the performance problems. Sithon argues that it relied on Mercury's repeated assurances and accordingly suffered the destruction of its business. Sithon cannot change its fraud theory at this late date. At this point, there is no pretrial order in the case. Pursuant to the Scheduling Order, however, any motions to amend the pleadings by the plaintiff were due on January 2, 1997. Plaintiff has not filed any motions to amend or motions to extend the deadline for filing motions to amend. Therefore, plaintiff's fraud claims are governed by its complaint. The court will not consider the new fraud theories presented in plaintiff's opposition memoranda. Plaintiff cannot present claims that are "moving targets," particularly with respect to claims of fraud which are governed by a heightened standard of pleading. In a footnote, Sithon requests leave to amend its fraud claims to add several new fraud theories. The court will deny Sithon's request for the reasons set forth above. In addition, Sithon has failed to comply with rule 15.1 of the Rules of Practice for the District of Kansas governing motions to amend the pleadings. In particular, Sithon failed to set forth a concise statement of the amendment sought and failed to provide a copy of the proposed amended complaint to the court. Without briefing on the motion or a copy of the proposed amended complaint, the court cannot analyze many of the factors relevant to motions to amend, such as Sithon's delay in seeking the amendment or any prejudice to Mercury. See Castleglen, Inc. v. Resolution Trust Corp., 984 F.2d 1571, 1585 (10th Cir.1993). Based on the record before us, however, we note that any proposed amendment by Sithon to add the referenced fraud claims likely would be futile. Sithon has not set forth facts which establish that (1) Mercury was under an obligation to communicate the material facts to Sithon, (2) Mercury intentionally failed to communicate the material facts to Sithon, or (3) Sithon justifiably relied on Mercury to communicate the facts to Sithon. For the above reasons, Sithon's request to amend its complaint is denied. I. Strict Liability In Tort (Count VI). Sithon alleges that the Mercury propulsion systems were defective and unreasonably dangerous to Sithon's boats. Sithon, as the ultimate purchaser of the propulsion systems, claims that Mercury is responsible for any damages from the propulsion systems under the legal theory of strict liability. Mercury moves for summary judgment on the ground that Sithon suffered only economic loss and therefore cannot recover in tort. In Kansas, "an action for damages from a product's qualitative defects alone without proof of the product's dangerousness cannot sound in tort." Daitom, Inc. v. Pennwalt Corp., 741 F.2d 1569, 1581 (10th Cir.1984); see Winchester v. Lester's of Minnesota, Inc., 983 F.2d 992, 996 (10th Cir.1993); AgriStor Leasing v. Meuli, 634 F.Supp. 1208, 1217 (D.Kan.1986). Thus, the repair or replacement of a defective product itself is considered economic loss for which a plaintiff generally cannot recover in tort. See Winchester, 983 F.2d at 996 (citing East River Steamship Corp. v. Transamerica Delaval, Inc., 476 U.S. 858, 871, 106 S.Ct. 2295, 2302, 90 L.Ed.2d 865 (1986)). Here, Sithon seeks recovery for damage to the propulsion systems and the water craft, as well as lost profits resulting from the failure of the propulsion systems. Although damage to a defective product itself often is characterized as economic loss, courts have allowed recovery of such losses if the product was "unreasonably dangerous." See Champlain Enterprises. Inc. v. United States, 945 F.Supp. 468, (N.D.N.Y.1996) (applying Kansas law) (plaintiff can recover for damage to the aircraft if plaintiff establishes that the aircraft was unreasonably dangerous); Fordyce Concrete, Inc. v. Mack Trucks, Inc., 535 F.Supp. 118, 126 (D.Kan.1982) (physical damage upon a defective product or upon other property resulting from an unreasonably *992 dangerous defective product is recoverable); see also Elite Professionals, Inc. v. Carrier Corp., 16 Kan.App.2d 625, 625, 633, 827 P.2d 1195, 1197, 1202 (1992) (damage to meat inside refrigeration unit did not constitute economic loss, issue of fact as to whether truck refrigeration unit was unreasonably dangerous); Mississippi Power & Light Co. v. Branson Aircraft Corp., 797 F.Supp. 871, 873 (D.Colo.1992) (applying Kansas law) ("tort recovery for injury to the defective product is not barred by the economic loss rule if the plaintiff is attempting to recover property damages, as distinguished from purely economic damages."). In Fordyce, we held that "the Kansas Supreme Court, if faced with the question before us, would once again follow the explicit language of § 402A [of the Restatement (Second) of Torts] and allow plaintiff to recover for physical damage to property resulting from an unreasonably dangerous defective product regardless of whether the damage is inflicted upon the defective product or upon other property." In Fordyce, we relied on Kansas cases that consistently interpreted section 402A broadly, permitting expansive recovery under a strict liability in tort theory. See id.; Kennedy v. City of Sawyer, 228 Kan. 439, 445-46, 618 P.2d 788, 794 (1980) (imposing liability for property damage incurred by bystanders or third parties under strict liability "is based on a desire to achieve maximum protection for the injured party and to promote the public interest in discouraging the marketing of products having defects that are a menace to the public."). We now must decide whether Sithon has presented sufficient evidence that Mercury's propulsion systems were unreasonably dangerous to survive summary judgment. The Kansas Supreme Court has found that a condition is unreasonably dangerous "if it is dangerous when used in the way it is ordinarily used considering the product's characteristics and common usage, and is dangerous to the extent beyond that which would be contemplated by the ordinary consumer who purchased it, with the ordinary knowledge common to the community as to its characteristics." Jenkins v. Amchem Prods., Inc., 256 Kan. 602, 623-24, 886 P.2d 869, 882 (1994), cert. denied, ___ U.S. ___, 116 S.Ct. 80, 133 L.Ed.2d 38 (1995). Mercury has not offered any evidence to controvert Sithon's evidence that its passenger boats lost all propulsion power on two occasions and broke down while at sea. On one occasion, the boat filled with passengers broke down in the middle of the night. The passengers were stranded, frightened, and many of them were screaming because of the threat of personal injury. Based on the record evidence, we cannot conclude as a matter of law that the Mercury propulsion systems were not unreasonably dangerous. If Sithon establishes at trial that the Mercury propulsion systems were unreasonably dangerous, Sithon may be able to recover on its strict liability claims for damages to the propulsion systems and its water craft. Neither party has addressed whether Sithon also can recover lost profits in the event it can establish that the propulsion systems were unreasonably dangerous. In light of the absence of briefing on this point, the court will not decide the issue at this time. For all of the above reasons, the court will deny Mercury's motion for summary judgment as to count VI of Sithon's complaint. II. Mercury's Motion For Summary Judgment On Holiday Mansion's Cross-Claim. Mercury has filed a motion for summary judgment on Holiday Mansion's cross-claim. Holiday Mansion has failed to file a response to this motion. Pursuant to rule 7.4 of the Rules of Practice for the District of Kansas, the court will consider defendant's motion as uncontested. Ordinarily, such motions are granted without further notice. A. Factual Background. For purposes of defendant's motion, the following is a brief summary of the material facts that are uncontroverted, deemed admitted, or where controverted viewed in the light most favorable to the non-movant, pursuant to Federal Rule of Civil Procedure 56 and District of Kansas Rule 56.1. Mr. Byquist, Holiday Mansion's vice president and individual in charge of the day-to-day operations of the company, testified that *993 he did not know if Holiday Mansion's allegation that Mercury represented what specific speeds Sithon's boats could achieve was true or the basis of the allegation. Mr. Byquist also testified that (1) no one at Mercury told anyone at Holiday Mansion that the boats sold to Sithon would travel 24 knots cruising speed or 28 knots maximum speed, or at any speed, when equipped with the Mercury stern drive engines; (2) no one at Mercury endorsed using the Mercury stern drive engines with the boats sold to Sithon; and (3) no one at Mercury told Holiday Mansion that the boats sold to Sithon would be a proper application for the Mercury stern drive engines. Mr. Brown of Holiday Mansion faxed a letter to Sithon on January 3, 1995, representing that the boats equipped with Mercury engines would have a cruising speed of 24 knots and a maximum speed of 28 knots. Mr. Brown testified that he had no factual basis for making the representation and that he did not consult with anyone at Holiday Mansion or Mercury before making the representation. B. Breach Of Express Warranty (Count I). Holiday Mansion alleges that Mercury expressly warranted that the engines would reasonably and properly perform. As noted previously, to prevail on an express warranty claim, a party must establish (1) there was an explicit written or oral statement of warranty prior to or contemporaneous with the execution of a contract and (2) reliance on the warranty statement. See Owens-Corning, 546 F.Supp. at 541. The only record evidence of an express warranty by Mercury to Holiday Mansion is contained in Mercury's operation and service manual. The warranty provides in relevant part that the Mercury stern drive power package, inboard engine, and accessories are warranted "to be free from defects in material and workmanship. This warranty shall apply only to pleasure craft and light-duty craft applications." Holiday Mansion has not offered any evidence suggesting either that (1) the Mercury engines and stern drives failed because of a defect in materials or workmanship or (2) the Mercury propulsion systems were used in a "light-duty craft" application. In the absence of such evidence, Holiday Mansion cannot establish that Mercury breached its express warranty. Indeed, the only record evidence on this point suggests that Mercury fulfilled its warranty obligations by supplying replacement engines and drive units for the boats at virtually no cost to Sithon or Holiday Mansion. Therefore, the court will grant summary judgment in favor of Mercury on count I of Holiday Mansion's cross-claim. C. Negligent Misrepresentation (Count II). Holiday Mansion alleges that Mercury negligently misrepresented that the 49-foot passenger boats, "when loaded with passengers, fuel and other miscellaneous items, could reasonably and appropriately operate for needed periods of time at cruising speed in excess of 20 knots [] with a maximum speed in excess of 24 knots." To prevail on its claim, Holiday Mansion must establish: (1) Mercury supplied false information to Holiday Mansion to benefit and guide Holiday Mansion in a business transaction; (2) Mercury intended to influence the transaction by providing the information; (3) Mercury was negligent in obtaining or communicating the information; and (4) Holiday Mansion reasonably relied and acted upon the information which caused Holiday Mansion to suffer damages. See Mahler v. Keenan Real Estate, Inc., 255 Kan. 593, 604, 876 P.2d 609, 616 (1994) (adopting section 552 of the Restatement (Second) of Torts). Holiday Mansion has not presented any evidence that Mercury ever made the alleged representation regarding speed. Indeed, Holiday Mansion's representatives testified that no such representation was made. Mr. Byquist, Holiday Mansion's vice president and individual in charge of the day-to-day operations of the company, testified that he did not know if Holiday Mansion's allegation was true or the basis of the allegation. Mr. Byquist also testified that (1) no one at Mercury told anyone at Holiday Mansion that the boats sold to Sithon would travel 24 knots cruising speed or 28 knots maximum speed, or at any speed, when equipped with the *994 Mercury stern drive engines; (2) no one at Mercury endorsed using the Mercury stern drive engines with the boats sold to Sithon; and (3) no one at Mercury told Holiday Mansion that the boats sold to Sithon would be a proper application for the Mercury stern drive engines. Finally, Mr. Brown of Holiday Mansion faxed a letter to Sithon on January 3, 1995, representing that the boats would have a cruising speed of 24 knots and a maximum speed of 28 knots. Mr. Brown testified that he had no factual basis for making the representation and that he did not consult with anyone at Holiday Mansion or Mercury before making the representation. In light of the above evidence, no reasonable juror could find that Mercury supplied Holiday Mansion with false information. Accordingly, the court will grant summary judgment in favor of Mercury on count II of Holiday Mansion's cross-claim. D. Negligence (Count III). Holiday Mansion alleges that Mercury "failed to use appropriate and reasonable care in selecting the Mercury engines and stern drives it did, which would not and could not operate at the desired cruising and maximum speeds." Holiday Mansion also alleges that Mercury "negligently and improperly failed to undertake and perform any and all testing that was needed to ascertain and make certain that its representations were reasonable and appropriate." Holiday Mansion has not presented any evidence in support of these allegations. First, the uncontested evidence establishes that no one at Mercury represented to Holiday Mansion that the boats could achieve certain cruising or maximum speeds and that no one at Mercury was aware of the desired cruising and maximum speeds. Moreover, Holiday Mansion has not presented any evidence suggesting that Mercury was negligent in selecting the engines for the passenger boats. For the above reasons, the court will grant summary judgment in favor of Mercury on count III of Holiday Mansion's cross-claim. E. Common Law Indemnity (Count IV). Holiday Mansion claims that it is entitled to indemnity from Mercury for any judgment that may be entered against Holiday Mansion on Sithon's claims. Mercury argues that Holiday Mansion has no legal right to indemnity under Kansas law. There is no evidence of any indemnity agreement between Holiday Mansion and Mercury. In addition, "the statutory adoption of comparative negligence in Kansas has had the effect of abrogating the concept of indemnification based on the dichotomy of active/passive negligence." Haysville U.S.D. No. 261 v. GAF Corp., 233 Kan. 635, 642, 666 P.2d 192, 199 (1983) (citation omitted). In the absence of any factual or legal basis for indemnification, the court will grant summary judgment in favor of defendant Mercury on count IV of Holiday Mansion's cross-claim. IT IS THEREFORE ORDERED that defendant Mercury Marine's motion for summary judgment on plaintiff's complaint (Doc. # 73) is granted as to counts I, II, V, VIII, and IX, granted in part and denied in part as to counts IV and VII as discussed herein, and denied as to counts III and VI. IT IS FURTHER ORDERED that defendant Mercury Marine's motion for summary judgment on defendant Holiday Mansion's Cross-Claim (Doc. # 124) is granted.
{ "pile_set_name": "FreeLaw" }
1. Field Subject matter disclosed herein relates to monitoring a concentration of an analyte in a physiological compartment. 2. Information The pancreas of a normal healthy person produces and releases insulin into the blood stream in response to elevated blood plasma glucose levels. Beta cells (β-cells), which reside in the pancreas, produce and secrete insulin into the blood stream as it is needed. If β-cells become incapacitated or die, a condition known as Type 1 diabetes mellitus (or in some cases, if β-cells produce insufficient quantities of insulin, a condition known as Type 2 diabetes), then insulin may be provided to a body from another source to maintain life or health. Traditionally, because insulin cannot be taken orally, insulin has been injected with a syringe. More recently, the use of infusion pump therapy has been increasing in a number of medical situations, including for delivering insulin to diabetic individuals or trauma patients. As of 1995, less than 5% of Type 1 diabetic individuals in the United States were using infusion pump therapy. Presently, over 7% of the more than 900,000 Type 1 diabetic individuals in the U.S. are using infusion pump therapy. The percentage of Type 1 diabetic individuals that use an infusion pump is growing at a rate of over 2% each year. Moreover, the number of Type 2 diabetic individuals is growing at 3% or more per year, and growing numbers of insulin-using Type 2 diabetic individuals are also adopting infusion pumps. Additionally, physicians have recognized that continuous infusion can provide greater control of a diabetic individual's condition, so they too are increasingly prescribing it for patients. External infusion pumps are typically provided to control a rate of insulin infusion based, at least in part, on blood glucose measurements obtained from metered blood glucose samples (e.g., finger stick samples) or from processing signals received from a blood glucose sensor attached to a patient to provide sensor glucose measurements. By processing signals from such a blood glucose sensor, a patient's blood glucose level may be continuously monitored to reduce a frequency of obtaining metered blood glucose sample measurements from finger sticks and the like. However, measurements of blood glucose concentration obtained from processing signals from blood glucose sensors may not be as accurate or reliable as blood glucose sample measurements obtained from finger stick samples, for example. Also, parameters used for processing blood glucose sensors for obtaining blood glucose measurements may be calibrated from time to time using metered blood glucose sample measurements as reference measurements obtained from finger sticks and the like.
{ "pile_set_name": "USPTO Backgrounds" }
15 June ’17 — 20:00 Fatou Diome Meet the writer Born in Senegal in 1968, Fatou Diome has lived in France since 1994. A politically engaged author, her literary work is nourished by her struggle against intolerance. Her most recent work, Marianne porte plainte! is an excellent example of this. In it she demonstrates how the concept of national identity fractures society, creating a barrier between ‘them’ and ‘us’, while ignoring the migratory flows that have always played an important role in history. It celebrates the emancipating virtues of education, enabling us to go beyond our strictly defined perceived affiliations, to combat amalgams and to focus on the collective destiny of the human species. Fatou Diome sees Humanity as something more than the sum of its artificially labelled subgroups. The encounter with the author is the start of Les Assises Citoyennes sur les Migrations organised by the CNCD 11.11.11 and is organised in the context of the Migrations campaign by 11.11.11.
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The present invention relates to projectiles and in particular to a projectile having a cavity containing a fluid. To obtain a satisfactory range from a projectile it is necessary to stabilize its orientation to prevent excessive yaw or pitch. While judicious design of the center of gravity or the inclusion of fins may provide an aerodynamic moment which assures stability, a large class of projectiles rely on spin stabilization. Through the use of rifling, a launched projectile is spun about its longitudinal axis so that it exhibits the wellknown gyroscopic effect. To ensure that a projectile is gyroscopically stabilized its spin rate must exceed a minimum which is determined by factors such as its mass distribution. A specific cannon or gun having standard rifling does not have the ability to adjust the spin rate or the stability of various projectiles. In order to vary the spin rate a known barrel employed two interlaced riflings having differing twist rates. A projectile having engravings matching the appropriate one of the riflings is manually inserted therein. This approach however, does not allow continuous adjustment of spin rate and does not affect projectile stabilizing characteristics such as its mass distribution. In a known projectile, a slipping obturator is used to reduce the spin rate. This apparatus is exposed to high stress and does not provide for adjustment of stabilizing factors such as the mass distribution of the projectile. In a known launcher, its barrel is spun at a rate appropriate for the projectile being fired. While the spin rate can be adjusted in this apparatus, the highest rate attainable is limited and wear is a problem. The present invention provides a projectile whose flight stability is controlled by a fluid disposed in a cavity of the projectile. The cavity is arranged to allow shifting of the fluid. The resulting mass redistribution can affect flight stability by altering the moment of inertia or the center of gravity as the projectile is trajected. Such mass redistribution can be utilized to increase or decrease the flight stability, in various embodiments. Also, prior to launch the flight stability can be set by the simple expedient of selecting a specific volume or density of fluid. The setting of stability in this fashion may be performed in the factory or in the field. This latter feature is also useful where a standard shell is to be fitted with any one of variously shaped explosives of differing densities. In addition, for some embodiments the fluid employed may be a liquid explosive so that dead weight is avoided. Moreover this shifting of fluid may be arranged to facilitate high angular acceleration during launch, thereby ensuring rapic attainment of the rated spin rate. In some embodiments the fluid shift may occur over a predetermined interval so that the projectile stability varies throughout its trajectory. This feature may be important where it is desired to destabilize the projectile and cause it to fall when it reaches a target.
{ "pile_set_name": "USPTO Backgrounds" }
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IL-12 gene-modified bone marrow cell therapy suppresses the development of experimental metastatic prostate cancer. To investigate the immunomodulatory effects of interleukin-12 (IL-12) for treatment of metastatic prostate cancer, we administered adult bone marrow cells (BMC) that were genetically modified by retroviral vector-mediated IL-12 gene transduction in an experimental mouse model of prostate cancer metastasis. This therapy produced significant anti-metastatic effects in bone and lung and prolonged animal survival. Flow cytometric analysis indicated donor BMC could effectively home to bone and lung after treatment. Intensive infiltration of CD4 and CD8T cells in lung metastases and increased systemic natural killer and cytotoxic T lymphocyte activities indicated induction of a significant anti-metastatic immune response after treatment with IL-12 transduced BMC. Our results demonstrate the therapeutic potential of gene-modified BMC gene therapy.
{ "pile_set_name": "PubMed Abstracts" }
/* * Licensed to the Apache Software Foundation (ASF) under one * or more contributor license agreements. See the NOTICE file * distributed with this work for additional information * regarding copyright ownership. The ASF licenses this file * to you 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. */ drop dataverse test if exists; create dataverse test; use test; create type test.MyRecord as { id : bigint, point : point, kwds : string }; create external dataset MyData(MyRecord) using localfs((`path`=`asterix_nc1://data/spatial/spatialData.json`),(`format`=`adm`));
{ "pile_set_name": "Github" }
Background {#Sec1} ========== The prevalence of obesity in the general population has increased dramatically over the last 30 years and it seems likely that the environmental changes that have provoked these increases have also affected people with severe mental illness (SMI); in fact, the rates of overweight and obesity have increased even more rapidly in this cohort \[[@CR1]\]. Obesity adversely affects the physical health and psychological well-being of people with SMI and if weight gain is attributed to treatment, this can lead to non-adherence and risk of relapse. Schizophrenia is a major psychiatric disorder that alters the individual's perception, thoughts, affect and behaviour and may involve a loss of insight and has a lifetime prevalence of approximately 1% \[[@CR2]\]. Schizoaffective disorder is recognised as a separate condition to schizophrenia and is more likely to occur in women at a later age. This disorder affects an individual's thoughts and emotions \[[@CR3]\]. Although individuals with first-episode psychosis do not fulfil the diagnostic criteria for schizophrenia or schizoaffective disorder, 90--95% of people presenting with a non-affective psychotic episode (i.e. not mania and not depressive psychosis) will still meet the criteria for a schizophrenia spectrum disorder 2 years later. Mortality rates are increased two to three fold in people with SMI and life expectancy is reduced by 10--20 years. Approximately 75% of all deaths in people with schizophrenia are caused by physical illness with cardiovascular disease being the commonest cause \[[@CR4]\]. Overweight and obesity contribute to this excess morbidity and mortality. Recent studies indicate that obesity is two to three times more common among people with SMI \[[@CR5]\]. Obesity occurs early in the natural history of schizophrenia with a significant proportion of people with first-episode psychosis being overweight prior to any treatment. Substantial weight gain (\> 7%) often occurs rapidly within 6--8 weeks after antipsychotic-treatment initiation \[[@CR6]\]. While most weight gain occurs early in treatment, longer-term observational studies suggest that weight gain continues for at least 4 years albeit at a slower rate \[[@CR7]\]. Individuals with schizophrenia are more likely to consume a diet that is rich in fat and refined carbohydrates while containing less fibre, fruit and vegetables than the general population \[[@CR8]\]. Although there are fewer studies, people with first-episode psychosis also have poor diets \[[@CR9]\]. Physical inactivity and the social and urban deprivation experienced by those with schizophrenia may contribute further to the increased obesity rates \[[@CR8], [@CR10]\]. There may be disease-specific effects of schizophrenia, such as genetic susceptibility, that have additive or synergistic actions to increase body weight further \[[@CR5]\]. However, the most important factor related to weight gain in people with SMI is the use of antipsychotic medications, which are among the most obesogenic drugs. Weight gain is the commonest side effect of second-generation antipsychotic medication, affecting between 15 and 72% of patients \[[@CR11]\]. Other psychotropic drugs are often prescribed to people with schizophrenia and include some antidepressants and mood-stabilising drugs, such as lithium and sodium valproate; these may also induce significant weight gain \[[@CR12]\]. Both lifestyle and pharmacological interventions lead to significant reductions in body weight in the general population. Not only are the interventions clinically effective, they are also cost-effective because of the benefits of long-term improved health outcomes, including decreased mortality \[[@CR13]\]. It is likely that similarly effective interventions for people with schizophrenia will also lead to improvements in health and would be a major step towards reducing the health inequalities experienced by people with schizophrenia. As the weight gain associated with antipsychotic medication result in some people discontinuing their medication, we hypothesis that effective weight-management strategies may also lead to improved adherence to antipsychotic medication and reduced relapse and hospitalisation rates. Some studies have suggested that short-term lifestyle interventions could support weight reduction in people with SMI. A meta-analysis of non-pharmacological interventions in people with SMI \[[@CR14]\] reported a mean reduction in weight of 3.12 kg over a period of 8--24 weeks. However, the results of longer-term studies are more mixed. A recent meta-analysis found significant weight loss in only two of six studies with interventions lasting longer than a year \[[@CR15]\]. Most studies have included a mixed population of people with SMI and two large studies, which included only people with schizophrenia, found no effect of a lifestyle intervention on body weight \[[@CR16], [@CR17]\]. These latter studies suggest the weight management in people with schizophrenia may require a different approach from other SMIs such as bipolar disorder. Given the challenges of implementing lifestyle change in people with schizophrenia and the lack of long-term effectiveness, alternative approaches are needed to manage overweight and obesity. A wide variety of treatments have been subject to clinical studies but currently no drug treatments are licensed for the treatment of antipsychotic-medication-associated weight gain or obesity in people with SMI with the exception of orlistat \[[@CR18]\]. The long-term use of the latter, however, is extremely limited by high discontinuation rates, making it of little value in routine clinical practice \[[@CR19]\]. To date, there have also been three completed trials of glucagon-like peptide 1 (GLP-1)-receptor agonists in people with SMI, two of which used exenatide and one used liraglutide (maximum dosage 1.8 mg) \[[@CR20]--[@CR22]\]. Liraglutide is a GLP-1-receptor agonist, with 97% homology to human GLP-1, which induces weight loss in humans mainly by reducing appetite and caloric intake, rather than increasing energy expenditure. There were contrasting results in the exenatide studies with one showing no difference between groups after 12 weeks of treatment \[[@CR20]\] but in the other the exenatide arm had greater mean weight loss (− 5.29 vs − 1.12 kg; *P* = 0.015), and reduced glycosylated haemoglobin (HbA~1c~) levels (− 0.21% vs 0.03%; *P* = 0.004) \[[@CR21]\]. In the liraglutide (maximum dosage 1.8 mg) study, glucose tolerance improved in the liraglutide group and body weight decreased compared with placebo (− 5.3 kg; 95% confidence interval (CI) − 7.0 to − 3.7 kg) \[[@CR22]\]. Liraglutide is approved for the management of obesity at a dosage of 3.0 mg daily, which is higher than the dosage used to treat diabetes \[[@CR23]\]. In a 56-week, double-blind trial involving 3731 participants without type-2 diabetes, 63.2% of the intervention arm compared with 27.1% in the placebo arm group lost at least 5% of their body weight, and 33.1% and 10.6%, respectively, lost more than 10% of their body weight \[[@CR23]\]. We have, therefore, chosen to use liraglutide (maximum dosage 3.0 mg) as we postulate that a higher dosage of liraglutide may offer even greater weight loss in people with SMI than the 1.8-mg dosage employed in the previous study or other currently available GLP-1-receptor agonists. Aims and objectives {#Sec2} ------------------- The aim of this pilot study is to undertake a double-blind, randomised controlled trial (RCT) of the use of liraglutide (maximum dosage 3.0 mg daily) in comparison to placebo in 60 obese or overweight people with schizophrenia, schizoaffective disorder or first-episode psychosis to assess the feasibility and acceptability of delivering a full-scale trial evaluating treatment with liraglutide in people with schizophrenia, schizoaffective disorder and first-episode psychosis. Methods {#Sec3} ======= Design {#Sec4} ------ This study is a double-blind, randomised pilot study of the use of liraglutide (maximum dosage 3.0 mg daily) in comparison to placebo (Fig. [1](#Fig1){ref-type="fig"}). It is important to include a double-blind placebo for two main reasons; there is evidence that people would be less likely to consent to a trial that includes a placebo arm because of the risk of not receiving an active treatment. As our ability to recruit to the trial was one of our key aims, it is important to assess whether the inclusion of a placebo prevented us from recruiting to the trial. Previous experience from weight-management trials that include pharmaceuticals have been plagued by high dropout rates in the placebo arm as the participants are able to assess the effectiveness of treatment. To adequately power a full RCT of liraglutide, we will need to know the likely dropout rate in the placebo group in this patient population. Fig. 1Consolidated Standards of Reporting Trials (CONSORT) study diagram Setting {#Sec5} ------- The study will be take place in a variety of community and inpatient mental health locations in the Southern Health NHS Foundation Trust. Public and Patient Involvement was actively included in the development of the trial and will continue throughout the trial. Ethics approval and consent to participate {#Sec6} ------------------------------------------ South Central -- Hampshire B Research Ethics Committee (REC) approved the study on 17 April 2018 with REC reference: 18/SC/0085. Only those who agree to provide written informed consent will be included in the study. The study will be conducted in keeping with Good Clinical Practice (GCP) and the International Conference of Harmonisation (ICH) standards. The Trial Steering Committee (TSC) includes an independent chair and two other independent members, including a service user. The main trial investigators will also attend the TSC. Participants {#Sec7} ------------ Adults are eligible to participate in the study if they: Are aged 18--75 yearsHave a clinical diagnosis of schizophrenia or schizoaffective disorder (defined by *International Classification of Diseases, version 10* (*ICD-10*) codes F20 and F25) or first-episode psychosis using case note review. There is no limit on the duration of illness for those with schizophrenia or schizoaffective disorder but first-episode psychosis is defined as less than 3 years since presentation to the mental health team or the use of the first antipsychotic medication prescriptionAre being treated with an antipsychotic medication, with a minimum duration of 1 month prior to entry in to the trial. No restriction is placed on the class or generation of the antipsychotic medicationAre able to give written informed consentAbility and willingness to take liraglutide or placeboAre able to speak and read EnglishHave a Body Mass Index (BMI, calculated as weight in kilograms divided by height in meters squared) *≥* 30 kg/m^2^ (obese), or *≥* 27 kg/m^2^ to \< 30 kg/m^2^ (overweight) in the presence of at least one weight-related consequence such as dysglycaemia (pre-diabetes or type-2 diabetes), hypertension, dyslipidaemia or obstructive sleep apnoea People are excluded from the study if they have a: Physical illnesses, e.g. cancer, that could seriously reduce their life expectancy or ability to participate in the trialA co-existing physical health problem that would, in the opinion of the principal investigator, independently impact on metabolic measures or weight, e.g. Cushing's syndrome, poorly controlled type-2 diabetes defined by HbA~1c~ level \> 8% (64 mmol/mol)Inflammatory bowel disease and diabetic gastroparesisContraindications to liraglutide: hypersensitivity to liraglutide or to any of the excipients Any condition which, in the investigator's opinion, might jeopardise a participant's safety or their compliance with the protocolFamily or personal history of multiple endocrine neoplasia type-2 or medullary thyroid carcinoma. Family is defined as a first-degreerelativeHistory or presence of pancreatitis (acute or chronic)History of diabetic ketoacidosisAny of the following: myocardial infarction, stroke, hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screeningParticipants presently classified as being in New York Heart Association Class IVPlanned coronary, carotid or peripheral artery revascularisation known on the day of screeningRenal impairment measured as an estimated glomerular filtration rate (eGFR) value of \< 30 ml/min/1.73 m^2^ as defined by the Kidney Disease Improving Global Outcomes (KDIGO) 2012 classificationImpaired liver function, defined as alanine aminotransferase (ALT) ≥ 2.5 times the upper normal limit at screeningProliferative retinopathy or maculopathy requiring acute treatmentPresence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous-cell skin cancer and any carcinoma in situ is allowedUse of other pharmacological products for weight managementMental illnesses that could seriously reduce their ability to participate in the trial, including significant suicidalityCurrent pregnancy or a desire to become pregnant. Mothers who are less than 6 months post-partum or breastfeeding will also be excluded. In line with the current EU licence and advice from the Medicines and Healthcare products Regulatory Agency (MHRA), sponsor and manufacturer, any women who may become pregnant during the trial but are unwilling to use a highly effective method of birth control (e.g. such as implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence or having a vasectomised partner) will not be eligible for the trialSignificant alcohol or substance misuse which, in the opinion of the principal investigator, would limit a participant's ability to participate in the trialA diagnosis or tentative diagnosis of psychotic depression or maniaA primary diagnosis of learning disability or cognitive impairment which would impair a participant's ability to self-administer trial medicationLack of capacity. Those who lose capacity any time during the study will not be eligible to continue and will be withdrawn from the study immediately with no further study procedures carried outHistory of type-1 diabetes.Current or previous use of incretin-based therapies (GLP-1-receptor agonist or dipeptidyl peptidase 4 (DPP-4) inhibitors) or insulin Sample size {#Sec8} ----------- This pilot trial will explore the feasibility and practical issues of conducting a future definitive trial and estimate the important parameters to help its design. In this regard, sample size is based on the need to estimate study parameters within a reasonable degree of precision rather than on hypothesis testing. Simulation work by Sim et al. (2012) recommended a minimum of 50 participants (25 per group) in order to achieve the pilot/feasibility objectives \[[@CR24]\]. A further paper by Whitehead et al. recommended pilot trial sample sizes per treatment arm of 75, 25, 15 and 10 for standardised effect sizes that are extra small (≤ 0.1), small (0.2), medium (0.5) or large (0.8), respectively \[[@CR25]\]. In the previous liraglutide study in people with SMI, 10% of the liraglutide arm and 2% in the placebo arm had dropped out of the trial after 16 weeks \[[@CR22]\]. Although dropout from obesity trials is non-linear as those on active treatment drop out earlier because of side effects while those on placebo drop out later because of lack of efficacy, we assume a conservative dropout rate at 6 months of between 15 and 20%. As such, we will need to recruit at least 60 participants (30 per group) to provide robust estimates that will inform the design of the definitive trial. In a pilot trial looking at the use of liraglutide (maximum dosage 1.8 mg) of 214 potential participants assessed for eligibility, 103 were randomised. Of the 111 excluded, 86 did not meet the final inclusion/exclusion criteria, 23 declined to participate and 2 had too severe a degree of mental illness to participate \[[@CR22]\]. However, in a similar study examining the use of once-daily exenatide in people with schizophrenia, out of 123 potentially eligible participants, only 28 were randomised with 63 declining to participate \[[@CR21]\]. We used these data to estimate our screen-to-randomisation rate. Selection {#Sec9} --------- The study will be promoted within clinical teams and in areas where community mental health services are delivered in the Southern Health NHS Foundation Trust. It is estimated that \~ 70% of those with a recorded diagnosis of schizophrenia or one of its subtypes attending community and inpatient settings of the Southern Health NHS Foundation Trust fulfil the inclusion criteria. This equates to approximately 500 individuals across the trust. Assuming that 30% of patients were willing to take part, we would be able to recruit up to 60 patients for the study within 12 months. Confirming these screening and enrolment rates is part of the reason for performing the study. In addition, the Early Intervention in Psychosis team in Southampton receives approximately 20 new referrals a month. Although these individuals do not fulfil the diagnostic criteria for schizophrenia, we intend to include them in the study for the following reasons: Up to 80% of individuals treated with antipsychotic medication during a first episode of psychosis gain more than 7% of their body weight within 12 weeks of treatment.People with first-episode psychosis are more likely to develop weight-induced metabolic abnormalities and consequently the benefits may be greater Participants will be advised verbally and in writing that they will be able to end their participation in the study at any point without affecting their clinical care. The investigators will also have the right to withdraw participants from the study if they lose capacity, develop any of the exclusion criteria or miss their 3-month study visit. The rationale for the withdrawal will be recorded and dated in the Case Report Form (CRF) accordingly. Participants withdrawing from the trial treatment will be encouraged to undergo the same final clinical evaluations. Randomisation {#Sec10} ------------- After baseline assessments, participants will be randomised to either daily subcutaneously administered liraglutide (maximum dosage 3.0 mg) or matching placebo. Equal numbers of participants will be randomised to each arm of the trial using simple randomisation with permuted, blinded, block size. Novo Nordisk prepares and provides the subject randomisation list (SRL) using a computer-based programme. All participants, carers and study personnel except the pharmacy team will be blinded to treatment assignment. This includes the statistician undertaking the data analysis. Emergency un-blinding will be undertaken if a participant develops an adverse event that requires knowledge of the treatment, an overdose of trial medication or there is a clinical need to start a participant on medication which has a risk of interaction with the trial drug. Intervention {#Sec11} ------------ Before screening, all potential participants will be provided with written information about the trial including the most common adverse event and the procedures involved in the study. All participants will receive standardised written information about healthy eating, physical activity, alcohol and smoking. Liraglutide will be used according to the current EU licence for Saxenda®; the starting dose will be 0.6 mg per day. Participants will be taught face-to-face about using the injection pen and will be witnessed giving the first injection. Participants will be given an instruction leaflet to take away with them. The dose will be increased each week by 0.6 mg to a maximum dosage of 3.0 mg per day. Participants who do not tolerate up-titration will remain on the highest tolerable dosage. Each participant will attend 4-weekly visits where concomitant medications and adverse events will be documented. In addition at the baseline, 3- and 6-month visits they will also have clinical data collected (secondary endpoints) including drawing blood samples. The blood samples will be analysed for fasting plasma glucose (FPG), lipid profile and HbA~1c~ level~.~ Participants will be invited at baseline and study completion to take part in one-to-one interviews with a psychologist, trained and experienced in qualitative research methodology, to explore expectations and experience of their participation in the trial. Outcome measures {#Sec12} ---------------- ### Primary objective {#Sec13} The primary objective of the pilot trial is to investigate the feasibility and acceptability of delivering a full-scale trial evaluating whether liraglutide 3.0 mg, once-daily injectable therapy, may be an effective treatment of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis. In order to achieve our primary objective, the study will gather data on: Time to reach the recruitment targetThe number of eligible participants required to be screened in order to reach the recruitment target. Key characteristics and reasons for not joining the trial will be recorded, in line with the Consolidated Standards of Reporting Trials (CONSORT) criteria for clinical trialsTo estimate participant attrition rateTo estimate adherence to the investigational medicinal product (IMP) ### Secondary exploratory outcomes {#Sec14} To estimate effect size and standard deviation (SD) of the change in weight at 6 months in order to inform a power calculations for a fully powered RCT based on this feasibility pilot study. Changes in waist circumference, BMI, FPG, HbA~1c~ level, blood pressure, lipid profile, adverse events and Brief Psychiatric Rating Scale (BPRS) score at 3 and 6 months will also be assessed.. The BPRS is an instrument used for assessing the positive, negative and affective symptoms of psychotic disorders, especially schizophrenia. The BPRS will, therefore, be used to assess any changes in mental health during the trial. Follow-up windows for 3- and 6-month follow-ups will be defined as minus and plus 2 weeks to allow for missed appointments. A schedule of follow-up activities is shown in Fig. [2](#Fig2){ref-type="fig"}. Fig. 2Schedule of outcome measures and trial-related activities Safety assessments {#Sec15} ------------------ Heart rate and glycaemia assessments will be taken at baseline and at 3 and 6 months post randomisation. Adverse events (AEs) are defined as the side effects listed in the Summary of Product Characteristics (SmPC) and include nausea, vomiting and diarrhoea. Medication error and laboratory outliers will also be considered as AEs. AEs will be monitored every 4 weeks. Serious Adverse Events (SAEs) are defined as per GCP. Any SAE which a member of the study team deems to be associated with the trial intervention will be assessed by the principal investigator. There are SAEs that are expected for the patient population: Psychiatric hospitalisationWorsening of psychiatric symptomsSelf-harmSuicide attemptDeath from suicide If the investigator deems that any of these expected events are at least possibly related to the study drug then these will be reported as serious adverse reactions (and not events). All SAEs that are both 'unexpected' (that is, the type of event is not listed in the protocol as an expected occurrence); and 'related' (that is, it resulted from administration of any of the research procedures) will be reported to the sponsor for expedited reporting to the TSC and the REC. No serious adverse outcomes are anticipated associated with use (or not) of the trial medication; therefore, no interim statistical analysis is planned regarding safety; however, the TSC will review all SAEs periodically. Data analysis {#Sec16} ------------- Data will be analysed in accordance with the trial's detailed Statistical Analysis Plan (SAP) (Additional files [1](#MOESM1){ref-type="media"} and [2](#MOESM2){ref-type="media"}), a summary of the main methods are as follows: All data will be analysed based on the intention-to-treat population. Continuous variables will be analysed by either mean or median, with groups compared statistically using either a paired *t* test or a Mann-Witney *U* test as appropriate. Categorical variables will be presented as *n* (%) with groups compared using chi-squared or Fisher's exact tests. The difference in weight change between groups will be analysed using generalised linear models (GLMs), both unadjusted and adjusted for covariates that are identified as potential confounders in univariate testing. All statistical tests will be two-sided with statistical significance assumed at 0.05. Key characteristics and reasons for not joining the trial will be recorded for all participants screened. A CONSORT diagram will be used to summarise this information and reasons will also be provided if applicable. Demographics and person-reported outcome data at baseline will be summarised using number and proportion, mean and SD or median and interquartile range (IQR) as appropriate. ### Analysis of primary objectives {#Sec17} This study focusses on the feasibility of recruiting from this patient population for a fully powered RCT. The following will be reported: Time to reach recruitment target (in weeks) ◦ Mean number of participants recruited per week◦ Rate of successful screens◦ Participant attrition rateAdherence to the IMP (defined as the proportion of medication used by each person ranging from 0 to 100%) ◦ Either mean (SD) or median (IQR) adherence will be presented as appropriate◦ Number of participants using at least 70% of the prescribed trial medication. Adherence to the IMP is defined as the number of empty cartridges returned at each visit divided by the total number of cartridges prescribed ### Analysis of secondary exploratory outcomes {#Sec18} Changes in weight (defined as weight in kilograms at 3 or 6 months minus weight in kilograms at randomisation), BMI, waist circumference, BPRS score, HbA1c level, FPG, lipid level, systolic and diastolic blood pressure, and adherence to randomised treatment (including the effect of the using the optional text-messaging reminder service or not), type of diabetes medication, change in type or dose of diabetes medication, type of antipsychotic medication, change in type or dose of antipsychotic medication between the two treatment groups will be summarised and tested for significance, as will the number of participants experiencing a weight loss of at least 5% from baseline to 3 to 6 months. Change in body weight between the two groups at 26 weeks will be further analysed using a GLM adjusted for baseline weight and other covariates. ### Missing data {#Sec19} Analysis will be completed using list-wise deletion of missing data. Participants with and without missing data will be compared for differences in demographic and physiological data where possible. ### Harms {#Sec20} The number (and percentage) of participants experiencing each AE/SAE will be presented for each treatment arm categorised by severity. Qualitative component of study {#Sec21} ------------------------------ One-to-one semi-structured interviews will be held with a sub-sample of liraglutide-treated participants and healthcare professionals delivering the intervention to provide data on the drug treatment. Purposive sampling will ensure diversity in terms of demographic and disease characteristics. Participants (10--12 from each trial arm) will be interviewed until data saturation is met. Semi-structured interview-topic guides will contain questions intended to elicit themes outlined in the existing published literature, after exploring more general open questions on the experience and acceptability of the treatments. Interviews will be held before, during and at the end of the trial. For mental health workers, key themes relate to the perception of pharmacological interventions as part of the care-coordinating role, workload, the need for specialist knowledge and views on client adherence. We will use May's normalisation process model as a theoretical framework to understand the conditions necessary to support the introduction, embedding and integration of a weight intervention as a routine element of care. All semi-structured interviews will be audio-taped and fully transcribed. Content and thematic analysis will use the National Centre for Social Research 'Framework' approach. Trial status {#Sec22} ============ Recruitment opened on 2 July 2018 and we aim to complete recruitment by 31 July 2019. Protocol version 1.6, dated 22 May 2018, is being used. Discussion {#Sec23} ========== Obesity adversely affects the physical health and psychological well-being of people with SMI. If weight gain is attributed to treatment, this can lead to non-adherence and risk of relapse. The provision of an effective intervention to reduce the burden of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis would improve physical health and reduce the risk of developing obesity-related illnesses as well as improving psychological well-being. This pilot study is a double-blind, randomised, placebo-controlled trial investigating the use of once-daily liraglutide subcutaneous injection in obese or overweight people with schizophrenia, schizoaffective disorder or first-episode psychosis. It aims to explore the feasibility and practical issues of conducting a future definitive RCT evaluating weight change with liraglutide in overweight or obese people with SMI. This feasibility trial should estimate important parameters to help its design. One potential limitation of this feasibility trial is the funding by the investigational drug manufacturer. In order to mitigate against this bias, the trial was sponsored by the Southern Health NHS Foundation Trust, which has the responsibility for the initiation, management, conduct, analysis, reporting and publication of the trial. Although Novo Nordisk is providing support financially and the product for the trial, Novo Nordisk is not involved in the conduct, management and delivery of the trial. Additionally, the initial idea, rationale and design for the trial came from the chief investigator. Nevertheless, the results of this study will need to be confirmed in a fully powered, investigator-led trial. This research should contribute to the development of effective weight-management intervention programmes for people with SMI. It should provide information on whether injectable GLP-1-receptor agonists are an acceptable weight-loss medication in this group of people. Further, potentially more effective, GLP-1-based medications are in development including once weekly and orally administered versions which may prove to be a better option for people with SMI if once daily injections are shown to be feasible. . Additional files ================ {#Sec24} Additional file 1:Statistical Analysis Plan (SAP). L. O. S. E. Weight Pilot Study. (DOCX 39 kb) Additional file 2:Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 Checklist: recommended items to address in a clinical trial protocol and related documents. (DOCX 121 kb) AE : Adverse event BMI : Body Mass Index BPRS : Brief Psychiatric Rating Scale CI : Confidence interval CRF : Case Report Form eGFR : Estimated glomerular filtration rate FPG : Fasting plasma glucose GCP : Good Clinical Practice GLM : Generalised linear model GLP-1 : Glucagon-like peptide 1 ICH : International Conference on Harmonisation RCT : Randomised controlled trial REC : Research Ethics Council SAE : Serious adverse event SD : Standard deviation SmPC : Summary of Product Characteristics TSC : Trail Steering Committee **Publisher's Note** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Not applicable. RIGH, HCP, SR, PP, KT, KBK and CAW wrote the original protocol. RIGH, HCP, SR, PP, KBK and CAW were co-applicants on the investigator-led Novo Nordisk grant application. CAW, HCP, SR, PP, KBK, KT, CR, RP, JM and RIGH refined the protocol. CA reviewed the protocol from a Patient and Public Involvement (PPI) point of view. All authors critically reviewed the protocol manuscript. All authors read and approved the final manuscript. The study team was awarded an investigator-led grant by Novo Nordisk Ltd. The protocol was designed by the investigators and the funder will have no role in the analysis of the results. Sponsor: Southern Health NHS Foundation Trust. Not applicable. South Central -- Hampshire B Research Ethics Committee (REC) approved the study on 17 April 2018 with REC reference: [@CR18]/SC/0085. Only those who agree to provide written informed consent will be included in the study. Not applicable. CAW, HCP, PP, SR and KT are employees of the Southern Health NHS Foundation Trust. HCP received fees for lecturing, consultancy work and attendance at conferences from Novo Nordisk. SR received fees for speaking at conferences from Janssen, Lundbeck and Otsuka. KBK received fees for advisory board participation, consultancy work and attendance at conferences from the following: Sanofi, Roche Diabetes Care, Lifescan, Novo Nordisk, Silvercloud, and Senseonics. RIGH received fees for lecturing, consultancy work and attendance at conferences from the following: Boehringer Ingelheim, Eli Lilly, Janssen, Lundbeck, Novo Nordisk, Novartis, Otsuka, Sanofi, Sunovion, Takeda, and MSD.
{ "pile_set_name": "PubMed Central" }
If people are stupid enough that they need a law to make them do the right thing then that gene pool needs chlorinated whether it's jaywalker and an escalade or whatever else. What's wrong with personal responsibility instead a nanny state? It may not be their own genes they're eliminating. It could be the neighbor kid's genes. So when someone walks into traffic and a car swerves and wrecks, how do you hold the jaywalker responsible if it's not illegal to jaywalk?
{ "pile_set_name": "Pile-CC" }
Google SSL Search - jamesbkel http://www.google.com/support/websearch/bin/answer.py?answer=173733&hl=en ====== wladimir This was available for quite a while already, though in beta/labs. I'm not sure what is new. ~~~ JonnieCache Yeah, it doesn't seem any different to how its been in the past year. The _beta_ sigil is still under the logo. I wish theyd put the links to maps and images back in, maybe with some visual warning that theyre not encrypted. I have SSL search as the default search in chrome, and I hate having to manually jump back to normal google to do image searches. While we're here, don't forget SSL wikipedia! <https://secure.wikimedia.org/wikipedia/en/wiki/Main_Page> ~~~ mike-cardwell If you're using the HTTPS-Everywhere Firefox addon (1), or the HTTPS- Everywhere Squid redirector (2), you don't need to know/remember about the SSL versions of Wikipedia or Google. You're just sent there by default. 1.) <https://www.eff.org/https-everywhere> 2.) <https://github.com/mikecardwell/perl-HTTPSEverywhere> ------ mahrain Been using this for a year now, there's also a hack to use it in the Chrome bar by entering a custom search engine. Very handy and works nice. Only miss is that I can't immediately click through to image searches, they're only available over unsecured HTTP. ~~~ lobster_johnson Unfortunately, you lose autocompletion (other than history autocompletion) when you use something other than the built-in Google search. ------ nodata Good, but to make this truly useful we need a really simple way to specify which country-specific google search engine we would like results from. ------ jamaicahest DuckDuckGo has been using this for many months, when you use the !g bang ~~~ rlpb Really? It doesn't seem to do it for me. Do you have some setting set somewhere? ------ lini Anyone that has the HTTPS everywhere extension (Firefox) is already using the SSL search in Google. As others noted it has been in beta for quite a long time and is missing some features like the image search or the doodles on the homepage. ------ buster Also, if you want to browse on SSL whereever possible: [https://chrome.google.com/webstore/detail/flcpelgcagfhfoegek...](https://chrome.google.com/webstore/detail/flcpelgcagfhfoegekianiofphddckof) Love this Extension! ------ RyanKearney The only thing I dislike about this is it hides the refer, screwing up my analytics. I'd have to completely convert all of my sites to HTTPS only to be able to make use of the additional headers for analytical purposes. Not really a big deal I guess, but kind of unnecessary to have to purchase wildcard certs if you have many sub domains. ~~~ dspillett The free certs from <http://www.startssl.com/> are apparently accepted by most browsers these days (the exception being IE6/7 users on XP who have not downloaded the optional CA cert updates): <http://en.wikipedia.org/wiki/Startssl#StartSSL> I've not used their cert for anything yet (I plan to test them on some personal sites when I get chance, before using them elsewhere), and wildcard certs are not free (but they do seem relatively cheap), but it might be worth looking into for someone in your position. ~~~ thepsi I've used them for a few personal sites and projects with no complaints. The fee for wildcard certs (~60USD) is a one-off to verify your identity - usually via a quick phone call to confirm details from your official documents. Once that's complete, you can generate as many certs as you need (incl. wildcards and Subject Alternative Name) from their control panel, subject to jumping through the usual hoops to prove that you have control of each domain. ~~~ RyanKearney I do use StartSSL but the problem just comes from having multiple sub domains. I get IPv4 addresses for $0.50/mo/each but I'd rather not setup each subdomain on its own dedicated IP for the sakes of using free SSL certs. ~~~ dspillett You don't need multiple IPv4 addresses to make use of a wild-card (or other multi-name) certificate. A wildcard certificate will verify any matching domain so you could have many sub-domains of the same domain (using a single certificate for *.domain.tld) on one address and browsers would not complain. Also you could run the distinct (sub)domains on different ports on the same address, though this is perhaps less useful. Also, with SNI you can use many single-name certificates on one address (and all on the same port) using SNI. Unfortunately there are a number of significant client combinations that won't play nice with this (most notably, if you can't guess, IE on Windows XP): <http://en.wikipedia.org/wiki/Server_Name_Indication#Support> ~~~ RyanKearney I know that. I'm saying I don't want to have to pay for a wildcard certificate since you can get free certs for individual domains. The alternative for me purchasing a wildcard domain would be to get many different single domain certs for free and assign each one to a different IP address.
{ "pile_set_name": "HackerNews" }
Ýazguly Hojageldiýew Yazguly Berdymuhammedovich Hojageldiyev (; born 16 February 1977) is a Turkmen football manager and former professional footballer who is currently the manager of the Altyn Asyr FK. Honored coach of Turkmenistan. Career Hojageldiyev was born in Büzmeýin. As a football player played as a midfielder for the Turkmen clubs FC Büzmeýin, FC Dagdan Aşgabat, FC Nebitçi, FC Garagum, Kopetdag and HTTU Aşgabat. Coaching career Turkmenistan national team In February 2010, led the Turkmenistan national football team. Under his leadership the team went to Sri Lanka to participate in the final tournament of the AFC Challenge Cup 2010. In a tournament team of Turkmenistan for the first time made it to the final of the AFC Challenge Cup, losing in the final match of the DPRK team in the penalty shootout. In March 2011, the national team of Turkmenistan has successfully entered the final round of the AFC Challenge Cup 2012, beating Pakistan, Taiwan, and played in a draw with India in the qualifying competition in Kuala Lumpur. In the summer of 2011 the first qualifying match against Indonesia in the race for getting into the final of the 2014 World Cup team beginning in Ashgabat draw (1:1), and the humiliating defeat in the party with a 4–3 team knocked out of the fight for the right to go to the World Cup 2014. In winter 2012 team gathered for a training camp in Turkey. In preparation for the AFC Challenge Cup 2012 team Yazguly Hodzhageldiev had a friendly match with Romania, as a result of devastating Turkmenistan team lost 4–0. In March 2012, the team went to Kathmandu to participate in the final tournament of the AFC Challenge Cup 2012. Turkmenistan national team beat the tournament hosts Nepal (0–3) and the team of the Maldives (3–1), the match with Palestine ended in a goalless draw. In the semifinals, Turkmen defeated the Philippines (2–1). Turkmenistan national team for the second time missed AFC Challenge Cup, losing to North Korea at the end of the match (1–2). In 2017, again headed the national team of Turkmenistan. Honours As a Coach Turkmenistan AFC Challenge Cup: Runners-up: 2010, 2012 HTTU Champion of Turkmenistan: 2006, 2009, 2013 Silver medalist in Turkmenistan: 2007, 2008, 2011 Bronze medalist in Turkmenistan: 2012 Winner of the Cup of Turkmenistan: 2006, 2011 Turkmenistan Cup finalist: 2008 Turkmenistan Super Cup: 2009 Turkmenistan President Cup: 2007, 2008, 2009 Semifinalist of the Commonwealth of Independent States Cup: 2010 Altyn Asyr FK Champion of Turkmenistan: 2014, 2015, 2016, 2017, 2018, 2019 Winner of the Cup of Turkmenistan: 2015, 2016, 2019 Turkmenistan Super Cup: 2014, 2015, 2016, 2017, 2018 Finalist 2018 AFC Cup References External links Profile in Goal.com Category:1977 births Category:Living people Category:Turkmenistan footballers Category:Turkmenistan football managers Category:People from Ahal Region Category:Turkmenistan national football team managers Category:Association football midfielders Category:2019 AFC Asian Cup managers
{ "pile_set_name": "Wikipedia (en)" }
Debit Card Loans: Use Debit Card to Arrange Instant Money Do you know how much important your debit card is for you? Do you know that it can also arrange you some finance in your tough period? Yes, you don’t need to cry for anything when you are not having money and you have some necessary issues to deal with them at the same time. Just use your debit card to borrow debit card loans that are frequently arranged for you by the online lending companies. When you are applying for this special loan deal, you don’t have to undergo any uncompromising situation or even lengthy documentation process that takes long span. Debit card loans come to you only when you are able to meet some requirements that are give below: First of all, you should not be below to 18 years, You should have regular employment, You should be UK based inhabitant, You should have a permanent job etc. When you are going to crack this deal of debit card loans, you are able to gain some more benefits tagged with these loans. They keep you out of any kind of formality including faxing papers, going through credit verification process or even anything else. There is no need to use any security when you are willing to have this deal. Simple applying process can be enjoyed through online mode that helps people living in any corner of the UK. Online lending companies have wide network in the whole nation and as they deal with whole issue through online mode, you are not asked to wait for long time. You can get direct cash deposition in your account within some hours when the approval is done. Moreover, you are also allowed to get money with any bad credit fault, such as arrear, default, CCJs, insolvency, foreclosure and so many hurdles. So, don’t run out of your home now as you can arrange money sitting at your own place with ease just by going with online applying method. Debit card loans would let you borrow money without any delay and without any formality.
{ "pile_set_name": "Pile-CC" }
Comparison of a foam rolling session with active joint motion and without joint motion: A randomized controlled trial. Foam rolling has become a popular form of self-myofascial release or roller massage among health and fitness professionals. Due to this popularity, foam roller devices can be found in many clinical and fitness settings. Despite the popularity, there are still several unknowns regarding foam rolling such the optimal technique. Specifically, there is a lack of research analyzing different foam roll techniques such as combining active joint motion with foam rolling. The purpose of this study was to compare the effects of a foam rolling session to the left quadriceps with active joint motion and without joint motion on passive knee flexion range of motion (ROM) and pressure pain thresholds (PPT). Thirty healthy adults were randomly allocated to one of two intervention groups: active joint motion and no joint motion. Each foam roll intervention to the left quadriceps lasted a total of 2 min. Dependent variables included passive knee flexion ROM and pressure pain threshold measures (PPT). Statistical analysis included subject demographic calculations and appropriate parametric and non-parametric tests to measure changes within and between intervention groups. For left knee ROM, the active joint motion group demonstrated the greatest immediate increase in passive ROM (8°, p < .001) than the non-motion group (5°, p < .001). For PPT, the active joint motion group demonstrated the greatest immediate increase (180 kPa, p < .001) followed by the non-motion group (133 kPa, p < .001). Between group comparisons revealed a significance between groups for passive knee ROM (p < .001) and PPT (p < .001). A short session of foam rolling with active joint motion appears to have a greater effect on passive joint ROM and PPT than rolling without motion. These observed changes may be influenced by the agonistic muscle activity during active motion. This activity may modulate activity of the antagonist muscle through reciprocal inhibition and other neural pathways. Future research is needed to confirm these findings.
{ "pile_set_name": "PubMed Abstracts" }
Q: jQuery changing font family and font size I am trying to change font family and font size of the text that appears in a textarea and a container by choosing the font from the list, font size should be fixed. I am also trying to change color of the background when a font is picked. That is my code: <script type="text/javascript"> function changeFont(_name) { document.body.style.fontFamily = _name; document.textarea = _name; } </script> </head> <body style="font-family"> <form id="myform"> <input type="text" /> <button>erase</button> <select id="fs" onchange="changeFont(this.value);"> <option value="arial">Arial</option> <option value="verdana">Verdana</option> <option value="impact">Impact</option> <option value="'ms comic sans'">MS Comic Sans</option> </select> <div align="left"> <textarea style="resize: none;" id="mytextarea" cols="25" rows="3" readonly="readonly" wrap="on"> Textarea </textarea> <div id='container'> <div id='float'> <p>This is a container</p> </div> </form> </body> When I try it in the browser the font family does not change in the text area. It only changes in the container. I also do now know how to set a new font size and background for the container and the textarea when the font family is picked. I will appreciate any help guys! A: Full working solution : HTML: <form id="myform"> <button>erase</button> <select id="fs"> <option value="Arial">Arial</option> <option value="Verdana ">Verdana </option> <option value="Impact ">Impact </option> <option value="Comic Sans MS">Comic Sans MS</option> </select> <select id="size"> <option value="7">7</option> <option value="10">10</option> <option value="20">20</option> <option value="30">30</option> </select> </form> <br/> <textarea class="changeMe">Text into textarea</textarea> <div id="container" class="changeMe"> <div id="float"> <p> Text into container </p> </div> </div> jQuery: $("#fs").change(function() { //alert($(this).val()); $('.changeMe').css("font-family", $(this).val()); }); $("#size").change(function() { $('.changeMe').css("font-size", $(this).val() + "px"); }); Fiddle here: http://jsfiddle.net/AaT9b/ A: In my opinion, it would be a cleaner and easier solution to just set a class on the body and set the font-family in css according to that class. don't know if that's an option in your case though.
{ "pile_set_name": "StackExchange" }
<!-- ~ Copyright 2019. Google LLC ~ ~ 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 ~ ~ https://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. --> <LinearLayout xmlns:android="http://schemas.android.com/apk/res/android" xmlns:tools="http://schemas.android.com/tools" android:layout_width="match_parent" android:layout_height="match_parent" android:background="@color/bg_blue" android:orientation="vertical" android:padding="20dp" tools:context="com.google.android.apps.santatracker.dasherdancer.CharacterActivity" > <LinearLayout android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:orientation="horizontal" > <View android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:visibility="invisible" /> <ImageButton android:id="@+id/btn_character_santa" android:layout_width="match_parent" android:layout_height="wrap_content" android:layout_weight="1" android:adjustViewBounds="true" android:background="@drawable/dasher_ripple" android:onClick="onCharacterClick" android:scaleType="fitCenter" android:layout_gravity="bottom" android:src="@drawable/santa" /> <View android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:visibility="invisible" /> </LinearLayout> <LinearLayout android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:orientation="horizontal" > <ImageButton android:id="@+id/btn_character_elf" android:layout_width="match_parent" android:layout_height="wrap_content" android:layout_weight="1" android:adjustViewBounds="true" android:background="@drawable/dasher_ripple" android:onClick="onCharacterClick" android:scaleType="fitCenter" android:layout_gravity="center" android:src="@drawable/elf" /> <View android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:visibility="invisible" /> <ImageButton android:id="@+id/btn_character_reindeer" android:layout_width="match_parent" android:layout_height="wrap_content" android:layout_weight="1" android:adjustViewBounds="true" android:background="@drawable/dasher_ripple" android:onClick="onCharacterClick" android:scaleType="fitCenter" android:layout_gravity="center" android:src="@drawable/reindeer" /> </LinearLayout> <LinearLayout android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:orientation="horizontal" > <View android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:visibility="invisible" /> <ImageButton android:id="@+id/btn_character_snowman" android:layout_width="match_parent" android:layout_height="wrap_content" android:layout_weight="1" android:adjustViewBounds="true" android:background="@drawable/dasher_ripple" android:onClick="onCharacterClick" android:scaleType="fitCenter" android:layout_gravity="top" android:src="@drawable/snowman" /> <View android:layout_width="match_parent" android:layout_height="match_parent" android:layout_weight="1" android:visibility="invisible" /> </LinearLayout> </LinearLayout>
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Pakistan 'militant leader' Malik Ishaq arrested Pakistani police have detained Malik Ishaq, founder and former head of militant group Lashkar-e-Jhangvi (LeJ), at his home in Punjab province. The group said that it carried out an attack in a Shia Muslim area of the southern city of Quetta last Saturday which killed almost 90 people. However, it is not clear whether Mr Ishaq's detention is directly related to the attack. Mr Ishaq spent a decade in jail before being released in 2011. A heavy contingent of police surrounded Mr Ishaq's residence and held negotiations with him, after which he gave himself over to the police, the BBC's M Ilyas Khan reports from Islamabad. He had been released from jail a few months ago, our correspondent adds. It is not clear whether Mr Ishaq has been formally charged with any offence. Under public order laws, suspects can be held in Pakistan for three months without any charge. Pakistani authorities have long been criticised for not taking enough action against groups such as LeJ that foment sectarian violence. When a local journalist asked Mr Ishaq in 2011 what intended to do after his release from jail, he replied his organisation would continue its "good work" - fighting those who opposed their version of Islam.
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To enable wireless device mobility, access nodes in communication with a wireless device are configured to perform a handover of the wireless device to another access node. Some access nodes can be further configured to maintain an indication of proximate access nodes, such as a neighbor relation table or another similar indication, and the indication of proximate access nodes can be used to facilitate a wireless device handover. Configuring the indication of proximate access nodes is typically performed manually by a network provider for each access node deployed in a communication system. Further, the presence of invalid entries, such as a false indication that an access node is capable of supporting a handover from another access node, can degrade network performance by causing interrupted communication sessions and failed handover attempts.
{ "pile_set_name": "USPTO Backgrounds" }
Relevance of accurate Monte Carlo modeling in nuclear medical imaging. Monte Carlo techniques have become popular in different areas of medical physics with advantage of powerful computing systems. In particular, they have been extensively applied to simulate processes involving random behavior and to quantify physical parameters that are difficult or even impossible to calculate by experimental measurements. Recent nuclear medical imaging innovations such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), and multiple emission tomography (MET) are ideal for Monte Carlo modeling techniques because of the stochastic nature of radiation emission, transport and detection processes. Factors which have contributed to the wider use include improved models of radiation transport processes, the practicality of application with the development of acceleration schemes and the improved speed of computers. In this paper we present a derivation and methodological basis for this approach and critically review their areas of application in nuclear imaging. An overview of existing simulation programs is provided and illustrated with examples of some useful features of such sophisticated tools in connection with common computing facilities and more powerful multiple-processor parallel processing systems. Current and future trends in the field are also discussed.
{ "pile_set_name": "PubMed Abstracts" }
Porous liquid zeolites: hydrogen bonding-stabilized H-ZSM-5 in branched ionic liquids. Porous liquids, as a newly emerging type of porous material, have great potential in gas separation and storage. However, the examples and synthetic strategies reported so far likely represent only the tip of the iceberg due to the great difficulty and challenge in engineering permanent porosity in liquid matrices. Here, by taking advantage of the hydrogen bonding interaction between the alkane chains of branched ionic liquids and the Brønsted sites in H-form zeolites, as well as the mechanical bond of the long alkyl chain of the cation penetrated into the zeolite channel at the interface, the H-form zeolites can be uniformly stabilized in branched ionic liquids to form porous liquid zeolites, which not only significantly improve their gas sorption performance, but also change the gas sorption-desorption behavior because of the preserved permanent porosity. Furthermore, such a facile synthetic strategy can be extended to fabricate other types of H-form zeolite-based porous liquids by taking advantage of the tunability of the counter-anion (e.g., NTf2-, BF4-, EtSO4-, etc.) in branched ionic liquids, thus opening up new opportunities for porous liquids for specific applications in energy and environment.
{ "pile_set_name": "PubMed Abstracts" }
Stamboul (film) Stamboul is a 1932 British drama film directed by Dimitri Buchowetzki and starring Warwick Ward, Rosita Moreno, Margot Grahame, and Garry Marsh. It was released by the British division of Paramount Pictures. The film's sets were designed by the art director Heinrich Richter, Hermann Warm and R. Holmes Paul. Buchowetski also co-directed El hombre que asesino with Fernando Gomis, the Spanish-language version of the film, also released by Paramount. The film is based on the novel L'homme qui assasina (1906) by Claude Farrère and on a play by Pierre Frondaie. Premise In the lead-up to the First World War, a French military attaché falls in love with the wife of a prominent German in Stamboul in the Ottoman Empire. Cast Warwick Ward as Col André de Sevigne Rosita Moreno as Baroness von Strick Margot Grahame as Countess Elsa Talven Henry Hewitt as Baron von Strick Garry Marsh as Prince Cernuwitz Alan Napier as Bouchier Abraham Sofaer as Mahmed Pasha Stella Arbenina as Mme. Bouchier Annie Esmond as Nurse Eric Pavitt as Franz See also The Right to Love (1920) The Man Who Murdered (1931) References External links Category:1932 films Category:British films Category:1930s drama films Category:English-language films Category:Films directed by Dimitri Buchowetzki Category:British drama films Category:British films based on plays Category:British multilingual films Category:British black-and-white films Category:1930s multilingual films
{ "pile_set_name": "Wikipedia (en)" }
More efficient breeding systems for controlling inbreeding and effective size in animal populations. A selection scheme and a mating scheme are proposed to control the inbreeding and genetic drift in conserved or control animal populations with different numbers of males and females. Recurrence equations for the inbreeding coefficient and formulae for effective size are derived for autosomal loci, sex-linked loci with males being heterogametic and sex-linked loci with females being heterogametic under each of four breeding systems. It is shown that both the selection scheme and the mating scheme proposed in this paper could increase the effective size and decrease inbreeding in any generation compared with the classical selection and mating schemes. Among the four breeding systems considered, the most efficient one could increase the effective size by as much as 19 per cent for autosomal loci and 50 per cent for sex-linked loci in comparison with the classical breeding system usually utilized in conserved or control populations.
{ "pile_set_name": "PubMed Abstracts" }
Pōmare Pōmare or Pomare may refer to: Pōmare Dynasty, the dynasty of the Tahitian monarchs Pōmare I (c.1742-1803), first king of the Kingdom of Tahiti Pōmare II (c.1774–1821), second king of Tahiti Pōmare III (1820-1827), third king of Tahiti Pōmare IV (1813-1877), queen of Tahiti (fourth monarch) Pōmare V (1839-1891), fifth and last king of Tahiti Notable New Zealand Māori people named Pōmare Pōmare I (Ngāpuhi) (d. 1826), Ngāpuhi leader, also called Whetoi Pōmare II (Ngāpuhi) (d. 1850), Ngāpuhi leader, nephew of Pōmare I, originally called Whiria, also called Whetoi Hare Pōmare (d. 1864), performer, son of Pōmare II Wiremu Piti (d. 1851), originally called Pomare and Pomare Ngatata, Ngāti Mutunga leader Māui Pōmare (1875 or 1876 – 1930), New Zealand Māori doctor and politician Places Pomare, Lower Hutt, New Zealand Pomare railway station, situated in the above suburb
{ "pile_set_name": "Wikipedia (en)" }
1. Field of the Invention This invention relates to basketball practice devices, and more particularly to a basketball hoop assembly which permits greater basketball accuracy by utilizing a plurality of hoop sizes during the practice sessions. 2. Prior Art Basketball players have been attempting for generations to improve their shooting capabilities. In addition to long hours of shooting practice, basketball players and inventors have attempted to provide devices for helping the players achieve their aims. One such early device is shown in U.S. Pat. No. 1,904,836 to Peoples. A standard basketball hoop is attached to a backboard. An inner ring, is attached by hook means to the standard basketball ring, so as to present a smaller hoop within the larger hoop. A further device of a multiple hoop nature, is shown in U.S. Pat. No. 2,918,283 to Marschalk. This patent shows a basketball practice device with a C-shaped ring which is connectively attached to the top side of a regulation sized basketball hoop. This upper- most ring has a frontal segment which is missing. The gap or open segment in the top most ring permits manipulation of the ring so as to easily remove it or attach it to the regular ring. U.S. Pat. No. 4,613,135 to Rush shows a ring replacement arrangement to enable players to change from the standard diameter ring to a larger diameter ring f or players of limited ability. U.S. Pat. No. 2,694,572 to Crisp shows a basketball practice device comprising a plurality of concentric rings which are supported upon the top of a hoop to facilitate the rebounding of the basketball. U.S. Pat. No. 3,348,840 to Dix shows a rebounding apparatus which attaches to the top of a basketball hoop to permit the basketball to bounce back from the top of the ring. Breakaway or slam-dunk mechanisms are somewhat more recent. U.S. Pat. No. 4,365,802 to Ehrat shows a swingable mount for a basketball hoop. A large compression spring is attached to the backside of the basketball board. A shaft through the spring attaches through the board into the basketball hoop. The spring permits a resilient return of the hoop once it has been knocked out of place and down angularly. U.S. Pat. No. 4,438,923 to Engle et al shows a shock absorber set up to permit pivoting of a single basketball hoop about an axis. A further breakaway arrangement for a basketball hoop, is shown in U.S. Pat. No. 4,534,556 to Estlund et al having a backboard with a tension spring extending therethrough and a release finger which holds the basketball hoop within its regular position. Force on the basketball hoop causes the finger to release and tension on the spring keeps the basketball hoop from excessive movement. Another breakaway basketball device is shown in U.S. Pat. No. 4,676,503 to Mahoney wherein an arrangement of springs or lever arms work adaptively to permit a basketball hoop to pivot in front of the backboard. U.S. Pat. No. 4,465,277 to Dittrich shows a somewhat complicated basketball goal structure wherein a plurality of parallel arm linkages and shock absorbers are arranged to hold a basketball hoop an elongated distance from the support. It is an object of the present invention to provide a basketball hoop arrangement which facilitates basketball players improvement in "making a basket" on a regulation size rim. It is a further object of the present invention to provide a kit wherein a basketball assembly has a series of improvement capabilities which are stepped so as to permit a gradual sharpening of a shooters skill. It is yet a still further object of the present invention to provide an improved breakaway support for the basketball hoop assembly of the present invention.
{ "pile_set_name": "USPTO Backgrounds" }
The present invention relates to an access controller and method for controlling access to a data store. In particular, the invention relates to a method operable in a mail client and a mail client for filtering incoming e-mail. When an e-mail message is sent, a receiver can discover the sender""s e-mail address from the information attached to the e-mail message. Thus, the receiver may subsequently send as many mails as the receiver wishes to the sender. The receiver may also inform someone else of the sender""s e-mail address and third parties may also do the same. Normally this wouldn""t be a problem but there is an increasing amount of unsolicited and useless xe2x80x98Spamxe2x80x99 mail which can choke in-boxes (in-folders) and make it difficult for a receiver to discern real or important e-mail from junk-mail. Accordingly, the present invention provides an access controller for a data store, said access controller being cooperable with means instantiable to send messages across a network to a plurality of clients and means instantiable to receive messages from said clients across said network, said access controller including: means instantiable to generate a token indicative of the number of times a client can access said data store; and authenticating means instantiable to validate any token included in a message from a client to allow or deny access to said data store and a method for controlling access to a data store comprising the steps of: generating a token indicative of the number of times a client can access said data store; and validating any token included in a message from a client to allow or deny access to said data store. The invention enables the sender to control the ability of 3rd parties to successfully send e-mail or to enable the classification of real e-mail from unsolicited possibly junk-mail.
{ "pile_set_name": "USPTO Backgrounds" }
Q: Use cases between interface implementations I know two ways to use an Interface. public interface MyInterface { void myMethod(); } Approach: Using implements: public class MyClass implements MyInterface { @Override myMethod(){} } I'm using an Interface this way most of the time, if the interface is a contract like: MyInterface foo = new MyClass(); Now I can control MyClass with the provided methods of the Interface. This is also nice for collections. If there are some classes which implements MyInterface I have a common thread: List<MyInterface> list = new ArrayList<MyInterface>(); Approach: Using it as an anonymous class: public class MyClass { public MyInterface myInterface = new MyInterface(){ @Override public void myMethod(){} }; } This approach I'm using for callbacks with dependcy injection like this: public class MyOtherClass { public MyInterface myInterface; // Using setter injection here public void setInterface(MyInterface interface){ myInterface = interface; } } MyOtherClass is calling myInterface.myMethod() where it is appropriate. A callback can be realized with the first approach by using the this pointer too. Now I would like to know which approach should be used for a callback and why? I have seen both and I don't know where the real benefit is. As I see it, that's the only difference where I can choose between the first and second approach. If I'm wrong here please tell me another difference. I'm asking this to be able to select the proper tool for different situations. In addition I would like to know another situation but a callback, where I can use the second approach. A: The choice of using a named or an anonymous interface implementation depends on several things: Are you planning to reuse some of the logic in the implementation? - If the answer is "yes", use the first approach; otherwise, use the second approach. Do you need to implement complex logic with lots of external interactions? - If the answer is "yes", use the first approach; otherwise, use the second approach. Does your interface have multiple methods, some of which may meaningfully do nothing? - If the answer is "yes", use the first approach, or make a "default" class with all implementations doing nothing; otherwise, use the second approach. In the end, the biggest difference between these two approaches is mostly non-technical: it has to do with readability of your resultant code. After all, anonymous classes are a little more than "syntactic sugar" - you can perfectly implement your system with only named classes. If you think that a named implementation reads better, use the first approach; if you think that an anonymous one works better, use the second approach.
{ "pile_set_name": "StackExchange" }
Introduction {#s1} ============ Traditionally, ecological and eco-evolutionary epidemiological models describe the dynamics of infectious diseases by considering susceptible, infected and recovered hosts with host-to-host, or host-environment-host transmission [@pone.0071621-Kermack1]--[@pone.0071621-Hudson1]. A number of modifications--such as seasonality [@pone.0071621-Altizer1], or within-host dynamics [@pone.0071621-Mideo1]--have been introduced to the SI- and SIR-models in various attempts to explain recurrent outbreak disease dynamics. However, natural epidemics often show a variety of dynamics that do not correspond to the predictions made by the classical models. One reason for this is that the underlying assumptions on disease transmission are unrealistic for pathogens that spend a considerable amount, or even the most part of their life cycle, in the outside-host environment. A large proportion of opportunist pathogen species also grow actively in the outside-host environment. These environmental pathogens form an increasing problem for human health [@pone.0071621-Cangelosi1], and thus a better theoretical understanding of their epidemiology is required. Currently, most models for environmental transmission allow only decay of pathogens in the outside-host environment [@pone.0071621-Codeco1], [@pone.0071621-Day1], but see [@pone.0071621-Merikanto1]. In addition, the outside-host environment is riddled with other microbes which frequently interact with the pathogen. This means that while active growth as well as ecological interactions in the environment are likely to be profoundly important, they are yet poorly understood factors in disease dynamics. The role of environmental transmission in disease dynamics and the evolution of virulence has attracted increasing interest [@pone.0071621-Day1], [@pone.0071621-Roche1], both due to human pathogen outbreaks such as cholera [@pone.0071621-Colwell1] and emergent animal diseases, e.g. columnaris disease [@pone.0071621-Pulkkinen1]. Worldwide, there is an ongoing battle against opportunistic infections, which are often persistent due to the pathogens' ability to grow outside hosts. Broad-spectrum antibiotics and disinfectants are used *en masse* to prevent environmental infections to humans and cultivated animals. This is likely to cause changes in the composition of environmental communities and have an impact on ecosystem functioning, health and disease [@pone.0071621-Ding1]. Theoretically, an environmentally transmitted pathogen can be highly lethal as the trade-offs between transmission and virulence associated with obligate pathogens are reduced [@pone.0071621-Walther1]. This is because by killing a host--which is not required to be alive for pathogen transmission--the pathogen gains access to an enormously rich resource for saprotrophic growth, which can lead to a positive transmission-virulence relationship [@pone.0071621-Kunttu1]. In most studies, however, the environment represents simply a reservoir into which the pathogen particles are shed from infected hosts and from which the surviving pathogen individuals may re-enter susceptible hosts, without explicit description of the outside-host dynamics other than the decay rate of the pathogen. Interspecific interactions, such as competition, mutualism, predation, and parasitism constitute the core of ecological research. An important implication of these interactions is that the dynamics and stability of individual populations within ecological networks (e.g., communities or food webs) can strongly depend on the composition of these networks and the details of between-species interactions [@pone.0071621-DeRuiter1]--[@pone.0071621-Pimm1]. In general, similar co-occurring species compete for limiting resources [@pone.0071621-Hibbing1] and are attacked by parasites and predators [@pone.0071621-Abedon1]. All of these different ecological interactions can affect the density of pathogens and other interacting species in the community, thereby affecting the probabilities of infection outbreaks. Therefore, understanding the role of ecological interactions in the outside-host environment is likely to be of great importance for uncovering mechanisms behind the dynamics of many environmentally transmitted diseases such as *Vibrio cholera* [@pone.0071621-deMagny1], group A *streptococci* [@pone.0071621-Beres1], *Staphylococcus aureus* [@pone.0071621-Eveillard1], and *Flavobacterium columnare* [@pone.0071621-Pulkkinen1]. We explore the dynamics of a model that combines environmental opportunist pathogen--host dynamics to community dynamics outside the host. By the term environmental opportunist pathogen we mean an organism that is both (i) able to grow in the environment in the absence of hosts and (ii) infect susceptible hosts. Whether the pathogen can infect one or several host species is not important in this simple model in which we consider all (susceptible) hosts similar from the pathogens perspective. The model contains susceptible and infected hosts as in a classical SI-model and a competitive community in the outside-host environment. One of the competitors is a pathogen that can return from a dead host to the environment and thus the host does not represent an ecological or evolutionary dead end for the pathogen. This is opposite to the common assumption of the theory of "co-incidental virulence" [@pone.0071621-Brown1]. Further, we assume that there is a trade-off between virulence and environmental competitive ability. This assumption also differs from the expectation under co-incidental virulence theory [@pone.0071621-Brown1], where resource acquisition or fighting against natural enemies outside the host are positively linked to a pathogens ability to cause infections. Life-history trade-offs can reduce virulence because the machineries for resource acquisition and defence in the outside- vs. inside-host environments require specialisation [@pone.0071621-Gower1], [@pone.0071621-Mikonranta1]. The choice of the functional form of the infectivity response can crucially affect the model dynamics [@pone.0071621-Boldin1], [@pone.0071621-McCallum1]. We explore both linear and sigmoidal infection rate in response to pathogen density, and assume that the infected hosts can either recover back to the susceptible class or die from the disease. The sigmoidal infectivity response incorporates dose-dependence, i.e., exposure to pathogen densities below a certain level is unlikely to cause an infection, as observed in many laboratory experiments [@pone.0071621-Aaby1]--[@pone.0071621-McLean1]. The model behavior is explored in a parameter range that is likely to cover typical environmentally growing opportunist micro-parasites (e.g., bacteria, protozoa, or fungi) that infect multicellular hosts ranging from taxa with fast growth rates (e.g., nematodes and insects) to taxa with slow growth rates (e.g., vertebrates). A striking feature of the model is that reducing competitor species richness in the outside-host environment can lead to an abrupt emergence of disease outbreaks. If the infectivity response of the pathogen is a sigmoidal function of pathogen density in the environment, epidemiological dynamics are sensitive to the intensity of competitive suppression by the outside-host community. With linear infectivity response and pathogen growth in the environment no disease outbreaks are observed, i.e. population dynamics remain stable, and pathogen and host densities are relatively insensitive to manipulation of diversity. Under sigmoidal infectivity, reduction of competitive pressure on the pathogen, either due to loss of diversity from the outside-host community (e.g., due to use of disinfectants), or increased loss rate of all species in the outside-host community (e.g., due to application of non-specific antibiotics) can lead to catastrophic disease outbreaks. Methods {#s2} ======= The dynamical model is a combination of the classical SI-disease dynamics [@pone.0071621-Kermack1] for hosts and the Lotka--Volterra competition model for an outside-host community. The susceptible and infected hosts at time *t* are denoted by *S*(*t*) and *I*(*t*), respectively. The pathogen, *P*(*t*), has *n* competitors, with densities denoted by *B~i~*(*t*), i.e., community size is *N* = *n* +1. The population densities vary according to the following differential equations: In the absence of an infection, susceptible hosts follow a logistic growth model with a growth rate *r~h~* and a carrying capacity *K~h~* (eqn. 1.1). In the presence of an infective pathogen infected host individuals are formed. The infected individuals compete for resources with the susceptible individuals, but do not contribute to host reproduction (this assumption has no qualitative effect on the dynamics). Susceptible hosts are infected with a rate *βSf*(*P*) depending on the infectivity response *f*(*P*). Two alternative infectivity response functions were explored. Most previous theoretical work has assumed a linear infectivity response. However, we argue that a more realistic assumption for many circumstances is a sigmoidal dose-dependent response that is supported by empirical data [@pone.0071621-Aaby1]--[@pone.0071621-McLean1] as well as theoretical analysis [@pone.0071621-Pujol1]. The sigmoidal infectivity function has the following mechanistic interpretation. With low pathogen densities the immune system can effectively overcome most pathogen invasions and therefore the probability of an infection per unit time must increase nonlinearly at low densities. With high pathogen densities the effect of increasing pathogen density on the probability of infection per time unit must saturate since the development of an infection is not an instantaneous process. This type of functional response has been studied by Regoes et al. [@pone.0071621-Regoes1] for direct transmission in the context of the classical SIR-model. Mechanisms behind sigmoidal infectivity response can also include saturation of the immune system with a large number of invaders, density-dependent accumulation of enzymes that allow breaching the immune system or expression of virulence factors due to density-dependent bacterial communication, i.e., quorum sensing [@pone.0071621-Kumar1]. A Hill function ([eqn. 2](#pone.0071621.e005){ref-type="disp-formula"}) was chosen as the functional form for the sigmoid infectivity response *f*(*P*), because it is a simple way to conceive this type of dose-dependence for infections [@pone.0071621-Regoes1]:where parameters *ID* ~50~ and *κ* affects the shape of the response. [Eqn. 2](#pone.0071621.e005){ref-type="disp-formula"} is used as a convenience function with no particular mechanistic underpinning. A classical linear term with *f*(*P*)* = P* was used for comparison. In either case, the infectivity rate is scaled by parameter *β* in eqn (1.1). In eqn. (1.2) infected hosts die from the disease with rate *ν* and recover from the infection with rate *δ*. With the parameter set in [Table 1](#pone-0071621-t001){ref-type="table"}, every 3/7:th infection leads to host death. In case of recovery the pathogens inside a host are killed by the host immune system. 10.1371/journal.pone.0071621.t001 ###### Model parameters and values used in the model. ![](pone.0071621.t001){#pone-0071621-t001-1} Parameter Interpretation Values used in simulations ----------- ----------------------------------------------------- ---------------------------- *n* Number of competitors in the environment 0--17 *r~h~* Host growth rate 0.1 *r~p~* Pathogen growth rate 2.0 *r~b~* Competitor growth rate 2.0 *K~h~* Host carrying capacity 100 *K~p~* Outside host pathogen carrying capacity 10000 *K~b~* Outside host community carrying capacity 10000 *ID* ~50~ Infectious dose at which 50% of hosts are infected. 3150 *κ* Slope parameter of the sigmoid infectivity function 4 *β* Maximum infectivity 4 *δ* Host recovery rate from infection 0.6 *ν* Infection kill rate 0.1 Between species competition strength 0.5 *α* Competitive ability reduction 0.05, 0--0.15 *k* Number of pathogens released at host death 500 *η* Pathogen mortality 1.0, 0--2.5 The parameters are chosen to represent a realistic scenario with a bacterial pathogen and a small multi-cellular host (see text). The pathogen (*P*) and the competing non-pathogenic strains (*B~i~*) grow logistically with rates *r~p~* and *r~b~*. Carrying capacities are *K~p~* and *K~b~* in a Lotka--Volterra competition setting, respectively (for simplicity, *r~p~* = *r~b~*, and *K~p~* = *K~b~*). The competition in the outside-host community was modeled with a very general diffuse competition model where the competitive ability of non-pathogens against the pathogen was varied. The intraspecific competition coefficients were set to 1, whereas between species interaction strength is given by (eqns. 1.3, 1.4; here set  = 0.5). It is assumed that the pathogen pays a cost of its ability to cause infections (e.g., due to extra biochemical machinery) in form of reduced competitive ability. This is realised as competition against the pathogen equal to +α, and for the pathogen in competition with other species -- α, with α being the reduction in pathogen competitive ability. A diffuse competition model is used as a simplification in this model. This is justified since generating between species coefficients randomly with a mean produces, on average, the same dynamics. In the case of positive correlation between virulence and competitive ability, i.e. negative α, a trivial result in our model is that the host is driven to extinction by the pathogen. A mortality term with rate *η* was included for scenarios where growth is not only self-limited but there is another density-independent mortality factor that removes bacteria from the system (e.g., antibacterial substances, or physical outflow from the system). If hosts are sparse, intense outside-host competition in addition to out-flow mortality *η* can drive the pathogen extinct while waiting for the next infection. The effect competition has on the pathogen species could be realised either through reduction in pathogen competitive ability (α) or increasing the number of competitors present in the outside host community (*n*). The equilibrium pathogen density reaches zero with *α = *1/(2*n*) in the absence of the host, due to competition. The survival of the pathogen beyond this level of competition is still possible via coupling to host dynamics due to fitness benefits gained by inside-hosts growth. On the other hand if the pathogen is very infective and lethal, it may kill all the suitable hosts and thereafter become extinct by competitive exclusion. This outcome resembles that of the classical trade-off between virulence and transmission, albeit via an entirely different mechanism. Equilibrium densities for the pathogen and non-pathogenic species in the absence of hosts are: where *r* is the common growth rate for all species. Note that *P\** is only positive when and *r*\>*η.* The model assumes that a burst of pathogens is released to the environment with the death of an infected host. This identifies to saprotrophy where the dead host body is consumed to some degree. As the dead host typically represents an extremely rich resource in comparison to the typical outside-host environment [@pone.0071621-Kunttu1], the number of pathogens released from the host can be extremely high. Thus the large flow of pathogens to the environment from the host can in turn lead to a rapid cascade of infections and host deaths that can ultimately result in host extinction [@pone.0071621-Godfray1]. The parameter ranges used in the simulations are given in [Table 1](#pone-0071621-t001){ref-type="table"}. The pathogen growth rate of two divisions per day represents the lower end of bacterial growth rates. The infected hosts remain infected for a relatively long period since both infection kill rate and recovery rate are low. This is plausible e.g. for an untreated bacterial disease many of which are very persistent. The host growth rate is suitable for a fish host [@pone.0071621-Merikanto1]. Outside host community densities are scaled down to make the numbers comparable in order of magnitude to that of hosts. Multiplying outside host carrying capacity and the number of pathogen units released from a dead host by 10^6^ leads to a scenario where the unit of area could be a cubic metre of water with 100 small fish hosts and 10^10^ bacterial cells. The infectivity parameter values used here allow for effective infecting without driving the host extinct too easily. Extensive simulations with randomly selected parameter values indicate that the results presented here are qualitatively robust ([Materials S1](#pone.0071621.s004){ref-type="supplementary-material"}, [Fig. S2](#pone.0071621.s002){ref-type="supplementary-material"}, [S3](#pone.0071621.s003){ref-type="supplementary-material"}). The model (eq. 1) behaviour was analysed numerically using a Runge-Kutta fourth order routine. Means, maxima, and standard deviations of population densities were recorded from the final 100 time units from each simulation in order to assess the type of the dynamics (e.g. outbreaks). The analysis focused on the asymptotic behavior of the model and excluded the initial transients. Trajectories were simulated for 200 time units that was a sufficiently long time interval for analysing the asymptotic behaviour of the model in all cases. The initial state in all simulations was *S = *100, *I = *0, *P* and *B~i~* chosen from uniform random distribution between 100 and 1600. Results {#s3} ======= The choice of the infectivity response function is crucial to the behaviour of the model. Therefore the following results are presented according to this dichotomy between linear and sigmoidal infectivity responses. A common assumption in epidemiological models is that there is a linear relationship between pathogen density and the number of infections (i.e., *f*(*P*) = *P*, [Fig. 1](#pone-0071621-g001){ref-type="fig"}). The linear response is a benefit to the pathogen since it remains infective even in small doses ([Fig. 2a](#pone-0071621-g002){ref-type="fig"}). However, the host is easily driven to extinction unless its growth is sufficiently fast. Under this assumption, increasing outside-host community size is associated with an initial reduction in the density of free-living pathogen, as expected from classical competition theory ([Fig. 3a](#pone-0071621-g003){ref-type="fig"}, see e.g., May 1972). Increasing competition in the outside-host community quickly drives the pathogen extinct in the absence of hosts. However, the pathogens ability to infect hosts and use them as resources for reproduction compensates for the reduced competitive ability in the outside-host environment ([Fig. 3a](#pone-0071621-g003){ref-type="fig"}). Pathogens persist at a stable density, which is relatively independent of the number of competitors. With the linear response cyclic pathogen dynamics were only observed when pathogens did not grow in the environment (*r~p~*\< *η*) and that there was no significant recovery of infected hosts. Linear response stabilises the dynamics because it prevents host supply re-growth by making the pathogen efficient in infecting also when the pathogen density is low. While pathogen infections reduce the number of susceptible hosts well below their carrying capacity ([Fig. 3b](#pone-0071621-g003){ref-type="fig"}), competition in the outside-host environment can prevent the pathogen from driving the host extinct. ![The infectivity response of the pathogen *f*(*P*) is assumed to be either linear (dashed line) or sigmoidal (solid line) function of pathogen density (P).\ To facilitate comparison, linear infectivity is modeled with rate constant *β*/2*ID* ~50~ and the parameters for sigmoidal response (eq. 2) are set to *ID* ~50~ = 3150 and *κ* = 4. The curves intersect at *ID* ~50~.](pone.0071621.g001){#pone-0071621-g001} ![Susceptible host response to increasing host growth rate depending on the form of pathogen infective response (either linear or sigmoidal).\ Here the competitive disadvantage (α) is fixed to 0.05 and the number of competitor species (*n*) to 6. Linear infectivity response with rate constant *β/*2*ID* ~50~ was used in panels (a) and (c), and *ID* ~50~ = 3150, *κ* = 4 for sigmoidal response (eqn. 2) in panels (b) and (d).The lines in (a) and (b) represent minima and maxima of population densities. In (c) and (d) the solid line is susceptible host density and the dotted line is infected host density.](pone.0071621.g002){#pone-0071621-g002} ![Pathogen and susceptible host response to increasing number of competitors in the outside-host community (*n* = *N* --1).\ Here α is fixed to 0.05 and linear mortality parameter *η* to 1.0. Linear infectivity response with rate constant *β/*2*ID* ~50~ was used in panels (a) and (b), and *ID* ~50~ = 3150, *κ* = 4 for sigmoidal response (eqn. 2) in panels (c) and (d). Filled symbols represent minimum and maximum densities. In the cyclic range in (c) and (d) open symbols show the alternative attractor and filled symbols show minima and maxima. The solid line is the equilibrium pathogen density without hosts.](pone.0071621.g003){#pone-0071621-g003} A pathogen with a sigmoidal transmission differs from the linear transmission in its response to increasing competition pressure in three important ways ([Fig. 2](#pone-0071621-g002){ref-type="fig"}, [3c, 3d](#pone-0071621-g003){ref-type="fig"}): (1) Near the point where pathogen growth rate in the absence of hosts approaches zero due to competitive exclusion, increasing outside-host community size gives rise to cyclic pathogen dynamics. (2) After this bifurcation an alternative attractor appears where the pathogen is excluded from the system. This happens because of the Allee effect associated with the sigmoidal dose-response function [@pone.0071621-Regoes1]; if the pathogen is initiated at a sufficiently low density, it is unable to infect susceptible hosts, preventing fitness gains through within-host growth. Also when the initial pathogen density is too high there is a rapid increase in density followed by a drop to very low density after which the pathogen density stays close to zero. (3) Increasing outside-host community size further amplifies the cyclic dynamics on the attractor where the pathogen is present. This continues up to a point where competitive pressure is sufficiently high to prevent pathogen infections independently of initial conditions, leading to an abrupt disappearance of the pathogen from the system. The range of cyclic dynamics depends on host growth rate ([Fig. 2B](#pone-0071621-g002){ref-type="fig"}). Outbreaks arise when the time scale of pathogen release from hosts is comparable to that of host growth rate. If pathogen release happens much faster than hosts grow or recover then no hosts are available for the released pathogen making further cycling impossible. The host growth rate of 0.1 per day used in our simulations is quite high for most large multi-cellular organisms. To represent diseases of slowly growing hosts the infectivity and host-pathogen interaction parameters need to be scaled accordingly to retain the same range of qualitative dynamics. For example cyclic dynamics can be retained at lower host growth rates by lowering infected host recovery and death rates at the same time. Similar patterns to those shown in [Fig. 3](#pone-0071621-g003){ref-type="fig"}, due to increasing size of the outside-host community *N*, can be generated by varying the competitive disadvantage of the pathogen, α, for this parameter set ([Fig. S1](#pone.0071621.s001){ref-type="supplementary-material"}). This is easy to understand, as increasing either the number of competitors (*n*) or competitive disadvantage (α) decreases the equilibrium density of the pathogen (eqn. 3). Under sigmoidal transmission this means that when the pathogen is unable to survive in the outside-host environment without fitness gains from host infection, the presence of susceptible hosts can be associated with two alternative attractors, with pathogens either present or absent. When competition is intensive enough, pathogens are unable to reach sufficiently high densities for infections to arise, inevitably leading to pathogen extinction. Increasing mortality (*η*) in outside-host environment reduces the competitive pressure from the rest of the outside-host community on the pathogen. When this density-independent mortality is intermediate, the pathogen can thrive in environments where competition would otherwise drive it to extinction ([Fig. 4c](#pone-0071621-g004){ref-type="fig"}). The reason for this is that increasing *η* reduces the density-dependent negative feedback from competitors to the pathogen, leading to better utilisation of the fitness benefits from within-host reproduction. This effect is not seen when the infectivity response is linear ([Fig. 4a](#pone-0071621-g004){ref-type="fig"}). ![Density-independent mortality *η* affects pathogen and susceptible host densities.\ Here the number of competitors is fixed to 15 and pathogen competitive disadvantage α is fixed to 0.05. Linear infectivity response with rate constant *β*/2*ID* ~50~ was used in panels (a) and (b), and sigmoidal response (eqn. 2) in panels (c) and (d). Filled symbols represent minimum and maximum densities. In the cyclic range in (c) and (d) open symbols show the alternative attractor and filled symbols show minima and maxima. The solid and dashed lines indicate the equilibrium pathogen and non-pathogenic competitor densities without hosts, respectively.](pone.0071621.g004){#pone-0071621-g004} If the mortality term is taken as non-specific antibiotic treatment, the effect of increasing mortality can depend on initial conditions with the sigmoidal infectivity: If the pathogen is present in the system, sufficient antibiotic treatment leads to pathogen extinction. In contrast, if the pathogen is initially at a very low density and antibiotics are applied as a precautionary measure, the treatment can paradoxically result in pathogen outbreaks. The scenario, where *η* is equal for all environmental species, represents a limiting case along a continuum where the pathogen is affected by the antimicrobial substance either more or less than on the competing species on average. If the treatment targets the pathogen more than other species, the probability of an outbreak is reduced. In the worst case the treatment targets the pathogen less than the competitors leading to an increase in pathogen density by reducing competition. Discussion {#s4} ========== Environmentally growing opportunists are common class of pathogens but there are few attempts to understand how environmental growth and ecological interactions outside the host affect epidemiological dynamics. We present here an analysis of the epidemiology of an environmental pathogen that has sustained growth in the absence of hosts and interacts with non-pathogenic organisms through competitive interactions. The results stress three important factors affecting the host--pathogen interaction: (1) The shape of the infectivity response has a strong impact on the dynamical behavior of the system; (2) Under a sigmoidal dose-dependent pathogen infectivity response reducing species richness of non-pathogenic competitors in the outside-host environment provides a novel mechanism for disease outbreaks; (3) With the sigmoidal infectivity too high pathogen virulence can lead to host extinction, which leads to virulence becoming useless for the pathogen. Microbial Diversity and Disease Dynamics {#s4a} ---------------------------------------- The importance of biodiversity on the stability and functioning of ecological communities continues to motivate ecological research [@pone.0071621-McCann1]--[@pone.0071621-Loreau2]. A common observation is that increasing diversity tends to promote stability of community biomass [@pone.0071621-Tilman1], [@pone.0071621-Hector1]. The importance of diversity in ecological systems and the ubiquitousness of environmentally growing pathogens are well known [@pone.0071621-Cangelosi1], but the theory connecting diversity to disease outbreaks is centred mainly on host diversity [@pone.0071621-Keesing1] with some work on pathogen diversity [@pone.0071621-Gupta1]. Our results show that the intensity of competitive interactions--modified either through community size or the strength of interspecific interactions--in outside-host environments can be very important for the dynamics of environmental opportunistic pathogens and the occurrence of disease outbreaks. These results are in agreement with numerous empirical observations promoting the importance of biodiversity for disease dynamics. For example, biodiversity loss has been associated with both increases and decreases in disease transmission [@pone.0071621-Keesing2]. Loss of fungal diversity in agricultural soil has been shown to result in higher incidence of fungal plant diseases, and it is noteworthy that even generally non-pathogenic fungi can cause diseases if they are the predominant species [@pone.0071621-Nitta1]. Loss of bacterial diversity has been linked to problems in the human intestine such as inflammatory bowel diseases [@pone.0071621-Round1], and low microbial diversity is also suspected to be the cause of several allergies [@pone.0071621-Hanski1]. The Role of the Pathogen's Infectivity Response {#s4b} ----------------------------------------------- Our results indicate that the way increasing competitive pressure on the pathogen in the outside-host community affects pathogen dynamics depends crucially on the shape of the pathogen's infectivity response (i.e., how pathogen infectivity depends on its own density) ([Figs. 3](#pone-0071621-g003){ref-type="fig"}, [S1](#pone.0071621.s001){ref-type="supplementary-material"}). A common assumption in epidemiological models is that the relationship between pathogen number and infections is linear [@pone.0071621-McCallum1]. In this case the pathogen (suffering a cost in competitive ability) is able to compensate for reduced density due to competition via fitness benefits from host infection, and is relatively unaffected by varying, e.g., community size in the outside-host environment ([Fig. 2a](#pone-0071621-g002){ref-type="fig"}). This is because the pathogen remains infective even at low densities. In contrast, under a sigmoidal infectivity response that incorporates an infective dose [@pone.0071621-Regoes1], [@pone.0071621-Joh1] increasing community size can either generate cyclic pathogen outbreaks, or drive the pathogen extinct ([Fig. 2c](#pone-0071621-g002){ref-type="fig"}). If pathogen densities are reduced sufficiently, the pathogen is unable to (re)enter the infection cycle. Similarly to the direct host-to-host transmission of obligatory pathogens studied by Regoes et al. [@pone.0071621-Regoes1], the sigmoidal infectivity response is a disadvantage to the pathogen also in our model with environmental transmission and growth. This is due to the Allee effect associated with sigmoid response [@pone.0071621-Regoes1]. Increasing competitive pressure on the pathogen eventually leads to a situation where the pathogen is unable to recover from low densities and cause infections, resulting in pathogen extinction. On the other hand, when competition is weak the pathogen can drive the host extinct, where after infectiveness becomes useless to the pathogen. This phenomenon resembles the consequences of the classical trade-off between virulence and transmission in obligate pathogens [@pone.0071621-Levin1], [@pone.0071621-Paul1], but arises from a completely different mechanism. The host represents simply a resource for the pathogen that may in cases be 'over-exploited' and lost, reducing the system to the outside-host community. Over-exploitation of the host is the mechanism behind cyclic host-pathogen dynamics, similarly to the mechanism underlying cyclic consumer-resource dynamics [@pone.0071621-Rip1]. As indicated above, the shape of the infectivity response at low pathogen densities has a profound impact on the dynamics. If infectivity is low (and increases slowly) at low pathogen densities, the pathogen needs to reach relatively high densities in the environment to become infective. This can in turn be prevented by, e.g., ecological interactions in the outside-host environment that reduce pathogen densities (such as competition, predation, and parasitism). The importance of the shape of infectivity response in environmental transmission has been recognized by Boldin & Kisdi [@pone.0071621-Boldin1] in evolutionary context. They argued that a concave infectivity response enables evolutionary branching. Here we have shown that convexity of the infectivity response at low pathogen densities can be very important for epidemiological dynamics of opportunistic, environmentally growing pathogens. Environmental Growth {#s4c} -------------------- Outside-host growth of pathogens is widespread in nature. Models of environmentally transmitted diseases typically allow only exponential decay of pathogens [@pone.0071621-Day1], [@pone.0071621-Roche1] or in some cases density-independent growth [@pone.0071621-Codeco1], [@pone.0071621-Joh1], [@pone.0071621-Capasso1], [@pone.0071621-Fisher1]. To our knowledge, density-dependent growth has been analysed only by Merikanto et al. [@pone.0071621-Merikanto1]. Outside-host growth and the recovery of infected hosts have a strong stabilising influence on pathogen dynamics. Density dependent growth dampens the influence of pathogens shed from infected hosts, when the outside-host pathogen population is near its carrying capacity [@pone.0071621-Merikanto1]. Recovery is stabilising because it moderates the decline of susceptible hosts after a disease outbreak. Under a linear infectivity response density-dependent pathogen growth in the outside-host environment effectively filters the inflow pathogens from infected hosts, resulting in stable population dynamics [@pone.0071621-Merikanto1]. Cyclic outbreaks can arise only when pathogens do not exhibit active growth in the outside-host environment (i.e., there is only an exponential decay of pathogen densities), and when the pathogen is extremely lethal. A sigmoidal infectivity response is more prone to generate cyclic population dynamics because after an outbreak host growth is more rapid than the increase in pathogens infectivity at low densities, allowing the host supply to recover before the next outbreak. Implications {#s4d} ------------ Multi-cellular hosts are high resource environments with a potentially deadly immune system for parasites. Parasites often have to allocate considerable amount of resources for infecting and overcoming the immune system, and sacrifice part of their competitive ability in the outside host environment [@pone.0071621-Godfray1]. However, the payoff is that once the immune system is defeated the nutrient rich body may be consumed to gain massive fitness benefits. An example of an effective and highly virulent environmental pathogen that grows slowly in the environment is *Flavobacterium columnare*, a saprotrophic fish pathogen that causes considerable economical losses in fisheries [@pone.0071621-Kunttu1]. Other examples of well-studied environmental saprotrophic pathogens are *Serratia marcescens* and *Pseudomonas sp*. both capable of infecting a wide range of hosts. Opportunism coupled with the ability to grow in the free-living environment, may be an important step in the evolution of virulence for bacteria. This naturally requires that pathogens are released from the infected host to the environment, i.e., the host is not an ecological or evolutionary dead end. Free-living bacteria may develop infectivity but lack the means for effective host-to-host transmission. Thus they would benefit from infectivity only if they are virulent enough to gain reproductive output from the host and survive in the environment until encountering a new host. The waiting time before a new infection may be long and the costs of maintaining infectivity traits are likely to restrict the growth rate of the pathogen. If the resources are sparse and there is competition for them, the non-pathogenic competitors are likely to out-compete the pathogen, and this may lead to local pathogen extinction. Applying a non-specific mortality factor upon the outside-host community can reduce competitive pressure on the pathogen. While the density of all species, including the pathogen, is reduced equally in the outside-host environment, the pathogen gets an indirect advantage through within-host reproduction ([Fig. 3](#pone-0071621-g003){ref-type="fig"}). This suggests that the use of antimicrobial substances as a means of controlling pathogen growth does not always have the desired effect. If all species in the outside-host community are similarly susceptible to the substance, its action is reasonably modeled as a linear mortality term imposed on all members of the outside-host community. This can in some cases help the pathogen by removing competition. It would then be crucial to use enough antimicrobial substances to reach the range where the pathogen cannot survive. It would also be possible that the introduction of effective non-pathogenic competitors could work as a defense measure in such conditions because treatment of hosts in environmentally growing pathogens is ineffective [@pone.0071621-Merikanto1], [@pone.0071621-Joh1]. Supporting Information {#s5} ====================== ###### **Equilibrium pathogen and susceptible host densities as a function of competitive disadvantage of the pathogen (α).** Black dots represent mean densities. At cyclic ranges open circles represent an alternative attractor and filled symbols indicate minima and maxima. Here the number of competitors is fixed to *n = *7 and linear mortality parameter *η* to 1.0. Linear infectivity response with rate constant *β*/2ID~50~ was used in panels (A) and (B), and sigmoidal response ([eqn. 2](#pone.0071621.e005){ref-type="disp-formula"}) in panels (C) and (D). The solid line is the equilibrium pathogen density without hosts. (TIF) ###### Click here for additional data file. ###### **Mean pathogen densities versus competitive disadvantages of the pathogen (α) from sensitivity analysis replicates.** In panel (A) with linear infectivity response red dots represent individual simulation outcomes. In panel (B) with sigmoidal infectivity response cyan dots represent outcomes from simulations resulting in stable dynamics (s.d.(*P*) \<10). Red and blue dots represent outcomes from simulations resulting in cyclic dynamics (s.d.(*P*) \>10). To distinguish between alternative outcomes, values above 1000 are coloured red and those below 1000 are blue. Grey dots represent standard deviations (s.d.(*P*)) above and below the mean value. The replicates resulting in host extinction (mean(*S*) \<5) have been excluded from both panels. Panel (A) has 50720 points and panel (B) has 86615 coloured points of which 14159 are cyclic and 72456 are stable. Total number of simulations is 100000 in both cases. (TIF) ###### Click here for additional data file. ###### **Posterior parameter distributions from sensitivity analysis replicates not resulting in host extinction (mean(*S*) \>5)**. The parameter values for unspecific mortality rate (*η*), host growth rate (*r~h~*), host recovery rate (*δ*), infected death rate (*ν*), and pathogen release (*k*) were picked from uniform random distributions. Selecting the cases with host persistence resulted in 50720 replicates in the upper panels (linear infectivity) and 86615 replicates in the lower panels (sigmoidal infectivity) from a total of 100000 replicates for each infectivity response. (TIF) ###### Click here for additional data file. ###### **Sensitivity analysis.** (DOCX) ###### Click here for additional data file. We thank Eva Kisdi, Lotta-Riina Sundström, Anna-Liisa Laine, Tarmo Ketola, and two anonymous reviewers for insightful comments and suggested corrections. [^1]: **Competing Interests:**The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: JA LR VK JL. Performed the experiments: JA. Analyzed the data: JA LR. Wrote the paper: JA LR VK JL. Provided the original idea: JL. Constructed the model: JA.
{ "pile_set_name": "PubMed Central" }
Arsenic- and mercury-induced phytotoxicity in the Mediterranean shrubs Pistacia lentiscus and Tamarix gallica grown in hydroponic culture. Hg and As resistance and bioaccumulation were studied in hydroponically grown Pistacia lentiscus and Tamarix gallica plants. Both elements caused growth inhibition in roots and shoots, with mercury showing greater phytotoxicity than arsenic. Accumulation of both elements by plants increased in response to element supply, with the greatest uptake found in T. gallica. Both elements affected P and Mn status in plants, reduced chlorophyll a concentration and increased MDA and thiol levels. These stress indices showed good correlations with As and Hg concentration in plant tissues, especially in the roots. Toxic responses to mercury were more evident than for arsenic, especially in shoot tissues. T. gallica showed higher resistance to both Hg and As than P. lentiscus, as well accumulating more As and Hg.
{ "pile_set_name": "PubMed Abstracts" }
Lorenzo Parodi Lorenzo Parodi (Genoa, 24 May 1926 – Genoa, 31 July 2011) was an Italian trade unionist, communist revolutionary and politician, founder in 1965 of Lotta Comunista with Arrigo Cervetto. From the small workshop to Ansaldo Lorenzo Parodi was born into a working-class family: his father "Bartolomeo Parodi" worked at the forging department "Ansaldo" of Genoa Sampierdarena. He started to work at fourteen years old in a small bolts of Genova Nervi, in the midst of World War II Lorenzo goes to the big factory, and the professional apprenticeship come before the first political experiences just over a year. Lorenzo Parodi starts to work at Ansaldo, as a turner at the department "small cars" (MAPI) in the summer of 1942. Half a century later, introducing the third edition of "Cronache Operaie", he remembers " We were among the boys entered the factories in the early forties to replace the "cannon fodder" sent to front ." The first political experiences in the fire of World War In the spring of 1943 Lorenzo Parodi joined the strike in progress at Ansaldo and in 1944, to escape the Nazi raids and deportation, he's forced to leave the factory. Parodi becomes partisan in SAP Brigade "Crosa" of Genova Nervi: here his political novitiate starts; due his anti-Stalinist choice, he meets the young libertarian communists of Nervi like Antonio Pittaluga, Vero Grassini, Agostino Sessarego and Mario Vignale and later the group of Genoa Sestri. It is especially "the refusal of Togliatti's opportunism" and the attempt "still confused to salvage the savable from the opportunistic wave that will block and overwhelm the class movement emerged from the struggle against fascism" the factors that will approaches him and his group to libertarian and anarchist ideas. The process of political maturation in the postwar The young Parodi return to Ansaldo at the end of the war. His political work is expressed in the commitment to bring the anarchist movement on a line of concrete political struggle; with Arrigo Cervetto and other people like them, he works for the foundation of the "Anarchist Groups of Proletarian Action" (GAAP), enshrined in the Convention of Genoa Pontedecimo of February 1951. "It is the search for another communism that was not the subjection to Moscow of stalinian PCI that will connect Lorenzo Parodi and Arrigo Cervetto between 1948 and 1949. The meeting land was an attempt of Pier Carlo Masini and Cervetto to group around the young of the FAI Italian Anarchist Federation in a libertarian communist movement, organized and federated, to leave the traditional anarchist individualism. The research for 'homogeneity as theoretical science of revolution' directs him to a serious study of "Capital" in Marx and to study Lenin. The Internationalist position on the uprising in Budapest The presence in the National Steering Committee of the CGIL provides the grandstand for a clear internationalist position on the workers' revolt in Budapest of October and November 1956. The Secretary-General Di Vittorio, after his deploring on Russia's military intervention expressed on October, made a rapid march back. Lorenzo Parodi supports the uprising in Budapest in connection with other significant events of that crucial 1956 (the Revolt of Poznan, the colonial war conducted in Algeria by the government of Guy Mollet, the Suez Crisis). The confluence in Azione Comunista After the confluence of the GAAP, in the spring 1957, in the group of "Azione Comunista" founded two years earlier by a "dissident" of PCI, Parodi is committed to the side of Arrigo Cervetto against the Maximalism of the group to attest an internationalist position. He presents with Cervetto, at the first conference of the Communist Left November 1957 in Livorno, the "Theses on imperialist development, the duration of the counter and on the development of the class party", that is now expressed in an organic strategic vision of the current Leninist. The Foundation of Lotta Comunista The strategic task for the proletariat, the class that can and should revolutionize the imperialist society, is now clearly outlined in the vision that Parodi shares with Cervetto's vision. The strategic vision of the Theses of '57 is in fact linked to the conception of the party's strategy: to Parodi Cervetto send in 1964 the drafts of the study (which will be collected two years later in volume, with the title of "Class Struggles and revolutionary party ", and over again until the sixth edition of 2004, which also republishes those letters) on the Leninist concept of political action, with the goal of having 'a text-based current Leninist in Italy". On that basis Cervetto and Parodi can turn the page on the experience of "Azione Comunista" in December 1965, year of the first issue of "Lotta Comunista" (which will Parodi director until his death) and begins a vast work of settlement organization. See also Arrigo Cervetto Lotta Comunista Category:1926 births Category:2011 deaths Category:People from Genoa
{ "pile_set_name": "Wikipedia (en)" }
Human peritoneal macrophages synthesize leukotrienes B4 and C4. Macrophages were isolated from the dialysis fluid of patients undergoing continuous ambulatory peritoneal dialysis and separated by gradient centrifugation and purification on 50% Percoll. The cells were prelabeled with [14C]arachidonic acid for 1.5 h. The labeled cells were then incubated with calcium ionophore A23187 (1 microM), serum-treated zymosan (200 micrograms/ml), and a lipoxygenase inhibitor, nordihydroguairetic acid (1 X 10(-5) M). The arachidonate metabolites in the medium were separated on Sep-Pak columns, and finally purified by reverse-phase high-pressure liquid chromatography (HPLC). The labeled products co-chromatographed with authentic leukotriene B4 and leukotriene C4 standards. Serum-treated zymosan and A23187 significantly stimulated and nordihydroguairetic acid significantly inhibited leukotriene synthesis. Leukotriene D4 was not detected, which suggests that these cells contain low gamma-glutamyltranspeptidase or high dipeptidase activity. These results establish, for the first time, that human peritoneal macrophages synthesize the lipoxygenase products, leukotriene B4 and leukotriene C4.
{ "pile_set_name": "PubMed Abstracts" }
# Airspeed Velocity `pandera`'s performance benchmarks over time can be [viewed on this airspeed-velocity dashboard](https://pandera-dev.github.io/pandera-asv-logs/). The [config](https://github.com/pandera-dev/pandera-asv-logs/tree/master/asv_bench/asv.conf.json) and [results files](https://github.com/pandera-dev/pandera-asv-logs/tree/master/results) files are tracked in the [pandera-asv-logs](https://github.com/pandera-dev/pandera-asv-logs) repo to avoid build files in the main repo. The [benchmarks](https://github.com/pandera-dev/pandera/tree/master/benchmarks/) are tracked in the main [pandera repo](https://github.com/pandera-dev/pandera). ## Running `asv` Ensure both the `pandera` and `pandera-asv-logs` repos are checked out to the same parent directory. From the `pandera-asv-logs` repo, run: ``` asv run ALL --config asv_bench/asv.conf.json ``` ## Publishing results: To build the html and preview the results: ``` asv publish --config asv_bench/asv.conf.json asv preview --config asv_bench/asv.conf.json ``` The `.json` results files are committed or PR'd into the master branch of `pandera-asv-logs`. The published html is pushed directly to the gh-pages branch of `pandera-asv-logs` by running: ``` asv gh-pages --rewrite --config asv_bench/asv.conf.json ``` The `--rewrite` flag overwrites the existing `gh-pages`, avoiding duplication of data. The `asv` docs are [here](https://asv.readthedocs.io/en/stable/index.html).
{ "pile_set_name": "Github" }
863*n**3 + 24773*n. -227178*n Find the second derivative of 3*m**5 - 12111*m**3 + 6*m - 1425. 60*m**3 - 72666*m What is the second derivative of -40*i**4*j + i**4 + 432*i**3 - 73*i*j + 9*i - 2*j - 1 wrt i? -480*i**2*j + 12*i**2 + 2592*i What is the third derivative of 381*w**6 + w**5 + 54*w**3 + 3*w**2 + 307*w wrt w? 45720*w**3 + 60*w**2 + 324 What is the third derivative of -3*o**4*z**3 + 6781*o**3*z - 57*o**2*z - 102*o*z**3 wrt o? -72*o*z**3 + 40686*z Find the third derivative of 1853752*k**4 + 196856*k**2 + 1 wrt k. 44490048*k What is the derivative of -4*i*l**3 + 2265*i + 2*l**3 - 1498 wrt i? -4*l**3 + 2265 Find the second derivative of 10*b**3*i*r + 3*b**2*i*r - 22*b**2*i + 19*b**2 + b*i + 7*i - 876*r wrt b. 60*b*i*r + 6*i*r - 44*i + 38 What is the third derivative of -q**4 + 2*q**3*r - 4435*q**3 - 2*q**2*r + 5*q**2 + q*r + 477*q + 27 wrt q? -24*q + 12*r - 26610 What is the derivative of 2*p**4 + 2*p**3 + 1651110*p**2 + 661611 wrt p? 8*p**3 + 6*p**2 + 3302220*p Find the third derivative of 52744*j**6 + j**2 - 16894. 6329280*j**3 Find the third derivative of 4*p**5 + p**4*w**2 + 85*p**3 + 17*p**2*w - p**2 - 20*p*w**2 - 2*w**2 wrt p. 240*p**2 + 24*p*w**2 + 510 What is the third derivative of -298*f**2*v**3 - 395*f**2*v - 4*f*v**3 + 4*v**3 + 10*v**2 - 1 wrt v? -1788*f**2 - 24*f + 24 What is the first derivative of 71188*g**2*t**3 + 11008*t**3 wrt g? 142376*g*t**3 Find the third derivative of 374602*y**3 - y**2 - 84*y - 41. 2247612 Find the first derivative of b*d**3 + 5937*b*d + 48989*b + 19*d**4 wrt d. 3*b*d**2 + 5937*b + 76*d**3 What is the third derivative of -90059*a**3*w**3 - a**3*w**2 - 2*a**3*w + 28*a**2*w**2 + 21*a**2*w wrt w? -540354*a**3 Find the second derivative of -830*p**4 + 9*p**3 + 3*p**2 + 688*p - 68 wrt p. -9960*p**2 + 54*p + 6 Find the second derivative of 552371*s**3 + 142423*s. 3314226*s What is the third derivative of -2320*k**5 + 9*k**4 + k**2 + 72185? -139200*k**2 + 216*k What is the second derivative of 675*b**4 - 21*b**3 - 8*b**2 + 10*b + 16138 wrt b? 8100*b**2 - 126*b - 16 Find the first derivative of -23*c**3*u - 2*c**3 - 6949*c + 189*u wrt u. -23*c**3 + 189 Find the third derivative of -438523*u**3 - 2*u**2 + 39*u + 160. -2631138 Find the third derivative of -152*v**6 + 14*v**5 - 2*v**3 + 969*v**2 - 1. -18240*v**3 + 840*v**2 - 12 Find the first derivative of -2266*i**3 - 70*i**2 - 1868529. -6798*i**2 - 140*i What is the second derivative of -10728*z**5 - 64*z - 19? -214560*z**3 Find the third derivative of -146706*v**5 - v**4 - 2*v**3 - 1824273*v**2 wrt v. -8802360*v**2 - 24*v - 12 What is the third derivative of -4*z**5 - 16*z**4 + 28*z**3 - 97542*z**2? -240*z**2 - 384*z + 168 What is the second derivative of 5710906*k**2 - 4649147*k? 11421812 Find the second derivative of -40694*m**4 + 27305*m. -488328*m**2 What is the third derivative of -682*r**4 + 713*r**3 - r**2 - 10260*r - 1 wrt r? -16368*r + 4278 What is the second derivative of 33*d**4 + 2*d**3 + 47*d**2 - 61817*d wrt d? 396*d**2 + 12*d + 94 Differentiate 2*y**4 + 1647*y**2 + 4*y + 137682. 8*y**3 + 3294*y + 4 Find the first derivative of 11432*q**4 - 79*q**3 + 4502783. 45728*q**3 - 237*q**2 What is the second derivative of -2*m**2*p**2 + 2179*m**2 + m*p**2 - 14589*p**2 - 3*p wrt m? -4*p**2 + 4358 Find the first derivative of 49851*p + 57744 wrt p. 49851 Differentiate 55*y**2 + 56*y - 20673. 110*y + 56 What is the third derivative of -331*g**2*n*z**2 + 4*g**2*z**3 + g*n*z**3 - 72*g*z**2 + 18*n*z**3 + 3*n*z**2 + 36*z**3 wrt z? 24*g**2 + 6*g*n + 108*n + 216 What is the first derivative of -27107*k**2 - 179860 wrt k? -54214*k Find the third derivative of 1217*k**5*p**3 - 260*k**3*p**3 - k**2*p**2 + 268880*k*p**3 wrt k. 73020*k**2*p**3 - 1560*p**3 What is the third derivative of 3*l**4 - 423538*l**3 + 1135*l**2 + 61? 72*l - 2541228 What is the third derivative of 2768218*f**4 + 117*f**2 + 134? 66437232*f Differentiate -2*f*j**2*v - f*j**2 - f + 697*j**2*v**3 + 1752 with respect to v. -2*f*j**2 + 2091*j**2*v**2 Find the second derivative of 24341*n**4 + n**3 + 5489*n wrt n. 292092*n**2 + 6*n Find the second derivative of -3*t**4*u**3 - 22814*t**4*u - 11*t*u**2 + t - 4*u**3 + 57*u wrt t. -36*t**2*u**3 - 273768*t**2*u What is the second derivative of -10203*f**3 - 15*f**2 - 303718*f? -61218*f - 30 Find the third derivative of -3*z**4 + 263973*z**3 - 3081394*z**2 wrt z. -72*z + 1583838 What is the derivative of -230620*t**3 - 444394? -691860*t**2 What is the third derivative of -5617*o**5 - 3*o**4 - 10*o**3 + 6199184*o**2? -337020*o**2 - 72*o - 60 Find the third derivative of -67321*o**4 - 8*o**2 - 15*o + 25. -1615704*o What is the third derivative of -914*b**4*n + 8*b**3*n**3 - 33*b**2*n - 1114*n**3 wrt b? -21936*b*n + 48*n**3 Differentiate 14400*c**4*y**3 - c**4*y - 2546*y**3 + 3 wrt c. 57600*c**3*y**3 - 4*c**3*y What is the second derivative of -24*f**5 + 500*f**3*z**2 + 7*f*z**2 - f*z + 711*f wrt f? -480*f**3 + 3000*f*z**2 Find the third derivative of -2*l**3*r*w - 406*l**3*w + 3*l**3 - 74*l**2*r*w + 3*l**2*r - 2*l - 10*r*w wrt l. -12*r*w - 2436*w + 18 Find the second derivative of -91836*x**2 + 8450*x + 1. -183672 What is the second derivative of 135351*g**3 - 4*g - 23490 wrt g? 812106*g What is the third derivative of 404214*w**6 + 1392004*w**2 + 2*w wrt w? 48505680*w**3 Find the third derivative of -18*m**6 + 22*m**5 + 6*m**4 + 8679*m**2 - 2. -2160*m**3 + 1320*m**2 + 144*m Find the second derivative of 46959*l**4 + 2*l**3 + 2*l**2 + 91*l + 472 wrt l. 563508*l**2 + 12*l + 4 Find the second derivative of -3642*b**3*j*n**2 - 84*b**3*j*n - 4*j*n**2 + 118*j*n wrt n. -7284*b**3*j - 8*j Differentiate -14*d**2*i - 24710*d**2 - 567*i**2 + 2 wrt i. -14*d**2 - 1134*i What is the second derivative of 1853*c**3*x**2 - 100*c**3 + c**2*x**2 + 221*c**2*x + x**2 wrt x? 3706*c**3 + 2*c**2 + 2 Differentiate 800066*p - 1349963 with respect to p. 800066 Find the third derivative of -18*j**4 - 3018*j**3 - 4395*j**2 + 143*j. -432*j - 18108 What is the third derivative of 3*m**5 - 7204*m**4 - 32527*m**2? 180*m**2 - 172896*m What is the third derivative of 15588*v**5 - 2*v**4 - 77255*v**2 wrt v? 935280*v**2 - 48*v What is the third derivative of -1135176*j**5 - 346216*j**2? -68110560*j**2 Find the first derivative of -2404*q**2 - 4*q - 22082 wrt q. -4808*q - 4 Find the second derivative of 4*g**3*p**2 - 2994*g**3 + 2*g*p - 17487*p**2 wrt g. 24*g*p**2 - 17964*g Differentiate 5*c*i**3*u - 169*c*i**2*u - 1223*c + 5*i**3*u + 4*i**3 - 547*i**2*u - 26*i*u wrt c. 5*i**3*u - 169*i**2*u - 1223 Find the first derivative of 17*f**3*o + 44*f**2*o**3 + 2*f**2*o + 2*o**3 + 6337*o wrt f. 51*f**2*o + 88*f*o**3 + 4*f*o What is the derivative of 8*z**4 + 1171*z**2 - 27778? 32*z**3 + 2342*z What is the third derivative of 10719*i**4 - i**3 - 97*i**2 - 2*i - 38 wrt i? 257256*i - 6 What is the third derivative of -7789*f**5*r**2 - 2*f**5 - 5*f**2 + 2*f*r - 108*r**2 + 6*r wrt f? -467340*f**2*r**2 - 120*f**2 What is the first derivative of 10*a**4 - 2*a**2 + 3530*a + 140485 wrt a? 40*a**3 - 4*a + 3530 What is the first derivative of -5*b**3*r - 186*b**3 + 31649*b**2*r**3 + 12*b + 5 wrt r? -5*b**3 + 94947*b**2*r**2 Find the second derivative of a**3*c*u**3 + 2*a**3*c*u - 43*a**3*c - 60139*a**3*u**3 - 42*a**2*c*u - 6*a**2*c + 2*a*u wrt u. 6*a**3*c*u - 360834*a**3*u What is the third derivative of 547090*j**5 + 2*j**4 - 2*j**3 + 999896*j**2 wrt j? 32825400*j**2 + 48*j - 12 What is the first derivative of 90827*s*t**3 + t**3 - 347*t**2 + 24*t wrt s? 90827*t**3 Find the third derivative of 55296*n**3 + 17*n**2 - 349 wrt n. 331776 Find the third derivative of 2*h**4 - 828501*h**3 + h**2 + 110*h - 1017. 48*h - 4971006 What is the second derivative of -1114026*c**2 - 1444293*c - 2 wrt c? -2228052 Differentiate 35*k**2*t + 554*k*t**2 - 7*t**2 + 18*t - 47 wrt k. 70*k*t + 554*t**2 Find the second derivative of 2413532*q**4 + 2324308*q wrt q. 28962384*q**2 Find the third derivative of 3571*f*o**3*u*x**4 - 2*f*o**2*u**2*x - f*u**2*x**4 - 29*f + o**3*u*x - 7*o**3*u + 2*u**2*x**2 + 4*u**2*x wrt x. 85704*f*o**3*u*x - 24*f*u**2*x What is the first derivative of -3*r**4 + 8672*r**3 + 2*r**2 - 43025? -12*r**3 + 26016*r**2 + 4*r What is the derivative of 48539*p**3 - 93345? 145617*p**2 Find the third derivative of 7*k
{ "pile_set_name": "DM Mathematics" }
var baseSum = require('./_baseSum'), identity = require('./identity'); /** * Computes the sum of the values in `array`. * * @static * @memberOf _ * @since 3.4.0 * @category Math * @param {Array} array The array to iterate over. * @returns {number} Returns the sum. * @example * * _.sum([4, 2, 8, 6]); * // => 20 */ function sum(array) { return (array && array.length) ? baseSum(array, identity) : 0; } module.exports = sum;
{ "pile_set_name": "Github" }
The American Society for Microbiology (ASM) is pleased to submit the following testimony on the Fiscal Year (FY) 2014 appropriation for the Department of Energy (DOE) science and research programs. The ASM is the largest single life science organization in the world with more than 37,000 members. The ASM mission is to enhance the science of microbiology, to gain a better understanding of life processes, and to promote the application of this knowledge for improved health and environmental well-being. The DOE Office of Science is the lead federal agency supporting research and development (R&D) in energy, a field rich with innovation possibilities and economic significance. The Office of Science manages a portfolio through six program offices: Advanced Scientific Computing Research, Basic Energy Sciences, Biological and Environmental Research, Fusion Energy Sciences, High Energy Physics, and Nuclear Physics. The Office of Science directly finances both DOE and non-DOE R&D projects, while operating unique federal facilities also made available to extramural scientists and engineers. The ASM is concerned that budget cut backs will negatively impact Office of Science programs that clearly contribute to US global competitiveness in science and technology. Although the specific effects of sequestration mandated cuts are still uncertain, the DOE anticipates a $215 million decrease for the Office of Science in FY 2013. Both academia and industry in the United States depend upon funding and facilities available through the Office of Science. For decades, it has been the dominant federal sponsor of physical sciences research, while also supporting advances in computer science, materials science, mathematics, biological and environmental science, nanotechnology, and engineering. DOE grants and contracts support researchers and their students at more than 300 US colleges and universities. Funding cuts will impact all scientific users of DOE facilities in addition to the probable reductions in both the size and number of extramural grants awarded. DOE has also predicted that sequestration would cause schedule delays and increased costs for planned new user facilities. Collectively, these declining resources negatively impact the training of the Nation’s future R&D workforce. DOE Funding Expands R&D Enterprise and Supports InnovationIn FY 2013 the DOE’s Office of Science was slated for increased funding to support physical sciences and engineering, guided by strategies to enhance US capabilities under the America COMPETES Act and the America COMPETES Reauthorization Act. The final Office of Science funding level still fell far short of the doubling pace of increases established by the America COMPETES Act. Federal R&D expenditures are far sighted investments in innovation and ultimately in US economic vitality. Although the United States today, remains the world’s single largest R&D performer, the Nation’s R&D growth has slowed and decreased in recent years, especially when compared to growth in other nations. Under the current DOE Strategic Plan, the agency’s priority goals include: “maintaining a vibrant US effort in science and engineering as a cornerstone of our economic prosperity, with clear leadership in strategic areas.” Last November, the President’s Council of Advisors on Science and Technology (PCAST) released its report on the future of the US research enterprise. Among its conclusions was that the US is “unique in the world in the range and quality of its Federal and National Laboratories” and that “the three pillars of the US research enterprise are its research universities, its National Laboratories, and industry's substantial commitment to basic and applied research.” The DOE’s national laboratories are integral to R&D innovation and economic success. The Office of Science manages 10 of the 17 DOE laboratories in this country, utilized each year by more than 25,000 non-DOE scientists nationwide. In 2012, updates to the DOE’s strategic plan specifically addressed the importance of Office of Science managed facilities: “prioritization of scientific facilities to ensure optimal benefit from Federal investments….By September 30, 2013, formulate a 10-year prioritization of scientific facilities across the Office of Science based on (1) the ability of the facility to contribute to world-leading science, (2) the readiness of the facility for construction, and (3) an estimated construction and operations cost of the facility.” Many Office of Science facilities host one of a kind, unique and difficult to access equipment; often too expensive to construct and operate elsewhere. The DOE points to the example of the pharmaceutical industry’s use of Argonne National Laboratory’s Advanced Photon Source to rapidly screen the molecular structure of candidates for novel drug design. The computing facility at the Oak Ridge National Laboratory recently screened 2 million different drug compounds against a targeted receptor in less than two days, using 3D biological simulations at a fraction of the cost and time typically required. DOE sponsored discoveries have evolved into valuable commercial products and processes through the agency’s emphasis on technology transfer (T2) to the private sector. In 2012, DOE researchers won 36 of the 100 awards announced each year by R&D Magazine for the most outstanding technology advances with commercial potential. Since competition began in 1962, DOE national labs have won more than 800 awards. T2 mechanisms like patent licensing and cooperative research and development agreements (CRADAs) have built strong collaborations among the Office of Science, other federal entities, and US industry. Annual T2 performance metrics underscore DOE’s importance to the US research enterprise: in FY 2010, 697 active CRADAs; 1,616 new inventions disclosed and 480 patents issued; 6,224 licenses granted for using DOE inventions or other intellectual property; and about $41 million in licensing income and $25 million in royalties. In 2012, the Lawrence Livermore National Laboratory licensed its microbial detection array technology to a company that supplies DNA microarrays and instruments, for eventual commercialization and sale to food safety professionals, law enforcement, medical professionals and others. The Lawrence Livermore Microbial Detection Array (LLMDA) technology can detect within 24 hours, more than 2,200 viruses and 900 bacteria currently among its probe array, which will be updated periodically. In February, DOE’s Advanced Research Projects Agency–Energy (ARPA-E) announced 17 of its projects have attracted more than $450 million in private sector funding after ARPA-E’s initial investment of approximately $70 million. Twelve have been leveraged to form new companies, and at least 10 have partnered with other government agencies for additional investment. ARPA-E was created under the America COMPETES Act, receiving its initial funding in 2009. The ARPA-E projects with current private sector investments include engineering bacteria for efficient fuel production and developing electrofuels; or liquid fuel derived from renewable electricity and bacteria. DOE Funding Promotes Biological Sciences and Sustainable EnergyWithin the Office of Science, the Biological and Environmental Research program funds cutting edge studies in environmental contaminants, biofuels, genomics and cross disciplinary research integrating biological and physical sciences. The ASM is particularly interested in BER’s broad utilization of microorganisms, including redesigning microbes for sustainable fuel production and optimal contaminant bioremediation. We recognize the invaluable contributions from BER’s Genomic Sciences Program and the DOE Joint Genome Institute (JGI), ambitious efforts of notable benefit to understanding the biological sciences that clearly justify strong funding in FY 2014 and beyond. Previous investments have generated a long list of results, including these recent examples: University scientists used X-ray crystallography to discover the structure of the regulator inside tuberculosis bacteria that control the pathogen’s efflux pump rendering the pathogens resistant to drugs. DOE scientists determined the genetic sequence of a group of microbes called SR1 bacteria that have not been cultivated in the laboratory, discovering that the bacteria employ a unique genetic code; human oral SR1 bacteria are elevated in the oral infection periodontitis. Scientists studying bacterial RNA-guided cleavage of foreign DNA have described a new approach to editing microbial genomes, a type of “programmable DNA scissors” that has promising R&D applications through new biofuels and therapeutic drugs. Scientists at the Pacific Northwest National Laboratory demonstrated for the first time that a cyanobacterium can produce hydrogen and oxygen simultaneously and steadily for at least 100 hours, potentially important to commercial hydrogen production. DOE chemists will use high-throughput technologies developed at Los Alamos National Laboratory to screen beef samples for shiga toxin-producing Escherichia coli (STEC), during a three-year project focusing on the early detection of STEC at all levels of the US beef production chain. DOE programs like BER and ARPA-E are leading the nation’s R&D on renewable energy sources. In 2012, DOE joined with the Department of Agriculture (USDA) in distributing $41 million among thirteen new biomass R&D projects aimed toward sustainable biofuel production, in addition to other funding for biomass genomics to improve biofuel feedstocks. The joint sponsorship is part of a much larger DOE initiative with USDA to increase US biofuels. JGI researchers recently sequenced the genomes of eleven strains of a group of bacteria called actinobacteria, which produce cellulose degrading enzymes of interest to the biotechnology and biofuels industries and identified eight cellulolytic species not previously known to degrade cellulose biomass. DOE scientists also described a unique molecular transporter mechanism to deliver molecules into algal cells, pointing the way to engineering algae that synthesize biofuels, vaccines, and other compounds. At DOE’s Joint BioEnergy Institute, researchers identified a tropical rainforest microbe that can survive high concentrations of ionic liquid used to dissolve cellulosic biomass in biofuel production, while others developed a new synthetic biology technique, dynamic sensor regulator system, which detects metabolic change and controls gene expression in microbes during biofuel production, increasing output. The ASM urges Congress to fund the Department of Energy’s Office of Science at the highest possible level in FY 2014. The DOE Office of Science programs enhance United States competitiveness through fundamental research and advanced scientific breakthroughs that revolutionize the Nation’s approach to challenging and ongoing, energy and environment challenges. The ASM appreciates the opportunity to provide written testimony and would be pleased to assist the Subcommittee as it considers the FY 2014 appropriation for the DOE. 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{ "pile_set_name": "Pile-CC" }
Re: Harrison Co KY Adams mar to Swinford Hello, I too am searching for Adams family of Harrison Co KY.Nora Adams (married John Q Groves, one child, Hattie Lee, died in 1893 from a tragic fire) amaternal great great grandmother.She lived in the Tricum area of Harrison County Route 36 west out of Cynthiana Kentucky. She is buried in the Rocky Springs Cemetery beside John, no marker, just two fieldstones.Any information you would have on the Adams would be greatly appreciated as I have hit a brick wall in locating her ancestors. thanks gb:)
{ "pile_set_name": "Pile-CC" }
Diarrhea in children and sanitation and housing conditions in periurban areas in the city of Guarulhos, SP. A cross-sectional study was carried out to identify the association between diarrhea in 0-2 year-old children and children's characteristics, access to sanitation and housing conditions in a periurban area served by the Family Health Program, in the city of Guarulhos, SP. Data were obtained from FHP registration forms. Multiple logistic regression showed interaction for Housing*Sewage (other materials and non collected wastewater, p < 0.001), age group (4-9 months old, p = 0.054; 10 months and older, p = 0.008) as risk factors for diarrhea. Information collected by the Family Health Program could be an excellent tool to identify populations with poor housing and sanitation conditions at locations where sanitation indicators are not efficient to identify populations living at risk.
{ "pile_set_name": "PubMed Abstracts" }
The present invention comprises a new and distinct variety of Calibrachoa plant, botanically known as Calibrachoa spp., and referred to by the variety name ‘SAKCAL112’. ‘SAKCAL112’ originated from a hybridization made in 2008 in Kakegawa, Japan. The female parent was the proprietary hybrid Calibrachoa breeding line named ‘7-3B-1A’ and had a lavender, pink and rose flower color, large flower size and a mounding plant growth habit. The male parent was the proprietary hybrid Calibrachoa breeding line named ‘7B-16A-1’ characterized by its lavender flower color, medium flower size and a compact plant growth habit. In November 2008, the parental lines ‘7-3B-1A’ and ‘7B-16A-1’ were crossed and 200 seeds were obtained. In February 2009, the F1 seed was sown in the greenhouse, cultivated and plant lines were produced with flower colors of rose, pink and lavender with a mounding and creeping plant growth habit. In May 2009, four plant lines were selected within the F1 plants that had lavender flowers and a compact plant growth habit. In June 2009, the four plant lines were intercrossed and 2,500 seeds were obtained from the group of F2 plants. In August 2009, 500 seeds were sown in the greenhouse, cultivated and plant lines were produced with flower colors of lavender with a mounding and compact plant growth habit. In November 2009, the line ‘K2010-062’ was selected for its lavender flower color and compact plant growth habit. In February 2010, line ‘K2010-062’ was first vegetatively propagated, cultivated and evaluated. In April 2010, line ‘K2010-062’ was confirmed to be fixed and stable. In July 2010, line ‘K2010-062’ was propagated and cultivated again to reconfirm the lines' stability. In November 2010, the line was confirmed to be fixed and stable. The line was subsequently named ‘SAKCAL112’ and its unique characteristics were found to reproduce true to type in successive generations of asexual propagation via vegetative cuttings in Salinas, Calif. Asexual propagation was performed via excising the terminal 1.0 inches to 1.5 inches of an actively growing stem of the variety.
{ "pile_set_name": "USPTO Backgrounds" }
Structural requirements for the growth factor activity of the amino-terminal domain of urokinase. High molecular weight urokinase-type plasminogen activator (uPA) in which proteolytic activity was inactivated (diisopropyl fluorophosphate (DFP)-uPA), its amino-terminal fragment (ATF, amino acids (aa) 1-143), and fucosylated and defucosylated growth factor domains (GFD, aa 4-43) were tested for growth-promoting effects and binding in human SaOS-2 osteosarcoma cells and U-937 lymphoma cells. DFP-uPA, ATF, and both the fucosylated and defucosylated GFD were capable of competing with 125I-ATF for binding to both SaOS-2 and U-937 cells. DFP-uPA, ATF, and fucosylated GFD were also mitogenic in SaOS-2 cells and increased cell numbers. However, defucosylated GFD was nonmitogenic in SaOS-2 cells and did not stimulate cell proliferation, even though it bound to these cells in a manner equivalent to the fucosylated GFD. A nonglycosylated high molecular weight uPA expressed and purified from Escherichia coli inhibited 125I-ATF binding to SaOS-2 cells but was also nonmitogenic. No mitogenic activity was observed in U-937 cells treated with the uPA forms capable of eliciting a mitogenic response in SaOS-2 cells. Proteolytically prepared kringle domain (aa 47-135) and low molecular weight uPA (aa 144-411) did not compete for 125I-ATF binding and did not elicit any mitogenic response in either of the cell lines tested. In addition, tissue plasminogen activator (tPA), which has been shown to be homologous to uPA in its growth factor domain and is also fucosylated, did not inhibit 125I-ATF binding nor elicit any mitogenic response. These results demonstrate that the GFD, implicated in binding to the uPA receptor, is also responsible for growth factor like activity in SaOS-2 cells and that the fucosylation at Thr18 within this domain may serve as a molecular trigger in eliciting this response.
{ "pile_set_name": "PubMed Abstracts" }
Structure-based virtual screening for insect ecdysone receptor ligands using MM/PBSA. The ecdysone receptor (EcR) is an insect nuclear receptor that is activated by the molting hormone, 20-hydroxyecdysone. Because synthetic EcR ligands disrupt the normal growth of insects, they are attractive candidates for new insecticides. In this study, the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method was used to predict the binding activity of EcR ligands. Validity analyses using 40 known EcR ligands showed that the binding activity was satisfactorily predicted when the ligand conformational free energy term was introduced. Subsequently, this MM/PBSA method was applied to structure-based hierarchical virtual screening, and 12 candidate compounds were selected from a database of 3.8 million compounds. Five of these compounds were active in a cell-based competitive binding assay. The most potent compound is a simple proline derivative with low micromolar binding activity, representing a valuable lead compound for further structural optimization.
{ "pile_set_name": "PubMed Abstracts" }
The role of Streptococcus pneumoniae in community-acquired pneumonia among adults in Europe: a meta-analysis. The primary objective of this meta-analysis was to estimate the prevalence of adult community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae in Europe, adjusted for possible independent covariates. Two reviewers conducted a systematic literature search using PubMed on English-language articles that involved human subjects with CAP during the period from January 1990 to November 2011 across European countries. A mixed-effects meta-regression model was developed and populated with 24,410 patients obtained from 77 articles that met the inclusion criteria. The model showed that the observed prevalence of S. pneumoniae in CAP significantly varies between European regions, even after adjusting for explanatory covariates, including patient characteristics, diagnostic tests, antibiotic resistance, and health-care setting. The probability of detecting S. pneumoniae was substantially higher in studies that performed more frequently a diagnostic polymerase chain reaction assay compared to all the other diagnostic tests included. Furthermore, S. pneumoniae was more likely to be confirmed as the cause of a CAP in studies with intensive care unit patients as compared to those with hospital- or community-treated patients. This study provides estimates of the average observed prevalence of S. pneumoniae, which could be used for projecting the health and economic benefits of pneumococcal immunization.
{ "pile_set_name": "PubMed Abstracts" }
Q: why does new Integer(i).hashCode() return i? I want to know why new Integer(i).hashCode() or new Long(i).hashCode() returns i but when hashCode() is invoked by some other object say new Double(345).hashCode(), it returns a random number. Why? A: Because the int value of an Integer perfectly satisfies and fully complies with the general contract of Object.hashCode(): The general contract of hashCode is: Whenever it is invoked on the same object more than once during an execution of a Java application, the hashCode method must consistently return the same integer, provided no information used in equals comparisons on the object is modified. This integer need not remain consistent from one execution of an application to another execution of the same application. If two objects are equal according to the equals(Object) method, then calling the hashCode method on each of the two objects must produce the same integer result. It is not required that if two objects are unequal according to the equals(java.lang.Object) method, then calling the hashCode method on each of the two objects must produce distinct integer results. However, the programmer should be aware that producing distinct integer results for unequal objects may improve the performance of hash tables. In short: The hash codes for 2 objects must be the same if equals() returns true and should be (but not required) different if equals() returns false. Also by the declaration of Object.hashCode() it must be an int. Ideally the hash code should depend on all the data that is hashed. Hash code of Long Long has to map 8 bytes to 4 bytes (size of an int). Current implementation of Long.hashCode() will only return i if it fits into an int, else it will be XOR'ed with the upper 32 bits (4 bytes): return (int)(value ^ (value >>> 32)); Hash code of Double Obviously the double value of a Double does not qualify for this. Double also has to map 8 bytes to 4 bytes. Double.hashCode() will return a seemingly random value because floating point numbers (float and double) are not stored "nicely" (e.g. 2's complement like int or long) in the bytes that are reserved for them but using IEEE 754 binary floating point standard and so mapping those 8 bytes to 4 (this is exactly what the implementation does) will not be a meaningful number as an int which uses 2's complement representation. long bits = doubleToLongBits(value); return (int)(bits ^ (bits >>> 32)); A: A value of an integer is a good enough hash because it is just as unique as the unique integer number itself. A double has to be hashed in some different manner because the hash here has to be an integer. A: Becase the implementation say it: Returns a hash code for this Integer. Returns:a hash code value for this object, equal to the primitive int value represented by this Integer object. 707 708 public int hashCode() { 709 return value; 710 }
{ "pile_set_name": "StackExchange" }
However, dampening the mood was the injury sustained by captain Paul Pogba, who was taken off after just 18 minutes following an apparent hamstring niggle. Fellaini calmed the nerves around the stadium when he opened the scoring after 35 minutes, nodding home Ashley Young's inch-perfect cross from close range. Lukaku doubled the advantage shortly after the restart, rising to meet Daley Blind's cross and heading home with power. United were untroubled in the second half, but a mistake from Victor Lindelof nearly allowed Mohammed Elyounoussi to pull one back from the Swiss side, however, David de Gea's strong hand denied his short-range effort. 19-year-old Rashford made sure the result was sealed six minutes from time, finishing off Fellaini's deflected cut-back. His goal made him the fourth United teenager to score in the Champions League.
{ "pile_set_name": "Pile-CC" }
Q: mySQL stored procedural with variable method, query and limit Hello I'm quite new to mySQL and I'm trying to write a stored procedure. I've searched on the internet to questions alike this one but I couldn't find any results for this. I'm trying to make search function for my webapplication where you can search in the database for results, yet there are different methods to search on (By name, last name, adres, etc). The query should also have a limit in results (1, 5, 10, 20). My idea was something like this: CREATE PROCEDURE SelectTopResults @query varchar(60), @method varchar(20), @limited int(3) AS SELECT * FROM customer WHERE @method = %@query% LIMIT @limited GO; This doesn't run. Is this idea of the procedure correct? And how should I fix it then? Or is there another better way to do this? Thanks in advance. Edit: This is to be accessed with PHP. My idea was to write a code that basically does: $sql = 'EXEC SelectTopResults @method = ?, @query = ?, @limited = ?;' Edit 2: Solved, thanks a lot! :) For those interested in the code: DELIMITER // CREATE PROCEDURE selectTopResults(IN col varchar(64), IN limited int(3), searchquery varchar(60)) BEGIN SET @s = CONCAT("SELECT * FROM customer WHERE ",col," LIKE '%",searchquery,"%' LIMIT ",limited); PREPARE stmt FROM @s; EXECUTE stmt; DEALLOCATE PREPARE stmt; END // DELIMITER ; Also works with wildcards and can be called upon with: CALL selectTopResults('column_name', 5, 'query'); whereby 5 is the limit A: Welcome to the forum. You've got it a bit wrong - there is something about stored procedures in the MySQL manual, but I can never find it in the first attempt. Luckily, there are many tutorials, if you search for them in google, bing or whatever. Try this, for example: https://www.mysqltutorial.org/introduction-to-sql-stored-procedures.aspx So, to get your procedure to work: DELIMITER $$ CREATE PROCEDURE SelectTopResults ( query varchar(60), method varchar(20), limited int(3) ) BEGIN ... END$$ DELIMITER ; It is normal to use the DELIMITER statement to change what signifies the end of a statement - otherwise, you are going to get error messages when you type in the statements that go into the procedure. Next, you need round brackets around your parameters and no @ before their names. You may wonder why I break the parameter list out over several lines; this is just my style - I feel it makes it easier to read where the parameters start and end. Finally, about your SELECT statement: SELECT * FROM customer WHERE @method = %@query% LIMIT @limited I'm not sure what you are trying here - firstly, you need to loose the @s - that is for variables you set with SET, I believe (I'm writing from memory, as I am not near my manuals), not for variables and parameters in a procedure or function. But more importantly, you can't use the parameter method as the name of a table column - for that you need to construct the SELECT as a string and execute. This is called 'dynamic SQL', as far as I recall; I think you can do this in MySQL, but I am not sure without looking it up. I hope this helps, and hopefully somebody with more immediate knowledge can help you better.
{ "pile_set_name": "StackExchange" }
As the value and use of information continues to increase, individuals and businesses seek additional ways to process and store information. One option available to users is information handling systems. An information handling system generally processes, compiles, stores, and/or communicates information or data for business, personal, or other purposes thereby allowing users to take advantage of the value of the information. Because technology and information handling needs and requirements vary between different users or applications, information handling systems may also vary regarding what information is handled, how the information is handled, how much information is processed, stored, or communicated, and how quickly and efficiently the information may be processed, stored, or communicated. The variations in information handling systems allow for information handling systems to be general or configured for a specific user or specific use such as financial transaction processing, airline reservations, enterprise data storage, or global communications. In addition, information handling systems may include a variety of hardware and software components that may be configured to process, store, and communicate information and may include one or more computer systems, data storage systems, and networking systems. An information handling system can include a communication interface for exchanging information with another information handling system. The communication interface can include a wireless interface utilizing radio signals to provide a data link between two or more information handling systems. The rate that information can be exchanged over a wireless data link is limited in part by the frequency of the radio signal used to carry the information, with higher frequencies generally capable of providing greater data throughput. For example, an extremely high frequency (EHF) wireless interface may operate at 60 gigahertz (GHz), a portion of the radio frequency spectrum known as the millimeter band. The use of the same reference symbols in different drawings indicates similar or identical items.
{ "pile_set_name": "USPTO Backgrounds" }
Immunologic basis of chronic allergic diseases: clinical messages from the laboratory bench. During the past decade there have been significant advances in our understanding of the mechanisms underlying allergic responses. Immediate hypersensitivity reactions are mediated primarily by mast cells in an IgE-dependent manner. After the local release of various mediators, proinflammatory cytokines, and chemokines, there is a cell-mediated response that is dominated by eosinophils and T lymphocytes. The majority of T cells in early allergic reactions are memory T cells secreting helper type 2 (TH2)-like cytokines, i.e. IL-4, IL-5, and IL-13, but not interferon-gamma. These cytokines regulate IgE synthesis and promote eosinophil differentiation and cell survival, thus contributing to allergic inflammatory responses. Failure to control immune activation early in the course of allergic inflammation may blunt the response to glucocorticoid therapy and contribute to long-term morbidity of disease. The identification of key cells and cytokines involved in the initiation and maintenance of allergic inflammation is likely to become an important therapeutic target in the future management of this important group of diseases.
{ "pile_set_name": "PubMed Abstracts" }
Vinchopolis In which our heroes meet in a tavern It was just another day in Vinchopolis. With a newly-conquered island kingdom under its thumb, the city’s supply of wood was suddenly quite well stocked. There were also rumours of a new race called “Eladrin” who carried with them a terrible plague. Although these creatures had officially been confined in quarantine, word had gotten out that some had escaped, and vigilantes had taken to killing them on sight as a public health measure. Penrhyn Firewing arrived for work at her miserable job in the Department of Fine Print Penmanship and Small Parcel Deliveries, where her gnoll boss yelled at her for being late despite the fact that she was on time. She went to her little cubicle and worked away filling out forms until she ran out of ink. She went to the supply room to replenish her ink, but there was none in the closet. In its place was a note instead saying “See boss about ink”. So she went to see her boss again (he was passed out from exhaustion) and got yelled at again (after she woke him). Eventually she figured out who she was supposed to see, and in exchange for the ink, she was required to deliver a few things, including a message to a certain police precinct. Meanwhile, Markto left his basement for the first time to wander the streets in search of his father. He saw the semanet urchins above, and watched as one keeled over and died, splatting in the street. Another urchin took its place almost immediately. Markto followed the flag messages, hoping they might lead to his father. Meanwhile, in a grimy bar in the anarchist district, Idril tried to gauge public attitudes toward the city, the system, and the rumoured existence of a Cult of the City and its purported messiah figure. Vicaun and Spire (in its female Tiefling disguise) were hanging out there and noticed Idril. They tried to run their usual 3-card monte scam, but she didn’t bite. Just as she was about to leave in search of the Cult, Spire called out to her. Spire questioned Idril about her intentions, then offered to set up a meeting with a cultist in one hour. Idril agreed. Then Spire and Vicaun went off to the side to discuss things privately. Vicaun didn’t think well of the Cult, and seemed unimpressed with his partner’s arrangement. But as soon as they were alone, Spire shapeshifted into Vicaun and started talking excitedly about this big score they could pull on Idril. Vicaun got all uncomfortable and asked Spire to shapeshift into something else. Spire responded by shapeshifting into Vicaun’s mother. Spire reasoned that if Idril knew the locations of other islands that could be exploited for resources, the information could be extraordinarily valuable. It suggested a plan to earn Idril’s confidence and get her to reveal it. Meanwhile, Sub-Patrolman Tomok Biter, the Orc watchman (who speaks with an Irish brogue) was sent on patrol as part of a new program with a really long, bureaucratic name, involving “cultural outreach” or somesuch. The program was primarily about pacifying and eliminating individuals who stuck out too much. His new partner was a stinky Troglodyte, Chegar, who enjoyed smashing things. Chegar was very pleased with himself, as he had made a xylophone out of the bones of a bunch of goblins he had killed the other night. Tomok sighed and humoured him, taking care to stay downwind. Their patrol turned up very little, so they headed back to the station. Meanwhile, the smog made it difficult for Penrhyn to fly, so she had to land. Lurching down the street toward her was a bizarre, complex, Rube-Golderg-ian robot. It had no standard parts, no serial number, no identification of any kind. This disturbed Penrhyn deeply, and she flew up to perch on its head. It asked Penrhyn if she had seen its father. Penrhyn questioned the automaton about its serial number, origins and so forth, but it seemed unable to answer. So she decided they should file a missing persons report in an attempt to find the automaton’s “father”. Since Penrhyn had to deliver her message to the police department anyway, it would not require her to go far out of their way. In addition, she could stay perched on the automaton’s head and get a ride. When they arrived at the station, message turned out to be for SubPatrolman Tomok Biter. The automaton (whose name turned out to be “Markto”) asked Tomok if Tomok has seen father. Penrhyn apologized for the strange machine and attempted to explain that it must be broken or something. Penrhyn and Tomok tried to ascertain Markto’s origins, but it was simply too strange to figure out. Then Tomok’s partner excitedly announced they got a hot tip about the Eladrin quarantine escapee. Tomok decided to leave and deal with the missing persons report later (that would have had to travel to the department of Missing Persons Forms). Markto followed Tomok out into the streets, and Penrhyn rode along on Markto’s head, still searching for a registration plate somewhere on its body. Meanwhile, as Vicaun and Spire prepared their Cult disguises, they got word from other cultists of trouble back at the dive bar. Apparently the Eladrin had been causing quite a stir, talking about how life doesn’t have to be like this, about how they have entire forests full of growing plants where she comes from. The treacherous duo rushed back to make sure their gravy train wouldn’t be derailed. And so it was that our heroes converged right around the time a local unofficial official public health vigilante organization jumped out screaming “Kill the filthy plague bearer!” The bar patrons screamed, and the fight began.Chegar just wanted to smash things, the goblins (vigilantes) just want to kill Idril, the duo wanted to keep Idril alive, Markto wanted to find his father and was convinced that Tomok could help, Penrhyn was disturbed at the continuing inappropriateness of Markto not having the correct paperwork, and Tomok… Tomok was getting a headache. Idril took a serious beatdown from the vigilantes. The duo burst in and fought back. Tomok decided to arrest the vigilantes and restore the peace. The vigilantes resisted arrest. Chegar just wanted to smash something, so he smashed Markto. Spire briefly switched to true form, admiring Markto’s beauty, then screamed in horror when Markto was struck. Spire then switched back to its cultist form (an intense Elf with male pattern baldness) and psychically assaulted the troglodyte. Only Penrhyn noticed this odd shift from a high window as she scorched the goblins with her magic. Under the combined assault, the vigilantes fell quickly, and as the last goblin standing surrendered, Idril teleported outside the building and fled. Moments later, Vicaun knocked Chegar unconscious. The battle was over, and our heroes had won, but the chaos would be difficult for Tomok to explain in his report, Spire was apparently unhappy with Idril’s hasty exit, Idril would need to go into hiding, Markto was damaged and no closer to finding his father, Penrhyn was still perturbed at the lack of proper paperwork, and Vicaun feared the loss of yet another potential big score to bad luck.
{ "pile_set_name": "Pile-CC" }
Universal nature of collective plasmonic excitations in finite 1D carbon-based nanostructures. We provide evidence of the plasmon resonances in a number of representative 1D finite carbon-based nanostructures using first-principle computational electronic spectroscopy studies. Our special purpose real-space/real-time all-electron time-dependent density-functional theory simulator can perform excited-states calculations to obtain correct frequencies for known optical transitions, and capture various nanoscopic effects including collective plasmon excitations. The presence of 1D plasmons is universally predicted by the various numerical experiments, which also demonstrate a phenomenon of resonance splitting. For the metallic carbon nanotubes under study, the plasmons are expected to be related to the Tomonaga-Luttinger plasmons of infinitely long 1D structures. In-depth quantitative understanding of such resonances which have not been clearly identified in experiments so far, would be invaluable for future generations of nano-photonic and nano-electronic devices that employ 1D conductors.
{ "pile_set_name": "PubMed Abstracts" }
Complicated Candida parapsilosis peritonitis on peritoneal dialysis in a neonate with renal failure because of bilateral adrenal abscesses. We present a full-term female infant with a difficult delivery course complicated with Escherichia coli sepsis and bilateral adrenal abscesses. She developed renal failure and received peritoneal dialysis. Peritonitis of Candida parapsilosis developed later. The infant was successfully treated with hemofiltration and a combination of antifungal agents.
{ "pile_set_name": "PubMed Abstracts" }
Q: Condition when I do not have a file in my list My script: #!/bin/bash NOW=$(date +"%Y%m%d%t%H%M%S") # Pour chaque dossiers "log" trouvé. for folder in $(find . -name "*log*" -type d ) do : # Pour chaque dossier log contenant des fichiers ".log" vieux de +30jours. tar czf archive-log.$NOW.tar.gz $(find $folder -name "*.log" -mtime +30) # On supprime les anciens fichiers de log rm $(find $folder -name "*.log" -mtime +30) done my question is: What test do I find out if I have files to be archived or not ? Thx A: If you want to skip the case in which there are no files to archive, this can help you: if [ ! -z $(find $folder -name "*.log" -mtime +30) ] then tar czf archive-log.$NOW.tar.gz $(find $folder -name "*.log" -mtime +30) rm $(find $folder -name "*.log" -mtime +30) else echo "there are no files to archive" fi The syntax if [ -z "string" ] checks if a string is empty or not. Negating it, if [ ! -z $(find...) ] we check if the result returns results or not.
{ "pile_set_name": "StackExchange" }
# coding=utf-8 # -------------------------------------------------------------------------- # Copyright (c) Microsoft Corporation. All rights reserved. # Licensed under the MIT License. See License.txt in the project root for # license information. # # Code generated by Microsoft (R) AutoRest Code Generator. # Changes may cause incorrect behavior and will be lost if the code is # regenerated. # -------------------------------------------------------------------------- from msrest.serialization import Model class StorageProfile(Model): """Storage Profile properties of a server. :param backup_retention_days: Backup retention days for the server. :type backup_retention_days: int :param geo_redundant_backup: Enable Geo-redundant or not for server backup. Possible values include: 'Enabled', 'Disabled' :type geo_redundant_backup: str or ~azure.mgmt.rdbms.mariadb.models.GeoRedundantBackup :param storage_mb: Max storage allowed for a server. :type storage_mb: int """ _attribute_map = { 'backup_retention_days': {'key': 'backupRetentionDays', 'type': 'int'}, 'geo_redundant_backup': {'key': 'geoRedundantBackup', 'type': 'str'}, 'storage_mb': {'key': 'storageMB', 'type': 'int'}, } def __init__(self, *, backup_retention_days: int=None, geo_redundant_backup=None, storage_mb: int=None, **kwargs) -> None: super(StorageProfile, self).__init__(**kwargs) self.backup_retention_days = backup_retention_days self.geo_redundant_backup = geo_redundant_backup self.storage_mb = storage_mb
{ "pile_set_name": "Github" }
Colicin typing of Shigella sonnei isolated in Northern Taiwan. Eighty-eight strains of Shigella sonnei isolated in northern Taiwan during the period of 1970-1974, were studied for their colicin types by a modified method of Abbott and Shannon. As a result, 67(76%) typable and 21(24%) non-typable strains were found. The prevalent colicin types of S. sonnei in northern Taiwan were types 15(52%) and 6(15%), followed by types 8(3%), 11(3%) and 12(3%). Other types were not found.
{ "pile_set_name": "PubMed Abstracts" }
Q: How to Disable JButton I want my JButton to be Disabled until all of the fields has inputs. package Grade; import javax.swing.*; import java.awt.*; import java.awt.event.*; public class GradeGUI extends JFrame { private JLabel quizL,exerL,partL,partLL,examL,finalSL,totalIL,totalL,blankL,blankL2,blankL3,blankL4,blankL5,blankL6,blankL7,blankL8; private JTextField quizTF,exerTF,examTF,partTF,quizTF1,exerTF1,examTF1,total1,total2,total3,total4,totalF,letterTF; private JButton calculateB,exitB; private CalculateButtonHandler cbHandler; private ExitButtonHandler exitHandler; public GradeGUI(){ blankL8=new JLabel(""); blankL7=new JLabel(""); blankL6=new JLabel(""); blankL5=new JLabel(""); blankL4=new JLabel(""); blankL3=new JLabel(""); blankL2=new JLabel(""); blankL=new JLabel(""); partLL=new JLabel(""); quizL=new JLabel("Quiz: "); exerL=new JLabel("Exercise: "); partL=new JLabel("Participation: "); examL=new JLabel("Exams: "); finalSL=new JLabel("Final Score"); totalIL=new JLabel("Total # of Items"); totalL=new JLabel("Final Score"); letterTF=new JTextField(25); quizTF=new JTextField(25); exerTF=new JTextField(25); examTF=new JTextField(25); partTF=new JTextField(25); quizTF1=new JTextField(25); exerTF1=new JTextField(25); examTF1=new JTextField(25); total1=new JTextField(25); total2=new JTextField(25); total3=new JTextField(25); total4=new JTextField(25); totalF=new JTextField(25); total1.setEditable(false); total2.setEditable(false); total3.setEditable(false); total4.setEditable(false); totalF.setEditable(false); letterTF.setEditable(false); calculateB=new JButton("Calculate"); exitB=new JButton("Exit"); calculateB=new JButton("Calculate"); cbHandler= new CalculateButtonHandler(); calculateB.addActionListener(cbHandler); exitB=new JButton("Exit"); exitHandler= new ExitButtonHandler(); exitB.addActionListener(exitHandler); setTitle("Grade Calculator"); Container p = getContentPane(); p.setLayout(new GridLayout(6,5)); p.add(blankL); p.add(finalSL); p.add(totalIL); p.add(totalL); p.add(blankL4); p.add(quizL); p.add(quizTF); p.add(quizTF1); p.add(total1); p.add(blankL5); p.add(exerL); p.add(exerTF); p.add(exerTF1); p.add(total2); p.add(blankL6); p.add(partL); p.add(partTF); p.add(blankL2); p.add(total3); p.add(blankL7); p.add(examL); p.add(examTF); p.add(examTF1); p.add(total4); p.add(blankL8); p.add(blankL3); p.add(calculateB); p.add(exitB); p.add(totalF); p.add(letterTF); setSize(500,400); setVisible(true); setDefaultCloseOperation(EXIT_ON_CLOSE); } private class CalculateButtonHandler implements ActionListener{ public void actionPerformed(ActionEvent e){ try{ double quiz,exam,exer,part,quizT,examT,exerT; double total11,total22,total33,total44,totalFf; double quizTT,examTT,partTT,exerTT; quiz=Integer.parseInt(quizTF.getText()); exam=Integer.parseInt(examTF.getText()); exer=Integer.parseInt(exerTF.getText()); part=Integer.parseInt(partTF.getText()); quizT=Integer.parseInt(quizTF1.getText()); examT=Integer.parseInt(examTF1.getText()); exerT=Integer.parseInt(exerTF1.getText()); quizTT=((quiz/quizT)*100)*0.20; examTT=((exam/examT)*100)*0.30; partTT=part*0.10; exerTT=((exer/exerT)*100)*0.40; total1.setText(""+quizTT); total2.setText(""+examTT); total3.setText(""+partTT); total4.setText(""+exerTT); total11=Double.parseDouble(total1.getText()); total22=Double.parseDouble(total2.getText()); total33=Double.parseDouble(total3.getText()); total44=Double.parseDouble(total4.getText()); totalFf=total11+total22+total33+total44; totalF.setText(""+totalFf); if(totalFf>=95){ letterTF.setText("A"); }else if(totalFf>=90){ letterTF.setText("B"); }else if(totalFf>=85){ letterTF.setText("C"); }else if(totalFf>=80){ letterTF.setText("D"); }else if(totalFf>=75){ letterTF.setText("E"); }else{ letterTF.setText("F"); } }catch(Exception s){ JOptionPane.showMessageDialog(null,"Please Try Again!!","ERROR",JOptionPane.ERROR_MESSAGE); } } } private class ExitButtonHandler implements ActionListener{ public void actionPerformed(ActionEvent e){ System.exit(0); } } public static void main(String[]args){ GradeGUI a=new GradeGUI(); } } A: Using the JTextField class's addCaretListener method, you can check for changes in each text field. When characters are typed into a text field, the caret's position will change, and a javax.swing.event.CaretEvent will be fired, which you can use to check if each text field is empty or not; based on this, you can then set your button to be enabled or disabled. For example: quizTF.addCaretListener(new CaretListener() { public void caretUpdate(CaretEvent ev) { calculateB.setEnabled(!quizTF.getText().isEmpty() && !exerTF.getText().isEmpty() && ...); } }); // code here Personally, I would place all your JTextField objects in an ArrayList or something similar so you can loop through and perform operations on them and it won't be tedious writing so much code.
{ "pile_set_name": "StackExchange" }
Q: How can I make the SpeechSynthesizer speak through a particular device? I am new to the Speech Recognition, so please excuse me if the question is very basic level. My application captures what I speak through my microphone. I have written some responses using my c# code for every command I say and the SpeechSynthesizer does this without any issues using the code mentioned below. But I want the SpeechSynthesizer to respond back through my laptop speaker, rather than my default input device (my microphone). Is it doable? The code I am currently using is given below. I am looking for something which can get all the playback devices available and then select and speak back using my speaker. public void SpeakTheText(string text) { SpeechInput = text; SpeechSynthesizer _synthesizer = new SpeechSynthesizer(); _synthesizer.SelectVoiceByHints(VoiceGender.Male); _synthesizer.SetOutputToDefaultAudioDevice();//Microphone _synthesizer.SpeakAsync(SpeechInput); } A: You could use the System.Media.SoundPlayer class to output the audio from a stream. See this example from MSDN public void SpeakTheText(string text) { // Initialize a new instance of the speech synthesizer. using (SpeechSynthesizer synth = new SpeechSynthesizer()) using (MemoryStream streamAudio = new MemoryStream()) { // Create a SoundPlayer instance to play the output audio file. System.Media.SoundPlayer m_SoundPlayer = new System.Media.SoundPlayer(); // Set voice to male synth.SelectVoiceByHints(VoiceGender.Male); // Configure the synthesizer to output to an audio stream. synth.SetOutputToWaveStream(streamAudio); // Speak a phrase. synth.Speak(text); streamAudio.Position = 0; m_SoundPlayer.Stream = streamAudio; m_SoundPlayer.Play(); // Set the synthesizer output to null to release the stream. synth.SetOutputToNull(); // Insert code to persist or process the stream contents here. } } I'm not sure if SoundPlayer can specify an output device, but it should output using your default output device.
{ "pile_set_name": "StackExchange" }
You are here Cigarette sales dive, hurting health funds Search form WARNING: Arizonans quitting smoking may be hazardous to the fiscal health of publicly funded programs that receive tobacco tax revenues. Tucson Citizen Friday, November 30, 2007 Heidi Rowley Sales of cigarettes in Arizona have fallen by millions of packs since voters approved a big tobacco tax increase and a ban on smoking in bars a year ago Tobacco tax revenue increased $57 million in the fiscal year that ended June 30, to $345.6 million. But all of that increase, and more, went into a new fund for early childhood education. The fund received $74 million, nearly all the revenue from an 82-cent per pack increase approved by voters. It means that other state funds and programs that get tobacco tax revenue, including the state's program to help people stop smoking and other health-care funds, have gotten less money. And the end of the decline is not yet in sight, said Kevin McCarthy, president of the Arizona Tax Research Association. "They are in the early stages of seeing diminishing returns," McCarthy said. "Their pots of money are only going to decrease over time." McCarthy's group warned last year that the higher tobacco tax would present the state with a fiscal hazard. In the last seven months of the 2006-07 fiscal year, cigarette sales fell so much that state funds dependent on tobacco tax revenues took in about $17 million less than they did in 2005-06. The program for the poor is known as the Arizona Health Care Cost Containment System. It used money from the state general fund to make up for declining tobacco tax dollars this time out. But the state's dark economic outlook and expected budget tightening could limit or eliminate that option in the future. "It will be a much more discussed issue next spring as the state tries to deal with its overall picture," AHCCCS Deputy Director Tom Betlach said. Even programs that help smokers quit are seeing their funding source shrink as the demand for their services increases. The state tax increase on a pack of cigarettes, from $1.18 to $2, took effect last Dec. 1, after voters approval in November. Eighty cents of the increase go to the Early Childhood and Development Fund, created by Proposition 203, known as First Things First for Arizona's Children. Two cents go to Smoke Free Arizona, an education program in the state Department of Health Services focusing on the smoking ban in public buildings. That ban took effect effect May 1. Sales of cigarettes in Arizona dropped 50 million packs, or 31 percent, in the first eight months of 2007, to 112 million packs compared to 161.6 million during the same period in 2006. AHCCCS took almost $10 million from the general fund in 2006-07 because of the drop in tobacco tax money, spokeswoman Rainey Day Holloway said. Although revenue from tobacco taxes is less than 1 percent of the agency's $7.5 billion budget, AHCCCS' Betlach said the agency monitors it regularly. From July through October, the first four months of fiscal 2008, Betlach said, AHCCCS received $8.7 million less in tobacco tax revenue than in the same period last year. He said the Legislature will have to reassign funds to make up the difference. AHCCCS has not had to cut any programs. AHCCCS gets tobacco tax revenue through both the Tobacco Tax and Health Care Fund and the Tobacco Products Tax Fund. The Tobacco Tax and Health Care Fund was created in 1994 when Arizonans voted to increase the cigarette tax by 40 cents a pack, from 18 to 58 cents, to pay for health care for the medically needy through AHCCCS, among other programs. The Tobacco Products Tax Fund was created in 2002 when voters approved increasing the tobacco tax to $1.18 a pack to help fund AHCCCS and the state's trauma centers. Together, the funds have shrunk more than $14 million with cigarettes sales down. In addition to AHCCCS, the Tobacco Tax and Health Care Fund supports the Tobacco Education and Prevention Program, run by the Arizona Department of Health Services. The Tobacco Education and Prevention Program funds local smoking cessation programs and the Arizona Smokers' Helpline. Since Dec. 1 - when the new tax kicked in - the number of calls to the line has more than doubled, to 425 a week from 175, said Stephen Michael, director of the program. Staff monitoring the line helps quitters by making weekly and sometimes daily phone calls of support. It also refers callers to local programs, such as Pima County's Tobacco Free Ways. The program has added 6 1/2 full-time positions since Dec. 1 to make and take calls. "Demand for our program is going up," Michael said. "We've had to increase employees. . . . If more people are going to quit, you are going to have to put money into it." Referrals from physicians to the line have increased to 750 a month from an average of 150 before the tax increase. A total of 2,700 referrals has come in since July, compared to 550 from July to November 2006. About 40 percent of the people using line to quit are on the prescription drug Chantix, Michael said. The state pays for 50 percent, or about $60, of a 30-day supply. The state also will help pay for nicotine patches. Byron Homer, administrative services officer for the Tobacco Education and Prevention Program, said the state is trying to lower the smoking rate from 20 percent of adults to 12 percent. "It's frustrating," said Marcy M. Flanagan, senior program director of Pima County's Tobacco Education and Prevention Program. "If we're going to get the rate down, we're going to have to fund these programs." As more people quit, the ones left are hard-core smokers who need costlier help. "It might take more medical intervention to get people to quit," Flanagan said.
{ "pile_set_name": "Pile-CC" }
Vasoactive intestinal peptide as a healing mediator in Crohn's disease. The vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide (VIP/PACAP) system is considered as a paradigm for the use of a neuroendocrine-immune mediator in therapy. We review the role of VIP in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis as a murine model of Crohn's disease. VIP treatment led to the recovery of clinical factors, the amelioration of parameters related to the recruitment and traffic of cell populations, and the balance of inflammatory mediators derived from granulocytes, antigen-presenting cells and T lymphocytes including Th1, Th2 and Th17. Finally, the most recent data validate its therapeutic role through the modulation of TLR2 and 4 receptors.
{ "pile_set_name": "PubMed Abstracts" }
The hydroxyphenylpyruvate dioxygenases (HPPDs) are enzymes that catalyze the reaction in which para-hydroxyphenylpyruvate (HPP) is transformed into homogentisate. This reaction takes place in the presence of enzyme-bound iron (Fe2+) and oxygen. Herbicides that act by inhibiting HPPD are well known, and include isoxazoles, diketonitriles, triketones, and pyrazolinates (Hawkes “Hydroxyphenylpyruvate Dioxygenase (HPPD)—The Herbicide Target.” In Modern Crop Protection Compounds. Eds. Kramer and Schirmer. Weinheim, Germany: Wiley-VCH, 2007. Ch. 4.2, pp. 211-220) Inhibition of HPPD blocks the biosynthesis of plastoquinone (PQ) from tyrosine. PQ is an essential cofactor in the biosynthesis of carotenoid pigments which are essential for photoprotection of the photosynthetic centres. HPPD-inhibiting herbicides are phloem-mobile bleachers which cause the light-exposed new meristems and leaves to emerge white. In the absence of carotenoids, chlorophyll is photo-destroyed and becomes itself an agent of photo-destruction via the photo-generation of singlet oxygen. Methods for providing plants that are tolerant to HPPD herbicides are also known. These methods have included: 1) overexpressing the HPPD enzyme so as to produce quantities of HPPD enzyme in the plant that are sufficient in relation to a given herbicide so as to have enough of the functional enzyme available for the plant to thrive despite the presence of the herbicide; and 2) mutating a particular HPPD enzyme into an enzyme that is less sensitive to inhibition by herbicides. Methods for mutating HPPD enzymes for improved HPPD herbicide tolerance have been described (see, e.g., PCT Application Nos. WO 99/24585 and WO 2009/144079), and some particular mutations of plant HPPD enzymes (e.g., mutation of G422 in the Arabidopsis HPPD sequence) are purportedly capable of providing some measure of tolerance to mesotrione and other triketone herbicides. However, the enzyme kinetic and whole plant data reported thus far are insufficient to conclude whether the reported mutational changes confer commercially significant benefits over the corresponding wild type enzyme(s). Furthermore, while a particular HPPD enzyme may provide a useful level of tolerance to some HPPD-inhibitor herbicides, the same HPPD may be quite inadequate to provide commercial levels of tolerance to a different, more desirable HPPD-inhibitor herbicide (See, e.g., U.S. Patent Application Publication No. 20040058427; PCT Publication Nos. WO 98/20144 and WO 02/46387; see also U.S. Patent Application Publication No. 20050246800 relating to the identification and labelling of soybean varieties as being relatively HPPD tolerant). Moreover, mutated versions of HPPDs from cool-climate grasses with improved resistance to triketone-type herbicides have yet to be reported. Such mutants would be highly desirable, as HPPDs from cool-climate grasses are preferable to other types (see, e.g., PCT Application No. WO 02/46387 and Hawkes et al. 2001 in Proc. Brit. Crop Prot. Conf. Weeds 2, 563). Accordingly, new methods and compositions for conferring commercial levels of HPPD herbicide tolerance upon various crops and crop varieties are needed.
{ "pile_set_name": "USPTO Backgrounds" }
Especially in the foundry field and, indeed, whenever sand castings are made, following the casting process a used sand becomes available which may have to be reprocessed, inter alia, to remove contaminants, and may have to be combined with new sand or fresh sand and, in some cases, with special sands for particular purposes in the foundry arts, before the sand is reused for the production of molds and the like. Apparatus for the processing of sand, both used sand and new sand, generally comprises a housing having a sand inlet and a sand outlet. The characteristics of the treated sand which are important are a uniform particle size, a freedom from detrimental contaminants, the presence of binder residues which may be advantageous, and, in the case of used sands, a freedom from dust, slime and the like. The product should also be free from large agglomerates and metal sputterings from the casting process as well as other impurities which may be detrimental to a subsequent casting process. In the past the apparatus has been designed to free the sand from contaminants and thus prepare the sand for reuse, both in the case of used sand and in the case of mixtures of used sand with fresh or new sand. By and large prior apparatuses for this purpose have proved to be unsatisfactory because the sand during the process was subjected to different temperatures and different humidity levels so that an optimal treatment could not be assured. Further a homogeneous reproducible product could not be ensured.
{ "pile_set_name": "USPTO Backgrounds" }
Map Of London 32 Boroughs Neighborhoods In Map Of London 32 Boroughs Neighborhoods In Map Of London 32 Boroughs Neighborhoods In is one from many image from this website. you can find the latest images of Map Of London 32 Boroughs Neighborhoods In on this website and other images. we hope this picture can be useful for you. Map Of London 32 Boroughs Neighborhoods In is a one of good picture from our gallery, you can save it here by full HD resolution which will make you comfortable and give you many details of Map Of London 32 Boroughs Neighborhoods In. in this website we recommend Images about Map Of London 32 Boroughs Neighborhoods In that we have collected from various sites of Europe, and of course what we recommend is the most excellent of Free World Map Wallpaper and Free World Map Wall Murals For Everyone for Map Of London 32 Boroughs Neighborhoods In. If you like the Free World Map Wallpaper and Free World Map Wall Murals For Everyone in our web, please feel free to visit again and get happiness in our web. And if you want to see more pictures more we recommend the gallery below you can see as a reference from your Map Of London 32 Boroughs Neighborhoods In.
{ "pile_set_name": "Pile-CC" }
[Effect of elevated hydrostatic pressure on the shape of human erythrocytes]. Influence of high hydrostatic pressure (2600-4300 atm) on the shape of human red blood cells was studied. An irreversible change of the shape was observed, which was similar to that seen in the case of a shift stress. The model modification dynamics of the erythrocyte shape was proposed. Activation energy and activation volume of the defects resulting in shape changes were calculated.
{ "pile_set_name": "PubMed Abstracts" }
Mastitis is an inflammation of the mammary gland of milk producing animals, for example dairy cows, most often caused by bacterial infection. Bacteria enter through the teat canal of the animal and can cause acute, clinical, or sub-clinical mastitis. Over 135 organisms have been documented as causative pathogens for bovine mastitis. Three of the major groups of pathogens are gram-positive cocci, gram-negative bacilli, and gram-positive bacilli. Hygiene, environmental factors, and metabolic disturbances deriving from high milk yield combine to create conditions favorable to the onset of mastitis. An increased somatic cell count, associated with mastitis, is positively correlated with infection and negatively correlated with milk production. Frequently, an infected cow must be removed from the herd and dried up. Mastitis often affects a cow during its entire life unless the disease is properly treated, and in extreme cases an animal may become so severely infected that she dies. Infection rates average from 10% to 30% of the cows in a typical herd, with losses per cow ranging from $185 to $250 per cow per year. Bovine mastitis is the most economically costly disease to the dairy industry, with losses estimated at two billion dollars annually in the United States alone. The majority of these losses are due to reduced milk production. Intramammary administration of compositions comprising an antibiotic for prevention and treatment of mastitis in milk producing animals is well known. Several compositions suitable for such administration are formulated in aqueous based vehicles. For example, British Patent Application No. 2,273,655 discloses compositions for intramammary use comprising an insoluble antibiotic in an aqueous suspension for treatment of mastitis. International Patent Publication No. WO 95/31180 discloses a composition comprising the antibiotic cloxacillin benzathine in an aqueous base, and additionally a teat seal composition, in injectors for intramammary application. European Patent Application No. 0 797 988 discloses a veterinary composition in the form of an aqueous gel containing an antibacterial agent, useful for intramammary administration for prevention and treatment of mastitis. The chemical stability of many antibiotics is, however, severely limited in aqueous based compositions. Hence, a number of oil based formulations for treatment and/or prevention of mastitis have also been developed. British Patent Application No. 1,456,349 discloses a composition of an anti-mastitis medicament dispersed in a gelled vehicle comprising a mineral oil or non-drying, semi-drying, or drying vegetable oil or a mixture thereof, other than a mixture of drying and semi-drying vegetable oils, and from 0.5% to 5% by weight of a fatty acid ester derived from a saturated or unsaturated monocarboxylic acid having from 12 to 20 carbon atoms, and glycerin, propylene glycol, a mono- or dihydric alcohol having from 1 to 12 carbon atoms, or a polyethylene glycol having a molecular weight of 200 to 6000. Such a composition is said to provide short milkout times. European Patent Application No. 0 058 015 discloses an intramammary formulation comprising isoxazolyl penicillin and rifampicin in an acceptable carrier. This formulation is said to substantially eliminate intracellular staphylococci. U.S. Pat. No. 5,342,612 to Daley et al. describes a composition comprising a potentiating or safening amount of an aqueous surfactant in combination with a tumor necrosis factor, wherein the surfactant is sterol, n-dodecylglucosid, decanoyl n-methylglucamid, dodecyl B-D-maltosid or octanoyl n-methylglucamid. Such a composition is said to provide an efficacious treatment for mastitis with minimal milk discard. U.S. Pat. No. 4,073,920 to Dowrick discloses an intramammary composition comprising a suspension of a semi-solid synthetic penicillin in an oily vehicle that comprises triglycerides or propylene glycol diesters of fatty acids containing 8-10 carbon atoms. Such a composition is said to provide short milkout times and good stability and shelf life. U.S. Pat. No. 5,064,815 to Szentmiklosi et al. relates to a primycin-containing colloidal basic gel comprising 5-30% of primycin and 95-70% of N-methyl-2-pyrrolidone. International Patent Publication No. WO 88/01504 discloses an intramammary infusion comprising a first dosage unit comprising a pharmaceutically acceptable vehicle and a substance active against mammary infection, and a second, optional, dosage unit of active substance, the particles of which are microencapsulated within a membrane capable of degrading. International Patent Publication No. WO 87/03876 discloses a veterinary composition for treatment of mammary disorders and keratoconjunctivitis comprising benzathine cephalothin and a veterinarily acceptable carrier. British Patent Application No. 2,273,443 discloses a composition for treating mastitis, comprising an antibacterial and a seal comprising a polyethylene gel. British Patent Application No. 2,273,441 discloses a composition for treating mastitis, comprising an antibacterial and a seal comprising a gel base containing a heavy metal salt. British Patent Application No. 1,089,523 discloses a composition comprising an antibiotic in a hydrophobic viscous or gel base, and comprising in addition at least 10% by weight of a solid, finely divided physiologically innocuous non-gelling water soluble compound of average particle size below 150 microns. U.S. Pat. No. 4,011,312 to Reuter & Tsuk discloses a prolonged release dosage form for treatment of mastitis consisting of an antimicrobial agent dispersed in a matrix of low molecular weight polyesters of glycolic and lactic acids, and shaped as a cylindrical bougie for insertion into the teat canal. British Patent No. 1,589,917 discloses a composition comprising a crystalline sodium salt of clavulanic acid methyl ether and a pharmaceutically acceptable carrier. High tissue levels of medicament are said to be produced after administration. European Patent Application No. 0 271 306 discloses a method of treating mammary disorders comprising administering an antibacterial in the form of particles, at least 65% of which have a size in the range 0-5 microns, suspended in a hydrophobic oily vehicle which comprises an oil and a gelling agent. Prolonged release of medicament is said to be achieved. U.S. Pat. No. 4,172,138 to Rhodes discloses an infusion of a limited solubility penicillin salt in a slow release base, optionally with neomycin. U.S. Pat. No. 3,636,194 to Parizeau discloses a composition for treating mastitis by intramammary infusion, comprising an antibiotic, a vegetable oil, an alcohol-soluble fraction of natural lecithin phospholipid material for promoting dispersion of the oil in milk, the phospholipid being selected from the group consisting of phosphatidyl choline and phosphatidyl ethanolamine and mixtures thereof and present in amount of at least 0.25% in said oil. Such compositions are said to provide rapid dispersion into milk and short milkout times. British Patent Application 1,181,527 discloses a composition for treating mastitis comprising an active substance and a pharmaceutically acceptable oil base, said composition containing phospholipid material consisting substantially entirely of alcohol-soluble material for promoting dispersion of the composition in milk. European Patent Application No. 0 222 712 discloses a composition which contains one or more antimicrobial agents dispersed in an oil consisting of a mixture of triglycerides of palmitic and stearic acid together with polyoxyethylenated cetyl alcohol and stearyl alcohol, and held in an oily medium of mineral, vegetable, synthetic or mixed extraction. Such compositions are said to speed up release of the antimicrobial agent in the udder, enhancing its biological potential, and reducing milkout time. A Labrafil product brochure (Notice OL 0050/5th edition) from Gattefossé Corporation contains an extract from a thesis by Valette (1957), discussing characteristics of Labrafil™ M-1944CS in the ear canal. The same thesis describes an experiment involving injecting Labrafil™ M-1944CS mixed with gentian violet into a cow teat. It was shown that Labrafil™ wetted the entire surface of the mammary parenchyma section and reached the retromammary ganglion. Non-aqueous aerosol mastitis formulations are disclosed in the patents cited individually below. U.S. Pat. No. 3,135,658. U.S. Pat. No. 3,144,386. U.S. Pat. No. 3,347,743. Canadian Patent No. 670,254. British Patent No. 980,282. In addition, amphipathic oils that are dispersible in water have been utilized in preparation of a number of pharmaceutical compositions not specifically developed for intramammary treatment and/or prevention of mastitis. European Patent Application No. 0 982 035 discloses an alcohol free transparent solution which comprises a cyclosporin in a hydrophilic carrier medium comprising propylene glycol, a transesterification product of a natural vegetable oil triglyceride and a polyalkylene polyol, a polyoxyethylene hydrogenated castor oil product and triacetin. International Patent Publication No. WO 00/48571 discloses a spontaneously dispersible composition for oral administration comprising N-benzoyl-staurosporine, a surfactant selected from the group consisting of a polyoxyethylene castor oil, a polyoxyethylene alkyl ether and a polysorbate and a transesterified ethoxylated vegetable oil as a co-surfactant. U.S. Pat. No. 5,314,685 to Tyle et al. discloses a method of making an anhydrous formulation by preparing an anhydrous hydrophilic phase comprising at least one hydrophilic vehicle which is solubilizing at least one lipophilic pharmaceutically active agent, preparing an oily phase comprising at least one oily component which is partially miscible with the at least one hydrophobic vehicle and combining the oily phase with the anhydrous hydrophilic phase to form the anhydrous formulation. European Patent No. 0 356 325 discloses a pharmaceutical composition for oral, topical, or parenteral administration containing a sparingly water-soluble active agent in an amount as high as 25% and at least one glyceride gelled with at least one cellulose polymer. International Patent Publication No. WO 96/06598 describes pharmaceutical compositions for aerosol delivery comprising a medicament, a non-chlorofluorocarbon propellant, and a polyglycolized glyceride or derivative thereof. U.S. Pat. No. 5,614,491 relates to a liquid preparation for oral and parenteral administration comprising a cyclosporin, a polyoxyethylene glycol fatty acid monoester, and a monohydric and/or polyhydric alcohol(s). International Patent Publication No. WO 99/61025 discloses microemulsion proconcentrates with a piperidine substance P antagonist. U.S. Pat. No. 6,054,136 describes compositions capable of forming a microemulsion, comprising an active principle, a lipophilic phase consisting of a mixture of fatty acid esters and glycerides, a surfactant, a cosurfactant, and a hydrophilic phase. International Patent Publication No. WO 99/56727 discloses self-emulsifying microemulsion or emulsion preconcentrate compositions containing a poorly water soluble active agent, an effective amount of a low HLB oil component, and a surfactant system consisting essentially of at least one surfactant having an HLB of about 10 to 20, wherein the composition contains minor amounts or is substantially free of a hydrophilic solvent system. European Patent Application No. 1 004 294 discloses a substantially anhydrous pharmaceutical composition comprising a nitric oxide donating compound, a mucoadhesive compound, and an emulsifier capable of forming a microemulsion on addition of water. European Patent Application No. 0 265 044 describes (Nva)2-cyclosporin compositions for treatment of autoimmune diseases. U.S. Pat. No. 4,388,307 to Cavanak discloses a pharmaceutical composition comprising an active monocyclic peptide and at least one of the following: a nonionic ester of a triglyceride and a polyalkylene polyol, a saturated fatty acid triglyceride, and a mono- or diglyceride having improved physical and absorption properties. Two articles by Gao et al. (1995) in Pharmaceutical Research 12(6), 857-868, “Controlled release of a contraceptive steroid from biodegradable and injectable gel formulations: in vitro evaluation” and “Controlled release of a contraceptive steroid from biodegradable and injectable gel formulations: in vivo evaluation”, describe preparation of gels containing levonorgestrel, Labrafil™ M-1944CS, and glyceryl palmitostearate. Formulations comprising an antibacterial agent and an anti-inflammatory agent, said to be suitable for otic administration to treat otic conditions, are disclosed in the patents and publications cited individually below. U.S. Patent Publication No. 2002/142999. U.S. Pat. No. 6,395,746 to Cagle et al. U.S. Pat. No. 6,440,964 to Cagle et al. U.S. Pat. No. 6,509,327 to Cagle et al. International Patent Application No. WO 01/89495. International Patent Application No. WO 01/89496. European Patent No. 0 592 348. All of the above patents and articles are incorporated herein by reference. The most commonly used packaging containers and delivery devices for compositions intended for intramammary administration to treat and/or prevent mastitis in milk producing animals as well as for compositions for otic administration to treat ear infections are constructed of oxygen permeable plastic materials, for example polyethylene, polypropylene, etc. and mixtures thereof. The use of oxygen permeable packaging containers and delivery devices for anti-mastitis formulations and for compositions for treatment and prevention of ear infections, poses serious problems for long term chemical and/or physical stability of compositions comprising an ingredient, for example an active medicament or an excipient, that is prone to oxidative degradation. Although the references cited above disclose a number of compositions for treatment of mastitis and other disease conditions, none addresses the problem of providing extended chemical and/or physical stability of compositions packaged in oxygen permeable containers, where the composition comprises a pharmaceutically active substance that is prone to oxidative degradation. Despite the above teachings, there still exists a need in the art for pharmaceutical compositions having one or more of the following advantages over prior art compositions used in treatment and prevention of mastitis by intramammary infusion: (a) extended chemical and/or physical stability even when packaged in oxygen permeable containers and delivery devices, particularly where the composition comprises a pharmaceutically active substance that is prone to oxidative degradation, (b) efficacy against a wide variety of infectious organisms, (c) rapid dispersibility in milk and in udder fluids to achieve efficacious medicament levels at sites of infection, (d) short milkout times for lactating cows, (e) zero day slaughter meat withdrawal period, (f) short milk withholding times post calving after dry cow treatment, and (g) minimal to no irritation after administration.
{ "pile_set_name": "USPTO Backgrounds" }
Mineral content of complementary foods. To document mineral contents iron, zinc, calcium, energy contents and nutrient densities in complementary foods commonly given to young urban slum children. Information on dietary intake was collected from 892 mothers of children aged 13-24 months, using 24 hour dietary recall and standardized measures. Three variations of 27 most commonly prepared recipes were analyzed and their energy (Kcal/g) and nutrient densities (mg/100 Kcal) were calculated. Considerable variations were observed in preparation of all items fed to the children. Cereal-based items predominated their diets with only small amount of vegetables/fruits. Fenugreek was the only leafy vegetable included, but was given to only 1-2% of children. Iron, calcium, zinc contents of staple complementary foods ranged from: 0.33 mg to 3.73 mg, 4 mg to 64 mg, and 0.35 mg to 2.99 mg/100 respectively. Recipes diluted with less water and containing vegetables, spices had higher mineral content. Minerals densities were higher for dals, fenugreek vegetable, khichdi and chapatti. Using the median amounts of the various recipes fed to children, intakes of all nutrients examined especially calcium and iron was low. There is an urgent need to educate mothers about consistency, dilution, quantity, frequency, method of preparation, inclusion of micronutrient-rich foods, energy-dense complementary foods and gender equality.
{ "pile_set_name": "PubMed Abstracts" }
Saturday, 29 October 2016 And more on Warlord Games Bolt Action as sanctimonious gits Apologies to regular viewers - this is a bit of a rant.As part of my Bolt Action purchases I got a British machine gun and crew. I couldn't quite see from online pictures how it all went together. Luckily in the box there was card which said go to their webpage for instructions. However when I tried to go there I got the message. "This is somewhat embarrassing isn't it. .... Either it as been moved or you typed a wrong address." And I thought is this a message for me as if I've made a mistake, or about them not having the advertised page available. But if it was them, then I'd expect an apology for it not being available and a redirect. Then I thought, what a bunch of arrogant smug sanctimonious gits. You provide a guide to a page then insult people who follow that guide. At the moment I'm not sure whether to buy anything else for Bolt Action, or from Warlord Games. Maybe I'm just being too reactionary, but stuff them; I'm a customer and I expect an advertised service. Bah humbug! Personally I have only bought their product second hand, so usually built and undercoated. Poor show that the link doesn't work, they need to have a look at battlefront, may be overpriced and out of scale but the website does help in the build. Had a very different experience with Warlord Games. Purchased at a show a SS boxed set which was missing a medic figure. Contacted the seller and not interested in resolving the problem. Contacted Warlord and happy to help. Too the point that they sent me a full box set with medic figure and all the other 20 figures too. That said I do think that they need to remove the wording about you getting the wrong address. Most people who use the net now understand the need for the correct data in the address or you don't get what you want.
{ "pile_set_name": "Pile-CC" }
Davis, Boone miss first day of mini-camp SANTA CLARA (AP) — The start of the San Francisco 49ers’ three-day mandatory minicamp was overshadowed more by the players who were absent than the ones in attendance. Two-time Pro Bowl tight end Vernon Davis and right guard Alex Boone skipped the first day of San Francisco’s minicamp Tuesday. Both starters are seeking raises despite two years left on their contracts. Coach Jim Harbaugh also said cornerback Eric Wright was not with the team because he’s contemplating retirement. Wright, a seven-year veteran who played in seven games for the 49ers last season, had participated in most of the team’s offseason conditioning program. Players can be fined nearly $70,000 if they miss all three days of the minicamp, per the NFL’s collective bargaining agreement. If Davis and Boone continue to hold out, they set the stage for what could be major distractions leading into training camp next month for a 49ers team that has Super Bowl aspirations. Harbaugh said he appreciates players who show up for the voluntary workouts in the offseason but expects everybody in attendance for the mandatory meetings. He said he was “disappointed” Davis and Boone are holding out. “Not the decision that I envisioned being the 49er way,” Harbaugh said. “Really nothing more to be said about it. The focus will be on what’s going on here.” Neither Davis nor Boone has been present during the first eight weeks of the team’s voluntary offseason program. Davis sacrificed a $200,000 bonus for missing the workouts. And while both are seeking new deals, Davis has been the most vocal about his situation. “In 2010 I signed a five-year, $37 million contract extension with $23 million guaranteed. It was the biggest contract for a tight end in league history. Four years later, and I’m playing at a higher level than I was then, which brings me to why I’m holding out,” Davis wrote in a guest column for MMQB.com on Monday. “It’s all about getting paid what you deserve. It’s not that complicated. I want the 49ers to win the Super Bowl, and I want to be on the field this summer working toward that goal, but I have to worry about my future first. “Most of my teammates and many players in the NFL understand that. A few don’t,” Davis continued. “Behind closed doors, they’ll say they’re all about the team and would run through a brick wall for the organization. But when you look closer, they’re doing things to contradict themselves. I can’t listen to anyone but my family and my advisors, because those are the people who are going to be there when football inevitably dumps me.” Davis, who initially acted coy about skipping the team’s voluntary offseason program, began making his displeasure known publicly shortly before the 49ers announced they had given quarterback Colin Kaepernick a six-year contract extension through the 2020 season that could be worth up to $126 million. Davis, who is now 30 years old, had 52 catches for 850 yards and accounted for 13 of Kaepernick’s 21 touchdown passes last season.
{ "pile_set_name": "Pile-CC" }
Q: how to carry a graphics card arround if I dont have anti static bag I want to carry a graphics card to a friends place. The Card is old and I don't have the original packaging. I know that best way to carry it will be in an anti-static polybag and I tried hard to get one at local stores without any luck. I tried looking for them online but they come as a bunch and cost does not suit the purpose. Is there any other way to safely do this? I got my hands on some packaging foam from a PC which looks like conductive black foam, will wrapping the card in it will make it safe? A: Carefully wrap it in aluminium foil ensuring that you touch the foil and card all the time while wrapping until wrapped. Do the same when unwrapping and keep hold of the card and touch whatever target system with your other hand (to equalize any potential differences) before inserting the card.
{ "pile_set_name": "StackExchange" }
Old White Lion, Bury The Old White Lion is a public house at 6 Bolton Street, Bury, Greater Manchester BL9 0LQ. It is on the Campaign for Real Ale's National Inventory of Historic Pub Interiors. It was built in the late 19th century. References Category:Pubs in Greater Manchester Category:National Inventory Pubs Category:Buildings and structures in Bury, Greater Manchester
{ "pile_set_name": "Wikipedia (en)" }
Queen Victoria’s private beach to open English Heritage has returned to the beach the original wooden bathing machine which ran down a ramp into the sea and from which Victoria – her modesty preserved – would emerge in her swimming suit. English Heritage has also restored the small covered seat – The Queen’s Alcove – where she sat and sketched the coastal views. "Queen Victoria is fixed in many people’s minds as ‘the Grandmother of Europe’, a Queen who spent most of her reign in mourning for her husband," said Simon Thurley, English Heritage’s Chief Executive. "Opening her beach at Osborne lets us show another side to her – this was a Queen who collected sea shells with her children, who sketched the changing sea, and who swam sometimes twice a day. Osborne was her seaside retreat from the formalities of Buckingham Palace, now people can visit that seaside." "It is impossible to imagine a prettier spot," Queen Victoria wrote after a visit to Osborne and Prince Albert likened the bay to that of Naples in Italy. The beach was a deciding factor behind their decision in 1845, to buy the seaside property as their private home. Osborne Bay was often used as a landing for both the royal family and visiting dignitaries while the royal children collected shells from the shore and learned to swim in the special floating bath (since destroyed) designed by their father, Prince Albert.
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1844 United States presidential election in North Carolina The 1844 United States presidential election in North Carolina took place between November 1 and December 4, 1844, as part of the 1844 United States presidential election. Voters chose 11 representatives, or electors to the Electoral College, who voted for President and Vice President. North Carolina voted for the Whig candidate, Henry Clay, over Democratic candidate James K. Polk. Clay won North Carolina by a margin of 4.63%. With 52.39% of the popular vote, North Carolina would be Henry Clay's fourth strongest state after Rhode Island, Vermont and Kentucky. This was also the last presidential election until 1992 when a Democrat would win without carrying the state of North Carolina. Results References North Carolina 1844 Category:1844 North Carolina elections
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Q: How to determine the confidence of a neural network prediction? To illustrate my question, suppose that I have a training set where the input has a degree of noise but the output does not, for example; # Training data [1.02, 1.95, 2.01, 3.06] : [1.0] [2.03, 4.11, 5.92, 8.00] : [2.0] [10.01, 11.02, 11.96, 12.04] : [1.0] [2.99, 6.06, 9.01, 12.10] : [3.0] here the output is the gradient of the input array if it were noiseless (not the actual gradient). After training the network, the output should look something like this for a given input. # Expected Output [1.01, 1.96, 2.00, 3.06] : 95% confidence interval of [0.97, 1.03] [2.03, 4.11, 3.89, 3.51] : 95% confidence interval of [2.30, 4.12] My question is how can a neural network be created such that it will return a predicted value and a measure of confidence, such as a variance or confidence interval? A: It sounds like you are looking for a prediction-interval, i.e., an interval that contains a prespecified percentage of future realizations. (Look at the tag wikis for prediction-interval and confidence-interval for the difference.) Your best bet is likely to work directly with NN architectures that do not output single point predictions, but entire predictive distributions. You can then directly extract desired prediction intervals (or mean, or median point predictions) from these distributions. I and others have been arguing that predictive distributions are much more useful than point predictions, but to be honest, I have not yet seen a lot of work on predictive distributions with neural nets, although I have been keeping my eyes open. This paper sounds like it might be useful. You might want to search a bit, perhaps also using other keywords like "forecast distributions" or "predictive densities" and such. That said, you might want to look into Michael Feindt's NeuroBayes algorithm, which uses a Bayesian approach to forecast predictive densities. A: I'm not sure you can compute a confidence interval for a single prediction, but you can indeed compute a confidence interval for error rate of the whole dataset (you can generalize for accuracy and whatever other measure you are assessing). If $e$ is your error rate while classifying some data $S$ of size $n$, a 95% confidence interval for your error rate is given by: $$ e \pm 1.96\sqrt{\frac{e\,(1-e)}{n}}$$. (see "Machine Learning" book from Tom Mitchell, chapter 5.) EDIT Guess I should state a more general case, which is: $$ e \pm z_N\sqrt{\frac{e\,(1-e)}{n}},$$ where common choices for $z_N$ are listed in the following table: confidence level 80% 90% 95% 98% 99% values of zN 1.28 1.64 1.96 2.33 2.58 A: Prediction intervals (PI) in non parametric regression & classification problems, such as neural nets, SVMs, random forests, etc. are difficult to construct. I'd love to hear other opinions on this. However, as far as I know, Conformal Prediction (CP) is the only principled method for building calibrated PI for prediction in nonparametric regression and classification problems. For a tutorial on CP, see Shfer & Vovk (2008), J. Machine Learning Research 9, 371-421 [pdf]
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Ask HN: What is best email client (to replace Inbox) - clarky07 I love Inbox and I&#x27;m dreading Google shutting it down. I&#x27;ve tried several others in the past but haven&#x27;t found anything else I like as much. At this point I suspect I&#x27;ll just go back to gmail and be less happy but I&#x27;m hoping there is an alternative I could like as much.<p>Tell me what you use for email and why it&#x27;s awesome.<p>only requirements are works on iOS and Mac. Doesn&#x27;t need desktop app, web is fine (perhaps even preferable). ====== PaulHoule fastmail
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Independence from Obamacare needed Legislative update Tonight in Prime Time BC News Friends to follow By U.S. Rep. Jack Kingston Special to the News POSTED:July 11, 2013 6:00 p.m. The Obama administration last week announced it would postpone a controversial mandate within Obamacare for one year. Without the delay, businesses with at least 50 employees would be subject to fines beginning next year if they failed to provide their employees with health insurance.The announcement conveniently came just before a long holiday weekend for many Americans and while the president was abroad. It also just happens to push the job-killing requirement past next year’s elections.The good news, though, is that employers are given a year of relief from this massive new regulatory requirement.The bad news is everything else.Already, businesses have spent millions preparing to comply with the new regulations. Hard-working Americans have seen their hours cut so as not to be classified as full-time employees under the law.The move does nothing to impact the individual mandate that will require all Americans to purchase health care or be subject to a penalty. Already expected to cost $4 billion, the delay could further drive up President Obama’s historic deficits, as more are forced onto government-subsidized insurance plans.Try as it might, the Obama administration cannot issue enough waivers, special-interest carve-outs or delays to hide the fact that Obamacare is the wrong prescription for America. It increases costs, takes away choices and does nothing to solve the underlying problems in America’s health-care system.Instead, the law’s 159 new agencies, bureaus and boards will churn out new regulations, requirements and mandates. Already, they have added some 20,000 new pages of government rules, adding to the regulatory burdens that hold back our economy.Instead of delaying aspects of Obamacare, the misguided law should be repealed in its entirety. We should replace it with common-sense legislation that will bring down costs and increase access to care without growing the size or scope of the federal government. Enacting medical-liability reform, expanding health-savings accounts and opening interstate competition for insurance plans would do a world more good to that end than Obamacare ever will.This disastrous law was ramrodded through Congress with such reckless abandon that Nancy Pelosi said, “We have to pass the bill so that you can find out what’s in it.” Now that President Obama and his allies are learning just what is, they should join us in giving the American people independence from Obamacare.
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718 S.E.2d 145 (2011) STATE of North Carolina v. Terry Adonis BALDWIN. No. 325P11. Supreme Court of North Carolina. October 6, 2011. Anne Bleyman, for Baldwin, Terry Adonis. Amanda Little, Assistant Attorney General, for State of N.C. Peter S. Gilchrist, III, District Attorney, for State of N.C. ORDER Upon consideration of the notice of appeal from the North Carolina Court of Appeals, filed by the Defendant on the 1st of August 2011 in this matter pursuant to G.S. 7A-30, and the motion to dismiss the appeal for lack of substantial constitutional question filed by the State of NC, the following order was entered and is hereby certified to the North Carolina Court of Appeals: the motion to dismiss the appeal is *146 "Allowed by order of the Court in conference, this the 6th of October 2011." Upon consideration of the petition filed on the 1st of August 2011 by Defendant in this matter for discretionary review of the decision of the North Carolina Court of Appeals pursuant to G.S. 7A-31, the following order was entered and is hereby certified to the North Carolina Court of Appeals: "Denied by order of the Court in conference, this the 6th of October 2011."
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MediaManager Description MediaManajer is a software, written in Java which aims to manage PC's media-files. It mays allow users to index their disk, to extract id3 tag, extract exif tags, to convert files from one format to another, to create playlist ...
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James Loney (peace activist) James Loney (born 1964) is a Canadian peace activist who has worked for several years with Christian Peacemaker Teams in Iraq and Palestine. On November 26, 2005, he was kidnapped in Baghdad along with three others: Harmeet Singh Sooden (Canadian) and Norman Kember (British), both members of the delegation he was leading; and Tom Fox (American), a full-time member of CPT who had been working in Iraq since September 2004. The widely publicized hostage crisis (see 2005-2006 Christian Peacemaker hostage crisis) ended on March 23, 2006 when Loney, Kember and Sooden were freed in a clandestine military operation led by British Special Forces. Tom Fox was killed on March 9, two weeks before the release of the other hostages. While Loney was held as a hostage, his family and partner Dan Hunt withheld the fact of his homosexuality out of fear for his safety. The media was aware of this fact but cooperated in keeping it secret. He made a brief media appearance on March 30: "I'll take things slowly until I can get through a day without shaking legs and a pounding heart," he said. Early life Loney was born in Calgary, Alberta, and was raised in Thunder Bay and Sault Ste. Marie, Ontario. During his late teens he worked as a counsellor at Columbus Boys' Camp near Orillia, Ontario, on Lake Simcoe. This was a summer camp for underprivileged boys, funded by the Knights of Columbus and staffed by senior high school students from various schools run by the Basilian Fathers until 2002, when it was sold to Stu Saunders, who turned it into a leadership camp. Loney was a founding member Zacchaeus House, one of several houses that were part of the Toronto Catholic Worker. From 1990 to 2001 he was a member of the Zacchaeus House community—a house of hospitality which welcomes people in need of housing. While no longer an active part of the community, Zacchaues House continues to function today. After release In June 2006, Loney entered headlines again for joining in the protest against the controversial use of security certificates to detain foreign residents in Canada for years without charges or trial. On June 20, 2006, Loney and several other staff members of the Ontario Catholic Youth Leadership Camp held a press conference in Toronto in which they claimed the Knights of Columbus, a Catholic charitable organization, shut down the camp after learning about Loney's sexual orientation upon his return from captivity. The Ontario Knights of Columbus denied this was the reason for closing the camp. The camp re-opened the following summer under the same name but with a new director and staff. On that same day, Loney and his partner Hunt were honoured at the Toronto 2006 Pride Day Gala with the Fearless Award. According to a November 11, 2006 report in the Guelph Mercury of a speech he'd given to university students on November 9, Loney refused to wear a poppy on Remembrance Day. Loney claimed that it "says we have to be ready for the next time - vigilance." Canadian singer-songwriter, Jon Brooks, wrote two songs on Loney's CD Ours And The Shepherds in response to the controversy. Jim Loney's Prayer Part I and Jim Loney's Prayer Part II were chosen as bookends to the track-list on a CD about Canadian war stories. On December 8, 2006, Loney, Kember and Sooden publicly forgave their captors at a press conference held at St. Ethelburga's Peace Center, London, England. On this same day a year before their kidnappers had threatened to execute them. In their joint statement of forgiveness they said, "We unconditionally forgive our captors for abducting and holding us. We have no desire to punish them," and "Should those who have been charged with holding us hostage be brought to trial and convicted, we ask that they be granted all possible leniency. We categorically lay aside any rights we may have over them." On May 23, 2007, Loney released a public statement saying that he would not be testifying against his captors who are now in U.S. custody citing the lack of transparency in Iraqi courts, the limited access to lawyers and the death penalty.I recently informed the RCMP that I will not testify. I cannot participate in a judicial process where the prospects of a fair trial are negligible, and more crucially, where the death penalty is a possibility. Loney and Harmeet Singh Sooden were among 250 Canadians who risked charges under Canada's anti-terrorism legislation in the spring of 2009 for contributing towards a plane ticket for Abousfian Abdelrazik, a Canadian man who was detained by the Sudanese government at Canada’s request, tortured, imprisoned for two years without charge and then denied travel documents to return to Canada. The ticket Loney helped purchase exposed how the government was actively blocking his return and led to the June 2009 court ruling which forced the Canadian government to bring him home. Loney was one of 30 supporters who were on hand to welcome Abdelrazik home upon his arrival at Toronto's Pearson International Airport on June 27, 2009. References External links Christian Peacemaker Teams profile March 30 video: speeches to media by James Loney, his partner, & others in his family March 30 'Emotional Loney speaks of small things he missed' 'More about James Loney', SooToday.com, December 9, 2005 'Brothers of hostage in Iraq describe "gut-wrenching" wait', CBC News, December 11, 2005 'Family waits as deadline passes in silence', The Globe and Mail, December 11, 2005 Free The Captives: Petition for the release of Christian Peacemakers being held in Iraq – includes latest news and daily updates. Catholic Worker Communities Video report March 28, 2006 Category:1964 births Category:Canadian anti-war activists Category:Foreign hostages in Iraq Category:Canadian people taken hostage Category:Roman Catholic activists Category:LGBT people from Canada Category:LGBT Roman Catholics Category:Canadian people of Irish descent Category:Living people Category:People from Calgary Category:Canadian anti–Iraq War activists Category:Catholic Workers Category:Canadian Christian pacifists
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The potential value of HIV-infected human peripheral blood mononuclear cells (PMB) cultured in vitro with phytohemagglutinin (PHA) in the anti-HIV evaluation of nucleoside analogs was examined. 2',3'-Dideoxy-3'-azidothymidine (AZT) exhibited 100-fold higher potency against HIV replication than did 2',3'-dideoxyinosine (ddI) in this system, an observation which does not readily correlate with clinical observations. Studies on metabolism showed that after 12 hr exposure to PHA, cellular AZT was preferentially phosphorylated to its mono-, di-, and triphosphates with 110, 30, and 40-fold increase of the pool sizes, respectively, whereas 2',3'-dideoxycytidine was only moderately phosphorylated, and ddl as well as 2',3'-dideoxyadenosine was poorly phosphorylated. Thymidine kinase activity was found to be the most sensitive to induction among all the cellular kinases regarding stimulation by PHA, and to be responsible for the extreme potency of AZT in this system. Sensitivity of cellular kinases to PHA activation was in the order: thymidine kinase is greater than uridine kinase is greater than deoxycytidine kinase is greater than adenosine kinase. The ratio of ddATP, the active form of ddI, vs. dATP was more than 10-fold higher in resting PBM cells than activated cells. Since the majority of lymphocytes in vivo are in the resting stage and HIV-1 proviral DNA synthesis can be efficiently initiated in resting cells, ddl may exert a disproportionate effect on resting cells rather than activated cells. These data suggest that PHA-stimulated PBM should not be used alone in the screening and evaluation of nucleoside analogues for possible use in the treatment of HIV infections.
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Why primary care will soon only treat chronic conditions - tomohawk https://www.kevinmd.com/blog/2019/11/why-primary-care-will-soon-only-treat-chronic-conditions.html ====== mean_gene_1976 I want everyone on the team. I want the best my budget can handle. I have requirements for technical positions that are posted with factors on how the candidates will he judged. Attributes of all the candidates will not be looked at by the technical review team. They will score and the winner gets an offer. There is one more thing. If I pull data on my NAICS code and see that women or minorities etc are not apart of the workforce, you bet your ass I’m going to put them first. Disabled veterans are prioritized. I do not believe the actual data pull for the rate of return specified. Statistics is something I want all the details, or it is just fluff.
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Q: Heroku-like services for Scala? I love Heroku but I would prefer to develop in Scala rather than Ruby on Rails. Does anyone know of any services like Heroku that work with Scala? UPDATE: Heroku now officially supports Scala - see answers below for links A: As of October 3rd 2011, Heroku officially supports Scala, Akka and sbt. http://blog.heroku.com/archives/2011/10/3/scala/ A: Update Heroku has just announced support for Java. Update 2 Heroku has just announced support for Scala Also Check out Amazon Elastic Beanstalk. To deploy Java applications using Elastic Beanstalk, you simply: Create your application as you normally would using any editor or IDE (e.g. Eclipse). Package your deployable code into a standard Java Web Application Archive (WAR file). Upload your WAR file to Elastic Beanstalk using the AWS Management Console, the AWS Toolkit for Eclipse, the web service APIs, or the Command Line Tools. Deploy your application. Behind the scenes, Elastic Beanstalk handles the provisioning of a load balancer and the deployment of your WAR file to one or more EC2 instances running the Apache Tomcat application server. Within a few minutes you will be able to access your application at a customized URL (e.g. http://myapp.elasticbeanstalk.com/). Once an application is running, Elastic Beanstalk provides several management features such as: Easily deploy new application versions to running environments (or rollback to a previous version). Access built-in CloudWatch monitoring metrics such as average CPU utilization, request count, and average latency. Receive e-mail notifications through Amazon Simple Notification Service when application health changes or application servers are added or removed. Access Tomcat server log files without needing to login to the application servers. Quickly restart the application servers on all EC2 instances with a single command. Another strong contender is Cloud Foundry. One of the nice features of Cloud Foundry is the ability to have a local version of "the cloud" running on your laptop so you can deploy and test offline.
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Gary B. Sanders, “Confederate Conflict in Jackson County, Alabama” Guest columnist Gary B. Sanders, who is kin to the Sanders family of Montgomery and Randolph Counties of North Carolina, has ancestors on both sides of the U.S./Confederate divide. Here, Gary tells the story of his great, great, grand uncle, Joseph Sanders of Jackson County, Alabama, who was murdered during the Civil War on account of his Unionist views. Vikki Bynum, Moderator Confederate-Unionist Conflict in Jackson County, Alabama: The Murder of “Uncle Joe” Sanders, 1863 By Gary B. Sanders Jackson County, Alabama, lies in the northeast Alabama hill country, near the Tennessee border, a region of yeoman farmers who were only reluctantly persuaded to join the Confederacy in 1861. As the war progressed and the fortunes of the Confederacy waned, there was a breakdown in social control in such counties, often leading to guerrilla warfare, revenge killings, and general lawlessness. The story of the murder of the elderly Joseph Sanders on April 10, 1863 on his own farm in Jackson County was one such incident, briefly mentioned in newspapers of the time but long remembered by Joseph’s descendants as they passed down the family tradition of their ancestor who died a martyr to his loyalty to the Union. As always with such stories, embellishments along the way and varying renditions of the event may not reflect what actually happened. A closer look at the life and death of Joseph Sanders, however, may help us understand the disrupting impact of the Civil War on life in Jackson County. Scene from Jackson County, Alabama. Photo courtesy of Gary B. Sanders Joseph Sanders was born in 1793, in Randolph County, North Carolina, the son of Joseph and Rebecca Sanders. The elder Joseph, a Revolutionary War patriot, died in 1803 and made provision in his will that if any of his children became orphaned before they came or age or were married that they should be apprenticed to Quakers. This provision of the will never took effect, as all the children were married within six years of their father’s death. Five of senior Joseph’s seven children married children or grandchildren of Isaac Saunders of Randolph County, who, according to DNA tests of his descendants, was not related to Joseph at all. This close relationship between these two unrelated Sanders lines has baffled genealogical researchers among their descendants, but it helped to cement family ties and loyalties whenever descendants of Isaac and Joseph moved from North Carolina. The younger Joseph was the last of his siblings to marry when he wed Martha Sanders on August 21, 1809 in Randolph County. In the late 1820s, Joseph and Martha, their large family of children, and many of their relatives moved to Jackson County, Alabama. As the Cherokee and other Indian groups were pushed further west, the northeast Alabama region along the Tennessee River became a prime destination for white settlement. Joseph bought land in Jackson County in 1831 and farmed there the rest of his life. Many of his Sanders cousins also moved to Jackson County as did his brother George and his brothers-in-law Francis Sanders and Benjamin Sanders, along with their numerous families. During the late 1830s, Martha died, and Joseph began seeking a new wife. He re-married about 1838 to Deborah Saunders who was another granddaughter of Isaac Saunders of Randolph County. One of the descendants of Joseph’s second marriage, Lottie Kingery Hoge, later wrote of Deborah, I don’t know how she first got acquainted with my Alabama grandfather, Mr. Joseph Sanders, but she went to Alabama and they were married. He was much older than her for he had been married before and had 12 children, most of them grown and married, probably at ages of 14-16. I don’t know when they [Joseph and Deborah] were married but probably about 1838 for their oldest son was born about 1840. That was Uncle Henry. Joseph and Deborah had three children together before she died about 1854. Joseph married for the third time on November 11, 1860 to a widow, Mahala Harper Shelton of Jackson County. The 1860 census list Joseph as age sixty seven with personal property worth $1500 and real estate worth $1500. While he was not a wealthy man, these assets were enough to indicate his farm was prosperous by the standards of the time. Joseph Sanders, by 1860, was the acknowledged patriarch of the Jackson County Sanders. Nearly everyone called him “Uncle Joe,” regardless of whether he was actually an uncle, cousin, granduncle, or some other relative. In fact, nearly every Sanders in the county was related to him, in some cases as double cousins. When the Civil War began, the citizens of Jackson County were split far more evenly in loyalty than in most southern counties. There were few large slave owners in the county and many residents were subsistence farmers who had little regard for the institution of slavery. In 1850 only one man named Sanders in the county owned slaves. Nevertheless, there was still substantial support for the Confederacy, and those who refused to accept secession were regarded as traitors by those who supported the Rebel cause. Although too old to serve as a soldier, Joseph Sanders remained loyal to the national government and his sons and many of his nephews and grand nephews joined the Union Army. The conflicting loyalties in northeast Alabama created a very chaotic and lawless situation in which it is often difficult to determine the motivations of the people involved. Confederate and Union armies moved back and forth across the county, as did bands of deserters, often with no loyalty to either side. Murders, shootings, and acts of violence were commonplace toward the end of the war. “Uncle Joe” Sanders was killed in one of these incidents in 1863 while at his farm at Mud Creek. The following letter by Louie Richard Davis of Texas was written to friends in Scottsboro, Alabama, July 24, 1974, and was published in Sanders Siftings, July 2000, p. 1: I know you have some information on the Sanders that was killed by bushwhackers. I have heard a story here in Texas passed down through generations (may have changed some). One of the Sanders, close relation to Phoebe was caught off guard while plowing in a field by bushwhackers. They took him and his horse to the top of a hill and made the Sanders dig a grave. Then the bushwhackers killed both man and horse and buried both in the grave with the legs of the horse sticking up out of the grave. This is some tale and may not be exactly true but is what I have heard. [This Phoebe was the daughter of Joseph’s sister Mary and her husband Benjamin Sanders. Louis Davis was a descendant of Phoebe.-gs] Other accounts of the killing differ somewhat in the details. A second version was e-mailed to me in 2007 by Bob Dean, a descendant of Rebecca Sanders, Joseph’s niece: Mud Creek is located north of Scottsboro, and there is a cave there, the one that we have always known as Blowing Cave. Joseph Sanders patented 80 acres of land in 1831 that contained this cave. I will tell you the story told [to] me as close as I can remember it. It is not exactly like the story that we have heard before but close. Bob’s informant, John Dolberry, owned the Mud Creek property that belonged to Joseph Sanders and he remembered listening to his grandmother talk about the murder many times when he was a child. His grandmother was the daughter of John Sanders, a son of Mary Sanders, Joseph’s sister, and her husband Benjamin Sanders. In his conversation with Bob Dean, John Dolberry pointed to the cove behind the house and said they hanged Joseph back in the cove at the foot of the mountain on a big mulberry tree. It had a big limb that ran out and then turned up. His grandmother said that was the limb that they hung Joseph on. He was hanged by southerners who thought he was giving help to the Yankees. There were three of the rebels, one a neighbor by the name of Barbee. After killing him they left with a horse they were using as a pack mule to carry, I suppose, the things that they had taken. After they killed Joseph, they left, leading their horse. That evening, not long after the rebels left, a group of Yankees came down out of the mountain and went after the rebels. They caught up with them near the foot of the mountain close to the old Moody Brick. The Yankees killed the horse and made the men dig a grave for it. When the grave was dug, they killed the men, put them in the hole and rolled the horse in on top of them. This could be the story of putting Joseph in the grave with the horse on top of him and the horse with its legs sticking up. They [Joseph’s family] buried Uncle Joe and there were four cedar posts put at the corners of his grave. These were moved after somebody in Texas had the marker put in. [This grave marker was erected in the 1990s.-gs]. The mulberry tree was there for a long time; it had a limb that stuck out and turned up. That was the limb upon which they hanged Uncle Joe. His [great] grandmother sat over there with the body until someone came to help get him to the house. So, apparently he was not killed where he was buried. But the fact that he was buried there would seem to indicate that he lived there. Bob concludes, “It may be as close to eyewitness information as we can get even though his information did not come directly from someone that was there. It did come in a direct line from someone that was a witness to the events. I’m sure that the story is not without flaws, mistakes, and bad memory but may be as close to the truth as we’ll ever get.” More detail about the identity of the men who killed Joseph Sanders is found in a January 27, 2004 posting on the Sanders Ancestry.com forum by Don E. Schaefer, editor of Sanders Siftings, and a descendant of Benjamin Sanders who married Joseph Sanders’ sister Mary: Here is some information about the Joseph Sanders (1793-1863) often referred to as Joseph, Jr.: Concerning the murder of Joseph Sanders, this is what I have picked up from several sources. From notes in the Scottsboro library: “Joseph Sanders was taken from his home during the Civil War and was shot while on his knees by a rock because his boys were in the Union Army. Everyone called him Uncle Joe. He was shot by Jeff Barbee, Thomps Houston, and John Teeters on his farm near Mud Creek, these men were tories never served on either side during the Civil War.” Ann Barbee Chambless of Scottsboro told me that she has been searching for the real story of what happened. A brother of her great-grandfather was one of the “whippersnappers” and she can find no record of a trial. Her ancestor had a record of an estate settlement about that time. Possibly some vigilante justice or Union troops took care of things, without leaving a record. With the lack of a trial or record, I guess many versions of what happened cropped up, slanted to whatever a person’s sympathies were during and after the war. Glenn (Chick) Sanders of Huntsville says that there was no marker for Joe Sanders and he and some other relatives had one put up on his grave. He also said he has been told that two of Joseph Sanders’ sons, Henry A. and John G., killed two of the men who murdered their father. Don Schaefer’s account is based partly on the testimony of Carroll Jackson Brewer in 1876 to the Southern Claims Commission concerning the compensation claim of John Sanders, Joseph’s nephew: “James Hawkins and others searched for his uncle often and did take out him, J. Sanders who was seventy years old, they taken him out of the field when he was at work and shot him on the side of the mountain.” Carroll Jackson Brewer was married to John Sanders’ half-niece and therefore related by marriage to Joseph. Don Schaefer also contributed some material he received from Ann Barbee Chambless who was related to one of the men who killed Joseph: I keep hoping you will unearth the real story about the murder of Uncle Joe Sanders, even though my great grandfather’s brother was one of the three culprits. One of the older men in this county has told me the “hanging tree” still stands at the head of Mud Creek where justice was administered. I still do not know if it would be labeled “roadside justice” or as you suggested Federal troop intervention. I do know that a group of Federal troops stationed in this area took over the Barbee home for their winter quarters one year. My great-great uncle was a very young boy at the time. He lived until I was about six or seven years old, so I remember hearing him repeat stories from that time period. Of course, he never told about his brother being hung. His stories were about his father’s death just before the Civil War (died in 1860) and how another brother died of measles after enlisting in the CSA. That brother was buried at Corinth, MS. My own great grandfather was a CSA Scout and was in the Federal prison at Rock Island. Uncle Lewis told what a difficult winter he, his mother, and his older sisters had the winter they were forced to live in what had been slave quarters. That is one reason I have always been so interested in learning more about the murder of Uncle Joe Sanders and what happened to the culprits. If your Madison County contact provides you with any part of the story, please be sure to share with me.” [From Ann Barbee Chambless, the Jackson County (Ala.) Historical Association]. Although John Dolberry’s family tradition was that Joseph was hanged, the only document contemporaneous with the murder, a brief newspaper article from the Huntsville Confederate for April 23, 1863, stated that Joseph was shot: “On the same day, we learn, an old man, named Saunders, who affiliated with the Abolition Army, when they occupied Jackson county, and went off with them, but returned to depredate on the neighborhood, was shot and killed by some unknown person, on Mud Creek in that county.” Just as we do not know for certain whether Joseph Sanders was shot or hanged (or possibly both), we have no firm documentation on what happened to the men who killed Joseph Sanders. The family tradition from John Dolberry states that the killers were slain by federal troops shortly after the murder; another account mentioned by Don Schaefer is that “vigilante justice,” possibly by Joseph’s sons, took care of the killers. Whatever may have happened during the war as the aftermath to the incident, after the war the event lived on for the most part only in the tradition of the Sanders family and their relatives. There are no records of legal investigations and no suggestion of any enduring blood feuds. Probably, for whatever reason, the murderers did not live long after the killing. The impact of the War, of course, endured for the rest of the lives of the participants. Joseph’s widow and her stepsons appear to have quarreled over his estate. In 1874, eleven years after his death, she was given as her dowry rights a one-quarter distribution from his estate. Three of Joseph’s sons served in the Union Army and two of them were wounded at the Battle of Nashville. When Henry, one of the sons, returned home and discovered that his young wife was pregnant, he divorced her and had nothing to do with her or the baby. He married again and eventually had eight children. Joseph’s nephew, John Sanders, returned home after serving in an Ohio Regiment and later became a justice of the peace in Jackson County. In 1876 in testimony to the Southern Claims Commission, John’s friend and relative by marriage, Carroll J. Brewer, stated that John had been a firm Union supporter even before the War: I knew him about twenty-five years for all that time and live about three miles from him at Mainard cove, PO, Jackson county. I have heard him discuss that he could not sustain the secession principles…all of his talk with me was in the side of the union and he always voted in support… Claimant went into the Regular Federal Army and served nearly three years, and he caused nineteen men with him when he went. The loyalty of the Sanders family of Jackson County to the Union probably had more to do with the unique political climate of the county rather than with any philosophy unique to this family. Close relatives of Joseph and his nephew John who lived outside the county often joined the Confederate Army. John Sanders himself recognized the influence of geographical location in his testimony to the Southern Claims Commission: I have a brother said to be in the Confederate army. I did not see him [join?] Isaac Sanders, forty-four or five years of age on entering the Confederate army in Montgomery County, Arkansas. I have no influence on him. He lived in Arkansas when he joined the army. [He or I?] contributed nothing to his outfit. [He] would not of have been living here. This may mean, possibly, that in John’s opinion Isaac would not have joined the Confederates if he had still been living in Jackson County. In John’s testimony and in that of his neighbors, we can ascertain his intense national loyalty. We see much the same intensity in the affidavits filed in support of pension claims of the other Sanders men who fought for the Union or in testimony to the Southern Claims Commission concerning their claims for compensation for property losses during the war. With Joseph Sanders, however, the record is silent on any voiced expressions or writings he may have made in support of the Union cause. All we have as a record is his actions in encouraging his sons and neighbors to support the Union, efforts that ultimately led to his death. John Dolberry, the descendant who still lived on Joseph Sanders’ farm as of 2007, stated that Joseph was not buried near the mulberry tree where he was killed. Instead, he was buried some distance away near where an infant child of Joseph and Deborah had been buried earlier. There may very well be other family members who are buried nearby, but no other markers are present today. Photo courtesy of Gary B. Sanders Originally four cedar posts were erected to mark Joseph’s grave. Later, in the early 1990s, someone erected a modern tombstone marker. Unfortunately, the dates on the new tombstone are incorrect and the name is given as Joseph B. Sanders, although there are no records that give him a middle name or initial. His real birth and death dates are 1793 and March 10, 1863, according to census records and the testimony to the Southern Claims Commission of his friend Carroll Jackson Brewer. Joseph Sanders gravestone, photo by Gary B. Sanders The grave is located under a tree at the end of County Road 111 in Jackson County. Local people call this site “Dolberry Hollow.” My sister and I visited the resting place of our ancestor in 2007. Today, one sees only a pastoral view of thriving fields of corn and mountain scenery. It is difficult to imagine the strife that engulfed the area at the time of Joseph Sanders’ death. Also located across the road is the “Blowing Cave,” which is something of a local tourist attraction. A strong breeze blows from the cave, hence the name by which it has been known since before the Civil War. In her book Sanders and Bean Families: Past and Present Virginia Retan describes the Blowing Cave as follows: Mother Nature provided an air conditioner during the terribly hot season of summer, known as the Blowing Cave. The cave was named Blowing Cave because of the cool breeze that forever flowed from the entrance in the summer and the warm breeze which flowed in the cooler months. This cave was, and is today, quite an attraction. Inside the cave, there are many rooms. People have used the Blowing Cave many times for shelter from tornadoes and other storms. Unfortunately, many of the rooms have been washed away by great gushes of water which are known to come unexpectedly from the cave. Some people say that the end of the cave comes out in Winchester, Tennessee. Some have said that they have traveled all through the cave and it took them three or four days to reach the other side. Photo courtesy of Gary B. Sanders Now (1986), many groups enjoy exploring the cave, with experienced guides, of course. Scouts enjoy staying overnight there, checking out the remaining rooms of the cave. The cave is now posted and people enter at their own risk. Young couples used to take walks there on Sunday afternoons; even now in 1986, it is said there is evidence of courtships of days long ago, in the names carved on trees or scraped in the rocks at the entrance of the cave. Although the cave is no longer open to the public (as of 2007, the time of my visit), one can still stand about several yards away and get a good view of the cave opening, and sometimes even feel the cool breeze from the cave, just as Uncle Joe Sanders and his family and friends probably used to do on hot summer days before the Civil War. Gary B Sanders’ story is continued proof that Vikki’s blog attracts terrific writers. Interesting indeed. In particular, I appreciated the comment about the two unrelated Sanders and Saunders families of Randolph County NC (as proven by DNA,) and the subsequent confusion this has caused later generations of family researches. Been there. Done that. Two un-related Wilbourn and Welborn famillies also settled (same time frame) in Wilkes Co NC, among other places. Mercy! The trouble this causes later generations when families of the same surname settle into rural areas during the same era. Excellent work. Thank you, Gary! This is a very interesting story, especially for me. My Mama’s family are Saunders from Tuckaseegee Valley NC. My 3X GGF Jordan Holland served from January 1863 to August 1863 with a Home Guard Unit called the Henry Mounted Rebels in Henry County Alabama, Afterward, he enlisted with the 22nd GA Heavy Artillery for the rest of the War. Page 89 of the History of Henry County Alabama(2002) states, “The Henry Mounted Rebels were organized to rid the Choctawhatchee River areas of Confederate Deserters led by Joseph Sanders. They terrorized local citizens all the way to the Florida line.” I am glad to hear the other side of the story. I am not sure how it really turned out, only that ole Jordan was with the group that hunted him. Only found that out yesterday at a library in Atlanta. I was doing a Google search on Joseph Sanders and the War in Alabama and came across this. Thanks for sharing. Jon, I didn’t make the connection when I first read your comment, but I believe the Joseph Sanders who led a group of Confederate deserters in southern Alabama and Florida was Joseph Ganes Sanders who was born in 1827 in South Carolina and and who died in Georgia in 1867. At the beginning of the Civil War, he was living in Dale County, Alabama. There is a Wikipedia article about him. Another source describes him when he served at Gettysburg as “a backwoods unlettered farmer and millwright.” ( http://www.history-sites.com/cgi-bin/bbs62x/alcwmb/arch_config.pl?md=read;id=35432). Gary, Thank you for sharing this. I now reside at the cave and take care of its visitors. For years I had heard many versions of the history and am delighted to come across this as it is by far the most accurate. Please contact me sometime as I would love to talk with you. Nathan, thank you (and all the others who commented on my article) for the kind words. When I was at the cave in June 2007, I was told it was in the possession of John Dolberry, a second great grand nephew of Joseph Sanders. A quick Google search appears to show that it was acquired by the Southeastern Cave Conservancy in January 2008. Is this correct? At any rate, I would be very interested in exchanging information with you and will send a message to your e-mail address that Vikki provided. I am a 3 greats back granddaughter of Joseph and would love to connect with you family to share my family line my great grandpa was John Crawfordberry Sanders hope I spelled that right ! Please contact me! I’m sorry Gary. I believe my father had a brother named Gary, along with Tone Leo, Wayne, David, Aunt Wanda, Larry. My grandfather’s name was Tony Leo. His mother was Rebecca Jane e, whose mom was Malinda,daughter of Brittain. I visited my Grandmother Hazel Maddox in 1990. I was sad to see during my research that grandpa Joe Maddox from Lane a Virginia ia had passed away. I was born in New Port News Virginia. My mom’s name was Diane Renee Sutherland. I grew up in Pascagoula, Ms. I hope this helps. I REALLY ENJOY READING YOU ARTICLES Hi I just recently moved to Pensacola and discovered my grandfather is Ernest Sanders, great great great grandson of Joseph Sanders through son Henry. I am truly interested in my southern history as I grew up in Seattle WA thinking I was Italian not a Sanders. Apparently my father had a falling out with family and changed his history to a stepparent. Please contact me anytime. Please see my Web site for other information on our Sanders familyhttp://home.earthlink.net/~garybsanders/ There are several mentions there of your ancestor Henry A. Sanders who served in the 18th Ohio Regiment, Company B., and was wounded in the right shoulder at the Battle of Nashville. He survived the war, returned to Alabama, divorced his first wife, then married two more times and had eight children. Henry was described by one contemporary as a “red-headed Irishman.” I am a relative to John Dolberry and have many fond memories as a child playing outside the “blowing cave” and drinking from the spring. My grandfather Marion Little is also buried at the nearby grave yard. I loved reading about my family history. Thank you. Hi Gary Sanders, Thanks for sharing the Sanders’ blood line. I really don’t know much about my family tree. I do have a U.S. WWII Draft Card with my grandfather’s name (Birl Sanders) on it. He lived in Eleazer, Randolph county (South of Asheboro near the Montgomery county line). I would love to find out more about my ancestry and DNA testing. Hi Jimmy, I don’t have your grandfather Birl listed in my files but send me a personal e-mail and we can discuss your descent from the Sanders of Randolph and Montgomery. Thanks. –Garyhttp://home.earthlink.net/~garybsanders Wow! my name is Jay Wilson. I live in Chattanooga Tn. My father was born @ Mud Creek near the blowing cave in 1933. He will be 81 in April. His mother (my grandmother) was Elizabeth Eliza Sanders. She was born Febuary 19, 1900 and died Febuary 21, 1998. I think she said she was John T. Dolberrys cousin. Her father was Jesse Sanders and I believe her mother was Sarah Jacks Sanders. Her siblings were Wallace, Annie, Ab, and Sally Sanders. Eliza married my grandfather James Riley Wilson from Fackler Al. I believe. I would be curious to know if you have any further info on where we all fit into this tree. Thanks, Jay Wilson Hi Gary My name is Jesse Sanders I live in Michigan. Jay Wilson is my cousin, his father is my uncle Gene. My father was his brother Jessie David Sanders who was born in 1920 in Mud Creek. He died in 1965. He served in the Army during World War II in Germany. He married twice and had four children Ronald David Sanders his oldest son,and Patricia Sanders with his first wife Gladys (Oakwood ) Sanders . Me and my sister Sandra Sanders- White are from his second marriage to Gloria ( Opdycke ) Sanders. I believe from your research that I come from the line of John G Sanders, Uncle joes son.
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Q: Looking for large GML files containing vector polygon data I have few vector data files with 500 to 700 MB GML files. But I am looking for files larger than these preferably 1 GB, 2 GB. It would be helpful if somebody can provide some pointers regarding the place to find such files. Note: I need to test polygon overlay over large data sets, so the two layers that I need should be intersecting. A: You can try some of the CanVec data, available here. Some of those files range from 4 MB to 50GB, depending on the one you choose.
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Launch of Maxxia & Remserv Claims The launch of the desktop and smartphone claiming platforms made claiming easier with automated processing and 24/7 access. My role: Leading the design I worked closely with multiple teams to develop a solid visual story that succeeded in driving customers to these new platforms. Claims app launch Educational flyer, promotional material Internal communications launched first to educate our customer facing employees. A visual guide to the app was desk dropped to staff on the internal launch day. 'Smart phone' chocolate bars came floor stickers were distributed around offices to add excitement and it helped to aid positive change. Claims for desktop launch Educational flyer, poster, DL, email template, digital banners A flyer was distributed internally with the same intention of educating employees about the platform and the positive affect it will have on our customers. ​​​​​​​ After internal education, the second step was launching to our customers. A range of digital and print pieces were rolled out nationally across all offices, over 50 client sites and 300,000 customers with the main goal of converting customers from manual call centre claiming to online claiming. The results Within six month of launch over 65 per cent of customers were using the new platforms. Both apps had over 22,000 downloads in two months. The Maxxia desktop portal had over 1.1 million logins in six months. These results in relieving the burden felt by the call centre who where manually entering and processing claims resulting in a more efficient process flow for the company.
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Which Wedding Gown Style Is Perfect For Your Personality? (Quiz) Like nearly every woman, you've had the perfect wedding gown dreamed up in your head since the first time you watched "Cinderella" at age 5. Like your taste in food, music and Disney princes, however, your personal style has vastly changed since then. It's only natural your shift in personality would make those once-beloved puffy Cinderella sleeves completely repulsive to you now. Sometimes, the best way to find the dress of your dreams is to pick a style that most closely matches your personality. After all, your brain and natural charisma are what led you to find the love of your life, and it's important to may homage to that when choosing a wedding gown. You want your outfit to feel like you, not some elaborate version of what you think a bride is supposed to look like. Still confused? Take this quiz to find the best dress silhouette for your personality type.
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1. Field of the Invention The present invention relates generally to uninterruptible power supplies. More specifically, the preferred embodiments of the present invention relate to an uninterruptible power supply with controllable leakage current. 2. Background Discussion Uninterruptible power supplies (UPSs) are commonly used to provide power to critical equipment that must not experience even short duration brownouts or blackouts. For example, computer servers, computer networks, telecommunications electronics and medical devices are often powered by an uninterruptible power supply. A UPS device typically has an AC-DC-AC converter and backup battery that is activated in case the alternating current (AC) line power is temporarily disconnected or falls below a voltage threshold. FIG. 1 shows a conventional UPS circuit according to the background art. The conventional UPS circuit includes an input rectifier (having switches Q1, Q2) and an output inverter (having switches Q3, Q4) connected in series. The input rectifier converts AC input power to DC power, and the output inverter converts the DC power to AC output power. Typically, the switches Q1, Q2, Q3, Q4 will be MOSFET devices or insulated gate bipolar transistors (IGBTs), though switches Q1 Q2 can also be diodes. The switches Q1, Q2, Q3, Q4 are controlled by a gate drive circuit (not shown). Storage capacitors C1, C2 store DC power. Typically, an isolation transformer T is provided. The input rectifier switches Q1, Q2 receive AC line power and provide direct current (DC) power to the inverter switches Q3, Q4. The inverter switches Q3, Q4 are typically operated according to a pulse-width modulation (PWM) scheme. The PWM waveform is filtered by output inductor Lo and output capacitor Co to create a smooth AC output waveform. With this arrangement, the voltage and frequency of the AC output can be accurately controlled and will be independent of the AC input. Leakage current is often a problem with the conventional circuit of FIG. 1 and similar UPS circuits. Leakage current results when AC signals (egg from the PWM waveform produced by the inverter switches Q3, Q4) couple to ground, the device chassis, or nearby electronic components. A typical UPS providing a kilowatt of power may experience several hundred microamperes of leakage current. In some applications, leakage current can produce ground loop currents, noise, and disturbances in sensitive electronic circuits. Leakage current is particularly a problem in medical device electronics because medical devices are often very sensitive to noise and ground loop current. Leakage current can be dangerous in medical applications as it may cause a malfunction of critical life support or monitoring equipment. Accordingly, there is a need in the art for a UPS circuit that has reduced leakage current. It would be particularly beneficial to provide a UPS circuit that has a leakage current less than an adjustable maximum level. Also, it would be beneficial to provide a UPS circuit that allows the maximum leakage current to be controlled by a user.
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Isomers in thioredoxins of spinach chloroplasts. We have developed a method for the concomitant purification of several components of the ferredoxin/thioredoxin system of spinach chloroplasts. By applying this method to spinach-leaf extract or spinach-chloroplast extract we separated and purified three thioredoxins indigenous to chloroplasts. The three thioredoxins, when reduced, will activate certain chloroplast enzymes such as fructose-1,6-bisphosphatase and NADP-dependent malate dehydrogenase. Fructose-1,6-bisphosphatase is activated by thioredoxin f exclusively. Malate dehydrogenase is activated by thioredoxin mb and thioredoxin mc in a similar way, and it is also activated by thioredoxin f but with different kinetics. All three thioredoxins have very similar relative molecular masses of about 12,000 but distinct isoelectric points of 6.1 (thioredoxin f), 5.2 (thioredoxin mb) and 5.0 (thioredoxin mc). The amino acid composition as well as the C-terminal and N-terminal sequences have been determined for each thioredoxin. Thioredoxin f exhibits clear differences in amino acid composition and terminal sequences when compared with the m-type thioredoxins. Thioredoxin mb and thioredoxin mc, however, are very similar, the only difference being an additional lysine residue at the N-terminus of thioredoxin mb. Amino acid analyses, terminal sequences, immunological tests and the activation properties of the thioredoxins support our conclusion that thioredoxins mb and mc are N-terminal redundant isomers coming from one gene whereas thioredoxin f is a different protein coded by a different gene.
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Main menu Monthly Archives: February 2020 All month, I’ve been writing poems each morning to a theme via CLMOOC’s Poetry Port — a project designed to spread collaboration and support through various networks. Along with the daily writing, a number of us were writing poems for others — sometimes as unexpected gifts and sometimes for the recipient’s request. The Thinglink above is my curation of my own poems, some via audio and some via text. Today, the last day, the daily poem theme was not Farewell, but instead, Welcome. Kevin’s Note: I signed up for a month-long Digital Detox project out of Middlebury College and enjoyed the email updates throughout January that got us thinking about our digital lives, and offered small steps and actions to take. I made comics about the concepts as a way to read deeper and think a little more critically about the ways digital devices and platforms are part of our lives. This is the last comic I made for that project. Kevin’s Note: I signed up for a month-long Digital Detox project out of Middlebury College and enjoyed the email updates throughout January that got us thinking about our digital lives, and offered small steps and actions to take. I made comics about the concepts as a way to read deeper and think a little more critically about the ways digital devices and platforms are part of our lives. One of the many topics that come up when I read Christopher Paul Curtis’ novel The Watsons Go to Birmingham 1963 is the role of young people in the civil rights movement. Although the novel never references the Birmingham Children’s Crusade, the movie adaptation does, through the memory of some cousins of the Watson children, and so we spend time discussing how young people took the streets in protest, were attacked by police with fire canons and dogs, and were sent to jail by the hundreds. Let The Children March, a picture book by author Monica Clark-Robinson and illustrator Frank Morrison is a powerful text companion to those discussions. With brilliant visuals and an engaging story (plus, a valuable timeline of 1963 in Alabama during the Civil Rights era), the book brings to the surface the courage of the kids who took to the streets, the wariness and worry of the parents who allowed the march (code-named D Day and Double D Day) to happen, and the movement leaders who accepted that children being arrested would create tension for the Kennedy White House to finally act against segregation. The picture book centers on a narrator voice of a child who takes part in the Birmingham Children’s Crusade, but it more of a universal voice, advocating for change against unjust rules and putting the self in danger to force confrontation against a police force that was part of the problem, not the solution. I appreciate how Let The Children March gives those young marchers a voice, and also, explores the results of the march (which the scenes in the Watsons movie does not do because of the time frame). President Kennedy did get involved after getting pressure from the country and the world. Birmingham did end official segregation (if not racial violence, as the bombing of the church that forms the center of the Watsons novel shows. Change happened, even if the results of those actions are still something we continue to reckon with as a country. (This is for the Slice of Life challenge, hosted by Two Writing Teachers. We write on Tuesdays about the small moments in the larger perspective … or is that the larger perspective in the smaller moments? You write, too.) I was wandering our small city’s downtown, a little bit bored and sort of wasting the hour. This is often when our attention to the small things of the world is at its finest — when we are not consumed by other tasks. I noticed the window of a public art gallery, and wandered in. I had time. The latest art show in the gallery is called Tiny Pricks, and it features embroidery of President Trump’s craziest quotes, with art as the lens of protest. It’s both amazingly insightful and sadly alarming (the things Trump says). Along with the art on display, the gallery has hosted sessions for more embroidery for visitors. At a table, all of the materials were laid out, at rest, as if the embroidery team had just suddenly gone off on coffee break and would be back soon. If I knew how to embroider with needle and thread and cloth, I might have sat down and continued their work. Instead, I kept making my way through the hanging wall displays. There must have been at least a 100 or more embroidered works of art. I wandered in the gallery for some time, just staring at the embroidery and appreciating how art is a way for us to express our political views, and then wondering if projects like this will translate into votes in November. I eavesdropped in on other patrons, who seemed to be asking some of the same questions. I left after a bit, still thinking about the artwork for hours later, which I suppose is a sign of the power of the embroidery, of the artists, to help us see the world — political, or otherwise — in a new way and to wonder about other paths forward. Kevin’s Note: I signed up for a month-long Digital Detox project out of Middlebury College and enjoyed the email updates throughout January that got us thinking about our digital lives, and offered small steps and actions to take. I made comics about the concepts as a way to read deeper and think a little more critically about the ways digital devices and platforms are part of our lives. I had this idea of going back to a poem that I wrote, rather quickly, for the theme of Memories for CLMOOC’s month of poetry, and think a bit deeper on why I wrote what I wrote. To be honest, the comment annotations are small — you can get a closer look here, if you want. My hope was to uncover some of my intentions with the small poem, to surface some of my moves. I would not call this poem anything extraordinary or special or even one of my best poems this month, but there are elements of personal story and intentional rhyming, as well as regrets about the ending, that made this poem worth a second look. For me, anyway. Last night was the second online session of an inquiry group project called The Grapple Series – hosted by the National Writing Project, Western Pennsylvania Writing Project and the CMU CREATE Lab — that is looking at the impact of AI and technology on our lives. The theme last night was algorithms and justice, a pairing that made for interesting conversations about how blind trust in both often lead to disastrous consequences. We explored some interesting reading and video pieces before gathering in our online session. The articles explored the issue from multiple angles, but the overall connecting concepts are clear: algorithms are created people, and people have bias, and so algorithms have bias, too, and when algorithms are embedded with bias, it impacts our notions of justice in the world. Sometimes, this is literal — as in the case of computer software being used to designate length of parole. Sometimes, it is more nuanced — the way search engines bring racial stereotypes to the surface. Sometimes it is not yet known — the way facial recognition is changing our sense of privacy in the public sphere. The Grapple gathering began with a large discussion and writing about justice and algorithms, and then broke into smaller groups, where we engaged in deeper debate about the role of algorithms on society. We also teamed up to create our own paper “algorithm” for fighting off the common cold, and while our group went a sort of silly route (Should a teacher call in sick or not?), the short flowchart activity reminded us how often we can fall into Yes/No binary decisions that can leave the humanity aspect out. Another small group did integrate ideas of humanity into their algorithm, and I found that quite interesting. I appreciate being able to work through and “grapple” with these complex questions rippling through society. There is no real solution — the algorithmic genie is long gone from its bottle. But we can be aware, and make some decisions about how what information we share and how we are being manipulated by technology. Second, this poem is for Ron, whose work as an artist is always interesting to me. He makes picture books and does daily artwork and sketches, and is always up for another connected adventure. Ron and I know each other through CLMOOC and DS106 and other adventures. His poem began in digital format, but then I wanted a more static version, too. Finally, this poem is for Raymond. Our paths crossed years ago in CLMOOC, and I bought his small book of poems, a book that inspired the poem. We still interact now and then, and although I think our political views are quite different, I enjoy understanding Raymond’s perspective and reading his poetry.
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The state's largely Democratic electorate, coupled with Warren's pulling women voters to her side, proved too much for Senator Brown to overcome. Brown was popular and benefited in this "blue" state by avoiding lock-step votes with Senate Republicans. But unlike 2010, when he won his seat in a special election, this was a presidential year that brought out a broader array of the state's electorate. The race this year also brought in massive amounts of campaign contributions on both sides, as Republicans sought to defend a seat and Democrats sought to reclaim it. Ms. Warren is a stalwart liberal who became known nationally as a crusader against the power of Wall Street banks and for her focus on the economic struggles of working-class families. "It was exactly 50 years ago tonight that Ted Kennedy was first elected to the United States Senate," Warren told cheering supporters Tuesday night. "We miss his passion, his commitment, his energy, and his fight for working families." Warren said that Mr. Kennedy's pledge back then – to devote all his strength and will to serving Bay State residents – is now hers as well. Both candidates maintained a positive impression with voters during the campaign. Yet the campaign was also rife with negative ads. Warren's ads appealed especially to women, and they did so successfully. "Don't let Scott Brown put women's health at risk," one Warren flier warned as Election Day neared. The mailing said Brown had, among other things, "stood with Republican extremists against Planned Parenthood, voting to limit access to preventive care." Warren also bored in on the national implications of the race, arguing that a vote for Brown would also be a vote for expanding the clout of Republicans in the Senate – many of whom are more conservative than Brown. She reminded voters that the next senator from Massachusetts could have a role to play in anointing Supreme Court nominees, and she sought to raise doubts about Brown's commitment to abortion rights. Warren fended off attacks by Brown, including his questioning of her integrity during her academic career. She had listed herself as a minority in a directory of law-school professors for many years, then dropped the listing after gaining a position at Harvard Law School. Warren rejected the implication that she had used the listing to advance her career, and most voters didn't hold the issue against her. After the hard-fought race, Brown was gracious in conceding defeat. "She won it fair and square folks," he told his campaign staff. "May she bring that Senate office great credit." Warren, too, sounded a magnanimous note. She said although Brown's supporters didn't vote for her, she embraced his message of being ready to work across party lines. "I promise I'm going to work to earn your support," Warren said.
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Q: Как сделать, чтобы String str = любому значению из массива? нужно чтобы String str = любому значению из массива, чтобы можно было написать public static void say() { Scanner in = new Scanner(System.in); Random random = new Random(); String str = in.nextLine(); switch(str) { case("Привет"): System.out.println(HELLO[random.nextInt(HELLO.length)]);break; case("Привет!"): System.out.println(HELLO[random.nextInt(HELLO.length)]);break; case("привет"): System.out.println(HELLO[random.nextInt(HELLO.length)]);break; } say(); нужно чтобы по несколько раз не писать case и не писать повторно Sout. A: Наверное Вам нужно что то подобное: Scanner in = new Scanner(System.in); Random random = new Random(); String str = in.nextLine(); Map<String, String[]> db = new HashMap<>(); String[] hellos = new String[]{"Привет", "Алоха"}; String[] helloAnswers = new String[]{"Здравствуй", "Добрых вечеров!"}; for (String hello : hellos) { db.put(hello, helloAnswers); } String[] goodbyes = new String[]{"Пока", "Прощай"}; String[] goodbyeAnswers = new String[]{"До свидания", "Ну пока"}; for (String goodbye: goodbyes) { db.put(goodbye, goodbyeAnswers); } if (db.containsKey(str)) { String[] answers = db.get(str); System.out.println(answers[random.nextInt(answers.length)]); } PS: могут быть ошибки, писано с телефона...
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Q: What is the proper way to fill a form with multiple data fields? I have been asked to create a vb.net WinForms app that automates the creation of this spreadsheet: Obviously, creating that spreadsheet manually is a back breaking task. I am very comfortable writing SQL to pull each individual field of data, however I've got to believe that there is a better way. Such a method would require 144 queries !! I've considered creating a form with individual labels for each field, or using a gridview. Either would be acceptable to the end user, but I'm really not sure how I would write a query to produce a dataset that look like the end product anyway. I'm not asking anyone to write any code for me, what I'm asking for help with is the concept of how I should attack this task. Here is a query that I wrote which returns the fields for Business Unit #1 for the first week on the spreadsheet. I don't think it helps much, but I'm adding it to show that I've put some effort into this. DECLARE @WeekEnding AS DATE DECLARE @DIV AS INT SET @WeekEnding = '11/13/2015' SET @DIV = 20 -- A/R downpayments OPCH SELECT SUM(OPCH.DocTotal - OPCH.VatSum - OPCH.TotalExpns) AS 'ARDownPaymentInvoice' FROM OPCH LEFT JOIN INV1 ON OPCH.DocEntry = INV1.DocEntry AND INV1.VisOrder = 0 LEFT JOIN OITM ON INV1.ItemCode = OITM.ItemCode LEFT JOIN OITB ON OITM.ItmsGrpCod = OITB.ItmsGrpCod LEFT JOIN OACT AS CurrCode (NOLOCK) ON OITB.RevenuesAc = CurrCode.AcctCode WHERE DATEPART(WEEK, OPCH.DocDate) = DATEPART(WEEK, @WeekEnding) AND YEAR(OPCH.DocDate) = YEAR(@WeekEnding) AND CurrCode.Segment_4 = @DIV -- Credits ORIN SELECT SUM(ORIN.DocTotal - ORIN.VatSum - ORIN.TotalExpns) * -1 AS 'Credit' FROM ORIN LEFT JOIN INV1 ON ORIN.DocEntry = INV1.DocEntry AND INV1.VisOrder = 0 LEFT JOIN OITM ON INV1.ItemCode = OITM.ItemCode LEFT JOIN OITB ON OITM.ItmsGrpCod = OITB.ItmsGrpCod LEFT JOIN OACT AS CurrCode (NOLOCK) ON OITB.RevenuesAc = CurrCode.AcctCode WHERE DATEPART(WEEK, ORIN.DocDate) = DATEPART(WEEK, @WeekEnding) AND YEAR(ORIN.DocDate) = YEAR(@WeekEnding) AND CurrCode.Segment_4 = @DIV --Invoices SELECT SUM(OINV.DocTotal - OINV.VatSum - OINV.TotalExpns) AS 'Invoice' FROM OINV LEFT JOIN INV1 ON OINV.DocEntry = INV1.DocEntry AND INV1.VisOrder = 0 LEFT JOIN OITM ON INV1.ItemCode = OITM.ItemCode LEFT JOIN OITB ON OITM.ItmsGrpCod = OITB.ItmsGrpCod LEFT JOIN OACT AS CurrCode (NOLOCK) ON OITB.RevenuesAc = CurrCode.AcctCode WHERE DATEPART(WEEK, OINV.DocDate) = DATEPART(WEEK, @WeekEnding) AND YEAR(OINV.DocDate) = YEAR(@WeekEnding) AND CurrCode.Segment_4 = @DIV` Thanks for any ideas. A: One way to achieve this: CREATE TABLE #tmpData (column1 varchar(50), column2 varchar(50), column3 varchar(50), column4 varchar(50), column5 varchar(50), column6 varchar(50), column7 varchar(50), column8 varchar(50), column9 varchar(50), column10 varchar(50), column11 varchar(50), column12 varchar(50)) Then you could insert a row displaying the dates of each column INSERT INTO #tmpData --Write your select query here for filling in all the dates Then you would insert the data for each line item in the rows. INSERT INTO #tmpdata SELECT 'Business Unit 1', -- insert remaining column data here
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Assessment of the Contractile Properties of Permeabilized Skeletal Muscle Fibers. Permeabilized individual skeletal muscle fibers offer the opportunity to evaluate contractile behavior in a system that is greatly simplified, yet physiologically relevant. Here we describe the steps required to prepare, permeabilize and preserve small samples of skeletal muscle. We then detail the procedures used to isolate individual fiber segments and attach them to an experimental apparatus for the purpose of controlling activation and measuring force generation. We also describe our technique for estimating the cross-sectional area of fiber segments. The area measurement is necessary for normalizing the absolute force to obtain specific force, a measure of the intrinsic force-generating capability of the contractile system.
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Q: How to use lower_bound to insert value into sorted vector I have a vector of pointer to class A which I want to keep sorted by int key using STL. To do this I defined an operator < in class A bool operator< (const A &lhs, const A &rhs){ return (lhs.key < rhs.key); }; and in my insert function it looks like vector<A*>::iterator it = lower_bound(vec.begin(), vec.end(), element); vec.insert(it, element); I expect lower_bound to return first place where the new element can be placed, but it does not work. Inserting A objects with keys 0,1,2,3 will result in vector in incorrect order (2,3,1,0). Why is that ? Probably I could also use comparator for this object: compare function for upper_bound / lower_bound but what's wrong with my code? A: From your example, you're using a vector of pointers: std::vector<A*>. Hence, you need to define a comparison for pointers which you pass in to std::lower_bound: bool less_A_pointer (const A* lhs, const A* rhs) { return (lhs->key < rhs->key); } auto it = std::lower_bound(vec.begin(), vec.end(), element, less_A_pointer); //... Of course, the question is why are you using pointers in the first place - just store A objects unless you really need to. If you do need to store pointers, look into std::shared_ptr which will handle this for you: std::vector<std::shared_ptr<A>> v; std::shared_ptr<A> element(new A(...)); auto it = std::lower_bound(v.begin(), v.end(), element); //Will work properly You can also use a lambda instead of having to write a free function: auto it = std::lower_bound(v.begin(), v.end(), [](const A* lhs, const A* rhs) { return lhs->key < rhs->key; });
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LINE’s Webtoon app updates its comics daily, and is optimized for mobile platforms without data restrictions, as you can download them over wifi and read them on the subway or at the Javitz Center, which is a data deadzone. It is available now via Google Playstore and the Apple store. The app launched in Korea in 2004, and launched in the US in 2014. It already has millions of users in both Korea and the US. The app will work with pros and with amateurs in a “challenge league.” The editorial team elevates some of the most popular webtoons to pro status, so its a good place to try and break in, if you’re so inclined. Matt Hawkins is launching a branch of his comic Cyber Force on the LINE Webtoon app in November which will run for 52 weeks. Cyber Force: Powers will fit into his work that is existing currently in trades (the first two volumes of which are readily available on the apl now, with one chaoter releasing every week), as well as the anime Witchblade, The Darkness video games, and Aphrodite Nine. Hawkins did accidentally spoil the news that there will be a third in The Darkness franchise. Michelle Phan’s webtoon Helios Femina will be about an alchemist who needs to find a songstress and from there embark on some kind of “odyssey.” Phan was much more excited to discuss how excited she is by the app. For those interested, she hand draws the comic, scans it, and inks it digitally. She posts photos of her process on SnapChat. Dean Haspiel is a veteran webcomic artist. His webtoon New Brooklyn is a superhero story in the spirit of “What if Jack Kirby and Alex Toth got together?” The impetus of Haspiel’s story were the white flags on the Brooklyn Bridge last year, and thus New Brooklyn is a story about Brooklyn being a sentient being that creates superheroes and villains. It is very much an outlet for Haspiel’s tech fatigue and malaise “What if Brooklyn has gotten fed up with the world and technology?” Rob Feldman is working on two webtoons for LINE, horror tale Chiller and Sci-Fi-meets-Evil Kineval-meets-UltraMan story Cyko KO. Chiller relies on sound effects from the FXToonEditor available to all Webtoon creators. Cyko KO was originally born as an animated series. Stephen McCraine’s Space Boy was the winner of the first challenge league contest. He called the challenge a “comics marathon” with no time to worry or over-plan. The top four comics get a publishing deal with LINE. The third contest is running now, sponsored by Stan Lee. Submissions close December 13, 2015. Submissions require the first three chapters of a webtoon. Has quietly been working at Bleeding Cool for over three years. He has written comics for Image, Top Cow, Shadowline, Avatar, IDW, Dynamite, Moonstone, Humanoids and Zenescope. He is the author of the Lucius Fogg series of novels and a published photographer.
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<html> <head> <meta HTTP-EQUIV="Context-Type" CONTEXT="text/html;charset=windows-1252"> <meta name="GENERATOR" content="Microsoft FrontPage 3.0"> <title>tr Summary</title> </head> <body> <h1>tr Summary</h1> <ul> <li><h2>tr input MUST come from standard input </h2> </li> </ul> <ul> <li><h2>tr does NOT change the input file but puts its modified values on standard output </h2> </li> </ul> <ul> <li><h2>recognizes the range, set regular expressions </h2> </li> </ul> <ul> <li><h2>if more than a single character then characters replaced match up on left with characters which replace them (i.e. &#147;qex&#148; &#147;abc </h2> <ul> <li>a for a </li> <li>b for e </li> <li>c for x </li> </ul> </li> </ul> <ul> <li><h2>characters can be deleted with the -d option </h2> </li> </ul> <ul> <li><h2>multiple characters removed with the -s option </h2> </li> </ul> <ul> <li>&nbsp;</li> </ul> <table> <tr> <td HEIGHT="100" WIDTH="100"><a HREF="tsld019.htm">Previous slide</a> </td> <td HEIGHT="100" WIDTH="100"></td> <td HEIGHT="100" WIDTH="150"><a HREF="tsld001.htm">Back to first slide</a> </td> <td HEIGHT="100" WIDTH="150"></td> </tr> </table> <p><br> </p> </body> </html>
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I am quite sure that when we hear of Trentino-Alto Adige/South Tyrol, most of us think of speck, strudel, and Muller-Thurgau. The same happens with the denomination of Veneto Valpolicella, which recalls some good red wines. Despite this, it should surprise no one that some portions of these two regions are devoted to the cultivation of olive trees and the production of great extra virgin olive oils. I am glad when people open the bottle of my oil and get excited.- Monica Vaccarella There is a part of the province of Trento which is tempered by the mitigating effects of Lake Garda and enjoys a sub-Mediterranean climate with moderately cold winters and hot summers, ideal conditions for growing olive trees up to an altitude of 300 meters (984.2 ft). Olio Cru’s olive groves in Arco, Trento A few miles from the northern shores of the lake, in the territories of Arco, Bolognano and Massone, lush olive groves give life to 7c, an olive oil producer and three-time Gold Award winner at the New York International Olive Oil Competition (including one Best in Class in 2016). “2,000 plants, mostly Casaliva, lie on the slopes of the hill overlooking the town of Arco, partly rooted on terraces and partly flourishing on the rough hillside,” said the head of manufacturing, Massimo Azzolini. “The challenging terrain makes harvest complex, and even though we can use mechanical facilitators in some plots, a large part of work is by hand,” he pointed out. Harvest usually starts in the last week of October; the liquid gold that comes out is light-to-medium fruity, moderately spicy and bitter, with hints of almond, artichoke, and grass. “Part of our product is made with de-pitted olives that must be picked when they are at least 70 percent green,” Azzolini explained, adding that the harvest must be anticipated to catch fruits at the beginning of veraison, in order to obtain a product characterized by decisive pungency and fruitiness. Olio Cru As we move to Veneto, Valpolicella is the protected designation of origin of an extra virgin olive oil produced in the area situated on the right side of the Adige river. Monica Vaccarella manages 1.5 hectares (3.7 acres) of olive grove with 500 plants at an altitude of 400 meters (1,312 feet), in Avesa, between the Val Borago and the Val Gavina. Two steps away from Verona, the native varieties Grignano and Favarol flank the more widespread Frantoio, Pendolino, Leccino and Leccio del Corno. “I produce two blends, of which the Veneto Valpolicella PDO is my flagship,” said Vaccarella, as she explained that she combines 60 percent of local cultivars with the other ones in accordance with the product specification of the protected denomination of origin which requires that at least half of the extra virgin olive oil consists of native types. Monica Vaccarella during harvest “These two local varieties make the oil enjoyable, while the early harvest gives energy to it and allows the taste to expand with formidable bitterness and pungency,” our producer said while describing her extra virgin olive oil with aromas of white fruit, grass and basil. The olive trees were planted by her father Angelo 27 years ago, and she started to manage the olive grove in 2010. They carry out a so-called balanced pruning which helps to avoid biological alternation of high and low yields. “It is a painstaking and draining work which takes two months since we operate on the smallest branches,” Vaccarella revealed. However, the flat landscape facilitates harvest and in one day they can collect 800 to 1,000 kilograms (1,764-2,205 pounds) of olives. “We crush them within 6 hours, that is the only way to get the most out of the fruits and reach such a low level of acidity,” she remarked. “I am glad when people open the bottle of my oil and get excited.”
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History of Schleswig-Holstein The history of Schleswig-Holstein consists of the corpus of facts since the pre-history times until the modern establishing of the Schleswig-Holstein state. Early history The Jutland Peninsula is a peninsula in Northern Europe with modern-day Schleswig-Holstein at its base. Schleswig is also called Southern Jutland (Sønderjylland). The old Scandinavian sagas, perhaps dating back to the times of the Angles and Jutes give the impression that Jutland has been divided into a northern and a southern part with the border running along the Kongeå River. Taking into account both archeological findings and Roman sources, however, one could conclude that the Jutes inhabited both the Kongeå region and the more northern part of the peninsula, while the Angles lived approximately where the towns Haithabu and Schleswig later would emerge (originally centered in the southeast of Schleswig in Angeln), the Saxons (earlier known apparently as the Reudingi) originally centered in Western Holstein (known historically as "Northalbingia") and Slavic Wagrians, part of the Obodrites (Abodrites) in Eastern Holstein. The Danes settled in the early Viking ages in Northern and Central Schleswig and the Northern Frisians after approximately the year 900 in Western Schleswig. The pattern of populated and unpopulated areas was relatively constant through Bronze Age and Iron Age. After the Dark Ages migrations After many Angles emigrated to the British Islands in the 5th century, the land of the Angles came in closer contact with the Danish islands — plausibly by partly immigration/occupation by the Danes. Later also the contacts increased between the Danes and the people on the northern half of the Jutish peninsula. Judging by today's placenames, then the southern linguistic border of the Danish language seems to have been (starting at the west) up the Treene river, along the Danevirke (also known as Danewerk), then cutting across from the Schlei estuary to Eckernförde, and leaving the Schwansen peninsula, while the West coast of Schleswig had been the area of the Frisian language. After the Slavic migrations, the eastern area of modern Holstein was inhabited by Slavic Wagrians (Vagri) a subgroup of the Obotrites (Obotritae). Nordalbingia and Wagria in 8th century-9th century Apart from northern Holstein and Schleswig inhabited by Danes there were Nordalbingia and Wagria in respectively, Western and Eastern Holstein. Nordalbingia (German: Nordalbingien, i.e. land north of the Elbe river) was one of the four administrative regions of the medieval Duchy of Saxony, the others being Angria, Eastphalia, and Westphalia. Nordalbingia consisted of four districts: Dithmarschen, Holstein, Stormarn (north of the Elbe) and Hadeln (south of the Elbe). The Wagri, Wagiri, or Wagrians were a tribe of Polabian Slavs inhabiting Wagria, or eastern Holstein in northern Germany, from the ninth to twelfth centuries. They were a constituent tribe of the Obodrite confederacy. Conquest of Nordalbingia by Obodrites and Franks In the Battle of Bornhöved (798) (German: Schlacht bei Bornhöved) on the field of Sventanafeld (Sventanapolje, Slavonic for "sacred field") near the village of Bornhöved near Neumünster in 798 the Obodrites, led by Drożko, allied with the Franks, defeated the Nordalbingian Saxons. Following defeat of Norgalbingians in the Battle of Bornhöved by combined forces of the Obodrites and the Franks, where the Saxons lost 4,000 people, 10,000 Saxon families were deported to other areas of the empire. Areas north of Elbe (Wagria) were given to the Obodrites, while Hadeln was directly incorporated. However, the Obodrites soon were invaded by Danes and only the intervention of Charlemagne pushed the Danes out of Eider river. Danish, Saxon, Franks struggle for control of Holstein As Charlemagne extended his realm in the late 8th century, he met a united Danish army which successfully defended Danevirke, a fortified defensive barrier across the south of the territory west of the Schlei. A border was established at the Eider River in 811. This strength was enabled by three factors: the fishing, the good soil giving good pasture and harvests in particular the tax and customs revenues from the market in Haithabu, where all trade between the Baltic Sea and Western Europe passed. The Danevirke was built immediately south of the road where boats or goods had to be hauled for approximately 5 kilometers between a Baltic Sea bay and the small river Rheider Au (Danish, Rejde Å) connected to the North Sea. There on the narrowest part of southern Jutland was established the important transit market (Haithabu, also known as Hedeby, near modern Haddeby), which was protected by the Danevirke fortification. Hedeby was located on the inlet Schlei opposite to what is now the City of Schleswig. The wealth of Schleswig, as reflected by impressive archeological finds on the site today, and the taxes from the Haithabu market, was enticing. A separate kingdom of Haithabu was established around year 900 by the Viking chieftain Olaf from Svealand. Olaf's son and successor Gnupa was however killed in battle against the Danish king, and his kingdom vanished. The southern border was then adjusted back and forth a few times. For instance, the Holy Roman Emperor Otto II occupied the region between the river Eider and the inlet Schlei in the years 974–983, called the March of Schleswig, and stimulating German colonisation. Later Haithabu was burned by Swedes, and first under the reign of King Sweyn Forkbeard (Svend Tveskæg) (986-1014) the situation was stabilised, although raids against Haithabu would be repeated. Haithabu was once again and ultimately destroyed by fire in 1066. As Adam of Bremen reported in 1076, the Eider River was the border between Denmark and the Saxon territories. From the time Danes came to Schleswig from today’s eastern part of Denmark and Germans colonised Schleswig migrating from Holstein, the country north of the Elbe had been the battleground of Danes and Germans, as well as certain Slavic people. Danish scholars point to the existence of Danish placenames north for Eider and Danevirke as evidence that at least the most of Schleswig was at one time Danish; German scholars claim it, on the other hand, as essentially "Germanic", due to the fact that Schleswig became an autonomous entity and a duchy (in the 13th century) since it has been populated and been dominated from the South. The Duchy of Schleswig, or Southern Jutland (Sønderjylland), had been a Danish fief, though having been more or less independent from the Kingdom of Denmark during the centuries, similarly to Holstein, that had been from the first a fief of the Holy Roman Empire, originating in the small area of Nordalbingia, in today western Holstein, inhabited then mostly by Saxons, but in 13th century expanded to the present Holstein, after winning local Danish overlord. Throughout the Middle Ages, Schleswig was a source of rivalry between Denmark and the nobility of the duchy of Holstein within the Holy Roman Empire. The Danish position can be exemplified with an inscription on a stone in the walls of the town of Rendsburg (Danish: Rendsborg) located on the border between Schleswig and Holstein: Eidora Terminus Imperii Romani ("The River Eider is the Border of the Holy Roman Empire"). A number of Holsatian nobles sought to challenge this. Danish, Saxon, Angles struggle for control of Schleswig The area of Schleswig (Southern Jutland) was first inhabited by the mingled West Germanic tribes Cimbri, Angles and Jutes, later also by the North Germanic Danes and West Germanic Frisians. Holstein was inhabited mainly by the West Germanic Saxons, aside Wends (such as Obotrites) and other Slavic peoples in the East. The Saxons were the last of their nation to submit to Charlemagne (804), who put their country under Frankish counts, the limits of the Empire being pushed in 810 as far as the Schlei in Schleswig. In 811 the river Eider was declared as borderline between the Frankish Empire and Denmark. Then began the secular struggle between the Danish kings and the rulers of the Holy Roman Empire, and in 934 the German king Henry I established the March of Schleswig (Limes Danarum) between the Eider and the Schlei as an outpost of the Empire against the Danes. South of this raged the contest between the Empire and Slavs. The Slavs, conquered and Christianised, rose in revolt in 983, after the death of the emperor Otto II, and for a while reverted to paganism and independence. The Saxon dukes, however, continued to rule central Holstein, and when Lothair of Supplinburg became duke of Saxony (1106), on the extinction of the Billung line, he enfeoffed Lord Adolphus of Schauenburg with the County of Holstein, as a Saxon subfief, becoming Adolphus I, Count of Holstein with the Saxon, later Lower Saxon dukes as liege lords. 12th century The Earl (jarl) Knud Lavard (Eng. Canute Lavard)(killed 1131), son of a Danish king, became Duke of Jutland or Southern Jutland. His son ascended the Danish throne, and the main branch continued as Kings, and a cadet branch descended from Abel of Denmark received Southern Jutland (Slesvig) as their appanage. During the rule of the dynasty Southern Jutland functioned as the Duchy which provided for the expenses of Royal Princes. Rivalry of royal succession and particularly the tendency of autonomy led to long-lasting feuds between the Dukes of Schleswig and the Kings of Denmark 1253–1325. At that time, the Holy Roman Empire expanded northwards and had set up the Schauenburg family as counts of Holstein, under German suzerainty, first located in Nordalbingia, the Saxon part of the region, in what now is western Holstein. Knud Lavard had also gained awhile parts of Holstein, and thereby came in conflict with Count Adolphus I (Schauenburg) in the part of Holstein within the Empire, as they both were very keen on expanding their influence and pacifying the Wagrian tribe (see: Wends). Count Adolphus II, son of Adolphus I, succeeded and established the County of Holstein (1143) with about the borders it has had since then. Holstein was Christianised, many of the Wagrians were killed and the land was inhabited by settlers from Westphalia, Friesland and Holland. Soon the Holsatian towns, such as Lübeck and Hamburg, became serious trade competitors on the Baltic Sea. 13th century Adolphus II (1128–1164), succeeded in re-conquering the Slavonic Wagri and founded the city and see of Lübeck to hold them in check. Adolphus III (d. 1225), his successor, received Dithmarschen in fee from the emperor Frederick I, but in 1203 the fortunes of war compelled him to surrender Holstein to Valdemar II of Denmark who mandated Albert of Orlamünde, the cession being confirmed in a Golden bull by the emperor Frederick II in 1214 and the pope in 1217, thus provoking the nobles in Holstein. Valdemar appointed his lieutenant in Holstein. In 1223, King Valdemar and his eldest son were abducted by count Henry I, Count of Schwerin (also known as Heinrich der Schwarze), and held captive in Castle Dannenberg for several years. Count Henry demanded that Valdemar should surrender the land conquered in Holstein 20 years ago and become a vassal of the Holy Roman Emperor who in fact tried to intervene and arrange the release of Valdemar. Danish envoys refused these terms and Denmark declared war. The war ended in defeat of the troops under the command of Albert of Orlamünde at Mölln in 1225, and Valdemar was forced to surrender his conquests as the price of his own release and take an oath not to seek revenge. Valdemar was released from captivity in 1226 and appealed to Pope Honorius III to have his oath repealed, a request the Pope granted. In 1226, Valdemar attacked the nobles of Holstein, and initially, had success. On July 22, 1227 the two armies clashed at Bornhöved in Holstein in the second Battle of Bornhöved. The battle ended in a decisive victory for Adolphus IV of Holstein. During the battle the troops from Dithmarschen abandoned the Danish army and joined Adolphus' army. In the following peace, Valdemar II relinquished his conquests in Holstein for good and Holstein was permanently secured to the house of Schauenburg. King Valdemar II, who had retained the former imperial March north of the Eider, in 1232 erected Schleswig as a duchy for his second son, Abel. Holstein on the other hand, after the death of Adolphus IV in 1261, was split up into several countships by his sons and again by his grandsons (1290): the lines of Holstein-Kiel (1261–1390), Holstein-Pinneberg and Schaumburg (1290–1640) south of the Elbe, Holstein-Plön (1290–1350), Holstein-Rendsburg (1290–1459), and at times also Holstein-Itzehoe (1261–1290) and Holstein-Segeberg (1273–1315), and again 1397–1403), all named after the comital residential cities. 14th century The connection between Schleswig and Holstein became closer during the 14th century as the ruling class and accompanying colonists intensely populated the Duchy Schleswig. Local lords of Schleswig had already early paid attention to keep Schleswig independent from the Kingdom of Denmark and to strengthen ties to Holstein within the Holy Roman Empire. This tradition of autonomy showed itself in future politics for centuries to come. The rivalry, sometimes leading into war between the kings of Denmark and the Abelian dukes of Schleswig was expensive, and Denmark had to finance it through extensive loans. The Dukes of Schleswig were allied with the Counts of Holstein, who happened to become the main creditors of the Danish Crown, too, in the reign of the utterly incompetent king Christopher II of Denmark. On the death of King Valdemar's descendant Eric VI of Denmark in 1319, Christopher II of Denmark attempted to seize the Duchy of Schleswig, the heir of which Duke Valdemar V (as of 1325) was a minor; but Valdemar's guardian and uncle, Gerhard III, Count of Holstein-Rendsburg (1304–1340), surnamed the Great and a notable warrior, drove back the Danes and, Christopher having been expelled, succeeded in procuring the election of Duke Valdemar to the Danish throne (as Valdemar III as of 1326), while Gerhard himself obtained the Duchy of Schleswig. King Valdemar III was regarded as a usurper by most Danish nobles as he had been forced by the Schleswig-Holstein nobility to sign the Constitutio Valdemaria (June 7, 1326) promising that The Duchy of Schleswig and the Kingdom of Denmark must never be united under the same ruler. Schleswig was consequently granted to Count Gerhard, being the leader of one of the three lines of the Schauenburg dynasty. The constitution can be seen as a first precursor to the Treaty of Ribe and similarly laying down the principle of separation between the Duchy of Schleswig and the Kingdom of Denmark and indeed uniting Schleswig and Holstein for the first time, though in personal union. In 1330, Christopher II was restored to his throne and Valdemar III of Denmark abdicated his untenable kingship and returned to his former position as Duke of Schleswig which he held as Valdemar V of Schleswig. As compensation, Gerhard was awarded the island of Funen as a fief instead. In 1331 war broke out between Gerhard and King Christopher II, ending in Danish defeat. The peace terms were extremely harsh. King Christopher was only left in effective control of the small island of Langeland and faced the impossible task of raising 100,000 silver marks to redeem his country. Denmark had effectively been dissolved and was left without a king between 1332 and 1340. Gerhard, however, was assassinated in 1340 by a Dane. In 1340, King Valdemar IV of Denmark began his more than twenty-year-long quest to reclaim his kingdom. While succeeding in regaining control of Zealand, Funen, Jutland, and Scania he, however, failed to obtain control of Schleswig, and its ducal line managed to continue its virtual independence. This was the time when almost all of Denmark came under the supremacy of the Counts of Holstein, who possessed different parts of Denmark as pawns for their credits. King Valdemar IV (Atterdag) started to regain the kingdom part by part, and married his rival's sister Hedvig of Schleswig, the only daughter of Eric II, Duke of Schleswig. Duke Valdemar V of Slesvig's son, Henry, was in 1364 nominally entfeoffed with the Duchy, although he never reached to regain more than the northernmost parts as he couldn't raise the necessary funds to repay the loans. With him, the Abelian line became extinct. The true holder of the lands was the count of Holstein-Rendsburg, but Henry's feudal heirs were his first cousin Margaret of Denmark, queen of several Scandinavian realms, and Albert of Mecklenburg, son of Margaret's elder sister Ingeborg of Denmark. In 1372, Valdemar Atterdag turned his attention to Schleswig and conquered Gram in 1372 and Flensburg in 1373. Southern parts of Schleswig had been mortgaged to several German nobles by Duke Henry I, Duke of Schleswig (d. 1375, a son of the former king Valdemar III of Denmark), the last duke of that line. The childless, elderly Henry transferred his rights to his kinsman and brother-in-law King Valdemar IV in 1373. The ethnically German nobles, however, refused to allow the king to repay the mortgage and redeem the area in question. In 1374, Valdemar bought large tracts of land in the province and was on the verge of starting a campaign to conquer the rest when he died on October 24, 1374 and shortly hereon Duke Henry I died in 1375. It was then when the male lines both in the kingdom and the duchy became extinct, that the counts of Holstein-Rendsburg seized on Schleswig, assuming at the same time the style of lords of Jutland. The nobles quickly took action and managed to regain more control of the Duchy which they emphasised to be independent of the Danish Crown. In 1386, Queen Margaret I of Denmark, younger daughter of Valdemar IV of Denmark and Helvig of Schleswig, granted Schleswig as a hereditary fief under the Danish crown to Count Gerhard VI of Holstein-Rendsburg, grandson of Gerhard III, provided that he swore allegiance to her son King Oluf, although Schleswig actually still was held autonomously by the Count of Holstein-Rendsburg. Gerhard - after the extinction of the lines of Holstein-Plön (1350) and Holstein-Kiel (1390) – finally obtained also Holstein-Segeberg in 1403, ruling thus all of Holstein except of Holstein-Pinneberg with the small Schauenburg territories in Lower Saxony. With this merging of power begins the history of the union of Schleswig and Holstein. 15th century Gerhard VI died in 1404, and soon afterwards war broke out between his sons and Eric of Pomerania, Margaret's successor on the throne of Denmark, who claimed South Jutland as an integral part of the Danish monarchy, a claim formally recognised by the emperor Sigismund in 1424, it was not till 1440 that the struggle ended with the investiture of Count Adolphus VIII, Gerhard VI's son, with the hereditary duchy of Schleswig by Christopher III of Denmark. In 1409, King Eric VII of Denmark (Eric of Pomerania) forced the German nobles to surrender Flensburg to him. War broke out in 1410, and Eric conquered Als and Ærø. In 1411, the nobles retook Flensburg, but in 1412 both sides agreed to a count of Mecklenburg to settle the dispute (Danish history claims his name was Ulrich of Mecklenburg). He awarded the city to Denmark, and Margaret I of Denmark took possession of the city. In Flensburg she was struck by the plague and died shortly after. A new mediation attempt was undertaken in 1416 by the Hanseatic League. Both sides accepted, and Denmark pledged the city of Schleswig as security, and the Holsteiners the stronghold of Tönning. The mediation was unsuccessful. In 1421, the Holsteiners succeeded in regaining Haderslev, Schleswig and Tønder. In 1422, Duke Henry X of Silesia-Sagan (also known as duke Heinrich Rumpold), envoy of the Holy Roman Emperor, was recognised by both sides as arbitrator. He died, however, on January 18, 1423 before reaching a settlement. His master, Emperor Sigismund now wished to settle the issue, a decision strongly opposed by the nobles of Holstein. In 1424, Emperor Sigismund ruled, based on the fact that the people of Schleswig spoke Danish, followed Danish customs and considered themselves to be Danes, that the territory rightfully belonged to the King of Denmark. Henry IV, Count of Holstein-Rendsburg, protested and refused to follow the verdict. In 1425 war broke out again. In 1431, a group of pro-German burghers opened the gates of Flensburg and an army of German nobles marched in. In 1432 peace was settled, and Eric recognised the conquests made by the German nobles. In 1439, the new Danish king Christopher III (also known as Christopher of Bavaria) bought the loyalty of count Adolphus VIII of Holstein-Rendsburg by granting him the entire Duchy of Schleswig as a hereditary fief but under the Danish crown. On the death of Christopher eight years later, Adolphus' influence secured the election of his nephew Count Christian VII of Oldenburg to the vacant Danish throne. In 1448 Adolphus, as Adolphus I Duke of Slesvig and as Adolphus VIII Count of Holstein-Rendsburg, who himself was one of the closest heirs to Scandinavian monarchies, was influential enough to get his nephew Count Christiern (Christian VII) of Oldenburg elected King of Denmark. When the Adolphus had died in 1459 without issue the Schauenburg dynasty in Holstein-Rendsburg had thus became extinct. The Schauenburg counts of Holstein-Pinneberg had no claim to succession in Schleswig; their election in Holstein-Rendsburg would have separated Schleswig and Holstein-Rendsburg. The separation of Schleswig and Holstein would have meant economic ruin for many nobles of Holstein. Moreover, the Holsatian nobles, mostly of German ethnicity, failed to agree on which course to take. Therefore, it was easy for King Christian I of Denmark (son of Hedwig, the sister of the late duke-count Adolphus) to secure his election both as duke of Schleswig and count of Holstein-Rendsburg. In 1460, King Christian called the nobility to Ribe, and on March 2, 1460, the nobles agreed to elect him as successor of Count Adolphus VIII as the new count of Holstein-Rendsburg, in order to prevent the separation of the two provinces. King Christian I, though he had been forced to swear to the Constitutio Valdemariana, succeeded in asserting his claim to Schleswig in right of his mother, Adolphus' sister. On 5 March 1460 Christian granted a coronation charter (or Freiheitsbrief), issued first at Ribe (Treaty of Ribe, , ) and afterwards at Kiel, which also repeated that Schleswig and Holstein-Rendsburg must remain united "dat se bliven ewich tosamende ungedelt" (Middle Low German or Low Saxon, i.e. that they remain for ever together undivided). Christian's ascension in the County of Holstein-Rendsburg was the first succession in Holstein in female line. The Treaty of Ribe was a proclamation made by King Christian I of Denmark to a number of German nobles enabling himself to become count of Holstein-Rendsburg and regain the Danish duchy of Schleswig. Another clause gave the nobility the right to revolt should the king break the agreement (a usual feature of medieval coronation charters). Regarding Holstein-Rendsburg, the arrangement was pretty straightforward, the King of Denmark became in personal union count of Holstein-Rendsburg but was not allowed to annex the county, which was part of the Holy Roman Empire, to Denmark proper in real union. Regarding Schleswig the arrangement seems at first rather odd, since Schleswig was a fief under the Danish crown, thus making the Danish king his own vassal. However, the nobles saw this arrangement as a guarantee against too strong Danish domination and as a guarantee against a partition of Holstein between Danish nobles. The most important consequence of this agreement was the exclusion of Schleswig in subsequent Danish laws (although the medieval Danish Code of Jutland (in Danish: Jyske Lov) was maintained as the legal code of the duchy of Schleswig. Finally, in 1472 the emperor Frederick III confirmed Christian I's overlordship over Dithmarschen (by claim, conquered only in 1559). Frederick III elevated Christian as Count of Dithmarschen, Holstein-Rendsburg, and Stormarn to Duke of Holstein, thus elevating Holstein-Rendsburg, a Lower Saxon subfief to imperial immediacy. In Holstein-Pinneberg, however, the emperor remained only the indirect overlord with the Lower Saxon Duke John V being the immediate liege lord. In the following period of a hundred years, Schleswig and Holstein were many times divided between heirs. Instead of incorporating South Jutland with the Danish kingdom, however, he preferred to take advantage of the feeling of the estates in Schleswig and Holstein in favour of union to secure both provinces. An important development was the gradual introduction of German administrators in the duchy of Schleswig leading to a gradual Germanification of southern Schleswig. The Germanification did not catch wind, however, before the end of the eighteenth century. Schleswig-Holstein soon got a better educational system some centuries before Denmark proper and Norway. The German nobility in Schleswig and Holstein was already a numerous range of people, and education added plenty of people to administrative officials pool of the kings. In 16th and 17th centuries particularly, educated Schleswig-Holsteiners were recruited to government positions in Norway (where they supplanted indigenous lower Norwegian nobility from its public positions, being a cause of them developing more like odalbonde class than privileged) and also in Denmark, where very many government officials came from German stock (but the Danish nobility was not suppressed, they other immersed most successful of the newcomers into their ranks). This feature of Schleswig-Holstein being an utilised source of bureaucrats was a reason of Denmark's governmental half-Germanisation in the subsequent centuries before 19th-century romantics. Early modern age 16th and 17th centuries Gradual Germanification of southern Schleswig became more intense following the Protestant Reformation, promoted by Duke Christian III in the duchies after his ascension there in 1523 as co-ruling duke with his father King Frederick I. After Christian had succeeded to become also King of Denmark and Norway in 1534 and 1537, respectively, he enforced Lutheranism in all his realm in 1537 (see Reformation in Denmark-Norway and Holstein). The Duchy of Holstein adopted its first Lutheran Church Order in 1542 (written by Bugenhagen). The Counties of Holstein-Pinneberg and Schaumburg remained Catholic until 1559. With Lutheranism the High German liturgy was introduced in churches in Holstein and the southern half of Schleswig (although the vernacular of more than half of this area was Danish). Whereas at the west coast North Frisian prevailed, about the other half of the South Schleswigers used Low Saxon, which had developed from Middle Low German, as their mother tongue, also prevailing in Holstein. High German started superseding the Danish, Low Saxon and Frisian vernaculars in the area. After Christian III had consolidated his reign in Denmark and Norway against his adversaries there he concluded with his younger half-brothers, having come of age, to share with them in the rule of the duchies in 1544. Christian III, John II the Elder and Adolf partitioned the Duchies of Holstein (a fief of the Holy Roman Empire) and of Schleswig (a Danish fief) in an unusual way, following negotiations between the brothers and the Estates of the Realm of the duchies, which opposed a factual partition, referring to their indivisibility according to the Treaty of Ribe. The brothers determined their youngest brother Frederick for a career as Lutheran administrator of an ecclesiastical state within the Holy Roman Empire. So the revenues of the duchies, deriving from the rights of overlordship in the various towns and territories of Schleswig and Holstein, were divided in three equal shares by assigning the revenues of particular areas and landed estates, themselves remaining undivided, to each of the elder brothers, while other general revenues, such as taxes from towns and customs dues, were levied together but then shared among the elder brothers. The estates, whose revenues were assigned to the parties, made Holstein and Schleswig look like patchwork rags, technically inhibiting the emergence of separate new duchies, as intended by the estates of the duchies. The secular rule in the fiscally divided duchies thus became a condominium of the parties. As dukes of Holstein and Schleswig the three rulers bore the formal title of "Duke of Schleswig, Holstein, Dithmarschen and Stormarn". With the independent peasant republic of Dithmarschen only claimed. The House of Schauenburg (Schaumburg) continued its rule in the Counties of Holstein-Pinneberg and Schaumburg. Adolf, the third son of Frederick I and the second youngest half-brother of King Christian III, founded the dynastic branch called House of Holstein-Gottorp, which is a cadet branch of the then royal Danish House of Oldenburg. The dynastic name Holstein-Gottorp comes as convenient usage from the technically more correct Duke of Schleswig and Holstein at Gottorp, the residential palace. John II the Elder, Duke of Schleswig and Holstein at Haderslev, produced no issue, so no branch emerged from his side. The Danish monarchs and the Dukes of Schleswig and Holstein at Gottorp and Haderslev ruled both duchies together as to general government, however, collected their revenues in their separate estates. In 1559 through the Final Feud they conquered and subjected the peasant republic of Dithmarschen, partitioning it into three shares. Similar to the above-mentioned agreement Christian III's youngest son John the Younger gained for him and his heirs a share in Holstein's and Schleswig's revenues in 1564, seated in Sønderborg, comprising a third of the royal share, thus a ninth of Holstein and Schleswig in fiscal respect. John the Younger and his heirs, the House of Schleswig-Holstein-Sonderburg (Danish: Slesvig-Holsten-Sønderborg), however, had no share in the condominial rule, they were non-ruling only titular partitioned-off dukes. John the Younger‘s grandsons again partitioned this appanage, Ernest Günther (1609–1689), founding the line of Schleswig-Holstein-Sonderburg-Augustenburg (Danish: Slesvig-Holsten-Augustenborg), and Augustus Philip (1612–1675) that of Schleswig-Holstein-Sonderburg-Beck (known since 1825 as Holstein-Sonderburg-Glücksburg). However, these had no share in the condominial rule and were always mediatised under the King as Duke in Schleswig and Holstein, and no immediate prince under the Emperor as liege lord of Holstein, where they held estates around Plön. The share of John II the Elder, who died in 1580, was halved between Adolf and Frederick II, thus increasing again the royal share by a fiscal sixth of Holstein and Schleswig. As an effect the complicated fiscal division of both separate duchies, Holstein and Schleswig, with shares of each party scattered in both duchies, provided them with a condominial government binding both together, partially superseding their legally different affiliation as Holy Roman and Danish fiefs. In 1640 the Princes of Schauenburg were extinct in the male line and the County of Holstein-Pinneberg was merged into the royal share of the Duchy of Holstein. Neither the agnatic heirs of Schauenburg nor Holstein-Pinneberg's liege lord the Lower Saxon Duke Augustus could help it. During the 30-years' War the relations between Duke and King worsened. Finally in 1658, after the Danes had invaded Swedish Bremen-Verden, the Duke cooperated with the Swedes in their counter-attack which almost eradicated the Danish Kingdom. The peace treaties (Treaty of Taastrup and Treaty of Roskilde) stipulated that the Duke of Holstein-Gottorp no longer was a vassal of the Danish Crown in Schleswig. Frederick III, duke from 1616 to 1659, established the principle of primogeniture for his line, and the full sovereignty of his Schleswig dominions was secured to him by his son-in-law Charles X of Sweden by the convention of Copenhagen (May 12, 1658) and to his son Christian Albert (d. 1695) by the Treaty of Oliva, though it was not till after years of warfare that Denmark admitted the claim by the convention of Altona (June 30, 1689). Christian Albert's son Frederick IV (d. 1702) was again attacked by Denmark, but had a powerful champion in King Charles XII of Sweden, who secured his rights by the Treaty of Travendal in 1700. Frederick IV was killed at the Battle of Kliszów in 1702, and his brother Christian August acted as regent for his son Charles Frederick until 1718. In 1713 the regent broke the stipulated neutrality of the duchy in favour of Sweden and Frederick IV of Denmark seized the excuse to expel the duke by force of arms. Holstein was restored to him by the peace of Frederiksborg in 1720, but in the following year king Frederick IV was recognised as sole sovereign of Schleswig by the estates and by the partitioned-off dukes of the Augustenburg and Glücksburg lines. 18th century As Sweden in the 1713 Siege of Tönning had lost its influence on Holstein-Gottorp, Denmark could again subjugate the entire Slesvig to the Danish realm; Holstein-Gottorps lost their lands in Schleswig, but continued as independent Dukes in their portion of Holstein. This status was cemented in the Treaty of Frederiksborg in 1720, by which the prior royal and ducal regions of Schleswig were united under the king, while the Duke remained Duke of Holstein-Gottorp under the German Emperor. The frustrated duke sought support for the recovery of Schleswig in Russia and married into the Russian imperial family in 1725. Russian Empress Elizabeth died childless in 1762, and she appointed her nephew, Duke Charles Peter Ulrich of Holstein-Gottorp, to be her successor in Russia. When he ascended the throne as Tsar Peter III of Russia, Holstein-Gottorp came to be ruled in personal union by the Emperor of Russia, creating a conflict of territorial claims between Russia and Denmark. Peter III threatened war with Denmark for the recovery of his ancestral lands, but before any fighting could begin he was overthrown by his wife, who took control of Russia as Tsarina Catherine II. Empress Catherine reversed Russia's stance, withdrawing her husband's ultimatum and even entering an alliance with Denmark in 1765. In 1767 Catherine resigned Russia's claims in Schleswig-Holstein, in the name of her son (later Paul I of Russia), who confirmed this action on coming of age in 1773 with the Treaty of Tsarskoye Selo. Oldenburg and Delmenhorst, surrendered by the Danish king in compensation, were handed over to Frederick August, bishop of Lübeck, the second son of Christian August, who thus founded the younger line of the house of Gottorp. Schleswig and Holstein were thus once more united under the Danish king (Christian VII), who now received all Holstein, but that formally under the Empire. 19th century On the abolition of the Holy Roman Empire in 1806, Holstein was practically, though not formally, incorporated in Denmark. Under the administration of the Danish prime minister Count Bernstorff, himself from Schleswig, many reforms were carried out in the duchies, for example, abolition of torture and of serfdom; at the same time Danish laws and coinage were introduced, and Danish was made the official language for communication with Copenhagen. Since, however, the Danish court itself at the time was largely German in language and feeling, this produced no serious expressions of resentment. The settlement of 1806 was reversed, and while Schleswig remained as before, the duchies of Holstein and Lauenburg, the latter acquired in personal union by a territorial swap following the Congress of Vienna, were included in the new German Confederation. The opening up of the Schleswig-Holstein question thus became sooner or later inevitable. The Germans of Holstein, influenced by the new national enthusiasm evoked by the War of Liberation, resented more than ever the attempts of the government of Copenhagen to treat them as part of the Danish monarchy and, encouraged by the sympathy of the Germans in Schleswig, early tried to reassert in the interests of Germanism the old principle of the unity of the duchies. The political atmosphere, however, had changed at Copenhagen also; and their demands were met by the Danes with a nationalist temper as intractable as their own. Affairs were ripe for a crisis, which the threatened failure of the common male heirs to the kingdom and the duchies precipitated. The Duchy of Schleswig was originally an integrated part of Denmark, but was in medieval times established as a fief under the Kingdom of Denmark, with the same relation to the Danish Crown as for example Brandenburg or Bavaria had to the Holy Roman Emperor. Holstein had as a fief been part of the Holy Roman Empire, and was eventually established as a single united province. Schleswig and Holstein have at different times belonged in part or completely to either Denmark, the Holy Roman Empire, or been virtually independent of both nations. The exception is that Schleswig had never been part of the Holy Roman Empire or the German Confederation before the Second War of Schleswig in 1864. For many centuries, the King of Denmark was both a Danish Duke of Schleswig and a Duke of Holstein within the Holy Roman Empire. The short version is: Schleswig was either integrated in Denmark or a Danish fief, and Holstein was a Holy Roman Imperial fief. Since 1460 both were ruled by the Kings of Denmark with the Dukes of Holstein and Schleswig (since 1544). In 1721 all of Schleswig was united as a single Duchy under the King of Denmark, and the Great Powers of Europe confirmed in an international treaty that all future Kings of Denmark should automatically become Duke of Schleswig and Schleswig would consequently always follow the same line of succession as the one chosen in the Kingdom of Denmark. The duchy of Schleswig was legally a Danish fief and not part of the Holy Roman Empire or, after 1815, of the German Confederation (German: Deutscher Bund, Danish: Tysk Forbund), but the duchy of Holstein was a Holy Roman fief and a state of both the Empire and later the German Confederation of 1815–1866. It was one of the oddities of both the Holy Roman Empire and of the German Confederation that foreign heads of state could be and often were also members of the constitutional organs of the Empire and the Confederation if they held a territory that was part of the Empire or the Confederation. The King of Denmark had a seat in the organs of the German Confederation because he was also Duke of Holstein and Duke of Lauenburg. Schleswig-Holstein Question The Schleswig-Holstein Question was the name given to the whole complex of diplomatic and other issues arising in the 19th century out of the relations of the two duchies, Schleswig and Holstein, to the Danish crown on one side and the German Confederation on the other. In 1806–1815 the government of Denmark had claimed Schleswig and Holstein to be parts of the monarchy of Denmark, which was not popular among the German population in Schleswig-Holstein, who had traditionally the majority in Holstein and had gradually increased its dominance in Schleswig as well. However, this development sparked a German national awakening after the Napoleonic wars and led to a strong popular movement in Holstein and Southern Schleswig for unification of both with a new Germany (see German unification), turning out to be Prussian-dominated, as it was. A controversy in the 19th century raged round the ancient indissoluble union of the two duchies, and the inferences to be drawn from it; the Danish National Liberals claimed Schleswig as an integral part of the Danish kingdom; Germans claimed, besides Holstein, being a member state of the German Confederation, also Schleswig. The history of the relations of Schleswig and Holstein thus became of importance in the practical political question. The childlessness of King Frederick VII of Denmark worked in favour of the movement for the German unification, as did the ancient Treaty of Ribe, which stipulated that the two duchies must never be separated. A counter-movement developed among the Danish population in northern Schleswig and (from 1838) in Denmark, where the Liberals insisted that Schleswig as a fief had belonged to Denmark for centuries and that the Eider River, the historic border between Schleswig and Holstein, should mark the frontier between Denmark and the German Confederation or a new eventually united Germany. The Danish nationalists thus aspired to incorporate Schleswig into Denmark, in the process separating it from Holstein. The movement for the German unity conversely sought to confirm Schleswig's association with Holstein, in the process detaching Schleswig from Denmark and bringing it into the German Confederation. The Danish succession When Christian VIII succeeded his first cousin Frederick VI in 1839 the elder male line of the house of Oldenburg was obviously on the point of extinction, the king's only son and heir having no children. Ever since 1834, when joint succession, consultative estates had been re-established for the duchies, the question of the succession had been debated in this assembly. To German opinion the solution seemed clear enough. The crown of Denmark could be inherited by female heirs (see Louise of Hesse); in the duchy of Holstein the Salic law had never been repealed and, in the event of a failure of male heirs to Christian VIII, the succession would pass to the Dukes of Augustenburg — although this was debatable as the dynasty itself had received Holstein by Christian I of Denmark being the son of the sister of the last Schauenburg, Adolphus VIII. Danish opinion, on the other hand, clamoured for a royal pronouncement proclaiming the principle of the indivisibility of the monarchy and its transmission intact to a single heir, in accordance with the royal law. To this Christian VIII yielded so far as to issue in 1846 letters patent declaring that the royal law in the matter of the succession was in full force so far as Schleswig was concerned, in accordance with the letters patent of August 22, 1721, the oath of fidelity of September 3, 1721, the guarantees given by France and Great Britain in the same year and the treaties of 1767 and 1773 with Russia. As to Holstein, he stated that certain circumstances prevented him from giving, in regard to some parts of the duchy, so clear a decision as in the case of Schleswig. The principle of the independence of Schleswig and of its union with Holstein were expressly reaffirmed. An appeal against this by the estates of Holstein to the German Federal Assembly received no attention. On January 28, Christian VIII issued a rescript proclaiming a new constitution which, while preserving the autonomy of the different parts of the country, incorporated them for common purposes in a single organisation. The estates of the duchies replied by demanding the incorporation of Schleswig-Holstein, as a single constitutional state, in the German Confederation. First Schleswig War In March 1848 these differences led to an open uprising by the German-minded Estate assemblies in the duchies in support of independence from Denmark and of close association with the German Confederation. The military intervention of Prussia helped the uprising: the Prussian army drove Denmark's troops from Schleswig and Holstein. Frederick VII, who had succeeded his father at the end of January, declared (March 4) that he had no right to deal in this way with Schleswig, and, yielding to the importunity of the Eider-Danish party, withdrew the rescript of January (April 4) and announced to the people of Schleswig (March 27) the promulgation of a liberal constitution under which the duchy, while preserving its local autonomy, would become an integral part of Denmark. A Liberal constitution for Holstein was not seriously considered in Copenhagen since it was a well-known fact that the German political elite of Holstein was far more conservative than the one in Copenhagen. This proved to be true, as the politicians of Holstein demanded that the Constitution of Denmark be scrapped, not only in Schleswig but also in Denmark, as well as demanding that Schleswig immediately follow Holstein and become a member of the German Confederation and eventually a part of the new united Germany. The rebels established a provisional government at Kiel; and the duke of Augustenburg had hurried to Berlin to secure the assistance of Prussia in asserting around 1848 his rights. This was at the very crisis of the revolution in Berlin, and the Prussian government saw in the proposed intervention in Denmark in a popular cause an excellent opportunity for restoring its damaged prestige. Prussian troops were accordingly marched into Holstein. This war between Denmark on the one hand and the two duchies and Prussia on the other lasted three years (1848–1850) and only ended when the Great Powers pressured Prussia into accepting the London Convention of 1852. Under the terms of this peace agreement, the German Confederation returned the duchies of Schleswig and Holstein to Denmark. In an agreement with Prussia under the London Protocol of 1852, the Danish government in return undertook not to tie Schleswig more closely to Denmark than to the duchy of Holstein. In 1848 King Frederick VII of Denmark declared that he would grant Denmark a Liberal Constitution and the immediate goal for the Danish national movement was to secure that this Constitution would not only give rights to all Danes, that is, not only to the Kingdom of Denmark, but also to Danes (and Germans) living in Schleswig. Furthermore, they demanded the protection of the Danish language in Schleswig since the dominating language in almost a quarter of Schleswig had changed from Danish to German since the beginning of the nineteenth century. Nationalist circles in Denmark advocated Danification of Schleswig (but not of Holstein) as Danish national culture had risen much in past decades. On April 12, 1848 the federal assembly recognised the provisional government of Schleswig and commissioned Prussia to enforce its decrees, General Wrangel was ordered to occupy Schleswig also. The new provisional government accounted for the respect of the two major languages, neglecting Frisian, in Schleswig and appointed two Lutheran general superintendents one each for parishes of Danish and of German language (Johannes Andreas Rehhoff and Nicolaus Johann Ernst Nielsen, respectively). But the German movement and Prussia had reckoned without the European powers, which were united in opposing any dismemberment of Denmark. Even Austria, like Holstein a member state of the German Confederation, refused to assist in enforcing the German view. Swedish troops landed to assist the Danes; Nicholas I of Russia, speaking with authority as Head of the elder Gottorp line, pointed out to King Frederick William IV the risks of a collision; Great Britain, though the Danes rejected her mediation, threatened to send her fleet to assist in preserving the status quo. Frederick William now ordered Wrangel to withdraw his troops from the duchies. The general refused to obey, pleading that he was under the command not of the king of Prussia but of the regent of the German Confederation, Archduke John of Austria, and proposed that, at least, any treaty concluded should be presented for ratification to the Frankfurt Parliament. This the Danes refused; and negotiations were broken off. Prussia was now confronted on one side by the German unification movement urging her clamorously to action, on the other by the European powers threatening with one voice dire consequences should she persist. On August 26, 1848, after painful hesitation, Frederick William chose what seemed the lesser of two evils, and Prussia signed at Malmö a convention which yielded practically all the Danish demands. The Holstein estates appealed to the Frankfurt Parliament, which hotly took up their cause; but it was soon clear that the provisional government in Frankfurt of the to-be-unified Germany had no means of enforcing its views, and in the end the convention was ratified at Frankfurt. The convention was only in the nature of a truce establishing a temporary modus vivendi, and the main issues, left unsettled, continued to be hotly debated. At a conference held in London in October, Denmark suggested an arrangement on the basis of a separation of Schleswig from Holstein, which was about to become a member of the eventually united Germany, Schleswig to have a separate constitution under the Danish crown. This was supported by Great Britain and Russia. On January 27, 1849 it was accepted by Prussia and the German Confederation. The negotiations broke down, however, on the refusal of Denmark to yield the principle of the indissoluble union with the Danish crown. On February 23 the truce was at an end, and on April 3, the war was renewed. The principles which Prussia was commissioned to enforce as the mandatory of the German Confederation were: that they were independent states that their union was indissoluble that they were hereditary only in the male line At this point the tsar intervened in favour of peace; and Prussia, conscious of her restored strength and weary of the intractable temper of the provisional Frankfurt government, determined to take matters into her own hands. On July 10, 1849 another truce was signed. Schleswig, until the peace, was to be administered separately, under a mixed commission. Holstein was to be governed by a vicegerent of the German Confederation – an arrangement equally offensive to German and Danish sentiment. A settlement seemed as far off as ever. The Danes of Schleswig still clamoured for the principle of succession in the female line and union with Denmark, the Germans for that of succession in the male line and union with Holstein. In 1849 the Constitution of Denmark was adopted. This complicated matters further, as many Danes wished for the new democratic constitution to apply for all Danes, including in the Danes in Schleswig. The constitutions of Holstein and Schleswig were dominated by the Estates system, giving more power to the most affluent members of society, with the result that both Schleswig and Holstein were politically dominated by a predominantly German class of landowners. Thus, two systems of government co-existed within the same state: democracy in Denmark, and pre-modern estates system in Schleswig and Holstein. The three units were governed by one cabinet, consisting of liberal ministers of Denmark who urged for economical and social reforms, and conservative ministers of the Holstein nobility who opposed political reform. This caused a deadlock for practical lawmaking. Moreover, Danish opponents of this so-called Unitary State (Helstaten) feared that Holstein's presence in the government and, at the same time, membership in the German Confederation would lead to increased German interference with Schleswig, or even into purely Danish affairs. In Copenhagen, the Palace and most of the administration supported a strict adherence to the status quo. Same applied to foreign powers such as Great Britain, France and Russia, who would not accept a weakened Denmark in favour of the German states, nor acquisition of Holstein (with its important naval harbour of Kiel and control of the entrance to the Baltic) by Prussia. In April 1850, in utter weariness Prussia proposed a definitive peace on the basis of the status quo ante bellum and the postponement of all questions as to mutual rights. To Palmerston the basis seemed meaningless, the proposed settlement to settle nothing. The emperor Nicholas, openly disgusted with Frederick William's weak-kneed truckling to the Revolution, again intervened. To him the duke of Augustenburg was a rebel; Russia had guaranteed Schleswig to the Danish crown by the treaties of 1767 and 1773; as for Holstein, if the king of Denmark was unable to deal with the rebels there, he himself would intervene as he had done in Hungary. The threat was reinforced by the menace of the European situation. Austria and Prussia were on the verge of war, The sole hope of preventing Russia from throwing her sword into the scale of Austria lay in settling the Schleswig-Holstein question as Russia desired. Frederick William's only alternative, an alliance with Louis Napoleon, who already dreamed of acquiring the Rhine frontier for France at the price of his aid in establishing German sea-power by the cession of the duchies, was abhorrent to him. After the First Schleswig War A peace treaty was signed between Prussia and Denmark on July 2, 1850. Both parties reserved all their antecedent rights. Denmark was satisfied, since the treaty empowered the King to restore his authority in Holstein as Duke with or without the consent of the German Confederation. Danish troops now marched in to coerce the refractory duchies; but while the fighting went on negotiations among the powers continued, and on August 2, 1850 Great Britain, France, Russia and Norway-Sweden signed a protocol, to which Austria subsequently adhered, approving the principle of restoring the integrity of the Danish monarchy. The provisional Schleswig government was deposed, as were the Lutheran general superintendents, who were even exiled from the Oldenburg-ruled monarchies in 1850. Their position remained vacant with Superintendent Christoph Carl Julius Asschenfeldt officiating per pro. The Copenhagen government, which in May 1851 made an abortive attempt to come to an understanding with the inhabitants of the duchies by convening an assembly of notables at Flensburg, issued on December 6, 1851 a project for the future organisation of the monarchy on the basis of the equality of its constituent states, with a common ministry; and on January 28, 1852 a royal letter announced the institution of a unitary state which, while maintaining the fundamental constitution of Denmark, would increase the parliamentary powers of the estates of the two duchies. This proclamation was approved by Prussia and Austria, and by the German Federal Assembly insofar as it affected Holstein and Lauenburg. The question of the succession was the next approached. Only the question of the Augustenburg succession made an agreement between the powers impossible, and on March 31, 1852 the duke of Augustenburg resigned his claim in return for a money payment. Further adjustments followed. Another factor which doomed Danish interests, was that not only was the power of German culture rising, but so were conflicts with German States in the south, namely Prussia and Austria. Schleswig and Holstein would, of course and inevitably, become the subject of a territorial dispute involving military encounters among the three states, Denmark, Prussia and Austria. Danish government found itself nervous as it became expected that Frederik VII would leave no son, and that upon his death, under Salic law, the possible Crown Princess would have no actual legal right to Schleswig and Holstein (of course that was debatable, as the dynasty itself had received Holstein by Christian I being son of the sister of last Schauenburg count of Holstein, but Salic Law was convenient to German nationalists in this case, furthermore Schleswig was a fief to the kings of Denmark with the Danish Kings Law, Kongeloven). Ethnic-Danish citizens of Schleswig (South Jutland) panicked over the possibility of being separated from their mother country, agitated against the German element, and demanded that Denmark declare Schleswig an integral part of Denmark, which outraged German nationalists. Holstein was part of the territory of the German Confederation, with which an annexation of whole Schleswig and Holstein to Denmark would have been incompatible. This gave a good pretext to Prussia to engage in war with Denmark in order to seize Schleswig and Holstein for itself, both by pleasing nationalists by 'liberating' Germans from Danish rule, and by implementing the law of the German Confederation. After the renunciation by the emperor of Russia and others of their eventual rights, Charlotte, Landgravine of Hesse, sister of Christian VIII, and her son Prince Frederick transferred their rights to the latter's sister Louise, who in her turn transferred them to her husband Prince Christian of Glücksburg. On May 8, 1852, this arrangement received international sanction by the protocol signed in London by the five great powers and Norway and Sweden. On July 31, 1853, Frederick VII of Denmark gave his assent to a law settling the crown on Prince Christian, prince of Denmark, and his male heirs. The protocol of London, while consecrating the principle of the integrity of Denmark, stipulated that the rights of the German Confederation in Holstein and Lauenburg should remain unaffected. It was, in fact, a compromise, and left the fundamental issues unsettled. The German Federal Assembly had not been represented in London, and the terms of the protocol were regarded in German states as a humiliation. As for the Danes, they were far from being satisfied with the settlement, which they approved only insofar as it gave them a basis for a more vigorous prosecution of their unionist schemes. On February 15 and June 11, 1854 Frederick VII, after consulting the estates, promulgated special constitutions for Schleswig and Holstein respectively, under which the provincial assemblies received certain very limited powers. On July 26, 1854 he published a common Danish constitution for the whole monarchy; it was little more unitary than a veiled absolutism. In 1854 the Lutheran church bodies of Schleswig and Holstein, until then led by general superintendents, until 1640 titled general provosts, were converted into Lutheran dioceses called Stift Schleswig (Danish: Slesvig Stift) and Stift Holstein (Danish: Holsten Stift), each presided by a Lutheran bishop. Ulrich Sechmann Boesen became Bishop for Schleswig (as of 1854), and Wilhelm Heinrich Koopmann was appointed Bishop for Holstein (offic. 1855–1871). On October 2, 1855 the common Danish constitution was superseded by a parliamentary constitution of a modified type. The legality of this constitution was disputed by the two German great powers, on the ground that the estates of the duchies had not been consulted as promised in the royal letter of December 6, 1851. On February 11, 1858 the federal assembly of the German Confederation refused to admit its validity so far as Holstein and Lauenburg were concerned. In the early 1860s the "Schleswig-Holstein Question" once more became the subject of lively international debate, but with the difference that support for the Danish position was in decline. The Crimean War had crippled the power of Russia, and France was prepared to renounce support for Danish interests in the duchies in exchange for compensations to herself elsewhere. Queen Victoria and her consort Prince Albert had sympathy for the German position, but it was tempered by British ministers who saw the growth of German sea-power in the Baltic Sea as a danger to British naval supremacy, and consequently Great Britain sided with the Danes. To that was added a grievance about tolls charged on shipping passing through the Danish Straits to pass between the Baltic Sea and the North Sea. To avoid that expense, Prussia planned the Kiel Canal, which could not be built as long as Denmark ruled Holstein. The secessionist movement continued throughout the 1850s and 1860s, as proponents of German unification increasingly expressed the wish to include two Danish-ruled provinces Holstein and Schleswig in an eventual 'Greater Germany'. Holstein was completely German, while the situation in Schleswig was complex. It was linguistically mixed between German, Danish and North Frisian. The population was predominantly of Danish ethnicity, but many of them had switched to the German language since the 17th century. German culture dominated in clergy and nobility, whereas Danish had a lower social status. For centuries, when the rule of the King was absolute, these conditions had created few tensions. When ideas of democracy spread and national currents emerged from ca. 1820, some professed sympathy with German, others with Danish nationality. The medieval Treaty of Ribe had proclaimed that Schleswig and Holstein were indivisible, however in another context. As the events of 1863 threatened to politically divide the two duchies, Prussia was handed a good pretext to engage in war with Denmark to seize Schleswig-Holstein for itself, both by pleasing nationalists in "liberating" Germans from Danish rule, and by implementing the law of the German Confederation. On July 29, 1853, In response to the renewed Danish claim to Schleswig as integral Danish territory, the German Federal Assembly (instructed by Bismarck) threatened German federal intervention. On November 6, 1853, Frederick VII issued a proclamation abolishing the Danish constitution so far as it affected Holstein and Lauenburg, while keeping it for Denmark and Schleswig. Even this concession violated the principle of the indissoluble union of the duchies, but the German Federal Assembly, fully occupied at home, determined to refrain from further action till the Danish parliament should make another effort to pass a law or budget affecting the whole kingdom without consulting the estates of the duchies. In July 1860 this happened, and in the spring of 1861 the estates were once more at open odds with the Danish government. The German Federal Assembly now prepared for armed intervention; but it was in no condition to carry out its threats, and Denmark decided, on the advice of Great Britain, to ignore it and open negotiations directly with Prussia and Austria as independent powers. These demanded the restoration of the union between the duchies, a question beyond the competence of the Confederation. Denmark replied with a refusal to recognise the right of any foreign power to interfere in her relations with Schleswig; to which Austria, anxious to conciliate the smaller German princes, responded with a vigorous protest against Danish infringements of the compact of 1852. Lord John Russell now intervened, on behalf of Great Britain, with a proposal for a settlement of the whole question on the basis of the independence of the duchies under the Danish crown, with a decennial budget for common expenses to be agreed on by the four assemblies, and a supreme council of state consisting in relative proportion of Danes and Germans. This was accepted by Russia and by the German great powers, and Denmark found herself isolated in Europe. The international situation, however, favoured a bold attitude, and she met the representations of the powers with a flat defiance. The retention of Schleswig as an integral part of the monarchy was to Denmark a matter of life and death; the German Confederation had made the terms of the protocol of 1852, defining the intimate relations between the duchies, the excuse for unwarrantable interference in the internal affairs of the Denmark. On March 30, 1863, as a result of this, a royal compact's proclamation was published at Copenhagen repudiating the compacts of 1852, and, by defining the separate position of Holstein in the Danish monarchy, negativing once for all the German claims upon Schleswig. Three main movements had evolved, each with its goal: A German movement in the two duchies dreamt of an independent Schleswig-Holstein under a liberal constitution. First a personal union with Denmark was outlined, as proposed by Uwe Jens Lornsen in 1830. Later, as it the succession problem appeared and the national sympathies of Danish royalty became evident, the Schleswig-Holstein movement called for an independent state ruled by the house of Augustenburg, a cadet branch of the Danish royal House of Oldenburg. The movement largely ignored the fact that the northern half of Schleswig was predominantly Danish-minded. In Denmark, nationalists wished a "Denmark to the Eider River", implying a reincorporation of Schleswig into Denmark and an end to the century-long German dominance in this region's politics. This scenario would mean a total exclusion of Holstein from the Danish monarchy, barring the conservative aristocracy of Holstein from Danish politics, thus easing liberal reforms. The Eider movement underestimated the German element of Southern Schleswig or thought they could be re-convinced of their Danish heritage. A less vociferous, but more influential stance was the keeping of the Danish unitary state as it was, one kingdom and two duchies. This would avoid any partition, but it would also not solve the ethnical controversy and the constitutional issues. Most Danish civil servants and the major powers of Russia, England and France supported this status quo. A fourth scenario, that Schleswig and Holstein should both be incorporated into Prussia as a mere province, was hardly considered before or during the war of 1864. However, it was to be the outcome after the Austro-Prussian War two years later. As the heirless king Frederick VII grew older, Denmark's successive National-Liberal cabinets became increasingly focused on maintaining control of Schleswig following the king's future death. Both duchies were ruled by the kings of Denmark and shared a long mutual history, but their association with Denmark was extremely complex. Holstein was a member of the German Confederation. Denmark, and Schleswig (as it was a Danish fief), were outside the German Confederation. German nationalists claimed that the succession laws of the two duchies were different from the similar law in Denmark. Danes, however, claimed that this only applied to Holstein, but that Schleswig was subject to the Danish law of succession. A further complication was a much-cited reference in the 1460 Treaty of Ribe stipulating that Schleswig and Holstein should "be together and forever unseparated". As counter-evidence, and in favour of the Danish view, rulings of a Danish clerical court and a German Emperor, of 1424 and 1421 respectively, were produced. In 1863 King Frederick VII of Denmark died leaving no heir. According to the line of succession of Denmark and Schleswig, the crowns of both Denmark and Schleswig would now pass to Duke Christian of Glücksburg (the future King Christian IX), the crown of Holstein was considered to be more problematic. This decision was challenged by a rival pro-German branch of the Danish royal family, the House of Augustenburg (Danish: Augustenborg) who demanded, like in 1848, the crowns of both Schleswig and Holstein. This happened at a particularly critical time as work on a new constitution for the joint affairs of Denmark and Schleswig had just been completed with the draft awaiting his signature. In the Duchy of Lauenburg the personal union with Denmark ended and her estates elected a new dynasty in 1865. The November Constitution The new so-called November Constitution would not annex Schleswig to Denmark directly, but instead create a joint parliament (with the medieval title Rigsraadet) to govern the joint affairs of both Denmark and Schleswig. Both entities would maintain their individual parliaments as well. A similar initiative, but also including Holstein, had been attempted in 1855, but proved a failure because of the opposition of the people in Schleswig and their support in German states. Most importantly, Article I clarified the question of succession: The form of government shall be that of a constitutional monarchy. Royal authority shall be inherited. The law of succession is specified in the law of succession of July 31, 1853 applying for the entire Danish monarchy. Denmark's new king, Christian IX, was in a position of extraordinary difficulty. The first sovereign act he was called upon to perform was to sign the new constitution. To sign was to violate the terms of the London Protocol which would probably lead to war. To refuse to sign was to place himself in antagonism to the united sentiment of his Danish subjects, which was the basis of his reign. He chose what seemed the lesser of two evils, and on November 18 signed the constitution. The news was seen as a violation of the London Protocol, which prohibited such a change in the status quo. It was received in German states with manifestations of excitement and anger. Frederick, duke of Augustenburg, son of the prince who in 1852 had renounced the succession to the duchies, now claimed his rights on the ground that he had had no share in the renunciation. In Holstein an agitation in his favour had begun from the first, and this was extended to Schleswig when the terms of the new Danish constitution became known. His claim was enthusiastically supported by the German princes and people, and in spite of the negative attitude of Austria and Prussia the federal assembly at the initiative of Otto von Bismarck decided to occupy Holstein pending the settlement of the decree of succession. Second Schleswig War On December 24, 1863, Saxon and Hanoverian troops marched into the German duchy of Holstein in the name of the German Confederation, and supported by their presence and by the loyalty of the Holsteiners the duke of Augustenburg assumed the government under the style of Duke Frederick VIII. It was clear to Bismarck that Austria and Prussia, as parties to the London Protocol of 1852, must and uphold the succession as fixed by it, and that any action they might take in consequence of the violation of that compact by Denmark must be so correct as to deprive Europe of all excuse for interference. The publication of the new constitution by Christian IX was in itself sufficient to justify them. As to the ultimate outcome of their effective intervention, that could be left to the future to decide. Austria had no clear views. King William wavered between his Prussian feeling and a sentimental sympathy with the duke of Augustenburg. Bismarck alone knew exactly what he wanted, and how to attain it. "From the beginning", he said later (Reflections, ii. 10), "I kept annexation steadily before my eyes." After Christian IX of Denmark merged Schleswig (not Holstein) into Denmark in 1863 following his accession to the Danish throne that year, Bismarck's diplomatic abilities finally convinced Austria to participate in the war, with the assent of the other European large powers and under the auspices of the German Confederation. The protests of Great Britain and Russia against the action of the German federal assembly, together with the proposal of Count Beust, on behalf of Saxony, that Bavaria should bring forward in that assembly a formal motion for the recognition of Duke Frederick's claims, helped Bismarck to persuade Austria that immediate action must be taken. On December 28 a motion was introduced in the federal assembly by Austria and Prussia, calling on the Confederation to occupy Schleswig as a pledge for the observance by Denmark of the compacts of 1852. This implied the recognition of the rights of Christian IX, and was indignantly rejected; whereupon the federal assembly was informed that the Austrian and Prussian governments would act in the matter as independent European powers. On January 16, 1864 the agreement between them was signed. An article drafted by Austria, intended to safeguard the settlement of 1852, was replaced at Bismarck's instance by another which stated that the two powers would decide only in concert on the relations of the duchies, and that they would in no case determine the question of the succession save by mutual consent; and Bismarck issued an ultimatum to Denmark demanding that the November Constitution should be abolished within 48 hours. This was rejected by the Danish government. The Austrian and Prussian forces crossed the Eider into Schleswig on February 1, 1864, and war was inevitable. An invasion of Denmark itself had not been part of the original programme of the allies; but on February 18 some Prussian hussars, in the excitement of a cavalry skirmish, crossed the frontier and occupied the village of Kolding. Bismarck determined to use this circumstance to revise the whole situation. He urged upon the Austrians the necessity for a strong policy, so as to settle once for all not only the question of the duchies but the wider question of the German Confederation; and Austria reluctantly consented to press the war. On March 11 a fresh agreement was signed between the powers, under which the compacts of 1852 were declared to be no longer valid, and the position of the duchies within the Danish monarchy as a whole was to be made the subject of a friendly understanding. Meanwhile, however, Lord John Russell on behalf of Great Britain, supported by Russia, France and Sweden, had intervened with a proposal that the whole question should once more be submitted to a European conference. The German powers agreed on condition that the compacts of 1852 (London Protocol) should not be taken as a basis, and that the duchies should be bound to Denmark by a personal tie only. But the proceedings of the conference, which opened at London on April 25, only revealed the inextricable tangle of the issues involved. Beust, on behalf of the Confederation, demanded the recognition of the Augustenburg claimant; Austria leaned to a settlement on the lines of that of 1852; Prussia, it was increasingly clear, aimed at the acquisition of the duchies. The first step towards the realization of this latter ambition was to secure the recognition of the absolute independence of the duchies, and this Austria could only oppose at the risk of forfeiting her whole influence among the German states. The two powers, then, agreed to demand the complete political independence of the duchies bound together by common institutions. The next move was uncertain. As to the question of annexation Prussia would leave that open, but made it clear that any settlement must involve the complete military subordination of Schleswig-Holstein to herself. This alarmed Austria, which had no wish to see a further extension of Prussia's already overgrown power, and she began to champion the claims of the duke of Augustenburg. This contingency, however, Bismarck had foreseen and himself offered to support the claims of the duke at the conference if he would undertake to subordinate himself in all naval and military matters to Prussia, surrender Kiel for the purposes of a Prussian war-harbour, give Prussia the control of the projected Kiel Canal, and enter the Prussian Customs Union. On this basis, with Austria's support, the whole matter might have been arranged without—as Beust pointed out (Mem. 1. 272) Austria, the other leading state of the German Confederation, was reluctant to engage in a "war of liberation" because of its own problems with various nationalities. After Christian IX of Denmark merged Schleswig into Denmark in 1863 following his accession to the Danish throne that year, Bismarck's diplomatic abilities finally convinced Austria to participate in the war, with the assent of the other European large powers and under the auspices of the German Confederation. On June 25 the London conference broke up without having arrived at any conclusion. On the 24th, in view of the end of the truce, Austria and Prussia had arrived at a new agreement, the object of the war being now declared to be the complete separation of the duchies from Denmark. As the result of the short campaign that followed, the preliminaries of a treaty of peace were signed on August 1, the king of Denmark renouncing all his rights in the duchies in favour of the emperor of Austria and the king of Prussia. The definitive treaty was signed at Vienna on October 30, 1864. By Article XIX, a period of six years was allowed during which the inhabitants of the duchies might opt for Danish nationality and transfer themselves and their goods to Denmark; and the right of indigency was guaranteed to all, whether in the kingdom or the duchies, who enjoyed it at the time of the exchange of ratifications of the treaty. This Second War of Schleswig of 1864 was presented by invaders to be an implementation of the law of the German Confederation (Bundesexekution). After the defeat in the Battle of Dybbøl, the Danes were unable to defend the borders of Schleswig, then had to retreat to Denmark proper, and finally were pushed out of the entire Jutland peninsula. Denmark capitulated and Prussia and Austria took over the administration of Schleswig and Holstein respectively under the Gastein Convention of August 14, 1865. Already in 1864 the Prussian occupying authorities had deposed Bishop Sechmann Boesen. The north border of Schleswig-Holstein as from 1864 to 1920 differs a little from the north border of the modern Danish county of Sønderjylland: in the east Hejls and the Skamlingsbanke hill were not in Schleswig-Holstein but are now in Sønderjylland county; in the west Hviding and Rejsby were in Schleswig-Holstein. They used to be in Ribe County before the 2007 Danish Municipal Reform. After the Second Schleswig War It did not take long for disagreements between Prussia and Austria over both the administration and the future of the duchies to surface. Bismarck used these as a pretext to engineer what became the Austro-Prussian War of 1866. Austria's defeat at the Battle of Königgrätz was followed by the dissolution of the German Confederation and Austria's withdrawal from Holstein, which, along with Schleswig, in turn was annexed by Prussia. Following the Austro-Prussian War of 1866, section five of the Peace of Prague stated that the people of Northern Schleswig should be granted the right to a referendum on whether they would remain under Prussian rule or return to Danish rule. This promise was never fulfilled, neither by Prussia, nor by united Germany (as of 1871). In any case, because of the mix of Danes and Germans who lived there and the various feudal obligations of the players, the Schleswig-Holstein Question problem was considered intractable by many. Lord Palmerston said of the issue that only three people understood the Schleswig-Holstein question: one was dead, the other had gone insane, and the third was himself, but he had forgotten it. This was convenient for Palmerston, as the government knew that Britain was almost powerless on the continent and had no chance of countering Prussia's military or manufacturing might. Meanwhile, in 1864, the Danish royal family, impressed by Victoria's trappings of Empire, arranged the marriage of the Princess to the future Edward VII, so helping to reverse the Anglo-German alliance, which led to the 1914 war. Niall Ferguson in Empire quotes Kitchener in 1914: "We haven't an army, and we have taken on the foremost military power in Europe". The Schleswig-Holstein Question from this time onwards became merged in the larger question of the general relations of Austria and Prussia, and its later developments are a result of the war of 1866. It survived, however, as between Danes and Germans, though narrowed down to the question of the fate of the Danish population of the northern duchy. This question is of great interest to students of international law and as illustrating the practical problems involved in the assertion of the modern principle of nationality. In the Austro-Prussian War of 1866 Prussia took Holstein from Austria, and seized Austria's German allies, the defeated Kingdom of Hanover, Electorate of Hesse, Duchy of Nassau, and the republic of the city-state of Frankfurt. The annexed states became provinces of Prussia, the Holstein and Schleswig merged in the Province of Schleswig-Holstein. The Lutheran Stifter Schleswig and Holstein were merged in the new Evangelical Lutheran State Church of Schleswig-Holstein in 1867. In 1868 the Holy See established the Prefecture Apostolic of Schleswig-Holstein for Catholic parishioners. Danes under German rule The position of the Danes in Schleswig after the cession was determined, so far as treaty rights are concerned, by two instruments: the Treaty of Vienna (October 30, 1864) and the Peace of Prague (August 23, 1866). Under Article XIX of the former treaty the Danish subjects domiciled in the ceded territories had the right, within six years of the exchange of ratifications, of opting for the Danish nationality and transferring themselves, their families and their personal property to Denmark, while keeping their landed property in the duchies. The last paragraph of the Article ran: "Le droit d'indigénat, tant dans le royaume de Danemark que dans les Duchés, est conservé à tous les individus qui le possèdent a l'époque de l'échange des ratifications du présent Traité". ("The right of an indigenous person, as well in the kingdom of Denmark as in the Duchies, is preserved for all individuals who have it at the time of the exchange of the ratifications of this Treaty.") By Article V of the Peace of Prague, Schleswig was ceded by Austria to Prussia with the reservation that the populations of the North of Schleswig shall be again united with Denmark in the event of their expressing a desire so to be by a vote freely exercised. Taking advantage of the terms of these treaties, about 50,000 Danes from North Schleswig (out of a total population of some 150,000) opted for Denmark and were expelled across the frontier, pending the plebiscite which was to restore their country to them. The plebiscite never came. Its inclusion in the treaty had been no more than a diplomatic device to save the face of the emperor Napoleon III; Prussia had from the first no intention of surrendering an inch of the territory that had been conquered; the outcome of the Franco-German War made it unnecessary to pretend that the plebiscite might occur; and by the Treaty of Vienna of October 11, 1878, the clause relating to the plebiscite was formally abrogated with the assent of Austria. Meanwhile, the Danish optants, disappointed of their hopes, had begun to stream back over the frontier into Schleswig. By doing so they lost, under the Danish law, their rights as Danish citizens, without acquiring those of Prussian subjects; and this disability was transmitted to their children. By Article XIX of the Treaty of 1864, indeed, they should have been secured the rights of indigenacy, which, while falling short of complete citizenship, implied, according to Danish law, all the essential guarantees for civil liberty. But in then Prussian law the right of Indigenat is not clearly differentiated from the status of a subject; and the supreme court at Kiel decided in several cases that those who had opted for Danish citizenship had forfeited their rights under the Indigenat paragraph of the Treaty of Vienna. Thus, in the frontier districts, a large and increasing class of people dwelt in a sort of political limbo, having lost their Danish citizenship through ceasing to be domiciled in Denmark, and unable to acquire Prussian citizenship because they had failed to apply for it within the six years stipulated in the Treaty of 1864. Their exclusion from the rights of Prussian subjects was due, however, to causes other than the letter of the treaty. The Danes, in spite of every discouragement, never ceased to strive for the preservation and extension of their national traditions and language; the Germans were equally bent on effectually absorbing these recalcitrant Teutons into the general life of the German empire; and to this end the uncertain status of the Danish optants was a useful means. Danish agitators of German nationality could not be touched so long as they were careful to keep within the limits of the law; pro-Danish newspapers owned and staffed by German subjects enjoyed immunity in accordance with the constitution, which guarantees the liberty of the press. The case of the optants was far different. These unfortunates, who numbered a large proportion of the population, were subject to domiciliary visits, and to arbitrary perquisitions, arrest and expulsion. When the pro-Danish newspapers, after the expulsion of several optant editors, were careful to appoint none but German subjects, the vengeance of the authorities fell upon optant type-setters and printers. The Prussian police, indeed, developed an almost superhuman capacity for detecting optants: and since these pariahs were mingled indistinguishably with the mass of the people, no household and no business was safe from official inquisition. One instance, out of many, may serve to illustrate the type of offence that served as excuse for this systematic official persecution. On April 27, 1896 the second volume for 1895 of the Sønderjyske Aarboger was confiscated for having used the historic term Sonderjylland (South Jutland) for Schleswig. To add to the misery, the Danish government refused to allow the Danish optants expelled by Prussia to settle in Denmark, though this rule was modified by the Danish Nationality Law of 1898 in favour of the children of optants born after the passing of the law. It was not till the signature of the treaty between Prussia and Denmark on January 11, 1907 that these intolerable Treaty of Conditions was ended. By this treaty, the German January government undertook to allow all children born of Danish optants before the passing of the new Danish Nationality Law of 1898 to acquire Prussian nationality on the usual conditions and on their own application. This provision was not to affect the ordinary legal rights of expulsion as exercised by either power, but the Danish government undertook not to refuse to the children of Schleswig optants who should not seek to acquire or who could not legally acquire Prussian nationality permission to reside in Denmark. The provisions of the treaty apply not only to the children of Schleswig optants, but to their direct descendants in all decrees. This adjustment, brought about by the friendly intercourse between the courts of Berlin and Copenhagen, seemed to close the last phase of the Schleswig question. Yet, so far from allaying, it apparently only served to embitter the inter-racial feud. The autochthonous Germans of the Northern Marches regarded the new treaty as a betrayal, and refused to give the kiss of peace to their hereditary enemies. For forty years Germanism, backed by all the weight of the empire and imposed with all the weapons of official persecution, had barely held its own in North Schleswig; despite an enormous emigration, in 1905 139,000 of the 148,000 inhabitants of North Schleswig spoke Danish, while of the German-speaking immigrants it was found that more than a third spoke Danish in the first generation, although from 1864 onward, German had gradually been substituted for Danish in the churches, the schools, and even in the playground. After 1888, German was the only language of instruction in schools in Schleswig. But the scattered outposts of Germanism could hardly be expected to acquiesce without a struggle in a situation that threatened them with social and economic extinction. Forty years of dominance, secured by official favour, had filled them with a double measure of aggressive pride of race, and the question of the rival nationalities in Schleswig, like that in Poland, remained a source of trouble and weakness within the frontiers of the German empire. After World War I After Germany had lost World War I, in which Denmark had been neutral, the victors offered Denmark a chance to redraw the border between Denmark and Germany. The sitting government of Carl Theodor Zahle chose to hold the Schleswig Plebiscite to let the inhabitants of Schleswig decide which nation they, and the land they lived on, should belong to. King Christian X of Denmark, supported by various groups, was opposed to the division. Using a clause in the Danish constitution that the king appointed and dismissed the Danish cabinet, and using the justification that he felt the Danish population was at odds with Zahle's politics, the king dismissed Zahle and asked Otto Liebe to form the Cabinet of Liebe to manage the country until a parliamentary election could be held and a new cabinet formed. Since Zahle's had support from a small majority in the Folketing his Social Liberal Party and the allied Social Democrats felt that the king had effectively staged a state coup against the Danish democracy. A general strike was organised by Fagbevægelsen to put pressure on the king and his allies. As Otto Liebe was unable to organise an election, M. P. Friis replaced him after a week, and succeeded in holding the election, and as a result the Social Liberal Party lost half their electoral support and their rivals the Liberal Party (Denmark) were able to form the minority cabinet led by Niels Neergaard: the Cabinet of Neergaard II. The whole affair was called the Easter Crisis of 1920. The Allied powers arranged a referendum in Northern and Central Schleswig. In Northern Schleswig on February 10, 1920 75% voted for re-unification with Denmark and 25% voted for Germany. In Central Schleswig on March 14, 1920 the results were reversed; 80% voted for Germany and just 20% for Denmark, primarily in Flensburg. While in Northern Schleswig some smaller regions (for example Tønder) had a clear majority of voters for Germany in Central Schleswig all regions voted for Germany (see Schleswig Plebiscites). No vote ever took place in the southern third of Schleswig, because the result for Germany was predictable. On June 15, 1920, North Schleswig officially returned to Danish rule. Germany continued to hold the whole of Holstein and South Schleswig, remaining within the Prussian province of Schleswig-Holstein. The Danish-German border was the only one of the borders imposed on Germany following World War I which was never challenged by Hitler. World War II In the Second World War, after Nazi Germany occupied the whole of Denmark, there was agitation by local Nazi leaders in Schleswig-Holstein to restore the pre-World War I border and re-annex to Germany the areas granted to Denmark after the plebiscite — as the Germans did in Alsace-Lorraine at the same period. However, Hitler vetoed any such step, out of a general German policy at the time to base the occupation of Denmark on a kind of accommodation with the Danish Government, and avoid outright confrontations with the Danes. After World War II After Germany had lost World War II there again was a possibility that Denmark could reacquire some of its lost territory in Schleswig. Though no territorial changes came of it, it had the effect that Prime Minister Knud Kristensen was forced to resign after a vote of no confidence because the Folketing did not support his enthusiasm for incorporating South Schleswig into Denmark. Although there was, as a result, a Danish minority in Southern Schleswig and a German minority in Northern Schleswig. Because of the Expulsion of Germans after World War II the population of Schleswig-Holstein increased by 33 percent (860,000 people). See also Danish exonyms for places in Germany David Blackbourn, History of Germany, 1780-1918 German exonyms for places in Denmark List of rulers of Schleswig-Holstein Timeline of Lübeck References Further reading Carr, Carr. Schleswig-Holstein, 1815–1848: A Study in National Conflict (Manchester University Press, 1963). Price, Arnold. "Schleswig-Holstein" in Encyclopedia of 1848 Revolutions (2005) online Steefel, Lawrence D. The Schleswig-Holstein Question. 1863-1864 (Harvard U.P. 1923). External links Historical Atlas of Schleswig-Holstein Searchable dictionary of German and Danish and Frisian forms of Schleswig placenames da:Slesvig-Holsten de:Schleswig-Holstein#Geschichte fi:Schleswig-Holstein
{ "pile_set_name": "Wikipedia (en)" }
Centrin4 coordinates cell and nuclear division in T. brucei. Centrins are Ca(2+)-binding proteins that have been implicated in a number of biological processes, including organelle duplication, mRNA export, DNA repair and signal transduction. In the protozoan parasite Trypanosoma brucei we have previously described TbCentrin2, which is present on a bi-lobed structure, and involved in the duplication and segregation of the Golgi complex. Recently, another centrin, TbCentrin4, was also found at the bi-lobe and has been implicated in organelle segregation and cytokinesis. We now show that cytokinesis is not inhibited, but that a dysregulation of nuclear and cell division leads to the production of zoids - daughter siblings that contain all organelles except the nucleus. Our results, therefore, suggest that TbCentrin4 is involved in processes that coordinate karyokinesis and cytokinesis.
{ "pile_set_name": "PubMed Abstracts" }
This invention relates to a structure with switchable magnetic properties. In certain applications it is advantageous if the magnetic permeability of a material can be tailored for that application at least within a specified frequency range and more especially if its magnetic permeability could be switched between selected values. In our co-pending UK Patent Application No. 2346485 (International Patent Application No. WO 00/41270) and in a publication entitled Magnetism from Conductors and Enhanced Non-Linear Phenomena, IEEE Transaction on Microwave Theory and Techniques, 1999, 47, 2075-2084, J B Pendry, A J Holden, D J Robbins and W J Stewart, a structured material is disclosed which exhibits a magnetic permeability at a selected frequency, typically a microwave frequency (GHz). The content of these documents is hereby incorporated by way of reference thereto. The structured material described in these documents comprises an array of capacitive elements which include a low resistance electrically conducting path and in which the elements are arranged such that a magnetic component of electromagnetic radiation within a selected frequency band induces an electrical current to flow around the path and through the associated element. The size of the elements and their spacing are selected such as to provide a selected magnetic permeability in response to the electromagnetic radiation. Such a structure allows a material to be fabricated which is designed to have a selected fixed magnetic permeability for a selected frequency of electromagnetic radiation. As shown in FIGS. 1(a) and (b) one such structured material 2 comprises an array of capacitive elements 4 each of which consists of two concentric metallic electrically conducting cylindrical tubes: an outer cylindrical tube 6 and an inner cylindrical tube 8. Both tubes 6, 8 have a longitudinal (i.e running in an axial direction) gap 10 and the two gaps 10 are offset from each other by 180xc2x0. The elements 4 are arranged in a regular square array and are positioned on centres at a distance a apart. The outer tube 6 has a radius r and the inner 8 and outer 6 cylindrical tubes are separated by a distance d. The gap 10 prevents the flow of dc electrical current around either of the cylinders 6, 8. However the self capacitance between the two cylindrical tubes 6, 8 allows an ac current, j, to flow when the material is subjected to electromagnetic radiation 12 having a magnetic field component H which is parallel to the axis of the tubes 6, 8. It is shown that such a structure has an effective magnetic permeability xcexceff (xcfx89) which is given by: μ eff ⁡ ( ω ) = 1 - [ π ⁢ xe2x80x83 ⁢ r 2 a 2 1 + 2 ⁢ σ ⁢ xe2x80x83 ⁢ i ω ⁢ xe2x80x83 ⁢ r ⁢ μ 0 - 3 ⁢ dc 0 2 π 2 ⁢ ω 2 ⁢ r 3 ] Eq . xe2x80x83 ⁢ 1 in which xcfx89 is the angular frequency, "sgr" the resistivity of the cylindrical tubes, i the {square root over (xe2x88x921)} and c0 the velocity of light. From Eq. 1 it can be seen that by appropriate selection of the size r and spacing a of the cylindrical tubes a structure having a selected magnetic permeability at a given frequency xcfx89 can be obtained. For ease of fabrication it proposed in UK Patent Application No. 2346485 (International Patent Application No. WO 00/41270) to construct each capacitive element 4 in the form of a stack of concentric split rings 26, 28 as shown in FIGS. 2(a) and 2(b). A stack of such rings is shown to be equivalent to the concentric cylindrical tubes described above and has a magnetic permeability given by: μ eff ⁡ ( ω ) = 1 - [ π ⁢ xe2x80x83 ⁢ r 1 2 a 2 1 + 2 ⁢ l ⁢ σ 1 ω ⁢ xe2x80x83 ⁢ r 1 ⁢ μ 0 ⁢ i - 3 ⁢ lc 0 2 πω 2 ⁢ r 1 3 ⁢ ln [ xe2x80x83 ⁢ 2 ⁢ c 1 d 1 ] ] Eq . xe2x80x83 ⁢ 2 where r1 is the inside radius of the inner ring 28, a the lattice spacing of the rings, l the separation between the rings in a given column in an axial direction, d1 the separation between the rings in a radial direction, c1 the width of each ring in a radial direction and "sgr"1 the resistance per unit length of each ring. A further microstructured material described in United Kingdom Patent Application No. 2346485 (International Patent Application No. WO 00/41270) is constructed using a stack of conducting elements which comprise a single spiral shaped conductor 34 as illustrated in FIGS. 3(a) and 3(b). It is also suggested that in United Kingdom Patent Application No. 2346485 (International Patent Application No. WO 00/41270) that the magnetic permeability of the structured material could he made to be switchable by incorporating an non-linear dielectric medium, such as Barium Strontium Titanate (BST) or other ferroelectric material, into the structure. The magnetic permeability of the structure is switched by changing the permittivity of the ferroelectric material by applying an electric field across the ferroelectric material. It is suggested that the ferroelectric material could be incorporated between the cylindrical tubes of each capacitive element (FIG. 1(b)) or between each of the concentric rings in a radial direction (FIG. 2(a)). The inclusion however of a ferroelectric material, such as BST, decreases the resonant frequency of the structure by a factor of more than 30 times. To increase the resonant frequency to a selected value to obtain the desired magnetic permeability at a given frequency requires the self capacitance of each capacitive element to be reduced by the same factor. When it is intended that the structured magnetic material is to operate at microwave frequency, that is in the GHz region, this would require a structure composed of capacitive elements which were impractical to fabricate. To overcome this problem it is proposed in United Kingdom Patent Application No. 2346485 (International Patent Application No. WO 00/41270) that the structure comprises an array of single, rather than concentric, cylindrical tubes each of which has two gaps running in an axial direction. A ferroelectric is provided in the gaps and the magnetic permeability switched by changing the permeability of the ferroelectric material using an electrical static switchable electric field. Although such a structured material is capable of operation at microwave frequencies it is impractical to fabricate capacitive elements sufficiently small for operation at radio frequencies in the MHz region. Furthermore even for microwave operation the construction of such a structured material is difficult and expensive. The present invention has arisen in an endeavour to provide a structured material having a magnetic permeability which can be switched between selected values at a selected wavelength of operation, which can be readily fabricated and which is suitable for operation at radio frequencies (MHz). According to the present invention there is provided a structure with switchable magnetic properties comprising an array of capacitive elements in which each capacitive element includes a low resistance conducting path and is such that a magnetic component of electromagnetic radiation lying within a predetermined frequency band induces an electrical current to flow around said path and through said associated element and wherein the size of the elements and their spacing apart are selected such as to provide a predetermined permeability in response to said received electromagnetic radiation, characterised in that each capacitive element comprises a plurality of stacked planar sections each of which comprises at least two concentric spiral conducting members which are electrically insulated from each other and which have a switchable permittivity material therebetween. The magnetic permeability of the structure can be readily switched to a selected value by applying a static electric field across the switchable permittivity material. This is conveniently achieved by applying a dc voltage between the conducting spiral members of each capacitive element. In the context of this patent application the term spiral is to be construed broadly and is not restricted to a plane curve which is traced about a fixed point from which it continuously recedes. The term includes any unclosed loop of more than one turn which recedes away from a centre point. As such the term encompasses spirals which are square, rectangular, triangular, hexagonal or have other geometric forms. Preferably the spirals are substantially circular in form. Alternatively they are square or rectangular in form. Advantageously the switchable permittivity material comprises a ferroelectric material, preferably Barium Strontium Titanate. Alternatively it can comprise a liquid crystal. Preferably the capacitive elements are arranged on a square array. Advantageously alternate spiral conducting members in a given row unwind in an opposite sense. With such an arrangement the structure advantageously further comprises electrically conducting connecting tracks connecting respective spiral members in a given column. Preferably the structure is configured for operation at radio frequencies (MHz). The structures of the invention are non-magnetic in a steady magnetic field.
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