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You are currently viewing our forum as a guest, which gives you limited access to view most discussions and access our other features. By joining our free community, you will have access to additional post topics, communicate privately with other members (PM), view blogs, respond to polls, upload content, and access many other special features. Registration is fast, simple and absolutely free, so please join our community today! Just click here to register. You should turn your Ad Blocker off for this site or certain features may not work properly. If you have any problems with the registration process or your account login, please contact us by clicking here. Interesting, it had me leaning towards INTJ until I specified a little more (F+T) than (N+S), and then it placed me correctly at INFP. It's interesting to me because I have Asperger's which can sometimes manifest some INTJ tendencies. Early on, it had me at INFJ or ENFP, which I can frequently look/act like to others. "You get what you're given, it's all how you use it." Pink - "God is a DJ" There were some issues with word choices and a few places re: how you described it. May be back later to give my thoughts on those. But, for now..... It's relevant to me. Probably moreso ENTP INXJ I often fall into what I call my "in the zone" mode, INTJ, when I have been overwhelmed by Ne. Burn-out. Ti can't keep up. Need to re-energize with some time out. Hyper-introversion. I also have high preference for falling back on Ni or interchangeably switching from Ne to Ni perspectives. I have this thought that when a preference manifests itself too strongly, for too long a time, then, my mind needs a break (as my mind can honestly exhaust me sometimes - too much external stimuli, too go-go-go). Thus, to instintually shut it off/surpress it, for a while, maybe it automatically turns to its mirror opposite as a crutch? Ne/Ni. I think it's cool I got INFP.. But there's another "mode" I have, and I guess I'm connecting with F (Fe?). I like to be relevant sometimes.. If that's what it is. And my question to that is, why wouldn't I? The world isn't perfect, but..umm.. well, so what. That's what I have to say sometimes. Either I'm an expressive INFP or something else (an ENFJ who likes solitude more than usual or a weird ESFJ). I got INTP....I'm not crazy about the T/F distinction. I think about truth a lot, but I am Fi-dom. In many ways, I relate much more to Ti than Fe, so lumping both Fs together often makes me test T. Often a star was waiting for you to notice it. A wave rolled toward you out of the distant past, or as you walked under an open window, a violin yielded itself to your hearing. All this was mission. But could you accomplish it? (Rilke)	{ "pile_set_name": "Pile-CC" }
H. Todd Van Dellen Henry Todd Van Dellen (born April 24, 1964) is an American politician in the state of Minnesota. He served in the Minnesota House of Representatives. References Category:1964 births Category:Living people Category:Minnesota Republicans Category:Members of the Minnesota House of Representatives	{ "pile_set_name": "Wikipedia (en)" }
Sediment quality evolution (2001-2011) in the Ebro River basin (Spain). Spatio-temporal variations in sediment quality (20 sample sites) of the Ebro River basin between 2001 and 2011 have been assessed. The self-organizing map classified the sediment samples according to similarities in their chemical compositions. Its powerful visualization tools helped establish the main pollution contribution on each sample. Most of the samples showed low values of the mean-probable effect concentration quotient through time. However, six samples presented several quality issues related to some trace elements or polycyclic aromatic hydrocarbons. Finally, geoaccumulation index values calculated using estimates of background trace element concentrations suggested anthropogenic influences in more than half of the samples.	{ "pile_set_name": "PubMed Abstracts" }
Council of Ministers (Northern Cyprus) The Council of Ministers () is the executive branch of the government of the unrecognized state Northern Cyprus, consisting of ministers. The council is chaired by the Prime Minister of Northern Cyprus and the ministers head executive departments of the government. The President of Northern Cyprus reserved the right to chair the Council of Ministers, albeit without voting. The maximum number of ministries, as defined by the constitution, is ten. The Council of Ministers is appointed by the Prime Minister, and the program of the government needs to be read out in the Assembly of the Republic within a week of the appointment. The cabinet then needs to receive a vote of confidence by the majority of the members of the Assembly. A vote of no confidence can be initiated after three months has elapsed, by nine members of the Assembly. Cabinet The current council, Tatar cabinet, which replaced the Erhürman cabinet is appointed on 22 May 2019 by the president, Mustafa Akıncı. The cabinet consists of 10 ministers formed by a coalition of the National Unity Party (UBP) and People's Party (HP). UBP got 7 and HP got 3 ministers in the cabinet. See also List of cabinets of Northern Cyprus Notes Category:National cabinets	{ "pile_set_name": "Wikipedia (en)" }
PITTSBURGH — Levi Brown failed to live up to his pedigree with the Arizona Cardinals. The winless Pittsburgh Steelers are hoping a change of scenery might help Brown turn his career — and Pittsburgh’s sagging season — around. Both teams announced Wednesday that the Steelers have acquired Brown for a conditional draft pick. The 29-year-old Brown never appeared comfortable in Arizona after the Cardinals selected him with the fifth overall pick in the 2007 draft, two spots ahead of Adrian Peterson. As a rookie, he started at right tackle for Arizona’s 2008 Super Bowl team, then was moved to left tackle. But he never became the dominant blocker the Cardinals envisioned. Advertisement After missing all of 2012 with a torn triceps, Brown was labeled an “elite” tackle by new coach Bruce Arians in the offseason. But Arians quickly lost faith in Brown as the big lineman struggled against the pass rush off the edge. He gave up three sacks to Robert Quinn in Arizona’s season opener at St. Louis. Presumably, he will be replaced by Bradley Sowell, claimed off waivers from the Indianapolis Colts on Sept. 1. Sowell played in 10 games for Indianapolis as an undrafted rookie last season, when Arians was offensive coordinator, then interim head coach. Regardless of Brown’s spotty record, the winless Steelers (0-4) desperately need help along the offensive line. Pittsburgh is off this week before traveling New York to face the Jets on Oct. 13. While coach Mike Tomlin declined to detail what kind of role Brown would play if he joins the team, Tomlin allowed there’s a chance for Brown to make an immediate impact. “I’ll wait until I get an opportunity to meet him and work with him and let that be the determining factor,” Tomlin said. “The great thing is that we obviously not only have a full week of work ahead of us, but we also have a Monday bonus day which we intend to take full advantage of.” Center Maurkice Pouncey is out for the year with a right knee injury and second-year left tackle Mike Adams has failed to adapt to the left side. Adams played well in spots at right tackle as a rookie before being moved to left tackle in the spring. The adjustment has been rocky at best. Adams surrendered 2 1-2 sacks to Minnesota defensive end Jared Allen in a 34-27 loss to the Vikings in London last weekend and was briefly replaced by Kelvin Beachum. Offensive coordinator Todd Haley, who coached Brown while serving in the same position with Arizona in 2008, declined to talk about the trade, but acknowledged the line play in Pittsburgh hasn’t been anywhere close to acceptable. The Steelers have allowed 15 sacks through four games. Only Miami, Jacksonville and Cleveland gave up more during September. “It’s not just left tackle, it’s across the board,” Haley said. “We’ve got to be better everywhere. We’ve got to be better getting rid of the football. We’ve got to be better blocking, the backs, everybody. When you’re getting pressure, it takes everybody, and everybody’s got to do a better job.” The Steelers have serious salary cap issues, though Brown does come at a bit of a discount. Pittsburgh will pick up the remaining $3.6 million of Brown’s contract. He will count for a $4.2 million cap hit for the Cardinals in 2014. Brown figures to step in for Adams rather than move over to right tackle, where Marcus Gilbert has shown signs of progress. “I think the coaches feel comfortable with where I’m at now, so they don’t want to make a move now that I’m getting better every week,” Gilbert said. “So, I guess I’ll be sticking to the right side right now. “Everybody’s looking to get better and to improve our offense. We know that there’s going to be changes, but we have to keep getting better and try to turn this thing around right now.”	{ "pile_set_name": "Pile-CC" }
t b(c) = 703c2 - 133c + 133. Let m(a) = -13a - 9a*2 - 2a - 3 - 7a2 + 18a. Give -3b(k) - 133m(k). 19k2 Let t(r) = -35r + 1. Let g(w) = 116w - 5. Let n(h) = -4g(h) - 14t(h). Let o(b) = -728b - 169. Calculate -169n(v) - 6o(v). -26v Let m(g) = -17g + 4. Let o(p) = -108 + 34p + 321 - 110 - 110. What is 5m(d) + 3o(d)? 17d - 1 Let v(u) = u*2 - u + 5. Let k(s) = 2s*3 - 223s*2 + 2648s - 197. Let j be k(98). Let i = 5 - -1. Let b(c) = ic - c - 1 - 4c. Calculate jv(l) - 3b(l). -l*2 - 2l - 2 Let t(j) = -4j - 108. Let l(c) = -13. Give 8l(q) - t(q). 4q + 4 Let z(b) = 201b + 71. Let w(f) = 200f + 79. Determine 8w(p) - 9z(p). -209p - 7 Let a(p) = -p*2 + 121p - 1408. Let q be a(108). Let k(b) = -3b - 10. Let x(t) = 3t + 9. What is qk(d) - 5x(d)? -3d - 5 Let u(y) = 36y - 16. Let g(a) = -2a + 3. Let h be g(0). Suppose m - 1 = -x + h, 4x + 2m - 12 = 0. Let t(q) = -3 - xq + 8q + q. What is 16t(p) - 3u(p)? 4p Let a(x) = -24x3 + 6x + 6. Let k be (168/78 + -2 + (-1056)/104)/(-2). Let z(b) = 23b3 - 5b - 5. Calculate ka(d) + 6z(d). 18d3 Let r(p) = -60p - 12. Let h(n) = 16n + 21 + 11 + 12 + 9 - 71n. Let z(k) = 18k - 19. Let a(d) = 6h(d) + 17z(d). Give 12a(b) - 5r(b). 12b Let b(x) = -27x2 - 7x - 8. Let m(c) = 46c2 + 13c + 15. Calculate 7b(z) + 4m(z). -5z2 + 3z + 4 Let l(b) = 8b - 1. Let s = 8278 - 8261. Let k(o) = 23o - 3. What is sl(q) - 6k(q)? -2q + 1 Let p be 138/(-8) - 3/(-12). Let y = 113759 + -113753. Let z(c) = -12c*2 - 14c - 3. Let x(w) = -4w2 - 5w - 1. Determine px(s) + yz(s). -4s2 + s - 1 Let z be 6/(-10) + (1764/(-35))/(-14). Let h(j) = -2 + 4 - 3 + j + 0j. Let v(y) = -9y + 3. Calculate zh(f) + v(f). -6f Let n(i) = -i2 + i - 1. Let t(v) = 3. Suppose -2k = -5 + 3. Let o be 5/(5/(-1)) - (0 - 2). Give kn(f) + ot(f). -f*2 + f + 2 Let q(m) = -18m - 1. Let o(a) = -19a - 1. Suppose -19n - 51 = -16n - 20n. Give no(r) - 4q(r). 15r + 1 Let w(r) be the first derivative of r3/3 + 5r*2/2 + r + 303. Let d(u) = -u. What is 10d(v) + 2w(v)? 2v*2 + 2 Let q(s) = 4780s + 28. Let f(y) = -4781y - 37. Give 3f(k) + 4q(k). 4777k + 1 Let s(v) = -9v + 44. Suppose -5u - 34 = -3w, -3u + 32w - 50w + 39 = 0. Let i(q) = -14q + 66. Determine ui(z) + 8s(z). -2z + 22 Let p(b) = 4b - 1105. Let l(t) = -3t + 1090. What is 7l(q) + 6p(q)? 3q + 1000 Let d(o) = 5o. Let s(r) = -12r + 58. Let v(a) = -5a + 25. Let b(z) = -3s(z) + 7v(z). Determine 2b(y) - d(y). -3y + 2 Let u be (-56)/(-10) - (-6)/15. Let f(s) be the third derivative of 24s2 + 0s + 0 + 1/3s3 + 1/6s*4. Let b(p) = p + 1. Calculate ub(g) - 2f(g). -2g + 2 Let d(v) = 150v - 2744. Let y(i) = -266i + 4802. Determine 16d(p) + 9y(p). 6p - 686 Let x(m) = 26m - 120m + 29m - 3 + 32m + 5 + 26m. Let o be (-1)/(1 + 12/(-9)). Let r(c) = 4c - 1. Determine ox(p) + 5r(p). -p + 1 Let c(z) = 6z*2 + z + 2. Suppose 436i + 120 = 412i. Let x = -6 - -6. Let y(b) = 4b*2 + 0b + xb - 5b*2. What is iy(l) - c(l)? -l*2 - l - 2 Let a(r) = -22r*2 - 40r + 36. Let p(c) = c*2 - 3c - 2. What is 2a(n) + 36p(n)? -8n2 - 188n Let p(f) be the second derivative of f*3/6 + 385f. Let d(t) = -3t - 19. Give -d(y) - 4p(y). -y + 19 Let f(d) = d*2 + 11d - 1. Let z(h) = -886h2 - 11h + 1. Give -f(a) - z(a). 885a2 Let a(k) = k2 - 5k + 6. Suppose 0 = 5u - 2u - 12. Let p be a(u). Let i be ((-1)/p)/((-9)/36). Let g(m) = -4. Let y(v) = v + 1. What is iy(q) + g(q)? 2q - 2 Let p(b) = 9b2 - 7b + 3. Let g(x) = 16x2 + 6x + 13. Let c(t) = 4t2 + t + 3. Let n(r) = -9c(r) + 2g(r). Calculate -5n(l) - 2p(l). 2l2 - l - 1 Let x(m) = -m2 + 4m - 4. Let p be (-32)/(-12) - 3 - (-17 + (-354)/(-18)). Let c(y) = -5y + 3. Determine px(o) - 2c(o). 3o2 - 2o + 6 Let n(f) be the second derivative of -f*3/6 - 2f*2 - 139f + 1. Suppose -3b + 4 = -b. Let v(d) = -5d - 21. What is bv(y) - 11n(y)? y + 2 Let r(o) = -7o3 + 5o - 5. Let z(h) be the third derivative of 0h5 + 36h*2 + 1/30h*6 - 1/8h*4 + 0h + 0 + 1/2h3. Determine 6r(d) + 10z(d). -2d3 Let n(y) = y2 + 17y - 6. Let b(z) = z2 + 16z - 7. Let o(w) = -w*3 + 6w*2 - 11w + 72. Let c be o(6). Calculate cb(r) - 7n(r). -r*2 - 23r Let q(g) = 84g - 35. Let k(f) = -5f - 4. Let r(n) = -5n - 1. Let w(d) = -k(d) + 2r(d). Calculate 4q(b) + 70w(b). -14b Let v(i) = -12i*2 + 2i. Let c(j) = -23j2 + 5j. Let s = -1127 + 1129. Determine sc(t) - 5v(t). 14t2 Let r(d) = 11d*2 + 1876d - 2. Let h(w) = 13w2 + 1877w - 2. Give -6h(s) + 7r(s). -s*2 + 1870s - 2 Let x(j) = 328j3 - 7j*2 - 14j + 14. Let h(y) = -328y3 + 6y*2 + 13y - 12. Give -7h(f) - 6x(f). 328f3 - 7f Let n(p) = 23p3 + 2686p*2 + 2. Let h(a) = 38a*3 + 5371a*2 + 3. What is -3h(j) + 5n(j)? j3 - 2683j*2 + 1 Let l(s) be the first derivative of 0s*2 - 79 + 13s + 11/3s3. Let w(p) = p2 - 6p - 4. Let k be w(6). Let v(y) = 5y2 + 6. Calculate kl(n) + 9v(n). n2 + 2 Let t(m) = 13m*2 + 2585m + 257. Let x(y) = -6y2 - 1293y - 114. What is -4t(p) - 9x(p)? 2p2 + 1297p - 2 Let o(x) = 101x + 4186. Let c(z) = -38z - 1395. Give -8c(r) - 3o(r). r - 1398 Let t(r) = -8r + 26. Let m(y) = 26y - 53. Determine 3m(g) + 7t(g). 22g + 23 Suppose -5a + 21 = -3t, a - 23 = -17. Let p(h) = -36h - 3. Let k(c) = 35c + 4. What is tk(r) + 4p(r)? -39r Let x(w) = -6w3 - 4w*2 + 148w + 20. Let l(n) = 5n3 + 3n*2 - 147n - 15. Calculate 4l(p) + 3x(p). 2p3 - 144p Let q(s) = -2697s2 - 21s - 75. Let x(r) = 1347r2 + 11r + 40. Determine -8q(n) - 15x(n). 1371n2 + 3n Let w be ((3192/12)/19)/2. Let l(n) = 2n3 + 2n*2 - 34. Let x(d) = 6d*3 + 7d*2 - 101. Give wl(a) - 2x(a). 2a*3 - 36 Let j(f) = 14f*3 + 4f*2 - 436f + 13. Let o(d) = -31d3 - 9d*2 + 872d - 27. Give 9j(l) + 4o(l). 2l3 - 436l + 9 Let m(d) = -6d3 - 35d*2 + 3d + 3. Let x(t) = 11t3 + 68t*2 - 5t - 5. Give 5m(z) + 3x(z). 3z3 + 29z*2 Let b(f) = 48f*2 + 54f - 3414. Let s(p) = -7p2 - 8p + 488. Give 4b(k) + 27s(k). 3k2 - 480 Let s(b) = -7b*2 + 2b - 1. Let p(h) = 0h + 14574h*2 + 0h + 14565h2 + 14639h*2 - 43779h*2. Let x be ((-5)/2)/(1/2). Calculate xp(v) + s(v). -2v2 + 2v - 1 Suppose -515y = -507y + 24. Let l(n) = 10n2 - n + 6. Let g(j) = 5j*2 - j + 3. Give yl(c) + 5g(c). -5c*2 - 2c - 3 Let n = 4874 + -4869. Let j(a) = -32a2 - 5a - 5. Let p(k) = -48k2 - 8k - 8. Calculate np(o) - 8j(o). 16o2 Let v(d) = 9d*3 - 8d*2 - 1584d - 8. Let s(g) = 3g3 - 2g*2 + 2g - 2. Give -4s(n) + v(n). -3n*3 - 1592n Let h(o) = 7549o3 + 5o*2 - 50o - 5. Let c(k) = -2k3 + k2 - 10k - 1. Determine -5c(j) + h(j). 7559j*3 Let y(x) = 6x3 + x2 + x + 2. Let h(t) = 52t3 - 8t*2 - 5t - 22. Determine -h(b) - 5y(b). -82b*3 + 3b*2 + 12 Let x(p) = -19p*3 - 7p. Suppose 0 = 41y - 39y - 3q + 23, 5y = -5q + 5. Let k(i) = 9i*3 + 4i. What is yx(n) - 7k(n)? 13n3 Let k(r) = 10r*2 + 39r + 4. Let l(j) = 9j2 + 28j + 5. Let b(i) = -2k(i) + 3l(i). Let y(a) = -7a2 - 7a - 8. Give 5b(q) + 4y(q). 7q2 + 2q + 3 Let q(d) = 20d - 8. Let w be q(2). Suppose w + 4 = -9x. Let l(s) = 3s + 2. Let t(a) = -48a - 33. Give xt(n) - 66l(n). -6n Let o(v) = 17v - 2. Let z(s) = 205s - 25. Suppose 0 = -36l + 461 + 439. Determine lo(p) - 2z(p). 15p Let w(d) = 3d*3 - 5d*2 - 5d + 16. Let l(f) = 4f3 - 7f*2 - 7f + 24. Let a be (-1)/(4/140-7). Calculate al(b) - 7w(b). -b3 + 8 Let j(y) be the first derivative of y4/4 - y3/3 - y - 2296. Let n(u) = 4u*3 - 3u*2 + 6u - 5. Determine -5j(w) + n(w). -w3 + 2w*2 + 6w Let i = -6766 + 6717. Let l(d) = 15d + 34d - 26d3 - 40d*3 - 46d*3. Let x(s) = -7s*3 + 3s. Calculate ix(z) + 3l(z). 7z3 Let w(u) = -105u*3 + 5u - 5. Let f(g) = 1628g3 - 77g + 77. Let a = -18342 + 18419. Calculate aw(n) + 5f(n). 55n3 Let b(p) = -2p + 3. Let z(m) = 86m + 7. Let v(w) = -108w - 8. Let r(j) = -4v(j) - 5z(j). Give -3b(a) - 2r(a). 2a - 3 Let w(c) = -7c*3 + 6c*2 - 4c - 9. Let r(b) be the first derivative of	{ "pile_set_name": "DM Mathematics" }
Introduction {#sec1} ============ Well-established methodologies have been developed for the selective deprotection of aryl, allyl, and benzyl ethers, which are commonly used by organic chemists. In contrast, selective cleavage of aliphatic ethers is much less explored. These ethers, which in fact are often used as solvents, are extraordinarily unreactive toward a variety of reagents,^[@ref1]^ including most well-known oxidants. Historically, the methyl group has been used as a protecting group for phenols and carboxylic acids, but rarely for aliphatic alcohols. For instance, the methyl group of an aryl methyl ether can be selectively removed by boron tribromide,^[@ref2]^ sodium ethanethiolate in refluxing DMF,^[@ref3]^ or lithium iodide in refluxing collidine,^[@ref4]^ whereas aliphatic methyl ethers remain unaffected. Due to its inertness, it is difficult to selectively remove the methyl group from an aliphatic methyl ether while keeping other functional groups intact. Rigorous conditions are required to successfully cleave off the methyl group of methyl ethers, such as aqueous sulfuric, hydroiodic, hydrobromic, or hydrochloric acid.^[@ref5]^ Other methods to transform methyl ethers into more reactive functional groups are based on oxidation. Olah et al.^[@ref6]^ utilized uranium hexafluoride as the oxidant to transform secondary methyl ethers into the corresponding ketones. Other research groups observed the same result by using HOF,^[@ref7]^ a manganese complex and m-CPBA as the stoichiometric oxidant,^[@ref8]^ hydrogen peroxide over titanosilicates,^[@ref9]^ and Bobbitt's salt (2,2,6,6-tetramethyl-1-oxopiperidinium tetrafluoroborate).^[@ref10],[@ref11]^ Mayhoub et al.^[@ref12]^ also showed the selective oxidation of benzyl methyl ethers using NBS and UV light to afford aldehydes or esters. It may be clear that oxidation of ethers requires either the ether to be prone to oxidation (such as benzyl and allyl ethers) or expensive transition-metal catalysts. Herein, we describe an oxidation method to selectively transform secondary methyl ethers into ketones with the versatile and cheap oxidant calcium hypochlorite under mild acidic conditions, without the aid of any transition-metal catalyst. Various oxygen- and nitrogen-bearing functional groups are compatible with the reaction. Other aliphatic ethers can undergo the same conversion, but we focused on the methyl ether, because of the observed regioselectivity, the unreactive nature, and the possible use as a versatile protecting group. It was previously reported by Nwaukwa et al.^[@ref13]^ that ethers can be oxidized with sodium and calcium hypochlorite. However, the reactions were only carried out on symmetrical ethers, such as tetrahydrofuran (THF) and diethyl ether. Remarkably, the examined ethers were oxidized to esters. We herewith report that the oxidation of methyl-protected secondary alcohols reproducibly afforded the corresponding ketones in up to 98% yield. Results and Discussion {#sec2} ====================== We envisioned that multifunctionalized molecules would selectively form ketones from methyl or benzyl ethers leaving other functional groups unchanged. First, we looked for mild reaction conditions to oxidize ethers. We observed that THF (1) was oxidized to γ-butyrolactone (9) using both sodium and calcium hypochlorite (entries 1--2, [Table [1](#tbl1){ref-type="other"}](#tbl1){ref-type="other"}). Calcium hypochlorite was the preferred oxidant, because it was easier to use stoichiometrically compared to the alkaline sodium hypochlorite solution. The oxidation of 2-methyl-tetrahydrofuran (2) was completely regioselective and overoxidation of primary alcohol 10 was not observed within 1 h (entry 3). Dioxane, 2-(chloromethyl)tetrahydro-2H-pyran, and isosorbide were completely unaffected under these reaction conditions. Several benzyl ethers (3--7) were synthesized and submitted to the conditions used by Nwaukwa et al.^[@ref13]^ for the oxidation of symmetrical ethers (6 equiv of oxidant, 9 equiv of acetic acid in a 1:3 mixture of acetonitrile/water). Benzyl ethers 3 and 4 (entries 4--5) were oxidized to ketones 11 and 12, respectively. The benzyl group of the ether was oxidized to chlorinated benzaldehydes and benzoic acids giving rise to an inseparable mixture. Primary alkyl benzyl ether 5 (entry 6) was partially oxidatively deprotected to give 13, but multiple unidentified side products were formed. Linear secondary alkyl benzyl ethers 6 and 7 (entries 7--9) were oxidized to the corresponding methyl ketones 14 and 15. Chlorination of the aromatic ring could be reduced (entry 9) by lowering the reaction temperature and by adding less oxidant portion wise. Then, we moved on to secondary methyl ether 8 for which similar conditions were used (entries 10--11) as for the oxidation of the aforementioned benzyl ethers. Reducing the amounts of oxidant (to 1.6 equiv) and acid (to 3.5 equiv) and lowering the reaction temperature to 0 °C (entries 12--13) eventually led to a clean reaction in which ketone 15 was obtained in 89% yield without the need for further purification. ###### Optimization of Ether Oxidation ![](jo-2017-00632r_0002){#fx1} Equivalents of oxidant; Ca(OCl)~2~ contains two equivalents of oxidant. Conversions are based on ^1^H NMR analysis. Isolation of products was only achieved for entries 11--13. NaOCl was used as oxidant in a pH 6 phosphate buffer. Optimal results were obtained when the methyl ether (1.0 equiv) was stirred for 20--24 h in a 1:1 mixture of acetonitrile/water (0.25 M) and acetic acid (3.5 equiv), while calcium hypochlorite (1.6 equiv) was added portion wise at 0 °C. To explore the scope and limitations of this oxidative demethylation various methyl ethers carrying other functional groups were synthesized from readily available starting materials (see [Supporting Information](http://pubs.acs.org/doi/suppl/10.1021/acs.joc.7b00632/suppl_file/jo7b00632_si_001.pdf)). Oxidation reactions were conducted under the optimal reaction conditions, typically on a 1 mmol scale, unless otherwise stated ([Table [2](#tbl2){ref-type="other"}](#tbl2){ref-type="other"}). If necessary, additional oxidant was added after 1 day. The reaction was tested in three series of compounds: acyclic compounds, cyclohexane derivatives, and functionalized piperidines. Benzoyl protected primary alcohol 16 (entry 1) gave the desired ketone 29 in excellent yield (98%). TBDMS-protected primary alcohol 17 (entry 2) was partially hydrolyzed to the hydroxy ketone 10, but still the corresponding ketone 30 was obtained in good yield (68%). ###### Scope of Methyl Ethers as Substrates ![](jo-2017-00632r_0003){#fx2} ![](jo-2017-00632r_0004){#fx3} The recovered starting material \[%\] is given between brackets. Additional oxidant was added after 1 day and stirring was continued for another day. Reaction was performed on smaller scale (see [Experimental Section](#sec4){ref-type="other"}). Isolated yield of the corresponding 2,4-dinitrophenyl hydrazone 34a. Conversion based on ^1^H NMR analysis of the crude mixture. Total reaction time exceeded 48 h (see [Experimental Section](#sec4){ref-type="other"}). Remarkably, compound 31 (entry 3) was the only product (87%) from the oxidation reaction of poly ether 18, leaving the ether tail completely intact. The explanation for this regioselectivity was supported by failed attempts to oxidize dioxane and isosorbide under similar conditions. All those substrates have their heteroatoms in an ethylene glycol-like connectivity. We hypothesize that the inductive effect of one of the oxygen atoms lowers the nucleophilicity of the other oxygen. We observed similar unreactivity of the 1,3-dioxolane toward oxidation while forming ketone 37 (entry 9). Finally, we tried the reaction with the corresponding unprotected primary alcohol (4-methoxypentan-1-ol), although without success. Primary amine 19 (entry 4) protected as phthalimide afforded the corresponding amino ketone 32 in good yield (82%). The reaction of nitrile 20 (entry 5) was stopped after 27.5 h, purified, and product 33 was obtained in 43% yield, alongside 17% of 20. As expected, the reaction with a tertiary amine as substrate failed. The reaction of secondary amide 21 (entry 6) worked to a certain extent, but eventually we discovered that the amide functionality itself was prone to oxidation, leading to several water-soluble unidentified side products (detected by NMR). Therefore, the crude mixture after aqueous extraction only contained methyl ether 21 and ketone 34. Due to negligible difference in polarity between these two compounds, we decided to isolate the ketone as the corresponding 2,4-dinitrophenyl hydrazone 34a (16%) using Brady's reagent (2,4-dinitrophenyl-hydrazine).^[@ref14]^ Benzylic methyl ether 22 (entry 7) heavily suffered from chlorination of the phenyl ring as a side reaction. Two successive rounds of silica gel column chromatography were insufficient to separate 35 from the complex mixture. Besides linear substrates, cyclic substrates derived from cyclohexane were considered to be suitable for this reaction. The acetoxy group of methyl ether 23 (entry 8) was completely unreactive under the mild reaction conditions and ketone 36 was formed in 81% yield. As expected, a TMS-protected secondary alcohol (1-methoxy-4-\[(trimethylsilyl)oxy\]cyclohexane) was hydrolyzed before any observable oxidation took place. The 1,3-dioxolane protecting group of compound 24 (entry 9) was not completely unreactive. The reaction was stopped after 20 h because of the formation of an additional product according to TLC. After purification, the monoprotected diketone 37 was isolated in 49% yield alongside 37% of the starting material. 4-Methoxycyclohexanone 25 (entry 10) reacted extremely slowly and after 5 days of stirring with additional oxidant, diketone 38 was isolated in only 20% yield, alongside 30% of the starting material. Then, we moved on to piperidine derivatives. Boc-protected 4-methoxypiperidine 26 (entry 11) was not unreactive under the acidic reaction conditions, giving rise to a number of unidentified side products. The corresponding 4-piperidone 39 was just isolated as a minor component (3% yield). Cbz-protection of compound 27 (entry 12) indeed made the carbamate functional group unreactive, but the aromatic ring was prone to chlorination. Within the crude mixture, product 40 was the predominant one, but isolation was not achieved. Sulfonamide 28 (entry 13) was cleanly converted into the corresponding ketone 41. However, the oxidation was extremely slow and after two successive rounds of oxidation (three and 6 days, respectively) the conversion was only 20%. Most of the material was recovered, but due to the negligible difference in polarity, attempts to isolate 41 were not successful, hence conversions are mentioned. We propose a reaction sequence for the oxidative transformation of secondary methyl ethers into ketones ([Figure [1](#fig1){ref-type="fig"}](#fig1){ref-type="fig"}). First, protonation of hypochlorite anion by acetic acid is required to generate hypochlorous acid, which is the active species. The chlorinating species hypochlorous acid is in equilibrium with acetyl hypochlorite and molecular chlorine, which are other chlorinating species. ![Proposed reaction sequence for the oxidation of methyl ethers to ketones.](jo-2017-00632r_0001){#fig1} Then, chlorination occurs at the nucleophilic ether oxygen of I to form oxonium ion II. Subsequent selective HCl elimination via an E2 mechanism at the most substituted carbon forms the most stable oxocarbenium intermediate III. The stabilized cation III is trapped by a water molecule and the formed hemiacetal IV collapses to form the corresponding ketone V upon release of one molecule of methanol. The regioselectivity is supported by the observation that during the oxidation of secondary methyl ethers, the corresponding secondary alcohol was never detected with TLC analysis. In contrast, this secondary alcohol was always detected as an intermediate in the oxidation of secondary benzyl ethers. Conclusions {#sec3} =========== A novel and versatile method to transform secondary methyl ethers into ketones has been developed. From our perspective, the secondary methyl ether can now be considered as a masked ketone, and hence, this reaction should find use in organic synthesis where it might reduce the number of protection and oxidation steps. The reaction is rather slow, but highly regioselective. The scope and limitations have been determined and we can safely state that a variety of oxygen- and nitrogen-containing functional groups are tolerated. Under the mild acidic reaction conditions used, in particular some acid labile groups are tolerated. However, nondeactivated aromatic systems were chlorinated, making this reaction not suitable for aromatic compounds of this particular kind. Experimental Section {#sec4} ==================== General Information {#sec4.1} ------------------- Reagents were obtained from commercial suppliers and were used without purification. Reactions were followed using thin-layer chromatography (TLC) on silica gel-coated plates (Merck 60 F254). Detection was performed with UV light and/or by charring at 150 °C after dipping in a solution of Brady's reagent (2,4-dinitophenylhydrazine) or a solution of KMnO~4~. Column chromatography was performed manually using Acros silica gel, 0.035--0.070 mm, 60 A. Low-resolution ESI mass spectra were recorded on a Thermo Finnigan LCQ Advantage Max Ion Trap mass spectrometer. Low-resolution EI mass spectra were recorded on a JEOL AccuTOF-GCv JMS-100GCv mass spectrometer. High-resolution ESI mass spectra were recorded on a JEOL AccuTOF CS JMS-T100CS mass spectrometer. High-resolution FD and FI mass spectra were recorded on a JEOL AccuTOF GC v 4g, JMS-T100GCV mass spectrometer. NMR spectra were recorded at 298 K on a Varian Inova 4003 spectrometer (400 MHz) and on a Bruker Avance III 400 spectrometer (400 MHz) in CDCl~3~. Chemical shifts (δ) are given in parts per million (ppm) with respect to tetramethylsilane (0.00 ppm) as internal standard for ^1^H NMR; and CDCl~3~ (77.16 ppm) as internal standard for ^13^C NMR. Coupling constants are reported as J values in Hertz (Hz). Data for ^1^H and ^13^C NMR spectra are reported as follows: chemical shift (multiplicity, coupling constant, integration). General Procedure for the Oxidation of Methyl Ethers to Ketones {#sec4.2} --------------------------------------------------------------- The methyl ether (1.0 mmol, 1.0 equiv) was dissolved in acetonitrile/water (1:1 v/v, 0.25 M, 4 mL). Acetic acid (0.2 mL, 3.5 mmol, 3.5 equiv) was added and the solution was cooled to 0 °C. Calcium hypochlorite (4 × 44 mg, 4 × 0.2 mmol, 4 × 0.4 equiv, 65%) was added in four portions over 3 h (one portion every hour). The solution was stirred at 0 °C until TLC indicated full conversion of the starting material (typically 20--48 h). Additional calcium hypochlorite was added after 20--30 h if necessary. Upon completion of the reaction, the ice bath was removed and the reaction was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (3 × 10 mL) and the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL); then dried over magnesium sulfate, filtered, and the solvent was evaporated in vacuo to obtain the crude mixture. The crude mixture was purified with silica gel column chromatography (different eluent systems) to afford the ketone when necessary. ### 2-Methoxyundecane (8)^[@ref15]^ {#sec4.2.1} Sodium hydride (865 mg, 21.6 mmol, 1.5 equiv, 60% dispersion in mineral oil) was added at 0 °C to a solution of undecan-2-ol 42 (2.48 g, 14.4 mmol, 1.0 equiv) in THF (20 mL). The mixture was stirred for 30 min; then methyl iodide (1.35 mL, 21.6 mmol, 1.5 equiv) was added. The mixture was allowed to warm to room temperature and it was stirred for 60 h. Then, the reaction was quenched with water (25 mL) and the product was extracted with ethyl acetate (3 × 40 mL), washed with brine (40 mL), dried over magnesium sulfate, and the solvent was evaporated in vacuo to afford a brownish oil. The crude mixture was dissolved in ethyl acetate (20 mL) and washed with aqueous sodium thiosulfate (10% in water, 20 mL), dried over magnesium sulfate and concentrated. Silica gel column chromatography (pentane/dichloro-methane, 4:1) furnished 8 (2.60 g, 97%) as a transparent yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.31 (s, 3 H), 3.33--3.23 (m, 1 H), 1.59--1.46 (m, 1 H), 1.43--1.20 (m, 15 H), 1.12 (d, J = 6.1 Hz, 3 H), 0.92--0.85 (m, 3 H); ^13^C NMR (101 MHz, CDCl3) δ 76.9, 55.9, 36.3, 31.9, 29.8, 29.7, 29.6, 29.3, 25.5, 22.7, 19.0, 14.1. ### Undecan-2-one (15)^[@ref16]^ {#sec4.2.2} According to the general procedure, substrate 8 (186 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. The reaction mixture was stirred for 21.5 h before it was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (3 × 10 mL), and the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL); then dried over magnesium sulfate and the solvent was removed in vacuo yielding ketone 15 (151 mg, 89%) as a white solid. ^1^H NMR (400 MHz, CDCl~3~) δ 2.43 (t, J = 7.5 Hz, 3 H), 2.15 (s, 3 H), 1.58 (p, J = 7.2 Hz, 2 H), 1.38--1.20 (m, 12 H), 0.95--0.85 (m, 3 H). ### 4-Methoxypentyl Benzoate (16)^[@ref17]^ {#sec4.2.3} Benzoyl chloride (209 μL, 1.8 mmol, 1.2 equiv) was added at 0 °C to a solution of alcohol 43 (177 mg, 1.5 mmol, 1.0 equiv), DMAP (37 mg, 0.3 mmol, 20 mol%), and triethylamine (314 μL, 2.25 mmol, 1.5 equiv) in dichloromethane (8 mL). The reaction was allowed to warm to 20 °C and it was stirred for 15 h. The reaction was quenched with saturated aqueous sodium bicarbonate (5 mL), stirred for another 30 min and then extracted with dichloromethane (3 × 5 mL). The combined organic extracts were washed with 1 M HCl (2 × 3 mL), saturated aqueous sodium bicarbonate (3 mL), and brine (3 mL); then dried over magnesium sulfate and the solvent was removed in vacuo to obtain ester 16 (317 mg, 95%) as a pale yellow liquid. ^1^H NMR (400 MHz, CDCl~3~) δ 8.07--8.02 (m, 2 H), 7.58--7.53 (m, 1 H), 7.47--7.41 (m, 2 H), 4.39--4.28 (m, 2 H), 3.42--3.32 (m, 1 H), 3.33 (s, 3 H), 1.95--1.74 (m, 2 H), 1.71--1.52 (m, 2 H), 1.17 (d, J = 6.1 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 166.6, 132.8, 130.4, 129.5, 128.3, 76.3, 65.1, 56.0, 32.8, 24.8, 19.0; MS (EI^+^) calcd for (C~13~H~18~O~3~ -- CH~3~)^+^ 207.102, found 207.126; HRMS (FD^+^) calcd for (C~13~H~18~O~3~)^+^ 222.1256, found 222.1261. ### tert-Butyl\[(4-methoxypentyl)oxy\]dimethylsilane (17)^[@ref18]^ {#sec4.2.4} Triethylamine (20.5 mL, 147 mmol, 3.75 equiv) was added at 0 °C to a stirring solution of TBDMSCl (5.9 g, 39.1 mmol, 1.0 equiv) in dichloromethane (60 mL) followed by addition of DMAP (0.6 g, 4.91 mmol, 12.5 mol%). Then, a solution of 5-hydroxypentan-2-one 10 (5.0 g, 49 mmol, 1.25 equiv) in dichloromethane (15 mL) was added to the stirring mixture at the same temperature. The reaction mixture was stirred for 30 min at 0 °C and then brought to 20 °C with continued stirring for another 3 h. The reaction mixture was then quenched with saturated aqueous ammonium chloride (40 mL) and the product was extracted with ethyl acetate (3 × 65 mL). The combined organic extracts were washed with water (15 mL) and brine (15 mL); then dried over sodium sulfate and the solvent was removed in vacuo to give the crude product (9.6 g), which was purified by flash chromatography (ethyl acetate/heptane 1:9) to recover starting material 10 (2.33 g) and to afford the silyl ether (3.74 g, 65% brsm) as a yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.61 (t, J = 6.1 Hz, 2 H), 2.51 (t, J = 7.3 Hz, 2 H), 2.15 (s, 3 H), 1.78 (tt, J = 7.2, 6.1 Hz, 2 H), 0.89 (s, 9 H), 0.04 (s, 6 H). Sodium borohydride (612 mg, 16.1 mmol, 1.0 equiv) was added portion wise over 5 min to a solution of the aforementioned silyl ether (3.5 g, 16.1 mmol, 1.0 equiv) in methanol (75 mL). The reaction was stirred at 20 °C for 15 min and then most methanol was evaporated under reduced pressure. Water (50 mL) was added to the residue, followed by 1 N HCl to make the solution acidic. The product was extracted with diethyl ether (3 × 20 mL). The combined ethereal extracts were washed with water (10 mL) and brine (10 mL); then dried over magnesium sulfate and the solvent was evaporated in vacuo to afford the secondary alcohol (3.52 g, 99%) as a yellow transparent oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.87--3.76 (m, 1 H), 3.73--3.61 (m, 2 H), 2.64 (bs, 1 H), 1.73--1.55 (m, 3 H), 1.55--1.41 (m, 1 H), 1.19 (d, J = 6.2 Hz, 3 H), 0.90 (s, 9 H), 0.07 (s, 6 H). Sodium hydride (660 mg, 16.5 mmol, 1.2 equiv, 60% dispersion in mineral oil) was added at 0 °C to a solution of the aforementioned secondary alcohol (3.00 g, 13.7 mmol, 1.0 equiv) in THF (20 mL). The mixture was stirred for 15 min and then methyl iodide (1.03 mL, 16.5 mmol, 1.2 equiv) was added. The mixture was allowed to warm to 20 °C and it was stirred for 18 h. Then, the reaction was quenched with aqueous sodium thiosulfate (5% in water, 30 mL) and the product was extracted with ethyl acetate (3 × 30 mL), washed with brine (15 mL), then dried over magnesium sulfate and concentrated. Silica gel column chromatography (pentane → ethyl acetate) yielded substrate 17 (3.05 g, 95%) as a transparent yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.67--3.57 (m, 2 H), 3.31 (s, 3 H), 3.35--3.27 (m, 1 H), 1.65--1.39 (m, 4 H), 1.13 (d, J = 6.1 Hz, 3 H), 0.89 (s, 9 H), 0.05 (s, 6 H); ^13^C NMR (101 MHz, CDCl~3~) δ 76.6, 63.2, 55.9, 32.5, 28.7, 26.0, 19.1, 18.4, -- 5.3; MS (ESI^+^) calcd for (C~12~H~28~O~2~Si + H)^+^ 233, found 233. HRMS (FI^+^) calcd for (C~12~H~28~O~2~Si -- C~4~H~9~)^+^ 175.1154, found 175.1160. ### 4-Methoxy-1-(2-methoxyethoxy)pentane (18) {#sec4.2.5} Sodium hydride (72 mg, 1.8 mmol, 1.2 equiv, 60% dispersion in mineral oil) was added at 0 °C to a solution of compound 43 (177 mg, 1.5 mmol, 1.0 equiv) in THF (4 mL). The mixture was stirred for 30 min and then 2-chloroethyl methyl ether (164 μL, 1.8 mmol, 1.2 equiv) was added. Stirring was continued for 2 h, while no conversion was observed. Sodium iodide (22 mg, 0.15 mmol, 10 mol%) was added to catalyze the reaction. After stirring for another 16 h, conversion was barely observed so additional THF was added (5 mL), together with sodium hydride (120 mg, 3.0 mmol, 2.0 equiv, 60% dispersion in mineral oil) and 2-chloroethyl methyl ether (275 μL, 3.0 mmol, 2.0 equiv). The temperature was elevated and the mixture was refluxed for 2 days. Then, the reaction was carefully quenched with water (6 mL) and 1 M HCl (3 mL) and the product was extracted with ethyl acetate (3 × 6 mL). The combined organic extracts were washed with brine (3 mL), dried over magnesium sulfate, and concentrated. Consecutive silica gel column chromatography (ethyl acetate/heptane 1:3) afforded ether 18 (124 mg, 47%) as a yellow oil which was slightly contaminated with unknown impurities originating from the eluent (bottle ethyl acetate). ^1^H NMR (400 MHz, CDCl~3~) δ 3.61--3.52 (m, 4 H), 3.51--3.44 (m, 2 H), 3.39 (s, 3 H), 3.31 (s, 3 H), 3.35--3.26 (m, 1 H), 1.75--1.41 (m, 4 H), 1.13 (d, J = 6.1 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 76.6, 72.0, 71.5, 70.0, 59.1, 56.0, 32.7, 25.6, 19.0; HRMS (ESI^+^) calcd for (C~9~H~20~O~3~ + Na)^+^ 199.1310, found 199.1296. ### 2-(4-Methoxypentyl)isoindoline-1,3-dione (19)^[@ref19]^ {#sec4.2.6} Sulfonate 44 (294 mg, 1.5 mmol, 1.0 equiv) was added to a suspension of potassium phthalimide (556 mg, 3.0 mmol, 2.0 equiv) in DMF (25 mL) and the mixture was stirred at 80 °C for 2 h until TLC indicated full conversion of the sulfonate. Upon completion, the mixture was cooled to 20 °C and subsequently diluted with dichloromethane (45 mL), washed with water (2 × 45 mL) and brine (2 × 45 mL); then dried over magnesium sulfate and the solvent was removed in vacuo yielding a crude mixture that still contained DMF. The crude mixture was redissolved in dichloromethane (30 mL) and washed with water (2 × 15 mL) and brine (15 mL); then it was dried over magnesium sulfate and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate/heptane 1:4) to afford compound 19 (271 mg, 73%) as a transparent sticky oil. ^1^H NMR (400 MHz, CDCl~3~) δ 7.87--7.81 (m, 2 H), 7.74--7.68 (m, 2 H), 3.70 (t, J = 7.3 Hz, 2 H), 3.37--3.28 (m, 1 H), 3.30 (s, 3 H), 1.86--1.66 (m, 2 H), 1.61--1.40 (m, 2 H), 1.12 (d, J = 6.1 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 168.4, 133.9, 132.1, 123.2, 76.2, 56.1, 38.0, 33.5, 24.7, 19.0; HRMS (ESI^+^) calcd for (C~14~H~17~NO~3~ + Na)^+^ 270.1106, found 270.1080. ### 5-Methoxyhexanenitrile (20)^[@ref20],[@ref21]^ {#sec4.2.7} Sodium cyanide (221 mg, 4.5 mmol, 3.0 equiv) was added to a solution of sulfonate 44 (294 mg, 1.5 mmol, 1.0 equiv) in DMSO (12 mL) and the mixture was stirred at 80 °C for 2.5 h, and subsequently cooled to 20 °C. Then, the reaction was carefully quenched with water (60 mL), and the reaction mixture was extracted with ethyl acetate (3 × 40 mL). The combined organic extracts were washed with brine (2 × 20 mL), dried over sodium sulfate and concentrated. Purification by silica gel column chromatography (dichloromethane) afforded nitrile 20 (130 mg, 68%) as a yellow liquid. ^1^H NMR (400 MHz, CDCl~3~) δ 3.39--3.30 (m, 1 H), 3.32 (s, 3 H), 2.46--2.28 (m, 2 H), 1.86--1.64 (m, 2 H), 1.62--1.56 (m, 2 H), 1.15 (d, J = 6.1 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 119.7, 75.8, 56.0, 35.3, 21.5, 18.9, 17.2; MS (EI^+^) calcd for (C~7~H~13~NO -- CH~3~)^+^ 112.076, found 112.089. ### 4-Methoxy-1-(piperidin-1-yl)pentan-1-one (21)^[@ref22]^ {#sec4.2.8} Trimethylaluminum (2 M in toluene, 2.5 mL, 5 mmol, 2 equiv) was added at −78 °C to a 1 M solution of freshly distilled piperidine (1.25 mL, 12.5 mmol, 5 equiv) in THF (12.5 mL) and the resulting mixture was stirred at −78 °C for 30 min. Then, a solution of γ-valerolactone 45 (0.24 mL, 2.5 mmol, 1 equiv) in THF (6 mL) was added dropwise to the stirring piperidine solution after which the reaction mixture was allowed to warm to 20 °C. Stirring was continued for another 1.5 h before the reaction was quenched by careful addition of dichloromethane (25 mL) and 0.1 M HCl (50 mL). The product was extracted with dichloromethane (5 × 10 mL) and the combined organic extracts were washed with 1 M HCl (25 mL), dried over magnesium sulfate and the solvent was removed in vacuo to afford alcohol intermediate as a sticky yellow liquid. Then, the alcohol was redissolved in THF (5 mL) and to this solution sodium hydride (120 mg, 3.0 mmol, 1.2 equiv, 60% dispersion in mineral oil) was added at 0 °C. The mixture was stirred for 30 min and then methyl iodide (188 μL, 3.0 mmol, 1.2 equiv) was added. The mixture was allowed to warm to 20 °C and it was stirred for 2 h. Then, the reaction was quenched with aqueous sodium thiosulfate (5% in water, 8 mL) and the product was extracted with ethyl acetate (3 × 10 mL), washed with brine (5 mL), dried over magnesium sulfate, and concentrated. Silica gel column chromatography (ethyl acetate) yielded ether 21 (408 mg, 82% over 2 steps) as a transparent yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.59--3.51 (m, 2 H), 3.44--3.40 (m, 2 H), 3.40--3.33 (m, 1 H), 3.32 (s, 3 H), 2.43 (ddd, J = 15.3, 9.2, 6.0 Hz, 1 H), 2.36 (ddd, J = 15.4, 9.0, 6.5 Hz, 1 H), 1.85 (dddd, J = 13.7, 9.2, 6.5, 4.4 Hz, 1 H), 1.74 (dddd, J = 14.1, 9.1, 7.4, 6.0 Hz, 1 H), 1.68--1.60 (m, 2 H), 1.60--1.49 (m, 4 H), 1.15 (d, J = 6.2 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 171.2, 76.1, 56.0, 46.6, 42.7, 31.8, 28.9, 26.5, 25.6, 24.6, 19.0; HRMS (ESI^+^) calcd for (C~11~H~21~NO~2~ + Na)^+^ 222.1470, found 222.1456. ### (1-Methoxyethyl)benzene (22)^[@ref23]^ {#sec4.2.9} Sodium hydride (180 mg, 4.5 mmol, 1.5 equiv, 60% dispersion in mineral oil) was added at 0 °C to a stirred solution of 1-phenylethanol (46, 363 μL, 3.0 mmol, 1.0 equiv) in THF (12 mL) and DMF (3 mL). After stirring for 40 min, methyl iodide (375 μL, 6.0 mmol, 2.0 equiv) was added and the reaction mixture was allowed to warm to 20 °C. After stirring for 21 h the reaction was carefully quenched with water (20 mL) and the product was extracted with ethyl acetate (3 × 40 mL). The combined organic extracts were successively washed with aqueous sodium thiosulfate (5% in water, 20 mL) and brine (2 × 20 mL); then dried over sodium sulfate and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate/heptane 1:9) to give compound 22 (276 mg, 68%) as a transparent liquid, which was not dried at the oil pump to avoid evaporation of the product. ^1^H NMR (400 MHz, CDCl~3~) δ 7.38--7.25 (m, 5 H), 4.29 (q, J = 6.5 Hz, 1 H), 3.23 (s, 3 H), 1.44 (d, J = 6.5 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 143.5, 128.4, 127.4, 126.2, 79.6, 56.4, 23.9. ### 4-Methoxycyclohexyl Acetate (23)^[@ref24]^ {#sec4.2.10} Acetic anhydride (350 μL, 3.7 mmol, 2.0 equiv) was added to a solution of compound 48 (237 mg, 1.8 mmol, 1.0 equiv, mixture of cis and trans) in pyridine (3 mL). The mixture was stirred at 20 °C for 20.5 h and subsequently diluted with ethyl acetate (50 mL); washed with 1 M HCl (2 × 20 mL), saturated aqueous sodium bicarbonate (2 × 20 mL), and brine (20 mL); and then dried over magnesium sulfate and the solvent was removed in vacuo to afford ester 23 (240 mg, 77%, mixture of cis and trans) as a yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 4.82 (tt, J = 7.1, 3.5 Hz, 0.7 H), 4.78--4.70 (m, 0.3 H), 3.34 (s, 0.9 H), 3.33 (s, 2.1 H), 3.29 (tt, J = 6.6, 3.3 Hz, 0.7 H), 3.25--3.18 (m, 0.3 H), 2.04 (s, 2.1 H), 2.03 (s, 0.9 H), 2.02--1.93 (m, 1.2 H), 1.86--1.70 (m, 2.8 H), 1.70--1.56 (m, 2.8 H), 1.46--1.37 (m, 1.2 H); ^13^C NMR (101 MHz, CDCl~3~) δ 170.7, 170.6, 77.3, 75.8, 71.8, 70.6, 55.9, 55.6, 28.3, 28.3, 27.1, 27.1, 21.4, 21.4. ### 8-Methoxy-1,4-dioxaspiro\[4.5\]decane (24)^[@ref25],[@ref26]^ {#sec4.2.11} Magnesium sulfate (361 mg, 3.0 mmol, 2.0 equiv) was added to a solution of ketone 25 (192 mg, 1.5 mmol, 1.0 equiv), ethylene glycol (0.3 mL, 5.3 mmol, 3.5 equiv) and a catalytic amount of p-toluenesulfonic acid (26 mg, 0.15 mmol, 10 mol%) in toluene (5 mL). The resulting mixture was refluxed for 4 h. The reaction was cooled to 20 °C and quenched with saturated aqueous sodium bicarbonate (10 mL). The product was extracted with diethyl ether (3 × 10 mL) and the combined ethereal extracts were successively washed with brine (10 mL), dried over sodium sulfate, and the solvent was removed in vacuo to obtain ketal 24 (219 mg, 85%) as a colorless transparent oil. NMR (400 MHz, CDCl~3~) δ 3.98--3.90 (m, 4 H), 3.33 (s, 3 H), 3.32--3.27 (m, 1 H), 1.88--1.65 (m, 6 H), 1.59--1.50 (m, 2 H); ^13^C NMR (101 MHz, CDCl~3~) δ 108.5, 76.2, 64.3, 64.3, 55.8, 31.3, 28.2. ### 4-Methoxycyclohexan-1-one (25)^[@ref27]^ {#sec4.2.12} A solution of alcohol 48 (520 mg, 4.0 mmol, 1.0 equiv) in dichloromethane (5 mL) was added slowly poured into a solution of PCC (1.7 g, 8.0 mmol, 2.0 equiv) in dichloromethane (10 mL). The resulting orange mixture was stirred for 3.5 h at 20 °C while the color changed from orange to brown. Upon completion of the reaction, the mixture was filtered through Celite, concentrated, and purified with silica gel column chromatography (ethyl acetate/heptane 1:1) to afford ketone 25 (416 mg, 81%) as a yellow transparent oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.62 (tt, J = 5.7, 3.0 Hz, 1 H), 3.41 (s, 3 H), 2.62--2.51 (m, 3 H), 2.31--2.22 (m, 2 H), 2.15--2.05 (m, 2 H), 1.99--1.89 (m, 1 H); ^13^C NMR (101 MHz, CDCl~3~) δ 211.2, 74.2, 56.1, 37.1, 30.1. ### tert-Butyl 4-methoxypiperidine-1-carboxylate (26)^[@ref28]^ {#sec4.2.13} Boc anhydride (982 mg, 4.5 mmol, 1.5 equiv) and palladium on carbon (750 mg, 10 wt% palladium) were added to a solution of compound 27 (748 mg, 3.0 mmol, 1.0 equiv) in ethanol (20 mL). The flask was placed under a hydrogen atmosphere and the mixture was stirred at 20 °C for 2.5 h. Upon completion, the mixture was filtered through Celite and the filtrate was concentrated in vacuo. Purification of the residue by silica gel column chromatography (methanol/dichloromethane 1:49 → 1:9) gave compound 26 (537 mg, 83%) as a yellow transparent liquid. ^1^H NMR (400 MHz, CDCl~3~) δ 3.83--3.69 (m, 2 H), 3.41--3.30 (m, 1 H), 3.35 (s, 3 H), 3.22 (ddd, J = 13.2, 9.2, 3.5 Hz, 2 H), 1.92--1.76 (m, 2 H), 1.56--1.40 (m, 2 H), 1.46 (s, 9 H); ^13^C NMR (101 MHz, CDCl~3~) δ 154.8, 79.4, 76.0, 55.6, 41.2, 30.6, 28.4; HRMS (ESI^+^) calcd for (C~11~H~21~NO~3~ + Na)^+^ 238.1419, found 238.1413. ### Benzyl 4-Methoxypiperidine-1-carboxylate (27) {#sec4.2.14} Sodium borohydride (189 mg, 5.0 mmol, 1.0 equiv) was added to a solution of ketone 40 (1.17 g, 5.0 mmol, 1.0 equiv) in methanol (20 mL) and the reaction mixture was stirred for 40 min. Upon completion, most methanol was evaporated under reduced pressure and the residue was diluted with water (15 mL) and 0.1 M HCl was added to adjust the pH to 7. The product was extracted with ethyl acetate (3 × 10 mL) and the combined organic extracts were washed with brine (10 mL), dried over magnesium sulfate, and the solvent was removed in vacuo to afford the secondary alcohol (1.19 g, 99%) as a sticky colorless oil, slightly contaminated with ethyl acetate. ^1^H NMR (400 MHz, CDCl~3~) δ 7.41--7.27 (m, 5 H), 5.13 (s, 2 H), 4.01--3.81 (m, 3 H), 3.15 (ddd, J = 13.3, 9.5, 3.5 Hz, 2 H), 1.95--1.76 (m, 2 H), 1.57--1.40 (m, 2 H). Sodium hydride (240 mg, 6.0 mmol, 1.2 equiv, 60% dispersion in mineral oil) was added at 0 °C to a solution of the aforementioned secondary alcohol (1.19 g, 5.0 mmol, 1.0 equiv) in THF (10 mL). After 25 min of stirring, methyl iodide (375 μL, 6.0 mmol, 1.2 equiv) was added. Then, the mixture was allowed to warm to 20 °C and it was stirred for another 18.5 h. The reaction was quenched with aqueous sodium thiosulfate (5% in water, 15 mL) and the product was extracted with ethyl acetate (3 × 15 mL). The combined organic extract were washed with brine (10 mL), dried over magnesium sulfate, and concentrated. Silica gel column chromatography (ethyl acetate/heptane 1:2) of the residue gave ether 27 (1.15 g, 89%) as yellow transparent liquid. ^1^H NMR (400 MHz, CDCl~3~) δ 7.41--7.28 (m, 5 H), 5.13 (s, 2 H), 3.88--3.73 (m, 2 H), 3.42--3.34 (m, 1 H), 3.35 (s, 3 H), 3.22 (ddd, J = 13.3, 8.8, 3.6 Hz, 2 H), 1.93--1.75 (m, 2 H), 1.60--1.45 (m, 2 H); ^13^C NMR (101 MHz, CDCl~3~) δ 155.3, 136.9, 128.5, 127.9, 127.8, 75.6, 67.1, 55.7, 41.2. HRMS (ESI^+^) calcd for (C~14~H~19~NO~3~ + Na)^+^ 272.1263, found 272.1250. ### 4-Methoxy-1-(4-nitrobenzenesulfonyl)piperidine (28)^[@ref29]^ {#sec4.2.15} A solution of compound 26 (249 mg, 1.16 mmol, 1.05 equiv) in TFA/dichloromethane (1:1, 25 mL) was stirred at 20 °C for 40 min. The solvent was evaporated and the residue was dissolved in dichloromethane (12 mL) and at 0 °C treated with triethylamine (383 μL, 2.75 mmol, 2.5 equiv) and p-nosyl chloride (244 mg, 1.1 mmol, 1.0 equiv). After stirring at 20 °C for 21.5 h, the reaction was quenched with saturated aqueous sodium bicarbonate (12 mL). The product was extracted with dichloromethane (3 × 25 mL) and the combined organic extracts were washed with brine (25 mL), dried over magnesium sulfate and the solvent was removed in vacuo to obtain an orange solid. The crude mixture was dissolved in dichloromethane (20 mL) and successively washed with 0.1 M HCl (20 mL), saturated aqueous sodium bicarbonate (20 mL) and brine (20 mL); then dried over magnesium sulfate and the solvent was removed in vacuo to give sulfonamide 28 (238 mg, 72%) as a pale orange solid. ^1^H NMR (400 MHz, CDCl~3~) δ 8.41--8.35 (m, 2 H), 7.97--7.92 (m, 2 H), 3.34 (tt, J = 6.3, 3.2 Hz, 1 H), 3.25 (s, 3 H), 3.20--3.06 (m, 4 H), 1.93--1.83 (m, 2 H), 1.83--1.72 (m, 2 H). ^13^C NMR (101 MHz, CDCl~3~) δ 150.1, 142.6, 128.7, 124.3, 73.2, 55.8, 42.7, 29.5. MS (EI^+^) calcd for (C~12~H~16~N~2~O~5~S -- CH~3~OH)^+^ 268.052, found 268.079; HRMS (FD^+^) calcd for (C~12~H~16~N~2~O~5~S)^+^ 300.0780, found 300.0783. ### 4-Oxopentyl Benzoate (29)^[@ref30]^ {#sec4.2.16} According to the general procedure, compound 16 (222 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. After stirring for 26 h, additional calcium hypochlorite (44 mg, 0.2 mmol, 0.4 equiv) was added at 0 °C and stirring was continued for another 20 h before the reaction was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (3 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and the solvent was removed in vacuo to afford ketone 29 (202 mg, 98%) as a yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 8.06--8.00 (m, 2 H), 7.60--7.53 (m, 1 H), 7.48--7.41 (m, 2 H), 4.34 (t, J = 6.4 Hz, 2 H), 2.61 (t, J = 7.2 Hz, 2 H), 2.18 (s, 3 H), 2.07 (tt, J = 7.2, 6.4 Hz, 2 H); ^13^C NMR (101 MHz, CDCl~3~) δ 207.7, 166.5, 133.0, 130.2, 129.5, 128.4, 64.1, 40.0, 30.0, 22.9. ### 5-{\[tert-Butyl(dimethyl)silyl\]oxy}pentan-2-one (30)^[@ref18]^ {#sec4.2.17} According to the general procedure, 17 (232 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. The reaction mixture was stirred for 23 h before it was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (3 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and the solvent was removed in vacuo. The residue was purified with silica gel column chromatography (ethyl acetate/pentane 1:5) to afford 30 (148 mg, 68%) as a yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.61 (t, J = 6.1 Hz, 2 H), 2.51 (t, J = 7.3 Hz, 2 H), 2.15 (s, 3 H), 1.78 (tt, J = 7.2, 6.1 Hz, 2 H), 0.89 (s, 9 H), 0.04 (s, 6 H); ^13^C NMR (101 MHz, CDCl~3~) δ 208.9, 62.1, 40.1, 30.0, 26.9, 25.9, 18.3, -- 5.4. ### 5-(2-Methoxyethoxy)pentan-2-one (31) {#sec4.2.18} According to the general procedure, methyl ether 18 (88 mg, 0.5 mmol, 1.0 equiv) was dissolved in acetonitrile (1 mL), water (1 mL) and acetic acid (0.1 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (88 mg, 0.4 mmol, 1.6 equiv) was added portion wise over 3 h. After stirring for 23 h, additional calcium hypochlorite (22 mg, 0.1 mmol, 0.4 equiv) was added at 0 °C and stirring was continued for another 24 h before the reaction was quenched with aqueous sodium thiosulfate (10% in water, 2.5 mL). The product was extracted with dichloromethane (3 × 5 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL),dried over magnesium sulfate, and the solvent was removed in vacuo to afford ketone 31 (70 mg, 87%) as a yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 3.58--3.50 (m, 4 H), 3.48 (t, J = 6.2 Hz, 2 H), 3.38 (s, 3 H), 2.54 (t, J = 7.2 Hz, 2 H), 2.15 (s, 3 H), 1.87 (tt, J = 7.2, 6.2 Hz, 2 H); ^13^C NMR (101 MHz, CDCl~3~) δ 208.7, 71.9, 70.3, 70.0, 59.1, 40.3, 30.0, 23.7; HRMS (ESI^+^) calcd for (C~8~H~16~O~3~ + Na)^+^ 183.0997, found 183.0980. ### 2-(4-Oxopentyl)isoindoline-1,3-dione (32)^[@ref31]^ {#sec4.2.19} According to the general procedure, phthalimide 19 (247 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL) and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. The reaction mixture was stirred for 22.5 h before it was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (3 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and concentrated. Purification by silica gel column chromatography (ethyl acetate/heptane 1:3) yielded ketone 32 (190 mg, 82%) as a white solid. ^1^H NMR (400 MHz, CDCl~3~) δ 7.87--7.82 (m, 2 H), 7.75--7.69 (m, 2 H), 3.71 (t, J = 6.7 Hz, 2 H), 2.50 (t, J = 7.2 Hz, 2 H), 2.14 (s, 3 H), 1.96 (p, J = 7.0 Hz, 2 H); ^13^C NMR (101 MHz, CDCl~3~) δ 207.4, 168.5, 134.0, 132.1, 123.2, 40.6, 37.2, 29.9, 22.7. ### 5-Oxohexanenitrile (33)^[@ref32]^ {#sec4.2.20} According to the general procedure, nitrile 20 (127 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 0.8 equiv) was added portion wise over 3 h. The reaction mixture was stirred for 27.5 h before it was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (3 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and concentrated. Purification by silica gel column chromatography (ethyl acetate/heptane 1:3) separately gave starting material 20 (22 mg, 17%) and ketone 33 (48 mg, 43%) as an off-white liquid. ^1^H NMR (400 MHz, CDCl~3~) δ 2.65 (t, J = 6.8 Hz, 2 H), 2.44 (t, J = 7.0 Hz, 2 H), 2.19 (s, 3 H), 1.92 (p, J = 6.9 Hz, 2 H). ### 4-\[2-(2,4-Dinitrophenyl)hydrazinylidene\]-1-(piperidin-1-yl)pentan-1-one (34a)^[@ref12]^ {#sec4.2.21} According to the general procedure, compound 21 (199 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. Stirring was continued for 46 h, while additional calcium hypochlorite (44 mg, 0.2 mmol, 0.4 equiv) was added after 24 h. Finally, the reaction was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (5 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and concentrated to give a transparent yellow oil (116 mg) that contained both starting material 21 and ketone 34. Separation of these two compounds by means of silica gel column chromatography was not achieved so another separation method was used. Treatment of the crude mixture with Brady's reagent (2,4-dinitrophenyl hydrazine in ethanol and sulfuric acid) transformed the ketone into the corresponding 2,4-dinitrophenyl hydrazone whereas the methyl ether remained intact. The solution was poured into diethyl ether (75 mL). The layers were separated and the ethereal extract was washed with water (25 mL) and concentrated to give a red precipitate. The red precipitate was redissolved in diethyl ether (10 mL) and successively washed with 0.1 M HCl (3 × 10 mL), dried over magnesium sulfate, and concentrated. The residue was purified with silica gel column chromatography (ethyl acetate/heptane 1:2 → 1:0) to give hydrazone 34a (59 mg, 16%, 8:1 mixture of E and Z, ratio based on the ^1^H NMR signals between 12 and 11 ppm) as an orange solid. E-isomer: ^1^H NMR (400 MHz, CDCl~3~) δ 11.06 (s, 1 H), 9.13 (d, J = 2.5 Hz, 1 H), 8.27 (ddd, J = 9.6, 2.6, 0.7 Hz, 1 H), 7.89 (d, J = 9.6 Hz, 1 H), 3.61--3.53 (m, 2 H), 3.53--3.47 (m, 2 H), 2.81 (t, J = 6.4 Hz, 2 H), 2.72 (t, J = 6.4 Hz, 2 H), 2.13 (s, 3 H), 1.74--1.60 (m, 4 H), 1.60--1.50 (m, 2 H); ^13^C NMR (400 MHz, CDCl~3~) δ 169.7, 157.4, 145.2, 137.6, 129.8, 129.0, 123.6, 116.2, 46.5, 42.9, 33.8, 28.8, 26.6, 25.6, 24.6, 16.9. Z-isomer: Signals could not be identified due to overlap with the signals of the E-isomer. HRMS (ESI^+^) calcd for (C~16~H~21~N~5~O~5~ + Na)^+^ 386.1440, found 386.1437. ### Acetophenone (35) {#sec4.2.22} According to the general procedure, compound 22 (136 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. The reaction was stirred for 26 h before it was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The products were extracted with dichloromethane (3 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and the solvent was removed in vacuo to afford a yellow oil (103 mg), that contained the product. The crude NMR spectrum revealed that a mixture of six compounds was obtained: (1-methoxyethyl)benzene (22), 1-chloro-2-(1-methoxyethyl)benzene, 1-chloro-4-(1-methoxyethyl)benzene, acetophenone (35), 1-(2-chloro-phenyl)ethan-1-one and 1-(4-chlorophenyl)ethan-1-one. The ratio 35:side products was roughly 1:1. Attempts to separate the product by silica gel column chromatography (pentane → dichloromethane) failed. ### 4-Oxocyclohexyl Acetate (36)^[@ref33]^ {#sec4.2.23} According to the general procedure, ester 23 (172 mg, 1.0 mmol, 1.0 equiv, mixture of cis and trans) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. The reaction mixture was stirred for 47 h before it was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (3 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and concentrated. Purification by silica gel column chromatography (pentane → methanol/dichloromethane 1:19) gave ketone 36 (126 mg, 81%) as a yellow oil. ^1^H NMR (400 MHz, CDCl~3~) δ 5.17 (p, J = 4.9 Hz, 1 H), 2.61--2.49 (m, 2 H), 2.42--2.32 (m, 2 H), 2.11 (s, 3 H), 2.13--2.03 (m, 4 H); ^13^C NMR (101 MHz, CDCl~3~) δ 209.8, 170.4, 68.6, 37.3, 30.4, 21.3. ### 1,4-Dioxaspiro\[4.5\]decan-8-one (37)^[@ref34]^ {#sec4.2.24} According to the general procedure, ketal 24 (172 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 0.8 equiv) was added portion wise over 3 h. After 20 h of stirring TLC analysis indicated that, besides the starting material and the desired product, a third compound was being produced. Therefore, the reaction was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The products were extracted with dichloromethane (5 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and concentrated. Purification by silica gel column chromatography (ethyl acetate/heptane 1:3) separately gave starting material 24 (64 mg, 37%) and ketone 37 (76 mg, 48%) as a white solid. The third compound, cyclohexane-1,4-dione (trace amounts), was detected in the crude mixture, but not isolated. ^1^H NMR (400 MHz, CDCl~3~) δ 4.03 (s, 4 H), 2.55--2.48 (m, 4 H), 2.06--1.97 (m, 4 H); ^13^C NMR (101 MHz, CDCl~3~) δ 210.4, 107.1, 64.7, 38.2, 33.9. ### Cyclohexane-1,4-dione (38)^[@ref35]^ {#sec4.2.25} According to the general procedure, compound 25 (128 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 0.8 equiv) was added portion wise over 3 h. Stirring was continued for 116 h, while additional calcium hypochlorite (308 mg, 1.4 mmol, 1.4 equiv) was added in portions after 19, 27, and 51 h. Finally, the reaction was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The product was extracted with dichloromethane (5 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and concentrated. Purification by silica gel column chromatography (ethyl acetate/heptane 1:1) separately gave starting material 25 (38 mg, 30%) and diketone 38 (22 mg, 20%) as a yellow solid. ^1^H NMR (400 MHz, CDCl~3~) δ 2.72 (s, 8 H). ### tert-Butyl 4-oxopiperidine-1-carboxylate (39)^[@ref36]^ {#sec4.2.26} According to the general procedure, compound 26 (215 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. Stirring was continued for 119 h, while additional calcium hypochlorite (2 × 44 mg, 2 × 0.2 mmol, 0.8 equiv) was added after 23 and 29 h. When TLC indicated that side products became abundant the reaction was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The products were extracted with dichloromethane (5 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and the solvent was removed in vacuo to afford a yellow mixture (32 mg), that predominantly contained the product. Gray crystals formed on the adapter of the rotary evaporator were compound 39 (6 mg, 3%). Most material lost the Boc group and therefore remained in the aqueous phases. ^1^H NMR (400 MHz, CDCl~3~) δ 3.75--3.68 (m, 4 H), 2.48--2.41 (m, 4 H), 1.50 (s, 9 H). ### Benzyl 4-Oxopiperidine-1-carboxylate (40) {#sec4.2.27} According to the general procedure, compound 27 (249 mg, 1.0 mmol, 1.0 equiv) was dissolved in acetonitrile (2 mL), water (2 mL), and acetic acid (0.2 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (176 mg, 0.8 mmol, 1.6 equiv) was added portion wise over 3 h. Stirring was continued for 70 h, while additional calcium hypochlorite (308 mg, 1.4 mmol, 2.8 equiv) was added after 23 (0.4 equiv), 47 (0.4 equiv) and 51 h (2.0 equiv). NMR analysis of an aliquot elucidated that besides the starting material and the product multiple side products had been formed so the reaction was quenched with aqueous sodium thiosulfate (10% in water, 5 mL). The products were extracted with dichloromethane (3 × 10 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (10 mL) and brine (10 mL), dried over magnesium sulfate, and the solvent was removed in vacuo to afford a yellow mixture (250 mg) that contained the product. The crude NMR spectrum revealed that a mixture of six compounds was obtained: benzyl 4-methoxypiperidine-1-carboxylate (27), 2-chlorobenzyl 4-methoxy-piperidine-1-carboxylate, 4-chlorobenzyl 4-methoxypiperidine-1-carboxylate, the desired product (40), 2-chlorobenzyl 4-oxopiperidine-1-carboxylate and 4-chlorobenzyl 4-oxopiperidine-1-carboxylate. The ratio 40:side products was roughly 1:1. Separation was not achieved. ### 1-(4-Nitrobenzenesulfonyl)piperidin-4-one (41) {#sec4.2.28} According to the general procedure, sulfonamide 28 (150 mg, 0.5 mmol, 1.0 equiv) was dissolved in acetonitrile (1 mL), water (1 mL), and acetic acid (0.1 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (88 mg, 0.4 mmol, 1.6 equiv) was added portion wise over 3 h. Stirring was continued for 72 h, while additional calcium hypochlorite (22 mg, 0.1 mmol, 0.4 equiv) was added after 22 h. According to TLC, the reaction was clean and proceeded well, whereas NMR analysis elucidated that the actual conversion after 72 h was only 10--15%. The reaction was quenched with aqueous sodium thiosulfate (10% in water, 2.5 mL). The products were extracted with dichloromethane (3 × 5 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL), dried over magnesium sulfate, and the solvent was removed in vacuo to afford a white-orange solid (144 mg), that exclusively contained starting material and the product. The crude mixture was submitted to the same reaction conditions: it was dissolved in acetonitrile (2 mL), water (1 mL), and acetic acid (0.1 mL, 3.5 equiv). The solution was cooled to 0 °C and calcium hypochlorite (88 mg, 0.4 mmol, 1.6 equiv) was added portion wise over 3 h. Stirring was continued for 7 days, while additional calcium hypochlorite (242 mg, 1.1 mmol, 4.4 equiv) was added after 22 h (0.2 equiv), 2 days (1.0 equiv), and 3 days (1.0 equiv). Apparently, the reaction did not proceed any further than 20% conversion. Eventually, the reaction was quenched with aqueous sodium thiosulfate (10% in water, 2.5 mL). The products were extracted with dichloromethane (3 × 5 mL), the combined organic extracts were subsequently washed with saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL), dried over magnesium sulfate, and the solvent was removed in vacuo to afford a white-orange solid (139 mg). Attempts to separate product 41 via silica gel column chromatography failed. Analytical data could be acquired from the crude ^1^H NMR spectrum. ^1^H NMR (400 MHz, CDCl~3~) δ 8.43--8.39 (m, 2 H), 8.02--7.99 (m, 2 H), 3.48 (t, J = 6.3 Hz, 4 H), 2.59 (t, J = 6.3 Hz, 4 H). ### 4-Methoxypentan-1-ol (43)^[@ref37]^ {#sec4.2.29} Compound 17 (2.32 g, 10 mmol, 1.0 equiv) was dissolved in THF (20 mL) and triethylamine trihydrofluoride (1.63 mL, 10 mmol, 1.0 equiv) was added. The mixture was stirred for 27.5 h at 20 °C before it was concentrated at the rotary evaporator. The residue was purified with silica gel column chromatography (ethyl acetate/heptane 1:1) to afford 43 (1.063 g, 90%) as a yellow liquid. ^1^H NMR (400 MHz, CDCl~3~) δ 3.64 (t, J = 6.0 Hz, 2 H), 3.41--3.32 (m, 1 H), 3.34 (s, 3 H), 2.09 (bs, 1 H), 1.74--1.54 (m, 4 H), 1.16 (d, J = 6.1 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 76.8, 63.0, 56.0, 33.2, 28.8, 18.8; MS (EI^+^) calcd for (C~6~H~14~O~2~ -- CH~3~)^+^ 103.076, found 103.089. ### 4-Methoxypentyl Methanesulfonate (44) {#sec4.2.30} Methanesulfonyl chloride (0.5 mL, 6.4 mmol, 1.3 equiv) and triethylamine (1.0 mL, 7.2 mmol, 1.4 equiv) were successively added at 0 °C to a solution of alcohol 43 (591 mg, 5.0 mmol, 1.0 equiv) in dichloromethane (50 mL). The reaction mixture was stirred for 1 h and then allowed to warm to 20 °C. The mixture was poured into water (50 mL) and the product was extracted with dichloromethane (3 × 25 mL). The combined organic extracts were dried over magnesium sulfate and the solvent was removed in vacuo to afford sulfonate 44 (987 mg, 99%) as a yellow oil. Compound 44 was immediately used in the next steps without further purification. ^1^H NMR (400 MHz, CDCl~3~) δ 4.31--4.20 (m, 2 H), 3.38--3.30 (m, 1 H), 3.31 (s, 3 H), 3.01 (s, 3 H), 1.94--1.74 (m, 2 H), 1.61--1.53 (m, 2 H), 1.15 (d, J = 6.1 Hz, 3 H); ^13^C NMR (101 MHz, CDCl~3~) δ 76.0, 70.2, 56.0, 37.4, 32.2, 25.3, 18.9. ### 4-Methoxycyclohexan-1-ol (48)^[@ref38]^ {#sec4.2.31} Sodium hydride (1.0 g, 25 mmol, 1.0 equiv, 60% dispersion in mineral oil) was added at 0 °C to a solution of cyclohexane-1,4-diol (47, 2.9 g, 25 mmol, 1.0 equiv, mixture of cis and trans) in THF (50 mL). The mixture was stirred for 30 min and then methyl iodide (1.9 mL, 30 mmol, 1.2 equiv) was added. NMR analysis showed an actual conversion of only 10% after stirring for 18 h. Therefore, extra sodium hydride (0.5 g, 12.5 mmol, 0.5 equiv, 60% dispersion in mineral oil) and methyl iodide (1.55 mL, 25 mmol, 1.0 equiv) were added. Stirring was continued for 60 h and the reaction was quenched by the careful addition of water (40 mL). The product was extracted with ethyl acetate (3 × 50 mL), and the combined organic extracts were washed with aqueous sodium thiosulfate (10%, 50 mL) and brine (50 mL), dried over magnesium sulfate, and concentrated. Purification with silica gel column chromatography (ethyl acetate/heptane 1:1) separately gave 1,4-dimethoxycyclohexane (375 mg, 10%, mixture of cis and trans) and 48 (580 mg, 18%, mixture of cis and trans) as a clear transparent liquid. ^1^H NMR (400 MHz, CDCl~3~) δ 3.74 (p, J = 5.8 Hz, 0.7 H), 3.71--3.64 (m, 0.3 H), 3.34 (s, 0.9 H), 3.32 (s, 2.1 H), 3.28 (tt, J = 6.1, 3.1 Hz, 0.7 H), 3.21--3.15 (m, 0.3 H), 2.07--1.94 (m, 1.2 H), 1.89--1.78 (m, 1.4 H), 1.69--1.62 (m, 2.8 H), 1.59--1.50 (m, 1.4 H), 1.36--1.28 (m, 1.2 H). The Supporting Information is available free of charge on the [ACS Publications website](http://pubs.acs.org) at DOI: [10.1021/acs.joc.7b00632](http://pubs.acs.org/doi/abs/10.1021/acs.joc.7b00632).Substrate synthesis schemes and copies of ^1^H and ^13^C NMR spectra ([PDF](http://pubs.acs.org/doi/suppl/10.1021/acs.joc.7b00632/suppl_file/jo7b00632_si_001.pdf)) Supplementary Material ====================== ###### jo7b00632_si_001.pdf The authors declare no competing financial interest.	{ "pile_set_name": "PubMed Central" }
No one ordered fatal shootings: ED PPRESIDENT-ELECT Emmerson Mnangagwa has sensationally claimed that none of his lieutenants gave orders for the fatal shooting of seven civilians, where soldiers opened fired into groups of protesters in Harare on August 1 to quell protests by opposition MDC Alliance activists. Independent Foreign Service/ Staff Reporter The picture of a soldier in kneeling position while shooting at fleeing civilians, while a colleague rushes to stop him during MDC Alliance protests that turned violent in the capital on August 1 In a recent interview with Independent Foreign Service, Mnangagwa said he regretted the killings, but insisted that no one among his lieutenants gave soldiers the order to shoot indiscriminately into the crowded city streets, killing seven people and injuring at least 14 others. “No one gave orders … there is this perception and it is disjointed. I explained, the army has a strict command structure, I am the commander-in-chief and matters are handled according to the process,” he said. “I consulted the commissioner-general of police (Godwin Matanga) and he indicated to me that in terms of the law, the commissioner of police can contact his counterpart who commands the local unit to give him immediate support while the process is ongoing,” Mnangagwa told Independent Foreign Service journalist Peta Thorncroft. “The entire country was in a jovial mood. No one expected the violence that happened so suddenly. The police were taken by surprise. They were deployed countrywide, covering the election process. So suddenly, the small unit (left in Harare) could not control what was happening: In terms of the law, police are allowed to summon assistance to bring order.” The matter has received international condemnation with human rights groups and victims’ families calling for trial of the killer soldiers and their commanders. The Zanu PF leader, whose recent electoral victory is being challenged at the Constitutional Court by his rival MDC Alliance leader Nelson Chamisa, said he had identified British and South African experts to help investigate the shooting incident. “We regret what happened thereafter and since then. This should not happen again. We are instituting a commission of inquiry and to give it more flavour and transparency we are bringing people in from abroad,” he said. “I have one name from South Africa, one from the United Kingdom to consider with three names to join us to look at the matter. The inquiry will begin immediately after the inauguration.” Mnangagwa claimed he had not yet seen a photograph shown in the media of a soldier shooting at fleeing protesters in kneeling position and another stepping forward to stop him on August 1. “I have not seen that picture. Orders have been given about all those people who took the law into their own hands, whether it was police or others who take the law into their own hands. I also don’t want to pre-empt the outcomes of the commission I am instituting.” “Let me assure you, the best thing to do is get the list of 150 cases and pass it onto us. This is fake news and it’s flying left, right and centre. We were told (of these cases) by Philippe van Damme, the EU ambassador here, and we took him to task and said let’s go around all the hospitals in Harare and see if there is any record of people in hospitals. He had to later apologise as this was not true,” he said. “Be wary of Zimbabwe human rights groups. They have an agenda. They have always been against the government. They have not changed their minds, they have not shifted their mindset to become democratic but that will take time. We must deal with facts and not any speculation. Whatever you hear try to check and I think the police will be able to assist you in checking.” Mnangagwa also dismissed reports that citizens were now afraid of the military and police following the post-election crackdown on opposition leaders and their supporters. “I have not received information from my party or from the general public or from any citizen saying I am fearful. Never, never. You will see the police walking in uniform. It is legitimate, it’s allowed by the law. You will see soldiers in their trucks. They are not on a mission to intimidate,” he said. “Our police and our army they are very friendly, we have defence forces week, where they go around building clinics, building schools to show the army and the public are in good relations. So this fake news about our people … that they are afraid of the army.” He also disclosed that former President Robert Mugabe would be stripped of all his farms and left with one. “It’s not a question of voluntary giving up, but about complying with the policy. I am still receiving evidence of what the (former) First Family had. When that process is complete they will select one farm and the rest will be given elsewhere,” Mnangagwa said. “We have the land commission, and this is one of the matters they are seized with attending to. It’s not on the basis of the family, (one family, one farm). It is on the basis of government policy. There are so many others families who have more than one farm. It must all be governed by the size of the farm,” he said.	{ "pile_set_name": "Pile-CC" }
Tom Keith Thomas Alan Keith (December 21, 1946 – October 30, 2011) was a radio personality who worked for Minnesota Public Radio in St. Paul, Minnesota. He was the engineer for Garrison Keillor when the latter began his early morning radio show from the St. John's University, Collegeville, Minnesota studio. Keillor wanted dialogue during the program and Keith was about the only other person around at that early hour. Keith was one of the primary sound effects performers for the radio show A Prairie Home Companion and was often an actor in sketches written by Keillor. Keillor created the persona of Jim Ed Poole for Keith on the old early morning show. Jim Ed was said to have grown up in West St. Paul, Minnesota and graduated from Henry Sibley High School. After serving in the Marine Corps, Keith earned a degree from the University of Minnesota. When production of the radio program moved to St. Paul, Tom Keith continued to play Jim Ed who lived in the Hotel Transom with his pet chicken, Curtis. When Keillor left the morning program, Keith was joined on The Morning Show by Dale Connelly. He maintained the Jim Ed Poole persona and developed several other characters (like Dr. Larry Kyle of Genway Laboratories and B. Marty Barry the self-described "bottomless well of wellness") in cooperation with Connelly. Keith developed his vocal and sound effects skills on the morning program and later on A Prairie Home Companion. On October 15, 2008, Keith announced his intention to retire on December 11. The Morning Show was discontinued after a final live performance at the Fitzgerald Theater in St. Paul that morning. Death Minnesota Public Radio announced that Keith died October 30, 2011 at his home due to a massive pulmonary embolism. He was 64 years old. See also References Category:1946 births Category:2011 deaths Category:American Public Media Category:American radio personalities Category:Minnesota Public Radio people Category:People from Saint Paul, Minnesota Category:United States Marines Category:University of Minnesota alumni	{ "pile_set_name": "Wikipedia (en)" }
Author Topic: New build from France (Read 2484 times) hello everyone, first of all my apologies for my bad english.I am a french who started in the world of drones and when I saw your construction I decided to start too!I printed all the pieces in pla on a small french printer. the arms in 70% and the rest in 30%.the motors are brushless 2212 980kv.esc 20a opto bhleli.the FC is the naza m lite with gps neo m8n.the transmitter is a ia6c with a radio turnigy evolution.I just finished all the config radio and FC and I look forward to my 8045 propellers for the first flights.I still have a doubt for the arms of the drone, even with the springs plungers I'm afraid that the arms fall back during the flight (and I tightened the m3 like a sick)when I understood how to put pictures I would show you the beast! Thank you very much Mkc2! I am really a beginner in the world of drones and modelism in general ... what do you mean by removing the negative cable of esc? are you talking about the esc / motor connection? If the first flight goes well, I would like to try to install a 3-axis gimbal with a small camera like the runcam split 2, I have an old gopro hd2 too but I think it will be too heavy. I hesitate between manufacturing the gimbal or buy a not too expensive like a tarot 3d ... is it complicated to do? I prefer to build it because it's more exciting but I do not know if I have the level to do it and if it is not more expensive in the end ... to see! hello patrick (and everyone)!I will not speak French on this topic if the others would not understand us! where are you from the construction of your drone? I wait impatiently propeller for the first flight ... or crash, we'll see ...in the meantime I ask myself a lot of questions about the configuration of naza lite.besides, I have a question about the blinking LEDs. I plug the lipo, I have the ignition sequence (I'm in manual mode) then it blinks 3 times then 2 times and 1 time and after nothing. when i switch to atti mode i have a regular blink in orange and in gps mode 1 regular blink green.everything seems ok but I read everywhere on the internet that there should be a quick flashing of green led for the recording of the home point and the end of the initialization ... but I do not have it .in the manual of the lite I have not seen a mention on this famous green flash so I think it's good but I prefer to seek the advice of experts!thank you in advance ! The wire from your esc that go to the naza (servo lead) you can just use the signal wire, its only an option to get rid of some wires and weight.The green flashing led on my naza light indicates enough satellites locked in and home position set, ready to fly hi!thanks for the information mkc2! I did not know that only the signal cable was enough for the connection to the naza.for the problem of LED and gps lock, after an afternoon of research on the web, I opted for a radical solution ... I upgrade the naza and the little has become big ... It worked, after the reconfiguration I finally had the green flash fast that indicates the gps lock.on the other hand, as much in lite as now, I have the impression that some of my motor turn slightly slower than others ...I took bhleli optos because I thought I did not need to calibrate them but I think it will be necessary ...What do you think ? knowing that I am in sbus, how to proceed?I also have another receiver in traditional connection. do you think I can do the calibration with another receiver bind to my radio and then change with the ia6c?Thank you again for your help !edit: i modify my post ... i am talking About receiver and not transmitter I use the traditonal setup for receiver, not familiar with the sbus setup.When you get your props on and engaged the motors it may seem different again as they will be spinning fast, see how it goes when you do your first test flight.. hi everyone,thank you all for your messages and your help!I received my props but I have not yet been able to fly the mavic.i tried to calibrate my esc with an old trafitional rx but it made the soul during the calibration of the first esc ... so I ordered a new rx expected to arrive sometime next week. I will do the calibration with the new rx and I will try to put the current one back in sbus, normally it should work (thank you for the information patrick57).I'll let you know if it helps other people in this case. Hi,Some news from my mavic, after receiving the rx and calibration of the esc everything was ok to start the first flight!So take off after waiting for gps and compass calibration. The mavic seems pretty reactive except that it vibrates a lot or rather it oscillates a lot and quite violently ... I go back on the computer to assign the x2 on roll and pitch of the basics gain.After several tests it vibrated a little less but I do not know why a propeller broke off in full flight ... followed a crash that broke the left back leg ...So I am good to restart my soldering and order new propellers. So I'm a bit in stress for the rest of the adventure because I did not understand why the propeller is gone in full flight. the prop was tight and in a good way.And why so much vibration I do not understand, if you have any ideas ?? The propellers are 8045 emax nylon bought on ebay, they are fixed (see photo).On the first flight I had set the gain high enough and by lowering it seemed better. but it still vibrated a lot ... maybe it's my propellers that are not adapted. otherwise I replaced the broken leg and redo all the welds and everything looks good.now waiting for new props , and and your advice on the props	{ "pile_set_name": "Pile-CC" }
Stem christie The stem christie or "wedge christie" is a technique used in skiing for turning. The turn comprises three steps: 1. Forming a wedge by rotating the tail of one ski outwards at an angle to the direction of movement, which initiates a change in direction opposite to the stemmed ski. 2. Bringing the other ski parallel to the wedged ski. 3. Completing the turn with both skis parallel as they carve an arcing turn sliding sideways together. History Austrian ski guide Hannes Schneider developed the stem christie. Having perfected it by 1910 he promoted it as the mainstay of the Arlberg technique, which he called the "Alpine System". It replaced the Telemark turn as the standard for descending on skis. The technique was widely used up until the late 1960s, when its use diminished in favor of the parallel turn. Skis with increasingly "parabolic sidecut" accelerated the obsolescence of the stem Christie, starting in the late 1990s, because of their improved turning characteristics over skis with minimal sidecut. The term, "christie", derives from the turning technique employed by Norwegian jumpers in Christiania, Norway, which was called the "stem Christiania" and became shortened to "stem christie". See also Snowplough turn - also known as the wedge turn or stem turn Parallel turn Skiing Topics Notes References Category:Skiing techniques	{ "pile_set_name": "Wikipedia (en)" }
Syntheses, molecular targets and antitumor activities of novel triptycene bisquinones and 1,4-anthracenedione analogs. Novel substituted triptycene bisquinones and 1, 4-anthracenediones were synthesized and screened for their anti-cancer activities. A number of analogs were synthesized utilizing various synthetic transformations and found to elicit interesting antitumor effects. Analogs included water-soluble pro-drugs and ammonium salts. These potent antitumor drugs are DNA topoisomerase inhibitors that induce DNA strand breaks, inhibit DNA, RNA and protein syntheses and reduce tumor cell proliferation in the nanomolar range in vitro. They induce cytochrome c release, caspase-9, -3 and -8 activities, poly(ADP)-ribose polymerase-1 (PARP) cleavage, and internucleosomal DNA fragmentation by a mechanism which involves caspase-2 activation but not Fas signaling. Moreover, these drugs remain effective in multidrug-resistant tumor cells and have the advantage of blocking nucleoside transport and inducing a rapid loss of mitochondrial transmembrane potential. Based on their effects in tumor cells and isolated mitochondria, it is hypothesized that these drugs might, directly and indirectly, target components of the permeability transition pore to induce mitochondrial permeability transition and the release of proapoptotic factors. This review provides a summary of synthetic efforts and mechanistic endeavor.	{ "pile_set_name": "PubMed Abstracts" }
Known methods of introducing additives to polymeric particles include dry blending the materials, melting, and compounding the melted blend with extruders and pelletizing or powdering to the desired physical form. The additives employed to treat polymeric particles include antioxidants, processing aids, slip agents, antiblocking agents, antistatic agents, lubricants, UV stabilizers, coupling agents and colorants. Another method of introducing additives to polymeric particles is to contact such particles with additive at the extruder hopper during end use processing. Additives such as colorants, slip agents, processing aids, blowing agents, and others are introduced to virgin polymeric particles at this stage usually in concentrate form. In many instances, difficulty is encountered in metering the exact amounts of additive concentrate necessary to do a specific job. This is especially true for additives such as processing aids and external lubricants which are used at very low levels and usually cannot be added in a concentrate form. Some polymers are presently being manufactured with technology that does not lend itself to such techniques as melt compounding and pelletizing. Many polymers such as high density polyethylene, linear low density polyethylene, and polypropylene emerge from the polymerization reactor in a dry granular form, i.e., in a form similar to that of a fluidized bed system. Presently, additives for these polymers must be introduced by melting, compounding, and then pelletizing. This extra step increases the cost of such polymer manufacturing operations and can adversely effect the properties of such polymers.	{ "pile_set_name": "USPTO Backgrounds" }
Shape deformation in two-dimensional electrical impedance tomography. Electrical impedance tomography (EIT) uses measurements from surface electrodes to reconstruct an image of the conductivity of the contained medium. However, changes in measurements result from both changes in internal conductivity and changes in the shape of the medium relative to the electrode positions. Failure to account for shape changes results in a conductivity image with significant artifacts. Previous work to address shape changes in EIT has shown that in some cases boundary shape and electrode location can be uniquely determined for isotropic conductivities; however, for geometrically conformal changes, this is not possible. This prior work has shown that the shape change problem can be partially addressed. In this paper, we explore the limits of compensation for boundary movement in EIT using three approaches. First, a theoretical model was developed to separate a deformation vector field into conformal and nonconformal components, from which the reconstruction limits may be determined. Next, finite element models were used to simulate EIT measurements from a domain whose boundary has been deformed. Finally, an experimental phantom was constructed from which boundary deformation measurements were acquired. Results, both in simulation and with experimental data, suggest that some electrode movement and boundary distortions can be reconstructed based on conductivity changes alone while reducing image artifacts in the process.	{ "pile_set_name": "PubMed Abstracts" }
High levels of C-reactive protein after simultaneous pancreas-kidney transplantation predict pancreas graft-related complications and graft survival. Although pancreas graft-related complications are frequent after simultaneous pancreas-kidney transplantation (SPK), there are no parameters predicting the risk for these complications. A two-center retrospective study was performed in 97 patients who underwent SPK to investigate the peak serum value of c-reactive protein (CRP) during the first 72 hr after SPK in view of graft-related complications and graft survival. Mean peak CRP was 115.6 +/- 71.5 mg/L. Mean peak CRP was higher in patients needing relaparotomy (n=31) (136.4 vs. 105.8 mg/L, P=0.048), especially when postoperative bleeding was excluded (P=0.015); in patients with graft pancreatitis (P=0.03); and in patients with graft loss (n=19; P<0.001) compared with patients without these complications. With a cut-off of peak CRP at the level of mean plus 1 SD (187.05 mg/L), there was a significantly higher incidence of relaparotomies (P=0.01; bleedings excluded: P=0.003), graft pancreatitis (P=0.03), and pancreas graft loss (P<0.0001) in patients with high peak CRP compared with patients with low peak CRP. No differences were noticed with regard to rejection rate, mortality, and kidney graft loss. Our findings suggest that peak CRP is a helpful parameter in predicting pancreas graft-related complications and pancreas graft survival after SPK. Our results also stress the importance of early graft damage in pancreas transplantation.	{ "pile_set_name": "PubMed Abstracts" }
BROWSE BY DATE Articles from 2011 I've been coaching a team of three eighth-grade girls for the North American Computational Linguistics Olympiad, as one of the co-curricular clubs that are offered at my sons' school. We've been having fun working what amounts to logic puzzles with a linguistic slant, and I've been introducing various linguistic concepts as they become relevant. A few weeks ago, as we worked our way through a puzzle whose solution depended on recognizing the length of a syllable, I decided it would be useful for the team to know the word diphthong. Continue reading... Article Topics: What's a Misle? December 7, 2011 Have you ever been misled by the spelling of a word into thinking that it's pronounced differently? Like, say, thinking that "misled" is pronounced like "mizzled"? Now you know what a "misle" is. On the Chronicle blog Lingua Franca, linguist Geoffrey Pullum investigates, inspired by a colleague's assumption that "biopic" rhymes with "myopic." Read Pullum's post here. Article Topics: It's difficult to talk about our problems, isn't it? I know I'd rather drink a pitcher of lava than discuss an ounce of truth. Maybe that's why, when troubles arise, we often bury them in a metric malarkey-load of poppycock, like a student of mine who once alluded to life problem issues: a trifecta of tripe for the ages. Continue reading... It's high season for X-of-the-year lists, especially words of the year. I'll leave it to my fellow language observers to decide whether volatility, occupy, squeezed middle, tergiversate, or some other word best sums up the year's prevailing mood. For my part, I'm focusing on a different corner of the linguaverse: brand names of the year. Continue reading... Oh, "effect" and "affect" -- why can't one of you be a noun and the other a verb? That would make life so much easier. But no, you are each a noun AND a verb and thus the inspiration for much head-scratching. Continue reading... Dennis Baron, English professor at the University of Illinois and author of the blog The Web of Language, writes: The Web of Language Word of the Year for 2011 is "volatility." Volatility may not be trendy like occupy or Arab Spring, but it's the one word that characterizes the bipolar mood of 2011 in everything from politics to economics. Continue reading...	{ "pile_set_name": "Pile-CC" }
We are having the best and valuable mobile recharge module script in India. We make easy online recharge. To start a dedicated Mobile Recharge online Business with online Mobile Recharge, then our script is the best application for your career. It offers success and complete target base business in recharge for Mobile, DTH and datacard. You can control your Recharge operators, Long Code, Bulk SMS and Mobile Recharge by this script. We offer complete script for online Recharge script excluding API. Quick and EasyDOD for you:In this business minded person living society our DOD IT Solutions leading the foot path for enduring the services. We the professional team are here to help the clients who are approaching through phone , online , face to face in establishing the business ideas , solutions .Designers and developers are putting hands together in a core process in our concern to be a part of business world .We are unique thinkers in handling the projects and lead you to the pathway as the client needs and requirements. Our concern works with the standard technological processing in updating towards the future society.	{ "pile_set_name": "Pile-CC" }
Andrews University recently hosted the 42nd annual conference of the International Association of Missionary Aviation (IAMA) from May 15–17, 2013. Over 90 pilots, professors and students from 20 different organizations gathered on Andrews’ campus for three days of keynote presentations, discussion and business. The featured speakers for the event were Ronald J. Maines, owner and founder of Crossroads Consulting Group, a strategic leadership group; David J. Schipper, president and CEO of the Schipper Group and founding member of the Spokane Turbine Center; and Dave Tanner, Safety Officer for Meijer’s Flight Department. Each speaker gave several talks throughout the conference; on Thursday Dave Tanner’s afternoon address was entitled “A Path to Excellence in Aircraft Operations: Our Guide—The Word of God.” As excellence in aviation becomes increasingly important, pilots, and especially Christian pilots, should cultivate “normalized excellence” in their lives, Tanner said. “God’s people should make excellence a part of their personal ethos,” said Tanner, connecting the Christian mission with the earthly one. Following IAMA’s annual Year in Review session on Thursday evening, conference attendees enjoyed a banquet and keynote presentation given by Terry and Debbie Montambo. The Montambos are active conference and ministry speakers, and served with the Mission Aviation Support Association for nine years. Several attendees flew in to the conference, including Tanner, who flew in from Grand Rapids, Mich. Many of the attendees have spent time flying in the mission field, and featured speakers Maines and Schipper flew as pilots for the United States Army during the Vietnam War. Dina Simmons, chair of the Department of Aviation, reported that attendees enjoyed the conference, the airport and aviation facilities, and the Andrews University campus. “They’re talking about coming back in the future,” said Simmons. “IAMA is a wonderful network for Christian pilots in the mission field.” Simmons noted that the majority of conference planning could not have been accomplished if not for her administrative assistant Jean Gustavsen, flight instructor Kathy Adrada, and student assistant Jose Quispe. IAMA is a non-denominational association of mission pilots that provides support, resources and guidance in best practices for small missionary aviation organizations across the globe. IAMA is very active at aviation events throughout the country, including the annual AirVenture aviation celebration in Oshkosh, Wisc., where they are yearly participants in Fly for Life. The next IAMA conference will be held in 2014 at the Prairie School of Mission Aviation in Three Hills, Alberta, Canada.	{ "pile_set_name": "Pile-CC" }
Q: NSRegularExpression on NSString not working InUITextBoxfield,i insert some value,and I Want to use RegularExpressions match the string ..now i want the text box text should be match for only numeric digits upto 3 when I press button then it should work... What I am trying is which is not working::- -(IBAction)ButtonPress{ NSString string =activity.text; NSError error = NULL; NSRegularExpression regex = [NSRegularExpression regularExpressionWithPattern:@"^[0-9]{1,3}$" options:NSRegularExpressionCaseInsensitive error:&error]; NSString modifiedString = [regex stringByReplacingMatchesInString:string options:0 range:NSMakeRange(0, [string length]) withTemplate:@""]; if ([activity.text isEqualToString:modifiedString ]) { // work only if this matches numeric value from the text box text }} A: - (BOOL)NumberValidation:(NSString )string { NSUInteger newLength = [string length]; NSCharacterSet cs = [[NSCharacterSet characterSetWithCharactersInString:@"1234567890"] invertedSet]; NSString *filtered = [[string componentsSeparatedByCharactersInSet:cs] componentsJoinedByString:@""]; return (([string isEqualToString:filtered])&&(newLength <= 3)); } in your button action event just use this like bellow... -(IBAction)ButtonPress{ if ([self NumberValidation:activity.text]) { NSLog(@"Macth here"); } else { NSLog(@"Not Match here"); } }	{ "pile_set_name": "StackExchange" }
1. Field of the Invention The present invention relates generally to a manipulator, and its control device and method. More specifically, the invention relates to a medical manipulator operative in a master/slave mode, and its control device and method. 2. Related Background Art In conventional laparoscope surgery such as laparoscopic cholecystectomy, an endoscope and forceps are inserted into an abdominal cavity through trocars set in small incisions made in the abdomen of a patient. Then, an operator conducts operation while watching the image acquired by the endoscope on a monitor. Since this type of operation does not need to open the abdomen, physical burden on the patient is alleviated, and the time required for recovery and discharge from the hospital after operation is greatly reduced. Therefore, its adaptation to wider fields of application is expected. Conventional laparoscope surgery, however, involves some problems. That is, the operator cannot directly observe the affected part of the patient. Additionally, there are used forceps only having an opening/closing gripper, not convenient to control and therefore unsuitable for surgery. Thus, the conventional laparoscope surgery needs high skills of operators. To cope with these problems, it has been studied and is now being employed to furnish the forceps end with some degrees of freedom of motion so that a work unit (slave unit) at the forceps end having a plurality of degrees of freedom works in accordance with movements of a control unit (master unit) controlled by an operator to execute laparoscope surgery in a master/slave operative mode. As one of master/slave medical manipulators, there is a remote-control device in which the master unit and the slave unit are normally located apart from each other. This is configured to set a plurality of slave arms on the patient and control positions and orientations of the medical manipulator's ends by controlling the master unit located apart from the patient. This system is complex and large-scaled, and needs high purchasing and maintenance costs. Moreover, it is not so convenient because of requiring much time to set the system ready for actual operation and being liable to interruption of operation. Furthermore, since the operator cannot attend closely to the patient during operation and is not available for quick treatment upon emergent accident, the system is insufficient from the viewpoint of safety. There is another master/slave medical manipulator in which some of axes in the master unit and the slave unit are common axes. This is a simple, easy-to-employ, unitary medical master/slave manipulator. As compared with the foregoing remote-controlled manipulator, the operator can attend closely to the patient and directly controls the manipulator. Therefore, this unitary manipulator significantly reduces the problem of safety. However, these medical manipulators have been developed mainly targeting their functions with affected parts to be operated or treated, and other issues remain unsolved, including how the system is easy to set in the operating room, easy for the operator to use, easy to sterilize and clean, easy to start its actual use, etc. as well as the issue of the cost. One of problems of conventional techniques is that, if the master/slave medical manipulator is started to move from a status where the control unit (master unit) and the work unit (slave unit) do not coincide in orientation, the slave unit does not move as the user (operator) intends. This is because, if the operator starts to control the manipulator from those both do not coincide in orientation, the operator cannot accurately recognize the difference between the orientation of the slave unit displayed on the endoscopic monitor and the orientation of the control unit and gets confused. Under the condition, the manipulator is unreliable in controllability and degrades in safety. Thus, it involves technical problems to be overcome. To overcome those problems, there is a method of bringing the master unit into agreement with the orientation of the slave unit held stationary (Japanese Patent Laid-open No. JP-H08-215204A). This method is a diversion of a method having been employed in an industrial robot. More specifically, in a manipulator having a detector means for detecting orientation angles of the slave portion and the master portion and a means for comparing results of their detection, while stopping the slave, the operator first controls and brings the master unit into agreement with the orientation of the slave, and thereafter starts the master/slave motion. However, this method fails to improve the controllability of the manipulator because the operator must conduct alignment of the orientations every time before starting or re-starting the master/slave motion. Moreover, since the operator must conduct the alignment for all of plural degrees of freedom of motion, it takes much time for the alignment. Furthermore, these problems cannot be disregarded also from the standpoint of quick attendance and treatment against unexpected accidents on site. There is another method for automatically move the master unit into agreement with the orientation of the slave unit (Japanese Patent Laid-open No. JP-2002-053685). In this method, a manipulator includes a detector means for detecting orientation angles of the slave unit and the master unit and a means for sequentially comparing results of their detection. Then, the manipulator is operative in a transitional master/slave mode in which the slave is moved based on the difference between the orientation of the master unit and that of the slave unit as well as the time required for alignment of the orientations. This method removes the troublesome process of alignment, which is one of disadvantages of the foregoing method, and realizes the motion faithful to the operator's intention even during the alignment operation of orientations. However, if the alignment of orientations is started under existence of a large difference in orientation, then the distance of automatic movement of the slave unit and its time are large, and the slave unit starts moving in response to the alignment start command. Therefore, automatic motion out of the operator's intention appears saliently, and the safety issue still remains unsolved.	{ "pile_set_name": "USPTO Backgrounds" }
Vulnerability to drought-induced cavitation of riparian cottonwoods in Alberta: a possible factor in the decline of the ecosystem? Vulnerability of xylem to loss of hydraulic conductivity caused by drought-induced cavitation was determined for three riparian cottonwood species in Lethbridge, Alberta: Populus deltoides Bartr., P. balsamifera L., and P. angustifolia James. These species suffered 50% loss of hydraulic conductivity in one-year-old stem segments when xylem pressure potential fell to -0.7 MPa for P. deltoides and -1.7 MPa for P. balsamifera and P. angustifolia, making them the three most vulnerable tree species reported so far in North America. The possible contribution of drought-induced xylem dysfunction to the decline of riparian ecosystems in dammed rivers is discussed.	{ "pile_set_name": "PubMed Abstracts" }
/* * Copyright (C) 2015 The Android Open Source Project * * Licensed under the Apache License, Version 2.0 (the "License"); * you may not use this file except in compliance with the License. * You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. / package com.aries.ui.view.title.util; import android.content.res.ColorStateList; import android.content.res.TypedArray; import android.graphics.Bitmap; import android.graphics.Canvas; import android.graphics.Color; import android.graphics.Paint; import android.graphics.Rect; import android.graphics.RectF; import android.graphics.Typeface; import android.os.Build; import android.text.TextPaint; import android.text.TextUtils; import android.view.Gravity; import android.view.View; import android.view.animation.Interpolator; import com.aries.ui.view.collapsing.R; import androidx.annotation.ColorInt; import androidx.annotation.RestrictTo; import androidx.appcompat.widget.TintTypedArray; import androidx.core.text.TextDirectionHeuristicsCompat; import androidx.core.view.GravityCompat; import androidx.core.view.ViewCompat; import static androidx.annotation.RestrictTo.Scope.LIBRARY_GROUP; /* * @Author: AriesHoo on 2018/7/19 10:48 * @E-Mail: AriesHoo@126.com * Function: 折叠文本帮助类 * Description: / @RestrictTo(LIBRARY_GROUP) public final class CollapsingTextHelper { // Pre-JB-MR2 doesn't support HW accelerated canvas scaled text so we will workaround it // by using our own texture private static final boolean USE_SCALING_TEXTURE = Build.VERSION.SDK_INT < 18; private static final boolean DEBUG_DRAW = false; private static final Paint DEBUG_DRAW_PAINT; static { DEBUG_DRAW_PAINT = DEBUG_DRAW ? new Paint() : null; if (DEBUG_DRAW_PAINT != null) { DEBUG_DRAW_PAINT.setAntiAlias(true); DEBUG_DRAW_PAINT.setColor(Color.MAGENTA); } } private final View mView; private boolean mDrawTitle; private float mExpandedFraction; private final Rect mExpandedBounds; private final Rect mCollapsedBounds; private final RectF mCurrentBounds; private int mExpandedTextGravity = Gravity.CENTER_VERTICAL; private int mCollapsedTextGravity = Gravity.CENTER_VERTICAL; private float mExpandedTextSize = 15; private float mCollapsedTextSize = 15; private ColorStateList mExpandedTextColor; private ColorStateList mCollapsedTextColor; private float mExpandedDrawY; private float mCollapsedDrawY; private float mExpandedDrawX; private float mCollapsedDrawX; private float mCurrentDrawX; private float mCurrentDrawY; private Typeface mCollapsedTypeface; private Typeface mExpandedTypeface; private Typeface mCurrentTypeface; private CharSequence mText; private CharSequence mTextToDraw; private boolean mIsRtl; private boolean mUseTexture; private Bitmap mExpandedTitleTexture; private Paint mTexturePaint; private float mTextureAscent; private float mTextureDescent; private float mScale; private float mCurrentTextSize; private int[] mState; private boolean mBoundsChanged; private final TextPaint mTextPaint; private Interpolator mPositionInterpolator; private Interpolator mTextSizeInterpolator; private float mCollapsedShadowRadius, mCollapsedShadowDx, mCollapsedShadowDy; private int mCollapsedShadowColor; private float mExpandedShadowRadius, mExpandedShadowDx, mExpandedShadowDy; private int mExpandedShadowColor; public CollapsingTextHelper(View view) { mView = view; mTextPaint = new TextPaint(Paint.ANTI_ALIAS_FLAG \| Paint.SUBPIXEL_TEXT_FLAG); mCollapsedBounds = new Rect(); mExpandedBounds = new Rect(); mCurrentBounds = new RectF(); } public void setTextSizeInterpolator(Interpolator interpolator) { mTextSizeInterpolator = interpolator; recalculate(); } public void setPositionInterpolator(Interpolator interpolator) { mPositionInterpolator = interpolator; recalculate(); } public void setExpandedTextSize(float textSize) { if (mExpandedTextSize != textSize) { mExpandedTextSize = textSize; recalculate(); } } public void setCollapsedTextSize(float textSize) { if (mCollapsedTextSize != textSize) { mCollapsedTextSize = textSize; recalculate(); } } public void setCollapsedTextColor(ColorStateList textColor) { if (mCollapsedTextColor != textColor) { mCollapsedTextColor = textColor; recalculate(); } } public void setExpandedTextColor(ColorStateList textColor) { if (mExpandedTextColor != textColor) { mExpandedTextColor = textColor; recalculate(); } } public void setCollapsedTextAppearance(int resId) { TintTypedArray a = TintTypedArray.obtainStyledAttributes(mView.getContext(), resId, R.styleable.CollapsingTextAppearance); if (a.hasValue(R.styleable.CollapsingTextAppearance_android_textColor)) { mCollapsedTextColor = a.getColorStateList(R.styleable.CollapsingTextAppearance_android_textColor); } if (a.hasValue(R.styleable.CollapsingTextAppearance_android_textSize)) { mCollapsedTextSize = a.getDimensionPixelSize(R.styleable.CollapsingTextAppearance_android_textSize, (int) mCollapsedTextSize); } mCollapsedShadowColor = a.getInt(R.styleable.CollapsingTextAppearance_android_shadowColor, 0); mCollapsedShadowDx = a.getFloat(R.styleable.CollapsingTextAppearance_android_shadowDx, 0); mCollapsedShadowDy = a.getFloat(R.styleable.CollapsingTextAppearance_android_shadowDy, 0); mCollapsedShadowRadius = a.getFloat(R.styleable.CollapsingTextAppearance_android_shadowRadius, 0); a.recycle(); if (Build.VERSION.SDK_INT >= 16) { mCollapsedTypeface = readFontFamilyTypeface(resId); } recalculate(); } /* * 设置最大化状态Text样式id * * @param resId / public void setExpandedTextAppearance(int resId) { TintTypedArray a = TintTypedArray.obtainStyledAttributes(mView.getContext(), resId, R.styleable.CollapsingTextAppearance); if (a.hasValue(R.styleable.CollapsingTextAppearance_android_textColor)) { mExpandedTextColor = a.getColorStateList(R.styleable.CollapsingTextAppearance_android_textColor); } if (a.hasValue(R.styleable.CollapsingTextAppearance_android_textSize)) { mExpandedTextSize = a.getDimensionPixelSize(R.styleable.CollapsingTextAppearance_android_textSize, (int) mExpandedTextSize); } mExpandedShadowColor = a.getInt( R.styleable.CollapsingTextAppearance_android_shadowColor, 0); mExpandedShadowDx = a.getFloat( R.styleable.CollapsingTextAppearance_android_shadowDx, 0); mExpandedShadowDy = a.getFloat( R.styleable.CollapsingTextAppearance_android_shadowDy, 0); mExpandedShadowRadius = a.getFloat( R.styleable.CollapsingTextAppearance_android_shadowRadius, 0); a.recycle(); if (Build.VERSION.SDK_INT >= 16) { mExpandedTypeface = readFontFamilyTypeface(resId); } recalculate(); } public void setExpandedBounds(int left, int top, int right, int bottom) { if (!rectEquals(mExpandedBounds, left, top, right, bottom)) { mExpandedBounds.set(left, top, right, bottom); mBoundsChanged = true; onBoundsChanged(); } } public void setCollapsedBounds(int left, int top, int right, int bottom) { if (!rectEquals(mCollapsedBounds, left, top, right, bottom)) { mCollapsedBounds.set(left, top, right, bottom); mBoundsChanged = true; onBoundsChanged(); } } void onBoundsChanged() { mDrawTitle = mCollapsedBounds.width() > 0 && mCollapsedBounds.height() > 0 && mExpandedBounds.width() > 0 && mExpandedBounds.height() > 0; } public void setExpandedTextGravity(int gravity) { if (mExpandedTextGravity != gravity) { mExpandedTextGravity = gravity; recalculate(); } } public int getExpandedTextGravity() { return mExpandedTextGravity; } public void setCollapsedTextGravity(int gravity) { if (mCollapsedTextGravity != gravity) { mCollapsedTextGravity = gravity; recalculate(); } } public int getCollapsedTextGravity() { return mCollapsedTextGravity; } private Typeface readFontFamilyTypeface(int resId) { final TypedArray a = mView.getContext().obtainStyledAttributes(resId, new int[]{android.R.attr.fontFamily}); try { final String family = a.getString(0); if (family != null) { return Typeface.create(family, Typeface.NORMAL); } } finally { a.recycle(); } return null; } public void setCollapsedTypeface(Typeface typeface) { if (mCollapsedTypeface != typeface) { mCollapsedTypeface = typeface; recalculate(); } } public void setExpandedTypeface(Typeface typeface) { if (mExpandedTypeface != typeface) { mExpandedTypeface = typeface; recalculate(); } } public void setTypefaces(Typeface typeface) { mCollapsedTypeface = mExpandedTypeface = typeface; recalculate(); } public Typeface getCollapsedTypeface() { return mCollapsedTypeface != null ? mCollapsedTypeface : Typeface.DEFAULT; } public Typeface getExpandedTypeface() { return mExpandedTypeface != null ? mExpandedTypeface : Typeface.DEFAULT; } /* * Set the value indicating the current scroll value. This decides how much of the * background will be displayed, as well as the title metrics/positioning. * <p> * A value of {@code 0.0} indicates that the layout is fully expanded. * A value of {@code 1.0} indicates that the layout is fully collapsed. / public void setExpansionFraction(float fraction) { fraction = constrain(fraction, 0f, 1f); if (fraction != mExpandedFraction) { mExpandedFraction = fraction; calculateCurrentOffsets(); } } public float constrain(float amount, float low, float high) { return amount < low ? low : (amount > high ? high : amount); } public final boolean setState(final int[] state) { mState = state; if (isStateful()) { recalculate(); return true; } return false; } public final boolean isStateful() { return (mCollapsedTextColor != null && mCollapsedTextColor.isStateful()) \|\| (mExpandedTextColor != null && mExpandedTextColor.isStateful()); } public float getExpansionFraction() { return mExpandedFraction; } public float getCollapsedTextSize() { return mCollapsedTextSize; } public float getExpandedTextSize() { return mExpandedTextSize; } private void calculateCurrentOffsets() { calculateOffsets(mExpandedFraction); } private void calculateOffsets(final float fraction) { interpolateBounds(fraction); mCurrentDrawX = lerp(mExpandedDrawX, mCollapsedDrawX, fraction, mPositionInterpolator); mCurrentDrawY = lerp(mExpandedDrawY, mCollapsedDrawY, fraction, mPositionInterpolator); setInterpolatedTextSize(lerp(mExpandedTextSize, mCollapsedTextSize, fraction, mTextSizeInterpolator)); if (mCollapsedTextColor != mExpandedTextColor) { // If the collapsed and expanded text colors are different, blend them based on the // fraction mTextPaint.setColor(blendColors( getCurrentExpandedTextColor(), getCurrentCollapsedTextColor(), fraction)); } else { mTextPaint.setColor(getCurrentCollapsedTextColor()); } mTextPaint.setShadowLayer( lerp(mExpandedShadowRadius, mCollapsedShadowRadius, fraction, null), lerp(mExpandedShadowDx, mCollapsedShadowDx, fraction, null), lerp(mExpandedShadowDy, mCollapsedShadowDy, fraction, null), blendColors(mExpandedShadowColor, mCollapsedShadowColor, fraction)); ViewCompat.postInvalidateOnAnimation(mView); } @ColorInt private int getCurrentExpandedTextColor() { if (mState != null) { return mExpandedTextColor.getColorForState(mState, 0); } else { return mExpandedTextColor.getDefaultColor(); } } @ColorInt private int getCurrentCollapsedTextColor() { if (mState != null) { return mCollapsedTextColor.getColorForState(mState, 0); } else { return mCollapsedTextColor.getDefaultColor(); } } private void calculateBaseOffsets() { final float currentTextSize = mCurrentTextSize; // We then calculate the collapsed text size, using the same logic calculateUsingTextSize(mCollapsedTextSize); float width = mTextToDraw != null ? mTextPaint.measureText(mTextToDraw, 0, mTextToDraw.length()) : 0; final int collapsedAbsGravity = GravityCompat.getAbsoluteGravity(mCollapsedTextGravity, mIsRtl ? ViewCompat.LAYOUT_DIRECTION_RTL : ViewCompat.LAYOUT_DIRECTION_LTR); switch (collapsedAbsGravity & Gravity.VERTICAL_GRAVITY_MASK) { case Gravity.BOTTOM: mCollapsedDrawY = mCollapsedBounds.bottom - mTextPaint.descent(); break; case Gravity.TOP: mCollapsedDrawY = mCollapsedBounds.top - mTextPaint.ascent(); break; case Gravity.CENTER_VERTICAL: default: float textHeight = mTextPaint.descent() - mTextPaint.ascent(); float textOffset = (textHeight / 2) - mTextPaint.descent(); mCollapsedDrawY = mCollapsedBounds.centerY() + textOffset; break; } switch (collapsedAbsGravity & GravityCompat.RELATIVE_HORIZONTAL_GRAVITY_MASK) { case Gravity.CENTER_HORIZONTAL: mCollapsedDrawX = mCollapsedBounds.centerX() - (width / 2); break; case Gravity.RIGHT: mCollapsedDrawX = mCollapsedBounds.right - width; break; case Gravity.LEFT: default: mCollapsedDrawX = mCollapsedBounds.left; break; } calculateUsingTextSize(mExpandedTextSize); width = mTextToDraw != null ? mTextPaint.measureText(mTextToDraw, 0, mTextToDraw.length()) : 0; final int expandedAbsGravity = GravityCompat.getAbsoluteGravity(mExpandedTextGravity, mIsRtl ? ViewCompat.LAYOUT_DIRECTION_RTL : ViewCompat.LAYOUT_DIRECTION_LTR); switch (expandedAbsGravity & Gravity.VERTICAL_GRAVITY_MASK) { case Gravity.BOTTOM: mExpandedDrawY = mExpandedBounds.bottom - mTextPaint.descent(); break; case Gravity.TOP: mExpandedDrawY = mExpandedBounds.top - mTextPaint.ascent(); break; case Gravity.CENTER_VERTICAL: default: float textHeight = mTextPaint.descent() - mTextPaint.ascent(); float textOffset = (textHeight / 2) - mTextPaint.descent(); mExpandedDrawY = mExpandedBounds.centerY() + textOffset; break; } switch (expandedAbsGravity & GravityCompat.RELATIVE_HORIZONTAL_GRAVITY_MASK) { case Gravity.CENTER_HORIZONTAL: mExpandedDrawX = mExpandedBounds.centerX() - (width / 2); break; case Gravity.RIGHT: mExpandedDrawX = mExpandedBounds.right - width; break; case Gravity.LEFT: default: mExpandedDrawX = mExpandedBounds.left; break; } // The bounds have changed so we need to clear the texture clearTexture(); // Now reset the text size back to the original setInterpolatedTextSize(currentTextSize); } private void interpolateBounds(float fraction) { mCurrentBounds.left = lerp(mExpandedBounds.left, mCollapsedBounds.left, fraction, mPositionInterpolator); mCurrentBounds.top = lerp(mExpandedDrawY, mCollapsedDrawY, fraction, mPositionInterpolator); mCurrentBounds.right = lerp(mExpandedBounds.right, mCollapsedBounds.right, fraction, mPositionInterpolator); mCurrentBounds.bottom = lerp(mExpandedBounds.bottom, mCollapsedBounds.bottom, fraction, mPositionInterpolator); } public void draw(Canvas canvas) { final int saveCount = canvas.save(); if (mTextToDraw != null && mDrawTitle) { float x = mCurrentDrawX; float y = mCurrentDrawY; final boolean drawTexture = mUseTexture && mExpandedTitleTexture != null; final float ascent; final float descent; if (drawTexture) { ascent = mTextureAscent mScale; descent = mTextureDescent * mScale; } else { ascent = mTextPaint.ascent() * mScale; descent = mTextPaint.descent() * mScale; } if (DEBUG_DRAW) { // Just a debug tool, which drawn a magenta rect in the text bounds canvas.drawRect(mCurrentBounds.left, y + ascent, mCurrentBounds.right, y + descent, DEBUG_DRAW_PAINT); } if (drawTexture) { y += ascent; } if (mScale != 1f) { canvas.scale(mScale, mScale, x, y); } if (drawTexture) { // If we should use a texture, draw it instead of text canvas.drawBitmap(mExpandedTitleTexture, x, y, mTexturePaint); } else { canvas.drawText(mTextToDraw, 0, mTextToDraw.length(), x, y, mTextPaint); } } canvas.restoreToCount(saveCount); } private boolean calculateIsRtl(CharSequence text) { final boolean defaultIsRtl = ViewCompat.getLayoutDirection(mView) == ViewCompat.LAYOUT_DIRECTION_RTL; return (defaultIsRtl ? TextDirectionHeuristicsCompat.FIRSTSTRONG_RTL : TextDirectionHeuristicsCompat.FIRSTSTRONG_LTR).isRtl(text, 0, text.length()); } private void setInterpolatedTextSize(float textSize) { calculateUsingTextSize(textSize); // Use our texture if the scale isn't 1.0 mUseTexture = USE_SCALING_TEXTURE && mScale != 1f; if (mUseTexture) { // Make sure we have an expanded texture if needed ensureExpandedTexture(); } ViewCompat.postInvalidateOnAnimation(mView); } private void calculateUsingTextSize(final float textSize) { if (mText == null) return; final float collapsedWidth = mCollapsedBounds.width(); final float expandedWidth = mExpandedBounds.width(); final float availableWidth; final float newTextSize; boolean updateDrawText = false; if (isClose(textSize, mCollapsedTextSize)) { newTextSize = mCollapsedTextSize; mScale = 1f; if (mCurrentTypeface != mCollapsedTypeface) { mCurrentTypeface = mCollapsedTypeface; updateDrawText = true; } availableWidth = collapsedWidth; } else { newTextSize = mExpandedTextSize; if (mCurrentTypeface != mExpandedTypeface) { mCurrentTypeface = mExpandedTypeface; updateDrawText = true; } if (isClose(textSize, mExpandedTextSize)) { // If we're close to the expanded text size, snap to it and use a scale of 1 mScale = 1f; } else { // Else, we'll scale down from the expanded text size mScale = textSize / mExpandedTextSize; } final float textSizeRatio = mCollapsedTextSize / mExpandedTextSize; // This is the size of the expanded bounds when it is scaled to match the // collapsed text size final float scaledDownWidth = expandedWidth * textSizeRatio; if (scaledDownWidth > collapsedWidth) { // If the scaled down size is larger than the actual collapsed width, we need to // cap the available width so that when the expanded text scales down, it matches // the collapsed width availableWidth = Math.min(collapsedWidth / textSizeRatio, expandedWidth); } else { // Otherwise we'll just use the expanded width availableWidth = expandedWidth; } } if (availableWidth > 0) { updateDrawText = (mCurrentTextSize != newTextSize) \|\| mBoundsChanged \|\| updateDrawText; mCurrentTextSize = newTextSize; mBoundsChanged = false; } if (mTextToDraw == null \|\| updateDrawText) { mTextPaint.setTextSize(mCurrentTextSize); mTextPaint.setTypeface(mCurrentTypeface); // Use linear text scaling if we're scaling the canvas mTextPaint.setLinearText(mScale != 1f); // If we don't currently have text to draw, or the text size has changed, ellipsize... final CharSequence title = TextUtils.ellipsize(mText, mTextPaint, availableWidth, TextUtils.TruncateAt.END); if (!TextUtils.equals(title, mTextToDraw)) { mTextToDraw = title; mIsRtl = calculateIsRtl(mTextToDraw); } } } private void ensureExpandedTexture() { if (mExpandedTitleTexture != null \|\| mExpandedBounds.isEmpty() \|\| TextUtils.isEmpty(mTextToDraw)) { return; } calculateOffsets(0f); mTextureAscent = mTextPaint.ascent(); mTextureDescent = mTextPaint.descent(); final int w = Math.round(mTextPaint.measureText(mTextToDraw, 0, mTextToDraw.length())); final int h = Math.round(mTextureDescent - mTextureAscent); if (w <= 0 \|\| h <= 0) { return; // If the width or height are 0, return } mExpandedTitleTexture = Bitmap.createBitmap(w, h, Bitmap.Config.ARGB_8888); Canvas c = new Canvas(mExpandedTitleTexture); c.drawText(mTextToDraw, 0, mTextToDraw.length(), 0, h - mTextPaint.descent(), mTextPaint); if (mTexturePaint == null) { // Make sure we have a paint mTexturePaint = new Paint(Paint.ANTI_ALIAS_FLAG \| Paint.FILTER_BITMAP_FLAG); } } public void recalculate() { if (mView.getHeight() > 0 && mView.getWidth() > 0) { // If we've already been laid out, calculate everything now otherwise we'll wait // until a layout calculateBaseOffsets(); calculateCurrentOffsets(); } } /** * Set the title to display * * @param text / public void setText(CharSequence text) { if (text == null \|\| !text.equals(mText)) { mText = text; mTextToDraw = null; clearTexture(); recalculate(); } } public CharSequence getText() { return mText; } private void clearTexture() { if (mExpandedTitleTexture != null) { mExpandedTitleTexture.recycle(); mExpandedTitleTexture = null; } } /* * Returns true if {@code value} is 'close' to it's closest decimal value. Close is currently * defined as it's difference being < 0.001. / private static boolean isClose(float value, float targetValue) { return Math.abs(value - targetValue) < 0.001f; } ColorStateList getExpandedTextColor() { return mExpandedTextColor; } ColorStateList getCollapsedTextColor() { return mCollapsedTextColor; } /* * Blend {@code color1} and {@code color2} using the given ratio. * * @param ratio of which to blend. 0.0 will return {@code color1}, 0.5 will give an even blend, * 1.0 will return {@code color2}. / private static int blendColors(int color1, int color2, float ratio) { final float inverseRatio = 1f - ratio; float a = (Color.alpha(color1) inverseRatio) + (Color.alpha(color2) * ratio); float r = (Color.red(color1) * inverseRatio) + (Color.red(color2) * ratio); float g = (Color.green(color1) * inverseRatio) + (Color.green(color2) * ratio); float b = (Color.blue(color1) * inverseRatio) + (Color.blue(color2) * ratio); return Color.argb((int) a, (int) r, (int) g, (int) b); } private static float lerp(float startValue, float endValue, float fraction, Interpolator interpolator) { if (interpolator != null) { fraction = interpolator.getInterpolation(fraction); } return startValue + Math.round(fraction * (endValue - startValue)); } private static boolean rectEquals(Rect r, int left, int top, int right, int bottom) { return !(r.left != left \|\| r.top != top \|\| r.right != right \|\| r.bottom != bottom); } }	{ "pile_set_name": "Github" }
March 5, 2020 Looking for a whole new experience in her beloved long-running career, Paramore wonder woman Hayley Williams has just announced her first-ever solo tour in support of her latest project Petals…	{ "pile_set_name": "Pile-CC" }
The Operate of a Sand H2o Filter and Its Benefits The Operate of a Sand H2o Filter and Its Benefits A sand drinking water filter has diverse features. It is a filter made out of sand that aids to get contaminants out of water (H2O), including sand by itself and particles similar to it. They are composed of a lot of ranges of gravel and sand that in the end turn into much more fantastic. It is ironic that sand is residentialwaterfiltersystems.com/designer-faucets of the substances that the filter requires out of ingesting resources. The technological innovation used to make these products is over one hundred many years old, and the filters are more generally utilized in considerably less created nations right now. These filters are recognized for taking away reliable particles out of drinking supplies. Individuals who get their h2o from municipalities do not need these items, as town departments currently execute this operate. It is folks who get their source from a private resource, such as wells, who would get the most use out of a sand filter. If a homeowner's properly H2O supply is completely examined to be free of debris, then a sand filter would in fact be all that he or she demands. Sand filters are not constructed to clear drinking water that is tainted with small particles. These are the sorts that can not be seen in a obvious container of liquid. Other than in the situation of a organic ingesting source, this kind of filter would need to be used in conjunction with an additional a single. In a good deal of cases, the second filter also wants to get out particulates, which are tiny particles not visible to the human eye. One of the ideal employs of a sand filter is for a swimming pool. They are a great deal less costly than cartridge filters are. Even so, while some money will be saved when the initial acquire of the filter is manufactured, getting a sand filter can really effectively result in a greater monthly bill for h2o every month. This is because it normally takes much more H2O to clear and clean these kinds of a filter than it would in any other case. For property owners with pools which are around trees, a sand filter is their greatest wager. The dirt from the surrounding area can far more very easily block up cartridge filters. This would call for cleansing the filters a handful of times every week, which can get the two wearisome and costly right after a although. In summary, sand filters have been all around for over a century. They are perfect for filtering out contaminants from wells and swimming pools, although they can guide to bigger H2O bills the place pools are involved.	{ "pile_set_name": "Pile-CC" }
Three weeks on the picket line will either weaken a strike or make it stronger. But workers at the Marriott hotels in eight cities around the US show no signs of wanting to go back to work anytime soon, at least not without resolving the reasons why they went on strike to begin with. Instead, the noise on the picket line is getting louder. Workers bang on pots, drums -- even old folding chairs -- making a racket loud enough to penetrate thick walls and double-paned windows. As a result, many hotel guests not dissuaded by their initial encounters with picketing workers are giving up and leaving.“Over 20 guests have told me they’re checking out and moving to the Waterfront Hotel,” said Kenneth Walker, the veteran head doorman at the Marriott City Center Hotel in Oakland, California. The Waterfront Hotel, just a dozen blocks down Broadway, is not on strike.It’s not just happening in Oakland. The San Francisco Chronicle’s Roland Li reports that organizers of the 2018 ComNet conference (a network of foundations and non-profits discussing better communications), which normally draws 1,000 attendees, moved their events out of the struck St. Francis Hotel. The St. Francis used to be a Westin property, but became part of the 700-hotel Marriott empire when Westin was bought out by what is now the world’s largest hotel chain.Other organizations pulling out of commitments at the Bay Area Marriotts include the Human Rights Campaign, the Shanti Project, the Chicana Latina Foundation and Bay Area Wilderness Training. In response, a huge wave of robocalls is hitting thousands of people in the region, trying to lure them into the Marriotts with offers of special deals. However, not everyone is avoiding the hotels where workers are on strike. For instance, in Boston, the New York Yankees and Los Angeles Dodgers did not cancel hotel reservations for their baseball teams. Instead, ballplayers, themselves members of a union, snuck into the rear entrances of struck hotels as workers yelled questions to them about their apparent lack of solidarity.To get Marriott’s directors to pay attention to the union’s demands, the picket lines have been augmented by street actions and marches. Forty-one hotel strikers and supporters were arrested on October 12 for sitting on Fourth Street in front of Marriott’s San Francisco flagship, the Marquis The slogan underlines the main demand by Unite Here in negotiations -- enough pay so that workers don’t have to work a second job in order to survive. While Unite Here locals in each city holds bargaining talks for the hotels located there, the strike has coordinated actions by more than 7,700 workers in San Francisco, Oakland, San Jose, San Diego, Detroit, Boston, Maui and Honolulu. Seattle Marriott workers have also voted to authorize a strike.Local 2’s strategy, helping workers organize in the middle of a strike, contradicts accepted wisdom among some organizers, who fear managers will use strike threats to discourage workers from union support. Local 2 organizers say their experience is the opposite -- that the strike shows that the union is willing and able to fight for improvements against their employer.In Oakland, Marriott workers are experiencing their first strike. At the beginning, they were unsure if the rest of the workers would support them, even though the strike vote was 98 percent in favor. “We weren’t really prepared for this on the first day,” said Tony Scott, a bellman for 35 years. Lee adds, “I came to work on Friday [October] 5th, and when it was time, I went in and told my coworkers to come out. I wasn’t sure they would. When they all did, I felt I was 10 feet tall.” Striking workers and supporters sit down in Fourth Street in San Francisco in an act of civil disobedience to dramatize the impact of the strike against Marriott hotels. Strikers sit in outside the flagship Marriott on Fourth Street in San Francisco. Anand Singh, president of Unitehere Local 2, is arrested.	{ "pile_set_name": "Pile-CC" }
Red, Yellow, and Blue, by Orly Genger, at Madison Square Park in New York From Antony Gormley’s 31 cast-iron figures ominously looming over Madison Square Park in 2010 to Leo Villareal’s LED-infused Buckyball sculpture flashing 16 million colors this past winter, the Mad. Sq. Art program consistently delivers the most cutting-edge public-art offerings in the country. This summer New York–based artist Orly Genger will install Red, Yellow, and Blue, three expansive undulating walls of painted hand-knotted nautical rope. (The artist employed enough rope to span the length of the island of Manhattan nearly 20 times over.) The piece is a nod to Barnett Newman’s “Who’s Afraid of Red, Yellow, and Blue” (1966–70), a series of four vibrantly colored paintings, two of which were vandalized at exhibitions. William Turnbull exhibition, at Chatsworth in Derbyshire, England Before the Scottish sculptor William Turnbull died last November, at the age of 90, he had been approached by the Duke and Duchess of Devonshire about doing a show at Chatsworth, their Derbyshire, England, estate. “Bill was still in very good health, so we had no idea it would become a posthumous exhibition,” says his son Alex Turnbull, who helped curate the exhibition with Yorkshire Sculpture Park’s Clare Lilley and Peter Murray. The show is a cross section of the artist’s six-decade career, including early figures and totems and a selection of steel works from the mid-1960s, as well as some of the elder Turnbull’s more refined later sculptures. “Chatsworth House and its grounds are a challenging space to curate, due to their sheer scale,” Alex says. While monumental pieces like Large Blade Venus and Horse are set in front of the Baroque palace, Lilley and Murray made use of less frequently traveled sites on the property as well, so they could be “chanced upon or discovered, almost like a journey,” Alex explains. “I’ve seen the work displayed in a variety of settings, but it was very satisfying to see it in such a grand environment.” The Shed, by Haworth Tompkins, at the National Theatre of Great Britain in London As part of its more than $100 million redevelopment program, London’s National Theatre tapped local firm Haworth Tompkins Architects to develop a temporary structure, dubbed the Shed, to replace the closed Cottesloe Theatre, which the firm is currently redesigning. “It was a way for [the theatre company] to play with new kinds of work and to do shorter runs,” says the firm’s lead architect, Paddy Dillon. The award-winning indie musical Mission Drift will take place in the venue from June 5 through 28, and British electronic-music pioneer Matthew Herbert will perform The Hush there in July. The 250-seat wood box is composed of rough-sawn boards, and its four chimneys naturally ventilate the inside with help from grates under the stage. As for the exterior’s high-wattage hue, Dillon explains, “It’s a festival building, and it’s somehow painting the town red.” Mobile Homestead, by Mike Kelley, at the Museum of Contemporary Art Detroit Before his untimely death 16 months ago, Detroit native Mike Kelley was one of the most successful artists living in Los Angeles, but in many ways his work always reflected his Motor City roots. “A lot of his art came out of growing up here—it was kind of a love-hate relationship,” says Museum of Contemporary Art Detroit founding director Marsha Miro. Kelley’s installation Mobile Homestead, an exact replica of the artist’s childhood home in Westland, Michigan, will serve as a visitors center and library on the museum’s campus. The sculpture comprises a movable section that will travel to local schools and a permanent (and private) portion that will also include subterranean work spaces for visiting artists. “There are no windows, no doors, the ceiling heights are all different—I think the idea of working in this strange space is what interested Mike, and I think it’ll interest a lot of other artists,” Miro says. “Who knows what they’ll do?” Serpentine Gallery Pavilion 2013, by Sou Fujimoto Architects in London At 41, Sou Fujimoto is the youngest architect ever invited to design a temporary structure for the annual pavilion at Kensington Garden’s Serpentine Gallery, which in previous years has served as a canvas for such top-notch names as Toyo Ito, Frank Gehry, and Zaha Hadid, who received the inaugural commission in 2000. The Japanese-born Fujimoto, celebrated for his bright, organically inspired structures—including his all-white, en-plein-air House N and the bookshelf-lined Musashino Art University Museum & Library, both in Japan—has chosen an even lighter approach for his 3,800-square-foot latticelike pavilion. Devised of .79-inch-thick white steel poles, the semitransparent installation will include a café and multilevel terraces for extra seating, which, Fujimoto explains, will allow visitors to stay dry while being “suspended in space.” He, by Bam!, at MAXXI in Rome MAXXI, Rome’s National Museum of the 21st Century Arts, is going kinetic. The Turin-based architecture collaborative Bam! (Bottega di Architettura Metropolitana) designed the installation He, an almost 30-foot-tall semitransparent helium-filled yellow balloon that will hover above the museum’s piazza, moving according to the wind and casting a shadow on the grounds. “The Maxxi is a massive structure, so we wanted to respond to that massiveness with something light, and also to create contrast with the surface of the concrete walls,” says Bam! spokesperson Simona Della Rocca. During the day, water will pour down the installation, producing a refreshing oasis on the 1,300-square-foot wood platform below, while at night the piece will be illuminated like a giant floating lantern. “Using shape, water, and volume, we’re making something that will interact like a person,” says Della Rocca. "Thomas Houseago: As I Went Out One Morning" at Storm King Art Center in Mountainville, New York Spread over 500 wooded acres along the lower Hudson Valley, the Storm King Art Center in Mountainville, New York, counts more than 100 outdoor sculptures from art icons like Louise Bourgeois, Donald Judd, and Richard Serra among its collection. This season, Los Angeles–based sculptor Thomas Houseago, best known for his raw, lo-fi representational pieces made of plaster, delivers his first large-scale exhibition in the U.S. to date, featuring 11 sculptures that trace his outdoor works from 2007 to 2013. "I think it'll be interesting for people to see his relationship with modernism, because at Storm King he'll be positioned with Calders in the background," says the center's associate curator Nora Lawrence, noting that Houseago's eight-foot-tall owl was given a black-green patina in tribute to a David Smith piece on the grounds. Elsewhere, thronelike chairs made from rebar, hemp, and plaster dot the lush landscape. Designed to weather, they're also meant for sitting on, says Lawrence: "So make use of them." The City is Wilder than You Think..., by Robert Montgomery, in Berlin Scottish artist Robert Montgomery is best known for his overtly political billboards—recent projects include pieces in support of the Occupy movement and the Stop the War Coalition campaign—which makes the artist’s latest installation in Berlin something of a departure. “I usually do work that’s against something, but this is more positive,” Montgomery says of The City Is Wilder Than You Think and Kinder Than You Think (Recycled Sunlight Poem), 2011, a nearly ten-by-20-foot LED sign located in a city section known as the Holzmarkt and overlooking the space that once housed the legendary underground club Bar 25. “I want to celebrate this city—Berlin is a place of healing and regeneration and creativity. The work is about the way the city is at once an outdoor and indoor space, both a landscape and a house, and that feeling of it being a place where all are protected against the wild.” Party Wall, by Caroline O’Donnell, at MoMA PS1 in Long Island City, New York After taking into account seating, shade, and water—the key considerations for MoMA PS1’s annual Young Architects Program series of competitions—Ithaca, New York–based designer Caroline O’Donnell of CODA decided to turn things upside down—literally. “We took a canopy and rotated it 90 degrees,” says O’Donnell, whose winning design, Party Wall, a canted word-based structure consisting of wood cutouts donated by an eco-friendly skateboard company, is meant to echo the graffiti and billboards found throughout Long Island City. O’Donnell also managed to include a misting station, removable benches, a cinema screen, and platforms for catwalks, lectures, and even a wedding (the nuptials will be between O’Donnell’s project leader and a team member, who got engaged during the competition). “One of the really fun things is that people wonder if it says something,” remarks O’Donnell. Spoiler alert: At the right time of day, the structure casts a shadow on the ground that spells out, appropriately enough, wall. Mark’s House, by Two Islands, in Flint, MI Flint, Michigan, has the unfortunate distinction of being both an epicenter of the American housing crisis and the most dangerous city in the U.S., so the town could use something to cheer about this summer. Cue Mark’s House, winner of Flint Public Art Project’s inaugural “Flat Lot” design-build competition. Dreamed up by the London-based design collaborative Two Islands, the mirrored Tudor-style abode—which appears to float above a downtown parking lot—represents the foreclosed home of fictional Michigander Mark Hamilton. “It highlights the footprint of something that’s somehow left you, but it’s temporal, ethereal,” Two Islands partner William Villalobos says of the firm’s first realized project. “And that’s the feeling you get when you lose a house full of memories.”	{ "pile_set_name": "Pile-CC" }
Optic nerve head parameters of an indigenous population living within Central Australia. Clinical examination of the optic disc is an essential element in the assessment of its health. Previous work has described normal optic disc appearance among different races. No such description of optic discs exists for indigenous Australians, who are at low risk of developing glaucoma. This study was designed to evaluate optic disc parameters of indigenous Australians. A sample of 208 indigenous Australians were recruited as they presented to remote clinics in Central Australia. Each subject underwent optic disc photography using a Topcon TRC-NW100 digital fundus camera. Optic discs were measured and analysed with Topcon ImageNet 2000 software. Among other parameters, mean vertical disc diameter and disc area were 2.13 +/- 0.21 mm (mean +/- SD) and 3.13 +/- 0.57 mm2, respectively, for right eyes and 2.14 +/- 0.21 mm and 3.16 +/- 0.58 mm2 for left eyes. When compared with published studies, these parameters were significantly larger than Caucasians, but similar to African individuals. Our results suggest that indigenous Australians have optic discs that are larger than those of Caucasians, but similar to those of Africans who are considered to at a greater risk of glaucoma. Factors other than optic disc area are likely to underlie the higher prevalence of primary open angle glaucoma among African individuals.	{ "pile_set_name": "PubMed Abstracts" }
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Ronn Torossian, CEO of 5WPR on Facebook IPO & PR May 24, 2012 It’s not so much the banks taking the beating as the social network. Ronn Torossian, the chief executive of 5WPR, said in an email to Portfolio.com that the company’s IPO disaster could have a long-term impact on its business. “From minute one of a delayed launch with Nasdaq’s technical problems to the lawsuits swirling around, Facebook is entering a danger zone,” Torossian said. Facebook, more than, say, a manufacturing company, is dependent upon the goodwill of the public to build its business, since what it’s selling the public is a positive experience on its service, Torossian argued. And so far, it’s failing the crucial public relations test, he said. If Zuckerberg and his team think they can go heads down and hack their way out of the PR crisis, they’ve got another thing coming. “Mark Zuckerberg-buy a suit!” Torossian said. “This is the big leagues, and your hoodies don’t work when you are talking about billions of dollars. Wall Street demands respect, and while individual style may be less formal, a hoodie is simply too much. Grow up, Mark! Clear, transparent communication is needed-and Facebook needs to positively communicate any good things.”	{ "pile_set_name": "Pile-CC" }
--- title: I.Assert.Text link: Text --- Assert that an element matching selector has the specified text. Works with any DOM element that has `innerHTML` or can provides its contents/value via text. Supports anonymous functions that return `true` or `false`. ```csharp // Header tag set to FluentAutomation I.Assert.Text("FluentAutomation").In("header"); // Content longer than 50 characters I.Assert.Text((text) => text.Length > 50).In("#content"); ``` ```vbnet // TODO - Visual Basic Code Sample ```	{ "pile_set_name": "Github" }
Welcome to Bimmerfest -- The #1 Online Community for BMW related information! Please enjoy the discussion forums below and share your experiences with the 200,000 current, new and past BMW owners. The forums are broken out by car model and into other special interest sections such as BMW European Delivery and a special forum to voice your questions to the many BMW dealers on the site to assist our members! I definitely agree with KAOSINLA...It's apples and oranges.. Corvette......500ish HP V8 ...... "Hint" "Hint" BMW Other than the obvious, by choosing the Z06, I would be loosing out on refinement, like a smooth running engine(even after a hard run), good closing doors, leather that doesn't crack within a year, an alternator that last past a year, no unnecessary road noise levels, cheesy chicken**** interior plastic that creaks and cracks...oh and a warning chime that will never shut up when my keys are in the ignition and/or lights are on..."you cannot program the thing to shut up!!!!" and the discomfort of high speed oversteer...... But the car does good numbers, and even though I have yet to drive the "brand new" Z06...I'll give it, the "Fun Factor" choice... apart from fun though..A true POS... You definitely lose out on refinement with the Corvette, but I've never had cracking of leather or any engine problems. Definitely higher road noise and cheaper plastic dash materials, but I never had a chime with the ignition because it's a push button start ( no keys ) Now, my above post was based on the C6 Z51.....The new Z06 will eclipse anything BMW has to offer. First, the M3 is an SMG, while the Vette is a 6 spd. No mods on either. In my opinion, the Vette wins hands down in acceleration and handling. My 0-60's are always in the 4.2's. I was able to get a 4.194 once, but think consistent 4.1's won't be a problem accomplishing once I trade out the Goodyead SC RF's. In handling, I have a much higher entrance speed and better exit power while still feeling comfortable steering and g reaction. Mistakes are correctable, but with the M3 the limitations are very noticeable and mistakes aren't easily correctable. Also, I found that the M3 has a considerable climbing lag at 125+, while the C6 is consistent through 170+. The last 16+ are really the only time I've felt the CD, but feel it very early on with the M3. I love my M3, but I consider it a sports coupe, while I consider the C6 a sportscar. It's all a matter of what your looking for. I once saw a guy driving on the street here in a pretty new M3. The street was heading off to end in what looks like a " T ". The guy tried to power slide and turn left, he ended up smashing directly into the barrier and wall. I was behind him in my VW R32. I could see that he had a very difficult time trying to correct . The guy came out really upset. The whole front end of the car was gone not to mention a good portion of the side. I know I could have taken that turn that he took with another 10-15 MPH on top of that easily in my R32. I felt sorry for him. Was a beautiful looking M3. How tall are you? You might fit better in an M3 rather than in a Vette. I had the same dilemma, and I chose the 325 conv. over the vette conv. I could barely squeeze in the vette, and then my buddy told me I looked funny in there, like I was driving a toy-car. I feel much more comfy in the Bimmer conv. although I once got a coupe loaner and my head was touching the moonroof lip. Are those times around the ring all by the same driver, I doubt it. The air temps and weather conditions make a big difference as well. This horsepower race will have to end at some point, I mean who needs over 400 HP for the street? No, those aren't by the same driver (drivers are usually designated per mfr.), but that would be the luckiest person in the world if it was!!! The temps and weather play a vital role in these times, but the mfr decides to stop when satisfied and can return at any point to best the times. In regards to HP war, yes, eventually, it will peak.....But, street is the key term....Personally, I like to have a street car that I can track too.... The New Subaru WRX STI which was just released in Japan is supposed to go around the track in Germany in under 8 minutes as well. Some where around 7.52 or so. That is not bad for an untuned car that is stock. That is running with a GT2 The New Subaru WRX STI which was just released in Japan is supposed to go around the track in Germany in under 8 minutes as well. Some where around 7.52 or so. That is not bad for an untuned car that is stock. That is running with a GT2 Is that the 2.0 version? I've noticed they made a lot of improvements for the USDM STi in the past 2 model years. I've been thinking about keeping my 330i and getting one again as a fun car. I used to have an 04, and while it was good I thought it could be better, I sold it and got the 330i. This horsepower race will have to end at some point, I mean who needs over 400 HP for the street? It has already ended in the states, many of years ago...It's Europe, that's now getting into the HP race..All along they have been concerned with making well designed vehicles that are economical to compensate for high fuel prices..With the exception of the Italians in which everyone drives 50+ mpg scooters, and only the riches of the rich drive Ferrari's and Lambo's..But now Euro car manufacturers' are taking on the American muscle genre in a different, more refined way...I hate to say it, but Japanese and Euro car manufacturers have always been ahead of the game as compared to U.S. car makers..in which are solely out to make profit instead of competing with the rest of the world..Make cars/trucks cheaply, sell plenty.. How many piss on BMW/Merc/Porsche stickers do you see on the streets? I do have to say that I'm somewhat impressed by GM and their LS7.. 7.0 Liter displacement, CNC??(variable valve timing, I guess), and dry sump oil system... It has already ended in the states, many of years ago...It's Europe, that's now getting into the HP race..All along they have been concerned with making well designed vehicles that are economical to compensate for high fuel prices..With the exception of the Italians in which everyone drives 50+ mpg scooters, and only the riches of the rich drive Ferrari's and Lambo's..But now Euro car manufacturers' are taking on the American muscle genre in a different, more refined way...I hate to say it, but Japanese and Euro car manufacturers have always been ahead of the game as compared to U.S. car makers..in which are solely out to make profit instead of competing with the rest of the world..Make cars/trucks cheaply, sell plenty.. How many piss on BMW/Merc/Porsche stickers do you see on the streets? I do have to say that I'm somewhat impressed by GM and their LS7.. 7.0 Liter displacement, CNC??(variable valve timing, I guess), and dry sump oil system... Why do you think it has ended here with cars like the Mustang GT500(450 HP est.) in the pipeline? Is that the 2.0 version? I've noticed they made a lot of improvements for the USDM STi in the past 2 model years. I've been thinking about keeping my 330i and getting one again as a fun car. I used to have an 04, and while it was good I thought it could be better, I sold it and got the 330i. Will have to double check. In the Japanese magazine they claim Torque at 43Kg.. I don't know they use that KG. Stuff. But I do know that 43 is quite high. If they brought that new STI into Taiwan my VW R32would be sold over night for one of those Babies. I never cared for an Aerican car in my life but I would buy a new Vette as a secondary car to cruise around in. WOuld be nice in california with the Targa Top off and 400 Horses on Tap, along with a nice navigation system and Leather. That cars gets looks every where it goes. For the Money, it is a heck of a car. I doubt one would look at $100K car and not bother having second looks at the Vette. Can pocket the other 30-40K in Savings and go travelling. With 30-40K one can hit a lot of Red Light Districts around the world Why do you think it has ended here with cars like the Mustang GT500(450 HP est.) in the pipeline? Ricer genre?? I think what I was mainly getting at is that domestic car makers are now shooting for more refinement and becoming of age...Whereas overseas have been there and are still keeping ahead of the GM/Ford..etc..More so, technology is advancing over time and you may notice that engine displacments have decreased since the 50-60's where the goats, chargers, mustangs, and camaros were battling the HP race..We have already seen 400+ hp production cars and trucks..And the HP has decreased, now their sales gimick is that this model has the most HP in it's class..From year to year, they(GM, Ford, Mopar) compete over small incriments of HP..Why not blow the competition out of the water... I think in terms of sales...a better MPG number on a window sticker, will outweight any high output engine performance number... Take an M3, you'll get it all.. refinement, good fuel economy for the performance, a usable rear seat, and just an all out fun car to drive... fun factor= Corvette smart buy factor= M3 But this comarison is two different class of car...	{ "pile_set_name": "Pile-CC" }
Cinedelphia Top 10’s of 2013 – Part 2 One of my favorite exercises of the year is creating my annual top ten list, but here are some “rules” before sharing everyone’s list: 1. This is just a list of each person’s favorite movies from the year. Because there is no such thing as “best.”2. Unfortunately, we did not see every movie that came out this year, including movies that could have very easily made our top ten lists.3. The lists might be different if we wrote them up tomorrow. My point is that Top 10 lists say more about the author/publication’s opinions than anything else, as you likely already realize, though some lose sight of this fact when presented with a list from a so-called expert on the subject. Let’s take a look at a range of Top 10 lists from Cinedelphia.com contributors of various ages and cinematic tastes… Ryan Silberstein Frances HaThis Greta Gerwig-Noah Baumbach collaboration is easily the film I connected with most in 2013. I swear it only has something to do with the fact that Frances and I are the same age, and that I finally feel like Frances at the end of the film. It’s not that I have everything figured out, but I’m on my way. It’s a powerful feeling, and I don’t think there is any other film that captures that feeling for my generation. The cinematography, and French New Wave stylings serve a story function as well, mixing the way Frances wants to see New York, but allowing enough realism to break through and communicate the real emotions underneath the day to day denial. I don’t want to make Fances Ha out to be a serious film, so much as an honest look that is unafraid to laugh with (and at) its protagonist when the occasion calls for it. Inside Llewelyn DavisFrom my review: There isn’t a strong plot, but the film doesn’t suffer from a slow pace or vignette feel. It’s not that each incident in the film seems like it has a monumental effect on Davis’ life, rather like a folk song, it reveals something about our perception of the man. It also helps that I’ve listened to the soundtrack for this a few dozen times. The World’s EndI have to admit, the first time I saw the third installment in the Cornetto Trilogy, I was a tad underwhelmed in comparing the film to Shaun of the Dead and Hot Fuzz, but after watching a couple more times, I have come to love it in a different way from the first two films. While those films explore male friendship and adulthood in a fairly straightforward way, The World’s End is much more about addiction and adjusting to middle age. It may be harder for me to relate at this point in my life, but Simon Pegg’s performance as Gary King is so layered that it just took time for me to “get” it. Another masterful film from him, Nick Frost, and director Edgar Wright. StokerA family horror/psychological thriller, Stoker is masterfully directed by Chan-wook Park. Never subtle, but often still, the film lives in the between moments just as much as the moments of intensity themselves. Wonderfully creepy in various ways, Stoker is a film that stuck with me weeks after seeing it the first time. GravityFrom my review: Gravity showcases Cuarón’s technical mastery and keen visual eye, but the performances of its small cast are just as vital…It’s not so much that Gravity is a deep film, it doesn’t have to be. But the humanity is the focus here, on the edge of where we live. It’s a simple concept wonderfully executed. This Is the EndI liked This Is the End the first time I saw it, thinking it was a clever premise with some great laughs. Seeing it a few times since then has made me appreciate the film all the more. The combination of the heightened personas of these celebrities and the high concept apocalyptic scenario makes this equal parts funny and clever. Pacific Rim If film can succeed purely on spectacle, Pacific Rim is as close as it gets. Even as a fan, I would describe the story as perfunctory, a means to an end. But what an end it is! A loving tribute to monster films and gigantic action of all kinds, Pacific Rim is a perfect Saturday film, put it on and forget the world for two hours. Short Term 12Bree Larson in the breakout role of the year, but everything about this film works so well.From my review:Short Term 12 is in part a dramatic exploration of the kind of person attracted to working with at-risk teens, and moreover that the mental hardships from abuse aren’t something that can be cured. The mental scars are there, and while not visible with the naked eye, can have longer lasting damage than the physical ones. NebraskaLike other Alexander Payne films, Nebraska deftly mixes the sweet and the sour, all against the backdrop of the upper Midwest. Anchored by Bruce Dern and Will Forte, the film features great performances from the supporting cast as well, especially June Squibb. It also operates in the same kind of heightened reality as Sideways and The Descendants, illuminating those little moments of life in the most entertaining way possible. Also, there are few things as bleak as the upper Plains in black and white. The Bling RingThere are two simple reasons this film made it onto this list. Firstly, Emma Watson’s performance is dynamic and engaging, and works on a meta level. It’s truly a performance of someone giving a performance, and the entire film’s subversiveness might be rooted in it. The second reason is the wide shot when the burglars ransack the modern glass home of Audrina Patridge. The entire robbery takes place in one long take, the entire house in frame, with the audience witnessing the robbery. Patridge left the curtains open and lights on, making the audience the voyeurs watching the fame hungry gang. J.T. Alvarez 2013 has been a heck of a year. Here’s what I liked…nay, LOVED. Inside Llewelyn Davis While still not my favorite Coen Brothers movie, this was easily my favorite movie of the entire year. So perfectly cast and beautifully shot, it has signature Coen Brothers elements while still remaining fresh and new. The World’s EndThe third installment of the Cornetto Trilogy, I will simply love anything that these Spaced alumni put out. MudExtra points for this movie being made by the brother of the lead singer from Lucero. Also, McConaughey. The ConjuringI can’t remember the last time before this movie that I was so honestly frightened. Place Beyond The PinesSuch a tragic tale, told in such a manner that tenderly handled the victims plight while still showing their cursed roles in their own sad fates. This Is The End Easily, the best use of Whitney Houston’s “I Will Always Love You” in any movie ever made. NebraskaHeart wrenching and lush, even in black and white, this movie probably had my favorite ending of the year. Pacific RimIf you don’t enjoy huge monsters coming out of the sea and fighting huge robots, then you probably don’t enjoy fun. Heavy handed sketchy racial undertones notwithstanding, a huge robot had a huge sword in it and used it to hack apart a huge monster. Total win. Stoker Chan-Wook Park’s offering this year was tension filled and off-putting, but in all of the best ways. The Dallas Buyers ClubCan 2013 be known as “The Year of McConaughey?” Jill Malcolm I feel like I may be in the minority here, but 2013 just did not do it for me. I wasn’t excited about anything (except Hunger Games) and after the dust seems to be settling around this most recent awards season sprint, I feel even more underwhelmed. It was really difficult for me to even cull the list I put together, because even though I like (and in some cases love) these movies, I also know they don’t really stack up against my favorites from previous years. But here we are. If I had to pick a theme for my list it would be “Dark.” Very dark. Dark comedies, gothic horror, quarter/mid-life crises, kids in rough situations, this list (in no particular order) is a giant decaying heart of despair, but in a good way. Enjoy? August: Osage CountyMan, is this film bleak. There’s very little to redeem any of the characters in August: Osage County, least of all the grande dame herself, played by Meryl Streep. The film is caustic, loud, angry, and absolutely hilarious. If you don’t like black comedy, I can’t see this film resonating with you. And that may be the downside to this adaptation from the original playright author Tracey Letts. I can imagine this story working much better as a play, and will admit that as much as I loved this movie, its jump to the big screen poses some problems. Namely, the melodrama that imbues every frame becomes overwhelming at times, as does the seemingly endless amounts of twists and turns this family goes through. I mean there’s only so much “messed up” a family can be all at one time right? But like any good family train wreck, it’s impossible to look away. NebraskaNot much to say here, other than Alexander Payne’s story of memory, family, and what it means to “go home again” has some of the best performances of the year. (My review) StokerHaving never seen a Park film prior to Stoker, there was a large possibility of me coming out of this film bewildered by the experience. Quite the contrary. I love morbid, I love goth, I love creepy fantastical humans that may or may not be supernatural and Stoker fits the bill all around. It’s a film that got me thinking about the role of family within the eternal struggle of nature vs. nurture. (My review) Pain & GainThere is a scene in this movie of Dwayne Johnson’s character roasting the fingerprints off of some freshly severed hands on a barbeque. I couldn’t write this if I tried, and neither could filmmaker Michael Bay or screenwriters Christopher markus and Stephen McFeely. It’s made abundantly clear on screen that this moment in the film is in fact based on real actions by some really dumb criminals. This film is about absurdity and living an American Dream that is quickly becoming a nightmare. The main characters played by Dwayne Johnson, Mark Wahlberg, and Anthony Mackie are pure comedic perfection. Yup, this is a comedy, and a damn good one. Let it be known across the land that I love a Michael Bay movie. (my review) Short Term 12A film about the hardships of the foster care systems as told through the eyes of a predominately young cast. It speaks volumes of truth and features some of the best intimate moments between characters onscreen I’ve seen in quite some time. For the first six months of the year, I lived in Oberlin, Ohio, a small town with one theater that predominantly screened blockbusters. And then I moved to Philadelphia and spent the next six months trying to figure out my life here which didn’t lend itself to a lot of recreational outings. Needless to say, it was not a great year for film and I and many of the films I did see left me with lukewarm feelings. Thus, for a variety of reasons, this will be a list of five. Frances Ha Blue Jasmine Inside Llewyln Davis Spring Breakers Philomena Eric Bresler I haven’t seen nearly enough films this past year to come up with a respectable Top 10 list so instead I’ll run down my10 MOST MEMORABLE MOVIE-RELATED EXPERIENCES OF 2013 10. THE CONJURING at ArcLight Hollywood – The Conjuring is my pick for best horror film of 2013, I really like that ghosthunting couple. The ArcLight was having an exhibition of drive-in/exploitation movie posters at the time, which was just as memorable as the film. 9. INVASION OF THE BODY SNATCHERS (1978) at New Beverly – This was screened as part of an Edgar Wright-curated series tied into the release of THE WORLD’S END. Didn’t really care for that film, but Body Snatchers is one of the greats. 8. Paul Lynde Halloween Special (1976) at PhilaMOCA – I closed out the Halloween edition of Video Party with a surprise screening of one of the most difficult to watch television variety shows of all-time, really only suitable for die-hard KISS or Paul Lynde fans (I’m in the latter camp). I was so impressed by the perseverance of the ten people in attendance who lasted through the whole special that I gave them free tickets to future events. It’s a real joy to share bad comedy with others. 7. KRRISH 3 at AMC Neshaminy 24 – One of my all-time favorite movie-going experiences was seeing Koi… Mil Gaya in Burlington back in 2003. Touted as Bollywood’s first major sci-fi film, Koi… was a really strange amalgamation of E.T., Close Encounters, Hoosiers, and Forrest Gump. My friend Dean and I were the only two people in the theater and we laughed for all 171 minutes. The sequel to Koi… was 2006’s Krrish, which was basically Bollywood’s first entry into the masked superhero genre. And then came this year’s Krrish 3, an uninspired take on the X-Men films that’s a ton of over-the-top fun though I still think that jumping from 1 to 3 is unnecessarily confusing. 6. SPRING BREAKERS at Ritz East – Girlfriend Carrie and I went to see this on our first date, so it’s memorable for that. I still don’t have an opinion on the film itself. 5. HEAVENLY BODIES (1984) – We watched this “Dance-ercize” film on my laptop while detained at an airport in Russia. The only food we had access to for 18 hours was a TGI Fridays. Dark times. 4. METALLICA THROUGH THE NEVER at AMC Loews Cherry Hill – I don’t know why this didn’t catch on with my fellow lovers of bizarro cinema, I was hooked as soon as I heard that it was a Metallica concert film with an interwoven fictional narrative. And it was an IMAX film! Just as engrossing as 12 Years a Slave. 3. Greg Sestero at PhilaMOCA – One of our very best events. We screened a retrospective video on THE ROOM, Greg read from his new book about the film, and he then joined audience members in an hour-long THE ROOM script reading that included pages from the original script. Really exciting stuff for the fans. Afterwards we took him to Tony Luke’s for a cheesesteak and then stopped by the Ritz at the Bourse for a surprise appearance at their midnight screening of THE ROOM. Check out some great videos of the script reading shot by Bob Sweeney here and here. 2. Everything Is Festival at the Cinefamily – Way ahead of the curve of 99% of the film festivals out there; an insane wealth of film and TV oddities and treasures. Over the course of the four days that we were able to attend we saw: Beauty Day with the director in attendance, a “best of” public access program (equally good was the Found Footage Festival public access-themed show recently held in Philly at Underground Arts), a program of weird video game highlights, Mike Judge presenting his favorite found footage clips, the brilliant Amy Fisher biopic mash-up Triple Fisher (coming soon to PhilaMOCA) with Joey Buttafuoco in attendance, and a 35mm print of the insane Bruce Leong film THE DRAGON LIVES AGAIN in which Leong plays Bruce Lee battling famous movie characters in the afterlife. 1. Cinedelphia Film Festival – C’mon, this thing was incredible! I’m still not over it. Memorable screenings that immediately come to mind were the World Premiere of VIDEO VIOLENCE: REDUX DELUXE at Viva Video with the director and writer in attendance, LIQUID SKY with a live score and the director in attendance at PhilaMOCA, and the debut of Joseph A. Gervasi’s Philly punk-centric Loud! Fast! Philly! program. But those are just three of the 40+ programs we hosted, it was all good. And yeah, we’re doing it again this coming April: CINEDELPHIA FILM FESTIVAL 2014 presented by VIDEO PIRATES. It’s gonna be crazier than last year, promise. And of course Exhumed Films’ eX-Fest and 24 Hour Horror-Thon remain the most exciting annual film events in Philadelphia. I just now realize that I didn’t go to the International House nearly enough this past year, I’ll definitely be there throughout January for the Free To Love program and on February 6 for this. And let’s acknowledge the tireless efforts of Jill and Ryan who picked up the reigns here at Cinedelphia earlier this year and guided the site towards its current state of legitimacy and productivity. They also got engaged this year…to each other! Congratulations, guys! Author: Ryan Silberstein Ryan spends his days at a company named one of the best to work for in the Philadelphia area, and his nights as a mysterious caped vigilante saving his city from the disease that is crime watching movies. He lives on a diet consisting of film, comic books, experimental beer, black coffee, and those big metal historical markers around town. Follow him on Twitter and Letterboxd.	{ "pile_set_name": "Pile-CC" }
Elements of Morals With Special Application of the Moral Law to the Duties of the Individual and of Society and the StateBy: Paul Janet (1823-1899) First Page: ELEMENTS OF MORALS: WITH SPECIAL APPLICATION OF THE MORAL LAW TO THE DUTIES OF THE INDIVIDUAL AND OF SOCIETY AND THE STATE. BY PAUL JANET, MEMBER OF THE INSTITUTE, OF THE ACADEMY OF MORAL AND POLITICAL SCIENCES, AUTHOR OF THEORY OF MORALS, HISTORY OF MORAL AND POLITICAL PHILOSOPHY, FINAL CAUSES, ETC., ETC. TRANSLATED BY MRS. C. R. CORSON. A. S. BARNES & CO., NEW YORK AND CHICAGO Copyright, 1884, by A. S. Barnes & Co. PREFACE. The Eléments de Morale , by M. Paul Janet, which we here present to the educational world, translated from the latest edition, is, of all the works of that distinguished moralist, the one best adapted to college and school purposes. Its scholarly and methodical arrangement, its clear and direct reasonings, its felicitous examples and illustrations, drawn with rare impartiality from the best ancient and modern writers, make of this study of Ethics, generally so unattractive to young students, one singularly inviting. It is a system of morals, practical rather than theoretical, setting forth man's duties and the application thereto of the moral law. Starting with Preliminary Notions , M. Janet follows these up with a general division of duties, establishes the general principles of social and individual morality, and chapter by chapter moves from duties to duties, developing each in all its ramifications with unerring clearness, decision, and completeness. Never before, perhaps, was this difficult subject brought to the comprehension of the student with more convincing certainty, and, at the same time, with more vivid and impressive illustrations. The position of M. Paul Janet is that of the religious moralist. "He supplies," says a writer in the British Quarterly Review ,[1] in a notice of his Theory of Morals , "the very element to which Mr. Sully gives so little place. He cannot conceive morals without religion. Stated shortly, his position is, that moral good is founded upon a natural and essential good, and that the domains of good and of duty are absolutely equivalent. So far he would seem to follow Kant; but he differs from Kant in denying that there are indefinite duties: every duty, he holds, is definite as to its form ; but it is either definite or indefinite as to its application. As religion is simply belief in the Divine goodness, morality must by necessity lead to religion, and is like a flowerless plant if it fail to do so. He holds with Kant that practical faith in the existence of God is the postulate of the moral law. The two things exist or fall together." This, as to M. Janet's position as a moralist; as to his manner of treating his subject, the writer adds: "... it is beyond our power to set forth, with approach to success, the admirable series of reasonings and illustrations by which his positions are established and maintained." M. Janet's signal merit is the clearness and decision which he gives to the main points of his subject, keeping them ever distinctly in view, and strengthening and supplementing them by substantial and conclusive facts, drawn from the best sources, framing, so to say, his idea in time honored and irrefutable truths. The law of duty thus made clear to the comprehension of the student, cannot fail to fix his attention; and between fixing the attention and striking root, the difference is not very great.	{ "pile_set_name": "Pile-CC" }
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Introduction {#sec0005} ============ Infections associated with breast augmentation with implants are one of the complications that frequently lead to their loss, with undesirable aesthetic consequences. The microorganisms that belong to the skin microbiota are regularly implicated in this type of infections. Staphylococcus aureus, and staphylococcal coagulase negative species are the most frequently isolated pathogens. Rarely, Gram-negative rods, mycobacteria and molds are reported \[[@bib0005],[@bib0010]\]. As part of microbiota, Cutibacterium (formerly Propionibacterium) species are associated with this type of infection, but currently, only cases of C. acnes infection have been reported \[[@bib0010]\]. We present the first case of C. avidum infection associated with breast implant augmentation. Case report {#sec0010} =========== A 50-year-old woman with a previous history of penicillin allergy, hypothyroidism, dyslipidemia and prediabetes, was admitted to the hospital with left breast pain, erythema and edema 16 days after having a mastopexy with breast implants. A single 900-mg dose of perioperative intravenously administered clindamycin was used. On examination, the patient had erythema and seropurulent drainage from the right breast surgical wound ([Figs. 1](#fig0005){ref-type="fig"}A, B), and cellulitis in the inferior quadrants of the left breast ([Fig. 1](#fig0005){ref-type="fig"}C). She had no signs of sepsis. She had operative surgical lavage of the right breast; cultures of the drainage and tissue were negative, then she received oral clindamycin 600 mg three times day. Eight days later, the patient continued with inflammatory signs and wound drainage; antimicrobials were discontinued and two days later she had repeat surgical lavage and removal of the implants. Bilateral tissue cultures were taken. Gram-positive rods were present on tissue Gram stains. Cultures grew Gram-positive bacilli identified by MALDITOF - MS as Cutibacterium avidum, no susceptibility testing were done due to lack of availability in the laboratory. The patient was treated with oral moxifloxacin 400 mg/day for seven days with complete resolution of her symptoms at one year follow-up.Fig. 1A. Erythema and swelling of the right breast. B. Seropurulent drainage through the surgical wound in the right breast. C. Cellulitis in the inferior quadrants of the left breast.Fig. 1 Discussion {#sec0015} ========== Cutibacterium avidum is a Gram-positive anaerobic rod, which belongs to the skin microbiota. It grows mainly in humid skin areas and pilosebaceous follicles of regions such as axilla, folds and perianal region \[[@bib0015]\]. Infections caused by this microorganism are usually associated to predisposing factors such as surgery, foreign bodies and malignancy. As a skin commensal, previously considered of low pathogenicity, it is now recognized as a causative organism of serious spontaneous and surgical site infections (SSI) \[[@bib0020]\]. Indeed groin colonization is a recognized risk factor for hip periprosthetic joint infection \[[@bib0025]\]. According to the literature available there have been reports of SSI after breast reduction \[[@bib0030],[@bib0035]\], post-mastectomy \[[@bib0040]\], abdominal parietoplasty \[[@bib0045]\], periprosthetic infections \[[@bib0050]\], prosthetic valve endocarditis \[[@bib0055]\], and sacroiliitis after herniorrhaphy \[[@bib0060]\]. Post-procedural infections, including splenic abscess after coronary bypass \[[@bib0065]\], and cardiac catheterization \[[@bib0070]\] have also been described in immunocompetent patients \[[@bib0075]\]. C. avidum is highly susceptible to multiple antimicrobials, including beta-lactam agents and fluoroquinolones. Clindamycin resistance has been described \[[@bib0020]\], and in our case, maybe could explain the failure of antibiotic perioperative prophylaxis and further empirical treatment, but unfortunately, we could not perform susceptibility testing. The treatment includes early surgical debridement and appropriate antibiotic therapy, and in some patients, implant removal is required to resolve the infection. Conclusion {#sec0020} ========== As a skin commensal, Cutibacterium avidum previously was considered of low pathogenicity, but is now recognized as a causative organism of serious spontaneous and surgical site infections. It should not be routinely disregarded without further investigation, particularly if clinical signs of infection are present. Declarations of interest {#sec0025} ======================== None. Compliance with ethical standards {#sec0030} ================================= This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent {#sec0035} ================ Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. Funding source {#sec0040} ============== This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ethical approval {#sec0045} ================ This report was approved by the ethics and research committees of the Institutions.	{ "pile_set_name": "PubMed Central" }
=head1 B<floorplan> =head2 SYNOPSIS NONE =head2 DESCRIPTION Provides a function to render an HTML table from the objects in the group passed as a parameter. Bugs: - Recursion is in use. Be carefull of problems with referencing the parent group from a child element. Someone could add a max_level in there to be safe. - If you overlap item co-ordinates, be carefull. I dont have Z-order checking in here either yet and can makes tables get goofy. Your table will look correct if all of your coords are correct. "Garbage in -> Garbage out" =head2 INHERITS B<NONE> =head2 METHODS =over =item B<UnDoc> =cut $^W = 0; # Avoid redefined sub msgs # Authority: anyone my $object_name = shift \|\| '$Property'; my $object = &get_object_by_name($object_name); return &html_page( 'FloorPlan', "No $object_name Group found to generate a floorplan from" ) unless $object; my $html = "<meta http-equiv='refresh' content='10;URL='>"; #$html .= "<title>Floorplan</title>"; #$html .= "Occupancy Count: " #. $om->min_count() . "<br>"; $html .= &web_fp($object); return &html_page( 'FloorPlan', $html ); sub web_fp #render table representation of objects and their co-ordinates { my ($p_obj) = @_; my @l_objs; my $l_html; my @l_fp; my ( $l_x, $l_y, $l_w, $l_h ); my ( $l_xmax, $l_ymax ) = ( -1, -1 ); my %l_rendered; my $l_obj; my $l_xscale = 12; my $l_yscale = 5; # my $l_xscale=30; # my $l_yscale=20; my $l_bcolor = '#CCCCCC'; my $l_acolor = '#00FF00'; if ( $p_obj->isa('Group') ) { @l_objs = @{ $$p_obj{members} }; for my $obj (@l_objs) { ( $l_x, $l_y, $l_w, $l_h ) = $obj->get_fp_location(); if ( $l_x ne "" ) { #Only do items with co-ordinates for ( my $h = $l_y; $h < $l_y + $l_h; $h++ ) # Create Virtual Frame Buffer of object blocks { for ( my $w = $l_x; $w < $l_x + $l_w; $w++ ) # Create Virtual Frame buffer of object blocks { $l_fp[$w][$h] = $obj; $l_xmax = $w if $l_xmax < $w; $l_ymax = $h if $l_ymax < $h; } } } } $l_html .= web_fp_item($p_obj) . "<br>"; if ( @l_objs > 0 ) { $l_html .= "<table border='0' width='" . $l_xmax * $l_xscale . "' height='" . $l_ymax * $l_yscale . "'>\n"; for ( my $x = 0; $x <= $l_xmax; $x++ ) #initialize table with (hopefully) accurate sizing { $l_html .= "<td></td>"; } for ( my $y = 0; $y <= $l_ymax; $y++ ) #Create HTML Table stucture of Virtual Frame buffer { $l_html .= "<tr>\n"; $l_html .= "\t<td width='" . $l_xscale . "' height='" . $l_yscale . "'>"; $l_html .= "</td>\n"; for ( my $x = 0; $x <= $l_xmax; $x++ ) { $l_obj = $l_fp[$x][$y]; if ( $l_obj ne "" ) { #Only do if object is at coordinates if ( $l_rendered{$l_obj} eq '' ) { $l_rendered{$l_obj} = 1; ( $l_x, $l_y, $l_w, $l_h ) = $l_obj->get_fp_location(); if ( $l_x eq '' ) { $l_x = 1; } if ( $l_y eq '' ) { $l_y = 1; } if ( $l_w eq '' ) { $l_w = 1; } if ( $l_h eq '' ) { $l_h = 1; } if ( $l_obj->isa('Group') ) { #recurse groups $l_html .= "\t<td bgcolor='$l_bcolor' width='" . $l_xscale * $l_w . "' height='" . $l_yscale * $l_h . "' colspan='$l_w' rowspan='$l_h'>"; $l_html .= web_fp($l_obj); } else { $l_html .= "\t<td bgcolor='" . web_fp_idle_color( $l_obj, $l_acolor, $l_bcolor ) . "' colspan='$l_w' rowspan='$l_h'>"; $l_html .= web_fp_item($l_obj); } $l_html .= "</td>\n"; } } else { #Blank space $l_html .= "\t<td width='" . $l_xscale . "' height='" . $l_yscale . "'>"; $l_html .= "</td>\n"; } } $l_html .= "</tr>\n"; } $l_html .= "</table>\n"; } for my $obj (@l_objs) { if ( $l_rendered{$obj} ne 1 ) { $l_html .= web_fp_item($obj); } } } else { $l_html .= web_fp_item($p_obj); } return $l_html; } sub web_fp_item #render all items based on type { my ($p_obj) = @_; my $l_html; my $l_text; my $l_state; my $l_image; # print "--$p_obj:". $p_obj->state; $l_text = $$p_obj{object_name} . ":" . $p_obj->state; if ( $p_obj->isa('Light_Item') or $p_obj->isa('Fan_Light') or $p_obj->isa('X10_Item') ) { if ( $p_obj->state eq 'off' ) { $l_image = 'fp-light-off.gif'; $l_state = 'on'; } else { $l_image = 'fp-light-on.gif'; $l_state = 'off'; } } elsif ( $p_obj->isa('Group') ) { $l_text = web_fp_filter_name( $p_obj->{object_name} ); } elsif ( $p_obj->isa('Motion_Item') ) { if ( lc( $p_obj->state ) eq 'on' ) { $l_image = 'fp-motion-on.gif'; } elsif ( $p_obj->state eq 'check' ) { $l_image = 'x.gif'; } else { $l_image = 'fp-motion-off.gif'; } } elsif ( $p_obj->isa('Door_Item') ) { if ( $p_obj->state eq 'open' ) { $l_image = 'fp-door-open.png'; } else { $l_image = 'fp-door-closed.png'; } } elsif ( $p_obj->isa('Photocell_Item') ) { if ( $p_obj->state eq 'dark' ) { $l_image = 'fp-dark-on.gif'; } elsif ( $p_obj->state eq 'check' ) { $l_image = 'x.gif'; } else { $l_image = 'fp-dark-off.gif'; } } elsif ( $p_obj->isa('Presence_Monitor') ) { if ( $p_obj->state eq 'occupied' ) { $l_image = 'fp-people.gif'; } elsif ( $p_obj->state eq 'predict' ) { $l_image = 'a1+.gif'; } else { $l_image = '1pixel.gif'; } } elsif ( $p_obj->isa('Appliance_Item') ) { # } elsif ($p_obj->isa('Camera_Item')) { # if ($p_obj->state eq 'on') { # $l_image="/usr/local/mh/web/graphics/" . web_fp_filter_name($p_obj->{object_name}) . ".gif"; # $p_obj->get_imagefile($l_image); # $l_anchor= "<a href='/bin/SUB;web_fp_camera_popup?" . $p_obj->{object_name} . "'>"; # } else { # $l_image='camera.gif'; # } } elsif ( $p_obj->isa('HVAC_Item') ) { } elsif ( $p_obj->isa('Temperature_Item') ) { $l_text = $p_obj->{object_name}; $l_text .= ':' . $p_obj->state(); } elsif ( $p_obj->isa('iButton') ) { $l_text = web_fp_filter_name( $p_obj->{object_name} ); $l_text .= ':' . $p_obj->read_temp(); } else { #Unknown object $l_text = web_fp_filter_name( $p_obj->{object_name} ); $l_text .= ':' . $p_obj->state(); } if ( $l_state ne '' ) { $l_html .= "<a href='/bin/SET;referer?" . $p_obj->{object_name} . "=$l_state'>"; } if ( $l_image ne '' ) { $l_html .= "<img src='/graphics/$l_image' border=0 alt='$l_text'>"; } else { $l_html .= "<font size='-2'>$l_text</font>"; } if ( $l_state ne '' ) { $l_html .= "</a>"; } return $l_html; } sub web_fp_idle_color #Fade color from acolor to bcolor over idle_time of object { my ( $p_object, $p_acolor, $p_bcolor, $p_maxtime ) = @_; my ( $l_ared, $l_agreen, $l_ablue ) = $p_acolor =~ /#(..)(..)(..)/; my ( $l_bred, $l_bgreen, $l_bblue ) = $p_bcolor =~ /#(..)(..)(..)/; ( $l_ared, $l_agreen, $l_ablue ) = ( hex $l_ared, hex $l_agreen, hex $l_ablue ); ( $l_bred, $l_bgreen, $l_bblue ) = ( hex $l_bred, hex $l_bgreen, hex $l_bblue ); my ( $l_red, $l_green, $l_blue ); my $l_time; # my $l_max=1060; $p_maxtime = 10 60 if !defined $p_maxtime; my $l_percent; my $l_basecolor = 40; my $l_maxcolor = 255; my $l_color; $l_time = $p_object->get_idle_time(); if ( $l_time > $p_maxtime ) { $l_time = $p_maxtime; } $l_percent = $l_time / $p_maxtime; if ( $l_ared > $l_bred ) { $l_red = int( $l_ared - ( ( $l_ared - $l_bred ) * ($l_percent) ) ); } else { $l_red = int( $l_ared + ( ( $l_bred - $l_ared ) * ($l_percent) ) ); } if ( $l_agreen > $l_bgreen ) { $l_green = int( $l_agreen - ( ( $l_agreen - $l_bgreen ) * ($l_percent) ) ); } else { $l_green = int( $l_agreen + ( ( $l_bgreen - $l_agreen ) * ($l_percent) ) ); } if ( $l_ablue > $l_bblue ) { $l_blue = int( $l_ablue - ( ( $l_ablue - $l_bblue ) * ($l_percent) ) ); } else { $l_blue = int( $l_ablue + ( ( $l_bblue - $l_ablue ) * ($l_percent) ) ); } return ( "#" . sprintf( "%02X", $l_red ) . sprintf( "%02X", $l_green ) . sprintf( "%02X", $l_blue ) ); } sub web_fp_camera_popup { } sub web_fp_filter_name { my ($p_text) = @_; $p_text =~ s/^\$//g; $p_text =~ s/^\S_//g; $p_text =~ s/_/ /g; return $p_text; } =back =head2 INI PARAMETERS NONE =head2 AUTHOR Jason Sharpee jason@sharpee.com Special Thanks to: Bruce Winter - MH =head2 SEE ALSO http://localhost:8080/bin/floorplan.pl http://localhost:8080/bin/floorplan.pl?Property http://localhost:8080/bin/floorplan.pl?Upstairs =head2 LICENSE This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; either version 2 of the License, or (at your option) any later version. This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details. You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301, USA. =cut	{ "pile_set_name": "Github" }
from Wiktionary, Creative Commons Attribution/Share-Alike License from the GNU version of the Collaborative International Dictionary of English adj. Full of juice; juicy. adj. plants (Bot.), plants which have soft and juicy leaves or stems, as the houseleek, the live forever, and the species of Mesembryanthemum. from The Century Dictionary and Cyclopedia Full of juice; specifically, in botany, juicy; thick and fleshy: noting plants that have the stems or leaves thick or fleshy and juicy, as in the houseleek and live-for-ever, the orders Cactaceæ, Crassulaceæ, etc. As to what all this looked like and how it tasted, well, you can't eat metaphors, and if I ever use words such as "succulent," shoot me, but suffice it to say that I remember thinking as I walked into the night: If the Roman emperors can be said to have missed out on anything, it was this. Wordmap Word visualization Comments STANLEY. Succulent.MEG. You shouldn't say that word.STANLEY. What word?MEG. That word you said.STANLEY. What, succulent—?MEG. Don't say it!STANLEY. What's the matter with it?MEG. You shouldn't say that word to a married woman.STANLEY. Is that a fact?MEG: Yes.STANLEY. Well. I never knew that.—Pinter, The Birthday Party	{ "pile_set_name": "Pile-CC" }
Have rural background students been disadvantaged by the medical school admission process? The proportion of rural background applicants to medical school does not reflect the proportion of the general population that resides in rural communities. It is also believed that rural background applicants are disadvantaged by the admission processes of urban-based medical schools. This study sought to examine how rural background applicants actually fare as they progress through the stages of admission. A 10-year cohort of Alberta applicants were tracked as they progressed through the interview and admittance stages. Background, grade point averages (GPAs) and Medical College Admission Test (MCAT) scores plus interview ratings were utilised in the analysis. Of the 4407 applicants, 1138 were interviewed. Significantly greater proportions of urban (26.8%) and rural (29.1%) background applicants than regional background (21.0%) applicants were interviewed, although the GPAs and MCAT scores of regional background applicants did not differ from those of the other applicant groups. Of those interviewed, 463 applicants were admitted. The proportions of urban (39.9%), regional (42.3%) and rural (46.3%) background applicants admitted were similar. Reviewers did not rate the files of urban, regional and rural background applicants differently. Only 6.7% of applicants admitted had rural backgrounds. Rural background applicants were not disadvantaged or discriminated against by the admission process. Although the backgrounds of applicants admitted reflect those of the original applicants, the proportion of rural background applicants is below the proportion of Albertans who reside in rural areas. Strategies to increase the number of applicants of rural origin are recommended.	{ "pile_set_name": "PubMed Abstracts" }
INTRODUCTION ============ Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed for the relief of arthritis pain; however, they have been shown to increase the risk of gastrointestinal (GI) ulcer bleeding ([@bib1],[@bib2],[@bib3],[@bib4],[@bib5]). Previous blinded, prospective randomized controlled trials (RCTs) have provided evidence of NSAID-induced GI toxicities and have suggested a lower rate of upper GI complications with cyclooxygenase (COX)-2--selective NSAIDs compared with nonselective NSAIDs (nsNSAIDs) ([@bib6],[@bib7],[@bib8],[@bib9]); however, the majority of these trials have focused on damage to the upper GI tract only ([@bib6],[@bib7],[@bib9],[@bib10],[@bib11],[@bib12]). In addition, because of the relative inflexibility of management options in their protocols, prior RCTs of NSAIDs have not captured the common characteristics of NSAID utilization in clinical practice, such as switching among NSAIDs ([@bib13]), modifications of dosing, drug holidays, and concomitant therapies used to potentially reduce GI symptoms and complications. Additional safety information that considers the potential for NSAID damage in both the upper and lower GI tract and better reflects standard clinical practice, could help clinicians make improved treatment decisions. Blinded RCTs are often regarded as the "gold standard" for assessing treatment effects of medications ([@bib14]). However, when attempting to extrapolate findings from RCTs to clinical practice, the ability to generalize these results is commonly limited by factors, such as strict inclusion and exclusion criteria, inability to switch among comparator medications, restriction of dose adjustment, or the inability to institute a drug holiday as would happen in routine clinical practice. Furthermore, the protocol-driven study requirements of RCTs may lead to informative censoring of patient participation because of perceptions of medication adverse effects, which may lead to patient discontinuation from the study. Informative censoring may result in an imbalance of exposure time and a compromised ability to accrue clinically relevant or valid information regarding the primary clinical study outcomes ([@bib15]). Noninterventional observational studies, compared with RCTs, may allow a better assessment of medication effects in typical clinical situations. However, as there is no randomization in these studies, it is difficult to draw firm conclusions about causation. Channeling, selection, and other biases inherent in nonrandomized studies may confound outcomes. Therefore, these types of studies often generate hypothesis rather than evidence of causality. Prospective, randomized, open-label, blinded endpoint (PROBE) studies are designed to address some of the potential limitations of RCTs and observational studies. A PROBE trial design assesses clinical outcomes in large simple studies that allow a broad patient population, in this case patients who require the long-term use of NSAIDs owing to chronic pain, which better reflects clinical practice but with the advantage of randomization and a rigorous evaluation of endpoints by blinded expert adjudication committees ([@bib16]). The GI Randomized Event and Safety Open-Label NSAID Study (GI-REASONS; NCT00373685) is a novel PROBE study conducted in the United States, which measured clinical outcomes throughout the GI tract using blinded adjudication ([@bib17]). Designed to address many of the potential limitations of RCTs and observational studies, the GI-REASONS tested the hypothesis that celecoxib use in patients with osteoarthritis of at least moderate GI risk (aged ≥55 years) would be associated with a lower incidence of clinically significant upper and/or lower GI events than nsNSAIDs in standard clinical practice. A prior double-blind RCT of celecoxib vs. diclofenac slow release plus omeprazole in patients with osteoarthritis and rheumatoid arthritis, the Celecoxib vs. Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis (CONDOR) trial, used a predefined primary endpoint of clinically significant upper and/or lower GI events to capture the spectrum of NSAID-associated GI damage throughout the entire GI tract ([@bib18]). Although a similar endpoint is used in GI-REASONS, the novel aspect of this study is its PROBE design, which allowed for the possibility of switching among multiple nsNSAID comparators, dose adjustment, and the discretionary use of concomitant proton-pump inhibitors (PPIs) in both arms. Inclusion and exclusion criteria in the GI-REASONS were simple compared with conventional RCTs, providing a patient population more reflective of those encountered in typical clinical practice. METHODS ======= Study design ------------ GI outcomes were evaluated in patients with osteoarthritis in need of daily NSAIDs (i.e., using celecoxib or nsNSAIDs) as a result of chronic pain, at moderate GI risk (defined as aged ≥55 years ([@bib12])), who were treated in a manner typical of US clinical patient care in 783 primary care and specialty practices. We hypothesized celecoxib would be associated with lower incidences of clinically significant upper and/or lower GI events compared with nsNSAIDs, with or without PPIs. Aspirin users were excluded to select a population with lower cardiovascular risk and to determine whether celecoxib has a greater GI benefit than nsNSAIDs, without the confounding use of aspirin. It has been reported that in patients taking COX-2 selective NSAIDs and low-dose aspirin, the GI advantages of COX-2 selective NSAIDs were reduced ([@bib19]). We estimated that 6,400 patients (3,200 per group) were needed to provide 90% power to detect a 56% reduction in the primary endpoint (from 1.6% for nsNSAIDs to 0.7% for celecoxib, observed in a similar population), ([@bib9]) based on a χ^2^-test with a two-sided α=0.05. Assuming a 25% discontinuation rate, the target enrollment was 8,000. Eligible patients were randomized via an interactive voice response system (1:1) in block sizes of 4 to either open-label celecoxib or an nsNSAID for 6 months. The nsNSAID in the comparator group was any nsNSAID of the investigator\'s choice, prescribed within the dosages allowed in the US package insert. Patients with osteoarthritis, who previously had been taking an NSAID, were switched to their assigned study medication after randomization without a washout period. Patients were provided a pharmacy card that allowed each patient to fill prescriptions for their allocated treatment only. This pharmacy card was also used to capture study medication utilization behavior, such as dose adjustment and switching among nsNSAIDs. Patients were stratified at baseline by Helicobacter pylori status (assessed by serological testing at a central laboratory). H. pylori-positive patients were not treated for their infection during the trial. During the 6-month study, patients were evaluated every 2 months and at end of study in office visits that included assessment of hemoglobin. Celecoxib or nsNSAID dosage could be adjusted within the US prescribing guidelines. Patients randomized to the nsNSAID arm could switch between nsNSAIDs, but crossover between the nsNSAID and celecoxib treatment arms was not allowed. PPIs and histamine-2 receptor antagonists (H~2~-RA) were allowed in either arm at the provider\'s discretion. This study was conducted in accordance with the International Conference on Harmonisation Good Clinical Practice guidelines and local regulatory requirements. The protocol was modified twice after study initiation: first to clarify the inclusion/exclusion criteria regarding estimation of cardiovascular risk, and second to include additional prespecified sensitivity analyses. These modifications did not result in any change in study conduct. Study eligibility ----------------- Patients aged ≥55 years with a clinical diagnosis of osteoarthritis, who required daily NSAID therapy for the management of osteoarthritis symptoms, were eligible. Key exclusions were active GI ulcer hemorrhage or gastroduodenal ulceration within 90 days of screening, known established cardiovascular disease, any patient who, in the opinion of the investigator, was at sufficiently high cardiovascular risk to require low-dose aspirin, or positive fecal occult blood test at screening. Acetaminophen for occasional treatment of nonarthritis pain (up to 4 g per day for no more than 2 consecutive days), narcotic analgesics, and gastroprotective agents were allowed. Study endpoints --------------- The primary endpoint was the incidence of clinically significant upper and/or lower GI events over 6 months, individual components of which are shown in the Results section ( [Table 1](#tbl1){ref-type="table"}). Potential GI endpoint events were adjudicated by an independent, blinded, expert GI events adjudication committee that evaluated whether the suspected GI event met predefined criteria for a component of the composite GI endpoint. The primary endpoint component, clinically significant anemia of presumed occult GI origin, was defined as a hemoglobin decrease of more than 2 mg/dl from baseline, which had no apparent non-GI cause to explain the decrease. Patients could have only one primary endpoint. Secondary endpoints included moderate to severe abdominal symptoms, withdrawal owing to GI adverse events, changes in hemoglobin and hematocrit from baseline, study and nonstudy drug utilization, gastroprotective drug use, and fecal occult blood test results. Patient satisfaction was measured with a validated instrument ([@bib20]) as a secondary endpoint to assess potential treatment benefit. Cardiovascular events were also assessed and adjudicated by an independent, blinded, expert cardiovascular adjudication committee. Statistical analysis -------------------- The primary and secondary endpoint analyses were based on the intent-to-treat population, defined as all randomized subjects. Statistical tests were significant at the 0.05 level. The primary endpoint was analyzed by comparing the incidence proportions between the treatment arms using a life-table (actuarial) extension of the Mantel--Haenszel method, stratified by H. pylori status at screening. As a secondary analysis to confirm robustness, the primary endpoint was analyzed using the Kaplan--Meier method and the log-rank test. Two sensitivity analyses were planned: a worst-case analysis, in which all patients who were lost to follow-up were conservatively assumed to have had a GI event meeting the criteria for a primary endpoint, and an analysis limited to patients with no protocol deviation. Incidences of hemoglobin and hematocrit drops were compared using a Cochran--Mantel--Haenszel test adjusted for H. pylori status at screening. Analysis of covariance was used to analyze continuous secondary endpoint variables, such as patient satisfaction. Secondary endpoint analyses were performed using the last observation carried forward, and were not adjusted for multiple comparisons. Safety data, physical examination, vital signs, laboratory data, and treatment-emergent adverse events were summarized. During the study, 36 patients were inadvertently randomized more than once. These patients were evenly distributed between groups and were excluded from analysis. Study governance ---------------- The data and safety monitoring committee met regularly during the study to review the safety outcomes. An interim futility analysis was performed to re-estimate sample size after 50% of patients completed, and no adjustment to sample size or alpha was needed. An executive committee (BC, LSS, MJS, and GS) oversaw study conduct, analysis of outcomes, and interpretation of results. RESULTS ======= Patient disposition ------------------- Between October 2006 and November 2010, a total of 4,035 celecoxib and of 4,032 nsNSAID patients were randomized and included in the intent-to-treat analyses ([Figure 1](#fig1){ref-type="fig"}). Baseline demographics were similar between treatment arms. Mean age (s.d.) was 63 (6) years, 76% were female, 259 patients (3.2%) had a history of GI ulcer or ulcer bleeding, 34% were H. pylori positive, and 15 patients (0.19%) had a history of coronary artery disease or myocardial infarction ( [Table 2](#tbl2){ref-type="table"}). In celecoxib-treated patients, 90% were initially prescribed celecoxib 200 mg daily. In nsNSAID-treated patients, the most common initially prescribed comparator nsNSAIDs were meloxicam (38%), naproxen (17%), nabumetone (11%), diclofenac (15%), ibuprofen (5%), and etodolac (5%). Because of switching, the number of patients who took these nsNSAIDs increased during the study, and the most common nsNSAIDs taken were as follows: meloxicam (42%, average total daily dose 13.0 mg); naproxen (21%, average total daily dose 819.8 mg); diclofenac (20%, average total daily dose 124.4 mg); nabumetone (14%, average total daily dose 1089.0 mg); ibuprofen (7%, average total daily dose 1453.2 mg); and etodolac (7%, average total daily dose 709.2 mg); and, as with celecoxib, the nsNSAIDs were taken at the usual US Food and Drug Administration-recommended dosages for management of osteoarthritis. Similar percentages of celecoxib and nsNSAID patients completed the study (2,596 (64.3%) and 2,611 (64.8%), respectively). Overall, 1,376 (34.5%) and 1,340 (33.9%) patients discontinued treatment in the celecoxib and nsNSAID treatment groups, respectively. Reasons for discontinuations were similar between the two treatment arms, and patients discontinued because of adverse events were 7.0 % and 6.4% of the celecoxib- and nsNSAID-treated patients, respectively. Approximately, 2.8% and 3.0% of the celecoxib and nsNSAID treated patients, respectively, withdrew from the study owing to GI adverse events. Discontinued patients were not censored from the analysis; 186 patients were lost to follow-up (2.1% celecoxib and 2.6% nsNSAID). Primary endpoint ---------------- Significantly more nsNSAID users met the primary endpoint (2.4% (98/4,032) nsNSAID patients and 1.3% (54/4,035) celecoxib patients; odds ratio, 1.82 (95% confidence interval (CI), 1.31--2.55); P=0.0003; [Table 1](#tbl1){ref-type="table"} and [Figure 2](#fig2){ref-type="fig"}). Of the patients who were H. pylori positive, 1.8% met the primary endpoint in the celecoxib group and 2.5% in the nsNSAID group; of the patients who were H. pylori negative, 1.1% met the primary endpoint in the celecoxib group and 2.4% in the nsNSAID group. In a sensitivity analysis, attributing the primary endpoint to all patients lost to follow-up (worst case; 2.1% of celecoxib and 2.6% of nsNSAID patients), the difference between treatment arms remained significant (odds ratio, 1.46; 95% CI, 1.18--1.82; P=0.0006). In another sensitivity analysis, excluding patients with protocol deviations, the difference between treatment arms also remained significant (odds ratio, 2.51; 95% CI, 1.35--4.65; P=0.0025). Secondary endpoints ------------------- A smaller proportion of patients receiving celecoxib (94 (2.3%)) experienced moderate to severe abdominal symptoms than those receiving nsNSAIDs (138 (3.4%); P=0.0035). However, withdrawals owing to GI adverse events were similar between groups (112 (2.8%) and 120 (3.0%), respectively; P=not significant). At baseline, mean hemoglobin levels were similar between treatment groups (13.6 g/dl in each group). At study completion, the hemoglobin decrease from baseline was significantly greater in those taking nsNSAIDs (treatment difference, 0.132; 95% CI, 0.10--0.16; P\<0.0001). Over the course of the 6-month study, 1.8% of celecoxib patients compared with 2.9% of nsNSAID patients had a ≥2-g decrease in hemoglobin or 10% or greater decrease in hematocrit (relative risk, 1.6; 95% CI, 1.2--2.2; P=0.0023). The proportion of patients taking gastroprotective agents (PPI or H~2~-RA) for ≥75% of the time under study was 22.4% in the celecoxib group and 23.8% in the nsNSAID group. The proportion of patients with clinically significant upper and/or lower GI events among those who took a PPI was approximately 1.4% in the celecoxib group and 3.0% in the nsNSAID group, and among those who did not take a PPI, the proportion was 1.3% and 2.3%, respectively. Furthermore, among patients who took a PPI, the proportion of patients with clinically significant anemia (defined as either clinically significant anemia of defined GI origin or clinically significant anemia of presumed occult GI origin, including possible small-bowel blood loss) was approximately 1.3% in the celecoxib group and 2.4% in the nsNSAID group. This rate changed to 1.2% and 1.9%, respectively, for those who did not use a PPI. The proportion of patients taking nonstudy analgesics for ≥75% of the time was comparable between treatment groups: 13.8% of patients in the celecoxib group (6.8% acetaminophen, 12.8% over-the-counter NSAID, 14.2% opioid) and 14.9% of patients in the nsNSAID group (6.5% acetaminophen, 13.3% over-the-counter NSAID, 15.6% opioid). Approximately 3.5% of celecoxib and 3.0% of nsNSAID patients used aspirin, which was noted as a protocol deviation. The most commonly used nsNSAIDs were meloxicam (42%), naproxen (21%), diclofenac (20%), and nabumetone (14%), but comparison of celecoxib with any of the individual nsNSAIDs was not conducted, as the study was neither designed nor powered for such comparisons. About one quarter (24.4%) of nsNSAID patients modified their drug regimen (dose changes, switching to another NSAID); 5.4% of celecoxib patients changed their dose. Treatment satisfaction improved from baseline in both groups. However, patients taking celecoxib reported greater treatment satisfaction than patients taking nsNSAIDs (P\<0.0001). Overall and cardiovascular safety evaluation -------------------------------------------- Overall, adverse events and serious adverse events were similar between groups ([Table 3](#tbl3){ref-type="table"}). Adjudicated cardiovascular events were similar in both groups (celecoxib 0.4% vs. nsNSAID 0.3%). These included both Antiplatelet Trialists\' Collaboration Combined Endpoint events (acute myocardial infarction, stroke, or cardiovascular death; eight celecoxib and six nsNSAID events) and cardiovascular events of special interest (unstable angina, coronary revascularization, transient ischemic attacks, venous and peripheral arterial vascular thrombotic events, and congestive heart failure; nine celecoxib and seven nsNSAID events; see [Table 4](#tbl4){ref-type="table"} for more detail). There were seven deaths in total, five in the celecoxib group (three adjudicated as cardiovascular-related) and two in the nsNSAID group (none adjudicated as cardiovascular-related). DISCUSSION ========== In this study, designed to reflect the GI consequences of NSAIDs in a typical clinical practice setting, celecoxib was associated with an approximately twofold lower incidence of clinically significant upper and/or lower GI events than nsNSAIDs. Even in the "worst-case" sensitivity analysis, the treatment effect of COX-2-selective inhibition remained significant. The GI-REASONS had proportionally fewer upper GI ulcer complications than historical comparator studies ([@bib6],[@bib8],[@bib9]), and changes in hemoglobin and/or hematocrit had a greater influence on the primary composite GI endpoint. A decline in clinically significant upper GI events and an increase in lower GI events have also been identified in some observational studies ([@bib21],[@bib22]). This phenomenon of suspected lower GI events taking on a greater proportion of the total GI tract events seen in the GI-REASONS is an important contribution that adds to our current understanding of the proposed burden of the effects of NSAIDs throughout the entire GI tract. In addition, the concomitant allowance of GI-protective therapies in both arms may have decreased the observed incidence of upper GI ulcers, contributing to the relative finding of increased suspected lower GI events. We have provided the data on the total number of adjudicated events based on individual NSAIDs, even though the authors do not believe that these data can be analyzed in any scientifically valid fashion, for the following reasons. To begin, the study was designed and powered to detect potential differences between celecoxib and nsNSAIDs as a collective group. The study was not designed to examine potential outcome differences among nsNSAIDs or between any single nsNSAID and celecoxib, and is therefore insufficiently powered to conduct valid subgroup analysis of any isolated nsNSAID comparator. Equally important, such analyses would be significantly biased. The major strengths of the GI-REASONS are (a) randomization and (b) the open-label PROBE design, which allows physicians to select any NSAID they want in the usual care arm, thus mimicking clinical practice. However, these strengths also make it uniquely ill-advised to conduct subgroup analyses of individual NSAIDs, because the selection of any individual nsNSAID in the usual care arm is not randomized. In fact, the decision of what nsNSAID to prescribe is made after randomization, in an open-label fashion. This introduces a strong channeling bias, similar to that often seen in observational studies. It is entirely possible that patients perceived to be at higher risk for GI complications in the usual-care arm will be selectively prescribed specific nsNSAIDs, which the physicians believe are "safer," based on prior perceptions or marketing (e.g., meloxicam). No such channeling will occur in the celecoxib arm. The channeling bias would then result in a significantly higher complication rate in those receiving the channeled "presumed safer" NSAID (e.g., meloxicam) compared with the non-channeled arm (in this case, celecoxib). Therefore, the authors believe that it is not possible to compare specific nsNSAIDs with celecoxib, or with each other in a quantitative and scientifically valid fashion. Not only are these analyses not prespecified, the authors had agreed during the conduct of the study that subgroup analyses would not be conducted because of their questionable scientific validity. Therefore, although the authors feel that no conclusions can be drawn from the following data, it is provided at the editor\'s request. The proportion of patients with clinically significant upper and/or lower GI events in the individual nsNSAID group (based on first prescription only) with ≥1 event was 9.1% (1/11 patients) in diflunisal-, 6.7% (7/105 patients) in oxaprozin-, 6.7% (1/15 patients) in indomethacin-, 3.3% (20/609) in diclofenac-, 2.8% (5/181 patients) in etodolac-, 2.7% (18/679 patients) in naproxen-, 2.7% (3/112) in piroxicam-, 2.2% (34/1514 patients) in meloxicam-, 1.4% (6/418 patients) in nabumetone-, and 1.4% (3/211 patients) in ibuprofen-treated patients. Recognizing the limitations of both RCTs and observational studies, recent discussions of the US Food and Drug Administration on the use of COX-2-selective NSAIDs and nsNSAIDs have proposed alternative clinical trial strategies, including the PROBE design as a novel method to be pursued for assessing the comparative effectiveness of these medications ([@bib23]). The strengths of the PROBE design are randomization, prospective follow-up, and a rigorous evaluation of study endpoints by a blinded, independent, expert adjudication committee ([@bib16]). Using a PROBE design, the GI-REASONS used simple inclusion and exclusion criteria to enroll a broad osteoarthritis patient population of moderate GI and low cardiovascular risk. Switching among nsNSAIDs, allowing dose adjustments, and drug holidays, along with use of PPIs and H~2~-RA as needed, more closely reflected daily clinical practice. Another strength of this study was providing pharmacy cards to each patient; this allowed tracking of prescriptions, evaluation of medication compliance, and monitoring of drug utilization and drug switching behavior, while preventing treatment crossover. The relative merits of the various methods used to assess NSAID-induced GI damage (e.g., endoscopy of the upper GI tract, a composite endpoint evaluation of the entire GI tract, or assessment of ulcer complications) have been the focus of the recent US regulatory discussions ([@bib24]). NSAID toxicity in GI-REASONS was assessed by a composite primary endpoint of clinically significant upper and/or lower GI events ([@bib17]). Historically, the most commonly employed investigational method in the study of NSAID-related GI damage is endoscopy. Although upper endoscopy is useful to assess the upper GI tract, it is not appropriate for the entire small intestine. In the small intestine, capsule endoscopy studies have shown differences in mucosal damage between COX-2-selective and nonselective NSAIDs ([@bib25],[@bib26]); however, the clinical relevance of these endoscopic findings is still unclear. In addition, a common gastroprotective strategy, PPI use, is not anticipated to have pharmacological effects extending beyond the duodenum. We believe a primary endpoint that assesses damage through the entire GI tract provides valuable safety data to guide management of arthritis patients, as well as methodological and regulatory discussions. Prior data indicate that the GI advantage of COX-2-selective NSAIDs may be compromised in patients taking concomitant aspirin ([@bib19]). Aspirin use was an exclusion criterion in this study. Although we avoided the potential confounding of the GI endpoint, this exclusion criterion means that our observations may not be generalizable to patients on prophylactic aspirin therapy. The largest proportion of the composite GI endpoint can be attributed to decreases in hemoglobin ≥2 g/dl and/or ≥10% hematocrit, and the clinical relevance of a 2-g/dl drop in hemoglobin is currently the subject of active debate. We believe that the difference reflects those taking nsNSAIDs, even with concomitant PPI use, are at increased risk of mucosal damage throughout the entire GI tract compared with the relative GI mucosa protection offered by COX-2 inhibition via celecoxib. On a large scale, such as that examined in this study, it is possible that this difference of protection between nsNSAIDs and celecoxib is likely enough to expose the smaller, nonscoped bleeding changes that can occur throughout the entire GI tract with nsNSAID use. These smaller bleeding changes would then be reflected in the hemoglobin differences seen in the two arms. We recognize the challenge of determining the significance of hemoglobin drops, which counted as a primary outcome but did not render a participant anemic by laboratory definition (e.g., a hemoglobin drop from 15.5 to 13.5 g/dl). Although the relative merits of using reference ranges to define anemia rather than relative change from baseline is not yet settled, we believe that drops in hemoglobin ≥2 g/dl represent a change from the patient\'s usual baseline that is clinically informative and may warrant further clinical examination. Two major risk factors for GI mucosal damage are H. pylori and NSAID use ([@bib27]). Historically, H. pylori has been the major cause of peptic ulcer disease. Many previous studies of NSAID GI injury excluded H. pylori-positive patients. By stratifying for H. pylori status in the current study, we believe that our analysis provides clinically relevant information on the use of NSAIDs in a patient population of mixed H. pylori status as found in typical clinical practice. In this study we did see a numeric but nonstatistically significant imbalance in rates of cardiovascular events between the two study groups. As the GI-REASONS trial is designed as a trial to evaluate GI endpoints, this study was not sufficiently powered to assess rates of cardiovascular events between celecoxib and NSAIDs. A larger trial is currently ongoing to evaluate cardiovascular events between celecoxib and NSAIDs (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs. Ibuprofen or Naproxen \[PRECISION\]) ([@bib28]). PROBE-designed studies have several limitations ([@bib29]). The open-label design presents the possibility of bias. That is, patients or investigators may add concomitant treatments to address lack of efficacy, or manage symptoms or risk based on their knowledge and beliefs of treatment allocation. However, although medications were open label, determination of endpoints was blinded and conducted by expert committees. In addition to these previously recognized limitations, our experience identified hurdles in the execution of a PROBE-designed study. Although assumed to be simple by design, in practice, incorporating the variety of therapeutic options and management strategies that are available in clinical practice, compared with the limited possibilities in an RCT, was challenging. However, greater investigator flexibility allowed outcomes reflective of actual clinical practice, and we believe that GI-REASONS has proven that clinically relevant comparative treatment data can be captured through a trial of PROBE design. In summary, the GI-REASONS provides valuable GI safety data relevant to clinical practice. A greater understanding of NSAID risk throughout the entire GI tract should lead to more effective patient management and identification of improved risk-reduction strategies. Finally, we think this trial will be historically important with respect to clinical trial design in NSAID-related GI bleeding, as it represents the successful execution of a PROBE study, incorporating the variety of therapeutic options and management strategies that are available in clinical practice, with the rigor of a prospective RCT ([Supplementary Information](#sup1){ref-type="supplementary-material"}). STUDY HIGHLIGHTS ================ ![](ajg2012467i1.jpg) We thank Dr Ha Nguyen (Pfizer) for many helpful and insightful comments on the manuscript. This trial was registered withclinicaltrials.gov identifier: NCT00373685. [SUPPLEMENTARY MATERIAL](#sup1){ref-type="supplementary-material"} is linked to the online version of the paper at http://www.nature.com/ajg Guarantor of the article: Byron Cryer, MD. Specific author contributions: B.C., L.S.S., G.S., and M.J.S. constituted the Executive Committee overseeing the study. M.F.B. designed the study with contributions from the other authors. C.L. performed the statistical analysis, and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors participated in drafting and revising the manuscript. Financial support: This study was sponsored by Pfizer. Editorial support was provided by William Watkins, of PAREXEL, and was funded by Pfizer. Potential competing interests: Byron Cryer has served as a consultant for Pfizer, Astra-Zeneca, PLx Pharma, McNeil Consumer Products, and Ritter Pharmaceuticals, and has received consulting fees, honorarium, and travel support from Pfizer. Chunming Li and Manuela Berger are full-time employees of Pfizer and own stocks and shares in Pfizer. Lee S. Simon has served as a consultant for Pfizer, Astra-Zeneca, PLx Pharma, Logical Therapeutics, Bayer Healthcare, Horizon Pharmaceuticals, Takeda, and Posen, and has received consulting fees and travel support from these companies. Gurkirpal Singh has received consulting fees and honorarium from Pfizer and has received grants from Pfizer, Novartis, Pozen, and Astra-Zeneca. Martin Stillman has served as a consultant for Pfizer, Alpharma, and NicOx S.A., and has received consulting fees and honorarium from Pfizer. Supplementary Material {#sup1} ====================== ###### Click here for additional data file. ![Patient disposition. nsNSAID, nonselective nonsteroidal anti-inflammatory drug.](ajg2012467f1){#fig1} ![Cumulative incidence of clinically significant upper and/or lower gastrointestinal events. CMH, Cochran--Mantel--Haenszel; nsNSAID, nonselective, nonsteroidal anti-inflammatory drug. Note: any potential event occurring during the 180 days of treatment plus 28 days after last dose would have been reviewed and adjudicated by design. Hence, the Kaplan--Meier (KM) plot is presented up to 210 days here. The KM estimate beyond that duration became unreliable owing to censoring.](ajg2012467f2){#fig2} ###### Primary endpoint analysis *Celecoxib (n=4,035)* *nsNSAID (n=4,032)* ----------------------------------------------------------------------------------------------------------------------------------- --------------------------- ------------------------- Clinically significant upper and/or lower GI events 54 (1.3) 98 (2.4) Gastroduodenal hemorrhage[a](#t1-fn3){ref-type="fn"} 0 2 (\<0.1) Gastric outlet obstruction[b](#t1-fn4){ref-type="fn"} 1 (\<0.1) 0 Gastroduodenal, small bowel or large bowel perforation^c^ 1 (\<0.1) 1 (\<0.1) Small bowel hemorrhage[d](#t1-fn6){ref-type="fn"} 0 0 Large bowel hemorrhage[e](#t1-fn7){ref-type="fn"} 3 (\<0.1) 6 (0.1) Clinically significant anemia of defined GI origin[f](#t1-fn8){ref-type="fn"} 4 (0.1) 6 (0.1) Symptomatic ulcers[g](#t1-fn9){ref-type="fn"} 0 5 (0.1) Small bowel obstruction[h](#t1-fn10){ref-type="fn"} 0 0 Acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage[i](#t1-fn11){ref-type="fn"} 1 (\<0.1) 3 (\<0.1) Clinically significant anemia of presumed occult GI origin including possible small bowel blood loss[j](#t1-fn12){ref-type="fn"} 44 (1.1) 75 (1.9) Odds ratio (95% CI) 1.82 (1.31--2.55) Hypothesis testing P=0.0003 Helicobacter pylori status Positive 25/1,401 (1.8) 34/1,386 (2.5) Negative 29/2,634 (1.1) 64/2,646 (2.4) CI, confidence interval; EGD, esophagogastroduodenoscopy; GI, gastrointestinal; nsNSAID, nonselective, nonsteroidal anti-inflammatory drug. Definitions of endpoint components Endoscopic evidence of gastroduodenal ulceration (mucosal break with definite depth) or erosion (mucosal break without depth), or other likely causative lesion and clinical evidence of hemorrhage (hematemesis or melena, or evidence of recent hemorrhage on EGD---e.g., clot, blood in stomach, or visible vessel). Clinical, surgical, endoscopic, or radiographic evidence with symptoms consistent with gastric outlet obstruction. Clinical, surgical, or radiographic confirmation associated with symptoms consistent with perforation. Melena or hematochezia with likely causative lesion on small bowel investigation. Melena or hematochezia with no evidence of source on EGD and likely causative lesion on colonoscopy. No overt clinical evidence of acute GI hemorrhage, but with fall in hematocrit ≥10% points and/or hemoglobin ≥2 g/dl from baseline, with likely causative lesion on upper GI or lower GI endoscopic investigation, and with no non-GI source of anemia identified. Ulcers without complications, which present with dyspepsia and have endoscopic or X-ray evidence of a gastric and/or duodenal ulcer. Clinical, surgical, endoscopic or radiographic evidence with symptoms consistent with small bowel obstruction. Hematemesis, melena, or hematochezia with no evidence of likely causative lesion on endoscopic investigation. No overt clinical evidence of acute GI hemorrhage, but with fall in hematocrit ≥10% points and/or hemoglobin of ≥2 g/dl without a GI lesion endoscopically identified and no non-GI source of anemia. ###### Demographic characteristics *Celecoxib (n=4,035)* *nsNSAID (n=4,032)* ---------------------------------------------------------------------- --------------------------- ------------------------- Female, no. (%) 3,049 (75.6) 3,064 (76.0) Age, mean (s.d.) 63.3 (6.3) 63.3 (6.4) Weight (kg), mean (s.d.) 83.5 (20.1) 83.5 (19.9) Duration of OA (years), mean (s.d.) 8.0 (7.7) 8.0 (7.6) H. pylori positive, no. (%) 1,365 (33.8) 1,350 (33.5) History of coronary artery disease or myocardial infarction, no. (%) 7 (0.2) 8 (0.2) nsNSAID, nonselective, nonsteroidal anti-inflammatory drug; OA, osteoarthritis. ###### Treatment-emergent adverse events *Celecoxib (n=4,035) no. (%)* *nsNSAID (n=4,032) no. (%)* ---------------------------------------------------------------------- ----------------------------------- --------------------------------- Total number of patients evaluable for AEs 4,018 (99.6) 4,022 (99.8) Patients with AEs 1,663 (41.4) 1,869 (46.5) Patients with serious AEs 100 (2.5) 96 (2.4) Patients with dose reduction or temporary discontinuation due to AEs 144 (3.6) 202 (5.0) AEs, adverse events; nsNSAID, nonselective, nonsteroidal anti-inflammatory drug. ###### Adjudicated cardiovascular events *Celecoxib (n=4,035) no. (%)* *nsNSAID (n=4,032) no. (%)* ------------------------------------------------- ------------------------------------- --------------------------------- Total CV events 17 (0.4)[a](#t4-fn2){ref-type="fn"} 13 (0.3) APTC-like events 8 (0.2) 6 (0.1) Acute myocardial infarction 2 (\<0.1) 3 (0.1) Stroke 3 (0.1) 3 (0.1) Cardiovascular death 3 (0.1) 0 CV events of special interest 9 (0.2) 7 (0.2) Unstable angina 2 (\<0.1) 1 (\<0.1) Coronary revascularization 4 (0.1) 0 Transient ischemic attack 2 (\<0.1) 2 (\<0.1) Venous and peripheral arterial thrombotic event 1 (\<0.1) 3 (0.1) Congestive heart failure 0 1 (\<0.1) APTC, Antiplatelet Trialists\' Collaboration Combined Endpoint; CV, cardiovascular; nsNSAID, nonselective, nonsteroidal anti-inflammatory drug. One patient in the celecoxib group had an acute myocardial infarction and coronary revascularization.	{ "pile_set_name": "PubMed Central" }
topic "S_type structures"; [2 $$0,0#00000000000000000000000000000000:Default] [i448;a25;kKO9;2 $$1,0#37138531426314131252341829483380:class] [l288;2 $$2,2#27521748481378242620020725143825:desc] [0 $$3,0#96390100711032703541132217272105:end] [H6;0 $$4,0#05600065144404261032431302351956:begin] [i448;a25;kKO9;2 $$5,0#37138531426314131252341829483370:item] [l288;a4;@5;1 $$6,6#70004532496200323422659154056402:requirement] [l288;i1121;b17;O9;~~~.1408;2 $$7,0#10431211400427159095818037425705:param] [i448;b42;O9;2 $$8,8#61672508125594000341940100500538:tparam] [b42;2 $$9,9#13035079074754324216151401829390:normal] [{_}%EN-US [ {{10000@(113.42.0) [s0; [@7;4 S`_][/@7;4 type][@7;4 structures]]}}&] [s0;i448;a25;kKO9;:noref:@(0.0.255)%- &] [s0; S`_[/ type] structures are generated (by multiincluding process) from .sch files that describe the database schema. Each TABLE or TYPE of .sch has correspending S`_[/ type] structure. This structure has member variables corresponding to database columns, with the same names and types. `'BOOL`' columns are represented as CHAR(1) in database, but as `'bool`' C`+`+ type in S`_[/ type]). ARRAY columns are represented as fixed C`+`+ arrays. If TABLE or TYPE has any base TYPEs or TABLEs, S`_[/ type] structure contains them as well.&] [s0; &] [ {{10000F(128)G(128)@1 [s0; [* Public Member List]]}}&] [s3;%- &] [s5;:S`_type`:`:TableName:%- [@(0.0.255) static]_[@(0.0.255) const]_[@(0.0.255) char]_[* Tabl eName][@(0.0.255) `[`]]&] [s2; The name of table or type.&] [s3;%- &] [s4;%- &] [s5;:S`_type`:`:ColumnSet`(`):%- [@(0.0.255) static] [@(0.0.255) const]_[_^SqlSet^ SqlSet][@(0.0.255) `& ]_[* ColumnSet]()&] [s2; The complete set of columns as SqlSet.&] [s3;%- &] [s4;%- &] [s5;:S`_type`:`:ColumnSet`(const String`&`):%- [@(0.0.255) static] [_^SqlSet^ SqlSet]_[* ColumnSet]([@(0.0.255) const]_[_^String^ String][@(0.0.255) `&]_[@3 pr efix])&] [s2; The complete set of columns as SqlSet, all columns prefixed with [%-@3 prefix].&] [s3; &] [s4; &] [s5;:S`_type`:`:Of`(SqlId`):%- [@(0.0.255) static] [_^SqlSet^ SqlSet]_[* Of]([_^SqlId^ SqlId]_ [@3 table])&] [s2; The complete set of columns as SqlSet, all columns expressed as part of [%-@3 table] (TABLE.COLUMN notation).&] [s3; &] [s4; &] [s5;:S`_type`:`:GetColumnIds`(`):%- [@(0.0.255) static] [@(0.0.255) const]_[_^Vector^ Vecto r]<[_^SqlId^ SqlId]>`&_[* GetColumnIds]()&] [s2; Returns all columns.&] [s3; &] [s4; &] [s5;:S`_type`:`:Clear`(`):%- [@(0.0.255) void]_[* Clear]()&] [s2; Sets all member variables to Null.&] [s3; &] [s4; &] [s5;:S`_type`:`:FieldLayout`(FieldOperator`&`):%- [@(0.0.255) void]_[* FieldLayout]([_^FieldOperator^ F ieldOperator][@(0.0.255) `&]_[@3 f])&] [s2; Calls FieldOpertator`::Field(const char `name, Ref f) and Table(const char `name) methods of [%-@3 f] to provide a visitor pattern for S`_[/ type].&] [s3; &] [s4; &] [s5;:S`_type`:`:operator Fields`(`):%- [* operator_Fields]()&] [s2; Returns callback(this, `&S`_[/ type]`::FieldLayout). This method provides unified access to all S`_[/ type]s, which is then used in Sql`::Fetch.&] [s3; &] [s4; &] [s5;:S`_type`:`:operator`=`=`(const S`_type`&`)const:%- [@(0.0.255) bool]_[* operator`=`= ]([@(0.0.255) const]_[_^S`_type^ S`_][/_^S`_type^ type][@(0.0.255) `&]_[@3 x])_[@(0.0.255) c onst]&] [s2; Returns true if all fields are the same.&] [s3; &] [s4; &] [s5;:S`_type`:`:operator`!`=`(const S`_type`&`)const:%- [@(0.0.255) bool]_[ operator!`=]( [@(0.0.255) const]_[_^S`_type^ S`_][/_^S`_type^ type][@(0.0.255) `&]_[@3 x])_[@(0.0.255) con st]&] [s2; Same as !operator`=`=(x).&] [s3; &] [s4; &] [s5;:S`_type`:`:ToString`(`)const:%- [_^String^ String]_[ ToString]()_[@(0.0.255) const]&] [s2; Converts S`_[/ type] to (multiline) text, mostly for debugging purposes.&] [s3; &] [s4;%- &] [s5;:S`_type`:`:GetCount`(`):%- [@(0.0.255) static] [@(0.0.255) int]_[* GetCount]()&] [s2; Returns a number of columns of this S`_[/ type].&] [s3;%- &] [s4;%- &] [s5;:S`_type`:`:GetId`(int`):%- [@(0.0.255) static] [_^SqlId^ SqlId]_[* GetId]([@(0.0.255) in t]_[@3 i])&] [s2; Returns a column ID for column at [%-@3 i].&] [s3; &] [s4;%- &] [s5;:S`_type`:`:GetIndex`(const String`&`):%- [@(0.0.255) static] [@(0.0.255) int]_[* GetIn dex]([@(0.0.255) const]_[_^String^ String][@(0.0.255) `&]_[@3 id])&] [s5;:S`_type`:`:GetIndex`(const SqlId`&`):%- [@(0.0.255) static] [@(0.0.255) int]_[ GetInd ex]([@(0.0.255) const]_[_^SqlId^ SqlId][@(0.0.255) `&]_[@3 id])&] [s2;~~~1792; Returns the index of column [%-@3 id] or negative number if not found.&] [s3; &] [s4;%- &] [s5;:S`_type`:`:GetWidth`(int`):%- [@(0.0.255) static] [@(0.0.255) int]_[* GetWidth]([@(0.0.255) i nt]_[@3 i])&] [s2; Returns the width of column (usually text) as defined in the schema. If column does not have width, returns 0.&] [s3; &] [s4;%- &] [s5;:S`_type`:`:GetWidth`(const SqlId`&`):%- [@(0.0.255) static] [@(0.0.255) int]_[ GetWid th]([@(0.0.255) const]_[_^SqlId^ SqlId][@(0.0.255) `&]_[@3 id])&] [s2; Returns the width of column (usually text) as defined in the schema.If [%-@3 id] is not in S`_[/ type], returns 0.&] [s3; &] [s4; &] [s5;:S`_type`:`:GetRef`(int`):%- [_^Ref^ Ref]_[* GetRef]([@(0.0.255) int]_[@3 i])&] [s2; Returns a reference to column at [%-@3 i].&] [s3; &] [s4; &] [s5;:S`_type`:`:GetRef`(const SqlId`&`):%- [_^Ref^ Ref]_[* GetRef]([@(0.0.255) const]_[_^SqlId^ S qlId][@(0.0.255) `&]_[@3 id])&] [s2; Returns a reference to column [%-@3 id ]or void reference if not in S`_[/ type].&] [s3; &] [s4; &] [s5;:S`_type`:`:Get`(const SqlId`&`)const:%- [_^Value^ Value]_[* Get]([@(0.0.255) const]_[_^SqlId^ S qlId][@(0.0.255) `&]_[@3 id])_[@(0.0.255) const]&] [s2; Returns a value of column [%-@3 id] or void Value if not in S`_[/ type].&] [s3; &] [s4; &] [s5;:S`_type`:`:Get`(int`)const:%- [_^Value^ Value]_[* Get]([@(0.0.255) int]_[@3 i])_[@(0.0.255) c onst]&] [s2; Returns a value of column at [%-@3 i].&] [s3; &] [s4; &] [s5;:S`_type`:`:Get`(`)const:%- [_^ValueMap^ ValueMap]_[* Get]()_[@(0.0.255) const]&] [s2; Returns a map of column names to column values.&] [s3; &] [s4; &] [s5;:S`_type`:`:Set`(int`,const Value`&`):%- [@(0.0.255) void]_[* Set]([@(0.0.255) int]_[@3 i ], [@(0.0.255) const]_[_^Value^ Value][@(0.0.255) `&]_[@3 v])&] [s2; Sets column at [%-@3 i] to [%-@3 v]. Type of [%-@3 v] must be convertible to the column.&] [s3; &] [s4; &] [s5;:S`_type`:`:Set`(const SqlId`&`,const Value`&`):%- [@(0.0.255) void]_[ Set]([@(0.0.255) c onst]_[_^SqlId^ SqlId][@(0.0.255) `&]_[@3 id], [@(0.0.255) const]_[_^Value^ Value][@(0.0.255) `& ]_[@3 v])&] [s2; If [%-@3 id] is in S`_[/ type], sets its value to [%-@3 v], otherwise does nothing.&] [s3; &] [s4; &] [s5;:S`_type`:`:Set`(const ValueMap`&`):%- [@(0.0.255) void]_[* Set]([@(0.0.255) const]_[_^ValueMap^ V alueMap][@(0.0.255) `&]_[@3 m])&] [s2; Keys in [%-@3 m] found as column ids in S`_[/ type] as assigned to respective values. Keys not found are ignored, columns not present in [%-@3 m] are left unchanged.&] [s3; &] [s4; &] [s5;:S`_type`:`:S`_type`(`):%- [ S`_type]()&] [s2; Sets all columns to Null.&] [s3; &] [s4; &] [s5;:S`_type`:`:S`_type`(const ValueMap`&`):%- [* S`_type]([@(0.0.255) const]_[_^ValueMap^ V alueMap][@(0.0.255) `&]_[@3 m])&] [s2; Keys in [%-@3 m] found as column ids in S`_[/ type] as assigned to respective values. Keys not found are ignored, columns not present in [%-@3 m] are set to Null. Overal effect is the same as using the default constructor and then Set([%-@3 m]).&] [s3; ]]	{ "pile_set_name": "Github" }
The present invention relates to a receiver, and more particularly, to a GNSS (Global Navigation Satellite System) receiver having a plurality of configurable calculating circuits. A conventional GNSS receiver generally includes at least a signal processing unit for removing a carrier of a received satellite signal, spectrum meters for obtaining spectrum information of the received satellite signal, and noise processing units for performing a noise cancellation operation. In addition, generally, the signal processing unit, the spectrum meters and the noise processing units are independent circuits, and each of these circuits includes a multiplexer, an oscillator and an accumulator. In practice, however, not all of the above circuits are in use when receiving the satellite signal most of the time, that is, some of these circuits are at idle states, causing low efficiency of the receiver. Particularly, in the GNSS receiver supporting GLONASS (GLObal NAvigation Satellite System) standard, because each GLONASS satellite signal has a unique carrier frequency, a plurality of signal process units are required to be built in the receiver for removing the carriers of the received GLONASS satellite signals. Similarly, not all of the signal process units are in use when receiving the satellite signals most of the time, and also causing low efficiency of the receiver.	{ "pile_set_name": "USPTO Backgrounds" }
Q: How to get excel to array in maatwebsite I am trying to convert an Excel file to an array using the latest version of Laravel-Excel (3.1.9) The code below will download the file: return Excel::download(new SalesOrderExport('columns'),'test.xlsx') But I need to convert it to get an array only. I don't want to store this Excel data in a database at this point. I tried with the code below but it did not work as the load method is not available in version 3. Excel::load($request->file('sampledata'), function ($reader) { return response()->json($reader); }); Please share your thoughts on how to get an array from Excel. A: I and @narayan tried hard to make requested excel file into array. Now I am able to get array properly with below code $rows = Excel::toArray(new SalesOrderImport, $request->file('sampledata')); In my SalesOrderExport class I have default function only, which is required as abstract method. namespace App\Exports; use App\SalesOrder; use Maatwebsite\Excel\Concerns\FromCollection; class SalesOrderExport implements FromCollection { public function collection() { return SalesOrder::all(); } } My Controller code public function importTest(Request $request) { $rows = Excel::toArray(new SalesOrderImport, $request->file('sampledata')); return response()->json(["rows"=>$rows]); } And in HTML <input class="" type="file" name="sampledata" id="sampledata"> I already created this export by php artisan make:import SalesOrder Attaching related images	{ "pile_set_name": "StackExchange" }
[Outpatient diagnostics of the initial stage of essential hypertension]. The informative value of functional diagnostic methods in the revealing of the initial stage of essential hypertension (EH) in patients with high risk of cardiovascular complications (CVC) and type 2 diabetes mellitus (DM2) was studied. The subjects of the study were 186 men considering themselves practically healthy, with high risk of CVC according to SCORE scale. Mean age of the subjects was 47.9 +/- 0.87 years; persons with various metabolic disorders prevailed. The patients were divided into two groups according to body mass index (BMI): group 1 patients (n = 142) had a BMI of > or = 25 kg/m2 (29.16 +/- 0.49); group 2 (n = 46) patients had a BMI of < 25 kg/m2 (22.95 +/- 0.37). The patients underwent clinical and laboratory examination including the measurement of biochemical parameters of lipid, carbohydrate, and purine metabolism. ECG, EchoCG, and 24-hour blood pressure monitoring (BPM) were performed. Office BP levels, 24-hour BMP data, and signs of left ventricular hypertrophy (LVH) according to ECG and EchoCG were evaluated. The study found that in persons with excessive body weight stable 24-hour arterial hypertension with both systolic and diastolic BP increased prevailed, while in subjects with normal body weight systolic arterial hypertension prevailed. The use of milder LVH criteria (left ventricular myocardial mass index > 116 g/m2) increased the number of persons with stage 2 EH. The prevalence of the initial stage of EH according to 24-hour BPM (87.4%) is 2.8 times higher than that according to office BP measurement (31.3%).	{ "pile_set_name": "PubMed Abstracts" }
Main Navigation Iditarod 2015 Thank you to everyone that made a donation or sponsored dogs for the 2014 Iditarod. All the dogs are currently available to sponsor, dog food can be purchased, and any type of donation is very much appreciated for the 2015 Iditarod. Without your help, we could not make in to the starting line! Please contact me via email at iditarodtrailkennel12@yahoo.com if you have any questions about being a sponsor. I am currently signed up for the following races for the 2015 season! Gin Gin 200 January 2nd Finished 13th out of 39 teams. Northern Light's 300 January 23rd Finished 3rd out of 31 teams.Knik 200 January 31st Scratched from race.Tustumena 200 February 21st Cancelled due to poor trail conditionsIditarod Ceremonial start in Anchorage March 7th at 10:00 am. Iditarod Re-Start in Fairbanks Monday March 9th at 10:00 am. The 2015 Iditarod will be starting in Fairbanks on Monday March 9 at 10:00 am. I have added new dog profile pictures and added some new race stories, feel free to check it out. There are still several dogs available for sponsoring. Enjoy the site! The final days of training before Iditarod. We are currently running the dogs away from the kennel as the trail conditions are unfavorable at home. This is Mrs. Sanasardo's class that I had the great opportunity to Skype with last week. The students are from St. Philip the Apostle School which is located in Addison, Illinois. They all had great questions to ask me about the upcoming Iditarod. A recent run while the sun is setting. Above is the route for the 2015 Iditarod. This map shows all the checkpoints and the mileage between each one. This map is courtesy of the Alaska Department of Natural Resources. On Wednesday February 18th, all the drop bags were unloaded by the volunteers to be weighted and stacked in the correct checkpoint location. I ended up sending out 1,643 pounds for this years Iditarod. I was really happy to get this done and behind me, as it is so much work preparing all these bags. On Tuesday February 17th around 10:30pm, I was finishing up packing my drop bags for Iditarod. With the warm weather lately, all the meat had to stay in the freezers to stay frozen. Inside these bags I have all the meat, kibble, dog blankets, personal food, supplements for dogs, dog booties, runner plastic, socks, gloves, etc. that I will need along the trail. These bags will be sent out to all the checkpoints along the trail. With the race now starting in Fairbanks, I had to make sure everything was packed properly as there are new checkpoints along the trail. On Tuesday February 17th all the dogs had ECG's performed and blood withdrawn to determine each dog's fitness and ability to run in this years Iditarod. I am currently working on putting together all my drop bags for the Iditarod. Pictured above are bags filled with just meat which includes: Pup Mix (beef, tripe & liver), Power (beef fat, beef, tripe, wheat germ oil, vitamins & minerals ), Beef Fat, Beef, Tripe, Fish and Chicken Skins. I like to send out a variety of meat, so the dogs have plenty of nutrition. I will also send out dry (kibble) dog food and other supplements for the dogs. These pups are 6 weeks old. (Photos courtesy of Jansen Cardy) On December 25th & 26th Hawk had her 1st liter of pups! She had a total of 9 but the smallest one died several days later as it was not strong enough to make it. The other 8 pups are doing great and there eyes are just starting to open. Yukon is the father of this liter. I have decided to name them after the reindeers as of now.	{ "pile_set_name": "Pile-CC" }
Evergreen Business System Review: Automated Webinar Software This web based software program will allow you to reply a previously recorded webinar without having to create a new one, and maintain all the best parts of a live event. You can reuse old webinars as often as you like, and still maintain the uniqueness and time sensitive benefits of producing a webinar. We have had many reviews of the Evergreen Business System and so far it is performing very well. I am planning on testing this out to be able to provide a perceived high value service that is scalable. This lets you reuse existing good content and place it at a premium for users. You can start the sales video at about 4:20 to get an idea exactly how it works. You really make it seem really easy with your presentation but I to find this topic to be really one thing which I believe I would never understand. Online marketing seems too complex and very large for me. I found the EBS website through Google but it was too expensive for our new online venture. There is software I have been using called Magic Submitter and I was able to get each one of my email lists 100o new subscribers, but we really need to automate doing our product webinars.	{ "pile_set_name": "Pile-CC" }
Below is a list of my favorite television productions set during the U.S. Civil War: FAVORITE TELEVISION PRODUCTIONS SET DURING THE U.S. CIVIL WAR 1. “The Blue and the Gray” (1982) – This three-part CBS miniseries focused on the experiences of two families linked by two sisters – the Geysers of Virginia and the Hales of Pennsylvania – during the U.S. Civil War. John Hammond and Stacy Keach starred. 2. “Copper” (2012-2013) – Tom Fontana and Will Rokos created this BBC America series about an Irish immigrant policeman/war veteran who patrols and resides in New York City’s Five Points neighborhood during the last year of the U.S. Civil War. Tom Weston-Jones, Kyle Schmid and Ato Essandoh starred. 3. “North and South: Book II” (1986) – James Read and Patrick Swayze starred in this six-part television adaptation of John Jakes’s 1984 novel, “Love and War”, the second one in John Jakes’ “North and South” Trilogy. David L. Wolper produced and Kevin Connor directed. 4. “Gore Vidal’s Lincoln” (1988) – Sam Waterston and Mary Tyler Moore starred in this two-part miniseries adaptation of Gore Vidal’s 1984 novel about the 16th U.S. President during the U.S. Civil War. Lamont Johnson directed. 5. “The Young Riders” (1989-1992) – Ed Spielman created this ABC television series about six riders who rode for the Pony Express between 1860 and 1861. Ty Miller, Josh Brolin and Anthony Zerbe starred. 6. “Class of ’61” (1993) – Steven Spielberg produced this ABC television movie about a few West Point graduates who found themselves on opposite sides of the U.S. Civil War. Dan Futterman, Clive Owen and Andre Braugher starred. 7. “Mercy Street” (2016-2017) – Lisa Wolfinger and David Zabel created this PBS series that followed two hospital nurses on opposite sides, at the Mansion House Hospital in Alexandria, Virginia during the U.S. Civil War. Mary Elizabeth Winstead, Hannah James and Josh Radnor starred. 8. “Lincoln” (1974-1976) – Hal Holbrook and Sara Thompson starred in this NBC six-part miniseries about the life of the 16th U.S. President. George Schaefer directed. 9. “The Million Dollar Dixie Deliverance” (1978) – Brock Peters starred in this Disney television movie about an escaped Union soldier who flees to the Union lines with five Northern children who had been snatched and held as hostages by Confederate soldiers during the war. Russ Mayberry directed. 10. “For Love and Glory” (1993) – Roger Young directed this failed CBS pilot about a wealthy Virginia family disrupted by the older son’s marriage to a young working-class woman and the outbreak of the U.S. Civil War. Daniel Markel, Tracy Griffith, Kate Mulgrew and Robert Foxworth starred. As I have stated in many previous movie reviews, I am a sucker for period drama. However, I am an even bigger sucker when said drama turns out to be something different from the usual narrative for this kind of genre. In the case of the 1979 movie, “THE FIRST GREAT TRAIN ROBBERY”, it turned out to be one of those rare kind of films. Like Michael Crichton’s 1975 novel, “The Great Robbery”, “THE FIRST GREAT TRAIN ROBBERY” is a fictional account of a famous robbery known as the “Great Gold Robbery of 1855”. Before one thinks that the movie is a faithful account of this historical event or a faithful adaptation of Crichton’s novel . . . you are bound to be disappointed. Not only did Crichton play a little fast and loose with history in his novel, he also wrote the movie’s screenplay and made even more changes to the tale. “THE FIRST GREAT TRAIN ROBBERY” began with a failed attempt by some nameless criminal to rob the gold used to pay the British troops fight in the Crimean War being shipped monthly on the London-to-Folkestone train. This failed robbery, which ended with the criminal’s death, had been masterminded by a successful criminal named Edward Pierce. Finally realizing that the gold is guarded in two safes with two locks each, Pierce and his mistress, Miriam, recruit a pickpocket and screwsman named Robert Agar to make copies of the safes’ four keys. They also set about attaining copies of the keys by exploiting the weaknesses of two key holders – bank president Edgar Trent and bank manager Henry Fowler. When they discover that the other two keys are locked in a cabinet, inside the office of the South Eastern Railway at the London Bridge train station, Pierce and Agar recruit a cat burglar named “Clean Willie” to help them break into rail office and make impressions of the keys. At first, Pierce is able to execute his plan with very few problems. But obtaining the keys inside the South Eastern Railway office and recruiting “Clean Willie” end up producing major obstacles that he and his accomplices are forced to overcome. I would not claim that “THE FIRST GREAT TRAIN ROBBERY” is a favorite movie of mine. But I must admit that every time I watch it, I usually end up enjoying it very much. And I cannot deny that it proved to be different than the usual period drama. Although “THE FIRST GREAT TRAIN ROBBERY” is a literary adaptation that also features a historical event, it is not the usual period piece. I mean . . . how many period dramas are about a real-life crime? Especially a crime that had occurred before the 20th century? If there is another movie with a similar narrative, I have yet to come across it. Even more interesting is that Crichton utilized great details to show audiences how the crime was planned and carried out. Yes, I realize that Crichton had made changes to his portrayal of the 1855 gold robbery, but I still cannot help but admire that he portrayed this crime in such a detailed manner. And this allowed me to enjoy the film even more, for it provided audiences a detailed look into the criminal and business worlds of the Victorian Age during the 1850s. This was especially the case in the movie’s second half in which the protagonists schemed to get their hands on copies of the third and fourth set of keys inside a London railway station. And if I must be honest, I enjoyed the movie’s first half even more – especially those scenes that featured the robbers’ attempts to acquire copies of the first two keys. Since those two keys were in the hands of bank executive Trent and bank manager Fowlers, the movie allowed peeks into the lives of an early Victorian family and a Victorian bachelor, all from the upper-middle-classes. These scenes included one featuring Pierce’s wooing of Trent’s only daughter, while riding along Hyde Park’s Rotten Row, a popular riding spot for upper and middle-class Londoners; and another featuring Miriam’s seduction of the always lustful Fowler inside an exclusive London bordello. Another aspect of “THE FIRST GREAT TRAIN ROBBERY” that I enjoyed was its production values. Crichton and producer John Foreman had gathered a first-rate crew for this movie. There were four aspects of the movie’s production values that I enjoyed . . . somewhat. I certainly had no problem with Maurice Carter’s production designs for the movie. I thought he did an excellent job in re-creating Victorian London – especially in crowd scenes like the Rotten Row sequence, the bordello and the railway station. I also enjoyed Jerry Goldsmith’s score. Although I did not find it particularly memorable, I thought it blended well with various scenes throughout the movie and was original enough in a jaunty way. I have slightly mixed feelings about Anthony Mendleson’s costume designs. On one hand, I thought many of them – especially those for the male characters – wonderfully recaptured the fashion styles of the mid-1850s. My feelings regarding his designs for the female characters were another matter. There were some designs that I admired very much – especially those for the Pamela Trent and Emily Trent characters. Yet, I found those designs for Lesley-Anne Down’s character rather theatrical. I also have mixed about Geoffrey Unsworth’s cinematography. On one hand, I found many of the film’s wide shots – especially in many of the exterior shots – rather colorful and beautiful. Unfortunately . . . I also noticed that Unsworth’s photography seemed to project this hazy film, indicating that the movie was a period drama. Personally, I found this . . . haze rather annoying and a bit detrimental to the movie’s sharp colors. I can only recall at least three or four sequences that might be considered action-oriented. Three of them involved the “Clean Willie” character and I found them well shot by Crichton. The fourth action sequence – the actual train robbery – was also well shot by Crichton. The problem is that I am not a big fan of the actual robbery sequence. What can I say? It bored me. I could explain that I am becoming less tolerant of action sequences in my old age. But if I must be honest, I never really liked this sequence when I first saw it when I was a lot younger. There is nothing like an actual action sequence on top a train to bore the living daylights out of me. It was not Crichton’s fault. This is simply a case of my personal preferences. I certainly had no problems with the cast. Sean Connery was the perfect embodiment of middle-age debonair as the charismatic, clever and occasionally ruthless criminal mastermind, Edward Pierce. I would not exactly regard this role as a challenge for him. But he seemed to be enjoying himself. The role of Pierce’s mistress, Miriam, seemed to be quite rare for Lesley-Anne Down. I can only recall her portraying a similar character in another heist film that released the same year. Personally, I thought she did a great job portraying Miriam not only as a sexy paramour for Pierce, but also as an equally intelligent and talented partner-in-crime. The movie also featured some interesting performances from Malcolm Terris as the lustful bank manager Henry Fowler with a penchant for prostitutes. Michael Elphick was effective as the cool and collected bank guard Burgess, who accepts Pierce’s bribe to be a part of the heist. Gabrielle Lloyd gave an interesting performance as Edgar Trent’s rather stuffy and plain daughter Elizabeth whom Pierce pretends to court. And Pamela Salem gave a sly performance as Elizabeth’s stepmother Emily Trent, who hides her lust for Pierce with a cool attitude and pointed comments. Other fine supporting performances came from Alan Webb, Wayne Sleep, Robert Lang and André Morell. “What about Donald Sutherland?” many might be thinking. Why was he left out of the praise? Trust me, he was not. If I must be honest, Sutherland gave my favorite performance in the film. I really enjoyed his colorful take on the witty and sly pickpocket/screwsman Robert Agar. However, I do have one complaint to make . . . and it not about Sutherland’s peformance. As I had just stated, I found it very enjoyable. But I had read somewhere that the real Agar was more or less the brains behind the bank robbery. Also, Crichton had somewhat “dumbed down” the character in his 1975 novel and in the movie. I noticed, while watching the film that Sutherland’s Agar seemed to flip-flop between an intelligent criminal and a buffoon. Personally, I found this inconsistent and unnecessary . . . especially for a successful criminal like Agar. Yes, I have a few quibbles regarding “THE FIRST GREAT TRAIN ROBBERY”. And if I must be honest, it is not a great favorite of mine. But I certainly do not regarding it as a mediocre piece of filmmaking. In fact, I thought it was not only an excellent movie, but also rather original for a period piece. Michael Crichton may not have been that faithful to what actually happened during the “Great Gold Robbery of 1855”, but I found his fictionalized account rather exciting. And the movie was topped by fine performances from a cast led by Sean Connery, Donald Sutherland and Lesley-Anne Down. I love John Jakes’ “NORTH AND SOUTH” Trilogy. Honestly, I do. I love it so much that I have copies of the novels published between 1982 and 1987 that make up the trilogy. I love it so much that I have also copies of the television adaptations (1985-1986; 1994) of the novels, produced by Wolper Productions. Unfortunately, the trilogy has a few narrative problems. And I feel that one of its biggest problems centered around a particular painting. I am referring to a certain painting that hung inside an expensive New Orleans. This particular painting depicted a beautiful young woman, who also happened to be one of the prostitutes that worked there. This particular prostitute was favored by the bordello’s owner. More importantly, she left the bordello and her profession in order to marry one of her customers. Despite her European ancestry, this woman was the granddaughter of an African-born slave. She also happened to be the mother of one of the “NORTH AND SOUTH” Trilogy’s main characters – Madeline Fabray. And she eventually became the mother-in-law of three other main characters. Before I continued, I want to say a few words about the painting of Madeline Fabray’s mother that was created for the first two miniseries, 1985’s “NORTH AND SOUTH: BOOK I” and 1986’s “NORTH AND SOUTH: BOOK II”. I did not find it impressive. Look at that dress worn by the painting’s subject. It looks cheap and tacky. Not even a high-priced prostitute like Madeline’s mother would wear such a dress. Even worse, the dress and hairstyle worn by the subject failed to reflect the right decade. Madeline Fabray had been born in the mid-1820s. This meant that her mother must have been a prostitute between the late 1810s and early 1820s. The hairstyle and dress worn by Madeline’s mother seemed to reflect that the painting had been created between in the mid-1840s and early 1850s – at least two to three decades after Mrs. Fabray’s death. Wolper Productions really made a mistake in allowing this painting to serve as an image of the late Mrs. Fabray. But the story that surrounded both the character and the painting struck me as a lot more problematic. And the trouble began in John Jakes’ 1982 novel, “North and South”. In 1846, two years after her marriage to South Carolina rice planter Justin LaMotte, Madeline Fabray LaMotte had traveled back to her hometown of New Orleans to care for her dying father. Before he finally passed away, Nicholas Fabray informed his daughter that both she and her mother were of mixed blood. One of Madeline’s ancestresses was an African-born slave, which meant the late Mrs. Fabray was one-fourth black and Madeline, one-eighth. Shocked by this revelation, Madeline kept this secret to herself for years, until she finally confessed it to her lover and husband’s neighbor Orry Main – one of the novel’s two main characters – after she left her brutish husband in the late winter of 1861. Despite his initial shock, Orry took the news rather well and eventually married Madeline, following Justin’s death during the early months of the Civil War. Unbeknownst to Madeline and Orry, an Army officer named Elkhannah Bent had already learned about her mother’s background . . . former profession. Bent first met Orry during their years at West Point. Orry, along with his best friend, Pennsylvania-born George Hazard, became Bent’s enemies. When they nearly caused his expulsion from West Point, he vowed to get his revenge. He nearly got Orry killed at the Battle of Churubusco, during the Mexican-American War. Neither the Hazards nor the Mains had heard about Bent for years, until they learned he was the immediate commanding officer of Charles Main, Orry’s younger cousin, in Texas during the late 1850s. Either in 1858 or 1859, Bent visited Charles’ quarters for a talk and spotted a photograph taken at a picnic held at the Main family’s estate, Mont Royal. Among the subjects in the photograph were Madeline and Justin LaMotte. Bent seemed taken by Madeline’s looks. In January 1861, Bent was recalled back to the War Department in Washington D.C. During his journey from Texas to the East Coast, Ben visited an expensive bordello in New Orleans – the same one where Mrs. Fabray had worked some decades ago. There, he spotted the infamous painting inside the office of Madam Conti, the bordello’s owner. Bent learned from Madam Conti that the painting’s subject was not only of mixed blood, but also a former prostitute who had married well. Noticing the physical similarities between Madeline LaMotte and the painting’s subject, Bent ascertained that the two women were related. For reasons that still amaze me, he decided that this bit of knowledge could serve as a weapon against Orry Main. In the 1984 novel, “Love and War”, Bent returned to New Orleans about a year-and-a-half later, during the second year of the Civil War, and stole the painting, jeopardizing his Army career. Realizing that he no longer had a military career, Bent deserted from the Union Army and journeyed toward Richmond, Virginia – the capital of the Confederacy. Nearly two years later, he managed to find and acquaint himself with one of Orry’s younger sisters, Ashton Main Huntoon. Bent had chosen well. Orry’s vain and unpleasant sister had estranged herself from the Main family, following her attempt to arrange the murder of her brother-in-law, Billy Hazard, for rejecting her years earlier for younger sister Brett. Once Bent had revealed the infamous painting, along with Madeline’s family history, to Ashton; the latter revealed everything to guests at a private reception that included Confederate Senator Judah Benjamin of Louisiana and Christopher Memminger, a South Carolinian resident who was serving as a Secretary of the Treasury for the Confederate States. Orry’s superior, General John H. Winder had “requested” that he send Madeline away from Richmond. Orry sent Madeline to the Hazards’ home in Lehigh Station, Pennsylvania and resigned his position at the War Department before assuming a field command toward the end of the Overland Campaign in June 1864. The adaptations of the 1982 and 1984 novels – 1985’s “NORTH AND SOUTH: BOOK I” and 1986’s “NORTH AND SOUTH: BOOK II” – took a different spin on the tale. One, Madeline did not learn the truth about her mother from her father until 1854, ten years following her marriage to Justin LaMotte. She told Orry about her secret some three months later, leading him to insist that she leave Justin and accompany him to the North. However, events involving Madeline and a secret abortion for a pregnant and still single Ashton Main led to the end of Orry’s plans. Madeline more or less became a prisoner of her husband for nearly six-and-a-half years. Justin LaMotte died during the summer of 1861 and a few months later, Madeline and Orry became husband and wife. As for Elkhannah Bent, his discovery of the painting also unfolded differently. In the television version, Bent (who was an amalgamation of the literary Bent and a character named Lamar Powell), was visiting New Orleans in 1856 or 1857, when he met Ashton’s new husband, James Huntoon. He was in New Orleans to give a pro-secession speech. The pair, along with two other men, proceeded to Madam Conti’s bordello. When James removed his wallet from his jacket, a photograph of his and Ashton’s wedding reception fell from his wallet. The photograph contained the bridal pair, the Main family and a few guests that included Justin and Madeline La Motte. Apparently, this was not Bent’s first visit to the bordello. While waiting for one of the madam’s prostitutes to finish with a customer, Bent and Madam Conti had refreshments in her private office that contained the painting of Mrs. Fabray. While the madam told Bent about the painting’s subject, he quickly surmised that Mrs. Fabray and the Mains’ neighbor were blood related. Some four years later – between the end of “NORTH AND SOUTH: BOOK I” and “NORTH AND SOUTH: BOOK II” – Bent managed to acquire the painting. Only neither miniseries revealed how he did it. I can only make the assumption that he had purchased it from Madam Conti. In Episode 2, Bent revealed the painting to Ashton, who had become his lover. Instead of revealing Madeline’s secret to Richmond society, Ashton used her knowledge of the painting and Mrs. Fabray’s past to blackmail Madeline into leaving Orry and Mont Royal for good. Two years later, days after the war ended, Madeline and Orry reconciled in Charleston. Superficially, there seemed to be nothing wrong with the narrative regarding Madeline’s mother and the painting in both Jakes’ novels and the television miniseries. Superficially. However, both the novels and the miniseries revealed a major blooper. Why on earth did Elkhannah Bent went out of his way to get his hands on that painting? Why? In both the 1982 novel and the 1985 miniseries, Madeline was revealed to Bent as the wife of a neighboring planter. Neither Charles Main in the novel or James Huntoon in the miniseries knew about Madeline’s romantic connection to Orry. Which meant that Bent was not aware of this relationship, as well. In both the novels and the miniseries, Bent did not find out about Madeline and Orry’s relationship until after he got his hands on the painting. so, Why would Bent risk his professional career in “Love and War” to steal the painting featuring Madeline’s mother, if he was unaware of Orry’s emotional connection to her daughter? Or pay good money to purchase the painting (which is my theory, by the way) in the television adaptations? I wish I could say that matters got better in the third act of Jakes’ trilogy. But it did not. Another mystery regarding the painting manifested. In both the third novel, 1987’s “Heaven and Hell” and the third miniseries, 1994’s “HEAVEN AND HELL: NORTH AND SOUTH BOOK III”, the locals who lived in the same neighborhood as the Mains seemed aware of Madeline’s African ancestry and the profession of her mother. My question is . . . how? How did locals like her first husband’s cousin, Gettys La Motte discover her family secret in the first place? Who had spilled the beans? In “Love and War”, Jakes had made a point of both Judah Benjamin and Christopher Memminger attending the reception where Ashton had revealed Madeline’s secret. However, Benjamin moved to Great Britain after the war and Memminger ended up in North Carolina, following his resignation as Secretary of the Treasurer in July 1864. Ashton, her husband James, and her lover Lamar Powell were forced to flee Richmond for the New Mexico Territory after Orry exposed their plot to assassinate the Confederacy’s president, Jefferson Davis. Lamar Powell killed James Huntoon before being killed by an Apache warrior upon their arrival in the Southwest. Ashton arrived in Santa Fe a few days later, stranded and without any funds. It took her at least four years to return to South Carolina. So none of the above could have revealed Madeline’s secret to the Mains’ neighbors. More importantly, Jakes never bothered to reveal how the news reached the South Caroline low country. “NORTH AND SOUTH: BOOK II” told a slightly different tale. A year after Bent had exposed Madeline’s secret to Ashton, she used the knowledge to blackmail her sister-in-law into leaving Mont Royal for good. However, neither Ashton or Bent ever told another soul. The only other people who knew about Madeline’s mother were her former maid, Maum Sally, who was killed by Justin LaMotte back in 1856, during the debacle regarding Ashton’s unwanted pregnancy; Orry; and his mother, Clarissa Main. And none of these people told a soul. Not even Ashton or Bent, which I find surprising. Like Jakes, the screenwriters for the second and third miniseries never made the effort to set up, let alone reveal how the Mains’ neighbors learned about Madeline’s secret. It is a pity that the storyline regarding Madeline and her mother was marred by sloppy writing. It had the potential to be one of the most interesting arcs in the entire saga, especially since it focused upon attitudes regarding miscegenation in the United States . . . attitudes that lasted for another century following the saga’s setting and still linger to this day. Oh well. There is nothing I can do about it. I suppose I can only regard it as a blooper and move on. I hate to say this, but whenever I watch “NORTH AND SOUTH: BOOK II”, I usually heave a sigh of relief after the last episode fades away. I have never done this with the other two miniseries – “NORTH AND SOUTH: BOOK I” and “HEAVEN AND HELL: NORTH AND SOUTH BOOK III”. But with the 1986 production, I usually do. There is something about watching this particular production usually ends up as hard work for me. Episode Six of “BOOK II” began at least a month after Episode Five ended. This episode began with Orry Main hiring a former Pinkerton detective to find his missing wife, Madeline Fabray LaMotte Main. The latter continues her efforts to feed Charleston’s poor by appealing to Union general William Tecumseh Sherman. With nothing else to do, Orry has no choice but to help the Confederacy defend Richmond, Virginia; which is under siege from the Army of the Potomoc under Ulysses S. Grant. The episode eventually leads into the Battle of Fort Stedman, in which Orry, his cousin Charles, George and Billy Hazard all participate. The Union victory at Fort Stedman eventually lead to another military victory for the Army of Potomoc and Confederate General Robert E. Lee‘s surrender to Grant at Appomattox Court House. Once the episode puts these series of historical events behind, Episode Six refocuses on the main characters’ personal lives. Episode Six closes more story arcs that began in Episode One than the previous episode did. The consequences of Charles Main and Augusta Barclay concludes in one stage and begins in another that will continue in 1994’s “HEAVEN AND HELL: NORTH AND SOUTH BOOK III”. The war’s end leads to a final romantic reunion for Billy and Brett Hazard. In fact, the Charles/Augusta and Billy/Brett relationships were not the only ones that came to fruition in this episode. Episode Sixalso resolved the romance between Semiramis and Ezra, with the former finally acknowledging her love for the latter. And yes, Orry finally finds Madeline and their son with the help of George and Madeline’s attorney, Miles Colbert. With war, there is always the chance for tragedy. While tragedy of one kind marked John Jakes’ 1984 novel, another kind of tragedy ends Virgilia Hazard’s relationship with Congressman Sam Greene and her character arc, which began in “BOOK I”. Tragedy also occurred during the attack upon Mont Royal near the end of the episode. Irony also seemed to be hallmark of this attack, for it was led by an alliance between former Mont Royal slave Cuffey and former overseer Salem Jones. I found it ironic that a black man and a white man, former enemies due to their positions as slave and overseer, should form an alliance against the very family that had controlled their lives in one form or another. Non-elites of two different races uniting against the elite. Talk about a rich man’s worst nightmare. There was a good deal about Episode Six for me to praise. One of the miniseries’ strengths has always been its battle scenes. And this particular episode featured an exciting interpretation of the Battle at Fort Stedman. As I had earlier noted, this episode also featured a poignant recreation of the Surrender at Appomattox. There were some dramatic scenes that I found very satisfying. One of them included George and Orry’s emotional reunion following the Appomattox surrender and Charles’ return to Barclay’s Farm. A part of me realizes this might be wrong, but I felt a great sense of satisfaction in the way Virgilia dealt with her situation with Congressman Sam Greene. However, her act landed her in serious legal trouble and a very tearful reconciliation with her brother George. Last, but not least was Cuffey and Salem Jones’ action-packed assault on Mont Royal. I have to give credit to several people for the manner in which both the action and dramatic sequences in this episode. One of them is Kevin Connor, who I must admit did a pretty solid job in helming this six-part, 540-minutes juggernaut for television from a script filled with plot holes. I also have to comment upon the work of cinematographer Jacques R. Marquette, whose excellent photography of the miniseries added a great deal of pathos to a story about one of the United States’ most traumatic periods in its history. I was especially impressed by how he handled the Fort Stedman sequence. Bill Conti’s score contributed a great deal to the production’s narrative. And I was also impressed by the work of the six men who served as the miniseries’ film editing team, especially for the Fort Stedman and Mont Royal attack sequences. And as usual, Robert Fletcher knocked it out of the ballpark with his costume designs . . . especially for the outfits shown in the images below: Judging from Fletcher’s filmography, I suspect that “NORTH AND SOUTH: BOOK II” was his best work on screen – movies or television. “NORTH AND SOUTH: BOOK II” also featured some fine performances. Aside from one particular scene that I found particularly hammy, I was satisfied with the performances featured in this episode. For me, the best performances came from Patrick Swayze, Lloyd Bridges, Parker Stevenson, Forest Whitaker, Tony Frank, David Ogden Stiers, Jean Simmons, Inga Swanson, John Nixon. I was especially impressed by James Read and Kirstie Alley’s performances in the scene that featured George and Virgilia’s emotional reconciliation and discovery of President Abraham Lincoln’s assassination. And the poignancy in the Appomattox surrender sequence greatly benefited from Anthony Zerbe and William Schallert’s portrayal of Generals Ulysses S. Grant and Robert E. Lee. On a minor note, if you look carefully during the miniseries’ last half hour, you might spot future star Bryan Cranston as a Union officer whom George questions about Orry whereabouts, following the Fort Stedman battle. Although there seemed to be a good about Episode Six that strikes me as praiseworthy . . . and there is, I found a good deal that I found problematic. Which strikes me as a pity, for the emotional levity featured in this episode could have made Episode Six my favorite in the entire miniseries. Alas . . . I have too much to complain about. Three of my problems centered around the Charles Main character. First of all, two months after he last saw Augusta Barclay in Episode Five, Charles discovered that he was the father of an infant boy. Apparently Augusta had died while giving birth to their son. Unfortunately . . . Augusta DID NOT look pregnant during her last meeting with Charles. And considering that they had made love in the previous episode, her pregnancy should not have come as a surprise to him. To make matters worse, young Augustus Charles Main looked as if he had been conceived nearly two years ago. Honestly. The kid looked at least one year old. And Charles and Augusta had started their affair eleven months before the end of the war. Unlike Jakes’ novel, Charles found his son being cared for by Augusta’s South Carolina relatives in Charleston. Really? Was that necessary? I found it ridiculously convee-ee-ee-ient that Augusta had Charleston relatives, who managed to be in Virginia at the time she gave birth to her son. My second problem with Charles is the fact that it took him less than a week to travel from Spotsylvania County, Virginia to Charleston, South Carolina. Less than a week? On horseback? Charles’ journey should have taken him longer. This seemed like an extreme reversal of Brett and Semiramis’ ludicrous four-month journey from Washington D.C. to Mont Royal. Quite frankly, I felt a bit put out that the screenwriters (which include John Jakes) dumped a tragic ending to Virgilia Hazard’s story arc. Unlike the miniseries, Virgilia survived her affair with Congressman Greene and ended up marrying another black man – the same man who had befriend George, Constance and Brett in the novel. Apparently, Wolper Productions felt that since Virgilia’s five-year marriage had ended in tragedy, it seemed proper to give her a tragic ending, as well. Or perhaps many of the trilogy’s fans had found Virgilia’s radical politics and marriage to Grady so off-putting that David Wolper and the screenwriters had decided to appease them by giving her a tragic ending. Regardless their reason, I found Virgilia’s tragic ending very annoying and clichéd. As much as Patrick Swayze’s portrayal of Orry Main had impressed me in this episode, there is one scene in which his acting skills failed to impress. I hate to say this, but I cannot hold it back. I refer to the scene in which Orry finds the body of his mother Clarissa Main, following the attack upon Mont Royal and expresses his grief. Can I say . . . OVER-THE-TOP? Seriously. I found it to be one of the hammiest moments in the entire television trilogy. But the episode’s real problems were made obvious during the Fort Stedman battle sequence. Granted, I was impressed by the visual style of this segment. But I noticed the screenwriters went out of their way to ensure that the major four military characters – George, Billy, Orry and Charles – all participated in this battle. In ensuring this, the screenwriters committed a great deal of inconsistencies and bloopers. Orry led a group of infantry troops into battle for the first time, since the Battle of Churubusco, nearly eighteen years earlier. Personally, I never saw the need for him to be put into the field. The Army of Northern Virginia still had enough commanders to lead men into battle. One of the officers under his command proved to be Charles. Charles? Charles, who spent the entire war as a cavalry officer and scout under Wade Hampton III? I am aware that Charles had led infantry troops during the Battle Antietam, during Episode Three. And I had pointed that this was a major blooper. Yet, the screenwriters repeated this same blooper by allowing him to lead infantry troops again during the Battle at Fort Stedman . . . this time, under Orry’s command. Also leading infantry troops for the Union was George Hazard. Now, I am baffled. George had command of Artillery troops during the Battle of Gettysburg in Episode Three and when he was captured during Episode Four. Could someone explain why the screenwriters had decided to have him lead Infantry troops in this episode? Among the troops under George’s command proved to be his brother Billy, who continued to serve with the Sharpshooters. It was bad enough that the writers had Charles serving under Orry during this battle. But they had Billy serving under George, as well? There is more, folks. Not only did Billy continued to serve with the Sharpshooters, he also seemed to be in command of them. For, I saw no other officers during this scene. I am aware that Hiram Burdan was no longer in command of this regiment by the end of the war. But what happened to the other officers in the regiment? What happened to Rudy Bodford and Stephen Kent? They seemed to have disappeared. And how did Billy end up in this position, considering that he had spent nearly 10 months AWOL between the summer of 1863 and the spring of 1864? What the hell, guys? Come on! Do not get me wrong. There is still plenty to admire about “NORTH AND SOUTH: BOOK II”. Like its predecessor,“NORTH AND SOUTH”; it has its share of good acting, exciting sequences, drama, superb production values, and probably the best costume design in the entire trilogy, thanks to Robert Fletcher’s work. Unfortunately, the 1986 miniseries has its share of major flaws that included clunky dialogue and probably some of the worst writing in the entire trilogy. And when I say the entire trilogy, I am including the much reviled “NORTH AND SOUTH III: HEAVEN AND HELL”. “NORTH AND SOUTH: BOOK II” might be my least favorite chapter in the television trilogy, thanks to a great deal of plot holes and historical inaccuracies . . . I still managed to enjoyed it anyway. “NORTH AND SOUTH: BOOK II” finally reached its home stretch in Episode Five, the penultimate episode. Well . . . almost. Beginning several weeks after the end of Episode Four, Episode Five continued the miniseries’ portrayal of the Civil War’s last year for the Hazards and the Mains. It also put three or four subplots to rest. Episode Five opened with George Hazard still imprisoned inside Libby Prison in Richmond, Virginia. The episode also continued with Madeline Main’s efforts to feed Charleston’s poor and war refugees, Charles Main and Augusta Barclay’s wartime romance, and the survival of Mont Royal’s remaining inhabitants. Episode Five also closed several subplots that included Stanley and Isobel Hazard’s war profiteering, Elkhannah Bent and Ashton Main Huntoon’s plot against Jefferson Davis’ administration, and Madeline’s relationship with former officer Rafe Beaudine. This episode featured some excellent dramatic moments. Lewis Smith certainly shined in his portrayal of Charles Main, who had hardened considerably after three-and-a-half years of war. This was especially apparent in scenes that included Charles’ reluctance to help his cousin Orry Main rescue George Hazard from Libby Prison, his cold-blooded killing of a Union prisoner, his attempt prevent fellow scout Jim Pickles from deserting and his emotionally distant attitude toward lady love Augusta Barclay and her manservant, Washington. Another well acted scene featured Brett Main Hazard and Semiramis’ encounter with former Mont Royal overseer, Salem Jones. Watching Erica Gimpel point a shotgun at Tony Frank, considering their characters’ past history, brought a smile to my face. I also enjoyed the poignant scene between Brett and her mother, Clarissa Main, while the latter painfully reminisced about the past; thanks to Genie Francis and Jean Simmons’ performances. And both James Read and Jonathan Frakes knocked it out of the ballpark in the scene that featured George’s confrontation with Stanley and Isobel over their war profiteering. They were supported by fine performances from Wendy Kilbourne and Mary Crosby. But another truly superb performance came from Terri Garber, who got a chance to portray Ashton Huntooon’s increasing doubts over Elkhannah Bent’s scheme against Davis. This was especially apparent in one scene in which Ashton silently expressed shame over her willingness to prostitute herself to a potential contributor for Bent’s plot. She received fine support from Jim Metzler as her husband James Huntoon and Patrick Swayze as Orry Main. But I felt that Philip Casnoff’s Bent nearly became slightly hammy by the scene’s end. Even Lesley Anne Down and Lee Horsley managed to shine as Madeline and the infatuated Rafe Beaudine. But I must admit that I found one of their later scenes slightly melodramatic. Yet, despite these dramatic gems, I was not particularly impressed by the writing featured in Episode Five. I had a problem with several subplots. One, I had a problem with the subplot involving Stanley and Isobel’s profiteering. It made me wish the screenwriters had adhered to author John Jakes’ original portrayal of the couple in his 1984 novel, “Love and War”. I felt this subplot had ended with a whimper. It was bad enough that George had killed Stanley and Isobel’s partner in a bar fight. But aside from the dead partner, the only way the couple could face conviction was to confess. And I found it implausible that a remorseful Stanley would still be willing to do that after receiving an earful of angry insults from George. Very weak. Episode Five also allowed Madeline and Bent’s subplots to interact for the purpose of killing off Rafe Beaudine. Frankly, I found the idea of Bent traveling from Richmond to Charleston for more funds . . . only to be told to seek hard cash from“the Angel of Charleston” – namely Madeline. The latter recruited a retired stage actress portrayed by Linda Evans to impersonate her and discover Bent’s plans. And what was Madeline’s next act? She left her boarding house (in the middle of the night) to warn . . . who? The script never made it clear about whom Madeline had intended to warn. Why? Because her night time task was interrupted by Bent, who had recognized the stage actress. And before Bent could lay eyes upon Madeline, Rafe comes to her rescue. What can I say? Contrived. I also found Bent’s scheme to get rid of Jefferson Davis and assume political and military control of the Confederacy rather ludicrous. Audiences never really saw him recruit any real political support for his scheme . . . just money from various wealthy Southerners. The screenplay never allowed Bent to make any effort to recruit military support for the weapons he had purchased. In the end, I found the entire subplot lame and a waste of my time. And finally, we come to the efforts of “Madeline the Merciful” to find food for Charleston’s poor. Personally, I found this subplot ludicrous. Madeline did not bother to recruit other women from Charleston’s elite to help her. And I suspect some of them would have been willing to help. I also found this subplot extremely patronizing. Again, it seemed to embrace the“savior complex” trope to the extreme. The subplot seemed to infantilize all social groups that were not part of the city’s white elite or middle-class – namely fugitive slaves, working-class whites and all free blacks. I found this last category surprising, considering that the screenwriters failed to acknowledge that not all free blacks were poor. In the end, this entire subplot struck me as a white elitist fantasy that Julian Fellowes would embrace. The production values featured in the episode struck me as top-notch. Both director Kevin O’Connor and the film editing team did excellent work for the actions scenes in Episode Five. I found myself impressed by the scenes that featured George’s escape from Libby Prison, his bar fight with Stanley and Isobel’s profiteering partner, Bent and Rafe’s fight in Charleston and the former’s encounter with Orry and the Huntoons back in Virginia. More importantly, Robert Fletcher continued to shine with his outstanding costume designs, as shown in the following images: Yes, Episode Five featured some fine dramatic moments and performances. It even featured some solid action scenes. But . . . I was not particularly happy with most of the subplots. I also found the ending of one particularly subplot rather disappointing. No one felt more relieved than me when Episode Five finally ended. Episode Four of the 1986 miniseries, “NORTH AND SOUTH: BOOK 2” picked up at least seven to eight months after Episode Three left off. The miniseries arrived at a point in which the Civil War began to embark upon its last year. And yet, the miniseries itself had reached its mid point. I found it odd that producer David Wolper, director Kevin Reynolds and the production’s screenwriters would portray the war’s last year (in reality, eleven months) within three episodes. Oh well. The episode began with a strong sequence that featured George Hazard’s capture by John Mosby’s Rangers, while he and his men were transporting artillery guns and units to the front. The episode would return to George’s travails as a prisoner of war at Libby Prison in two more sequences. This first half hour also featured the beginning of Charles Main’s affair with Augusta, Billy Hazard’s return to the Sharpshooters’ regiment and the Battle of the Wilderness. Episode Four also portrayed the marriage woes of Ashton and James Huntoon, along with Elkhannah Bent’s attempt to woo Huntoon into his conspiracy against Confederate President Jefferson Davis; Madeline Main’s first meeting with former army officer Rafe Beaudine and her efforts to raise food and money for war refugees in Charleston; and Virgilia Hazard’s feud with her nursing supervisor, Mrs. Neal. I have mixed feelings about Episode Four. I did not harbor a low opinion of it, as I did Episode Two and Episode Five. But I did not love it. I thought it began on a strong note with George’s capture and the Battle of the Wilderness. It also ended on a strong note with George’s experiences at Libby Prison and Virgilia’s troubles with Mrs. Neal. I must admit that I had a problem with the episode’s second act. Aside from the interesting scene that featured George’s arrival at Libby Prison and the revelation of the state of the Huntoon marriage, I had a bit of a struggle staying awake. One again, the 1986 miniseries managed to provide a battle sequence interesting enough to maintain my interest and impress me at the same time. Director Kevin Connor did an excellent job with this sequence by shooting it in a documentary style that gave it a stark and realistic look. And he was aptly supported by Jacques R. Marquette’s photography. For once, Marquette’s hazy photography served the narrative very well. The episode also benefited from Robert Fletcher’s lovely costumes, as shown in the images below: I found General Ulysses Grant’s angry response to his staff’s fears over Robert E. Lee, following the Wilderness battle particularly enjoyable. What is interesting about this moment is that it actually happened. And I noticed that actor Anthony Zerbe not only used Grant’s actual words, but also improvised a few words into the speech. Actually, I felt it was the episode’s highlight, thanks to Zerbe’s performance. Another positive aspect of Episode Four turned out to be Ashton and James Huntoon’s marriage woes. Terri Garber and Jim Metzler did an excellent job of conveying how Ashton’s infidelity, Huntoon’s political failures and the war had put a toll on a marriage that had been loveless from the start. The venomous conflict between Virgilia Hazard and her supervisor, Mrs. Neal proved to be very interesting, thanks to Kirstie Alley and Olivia De Havilland’s excellent performances. I found both ladies unsympathetic, until Mrs. Neal decided to harass Virgilia, while the other was having trouble staying awake after long hours of work. I found the older woman’s attitude simply bitchy. I also noticed that despite Mrs. Neal’s accusations of Virgilia’s poor ministrations to Confederate patients, the miniseries failed to substantiate her claims. And I found myself wondering if Mrs. Neal simply disliked Virgilia for the latter’s abolitionist leanings and marriage to a former slave. Kirstie Alley had another chance to shine in a sequence that involved Virgilia’s reconciliation with none other than Orry Main, who had been injured and captured by Union troops. No only did Alley give an excellent performance in this poignant sequence, but so did Patrick Swayze. I also have to give kudos to both James Read and Wayne Newton for the crackling hostility they managed to produce between George Hazard and his Libby Prison tormentor, Captain Thomas Turner. In fact, I never thought I would say this, but Newton made a damn fine villain. He nearly put Philip Casnoff, David Carradine and Terri Garber to shame. His performance certainly gave the Libby Prison sequence a creep factor that I found very effective. And if you look carefully, you might find actor Billy Drago (of “THE UNTOUCHABLES” fame) as one of the Union prisoners. I do have several problems about this episode. One, I wish that Charles and Augusta’s affair had begun a lot sooner than three years after they first met. In other words, I wish the screenwriters had followed Jakes’ original portrayal of their relationship. I believe this could have given Charles and Augusta’s affair more depth and paced a lot better. The portrayal of their affair developed into a major problem in Episode Six. Their affair began in the aftermath of one of the battles during the Wilderness Campaign. And for the likes of me, I could never understand what Charles was doing there, while wearing a heavy overcoat in the middle of May. The screenplay never explained why he was there. Then we come to the problem of Billy’s return to his regiment after deserting for nearly ten months (he departed right after the Gettysburg battle in July 1863 and returned to his regiment either in late April 1864). The consequences he paid for deserting were ridiculous. Billy received a lecture from Colonel Hiram Burdan, passed over for a promotion to captain and threatened with court martial if he ever deserted again. What on earth were the writers thinking? Billy should have faced a court-martial or forced to resign his commission for being absent without leave for nearly ten months. Whoever had written this episode must have been completely ignorant of military protocol . . . or smoking something. And what was Berdan’s excuse for his leniency toward Billy? He needed all available men. Hogwash! This was the spring of 1864, when the Union Army’s ranks were literally swollen for the remainder of the war, despite desertion. No other TV show, novel, play or etc., would have featured such a major writing gaffe. Then again, you never know. And why was Berdan still in command of the Sharpshooters in this episode? By keeping Berdan as Billy’s commanding officer in this episode, the writers committed a historical gaffe. Berdan had decided to leave the Union Army by the late winter/early spring of 1864. On the other hand, I found Madeline Main’s efforts to help the poor – refugee slaves, free black and poor whites – in Charleston rather noble and dull as hell. Madeline’s first husband, Justin LaMotte, had contemptuously given her the nickname – “Madeline the Merciful” in the first miniseries. I hate to say this, but after viewing the beginning of this story line in Episode Four, I found myself sharing his contempt. Her actions were admirable, but I feel the writers went too far in portraying her in a noble light. Quite simply, one could easily accuse Madeline of harboring a savior complex – one that struck me as incredibly pretentious. This sequence also introduced a young former slave named Michael and his mother, who came from Tennessee. I really had a problem with this. Why on earth would Tennessee slave refugees head deep into Confederate territory, when they could have easily ended up in Union held cities like Nashville, Memphis and Vicksburg? However, this sequence featured a young Bumper Robinson as Michael, who managed to act circles around Lesley Anne Down (as if that were possible). And it also introduced the delicious Lee Horsley as a disgraced army officer-turned-wastrel named Rafe Beaudine, who came to Madeline’s aid against a band of scavengers. Horsley and Lesley Anne Down managed to create a sparkling screen chemistry that nearly put all of the other on-screen romantic pairings to shame. In the end, Episode Four proved to be a mixed bag. It featured some excellent dramatic scenes and a well-shot battle sequence that helped me maintained my interest. On the other hand, it also featured some questionable writing that left me shaking my head with disappointment. It was not one of my favorite episodes, but was certainly not a disappointment either. I have mixed feelings about Episode Three of “NORTH AND SOUTH: BOOK II”. Fortunately, most of my feelings are positive. This episode featured the Battle of Antietam, the Battle of Gettysburg, and a major schism in the Main family, regarding Madeline Main and her two sisters-in-law – Brett Hazard and Ashton Huntoon. But there was still certain aspects of this episode that I did not find particularly appealing. I found the first half of this episode to be rather dull. Those reading this article would find this statement surprising, since the Battle of Antietam was featured in this first third of the episode. But I did. Following President Abraham Lincoln’s Emancipation Proclamation, one of the Mains’ slaves, Jim, decided to take matters into hands and run away. Unfortunately, he was caught and killed by the Mains’ former overseer, Salem Jones. I will admit that the reaction to Jim’s death proved to be slightly interesting, thanks to the excellent acting by Erica Gimbel, Beau Billingslea and especially Forest Whitaker; who portrayed Semiramis, Ezra and Cuffey. I was especially impressed by Whitaker’s performance as he conveyed Cuffey’s bitterness over being owned by the Mains. However, I found Brett and Madeline’s presence at Jim’s funeral to be a touch patronizing. But that is merely a private opinion. Now, I had no problems with Kevin Connor’s direction of the Battle of Antietam. I believe he did the right thing by keeping the battle solely focused upon Billy Hazard and Charles Main. This allowed their brief reunion to be not only surprising, but dramatic. But I do have one major quibble about this particular sequence. How did Charles and his fellow officer, Ambrose Pell go from being cavalry scouts to leading large bodies of infantry troops on the field? If the miniseries had earlier included a small band of scouts under their command, I could see them leading these men into battle. But large bodies of infantry troops? Were the officers of these troops dead? And what kind of troops were they leading? Infantry or dismounted cavalry? I found this kind of inconsistent vagueness very irritating. The Battle of Gettysburg was better handled . . . somewhat. Considering it was one of the major conflicts of the war and fought in the same region – Southern Pennsylvania – as the Hazards’ hometown of Lehigh Station, I was surprised that the screenplay did not focus too highly on it. The battle was simply used as a literary device for the reunion of George and Billy Hazard and an excuse for the latter to go AWOL and see Brett. The second half of Episode Three turned out to be a big improvement. Most of the slaves left Mont Royal and I did not blame them one bit. Orry’s reaction to their departure was interesting, considering how “BOOK I” had established his slight aversion to slavery. More importantly, his character came off as increasingly conservative. I found this surprising, considering that in the novel, “Love and War”, his views on slavery and racial relations had become slightly more radical. I found that little moment in which Orry bid his mother Clarissa Main good-bye, following his furlough, rather lovely and touching, thanks to the performances of Patrick Swayze and Jean Simmons. But I have mixed feelings about Billy’s decision to go AWOL in order to see Brett in South Carolina. Frankly, I found it disturbing. I do not blame him for missing Brett. But if the writers had not sent her to South Carolina in that ridiculous story line in Episode 2, she would have remained in the North and Billy would not have went AWOL. And his decision to head for South Carolina will prove to be troublesome for Episode Four‘s plot. I am also remain dumfounded by George’s position in the Union Army. During his reunion with Billy before the Gettysburg battle, he claimed that he had been transferred to field duty. And he was seen commanding artillery units. Yet, after the battle, he was seen attending another meeting with President Lincoln and his Cabinet. What the hell? The screenwriters really screwed up this time. The episode’s second half, Ashton Main Huntoon’s appearance at Mont Royal really stirred things a bit. I found it to be the episode’s most enjoyable segment. Before I explain why I enjoyed it, I have to say a few words regarding Ashton’s reason for visiting her home – namely to confront Madeline about her African ancestry and drive her from Mont Royal and Orry’s radar. If I must be frank, I found Ashton and Bent’s revenge against Orry by using Madeline’s family secret, a bit . . . anti-climatic. Frankly, I thought they could have exposed Madeline’s secret in a more dramatic and satisfying moment – like during a political party in Richmond (which happened in the novel) or expose the secret to the Mains’ neighbors. However, their act of revenge did result in a marvelous scene well acted by Terri Garber and Lesley Anne Down. Semiramis’ rant against Ashton, thanks to another great piece of acting from Gimpel, was nice touch, although a bit fruitless. But it was Brett’s confrontation with Ashton that really did justice to this episode. Kudos to Garber and especially Genie Francis. Francis also shared an excellent scene with Parker Stevenson, who as Billy Hazard expressed his growing discontent with the war. There is one major problem with this sequence. When Ashton arrived at Mont Royal, she carried foodstuff for the plantation. This makes no sense whatsoever. Ashton was traveling from a state – namely Virginia – that had been ravaged by two years of war. The amount of foodstuff she was carrying from Virginia should have been rare. South Carolina, on the other hand, had been freed of any battles by 1863, aside from the Sea Islands and the forts off the coast of Charleston. There should have been plenty of foodstuff at Mont Royal, thanks to Madeline, Brett, Semiramis and Ezra. Anthony Zerbe made his first appearance as General Ulysses S. Grant, whom George had traveled all the way to Tennessee to meet, on behalf of President Lincoln. Veteran stars James Stewart and Olivia De Havilland appeared near the end of this episode. Did anyone know that those two had once dated in the late 1930s? Anyway, Stewart gave a charming performance as Madeline’s Charleston attorney, despite his Midwestern accent. However, De Havilland’s portrayal as Virgilia Hazard’s field hospital supervisor, Mrs. Neal, proved to be more interesting and complex. I could not decide which character was more irritating – Virgilia’s arrogant disregard for Mrs. Neal’s advice, or the latter’s patronizing concern for Southern patients at the expense of the other patients and her unfounded suspicions that Virgilia was ignoring them. Both De Havilland and Kirstie Alley gave superb performances in their scenes together. Although Episode Three had its flaws, I cannot deny that Kevin Connor did an excellent job as the director. But I believe he was ably supported by the miniseries’ crew. Once again, Jacques R. Marquette’s photography provided a good deal of color and style to this episode – especially in the Battle of Antietam sequences. Jospeh R. Jennings continued his excellent production designs, ably transforming viewers back to the United States of the early 1860s. I could say the say about Robert Fletcher’s costume designs. I was especially impressed by his wardrobe for Maude and Isobel Hazard, along with Ashton Huntoon, who ended up being the best-dressed character of the episode. Below are examples of Fletcher’s work: Despite a some quibbles and a dull first half hour, Episode Three was an improvement over Episode Two. I was surprised by the number of excellent dramatic moments and first-rate acting in this episode. Also Kevin Connor’s direction of the Battle of Antietam and Gettysburg struck me as pretty damn good. I could say that Episode Three was the highlight of the 1986 miniseries. But I do not believe I would go that far.	{ "pile_set_name": "Pile-CC" }
Peter May Engineering Ltd. is providing this list of links as a service to its customers. Inclusion on the list does not imply that Peter May Engineering Ltd. can guarantee the quality of products or services offered by the organisations. The Austin Healey Sprites are now racing with the MG Midgets and forming a large grid of similar cars providing close and exiting racing. Also information on the Austin Healey Sprint and Hillclimb series. Motor Sports Association Clubs/Info What else could you possibly want to know ? Links to every concievable club/association/commercial enterprise. A real Aladdin’s Cave. News/History/Extensive links section/Excellent bulletin board. Lots of background information including the full history of the Midget .	{ "pile_set_name": "Pile-CC" }
Q: jQuery .css body opacity I have a news tab where whenever an user clicks it, the popup box shows up with the details, however I want the background or the body tag itself to dim so I wrote: $("#read").click(function(){ $("#pbox").fadeIn('slow'); $("body").css({"opacity": "0.5"}); }); However the box itself dims either. Is there a way to make the box ignore this command? Or maybe there is another way around? A: As body contains the #pbox then the box itself will be subject to the 50% opacity you have applied. A better method would be to overlay a semi opaque div over your entire window, and then position #pbox above it, a little like so: #overlay { position: fixed; top: 0; left: 0; background-color: #fff; width: 100%; height: 100%; display: none; } #pbox { z-index: 1; } So here you have the white #overlay div appearing over all your content with 50% opacity. Above it is #pbox with a z-index specified to ensure it appears on top. The jQuery code would be a little like this: $("#read").click(function(){ $("#pbox").fadeIn('slow'); $("#overlay").show().css({"opacity": "0.5"}); }); A: Unfortunately, there isn't. Since the popup is inside the body tag, it is included in the change in opacity. The only way to do this would be to make an overlay layer which covers the entire body and is translucent, and then place your popup above that.	{ "pile_set_name": "StackExchange" }
Q: Unable to Centre a div inside a JS rendered div I have been trying to use particle effect in the background and have some text centred in that div and have the particle effect in the background. The javascript files refer to the particleJS files which you can find here.Github ParticleJS. But Im just not able to centre it in the middle, is it because JS is rendering it simultaneously is there a way I can do it. Link to codepen body{ margin:0px; padding: 0px; } canvas{ display:block; height: 100%; vertical-align:bottom; } #particles-js{ background-color: black; display: flex; flex-direction: column; justify-content: center; align-content: center; } #name{ color: white; text-align: center; } <!DOCTYPE html> <html> <head> <script type="text/javascript" href = "particle.js"></script> <link rel="stylesheet" media="screen" href="style.css"> <title>Linko</title> </head> <body> <div id="wrapper"> <div id="particles-js"> <script src="particles.js"></script> <script src="app.js"></script> <div id="name"> <p>Hello there</p> </div> </div> </div> </body> </html> A: You can add position: absolute; to the #name div for him to go above the canvas. Then change align-content:center by align-items:center in #particles-js div. Here is a updated codepen :) https://codepen.io/anon/pen/vqWePJ The position:absolute is needed because HTML element by default (posistion:static) are positioned as a flow, one after another in their parents, so you can't have one overlapping another. Adding the position:absolute to one of the element will remove it from this flow, and position it as if it was alone in his parent, so now it can overlap the others. You can see this link for more complet explanations on CSS positionning. https://www.w3schools.com/css/css_positioning.asp For the align-content/align-items issue, align-content is used for multi line alignement, and align-items for alignement in the inverse of the flex box direction. The naming here is discutable and a bit confusing since justify-content is used for single line alignement in the flex box direction I think, but I was not here during this discussion, they probably had a reason to do it this way. You can see this question What's the difference between align-content and align-items? for more details on that.	{ "pile_set_name": "StackExchange" }
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1111/bdi.12949 [^1]: These two authors contributed equally.	{ "pile_set_name": "PubMed Central" }
n 6.529153mm? 0.6529153 How many months are there in 65.68831 centuries? 78825.972 What is 4/75 of a minute in milliseconds? 3200 How many kilograms are there in 8460.704ng? 0.000000008460704 What is 45/8 of a litre in millilitres? 5625 What is thirteen quarters of a millisecond in microseconds? 3250 Convert 0.9472341 weeks to microseconds. 572887183680 Convert 0.5223078km to meters. 522.3078 How many months are there in 21/2 of a year? 126 What is 2.4706806 nanoseconds in minutes? 0.00000000004117801 Convert 0.4300652 litres to millilitres. 430.0652 What is one quarter of a litre in millilitres? 250 What is fourty-eight fifths of a centimeter in millimeters? 96 Convert 2489.848 days to hours. 59756.352 What is 37/2 of a litre in millilitres? 18500 What is 9317.104 grams in milligrams? 9317104 Convert 85265.74mg to nanograms. 85265740000 How many milliseconds are there in 838.9628 days? 72486385920 Convert 87712.77l to millilitres. 87712770 How many nanometers are there in 1/4 of a micrometer? 250 How many nanograms are there in 3/8 of a microgram? 375 How many months are there in 1/6 of a year? 2 How many centimeters are there in 76/5 of a meter? 1520 Convert 4.462065 millimeters to centimeters. 0.4462065 Convert 286902.3 hours to microseconds. 1032848280000000 How many months are there in 25/4 of a decade? 750 How many hours are there in 225828.4 weeks? 37939171.2 Convert 88.49806 millennia to months. 1061976.72 What is 8.242511kg in milligrams? 8242511 How many millennia are there in 300.619 decades? 3.00619 What is 8/7 of a week in hours? 192 Convert 4148.051l to millilitres. 4148051 Convert 50180.19 tonnes to grams. 50180190000 How many months are there in twenty-nine thirds of a decade? 1160 What is 11/4 of a centimeter in micrometers? 27500 How many hours are there in five sixths of a day? 20 What is 13/5 of a gram in milligrams? 2600 What is 44.09487cm in millimeters? 440.9487 How many years are there in 4.386613 millennia? 4386.613 What is 44/5 of a gram in milligrams? 8800 What is 19.85796 micrograms in tonnes? 0.00000000001985796 What is three tenths of a gram in milligrams? 300 How many minutes are there in thirty-four fifths of a week? 68544 Convert 0.1308962 centuries to millennia. 0.01308962 What is 74.92048 litres in millilitres? 74920.48 How many millimeters are there in 0.7092635 nanometers? 0.0000007092635 What is three sevenths of a week in hours? 72 What is 0.0828613ml in litres? 0.0000828613 How many months are there in one sixth of a year? 2 What is 3/32 of a kilogram in milligrams? 93750 How many micrometers are there in thirteen fifths of a millimeter? 2600 How many kilograms are there in seventy-one fifths of a tonne? 14200 What is seventeen quarters of a hour in seconds? 15300 How many months are there in 11/2 of a year? 66 What is 69.08777um in kilometers? 0.00000006908777 How many grams are there in 3848.137mg? 3.848137 How many hours are there in seven thirds of a day? 56 What is 81.85703 millimeters in micrometers? 81857.03 How many millilitres are there in 17/4 of a litre? 4250 What is 0.0644906 litres in millilitres? 64.4906 How many nanoseconds are there in 1/20 of a microsecond? 50 What is 69/2 of a litre in millilitres? 34500 What is 420.574t in nanograms? 420574000000000000 Convert 153.2792 millilitres to litres. 0.1532792 Convert 0.5176937 meters to millimeters. 517.6937 Convert 74942.9 micrograms to kilograms. 0.0000749429 How many minutes are there in one twentieth of a hour? 3 What is 26/5 of a centimeter in millimeters? 52 How many litres are there in 0.6065195 millilitres? 0.0006065195 What is 7.373863l in millilitres? 7373.863 What is 3/5 of a day in seconds? 51840 How many weeks are there in 214294.248ms? 0.0003543225 Convert 0.674965 weeks to nanoseconds. 408218832000000 Convert 63039.89um to centimeters. 6.303989 How many grams are there in 72/5 of a kilogram? 14400 How many milligrams are there in 47.95985t? 47959850000 How many months are there in 1/30 of a century? 40 Convert 451244.5 days to hours. 10829868 How many millilitres are there in 21.98739l? 21987.39 Convert 1395.596mg to tonnes. 0.000001395596 What is 56097329.4 minutes in weeks? 5565.21125 What is thirteen fifths of a micrometer in nanometers? 2600 How many micrometers are there in twenty-one quarters of a centimeter? 52500 What is 90.7321149ns in weeks? 0.00000000000015002003125 How many nanograms are there in 6094.93t? 6094930000000000000 What is fifteen quarters of a minute in seconds? 225 What is seventeen tenths of a litre in millilitres? 1700 How many nanometers are there in 379.5682um? 379568.2 What is five eighths of a litre in millilitres? 625 How many months are there in 31/6 of a decade? 620 What is 0.4687489m in kilometers? 0.0004687489 Convert 309965.4 months to decades. 2583.045 How many millilitres are there in 0.401492l? 401.492 What is 0.4595726 microseconds in milliseconds? 0.0004595726 What is 24.437562 months in centuries? 0.020364635 What is 51/2 of a litre in millilitres? 25500 How many nanometers are there in eleven quarters of a micrometer? 2750 What is 507739.6l in millilitres? 507739600 What is twenty-seven fifths of a kilogram in grams? 5400 Convert 4073.6961ms to hours. 0.00113158225 What is three tenths of a minute in seconds? 18 What is 38329.57 days in minutes? 55194580.8 What is 1/16 of a centimeter in micrometers? 625 What is 29/5 of a kilometer in meters? 5800 Convert 534.2155 years to centuries. 5.342155 Convert 5.041673mg to kilograms. 0.000005041673 How many minutes are there in 11/2 of a week? 55440 How many centuries are there in 247.2308 millennia? 2472.308 How many kilometers are there in 70765.19 meters? 70.76519 How many kilograms are there in 50.36765 milligrams? 0.00005036765 What is 54/5 of a millennium in years? 10800 How many minutes are there in 11/4 of a day? 3960 How many micrometers are there in 5.332545 nanometers? 0.005332545 What is 8/25 of a century in months? 384 How many months are there in 8/3 of a century? 3200 How many grams are there in three tenths of a kilogram? 300 How many millimeters are there in 11/2 of a centimeter? 55 How many micrograms are there in three tenths of a milligram? 300 Convert 542149.2ns to hours. 0.000000150597 What is 43/2 of a meter in centimeters? 2150 How many minutes are there in 44/5 of a week? 88704 What is seven eighths of a kilometer in centimeters? 87500 How many years are there in 14.26041 millennia? 14260.41 What is 8/25 of a millisecond in microseconds? 320 How many seconds are there in 0.3498241 days? 30224.80224 What is 10/3 of a minute in seconds? 200 What is 12/25 of a millimeter in micrometers? 480 What is sixty-eight thirds of a week in hours? 3808 How many micrometers are there in 17/4 of a centimeter? 42500 What is 290499.4 kilometers in micrometers? 290499400000000 What is twenty-six fifths of a decade in months? 624 What is 2131.1847 months in years? 177.598725 What is 1/24 of a century in months? 50 How many centimeters are there in 29/5 of a meter? 580 What is 37/2 of a litre in millilitres? 18500 How many meters are there in twenty-nine halves of a kilometer? 14500 How many seconds are there in 864726.4 milliseconds? 864.7264 How many millilitres are there in seven eighths of a litre? 875 What is 25/8 of a centimeter in micrometers? 31250 Convert 40035.861 nanoseconds to hours. 0.0000000111210725 How many tonnes are there in 694.638ug? 0.000000000694638 Convert 298918.5kg to grams. 298918500 What is five eighths of a kilogram in grams? 625 How many years are there in 3/10 of a decade? 3 Convert 4200.05nm to kilometers. 0.00000000420005 What is 7/4 of a kilometer in meters? 1750 How many millilitres are there in twenty-one halves of a litre? 10500 What is 0.9837327ug in tonnes? 0.0000000000009837327 How many milligrams are there in 8.469007 kilograms? 8469007 Convert 0.7376598 millennia to decades. 73.76598 How many micrometers are there in 6/25 of a centimeter? 2400 Convert 7.398847 tonnes to kilograms. 7398.847 What is 13/4 of a tonne in kilograms? 3250 How many nanograms are there in 50.91258kg? 50912580000000 How many kilograms are there in 6/5 of a tonne? 1200 How many millilitres are there in 3/10 of a litre? 300	{ "pile_set_name": "DM Mathematics" }
Birds fly in the foreground as a plume of ash and steam rise from Popocatepetl volcano, as seen from San Andres Cholula, Mexico, Wednesday. Mexico's Popocatepetl volcano is continuing to spout gases and hot rock fragments and it is dusting towns on its flanks with volcanic ash. Mexico City — When Mexicans shudder with fear, they are usually thinking about decapitated bodies, stories of family members being kidnapped for ransom, or other consequences of the nation's deadly drug war. But today, it is the image of erupting volcanoes and trembling homes that has captivated their attention. With four earthquakes or aftershocks over 6.0 in four months, and now Popocatepetl volcano spewing ash, water vapor, and rock fragments into the air, catastrophes have officially overtaken public security as what's most on the public mind, according to a new survey by the polling group Con Estadistica and media company Grupo Formula in Mexico City. In the national poll carried out this month, 65 percent of respondents cited catastrophes and accidents as one of the top three things on their minds, while public security was indicated by 48 percent of respondents. The presidential elections slated for July 1 trailed at a distant third, at 28 percent. Unfortunately, some of the more joyous images, like recent Easter vacations, only ranked at one percent. These shifting concerns are easily understood: Mexico raised the alert level for Popocatepetl, known as “Popo” to locals, after hot rock fragments were hurled into the air early this week. The dome of the volcano, which sits at nearly 18,000 feet just southeast of Mexico City, began to expand Friday, according to the National Center for Disaster Prevention. The volcano's last major eruption occurred in 2000, forcing the evacuation of tens of thousands of residents who live at the base of the peak. Volcanic activity has increased this year, and experts say that while it is a scary prospect, it can help prevent a larger-scale disaster as the plumes of water and ash release mounting pressure. The series of quakes in western Mexico, including a March 20 noon tremblor of 7.4, felt as far away as Mexico City has some optimistic-minded Mexicans relieved that tension is being released, but as Don Blakeman, a geophysicist with the Colorado-based US Geological Survey says, that pressure release doesn't foretell what will happen along the rest of the faultline. And for the pessimists out there, the earth's movements make it easy to keep focusing on when it could tremble again. That's why, as the new poll shows, earthquakes are what's most on people's minds, with 50 percent of respondents citing seismic activity, far surpassing any other singular issue on the Mexican political and social scene.	{ "pile_set_name": "Pile-CC" }
I’m currently reading The girl with the dragon tattoo – three years after the rest of the English-speaking world, I know. For me, that’s cutting edge. It’s pretty good so far. Well, the actual printed text is pretty good. I wish I could say the same of the pencilled note left in the margin of page 210 by a previous library user: Love that full stop after the 'I'. Assertive or what? So, our unknown pedant appears to have a problem with “older than Anita and me”. Let’s see. The usual rule when dealing with a …and I or …and me situation is to remove the bit immediately before I or me. Then you know which is correct. In this case, older than I happens to be more grammatically correct… if you wish to sound like Stephen Fry in full Jeeves mode, that is. Since the character isn’t an Oxford don, this is an informal conversation and there is more to the art of translation than being grammatically correct at all times, I’m firmly in the translator’s camp on this one. Plus, anyone who writes in a library book – for whatever reason – is a vandal and a cretin.	{ "pile_set_name": "Pile-CC" }
Infrastructure & Communication Infrastructure & Communication Hello Fellow Committee Members! Following up on the official announcement, here's a few basic things we should get agreement over before proceeding. First off, I'm hoping we can manage to avoid confusing email-threading in the interest of finding information easier lateron in the email archives. To this end, I'd like to ask you to consider changing the subject of your reply if you realise that the topic discussed is diverging significantly from the one advertised in the Subject-header. I'll start with the following basic topic ## Infrastructure & Communication Obviously, we have this public (archived) mailing list "[hidden email]". There's also a (registered) IRC channel "#haskell-prime" on freenode where many of us will probably hang around. In the past, the Prime committee used Trac (currently at https://prime.haskell.org/ ) to organise its work. Trac provides a wiki, source-browser, and a ticket tracker (which is familiar to GHC developers, and e.g. allows easy migration of wiki-content to/from the GHC Wiki). Some time ago, I converted the original Haskell-Report Darcs repositories into a single Git repository (with branches) at GitHub However, since Trac has accumulated quite a bit of old content in its ticket-tracker over the years, and "Haskell 2020" has been coined a reboot. Maybe it wouldn't be such a bad idea to start over at GitHub, and consider the Trac instance mostly as a legacy archive of historic content. GitHub allows for Git-based workflows, and there's prior art related to language design we could steal ideas from, for instance: IMO, GitHub's issue tracker has become flexible enough for our needs and its integration with Git pull-requests allows to e.g. group together change proposal description/motivation, discussion, and finaly the delta to the haskell-report (with inline annotations/reviews) and so on. (However, I consider GitHub's Wiki-component quite weak. I'm not sure what to do about that. Maybe keep using Trac's wiki for that?) Moreover, we can have CI (I've actually set up a TravisCI job which builds the LaTeX code) for the Haskell Language report drafts. One benefit I see from using GitHub is that this way would we be closer to the Haskell community (given the majority of Hackage packages are hosted on GitHub), and our work would be more transparent for the community as well as offering a lower barrier to participation/contribution. Moreover, I think GitHub would also help make our efforts/progress towards a revised Haskell Report more visible to the community, which in turn may even provide us the motivation to carry on... So... Does anyone object to using GitHub? In case there's no objection, which of the existing language-design GitHub projects do you consider a good fit for Haskell Prime and therefore worthy of imitation? Re: Infrastructure & Communication > > However, since Trac has accumulated quite a bit of old content in its > ticket-tracker over the years, and "Haskell 2020" has been coined a > reboot. Maybe it wouldn't be such a bad idea to start over at GitHub, > and consider the Trac instance mostly as a legacy archive of historic > content. > > > GitHub allows for Git-based workflows, and there's prior art related to > language design we could steal ideas from, for instance: > > - https://github.com/fsharp/FSharpLangDesign> - https://github.com/rust-lang/rfcs> - https://github.com/golang/proposal> - (any others noteworthy?) > This seems like the pragmatic way forward. And, as you say, there's plenty of evidence from other language communities that it can work effectively. > IMO, GitHub's issue tracker has become flexible enough for our needs and > its integration with Git pull-requests allows to e.g. group together > change proposal description/motivation, discussion, and finaly the delta > to the haskell-report (with inline annotations/reviews) and so on. > (However, I consider GitHub's Wiki-component quite weak. I'm not sure > what to do about that. Maybe keep using Trac's wiki for that?) > I personally have no problem with a Trac wiki. That being said, the Rust model of having an RFC repo seems to have worked really well for them and allows for easy discussion and comments from the community at large. If we choose to go that route I would gladly take the time to gather relevant info from the Trac wiki and organize it similarly to the way the Rust team has. > Does anyone object to using GitHub? > I think it's great. > In case there's no objection, which of the existing language-design > GitHub projects do you consider a good fit for Haskell Prime and > therefore worthy of imitation? > Re: Infrastructure & Communication Hi. I'm ok with the general proposals made by Herbert. I'm not a huge fan of github myself, but it seems like the most pragmatic choice right now, and I wouldn't know anything else that is clearly better, so I'm in favour. I'd somewhat prefer to have everything (wiki etc) in one place then, but I don't have strong opinions on this topic. Re: Infrastructure & Communication -----BEGIN PGP SIGNED MESSAGE----- Hash: SHA512 On 29/04/16 09:02, Andres Loeh wrote: > I'm not a huge fan of github myself, but it seems like the most > pragmatic choice right now, and I wouldn't know anything else that > is clearly better, so I'm in favour. I'd somewhat prefer to have > everything (wiki etc) in one place then, but I don't have strong > opinions on this topic. I'm not on the committee, but I would suggest having everything available from haskell.org. I'm in general not fond of free software projects relying on proprietary software; especially not SaaSS which theoretically can just get rid of all your data without you having a say. As such, I would recommend at least synchronising or snapshotting things to haskell.org infrastructure. - -- Alexander [hidden email]https://secure.plaimi.net/~alexander-----BEGIN PGP SIGNATURE----- Version: GnuPG v2 Re: Infrastructure & Communication On Thu, Apr 28, 2016 at 11:56:51PM +0200, Herbert Valerio Riedel wrote: > One benefit I see from using GitHub is that this way would we be closer > to the Haskell community (given the majority of Hackage packages are > hosted on GitHub), and our work would be more transparent for the > community as well as offering a lower barrier to > participation/contribution. > > Moreover, I think GitHub would also help make our efforts/progress > towards a revised Haskell Report more visible to the community, which in > turn may even provide us the motivation to carry on... Hello, personally I would be more likely to read/participate in the discussions if such discussions were hosted here or on Trac rather than Github. haskell-prime@ is just one 'subscribe' away, comes in a familiar package to haskell-cafe@ participants (a mailing list) and interface (their mail client); I cannot say the same about Github. Similarly, Trac allows me to follow new issues (new tickets notifications or the life of a single ticket in particular) via rss, without having to register to a new service. Of course: 1. this is just my experience -- there are many haskell developers on Github and they probably like the workflow there (I would still say the haskell-cafe@ audience is bigger though). 2. I am not a committee member. In the end it's them who are going to pour blood/sweat/tears in the report; whichever tool the committee chooses is the right one Re: Infrastructure & Communication On Thu, Apr 28, 2016 at 11:56:51PM +0200, Herbert Valerio Riedel wrote: > One benefit I see from using GitHub is that this way would we be closer > to the Haskell community (given the majority of Hackage packages are > hosted on GitHub), and our work would be more transparent for the > community as well as offering a lower barrier to > participation/contribution. > > Moreover, I think GitHub would also help make our efforts/progress > towards a revised Haskell Report more visible to the community, which in > turn may even provide us the motivation to carry on... Hello, personally I would be more likely to read/participate in the discussions if such discussions were hosted here or on Trac rather than Github. haskell-prime@ is just one 'subscribe' away, comes in a familiar package to haskell-cafe@ participants (a mailing list) and interface (their mail client); I cannot say the same about Github. Similarly, Trac allows me to follow new issues (new tickets notifications or the life of a single ticket in particular) via rss, without having to register to a new service. Of course: 1. this is just my experience -- there are many haskell developers on Github and they probably like the workflow there (I would still say the haskell-cafe@ audience is bigger though). 2. I am not a committee member. In the end it's them who are going to pour blood/sweat/tears in the report; whichever tool the committee chooses is the right one Re: Infrastructure & Communication On 04/29/2016 07:15 AM, Francesco Ariis wrote: > Hello, > personally I would be more likely to read/participate in the > discussions if such discussions were hosted here or on Trac rather > than Github. There are two or three distinct components we need to keep track of: the draft standard, discussions, and potentially RFCs. Discussions can be hosted on this mailing list, on Trac, or as Git issues. Each of them would serve fine, but we should choose exactly one and stick to it. The mailing list looks pretty good in isolation, but the best choice depends on whether we want to have RFCs or not. If we support Requests for Comments, we'll need to also support their public submissions and Git pull requests or something to the same effect. In that case, at least the inevitable comments on RFCs would best be placed close to the RFCs themselves - if the RFCs end up on GitHub the discussions of them should be kept as GitHub issues. > On 04/29/2016 07:15 AM, Francesco Ariis wrote: >> Hello, >> personally I would be more likely to read/participate in the >> discussions if such discussions were hosted here or on Trac rather >> than Github. > > There are two or three distinct components we need to keep track of: the draft standard, discussions, and potentially RFCs. > > Discussions can be hosted on this mailing list, on Trac, or as Git issues. Each of them would serve fine, but we should choose exactly one and stick to it. The mailing list looks pretty good in isolation, but the best choice depends on whether we want to have RFCs or not. > > If we support Requests for Comments, we'll need to also support their public submissions and Git pull requests or something to the same effect. In that case, at least the inevitable comments on RFCs would best be placed close to the RFCs themselves - if the RFCs end up on GitHub the discussions of them should be kept as GitHub issues. > > _______________________________________________ > Haskell-prime mailing list > [hidden email]> http://mail.haskell.org/cgi-bin/mailman/listinfo/haskell-prime Re: Infrastructure & Communication On 16-04-29 09:22 AM, Richard Eisenberg wrote: > I think the general interplay between mailing lists / wiki pages / > Trac issues that GHC uses works well. Specifically: > > - Mailing list for routine communication. > - Trac tickets / Git issues / Phab something-or-other for discussion on a specific proposal. > - Wiki page to present a specific proposal. > > Wiki pages and tickets are therefore often linked together, and > sometimes a conversation has to move from the mailing list to a > ticket (though rarely the other way around). > > I specifically vote against using the mailing list to debate > well-defined issues that need to be resolved, as it's far too easy to > lose signal in the noise and hard to see the thread all in one > place. I fully agree with this point. I also agree that this particular discussion is in happening the right venue. Re: Infrastructure & Communication > There are two or three distinct components we need to keep track of: the > draft standard, discussions, and potentially RFCs. > > Discussions can be hosted on this mailing list, on Trac, or as Git > issues. Each of them would serve fine, but we should choose exactly one and > stick to it. The mailing list looks pretty good in isolation, but the best > choice depends on whether we want to have RFCs or not. > > If we support Requests for Comments, we'll need to also support their > public submissions and Git pull requests or something to the same effect. In > that case, at least the inevitable comments on RFCs would best be placed > close to the RFCs themselves - if the RFCs end up on GitHub the discussions > of them should be kept as GitHub issues. I agree with all of this, and think this distinction should be kept in mind in terms of keeping things organized to whatever tools we choose. For general discussions I think this mailing list is best. I'm cool for keeping irc as a side channel for hashing things out more interactively, but it's all to easy to miss things there so I think it's best kept as a side channel not a main one. I like (something like) GitHub issues for tracking the exact content of proposed changes and their (direct) commentary. As far as the particular tool I'm mostly agnostic, but lean slightly towards github over trac. I've never used phabricator so can't say there (though I'm slightly against, as it'd be another tool to learn.) As far as wiki stuff goes, to be honest I'm kinda against it. I see how it might could be helpful as a sort of staging ground prior to actual RFCs, or as an edited synopsis of email discussion; but in my experience the wiki proposals for Haskell changes tend to get very crufty and hard to follow after a few changes have been made. I think I'd rather see specific versioning on proposals, so it can be clear when/which parts of the proposal are retracted, amended, etc. This may very well be a reason to prefer github, since such development can happen in branches where we can see the iteration of changes prior to merging a specific one into the master branch. Re: Infrastructure & Communication On April 29, 2016 at 10:49:38 PM, wren romano ([hidden email]) wrote: > > I like (something like) GitHub issues for tracking the exact content > of proposed changes and their (direct) commentary. As far as the > particular tool I'm mostly agnostic, but lean slightly towards github > over trac. I've never used phabricator so can't say there (though I'm > slightly against, as it'd be another tool to learn.) > If github makes sense but there is a concern over a permanent record that is not in the custody solely of a private company, then there is a nice tool (in haskell no less) that will pull the various associated data of a repo (including issues) into a branch in the repo itself [1]. We could then script a regular pull of the repo into some common haskell community infrastructure. Re: Infrastructure & Communication Some random meta thoughts: I'm generally OK with using some newer, external service over Trac for our work. My impression is that everyone on board is probably OK with starting fresh for this iteration of the committee, and recycling/cleaning up any proposals or data we deem important anyway. The 'technical debt' here is very minimal. So whatever we choose, I think as long as we're happy, it will be OK. I understand the complaint about SaaS/proprietary services, and do think it's important. But I'm not going to cast an enormous vote of strong disapproval or anything if I lose that, or anything. (Getting work done on Prime itself is a more important battle to fight, honestly). Phabricator might have some OK advantages. It's a bit unfamiliar, but does have some technical bonuses, and isn't likely to go away soon thanks to its infrastructure/GHC use: - We can have something like an indexable, persistent IRC room we can all use. I do generally prefer immediate methods of discussion, but asynchronous messaging and persistent logs (even when offline) are an important value add, and IRC fails here IMO. - It has strong access control mechanisms. This means the Prime committee can do things like have private discussion, outside of usual e.g. email. I know people are intimately leery of this, but I think in practice people form private discussion channels anyway, and having private avenues for discussing larger public things in an easy way (chat rooms, tickets etc) is desirable. The lack of a sanctioned private channel IMO will only cause Prime members to discuss in private anyway, but in disjoint groups probably. I don't think we should use it all the time, but I can imagine we might want this - I didn't see it brought up. - It has some other useful facilities aside from bug-tracking obviously, like voting tools, which could come in handy for some things. I personally hate using mailing lists for outright voting processes. (For example, see a vote a while back about GHC buildbots: https://phabricator.haskell.org/V3) Note: None of these (except point #2) is important to inspire 'clear superiority', IMO. It's mostly just technical icing on top of the rudimentary things we need. I think #2 is important, but we can use other private means of course. (I'd prefer not to get derailed at all on the meager technical bits above - although I would like to know in general what people think about #2) I do think GitHub would be nice for it's workflow features, however. Phabricator doesn't allow patches with 'git push' yet (it will soon) and I know people get anxious about arcanist. Obviously we value outside input, so 3rd party reach and low friction is an important factor to keep motivation, which Phabricator is behind on. (It's engineered as a long-term productivity tool by the devs - so immediate familiarity is seen as a low cost on the long scale for the vast array of users.) Even then, just the difference in the tool may be enough to deter some people. On that note, I generally think that with a good edit workflow, we shouldn't really need wiki processes at all. I'm with Wren, here - wikis are nice for a draft, but in practice it's very. very nice to have drafts publicly version controlled, in the same way code is. In light of that, an issue tracker for discussion, + a formative patch is enough, I think. I'm reading into the specifics of the Rust/Go/etc RFC process. Python also has a similar one I believe, although PEPs predate these other languages quite a lot, and probably served as their own inspiration, too. So, another useful data point to think about. > On April 29, 2016 at 10:49:38 PM, wren romano ([hidden email]) wrote: >> >> I like (something like) GitHub issues for tracking the exact content >> of proposed changes and their (direct) commentary. As far as the >> particular tool I'm mostly agnostic, but lean slightly towards github >> over trac. I've never used phabricator so can't say there (though I'm >> slightly against, as it'd be another tool to learn.) >> > > If github makes sense but there is a concern over a permanent record that is not in the custody solely of a private company, then there is a nice tool (in haskell no less) that will pull the various associated data of a repo (including issues) into a branch in the repo itself [1]. > > We could then script a regular pull of the repo into some common haskell community infrastructure. > > Cheers, > Gershom > > [1] https://github.com/joeyh/github-backup> _______________________________________________ > Haskell-prime mailing list > [hidden email]> http://mail.haskell.org/cgi-bin/mailman/listinfo/haskell-prime Re: Infrastructure & Communication On 29/04/2016, wren romano <[hidden email]> wrote: > For general discussions I think this mailing list is best. I'm cool > for keeping irc as a side channel for hashing things out more > interactively, but it's all to easy to miss things there so I think > it's best kept as a side channel not a main one. > I like (something like) GitHub issues for tracking the exact content > of proposed changes and their (direct) commentary. > As far as wiki stuff goes, to be honest I'm kinda against it. I see > how it might could be helpful as a sort of staging ground prior to > actual RFCs, or as an edited synopsis of email discussion; but in my > experience the wiki proposals for Haskell changes tend to get very > crufty and hard to follow after a few changes have been made. I agree on all these points. I lean slightly towards Trac rather than Github myself, being a little wary of enshrining other-party-hosted SaaS in a communal effort like this, but i shan't make a fuss about it. I'm slightly against Phabricator as installing PHP to work on Haskell feels very wrong. _______________________________________________ Haskell-prime mailing list [hidden email]http://mail.haskell.org/cgi-bin/mailman/listinfo/haskell-prime > I think we ought to make a choice quite soon. Proposals are already > being made on this list, but i hesitate to make comment lest it be > forgotten when we move to our new medium. > > My opinion on our choice of medium is known, i believe. Who or what > makes the final call? hvr? committee member votes? > _______________________________________________ > Haskell-prime mailing list > [hidden email]> http://mail.haskell.org/cgi-bin/mailman/listinfo/haskell-prime > I think we ought to make a choice quite soon. Proposals are already > being made on this list, but i hesitate to make comment lest it be > forgotten when we move to our new medium. > > My opinion on our choice of medium is known, i believe. Who or what > makes the final call? hvr? committee member votes? > _______________________________________________ > Haskell-prime mailing list > [hidden email] > http://mail.haskell.org/cgi-bin/mailman/listinfo/haskell-prime > I think we ought to make a choice quite soon. Proposals are already > being made on this list, but i hesitate to make comment lest it be > forgotten when we move to our new medium. > > My opinion on our choice of medium is known, i believe. Who or what > makes the final call? hvr? committee member votes? > _______________________________________________ > Haskell-prime mailing list > <a href="javascript:_e(%7B%7D,'cvml','Haskell-prime@haskell.org');" target="_blank">Haskell-prime@... > http://mail.haskell.org/cgi-bin/mailman/listinfo/haskell-prime	{ "pile_set_name": "Pile-CC" }
1955 Baltimore mayoral election The 1955 Baltimore mayoral election saw reelection of Thomas D'Alesandro Jr. to a third consecutive term as mayor. General election The general election was held May 3. References Baltimore mayoral Category:Mayoral elections in Baltimore Baltimore	{ "pile_set_name": "Wikipedia (en)" }
Our Eight Bass design is the result of several years of research at Panyard. We have eliminated the harmonic conflicts that plague many sets of Bass Pans. The careful placement of the notes in this design also makes playing these Pans really comfortable. The top four drums are fitted with our Low Frequency Modifiers™ (LFM), which negate interference from the naturally occurring pitch produced by the column of air inside the bass barrel. Additionally, every pitch has a high and low octave, which means that the sound on this instrument is unsurpassed for volume and warmth. An all-Solid Hoop construction ensures that this instrument is firm, loud, and will provide a life-time of enjoyment. Stands and Cases Sold Separately! ITEM ID: 1046 Do to Different Shipping Rates, Please Contact Us to Purchase this Item.	{ "pile_set_name": "Pile-CC" }
[Ovarian tumors located in the hilus. Analysis of 126 publications of the literature]. One hundred and twenty six reported cases of ovarian tumors located in the hilus (OTLH) are analyzed. They represent a special sub group of ovarian steroid cell tumors (former "lipid cell tumors"). A number of these neoplasms are Leydig-Berger cell tumors (LBCT), which are characterized by the presence of the crystal of Reinke, a specific proteinaceous inclusion, whose detection may be improved by new available methods. Crystal-free steroid cell tumors located in the hilus are in most cases true leydigoma of the ovary whose features are indiscernible from LBCT's. They are revealed after years of evolution by signs of hyperandrogeny or post menopausal bleeding. Plasma testosterone levels are always elevated while urinary 17 keto steroid cytoplasmic values are normal in 50% of cases. Three main features distinguish ovarian tumors located in the hilus from others ovarian steroid cell tumors: the occurrence in aged women, the small size of the tumors, and the excellent prognosis.	{ "pile_set_name": "PubMed Abstracts" }
Books bound by human skin. True story. I hate stories like this that pose more questions than answers. How, exactly, did this come about? Is this a book that they just recently aquired or has it been sitting on the shelf in all it's creepy glory for.ev.er!? (clicky on the title for link)	{ "pile_set_name": "Pile-CC" }
from random import randint import cv2 import sys import os import traceback CASCADE="Face_cascade.xml" FACE_CASCADE=cv2.CascadeClassifier(CASCADE) def detect_faces(image_path,display=True): image=cv2.imread(image_path) image_grey=cv2.cvtColor(image,cv2.COLOR_BGR2GRAY) faces = FACE_CASCADE.detectMultiScale(image_grey,scaleFactor=1.16,minNeighbors=5,minSize=(25,25),flags=0) for x,y,w,h in faces: sub_img=image[y-10:y+h+10,x-10:x+w+10] os.chdir("Extracted") cv2.imwrite(str(randint(0,10000))+".jpg",sub_img) os.chdir("../") cv2.rectangle(image,(x,y),(x+w,y+h),(255, 255,0),2) if display: cv2.imshow("Faces Found",image) # if (cv2.waitKey(0) & 0xFF == ord('q')) or (cv2.waitKey(0) & 0xFF == ord('Q')): # cv2.destroyAllWindows() if __name__ == "__main__": if not "Extracted" in os.listdir("."): os.mkdir("Extracted") if len(sys.argv) < 2: print("Usage: python Detect_face.py 'image path'") sys.exit() if os.path.isdir(sys.argv[1]): for image in os.listdir(sys.argv[1]): try: print ("Processing.....",os.path.abspath(os.path.join(sys.argv[1],image))) detect_faces(os.path.abspath(os.path.join(sys.argv[1],image)),False) except Exception: print ("Could not process ",os.path.abspath(os.path.join(sys.argv[1],image))) else: detect_faces(sys.argv[1])	{ "pile_set_name": "Github" }
Q: Reset local area connection My internet connection gets disconnected sometimes so I click on Troubleshoot problems in Windows 7 and it gets fixed when the troubleshooter resets the Local area connection. The problem is that it takes sometime for it to reset and verify that the issue has been fixed,so I'm wondering if there's a Command which automatically does that ? A: You can do ipconfig /release followed by ipconfig /renew A: To Disable: netsh interface set interface "Local Area Connection" DISABLED You can create .bat script.	{ "pile_set_name": "StackExchange" }
Notes: Image: Image 1. Photo 1-2: Two cases with coxa valga of the right (Photo 1) and left (Photo 2) lower limb due to proximal femur hypoplasia. Image 4. Photo 1-2: One case with coxa valga of the left lower limb due to proximal femur hypoplasia.	{ "pile_set_name": "Pile-CC" }
The present invention relates to harvesting machines such as combine harvesters (also referred to hereinafter as combines) and, more particularly, to the threshing and separating mechanisms of harvesting machines.	{ "pile_set_name": "USPTO Backgrounds" }
Introduction ============ Cocaine dependence remains a challenging public health problem with relapse cited as a major determinant in its chronicity and severity.^[@bib1]^ With a history of cocaine use, environmental contexts and stimuli (for example, paraphernalia) become reliably associated with its use leading to durable conditioned responses ('cue reactivity\') that can predict relapse as well as treatment success.^[@bib2],\ [@bib3],\ [@bib4],\ [@bib5]^ Drug cue reactivity is the attentional orientation toward such drug-associated cues that are measurable as conditioned physiological effects (for example, heart rate), subjective properties (for example, craving), appetitive approach behaviors (for example, drug-seeking) and activation of specific corticostriatal subcircuits.^[@bib1],[@bib5],[@bib6]^ Individual variation in the magnitude and influence of cue reactivity over behavior in humans^[@bib7],[@bib8]^ and animals^[@bib9],[@bib10]^ suggest that cue-reactive individuals may be at greater risk for the progression to addiction and/or relapse.^[@bib8],[@bib11],[@bib12]^ A greater understanding of the neural underpinnings of cocaine cue reactivity promises to shed light on therapeutic approaches to effectively intervene in cocaine dependence and improve recovery outcomes. The distributed corticostriatal circuitry that controls the incentive-motivational properties of drug-associated cues involves a key modulatory role for dopamine neurotransmission.^[@bib13]^ Serotonin (5-HT) innervation of these interlooping pathways is also prominent^[@bib14],[@bib15]^ and evidence suggests a modulatory role for 5-HT neurotransmission in cue reactivity processes (for review^[@bib16]^). The 5-HT~2C~ receptor (5-HT~2C~R) is one of fourteen 5-HT-receptive proteins in brain and is prominently localized to corticostriatal subregions including the medial prefrontal cortex (mPFC) in rodents,^[@bib17]^ a homolog of the orbitofrontal cortex in humans.^[@bib18]^ This cortical region is a critical component within the circuit responsive to cocaine-associated cues in humans^[@bib19]^ and animals.^[@bib20],[@bib21]^ Stimulation of the 5-HT~2C~R localized to the mPFC suppressed cocaine-seeking in rats,^[@bib22]^ an observation that recapitulates the efficacy of systemic administration of selective 5-HT~2C~R agonists (RO 60-0175, WAY163909) to consistently reduce cue- and cocaine-primed drug-seeking.^[@bib23],\ [@bib24],\ [@bib25],\ [@bib26],\ [@bib27]^ This 5-HT~2C~R agonist-induced functional antagonism of cocaine cue reactivity is reversed by the selective 5-HT~2C~R antagonist SB242084 and occurs at doses of the 5-HT~2C~R agonists that do not significantly alter general behaviors (for example, locomotor activity).^[@bib23],\ [@bib24],\ [@bib25],\ [@bib26],\ [@bib27]^ Consistent with this behavioral profile, SB242084 also increased cocaine-seeking although inter-individual variability in its efficacy was observed.^[@bib25],[@bib28],\ [@bib29],\ [@bib30]^ Finally, we recently demonstrated that cocaine cue reactivity was significantly elevated in rats following virally mediated loss of the 5-HT~2C~R in mPFC,^[@bib31]^ establishing that reduced mPFC 5-HT~2C~R function is a neurobiological mediator of cocaine cue reactivity. Natural variation within the 5-HT~2C~R system through single nucleotide polymorphisms (SNPs) could contribute to individual differences in sensitivity to reward-associated cues in humans. The single nucleotide variant Cys23Ser (rs6318) in the human 5-HT~2C~R gene (HTR2C) results in the substitution of a serine for a cysteine in the extracellular N-terminus of the receptor.^[@bib32]^ This SNP is predicted to alter protein structure and/or stability^[@bib32],[@bib33]^ which would be expected to alter the ability of a ligand to bind to the receptor and initiate downstream signal transduction.^[@bib34],[@bib35]^ In support of this concept, there is evidence that the Ser23 variant has been associated with lower sensitivity to the effects of 5-HT~2C~R agonists in human studies.^[@bib36],\ [@bib37],\ [@bib38]^ As a putative reduced-function SNP in the HTR2C in humans, we tested the hypothesis that the Ser23 variant may associate with higher cocaine cue reactivity^[@bib31]^ measured as attentional bias (attentional orienting response in a computerized cocaine-word Stroop task).^[@bib6]^ Alignment of the human and rat 5-HT~2C~R gene shows no sequence homology at the rs6318 position.^[@bib39],[@bib40]^ However, given our recent finding that knockdown of the 5-HT~2C~R in the mPFC resulted in vulnerability to the expression of cocaine cue reactivity in rats,^[@bib31]^ we tested the hypothesis that individual differences in cocaine cue reactivity as measured as appetitive approach behavior \[lever presses reinforced by the discrete cue complex (for example, stimulus light, pump)\]^[@bib6]^ would associate with reduced 5-HT~2C~R protein expression and sensitivity to a selective 5-HT~2C~R agonist. Materials and methods ===================== Assessment of 5-HT~2C~R genotype and cue reactivity in cocaine-dependent subjects --------------------------------------------------------------------------------- ### Subjects Subjects (n=114) who met DSM-IV criteria for current cocaine dependence were recruited within three ongoing studies measuring cue reactivity using the same diagnostic, psychometric and advertising procedures. Subjects were recruited via newspaper advertisements, screened for psychiatric disorders using the structured clinical interview for DSM-IV (SCID-I),^[@bib41]^ and completed a medical history and physical examination. All subjects were tested for urine cocaine (benzoylecgonine), tetrahydrocannabinol, opioids, amphetamine, methamphetamine and benzodiazepines using the integrated E-Z split key cup II (Innovacon Company, San Diego, CA, USA) on each visit. All subjects had at least one cocaine-positive urine during screening; did not meet DSM-IV current dependence criteria for abused drugs other than cocaine, marijuana, nicotine or alcohol; did not have current or past medical disorders affecting the central nervous system; and did not have axis I disorders other than substance abuse or dependence. The subjects included non-treatment-seekers (n=21) and treatment-seekers (n=93). All subjects were tested during the baseline period of the studies. All subjects were free of alcohol at the time of testing as determined by a breathalyzer (Intoximeters, St Louis, MO, USA). Female subjects with a positive urine pregnancy test were excluded from the study. All data were collected in the Center for Neurobehavioral Research on Addictions at the University of Texas Health Science Center at Houston. All subjects were provided with written informed consent after being fully informed of the nature of the research in accordance with the Declaration of Helsinki. The consent form included agreement to participate in the genetic study. The study was approved by the Committees for the Protection of Human Subjects, which are the Internal Review Board of the University of Texas Health Science Center at Houston and the Baylor College of Medicine. ### Cocaine-word Stroop task The cocaine-word Stroop task was designed to measure attentional bias to cocaine-related stimuli.^[@bib42],\ [@bib43],\ [@bib44]^ It is a widely used implicit task^[@bib45]^ in which the participant is presented with words printed in color, and asked to discriminate the color of each stimulus; the participant is instructed to ignore the meaning of the words and concentrate only on responding to the color in which the word is written. The stimuli presented include neutral words and words that are related to the concerns or pathology under study, in this case, cocaine dependence. Slowness in responding to a color suggests distraction from color discrimination due to attention being 'captured\' by the meaning of the stimulus (that is, cocaine) word.^[@bib46]^ Each analyzed session began with a block of 60 practice trials, followed by 30-trial blocks of test trials.^[@bib43],[@bib44]^ The test trials included two blocks of 30 trials with cocaine-related words, and two blocks of 30 trials with neutral words. Within each block type, each word was randomly presented three times in three different colors. Block type was alternated within each session (for example, cocaine, neutral, cocaine, neutral), and the order of block type was counterbalanced across subjects. Trials with correct responses and reaction times larger than 200 msec were used to calculate mean reaction times.^[@bib43],[@bib44]^ Attentional bias was operationalized as the difference between the reaction times (in msec) observed in trials with cocaine-related words and trials with neutral words, calculated for each subject and averaged across subjects. This calculation corrects for any difference in overall reaction times between cocaine-dependent and control subjects.^[@bib46]^ A correct response was defined as responding to the word color on an appropriately colored response button. Accuracy was assessed as the ratio of correct trials to total trials within each block type. ### DNA preparation Venous blood (10 ml) from each subject was centrifuged at 2000 r.p.m. for 30 min (Eppendorf North America, New York, NY, USA). The buffy coat was removed and stored in 2.0 ml cryogenic vials at −80 °C. DNA was isolated from the buffy coat using the Puregene Kit (Qiagen, CA, USA) according to manufacturer\'s recommendation. Purified DNA for each subject was dissolved in 0.25 ml DNA hydration solution. ### HTR2C genotyping The HTR2C has been localized to chromosome X, band q24 (female genotypes: CC, CG or GG; male genotypes: C or G).^[@bib32]^ All samples were assayed in duplicate on an Applied Biosystems ViiA 7 Real-Time PCR System (Applied Biosystems, Grand Island, NY, USA). Genotyping was performed with 10 ng of DNA, 1.5 μl of Taqman Genotyping Master Mix, 0.03 μl of pre-designed TaqMan primer-probe set (Applied Biosystems; Assay ID C_2270166_10) and 2.47 μl of water. PCR amplification consisted of 10 min at 95 °C, 40 cycles of 15 s at 92 °C and 1 min at 60 °C. ### Statistical analyses Reaction times and accuracy on the cocaine-word Stroop task were analyzed with a paired Student\'s t-test. Differences in age, sex, race, years of cocaine use, percent treatment-seekers, percent positive urine cocaine screens, percent alcohol abuse and percent cannabis abuse among subjects with different HTR2C genotypes were analyzed using one-way analysis of variance (ANOVA; age and years of cocaine use) or Fisher\'s exact test (sex, race, percent treatment-seekers, percent positive urine cocaine screens, percent alcohol abuse, percent cannabis abuse). Differences in attentional bias among subjects with different HTR2C genotypes were analyzed using one-way analysis of covariance (ANCOVA) with gene polymorphism as the independent variable and sex or race as the covariate in a general linear model. All reported P values for post hoc comparisons were Tukey--Kramer adjusted for multiple comparisons. To determine the population structure, genotypic data for ancestral informative markers for our cohort was compared against Centre d\'Etude du Polymorphisme Humain--Human Genome Diversity Panel (CEPH--HGDP) samples (1035 subjects of 51 populations).^[@bib47],[@bib48]^ The obtained values were similar to those calculated without correction for these covariates. The alpha level for all analyses was set at P=0.05. Assessment of the 5-HT~2C~R system and associated cocaine cue reactivity in rodents ----------------------------------------------------------------------------------- ### Animals Experimentally naive, male, Sprague--Dawley rats (n=105) weighing 225--250 g at arrival were housed two per cage under a 12-h light-dark cycle at constant temperature (21--23 °C) and humidity (40--50%). Food and water were available ad libitum. All experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (2011) and with the approval of the Institutional Animal Care and Use Committee at the University of Texas Medical Branch. ### Drugs (--)-Cocaine (National Institute on Drug Abuse) was dissolved in 0.9% NaCl. WAY163909 ((7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-\[b\]\[1,4\]diazepino \[6,7,1hi\]indole; a gift from Pfizer, New York, NY, USA) was dissolved in 0.9% NaCl. ### Cocaine self-administration and cue reactivity assessments Implantations of intravenous catheters with back mounts were performed under anesthesia with a cocktail containing xylazine (8.6 mg kg^−1^), acepromazine (1.5 mg kg^−1^) and ketamine (43 mg kg^−1^) in bacteriostatic saline. Self-administration took place in standard operant chambers equipped with two retractable levers, a stimulus light above each lever, and a houselight housed within ventilated and sound-attenuating chambers (Med-Associates, St Albans, VT, USA). Cocaine infusions were delivered by a syringe attached to an infusion pump located outside the chamber. Daily flushes with a solution of bacteriostatic saline containing heparin sodium (10 U ml^−1^), streptokinase (0.67 mg ml^−1^) and ticarcillin disodium (66.67 mg ml^−1^) were performed to maintain catheter patency. Self-administration consisted of 14 days of 180-min sessions, during which rats were trained to lever press to obtain a cocaine infusion (0.75 mg kg^−1^per 0.1 ml infusion) on a fixed ratio (FR) 1 schedule before progressing to an FR5.^[@bib23],[@bib27],[@bib31],[@bib49]^ Schedule completions on the active lever resulted in delivery of cocaine over a 6-s period along with simultaneous illumination of the house and stimulus lights and activation of the infusion pump (discrete cue complex paired with delivery of cocaine); responses on the inactive lever were recorded but had no scheduled consequences. After cocaine delivery, the pump and stimulus light were inactivated simultaneously. The house light remained illuminated for a 20-s timeout period, during which lever presses had no scheduled consequences. Following stable self-administration on an FR5 (seven infusions per hour for at least three sessions with \<10% variation in the number of infusions received for three consecutive sessions), cocaine-trained rats were subjected to a probe trial on self-administration day 12 to stratify individual rats as high cue reactive (HCR) or low cue reactive (LCR). During this 60-min probe trial, responses on the active lever were reinforced by presentation of the discrete cue complex (stimulus light, pump) previously associated with cocaine delivery. Self-administration was reinstated immediately following the end of the probe trial followed by an additional two self-administration sessions. The number of previously active lever presses during the probe trial was used to stratify rats within the HCR or LCR phenotype; a median split was used. The probe session did not interfere with the stability of self-administration as performance on the post-probe sessions was identical to the stable baseline established before the probe trial (data not shown). Rats were returned to their home cage after 14 days of cocaine self-administration. In Experiment 1, rats (n=12 rats per phenotype) were reintroduced to the self-administration chambers 24 h later and assayed in a test session comprised of two sequential components. The first component evaluated whether HCR and LCR rats would exhibit differential levels of lever presses when placed in the context in the absence of the discrete cue complex. To this end, responses on both levers on an FR1 schedule were recorded but no discrete cues (for example, stimulus light, pump) were present nor delivered during the initial 10 min of the session. The second component was signaled by a single, non-response contingent delivery of the discrete cue complex presented at the termination of the first 10-min component. To assess cocaine cue reactivity, presses on the previously-active lever in the 60-min (second component) were reinforced by the discrete cue complex on an FR1; inactive lever presses were recorded but produced no scheduled consequences.^[@bib31]^ In Experiment 2, rats were stratified as HCR or LCR on the basis of their performance on the probe trial (above) and returned to the self-administration chambers at 24 h of withdrawal. To assess cocaine cue reactivity, presses on the previously-active lever were reinforced by the discrete cue complex on an FR1 during a 60-min session;^[@bib31]^ inactive lever presses were recorded but produced no scheduled consequences. For ex vivo neurochemical studies, rats were sacrificed immediately after the cue reactivity test session \[HCR (n=5), LCR (n=6)\] or upon removal from their home cage at the expected time of that test session without re-exposure to the self-administration chambers \[HCR (n=6), LCR (n=6)\] this second group of rats served as control for the behavioral experience during the cue reactivity session. For pharmacological analyses, a cohort of HCR (n=16 per treatment) and LCR rats (n=16 per treatment) were administered vehicle (saline, 1 ml kg^−1^, intraperitoneal) or WAY163909 (0.5 mg kg^−1^, intraperitoneal) 15 min before the start of the cue reactivity test session. ### Immunoblotting The HCR or LCR rats stratified on the probe test in Experiment 2 were evaluated for cue reactivity at 24 h of withdrawal and sacrificed immediately following the cue reactivity test session or remained in their home cages and sacrificed at 24 h of withdrawal. Rats were anesthetized \[chloral hydrate solution (400 mg kg^−1^)\] and decapitated; the mPFC was microdissected and flash frozen in liquid nitrogen and stored at −80 °C for subsequent crude synaptosomal protein extraction and immunoblotting.^[@bib50],[@bib51]^ Equal amounts of protein were separated by SDS--PAGE using 4--12% Bis-Tris gels and transferred to a PVDF membrane for immunoblotting with 5-HT~2C~R antibody (D-12, sc-17797, Santa Cruz, Dallas, TX, USA; 1:100) or pan-cadherin antibody (AB6528, Abcam, Cambridge, MA, USA; 1:10 000). Membranes were incubated with mouse IgG IRDye (1:10 000) for detection by Odyssey Imaging System (LI-COR Biosciences, Lincoln, NE, USA). The integrated intensity of each band (arbitrary units) was analyzed with the Odyssey Software. The ratio of the intensity of the 5-HT~2C~R-immunoreactive band to the cadherin-immunoreactive band was determined for normalization. ### Statistical analyses A one-way ANOVA (SAS 9.3) for repeated measures was used to analyze the dependent measures of the total number of active and inactive lever presses per session over the last three sessions of the self-administration phase. Student\'s t-test was employed to compare HCR and LCR rats on the total number of responses (previously active and inactive levers) and the latency to respond on the previously-active lever during the probe trial, the context-associated and cue reactivity test sessions as well as the density of 5-HT~2C~R protein expression. For pharmacological analyses, a two-way ANOVA for the factors of phenotype and treatment was conducted; a priori comparisons between the total number of responses on the previously-active and inactive levers as well as the latency to respond on the previously active lever during the test session were made using Student\'s t-test. The experimentwise alpha level was set at P=0.05. Results ======= Assessment of 5-HT~2C~R genotype and cue reactivity in cocaine-dependent subjects --------------------------------------------------------------------------------- The demographics of the study population are presented in [Table 1](#tbl1){ref-type="table"}. Cocaine-dependent subjects were stratified into three groups, those homozygous (CC; females) and hemizygous (C; males) for the C allele which encodes for the Ser23 variant, those homozygous (GG; females) and hemizygous (G; males) for the G allele or heterozygous (CG; females only) which encodes for the Cys variant. Genotype was not associated with the distribution of age (F~2~,~111~=0.78; NS) or race (Fisher\'s exact test, NS), but was associated with sex (Fisher\'s exact test, P\<0.01) ([Table 1](#tbl1){ref-type="table"}). Genotype was not associated with years of cocaine use (F~2,111~=0.15, NS), percent positive cocaine urine screens (Fisher\'s exact test, NS), percent alcohol abuse (Fisher\'s exact test, NS), percent cannabis abuse (Fisher\'s exact test, NS), or percent treatment-seekers (Fisher\'s exact test, NS) ([Table 1](#tbl1){ref-type="table"}). The response to presentation of cocaine-associated cues ('cue reactivity\') was measured as attentional bias in the cocaine-word Stroop task in cocaine-dependent subjects. Several studies have reported that cocaine-dependent subjects show attentional bias to cocaine-related words whereas healthy control subjects do not.^[@bib42],[@bib44]^ Here, cocaine-dependent subjects had significantly longer reaction times to indicate the word color in trials with cocaine-related words than in trials with neutral words ([Figure 1a](#fig1){ref-type="fig"}; t=6.96; P\<0.01). Accuracy did not differ between cocaine-related and neutral word trials ([Figure 1b](#fig1){ref-type="fig"}; t=−0.49; NS). Attentional bias did not differ between cocaine-dependent treatment-seekers (48.18±8.2 msec) and non-treatment-seekers (52.97±14.2 msec; t=0.29; NS). Our effect size is consistent with other published studies of attentional bias conducted in drug-dependent subjects.^[@bib52]^ Cue reactivity was evaluated in subjects stratified for the HTR2C genotype. An ANCOVA demonstrated a main effect of genotype on attentional bias after adjusting for sex ([Table 2](#tbl2){ref-type="table"}; F~2,108~=3.79; P\<0.05). Post hoccomparisons revealed that attentional bias for both sexes with the C or CC genotype was significantly greater than that for subjects with the G or GG genotype ([Table 2](#tbl2){ref-type="table"}; P\<0.05). As 97 of 114 subjects were male and the HTR2C gene is X-linked, an ANOVA for male subjects only was performed. A main effect of genotype on attentional bias for male subjects was detected ([Table 2](#tbl2){ref-type="table"}; F~1,93~=4.91; P\<0.05); male subjects with the C genotype displayed significantly higher attentional bias than male subjects with G genotype ([Table 2](#tbl2){ref-type="table"}; P\<0.05). Post hoc comparisons indicated that attentional bias for females with the CG genotype was not different from those with the CC or GG genotype in this small sample of female subjects ([Table 2](#tbl2){ref-type="table"}, NS). An ANCOVA for all African-American (AA) subjects was also performed as 84 of 114 subjects were AA; a main effect of genotype on attentional bias was observed ([Figure 2](#fig2){ref-type="fig"}; F~2,81~=4.43; P\<0.05). Post hoc comparisons demonstrated that attentional bias for AA subjects with the C/CC genotype was significantly higher than AA subjects with the G/GG genotype ([Figure 2](#fig2){ref-type="fig"}; P\<0.05). Assessment of cocaine cue reactivity in rodents ----------------------------------------------- We tested the hypothesis that individual differences in HCR vs LCR rats would be observable within the context (self-administration chambers) or in the levels of cocaine cue reactivity (lever presses reinforced by the discrete cue complex). Rats in Experiment 1 readily acquired cocaine self-administration to stability; across the last three sessions (data not shown), there was no main effect of session for the number of active lever presses (F~2,29~=0.14; NS), inactive lever presses (F~2,29~=1.07; NS) or the number of infusions received (F~2,29~=0.05; NS). Rats were stratified (median split) as HCR or LCR on the basis of the number of lever presses for cocaine-associated cues during the probe session (data not shown; see Methods). Total cocaine intake did not differ between HCR rats (373.9±18.3 mg kg^−1^) and LCR rats (395.4±16.6 mg kg^−1^; NS). There was a positive correlation between previously active lever presses on the probe session with that seen on the cue reactivity test session for individual animals (r=0.304; P\<0.05). The levels of operant behavior within the cocaine-taking context only or reinforced by the discrete cue complex were assessed in HCR vs LCR rats at 24 h of withdrawal. Previously active lever presses did not differ between HCR and LCR rats upon exposure to the cocaine-taking context in the absence of the discrete cue complex ([Figure 3](#fig3){ref-type="fig"}, left; t=0.77; NS). HCR rats displayed significantly higher previously active lever presses that were reinforced by the discrete cue complex vs LCR rats ([Figure 3](#fig3){ref-type="fig"}, right; t=2.81; P\<0.05). Inactive lever presses did not differ between HCR and LCR rats during the context only component (HCR=2.5±0.4; LCR=2±0.9; t=0.77; NS) or the cue reactivity component (HCR=8.4±1.5; LCR=6±1.3; t=1.17; NS). These data suggest that HCR and LCR rats exhibit distinct appetitive approach behavior when provided with the opportunity to deliver the discrete cue complex. The propensity to engage in appetitive behavior to deliver the discrete cue complex may represent a useful construct within which to investigate individual differences in cocaine cue reactivity. Assessment of the 5-HT~2C~R system and associated cue reactivity in rodents --------------------------------------------------------------------------- We tested the hypothesis in Experiment 2 that individual differences in levels of cue reactivity would correlate with the expression of 5-HT~2C~R ex vivo. HCR rats displayed significantly higher previously active lever presses for the discrete cue complex vs LCR rats ([Figure 4a](#fig4){ref-type="fig"}; t=3.65; P\<0.01). Inactive lever presses ([Figure 4a](#fig4){ref-type="fig"}; t=0.5; NS) and the latency to the first lever press (data not shown; t=0.97; NS) were not different between HCR and LCR rats. A two-way, repeated measures ANOVA on the last three sessions of stable self-administration indicated no main effect of phenotype (F~1,29~=0.02; NS), day (F~2,29~=1.43; NS), and no phenotype × day interaction (F~2,29~=1.02; NS) for active lever presses, indicating that individual differences in cue reactivity in rats are unrelated to previous cocaine-taking history. [Figure 4b](#fig4){ref-type="fig"} depicts representative immunoblots for mPFC synaptosomal protein from HCR and LCR rats sacrificed immediately following the cue reactivity test session. HCR rats displayed significantly lower 5-HT~2C~R synaptosomal protein levels in the mPFC vs LCR rats ([Figure 4c](#fig4){ref-type="fig"}; t=−3.75; P\<0.01); an inverse correlation was observed between mPFC 5-HT~2C~R synaptosomal protein and responses on the previously-active lever for the discrete cue complex in individual rats ([Figure 4d](#fig4){ref-type="fig"}; r=0.69; P\<0.05). Because these rats underwent the cue reactivity session, such exposure could account in part for the observed changes in mPFC 5-HT~2C~R protein levels. Thus, 5-HT~2C~R protein levels were assessed in a cohort of cocaine-trained rats that were retained in their home cage and sacrificed 24 h after termination of cocaine self-administration sessions (that is, not tested for cue reactivity). The differential protein expression observed in HCR (0.051±0.002 arbitrary units) and LCR (0.076±0.008 arbitrary units) ([Figure 4](#fig4){ref-type="fig"}) rats (stratified on the probe session) is not related to the cue reactivity test itself as comparable 5-HT~2C~R mPFC protein levels were observed in HCR (0.049±0.01 arbitrary units) and LCR rats (0.087±0.02 arbitrary units) that were not exposed to the cue reactivity test session. These data suggest that high levels of cue reactivity are associated with lower 5-HT~2C~R expression in the mPFC supporting our hypothesis that differential 5-HT~2C~R neurobiology may contribute to individual differences in cocaine cue reactivity. We then tested the hypothesis that HCR and LCR rats during early withdrawal would exhibit differential pharmacological sensitivity to the suppressive effects of the selective 5-HT~2C~R agonist WAY163909 over cocaine cue reactivity ([Figure 5](#fig5){ref-type="fig"}). A main effect of phenotype (F~1,41~=30.93; P\<0.0001), treatment (F~1,41~=11.34; P\<0.01), and a phenotype × treatment interaction (F~1,41~=4.23; P\<0.05) for previously active lever presses was observed. Saline-treated HCR rats displayed higher previously-active lever presses vs saline-treated LCR rats ([Figure 5](#fig5){ref-type="fig"}; P\<0.05). LCR rats treated with WAY163909 exhibited lower previously-active lever presses vs saline-treated LCR rats ([Figure 5](#fig5){ref-type="fig"}; P\<0.05); WAY163909 did not significantly alter previously-active lever presses vs saline in HCR rats ([Figure 5](#fig5){ref-type="fig"}; NS). WAY163909 (0.5 mg kg^−1^) suppressed previously-active lever presses \~48% in LCR rats and \~12% in HCR rats. No main effect of phenotype (F~1,41~=1.1; NS), treatment (F~1,41~=0.01; NS), and no phenotype × treatment interaction (F~1,41~=1.37; NS) for inactive lever presses during the cue reactivity test session was observed. Mean (±s.e.m.) inactive lever presses did not differ between saline-treated HCR (14.9±4.3; NS) and LCR rats (10.8±4.6), between saline- and WAY163909-treated HCR rats (13.9±6.9; NS), or saline- and WAY163909-treated LCR rats (13.2±4.7; NS). No main effect of phenotype (F~1,41~=3.11; NS), treatment (F~1,41~=0.25; NS), and no phenotype × treatment interaction (F~1,41~=1.34; NS) for latency to the first lever press during the cue reactivity test session was observed. Mean (±s.e.m.) latency (sec) did not differ between saline-treated LCR (29.4±8.1) and HCR rats (24.5±9.6; NS), saline- and WAY163909-treated LCR rats (42.9±7.1; NS), or saline-and WAY163909-treated HCR rats (19.1±6.4; NS). Taken together, these data demonstrate that HCR rats are less sensitive than LCR rats to the suppressive effects of WAY163909 on cue reactivity at 24 h of withdrawal. Discussion ========== The present study demonstrated that cocaine-dependent subjects who carry the less-common Ser23 variant of the HTR2C exhibit significantly higher cocaine cue reactivity than did those who carry the Cys23 variant, adding the HTR2C to handful of genes potentially identified as candidates involved in cocaine cue reactivity.^[@bib53],[@bib54]^ Likewise, in a model of individual differences in cocaine cue reactivity in rats, we identified that high cocaine cue reactivity correlated with lower levels of mPFC 5-HT~2C~R protein expression and a blunted sensitivity to the suppressive effects of the selective 5-HT~2C~R agonist WAY163909. Interestingly, we discovered that individual differences in drug-seeking were evident when rats were given the opportunity to deliver the discrete cue complex but not when given the opportunity to simply press levers in the cocaine-taking context, supporting the incentive-motivational value of the discrete cue complex as a key defining characteristic in provoking cocaine-seeking.^[@bib55]^ Together with our previous observation that knockdown of the mPFC 5-HT~2C~R resulted in vulnerability to the expression of cocaine cue reactivity in rats,^[@bib31]^ we propose that the functional status of the 5-HT~2C~R system is a mechanistic driver in the generation of vulnerability to cocaine-associated cues. Our new finding that the Cys23Ser SNP aligns with cue reactivity in cocaine-dependent subjects supports the concept that inherent variability in 5-HT~2C~R neurobiology may contribute to the liability of individuals to cocaine cues and cue-related relapse phenomena. The manner in which the Ser23 variant impacts baseline 5-HT~2C~R function is not yet fully defined. The replacement of the cysteine in the extracellular N-terminus of the 5-HT~2C~R is predicted to eliminate the formation of a disulfide bond, which would be expected to destabilize the receptor structure.^[@bib32],[@bib33]^ The impact of the Ser23 SNP on the structural integrity of the 5-HT~2C~R protein could include alterations in ligand binding and downstream signaling responsivity. In COS-7 cells, the Ser23 variant exhibited lower high-affinity, but not low-affinity, binding to the 5-HT~2C~R and the agonist response in these cells was more markedly desensitized relative to the Cys23 variant.^[@bib34]^ The 5-HT~2C~R encoded by the Ser23 variant localized predominantly to the cell surface in HEK293 cells and was aligned with faster recovery of 5-HT-evoked cellular signaling following prolonged exposure to an inverse agonist.^[@bib35]^ It is possible that aberrant 5-HT~2C~R-mediated functions in Ser23 carriers may exhibit differential responsivity to stress^[@bib56],[@bib57]^ or pharmacological triggers, including 5-HT~2C~R agonists.^[@bib36],\ [@bib37],\ [@bib38]^ However, there have been no experimental evaluations in animal models in vivo which would be valuable to tease apart the mechanisms by which the Cys23Ser SNP may drive 5-HT~2C~R neurobiology and its impact on cocaine cue reactivity. Such studies are vital as a recent publication found that the Ser23 and Cys23 variants behaved indistinguishably in HEK293 and NIH-3T3 cells.^[@bib58]^ Thus, although there is in vitro evidence that the Ser23 variant leads to altered cellular responses to stimuli, definitive information remains to be collected to best understand the association reported here between expression of the Ser23 variant and enhanced cocaine cue reactivity, as well as in the clinical course of some psychiatric disorders (for review^[@bib59],[@bib60]^). There are reports of altered 5-HT~2C~R responsivity after cocaine exposure in humans^[@bib61],[@bib62]^ and experimenter-delivered cocaine in animals.^[@bib63]^ Our observations that mPFC 5-HT~2C~R expression and pharmacological sensitivity to a selective 5-HT~2C~R agonist associate with individual variations in levels of cue reactivity in rodents are consistent with the possibility that reduced mPFC 5-HT~2C~R function is a neurobiological mediator of cocaine cue reactivity.^[@bib31]^ These findings may be related to pre-existing neurochemical vulnerabilities specific for reward-predicting cues^[@bib31],[@bib64]^ or to the cyclical variations in 5-HT efflux consequent to cocaine self-administration.^[@bib65]^ It is currently unknown whether the difference in cortical 5-HT~2C~R expression observed here translates directly to differential functional output of the receptor to manifest cue reactivity, however, high cue reactive rats were less sensitive to the suppressive effects of WAY163909. The composition of the cellular microenvironment (that is, protein-binding partners) also contributes to 5-HT~2C~R-mediated signaling and agonist responsiveness.^[@bib66]^ We have reported that the 5-HT~2C~R is localized to the postsynaptic density in PFC^[@bib50]^ and thus positioned to directly modulate synaptic plasticity in cortical neurons; the 5-HT~2C~R agonist MK212 is reported to enhance long-term potentiation in forebrain.^[@bib67]^ Taken together, these biochemical and behavioral data suggest that high cocaine cue reactivity (but not sucrose cue reactivity) (Swinford-Jackson and Cunningham, unpublished)^[@bib27]^ may be governed by a blunted response capacity of the 5-HT~2C~R. The discovery that individual differences in cue reactivity coexist concomitantly with distinct 5-HT~2C~R expression patterns in the synaptosomal compartment indicates that balance in the cortical 5-HT~2C~R functional status may be the key to shaping the neural state that contributes to cocaine-associated cue reactivity during abstinence. Some limitations of this study should be noted. With the small number of female subjects in the human data set in this study and the exclusion of females in the rodent data set, the findings of this study cannot be extrapolated to women. As the HTR2C is X-linked, future studies should investigate the role of 5-HT~2C~R neurotransmission in sex differences observed in cocaine cue reactivity as sex may be a factor that contributes to cocaine cue-related neurobiology.^[@bib68]^ The direct translatability of the studies presented herein is somewhat limited as there are key discrepancies in cocaine exposure patterns and cocaine use history between humans and rodents. The human data set included subjects with extensive cocaine histories, whereas the rodent data set included animals with shorter exposures to cocaine self-administration. Further, the Cys23Ser SNP has not been identified in rodents nor has the Cys23Ser SNP been tied directly to frontocortical activation patterns in response to drug-associated cues or the cortical 5-HT~2C~R functional status in cocaine-dependent subjects. Nonetheless, the inclusion of the rodent study allowed for the experimental test of the hypothesis that individual differences in cocaine cue reactivity during early abstinence are associated with differential measures of cortical 5-HT~2C~R neural integrity. Our translational findings cumulatively suggest that susceptibility to cocaine cue reactivity may be related to inter-individual variation within the 5-HT~2C~R system. Although other studies have examined the association of genotype with cue reactivity in cocaine users,^[@bib53],[@bib54],[@bib69]^ our study employed the largest sample size to date, and we are the first to have examined the association of the HTR2C genotype in experimentally measured cue reactivity. The rodent studies suggest that a differential 5-HT~2C~R functional status, marked by lower cortical 5-HT~2C~R synaptosomal protein expression and reduced pharmacological sensitivity, associates with greater reactivity to cocaine-associated cues. Future studies are required to expand on our observations to consider the 5-HT~2C~R system as a risk factor or predictor of cocaine cue reactivity, and perhaps explore as a biological marker of propensity toward craving and relapse in cocaine dependence. We thank Dr David Goldman (Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism) for thoughtful discussions and comments on the manuscript. We thank Ms Sonja J Stutz (UTMB) for assistance with rat self-administration surgeries and procedures. This work was supported by the National Institute on Drug Abuse grants K99 DA033374 (NCA), P20 DA024157 (KAC), K05 DA020087 (KAC), K02 DA000403 (FGM), P50 DA009262 (FGM), MD Anderson\'s Cancer Center Support Grant DA026120 (SL) and the Center for Addiction Research at the University of Texas Medical Branch. The work was also supported in part by the Toomim Family Fund (DAN). This material is the result of work supported in part by resources and the use of facilities at the Michael E DeBakey VA Medical Center, Houston, TX, USA. Dr Moeller is a consultant for Boehringer-Ingelheim. Dr Cunningham is a consultant for Arena Pharmaceuticals and an editor of Neuropsychopharmacology Reviews for which she receives compensation from the American College of Neuropsychopharmacology. The remaining authors declare no conflict of interest. ![Cocaine-dependent subjects exhibit attentional bias toward cocaine-related words on the cocaine-word Stroop task. The difference in mean reaction times between trials with cocaine-related words and those with neutral words was used as a measure of attentional bias toward cocaine-related words. (a) Cocaine-dependent subjects displayed longer reaction times (msec; mean±s.e.m.) to indicate the word color in trials with cocaine-related words vs trials with neutral words (P\<0.01 vs neutral words). (b) Accuracy (ratio of correct responses to total trials on either neutral or cocaine-related word trials) did not differ between cocaine-related and neutral word trials in cocaine-dependent subjects.](tp2013131f1){#fig1} ![The highest attentional bias is seen in African-American cocaine-dependent subjects with the Ser23 protein variant. Mean reaction times (msec±s.e.m.) for African-American subjects with the C/CC genotype which encodes for the Ser23 protein variant were significantly greater than that for African-American subjects with the G/GG genotype (\*P\<0.05 vs G/GG genotype).](tp2013131f2){#fig2} ![Individual differences in appetitive approach behavior in rats are driven by discrete cocaine-associated stimuli. The levels of operant behavior within the cocaine-associated context (left) or reinforced by the discrete cue complex (right) at 24 h of withdrawal were assessed in rats stratified as high (HCR) vs low cue reactive (LCR). Previously-active lever presses did not differ between HCR (n=12) and LCR (n=12) rats upon exposure to the context in the absence of the discrete cue complex (first 10 min of session; NS). HCR rats displayed significantly higher cue-reinforced lever presses (second 60 min of session) vs LCR rats (\*P\<0.05 vs LCR rats).](tp2013131f3){#fig3} ![High cue reactive (HCR) rats exhibit lower 5-HT~2C~R protein expression in medial prefrontal cortex (mPFC) relative to low cue reactive (LCR) rats. (a) Mean total lever presses (±s.e.m.) on the previously-active and inactive levers are presented for the cue reactivity test session. Each previously-active lever press resulted in the presentation of the discrete cue complex in the absence of cocaine delivery on an FR1. Rats identified as HCR (n=5) displayed significantly higher lever presses for cocaine-associated cues vs LCR rats (n=6; \*P\<0.01). Inactive lever presses did not differ between HCR and LCR rats. (b) Qualitative and (c) quantitative data demonstrate phenotypic differences in mPFC 5-HT~2C~R synaptosomal protein expression. HCR rats displayed lower cortical synaptosomal 5-HT~2C~R protein levels relative to LCR rats (\*P\<0.05). (d) An inverse correlation was observed between mPFC 5-HT~2C~R synaptosomal protein and responses on the previously-active lever for cocaine-associated cues in individual rats (r=0.815; P\<0.01). The differential protein expression observed in HCR (0.051±0.002 arbitrary units) and LCR (0.076±0.008 arbitrary units) rats was not related to the cue reactivity test itself as comparable 5-HT~2C~R mPFC protein levels were observed in HCR (n=6; 0.049±0.01 arbitrary units) and LCR rats (n=6; 0.087±0.02 arbitrary units) that remained in their home cage until sacrifice.](tp2013131f4){#fig4} ![High cue reactive (HCR) rats exhibit lower sensitivity to the suppressive effects of the selective 5-HT~2C~R agonist WAY163909 relative to low cue reactive (LCR) rats. Mean active lever presses (±s.e.m.) are presented for the cue reactivity test session. Each previously active lever press resulted in the presentation of the discrete cue complex in the absence of cocaine delivery on an FR1. Rats identified as HCR (n=16 rats per treatment) and LCR rats (n=16 rats per treatment) were injected with saline (15 min; 1 ml kg^−1^, intraperitoneal) or WAY163909 (15 min; 0.5 mg kg^−1^; intraperitoneal) prior to a cocaine cue reactivity test session on FA day 1. WAY163909 significantly attenuated lever presses for cocaine-associated cues in LCR, but not HCR, rats (\*P\<0.05 vs saline-treated LCR rats). FA, forced abstinence.](tp2013131f5){#fig5} ###### Demographic and clinical characteristics of cocaine-dependent subjects by HTR2C genotype Genotype -------------------------------- -------------- ------------ -------------------- Subjects (n) 27 6 81 Age (years±s.e.m.) 45.37±1.50 41.33±2.32 43.64±0.93 Sex[a](#t1-fn1){ref-type="fn"} 26 M, 1 F 6 F 71 M, 10 F Race 24 AA, 3 Cau 6 AA 54 AA, 18 Cau, 9 O Cocaine (years±s.e.m.) 15.56±1.5 17.50±2.2 15.25±0.9 %Positive cocaine 78 75 74 %Alcohol abuse 31 17 25 %Cannabis abuse 22 33 10 %Treatment-seekers 70 67 86 Abbreviations: F, female; M, male; AA, African-American; Cau, Caucasian; O, other races (Hispanic, Asian). Fisher\'s exact test, P\<0.01. ###### Genotype, sex and attentional bias in cocaine-dependent subjects Genotype Male[a](#t2-fn1){ref-type="fn"} Female Both ------------ ----------------------------------- --------------------------------------------- ------------------ --------------------- C CC 75.88±14.13 (26)[b](#t2-fn2){ref-type="fn"} 152.83 (1) 78.73±13.89 (27)^c^ CG -- 26.03±11.04 (6) 26.03±11.04 (6) G GG 37.80±9.02 (71) 68.95±27.94 (10) 41.65±8.64 (81) The numbers in the parenthesis indicate the subject number. Data are presented as mean (±s.e.m.) attentional bias in msec calculated for each subject and averaged across subjects. P\<0.05 vs G (males only). P\<0.05 vs G/GG (both males and females). [^1]: These authors contributed equally to this work.	{ "pile_set_name": "PubMed Central" }
[Study and realization of multidimensional visualization techniques for multimodality medical images]. This paper designed a multimodal medical image visualization system using open source VTK on platform VS2008. The system can visualize CT, MR, PET and SPECT using different visualization methods, such as multi-planar reconstruction (MPR), curved planar reformation (CPR), direct volume rendering (DVR), indirect volume rendering (IVR) and maximum intensity projection (MIP). Clinical practice shows that the system has stable performance and the visualization methods which make the reading of different modal medical images more convenient. The maximum number of CT slices the system can reconstruct is more than 2 000, and the reconstruction speed and quality meet the clinical requirements.	{ "pile_set_name": "PubMed Abstracts" }
Q: Не запускается приложение на Laravel из-за проблем с ключом шифрования Laravel 5.3. Не запускается приложение. Вылетает: RuntimeException in Encrypter.php line 43: The only supported ciphers are AES-128-CBC and AES-256-CBC with the correct key lengths. Нагуглил три команды для решения проблемы: php artisan key:generate php artisan config:clear php artisan config:cache Выполнил все три, проблема плевать на них хотела и не собирается уходить. По-прежнему выскакивает та же ошибка. A: Запускаем команду php artisan key:generate. Копируем ключ в файл .env в строку APP_KEY=base64:ВАШ_КЛЮЧ_ЗДЕСЬ. Затем запускаем команду php artisan config:clear, а после команду php artisan config:cache.	{ "pile_set_name": "StackExchange" }
Seela Sella Seela Maini Marjatta Sella (née Virtanen, b. 30 December 1936) is a Finnish film actress. She was born in Tampere, Finland. During her career, which has spanned more than 40 years to date, Seela Sella has had roles in productions at the Finnish National Theatre, the TTT-Theatre, the Tampere Comedy Theatre, etc. and has made almost 35 appearances in film and television. She has also organized monologue, song and recital nights. Lately, Sella has been working with Finnish director Timo Koivusalo on a number of films such as Aino Sibelius in his movie Sibelius in 2003 as well as in several other Finnish movies and TV series. In 2006, she once again worked with Koivusalo, this time in his movie Kalteva torni. Sella has also done voice-overs for the Finnish versions of such animated movies as A Bug's Life and The Emperor's New Groove. Sella received an award for her work from the Alfred Kordelin Foundation in 2000. Personal life Seela has two children, Ariel and Ilana. She converted to Judaism when she married the Finnish Jew Elis Sella. References External links Category:1936 births Category:Living people Category:People from Tampere Category:Finnish Jews Category:Finnish actresses Category:Converts to Judaism	{ "pile_set_name": "Wikipedia (en)" }
Application of Orem's conceptual framework to patients with hypercalcemia related to breast cancer. Breast cancer is the most common malignancy in women in the United States. Although the disease itself may be chronic in nature, it may give rise to oncologic emergencies, such as hypercalcemia, superior vena cava syndrome, or spinal cord compression. If these emergencies are not prevented or treated promptly through early detection, premature death or disability may occur. Because it presents with general symptoms, hypercalcemia may be difficult to diagnose; however, early recognition and intervention may reverse the sequelae of this condition, and prevent recurrence. This article will focus on the pathophysiology, epidemiology, nursing assessment, and intervention in a case study of this oncologic emergency based on the Orem model.	{ "pile_set_name": "PubMed Abstracts" }
Ajmer Military School Rashtriya Military School – Ajmer (formerly King George’s Royal Indian Military School), established in 1930, is a boys educational institution located in Ajmer, Rajasthan, India. Managed by the Indian Army, the institution offers education mainly to the wards of defence personnel but civilians are also offered admission. The faculty includes, the "Academic Block, student hostels, teacher’s residence, support staff residences, Mess, grounds, gymnasium, swimming pool, MI room, stores, and Dhobi Ghats. There is a very old Shiva Temple along with one prayer cum Pooja Hall." Admission requirements are apparent as age, a common entrance test, provided documents and medical standards are required apart from the fees. See also Indian Naval Academy References Further reading Category:Schools in Rajasthan Category:Military schools in India Category:Educational institutions established in 1930 Category:Education in Ajmer	{ "pile_set_name": "Wikipedia (en)" }
This invention relates to a motor vehicle inflatable restraint system, and more particularly to a system and method for detecting an out-of-position occupant. Vehicle occupant position detection systems are useful in connection with air bags and other pyrotechnically deployed restraints as a means of judging whether, and/or how forcefully, to deploy the restraint. Ideally, the system should be capable of classifying the type of occupant (i.e., large adult, small adult, child, etc.) and the position of the occupant relative to the point of deployment of the air bag. Various systems incorporating one or more infrared and/or acoustical ranging sensors have been proposed for this purpose; see, for example, the U.S. Pat. Nos. 5,330,226, 5,785,347, 5,737,083 and 6,113,137. In general, such systems emit one or more beams of infrared energy to define a corresponding number of viewing fields, and detect the received energy to determine occupant presence and position within the viewing fields. Unfortunately, such systems tend to be quite costly, and are difficult to package in the automotive environment. Moreover, a relatively high speed of response is required so that deployment can be properly inhibited or allowed when the occupant position quickly changes, possibly in anticipation of an impending collision. Accordingly, what is needed is a low-cost system that accurately and occupant position quickly changes, possibly in anticipation of an impending collision. Accordingly, what is needed is a low-cost system that accurately and quickly characterizes occupant intrusion into a defined out-of-position area for purposes of deciding whether, or how forcefully, to deploy an inflatable restraint in the event of a serious crash. The object of this invention is directed to an improved infrared (IR) occupant detection system that is low in cost, and provides accurate and reliable occupant intrusion information at a speed sufficient to timely inhibit or otherwise control deployment of occupant restraints. An array of IR emitters is selectively activated to emit a predetermined pattern of IR beams in an area between the passenger seat and the point of deployment of the restraint, and the reflected IR energy is detected by a photo-sensitive receiver and analyzed to determine whether an occupant is out of position for deployment of the restraint. In the preferred embodiment, the intensity of the received beam energy and the position of the respective beam are used to construct a table of individual intrusion factors, and a composite intrusion factor based on the individual intrusion factors is categorized by magnitude to form an indication of occupant intrusion level, which in turn, is used to determine whether, or how forcefully, to deploy the restraint in the event of a serious crash.	{ "pile_set_name": "USPTO Backgrounds" }
Q: Resizing image before upload (my upload take/pick is ok) After almost two weeks... I give up!!! I achieve upload an image from gallery and camera... startActivityForResult... ok! EXTERNAL_CONTENT_URI... ok! ACTION_IMAGE_CAPTURE... ok! onActivityResult... ok! Activity.RESULT_OK ('cause I'm on Fragment)... ok! getActivity().getContentResolver().query()... ok! BitmapFactory.Options, opts.inSampleSize, .decodeFile... ok! but I can't reduce the size of image to 900px, before upload to server using... - FileInputStream(sourceFile); - HttpURLConnection - DataOutputStream( getOutputStream) - dos.writeBytes(form... name... file name...) - dos.write(buffer, 0, bufferSize) I can't understand... - How use "createScaledBitmap" in this case. - How can I use "writeBytes(...filename=?)" if when I create a new bitmap, it doesn't have a path (at least I think so). - If I have an original image on disk, what it's the path of result of "createScaledBitmap"? - How buffer work (Step by Step would be great), and why in others examples on stackoverflow don't use it? I have read many references including: http://developer.android.com/training/displaying-bitmaps/load-bitmap.html But I already used "options.inSampleSize" for make a Preview on my Fragment, and I think I need (in my case) "createScaledBitmap" for achieve my 900x900px image for upload. If there is another way to upload images with resize include... let me know! (Any links would be helpful) I know... I should use AsyncTask... I'm working on that! ;) Please consider not talk so technical because I have the worst combination for learning Android: newbie and speak spanish! xD ADDED: Anybody can help with the thing that @GVSharma says here? Upload compressed image "you got string path first na.so convert it to bitmap and compress it. instead of sending string file path as first argument to that method change that first argument to Bitmap bitmap. or you need String file path only then again convert the compressed bitmap to String. hope this one could help you" (I have no idea how to do this) public int uploadFile(String sourceFileUri) { final String fileName = sourceFileUri; HttpURLConnection conn = null; DataOutputStream dos = null; String lineEnd = "\r\n"; String twoHyphens = "--"; String boundary = "****"; int bytesRead, bytesAvailable, bufferSize; byte[] buffer; int maxBufferSize = 1 1024 * 1024; File sourceFile = new File(sourceFileUri); if (!sourceFile.isFile()) { ... } else { try { // open a URL connection to the Servlet FileInputStream fileInputStream = new FileInputStream(sourceFile); URL url = new URL(upLoadServerUri); conn = (HttpURLConnection) url.openConnection(); conn.setDoInput(true); conn.setDoOutput(true); conn.setUseCaches(false); conn.setRequestMethod("POST"); conn.setRequestProperty("Connection", "Keep-Alive"); conn.setRequestProperty("ENCTYPE", "multipart/form-data"); conn.setRequestProperty("Content-Type", "multipart/form-data;boundary=" + boundary); conn.setRequestProperty("uploaded_file", fileName);//This is just for info? dos = new DataOutputStream(conn.getOutputStream()); dos.writeBytes(twoHyphens + boundary + lineEnd); dos.writeBytes("Content-Disposition: form-data; name=\"uploaded_file\"; filename=\""+fileName+"\"" + lineEnd);//How put in here a resized bitmap? dos.writeBytes(lineEnd); //Here I'm lost! bytesAvailable = fileInputStream.available(); bufferSize = Math.min(bytesAvailable, maxBufferSize); buffer = new byte[bufferSize]; bytesRead = fileInputStream.read(buffer, 0, bufferSize); //I think... //this is a way to transfer the file in little pieces to server, right?, wrong? //If anybody can explain this, step by step... THANKS!!! while (bytesRead > 0) { dos.write(buffer, 0, bufferSize); bytesAvailable = fileInputStream.available(); bufferSize = Math.min(bytesAvailable, maxBufferSize); bytesRead = fileInputStream.read(buffer, 0, bufferSize); } dos.writeBytes(lineEnd); dos.writeBytes(twoHyphens + boundary + twoHyphens + lineEnd); serverResponseCode = conn.getResponseCode(); String serverResponseMessage = conn.getResponseMessage(); Log.i("uploadFile", "Respuesta HTTP es: " + serverResponseMessage + ": " + serverResponseCode); if(serverResponseCode == 200){ ... } fileInputStream.close(); dos.flush(); dos.close(); } catch (MalformedURLException ex) { ... } catch (Exception e) { ... } dialog.dismiss(); return serverResponseCode; } // End else block }//End uploadFile() A: Actually there are 2 ways to handle above case, mentioned below : 1] Make some arrangement at server side (in your webservice) so you can pass height & width while uploading image on server, this will reduce image size whatever height/width dimension you pass. This is first solution. 2] As per my understanding if you can reduce bitmap dimension by this code : try { int inWidth = 0; int inHeight = 0; InputStream in = new FileInputStream(pathOfInputImage); // decode image size (decode metadata only, not the whole image) BitmapFactory.Options options = new BitmapFactory.Options(); options.inJustDecodeBounds = true; BitmapFactory.decodeStream(in, null, options); in.close(); in = null; // save width and height inWidth = options.outWidth; inHeight = options.outHeight; // decode full image pre-resized in = new FileInputStream(pathOfInputImage); options = new BitmapFactory.Options(); // calc rought re-size (this is no exact resize) options.inSampleSize = Math.max(inWidth/dstWidth, inHeight/dstHeight); // decode full image Bitmap roughBitmap = BitmapFactory.decodeStream(in, null, options); // calc exact destination size Matrix m = new Matrix(); RectF inRect = new RectF(0, 0, roughBitmap.getWidth(), roughBitmap.getHeight()); RectF outRect = new RectF(0, 0, dstWidth, dstHeight); m.setRectToRect(inRect, outRect, Matrix.ScaleToFit.CENTER); float[] values = new float[9]; m.getValues(values); // resize bitmap Bitmap resizedBitmap = Bitmap.createScaledBitmap(roughBitmap, (int) (roughBitmap.getWidth() * values[0]), (int) (roughBitmap.getHeight() * values[4]), true); // save image try { FileOutputStream out = new FileOutputStream(pathOfOutputImage); resizedBitmap.compress(Bitmap.CompressFormat.JPEG, 80, out); } catch (Exception e) { Log.e("Image", e.getMessage(), e); } } catch (IOException e) { Log.e("Image", e.getMessage(), e); } After doing above coding steps, then you can use your image/bitmap uploading logic/code.	{ "pile_set_name": "StackExchange" }
package drds //Licensed under the Apache License, Version 2.0 (the "License"); //you may not use this file except in compliance with the License. //You may obtain a copy of the License at // //http://www.apache.org/licenses/LICENSE-2.0 // //Unless required by applicable law or agreed to in writing, software //distributed under the License is distributed on an "AS IS" BASIS, //WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. //See the License for the specific language governing permissions and //limitations under the License. // // Code generated by Alibaba Cloud SDK Code Generator. // Changes may cause incorrect behavior and will be lost if the code is regenerated. // RdsInstInfosInDescribeEvaluateTaskReport is a nested struct in drds response type RdsInstInfosInDescribeEvaluateTaskReport struct { RdsInstInfosItem []RdsInstInfosItem `json:"RdsInstInfos" xml:"RdsInstInfos"` }	{ "pile_set_name": "Github" }
Mount Capps Mount Capps is a mountain in the Alaska Range, in Denali National Park and Preserve, southwest of Denali on a ridge between Denali and Mount Crosson, close to Kahiltna Dome and at the heads of Peters Glacier and Kahiltna Glacier. Mount Capps was named in 1952 by after U.S. Geological Survey geologist Stephen Reid Capps. See also Mountain peaks of Alaska References Category:Alaska Range Category:Mountains of Denali National Park and Preserve Category:Mountains of Alaska Category:Mountains of Denali Borough, Alaska	{ "pile_set_name": "Wikipedia (en)" }
library("matrixStats") fcns <- list( varDiff = c(rowVarDiffs, colVarDiffs), sdDiff = c(rowSdDiffs, colSdDiffs) ) # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - # Subsetted tests # - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - source("utils/validateIndicesFramework.R") trim <- runif(1, min = 0, max = 0.5) for (fcn in names(fcns)) { cat(sprintf("subsetted tests on %s()...\n", fcn)) row_fcn <- fcns[[fcn]][[1L]] col_fcn <- fcns[[fcn]][[2L]] for (mode in c("numeric", "integer")) { x <- matrix(runif(6 * 6, min = -6, max = 6), nrow = 6L, ncol = 6L) storage.mode(x) <- mode if (mode == "numeric") x[1:2, 3:4] <- Inf for (diff in 1:2) { for (rows in index_cases) { for (cols in index_cases) { for (na.rm in c(TRUE, FALSE)) { validateIndicesTestMatrix(x, rows, cols, ftest = row_fcn, fsure = row_fcn, na.rm = na.rm, diff = diff, trim = trim) validateIndicesTestMatrix(x, rows, cols, fcoltest = col_fcn, fsure = row_fcn, na.rm = na.rm, diff = diff, trim = trim) } } } } } cat(sprintf("%s()...DONE\n", fcn)) }	{ "pile_set_name": "Github" }
Liberty Monument Liberty Monument may refer to: Liberty Monument (Ticonderoga), monument to the history of Fort Ticonderoga, erected 1924 Liberty Monument (Nicosia), monument to Cyprus independence fighters, erected 1973 Liberty Monument (Seychelles), monument to independence, erected 2014 Liberty Statue (Budapest), erected 1947 Battle of Liberty Place Monument, New Orleans monument to the Battle of Liberty Place, erected 1891 and dismantled 2017 See also Monument of Liberty (disambiguation) Freedom Monument (disambiguation) Statue of Liberty in New York	{ "pile_set_name": "Wikipedia (en)" }
return Byte(this.val$^0xff);	{ "pile_set_name": "Github" }
package me.loda.spring.springsecurityhibernate; /******************************************************* * For Vietnamese readers: * Các bạn thân mến, mình rất vui nếu project này giúp * ích được cho các bạn trong việc học tập và công việc. Nếu * bạn sử dụng lại toàn bộ hoặc một phần source code xin để * lại dường dẫn tới github hoặc tên tác giá. * Xin cảm ơn! *****************************************************/ import org.springframework.beans.factory.annotation.Autowired; import org.springframework.boot.CommandLineRunner; import org.springframework.boot.SpringApplication; import org.springframework.boot.autoconfigure.SpringBootApplication; import org.springframework.security.crypto.password.PasswordEncoder; import me.loda.spring.springsecurityhibernate.user.User; import me.loda.spring.springsecurityhibernate.user.UserRepository; / * Copyright 2019 {@author Loda} (https://loda.me). * This project is licensed under the MIT license. * * @since 4/30/2019 * Github: https://github.com/loda-kun */ @SpringBootApplication public class App implements CommandLineRunner { public static void main(String[] args) { SpringApplication.run(App.class, args); } @Autowired UserRepository userRepository; @Autowired PasswordEncoder passwordEncoder; @Override public void run(String... args) throws Exception { // Khi chương trình chạy // Insert vào csdl một user. User user = new User(); user.setUsername("loda"); user.setPassword(passwordEncoder.encode("loda")); userRepository.save(user); System.out.println(user); } }	{ "pile_set_name": "Github" }
Konstantinos Rigos, the newly appointed director of the Greek National Opera Ballet, made his debut as the founder of OKTANA Dance Theatre (1990) and has since choreographed and directed numerous performances, many of which have toured around the world. The year 1999 marked his first collaboration with playwright Elena Penga. Already noted for her postdramatic plays in the ‘90s, Penga is also an acclaimed writer of short stories (recipient of the Ourani Foundation Award, Academy of Athens, 2012). Rigos and Penga first collaborated on Penga’s play The Emperor’s New Clothes, famously staged at the catwalk of a nightclub and later presented at Roes Theatre (2009). The two artists now join forces to bring Penga’s new play to the stage. Inspired by two short stories by writer Roberto Bolaño, Pornstar is set in contemporary Greece. With its rich, literary language, the play unveils the secret stories of pornstars, the stars of an artificial world full of clichés, a reflection of our loneliness. Refraining from stereotypes and without passing judgment, Penga goes beneath the façade of a faceless industry to shed light to these people’s stories, revealing their quest for an authentic identity, a quest that is at once mysterious and moving.Lalo, a young man from Peristeri, a rundown suburb of Athens and son of a 1980s Greek porn actress decides to track down Jack Rio, his mother’s partner in adult films when she was pregnant to Lalo. His quest takes him from the kitchen of a German director to a clinic in Italy where he visits a patient under a false name, before ultimately travelling to USA. Inside a bungalow, he finally confronts the man behind the legend, whom Lalo thinks is his father. The characters pursue their individual, troubled destiny. Lalo struggles to cross his personal abyss, seeking answers to existential questions and trying to settle accounts with the past.	{ "pile_set_name": "Pile-CC" }
In Brampton, a three-vehicle collision at Goreway and Deerhurst Drs. sent a child to hospital with serious head injuries around 7 a.m. Peel police’s Major Collision Bureau is currently investigating the incident. Slippery spots were also reported in Mississauga, where numerous buses and vehicles were unable to drive uphill at Burnhamthorpe and Dixie Rds. due to icy roads. At least 25 collisions have been reported in Peel region, according to police. Most expressways have since been salted, but smaller side streets are still very icy, according to Stibbe. Toronto broke a warm-weather record yesterday when the temperature climbed past the 9.1C record set in 2006. Environment Canada issued a snow squall watch for the GTA today, warning motorists of poor visibility due to blowing snow. A high of -4 C and strong gusts of up to 70 km/h are expected across the GTA this afternoon. More on thestar.com We value respectful and thoughtful discussion. Readers are encouraged to flag comments that fail to meet the standards outlined in our Community Code of Conduct. For further information, including our legal guidelines, please see our full website Terms and Conditions.	{ "pile_set_name": "Pile-CC" }
Pages 26 August 2010 And the NAFTA/expropriation winner is… In their offices in the Sun Life Building in the heart of Montreal’s financial quarter, the boys at AbitibiBowater are likely making toasts using the finest single malt scotch they save for just these special business occasions. There haven’t been too many of them for the managers at the financially troubled company lately but this week, they can crack open the bottle and enjoy themselves. And while they are at it they can make two toasts. Their first one should be to Danny Williams. Were it not for the Premier’s unshakeable - and entirely unfounded - belief in his own infallibility, AbitibiBowater could not have achieved its monumental success in Newfoundland and Labrador. Not only did Danny Williams’ astonishing business and legal prowess relieve them of the huge liability for environmental cleanup in Newfoundland and Labrador, he voluntarily took their financial liabilities to some of their former employees and handed them all to taxpayers in his own province. On top of all that, AbitibiBowater will get a nice cheque from the federal government for their troubles. That money will easily cover the minor costs for remediation at the couple of properties they still own in this province and leave pretty much all of Stephen Harper’s $130 million intact. Sweet. And if all that were not good enough, they still get to watch their lawyers humiliate the provincial government in its own courts over those environmental orders cooked up during the NAFTA war. Lay money on judge after judge stuffing the orders up Danny’s nose for as many appeals as he may want to make. AbitibiBowater could use more enemies like Danny Williams. If he wants to practice corporate law after he retires, AbitibiBowater would hire him in an instant to go to work for their competitors. He’s just that good. The other toast would be to the biggest losers in the expropriation, namely the people of Newfoundland and Labrador. The five hundred odd thousand people of the island – and Labrador - are stuck with the bill for all this. The environmental messes, the legal bills to Toronto and Montreal firms, the severance and all the rest of it. But supposedly the raggedy arsed artillery of Newfoundland and Labrador have mighty assets now, according to Danny Williams, to cover those liabilities. These assets would have been sold to unnamed others had Williams not struck with his expropriation sword. Of course, he fails to mention that the liabilities go with the assets such that who ever owns them cannot get one without the other. But then again Williams the Great Lawyer knows this already even if he does not share his knowledge with his clients. That is really part of Williams’ brilliance as a lawyer, however and why companies like AbitibiBowater will want him to work for their competitors once he leaves politics. Only a truly amazing talent could shag his own clients so completely and yet have them lust for the rogering like a pubescent suicide bomber eager to get down with the 72 virgins he’s been promised. Both are in for a rude shock, of course. But unlike the child-fanatic, the people of Newfoundland and Labrador have a good clue that these very expensive assets are far less valuable than they’ve been made out to be. One of the three companies interested in the timber – and one very seriously considered for a while – was a bankrupt German paper maker looking for massive government hand-outs. Another even less appealing prospect wanted to turn prime logs to sawdust in order to make wood pellets out of them. To appreciate just exactly how lame is that idea, one need only realise that wood pellets are most often cited as a way of using the scraps left over from making major wood products like furniture or paper. Anything else is a waste of a very valuable log. Yet to be tallied into the cost of this expropriation fiasco are the payments the taxpayers in Newfoundland and Labrador will have to make to a bunch of companies who are essentially collateral damage in Danny Williams war against – or is it on behalf of? – AbitibiBowater. Settling fairly with these companies was a condition of the federal government’s payment to AbitibiBowater, according to Danny Williams. Undoubtedly the rather obvious preferential treatment given to these other companies compared to AbitibiBowater, not to mention Williams’ own comments attacking AbitibiBowater, coloured the expropriation bill to the point where the lawsuit could have cost the federal government much more dearly than the $130 million it did. As it is, Fortis, ENEL, Clarica, Sun Life Assurance, Mutual Life Assurance, Standard Life Assurance, and Industrial Life Assurance will all be restored to their former financial position, according to the Premier during his scrum with local reporters. Talks are still going on, but according to the Premier, they will get cash or a power purchase agreement or some other arrangement. Fortis is already getting cash: the provincial government assumed responsibility last year for a $60 million loan Fortis and AbitibiBowater had for their hydroelectric partnership. Keep an eye on those talks. Their outcome could be most interesting indeed. Whatever the conventional media may be saying about the latest part of the expropriation saga, the winners and losers are not as they initially appear, nor is the magnitude of the loss yet known.	{ "pile_set_name": "Pile-CC" }
[Study on third-type immunoliposomes loaded drugs and the targeting in vitro and in vivo]. To study the preparation, targeting and pharmacodynamics of third-type immunoliposome loaded anticancer drugs. The monoclonal antibody of human bladder cancer was combined with the terminal of PEG-COOH (polyethyleneglycol carboxylic acid) that make the liposomes not only prolong circulation by the membrane protection of PEG, but also target by spreading the antibody on the liposomes surface. That was the third type immunoliposomes. According to this scheme, the IML-ADM (immunoliposome carried adriamycin) wes prepared in which ADM entrapment was efficient and stability was high and the antibody activity was kept. The % survival of the targeting EJ cells treated with IML-ADM (ADM = 45.45 micrograms.mL-1) was 4.3% +/- 1.0%, but 72% +/- 6% for non-targeting LOVO cells in vitro; the tumor weight in nude mice which were implanted by EJ cells after 27 days were (39 +/- 25) mg, (135 +/- 32) mg, (598 +/- 240) mg treated by IML-ADM, SSL-ADM (steric stable lipsomes carried Adriamycin) and normal saline, respectively, in vivo. The results confirmed that the immunoliposme-mediated targeting anticancer drug is a feasible way.	{ "pile_set_name": "PubMed Abstracts" }
Wow! Look who bumped into each other.. Candace Cameron (Bure) chilled with fellow Full House alumni, John Stamos and Bob Saget at the Starlight Awards in Los Angeles‘s Skirball Cultural Center on Wednesday! You just know the subject of “reunion” had to have come up..	{ "pile_set_name": "Pile-CC" }
Tag: onam Onam, the biggest festival of Malayalis, falls tomorrow. For me, the day is all about food, family, friends and a lot of fun. Onasadhya, the Onam lunch, is the most delicious part about this festival of Kerala. It’s a feast, if enjoyed once, will be relished forever! Legend goes that Onam is celebrated to invite the spirit of King Mahabali, a former king of Kerala in whose reign there was no unhappy person. Meals are strictly vegetarian on Onam and there are essentially 13 food items served on a banana leaf. There are pickles of various kinds, banana chips for crunch, fruits, chutneys, curries, side-dishes, buttermilk and two or three types of payasam (kheer/pudding). Rice is the main component of this elaborate meal. We Malayalis don’t need a reason to celebrate Kerala cuisine but we look forward to Onam to enjoy a combination of deliciousness on this day. Here, I am sharing the recipe of Avial, a mixed vegetable side dish, without which any Onasadya is incomplete. Kerala’s Avial Packed with veggies, this Onam special Avial can be relished all round the year In a deep pan, cook together yam and plantain with a little salt and turmeric. Once half done, add winter melon and other vegetables with some more salt and cook till soft but not mushy. Use very less water to cook but make sure it does not get overcooked. Each vegetable should hold its individual identity and taste. Add the ground paste and cook for a few minutes. Add curd and remove switch off the flame. Add coconut oil and curry leaves. Serve with rice and rasam.	{ "pile_set_name": "Pile-CC" }
Ambulatory intravenous antibiotic therapy for children with preseptal cellulitis. This study aimed to compare the use of outpatient ambulatory care versus admission for intravenous antibiotics in the management of preseptal cellulitis. This is a retrospective consecutive cohort study of children younger than 16 years presenting to an Inner London Paediatric Emergency Department with signs and symptoms of preseptal cellulitis. A total of 94 cases were identified during a 17-month period. Of them, 30 children were prescribed oral antibiotics. One child did not receive treatment. Of the 63 children prescribed with intravenous antibiotics, 42 were managed on an ambulatory basis and 21 were admitted. There was no significant difference in duration of treatment in days between those on ambulatory management and those admitted (2.79 ± 0.8 vs 2.76 ± 1.9, P = 0.94) or in the rate of complications. The net cost saving was $205,924 (£131,065; &OV0556;147,578) overall, equal to $4900 (£3120; &OV0556;3513) per patient. Ambulatory intravenous antibiotics with daily review are a safe and cost-effective alternative to inpatient admission in simple preseptal cellulitis for children in our population who require parenteral antibiotics.	{ "pile_set_name": "PubMed Abstracts" }
Coors Light A market research company called YouGov surveyed people nationwide and asked them which brands of beer they’d heard positive or negative things about in the last two weeks. And the beer that has the most […]	{ "pile_set_name": "Pile-CC" }
Q: Inverted exclamation mark in Mathmode What is the command/package used to give the Inverted exclamation mark in Mathmode. I have tried the following: \mbox{!`}_A - The output is not at the same margin level as !. \mbox{\textexclamdown}_A - The output is again not at the same margin level as !. \rotatebox[origin=c]{180}{!}_A - The output is at the same margin, and this is what is required. However, I find this too complex for a simple inverted exclamation mark. A: Taking code from https://tex.stackexchange.com/a/312530/4427, here is a version that raises the inverted exclamation mark to sit on the baseline. \documentclass{article} \usepackage{amsmath} \DeclareMathSymbol{\mathinvertedexclamationmark}{\mathclose}{operators}{'074} \DeclareMathSymbol{\mathexclamationmark}{\mathclose}{operators}{'041} \makeatletter \newcommand{\raisedmathinvertedexclamationmark}{% \mathclose{\mathpalette\raised@mathinvertedexclamationmark\relax}% } \newcommand{\raised@mathinvertedexclamationmark}[2]{% \raisebox{\depth}{$\m@th#1\mathinvertedexclamationmark$}% } \begingroup\lccode`~=`! \lowercase{\endgroup \def~}{\@ifnextchar`{\raisedmathinvertedexclamationmark\@gobble}{\mathexclamationmark}} \mathcode`!="8000 \makeatother \begin{document} $n! + n!`$ $\scriptstyle n! + n!`$ \end{document} You might want to use \mathord instead of \mathclose throughout, if your symbols are to denote objects of a category. Or, better, define semantic commands. \documentclass{article} \usepackage{amsmath} \DeclareMathSymbol{\mathinvertedexclamationmark}{\mathord}{operators}{'074} \DeclareMathSymbol{\mathexclamationmark}{\mathord}{operators}{'041} \makeatletter \newcommand{\raisedmathinvertedexclamationmark}{% \mathord{\mathpalette\raised@mathinvertedexclamationmark\relax}% } \newcommand{\raised@mathinvertedexclamationmark}[2]{% \raisebox{\depth}{$\m@th#1\mathinvertedexclamationmark$}% } \makeatother \newcommand{\terminal}{\mathexclamationmark} \newcommand{\initial}{\raisedmathinvertedexclamationmark} \begin{document} $\terminal\to\initial$ \end{document}	{ "pile_set_name": "StackExchange" }
(Newser) – Details related to the shocking death of Andrew Breitbart are beginning to trickle out, with father-in-law Orson Bean telling the AP that the conservative firebrand was walking near his Brentwood home shortly after midnight when he collapsed. Someone apparently saw him do so, and called paramedics. Breitbart had suffered heart problems a year earlier, but the cause of death remains unknown, pending an autopsy. He is survived by his wife, Susannah Bean Breitbart, and four children. Meanwhile, the reflections are pouring in: Rick Perry: "RIP 'O Mighty Warrior!" Mitt Romney: "Ann and I are deeply saddened by the passing of @AndrewBreitbart: brilliant entrepreneur, fearless conservative, loving husband and father." Rick Santorum: "I'm crestfallen. What a powerful force. What a huge loss, in my opinion for our country, and certainly for the conservative movement. My prayers go out to his family." If only I had no conscience, I could do what Brietbart did...make a living exploiting the gullibility of the ignorant masses who accept propaganda and lies as truth because it lines up with their uninformed views, and because they wish it to be so. I have just a bit more respect for Televangelists than I did for Breitbart. dosdiverz Mar 1, 2012 6:37 PM CST Who? Scaramouche Mar 1, 2012 1:42 PM CST I'm betting someone offed this dude for something related to the elections.	{ "pile_set_name": "Pile-CC" }
// // YiXinConnector.h // ShareSDKConnector // // Created by 冯鸿杰 on 16/9/29. // Copyright © 2016年 mob. All rights reserved. // #import <Foundation/Foundation.h> /** * 易信连接器 / @interface YiXinConnector : NSObject /* * 链接易信以供ShareSDK可以正常使用易信的相关功能（包括授权、分享） * * @param yxApiClass 易信SDK中的类型，应先导入YXApi.h，再将[YXApi class]传入到参数中。 */ + (void)connect:(Class)yxApiClass; @end	{ "pile_set_name": "Github" }
Blizzard / World of Warcraft lose 1.1 million subscribers If you look back at our history, you’ll see that World of Warcraft has gotten a little bit of hate from us here at FleshEatingZipper, both in written articles and in our podcast. this isn’t because it is a bad game or because Blizzard’s a bad company or anything like that. No, we aren’t so picky as all that. It all boils down to direction…Read on for more. Yes, it is all about direction – the direction the game has gone in the last couple of years and the direction the devs seem obsessed in forcing the player to go. I’ve ranted before about Blizzard forcing gear score down people’s throats and how they’ve dumbed the game down to the point where the back tire of my motorcycle is just as capable of playing an end-game raider as any person is, and how sad it is that they have ditched the entire concept of community, the need for guilds and communication and cooperation and teamwork and how they’ve turned the whole thing in to one long grind, accentuated by the voices of young teens calling you a n00bfaggot because your ever-precious gear score is 1 point below theirs and you can’t crank out 1.21 jiggadamage per second like their 8 year old sister can. Well, my friends, it now seems that Blizzard – and ultimately Activision – is feeling the sting from their lack of foresight. Reports have indicated that World of Warcraft had lost as many as 1.1 million subscribers in the six months after the release of Cataclysm – that’s 10 percent of their total player-base – and that they continue to hemorrhage players at a frightful rate, despite a limited “free to play” model, free trials, and new content being pushed out to players on a regular basis. Did Blizzard’s own arrogance get the better of them? It is certainly possible. It has never been a secret that many promises made by Blizzard have been fulfilled, just as it is no secret that they favor certain play-styles and character classes. Rather than allow players to play the way they want, Blizzard has spent an inordinate amount of time forcing players to play the way someone there envisioned it at some point. I can’t help but wonder if some internal memo was sent out by a big-wig at Blizzard, a few years ago – “I’m sick and tired of seeing these players working together and devising strategies to get ahead in raids while my button-mashing, anti-social nephew can’t get the best gear in the game! From now on, every fight is a DPS race and every boss drops epic gear and if you even dream about incorporating strategy into a raid, you’d better wake up and hand in your resignation! Also, we are doing away with the need for guilds because little Stevie can’t go 5 minutes without calling someone a pole-smoking douchebag and he keeps getting gkicked. Make it so they can raid by just clicking a button or you’re all fired!”. That’s probably not what actually happened but it sure felt like it. When Blizzard decided to strip all of the individuality out of the game, making it so both factions had access to the same classes and there was no need for strategy or teamwork or leadership or communication, the whole thing started to fall apart. They got some players back with talk of Nefarian, in Cataclysm but that was a bust and pissed a lot of people off and now they seek to placate users with yet another expansion, “Mists of Pandaria” which will feature kung fu pandas and a couple more raid bosses. yay… Meanwhile, Bobby Kotick yammers on about how he isn’t even slightly concerned about losing players to EA/BioWare and their very soon to be released MMO Star Wars : The Old Republic but that’s already seen nearly a million pre-orders and the hype train hasn’t even started rolling yet. You see, Bobby is too busy focusing on how to double the price of games to think about anything as pedestrian as his golden goose losing all its eggs. oops… One has to wonder when these people are going to learn…one also has to hope that other companies won’t repeat Blizzard’s mistakes and end us all up with nothing to do but watch television. Blah, television. Articles from Around the Web Which part is untrue, Glen? The subscriber numbers? Those are well documented. The changes that have been made which have cheapened the game? Those issues are also well documented and the outrage can be witnessed with a single visit to the wow forums. The broken promises and class favoritism? Again, take a peek at their forums. If you want to be a WoW fanboy, that’s fine, that’s your right. I played WC, WC2, WC3 and when WoW hit, I played that game from beta, through the release day inventory database woes, through MC and BWL, and right on through cataclysm and am part of that 1.1 million. I’ve been there and back again. None of this is news to anyone who reads the news…It’s just my opinion. The insights you may or may not have received as to where they want to take the game (which, by the way, would breech their internal NDA so badly that Bobby Kotick would die and then roll over in his grave if he got wind of it) are irrelevant. We’re not talking about where they want to take the game (which is going to be decommissioned eventually, anyway) we’re talking about where the game has been and where it is NOW. I know the game backward and forward. I used to be a HUGE fan. Now I’m just part of that 1.1 million who got tired of the empty promises and useless expansions. It is what it is. LordShad0w Me thinks the lady doth protest too much. lol Just because you don’t share the same opinion does not invalidate the writers(opinion). Besides, some of us care about more than rollseyes gasp WOW. Now, go lead your epicpwnxxorzcrusade against some imaginary hellbeast and tell your eleven-teener guild friends how much this article sucks. (and why life in moms basement rules yo!) yes my comment was over the top. However, it still stands that you have a very firm stance on what YOU think the article should have covered. Rather than criticize in your initial post (which was what I responded to) you could have shared some of the points that you did later in the discourse. You instead chose to just belittle the writers efforts. Which is just rude. Just because you have insider knowledge and are obviously a fan of the series it does not disprove the writers opinions. Which are simply that. The writers opinion. So agree or disagree, you should be a bit more polite if you want to make a point and retain any credibility. Yes, it is all about direction – the direction the game has gone in the last couple of years and the direction the devs seem obsessed in forcing the player to go. I’ve ranted before about Blizzard forcing gear score down people’s throats and how they’ve dumbed the game down to the point where the back tire of my motorcycle is just as capable of playing an end-game raider as any person is, and how sad it is that they have ditched the entire concept of community,the need for guilds and communication and cooperation and teamwork and how they’ve turned the whole thing in to one long grind, The made the game a little easier for the largest target consumer, the casual gamer. The game should be open to everyone not just the people that play eight hours a day. It is all about community, the more perks you get if you group up with your friends and guildmates. The group finder for the most part works, and there are several levels. I remember in the days before the the finder that I could only run 1 or 2 dungeons after hours of asking in a day if I was lucky enough to find a group, now I can run a dungeon whenever within minutes. accentuated by the voices of young teens calling you a n00bfaggot because your ever-precious gear score is 1 point below theirs and you can’t crank out 1.21 jiggadamage per second like their 8 year old sister can. If this happens it is very rare and unfortunate, but not even close to being the truth for normal every day activities. Well, my friends, it now seems that Blizzard – and ultimately Activision – is feeling the sting from their lack of foresight. Reports have indicated that World of Warcraft had lost as many as 1.1 million subscribers in the six months after the release of Cataclysm – that’s 10 percent of their total player-base – and that they continue to hemorrhage players at a frightful rate, despite a limited “free to play” model, free trials, and new content being pushed out to players on a regular basis. With the new playpass(Get a Mount, Diablo 3 for free, and access to Mist of Pandaria Beta) and Patch 4.3 is being used to offset this, I think that they may have even risen in population since announcing the loss of customers which was frankly over 3 months ago. Did Blizzard’s own arrogance get the better of them? It is certainly possible. It has never been a secret that many promises made by Blizzard have been fulfilled, just as it is no secret that they favor certain play-styles and character classes. Rather than allow players to play the way they want, Blizzard has spent an inordinate amount of time forcing players to play the way someone there envisioned it at some point. Warcraft is not a sandbox, there are other sandbox out there for players. What Warcraft does, it does really well, otherwise it would not be as popular. What do expect from the game? How are they force player to do to something? This statement confuses me. The biggest reason they had people leave the game was that it became stale. In Cataclysm they went out to get people to reroll and new customers, it greatly improved the new player areas but majorly ignored the end-game users, which was rolling out the same stuff they did in Wrath of the Lich King. They set out to fix this with 4.2 and 4.3. Firelands has been a huge success and End of Time is being applauded as being the best dungeons Warcraft has ever done. I can’t help but wonder if some internal memo was sent out by a big-wig at Blizzard, a few years ago – “I’m sick and tired of seeing these players working together and devising strategies to get ahead in raids while my button-mashing, anti-social nephew can’t get the best gear in the game! From now on, every fight is a DPS race and every boss drops epic gear and if you even dream about incorporating strategy into a raid, you’d better wake up and hand in your resignation! Also, we are doing away with the need for guilds because little Stevie can’t go 5 minutes without calling someone a pole-smoking douchebag and he keeps getting gkicked. Make it so they can raid by just clicking a button or you’re all fired!”. This is just plain uncalled for bashing. I expect more from FEZ articles. That’s probably not what actually happened but it sure felt like it. When Blizzard decided to strip all of the individuality out of the game, making it so both factions had access to the same classes and there was no need for strategy or teamwork or leadership or communication, the whole thing started to fall apart. Again not true, for the most part there is no difference in races, they are just there for looks and always have been. Also in 4.3 they added the option to change the look of your armor. They got some players back with talk of Nefarian, in Cataclysm but that was a bust and pissed a lot of people off and now they seek to placate users with yet another expansion, “Mists of Pandaria” which will feature kung fu pandas and a couple more raid bosses. yay… I never really cared for Deathwing’s story, until the new dungeons now. It is cool to relive his story and now one of the best expansion ending raids. Do not bash Mist of Pandaria, Pandaren have always been part of Warcraft lore. This was written last year, a whole year before the expansion announcement: wow.joystiq.com/2010/10/03/know-your-lore-the-pandaren/ This is was something as a warcraft fan I’ve always wanted to see. They were suppose to be introduced during the Burning Crusade, but got pushed back, and never had a real way to properly introduce them into the game until now. FYI: Pandaren have been part of Warcraft lore before the Kung Fu Panda movie. I can guarentee the expansion after that will be dealing with Sargaras once and for all, and that will be pretty much it for Warcraft, but they’ll also have the new MMO out by then too. I wrote an opinion piece. Mine is an opinion which was built and educated by years of playing this game. I never played 8 hours a day but I was and am a “hardcore gamer”. When WoW was in its pre BC life, it was intended for all audiences and the big end-game raids were for the hardcores. The philosophy back then (Blizzard’s philosophy, per their own admin posts on their own forums) was simple. If you want to play the end game raid, get serious. If you don’t, don’t. I can’t tell you how many times they told players “Less QQ, more pew-pew” and stood by it. As time went on, though, more and more parents succumbed to the whining of their children and started letting them play. Blizzard got more and more money and they REALLY liked it. Then those same kids started whining because they couldn’t do the end game content. WHY couldn’t they? Because it was too hard for them. They couldn’t get into raids because they couldn’t go 5 minutes without flapping their suckholes about how the other people in the raid were noobs, etc…So then they complained and it was about “accessibility”. Then it was people crying about not being able to get the good gear because they couldn’t be in a guild and earn DKP to get the stuff. Then they were crying about not being able to assemble large scale raids because they didn’t have enough friends (mostly because the dicks ruined it for all the kids) so then Blizz decided to dumb the whole thing down and put the dungeon finder in. NOW they’re introducing the RAID finder, which is a huge bag of fail. They’re just making it easier and easier and easier so they can keep the kids around and keep raking in the money. I was one of those end-game raiders back in the day and there’s not a single person I used to play with who still plays WoW. The most popular reason? Because Blizzard ruined the game when they made it too easy…when they turned the whole thing into a face-rolling, dps-racing, dungeon finder clicking, ninja-fest. Also, I didn’t randomly pull those numbers out of my ass, bro. I DO perform research before I write an opinion piece, to make sure I have my facts straight. 800,000 players walked in July, August and September, alone. This is a published FACT and it is indisputable. Blizzard doesn’t even dispute it. Well, that’s your very narrow opinion, then. I know many, many people who would disagree with you. Like I said, if you want to fanboy the game until they shut it down, you go for your life, man. As for me, I’m done with it. I’ll never go back and my reasons, while you may not agree with them, are valid and truthful. How a person’s individual reasoning and opinion can be a “lie” I have no idea. Narrow, look at the mirror, my friend. I provided ample evidence of why you were wrong and what was untrue. But instead of having a reasonable disagreement, you insult me and hide behind faulty logic. I’m done with this topic. It’s funny when people say that, trying to bait an argument. This is what’s called an op-ed. It is an opinion piece. How else is it supposed to be presented? As for defense, it is also funny that people think we have limitless time to debate our opinion vs. theirs. We have research to do, games to play, movies to watch, hardware to test, videos to compile, articles to write, advertisers to deal with, PR departments to talk to, broken code to clean up, graphics to create, emails to answer, a forum to administer, comments to moderate, a business to deal with and then, at some point, we have to sleep. Forgive me for not writing a 15,000 word manifesto detailing why my personal opinion and the opinions of dozens of former WoW players I know in the real world are divergent from those of someone who got offended when they read my opinion. You have yours, too. Everyone does. I’m sure you don’t have limitless time to defend yours to the internet, either. Remember that it’s an opinion and just because someone disagrees doesn’t mean it stops being just that. Gonna run along now…By all means keep reading, though. You may just find that you agree with some of my opinions. This was not presented as a op-ed, it was presented as a traditional news article. The title is: Blizzard/World of Warcraft lose 1.1 million subscribers That is a news story. If you look back at our history, you’ll see that World of Warcraft has gotten a little bit of hate from us here at FleshEatingZipper, both in written articles and in our podcast. Statement this isn’t because it is a bad game or because Blizzard’s a bad company or anything like that. Declarative opinion No, we aren’t so picky as all that. It all boils down to direction…Read on for more. Yes, it is all about direction – the direction the game has gone in the last couple of years and the direction the devs seem obsessed in forcing the player to go. Statement I’ve ranted before about Blizzard forcing gear score down people’s throats and how they’ve dumbed the game down to the point where the back tire of my motorcycle is just as capable of playing an end-game raider as any person is, and how sad it is that they have ditched the entire concept of community, the need for guilds and communication and cooperation and teamwork and how they’ve turned the whole thing in to one long grind, accentuated by the voices of young teens calling you a n00bfaggot because your ever-precious gear score is 1 point below theirs and you can’t crank out 1.21 jiggadamage per second like their 8 year old sister can. Statement Well, my friends, it now seems that Blizzard – and ultimately Activision – is feeling the sting from their lack of foresight. Reports have indicated that World of Warcraft had lost as many as 1.1 million subscribers in the six months after the release of Cataclysm – that’s 10 percent of their total player-base – and that they continue to hemorrhage players at a frightful rate, despite a limited “free to play” model, free trials, and new content being pushed out to players on a regular basis. Statement Did Blizzard’s own arrogance get the better of them? It is certainly possible. Declarative opinion It has never been a secret that many promises made by Blizzard have been fulfilled, just as it is no secret that they favor certain play-styles and character classes. Rather than allow players to play the way they want, Blizzard has spent an inordinate amount of time forcing players to play the way someone there envisioned it at some point. I can’t help but wonder if some internal memo was sent out by a big-wig at Blizzard, a few years ago – “I’m sick and tired of seeing these players working together and devising strategies to get ahead in raids while my button-mashing, anti-social nephew can’t get the best gear in the game! From now on, every fight is a DPS race and every boss drops epic gear and if you even dream about incorporating strategy into a raid, you’d better wake up and hand in your resignation! Also, we are doing away with the need for guilds because little Stevie can’t go 5 minutes without calling someone a pole-smoking douchebag and he keeps getting gkicked. Make it so they can raid by just clicking a button or you’re all fired!”. Statement That’s probably not what actually happened but it sure felt like it. Declarative When Blizzard decided to strip all of the individuality out of the game, making it so both factions had access to the same classes and there was no need for strategy or teamwork or leadership or communication, the whole thing started to fall apart. They got some players back with talk of Nefarian, in Cataclysm but that was a bust and pissed a lot of people off and now they seek to placate users with yet another expansion, “Mists of Pandaria” which will feature kung fu pandas and a couple more raid bosses. Statement yay… Declarative Meanwhile, Bobby Kotick yammers on about how he isn’t even slightly concerned about losing players to EA/BioWare and their very soon to be released MMO Star Wars : The Old Republic but that’s already seen nearly a million pre-orders and the hype train hasn’t even started rolling yet.You see, Bobby is too busy focusing on how to double the price of games to think about anything as pedestrian as his golden goose losing all its eggs. oops… Declarative One has to wonder when these people are going to learn… Question one also has to hope that other companies won’t repeat Blizzard’s mistakes and end us all up with nothing to do but watch television. Blah, television. Declarative Opinion There a difference when presenting a statement and an opinion. For example: The president is bad at his job. or I think, the president is bad at his job. By adding the qualifier, I think It turned the statement into my opinion. I know FEZ is a little opinionated but this is a news story, not a review or critique. You break traditional journalistic reporting by opinionating the story. That why it is so much more important to add those qualifiers that it is your opinion, and not statements of facts. Anubisval Excellent article and very true. This latest upcoming expansion is evidence of the downward Spiral. The Pandas, The Theme (yeah…please…take up to goldseller haven please), and THE DAMN POKEMON crap are too much. Activision’s taint is now killing Blizzard. They were fine before they sold themselves to the devil. Funny how the sub numbers are important when they were gaining subs, not that they are losing subs, players act like it’s not a big deal. The Acti CEO is going to kill this game with his arrogance the same way CCP’s CEO killed EvE as it slowly continues to die. Not quite. Angry much? You have a flimsy argument and when you have it torn to pieces, you either use “opinion” as a defense or hide behind numbers. Which, you know, are maybe… three, four people, total? 1234fifth Go back to wow forums G W mop sucks and many agree with me on that no mater what you think. Andreas I must say I agree with everything in this acticle, and I played since beta too. I have a few things I want like to add. But this is almost 100% why I left wow. And for those who say wow losing players because it getting old don’t have a clu about the game. For me it was my life, it felt even better then irl call me crazy but it did, I met some of my best friends there and I’d had my time of my live there untill blizzard started to change everything…. now it’s not the same game anymore and that is why I left, not because it was old because it was a “new” game that I do not like!	{ "pile_set_name": "Pile-CC" }
Navigation Asset Publisher National Poisoning Management Guidelines Launches National Poisoning Management Guidelines Launches 13/12/2018 The Ministry of Health (MOH), represented by the Directorate General of Diseases Surveillance & Control (DGDSC), the Environmental & Occupational Health Department Launched on (Tuesday) the National Management Guidelines of Poisoning under the patronage of H.E. Dr. Darweesh bin Saif Al-Muharbi, MOH Undersecretary for Administrative & Financial Affairs at Crown Plaza Hotel. The launching ceremony followed by a clinical workshop, which highlighted the impact of poison control centers on health service, the management of Acetaminophen/ Paracetamol overdose, management of pesticide poisonings, iron toxicity, management of cardiac drug overdose…etc. Around 120 medical cadres working in the emergency field from different government hospitals in the Sultanate have attended the workshop. The Guidelines covers various topics concerning the treatment methods of drug poisoning, as well as poisoning cases of snakes and scorpions bites, some aquatic organisms and poisonous plants. The Guidelines also provides an overview of the toxicity of some chemicals found in the houses. Dr. Saif bin Salim al-Abri, DGDSC Director General clarified that preparation of this Guidelines has continued for three-year of effort and joint work between all the specialists from various health institutions in the Sultanate. He also added that the Guidelines has been reviewed by the Middle East And North Africa Association of Toxicology (MENATOX), as well as the specialists from the Emory University in the USA. The DGDSC Director General stated that "We are proud that Sultanate of Oman is one of the first countries in establishing a national poisoning control center. Establishment of this center comes at a time of challenges in the Middle East region including the armed conflicts, increasing the number of displaced population and the political climate in many parts of the region, which increased the potential impact of chemicals, toxins and radioactive material to the health of our societies". Dr. Al-Abri pointed out that the National Management Guidelines of Poisoning is an important step in achieving the institutional work and medical practice based on the scientific evidence in order to be a reference for the health workers in the fields of emergency and primary health care. Prof. Ziad Kazzi, MENATOX President praised the Sultanate's positive step in establishing a specialized center for toxicology. He added that existence of such center in the Sultanate will raise the awareness about poisoning among the community members and improve its treatment mechanisms when it happens.	{ "pile_set_name": "Pile-CC" }
Q: Will people automatically look at the person they feel closest to when laughing? In the post: 31 Psychological Life Hacks That You Can Exploit To Give Yourself An Advantage In Social Settings by thoughtcatalog, it said: When a group of people laugh, people will instinctively look at the person they feel closest to in that group. The claim is repeated by distracity in a post showing psychological life hacks that'll make you more successful. Also the claim is widely and internationaly believed, a simple google query will show you. I often catch myself looking at good friends or someone I'm interested in when laughing. But does this apply to the majority of people? I'm really skeptical of this claim. A: When a group of people laugh, people will look at the person they feel closest to in that group due to interest indicators per supporting research by Norman P. Li et.al. in 2009. "Humor plays a large role in our everyday lives and is pervasive across all cultures. We seek and rapidly notice humor whether we are going to the movies, interacting with a stranger or a friend, or looking for a potential romantic partner." The interest indicator model suggests that humor can function as a key tool for both facilitating and maintaining social relationships within a group of people. The interest indicator model also proposes that humor is inherently different from intelligent conversation and serves an important function beyond courtship or intrasexual competition. Humor also functions to indicate interest in social relationships to initiate new relationships and to monitor existing ones. Co-evolution of laughter and language, humor initiation and appreciation may have developed as a way for individuals to initiate and maintain different social relationships. For ongoing relationships, the relative costs and benefits underlying the relationships may change over time for each person, hence the need for ongoing assessment of the relationship. In this process of establishing new relationships and assessing existing ones, humor may allow individuals to implicitly communicate their interest and gauge the corresponding level of agreement from others. That is, by initiating humor, a person may be implicitly suggesting interest in a new or already established relationship. To the extent that the audience is also interested, they will respond positively. Results of the 2009 paper 'An Evolutionary Perspective on Humor: Sexual Selection or Interest Indication?' across three studies supported predictions derived from this model. In Study 1, both sexes reported being more likely to initiate humor and to laugh in response to humor when they were initially attracted versus not attracted to a potential mate. In Study 2, experimental evidence was found for the view that initial attraction and interest in a potential relationship predict judgments of humor. In Study 3, people viewed male female pairs interacting in speed dating sessions and indicated that they recognized the relationship dynamics of humor predicted by the interest indicator model. This suggests that humor can ultimately function as a strategy to initiate and monitor social relationships. The reasons why a more indirect approach of humor such as describing interest overtly asking for agreement might be advantageous and adaptive than a direct approach of implicitly conveying relationship interest is as follows: "There may not be enough information to make an outright commitment to or rejection of a relationship. For instance, when individuals initially meet, it may be unclear to either side whether the other person would make a good romantic partner, friend, or coalitional ally. Similarly, partnered individuals who are losing interest in each other may not be ready to abruptly end a relationship. As such, humor may allow individuals to indicate the direction of their interest and to build (or deconstruct) relationships incrementally." "Since an indication of interest conveys much less information than an evaluation of a full relationship, the costs of being rejected for an indication should be lower. Such costs include future possibilities for the relationship and one’s reputation. Humor initiation may yield an indication of interest without incurring such consequences." "By using humor, one can gauge the strength of a potential or existing relationship without revealing his or her ultimate motives, which may extend beyond the establishment of a relationship. For example, if one needs to confide in and elicit the assistance of someone concerning an important matter, he or she may wish to first assess the strength of various relationships before choosing who."	{ "pile_set_name": "StackExchange" }
Q: How to create a scrolling table with fixed headers Possible Duplicate: HTML table with fixed headers? I want to know what is the best way of creating a scrolling table with fixed headers for this fiddle here: http://jsfiddle.net/LKB9e/9/ I don't want separate table headers and table body and I want the columns to stay matching. Can somebody get my fiddle working to match this? To use fiddle just click on the "Add Question" button in the demo and it will keep appending rows into a table below. At moment the table is scrolling with no fixed headers which is done by this: #details{ height:500px; overflow:auto; } Below is the source code: HTML table: <table id="questionBtn" align="center"> <tr> <th> <input id="addQuestionBtn" name="addQuestion" type="button" value="Add Question" onClick="insertQuestion(this.form)" /></th> </tr> </table> </div> <hr/> <table id="qandatbl" align="center"> <thead class="tblhead"> <tr> <th></th> <th class="qid">Question No</th> <th class="question">Question</th> <th class="optandans">Option and Answer</th> <th class="noofreplies">Number of Replies</th> <th class="weight">Number of Marks</th> <th class="image">Image</th> <th class="video">Video</th> <th class="audio">Audio</th> </tr> </thead> <tbody class="tblbody"></tbody> </table> Below is the javascript code where it append rows into the html table above: function insertQuestion(form) { var $tbody = $('#qandatbl > tbody'); var $tr = $("<tr class='optionAndAnswer' align='center'>"); var $td = $("<td class='extratd'>"); var $plusrow = $("<td class='plusrow'></td>"); var $qid = $("<td class='qid'></td>").text(qnum); var $question = $("<td class='question'></td>"); var $noofanswers = $("<div class='noofanswers'>2. Number of Answers:<br/></div>"); var $options = $("<div class='option'>1. Option Type:<br/></div>"); var $answer = $("<div class='answer'>3. Answer:<br/></div>"); var $replies = $("<td class='noofreplies'><div class='wrapper'></div></td>"); var $weight = $("<td class='weight'></td>"); var $image = $("<td class='image'></td>"); var $video = $("<td class='video'></td>"); var $audio = $("<td class='audio'></td>"); $tr.append($plusrow); $tr.append($qid); $tr.append($question); $tr.append($td); $td.append($options); $td.append($noofanswers); $td.append($answer); $tr.append($replies); $tr.append($weight); $tr.append($image); $tr.append($video); $tr.append($audio); $tbody.append($tr); } Below is the css: /css for QandATable.php/ body{ font-size:85%; } #qandatbl{ border:1px black solid; border-collapse:collapse; } #qandatbl td { vertical-align: middle; } #qandatbl th{ border:1px black solid; border-collapse:collapse; text-align:center; } .tblhead, .tblbody { display: block; } .tblbody{ height: 500px; overflow: auto; width:100%; } .extratd{ border:1px black solid; border-collapse:collapse; } .qid { min-width:3%; max-width:3%; font-weight:bold; border:1px black solid; border-collapse:collapse; } .question { min-width:25%; max-width:25%; border:1px black solid; border-collapse:collapse; } .noofanswers{ min-width:100%; max-width:100%; padding-top:5%; padding-bottom:5%; } .noofreplies{ min-width:3%; max-width:3%; border:1px black solid; border-collapse:collapse; } .optandans{ min-width:30%; max-width:30%; border:1px black solid; border-collapse:collapse; } .option{ min-width:100%; max-width:100%; padding-top:5%; padding-bottom:5%; } .weight { min-width:3%; max-width:3%; border:1px black solid; border-collapse:collapse; } .answer { min-width:100%; max-width:100%; padding-top:5%; padding-bottom:5%; } .audio{ min-width:11%; max-width:11%; border:1px black solid; border-collapse:collapse; } .video{ min-width:11%; max-width:11%; border:1px black solid; border-collapse:collapse; } .image{ min-width:11%; max-width:11%; border:1px black solid; border-collapse:collapse; position:relative; } .plusrow{ min-width:2%; max-width:2%; border:1px black solid; border-collapse:collapse; } UPDATE: I have attempted created a scrolling table with fixed headers but problem is that columns are not matching: http://jsfiddle.net/heA2b/1/ A: Here are some examples that use different methods: jsfiddle.net/FeU3T/2/ http://www.imaputz.com/cssStuff/bigFourVersion.html http://imar.spaanjaars.com/357/a-scrollable-table-with-a-fixed-header	{ "pile_set_name": "StackExchange" }
Treatment algorithms for patients with (sub)acute type B aortic dissections. Aortic dissection is the most common acute aortic syndrome and constitutes a potentially catastrophic cardiovascular condition. Traditionally, complicated acute type B dissection has been considered an indication for surgical treatment, whereas patients with uncomplicated dissection have been treated medically. In recent years, there has been a clear paradigm shift towards endovascular treatment of complicated type B dissection. This is founded in numerous reviews and meta-analyses demonstrating a lower perioperative mortality and morbidity for TEVAR in comparison to open surgical repair. In uncomplicated patients, treatment options are still a matter of debate. Best medical therapy shows acceptable early results with respect to in-hospital mortality and morbidity but fails to address the issue of late aortic expansion and aortic-related adverse events in a significant number of patients. There is increasing evidence that early TEVAR promotes false lumen thrombosis, induces remodeling of the aortic wall and should be considered preventively in selected patients with suitable anatomy. This report gives an overview of current literature on treatment options and optimal time of intervention, and finally proposes a treatment algorithm for acute type B aortic dissection.	{ "pile_set_name": "PubMed Abstracts" }
Q: Divs not aligning I have 3 simple divs with some cosmetic styles that are supposed to be aligned in a row, Two of them have images that are on the left and right sides while middle one contains another div containing text. I am able to fit the image in divs but the middle one that contains text is not aligning horizontally with other two. Following is the html <div class="eggpic"> <img src="smiley.gif"/> </div> <div class="timersection"> <div class="timersectiontext">Hello</div> </div> <div class="buttonpic softboil"> <img src="smiley.gif"/> </div> Here is the jsfiddle link or that http://jsfiddle.net/4bg7uyoj/1/ Please help in aliging all the divs. Thanks in advance. A: use float:left instead of display:inline-block and give the parent div some height.	{ "pile_set_name": "StackExchange" }
LG BD550 If you have Ethernet connectivity in your living room, the smart move is to go with an entry-level Blu-ray player. Most such players available in 2010 offer much of the functionality of step-up models, minus built-in Wi-Fi. That's the case with the LG BD550 ($150 street), which is nearly identical to the step-up BD570, except it lacks Wi-Fi and DLNA compatibility and costs about $100 less. If you can live without those features, the BD550 still delivers excellent image quality, relatively speedy load times, and a generous suite of streaming-media services, including Netflix, Vudu, Pandora, and YouTube. It's missing the expandable Apps platform of the competing Samsung BD-C5500, but if you mostly care about core streaming services, the BD550 is a solid entry-level choice. Design At first glance, the exterior design of the BD550 looks almost identical to the step-up BD570, but we actually liked it a little better. The main difference is that the BD570 has one long flip-down panel that covered the entire front panel, whereas the BD550 is broken up into three sections: disc tray on the left, power and eject buttons in the middle, and a flip-down panel on the right. We preferred the partitioned design since the BD550's automatic door mechanism tends to work better. We also favored the LG's more low-key look compared with the Samsung BD-C5500. Flip-down panel User interface We loved the dead-simple user interface on last year's BD390, so we were a little dismayed to see that LG has given this year's model a complete interface overhaul. The redesign moves all the streaming-media features off the main page onto the separate Netcast interface. We see why that makes sense--there are simply too many streaming-media services to fit them all on the main page--but Samsung's new interface does a better job of letting you quickly jump to the service you want. We also found the "floating ice cubes" design a little goofy and slightly slower to navigate. Netcast Netcast is the name of LG's suite of media-streaming services, and once you enter the Netcast section, you're greeted by large tiles with the names of services. LG's lineup of services is impressive, including Netflix, Vudu, CinemaNow, YouTube, Pandora, Picasa, and AccuWeather. Remote LG's included remote control is a complete redesign over last year's clicker. The main surface is glossy black, which looks sleek coming out of the box, but being a remote, it naturally accumulates fingerprints quickly. Its button layout is mostly straightforward. Playback controls have a "hill" that runs underneath them, making it easy to find by feel; there are also nubs on the rewind/fast-forward buttons. The remote's main directional pad is surrounded by six buttons, which is a little more cluttered than most Blu-ray remotes we use, but we didn't find it that troublesome. Along its bottom are a few buttons for controlling a TV.	{ "pile_set_name": "Pile-CC" }
Filter by Type: Filter by Title Filter by Writer Filter by Artist Filter by Date Robocop: Last Stand #8 $3.99 Writer(s): Frank Miller, Steven Grant Artist(s): Declan Shalvey, Korkut Öztekin Ed Brisson (SHELTERED, SECRET AVENGERS) finishes the series with an original, self-contained story set in the world of classic RoboCop! You’ve seen The Last Stand...but for RoboCop the war on crime is never over!	{ "pile_set_name": "Pile-CC" }
Q: NuGet add reference error while installing package I am not able to install any package by Nuget. Install-Package MyToolkit.Extended Attempting to resolve dependency 'MyToolkit (≥ 2.2.3.0)'. Attempting to resolve dependency 'Microsoft.Bcl.Async (≥ 1.0.166)'. Install-Package : The 'Microsoft.Bcl.Async 1.0.168' package requires NuGet clint version '2.8.1' or above, but the current NuGet version is '2.7.40911.287'. At line:1 char:1 + Install-Package MyToolkit.Extended + ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ + CategoryInfo : NotSpecified: (:) [Install-Package], NuGetVersionNotSatisfiedException + FullyQualifiedErrorId : NuGetCmdletUnhandledException,NuGet.PowerShell.Commands.InstallPackageCommand A: I just ran into this problem. Even if the system Nuget is updated, the NuGet.exe in the .nuget directory could be older. Adding/removing the extension and playing around inside VS does not seem to update the NuGet.exe inside the solution. Even when you explicitly update Nuget inside VS, the solution's copy stays old. Go into the .nuget folder and do "NuGet update -self". A: According to the error message you got, I'd suggest to check and update your NuGet Visual Studio Extension (Tools > Extenstions and Update) before installing the library package. Note: Restart visual studio after updating Nuget VS extension and before downloading your library package.	{ "pile_set_name": "StackExchange" }
Expression of alternatively spliced growth factor receptor isoforms in the human trabecular meshwork. Growth factors act through high-affinity cell surface receptors expressed by target cells and are critical modulators of cell function. Because aqueous humor is known to contain growth factors, these molecules may play a key role in maintaining the normal function of the human trabecular meshwork (HTM). Alternate mRNA splicing is an important mechanism used by cells to generate diverse isoforms of growth factor receptors. Although previous investigators have suggested that HTM cells may express alternative isoforms of several growth factor receptors, there have been no studies to verify these preliminary findings. The objective of this study was to determine whether cultured and ex vivo HTM cells express alternate isoforms of hepatocyte, keratinocyte, and transforming growth factor beta (TGFbeta)-II receptors and to characterize the isoform molecular sequences. To determine whether cells within the HTM express mRNA for alternate isoforms of growth factor receptors, total RNA was isolated from several well-characterized HTM cell lines that were established from donors of various ages and from fresh ex vivo HTM tissues from healthy donors. After cDNA synthesis, polymerase chain reaction was initiated using specific primers for alternate forms of the following receptors: hepatocyte growth factor (HGFR), keratinocyte growth factor (KGFR), and transforming growth factor beta receptor II (TGFbetaR-II). Specificity and characterization of the polymerase chain reaction amplification products were determined by nucleic acid sequencing. Amplification products of the expected size for the growth factor isoforms were expressed in cell lines and in ex vivo tissues. Nucleic acid sequencing showed that cultured HTM cells and fresh ex vivo trabecular meshwork tissues expressed specific mRNA for alternatively spliced isoforms of HGFR, KGFR, and TGFbetaR-II The HGFR alternate isoform contained a 96-bp insert in the C-terminal coding region of the cytoplasmic tyrosine kinase domain. The KGFR alternate isoform is a soluble, truncated form, because it has no transmembrane or cytoplasmic domain as does the normal membrane-associated form. The TGFbetaR-II alternate isoform contained a 75-bp insert in the N-terminal coding region of the extracellular domain. In vitro and ex vivo HTM cells express mRNA for alternatively spliced isoforms of HGFR, KGFR, and TGFbetaR-II. These alternatively spliced receptor isoforms may be functional within the HTM and may play a critical role in maintaining the normal microenvironment of this important tissue.	{ "pile_set_name": "PubMed Abstracts" }
1. Background {#sec20532} ============= Correction and palliation of some congenital heart diseases requires the use of cardiopulmonary bypass ([@A8105R1]). Cardiac surgeries under cardiopulmonary bypass induce the systemic inflammatory response with a multifactorial etiology, including direct tissue damage, ischemia, and stimulation of the immune system by CPB cycle ([@A8105R2]).This inflammatory response is very similar to the inflammatory response in sepsis, burns and multiple traumas, and it damages target organs ([@A8105R2]). Inflammatory effects followed by CPB are known and prevalent; and 25% of patients with LCOS (Low cardiac output syndrome) after this procedure ([@A8105R3]). CPB- dependent inflammation is the initial cause for tissue damage and impaired heart, kidney and other organs performance ([@A8105R4]). The amount of tissue damage depends on inflammation response to some degree. Therefore, different strategies for reducing the inflammatory response are to be used ([@A8105R5]). For a long time, steroids were used to reduce the inflammatory response and they are well-known for their anti-inflammatory effects. Although steroids reduce inflammatory cytokine and increase anti-inflammatory cytokine, and improve heart performance, in some studies, clinical improvement including reduced need for fluid therapy, fever reduction, did not show shorten hospital stay and mechanical ventilation with steroids ([@A8105R6]-[@A8105R8]). Noting the peak effect of methylprednisolone is 1 to 4 hours after its administration and the duration of action is 12 to 24 hours, it seems that an extra dose of methylprednisolone given one to four hours before the operation (in addition to routine intraoperative dose) inhibits the inflammatory reaction more than the intraoperative dose ([@A8105R9]-[@A8105R11]). We administered a single dose of methylprednisolone based on our local protocol. The clear point is that this inflammatory response after surgery affects clinical signs caused by the systemic inflammation including length of stay in ICU, duration of mechanical ventilation, hemodynamic status, and heart dysfunction. Therefore, determination of steroid effects and different methods of its prescription is necessary in response reduction, results improvement, and finding a way to reduce the inflammatory response to reduce deaths. 2. Objectives {#sec20533} ============= The purpose of this study is to determine and compare clinical signs of systemic inflammatory response after cardiopulmonary bypass in patients receiving multidose methylprednisolone (prior and during surgery) with patients receiving mono-dose methylprednisolone (during the surgery). 3. Materials and Methods {#sec20534} ======================== This study was performed as a double-blind clinical trial from September 2010 to September 2011 on 60 children younger than 5 years who underwent cardiopulmonary bypass (CPB) for repair of congenital heart disease in Open Heart Surgery of Imam Reza hospital in Mashhad. The trial was performed in accordance with the declaration of Helsinki and approved by the ethic committee at Mashhad University of Medical Sciences. After explaining this research to supervisors of patients, consent form and information sheet were completed by them, and then the patients were enrolled in the research. Patients with corticosteroid allergy, chronic corticosteroid recipients, those who had received Aprotinin during surgery, patients with upper airway infection, and patient with sepsis and diabetes, patients with GI bleeding and cardiac arrest in a week before the operation were excluded. Determining of sample size was performed by using results of Valerie et.al study ([@A8105R1]), 30 people were considered for each group. Sampling was conducted in two stages, first stage nonrandom, based on objective and second stage in a random allocation. Thus, the first patient was placed in group A (case group), and then patients were placed in each of the two groups one by one. In mentioned manner patients were placed in two groups of multidose methylprednisolone (case group: before and during surgery) and mono-dose methylprednisolone (control group: during surgery). The case group received 30mg/kg intravenous methylprednisolone 4 hours before the operation, and they also received the same amount of drug in prime liquid during the beginning of the operation. Control group just received 30 mg/kg methylprednisolone during the beginning of the operation in prime liquid. Patients were placed under general anesthesia by fentanyl, muscle relaxants, and isoflurane. For circulatory support full-flow bypass with relative hypothermia was used. During aorta cross- clamp Cold-blood cardioplegia with additional dosing at 20- to 30-minute intervals was used. Ultra filtration was used in all cases. After the operation, all patients were ventilated with a volume of 10-15 mL / kg, and the ventilation rate to control Pco2 was matched at 35 mm hg. Fluid therapy was monitored by the anesthesiologist, and diuretic began the day after the operation. Postoperatively the peak and average 24 hours fever were measured in the ICU (rectal temperature was measured every hour and the average 24-hour was calculated based on this), duration of ventilation, length of stay in ICU, and the rate of drug Inotrop use within 24 hours after the operation were checked, and the two groups were compared. Regarding that the above mentioned cases show the amount of tissue damage and inflammatory response, significant difference in emergence of these effects shows the different effects of the two types of methylprednisolone administration on clinical outcomes of this surgery. Aortic clamping time (minutes), time of CPB (minutes), time of ventilation (h), the amount of prescribed Inotrop, the dosage of prednisolone, duration of hospitalization in ICU, temperature, experimental data such as: White blood cell (WBC), Blood urea nitrogen (BUN), Creatinine (Cr), and C-reactive protein (CRP) and information such as age, weight and sex were also recorded by one of the nurses. And all operation were performed by one surgeon, and all experiments were performed by a specialist of laboratory science. After surgery, all obtained data were collected and entered SPSS ver11.5 software. To study homogeneous distribution for age, sex, cardiopulmonary (CPB) and aortic clamp time, ANOVA was used in the two groups, and these variables were described by indices, charts and tables. In this analysis at first, normality of quantitative variables was determined by Kolmogorov- Smirnov test, in which among variables, hospital stay, and dose of administrated Inotrop did not follow normal distribution but ventilation time, and temperature followed the normal distribution. In the case of normality, T-test was used and otherwise Man-Whitney test was used for comparison. The significance level in this study was considered 0.05. 4. Results {#sec20535} ========== 60 children (25 females and 35 males) younger than 5 with congenital heart diseases, who underwent elective heart surgery under cardiopulmonary bypass, were randomly placed in two groups; mono-dose prednisolone (n = 30) and multidose prednisolone (n = 30). On the basis of ANOVA, the two groups did not show significant differences in mean age, weight, sex, CPB time, and aorta clamping. The two groups were homogeneous ([Table 1](#tbl5679){ref-type="table"}). ###### Characteristics of Patients Underwent Cardiopulmonary Bypass (CPB) for Repair of Congenital Heart Disease Multi-dose group, n = 30 Mono-dose group (n=30) P Value -------------------------------------- -------------------------- ------------------------ --------- Age, y 40.1 ± 18.0 39.5 ± 18.2 NS Gender Male 18 12 NS Female 17 13 NS Weight, Kg 25.6 ± 12.4 30.6 ± 9.8 NS CPB time, min 32.2 ± 9.7 32.2 ± 12.5 NS Ventilation time, h 8.6 ± 7.1 12.7 ± 7.9 NS Aortic cross-clamp time, min 23.1 ± 12.1 22.8 ± 13.1 NS The amount of prescribed Inotrop 290.5 ± 201.2 209 ± 204.5 NS Patients who had received mono-dose prednisolone, compared to the patients who had used multidose prednisolone, had more ICU stay, although this difference was not significant (2.15 vs. 2.02 days, P = 0.59). The mean body temperature and maximum mean body temperature in multidose patients after surgery were more than patients with mono-dose within 24 hours. However, none of the mentioned differences were statistically significant (P = 0.44, P = 0.40) ([Table 2](#tbl5680){ref-type="table"}). ###### Clinical Changes of Patients Underwent Cardiopulmonary Bypass (CPB) for Repair of Congenital Heart Disease Multi-dose, n=39 Control group, n=40 P Value ---------------------------------------------------------- ------------------ --------------------- --------- WBC^[a](#fn3637){ref-type="table-fn"}^, 10.8 x 109/L Before surgery 9.3 ± 2.6 8.8 ± 1.8 NS After surgery 14.6 ± 5.0 13.0 ± 3.8 NS BUN^[a](#fn3637){ref-type="table-fn"}^, mg/dL Before surgery 17.0 ± 6.4 18.6 ± 7.7 NS After surgery 18.5 ± 7.6 18.1 ± 6.3 NS Creatinine, mg/dL Before surgery 0.5 ± 0.1 0.5 ± 0.1 NS After surgery 0.6 ± 0.1 0.6 ± 0.2 NS C-reactive protein, mg/L After surgery 2.5 ± 1.2 4.3± 4.7 NS Mean body temperature, C After surgery 37.3 ± 0.5 37.2 ± 0.4 NS Maximum mean body temperature, C After surgery 38.2 ± 0.6 38.2 ± 0.5 NS ^a^ Abbreviations: WBC, white blood cell; BUN, blood urea nitrogen Two groups were not significantly different in laboratory criteria including WBC, BUN, creatinine, before and after the intervention and CRP after the intervention ([Table 2](#tbl5680){ref-type="table"}). In the multidose group, WBC after the operation was more than mono-dose group (14.6 vs. 13.0, P = 0.18). Of course this level was reported in multidose group significantly higher than mono-dose group before the operation, (9.3 vs. 8.8, P = 0.32). However, in the mono-dose group, taking a dose of prednisolone significantly increased the level of WBC after the operation (P = 0.00), while in multidose group with increasing WBC, this value was not statistically significant (P = 0.18). Although before surgery BUN level in the multidose group was lower than the mono- dose group (17.0 vs. 18.6, P = 0.41), but at 24 hours after the operation, BUN level in the multidose group was higher than the mono- dose group. However, in multidose group the intervention of two doses prednisolone before and during the operation significantly increased the BUN level after the operation (P = 0.05), while in mono-dose group, with increasing BUN this value was not statistically significant (P = 0.48). Creatinine levels after the operation in multidose groups was increased more than the mono-dose group (P = 0.76). After the operation, CRP had a higher level in the multidose group compared to the mono-dose group (4.3 vs. 2.5, P = 0.10). Mono-dose group needed longer mechanical ventilation (12.70 ± 7.9 hours vs. 8.66 ± 7.1 for the multi-dose group), but these differences were not statistically significant (P = 0.71). During this study, all patients were discharged from hospital with no unusual signs. In none of the patients, signs of drug therapy such as postoperative bleeding, hypertension, gastrointestinal bleeding, and severe water and electrolytes disorders were observed, and all patients completed the study. 5. Discussion {#sec20536} ============= In our study the comparative analysis was performed between the two types of mono-dose and multidose methylprednisolone (30 mg/per kg) and its impact on clinical outcome after the operation was studied on the two groups of 30 children younger than 5 years old with congenital heart disease undergoing open heart surgery (cardiopulmonary bypass). Considering that the peak of methylprednisolone effect is 1 to 4 hours after the administration, the idea of an additional dose methylprednisolone administered one hour before the operation (in addition to routine intraoperative dose) with the possibility of more effects on inhibiting the inflammatory reactions has provided the motivation for performing this investigation in minds of previous and this study researchers. A study similar to us was conducted by Dr. Valerie et al. ([@A8105R1]) on 29 patients who were divided into two groups (14 cases of multidose and 15 cases in mono-dose group). Given the limitations of their study\'s sample size as well as statistical analysis, our study was conducted on more patients (two groups of 30 persons). As Valerie et al study, in our study the two groups were homogeneous in age, sex, duration of aortic clamping time, and weight. In Valerie et al study, patients who received multidose methylprednisolone, had shorter ICU stay (4/4 days versus 6/1 day), although it was not statistically significant. In another study by Eric M. Graham et al. ([@A8105R12]) on 76 patients (39 multidose patients and 37 mono-dose patients), there was also no difference between the two groups in the ICU and hospital same as our study. Another study by Bronicki et al. ([@A8105R13]) showed that patients who received dexamethasone (1 mg / kg) compared to a group that received normal saline one hour before CPB had less ICU stay. In Valerie study, the average temperature and peak temperature were clearly less than mono-dose group in multidose group; but in our study there was no significant difference in peak temperature and the average temperature of mono-dose and multidose groups. Preoperative laboratory amounts including WBC, BUN, and creatinine were homogeneous in the two groups; but in the statistical analysis performed to compare changes in the laboratory indices after surgery and before it, between the two groups, a significant increase was observed in WBC in mono-dose group, this increase in multidose group was not significant. CRP levels were compared after the operation in the two groups, though the level was higher in mono-dose group, but it was not significantly different with multidose group. In the study by Eric M. Graham et al. serum creatinine in multidose group was significantly higher compared to the mono-dose group (0.6 ± 0.1 mg /dl vs 0.5 ± 0.1 mg /dl, P = 03). In the study by Bronicki et al. the number of patients receiving dexamethasone whose serum creatinine has increased 0.2 mg/dl or more than before the operation, was significantly lower in comparison to control group (1 of 15 versus 7 of 14; P = 0.014). In our study, like Valerie study, no cases were observed of dehiscence and wound infection, resistant hyperglycemia, and sustained hypertension. In this study, a control group that did not receive methylprednisolone was not available to compare with these two groups, so it is recommended to compare these three groups in future studies. Although a high percentage of patients in our study had ASD and VSD, but because of the diversity of these congenital heart disorders and their association with other heart disorders, including PS, TOF, PDA, with different intensity and congenital heart disease association with other genetic and chromosomal structure disorders which creates a specific background for patients, the precise integration of the patients was not possible in this regard. It is recommended to perform further investigations with a more limited type of heart disease (only 2 or 3 common types), more careful selection of patients based on preoperative status, the type of disorder and pulmonary hypertension, and presence or absence of cyanosis. Quality and quantity of repaired organs and the extent of the deficiencies that are remained have direct and obvious effects on patients' clinical outcomes, therefore, in the future studies; these criteria should also be considered for the comparison of groups In summary, in our study the clinical criteria including length of stay in ICU, duration of mechanical ventilation, peak and average temperatures, inotrop need and the laboratory criteria including CRP, BUN, and creatinine were of minor importance and worthless statistically. WBC Increase in mono-dose group was significantly higher than multidose group. Thus, currently administration of multidose methylprednisolone as routine is not recommended. None declared. Implication for health policy/practice/research/medical education: In summary, in our study the clinical criteria including length of stay in ICU, duration of mechanical ventilation, peak and average temperatures, inotrop need and the laboratory criteria including CRP, BUN, and creatinine were of minor importance and worthless statistically. WBC increase in mono-dose group was significantly higher than multidose group. Thus, currently administration of multidose methylprednisolone as routine is not recommended. There was no difference in clinical outcome after cardiac surgery when we administered an additional dose of methylprednisolone compared to a single dose of methylprednisolone. Authors' Contribution: The contribution of the authors as mentioned below with their responsibility in the research. Ghasem Soltani: writing the manuscript, conception and designing. Mahmoud Hosseinzadeh: obtaining findings. Nahid Zirak: writing the manuscript, final approval of the manuscript. Mahmoud Ganjifard: writing the manuscript, data collection, literatures search. Mohammad Abbasi: critical revision of the manuscript, provision materials, patients, or resources. Aliasghar Moeinipour: critical revision of the article, provision materials, patients, or resources. Alireza Sepehri Shamloo: writing the manuscript, administrative support. Seyed Javad pourafzali: critical revision of the manuscript, analysis and interpretation. Financial Disclosure: The authors have no financial interests related to the material in the manuscript. Funding Support: Our Research Project was partially or fully sponsored by Mashhad University of Medical Sciences, Ma shhad, Iran grant number 89570.	{ "pile_set_name": "PubMed Central" }
EMAILS/LETTERS OF THE WEEK 2/13/14 But here’s the thing. I was never surprised that I can relate to your strip. What shocks me is that — as I can see now from viewing the KQED doc at your site, which I finally looked up online — you’re so young! I totally thought you were my age. Maybe a dude who grew up on R&B and was now totally cool still but at or nearing 50-something, somewhat settled in life. It shocks me, not in a bad way. Just not what I was thinking from reading your strip. (Funny Times every month.) As I say, not a bad thing at all. Hmmm. Has me wondering, though. Underneath it all, do you really have the soul of a 53-year-old white guy? I noticed you have used the word ”DISCERN” in your subtle drawings……….That is a Biblical word reference and term!!!!! (you have used it OUT of content)………… I DARE YOU! God is NO respecter of person’s.Judge not,lest ye be judged.You are very disrespectful!!!! You are ignorant to the facts,uneducated and misinformed and are relaying that stupidity to the SLC residents and community!!!!! Further more,you are a racist,bigot,who discriminates and suffers from a bias stigma.You more than likely suffer various forms of mental illness health issues that require prescribed medication and intervention from a medical professional. Just to make you aware and provide you with the knowledge you lack…………according to statistics at jails and morgues nation wide and globally while employed with the police department.45% of all cultures, nationalities,ethnicities who make up the gang population are ”NOT” that of the African American/ Black race.CRIME HAS NO COLOR!!!!! CRIMINALS ARE COLORLESS!!!! And yes ,I did take a closer look……..at you, your heart is evil, wicked and corrupt with hate,prejudice and discrimination!!!!!! Try throwing up the cross ….it’s the only way to save YOUR soul! It’s color is red for the blood of Jesus Currently you yourself are in a gang…….probably ugly, a mormon and gay with a extremely small penis !!!! And there is a space in hell being reserved for people like you. Have you even been to the ghetto or around gangs at all????? I have, my family and I are surviving violated victim’s of their crimes against us THEY WEREN’T MINORITIES EITHER!!!!! Do yourself a favor……… Know the facts and educate yourself, get informed………by the way ;” Oakey Dokey” was invented by a Black boy!!!!! It is February, Black History month do your research before you go making a fool of yourself…..your ignorance sure made me laugh though. Good bless you and have mercy on you! B. ———————————– If you haven’t seen it yet, check out my Thuggers strip at Medium.com: Wow — the second “B.” totally lost me with that rant. (I’m the first “B,” hopefully not to be confused AT ALL with psycho-“B”-#2 just because both of our names start with the second letter of the danged alphabet.) Couldn’t read any of it after his first extra-long ellipsis [……….]. That’s way too many periods for my taste. And then I glanced down and noticed five exclamation points in a row and that word “Biblical.” Nope. Not touching any of that poison. The post was a hate crime, if you ask me. So.. Discern was only used from the 1400 AD forward. You may have used it out of context but not out of “content”. The bible was written in Aramaic, not English. SO, do not use any Aramaic words or even English words. What were you thinking? Your fanboy, Barry Ha! When I got to “small penis” I burst out laughing and fell on the floor. It’s like they were playing the hater’s mad libs. “Hmmm, what can I throw in here to REALLY show everyone how dumb and small-minded I am?” Hahaha!! I could see making a cartoon out of that. LOVED the Fan Mail from B. I haven’t laughed so hard since my cousin’s annual christmas letter came in. It’s always a joy, especially when read aloud; she’s got a Master’s in English, and teaches in a public school as a ‘missionary duty’, but won’t allow her own larvae to be so contaminated. Instead, they go to one of the ‘christian academies’ that were formed back in the Sixties as a way to sneak around the school desegregation laws. It’s always a treat getting her to explain that the icthus fish on her car isn’t a direct violation of the Third Commandment’s prohibition “You shall not make for yourself a carved image, or any likeness of anything that is in heaven above, or that is in the earth beneath, or that is in the water under the earth.” Wow, that person really needs to be medicated with something really good and strong! Is there a therapy (inpatient) program for someone like “B”? Has this person ever been to your site and read your bio? Or better yet, met you? You only slightly winced when I did my high pitched “E” when we met you at Wonder Con! Best wishes to you and your family from the city that never forgot you. Mr. McNabbem, we might be related to the same people. While my family isn’t quite at faith healing and snake handling (yet), they might pray over your dead Delco battery when your car won’t start, and have a ‘laying of hands’ on the hood. As a scientist (I’m a physicist), even when I have solid proof, my natural inclination is to doubt what I see. My family not only believes what they CAN’T see, but tells me I”m blind because I can’t see it, too. The result seems to be that I’m far happier and much less filled with doubt then they seem to be.	{ "pile_set_name": "Pile-CC" }
/* * 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. / package org.apache.usergrid.corepersistence.pipeline.read.traverse; import org.apache.usergrid.corepersistence.pipeline.read.AbstractFilter; import org.apache.usergrid.corepersistence.pipeline.read.FilterResult; import org.apache.usergrid.persistence.model.entity.Id; import com.google.inject.Inject; import com.google.inject.assistedinject.Assisted; import rx.Observable; import java.util.List; /* * This command is a stopgap to make migrating 1.0 code easier. Once full traversal has been implemented, this should * be removed */ public class IdFilter extends AbstractFilter<FilterResult<Id>, FilterResult<Id>>{ @Inject public IdFilter() {}; @Override public Observable<FilterResult<Id>> call( final Observable<FilterResult<Id>> filterValueObservable ) { //ignore what our input was, and simply emit the id specified return filterValueObservable.map( idFilterResult -> new FilterResult( idFilterResult.getValue(), idFilterResult.getPath() )); } }	{ "pile_set_name": "Github" }