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Release of oxytocin into blood and into cerebrospinal fluid induced by naloxone in anaesthetized morphine-dependent rats: the role of the paraventricular nucleus. Abstract Opioid actions on oxytocin secretion into blood and cerebrospinal fluid (CSF) were investigated in urethane-anaesthetized female rats after intracerebroventricular (icv) infusion of morphine sulphate or vehicle for 5 days. Serial femoral arterial blood samples and cisterna magna CSF samples were collected for radioimmunoassay. Naloxone was given to assess endogenous opioid tone in icv vehicle-infused rats and to precipitate withdrawal in morphine-dependent animals. Initial plasma oxytocin concentration was not affected by icv morphine infusion. In control rats receiving icv vehicle, naloxone increased plasma oxytocin 11-fold within 5 min, and in icv morphine-infused rats, naloxone increased plasma oxytocin 80-fold within 5 min. In both groups, 90 min after naloxone plasma oxytocin was still 5 and 10 times, respectively, the initial concentration. Without naloxone, neither plasma nor CSF oxytocin concentration changed significantly with time (up to 90 min) in either icv treatment group. In the icv vehicle group, there was a 2-fold increase in CSF oxytocin 90 min after naloxone. In the icv morphine-infused group, CSF oxytocin was increased 5-fold 40 min after naloxone. In another group of icv morphine-infused rats, intravenous infusion of oxytocin to achieve plasma levels similar to those seen after naloxone, did not significantly increase CSF oxytocin. In a further group of icv morphine-infused rats, [(3)H]oxytocin was infused intravenously immediately after naloxone was given; in these rats oxytocin transfer from blood to CSF could account at most for only 20% of the increase in CSF oxytocin after naloxone. A further group of rats underwent bilateral microknife ablation of the paraventricular nuclei (PVN) 9 days before icv vehicle or morphine infusions were started; blood and CSF samples were collected under urethane anaesthesia. Initial concentrations of oxytocin in CSF and in plasma were similar in both groups with PVN ablation. In all PVN-lesioned rats initial plasma concentrations of oxytocin were undetectable (<5 pg/ml) and thus less than in intact rats. In contrast, initial levels of oxytocin in CSF were 8-fold greater in PVN-lesioned rats than in intact animals. Naloxone increased plasma oxytocin concentration in the icv vehicle group at least 10-fold within 30 min and in the icv morphine group at least 100-fold within 5 min. CSF oxytocin in the icv vehicle group was not altered by naloxone, but in the icv morphine group CSF oxytocin was increased 5-fold 40 min after naloxone. There were no consistent differences between the icv vehicle- and icv morphine-treated groups in the initial plasma levels of vasopressin, growth hormone and adrenocorticotrophin; PVN ablation did not affect adrenocorticotrophin levels. After naloxone growth hormone levels did not change, vasopressin concentration rose moderately only after 90 min and only in the icv vehicle-treated group, and adrenocorticotrophin concentrations decreased with time whether or not naloxone was given. The results imply an endogenous opioid tone on neurons releasing oxytocin into CSF, and morphine-dependence of these neurons. Furthermore, in PVN-lesioned rats, magnocellular supraoptic neurons could be a source of oxytocin release into CSF.
tomekkorbak/pile-curse-small
PubMed Abstracts
Peep! Peep! Peep! It's all over and Chelsea have been well and truly thrashed. The 3-0 scoreline barely does the superiority of Juve justice. They took Chelsea to school in that second half and with Shakhtar Donetsk having seen off Nordsjaellend 5-2 in Denmark, Chelsea's fate is no longer in their own hands. Shakhtar are already through and a draw in Donetsk will be enough to send Juventus through to the knockout stages with them. 9.34pm: 90+1 min: Giovinco gets booked for removing his shirt during his goal celebration. 9.33pm: GOAL! Juventus 3-0 Chelsea (Giovinco 90) Comedy goalkeeping from Petr Cech, who charges off his line and out of his penalty area in a bid to hack clear a through-ball from deep. What happens next? The substitute Giovinco beats him to the ball, prods it past him and wheels away in celebration as it rolls into the empty net. 9.31pm: 88 min: Juventus substitution: Paul Pogba on, Fabio Quagliarella on. If Pogba's name rings a bell, it's because he's the player Sir Alex Ferguson poached from Le Havre, who then went to Juventus because he couldn't get a game ahead of Paul Scholes, prompting Sir Alex Ferguson to whinge about Juventus poaching him from Manchester United. 9.28pm: 87 min: Chelsea win a free-kick wide on the left. Mata sends an up and under into the box, which Asamoah hacks clear. 9.27pm: 85 min: Claudio Marchisio takes one for the team, picking up a yellow card for sticking out a foot and tripping Ramires when the Brazilian looked to be on the verge of advancing through midfield while Juve were short in numbers at the back. 9.26pm: 84 min: Moses and Torres combine on the outside of the Juventus penalty area to tee up Oscar. He jinks right and left before running down a blind alley and squandering possession. 9.24pm: 83 min: Fernando Torres wins a corner, which is played short to Oscar. His cross to the far post is lamentable, enabling Buffon to gather the ball and send his team away on the counter-attack. Nothing comes of it and it's time for Juventus to make a substitution: Mirko Vucinic off, Sebastian Giovinco on. 9.22pm:9.21pm: 78 min: Pirlo has a pop and wins a corner when his effort is deflected wide. He sends his outswinger deep and when the ball's pinged back towards the mixer, BVonucci trips over his own feet and clatters into Gary Cahill, giving Chelsea a free-kick and the opportunity to clear their lines. 9.19pm: 77 min: David Luiz tries a shot from distance. Do you really need me to tell you how that went? 9.18pm: 76 min: "I suppose I shouldn't be surprised, but I don't think ITV's men are giving Juventus enough credit for how much of a hiding this is," writes Chris Burke. "If Chelsea were up against any other front two besides Quagliarella and Vucinic, who both combine that classic striker's selfishness without any of a classic striker's ability, the scoreline would probably be worse." 9.17pm: 75 min: Yellow card for Ramires, whose name goes in the book for a foul on Chiellini. 9.16pm: 74 min: Caceres squares the ball across the face of goal and from seven yards out and with the goal gaping, Mirko Vucinic somehow manages to spoon the ball high over the crossbar. That's a dreadful miss and a real let-off for Chelsea. 9.15pm: 72 min: Juventus are playing with all the stress of somebody reclining on an armchair with their feet up, casually tossing playing cards into an upturned top hat. They're two goals up and lording it over Chelsea, whose players are largely chasing shadows. 9.13pm: 70 min: Chelsea substitution: Fernando Torres on, John Obi Mikel off. This could probve to be an inspired substitution or it could be the managerial equivalent of Roberto Di Matteo climbing into his own coffin, pulling the lid after him and asking somebody to hammer it shut. 9.11pm: 68 min: Chelsea try to launch an attack down the left flank, with Cole and Moses linking up before switching the play to Ivanovic on the right. To which of Chelsea's diminutive, teeny-weeny front men will he cross the ball? 9.09pm: 67 min: Juventus substitution: Right-winger Stephan Lichsteiner off after a good showing, the more defensively minded Martin Caceres on. 9.08pm: 67 min: Ivanovic wins a corner for Chelsea after some less than glamourous grunt-work down the right flank. Mata takes it and pings the ball straight into the hands of Gigi Buffon, who is a vision in pink. 9.07pm:9.06pm: GOAL! Juventus 2-0 Chelsea (Vidal 61) No sooner does Cesar Azpilicueta go off, than the man he was marking tees up Juve's second goal. Asamoah canters in from the left flank and pulls a diagonal pass behind him to Arturo Vidal. The Chilean midfielder's shot from distance takes a deflection on its way past Petr Cech and Juventus go 2-0 up. That's Arturo's fifth goal in six games, I believe. 9.02pm: 60 min: Chelsea substitution: Victor Moses on, Cesar Azpilicueta off. 9.01pm: 58 min: A beautifully timed run from Quagliarella, who sprints down the inside-right channel and latches on to a through-ball. Petr Cech scampers along the byline and narrows the angle, refusing to commit himself so the striker is unable to take the ball around him and try a shot from a narrow angle. 8.59pm: 57 min: Selfish play from Quagliarella, who turns a defender and tries a shot from a narrow angle, when he should have squared the ball across the face of goal for the unmarked Lichsteiner to tap home. 8.58pm: 55 min: Elsewhere in Group E, it's now Nordsjaellend 2-4 Shakhtar Donetsk. Shakhtar winning and Chelsea losing is the worst-case scenario for the European Champions this evening. 8.57pm: 51 min: Juan Mata takes the free-kick, but shoots straight into the Juventus wall and the Italian champions clear with an agricultural welly down the field. It would have been a grave injustice if Chelsea had scored from that free-kick, when Juventus were unjustly denied a penalty just seconds previously. 8.54pm: 50 min: Chelsea break down the other end of the pitch, where Juan Mata wins a free-kick just to the right of the D on the edge of the Juventus penalty area, after a foul from Chiellini. 8.53pm: 49 min: Mirko Vucinic appeals for a penalty after being blatantly yanked off the ball by Gary Cahill as he tried to skip around the defender and unleash a shot on goal. In the ITV commentary box, Andy Townsend insists it wasn't a penalty, because Cahill didn't foul him enough. Because that's how it works, see. Good grief. 8.50pm: 47 min: That's a comically poor cross from the right from Mirko Vucinici. In a great position to stand the ball up for Claudio Marchisio, he tried to beat Petr Cech with a shot from a preposterous angle and succeeded only in blasting the ball out over the far touchline. 8.48pm: Second half: Juventus get the second half started and Ashley cole is immediately pressed into service to head clear another piercing Kwaddwo Asamoah cross from the left. 8.46pm: Some half-time stats for you ... Not that you'd know it from reading this drivel, Juventus have had 10 shots, eight of which have been on target. Chelsea, by comparison, have had seven shots, just two of which have been on target. Juve's pass success has been 84%, compared to Chelsea's 81%. Juventus have also picked up the only booking of the night, with Leonardo Bonucci being shown a yellow card just before half-time. 8.37pm:8.34pm:8.33pm: Half-time:After a decent first half display in which they created at least two clear scoring chances, Chelsea go in a goal down at the break. They can consider themselves rather unlucky, as replays show that Petr Cech was completely wrong-footed when Quagliarella diverted that long-range Pirlo effort past him. It was rather harsh of me to suggest it was the Chelsea goalkeeper's fault before I'd seen a replay. 8.31pm: 44 min: Chelsea go forward again, with Eden Hazard crossing from the left in a bid to try to pick out his pint-sized team-mates Juan Mata or Oscar. Giorgio Chiellini clears. Elsewhere in Group E, it's now Nordsjælland 2-2 Shakhtar Donetsk. 8.29pm: 41 min: Juventus almost go two up, but Ashley Cole clears what appears to be a goal-bound effort off the line. Chelsea break on the counter-attack and Buffon has to be quick off his line to deny Jaun Mata in a one-on-one. 8.25pm: GOAL! Juventus 1-0 Chelsea (Quagliarella 38) Andrea Pirlo has a shot from distance, Qualiarella sticks out a boot to help it along its way and Petr Cech gets a hand to the ball. His wrist is limp and he can only divert the ball into the bottom right-hand corner. 8.23pm: 35 min: Another searing burst of pace from Oscar, who zooms into the Juventus penalty area after sprinting down the inside left channel. He's forced to check his run before shooting when Barzagli gets in his way and the Italian defender ends up blocking his shot more by accident than design when the Brazilian eventually pulls the trigger. 8.21pm:8.19pm: 30 min: Ramires shanks the ball wide from the edge of the area after being set up nicely by Oscar. 8.17pm: 29 min: For Juve, Stephan Lichsteiner sends a delightful cross in from the right corner and Branislav Ivanovic completely misjudges the header at the far post. Perhaps caught unawares because he wasn't expecting to get a free header, Kwadwo Asamoah makes a complete dog's breakfast of what should have been a very straightforward attempt on goal. 8.15pm: 28 min: "I realise that strength and aerial prowess aren't what his game is about, but Hazard isn't even challenging for headers, rendering Cech's long punts upfield completely ineffective," writes Matt Dony. "Torres would at least be jumping for it." I'd jump for it too, Matt, but it doesn't mean I should be playing either. 8.13pm: 26 min: Free-kick for Chelsea, out by the right touchline, halfway inside the Juventus half. David Luiz and Gary Cahill lumber up from the back to take their places in the penalty area, but Gianluigi Buffon dashes off his line and leaps into to the air to gather Juan Mata's looping delivery without any problems. 8.12pm: 26 min: Elsewhere in this group, Shakhtar Donetsk have fallen behind to Nordsjaelland in Denmark. There's a turn-up for the books, eh? 8.11pm: 25 min: Pirlo shoots low and hard along the ground, underneath the leaping members of the defensive wall. Petr Cech gets down to block his decidedly feeble shot. 8.09pm: 23 min: Arturo Vidal goes down under a challenge from Ivanovic and the referee awards Juventus a free-kick right on the edge of the Chelsea penalty area, a couple of yards to the left of the D. Over to you, Mr Pirlo ... 8.08pm: 20 min: With nearly a quarter of the match gone, Juventus are very much in control. Andrea Pirlo, as expected is running proceedings from midfield and being given plenty of time to pick out runners from midfield. Many of his passes are being sprayed towards Asamoah on the left wing, but he's yet to provide much in the way of service for Quagliarella or Vucinic. Having said that, Chelsea aren't being completely dominated - they're giving Juventus plenty to think about and have had one great chance of their own. 8.05pm: 18 min: Personally, I think the most direct and honest response to the question: 'Why have you decided to drop Fernando Torres?' that Roberto Di Matteo could have given would have been something along the lines of "Have you seen him play recently?" or "Because he's not very good at the moment." 8.03pm: 17 min: "In fairness, 'point of reference' does (to me at least) suggest something staid and predictable, a logical opposite to the 'unplayable' player, which would surely be an apt characterisation of Torres," writes Ryan Dunne. "Given that the cliche is that Torres doesn't score but (supposedly) has splendid, defence-shreading off-the-ball movement, it sounds like Di Matteo is being pretty direct and honest." You think? 8.02pm: 15 min: Another corner for Juventus, which Pirlo swings in towards the near post from the left. With his back to goal, Vucinic plays the ball back to Marchisio, who forces Petr Cech into a theatrical save with a low drive from about 18 yards. Another corner for Juventus, but Quagliarella is penalised for a foul on Cesar Azpilicueta as the ball comes in from the quadrant. 7.59pm: 14 min: Juventus win a corner from which nothing comes. 7.59pm: 12 min: Oooh ... Chelsea should have gone one up there. On the breakaway, Oscar went on a slaloming gallop up the field, took on and beat Andrea Barzagli and then played the ball into the path of Eden Hazard, who was up in support. The Belgian was unable to slot the ball past Gianluigi Buffon when he probably should have done better and the Italian goalkeeper turns the ball out for a corner. It was close ... so close that ITV commentator Clive Tyldesley mistakenly awarded Chelsea a goal. 7.54pm: 8 min: Bonucci steals the ball from Mata in midfield and advances up the field. The ball is worked to the left touchline, where Asamoah tries to get around Cesar Azpilicueta. He does exactly that, but his cross is poor and Chelsea break on the counter. 7.52pm: 6 min: Juventus win a corner. Pirlo sends it into the penalty area with a swish of his foot and Vucinic sends a flick-on over the bar. 7.51pm: 4 min: Superb save from Petr Cech, who flings himself to his right to block a Lichsteiner shot from close range, turn it on to the right upright. Juventus should have taken the lead there, but Chelsea's marking is abysmal. 7.48pm: 2 min: Ashley Cole only half-clears a Kwadwo Asamoah cross from the left, allowing Claudio Marchisio to head towards goal. His effort is very weak and causes Petr Cech no problem. 7.46pm: 1 min: To a cacophony of jeers,Chelsea kick off, playing from right to left in the Juventus Stadium. 7.44pm: Not long now ... The teams make their way down the tunnel and out on to the pitch, with both sets of players wearing the home colours with which they're most readily associated, which is a rare treat in an era when the marketing men have no problem sending the England rugby team out to face the Wallabies at Twickenham wearing skintight mauve, or forcing Tottenham to turn up for a north London derby wearing body-hugging grey and black. 7.41pm: Ah bless ... Robbie Di Matteo has just told ITV that Fernando Torres is not playing because he doesn't want to give Juve's defenders a point of reference. I wonder if that's what he told the player himself? I've never heard such cobblers. 7.40pm: How Juve will line up ... In a 3-5-2, with Andrea Barzaghli, Leonardo Bonucci and Giorgio Chiellini making up the back three, Stephan Lichsteiner and Kwadwo Asamoah book-ending a central trio of Arturo Vidal, Andrea Pirlo and Claudio Marchisio, and Mirko Vucinic and Fabio Quagliarella up front. 7.37pm: How Chelsea will line up ... I'm not afraid to make the big calls, so here goes ... Eden Hazard will play alone up front, with Juan Mata behind him and Oscar and Azpilicueta to the Spaniard's right and left. John Obi Mikel and Ramires will play in the centre of midfield, with Ivanovic at right-back, Gary Cahill and David Luiz at centre-back and Ashley Cole at left-back. Petr Cech will probably be in goals. If you disagree with me, please keep your thoughts to yourself - I genuinely don't want to hear them and can't think of a more boring topic for debate. 7.28pm: To see lots of people tying them in knots ... Take a wander over to Zonal Marking's Twitter feed right now as he fields questions from a load of disciples about False Nines, holders, inverted sevens and inside-out two-and-a-halves,. I'm a big fan of that Michael Cox, not least because we share an impeccable taste for purple woolen pullovers, but he has a hell of a lot to answer for. 7.20pm: So, no Torres in the Chelsea line-up Is this a brave call from Roberto Di Matteo, a complete no-brainer or a mixture of both? Considering how poor the Spaniard's form has been in a season where every dog and devil agrees he's been more of a hindrance than a help to his team-mates, it would surely have been more strange to see him selected than left out. His performance against West Brom on Saturday was woeful and his Chelsea jig must surely be nearly up. What's far more intriguing is the kind of formation Chelsea are going to line up in tonight - a number of football writers are currently trying to figure it out on Twitter, but very few of them seem to agree. Where's Antonio Conte? Don't forget, Juve's manager is still serving a four-month suspension from match-day activity for his part in the Scommessopoli scandal and will be absent from the Juve dug-out until 8 December. The 43-year-old was banned after being found guilty of failing to report attempts to influence the outcome of a Serie B matches in the 2010-11 season, when he was in charge of Siena. It is a ban the Juventus manager went totally berserk over in quite spectacular fashion, albeit to no avail - his place in the dug-out tonight will be taken by his No2, Angelo Alessio. You don't have to understand Italian to get the jist of Conte's rant in the video clip below, although it probably helps. 5.40pm: Preamble Greetings everybody and welcome to this evening's coverage of what should be a fascinating - or potentially snooze-inducing - Group E contest between Juventus and Chelsea. Just one point separates the top three in this group, with Shakhtar Donetsk and Roberto Di Matteo's side first and second on seven points each (the Ukrainian side have the edge on head-to-heads) and Juventus in third place on six points. With whipping boys FC Nordsjaelland already out of contention, this group could throw up all sorts of complicated permutations and combinations over the next two rounds of matches, but as things stand a win would leave Chelsea in the box-seat to qualify (or through to the last 16 with a match to spare if Shakhtar win in Denmark), a draw would suit them just fine and defeat would leave them in all sorts of bother and in danger of becoming the first defending champions in tournament history to exit at the group stage. In their previous Group E encounter at Stamford Bridge in September, Chelsea carelessly threw away a two-goal lead, with silly mistakes allowing Juve to return to Turin with a point they scarcely could have hoped for after finding themselves a brace behind away from home. With Chelsea's Premier League form anything but inspiring, their defence ludicrously porous and their clownish owner rumoured to be suffering from an itchy trigger-finger again, it would take a brave man to bet confidently on them escaping from the Juventus Stadium with all three points tonight, but their hosts have suffered a bit of a wobble of their own in recent weeks. A scoreless draw at home to Lazio was the best they could muster last weekend, having had their their bid to notch up a half-century of Serie A matches unbeaten ended on the 49-mark by Inter earlier this month. For all that, they still managed to hammer FC Nordsjaelland (4-0) and Pescara (6-1) in the interim, so their decline is hardly the stuff of nightmares. Roberto Di Matteo and Gary Cahill fronted up for Chelsea's press conference in Turin yesterday – you can read what they had to say in this report from Dominic Fifield. Once you're all clued up on the party line coming out of Stamford Bridge, why not immerse yourself in this Richard Williams comment piece about the likely influence of Juve's bearded orchestra conductor on tonight's match. For anyone who's forgotten what he's capable of, here's a reminder. I remember wondering at the time if, in the build-up to this penalty, Joe Hart's risible, nervously half-hearted and self-conscious attempt to put the Italian off as he waited to take his spot-kick (sadly isn't in the clip), played any part in Pirlo's decision to make the England goalkeeper look a fool. Anyway, I'll be back with the team news and build-up from 7pm.
tomekkorbak/pile-curse-small
Pile-CC
INTRODUCTION {#sec1-1} ============ There is growing evidence that coronary artery disease (CAD) is seen in relatively younger Pakistani population. In a published report, 28.3% of patients with acute myocardial infarction (AMI) in 17 coronary care units (CCU) in all 4 provinces of Pakistan were found to be younger than 45 years of age.[@ref1] In another study in Faisalabad, 35% of AMI patients admitted in CCU of Divisional Headquarter Hospital and Faisalabad Institute of Cardiology were found to be below the age of 45 years.[@ref2] These reports are indicative of early onset of this disease in Pakistan. An unhealthy dietary intake has been shown to increase the risk of AMI globally.[@ref3]-[@ref5] Low consumption of fruits and vegetables and high intake of fat diet have been identified (among others) as risk factors for development of premature CAD.[@ref6] Since Pakistanis are known to consume high fat diet and low amounts of green leafy vegetables[@ref7]-[@ref9], we embarked on investigating the role of dietary intake and its association with premature AMI in a hospital-based study conducted in Karachi, Pakistan. Most researchers examine the relationship between nutrients intake or individual food items intake (such as fish intake) and their association with AMI, while food consumption is complex phenomena with most individuals consuming a mix of food items in their daily diet with both protective and harmful effects with respect to development of disease such as AMI.[@ref10] The study of dietary patterns has emerged as an important component of nutrition science as it allows researchers to look at the clustering of food items in diet. It also enables easy communication of health messages to the population as they are based on dietary patterns rather than nutrients or individual food items which are less meaningful. This study is a relatively large, hospital-based study conducted in Karachi, Pakistan to assess the association between dietary patterns and AMI in this population. METHODS {#sec1-2} ======= Participants {#sec2-1} ------------ Two hundred and three consecutive patients (146 males and 57 females) with their first AMI and below the age of 45 years admitted to the National Institute of Cardiovascular Diseases (NICVD), Karachi from June 2010 to July 2011 were included in this study with informed consent. Criteria for premature AMI were: age 18-45 years; both males and females; had confirmed diagnosis of AMI on the basis of clinical examination, ECG and biochemical data; and had no history of consuming B-vitamins (B~6~, B~12~ and folate) during the last 4 months. Individuals who were found to be pregnant or having malabsorption syndrome or suffering from tuberculosis or liver disease, or uremia or cancer were not included in the study because these chronic diseases/conditions may lead to compromised dietary consumption and therefore could function as confounders of diet-AMI relationships. Similarly, 205 gender, and age matched (within 3 years) healthy controls from the personnel of the Aga Khan University and other health-care facilities in Karachi were also included in the study as controls. All these controls were not suffering from any of the above mentioned diseases or conditions and were not taking B vitamin supplements. Both cases and controls belonged to a low socio-economic group as 83% of controls and 90% of cases had monthly house-hold income less than US\$ 150. Determination of food frequency {#sec2-2} ------------------------------- Using a simple 14-item food frequency questionnaire (FFQ), the eating habits of both cases and controls were determined. This food frequency questionnaire has been used previously in a population-based study.[@ref11] Information about the number of times each commonly used food item was consumed per month, per week or per day was recorded and then the frequency of each food/drink item was converted to its consumption per day as described previously.[@ref11] To clarify it further, if there was a response of 6 servings per month of a food item, then it was converted to 0.2 serving per day. Study had been approved by the Ethics Review Committees of the Aga Khan University as well as NICVD. Since no nutrient analysis was done, therefore a food composition table was not used. Measurements of biochemical parameters {#sec2-3} -------------------------------------- Ten mL of fasting blood was obtained within 24 hours of the admission and analyzed for serum folate, homocysteine, glucose, total cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, triglycerides and ferritin using commercially available kit methods (Roche Diagnostics, USA), while serum vitamin B~12~ was assayed using a radioassay.[@ref12] The minimum limits of detection for serum/plasma folate, homocysteine, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, ferritin and vitamin B~12~ were 0.64 ng/mL, 4 mmol/L, 2 mg/dL, 9.7 mg/dL, 3.9 mg/dL, 3.0 mg/dL, 8.9 mg/dL, 0.5 ng/mL and 50 pg/mL, respectively. Statistical analysis {#sec2-4} -------------------- Using factor analysis, major dietary patterns were developed and then conditional logistic regression analysis was used to predict the association of dietary patterns with AMI. Factor analysis was used to identify common dietary patterns from dietary intake data. For the generation of uncorrelated factors, factors were rotated orthogonally. Determination of number of factors to be retained in the model was carried out on the basis of Eigenvalue (\>1), scree plot and factor interpretability.[@ref13] The analyses were run in Statistical Package for Social Sciences^®^ (SPSS; version 16 for Windows, Apache Software Foundation, USA) using the data reduction procedure. As a result, three major dietary patterns were identified in this population, which were similar to the dietary patterns identified earlier in a Pakistani population based study in Karachi.[@ref11] The three dietary patterns were then divided into quartiles. All cases and controls were matched for age and gender, and conditional logistic regression analysis was carried out to find out the association between each dietary pattern and AMI while adjusting for BMI, ferritin, total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol. Values have been presented as OR (95% CI). Continuous variables have been presented as means±SD. Analysis of variance (ANOVA) was used for comparing means of quartiles across each dietary pattern. A p-value of \<0.05 was considered significant. RESULTS {#sec1-3} ======= Eating habits of both cases and healthy controls were assessed using a 14-item food group frequency questionnaire ([Table-I](#T1){ref-type="table"}). Mean intake per day of all food items with standard deviations is reported in [Table-I](#T1){ref-type="table"}. Some of the food items used in this questionnaire have been previously studied for association with B-vitamins, plasma homocysteine and cardiovascular disease.[@ref11],[@ref14] ###### Factor loadings for varimax rotated factors[\*](#t1f1){ref-type="table-fn"} Food items Mean intake per day±SD Prudent diet Combination diet Western diet --------------------- ------------------------ -------------- ------------------ -------------- Meat 0.27±0.33 \- \- 0.58 Egg 0.22±0.31 \- 0.61 \- Fish 0.06±0.10 \- 0.41 0.47 Chicken 0.21±0.20 0.51 \- \- Cooked vegetables 0.64±0.35 0.66 \- \- Uncooked vegetables 0.42±0.49 0.66 \- \- Legumes 0.35±0.31 0.72 \- \- Wheat 1.86±1.11 0.59 \- \- Fruits 0.46±0.40 0.37 0.53 \- Tea with milk 2.9±2.63 \- \- 0.55 Tea without milk 0.14±0.56 \- \- \- Green tea 0.16±0.46 \- \- \- Coffee 0.03±0.22 \- 0.34 \- Juices 0.13±0.48 \- 0.49 \- Eigen value 2.46 1.32 1.18 \% of variance 17.6 9.4 8.4 Factor loadings less than 0.3 are not shown. Factor analysis revealed 3 major dietary patterns. These were labeled as " prudent dietary pattern", which was characterized by high consumption of legumes, cooked and uncooked vegetables, wheat, chicken and fruits; "combination dietary pattern" which was characterized by high consumption of eggs, fish, fruits, juices and coffee; and "western dietary pattern", which was characterized by high intake of meat, fish and tea with milk ([Table-I](#T1){ref-type="table"}). Each of these 3 dietary patterns was further classified into quartiles. The descriptive information presented in [Table-II](#T2){ref-type="table"} shows that mean concentrations of serum ferritin and LDL-cholesterol were lower in the highest quartile of prudent dietary pattern compared to the lowest quartile (p-value \<0.01). On the other hand, mean concentrations of total cholesterol, HDL-cholesterol and triglycerides were higher in the highest quartile of prudent diet compared to the lowest quartile (p-value \<0.01). Regarding the western dietary pattern, individuals in the highest quartile (quartile 4) appear to have increased concentrations of serum ferritin, LDL-cholesterol and triglycerides compared to individuals in the lowest quartile, however, the values were not found to be statistically significant. It was observed that consumption of prudent diet was protective against the risk of premature AMI, however, p-value for trend was insignificant (p-value for trend \> 0.05) ([Table-III](#T3){ref-type="table"}). ###### Anthropometric measures and concentration of biomarkers by quartiles of dietary patterns[\*](#t2f1){ref-type="table-fn"} Characteristics Prudent diet Combination diet Western diet ------------------------- -------------- ------------------ -------------- ----------- ----------- ------ ----------- ----------- ------- BMI (kg/m^2^) 25.2±3.67 25.8±4.68 0.11 25.9±4.7 25.8±4.3 0.95 25.6±4.6 25.7±3.9 0.78 Homocysteine (µmol/L) 19.96±8.49 26.1±23.8 0.059 24.9±20.7 24.6±19.4 0.32 23.9±18.7 23.5±19.4 0.74 Folate (ng/mL) 6.35±3.4 7.3±3.8 0.25 6.88±3.55 6.53±3.57 0.31 6.59±3.7 6.83±3.6 0.71 Vitamin B12 (pg/mL) 318±162 362±197 0.39 335±201 350±193 0.75 344±202 340±169 0.68 Blood Pb (µg/dL) 15.2±6.6 16.3±8.49 0.096 15.57±8.7 15.29±7.1 0.53 15.81±8.6 14.22±6.3 0.34 Ferritin (ng/mL) 157±140 106±96 0.004 125±103 135±141 0.51 115±93 144±149 0.17 Cholesterol (mg/dL) 153±39 160±40 0.003 160±42 162±39 0.70 160±43 162±41 0.84 LDL-cholesterol (mg/dL) 102±34 95±35 0.006 99±40 103±33 0.79 96±37 101±33 0.155 HDL-cholesterol (mg/dL) 29.4±10.1 33.6±8.9 \<0.001 33.7±13.6 33.4±10.7 0.30 34.3±10.0 31.7±11 0.38 Triglycerides (mg/dL) 107±58 156±96 0.003 140±74 142±69 0.98 136±85 152±74 0.08 Values are means±SD Lowest quartile. P was based on ANOVA comparing means of quartiles. ###### OR for premature acute myocardial infarction by quartiles of different dietary patterns. Dietary pattern Q1 Q2 Q3 Q4 P for trend -------------------------------------------- ---- ---------------------------------------------------- ---------------------------------------------------- ----------------------------------------------------- ------------- *Prudent diet* Crude[^+^](#t3f1){ref-type="table-fn"} 1 0.01 (0.00-0.06)[\*\*](#t3f4){ref-type="table-fn"} 0.02 (0.00-0.01)[\*\*](#t3f4){ref-type="table-fn"} 0.04 (0.01-0.17) [\*\*](#t3f4){ref-type="table-fn"} \> 0.05 Adjusted[^\#^](#t3f2){ref-type="table-fn"} 1 0.01 (0.00-0.07)[\*\*](#t3f4){ref-type="table-fn"} 0.01 (0.00-0.05)[\*\*](#t3f4){ref-type="table-fn"} 0.035 (0.01-0.25)[\*\*](#t3f4){ref-type="table-fn"} \> 0.05 *Combination diet* Crude[^+^](#t3f1){ref-type="table-fn"} 1 0.95 (0.50-1.83) 0.31 (0.16-0.59)[\*](#t3f3){ref-type="table-fn"} 0.42 (0.22-0.80)[\*\*](#t3f4){ref-type="table-fn"} \< 0.05 Adjusted[^\#^](#t3f2){ref-type="table-fn"} 1 0.54 (0.19-1.55) 0.19 (0.07-0.54)[\*\*](#t3f4){ref-type="table-fn"} 0.27 (0.10-0.77)[\*](#t3f3){ref-type="table-fn"} \< 0.05 *Western diet* Crude[^+^](#t3f1){ref-type="table-fn"} 1 1.08 (0.59-1.97) 2.01 (1.05-3.84)[\*](#t3f3){ref-type="table-fn"} 2.17 (1.15-4.09)[\*](#t3f3){ref-type="table-fn"} \< 0.05 Adjusted[^\#^](#t3f2){ref-type="table-fn"} 1 1.29 (0.52-3.24) 1.30 (0.46-3.62) 2.26 (0.83-6.18) \< 0.05 ***Note:*** Q1 is the lowest quartile of dietary intake, while Q4 is the highest quartile. Values are OR (95% CI) from conditional logistic regression. Values are OR (95% CI) from conditional logistic regression adjusted for BMI, ferritin, total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol. P \< 0.05 P \< 0.01 It was also observed that moderate to high consumption of combination diet was protective against the risk of premature AMI after adjusting for BMI, ferritin, total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol (p-value \< 0.05). Compared to the first quartile, the adjusted odds ratios were 0.19 (95% CI, 0.07-0.54) and 0.27 (95% CI, 0.10-0.77) for the third and fourth quartiles, respectively (p-value for trend \< 0.05). Consumption of western diet was not found to be associated with the risk of premature AMI. DISCUSSION {#sec1-4} ========== Three major dietary patterns labeled as prudent dietary pattern, combination dietary pattern and western dietary pattern were obtained after using factor analysis of the 14 food items. Western dietary pattern was similar to the dietary pattern defined in an earlier study in Karachi,[@ref15] while prudent diet was similar to the patterns generated from INTERHEART, Health Professional Follow-up Study and Nurses' Health Cohort.[@ref3],[@ref14],[@ref16] High loading of eggs in the combination diet in the present study is, however different from the afore-mentioned research studies because eggs have been part of the western diet in those studies. Other investigators have also reported a combination dietary pattern where a mix of food items belonging to different food groups has been observed.[@ref17] In a previous communication from our laboratory, an association of 3 dietary patterns with hyperhomocysteinemia has been reported.[@ref11] However, in the present study an association of some of these dietary patterns has been found with premature AMI in a Pakistani population. Findings of this study are consistent with previous results that consumption of a prudent diet is protective against the development of heart disease after adjusting the model for BMI and other covariates as has been reported by in the INTERHEART study,[@ref3] and by Hu et al.[@ref16], however, no adverse association was observed between consumption of a western diet and risk of developing premature AMI after adjusting for the above mentioned covariates. In combination dietary pattern, an association with the risk of AMI was such that moderate to high consumption of a combination dietary pattern is associated with a reduced risk of AMI. This is indicative of a protective effect for the individuals in the third and fourth quartiles of consumption in this dietary pattern. A combination dietary pattern in Pakistani population is a unique finding of the present study. It is possible that moderate to high consumption of animal source food items combined with plant source food items exerts a beneficial effect; while no protective effect is observed when the intake is small. In the present investigation, some biomarkers of myocardial infarction were associated with the prudent dietary pattern, while other biomarkers and physical measures were not significantly associated. Furthermore, no association was found between the combination dietary pattern and the western dietary pattern and any of the biomarkers and physical measures. Significantly low level of serum ferritin observed for individuals in the highest quartile of prudent dietary pattern compared to the lowest quartile of intake is consistent with the fact that dietary iron from plant sources is less bio-available compared to iron from animal sources,[@ref18] consequently individuals consuming more of the prudent dietary pattern were likely to have low serum ferritin levels. Lower mean level of LDL-cholesterol and a higher mean level of HDL-cholesterol in individuals in the highest quartile of prudent dietary intake compared to those in the lowest quartile of intake was an important observation in the current study. This is consistent with findings of a study in Korea in which individuals in the lowest quartile of a similar dietary pattern that they termed as "Korean Healthy pattern" had higher concentrations of total cholesterol and triglycerides compared to individuals in the highest quartile of intake.[@ref19] Relatively high serum ferritin levels observed in the highest quartile of western dietary intake compared to the lowest quartile of intake (though not statistically significant due to large variance) are suggestive that consumption of red meat could be one of the major contributors of iron to body stores.[@ref20],[@ref21] High body iron status has been reported to be associated with premature AMI in Pakistani population.[@ref22] Therefore, it is conjectured that increased consumption of western diet rich in red meat could be contributing to high body iron stores, thereby increasing the risk of AMI. However, results of the present investigation did not show an association of western dietary pattern with the risk of AMI in this population. Results obtained in this investigation must be viewed within the context of certain limitations of this study. This was a case control study and there might be a possibility of recall bias between the cases and controls for dietary intake assessment. Moreover, it is likely that the cases may have changed their diets due to other preceding conditions such as hypertension or abnormal lipid profile which would minimize the association between AMI and diet. However, such a situation would lead to attenuation in the association between dietary patterns and AMI suggesting that our results might be conservative estimates. The FFQ that was used for collection of dietary data has not been validated, however similar FFQs have been used in other studies in Pakistan and they appear to have face validity.[@ref11] Furthermore, as a short (14 items) food intake questionnaire was used, it was not possible to estimate and consequently adjust our analysis for total energy intake. However, adjustment was made in the analysis for significant determinants of energy intake i.e. age, sex and BMI[@ref23], and this should lend credence to our findings. Matching of cases and controls for age and sex in the design of the study has been the main strength of this study. This was a hospital-based study conducted at a large cardiovascular diseases hospital but larger, community based studies that would include participants from urban as well as rural areas of Pakistan are required for further confirmation of our findings. CONCLUSIONS {#sec1-5} =========== Consumption of prudent diet which is rich in legumes, vegetables, wheat, chicken and fruits is protective against the risk of premature AMI in a Pakistani population. Moderate to high intake of combination diet which is rich in eggs, fish, fruits, juices and coffee is associated with reduced risk of AMI. Western dietary pattern which is characterized by high intake of meat, fish and tea with milk does not appear to be associated with risk of AMI in Pakistani population. The study has been supported by a grant from Pakistan Academy of Sciences/Higher Education Commission to Mohammad Perwaiz Iqbal. Analysis and interpretation by Mohsin Yakub were supported by a grant \# 614 of the Bill and Melinda Gates Foundation. ***Funding:*** Pakistan Academy of Sciences/Higher Education Commission. ***Conflict of interest:*** Authors declare that they have no conflict of interest. {#sec1-6} Authors Contribution {#sec2-5} -------------------- **RI:** Designed the study, interpreted the data and drafted the manuscript. **MY:** Designed the study, analyzed and interpreted the data. **AKT:** Helped in the design and conduct of the study and interpreted the clinical data. **SPI:** Analyzed and interpreted the data. **MPI:** Conceived and designed the study, interpreted the data and drafted the manuscript.
tomekkorbak/pile-curse-small
PubMed Central
Inferring lanosterol functions in the female rabbit reproductive tract based on the immunolocalization of lanosterol 14-demethylase and farnesoid beta-receptor. Female reproductive organs have de novo synthesis of cholesterol. Some sterol molecules, intermediaries in the cholesterol synthesis, have important paracrine/autocrine actions. Lanosterol binds to the farnesoid beta-receptor (FXRβ), a molecule widely expressed in the ovaries, suggesting that it may play a role in reproduction. Up to date, we know little about lanosterol functions across female reproductive organs. We described immunolocalized lanosterol 14-demethylase (LDM or CYP51A1), responsible for catalyzing the conversion of lanosterol in cholesterol, and FXRβ in the ovary, oviduct, uterus, and vagina of virgin and pregnant rabbits. In virgin rats, we found CYP51A1 and FXRβ immunoreactivity was found in all ovarian follicles, epithelial cells, stroma, and Graafian follicles. Also, the epithelium and stroma, as well as the smooth muscle of the oviduct, vagina, and uterus showed CYP51A1 and FXRβ immunoreactivity. In pregnant dams, we observed the presence of CYP51A1 and FXRβ immunoreactivity in the corpora lutea, giant uterine cells, and trophoblastic cells. The presence of CYP51A1 and FXRβ support that lanosterol participates in diverse reproductive processes, including follicular maturation, transport of gametes and zygote, implantation of blastocyst, lubrication, and contraction of the vagina, secretion of female prostate, and control of delivery mediated by pelvic muscles contraction.
tomekkorbak/pile-curse-small
PubMed Abstracts
Introduction {#s1} ============ Reversible protein phosphorylation is a post-transcriptional event that is regulated by both protein kinases and phosphatases (PPs). This is a crucial intracellular control mechanism in eukaryotes, being involved in almost all cellular functions, from metabolism to signal transduction and cell division ([@b5]). Phosphoprotein phosphatase 1 (PPP1), one of the major eukaryotic Ser/Thr-PPs, has exquisite specificities *in vivo*, both in terms of substrates and cellular localization. Over the past two decades, it has become apparent that PPP1 versatility is achieved by its ability to interact with multiple targeting/regulatory subunits known as PPP1 interacting proteins -- PIPs ([@b5]; [@b54]). PPP1 catalytic subunit (PPP1C) is encoded by three different genes giving rise to α/A, β/B, and γ/C isoforms. After transcription, *PPP1CC* undergoes tissue-specific splicing, originating a ubiquitously expressed isoform, PPP1CC1 and a testis-enriched and sperm-specific isoform, PPP1CC2 ([@b6]). To date, more than 200 PIPs have been identified, most of them having the consensus PPP1 binding motif (PPP1BM) RVxF that binds to the catalytic subunit of PPP1, determining its function and specific cellular location ([@b15]; [@b21]). Several PPP1-PIP complexes are involved in cytoskeleton functions. For instance, PPP1-Phostensin holoenzyme has been implicated in actin rearrangements ([@b26]). Phostensin targets PPP1 to F-actin, being an actin filament pointed end-capping protein that is capable of modulating actin dynamics ([@b29]). The protein family PHACTR (all members 1--4) is involved in synaptic activity through the control of the actin cytoskeleton and by regulating PPP1 and actin ([@b1]). The above mentioned PIPs bind actin through the amino acids Arg--Pro--Glu--Leu and may direct PPP1 to a panoply of actin-associated substrates. Thus, several lines of evidence imply PPP1 in the regulation of cytoskeleton dynamics, together with various PIPs. This not only occurs at the actin level but also at the tubulin level. PPP1 has been shown to be anchored to *Chlamydomonas* central pair apparatus axoneme, associated with the C1 microtubule, and to a lesser extent to the outer doublet microtubules, suggesting that PPP1 can control both dynein arms and thereby flagellar motility ([@b65]). Also, recent data from our laboratory showed that PPP1 co-immunoprecipitates with tubulin from human sperm ([@b16a]). Clearly the key to characterize the diverse roles of PPP1 relies on the identification of novel PIPs, and in the understanding of the specific functions of these complexes. Therefore, we focused on the identification of novel PIPs, through yeast two-hybrid screens where PPP1CC isoforms were used as baits ([@b3]; [@b16a]; [@b12]; [@b60]). In this study, we present a novel partner of PPP1, the T-complex testis expressed protein 1 domain containing 4 (TCTEX1D4/Tctex2β), which has recently been described as a novel Tctex1 dynein light chain family member ([@b35]). Further, the TCTEX1D4/PPP1CC subcellular co-localization and its dependence on TCTEX1D4-PPP1CC binding, support functions for the complex in microtubules dynamics. Simultaneously, the data also contribute to our understanding of the molecular basis of sperm motility as well as the dynamic and varied functional nature of PPP1. Results {#s2} ======= Identification and *in silico* characterization of TCTEX1D4, a novel PPP1CC binding protein {#s2a} ------------------------------------------------------------------------------------------- A yeast two-hybrid screen was performed against a human testis cDNA library using the C-terminus portion of PPP1CC2 as bait ([@b16a]). Four clones were obtained encoding the T-complex testis expressed protein 1 domain 4 (TCTEX1D4). TCTEX1D4 is a novel member of the dynein LC Tctex1 family that was recently identified as a binding partner of endoglin, a transmembranar glycoprotein involved in the transforming growth factor β (TGFβ) signaling ([@b35]). TCTEX1D4 has 221 amino acids, with an expected molecular mass of 23352 Da. The gene maps to human chromosome 1p34.1 and has 2 exons ([@b35]). In order to identify physiologically relevant motifs and phosphorylation sites from the signaling perspective, we performed a bioinformatic analysis using the human TCTEX1D4 protein sequence in ELM ([@b43]), PsiPred ([@b25]), ScanProsite, NetPhos and NetNGlyc1.0 servers. The conservation of motifs identified was analyzed by comparison with other mammalian sequences, and only results with high scores are shown. Based in ELM and Psipred, the TCTEX1D4 sequence was first divided into two domains: the disordered domain (residues 1 to 95) and the globular domain (residues 96 to 221) ([Fig. 1A](#f01){ref-type="fig"}). Secondary structure prediction of the globular domain suggests two alpha helices, followed by four β strands resembling that of DYNLT1. Since amino acids from the disordered domain should be more accessible to kinases and phosphatases, only the putatively phosphorylatable motifs of the disordered domain are shown in [Fig. 1A](#f01){ref-type="fig"}. The bioinformatic approach revealed that the TCTEX1D4 disordered domain contains many putative Ser phosphorylation sites, such as consensus sites for protein kinase A (PKA, Ser24/53/66/92), B (PKB, Ser53/66) and C (PKC, Ser49), cyclin dependent kinase 1 (CDK1, Ser24), casein kinase 1 (CK1, Ser92) and 2 (CK2, Ser34), mitogen-activated protein kinase (MAPK, Ser24), and glycogen synthase kinase 3 (GSK3, Ser49). Remarkably, no potential Thr and Tyr phosphorylation sites were found. ![Schematic representation of the human TCTEX1D4 and its family members.\ The human sequences of Tctex1 family proteins were obtained from Ensembl database. (**A**) The human protein sequence of TCTEX1D4 was submitted to ELM to appoint relevant motifs. TCTEX1D4 disordered (amino acids 1--95) and globular domains (amino acids 96--221) are shown. Putative conserved motifs and phosphorylation sites for specific kinases are indicated. (**B**) Sequences were submitted to ClustalW2 and the resulting aligning output file shaded with BOXSHADE. Open squares indicate the PPP1BM RVSF of TCTEX1D4 and the KVLF motif of TCTEX1D3. (**C**) Schematic representation of human Tctex1 family members with their respective TCTEX1 globular domains (dark gray). The black squares show the position of the PPP1BM of TCTEX1D4 and TCTEX1D3.](bio-02-05-453-f01){#f01} The NetNGlyc1.0 server indicated a putative N-glycosylation motif in the extreme C-terminus (residues 205 to 210). Putative binding domains were also identified for the motif "anaphase-promoting complex (APC/C) binding site through the destruction box" (residues 28 to 36), for cyclins (residues 161 to 165), for MAPK (residues 167 to 176) ([Fig. 1A](#f01){ref-type="fig"}). Additionally and particularly relevant to PIPs, the canonical PPP1BM RVxF was detected in the bioinformatics analysis, ^90^RVSF^93^, and reinforces the assertion that TCTEX1D4 is a PPP1 binding partner ([Fig. 1A](#f01){ref-type="fig"}). TCTEX1D4 belongs to the Tctex1 family of dynein LCs that share the Tctex1 globular domain, a region of high homology present among the different family members ([Fig. 1](#f01){ref-type="fig"}). The human Tctex1 family comprises 6 members: DYNLT1 (Tctex1), DYNLT3 (RP3), TCTEX1D1, TCTEX1D2 (Tctex2b), TCTEX1D3 (Tctex2/Tcte3), and TCTEX1D4 (Tctex2β). A ClustalW2 protein alignment with full-length protein sequences ([Fig. 1B](#f01){ref-type="fig"}) revealed that the Tctex1 domain is common to all proteins studied. A score of 57% was obtained between DYNLT1 and DYNLT3 when using only the TCTEX1 globular domain. For the other four family members of the Tctex1 domain containing proteins, the score varied between 25% and 33% (alignment not shown). This implies the formation of two distinct groups, one that contains DYNLT1 and DYNLT3 and one that contains the Tctex1 domain containing proteins. These results are in accordance with the work of DiBella and Meng ([@b10]; [@b35]). Since reversible protein phosphorylation is an important mechanism involved in the control of dynein function ([@b51]; [@b58]), a bioinformatics analysis was carried out for all the PPP1 binding motifs known in all dynein LCs, light intermediate chains (LICs), and intermediate chains (ICs) ([@b42]). Interestingly, from all LCs, besides TCTEX1D4, only TCTEX1D3 possesses a consensus PPP1BM ([Fig. 1B,C](#f01){ref-type="fig"}). Between the ICs and LICs, the IC2, DYNC1LI1 and DYNC1LI2 proteins also have a canonical PPP1BM. In order to evaluate the evolutionary conservation of the phosphorylation sites and motifs described above ([Fig. 1A](#f01){ref-type="fig"}), a ClustalW2 alignment was performed using representative orthologs of TCTEX1D4 ([Fig. 2A](#f02){ref-type="fig"}). A phylogenetic tree was further constructed using either the Neighbor-Joining or the Maximum likelihood methods (given the similar results, only one of the methods is shown), revealing that TCTEX1D4 follows the modern mammalian taxonomy ([Fig. 2B](#f02){ref-type="fig"}). Besides being present in placental mammals, TCTEX1D4 is also present in marsupials (*Monodelphis domestica*) and monotremes (*Ornithorhynchus anatinus*), birds (*Gallus gallus*) and fishes (*Danio rerio*, outgroup of the evolutionary tree). The results show that phosphorylation sites Ser34/49/53/66, consensus sites for CK2, GSK3, PKA, PKB and PKC, are conserved in all mammals, Ser92 is present in all mammals except for pig (*Sus scrofa*) and kangaroo rat (*Dipodomys ordii*), and Ser24 is present in all primates (except *Microcebus murinus*, a representative of lower primates Stepsirrhini, lemurs), Artiodactyla, Carnivora (except dog, *Canis familiaris*) and Chiroptera. The N-glycosylation motif is highly conserved in mammals but not in Murinae. The APC/C binding site is conserved in all mammals with the exception of *Cavia porcellus*. The cyclins binding site is present in all mammals but not in *Felis catus*, Insectivora and Rodentia (excluding *Dipodomys ordii*), and the MAPK binding site is conserved in all mammals, fish and birds. Finally, the PPP1BM is conserved in all placental mammals, with the exception of *Pteropus vampyrus* from the order Chiroptera ([Fig. 2A](#f02){ref-type="fig"}). ![Alignment and phylogenetic relationship between human TCTEX1D4 and its homologues.\ The protein sequences of TCTEX1D4 homologues were obtained from the Ensembl database by performing a Blastp search through the metazoans group using the human TCTEX1D4 sequence. (**A**) The chosen sequences were submitted to a ClustalW2 alignment. Open box indicate conservation of the RVSF motif across the placental mammals. (**B**) The resulting phylogenetic tree output was obtained by employing a Neighbor-Joining method with bootstrap test in MEGA program. *D. rerio* (zebrafish) was chosen as out-group. Scale bar: 0.05 substitutions per residue.](bio-02-05-453-f02){#f02} Validation of the TCTEX1D4--PPP1 interaction {#s2b} -------------------------------------------- To prove the interaction between TCTEX1D4 and PPP1C isoforms, AH109 yeast strain was co-transformed with pACT-2-TCTEX1D4 and with *PPP1CA*, *PPP1CC1*, *PPP1CC2* or the *PPP1CC2end* in pAS2-1 ([@b12]; [@b16a]). After growing in selective media, colonies were transferred to plates with X-α-Gal, and all colonies turned blue, indicating that TCTEX1D4 interacts with the PPP1C isoforms ([Fig. 3A](#f03){ref-type="fig"}). ![TCTEX1D4 binds to PPP1.\ (**A**) Yeast co-transformation of pACT-2-TCTEX1D4 with PPP1CA, PPP1CC1, PPP1CC2 or PPP1CC2end in pAS2-1 vector, using the Li-Ac method. For negative and positive controls pAS2-1/pACT-2 and pVA3/pTD1 vectors were used, respectively. (**B**) Western blot showing that TCTEX1D4 binds to and co-immunoprecipitates PPP1CC in COS-7 cells transfected with Myc-TCTEX1D4. Non-transfected and transfected COS-7 cells were used as negative and positive controls, respectively. (**C**) Bacterial extracts expressing pET-TCTEX1D4, pET-TCTEX1D4-AAAA, pET-TCTEX1D4-NT (NT) and pET-TCTEX1D4-CT (CT) were run in an SDS-PAGE gel and overlaid with purified PPP1CC isoforms. pET vector alone was used as negative control and pET-NEK2C, a known PIP, was used as positive control. All experiments were repeated at least three times.](bio-02-05-453-f03){#f03} The existence of TCTEX1D4-PPP1 complexes *in vivo* was shown by co-immunoprecipitation of the latter from cell lysates of COS-7 that were transfected with Myc-TCTEX1D4 ([Fig. 3B](#f03){ref-type="fig"}). When PPP1CC was immunoprecipitated from cells transfected with Myc-TCTEX1D4, the protein was highly co-immunoprecipitated, as denoted by the intense Myc-immunopositive band in Western blot analysis ([Fig. 3B](#f03){ref-type="fig"}). In order to test the direct interaction between TCTEX1D4 and PPP1, a membrane overlay was performed using bacterial cell lysates expressing recombinant TCTEX1D4 ([Fig. 3C](#f03){ref-type="fig"}). The results show that TCTEX1D4 binds directly to both PPP1CC1 (upper panel) and PPP1CC2 (lower panel) purified proteins. It is demonstrated that mutation of the PPP1BM either to AAxA ([@b33]), RAxA or to RVxA abolish the PPP1/PIP interaction, although some cases exist where interaction still occurs at a lesser extent ([@b2]; [@b4]; [@b50]; [@b55]). We tested whether a mutation of the TCTEX1D4 PPP1BM is crucial to the complex formation. The results reveal that mutation of the TCTEX1D4 PPP1BM RVSF to AAAA only partially reduces the binding (35%, pET-TCTEX1D4-AAAA lanes), with the same being true when RVSF is mutated to RVSA (data not shown). Furthermore, when using TCTEX1D4 N-terminus (NT) and C-terminus (CT) truncated forms in the overlay assay ([Fig. 3C, right panel](#f03){ref-type="fig"}), it was shown that the important motifs for PPP1C binding, such as the RVSF, were present in the N-terminus portion of the TCTEX1D4 protein. However, it cannot be excluded that the C-terminus might be important for binding stabilization. TCTEX1D4 expression in different tissues {#s2c} ---------------------------------------- By performing a NCBI EST database analysis with *TCTEX1D4* mRNA (NM_001013632.2) a total of 42 hits in *Sus scrofa*, *Rattus norvegicus*, *Mus musculus*, *Homo sapiens* and *Danio rerio* were retrieved. From the total ESTs identified, 45% corresponded to female reproductive tract related tissues (ovary, oviduct, placenta, uterus and embryonic tissue). Head related tissues (head, hypothalamus, brain, corpus striatum and tongue) corresponded to 21% and lung to 17% of the total ESTs. Moreover, in the databases no ESTs were found in testis, although it was already described in previous work by Northern blot ([@b35]). A tissue screen of TCTEX1D4 protein expression was consequently performed on several rat tissues and human testis ([Fig. 4](#f04){ref-type="fig"}). The results show that TCTEX1D4 is highly expressed in ovary, spleen, lung, placenta and kidney. It is also expressed in the other tissues tested, but in lower amounts, including human testis. Interestingly, both antibodies, recognizing the N- or the C-terminus of TCTEX1D4, revealed the same immunoreactive profile, meaning that the two bands detected with each of the antibodies (24.9 and 28.4 kDa) correspond to the full-length TCTEX1D4. ![TCTEX1D4 protein expression profile.\ Rat tissues and human testis extracts were prepared as described in [Materials and Methods](#s4){ref-type="sec"}. A tissue protein expression profile (100 µg) of TCTEX1D4 was performed by Western blot using CBC8C (anti-TCTEX1D4C) and anti-TCTEX1D4N antibodies. The negative control consisted of bacterial extract expressing the pET vector alone, and the positive control of a bacterial extract expressing pET-TCTEX1D4. A loading control, β-tubulin, was also performed. Image shows representative blots from three independent experiments.](bio-02-05-453-f04){#f04} Cellular localization of TCTEX1D4 in mouse testis and human spermatozoa {#s2d} ----------------------------------------------------------------------- To validate the expression of TCTEX1D4 and to further specify the expression pattern in the testis we have performed immunohistochemical and qRT-PCR analyses on mouse testes. We found that TCTEX1D4 was expressed differentially ([Fig. 5A](#f05){ref-type="fig"}). Within the seminiferous tubules, TCTEX1D4 immunoreactivity was localized in the basal part in a pattern that was typical for the blood--testis barrier (BTB) ([Fig. 5D,G,J](#f05){ref-type="fig"}, arrows). The same pattern was shown after immunostaining of the testis with antibodies against Claudin-11 ([Fig. 5C](#f05){ref-type="fig"}), which is an established marker for the BTB. In addition to the BTB localization, we found that TCTEX1D4 was expressed in spermatids in different patterns depending on the stage of seminiferous tubules. During the course of spermatid differentiation, TCTEX1D4 immunoreactivity was first observed in early elongating spermatids in a typical acrosome-like manner ([Fig. 5J](#f05){ref-type="fig"}; stage X tubules, closed circles). This localization of TCTEX1D4 was consistent throughout spermiogenesis as shown in [Fig. 5D,G](#f05){ref-type="fig"}. In late elongating spermatids, however, an additional strong focal immunoreactivity appeared in the cytoplasm of the spermatids. In late elongating spermatids of stage IV tubules, the immunoreactivity was within the adluminal cytoplasmic area ([Fig. 5D](#f05){ref-type="fig"}, arrowheads) whereas the reactivity was shifted to the level of the nuclei of the almost mature spermatozoa at stage VII tubules ([Fig. 5G](#f05){ref-type="fig"}, arrowheads). Specific immunostaining could not be observed in spermatocytes, peritubular myoid cells or in cells of the interstitial compartment of the testis. To test the specificity of TCTEX1D4 immunoreactivity, we also performed pre-absorption experiments. Prior to the regular immunostaining procedure, we incubated the polyclonal TCTEX1D4 antibody with a recombinant TCTEX1D4 peptide. The immunostaining was completely abolished indicating that the differential staining pattern that we observed was indeed reflecting the TCTEX1D4 localization within the seminiferous tubules ([Fig. 5B](#f05){ref-type="fig"}). Quantitative analysis of mRNA abundance in isolated germ cell populations by qRT-PCR revealed that relative expression levels of Tctex1d4 is elevated in spermatocytes fraction ([Fig. 5M](#f05){ref-type="fig"}). This expression is maintained high in the round spermatids fraction being, however, markedly decreased in elongated spermatid fraction. ![TCTEX1D4 localization in testis.\ Mouse testis sections were stained with DAPI (nucleus, gray in A--C,E,F,H,I,K,L), and an anti-TCTEX1D4 antibody (CBC8C), and visualized by Cy3-labeled secondary antibody (red in A,B,D,F,G,I,J,L). (**A**) Mouse testis stained with antibodies to TCTEX1D4 (CBC8C) and Cy3-labeled secondary antibody. (**B**) TCTEX1D4 antibody pre-absorbed to a TCTEX1D4 peptide. (**C**) Mouse testis stained with antibodies to Claudin-11 and Cy3-labeled secondary antibody for visualization of the BTB. Different stages of spermatid differentiation are shown as enlarged images: (**D--F**) stage IV, (**G--I**) stage VII and (**J--L**) stage X. Overlays of DAPI and Cy3 staining are shown in A--C,F,I,L. Arrows indicate the BTB, asterisks indicate late elongating spermatids, closed circles indicate acrosome-like structures of early elongating spermatids and arrowheads point to focal regions within the spermatid cytoplasm. (**M**) Relative expression values for the isolated cell fractions were calculated by the ΔΔ Ct-method. \*Increased mRNA expression compared to the control (testis) above 1.5-fold or below 0.75-fold. \*\*Changes in expression levels of more than 2-fold or below 0.5-fold. Sg, spermatogonia; Spc, spermatocyte; rSd, round spermatid; eSd, elongated spermatid; Srt, Sertoli cell. Scale bars: 50 µm in A--C and 10 µm in F,I,L.](bio-02-05-453-f05){#f05} Given the presence of TCTEX1D4 in late stage germ cells, we further analyzed the subcellular localization of this protein in mature human sperm ejaculate ([Fig. 6](#f06){ref-type="fig"}). The results show that TCTEX1D4 is present along the entire length of the flagellum, including principal and endpiece, and more predominantly in the midpiece region, where mitochondria are concentrated ([Fig. 6A](#f06){ref-type="fig"}). TCTEX1D4 is also present in the head, particularly in the acrosome, but this pattern is only visible in some spermatozoa ([Fig. 6A,B](#f06){ref-type="fig"}, asterisks). Of note, the subcellular localization pattern is similar when using either the N- or the C-terminus anti-TCTEX1D4 antibodies (data not shown). To confirm and further characterize TCTEX1D4 subcellular localization, antibodies against the axonemal component tubulin (anti-acetylated-α-tubulin) and mitochondria (TOM20) were used ([Fig. 6A,B](#f06){ref-type="fig"}, respectively). Merged images clearly show that TCTEX1D4 co-localizes with axoneme and mitochondria. Relatively to the potential subcellular sites of PPP1CC2-TCTEX1D4 co-localization in human sperm, PPP1CC2 was observed in the posterior, equatorial and acrosomal regions of the head and along the entire flagellum, including the mid-piece, upon sperm staining with the CBC502 antibody ([Fig. 6C](#f06){ref-type="fig"}). This is the expected PPP1CC2 sperm distribution and past work from our laboratory has shown the interaction of PPP1CC2 with β-tubulin by mass spectrometry in human sperm ([@b16a]). ![TCTEX1D4 subcellular localization in human sperm.\ (**A**) Human ejaculate sperm was stained with α-tubulin (anti-acetylated-α-tubulin, red), TCTEX1D4 (CBC8C, green) and nucleus (Hoechst, blue), and subjected to confocal microscopy analysis. ROI image on the right is shown for an easier visualization of the co-localization in the axoneme (white arrowheads) and in the acrosome (white asterisks). (**B**) Spermatozoa were stained for mitochondria (TOM20, red), TCTEX1D4 (CBC8C, green) and nucleus (Hoechst, blue). ROI image on the right is shown for an easier visualization of the co-localization in the midpiece (white arrowheads) and in the acrosome (white asterisks). (**C**) Spermatozoa were stained for PPP1CC2 (CBC502, green) and nucleus (Hoechst, blue). ROI image on the bottom is shown for a closer visualization of the PPP1CC2 localization. Images are representative of three independent experiments. All images were obtained at 100× magnification. Scale bars: 5 µm.](bio-02-05-453-f06){#f06} TCTEX1D4 and PPP1 co-localize at MTOC/microtubules in mammalian cells {#s2e} --------------------------------------------------------------------- A Myc-TCTEX1D4 construct and mouse anti-Myc antibodies were used to confirm TCTEX1D4 subcellular localization and address TCTEX1D4-PPP1 co-localization in mammalian cells. The subcellular localization of transfected TCTEX1D4 was first analyzed in a spermatogonia cell line, GC1-spg, where TCTEX1D4 was detected in the nucleus and cytoplasm, being enriched in the MTOC and in the emergent microtubules. These data are confirmed by the co-localization with specific subcellular markers: centrin, that specifically stains the centrioles present in MTOC, and β-tubulin, that stains the microtubules ([Fig. 7A](#f07){ref-type="fig"}). ![TCTEX1D4-PPP1 binding regulates the localization of the holoenzyme at microtubules and MTOC.\ (**A**) GC1-spg cells (top) and COS-7 cells (bottom) were transfected with Myc-TCTEX1D4, labeled with anti-Myc and Texas-Red anti-mouse antibodies. GC1-spg cells were also immunostained with anti-β-tubulin antibody to visualize microtubules (confocal microscopy analysis), while COS-7 cells were immunostained with anti-centrin antibody to label the microtubule organizing center (MTOC) (epifluorescence microscopy analysis). All images are at 100× magnification. Scale bars: 10 µm. Negative controls only with secondary antibodies were performed (data not shown). (**B**) COS-7 cells were transfected with wild-type Myc-TCTEX1D4 or the Myc-TCTEX1D4-RVSA mutant, which has reduced ability to bind PPP1C. Arrowhead indicates MTOC. All images are at 100× magnification and were visualized in a confocal microscope. Scale bars: 10 µm (top and bottom rows), 5 µm (middle row). White arrows indicate the profiles localization. (**C**) Fluorescence intensity profiles representing the voxels through the white arrowed lines indicated in B. (**D**) Co-localization coefficients were determined for the percentage of PPP1CC co-localizing with TCTEX1D4 (black columns), and the percentage of TCTEX1D4 co-localizing with PPP1CC (gray columns), in cells transfected either with wild-type (Myc-TCTEX1D4) or mutated (Myc-TCTEX1D4-RVSA) TCTEX1D4. Results were plotted and significant differences were found (\**P*\<0.001; *n* = 15).](bio-02-05-453-f07){#f07} To further characterize the TCTEX1D4-PPP1 holoenzyme, COS-7 cells were transfected with Myc-TCTEX1D4 and stained with anti-Myc (TCTEX1D4 detection, red) and CBC3C (endogenous PPP1 detection, green) antibodies ([Fig. 7B](#f07){ref-type="fig"}). Again, TCTEX1D4 was observed in the cell nucleus and cytoplasm, where it was present in microtubules and enriched in the MTOC ([Fig. 7B](#f07){ref-type="fig"}). PPP1CC co-localizes with TCTEX1D4 mainly in these regions: inside the nucleus and in the MTOC ([Fig. 7B](#f07){ref-type="fig"}). Interestingly, PPP1CC also accompanies TCTEX1D4 in the microtubules emerging from the MTOC, suggesting that TCTEX1D4-PPP1CC binding might be important for PPP1CC microtubular localization. In order to address this hypothesis, we used the Myc-TCTEX1D4-RVSA mutant that is characterized by a 35% decrease in the TCTEX1D4-PPP1CC binding ([Fig. 3C](#f03){ref-type="fig"}). Remarkably, PPP1CC/TCTEX1D4-RVSA co-localized to a much lower extent in the MTOC and along the microtubules emerging from the MTOC ([Fig. 7B](#f07){ref-type="fig"}). This is clearly indicated by the fluorescence intensity profiles ([Fig. 7C](#f07){ref-type="fig"}) representing the voxels through the white arrows indicated in [Fig. 7B](#f07){ref-type="fig"} microphotographs. The PPP1CC signal was particularly decreased in both the MTOC and in microtubules, suggesting that TCTEX1D4 is at least partially responsible for PPP1C MTOC/microtubular localization/transport. Results were further confirmed by quantitative correlation analysis of PPP1CC/TCTEX1D4 co-localization percentages in the cytoplasm of TCTEX1D4 transfected cells ([Fig. 7D](#f07){ref-type="fig"}). While the percentage of cytoplasmic PPP1CC co-localized with TCTEX1D4 decreased by ∼34% (from 41.5±2.5 to 27.5±2.7%), when the RVSF motif was mutated to RVSA the percentage of the TCTEX1D4 cytoplasmic pool co-localizing with PPP1CC also decreased by ∼27% (85.9±1.3 to 62.7±2.2%). Furthermore, the percentage of transfected cells in which PPP1CC/TCTEX1D4 co-localizes decreased 3-fold in case of the TCTEX1D4-RVSA mutant. Essentially, both PPP1CC localization at the MTOC and its microtubular transport appear to be dependent on PPP1CC binding to the dynein LC TCTEX1D4. Discussion {#s3} ========== The present work gives an insight into the putative role of the dynein light chain protein TCTEX1D4 within the testis. TCTEX1D4 forms a complex with PPP1CC2, a phosphatase that was shown to play a role in sperm motility ([@b16]). The PPP1-TCTEX1D4 interaction was first identified by a yeast two-hybrid approach. The results were further confirmed by overlay and co-immunoprecipitation techniques ([Fig. 3](#f03){ref-type="fig"}). TCTEX1D4 has a PPP1 binding motif that is evolutionarily conserved among species ([Fig. 2](#f02){ref-type="fig"}). Studies with TCTEX1D4 PPP1-binding mutants strengthened the importance of this PPP1 interaction motif for complex formation ([Fig. 3C](#f03){ref-type="fig"}). The only dynein light chain that processes a putative motif, besides TCTEX1D4, is TCTEX1D3 (^150^KVLF^153^), but the motif is mapped to the globular domain Tctex1, which might be masked and thus not as easily accessible for PPP1 binding as for TCTEX1D4 ([Fig. 1B,C](#f01){ref-type="fig"}). Functionally, while the ICs/LCs form the cargo complex, the LC confer specificity to this binding ([@b34]; [@b46]), regulate other molecules or stabilize the assembly of the motor dynein complex ([@b11]). PPP1CC is known to bind to and dephosphorylate the IC ([@b57]), and most probably PPP1 binding to TCTEX1D4 would facilitate its access and binding to the IC. Furthermore, PPP1 may additionally dephosphorylate TCTEX1D4 itself, and therefore regulate its function. Of note, TCTEX1D4 has a comparatively longer disordered N-terminus ([Fig. 1B,C](#f01){ref-type="fig"}) that potentially gives it a more flexible and exposed arm to bind different cargo and diverse regulatory proteins, as well as being regulated by reversible phosphorylation. Serine phosphorylation appears to be the most relevant post-translational modification for TCTEX1D4, with several putative target kinases identified, supporting the relevance of its binding to the Ser/Thr phosphatase PPP1 ([Fig. 1A](#f01){ref-type="fig"}). Also, the results of the putative binding sites for cyclins and MAPK reinforce the Ser24 phosphorylation site predicted for cyclin/CDK complex and MAPK, which sustain a possible role for TCTEX1D4 in the cell cycle, proliferation and differentiation processes, also controlled by the TGFβ signaling pathway ([@b48]). However, the binding sites for cyclins and MAPK are localized in the globular domain; thus, the motifs\' availability, for example in loops within the globular domain, requires further confirmation ([Fig. 1A](#f01){ref-type="fig"}). In contrast to TCTEX1, TCTEX1D2 and TCTEX1D3 that have orthologs in *Chlamydomonas* genus ([@b10]; [@b19]; [@b41]), TCTEX1D4 emerged only in vertebrates, possibly by duplication, which may suggest the gain of novel and specialized functions for this protein in this phylum ([Fig. 2](#f02){ref-type="fig"}). One of these functions might imply the binding to PPP1. Interestingly, the TCTEX1D4 PPP1BM emerged in the placental mammals at the same time as PPP1CC2, the testis enriched and sperm specific isoform. The TCTEX1D4 binding mutants experiment show a decrease in binding but not a complete loss. This may be explained by the unusual sequence surrounding the TCTEX1D4 RVSF motif, which is similar to a palindrome with a high percentage of prolines -- **P**SLG**P**V**P*P****LGS*[RVSF]{.ul}*SGL****P***LA**P**ARWVA**P** (**bold**: prolines; *italic*: palindrome; [underlined]{.ul}: PPP1BM). This sequence is likely to form a structured arm forcing towards the RVSF motif, even when it is mutated to AAAA, to enter the PPP1 hydrophobic pocket to which the RVxF motif is known to bind. It is possible that RVSF ablation leads to the destruction of the arm, and consequently to the ablation of TCTEX1D4-PPP1 binding, but this needs further proof. Another possible hypothesis to explain the observed partial reduction in binding is that other important binding sites, which are not yet described, could also be present. TCTEX1D4 tissue expression profile indicated that the protein is expressed in several tissues, but to a higher extent in ovary, spleen, lung and placenta, where PPP1 is also present ([@b6]) ([Fig. 4](#f04){ref-type="fig"}). These results are in agreement with the EST *TCTEX1D4* profile, and also with previous results, describing *TCTEX1D4* in a human placenta cDNA library by yeast two-hybrid and by RT-PCR in human testis and placenta ([@b35]). Since the predicted molecular mass of TCTEX1D4 is 23.4 kDa, the observed band shift from 24.9 kDa to 28.4 kDa most probably results from post-translational modifications in the predicted sites, such as phosphorylations and/or glycosylations ([Fig. 1A](#f01){ref-type="fig"}). By immunofluorescence analysis we showed that TCTEX1D4 is expressed differentially in the seminiferous tubules of mouse testis. TCTEX1D4 is enriched at the cell--cell junctions of the BTB. It is stated that TCTEX1D4 interacts with endoglin and TGFβRII receptors in placenta and in Hela cells ([@b35]). Also, in Mv1Lu cells TCTEX1D4 inhibits both TGFβ1/3 signaling by increasing the retention time of both receptors at the cell surface and blocking their internalization ([@b35]). TGFβ signaling has also been shown to participate in the regulation of the BTB physiology ([@b62]; [@b64]). Although the BTB is one of the tightest blood--tissue barriers, it has some permeability in the stages VIII to IX of the germ cell cycle to allow for the migration of preleptotene/leptotene spermatocytes into the adluminal compartment. The current hypothesis is that the internalization (endocytosis) and recycling events are evenly balanced. However, during the stages VIII to IX the internalization event is increased leading to an imbalance and a permissive BTB ([@b64]). Cytokines, TGFβ3 and TNFα, were already shown to be involved in these phenomenon by increasing endocytosis of the membrane receptors ([@b31]; [@b63]; [@b64]; [@b61]). Therefore, TCTEX1D4 might have an important role in the regulation of the BTB, either by preventing higher levels of receptor internalization and thereby maintaining the balance before the stages VIII to IX, or by stopping the effect of the cytokines and re-establishing the balance after the preleptotene/leptotene spermatocytes migration. TCTEX1D4 is also present in spermatids in an acrosome-like pattern and in focal regions of the cytoplasm ([Fig. 5](#f05){ref-type="fig"}). The acrosome-like pattern might indicate a role in the acrosome cap formation whereas the focal cytoplasmic staining might indicate the preassembly of the axonemal components within the cytoplasm or cytoplasmic droplets with excess cytoplasm targeted for removal. These localization patterns resemble that of focal adhesion kinase (FAK) protein that displays phosphorylation-dependent localization in the testes ([@b32]). The immunohistochemistry and qRT-PCR analysis suggest that *Tctex1d4* mRNA level is increased in spermatocytes, being only translated in round spermatids since no significant staining was seen in these germ cells ([Fig. 5](#f05){ref-type="fig"}). This delay between transcription and translation events is common in testis ([@b20]; [@b22]). Also, during spermatid differentiation a strong downregulation of this gene was observed ([Fig. 5M](#f05){ref-type="fig"}). Furthermore, immunocytochemistry analysis confirmed that TCTEX1D4 is present in mature spermatozoa, particularly in the flagellum, being enriched in the midpiece region ([Fig. 6A,B](#f06){ref-type="fig"}). The differential expression and the multiple subcellular localizations of TCTEX1D4 in testicular cells may indicate that TCTEX1D4 has several functions. Based on our data, TCTEX1D4 has yet unknown functions at the BTB but is involved in the spermatid differentiation in mouse testis. The co-localization with microtubules in Cos7 cells and in human spermatozoa suggests a role of TCTEX1D4 in both organelle rearrangements and protein transport (cytoplasmic functions) and in ciliar/flagellar motility (axonemal functions). Similar functions have been described for its family member DYNLT1, which is both axonemal and cytoplasmic ([@b19]; [@b27]). In sperm immunofluorescence microphotographs it is difficult to distinguish between different structures, thus it remains unclear whether TCTEX1D4 will have a role in the axoneme apparatus flagellar function (for sperm motility) or as a minus-end cytoplasmic dynein motor in the intraflagellar transport (IFT) ([@b40]) ([Fig. 6A](#f06){ref-type="fig"}). IFT is a motility event in flagella, unrelated to dynein-based motility, which has been observed as a bidirectional transportation of granule-like particles along the length of flagella ([@b28]). According to both PPP1C and TCTEX1D4 distribution in sperm, the localization of the TCTEX1D4/PPP1CC2 complex appears to be primarily restricted to the flagellum and to a lesser extent in the head ([Fig. 6](#f06){ref-type="fig"}). This suggests a putative role for the TCTEX1D4-PPP1CC2 holoenzyme in sperm motility, where TCTEX1D4 could have its dynein functions altered by PPP1CC2 dephosphorylation and/or would function to transport PPP1CC2 to other possible motility-related PPP1C targets. Studies in rainbow trout and chum salmon sperm have shown that a TCTEX1D3 homologue (LC2) of the outer dynein arm is phosphorylated when sperm is activated ([@b24]) and that dephosphorylation by PPP2 induces immotility in sperm ([@b23]). This model could be similar to what happens in human sperm with TCTEX1D4 and PPP1CC2 ([Fig. 8](#f08){ref-type="fig"}). Since mammalian sperm contains a different isoform of PPP1C, the sperm-specific PPP1CC2, and TCTEX1D4 only appeared in vertebrates, this dynein light chain could be the effector of PPP1CC2 activity in mammals, inducing sperm immotility. [Fig. 8](#f08){ref-type="fig"} depicts other possible functions of the complex TCTEX1D4/PPP1CC2 in sperm physiology. ![Schematic representation of TCTEX1D4 and TCTEX1D4-PPP1CC2 localization in sperm.\ TCTEX1D4 is present in the head and along the tail of human mature spermatozoa. PPP1CC2 is present in the posterior, equatorial and acrosome regions of the head, as well as in the entire tail, including midpiece. PPP1 was shown to be present in the central pair apparatus axoneme, associated with the C1 microtubule, and to a lesser extent in the outer doublet microtubules, in *Chlamydomonas*. The diagram shows the putative roles that could be assigned to TCTEX1D4 (and the TCTEX1D4-PPP1CC2 complex) at these locations. In the head, TCTEX1D4 may have a role in the acrosome reaction, while along the tail it could have a function in sperm flagellar motility and/or in vesicular intraflagellar transport (IFT). In the midpiece, where mitochondria are concentrated and TCTEX1D4 is highly enriched, TCTEX1D4 may be involved in the energy production necessary for the flagellar motility. Rsp, radial spoke; C1, central pair microtubule 1; B, tubule B; A, tubule A; IDA, inner dynein arm; ODA, outer dynein arm.](bio-02-05-453-f08){#f08} Furthermore, PPP1 and TCTEX1D4 co-localize in the MTOC and microtubules, and TCTEX1D4 appears to be at least partially responsible for PPP1 transport along microtubules and PPP1 targeting to MTOC ([Fig. 7](#f07){ref-type="fig"}). This localization is consistent with the role of TCTEX1D4 as a dynein LC thus linked to microtubules and responsible for PPP1C microtubule-dependent retrograde transport. In this way, TCTEX1D4 may regulate PPP1 functions since PPP1 localization at microtubules is important to regulate microtubule dynamics (e.g. in mitosis ([@b49])) and to regulate cargo transport, by mediating cargo dissociation from the kinesin motor unit ([@b37]; [@b36]). Of note, only part of the TCTEX1D4 cytoplasmic pool is associated with microtubules, as it was also reported to occur for TCTEX1, suggesting several distinct roles for these proteins ([@b45]). The presence of TCTEX1D4 in the microtubules and MTOC is in accordance with the previous immunohistochemistry observations, and strongly suggests a role for TCTEX1D4 in microtubules organization and dynamics. Indeed, dyneins were previously shown to have an important role in MTOC cellular positioning, re-orientation throughout the cell cycle and migration, and in microtubule dynamics ([@b18]; [@b39]; [@b44]). Interestingly, the testis protein TLRR (lrrc67), found in the MTOC of germ cells and in cell cultures ([@b56]), binds to PPP1CC2, β-tubulin, KIF5B (Kinesin-1B), DYNC1I1, and was suggested to have a role in sperm flagellum formation ([@b56]). The authors further proposed that the TLRR-PPP1CC2 complex regulates the activity of the (plus end) kinesin-1B motor unit in testis. In light of our studies, we suggest that the TCTEX1D4-PPP1CC2 complex may function in the opposite direction, regulating the (minus end) motor unit dynein that comprises TCTEX1D4 as its LC. Additional questions regarding the specific role of this complex in spermatogenesis and sperm physiology will require further work, but will provide new insight into the biology of human reproduction. Materials and Methods {#s4} ===================== Plasmid constructs {#s4a} ------------------ Construction of plasmids was carried out as described previously ([@b60]). The following plasmids were prepared: [pAS2-PPP1CA]{.ul} -- *PPP1CA* cDNA was directionally subcloned into *Eco*RI/*Bam*HI digested pAS2-1 (Clontech, Saint Germain-en-Laye, France) to produce pAS2-PPP1CA. [pAS2-PPP1CC1]{.ul} -- *PPP1CC1* cDNA was directionally subcloned into *Sal*I/*Sma*I digested pAS2-1 (Clontech, Saint Germain-en-Laye, France) to produce pAS2-PPP1CC1. [pAS2-PPP1CC2/pAS2-PPP1CC2end]{.ul} -- The 200 bp *PPP1CC2*-specific C-terminus-containing *Pst*I fragment was transferred from pTacTac-PPP1CC2 into *Pst*I digested pAS-PPP1CC2 to produce pAS-PPP1CC2 or into *Pst*I digested pAS2-1 to produce pAS-PPP1CC2end ([@b12]). The pAS2-PPP1CC constructs were used in the yeast two-hybrid screening. [pET-TCTEX1D4]{.ul} -- *TCTEX1D4* cDNA was PCR-amplified forward (5′-gcgaattcatggccagcaggcctc-3′) and reverse (5′-ccgctcggtcactcgcagtagagc-3′) from clone IMAGE 30531412 and inserted into pET-28a vector (Novagen, Madison, Wisconsin, USA). [pET-TCTEX1D4-NT/CT]{.ul} -- The N-terminus portion of the *TCTEX1D4* cDNA was PCR amplified with pET forward primer and an internal reverse primer (5′-ccgctcgagtcaggcgggcgccaggg-3′). The pET-TCTEX1D4-NT construct comprises amino acids 1--101. Likewise, the C-terminus portion of the *TCTEX1D4* cDNA was PCR amplified with an internal forward primer (5′-gcgaattccgttgggtggcgcc-3′) and pET reverse primer. The pET-TCTEX1D4-CT construct comprises amino acids 102--221. The pET-TCTEX1D4 and NT and CT constructs were used in the overlay assay for PPP1C binding. [Myc-TCTEX1D4]{.ul} -- *TCTEX1D4* cDNA was PCR-amplified from pET-TCTEX1D4 with primers forward (5′-gcgaattccgatggccagcaggcctc-3′) and reverse (5′-ccgctcggtcactcgcagtagagc-3′), and inserted into *Eco*RI/*XhoI* sites of pCMV-Myc vector (Clontech, Saint Germain-en-Laye, France). This construct was used in immunoprecipitation and immunofluorescence. [pACT-TCTEX1D4]{.ul} -- *TCTEX1D4* cDNA was digested from Myc-TCTEX1D4 with *Eco*RI*/XhoI*, and inserted into *Eco*RI/*XhoI* digested pACT-2 (Clontech, Saint Germain-en-Laye, France), using standard molecular biology procedures. The pACT-TCTEX1D4 and pAS2-PPP1C constructs were used in the co-transformation assay. The pAS2-1/pACT-2 and the pVA3/pTD1 vectors (Clontech, Saint Germain-en-Laye, France) were used as co-transformation controls. [pET-TCTEX1D4-AAAA/Myc-TCTEX1D4-RVSA]{.ul} -- Mutagenesis of PPP1BM RVSF in *TCTEX1D4* cDNA was performed using the QuikChange Site-Directed Mutagenesis Kit (Stratagene, now Agilent Technologies UK Ltd, Edinburgh, UK) by mutating just the last or all the four amino acids to alanine in order to disrupt the PPP1BM. The pET-TCTEX1D4-AAAA was used in the overlay assay, whereas Myc-TCTEX1D4-RVSA construct was used in immunofluorescence studies. Antibodies {#s4b} ---------- The mouse anti-Myc tag (Cell Signaling, Danvers, Massachusetts, USA), the mouse acetylated anti-α-tubulin (Zymed Laboratories Inc., Cambridge, UK), the mouse anti-β-tubulin (Zymed Laboratories Inc., Cambridge, UK) and the rabbit anti-TCTEX1D4N (N-terminus of TCTEX1D4, PGGQRPSLGPVPPLGSRVSFSGLPLAPARWVAPSYRTEPVPGERWEAARA, Sigma--Aldrich Química, S.A., Sintra, Portugal) antibodies were purchased from the respective companies. The antibodies CBC3C (against the C-terminus of PPP1CC, detects both isoforms ([@b6])), CBC502 (specific for the C-terminus of PPP1CC2) and CBC8C (C-terminus of TCTEX1D4, WDVARDGLASVSYTNTSLFAVATVHGLYCE) were raised in rabbit and were already described ([@b3]; [@b14]; [@b38]; [@b53]). The mouse TOM20 (translocase of outer membrane 20 kDa subunit) antibody was a kind gift of Dr Michael Schrader (University of Aveiro, Aveiro, Portugal) ([@b9]). Yeast two-hybrid screening {#s4c} -------------------------- The methods for yeast two-hybrid screening of a human testis cDNA library using human PPP1C have been described previously ([@b3]; Fardilha et al., 2011b; [@b12]). Bioinformatics analysis {#s4d} ----------------------- Full protein sequences of intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs) were obtained from Ensembl database to check for PPP1 binding motifs. The ICs human homologues are: the axonemal inner arm IC1 (ENSP00000242317) and IC2 (ENSP00000308312), axonemal outer arm IC138 (ENSP00000360065) and IC140 (ENSP00000294664), and cytoplasmic DYNC1I1 (ENSP00000320130), DYNC1I2 (ENSP00000380308). The LICs human homologues are the cytoplasmic DYNC1LI1 (ENSP00000273130), DYNC1LI2 (ENSP00000258198) and cytoplasmic from intraflagellar transport DYNC2LI1 (ENSP00000330752). The LCs human homologues are the DYNLRB1/LC7/Roadblock (NP_054902.1), DYNLRB2/LC7/Roadblock (ENSP00000302936), DYNLL1/LC8 (ENSP00000376297), DYNLL2/LC8 (ENSP00000240343), TXNDC3/LC5 (ENSP00000199447), TXNDC6/LC5 (ENSP00000372667), DNAL1/LC1 (ENSP00000310360), DNAL4/LC6 (ENSP00000216068) DYNLT1/Tctex1, DYNLT3/RP3, TCTEX1D1, TCTEX1D2/Tctex2b, TCTEX1D3/Tctex2/Tcte3, and TCTEX1D4/Tctex2β. The last 6 comprise the Tctex1 family and the respective Ensembl IDs are depicted in the alignment [Fig. 2A](#f02){ref-type="fig"}. Eukaryotic Linear Motif (ELM) ([@b43]), Psipred ([@b25]), ScanProsite (ExPASy Proteomics Server), NetPhos, and NetNGlyc1.0 (CBS Prediction Servers) search engines were used to further characterize relevant motifs and post-translational modifications. For homology and evolutionary purposes, ClustalW2 and MEGA programs were used ([@b30]; [@b47]). Yeast co-transformation {#s4e} ----------------------- Yeast competent AH109 cells were co-transformed with pACT-TCTEX1D4 and pAS2-PPP1CA, pAS2-PPP1CC1, pAS2-PPP1CC2 or pAS2-PPP1CC2end, by the lithium acetate method (Fardilha et al., 2011b; [@b12]). Afterwards, the transformation mixture was plated on selective media containing X-α-Gal and incubated at 30°C to check for MEL1 expression as indicated by the appearance of a blue color (Clontech, Saint Germain-en-Laye, France). Co-immunoprecipitation and TCTEX1D4 tissue expression screening {#s4f} --------------------------------------------------------------- African green monkey (*Cercopithecus aethiops*) SV40-transformed kidney cells (COS-7, fibroblast-like, ATCC CRL-1651, Manassas, Virginia, USA) were grown in the appropriate medium (DMEM) and transfected with Myc-TCTEX1D4, harvested and lysed in lysis buffer (50 mM Tris-HCl, 120 mM NaCl, 4% CHAPS, 0.1 mg/ml Pepstatin A, 0.03 mM Leupeptin, 145 mM Benzamidine, 0.37 mg/ml Aprotinin and 4.4 mM PMSF in isopropanol). The lysates were pre-cleared with protein A sepharose slurry (Pharmacia, LKB Biotechnology, Bromma, Sweden) for 1 hour at 4°C with shaking. After centrifugation, protein sepharose and CBC3C (2 µg) were added to the supernatant, followed by overnight incubation at 4°C with shaking. Subsequently, the beads were washed three times with 50 mM Tris-HCl, 120 mM NaCl and resuspended in loading buffer. Samples were loaded in SDS-PAGE gel, and transferred to a nitrocellulose membrane. Immunodetection was performed using anti-Myc antibody (1:5000). For the tissue screening, tissues from adult Wistar rat strain (2--3 months) and human testis were lysed using a homogenizer in 1% SDS. Human testis biopsies were collected *in vivo*, in Hospital Central (Centro Hospitalar de Coimbra, Coimbra, Portugal), during procedures to collect organs for transplantation from adult healthy man donors. Biopsies for research purposes are covered by the legislation of the Portuguese Constitution (decreto-lei no. 274/99 of 22 July 1999). Both CBC8C (1:100) and anti-TCTEX1D4N (1:1000) antibodies were used in separate blots for immunodetection of protein expression. Immunoreactive bands were detected by enhanced chemiluminescence (ECL, GE Healthcare, Amersham Biosciences Europe GmbH, Freiburg, Germany) ([@b13]). Overlay assays {#s4g} -------------- A single *Rosetta* (DE3) (Novagen, Madison, Wisconsin, USA) colony expressing His-tagged TCTEX1D4 was selected and grown overnight in 3 ml Luria Bertani medium containing ampicillin (50 µg/ml) at 37°C. Expression was induced with 0.1 mM isopropyl-β-D-thio-galactopyranoside at 37°C. Samples were then treated as described elsewhere ([@b3]). The same procedure was also performed for TCTEX1D4-AAAA, TCTEX1D4-NT and TCTEX1D4-CT. Blots were overlaid with purified PPP1CC1 or PPP1CC2 (25 pmol/ml) and detected with CBC3C (1:5000) ([@b3]). Immunohistochemistry {#s4h} -------------------- For fluorescence microscopy analysis, cryosections were prepared. C57/Bl6 mice testes were fixed by perfusion with 4% paraformaldehyde, 0.1 M HEPES, pH 7.4 and immersed in 0.1 M phosphate buffer at room temperature for 6 hours, followed by immersion in 30% (w/v) sucrose solution at 4°C overnight. The tissue was frozen in isopentane at −30°C and stored at −80°C. Cryosections of about 8--10 µm were cut using a Cryostat (Leica Biosystems, Wetzlar, Germany). For immunohistochemistry, tissue sections were initially rehydrated and permeabilized in TBS-TT (TBS with 0.2% Triton-X and 0.2% Tween 20) for 30 minutes and then incubated with 10% (v/v) Roti-Block (Roth, Karlsruhe, Germany; diluted in dH~2~O) for 1 hour to reduce non-specific binding of antibodies. Sections were further incubated with primary antibodies against TCTEX1D4 (CBC8C, 1:150) or Claudin-11 (Claudin-11/OSP anti-rabbit; polyclonal antibody, Invitrogen, diluted 1:150) in 10% (v/v) Roti-Block in PBS for 1 hour at room temperature. After extensive washing with TBS, tissue sections were incubated with a secondary antibody (Cy3-conjugated goat anti rabbit IgG, diluted 1:500, Sigma, Taufkirchen, Germany) suspended in 10% (v/v) Roti-Block, for 1 hour, to visualize immune complexes. For DNA labeling, the secondary antibody was supplemented with 1 µg/ml 4′,6-Diamidino-2-phenylindole (DAPI, Gibco BRL). Sections were washed in TBS and mounted with Mowiol 4--88 (Roth). Specimens were analyzed using Nikon Instruments A1 Confocal Laser Microscope with standard filters for detection of Cy3 and DAPI. Digital images were obtained with a Nikon A1plus camera using the Nikon NIS Elements Advanced Research software. The use of mice was in accordance with the Guide for the Care and Use of Laboratory Animals from the Institute for Laboratory Animal Research. The local Ethics Committee approved the study and the procedures were in compliance with the current national laws. Expression analysis in isolated testicular germ cells {#s4i} ----------------------------------------------------- Isolation of cell populations from mouse testis was performed as described elsewhere ([@b8]). Isolated cells were analyzed by phase contrast microscopy and DAPI staining, and homogeneous cell populations were used for further analysis. Isolated cells were processed for RNA isolation (RNeasy mini kit, Qiagen, Hilden, Germany). Total RNA from the isolated cells was prepared using the RNeasy Plus Universal Midi Kit (Quiagen, Germany). The concentration of RNA was determined spectrophotometrically (NanoDrop 1000 Spectrophotometer, Thermo Scientific, Germany). For synthesis of cDNA, a reverse transcription reaction was carried out using 1 µg of RNA and the Transcriptor First Strand cDNA Synthesis Kit (Roche, Germany). Expression levels of distinct mRNAs were determined by qRT-PCR using the LightCycler 480 SYBR Green I Master (Roche, Germany) on 96-well plates with the LightCycler® 480 Real-Time PCR System (Roche, Germany) as already described ([@b8]). A combination of *Gapdh* and *Hprt* was used as reference genes for the testis and all expression levels were calculated as relative values using the mean of both reference genes. The samples were run in triplicate and the averages were used for calculation of expression levels of the different genes. The expression quantification of the *Tctex1d4* gene was calculated as described before ([@b8]) using the forward (5′-aggcacacagccccaatctgac-3′) and the reverse (5′-agccaggtctttggtagtctcctc-3′) primers. A cDNA obtained from the cell suspension of whole testis was used as control sample for qRT-PCR reactions. Markers specific for each germ cell were used to further reconfirm the purity of the isolated germ cells. All primers are listed in [supplementary material Table S1](http://bio.biologists.org/lookup/suppl/doi:10.1242/bio.20131065/-/DC1). Immunocytochemistry {#s4j} ------------------- GC1-spg (ATCC CRL-2053, Manassas, Virginia, USA) and COS-7 cell lines were grown using previously established conditions ([@b7]). GC1-spg are *Mus musculus* (strain BALB/c) type B spermatogonia cells, epithelial-like, that show characteristics of a stage between type B spermatogonia and primary spermatocytes. Cells were transfected with Myc-TCTEX1D4 or Myc-TCTEX1D4-RVSA with Lipofectamine 2000 (Invitrogen, Life Technologies S.A., Madrid, Spain) using standard procedures ([@b52]; [@b60]). Preparation of cells for immunocytochemistry was achieved by cold methanol fixation as described previously ([@b13]). Human ejaculated sperm was first washed three times in PBS, diluted and applied to coated coverslips. Subsequent steps were similar to those applied for the COS-7 cells. Ejaculated sperm was collected from healthy donors by masturbation into an appropriate sterile container (informed consents were signed allowing samples to be used for scientific purposes). Spermograms were performed by experienced technicians and only samples with normal parameters were used ([@b59]). For all methods, sperm was washed three times in 1× PBS. Anti-Myc (1:5000), CBC3C (1:1000), CBC8C (1:100) and CBC502 (1:1000) primary antibodies were used to detect the respective proteins. Fluorescent secondary antibodies anti-mouse Texas-Red (1:300) and anti-rabbit Alexa488 (1:300) were subsequently used. Nuclei were stained with Hoechst 33258 (1:2000, Polysciences Europe GmbH, Eppelheim, Germany) or DAPI (1:200, Vectashield, Vector Laboratories Burlingame, California, USA). Fluorescence images were acquired in an Olympus IX-81 inverted epifluorescence microscope (Olympus Portugal -- Opto-Digital Tecnologias, S.A., Lisboa, Portugal) using a ×100 objective, or on a Zeiss LSM-510 confocal microscope (Carl Zeiss Ltd, Wetzlar, Germany). For confocal microscopy, quantitative correlation analysis of PPP1CC and wild-type and mutant TCTEX1D4 was carried out with the Zeiss LSM 510 4.0 software ([@b52]), using images of delimited TCTEX1D4 transfected single cells. The co-localization coefficients were determined as the percentage of PPP1CC/TCTEX1D4 co-localizing pixels relatively to the number of pixels in the PPP1CC and in the TCTEX1D4 channels. Statistical analysis {#s4k} -------------------- SigmaPlot statistical package (SigmaPlot v.11, Systat Software Inc.) was used for statistical analysis. The Kolmogorov--Smirnov test was employed to test normality of distribution of the data. Significant differences between co-localization coefficients were evaluated with the unpaired Student\'s *t*-test (*P*\<0.001, alpha = 0.050). Supplementary Material ====================== ###### Supplementary Material This work was supported by the Centre for Cell Biology of the University of Aveiro, by grants from FCT of the Portuguese Ministry of Science and Higher Education to L.K.-G. (SFRH/BD/42334/2007), S.I.V. (SFRH/BPD/19515/2004), S.L.C.E. (SFRH/BD/41751/2007), J.A. (SFRH/BPD/73512/2010), P.J.E. (SFRH/BPD/27021/2006), E.F.C.S. (POCI/SAU-OBS/57394/2004; PPCDT/SAU-OBS/57394/2004) and M.F. (PTDC/QUI-BIQ/118492/2010), by a Re-equipment Grant (REEQ/1023/BIO/2005), by CRUP (E-92/08;B-32/09) and by the German Academic Exchange Service (DAAD) with a grant to G.L. (DAAD/50112116). **Competing interests:** The authors have no competing interests to declare. [^1]: Deceased 2nd March 2010
tomekkorbak/pile-curse-small
PubMed Central
Q: failed command: WRITE FPDMA QUEUED - cause of server running slow? A headless Linux NFS fileserver has been running slow for the last couple days (based on subjective reports from users). I checked journalctl did not see any relevant errors. However, when I connected a monitor, I was greeted by a screen full of these errors: failed command: WRITE FPDMA QUEUED Here's a photo: What are some suggested next steps? Should I just replace the disk? A: Only one disk is having issues, according to what is visible here. But it's not obvious whether it's the drive, or the cable, or the controller. I would first reboot, to reset the hardware. It could just be that the controller was temporarily confused and literally turning it off and on again would help. If the error comes back after rebooting, then I would plug that drive into a different SATA port, and if necessary plug some other drive into that port. If the error is still on the same port, then the problem is with the controller. But if the error "moves" to the new port, then it's either the cable or the drive. At this point I would replace the SATA cable. If the error goes away, then it was a bad cable. If you still have the error, then it's the drive.
tomekkorbak/pile-curse-small
StackExchange
Last year’s Oscar nominations drew howls of protests for their lack of diversity. This year, it’s even worse. “Creed” was written and directed by the black Ryan Coogler and starred a black man, but the only nominee was a white man. “Straight Outta Compton” had a great acting ensemble of mostly young, black unknowns, and was directed by the black F. Gary Gray. But the film’s only nomination: for its screenplay, written by two Caucasians. Last year, the hopes for diversity were based on one film, Paramount’s “Selma,” which earned two nominations, for best pic and song (winning the latter). This year, there were more opportunities, including “Creed,” “Straight Outta Compton” and “Chi-raq,” as well as “Beasts of No Nation” (directed by Cary Fukunaga). As with last year, the Hispanic/Latino filmmakers were represented only by Alejandro Gonzalez Inarritu and his team in the “money” categories. Some may conclude that the nominations reflect institutional bias against minorities and women within the Academy of Motion Picture Arts & Sciences, but the problem is with Hollywood’s major studios and agencies. There were 305 films eligible this year. If hiring reflected the U.S. population, Oscar voters would have weighed 150-plus films directed by women, 45 directed by blacks, 50 by Hispanics, and dozens of movies by directors who are Asian-American, LGBT individuals, people with disabilities and members of other minorities. Of course, the actual tallies were a fraction of those numbers. Surprising omissions from the actor race this year included Idris Elba for “Beasts of No Nation,” Will Smith for “Concussion,” Michael B. Jordan from “Creed” and the many young actors in “Compton.” Last year, #OscarSoWhite lit up the Twitter-sphere, generally focused on the acting and directing categories, mostly due to omission of actor David Oyelowo and director Ava DuVernay from “Selma.” But in fact, the imbalance carries into the majority of categories due to lack of opportunity. In the Jan. 14 announcement, the Academy of Motion Picture Arts & Sciences listed 23 total producers for the eight movies picked in the best-pic race; seven were women. For the two screenplay races, 17 individuals are nominated, with four women and no racial minorities. The sole nom for “Straight Outta Compton” went to a self-described “white Jewish gay guy from Connecticut” and his white writing partners, Jonathan Herman and Andrea Berloff.) Several Oscar categories traditionally offer a mix of gender, race and sexual orientation among nominees, including documentaries, shorts, feature-animation, costume design, hair/makeup and editing. That’s true this year too. But in many of the artisan races, it’s an almost all-male list (e.g., cinematography, sound editing, sound mixing). One breakthrough this year: Sara Bennett joined two colleagues in the visual effects category, grabbing a nom for “Ex Machina.” That makes one woman of the 19 total nominees (for five films) in that category. The guilds don’t keep records on the racial breakdown of their membership. But most have training programs designed to help foster more career advancement opportunities for minorities and women. But so far, hiring in Hollywood is still overwhelmingly dominated by white men. For optimists, change is in motion. At the Governors Awards in November, AMPAS president Cheryl Boone Isaacs, who is African-American, announced the formation of A2020, a five-year plan in which the Academy and the studios will work on programs to ensure that top executives expand their thinking when hiring, mentoring and encouraging new talent. For pessimists, a five-year plan is too slow. But the harsh reality is that the film industry works at a glacial pace, locking in stars, writers and directors several years in advance. So even though studios and agencies may say they want immediate change, it’s a question-mark how realistic that is; an overhaul was not evident in this year’s nominations, and it may not be apparent next year either. Awareness of the problem isn’t new in the film industry; various solutions have been proposed, only to fade away. In 1956, Variety ran a series of articles asking why there aren’t better roles for black actors. Three decades later, the situation hadn’t improved. On Feb. 19, 1982, Variety carried the front-page banner “NAACP faults film employment.” At a press conference, the group released a “white list,” naming 43 films “in which the organization says blacks have been excluded from significant roles in front of and behind the cameras.” The story added that every major studio was represented on the list of movies. Similarly, on Feb. 12, 1991, Variety ran a front-page story about the findings of the DGA Women’s Steering Committee: Of 207 feature-film assignments, 11 went to women. That’s 5.3%. Nearly 25 years later, the number had barely moved: Women comprised 9% of directors on the top 250 domestic grossing films and 12% of directors on the top 500 domestic grossing films, according to a new report by the Center for the Study of Women in Television and Film at San Diego State University. The few 2015 Hollywood films from women directors included “Fifty Shades of Grey,” “The Intern,” “Suffragette,” “The 33,” “By the Sea” and “Pitch Perfect 2.” Films directed by blacks, Asian-Americans and Hispanics included “Straight Outta Compton,” “Creed,” “Beasts of No Nation,” “The Revenant” and “Chi-raq.” They got some Oscar attention, but the diversity factor overall is still low. The Academy in June invited a record 322 new members, with many reflecting the Academy’s push for greater diversity among its membership. But the current membership — overwhelmingly Caucasian and over-50 — won’t see a fast overhaul soon, due to membership rules. The Academy is an honor society, in which industry experience is the primary consideration to join. Hollywood history has been filled with those demographics, and AMPAS is not about to kick out its current members. The film industry is about two decades behind television. The boom in cable channels means more risks and more diversity, in terms of gender, race and sexual orientation. This year’s Emmy Awards marked a milestone as Viola Davis became the first African-American to win for lead actress in a drama for ABC’s “How to Get Away with Murder.” The success of shows that run the gamut of “Scandal” and “Empire to “Key & Peele,” “Black-ish,” “Orange is the New Black” and “Transparent” offer a reminder that diversity is good for showbiz, in front of and behind the camera. UPDATE: Gil Robertson, president of the African-American Film Critics Association, told Variety that he was “shocked but not entirely surprised” over the lack of diversity in nominations Thursday. “I think there’s an ongoing disconnect with the Academy members,” he said. “We have to re-double our efforts to convince them that diversity is important and that they should be open to the stories of other people.” The AAFCA recently named Universal’s N.W.A biopic “Straight Outta Compton” the best film of the year, with runner-up going to Ryan Coogler’s “Creed.” Robertson admitted that he was perplexed that “Straight Outta Compton” had not received more traction among Academy members. The film landed a single nomination for screenwriting. “Even the oldest Academy members have been exposed to hip-hop culture becoming part of the mainstream,” he said. “So this makes them look totally out of step.” Robertson expressed disappointment over the exclusions of Idris Elba for “Beasts of No Nation” and Will Smith for “Concussion” and noted that Oscarcast host Chris Rock is likely to highlight the lack of diversity during the ceremonies. Joe Hall, founder and president of The Ghetto Film Schools in New York and Los Angeles, said he was unsurprised by the exclusions due to the lack of effort at public high schools to train minority students in filmmaking. “The nominations are actually a distraction from the question of why we are not building a pipeline to generate diverse candidates,” Hall said. Jeff Friday, founder of the American Black Film Festival, said the lack of diversity in nominations stems from the lack of diversity in the Academy membership. “The composition of the membership is very homogeneous and that’s going to be reflected in their choices,” he added. “I know the issue is close to the heart for Cheryl Boone Isaacs but it’s also not something that will change right away.” (Pictured, left to right: “Concussion,” “Straight Outta Compton,” “Creed,” “Beasts of No Nation”)
tomekkorbak/pile-curse-small
OpenWebText2
Feh and the identify command are two of the tools I use for viewing and managing images on Linux. They are fast, flexible, and can be stuffed into scripts for automating operations, which is especially valuable when you work with artists or marketing people who have large image galleries to maintain. For me, they are faster and better for managing large numbers of images than graphical image managers, which tend to require too much clicking and poking through nested menus to find what I want, if they even have it. feh The feh X11 image viewer is my favorite fast, lightweight image-viewing tool. Feh runs in any X terminal. Feh displays single images, slideshows, montages, thumbnails, and lists of images. It runs primarily from the command line, though it also has a right-click menu on open images. Firecracker Feh supports all the image file formats supported by Imlib2, which includes PNG, JPEG, TIFF, PNM, BMP, GIF, XPM, and TGA. It simplest usage is to open a single image. feh crackerdog.jpg shows a picture of my dog Firecracker. feh displays images at their native resolution. You can shrink large images by specifying a smaller geometry in pixels: $ feh -g 400x300 image.png Your image proportions are preserved, so you don’t have to figure out the exact proportional geometry. feh --multiwindow opens all images in the current directory in their own windows. Closing any single window closes all of them, or right-click on any image to open a menu and click Exit. Launch a slideshow from the current directory with a duration of 5 seconds per slide, in fullscreen: $ feh --fullscreen --slideshow-delay 5 Press Alt+tab to cycle back to your console and stop the slideshow by pressing Ctrl+c , or right-click any image, and click Exit from the menu. When I have a lot of images to review, I put the filename at the top left and display EXIF data at the bottom left. --draw-tinted puts a background on the EXIF data to make it more readable: $ feh --draw-filename --draw-tinted --draw-exif --fullscreen --slideshow-delay 5 Displaying image with feh. This example displays all the images in a directory one at a time, limited to a size of 640×480, sorted by filename, with filenames displayed in the image window. feh -g 640x480 -d -S filename images/ Press the spacebar to advance through the images. The right and left arrow keys navigate forward and backward, and the up and down arrow keys zoom in and out. This command creates a thumbnails gallery from the current directory, with each thumbnail sized to 200×200 pixels, and displays the name and size of each image: $ feh --thumbnails --thumb-height 200 --thumb-width 200 --index-info "%nn%wx%h" Click on any thumbnail to open the full image. You can save an image of your thumbnails by appending the --output option, for example --output thumbnails.png . You can create a montage, and preserve it as a new image: $ feh --montage --thumb-height 200 --thumb-width 200 --index-info "%nn%wx%h" --output montage.png List images in a directory with their dimensions and file sizes: $ feh -l NUM FORMAT WIDTH HEIGHT PIXELS SIZE ALPHA FILENAME 1 jpeg 1200 800 960k 529k - ./backhoe-munch.jpeg 2 jpeg 1200 800 960k 534k - ./backhoe-spit.jpeg 3 jpeg 1200 1086 1M 663k - ./chipper-dogs.jpeg 4 jpeg 1200 834 1M 242k - ./cinder-donut-shop.jpg 5 jpeg 800 1200 960k 353k - ./dee-walt-table-saw.jpg Getting Image Information with Identify Graphical file managers don’t always display the image file information you want, or they make you wade through menus that let you select only one option at a time and then close, so you have to keep going back over and over to configure multiple options. The identify command, which is part of the fabulous ImageMagick suite of image manipulation tools, quickly extracts the image type, width and height, bit depth, file size, and color profile: $ identify sheba.png sheba.png PNG 1280x720 1280x720+0+0 8-bit sRGB 1.298MB 0.000u 0:00.000 The zeroes at the end report how long it took to read and process the image. The -verbose option dumps all possible information about your image, including EXIF data: $ identify -verbose image.jpg Most identify options alter images, so the safe way to extract specific information is with egrep. This examples filters some of the information I like to have when I am printing images: $ identify -verbose image.jpg|egrep -iw 'print size|resolution| filesize|background color' Resolution: 72x72 Print size: 35.5556x26.6667 Background color: white Filesize: 1.327MB Combine identify with find to generate a plain-text report of all JPG and PNG files in the current directory: $ find . -iregex ".*.(jpg|png)" -exec identify {} ; > image-report.txt -iregex performs a case-insensitive search to find jpg, JPG, png, and PNG files. You can add more file extensions such as (jpg|png|jpeg|gif) , and remember to escape the pipes and parentheses. See Supported Image Formats for a list of supported image formats. Bonus: xcowsay All work and no play makes Jill dull, so take a break from your serious duties with xcowsay. This is the graphical version of the beloved classic cowsay. xcowsay requires an X terminal. Try xcowsay Hello, I am Xcowsay!: Graphical version of beloved cowsay. xcowsay closes after a few seconds. It has a number of fun options: –time= to control duration, –font= to select a different font, –think to display a thought bubble instead of a speech bubble, –dream= to display your own image instead of text in the speech bubble, and –image= to select your own image instead of the cow. See man xcowsay for a complete option list. Advance your career in Linux System Administration! Check out the Essentials of System Administration course from The Linux Foundation.
tomekkorbak/pile-curse-small
OpenWebText2
Fukang (meteorite) The Fukang meteorite is a meteorite that was found in the mountains near Fukang, China in 2000. It is a pallasite—a type of stony–iron meteorite with olivine crystals. It is estimated to be 4.5 billion years old. History In 2003, near Fukang, China, a Chinese dealer obtained a mass from Xinjiang Province, China, with a weight of . He removed from the main mass about , and in February 2005, the meteorite was taken to the Tucson Gem and Mineral Show, where it was seen by Dr. Dante Lauretta, a professor of Planetary Science and Cosmochemistry at the University of Arizona. Subsequently, the mass was investigated at the Southwest Meteorite Center, Lunar and Planetary Laboratory, University of Arizona in Tucson, Arizona by Dr. Lauretta and a team of research scientists including Dolores Hill, Marvin Killgore, Daniella DellaGiustina, and Dr. Yulia Goreva, and joined by Dr. Ian Franchi of Open University. Classification and composition The Fukang pallasite contains large, gem quality olivine, or peridot, in a nickel-iron matrix. The olivines vary in shape from rounded to angular, many are fractured and they range in size from less than five millimetres to several centimetres. The main mass contains several regions of massive olivine clusters up to eleven centimetres (4.3 inches) in diameter with thin metal veins. Fo86.4 with molar Fe/Mg = 0.1367, Fe/Mn = 40.37, and Ni = 0.03 wt%. The metal matrix is mostly kamacite with an average nickel content of 6.98 wt%. Vermicular sulfide (troilite) is present in some olivine. Oxygen isotopes: δ18O 2.569 ‰, δ17O 1.179 ‰, ∆1 7O = −0.157 ‰. Specimens A section weighing of type specimen is on deposit at the University of Arizona. Marvin Killgore holds an additional section weighing the same amount, as well as the balance of the main mass. In April 2008, Bonhams offered the main mass for auction at their Manhattan auction. Bonhams expected to fetch US$2,000,000, but the lot remained unsold. A "window" area of was cut and polished to provide a view into the gem areas of the meteorite. See also Glossary of meteoritics References External links Southwest Meteorite Laboratory - Fukang Pallasite Category:Meteorites found in China Category:Stony-iron meteorites Category:Changji Hui Autonomous Prefecture Category:2000 in science Category:2000 in China
tomekkorbak/pile-curse-small
Wikipedia (en)
I was not born a superhero. I was born a mutant, and gifted a body unruly and strange. A twisted foot, a limp. A young girl who took her time to walk, a child who couldn’t dance as others did. A series of surgeries and a stint in a wheelchair marked my childhood the way that spider bites and accidents have marked our comic-book and big-screen heroes, except without any of the attendant power. I did not develop superhuman coordination in response to lopsided hips. Didn’t find my eyesight sharpened or my hearing increased to compensate for less-than-stellar muscular performance. Cerebral palsy: an umbrella term for a variety of muscle disorders that impair or restrict movement. Mild spastic right hemiparesis: partial weakness on the right side of the body. Marvel: as a noun, a miracle or event that causes astonishment and surprise. Also, a wonderful story or legend. As a verb, marvel comes from the Old French merveillen, which means to be filled with wonder. The connecting verb is the Old French merveillier—to wonder at, be astonished. Always the wonder, always the surprise. With superheroes, and then, also, with disabled people. Surprise when disabled people wheel down the street, when they struggle onto public transportation with a cane and walker, when they go to the movies, when they get groceries. All by themselves. I don’t know how you do it, passers-by have said to disabled friends of mine, wheelchair users, those with canes. If I were you, I would have killed myself a long time ago. Surprise. People were surprised by the bearded lady at the circus, by the dwarf who danced atop the bear. They came in droves in the late 19th century to see the deformities of Joseph Merrick, forever known to history as the Elephant Man. In the 16th century, they came to the French court to see Petrus Gonsalvus, originally from Tenerife, Spain, who had a hypertrichosis universalis mutation which made him excessively hairy. Petrus lived at the court as a pet of Henry II. He was taught to speak Latin and dressed in fine clothes. Catherine de Medici, the French queen, found him a wife, also named Catherine. (Portraits of them, thought to influence the image of the Beast in Villeneuve’s Beauty and the Beast, are still stared at in museums.) They had seven children, five of whom also bore the mutation. His daughters were called monsters, marvels, beasts. * As a young girl growing up in southwestern Ontario, royalty felt easier to believe in than mutation, mutant though I was. I dreamt often about being a princess. Those were the stories I saw in books and on TV and so I did not think about what it might mean to be a superhero, to tell that kind of story. Princesses were always perfect, and perfect was what I longed to be. Superheroes required an entirely different kind of magic. It was easier to believe in the magic of fairy godmothers than to believe in the possibility of superhuman strength. Easier to believe that a girl might grow up and fall in love with a prince than to believe that that same girl might grow up into a body that might be considered beautiful, that did what she wanted it to do all of the time. I took it for granted that the bullying would come because I walked differently and occupied a different space. You walk like you have a pickle stuck up your ass, the children said to me at school. Pickle! Pickle! Pickle! What are you going to do—pull it out AND EAT IT? * Marvel: a comic book universe. The franchise began in 1931 under the mantel of Timely Comics, and rebranded as Marvel in 1961. The franchise oversees some of the most beloved superheroes and superhero teams in the world today: the Avengers, the Guardians of the Galaxy, Iron Man, the Hulk. Captain America. The X-Men. Spiderman. Deadpool. Dr. Strange. Thor. Captain Marvel. She is a blonde woman, young and pretty. Thin and stylish—someone who can wear a skin-tight armored suit as easily as a baseball cap and leather jacket. She takes no prisoners, and after a brief beginning of unknowns, makes no prisoner of herself. Once a fighter pilot, she now commands the space between the galaxies. Her name, when we first meet her, is Vers. She is not a princess, not exactly. She’s something else—something bigger, larger, more. Captain Marvel, née Carol Danvers, née Mar-Vell. As I write this, in early April 2019, she is—according to an interview with Kevin Feige, president of Marvel Studios—currently slated to become the most powerful superhero in the Marvel Universe. (We are several weeks out from Avengers: Endgame. Tickets for the first screening of Endgame sold out within minutes.) I saw Captain Marvel right when it came out, earlier this March. I loved everything about it—the sarcasm, the power, the joy. How refreshing to see a woman delight in her powers that way—how gleeful, how astonishing to see someone rejoicing in the death meted out by her hands. How unbelievably powerful to see Brie Larson, as Carol Danvers, look Jude Law’s Yon Rogg straight in the face and say I have nothing to prove to you. What might it have felt like, back when I was ten, to say those words to my classmates and know that they were true? But then, I’m getting ahead of myself. A superhero narrative—or a fairy tale—means nothing if there’s no adversity to overcome. * In Angela Carter’s short story, “The Bloody Chamber,” her gothic retelling of the Bluebeard fable, our young unnamed narrator begins the tale newly married to a much older French Marquis. She doesn’t love him but is drawn to him nonetheless; she shrugs off the misgivings about his previous history—three wives, all dead, the latest gone only three months when our narrator meets him—and flocks to his magnetism, his wealth, his power. When I said that I would marry him, not one muscle in his face stirred, but he let out a long, extinguished sigh. I thought: Oh! How he must want me! On her wedding night, the narrator, wearing her wedding ring (a maternal heirloom first given to her husband’s ancestor by Catherine de Medici), is brought by train to the castle where her husband lives. It is gigantic and hollow and huge, filled with servants who disdain the narrator but put up with her as they have with so many of their master’s whims. The wedding night is one of thrills and quaked anticipation; in the morning, the husband informs his wife that he must go away on business, and leaves her a ring filled with keys. The key to his office, the kitchens, the study. On and on and on until there is only one left. One single key remained unaccounted for on the ring and he hesitated over it; for a moment, I thought he was going to unfasten it from its brothers, slip it back into his pocket and take it away with him. But the Marquis doesn’t do this. Instead, he asks his bride not to enter this one last room. “Every man must have one secret, even if only one, from his wife,” he said … “All is yours, everywhere is open to you—except the lock that this single key fits.” The husband leaves on his journey and our narrator tries, at first, to distract herself with the rest of the castle. She is an accomplished pianist, a prodigy, and her husband has paid for the beautiful blind piano tuner from a nearby village to come and take up residence at the castle solely to keep the narrator’s instrument in tune. They strike up a friendship. The boy is sweet and kind. But our narrator, alas, cannot forget the room. She ventures down into the bowels of the castle and finds that last locked door. Inside it, she discovered the bodies of her husband’s last three wives. In her terror she drops a key into the pool of blood on the floor and then, after escaping from the room, discovers that the blood has stained the key. How unbelievably powerful to see Brie Larson, as Carol Danvers, look Jude Law’s Yon Rogg straight in the face and say I have nothing to prove to you. Her husband, having completed his business early, is on his way back to the castle. Terrified at the wave of anger that she knows will come, the narrator finds herself abandoned in the castle, as the servants have left her alone—abandoned by all, that is, except for the lovely blind piano tuner, who stays with her to the end, a friend to be there with her as she meets her end at the hands of her husband. But then, just in time, there is redemption. As the narrator’s enraged husband accosts her at the front of the castle, the gleam in his eyes and fanatical voice hinting at her final end among the bodies in his basement chamber, the narrator is saved—not by the sweet young blind man, who remains innocent and useless, but by her mother, who left her own home due to a creeping sense of fear for her daughter and comes charging up the causeway to the castle on a horse, her pistol held high and aimed perfectly at the evil husband’s heart. The Marquis dies; the narrator inherits the castle and gives it away to a school for the blind. At the end of the tale, she lives with her mother and the blind piano tuner in a little music school on the outskirts of Paris. One doesn’t often think of mother when one thinks of a superhero, but Angela Carter was good at subverting expectations—in certain ways, at least. Her blind piano tuner is portrayed the way that most disabled bodies are, on the screen and on the page. If not monstrous and evil, then pitiful and useless, sweet though their souls might be. It does not do, it would seem, to be subversive in more than a few ways at once. * Steve Rogers, in the context of his life before World War II, could perhaps be said to have a disability. At the least, his physicality at the start of his narrative as Captain America in the Marvel films is an impediment to progress; he wants to be a soldier, but his big heart is no match for the smallness of his form. His is not a body in demand—he isn’t useful by the standards of war and so he is overlooked, ignored, laughed at, forgotten. His desire to fight in the war is seen at best as cute, at worst as laughable. I can do this all day, he says at the beginning of his journey, as he faces off with a group of bullies in an alleyway. The bullies laugh because they know how society sees him—pitiful and useless, despite the vastness of his soul. Look at you, they might as well be saying. Still wanting to be a soldier! (Still going out into the world, still doing things, still watching movies.) I don’t know how you do it. If I were you, I would have killed myself a long time ago. * “From a narratalogical standpoint, it is not surprising that a genre so often associated with magical or extraordinary abilities portrays disability with such great frequency.” The scholar who wrote this, Ann Schmiesing, is speaking of fairy tales. But she could just as easily have been speaking about the superhero narrative—which is, after all, nothing more than the fairy tale updated for the 21st century. Instead of a ballgown, a superhero’s cape. Instead of a pumpkin, a jet. Good triumphs here, too, and order is restored. A happily ever after with technology and modified bodies—a spider’s bite, then a genetic mutation—taking the place of a magic wand or spell. I don’t know what it means to have your body represented on screen in a way that isn’t somehow tied to magic. If the disabled body isn’t evil or mistaken (the hairy Beast, the green skin of the Wicked Witch, the disfigured face of Red Skull), it is always redeemed in the end—either through actual magic, like when the Maiden Without Hands has her hands grow back in the tale from the Brothers Grimm, or through the magic of the compensation theory of disability, which is what happens a lot with our superheroes. Daredevil loses his sight but develops supersonic hearing as a response to this bereavement; Charles Xavier loses the ability to walk but grows ever more powerful in the realm of the psychic mind. Jean Grey is ostracized and shunned because of how people’s marvelling turns into fear—but her powers are extraordinary, so in the end it balances out. Steve Rogers doesn’t really have a disability in the strict sense of the term. His disability is only a metaphor—a slight against the unfair nature of the world in which he lived, a commentary on the preposterous idea of sending bodies off to fight wars in the first place. Even so, the serum that transforms him into a superhuman is a double act of erasure—erasure of the body that once was his and is no longer important, and erasure of the lived reality of those whose own bodies are seen to be an impediment to thriving. It is useful, for purposes of the superhero narrative, to see how the sheer force of Rogers’ soul is matched in the end by his physique. The superhero narrative is nothing more than the fairy tale updated for the 21st century. Instead of a ballgown, a superhero’s cape. Instead of a pumpkin, a jet. But what does it mean to know that Steve Rogers’ capacity for goodness is only reached once he is given a body that speaks to his soul’s power? What does it mean, as a disabled person, to watch Steve’s struggle and realize that your own potential will never be fulfilled in the eyes of the world—to realize that the world expects so much less from you as a result of your body that even the simplest of actions is treated like a galactic event? A broken body with a bright, pure soul. A superhero who is a superhero simply for getting up and getting coffee down the street. The disabled body is less; the disabled body must therefore be content with less, no matter how bright one’s soul might be shining. Look at you, getting coffee, getting groceries, going on trips in an airplane. Pretending that you’re as able-bodied as the rest of us! It’s all just so inspiring. At the beginning of Captain Marvel, Carol Danvers is disabled in several ways. She has amnesia and can’t recall her life beyond the six years immediately preceding her present. As the film progresses, we come to understand that she is also intentionally being disabled by her captors, the Kree, who are dampening her powers by keeping them artificially restrained. But Carol, as most superheroes are wont to do, wrestles her way through to a happy ending. She does this both physically—through wreaking joyous, unrestrained havoc on her enemies—and emotionally, by distancing herself from the wild, perseverant machinations of Yon-Rogg and asserting her right to occupy her body and power in whatever way she sees fit. I don’t have anything to prove to you. I don’t have anything to prove to you. I don’t have anything to prove to you. I whisper the same thing to myself at night. The “you” wears many faces. * Once, while sitting at my desk during lunch period in fifth grade, a student sitting beside me asked if I could reach under my seat to grab her pencil, which had rolled under my chair. “She can’t,” a girl said behind me. “She’ll have to bend over and take the pickle out of her ass first.” The rage that came over me was immediate and hot, overwhelming. I slammed my chair back into her desk so hard that it tipped her own desk over, pushing her so that the chair she sat on teetered back on its hind legs. Wobbly and ready to collapse, exactly the way I felt. Her laughter was immediate, tinged with surprise and a sliver of terror. I heard the rest of the class laugh, too. Twenty-seven years later, I can close my eyes and hear that laughter exactly as it sounded on that day so many days ago. I have never wanted to be a superhero, or a demon, something other than I was, as much as I did in that moment. To push the chair away from my desk and turn around and send that girl sweeping up through the air and back against the wall so hard that her skull cracked; to see her face split open upon impact and watch the blood and the brain matter trickle out down her cheeks. I wanted to stand over her as she screamed and grind her face into the floor. I wanted to turn an arm back toward the rest of the class who had laughed with her—who had always laughed with her—and do it to them, too. I wanted to see them cower, to see them lose themselves in awe. I wanted them to cry and scream and beg for mercy. But I also wanted to be right to withhold that mercy—I wanted my anger to be justified, to make sense, to be understandable. To mete out punishment that was as clear and unbiased as that from a goddess. I wanted them to love me, to be terrified of me, to want to be me. I wanted all of this even though I knew, already, that in a few years I would go to a different high school and meet other people and move on from this part of my life. I wanted all of this even as I gasped in my rage and pulled my chair back up to its regular position and heard the girl behind me right her own desk and chair, her laugh shaky and hard. I wanted all of this through the rest of that afternoon as I stared at my desk red-faced and hot. I wanted all of this through the next day, and the next, and the day after that one and the week after that. Limping through the hallways, limping through my life. I moved on to high school, eventually. I met other friends; life was indeed different. I traveled and lived in different cities and had lovers and felt beautiful and many of the things that I had wanted came true. I have not stopped wanting this. I still go back to that day. I still want them to love me, even though I know it isn’t worth it—even though I know, more importantly, that my anger and rage at the unfairness of it all is directly tied to the fairytale/superhero lens through which I was already, unconsciously, viewing the world. If my world was unfair, surely that meant that things would swing back around eventually. Surely events would put themselves to rights, surely I would get my happy ending, too, even if it took a little while—because isn’t that what happened in all of the stories I was told? Life could be unfair but the world itself was a fair place. Be good, do good work, and you would either be rewarded or find the strength within yourself to put your world to rights. That’s just how it went. I didn’t fantasize, back then, about what the world might look like if it was fair, if there was no need for superheroes at all. I didn’t imagine what life might have been like in a world without bullying. I took it for granted that the bullying would come because I walked differently and occupied a different space, and the world that I lived in told me that that was what happened to bodies that were different. It seemed easier to imagine a world where I had magical powers than it did to imagine a world where different bodies just existed together side by side. The arc of the moral universe bends toward justice, yes, but sometimes that arc takes a preposterously long time. And in the world that we’ve built, it’s easier for us to imagine that only superheroes can bend the arc for us. Everything else just takes too long. * What might it have meant to me—at eight years old, at ten—to know, deep in my bones, that I didn’t have anything to prove to the classmates who told me that I walked funny, who sneered at the way I ambled through class? To understand that I wasn’t waiting to become a princess or a superhero or even waiting for an unconventional rescuer, but instead was not in need of rescuing at all because there was nothing wrong with my body? What does it mean for me now, at 37, to understand that the world still sees my body in this different way? As a disabled woman, I am at once hyper-present and completely invisible. My limp can at times be mild and so I can sink into the background—an undercover agent in the able-bodied world, which is a kind of superpower and disguise that doesn’t feel quite right, although it feels better than those long ago days at school. My disabled body, bereft of both fairy godmothers and superhero change, is either an object of pity or an object of tender fascination, but rarely something other than this. We are sad Tiny Tims or we are everyday superheroes, inspiring those who can walk and run just fine with our inhuman strength in completing the impossible ordinary. Shopping in our wheelchairs, walking with our canes. Navigating the world with our guide dogs and scooters and other supports—augmentations that aren’t sexy like the claws that come racing out of Wolverine’s hands or the arc reactor in Tony Stark’s chest or the impossible body that gets to be Steve Rogers’, but are nonetheless tools that we use to make ourselves be more. Building a world that either accommodates these tools or makes it so the tools aren’t necessary in the first place (why the need for a body that can fight wars if you build a world where there are no wars?) is a particular kind of magic, it would seem. One that still eludes us all. * A little over two years ago, I walked to work one day in my mid-sized Canadian city and felt, as I battled the wind, the familiar words that pound through my head on a regular basis, in rhythm to my lopsided, hurried gait. You don’t walk like everybody else. YOU DON’T WALK LIKE EVERYBODY ELSE. It’s not unusual, this refrain. I think it every time I hear my footsteps on the ground. I hear it every time I catch my body passing by a window. And yet, for some reason, that day something changed. It’s not that you don’t walk like everybody else, the little voice continued. It was my voice speaking something I had known all along. It’s that no one else in the world walks like you. Why did it take me 35 years to realize this? Something to do with the way that we tell stories—something to do with how we understand the body in both its regular variety and in what we perceive as its superhuman form. “We are capable,” wrote the disabled academic Tobin Siebers, “of believing at once that the body doesn’t matter and that it should be perfected.” And so we fantasize about eradicating disability in the same way that we fantasize about superheroes and magic—taking it for granted that the different body is aberrant in the same way that superheroes are aberrant, though gifts—an act through which we will individually restore the world because systemic overhaul is too grand an undertaking. We’re all for subverting stories until it’s a change in the real world that needs work, at which point we fall back to our regular narratives and look to the one who’ll come to rescue us. We take it for granted that the world is flawed and in need of a Captain Marvel to save it; we take it for granted that the disabled body is a bug in the system and do not, instead, celebrate its difference as a feature. But my walk, my legs, my body—I am, all of me, a feature. (We are, all of us, a feature.) I have no fairy godmother because I have no need of one. I am not waiting for an unconventional white knight to come crashing up a causeway to my castle because I have seen the castle and its darkest heart and nothing in it scares me anymore. I have no need of rescue. I want more than the stories that posit the strong as those who survive and protect the rest of us. I want stories where people are not applauded for embracing difference but instead reshape the world so that difference is the norm. I have nothing to prove to the world because the world has everything to prove to me. It is the world’s responsibility to make space for my body, my words, my lopsided gait—our bodies, our words, our ways of moving through the world—to hold my childhood dreams of being a princess and a superhero close and help me understand that there is no need to want to be either. To start telling different stories about a body that might just look like mine, and reshaping the world to fit them. I am already enough. There is no need to be more.
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OpenWebText2
Suck It! Only Lovers Left Alive is Jim Jarmusch’s take on bloodsuckers. It’s only fitting he would get around to vampires eventually—if you’re not given to his particular bent, his work can be exhausting, just like the vampire genre. Vampire/musician Adam (Tom Hiddleston) lives in Detroit in an out-of-the-way house. He has a human acquaintance, Ian (Anton Yelchin), bring him supplies. One day, with the weight of his existence bearing down on him, Adam asks Ian to bring him a wood bullet. And Ian does. If you know your vampire lore, wood means one thing. Luckily for Adam, he’s graced with a visit from his wife, Eve (Tilda Swinton). She spends most of her time in Tangier hanging out with Christopher Marlowe (John Hurt). Adam and Eve’s tender and much-needed tryst is interrupted by the arrival of Eve’s sister, Ava (Mia Wasikowska), a free-spirited and immature vampire who only wants to have fun. Her presence throws everything off balance and in the second half of the movie, the lovers struggle with a decision: Keep (un)living or, finally, die. Jarmusch taps into existential loneliness with Only Lovers Left Alive. It’s morose, but also quietly appealing. Maybe that’s why his vampire story is effective when so many others suck. Yorik Le Saux’s cinematography is spectacular. To call it a vampire movie isn’t quite fair, but it’s the best vampire movie in a long, long time.
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Pile-CC
Q: Why can't I adopt kids in Skyrim? I killed Grelod and bought a house but I never got the letter from Constance? Why? A: You must own a house that has at least one child bed in order to adopt. If your only home is Breezehome, for example, then you would need to remove the Alchemist's room addon by purchasing the Child's Room addon from Proventus Avenicci.
tomekkorbak/pile-curse-small
StackExchange
Q: Delete files based on pattern This may have been addressed somewhere but unable to find command that meets my requirement. So basically lets say there are 51 files starting with aaa.log aaa.log.1 aaa.log.2 . aaa.log.4 aaa.log.40 aaa.log.41 . . aaa.log.50 Now, I intend to delete files with aaa.log.40 to aaa.log.50. If i run rm -f aaa.log.4* it will delete everything including aaa.log.4 What tweak should I use so that it deletes only aaa.log.40 through 50 but not aaa.log.4 ? A: The default shell in Ubuntu is bash. In bash (and probably many other shells as well) you can do it like this: rm -f aaa.log.{40..50} The expansion {40..50} expands to the range of number from 40 to 50 and automatically cause the rest of the word to be duplicated with each expanded number. It will not verify the existence of the file names, so it may cause rm to be given names of non-existing files. However since you apparently wanted to use the force option anyway, this is not a problem. When you type rm -f it will not print any error messages about missing files. It is usually a good idea to test the command with echo in front if you are unfamiliar with the expansion. Then you can see what the arguments expand to: echo rm -f aaa.log.{40..50}
tomekkorbak/pile-curse-small
StackExchange
Hanoi summit reveals hardship of Kim regime By Lee Kyung-min International sanctions have pushed North Korea to the edge of economic collapse, with its trade deficit with China hitting a record high due to a plunge in exports and imports, according to analysts. They said Pyongyang's failed yet consistent demands during the second U.S.-North Korea summit that sanctions be partially lifted is a strong indication of how dire its economic situation is. The view came after the Feb. 27 summit was cut short as neither side was willing to compromise. The North demanded some sanctions be lifted first and foremost prior to denuclearization, while the U.S. said the reclusive regime should take more concrete steps toward nuclear disarmament. "Looking at China's January trade data, it is clear that North Korea's exports remain at rock bottom and that imports also are very weak and probably falling, as North Korea doesn't have the hard cash to buy anything of an investment nature," William Brown, adjunct professor at Georgetown School of Foreign Service, told The Korea Times. "Some consumer goods continue to flow in, almost normally, but there are almost no imports of any kind of machinery, or trucks or tractors for that matter. Without these kinds of imports, little investment can take place and the economy will continue to falter."
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OpenWebText2
Q: Re-mounting an un-mounted USB stick Is there a way to mount back a USB stick that is once ejected, without physically detaching it and then plugging it in? It was a live-usb of Linux Mint 14 in it, if it helps. A: You can mount a device by typing i.e. sudo mount /dev/sdxX /mnt (change "xX" to your device) Identify your USB-Stick by sudo fdisk -l to know the devicename and partition number which looks like sdbxX i.e. sdb1
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StackExchange
Is Lyricism In Hip-Hop Really Dead? Dariel Figueroa | August 1, 2017 Is Lyricism In Hip-Hop Really Dead? It’s a war cry that’s been bellowed for years now: “Hip-hop is dead.” The cynical phrase has a variety of connotations, from the current absence of dynamic lyricism in pop-culture to the supposed whoring of the culture (is it culture? art? both?) by those who have no interest in its humble beginnings and history. As for the former, it’s a pinpoint of many debates these days — those ranging from contemporary radio play containing more style than substance, to the youth and flag-bearers of the musical genre declining to provide complex rhyme structures and witty lyrical salvos in their work.If you’re reading this, it’s likely that you subscribe to one of two parties: those who believe the era of lyricism in hip-hop is a bygone, golden time that has met its demise, and those who think that the current climate of rap music is simply its newest evolution, one that does not deserve scoffing or demeaning.First, it’s probably best to confront the elephant in the room when it comes to this discussion: Is contemporary hip-hop — compared to the era of rap that was championed by the likes of Rakim, Nas, and then JAY Z, Eminem and others — really inferior in terms of lyrical content? The easy answer is “yes.”Before you get in a huff and proclaim that I have no clue what I’m talking about (I’m trying to be objective here while maintaining a stance that does not make me look like a generational curmudgeon — a difficult feat), all one needs to do is analyze the rhyme structure of someone like, let’s say, Lil’ Yachty, and compare that with the complex standard of an artist whose heyday has passed — let’s say MF DOOM — and you’ll come to an educated conclusion that, yes, “lyricism” in its most standard and accepted definition is no longer an attribute at the forefront of today’s artist.So, the question then refers back to the title of this blog: has the decline in the quality of lyricism in hip-hop resulted in the genre facing a overall decline in its quality?To answer that, let’s take a brief look back at the roots of hip-hop.When hip-hop first began, the lyrical content of the art form and culture was not really a highpoint nor was it the primary element in the budding genre. All one has to do is listen to those early records; cuts by the likes of Grandmaster Flash and The Sugarhill Gang were more about the feeling and groove of the record rather than the weaving of words.It wasn’t until “lyricists” were born in the ’80s — Rakim was one of these initial champions of lyrical complexity — that the classification of rap music began to change. Along with the evolving sonic quality of the music, lyricism became one of the focal points of hip-hop. The art of knitting rhymes and metaphors within a fabric of intricate sonnets further intensified with the debut of Nas’ 1994 magnum opus, Illmatic. (There were other proponents of lyrical “art” in the early ’90s — Nas is just one example.)It was around this time that the quality of a rapper’s verse gained so much importance that “lyricism” instituted itself as a primary trait of rap music. For over a decade after Nas’ debut, rappers strove to present a higher aesthetic of poetry within their music: Big Pun, the aforementioned JAY Z, Tupac, The Notorious B.I.G. and more all carved a name for themselves by delving deep inside the creative process to extract concentrated doses of high-caliber ditties. For their efforts, these artists were awarded with being labeled the kings of kings in the genre — awards, praise and skyrocketing record sales were all lavished upon them.When did the balance of style and substance begin to shift then? Well, that’s a deeper question, one that needs a thorough examination and analysis of singular points inside the hip-hop timeline. (It’s also a question that will be explored in a future post, but for now we’ll focus on a more abstract, overall thematic artifact.) If I were to take a brief stab at answering that very specific question, though, I’d probably say lyricism began to decline with the advent of The Ying-Yang Twins. (I’m kidding… kind of.)Beyond pointing fingers to who, what, or even when lyricism in hip-hop’s forefront (i.e. pop-culture plane) began to lessen in quality (“lyricism” as we know it is still very much alive in other subgenres of rap music), it seems like it’s the proper time to confront the basis of this post: Is hip-hop better or worse than it was in the ’80s, ’90s, and 2000s? I’ll answer that in a moment, but first, it’s important to note that quality lyrics in rap aren’t “dead.” Kendrick Lamar just dropped another album that’s certain to go platinum, with every song on Damn charting on the Billboard 200 as of this writing. K. Dot is arguably one of the best lyricists of all-time, certainly of his generation. There’s also J. Cole, Big Sean and several other high-profile artists that maintain a high level of lyrical content while achieving commercial success.That said, there’s a deluge of records on the radio and in the Billboard charts that wouldn’t necessarily qualify as “lyrical” in nature. (I’m going to refrain from naming specific artists, as many have done that already and I don’t think it’s quite fair to continue to point out those who aren’t able to produce fire “bars.”) If we’re to take this notion that “lyricism” is no longer a focal point in rap music — and certainly that’s still up for debate in some circles — what is the impact it’s having on the overall quality of the music?Well, there’s a reason that I pointed out the earlier roots of hip-hop. To say that today’s hip-hop is not “real” rap music is a misnomer. Rap music started off about the “feeling” and groove rather than the lyrical content, so I think to say that today’s trap-heavy rap is getting away from the culture and essence of what the genre is, at its core, is incorrect. Also, lyricism still thrives, not only in the standard-bearers like the aforementioned Cole and Sean, but even in the Yachtys and Futures of the game.It might not be quite to the standard that Eminem set the mark, but there’s still witty wordplay at work with many of the records being spun at top 40 radio stations. Are emcees striving to be the next Rakim or Nas? Hell no, but that’s not a terrible thing.Like I said earlier, you can still find large amounts of lyricism if you look in the right places — top 40 radio is probably not one of those places, but to say that “hip-hop is dead” solely because the tastes of the mainstream have changed, is akin to cutting open the steak well before it’s had a chance to cook.Instead, we should look at this current trend of “mumble rap,” trap rap and Auto-Tune, as a forecast to the next golden era of lyricism in hip-hop, one where new stars will emerge; where new methods and messages will take precedent and the art form and culture as a whole will rise like a fiery phoenix into a stratosphere that was only reserved for the van Goghs and Mozarts.I know, I know… it’s probably much easier to be cynical about this whole thing. I mean, who doesn’t miss that time when deconstructing a verse was actually hard work?But, patience goes a long way. Like the weather, if you truly hate something in pop-culture or the mainstream, all you have to do it wait. Or, you could write a really complex verse about it.Maxxbeats.com is dedicated to helping the music artist develop into a superstar. With instrumentals for sale, mixing/mastering/recording services, chances at getting radio airplay and so much more, make Maxxbeats.com your first stop on the road to becoming a household name. For more information on our services, please check out our PRO MUSIC SERVICES page.
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Take NATURAL erectile dysfunction pills with folic acid Did you know if your body isn’t getting enough folic acid then you are more at risk of erectile dysfunction (ED) and premature ejaculation (PE)? When most people discuss folic acid (also known as B6) they are referring to its importance to women’s health, especially in the lead-up and during pregnancy. Folic acid is one of those essential nutrients that helps to prevent birth defects and supports normal development in infancy. However, new research is highlighting how important folic acid is for men in maintaining healthy sexual function. Researchers from the Wuhan University in China have found a link between low levels of folic acid and ED/PE. Through blood analysis, Yan and colleagues measured the concentration of folic acid in men suffering from ED and/or PE. They also measured the levels of key sex hormones (testosterone, luteinizing hormone, and follicle-stimulating hormone) and the metabolic waste product homocysteine. Over the four week study period the mean intravaginal ejaculation latency time (IELT) was also measured. All the results were then compared with samples and measurements obtained from men with a healthy sexual function. There were no significant differences observed between the groups in terms of sex hormone concentrations. However, folic acid levels did vary significantly and this had repercussions for ED and/or PE. Men with low levels of folic acid had higher concentrations of homocysteine and experience ED and/or PE. How do folic acid levels affect male sexual function? To achieve an erection and ejaculate there are a number of neurotransmitters involved. If there are problems with these neurotransmitters, sexual function will be adversely affected. Folic acid plays an important role in sexual function as it’s involved in the metabolism of 5-hydroxytryptamine (5-HT), nitric oxide (NO), and the waste product homocysteine. The neurotransmitters NO and 5-HT are involved in the control of ejaculation. Insufficient NO will also adversely affect vasodilation, making it difficult to achieve and maintain an erection. This can further be compounded by increased homocysteine levels which will damage the arteries and reduce the ability to have an erection. So what does all this mean? If you are concerned about PE and/or ED increasing your intake of folic acid along with other key nutrients may help. Some foods that are naturally rich in folic acid include lentils, pulses, green vegetable and citrus fruits. The best way to ensure you are getting enough folic acid is to take a quality supplement. If you combine folic acid with the amino acid arginine and pine bark extract, you’ll be doing your sex life a great favour. There are some excellent natural supplements combining these ingredients which can make a big difference. Unlike many medications prescribed for ED and/or PE, these natural nutrients don’t have adverse health effects, so you can take them with confidence. It’s important to note that with any supplement the results are not instant. You’ll need these compounds to gradually build up in your system before you can expect to notice physical improvements. ED and PE are complex conditions. In some cases there may be other factors influencing sexual dysfunction. So it’s always a good idea to have a chat to your doctor about possible causes in addition to taking a quality natural supplement.
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Chest wall resection and reconstruction for lung cancer. Patients who have lung cancer that invades the chest wall should undergo careful preoperative screening to ensure there is no distant disease. A preoperative mediastinoscopy is generally indicated to exclude the presence of mediastinal nodal metastases. At the time of exploration, the surgeon should open the chest away from the tumor and carefully assess whether it can be resected. If there is a question of invasion into the chest wall, an en bloc chest wall resection should be performed. The risks of postoperative complications are low, and a favorable long-term survival is definitely possible in this subgroup of patients who have lung cancer.
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Clusterfuck Nation Now appearing Mondays and Fridays Support this blog by visiting Jim’s Patreon Page! It wasn’t until more than a week after Hurricane Katrina slammed into New Orleans in 2005 that the full extent of the damage was recognized and so it will go with the hot mess where Houston used to be. Mostly, it is inconceivable that the business activity which made Houston the nation’s fourth largest city and, according to Chris Martenson, equal to the 10th largest economy in the world, will ever return to what it was before August 26, 2017. The major activity there has been the refining and distribution of oil products, and no activity is more central to the functioning of the US economy. So the public and our currently clueless leaders across the political spectrum, plus a legacy news media lost in the carnival of race and gender freak shows, is about to discover the dynamic relationship between energy and an industrial economy. The pivot in this relationship is banking, which enables the conversion of oil’s raw power into everything else that goes on in a so-called advanced economy. The popular assumption is that federal disaster relief can compensate for all losses. That assumption may go out the window with the Houston flood of 2017. And no amount of federal aid can compensate for the hours, days, and weeks that will tick by as businesses struggle to return to something like their former level of normal operation. Many businesses will never recover, especially the smaller ones that support the big one — the little tool and die shops, the construction outfits, the trucking and shipping concerns, the riggers and pipefitters, the cement companies, and so on. All of that activity existed in highly rationalized chains of on-time production and service and nothing will be on-time in Houston for a long time to come. The arguments over insurance coverage have not even begun, and then there is the question of how businesses in this perpetual flood zone will renew their insurance. Or how might they relocate to higher ground? And how do they pay for that? And where is higher ground in this vast, swampy lowland? The public has been conditioned by frequent natural disasters to think that nobody has to eat the losses, so that in effect loss doesn’t exist, just as the nation’s central bank has engineered the belief that risk no longer exists in the management of capital. We sure had a nice demonstration of the latter, with the Dow inching over the 22,000 hashmark in overnight futures trading today. The exertions of the Federal Reserve in propping up the stock markets will have to go pedal-to-metal now to make up for the hole in economic activity that Houston represents. Meanwhile congress is left to dither over two conjoined financial emergencies at once: authorizing emergency aid to Houston, and resolving the debt ceiling problem. The fault lines are already visible in the ill-feeling left over from Texas’s congressional delegation voting against aid for Hurricane Sandy’s rip through New York and New Jersey. Texas Senator Ted Cruz, for one, has reinvented his political philosophy overnight to accommodate federal aid for natural disasters, something he was not keen on before September 26. I’d assume that these politicians have some normal human sympathies — yes, really — but that these emotions won’t stand in the way of their agenda for mutual self-destruction. Even if they manage to cobble together some kind of emergency aid package for Houston, the process will coincide with the Treasury running out of supposedly “actual” money — that is, money which can be accounted for by some method besides check-kiting. Another assumption du jour is probably the idea that accounting no longer matters, that bankruptcy no longer means anything. Pretty soon, those logical fallacies will manifest in an accelerated falling value of the US dollar. Somewhere in this reverberating hot mess stands a character named President Trump. He acted out the customary disaster visitation ceremony last week, but I predict that the as-yet-revealed after-effects of Hurricane Harvey will put him in deeper and stinkier hot water than George W. Bush splashed through with Katrina. Meanwhile, what’s that monster called Irma doing out there in the Atlantic? Great Summer Reading… JHK’s new book! “Simply the best novel about the 1960s.” Read the first chapter here (click) on Patreon Buy the book at Amazon or click on the cover below or get autographed copies from Battenkill Books Other Books by JHK The World Made By Hand Series: Book 1: Book 2: Book 3: Book 4: Support this blog by visiting Jim’s Patreon Page
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Just Cause and Occupy Oakland Fight Fannie Mae and Banks A statement by Causa Justa asked, 'If we can ensure that big banks don't go under, why can't we ensure that American families stay in their homes? ... To stop the displacement of long-term residents from Oakland and amplify the fight to keep families in their homes, we are OCCUPYING our homes in solidarity with 27 cities across the nation! We are the 99%!'. Photo by Peter Schurmann at New American Media. Activists from Causa Justa:Just Cause and Occupy Oakland protested foreclosures, and demanded that banks stop foreclosures and allow families to move into foreclosed and vacant homes in Oakland. The action was one of over two dozen carried out by Occupy activists and supporters across the country to protest foreclosures and the refusal of banks to renegotiate loans. After a march, people occupied a home owned by Fannie Mae, and announced they would make it a community center, as part of an effort to force Fannie Mae to allow people to live in the many vacant homes it owns as a result of foreclosures. In front of the occupied home, poets recited, activists made speeches, and neighbors poured through the gates. Causa Justa announced it was holding the occupied house to demand that Fannie Mae turn it into low-income housing, and in support of the Ramirez family, whose home was improperly foreclosed on by Fannie Mae. Bank of America sold the Ramirez home while suppossedly renegotiating the loan, and the family now rents the home they once owned. Fannie Mae took $169 billion in bailout money, while its six top executives received $35 million in income, including bonuses.
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Main menu Sammy Samford Radio Hosting SEAL We did not out Mr. Samford, the guys over at SOCNET.com and Fakewarriors.org had already begun the investigation when he was brought to our attention, and they have concluded that not only was Mr. Samford never an elite Navy SEAL, but also never served in any branch of the U.S. Military. Mr. Samford likes to tell people who listen or call in to his webhosted Radio show that he was a Navy Seal, who saw action in Grenada and Iran. Seems his plane crashed in Iran years ago and he had to fight his way out. Here is a link to part of a radio show where he makes his SEAL Claims, saying he first saw action in Iran in the early 80’s when his plane crashed. Then in Grenada, this is were it got tough, he says.: (Links are in MP3 format) Here is a clip where he is talking about the guys that exposed him as a fake, claims his records are classified. This is something we received from a real Navy SEAL, “Before any classified operations may be undertaken as a SEAL Operator, a man must first successfully complete the Basic Underwater Demolition/SEAL (BUD/S) Training program and then the follow-on secondary training program. The names of all those who successfully graduate from that training program sequence are compiled in the SEAL database. Later participation in classified operations has no impact on whether or not a person is listed as a graduate of the training program. There are records of every man who has qualified for the title of “SEAL”; there have been and will continue to be secret missions, but there are NO secret SEALs.” As stated earlier this was investigated mainly by our comrades at SOCNET and fakewarriors.org. Our colleague at fakewarriors received this in reference to his SEAL Claims: I greatly appreciate your interest in upholding the honor of the US Navy SEAL Teams, and your search for the TRUTH. Before answering your questions I must make clear that I am a private individual, not affiliated with the US Dept. of Defense or any other government organization. My efforts to expose SEAL imposters are performed as a service to the public, and in honor of my fallen SEAL Teammates… men who truly earned the right to the title “US NAVY SEAL” but who are no longer able to stand forward in defense of their honor, their reputations, and their TEAMs. If the name you provided is spelled correctly, I do NOT find a listing in the SEAL Database (SEAL Teams and predecessor units from1943 to the Present Day) for anyone named SAMUEL SAMFORD. I have also examined possible alternate spellings, and names with similar pronunciations without finding any that appear to be applicable. The last name SAMFORD does not appear anywhere among the 17,900+ entries of the SEAL Database. Unless he has undertaken the unlikely action of a legal name change (an action for which there would be evidence in the form of court documentation) since his claimed participation in SEAL training, and based upon the information you have provided, I can state conclusively that SAMUEL SAMFORD has NEVER COMPLETED SEAL training, and he is not now, nor was he ever a Navy SEAL, a Navy UDT “Frogman”, a member of any Naval Combat Demolition Unit (NCDU), or a member of the Naval Amphibious Scouts & Raiders (S&R). When members of the Naval Special Warfare community meet others who claim similar service, but whom they do not recognize, there is a conversational exchange of information that establishes the bona fides of each to the other. There is no set formula for this exchange, nor for the information that is exchanged, but it ALWAYS takes place, and the REAL Naval Special Warfare members can ALWAYS spot an imposter as a result of this exchange. If Mr. SAMFORD persists in insisting that his SEAL claims are legitimate, I might suggest that you ask him these questions: -Since there is no listing in the SEAL Database for the name you are currently using, WHAT NAME DID YOU USE during SEAL training? -What was his Training Class Number? (No SEAL ever forgets his class number, and there have never been any secret classes)? -When did he graduate from SEAL training? (i.e. a specific graduation DAY/DATE)? -Which SEAL Team(s) did you serve on, and when? The answers to those questions are totally UNCLASSIFIED, and every real SEAL will gladly provide that substantiating information upon request. Asking him these questions will make it very clear to him that you are not only informed on the subject of Navy SEALs, but that you are aware of the truth regarding his fraudulent claims. Before any classified operations may be undertaken as a SEAL Operator, a man must first successfully complete the Basic Underwater Demolition/SEAL (BUD/S) Training program and then the follow-on secondary training program. The names of all those who successfully graduate from that training program sequence are compiled in the SEAL database. Later participation in classified operations has no impact on whether or not a person is listed as a graduate of the training program. There are records of every man who has qualified for the title of “SEAL”; there have been and will continue to be secret missions, but there are NO secret SEALs. NOTE: Mr. SAMFORD’s Facebook page indicates he graduated from High School in 1979 (presumably in/around MAY of that year). If he entered the US Navy the day he graduated and immediately reported for basic training (boot camp), then followed the normal stepwise process of attending a Navy “A School” (primary training for each skill the Navy uses) before engaging in any Naval Special Warfare training, he would not have even begun the most rudimentary SEAL Training until the first calendar quarter of 1980. The process of training a SEAL is longer now than it was in 1980 (due to the added technology being employed by the SEALs), but even if everything happened in precise order with no hitches or delays, and he successfully completed that training, he wouldn’t have been credentialed as a SEAL until early 1981. His claims of being a SEAL for 7 years, the first year of which coincides with his last full year of attendance at High School, is not only ludicrous, it is impossible! The SEAL Database which I use for confirming SEAL credentials is HISTORICAL in nature, created by the Naval Special Warfare Archives and derived from official military records. It is the database used by unofficial, fraternal and historical UDT/SEAL organizations for verifying successful graduates of the Naval Special Warfare (NSW) training course, and it contains only the names and very (VERY!) abbreviated information regarding successful graduates of NSW training. The NAVAL SPECIAL WARFARE COMMAND maintains an official master STUDENT database which not only includes the names and detailed information about every successful graduate, but also all of the names and data for all those who started the training program but did not successfully complete the course. While there is a complete overlap of graduates’ names between the HISTORICAL database I use and the official master STUDENT database maintained by NSWC, the amount of data appearing in the official NSWC Database is far more detailed and comprehensive. I must stress that although I am a US Navy veteran, and a former SEAL, I am a civilian performing in an entirely unofficial role. I therefore strongly recommend that you obtain a formal/official US NAVY statement regarding Mr. SAMUEL SAMFORD’s claimed SEAL credentials. To do so you may contact the PUBLIC AFFAIRS OFFICE at the NAVAL SPECIAL WARFARE COMMAND in San Diego by calling (619) 522-2822, or you may contact the FOIA COORDINATOR at the NAVAL SPECIAL WARFARE COMMAND in San Diego, California, and submit a formal FREEDOM OF INFORMATION ACT inquiry in writing addressed to: I will pass your letter of inquiry and this response to others who may wish to pursue this matter further. If you wish to confront Mr. SAMFORD, you may use this letter as you wish without limitations. Thank you again for your concern in this matter, and for your assistance in upholding the honor of the US Navy SEAL Teams. If I can be of any further assistance to you in this matter, please contact me at your convenience. And here is the response under the Freedom Of Information Act pertaining to records for Mr. Sam Samford. And according to them, they can find no one by that name that has ever even served in any branch of the Armed Services. So it would seem that not only was Mr. Samford never a SEAL, but has never served in the armed services period. As anyone can tell you, service is not classified, but missions may be. The NPRC houses all records for retired and discharged veterans from all service branches. So if he had even served in the Navy, they would have found something. But there conclusion is that they could not verify his service, and could not locate any records by that name and date of birth. So unless he changed his name since then, Mr. Samford is not a Navy SEAL, nor a veteran of the Military. Seems Sammy has been investigated by a local Investigative Reporter. She contacted us awhile back to let us know she had begun the investigation. She contacted us today and her investigation will be airing tomorrow, Monday November 12th 2012. You can watch her bust him out between 10 and 1030 on fox in jax, Then around 1110 on cbs in jax. It will also be available online. “No, I was never a Navy Seal. I am tired of the death threats coming to my house and I apologize to all the awesome veterans out there that have served our country,” said Sam Samford by phone Monday night. Samford recently pulled his online radio show and all archives online. This guy sounds like an inbreed moron. Now, for all you posers out there, just say that there were “classified” SEALS, Rangers, SF, etc. and you were one of these people and your records were sealed, don’t you think that you also would not be allowed to talk about anything that resides in those sealed records? That would seem like common sense. Yet, there are no secret SEALS, Rangers, SF, etc. and to lie about service to this country especially in any special operations units is disrespectful and utterly retarded in this day and age of the internet. The only classified part I know about is DEVGRU-again, locations and missions classified-but not the personnel-that I know of. Just like the guys that claim they serve with SEAL 6 currently, when Team 6 was officially disbanded in 1986 A few months back I confronted a guy claiming to be with SEAL Team 6, he tried to pull the whole ‘top secret’ act until I pulled my trump (read CAC) card. Then he confessed he learned the name from Counter-Strike. The personnel of DEVGRU are classified. You can probably do a FOIA request and get that the guy served, is in the Navy, and probably a SEAL, but they aren’t going to say they’re in DEVGRU or any specifics about them or their unit. Seal Team 6, DEVGRU, etc is semantics. Same with Delta Force .. or CAG … or 1st SFOD-D. Whatever you want to call it, or whatever they call it, it’s the same thing. Yea team 6 is a “generic” term for the DEVGRU. We had those guys at my FOB in Afghanistan. I honestly never knew it was disbanded until I read this and researched it lol. They themselves even referred to themselves as being Team 6 lol. Learn something new every day. Sammy is not a phony. We went through SEAL training together at a secret Naval Base in Montana (I think). We went to secret places overseas and did some real scary stuff. It was awsome. Anyway, that’s our story and we’re sticking to it. So if your service was so classified and top secret and hush hush that your seal class records got deleted … wouldnt there be some form of retaliation for discloseing your crazy secret life over open channels like the radio? As a Navy Veteran, and close family member of a Retired SEAL who is Still dealing with debilitating PTSD from Vietnam, I find this man so Loathsome and Dishonorable as to make me physically ill to read all the claims he has about his Non-existent Service!!! My missions were so classified that the US government refuses to even admit they ever happened, but I can tell you, John Q Public, all about them in precise detail on my web-hosted radio show – wow, just !@#$%^ wow! Ah… Sammy, et al posers, SEAL stuff 101: NEVER lie about your military service, especially about being in a community as small as the Teams. Gee, seeing the original story I thought he was some sort of radio-host along the lines of Stern/Limbaugh/Savage. Then I see its just some dude in a beat up house who talks to people via the internet,,, $2.50 contribution to Newt ,,, big spender,,, Just someone with an opinion and agenda that wants to lie to make his points seem more valid. Sorry excuse for a human being. absolutely pathetic…i love how he plays the victim….you are probably reading this sammy, take accountability for your actions and YOU get a fucking life….you are the one who is spineless considering you lie about being in combat and couldnt even hack it in navy bootcamp for a full month….as a former marine, Iraq combat veteran and purple heart recipient, and yes i have records to back it up, you make me sick What bothers me most is the implication that if a soldier isn’t a SEAL, Ranger, or other special operations, that his/her contribution is less important. It takes all of our service people working together to guarantee our freedom. So, cheers to All who serve. Wow, way to go Action News!! So now, I wonder if that investigative reporter would consider traveling to Burnet, Texas…I think every veteran that ever wore the uniform deserves to hear Mrs. Lightfoot’s retraction of all her lies and hear her apologize. “Late Monday night, Sam Samford called Action News wanting to tell his side of the story. We did give him opportunities while we were investigating, but he decided Monday he wanted to talk. He had this message for the community. “No, I was never a Navy Seal. I am tired of the death threats coming to my house and I apologize to all the awesome veterans out there that have served our country,” said Sam Samford by phone Monday night. Samford recently pulled his online radio show and all archives online.” At least he has the guts to admit when he has lost. It doesn’t surprise me that he pulled all his archives, though. Without those archives, the proof is harder to find if an attempt is made to prosecute for Stolen Valor.
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University Communication Multimedia Tina Knowles, Joanne Herring Share Histories with UH ‘Living Archives’ Series Women’s Archive and Research Collection to be Named for UH Supporter Carey C. Shuart September 27, 2011-Houston- Tina Knowles and Joanne King Herring are among the guests for the 15th annual University of Houston’s “Living Archives” interview series, a live conversation with influential Texas women, recorded before an audience at the UH Rockwell Pavilion and archived in the newly named Carey C. Shuart Women’s Archive and Research Collection. The archive collects the oral histories of Texas women and Houston area women’s organizations, and the papers of individual Houston women who've made history. “This fall’s stellar 'Living Archives' lineup demonstrates again that Houston is full of amazing women,” said Elizabeth Gregory, professor and director of the UH Women’s, Gender & Sexuality Studies program, which hosts the interview. “We are proud to document their stories for Houstonians of today, and of the future, to draw upon.” This season the UH Library celebrates the naming of the archive in honor of Shuart—a founding member of the Friends of Women’s Studies, which originated in 1996—and a longtime Houston arts and women’s history supporter. “Through her steadfast support of the collection the Shuart Women’s Archive will continue to grow and garner prominence as a nationally recognized research collection of our outstanding Texas women,” said Dana C. Rooks, dean of UH libraries. “The Shuart Women’s Archive will continue to celebrate women’s history and provide students and scholars alike with a window into the lives of many inspirational foremothers.” The archive includes the histories of such women as Houston mayors Kathy Whitmire and Annise Parker, and groups including the Houston Area Women’s Center, Hispanic Women in Leadership; the Association for Women in Science records; and Top Ladies of Distinction, an African American philanthropic group, to name a few. “The Friends of Women’s Studies have been collecting papers and stories for 15 years and the collection has evolved into an extremely valuable research tool,” Shuart said. “Our intent is to share this information, even more widely, by making the documents, videos and photographs available online.”
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The Charge Opening Statement Considered to be one the best Sherlock Holmes films ever made, Murder By Decree finally makes its appearance on DVD. It may not be the feature laden extravaganza all its fans have wished for, but it does boast a nice transfer and an informative commentary from director Bob Clark. Facts of the Case A vicious killer is slicing up the prostitutes of London's Whitechapel area, but as is often the case, there is more going on than meets the eye. So who better than the world's most famous consulting detective, Sherlock Holmes (Christopher Plummer, The Insider) and his comrade-in-arms Dr. John Watson (James Mason, Lolita) to investigate the case? Becoming involved in a most personal fashion, Holmes soon finds there are powerful forces at work in Whitechapel, hidden forces that seek to hide the truth from the light and forces that would just as soon see Holmes disappear from the scene. Permanently. The Evidence Director Bob Clark has certainly had a varied career. The man behind Porky's, Black Christmas, and A Christmas Story may seem like an unlikely candidate to bring to life the world of Arthur Conan Doyle's classic character, but with 1979's Murder By Decree, that is exactly what he did. Taking some popular theories of the time as they related to who Jack the Ripper was and why he was able to get way with the horrors he committed, Clark and writer John Hopkins (The Offence) tell a tale of two Londons, one of the rich and privileged and one of the poor and the forgotten masses. Weaving historical figures and events seamlessly with their fictional characters, Clark and Hopkins speak to the horrors and class struggles of the period. It's to their credit that it is difficult to tell when the movie is playing with fact or tossing out well dressed fiction. Behind the camera, Clark shows an excellent sense of pace and structure. The atmosphere is laid on thick, but it never overpowers the story, instead giving it weight and breadth. Add into the mix the excellent work of production designer Harry Pottle and cinematographer Reginald Morris, and we can believe we are looking at the London of the 1880s. Originally intended as a vehicle for Peter O'Toole and Laurence Olivier, the two were unable to overcome their intense dislike for one another and Clark had to "settle" for Christopher Plummer and James Mason in the leading roles. While other actors may have borne a stronger resemblance to Doyle's classic detective, few have captured the Sherlock Holmes of the written page better than Christopher Plummer. I'd go as far to say that only Jeremy Brett's portrayal as Holmes stands above Plummer's. As for Mason, well, for me no one has played a better John Watson than James Mason. Both Plummer and Mason choose the road least traveled when creating their characters. For Plummer's part, he brings a rare humanist warmth to Holmes. Certainly it's easy to see the gears hard at work inside of Holmes' head, but Plummer allows us to also see a man enraged by the crimes that are being committed and moving with a steely determination to punish the guilty parties. His Holmes is graceful, yet manly. Brilliant, but not sterile and detached. Too often actors take a superior tone when playing Holmes, to the point where it's almost a time honored tradition to be smug and self satisfied. This approach allows the viewer to hold Holmes' intellect in awe while leaving the man as an afterthought. The fact that Holmes is a genius is of equal importance to the fact that he is still just a man. It's an approach that works and makes the viewer an equal partner in the proceedings. I'm sure some purists would complain of Plummer's choices, but for me if you look below the surface of Doyle's writing, you can find the inspiration for Plummer's version of Holmes. To look at James Mason is to see Dr. John Watson personified. Unwilling to play the doltish sidekick, in Mason's hand Watson is the equal partner. If Plummer tempers Holmes' genius with a healthy dose of humanity, then Mason balances his comrade's intellect with humility and humor. Mason's Watson has the wonderful ability to look at Holmes' brilliance with amusement and wonder instead of confusion and bluster. It's a not a small distinction and one that elevates Holmes' abilities without denigrating Watson's skills. Together, the pair make quite the team. It's easy to know who was originally thought of for the roles and wonder what might have been, but what the film ended up with is quite remarkable. Plummer and Mason play off each other beautifully, and there is a simple elegance to their work together. It's so nice to just sit back and watch two actors play off on another with the give and take of seasoned professionals. Watching these men work their way from matters of the gravest importance to the silliest bits of business involving a pea is to know you are watching two masters at work. There is great humor between the two actors as well as respect, affection, and love. I suppose it should be noted that similar themes and plot lines were examined in a 1965 film called A Study in Terror, but with Murder By Decree, director Clark surrounds his central players with a supporting cast full of star power and vastly superior production values. Since this was an English/Canadian co-production, the cast had to be 50/50 from each country, thus with the leads you had Canadians Plummer, Susan Clark (Night Moves) in the pivotal role of Mary Kelly, Genevieve Bujold (Star Trek: Voyager) as Annie Crook, and Donald Sutherland (Panic) as psychic Robert Lees. On the British side, you had Mason, David Hemmings (Spy Game) as Inspector Foxborough, Anthony Quayle (Masada) as Sir Charles Warren, John Gielgud (Becket) as Prime Minister Salisbury, and in the same role he played in A Study in Terror, Frank Finlay (The Three Musketeers) as Inspector Lestrade. All have their moments and all contribute mightily to the proceedings. I probably sound like a broken record, but once more Anchor Bay has done everyone a favor and rescued a beloved cult movie from film purgatory. One of the biggest nightmares when working on a film of this kind is excessive fog, and there is lots of fog throughout Murder By Decree. Well, hats off to the firm that handled this transfer because there is hardly a compression artifact to be found. The picture is remarkably solid on all counts, with the barest hint of edge enhancement visible. Plaids remain firm, flesh tones appear natural, and the colors are true. Blacks remain consistent, with shadow detail being a strength. It almost goes without saying that the 1.85:1 aspect ratio of the film is given anamorphic enhancement, but there you have it, there it is. Sound is not quite so happy a tale. It's of the 1.0 Mono variety, and it is pretty limited. Dialogue is clearly heard but sounds thin, while Carl Zittrer and Paul Zaza's weak score is not heard to good effect. The mix is quite closed off with little room to breathe, while there is more audible background distortion than I'm used to. It all adds up to a listening experience that is rather rough. It's certainly not one of Anchor Bay's better efforts. On the extras front, the center attraction is a scene specific commentary by director Bob Clark. Clark seems a pleasant fellow and he is not afraid to go into detail with how this film was made. He does confirm the O'Toole and Olivier factor and then goes on to explain how he sold Mason on the project. He is justifiably proud of his work all these years later, but he never comes off as cocky or arrogant. Be aware there are gaps in his commentary, but they are well timed and never go on for so long that I lost interest. In addition to the commentary, there is also a couple of still galleries that show behind-the-scenes activities, some fairly extensive talent bios, a trailer for the film in anamorphic widescreen, and a DVD-ROM feature that allows access to the film's complete script. All you need is a computer with a DVD-ROM drive and Adobe Acrobat Reader, and you are good to go. The Rebuttal Witnesses For those going in looking for a Jack the Ripper tale featuring plenty of blood and guts a la From Hell, don't look here. The blood and terror is hinted at but never really shown. I find this restraint admirable. Also, for purebred fans of Sherlock Holmes who hold fast to one style of interpretation may be quite put out by Christopher Plummer's most human detective. Go in with an open mind, and I think you will find the same joys I did. Otherwise, I have few reservations about either the film or the disc. As noted, the sound is less than ideal, but given Anchor Bay's track record one has to wonder if the problems lie with the source materials and not Anchor Bay's production team. Closing Statement Murder By Decree is an excellent addition to both the lore of Sherlock Holmes and Jack the Ripper. It's entertaining, warm, and creepy. That, and its always fun to watch so many wonderful actors do their thing in high style. Anchor Bay offers up a solid presentation of the movie at a price commonly found for under $16.00. I found it a solid purchase, and like-minded fans will probably feel the same. The Verdict The jury has spoken and Murder By Decree is acquitted of all charges. Time may have disproved the theories at the center of its story, but that hasn't dulled its power.
tomekkorbak/pile-curse-small
Pile-CC
Q: Django Website Administration Broken I have recently updated and the Django Website Administration has broken (I must add I do not know if that is the root cause of the problem as I have not used it for some time and have only just noticed it. I get the following error: Internal Server Error: /admin/ TemplateSyntaxError at /admin/ 'future' is not a registered tag library. Must be one of: account account_tags admin_list admin_modify admin_static admin_urls avatar_tags cache crispy_forms_field crispy_forms_filters crispy_forms_tags crispy_forms_utils dwadfilters humanize i18n l10n log mathfilters socialaccount socialaccount_tags static staticfiles tinymce_tags tz I have had a look round and some are suggesting it is a bug. Some say to downgrade to 1.8 (which is not an option). I will place the traceback at the bottom of this email. Many thanks in advance for any help. Traceback: File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/core/handlers/exception.py" in inner 39. response = get_response(request) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/core/handlers/base.py" in _legacy_get_response 249. response = self._get_response(request) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/core/handlers/base.py" in _get_response 217. response = self.process_exception_by_middleware(e, request) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/core/handlers/base.py" in _get_response 215. response = response.render() File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/response.py" in render 109. self.content = self.rendered_content File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/response.py" in rendered_content 86. content = template.render(context, self._request) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/backends/django.py" in render 66. return self.template.render(context) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/base.py" in render 208. return self._render(context) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/base.py" in _render 199. return self.nodelist.render(context) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/base.py" in render 994. bit = node.render_annotated(context) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/base.py" in render_annotated 961. return self.render(context) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/loader_tags.py" in render 152. compiled_parent = self.get_parent(context) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/loader_tags.py" in get_parent 149. return self.find_template(parent, context) File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/loader_tags.py" in find_template 129. template_name, skip=history, File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/engine.py" in find_template 134. name, template_dirs=dirs, skip=skip, File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/loaders/base.py" in get_template 44. contents, origin, origin.template_name, self.engine, File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/base.py" in __init__ 191. self.nodelist = self.compile_nodelist() File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/base.py" in compile_nodelist 233. return parser.parse() File "/usr/share/str8RED-virtualenv/local/lib/python2.7/site-packages/django/template/base.py" in parse 518. raise self.error(token, e) A: Almost impossible to know for sure given what you've written but likely you upgraded past the point of a deprecated templatetags feature (load ... from future) and you need to go through and either upgrade the packages that have them or update your templates to no longer have the from future in the load tags.
tomekkorbak/pile-curse-small
StackExchange
Influence of maternal dexamethasone treatment on morphometric characteristics of pituitary GH cells and body weight in near-term rat fetuses. Growth hormone (GH) and glucocorticoids have a powerful influence on controlling fetal growth, differentiation and maturation of numerous tissues. In the present study, the effect of maternal dexamethasone (Dx) treatment on GH cells and body weight in 19- and 21-day-old rat fetuses was investigated using immunocytochemical and morphometric methods. Pregnant female rats received daily injections of 1.0-0.5-0.5 mg Dx/kg b.w. on days 16-18 of pregnancy (experimental group), while the control group received an equal volume of saline. Dx treatment of pregnant rats enhanced immunostaining intensity and significantly increased (p<0.05) GH nuclear and cell volume, as well as volume density and number of GH cells per square millimeter in 19-day-old fetuses compared to the controls. In 21-day-old fetuses after maternal Dx administration, immunoreactivity, volume density and number of GH cells remained significantly increased (p<0.05). Dx treatment of pregnant rats resulted in marked body weight reduction of 21-day-old but not 19 days old fetuses in comparison with the corresponding controls. The presented results demonstrate that maternal Dx application has pronounced effect on morphometric parameters of GH cells of 19- and 21-day-old fetuses. Also, in near-term rat fetuses body weight was largely independent of pituitary GH cell activity.
tomekkorbak/pile-curse-small
PubMed Abstracts
The assignee of the present invention manufactures and deploys spacecraft for, inter alia, communications and broadcast services. Spacecraft often include various deployable structures, e.g., solar arrays, antenna reflectors, antenna masts, etc. Such structures may, for example, often be folded flat against a side of the spacecraft during launch and may then subsequently be deployed using, for example, positioning mechanisms when the spacecraft is on-orbit. The positioning mechanisms may also be used, in some cases, to re-orient such deployable structures after the spacecraft is on-orbit. Due to the fact that the deployable structures are typically only operationally deployed in the zero-gravity environment experienced when the spacecraft is on-orbit, the positioning mechanisms used are preferably designed for lower loads than might be the case were they intended to be operational in a 1 G field. This allows a positioning mechanism to be smaller and to have a reduced weight than it might have in a normal Earth-gravity environment. However, while the spacecraft is generally in a weightless environment once on-orbit, such is not the case during launch. In a launch environment, the spacecraft may experience accelerations of multiple G's that may exert forces on the deployable structures that are beyond the positioning mechanism's ability to withstand and that may result in damage to the bearings, motors, or other components of the positioning mechanism. One current practice to avoid damaging the positioning mechanism for a deployable structure on a spacecraft is to temporarily anchor the deployable structure to the spacecraft body using one or more releasable standoffs, e.g., frangible bolts. Such arrangements may be referred to generically as “caging mechanisms”. The present inventor has recognized that there is a need for positioning mechanisms that may replace one or more such releasable standoffs.
tomekkorbak/pile-curse-small
USPTO Backgrounds
Q: When importing a module, how do I specify an interpreter to compile the module? I wrote a module (mymodule32.py) that contains a library that only supports 32 bit Python. I want to import this module in a 64 bit Python file (main64.py). But after searching, I realized that if I import the module in 64 bit Python, it will be compiled with the 64 bit interpreter. I will import mymodule32.py in main64.py, but I want to interpret it with a 32 bit interpreter. I installed Python 3.5 64 bit, and in addition I installed Python 3.5 32 bit under the name py35_32 in the Anaconda virtual environment. I wrote the pseudo code below I wanted(it does not work, of course). import(interpreter = py35_32) mymodule32 A: You can't do what you want with import. The interpreter is a single process, and can't switch between 64-bit and 32-bit modes. Your options are to Run all your code in a Python 32-bit binary. You can guard against using a 64-bit binary by testing for sys.maxsize == (2 ** 31 - 1). Make your library work correctly on a 64-bit interpreter too (just make sure your 32-bit arithmetic is properly masked). Run another Python process as a subprocess; that child process would import your module and use some form of IPC (interprocess communication) to pass data and results between the parent 64-bit process and the child 32-bit interpreter. There are no ready-made solutions here, however.
tomekkorbak/pile-curse-small
StackExchange
Equal Pay for women at risk? Equal pay for women just took a beating in some backwoods state of the USA on March 31, 2012 in a very quiet way. My apologies to followers of ours who live in Wisconsin (I know there are a few) but for goodness sake, how the hell did this happen? I don’t often stray from the primary focus of this site and even less often comment on happenings in the USA, however I smell danger here for woman in any western society if this is not stopped and stopped now. I am a woman and I have three daughters, several nieces, two grand-nieces and a sister. I care what happens. When I was alerted to this today I thought it had to be a somewhat belated April Fool’s Day joke, but it seems not. There is a word in the Great Seal to the right: Forward. Really? Seems not. On Thursday, with little fanfare, Wisconsin governor Scott Walker signed a bill repealing the state’s 2009 Equal Pay Enforcement Act, which allowed victims of workplace discrimination to seek damages in state courts. In doing so, he demonstrated that our political battles over women’s rights aren’t just about sex and reproduction—they extend to every aspect of women’s lives. Now, I’m no American constitutional lawyer, but I had to ask is it only women at risk here, or does the 2009 Equal Pay Enforcement Act cover other groups as well? The Equal Pay law wasn’t just about women—it also offered protection from discrimination based on race, age, disability, religion, sexual orientation, and other factors. But it was enacted largely in response toa large gap between men and women’s compensation, one that was worse than average in Wisconsin—in 2009 the state ranked 36th in the country in terms of workplace gender parity. Well, that answers that question. Not just about women, so we had better keep our wits about us. “You could argue that money is more important for men,” he told Goldberg. I am sure that Goldberg will have no problem, then, in increasing the amounts fathers’ pay in child support when marriages fail and the mother, with custody of the children, can not afford to feed the kids because “money is more important for men”. Is this just white men, just for the record? Where are the women of Wisconsin? I checked a Milwaukee on-line media outlet to see if I could find out. No mention of the eradication of protection of equal pay, however the number of women-owned firms are on the increase in Wisconsin. I’m sure that is comforting for female employees everywhere. Wisconsin ranked 40th in the nation in the number of women-owned businesses, according to the State of Women-Owned Businesses Report by American Express OPEN. The number of women-owned businesses in Wisconsin has spiked 33.5% since 1997, but it’s still below the national average of 54%. “We are finally starting to see progress here in Wisconsin, yet like their counterparts across the country, Legislative Republicans want to turn back the clock on women’s rights in the workplace,” said Hansen. Women earn 77 cents for every dollar that men make. In Wisconsin, it’s 75 cents, according to the Wisconsin Alliance for Women’s Health (WAWH), which also estimates that families in the state “lose more than $4,000 per year due to unequal pay.” Australian women: DO NOT think this couldn’t happen here. Minority groups everywhere: DO NOT think this can’t happen to other groups in society. Maybe the right to vote isn’t really important to women either, you think? I am wondering when the witch hunts in Salem will be started up again. Perhaps we are heading for another Spanish Inquisition? How far back are we going to go? Maybe I am concerned because I am old enough to remember some of the fight. I personally fought for my female staff to be able to wear trousers to work in the 1980s. I know when I started work, city councils still expected women who got married to LEAVE WORK. What are your views? Why aren’t American women up in arms over this? Is this the thin edge of the wedge? Should other states in the USA be worried? Should Australian women and minority groups be worried? What can we do to stop this insanity before it goes any further? Please share your thoughts. #KeepEqualPay 24 comments on “Equal Pay for women at risk?” […] at the type of men in America, another western nation. There was the Governor who thought women don’t really need money, the politician who believes women can’t get pregnant from “legitimate rape” and […] […] Today I got yet another shock. I have written recently about attacks on women from men who live in a delusional fantasy world about the roles of the sexes in life. Dear Max Tomlinson was written in response to a particularly strange Australian and before that I wrote about the repeal of some legislation in Equal Pay for women at risk? […] Yes, Scott’s action was quite bold but he’ll soon be gone and done (recalled) with leading that state. Lots of activity going on inclduing all nentioned above. Sadly, it does seem with each day that we are stepping back into the dark ages for women over here.. . Great piece — but be sure: American women, and especially women in Wisconsin (including me) are up in arms. There is a recall election (of Governor Walker) underway because a half a million people signed recall petitions. We’re not sitting here knitting. 🙂 Good to hear it! Actually, Nancy (see her comments below) did forward to me some fund raising material indicating very strongly that people ARE on the move! I am sorry if I made it sound as if you were just sitting there knitting – I will admit I wrote when I was in the shocked phase and believe it or not, I could find very little in the on-line papers in Wisconsin to give me a feel for the local reaction at all! ‘Equal pay for equal work’ What’s the difficulty of understanding this? I don’t get it. That men will always struggle to get into the better positions, this is something that won’t ever change, I think. I just would like to see more justice in this world. We should aim for supporting people who fight for justice rather than those who are out to exploit the underprivileged. Just amazing, isn’t it? I agree, do idea why ‘Equal pay for equal work’ is such a difficult concept at all. There is a movement afoot in to counter this particular action, so I hear. And so there should be! Oh this is just the tip of the iceberg. Women’s rights are sliding backwards in many ways here in the U.S. I think we got complacent and forgot the laws can be ignored, or reversed, or new laws put in place that are even more draconian than previous laws. Don’t mention the buying of cars! 😆 I’ve walked out of car yards if the salesman doesn’t talk to me – actually, I don’t think any Australian car salesmen are that stupid any more: most Aussie women are pretty specific about who is actually buying their car when they go car shopping – and it IS NOT their husbands! Let me know when that article is up! 🙂 As to was it legal: A) It was in America, B) he just made it legal by repealing the law. 😀 It is a worrying development. I would not be surprised if there were further erosions to follow in the coming months. How enabling discrimination solves economic problems is beyond me (that seems to be one of the “reasons”) but then thankfully I don’t live in Wisconsin. The Winconsinites seem to be remarkably quiet about it. The comment about the extra cost of an extra agency actually don’t wash – after all, there is no need for an agency for EVERY piece of legislation. I am just very concerned there seems to be a lot of places around the world taking backward steps at the moment and I wonder what will be next. As I said in the article of mine I link to at the bottom – these things start small and grow slowly, until one day we turn around and we have lost what we fought hard to attain. Mind you, let us not forget the USA doesn’t have terrific industrial relations laws in the first place. Some states don’t even have an annual leave provision, while in California you can take leave if you get burgled. All very odd. Employ at will is hardly civilised either. When Barack Obama became president of the United States many people who have been bigots all their lives were surprised and shocked because they believed that an African American would never become president. Accepting Obama as President would mean that the bigots no longer held superiority over African Americans. They did not want to lose their feeling of power and priviledge so they went on the attack. Part of that attack was formed in the phrase “take back our country.” What, exactually did that mean? This is the place where Gov. Walker and his colleagues come into play. They want to return the country to the pre-civil rights years where women and minorities were descriminated on a regular basis with little or no legal recourse. Because of the political power enjoyed by Walker and his colleagues, they want to try and retain/regain some of that power. The law was unnecessary and added high civil penalties on top of normal compensation. Without the law, anyone who feels they have been discriminated against can file a complaint with the Wisconsin’s Equal Rights Division which reviews accusations of workplace discrimination, and if founded, can order the employer to pay a worker back wages and perhaps rehire the person. Then there’s the federal anti-discrimination laws still in place as well. The state is in financial trouble so cuts had/have to be made to save money or education and other important programs are going to have to be cut even more. The law created a new and unnecessary agency with more bureaucrats and paperwork, which cost the state money. The fact is that even though tax payer money was going out to maintain the new agency, it wasn’t doing anything for workers so was a waste of money. Workers who felt discriminated against continued to go to the WERD (Equal Rights Division- state) or EEOC (Equal Opportunity Commission-federal) so the agency employees were left playing with paperclips on the tax payers’ dime. That was the reasoning for the repeal, not as cited in the left wing articles you used for reference. I think the average wage always will be. Many factors affect women’s working patterns that do not affect men’s. The mathmatical calculation is therefore not a wonderful indicator. HOWEVER equal pay for equal work is just mandatory in any civilisation that considers itself civilised! The USA doesn’t have great industrial relations laws to start with and we saw the last Australian LNP government try to erode worker’s rights in a similar fashion. 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tomekkorbak/pile-curse-small
Pile-CC
Bolling v. Sharpe, 347 U.S. 497 (1954), is a landmarkUnited States Supreme Courtcase which deals with civil rights, specifically, segregation in the District of Columbia's public schools. Originally argued on December 10–11, 1952, a year before Brown v. Board of Education, 347 U.S. 483 (1954), Bolling was reargued on December 8 and 9, 1953, and was unanimously decided on May 17, 1954, the same day as Brown. The Bolling decision was supplemented in 1955 with the second Brown opinion, which ordered desegregation "with all deliberate speed." Bolling did not address school desegregation in the context of the Fourteenth Amendment's Equal Protection Clause, which applies only to the states, but held that school segregation was unconstitutional under the Due Process Clause of the Fifth Amendment to the United States Constitution. In Bolling, the Court observed that the Fifth Amendment to the United States Constitution lacked an Equal Protection Clause, as in the Fourteenth Amendment to the United States Constitution. The Court held, however, that the concepts of Equal Protection and Due Process are not mutually exclusive. Background Beginning in late 1949, a group of parents from the Anacostia neighborhood of Washington, D.C., calling themselves the Consolidated Parents Group, petitioned the Board of Education of the District of Columbia to open the nearly completed John Phillip Sousa Junior High as an integrated school. The school board denied the petition and the school opened, admitting only whites. On September 11, 1950, Gardner Bishop, Nicholas Stabile and the Consolidated Parents Group attempted to get eleven African-American students (including the case's plaintiff, Spottswood Bolling) admitted to the school, but were refused entry by the school's principal. James Nabrit, a professor of law at the historically black Howard University, filed suit on behalf of Bolling and the other students in the District Court for the District of Columbia seeking assistance in the students' admission. When the court dismissed the claim, the case was granted a writ of certiorari by the Supreme Court. While Nabrit's argument in Bolling rested on the unconstitutionality of segregation, the much more famous Brown v. Board of Education (decided on the same day) argued that the idea of 'separate but equal' facilities sanctioned by Plessy v. Ferguson, 163 U.S. 537 (1896) was a fallacy as the facilities for black students were woefully inadequate. The lead attorney for Bolling was George Edward Chalmer Hayes. The decision The court, led by newly confirmed Chief Justice Earl Warren decided unanimously in favor of the plaintiffs. In his opinion, he noted that while the 14th Amendment, whose Equal Protection Clause was cited in Brown in order to declare segregation unconstitutional did not apply in the District of Columbia, the Fifth Amendment did apply. Thus setting up the theory of "reverse incorporation." While the 5th Amendment which was applicable in D.C. lacked an equal protection clause, Warren held that "the concepts of equal protection and due process, both stemming from our American ideal of fairness, are not mutually exclusive." While equal protection is a more explicit safeguard against discrimination, the Court stated that "discrimination may be so unjustifiable as to be violative of due process." Referring to the technicalities raised by the case's location in the District of Columbia, the Court held that, in light of their decision in Brown that segregation in state public schools is prohibited by the Constitution, it would be "unthinkable that the same Constitution would impose a lesser duty on the Federal Government." The Court concluded: "racial segregation in the public schools of the District of Columbia is a denial of the due process of law guaranteed by the 5th Amendment". The Court restored both Bolling and Brown to the docket until they could reconvene to discuss how to effectively implement the decisions. Controversy Some scholars have argued that the Court's decision in Bolling should have been reached on other grounds. For example, Judge Michael W. McConnell of the United States Court of Appeals for the Tenth Circuit wrote that Congress never "required that the schools of the District of Columbia be segregated."[1] According to that rationale, the segregation of schools in Washington D.C. was unauthorized and therefore illegal. In a debate, law professors Cass Sunstein and Randy Barnett agreed that while the result was desirable, Bolling does not reconcile with the Constitution, with Barnett saying: "You are right to point out that the Supreme Court's decision in Bolling v. Sharpe is very difficult to reconcile with the text of the Constitution. For this reason, you know that among constitutional scholars of all stripes Bolling is one of the most controversial and difficult cases ever decided by the Court."[2]
tomekkorbak/pile-curse-small
Pile-CC
Post traumatic stress disorder was included in the Diagnostic and Statistical Manual of Mental Disorders-III (DSM-III) in the 1980s. Post traumatic stress disorder falls into the broad diagnostic category of anxiety disorders. But unlike most anxiety disorders post traumatic stress disorder (PTSD) can be traced back to a single or reoccurring traumatic incidence. The trauma may be triggered by natural disaster, for instance, fire, earthquake, flood, hurricane, etc. Or PTSD may be a response to; an act by individuals, rape, assault, war, torture, motor vehicle accident, etc. PTSD may develop when a person is exposed to a traumatic event where they feel fear, helplessness or horror. After the event the victim may relive the experience through nightmares, flashbacks, and vivid memories. To manage their stress, the victim may avoid anything that reminds them of the traumatic event. Those who experience PTSD may feel a numbing of their emotions which can lead to relationship difficulties. They may experience disturbed sleep and intense feelings of guilt. In some instances, they are unable to remember specific details of the event. Typically, the victim is over aroused or vigilant, and is easily startled or quick to anger. Survivor guilt is widespread among those suffering from post traumatic stress disorder. Survivor guilt is where the individual feels guilty because they believe their actions were not sufficient to assist the victim or they should have been the victim. The DSM-V suggests that statistically women are more likely to experience PTSD due to rape, sexual assault or domestic violence. Not all those who experience PTSD are the direct victims of a traumatic event. Individuals who are witnesses to a traumatic event may also experience PTSD. Professional employees in the police force, fire brigade, health workers, armed services, and the state emergency services, etc., are also at high risk of developing PTSD. Statistically it is difficult to estimate the number of people suffering from PTSD in any community or worldwide. It is evident that individuals who are exposed to severe trauma are more likely to develop PTSD than those exposed to low level traumatic events. For instance, refugees from war torn countries fleeing persecution may experience chronic PTSD. Men may be the hidden victims of PTSD. Research suggests that men are predisposed to self medicate with alcohol and drugs rather than seek professional help. There is strong evidence that it is the proximity to an event that may lead to the development of PTSD. Proximity can be understood in connection to the aerial bombing of London during the Second World War. Bombs were falling all over London but most residents were in underground bomb shelters. Research suggests that the Londoners who did not directly experience the bombing, did not go on to develop PTSD. PTSD is the one disorder for which mental health professionals are sure of the cause. Someone experiences a trauma and then they develop a disorder. But the difficulty is in identifying who may develop PTSD after a traumatic event. It appears there is a combination of biological, psychological and social factors that may influence the development of PTSD. Some research has indicated that it may be the intensity of the exposure to events. For example, combat exposure contributed to PTSD for many Vietnam war veterans. In contrast 67% of prisoners of war from the Vietnam conflict developed PTSD. Which implies that for some reason the other 33% who also experienced long-term deprivation and torture did not develop PTSD. PTSD is more likely to develop in individuals who have a vulnerability towards high levels of anxiety. This can be particularly true for individuals who come from a family with a history of anxiety. Other factors which may influence the susceptibility to PTSD is behaviour. An individual’s general behaviour may lead them into situations where they will experience traumatic events. As similar to other anxiety disorders, the recommended treatment for PTSD is a combination of psychotherapy and medication. The medications Prozac and Paxil are effective in treating the symptoms of post traumatic stress disorder. Currently cognitive behaviour graded exposure therapy is recommended for the treatment of PTSD. Anxiety provoking psychotherapy has also been shown to be effective in the treatment of PTSD. Chris has an open communication counselling style, friendly and professional. He quickly made me feel at ease and prepared to discuss openly and honestly the issues that came up in our sessions. He checked in with me when issues were potentially emotionally challenging and made me feel safe in our counselling relationship. He is quite intuitive and has introduced a range of counselling/therapy during our sessions. Including cognitive behavioural, relationship and psycho dynamic processes in the exploring my issues. He has very effectively facilitated exploration of my family narrative which has assisted my recognition and understanding of several important emotional experiences and challenges which I am currently understanding and addressing. Narelle - Retail Manager I initially first started to see Chris as I was struggling with health and confidence issues as a result of an accident and the end of a significant long term relationship. In the time I was fortunate enough to see Chris I was able to move from someone who didn’t really want to face anotherdayto someone who could and wanted to navigate through whatever lay ahead. Chris helped guide me through these events whilst challenging and supporting me to work through them. Most importantly he found a way to help me see the possibilities of a happier healthier future. He provided a safe environment where I could take off my victim t-shirt and move on. Ian - Industrial Manager Working with Chris has given me the skills to empower myself. I've taken control of my life to pursue challenges and rewards that give me personal satisfaction. Matthew - Police Officer Chris is a very warm caring person, he had a peaceful & comfortable presence about him. his insights, way of explaining and "unpacking" what's discussed is what makes him unique.The therapy he's conducted has been very beneficial. Jealousy is often experienced within intimate relationships due to perceived infidelity by a partner. But what is jealousy? Jealousy has been defined as, the cognitions, emotions, and behaviours that follow a loss or threat to self-esteem and/or existence or quality of a romantic relationship, How we communicate within our intimate relationships can contribute to our overall happiness. It is not only important to listen to one’s partner it is also important to develop speaking skills that increase connection and lower the negative impact of disagreements. We have all experienced jealousy at some time in our lives. But what is jealousy? Jealousy has been described as a complex range of emotions that affect both men and women. Jealousy stems from a fear of being abandoned, and may include feelings of rage and humiliation. There is a general belief that people who identify as asexual do not form romantic relationships. New research indicates that this is not the case. Lori Brotton of the University of British Columbia suggests that there has always been a general assumption that sexual attraction and romantic attraction happen at the same time. We all know that the internet has changed the way we communicate and how we experience the world, but new research indicates that the internet may also be adding excitement to monogamous relationships. How we give and receive feedback in romantic relationships may be an indication of our overall happiness. Research suggests that feelings of love, bliss, emotional connection, and physical attraction lie at the heart of how happy we are as individuals. Are there any similarities between how same sex attracted couples and opposite sex attracted couples view relationships? Research indicates that same sex attracted couples may have very similar relationship desires and needs as opposite sex attracted couples. During the 1970s and 1980s popular print media highlighted the importance of sexual pleasure and happiness for many in the western world. The emphasis was on liberating both men and women from the sexually oppressive 1950s. After many years together couples may begin to feel that monogamy is slowly slipping into monotony. The once exciting sex life has disappeared under the weight of a mortgage, work, children, family commitments, and life in general. Recent research has explored the effect of yoga on a person’s overall health. A lot of the focus has been on the physical benefits of yoga. This is particularly about the impact yoga may have upon the symptoms associated with osteoarthritis, carpal tunnel syndrome and lower-back pain. Men generally tend to sabotage their chances of good health because they are too shy, too macho, too busy, or too afraid to ask for help. Statistically men visit their GP half as often as women but globally men die younger than women. In contrast men are more sensitive to mild ailments such as flu and tend to over-rate how bad the symptoms are in comparison with women.
tomekkorbak/pile-curse-small
Pile-CC
Yes. It'll be the "sexy" issue. He's been named the sexiest baby. Someone like Matthew McConaughey will be on the cover. No, really. As ridiculous as it sounds, he won a "celebrity baby" look-a-like contest. Seriously. He apparently looks like Gwen Stefani's son Zuma. I think the fact that he has a blond mohawk and a Z name helps. _________________ "He's one of those who knows that life is just a leap of faith.Spread your arms and hold your breath and always trust your cape" Who is online You cannot post new topics in this forumYou cannot reply to topics in this forumYou cannot edit your posts in this forumYou cannot delete your posts in this forumYou cannot post attachments in this forum
tomekkorbak/pile-curse-small
Pile-CC
I am very interested in obtaining a peacock eel. I work with aquariums for a living and the eels we have are in a tank at work with barbs. They are labeled as "Semi aggressive". However, the eels are lazy at best. They pretty much act as if they are the only ones in the tank as they take no notice of the other fish. The eels are amazing at cleaning the gravel as they are constantly hiding in it forcing the debris into the filtration system. I can tell you beyond a doubt that the eel tank is the easiest to clean. Anyways, my question is a question of compatibility between the eel and community fish. I would be adding him into a large aquarium that has the following species: 3 tetra von rios 1 male betta 5 neon tetras 2 black neons 2 zebra danios 3 glass fish 2 fancy guppies. yes theres room for the eels adult size. I am mainly concerned with how his behavior will be towards the smaller docile community fish. I have asked many colleagues at work and like me, they feel this eel is particularly laid back and probably will not feed on the other fish...however none of us have ever tried a peacock eel with small tropical community so i was hoping someone had some experience with this. Thank you so much Spiney eels behave very differently in a tank in which they feel secure than in one that does not provide them the cover they like. I have seen very few heavily planted tanks in stores. Spiney eels in a tank with a thicket or two of leafy stem plants will spend much more time hanging out in the plants waiting for delectable morsels such as neon tetras to swim by than they will buried in the substrate. In fact, digging themselves in is a sign of stress. I cannot recall which forum I was reading this on, but there is a fellow who keeps several and swears by it. I am convinced. Frankly, I think the betta will be OK, and the glass fish probably. The Danios might be just too fast. Beyond that, you'll have some restocking to do. I'd make sure that any fish I had in with a spiny eel was over 2", and over 3" if it were torpedo shaped. That said, if you did this anyway, after your schooling fish evaporate, you might consider replacing them with Congo Tetras or Giant Danios or SAEs or Roseline sharks. Also, sooner or later your betta is going to have a go at your guppies.
tomekkorbak/pile-curse-small
Pile-CC
Wednesday, October 28, 2009 I've been a recipient on Peter Myer's elist for several years. I found his website Neither Aryan nor Jew to be a solid academic resource for historical references. I also get a lot of the Asian-Pacific and banking/financial perspective from his forwarded mainstream news articles. I found him to be an interesting man who shared similar interests in self sufficency and learning to build cool things. He's never once discussed communitarianism with me, and it's only been introduced to his list a couple times. When it is, it's always ignored. So this week I sent him the Clinton calls for Communitarianism in Quebec speech and asked him if we could finally open up the topic, since it's so current. He responded how he would free Australians by taking control of their lives by regulating television and shutting down gambling and other things that hurt people. His policy ideas are what he calls Authoritarian. After he responded, I told him his response sounded very communist and he assured me he is a Socialist. He explained his understanding of communitarianism without ever saying the word, not once: "Tony Blair is quoted as an exemplar of the "Third Way" path. Let's suppose this refers to a synthesis between Capitalism and Communism, in which case it combines the WORST features of each (Laissez-Faire from Capitalism, and Hate Laws ie Totalitarianism from Communism). "If we are to have a synthesis between the two, why not, instead, combine the BEST part of each: Free Speech from Capitalism with Full Employment (a managed economy) from Communism. East European Communism had some private ownership - a mixed economy to a degree - unlike the USSR. Australia of the 1950s & 60s was a much better example of a mixed economy." Key words: "if we are to have a synthesis." Peter Myers advocates for friendlier communitarianism as if it is inevitable. He obviously believes in the Hegelian theory of forced social evolution and only differs on the exact tactics a national system for the global common good should use on the citizenry. He's what Etzioni would call a "soft communitarian" as opposed to the more sadistic change agents who advocate for violent change. For perspective, he posted a nice article by Etzioni published in a London paper in 1995 after my response. Peter told me what he would do if he were running his county, and when I ignored that except to ask if there would be limitations on his power, (in almost the same way he ignored my Jesuit quote about the Hegelian communitarian synthesis), his next response insisted I tell him where I stand: "What ARE your policies on those and other matters? You can't just say, "I'd leave that to Congress" - you've got to say where you stand - how you'd run things if you were in a position of power. It's time to Come Out." I never said I'd leave anything to Congress, I never even mentioned the Congress. He's arguing against me for something I never said. Pretty slick moves there Peter. I'm impressed. I also never heard the term American Exceptionalism until he said my philosophy sounds like it. When I looked it up I was amazed at how much foreigners who write about Americans don't know about Americans. Foreigners don't get to use American communitarian policies and wars to describe American sentiments to me. Socialist and Hollywood views based in dialectical social evolution theory are not valid assumptions and have previously been rendered moot in the ACL manifesto. The current debate is over communitarianism being an illegal action plan for changing America and not which inevitable communitarian system is a "better" synthesis. My problem is I know debating social issues like gambling and health care is a Marxist dialectical trap. I saw exactly where he wanted me to take our discussion; right back to Nowhere. I was supposed to change the topic from my ACL thesis and ongoing research, ignore what Clinton said and forget my documented charges against seditious communitarianism. What's more important to Socialists is my personal beliefs about what people should have to do. Not only is it irrelevant, but I don't have those. I really don't care if Americans go bowling alone or in groups. So I sat down to write a response, planning to call him out on avoiding the topic, and instead I wrote this: Response to peter 10-28-09 Dear Peter, At first I was going to explain to you that as an American I don't have any policies or plans for what I'd do if I was running my country. I have no desire to take on that job and most average Americans like me don't think in your sociological terms. But then I thought about it and wondered what I would do if I were somehow thrown into a position where Americans would ask me to lead them. This will never happen, but okay, I'll bite. Here's what I would do if I were running my country after my countrymen elected me: What I would do if I were "running the country" I would ask the duly elected representatives in our state legislatures to examine my charges against the communitarians during open, public hearings. I would ask them to vote for or against communitarianism. If 3/4 of our state legislatures vote against me and instead agree to ammend the US Constitution in favor of communitarianism, I would retire from public life, and immigrate. If I'm still in "power" after the states decide to keep me as their temporary "emergency" leader, and nobody's assassinated me yet, The first act of my public office would be to acknowledge the declaration of WAR against the United States by international communitarians. I would declare null and void all US policy that places communitarian law over US constitutional law. If the communitarians resist our restoring the legitimate legal order, the ensuing bloodbath would be horrendous, and is to be avoided as much as possible, I agree, but actually fighting in this war is of vital importance and necessary for the future general welfare of our nation. Indeed, if we do not fight now, we will forever lose our children's rights to life, liberty and property. I would void ALL international trade and security agreements that place communitarian law over US constitutional Law and restore the legitimate rule of law to the American people. I'd put out arrest warrants upon every Americans suspected of implementing communitarianism in these United States to be tried in new American courts adhering to ONLY Constitutional law. If I was granted the kinds of powers Peter Myers seems to think a president (or King) should have, I might go even further with my plans for restoring legitimacy here. Given the green light by my countrymen to pursue the communitarians until they are purged from our shores, I would void any law enforcement authority bestowed upon government agencies or departments that adopted communitarian visions for achieving sustainable development. I would restore separation of powers, as per constitutional requirements, right after the states replace every seditious congressional representative who clings to communitarian rule of law I would forbid the continuance of American military/CIA covert operations in foreign nations. I would withdraw US membership from the communitarian United Nations. I would revoke US support for the communitarian Earth Charter. I would void every communitarian UN Local Agenda 21 Plan active in the United States. I would dismantle the communitarian banking cartel starting with abolishing the Internal Revenue Service. I would ask the states for the money to hire 100 small town accountants (two from each state) to balance our federal budget, release the report to the public and ask them to suggest innovative, legal ways to quit using the communitarian's Federal Reserve Notes as our currency. Yes, I would crash American participation in the world "free" market and bring the whole British Rothschild financial scam to a screeching halt. The pain and misery it would cause would be nothing compared to the death and destruction we will experience if we do nothing to stop them. I would replace the Feds money with new American currency backed by gold, silver, copper, US oil and gas reserves, or any other tangible commodity available in the USA. I'd make every assurance that we as a nation will uphold our nation's legitimate debts to every nation and private contractor that can extablish evidence theirs was not a communitarian agreement with the now banished American communitarian traitors. I would redesign the communitarians' 1992 Rebuilding America plan using the textbooks describing the American System of Political Economy as guides. I would outlaw any programs based in dialectical materialism or dialectical idealism. We would proceeed by way of observation and not by the communitarian way of illusion. I would call out the state militias and deputize every law abiding citizen in the country who swears to uphold the constitution of their states. I would assign professional soldiers and private mercenaries to assist in building the militias into a well organized units prepared to protect American borders and homes from communitarian terrorists, both foreign and domestic. I would end the Wars in Iraq and Afghanistan and pull our troops out of every other foreign conflict that involves ANY collaboration with communitarians from Israel or Great Britian. I would cease the War on Terror, both domestically and overseas. I would command our Armed Forces personell in combat zones to make plans to return home in 90 days. I would ask them to search their hearts for what's right and just, and to remember what they swore to defend and uphold. I would plead to them to do their part in healing the terrible rift the communitarians have caused using our country's strength and bravery. I would ask our soldiers to become our emmisaries of real peace by buying all their goods from local merchants wherever they're stationed, to help establish a firm, friendly trading foundation for their children's future, while under command to shoot anyone who continues to take up arms against them. I would issue the final above directive to every American who, under their constitutions, is required to participate in their own defense. I would also run this drastic idea past every loyal American military professional under my command. I would need moral men capable of taking on the challenge of making my last ditch effort plan work. I would quit NATO. I would not allow our nation to depend on NATO for assistance in any disaster. No foreign troops would be allowed on American soil, every country with troops staioned in the US would have 30 days to pull every last one out. The only Rapid Defense we need right now is aganst the communitarians. I would make sure FEMA is fired for their role in Katrina. Using the same power, I would delete The Department of Homeland Security and DARPA from legitimate government operations. We need professional Americans to take back the reigns of American government. All legitimate law enfocrcement programs at the local and state levels would be returned to lawfully elected local law enforcement personel. The FBI would be encouraged to mend their ways. I'd open a new investigation into 9/11, Waco, and Oklahoma under the judicial direction of rank and file professional and volunteer American firefighters and demolition experts. I would cancel all government no-bid contracts and sever all financial ties to the state of Israel. Americans caught sending money to Israel would be deported to Russia. I would impose ridiculously high National Tariffs on all foreign imports; Chinese, and all other communist made goods would be stamped MADE by SLAVE LABOR. I would remove all federal taxes from American made goods and eliminate bureaus and agencies that survive by extortion. I would politely suggest Americans buy up all the goods they can from large scale, foreign made manufacturers because everything will be legal barter after the Fed collapses and the Tariffs are imposed. I would suggest Americans think of things they can learn to produce for themselves and their neighbors once the foreign goods left on American shelves or in the hands of local scalpers are insanely expensive. Our people will have to become self producing and completely self-sustaining before our nation is healthy and strong enough to re-enter the global market. We must recreate what our enemy Lenin complained was a solid equilibrium between agriculture and industry before we can begin importing foreign made goods again. Only after we are no longer weak and dependent (like only a British colony can be) can we allow foreign competition into US local markets. I would revise the communitarian's call to "national and local service and volunteerism "and ask our people to volunteer 2 years or 4000 hours to helping their neighborhoods repair the damage communitarianism has wreacked on American towns, farms, forests, cities, rivers, and people from all races, religions and classes. It will require all of America to dismantle local Agenda 21 at the local levels. American hands-on collaboration with foreigners dismantling LA-21 and establishing a protected economy in their home countries would be encouraged and rewarded. I would shut down, banish the members and confiscate the properties of all academic institutions, think tanks, civil society organizations, churches, law firms and NGOs registered to do buisness in the USA connected to the UN who introduced seditious communitarian programs into the USA, to be divided equally between every American state citizen who files for a piece of it. I would dismantle the communitarian program called Community Oriented Policing and all it's branches, Fusion Centers, Mapping, Interdepartmental Information Gathering et. al. I would empty the prisons of all victimless criminals, starting with marijuana possession, DUIs, and all communitarian driving regulations. I would restore 2nd Amendment rights to American men charged and convicted under the communitarian's Domestic Violence Act of 1995. I would give orders for law abiding, armed Americans to detain for questioning any police officer who arrests law abiding Americans for communitarian crimes. I would ask the counties, boroughs and parishes to form republican citizen's courts operating under state constitutional laws to try, convict and sentence, if found guilty, any federal or state prosecutor in the country who continues to prosecute Americans for committing communitarian crimes. I would recall all grants to communitarian environmental and earth stewardship agencies and cancel all communitarian based Conservation Land Ownership contracts. I would open up all communitarian controlled lands to US state citizens for economic redevelopment, starting with National Parks designated as UN Heritage Sites. I would open all public lands to rebuilding new towns, organic farms, using the fresh water supply, homesteading, logging operations, hunting, fishing, mining and other natural resource extractions. I would put back the management of these lands and operations under elected state and local officials. I would command the FBI to "bring in" Dr. Amitai Etzioni on charges of treason and sedition. I would command the FBI to expand their investigation of "Mega," (the high ranking Israeli spy the FBI suspects of being in the White House), to include Dr.Amitai Etzioni. I would tell all known associates and followers of Etzioni's to leave this country immediately or face criminal charges for conspiracy to overthrow the lawful government of the United States. This would eliminate the Clintons, the Bushes and Obama from the American political scene, which would put a big crimp in the Rothschilds' communitarian control in the US. I would dismantle the entire communitarian system in the US, starting with public education and all the other communitarian programs used to dumb my country down. Then I would think that's probably enough for my first week on the job. My next week's activities would be determined by American reaction to the first. He posted my above email to his list with his reponse tonight: Comment (Peter M.): That's more like it. This is the first time I've seen you say what should be done. Before your email arrived, I was thinking of some "test cases" to put to you. One concerned MacDonalds and other "junk food" purveyors. They are causing obesity and diabetes type II. They are reaching into homes via ads on TV, enticing children to eat their junk instead of home-cooked meals. They are supplying toys to children, with the junk food, to get them to pressure their parents to keep coming back. Before thse Fast Food chains became entrenched, people either ate at home, or ate at Cafes which were separate small businesses rather than Franchises of a big chain. Those Cafes were all different; they served more wholesome food, without the hype and the pressure of TV ads, and without roadside signs producing salivating Pavlovian reactions in those conditioned to eat this food. Suppose that you took action against MacDonalds and the like, they would say that you were infringing their "individual rights" (and those of their customers). Their right to undermine your children; to reach into your house and appeal to your children over your head; to spread health problems like obesity and diabetes, leaving the public purse to foot the bill. You may recall that George W. Bush signed a bill granting these Fast Food chains immunity from prosecution over the harm they've caused to individuals. In your committment to the US Constitution, you spoke of the defence of individual rights. But what of cases where there's a conflict of rights - MacDonalds' "rights" vs the right of (dare I say it) Society? You may recall that Margaret Thatcher said, "There is no such thing as Society". But I'm arguing that there's a Public Interest issue here: that MacDonalds are undermining the good of Society - the Common Good - and using the concept of "individual rights" in their defence. The Communitarians you'd bring into line might also appeal to their "rights", and say they were protecting other "rights", namely the rights of Women, Gays, Children, threatened species etc.: a litany of "minorities". So, each side would appeal to "rights". That's why I wanted you to go beyond abstract terms, to "Come Out". And you have, as a would-be Joan of Arc. Monday, October 26, 2009 Gisela from Alaskans Against the National Animal Identification System (NAIS) sent this with a warning to be careful what I say. She knows I don't advocate against any group, race, or religion except the communitarians. (As far as I know Etzioni's not a homosexual, I never felt the need to take my research in that direction). So why would she warn me about this? Well, she knows this is just the first stage of the extensive and far reaching planned Hate Crime legislation, and that once it passes it opens US doors to enacting harsher enforcement and expanded meanings that include international communitarian definitions of "hate". So okay, I've been warned by a very compassionate fellow Alaskan who has studied the new system as well as any Alaskan I've met (or more). But, no way. I will never stop calling Etzioni a liar and a scam artist. Until the day I die I will openly and frequently refer to communitarians as traitors and terrorists. I will sing it loudly, write it with all the passion I feel, and learn to sign it if they cut out my tongue. I was born endowed with my individual right to express myself freely, no man or act of man's law can ever take that away. And yes, the ADL henchmen will keep pushing to include the Jews. We all know what a wimp Etzioni is when it comes to debate. He needs this protection from solid American researchers like me. Etzioni's always crying about how mean people are to him. He always pulls the Holocaust survivor (which is a boldfaced lie) card to shut down any serious attempts to challenge his loopy ideology and Hegelian solutions. I don't hate Etzioni because he's a Jew, that matters about as much to me as whether he's a fag or not. I hate Etzioni because he used my nation to destroy what little freeedom existed in the world. National Defense in my playbook actually means protecting the USA from Israeli Mossad agents working under cover in the White House as gurus, advisers, and "everything experts". The FBI and the Pentagon need to start sending me a regular paycheck since I'm still doing their job for them. (According to the Army analyst who visited us summer of 2008, Etzioni was not even in the Pentagon datatabase of foreigners known to be terrorists living in the US.) In case you're wondering, both Senators from Alaska are committed communitarians. Both the Republican Party and the Democratic Party have a shared communitarian consciousness. National Defense Authorization Act for Fiscal Year 2010 - Vote Agreed to (68-29, 3 Not Voting)The Senate gave final approval to this bill authorizing defense spending, which also contains a provision that extends the definition of federal hate crimes to include crimes in which victims are targeted because of their sexual orientation and gender identity.Sen. Lisa Murkowski voted Not Voting......send e-mailor see bioSen. Mark Begich voted YES......send e-mailor see bio "It's important that we are in a conscious discussion and a conscious process to evolve options for regional institutions in the future rather than just sitting back and waiting for big problems to emerge." Kevin Rudd Doesn't Rudd sound a lot like Clinton last week? :) Wouldn't a conscious person also want to know the idea and the formula for global forced social evolution into regional communities? It's not an accident that this regional community plan for Asia and the Pacifice includes providing "$50 million to help deploy civilian experts into disaster and conflict zones in the Asian region." As we learned from the Katrina fiasco, locals are NOT allowed to react to their own local disasters anymore. In an evolved, enlightened, conscious community, only outside "experts" are allowed to lead. And they're also the only ones allowed to "rebuild" after their ineptness causes complete demolitions. Here's the emerging communitarian legal synthesis happening right now, in Asia and the Pacific. Apparently the Australians, like the Americans, aren't going to be told exactly what system of law this new trade agreement brings into every home in Australia. The reason we gave our book the title 2020: Our Common Destiny is because 2020 is the communitarians target year for completing regional integration. Many LA-21 plans use the year 2020 in their title, even here in independent Alaska there's an Anchorage 2020 Comprehensive Plan. All of these communitarian regional plans begin as trade agreements, like the EU, and ALL of the plans are now based on the EU "model." There's not one original thing about this "community" plan, it follows the global community plan to a T. The actual legal ramifications of integration are cloaked behind lofty, idealistic phrases that describe how to build a regional architecture.(and I think this is a reference to freemasonry, Etzioni also calls himself "a global architect"). So here we have the National Security editor at the Australian News leading his countrymen by the nose into communitarian slave agreements. Whose security is Patrick Walters protecting with his fluffed up newspiece that leaves out the most important FACTS? And yeah, the closer we get to global communitarian integration the further the left distances itself from the root philosophy driving our social evolution. The right stays in their anti Obama/healthcare mode... HOW is it possible I'm still one of a handful of researchers identifying the communitarian synthesis? Even people who claim they've heard the term continue to ignore it. That sure makes things a lot easier for the global communitarian cartel. From Peter Myer's elist: KEVIN Rudd's concept of an Asia-Pacific community by 2020 has been canvassed at the weekend's East Asia summit in Thailand together with a rival vision from new Japanese leader Yukio Hatoyama. East Asian leaders meeting in Hua Hin yesterday discussed the broad regional architecture, with the Prime Minister promoting his plan both at the formal leaders' meeting and in a series on bilateral discussions. "What I detect across the region is an openness to a discussion about how we evolve our regional architecture into the future," Mr Rudd said yesterday. "It's important that we are in a conscious discussion and a conscious process to evolve options for regional institutions in the future rather than just sitting back and waiting for big problems to emerge." Mr Hatoyama's plan is for the creation of an East Asian Community based firmly on the existing ASEAN regional institutions, which could exclude the US. "You might ask Mr Rudd if his idea is more of an institutional approach than a functional approach," Japanese government spokesman Kazuo Kodama told journalists at the summit. Mr Rudd also took the opportunity to lobby regional leaders on his plan in a series of bilateral talks with heads of government from South Korea, Japan, New Zealand and The Philippines. Mr Rudd also announced Australia would provide $50 million to help deploy civilian experts into disaster and conflict zones in the Asian region. "The government will create a register of up to 500 Australian specialists who will be able to be deployed overseas at rapid notice. "They will be drawn from both the public and private sectors," he said. Mr Rudd also confirmed the ASEAN-Australia-New Zealand free trade agreement, signed this year, will formally come into force on January 1. The agreement between the 10 ASEAN economies and Australia and New Zealand brings closer together 12 regional economies, with more than 600 million people and a combined GDP of $3.1 trillion. Mr Rudd said the agreement would cover 20 per cent of Australia's two-way trade, worth $112 billion, and eliminate tariffs on 96 per cent of our exports to ASEAN nations by 2020. The FTA covers tradable goods as well as services, investment, intellectual property and e-commerce. The nations covered by the AANZFTA are the 10 ASEAN member states: Brunei, Cambodia, Indonesia, Laos, Burma, The Philippines, Singapore, Malaysia, Thailand and Vietnam, as well as Australia and New Zealand. On Saturday, Mr Rudd met Chinese Premier Wen Jiabao to discuss the proposed Asia-Pacific community as well as the upcoming Copenhagen climate summit and bilateral issues, including the case of Stern Hu, the senior Rio Tinto executive held in detention by Chinese authorities since early July. Mr Rudd said the Hu case was the subject of "intense and continuing discussion between the foreign ministries of China and Australia". "My purpose in raising these matters today was simply to highlight the fact that this was a continuing matter of concern to Australia, and I will continue to do so in the future," he said. Foreign Minister Stephen Smith said yesterday that bilateral relations with Beijing were getting back to "business as usual" in the wake of the Hu case. "Whilst we've had some significant tensions in the relationship, we believe very much in the last month or so things are getting back to business as usual, and that's a very good thing with a very important relationship," Mr Smith said. "We continue to urge the Chinese authorities to bring this matter to a conclusion as quickly as possible, to expedite it." So what's more important, as in what's "hard news" as opposed to "fluff?" I studied journalism at UMass, Amherst under profs who also sat on city desks. I think Professor Howard Ziff would have flunked me for sure if I'd have chosen Bill's opinion of the Canadian referendum over his call for communitarian consciousness. Such an unfamiliar term gives it a higher placement in the story, but hmm. Did Clinton's speechwriters include the "joke" about separation to give the Canadian press something to write about other than his communitarian "call"? So where's the US Press coverage of this historical speech? Notta. Zip. Zero. As far as the American press, BOTH RIGHT and LEFT, is concerned, this is NOT NEWS. But as we know, most Americans have never even heard of it. What is news in America nowadays anyway? So here's Makegood blog about what else was going on at McGill University when Clinton was there telling us about our shared communitarian consciounsess: "I chaired two sessions titled “Engaging the Next Generation of Volunteers” at the McGill Leadership Summit on Thursday, October 15th in Montreal. McGill is in the midst of a $750 million capital campaign; they recently passed the $500 million mark. The Leadership Summit is a gathering of campaign volunteers from far-flung committee outposts throughout Canada, the US and beyond." So others attended from the US and beyond (as Buzz Lightyear says, to infinity.. and beyond!). Why didn't ONE of the attendees from the US send a news story or something to an American newspaper about it? Do they all sign non disclosure agreements like that Ophra class at Northwestern or lke what the reporters sign who attend Bilderberg meetings? "Clinton concluded by cautioning that an unequal world is not a sustainable world and it is not a safe world. He suggested that it is only by addressing these global inequities, and creating a great balance through the world, and spreading hope for a better future, that the challenges of the 21st century will be met. He believes a communitarian consciousness will be build hope in the world." Now we're "building hope" too. Great. I'm on a budget here. How much does that cost? Does it matter to the American "anti" LA-21 programme for sustainable development crowd that Bill made the EXACT same connection I made, and Bill said the EXACT same thing I said? Bill Clinton just told the world that communitarians are building a sustainable world, and nobody in America needs to be told what that means or that he said it at all? And yes it sounds perfect, beyond religion, beyond mere spirituality. It's so profound only a few special people understand it, and they are the leaders training NOW to show the rest of us sinners the path to communitarian freedom (which only looks like slavery to the unenlightened). How many suckers worldwide are convinced they are more spiritually evolved and now happily consider themselves communitarians, without the first clue communitarians are liars, thieves and murderers? And I'll just bet the faithful will deny it, no matter how much evidence they see that proves the concept of sustainability is a total lie. Once we come to believe in a power greater than ourselves that can heal the world...we just don't let go of that power very easily. Just stumbled on this long, referenced academic article by Menno R. Kamminga (International Relations and International Organization, University of Groningen) article that argues: Posted on October 24th, 2009 by Bob Bailey Common Purpose is part of the New World Order and sustainable development movement. The main objective of Common Purpose is social control in a collectivist and corporatist society. The philosophy behind Common Purpose is a strange mixture of Capitalism and Communism called Communitarianism. Communitarianism – which is difficult to pin down – is a type of Neo-Communism that owes some of its ideas to Gramsci and the Fabians. When Tony B Liar talked about the ‘Third Way’, he meant Communitarianism. Communitarianism is a “Big Brother knows best” type of philosophy. Barack Obama is a Fabian Communitarian, although you will not have heard him use the term during his election campaign. Americans will get a shock when the truth of his hidden agenda becomes known and they find out his real intentions. Bear in mind that Obama is simply a front-man for the New World Order Communitarians. Communitarians want to create a post-modern, post-democratic feudal society run by a small number of rich and powerful people with everyone else working as peasants. In order to achieve their objectives they must destroy the middle class and the nation state. These links will explain more about this evil and dictatorial philosophy: Slightly OT, here is sound advice from someone who understands the economics of what is going on (also from a US perspective): Europac (Peter Schiff). Quotes “In a communitarian society, which is inherently coercive, it isn’t just the majority view that prevails and becomes policy, the majority view is the only one which can be spoken, the only one which can be even heard.”Medawar “Communitarianism is a collectivist philosophy that explicitly rejects individualism.”Black Crayon “…ideology of ‘civic society’ (or communitarism), which is nothing less than one version of post-Marxist collectivism which wants privileges for organized groups, and in consequence, a refeudalization of society.”Vaclav Klaus “In general communitarians emphasize society rather than the individual and believe that group responsibilities (to family, community, nation, the globe) should trump individual rights.”Libertarians vs. Communitarians “The communitarians work behind the scenes. Élite communitarian ‘thinkers’ quietly slide their new laws inside projects and programs few regular folks will think (or dare) to question. And, just so you won’t look any closer, (or open your mouth to ask one dumb question) the communitarians mask their fascist programs behind all kinds of lovely phrasing. The new phrases work so well that if you do speak up with a debateable question, it means you don’t want to live in a ’safe and healthy community.’ And since everyone has to agree in order to reach communitarian consensus, you will be shunned and excluded from the decision making ‘councils’ that control the new districts. Go ahead and try, but the shifty communitarians will NEVER debate you because their programs are based entirely in a lie called communism.”The Anti-Communitarian League (ACL) “We are witnessing a seizure and redirection of power through legitimate means. This is not a dictatorship but something more complex: the tyranny of popularity.”Utopian Delusions – Communitarianism “There has been very little systematic criticism of ideological communitarianism, if only because its exact premises and policy consequences are difficult to pin down. Those wary of it tend to be individualist thinkers who worry that self-described communitarians are actually stealth collectivists; or, more plausibly, that the main effect of well-intentioned communitarian rhetoric is to provide cover for collectivists with a much farther-reaching and harsher agenda than the communitarians intend.”Wikipedia – Communitarianism “The Communitarian pitch to balance rights and responsibilities thus masks an attempt to shift the basic nature of rights and responsibilities from individuals to the community, i.e. to the state.”Rights, Responsibilities, and Communitarianism “The cult television series ‘The Prisoner’ tells the story of a man who, after losing and then regaining consciousness, opens the blinds of his London flat to find that the world outside has undergone a Kafkaesque transformation: the skyscrapers and city streets visible from his window have been replaced with a small and serene village. (2) Accompanying this stark change in his external environment is a sharp decrease in his freedom. Whereas his life in London was his own, he discovers upon venturing out into the village (3) that his decisions and actions are now community property. He is watched everywhere he goes both by neighbors and hidden cameras. (4) He is expected to be an enthusiastic participant in all communal events, and is ostracized as ‘unmutual’ when he instead seeks out privacy and seclusion. (5) The town’s authorities are intent on ensuring that residents cannot opt out of village life: quaint taxis transport people within the village, but never outside of it; phone service is strictly local; maps at the village store show nothing beyond the community’s boundaries. (6) Each showing of independence or defiance by the protagonist brings strong pressure from the authorities to fully account for (and recant) his actions. (7) In short, his familiar urban life is replaced with a communitarian dystopia, hostile to privacy and deeply suspicious of every act of individuality.”The dangers of fighting terrorism with technocommunitarianism This has certainly been a year for bears around here. We've had several carousing the neighborhoods over the summer. After one griz broke into 5 houses and actually tore huge logs off the back of one a 1/2 mile away, Nordica made me let her brings the dogs back inside gertee. Can't imagine what it'd be like if one of these broke into gertee but it's another good reason to keep up with the slop buckets and dirty dishes. :) Tim's nephew Ray Jr. got this 800 lb griz last night. It charged them on the trapline, very scary story. Ray Jr. has run the Iditarod 8 times and usually places in the top 20. I think Ray Jr. may become the first Redington to win the race, although I'm guessing his cousin Ryan would disagree with that prediction. The paws are 8 inches wide I took video of Tim skinning it; usually leave before that part. Nordica made me change clothes and put them in a plastic bag when I got home. :) Friday, October 23, 2009 Some of my readers may remember my article last spring, "Join the Quiet Revolution" where I detailed the quiet revolution of US policing. At the end I used a quote from the Harvard Crimson Review about Emanuel's philosophy of "universal citizen service" in the style of the IDF. "It’s not only the promise of money that is motivating change." David Brooks The Quiet Revolution A few weeks ago, “Saturday Night Live” teased President Obama for delivering great speeches but not actually bringing change. There’s at least one area where that jibe is unfair: education. David Brooks When Obama and Education Secretary Arne Duncan came to office, they created a $4.3 billion Race to the Top fund. The idea was to use money to leverage change. The administration would put a pile of federal money on the table and award it to a few states that most aggressively embraced reform. Their ideas were good, and their speeches were beautiful. But that was never the problem. The real challenge was going to be standing up to the teachers’ unions and the other groups that have undermined nearly every other reform effort. The real questions were these: Would the administration water down their reform criteria in the face of political pressure? Would the Race to the Top money end up getting doled out like any other federal spending program, and thus end up subsidizing the status quo? Would the administration hold the line and demand real reform in exchange for the money? There were many reasons to be skeptical. At the behest of the teachers’ unions, the Democrats had just shut down a successful District of Columbia voucher program. Moreover, state legislatures around the country were moving backward. They were passing laws prohibiting schools from using student performance as a criterion in setting teacher pay. But, so far, those fears are unjustified. The news is good. In fact, it’s very good. Over the past few days I’ve spoken to people ranging from Bill Gates to Jeb Bush and various education reformers. They are all impressed by how gritty and effective the Obama administration has been in holding the line and inciting real education reform. Over the summer, the Department of Education indicated that most states would not qualify for Race to the Top money. Now states across the country are changing their laws: California, Illinois, Ohio, Wisconsin and Tennessee, among others. It’s not only the promise of money that is motivating change. There seems to be some sort of status contest as states compete to prove they, too, can meet the criteria. Governors who have been bragging about how great their schools are don’t want to be left off the list. These changes mean that states are raising their caps on the number of charter schools. When charters got going, there was a “let a thousand flowers bloom” mentality that sometimes led to bad schools. Now reformers know more about how to build charters and the research is showing solid results. Caroline Hoxby of Stanford University recently concluded a rigorous study of New York’s charter schools and found that they substantially narrowed the achievement gap between suburban and inner-city students. The changes also will mean student performance will increasingly be a factor in how much teachers get paid and whether they keep their jobs. There is no consensus on exactly how to do this, but there is clear evidence that good teachers produce consistently better student test scores, and that teachers who do not need to be identified and counseled. Cracking the barrier that has been erected between student outcomes and teacher pay would be a huge gain. Duncan even seems to have made some progress in persuading the unions that they can’t just stonewall, they have to get involved in the reform process. The American Federation of Teachers recently announced innovation grants for performance pay ideas. The New Haven school district has just completed a new teacher contract, with union support, that includes many of the best reform ideas. There are still many places, like Washington, where the unions are dogmatically trying to keep bad teachers in the classrooms. But if implemented well, the New Haven contract could be a sign of perestroika even within the education establishment. “I’ve been deeply disturbed by a lot that’s going on in Washington,” Jeb Bush said on Thursday, “but this is not one of them. President Obama has been supporting a reform secretary, and this is deserving of Republican support.” Bush’s sentiment is echoed across the spectrum, from Newt Gingrich to Al Sharpton. Over the next months, there will be more efforts to water down reform. Some groups are offering to get behind health care reform in exchange for gutting education reform. Politicians from both parties are going to lobby fiercely to ensure that their state gets money, regardless of the merits. So will governors who figure they’re going to lose out in the award process. But President Obama understood from the start that this would only work if the awards remain fiercely competitive. He has not wavered. We’re not close to reaching the educational Promised Land, but we may be at the start of what Rahm Emanuel calls The Quiet Revolution. Thursday, October 22, 2009 This came today from Kathleen at Habeas Corpus Canada. Her commentary about it was penetrating and knowledgable, she's done a lot of research into the Canadian players and their associations. She's reinspired me today... after the past couple weeks of web updates, videos and radio interviews, 'm fried and was thinking of taking a break. Heh. As my ex-husband used to tell me all the time, "Man he works from sun to sun but women's work is never done." Exactly what part of global communitarianism is a "conspiracy theory?" Former U.S. president Bill Clinton put out a clarion call for people to engage in “communitarianism”, doing one’s part for those on the disadvantaged side of the inequality that exists around the world. Clinton was at Centre Mont Royal downtown Friday morning to receive an honourary degree in Doctor of Laws from McGill University for his achievements in leadership, as part of McGill’s Leadership Summit ‘09. McGill principal Heather Monroe-Blum, who introduced Clinton, noted that only one other U.S. president received a McGill honourary degree — Franklin Roosevelt in 1944. After opening with some self-deprecating remarks, and noting that he was happy that Quebec and the rest of Canada “didn’t get a divorce” back in 1995, Clinton focused on the work of his William J. Clinton Foundation, which tackles the challenges of global interdependence, helping people with HIV and AIDS, fighting climate change and develop sustainable economic growth in Africa and Latin America. Clinton has also been, sometimes with former president George H.W. Bush, raising funds for recovery efforts after recent devastating natural disasters.Clinton told the appreciative audience that he likes Canada because “in many ways, it was like America but with one fundamental difference over the last 25 years. “There’s a great appreciation for individualism, a great belief in the power of free enterprise, and yet there was a certain communitarianism that persisted in Canada that has been lacking in America, but has been building steadily there for the last 10 years,” he explained. “Communitarianism is neither left nor right, it simply recognizes that we are mutually dependent on each other, that it is inconceivable that we can find personal fulfillment or family success unless we have some concern or care for the general conditions under which we all live. “The whole world is interdependent to an extent it has never been before. “I would like to make the argument today that this is basically the mission we have to undertake for the world... We have to have a world consciousness. In the absence of that, we will not make good decisions.” The former president added that one focus of his foundation is to rectify a 25-year-old policy that saw developed countries deliver food to famine-stricken nations, which became impractical and expensive, rather than promoting the development of local agriculture. He credited Canada for moving away from this policy and noted that former president George W. Bush also wanted to do so. In general, Clinton said the world is “too unequal, with half the world living on less than $2 a day, a billion people who go to bed hungry, a billion having no access to clean water, 2.5 billion having no access to sanitation and 130 million who will never go to school. One in four people this year will die of AIDS, tuberculosis, malaria and infections related to dirty water. Eighty percent of the people who die of water-borne diseases are five years of age or younger.” And yet, he also related stories of children and adults either impoverished or devastated by death or natural disaster who choose to persevere. In the 21st century world, “citizens have the power to affect the course of their own destiny, and the world’s destiny is greater than it has ever been.” He cited the numerous NGOs — non-governmental organizations— around the world as taking such initiatives that governments do not. “They believe they can change the world from the ground up... When you have the ability to do something that is good, you have a moral responsibility to try and do it. Most of what I spend my time doing now is trying to get people to understand that you don’t have to be president, a member of Parliament or Congress, or a prime minister, to have a positive impact around the world. You don’t have to be rich... if a large number of people with a limited amount of money each agree that something is a problem, they can move the world.”Mount Royal MP Irwin Cotler, one of those in the audience, said the speech was “extraordinary.” “One of the most inspiring I’ve ever heard — moving, with great content. He summed it up by saying we live in an interdependent world and we have to see ourselves as a communitarian people, and look out for one another or the nature of the universe in which we live with its instability, injustice, inequality and the like will take us down the road to disaster. That plea for working on behalf of our common humanity, the stories he told, this was one of the greatest speeches I’ve ever heard.” Do we really have to see ourselves as "communitarian people?" I don't think we know enough about communitarianism to make a healthy choice about it. Why didn't former President Bill Clinton tell the American people about it when they elected him in 1992? Why doesn't President Obama tell the American people about it now. Do we all just become communitarians by default, with nobody really knowing what it is? Oh, okay, yeah...that's real freedom, right? Wednesday, October 21, 2009 Stayed up all night to be sure I'd be awake for my interview this am. Thought I'd make a mini to relax but here I am. Found this post Etzioni made in Jan 2009 about the visions for a White House Council for Social Advisors. Etzioni was on the Americorps Lauch Committee in 1994. He was on the Launch Committees for Citizen's for Service and Character Education in the early 90s. He was a Member of the Special Committee on Lawyering in the 21st Century, American Association of Law Schools in 1989. He was a Member of the Research Advisory Committee of Resources for the Future from 1976-1980. He was a Member of the Administrative Board, Research Institute on Communist Affairs, Columbia University 1970-1974... ? Anyone who thinks Etzioni's influence is minimal needs to read his bio at Sourcewatch, just for starters. Still don't understand why they begin his Affiliations in 1958; his political carreer began 15 years before that. http://www.sourcewatch.org/index.php?title=Amitai_Etzioni Etzioni wanted his council to advise the President on ALL matters of social policy, in order to strengthen the Third Sector. Did he succeed? His 2001 views on mandatory vaccinations were recently posted here. 2. Our version of a CSA We envision the goal of the CSA as to advise the President on all matters of social policy other than those concerning economics or security. These include policies that strengthen the third sector, especially the country’s hundreds of thousands of voluntary associations and civic bodies; that encourage faith based work within the confines of the 1st Amendment; that promote the fulfillment of civic duty via agencies such as the Peace Corps, Vista, AmeriCorps, the Teacher Corps, and the Citizen Corps; promote understanding and dialogue among social groups that differ in their social backgrounds, identities, and beliefs (including racial, ethnic, and sexual orientation); promote assimilation of new immigrants while assisting them in maintaining their sub-cultural heritages (i.e., promoting diversity within unity); promote community organizations; promote dialogues about our responsibilities to one another, to the nation, and to the inchoate global community. The CSA will be composed of social scientists who have shown a capacity to develop public policies. It could incorporate several existing bodies such as the White House Office of Faith Based and Community Initiatives. To measure and call attention to the social state of union, the CSA would publish an annual report on various social indicators such as the number of Americans who served as voluntary firefighters, emergency medical technicians, or in other forms of volunteerism; the amount of funds raised for social purposes by various foundations and charities; and the number of hate crimes committed, among others, along the lines of the Mondale proposal. For more information, contact Amitai Etzioni at [email protected] or (202) 994-8190. Made this for all the people wo ask me to dumb this topic down. Wonder if my dumb talking and singing helps keep it in perspective. These shorts are just plain fun to make even with my stupid moviemaker program and no audio recording equipment other than my camera. I think I could make some damn fine videos with a production budget. I almost forgot how much I loved making the documentaries at UMass, all except for the interviews where I had to be on camera. I don't have any problem singing for an audience and had many parts in different kinds of musicals, but I avoided dramtic plays like the plague. If I'd have been taller I would have been a Vegas Showgirl. "Adaptation to climate change is vital in order to reduce the impacts of climate change that are happening now and increase resilience to future impacts. The UNFCCC webpages on adaptation highlight the negotiations and action being carried out on adaptation by governments and stakeholders as guided by the Convention (particularly Article 2 and Article 4)."http://unfccc.int/adaptation/items/4159.php The communitarian nature of the new constitution is based on the recognition of the cultural institutions that give form to the behaviours not only of rural communities, but also urban ones. We speak about the ayllus, the tentas, the capitanias, the organising structures that give meaning to migration, migrant settlements, holidays, festivals, challas, rituals and ceremonies, where collective symbolism lies. An initial conclusion could be the following: the new constitution represents a transition from the unitary and social nature of the state to a plural-national and communitarian one. It is also a constitutional transition, as developments in liberal rights, obligations and guarantees are combined with constitutionalised indigenous demands, and with legal and political forms that give a constitutional framework to the process of nationalisation and recovery of natural resources. In other words, it does not cease to be a liberal constitution, albeit in a pluralist version, incorporating four generations of rights: individual rights, social rights, collective rights and environmental rights. It is also an indigenous and popular constitution in that it incorporates the indigenous nations’ and peoples’ own institutionality, their own structures and practices. In the same way, it is a constitution that recognises the fundamental role of the public realm as an interventionist, welfare and industrialising state. Bolivia's New Political Constitution of the State, by Raul Prada (link below, emphasis mine) The direct link to EU Communitarian Law has moved, hard to find it since I only read and speak in english. Here's how it's explained in Europe: Environmental Law Are you aware of all of the obligations imposed on your company by legal regulations with respect to the environment? Are you sure that your company fulfils these obligations duly and reliably? Are you aware that the penalties for breach of these obligations amount to millions of crowns? This article analyzes, on the one hand, the role of services of general interest and the notion of public service obligation under the Communitarian law, and on the other hand, the way in which Communitarian law (which, after Romania's adhesion, became national law by transforming the communitarian acquis into the preferred national law) will influence and enrich Romanian public service. The article deals with the new obligations imposed by the Communitarian law to the Romanian public services. In this article, the author analyses the characteristics of the new political constitution of the state, passed after Evo Morales took office as the president of Bolivia. This new con-stitution redefines the concept of the state as well as that of citizenship from a plurinational, multicultural and communitarian perspective. The development of liberal rights, obligations and guarantees is combined with grassroots indigenous claims, which are thereby included in the new legal and institutional framework. Hence, the notion of an interventionist, welfare state that protects natural resources takes shape, which incorporates the ways and practices of first peoples and nations into its institutional life. The state thus becomes a tool for equitable, sovereign and sustainable development. Raúl Prada Alcoreza - Professor and Researcher. Coordinator of Doctorate Studies on Epistemology at the Universidad Autónoma Gabriel René Moreno. Member of the Research Group La Comuna. ... The characterisation of the Bolivian state as a social unitary state of plurinational and communitarian law is new; this broad and complex description is not found in the old constitution. The characterisation of the state is a thorny subject. It articulates the legal sphere with political urgencies, and the social unitary rule of law with its plurinational, community and intercultural nature, ratifying its condition as free, independent, sovereign and democratic. It is founded on plurality and pluralism that operate in distinct spheres: political, economic, legal, cultural and linguistic. It is based on the recognition of the pre-existence of the originary indigenous peoples and nations, which implies the recognition of their right to self-determination. The characterisation of the state offers a description of the Bolivian people in its diversity and multiplicity, identifying its multicoloured composition with respect to nations, classes(1) and social strata, scattered around the cities and the countryside. The characterisation of the state describes a democratic and participatory government, and opens up multiple types of direct, universal and communitarian representation. It also combines the cultural values of originary peoples and nations with liberal principles. This composite understanding of the characterisation of the state includes liberal constitutional developments and is enriched by the indigenous contributions of new constitutional and political forms. Book Reviewstheory and philosophy. The not-so-rarebibliographical pointers in bracketsscattered throughout the text illuminate animmense variety of theoretical conceptionsbuilt upon. However, there are a lot ofthoughts that will not feature an explicitreference to a particular author - but allthese conceptions that are indirectly beingmade use of will slowly dawn upon thereader as an unmentioned yet clearly visiblebackground that enriches March's andOlsen's narrative.In remarkable difference to other worksof democratic theory, 'DemocraticGovernance' does not have the sometimesdusty smell of academic self-reference.While informed by traditional as well asless traditional sources, it never comesclose to scholarly rumination. Indeed,March and Olsen assemble a whole newworld of thinking about the basic issues ofdemocracy. Sometimes it seems to bepossible to locate them in the vicinity ofsome familiar political conception (such assome strands of communitarian thought, ornew republicanism, or Habermassiandiscourse ethics), but as soon as thisfamiliarity is graspable the authors subtly,albeit quickly and unmistakably, distancethemselves from it. It is impossible to putthem into a drawer with a traditional label -they are simply March and Olsen.Why is it so worthwhile for legalscholars to invest in this book? Because itcasts a new light on many, if not all,preconceptions and Vorversta'ndnisse oflegal thought. For instance, is it notcommon legal knowledge in moderndemocracies that democratic accountabilityis the centre-piece and Archimedean pointof conceptualizing democratic legitimacy?March and Olsen, of course, do not argueagainst accountability - but relying onfindings of psychology and politicalscience, they manage to drag this theoreminto the twilight of ambiguity and implantthat grain of doubt into the reader's brainthat will force her to go on thinking aboutaccountability and to question some of thebasic knowledge we already believed to beuncontestedly received. In addition, theauthors place our legal beliefs into a widercontext (of ideas about the common good,or a civilized society), connect them tothoughts about learning, ideology,aspirations, solidarity, virtue, faith, or thedevelopment of political identities, andthus broaden our horizons in the true senseof the word. Starting out with a brilliantanalysis of democratic governance, Marchand Olsen eventually arrive at a democraticagenda of how individuals and societiescan achieve institutions that make politicscivil and capable. Anyone with only aslight interest in political theory who isbored by self-referring accounts of theexaggerated antinomies between substanceand process or between liberalism andcommunitarianism should buy and readthis book.Ulrich R. HalternHarvard Law SchoolBoyle, A.E. (ed.), EnvironmentalRegulation and Economic Growth, Oxford:Clarendon Press (1994) xxix + 252 pages +Index. $65.Increasingly stringent environmentalregulation in industrialized States has givenrise to fears of decreasing competitiveness,and of a curbing of economic growth.Simultaneously the possibility ofimposition by these countries of greenbarriers to regional and international tradethreatens to restrict imports from countrieswith lower environmental protectionstandards. Fears of economic inhibition arejustified only to the extent that the conceptof sustainable development demands a halton indiscriminate economic developmentin favour of environmental protection. Yetthe practical meaning of such a conceptand the implementation of leadingcomplementary environmental principles,such as the 'polluter pays' principle,remain full of uncertainties. Focusing onthe interconnection between environmentallaw and economic development.Environmental Regulation and EconomicGrowth, fleshes out some of the key legal136Book Reviewsissues underpinning any future synthesisbetween economic growth andenvironmental protection.The book is basically a collection ofpapers presented at the 1993 Oxford LawColloquium, in which the concept of'sustainable development' and the 'polluterpays' principle serve as the guiding linesthrough which the authors discuss varioustopics, ranging from the interconnection ofdomestic, European, and Internationalenvironmental law, through the role ofinformation, auditing, and liability regimesin environmental protection, to therelationship between free trade policy andenvironmental protection, the effects ofenvironmental regulation on business, andthe costs of compliance with acontinuously growing environmentalregulation.Therefore, as the editor points out in theIntroduction, the book tackles manyimportant problems of practical importanceto all those dealing with environmental law,but it does not attempt to present acomprehensive account of what in anyevent is an extremely wide-ranging issue.However, as he acknowledges, the confinesof the colloquium and of this book did notpermit the inclusion of contributions byenvironmental economists. Nor does itafford attention to developmental issues assuch, which could be regarded as a ratherimportant omission, although some aspectsof North-South relationships are touchedupon in chapters devoted to the relationshipbetween trade and environment.The book has two particular strengths.First, its blend of expertise and views ofacademics, practicing lawyers, regulators,and figures in industry and commercewhich presents a multilateral and quitecomprehensive account of the relationshipbetween environmental law and economicgrowth (though it is somewhat surprisingthat the perspectives of Non-GovernmentalOrganizations have not beenaccommodated). And second, its constantdrawing upon the interplay of international,Community and national law, whichprovides the reader with insights to thedifferent policy levels and legal solutionsbearing upon the subject. Thus, forexample, in the national arena specialconsideration is given to an analysis of therelevant legal issues in the UnitedKingdom, with occasional references toother Anglo-American legal systems(United States, Canada and Australia) andto other European Union Member States(mainly to northern partners such asGermany , The Netherlands and Denmark).However, while accepting the logicalconstraints of the colloquium and the book,a more detailed analysis of the costeffectiveness of the environmentallegislation under assessment would haveserved to further illustrate the extent towhich different levels of environmentalprotection allow economic development, aswell as establishing criteria to select themost appropriate legal instruments for theattainment of joint environmental andeconomic goals.Overall, the approach followed inEnvironmental Regulation and EconomicGrowth constitutes a worthwhilecontribution to the ever expandingliterature on environmental law which,hopefully, will trigger further research onmethods and processes best suited to realizesustainable growth.Carmen Plaza MartinLLM. (University of Essex)S.J.D. candidate (Universidad Complutensede Madrid)HauBler, Richard, Der Konflikt zwischenBundesverfassungsgericht und politischerFuhrung, Berlin: Duncker & Humblot(1994) 286 pages. DM 108; 6S 843; sFr108.The expansion of judicial power, above allof Constitutional Courts, has been thesubject of a flood of publications aroundthe world (the latest example being Tateand Vallinder's compilation, reviewed inthis issue). In the United States alone, the'countermajoritarian difficulty' (Alexander137 Put my latest mini up on ebay last night. Last week I put one of my tables up with one of Catherine's baskets and 10 glass jars filled with plants and balms and it sold for $49.99; that inspired me to make this roombox. It's stuffed with some of my nicest items and should make a lovely addition to anyone's home. It's very Alaskan in that it's tiny (most old Alaskan buildings are quite small) and made of recycled boards. We want to build a "real" gift shop just like it now! More news from Consuelo; her efforts are becoming a major contribution to our body of work. I may plan an ACL award for genuine "service" to freedom, I'd love to be in a position to give out certificates of achievment to people for exposing the enemies of individual liberty. For now my personal, hearty thanks go out to our dear friends all over the world for their continued interest and deep background studies... we all benefit from your devotion. October 16, 2009 ENTERTAINMENT INDUSTRY FOUNDATION, MAYORS FROM ALL OVER THE U.S. KICK OFF TWO MAJOR INITIATIVES ENCOURAGING VOLUNTEERISM Today in the heart of Times Square, actors and executives representing the Entertainment Industry Foundation (or EIF, the entertainment community’s collective charitable organization) joined New York City Mayor Michael R. Bloomberg and 15 mayors from around the country, numerous celebrities, and key service groups to launch two new initiatives aimed at fostering a new era of volunteerism: EIF’s I PARTICIPATE and the mayors’ Cities of Service coalition. EIF is mobilizing the entire entertainment community around the ground-breaking, multi-year I PARTICIPATE, which will promote a new way of thinking about service [emphasis mine] and seek to persuade millions more Americans to volunteer regularly.* To jumpstart the campaign, Entertainment Industry President and CEO Lisa Paulsen, Tyler Perry and Ashton Kutcher announced its 2009 centerpiece: a week-long television event running from October 19th to the 25th, when America’s most-loved TV shows on ABC, CBS, FOX and NBC and other broadcast networks will spotlight service through scripted programming, segments and PSAs with inspirational messages and storylines about volunteerism. Randy Jackson (FOX), Christine Baranski (CBS), Tim Daly (ABC) and Michelle Trachtenberg (NBC) also participated in the announcement. “…which will promote a new way of thinking about service…” TRANSLATION: “Voluntary Service” will soon mean “Compulsory Duty.” If you notice, even the above phrase subtlety omits the word “voluntary” before the word “service.”________________________________*What’s “regularly”? Will the government soon set guidelines as to what is considered “regularly”? You can bet on it. Are Americans really starting to ask what the newspeak means? Sure looks like it. Hooray! Donate Here! About Me 2020 / TACM Available NOW in PDF eBook Translate Search This Blog I'm Niki Raapana, an independent researcher, co-founder of the Anti Communitarian League (ACL) with Nordica Friedrich, co- author of 2020: Our Common Destiny and co-author of the Anti Communitarian Manifesto.
tomekkorbak/pile-curse-small
Pile-CC
by Brennan J. Bennett Four days, he thought, stepping out of the battered cabin he’d rented when he’d first arrived in Hog-Jaw. It had been four lousy days in this cold, Canadian piss-pot of a town and Jack Bradley still hadn’t figured out why he’d even come in the first place. It was because of her, he could remember that much. That bitch. Before stopping in Hog-Jaw, Jack had been a week into getting-the-fuck-out-of-Dodge—“Dodge” being his marriage and the shit-storm he’d left behind. He’d left his driveway in Maine with “If I ever see you again, I’ll cut your fucking face off!” echoing in his ears and had wound his way through Canada to Newfoundland, where he’d been barrel-assing across the island when he’d seen the sign for Hog-Jaw. It had been the name “Hog-Jaw” that had reminded him of something she’d said early in their marriage—though he’d never made a habit of listening to her—and he’d been compelled to stop. He’d spent the next four days getting righteously, rip-roaringly drunk, and trying to remember what she’d said that had made him stop and spend the week of Christmas in this Podunk little shit-tank. And as he heard the burping and coughing of the ancient truck on the morning of his fifth day in Hog-Jaw, he still couldn’t remember a thing. The truck was rumbling toward him up the neglected dirt road that ended abruptly at his front door, and he descended the cabin’s four-step front porch to meet it. The rust-colored Chevy rolled to a stop, and the driver killed the engine and swung open the rust-pocked door. He seemed to emerge in segments. By the way he moved, Jack had expected to see an old-timer—a grizzled, leathery woodsman—but the man who uncoiled himself from the Chevy was no more than forty, about his own age. He was broad-shouldered and sturdy, with the thick arms and chest of an athlete (or a lumberjack, Jack thought). Dense hair spilled out over his shirt and seemed to climb like ivy toward his neck where it merged with thick stubble that swallowed most of his face. Messy shocks of reddish-brown hair fell from his head, leaving only a narrow slot for his sunken eyes. Jack thought of medieval knights and the tiny eye slots of their visored helmets. The man shut the door of the truck and took a few aimless steps toward him. As he approached, Jack could see a deep, twisting scar that began at the corner of his eye and plunged down somewhere into the wild, endless stubble. He stopped ten feet from where Jack stood and said nothing. “Morning,” Jack offered. Silence. “What can I do you for, Chief?” Jack said, grinning. Again, silence. “Everyone in this town this damn chatty? You know, on that note, does thirty people in the woods even constitute a town? I mean, this–” “Morning,” the man said, suddenly. It was neither a pleasantry nor a greeting, but a simple statement of fact. The flatness in his voice matched the lifelessness in the eyes that peered not at Jack, but past him into the woods, from behind the wild visor of hair. Jack hesitated, eyeing the man suspiciously, not sure if he might offer more. Finally he said, “Okay, can I help y–?” “See you tonight,” the man said flatly, suddenly—strangely suddenly, Jack thought. The vacant eyes continued to stare. Jack furrowed his eyebrows. He opened his mouth to speak, but just as he did, the dead-eyed hair-knight snapped his head a quarter-turn to the right with surprising quickness. The abruptness of the movement startled Jack and his mouth hung open. Hair-Knight seemed to be looking at the cabin. Jack swallowed hard. His mouth felt dry and the spit stuck in the back of his throat. He traced Hair-Knight’s line of sight and realized, with sudden confusion, that there was something—maybe a flyer—taped to the outside of his cabin door. Before Jack had much time to think, Hair-Knight’s head began to turn back toward him. It moved slowly, deliberately. All sound seemed to fade and Jack could feel his eyes darting with metronome quickness, anticipating that something—anything—might happen. As Hair-Knight’s face became visible to him, Jack could see that his formerly dead, sunken eyes were now wide and popping from his skull. Jack felt the hackles rise on his neck, sick gooseflesh leap from his skin. Despite the freezing air, hot waves of steam rippled from his chest and made his cheeks flushed. Without a word, the man turned toward his old truck and pulled open the door. The door gave a shrill whine and Jack winced. And before he could really understand what had transpired, the man folded himself back into the old Chevy with his same meandering slowness and was gone. ***** When Jack arrived at Clapper’s a half-hour later, the barroom was nearly empty, other than a few shrunken old men scattered about the place and a tired-looking bartender. Jack plopped himself down at the bar and slouched onto his elbows, his head in his hands. Replayings of his peculiar encounter with the stranger outside his cabin flashed before his eyes. His skin crawled and pricked with each replay, as if suffering bites from a swarm of fire ants all over his body. His muscles were tense, and the innocuous sounds of the barroom made his bones pulse and caused him to cower reflexively for an instant each time one disrupted the heavy stillness of the room. He replayed the stranger’s words—see you tonight—like his mind was stuck in a record-player-skip, until his face felt numb. The flyer pinned to his door was perhaps the most troubling part of the encounter. It had been pinned to his door in the wee-hours of the morning—he’d been up, piss-drunk, by the fire until at least midnight, and the flyer hadn’t been there when he went in for the night. That meant someone had been watching him, waiting for him to turn in, had crept up to his door… He shivered. What was more concerning, though, was the way Hair-Knight seemed to look right at it—the only thing he looked clearly at—like he wanted him to see it. When Jack had snatched the paper from the door after Hair-Knight left, he was even more perplexed. “Annual Night of the Mummers,” the headline had read. Below it: “December 23.” Tonight. Underneath that, a peculiar picture of what he could only describe as a “fucked-up clown” had smiled out at him. At the bottom of the page, he’d noticed a few lines of verse that read, “There’s big ones and small ones, and tall ones and thin, / Boys dressed as women and girls dressed as men, / Humps on their backs and mitts on their feet, / My blessed we’ll die with the heat. –Simani.” He’d seen the same flyer plastered to the window of Mack’s Market as he’d passed a few minutes before, and the same fucked-up clown—“the mummer,” apparently—was staring at him presently from the flyer pinned behind the bar. “Get’cha, b’y?” the old barman said, startling Jack out of the dark mire of his thoughts. Jack looked up and said nothing. “Whadda ya want, b’y,” he asked again in thick Newfoundland English. “Beer. Don’t care which.” “Black Horse?” The old bartender’s face was a reddened and weathered patchwork of wrinkles, and Jack could see exhaustion plain and true. His eyes, though, seemed sharp. “Oh, me nerves,” the barman said under his breath when Jack didn’t answer, and then more forcibly, “Black Horse, eh, b’y?” “Sure, yeah.” Jack watched him as he snatched a mug and pulled the tap. He was a stout little man, and he lumbered when he walked, like a man who had seen too much to worry about being in a hurry. Presently, he plodded toward Jack with the amber beer. Jack noticed his eyes again when he set down the mug, the sharpness there that stuck in his mind like a thorn. “So, what’s the deal with this Mummer thing?” Jack asked, taking a long, calming sip of his beer and gesturing to the flyer behind the bar. “I’ve seen the flyers everywhere.” Like my fucking cabin, he thought. “Local ting,” the barman said, turning to eye the poster. “Sort of a game ’round Christmas every year. Yer friends dress up in masks and come to yer house, see if ya can guess who they be. Ya give ’em drinks fer clues, and when ya guess ’em all and the masks come off… well that’s when the real drinkin’ begins, eh, b’y?” “Sounds…” Jack trailed off and slugged the rest of his beer. “Yes, b’y, t’sumtin’, tat’s fer sure.” He held Jack’s gaze a bit longer than was comfortable and Jack sensed that sharpness once again, like the old barman was trying to tell him something. “Anyway, tis place’ll be empty. Whole town’ll be mumm’rin’. Anotter?” he said, scooping up Jack’s empty mug and heading for the taps. But just as he did, the tavern door swung out furiously and three feral-looking men shoved in. The barkeep eyed them skeptically, almost vigilantly, and turned back to Jack. He lowered his red-leather face, that sharpness blazing behind his eyes, and whispered, “I’d say t’sabout time ya headed back to where ya come from, me son.” He stepped back, shot Jack one final knowing glance and greeted the three men with “Get’cha, b’ys?” in the same tired, banal voice he’d used on Jack. ***** “Fuck me!” Jack yelled as he slammed down his third pint to a chorus of cheers. His three new friends slapped him on the back. When they’d first arrived, Jack had noticed two things simultaneously: first, each had a scar on his face similar to Hair-Knight’s, and second, almost as soon as they’d come through the door, the handful of old-timers in the room scattered as if they’d caught the fresh scent of death on the wind. But those things were long gone from him. Now, he was quite enjoying their company. “Bring me another round, b’y!” Jack yelled to the barkeep, mimicking the local Newfie accent, to another round of wild cheers. The bartender ambled over with another pint. Jack grabbed the beer and spun on his stool to face the men who were standing behind him in a tight half-circle. He thrust his glass toward them, and as he did, the three men raised theirs in odd unison, as if their arms were all tied to the same string. Jack smiled and teetered forward, sliding half off the barstool, not seeming to notice the strange uniformity of the men standing before him—the way they moved, spoke, laughed. “Okay, b’ys,” he said, “what is it we’re toasting this time?” A furtive glance passed among the three men, but again, Jack didn’t notice; his head danced in a warm haze. “To ex-wives,” one of the men, Daniel, said after a moment’s pause, and raised his glass. He was a big bastard, probably six-foot-four, the kind of guy Jack would call a brick shithouse. “You, Daniel-san?” Jack said stupidly in his Mr. Miyagi voice, pinching Daniel’s cheek. “With that handsome punim?” “Believe it, brother,” Daniel said, clinking his glass against Jack’s. “She’s sort of the reason I ended up here. I was an ass. I’m getting what I deserve, really.” “She do that to you?” Jack asked, half-serious, reaching up a hand to finger the ragged scar that twisted from under Daniel’s nostrils and tucked underneath his chin along his jawline. “Something like that,” Daniel said. When he didn’t say more, Jack said, “Women,” and downed a healthy gulp of beer. Shaking his head, he added, “Can’t live with ’em, can’t live with ’em. My old man used to say that.” This brought another round of cheers and more clinking glasses. “You said it, pal,” Daniel agreed. Though Jack hadn’t noticed, his head beginning to swim in inebriation, Daniel hadn’t touched his beer. In fact, none of them had taken a single sip the whole night. “You married, Jack?” another of the men, Jordan, asked. “Me? Fuck no. Well, shit, technically, yes, I still am. But let’s just say things didn’t end too well between me and the missus.” Jack finished off the pint in a heaping gulp. “No?” Jordan asked, his expressionless face belying the false emotion in his voice. Jack narrowed his eyes. “There’s something about you, Jordan. Something I can’t quite…” If he hadn’t been drunk, Jack may have placed his finger on what didn’t sit quite right about Jordan—the way he stood, too upright, or the way he never shifted his weight. He may have thought Jordan was a little too robotic, his movements too stiff, his skin too smooth—except for the faded pink gash-scar that split his cheek in two from ear to nose. What Jack might have noticed most of all about Jordan—about all of them—is that he didn’t speak with a Canadian accent—Newfie or anything else. Instead, when Jordan told him he didn’t have to talk about it, Jack replied with, “You want a story, fuckers? Then I’ve got one hell of a tale for you.” “Bartender—another pint!” Daniel yelled and Jordan cheered. With fresh beer in hand and bright lights bursting behind his eyes, Jack began his story. “You see, b’ys, ol’ Jackie went and screwed the pooch, as they say. Well, if we’re being technical, I’d been screwing it just about every day.” “Other women?” Jordan said. “Everything that moved.” He was starting to slur his words. “You see, my missus… well, she just stopped putting out. It wasn’t always like that. She gave great head when I first met her, really rocked my fucking world. You find a girl who sucks cock like that and you lock her down—my old man never said that, but there would have been some practical advice!” His three friends laughed a tinny, mechanical laugh in unison. Jack didn’t know why but he thought the laughter sounded like dead leaves scraping across pavement in the dark. Jack took a long sip and continued his story. “Anyway, the fun stopped right after we got hitched. The fuck am I telling you for? Daniel, you were married; you know all about it.” Daniel nodded and flashed a hollow grin. “You other two twats ever married?” Jack asked, looking from Jordan to Nate, the third of the men. Both nodded. “Yeah, I could tell. Both divorced right?” They nodded again and Jack echoed their nods. “Knew it. We divorced guys have a certain look, a certain je ne sais quoi,” he said, nose upturned in mock-sophistication. Jack noticed—the first thing he had noticed all evening—that Nate’s mouth took a downward dip at this. “Yours did a particular number on you, huh, Nate?” “I deserve what I got,” he said flatly, looking down. “Oh come on, boys! I’ve heard enough of that,” Jack groaned. “First Daniel and now Nate… Jordan, straighten them out!” “Sorry, Jack,” Jordan said. “I, too, have reaped what I’ve sown.” “Bullshit!” Jack yelled. “Bullshit! A hot, steamy pile of it! Come on, boys! The bitch is to blame! Mine caught me in the act! Came home early one day and caught me laying pipe right there on the living room couch. Some young slut. Big tits.” Jack grinned and lost himself in memory. “Why are you here?” Nate said with a bluntness that woke Jack from his daydream. He was glowering darkly. Jack looked up at him through glossy eyes that became suddenly lucid. “What do you mean?” Nate, Jack had learned, was a sullen son-of-a-bitch, and he hadn’t done much more than grunt since they’d met. Jack could tell he was a man of few words, but he seemed particularly surly this evening, really just going through the motions. His face was a permanent scowl and his wild-horse eyes were near-black. His scar, too, was unlike those of the other two (three—he remembered Hair-Knight and shivered). While theirs gave their faces a pitiful, victimized quality, his added an element of antagonism. It cut sharply across his lips, from nose to chin. “You should leave and never come back,” Nate said, his face impassive. “What Nate means to say,” Daniel broke in, turning toward Nate and glaring feverishly, “is how did it end with your wife?” Though Daniel had been speaking to him, Jack thought the words were more for Nate. “Jack?” Daniel said. Jack, still watching Nate, jumped, startled. “Huh? Oh—sorry. What did you ask?” “How did things end with your wife?” “Ehh, you know,” he said dismissively. “Do tell,” Jordan said. His robotic cadence again shocked Jack, furthering sobering him. “Not much to tell, man,” he said almost defensively. “My wife’s crazy. She told me to get the hell out, that she’d kill me if she ever saw me again.” I’ll cut your fucking face off. “Did you believe her?” Daniel said. “I’m sitting at a hole-in-the-wall bar on an island in Canada, aren’t I?” “Fair point,” Jordan said. “I mean, I don’t think she’d ever hurt me. I don’t know; maybe she would. I guess I must have believed her because here I am.” Jack grew suddenly pensive. “I guess she does have something about her that is sort of scary.” “She sure does,” Daniel said. Nate jerked up his head and locked eyes with Jack as soon as Daniel spoke. “What did you say?” Jack said, confusion plain on his face, his mouth suddenly dry. “I said, ‘I’m sure she does.’ She must scare you to get you to leave home.” “Yeah,” Jack said slowly, suspiciously. He stared at Daniel, afraid to break eye contact. He was just about to look away, to accept that maybe he had heard Daniel wrong, when he saw Daniel grin. Jack stood up and retreated a half-step. He scanned the faces of the three men, feeling suddenly alone and vulnerable. And then he saw Jordan grin. Their grins seemed to be alive, spreading like ink in water, malignant and black, across their faces. Jack felt a pressure begin to build in his chest like he were in a too-fast car going zero-to-infinity. He couldn’t breathe. He knew, suddenly, that he had to get away. He recoiled back into his barstool and stumbled hard into the bartop. He caught himself just before he fell and hurried for the door. Once onto the sidewalk, he took a deep breath of cold afternoon air and glanced back into the bar through the storefront window. Daniel and Jordan were still watching him with their wicked faces. Nate, though, was looking down, his hands in his pockets. ***** When he awoke, face-down on the tweed sofa in his cabin, Jack was chilled and shivering. The room was dark, except for the sliver of dingy light that shone in, horizontal, through a window by the door. The sky was a quickly-fading orange and the little light slanting in through the blinds made his head throb like an ever-expanding balloon. He sat up slowly, his body heavy, and massaged his temples with trembling fingers. He wobbled to his feet and shuffled to the refrigerator, where he found a single Budweiser tucked away in the back. He snatched up the can and took a long, purposeful sip which eased his trembling momentarily. He stumbled back toward the sofa and sat facing the door. His mind reeled with a thousand thoughts at once. The Hair-Knight. The mummers. Daniel and Jordan with their scars… and their grins. Why had Nate told him to leave? He took another sip of beer, holding it on his tongue, and exhaled forcefully through his nose. His knees bobbed, piston-like, as the slice of light around him thinned to a single strip of brightness. In another minute, the light had receded from the cabin entirely, just a pinhole glare on the horizon. And then it was gone, replaced by a twilight glow that melted away into the starless blue-black of night. Jack drank the last sip of his beer, and as he did, there were three slow, light knocks at the door. See you tonight, he remembered in the echoes. “Who is it?” he called. Another round of knocking sounded at the door, quicker this time. “Who is it?” he tried again, voice faltering. A third round, heavy and aggressive now, boomed as if in response. Jack’s pulse crashed in his ears like tidal waves pounding the shore. Cold sweat broke over his body. Suddenly, the knocking became a violent, hateful rapping that seemed to surround him. Loud crashes enveloped him as fists pounded the cabin from all angles. He whipped his head around frantically, trying to catch glimpses of the figures in the darkness through the windows. The banging on the door thundered in ever-quickening, mallet-fisted blasts. The door leapt on its hinges, threatening to give way at any moment. “Fuck it,” Jack said aloud. Before he could stop himself, he was on his feet, flipping on the overhead light, and unlocking the door. When he did, the pounding stopped at once in a single reverberating note. A cruel silence settled over him. And then the cabin door pulled open. He hadn’t known what he would see when the door opened, when the overhead light spilled out into the darkness and spotlighted whoever was there. He certainly hadn’t expected to see the clown. It wasn’t so much a clown, he thought as the man crossed the threshold, but a thing of nightmares. The man, whoever he was, wore a mask. It was the wizened, deep-wrinkled face of an old man—heavy brows, sunken cheekbones, bulbous nose—but there was a cartoonish quality to it, like a caricature gone horribly wrong. The old man’s mouth twisted downward into a red-lipped grimace that revealed black gums and rotting teeth. The worst part of the mask, Jack thought, was the empty eye sockets, black and sinister, and the very real, very hateful human eyes beneath. Hair-Knight. He’d know those eyes anywhere. Hair-Knight said nothing under his mask. He breathed heavily, threateningly, and stepped toward Jack. Jack recoiled quickly, slamming his heels into the base of the sofa and crashing down into a seated position. He looked up dumbly, helplessly, and saw the rest of Hair-Knight’s outfit. He wore a black tuxedo-looking getup, though, Jack noticed, the entire thing was one piece, like the denim jumpsuit a mechanic might wear. A grotesque hump—obviously fake—protruded from his back. It looked airy and flopped side-to-side as he moved. The whole thing was so absurd, so ironically comical, that Jack wanted to laugh, and he might have, if not for the eyes that burned from behind the mask. Jack was suddenly aware that two other people, each as oddly dressed as the first, were stepping through the door. None made a sound. “What…” Jack started but stopped. The first figure stepped forward and cocked his head at Jack as if in confusion. He wore a white sheet over his face, held tightly to his skin by black cords around his forehead and neck. Mismatching holes revealed eyes that never broke from his. In the droop of the right eye-hole, Jack could see the thin scar across his cheek. If the strange, robotic movements hadn’t given him away, the scar surely had. Jordan. Around the white sheet, Jordan wore what looked like a lion’s mane, the hair kinky and rainbow-colored. It billowed like a windy grainfield each time he alternated the tilt of his head. His stare cut into Jack and he said nothing. A minute or more passed in the silence of this bizarre stare-off, and finally, bewildered, Jack said, “What–” “Quiet,” Hair-Knight said. Though his voice was barely above a whisper behind the old-man mask, his baleful glare turned Jack’s stomach to knots. Jack held his breath, afraid to make a sound. “We are the mummers!” Lion’s-Mane-Jordan said suddenly. His voice was high-pitched and squeaky. “We are the mummers, and we’re sorry for this fright! But we’re here for fun, to dance and pun, for you this winter’s night!” When he finished his song, Jordan stepped back into line and the tall mummer at Hair-Knight’s left shoulder stepped forward. Jack knew him instantly. Daniel. Where’s Nate? Jack wondered. Why isn’t he with them? Daniel had a waterfall of curly blond hair masking his face. Clipped to the hair were two prosthetic-eyes-on-springs, lifeless gray and jouncing wildly. He was shirtless and on his stomach was a tattoo of Siamese cowboys riding Siamese horses. He was holding a strange-looking stick—a broom handle—about four feet long. Attached to the bottom of the stick was an old work boot, the sole at the steel toe flapping like a lolling tongue. Nails were driven into the wood all along the length of the stick, and from each, dangled bottle caps, marbles, or silver jingle bells. Siamese-Cowboy-Daniel opened his mouth and said, “It’s really quite simple! Just guess our names! That’s how you win this mumm’ring game!” As he sang, he held the strange stick out from his body with one hand and let it slam, boot-first, to the ground with a discordant crash. Every few seconds, he’d let it fall again. He continued his song. “We’ll give you clues to help you out. When you know, let out a shout! Call the name and we’ll be done, then you’ll be on to another one!” At this, he brayed chilling laughter—part animal, part demented circus-clown. Jordan, also giggling maniacally, his mane undulating like underwater plantlife, picked up the verse. “Can’t solve the riddles? That’s no problem. For a price, we’ll help you solve ’em! A drink as bribe will buy a clue. That will make it clear to you. When all unmasked, we’ll be away, and you’ll have learned a truth today.” “What tru–” “Shut up!” Hair-Knight roared. Jack was poleaxed by fear. He had been confused before that moment—afraid even—but when Hair-Knight yelled, Jack understood immediately that he was in real danger. The silence that followed was deafening. The three mummers stared in unison. And then the ugly broom-handled instrument began to bang. It’s beat was steady. One-two-three-CLANG!-one-two-three-CLANG!-one-two-three-CLANG! It was the tolling of a funeral bell. Get up! he thought. Get up and run! One-two-three-CLANG! Jack squeezed his fingers into a tight ball. His pulse thrummed behind his knuckles. Hair-Knight. Have to get past the fucking Hair-Knight. The savage yawp of a cornered animal erupted from within him suddenly and Jack was on his feet. He took two loping strides and drove his fist into Hair-Knight’s face. The old-man-face absorbed much of the blow, but it was enough to knock him off balance, and Jack pushed past him and shouldered through the door. It gave way with surprising ease and he stumbled, plunging headlong down the stairs, flipping and landing hard in the snow. Before he could think of the pain or the cold, he was up and running. He glanced over his shoulder and saw the mummers piling through the door, Daniel already to the bottom of the steps, the asinine pole-instrument gripped like a bo staff in his hands. Jack whipped his head forward and sprinted wildly toward the dirt road. Get to town! he thought. Get help! Before he’d taken three steps, though, he stopped cold. Standing at the edge of the road was another mummer, a long-bladed kitchen knife in his hand. He rolled the knife between his thumb and fingers and the moonlight glinted menacingly off the blade. Then everything went black. ***** When he came to, he was only faintly aware of where he was. His vision was blurred, but a musty smell told him he was still in his cabin. The moving shapes across the room told him the mummers were still there, too. He tried to move but found that he was bound, wrists and ankles, to a wicker chair. Panic set in immediately. He yanked feverishly against the ropes, arching his back and throwing his weight against them, but the more he struggled, the tighter they seemed to get. After a few seconds, he gave up and fell heavily into the chair. He was suddenly aware of the blaring pain in the back of his skull and he closed his eyes tightly. Something warm beaded across his hairline and trickled behind his right ear. Tears came, and then great ragged heaves. “Shut the fuck up,” he heard and then felt the explosion of pain as knuckles shattered his cheekbone. He made a gurgling sound in his throat and began to sob. Hair-Knight, still wearing his mask, massaged his knuckles. He tensed when he heard Jack’s cries and was back on him in an instant, his hand wrapped around Jack’s throat, fist clenched and cocked. “I said shut the fuck UP!” “Enough,” a voice called lackadaisically from across the room. Hair-Knight released his throat and joined the other two mummers by the door. The voice belonged to the fourth mummer, the one who he’d seen on the road just before he’d blacked out. Now the man was reclining on the sofa, one leg draped over the other. He still held the knife. Jack watched as he picked at the undersides of his fingernails nonchalantly with the tip of the blade. Nate. He was dressed in much the same way as the others. Over his face, he wore a burlap sack, black Xs across the eyes and a cross-stitched zipper-pattern smile that traced across the bag. “Back to the game then, hmm?” Burlap-Sack-Nate said without emotion. Jordan stepped forward in his preposterous lion’s mane and cocked his head maniacally again. “Take a guess at who I am. Jim or John or maybe Sam. If you think you need a clue, try blueb’rry wine, yes that’ll do,” he sang. The ugly-stick in Daniel’s hand clanged miserably along. “Please,” Jack begged the mummer on the couch. “Please just let me go. I won’t say anything about this. I just want to go home. Please.” The mummer sighed. Exasperation maybe. Jack saw him nod at Hair-Knight and flick the knife toward Jack. An instant later, Hair-Knight was hovering over him, fist raised. This time, pain followed, like nothing Jack had ever felt. His already-shattered cheekbone felt as if it had been ground to dust. The fat knuckles had also caught part of his nose and blood poured out. Jack leaned his head back and blood rushed down his throat, making him sputter. He found himself crying again through gulps of metallic blood. “Do you enjoy the pain, Jackie?” the fourth mummer said. His voice was calm. “No,” Jack whispered, steadying himself the best he could. “No. Of course you don’t.” The mummer spoke as if answering his own question. “See, but here’s the thing: I think… you fucking… do.” “Ple-ea-ease,” Jack mewed. “Please, no.” “Then play the game. Guess the names and it all ends.” He flicked his hand in a whimsical, dismissive gesture. “If I play the game, I can leave?” Jack asked, hope rising in the pallor of his face. Silence. “It’s Jordan,” Jack said, wheezing through his broken nose. “It’s Jordan in the white sheet. Jordan.” Jordan stepped forward and slipped the sheet over his face, revealing the rotting grin Jack knew he’d see there. Jack’s skin prickled at the sight. The Siamese-Cowboy was next. He stepped forward, eyes dangling morbidly on their springs on the blond wig. “My dance–” “Daniel,” Jack interrupted. “It’s Daniel. And that’s the fucking Hair-Knight,” he said, pointing to the old-man-face mask. They removed their masks. Daniel was grinning. Hair-Knight was glaring. “Hair-Knight,” the fourth mummer repeated, amused. He was on his feet now, ambling toward Jack, still flourishing the long knife in his hand. Jack felt cold, suffusive fear seeping through his pores, smelled its sour tang in an instant. He bucked his hips and arched his back against the ropes. “Stop that,” the mummer said, walking past him and touching him lightly on the shoulder with the flat side of the blade. Jack eyed the knife and then swung his head around as far as he could to watch the mummer. He heard the heavy clink of steel on laminate as the mummer laid the knife on the countertop in the kitchen just out of his view. Cords stood out on Jack’s neck as he strained to see. He heard what sounded like twisting and then tat-tat-tat-tat-tat. Then a quick fffwoop. His heart raced. Moments later, he heard another clank as the knife hit the cast iron of the burner on the gas range. “What do you want from me?” Jack said softly. Behind him, Jack heard the audible expansion of the plume of flame on the burner. After a minute or more of silence, he heard, “I want you to play the game.” The burner turned off with a quick pop. “I don’t want to play anymore,” he whimpered. The mummer appeared in his periphery, the knife, now gleaming red-hot, back in his hands. He lowered his burlap-sacked face directly in front of Jack’s and said, “Are you ready for my clue?” “Nate! You’re Nate,” Jack yelled, desperation thick in his voice. Without a word, the mummer climbed onto him, draping either leg around the outside of Jack’s until he was in an erotic straddle across his lap. He held the hot knife aloft, the point only a few inches from Jack’s left eye, and twirled the blade in a tight circlet. Jack squeezed his eyes shut and drew back his head as far as he could. The blade inched closer. “Please, just leave me alone,” Jack begged. “Oh, if only I’d said that when we first met.” “But–” he said and then screamed as the mummer touched the point of the blade to the soft flesh under his eye. He saw the tiny curl of steam and screamed again. “Are you ready for my clue now?” “Yes,” Jack heard himself say, afraid anything else might get him burned again. “Good. Here goes. You didn’t know this when we met, and I never did quite clue you, but it’s a fact and you can bet, that I already knew you. Not you, per se, but your type indeed; in fact, I’ve known quite many. Selfish ones, and arrogant; oh, yes, there have been plenty.” “I don’t know,” Jack said softly, starting to cry again. “Nate. Nate!” The mummer sang on. “I mark them out, I reel them in; it’s really not that hard. I hunt them down when they run off; leave them broken, beaten, scarred. You, too, I chose, flaws I could tell, when we met that spring in Maine. A year of marriage, a year of hell; I thought only of your pain.” Jack opened his eyes wide, eyes suddenly alight with understanding. The mummer continued, “And now here you sit, in my hometown, the seed I planted grown. I led you here, to break you, dear; your life now I do own. So the next time you run out on me, look only to your face; the scar you bear will long remind you of your true disgrace.” Tears streamed down Jack’s face now; blood and snot poured from his nose. “Say my name, Jackie,” the mummer said. He shook his head slowly and said, barely audibly, “No. No. I–” “Say… my… name!” the mummer yelled, ripping off the burlap sack in one fluid movement. Raven-black hair spilled out and eyes darker-still bore into him. Her face was beautiful and malicious. ***** Jack was paralyzed by his wife’s wicked smile. He didn’t struggle even when she shifted her weight forward on his lap and put the palm of her free hand on his forehead to press his face parallel to the ceiling. But then he saw the sheen of the blade in her other hand. And he felt the three sets of hands on him. Only then did Jack let out a pitiful scream. But then the knife stole his breath. The blade bit deep into the flesh of his upper cheek where she’d burned him moments before. It had cooled considerably, but it cut with a bitter sting nonetheless. She ripped the blade from the soft skin under the eye down across his left cheek, using just the point and tip of the knife for her incision. A thin, red line appeared in its wake. As she turned under his nose, she laid the blade flat and let the cutting edge work. A bright red chasm appeared between his nostrils and lips, blood sliding in sheets across his mouth instantly. She finished the job by dragging the blade’s tip across his right cheek and jawline. And then she kissed him on the mouth. And licked her lips. The hands released him all at once, but Jack felt glued to the chair. His mouth arched in a terrible grimace. His breath came in shallow gasps. His face burned with venomous flame. “Say my name, Jack,” she whispered, her lips to his ear, the knife pressing just below it. “Olivia.” His lips barely moved. “Good. That’s good,” she said and hopped off his lap. She floated back to the stove, and through his agony, Jack once more heard the range flame to life, the blade clang against it. “Why?” Jack exhaled to the ceiling. “It’s not so complicated, really, Jackie,” she yelled from the stove. “My motivations are simple. I grew up here, just down the road actually—you probably didn’t even fucking know that… You never could listen to me, could you?—and my father was a cheating scumbag piece-of-shit who walked out on my mother and me. Now I’m making sure that never happens to anyone again, one arrogant shitsack at a time. Simple, right? So I have daddy issues. Whatever. Know thyself. “You’re not the first arrogant shitsack though. You’ve probably figured that out by now—I’m sure you’ve seen the scars. You’re actually the fifth. Lucas was first,” Hair-Knight, Jack thought through his disorientation, “then Danny, then Jordy. Nathan was last. He’s still learning.” Jack could hear the control in her voice. The dominance. “We had to remind him just who is in charge after the way he acted today at Clapper’s.” He’d tried to warn me, Jack thought. Just like the bartender. Olivia continued, “Nathan had to be taught a lesson. But I think he’ll remember now.” Hair-Knight stepped forward as Olivia finished speaking and held out his hand. In it, Jack saw a bloody human ear. He made a pathetic mewling sound and closed his eyes. The twisting line on his face throbbed wickedly. “And now you’re one of mine, Jackie,” Olivia said, still standing by the stove. “You know, I told you Lucas was the first. That’s only partially true. He was my first husband, the first cheating asshole I took up here to break. But my father was really my first. Know what I did to him? I took his balls with an old kitchen knife when I was sixteen.” A feeling of inevitability soaked through Jack. She’d hunted her own father… She’d tracked him down and… He knew in that moment that it wouldn’t have mattered if he’d come to Hog-Jaw or not. She’d have found him wherever he went. She continued. “I didn’t even heat the blade. He almost bled out. But I didn’t let him. I thought he should have to live with what he’d done—and what I’d done to him.” “I’m sorry,” Jack breathed. “For what I did to you.” “Jack,” she sneered. “Don’t do that. You’re not sorry. You’re not capable of being sorry. Not yet anyway.” Suddenly, the others were on him. Hair-Knight had his hand around his throat again, and Daniel pinned his legs. Jordan fingered Jack’s belt furiously. In a matter of seconds, he’d unfastened the clasp and shimmied the jeans and briefs down to his ankles. Olivia, the red-hot knife in hand again, knelt between Jack’s legs and grabbed his balls in one hand like she were collecting wildflowers. He screamed and begged for mercy. He thrashed wildly in the chair, but the men held him firm. Olivia pressed the fat edge of the blade against the delicate skin between her fingers. Jack threw his head back in agony, begging for an end. His skin hissed under the blade. The stench of burning flesh filled the air. And then the branding was over. “Get him into the snow,” Olivia said. Jack’s binds were cut and he was hoisted, his pants still around his ankles, out into the snow. The air rushing over his branding sent him into fresh bouts of agony. The snow, too, seemed to torch his seared flesh. Tears began to fall again and he hung his head, afraid to look at her as she descended the cabin’s steps, her burlap-sack mask in her hand. She didn’t look at him either; she didn’t need to. Her power was clear. “You know what you are now.” There was no question in her words. “You are nothing. You are mine. Now get in the car.” She pulled a set of keys—his keys—from her pocket and slid into the driver’s seat of Jack’s Mercedes. Jack rose and pulled up his pants. He limped wearily toward the car, watching his feet as he walked. When he reached the door, he hesitated, his hand on the handle. Maybe I can make a run for it, he thought. If I can get to the bartender… But they might catch me. That knife. The pain. He opened the door and sat down, another wave of pain sweeping through him. Olivia started the car and pulled slowly down the dirt road. Jack could see the three others standing like sentinels. He realized, morosely, that he might soon be standing next to them as some other poor bastard made this drive. “Put your head on my shoulder and close your eyes,” she said in the darkness. Jack peeked at her furtively but didn’t move. He thought again of the bartender. He knows I’m here. He’ll send help. Olivia turned the car onto Hog-Jaw’s main drag, and Jack began to see other mummers through his window. He watched them, the merry and the absurd, children and adults alike, laughing, prancing down sidewalks, knocking on doors. People in their homes smiling, inviting the mummers—their friends and neighbors—in. All fun. All happy. And then he saw Olivia’s mask on the floor by his feet and shivered. “Put your head on my shoulder and close your eyes,” she said again as they passed Mack’s Market, an edge to her voice now. Jack refused to look at her. He could see Clapper’s just ahead. Suddenly the car slammed to a stop. “Jack,” she growled in the dark. He could feel her glare but still didn’t look. And then he saw the bartender. He was on the sidewalk in front of the bar, almost like he was waiting for them. Jack’s heart raced. Help was so close. He had to get the barman’s attention. He felt the power window switch with his finger but didn’t dare press it. He didn’t have time. She’d speed away the second the window moved and it would be all over. But he had to do something. This might be his only chance. Suddenly, furiously, he pounded the car window with his open palms and screamed. The barman looked up. He looked right at Jack. Thank Christ! Jack thought as he kept banging. And then his window began to lower. He looked at Olivia, and in astonishment, saw her finger pressing the driver’s side window switch. She leaned toward him and lowered her head, looking past him toward the bartender on the sidewalk. “Hi, Daddy,” she called through the open window. Jack’s blood ran cold. His face turned ashen. In the halo of yellow light from the bulb above the tavern’s door, Jack watched the barman raise a trembling palm to her, the rest of his body rigid at her words. The fear was plain in his eyes, as simple and true as anything Jack had ever seen. And then the barman turned, walked back into the bar, and turned off the light. A thick darkness settled over the street. A heavy numbness settled over Jack. He heard the hum of his window closing, and all he could do was sink into his seat. After a moment of silence, he forced himself to look at Olivia. She was smiling devilishly. “Put your head on my shoulder and close your eyes, Jackie.” A shadow fell over her face then—not a shadow, Jack thought, but a darkness. A thing almost alive, wicked and ancient. Evil. Under that mask of primal darkness, her eyes turned to white fire. Jack Bradley laid his head against her shoulder and closed his eyes. Liked it? Take a second to support Contributor on Patreon!
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Going over the fiscal cliff could cost the Big Apple more than 600,000 jobs, experts tell The Post. The job losses would cause New York City’s unemployment rate to spike more than two percentage points to more than 11 percent, these experts warn. “This can be devastating,” said Kathryn Wylde, president and CEO of the New York City Partnership, an organization made up of business leaders. Economists fear the $600 billion in automatic tax hikes and spending cuts that are scheduled to kick in Jan. 1 — the so-called fiscal cliff — will push the fragile US economy back into a recession. The economic tremors will certainly be felt here in Gotham. The huge Big Apple jobs wipeout — pegged at roughly 614,000, or 15 percent of the city’s 3.88 million jobs — was projected by two prominent economists at the American Action Forum, a not-for-profit think tank. The frightening forecast, using tools developed by the Federal Reserve Bank of Kansas City, was put together by Princeton- and Columbia-trained economist Douglas Holtz-Eakin, a former director of the Congressional Budget Office. “I take his research very seriously,” said Wylde. In the city, the tax hikes would cut the take-home pay of someone earning $90,000 by about 6 percent — or about $450 a month in after-tax pay, said a JPMorgan report, adding that the lost income would “significantly” crimp consumer spending. That drop in consumer spending would force employers to cut payrolls to match the lower volume of business. The state Labor Department said yesterday the city’s jobless rate dropped to 9.3 percent in October from 9.5 percent a month earlier. The number of jobless in the city now stands at 830,600, it said. President Obama and congressional leaders are set to meet today to discuss taxes and federal spending to keep the economy from heading off the fiscal cliff. City Hall stands to suffer hugely from federal aid cuts envisioned in the Dec. 31 reckoning.
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If you like your sex outside in the fresh air, you’ll love Hardwood: TitanMen in the Great Outdoors a collection of six of the best outdoor hardcore sex scenes from the TitanMen vault. Join TitanMen exclusives Francois Sagat, Dean Flynn and Dario Beck and many more as they suck and fuck in the Great Outdoors. ENJOY! Follow us on twitter @Blue_Fantasy Trailer
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Priest's tale kickstarts a holy row Preview by Jack Foley MEXICAN cinema continues to set new standards in both daring bravado and controversy with the release of El Crimen del Padre Amaro (The Crime of Father Amaro), a film about a priest who falls in love with a teenage girl. Starring the rapidly emerging star, Gael Garcia Bernal (of Amores Perros and Y Tu Mamá También), the movie is based on a Portuguese novel by Eca de Queiroz and has been updated to contemporary Mexico. Prior to its release in its homeland, the movie courted all manner of controversy, with Luis Morales, the head of the Mexican Bishops' Conference, claiming that it made fun of 'the most sacred religious symbols of the Catholic community', before protesting 'firmly and openly' about the content contained within. Riots were also predicted outside some cinemas, particularly given that 90% of Mexico's population is made up of church-going Catholics. But the gamble appears to have paid off, for the movie is one of the most successful of all time in Mexico. El crimen del Padre Amaro earned over 31 million pesos in its first three days, breaking the previous record for a Mexican film, ironically set by Bernal's Y Tu Mamá También, even though it opened in over 100 cinemas more. This is no mean feat for a Mexican film, particularly when compared with the likes of Box Office giants such as Spider-Man, which debuted with a colossal 80 million pesos in its first weekend in Mexico, with twice as many copies in circulation. Needless to say, Bernal has defended the content and believes people should see it before criticising it. He claims the controversy has arisen because 'it is an honest movie'. As a result of the affair, the young parishioner with whom Father Amaro has an affair gets pregnant, and he advocates an abortion. In the meantime, fellow clergymen dabble with drug traffickers and leftist guerillas. Conservative Catholics maintain the content is 'grotesque', with one group reportedly filing a lawsuit against the federal government for partially funding the film. They allege that the film is in violation of Mexico's constitutional protection from religious persecution. Its director, meanwhile, hit back by dismissing claims that the movie is an attempt to harm the Catholic Church. He maintains that 'the church is hurt, not by the existence of priests who are fictional characters in a movie, but those made of flesh and blood who commit illegal acts." As yet, there has been no release date set for the film's debut in the UK or US cinemas. PAST FOREIGN LANGUAGE/INDIE PREVIEWS: Williams develops a darker reputation. Click here for One Hour Photo... The most frightening horror since The Shining? Click here for Frailty.... Irréversible, a life-affirming film about rape? Click here... 28 Days Later. Click here... Talk To Her, the new Almodovar. Click here... Lantana, one of the movies of the year? Click here... Trouble Every Day, French vampire/cannibal flick. Click here...
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Kitchen Areas with Cheery Color Block Theme It would be really boring if your kitchen set in a usual kitchen areas theme. Then you will need the unusual kitchen look that will make you cheer up and happy to linger longer there. Then the cheery mood of the color block will give you the different sensation to your kitchen. Just play with the colors and make your kitchen shining out and boost your everyday mood. Before you paint the wall and set the floor, you can try to obtain the wide windows in it to make your kitchen more fresh and spacious. The colors that usually include to the cheery mood are yellow, orange, red, electric blue and lime green. Do not forget to set the neutral color like black, white or wooden colors to make the colors blend perfectly. This kinds of colors not only you can set to the wall and the floor, you can trim your kitchen with the colorful kitchen appliances like the teapot, pans, bowls, plates, and the mugs. Just freely set them in an arrangement that not only to make them tidy but also can trim your kitchen perfectly. The Wall and the Floor Because you try to make your kitchen in a cheery mood, it is better to set them in colors that I mentioned in the previous paragraph like yellow, orange, red, electric blue and lime green. Then you can set the wall in a school bus yellow or sunglow that will make your wall in a total cheery mood. If you want to make it little bit calm, you can combine it in with the stony wall as the half of the wall. After the wall is set, you can set the floor in black or the other natural colors. If you prefer the other color for your wall it is okay, just make sure that the colors that you choose are include to the cheery colors. Juggle the Colors After you get your yellow wall and the black floor, you can start to set the counter and the cabinets. You can make it in red, electric blue or even lime green. Said it that you set the counters and the cabinets in lime green, then you can set the round wool rug there in red and the bar stools in electric blue. Do not forget that you are also having windows. You can set the curtains there in a red like the rug or the electric blue like a bar stools. Just feel free to set the colors in your kitchen to make you comfortable to linger there longer. Gallery of Kitchen Areas with Cheery Color Block Theme There are 12 high resolution photos again to check, so do not miss to see Surprising images all in Kitchen Areas with Cheery Color Block Theme article galleries for your next inspiration by clicking the thumbnail below. Beautiful Chandelier and Wall Lamp for Vintage Kitchen Lighting Kitchen Designs with Islands for Small House Posted at January 19th, 2014, Dick Oatts talk about Kitchen Designs with Islands for Small House. Kitchen designs with island are a must for a small and limited-space house. The usage of space can.. Kitchen Cabinet for Storage Ideas Make Our Dream Come True Posted at August 7th, 2013, Dick Oatts share about Kitchen Cabinet for Storage Ideas Make Our Dream Come True. A messy kitchen is the most disgusting thing we seen on our house and that’s why we need kitchen..
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Jesus would “beat the crap” out of former National Security Advisor John Bolton, according to a Christian pastor who never read about that whole “turn the other cheek” thing. Conspiracy theorist Rodney Howard-Browne, best known for his “Holy Laughter“-based religious ceremonies, has said in the past that Donald Trump isn’t cruel enough. He’s now following suit by expressing his own violent rage. While the tweet is now deleted, a screenshot is below. The thread came in response to an unrelated Bolton tweet. You are a slime ball of the highest order …. I should have knocked your sorry butt through the door of the Oval Office into the rose garden when I saw you. I would have gladly been arrested …. what a Benedict Arnold ….. I am glad you were fired !!!!! https://t.co/vZWif9ohjV — Rodney Howard-Browne (@rhowardbrowne) January 28, 2020 To be fair, there are plenty of reasons to dislike Bolton: He’s a war-monger with enough bigotry in his heart to make him a perfect fit for the Trump administration. Quitting his position was the only somewhat decent thing the man has ever done — even if it was only to avoid going down with the rest of the ship. But the story here isn’t about Bolton. It’s about a Christian who believes Jesus would resort to violence to punish a man who’s finally (finally!) doing the right thing.
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Who Was That Stranger Who Was That Stranger is the thirty-eighth solo studio album by American country music singer-songwriter Loretta Lynn. It was released on May 24, 1988, by MCA Records. This was Lynn's first album to be issued on CD at the time of its release. Track listing Personnel Paul Anastasio – fiddle Eddie Bayers – drums Mike Caldwell – harmonica Béla Fleck – banjo Bill Hullett – dobro, acoustic guitar David Hungate – bass guitar Loretta Lynn – lead vocals, background vocals Weldon Myrick – steel guitar Peggy Sue – background vocals Matt Rollings – piano Billy Joe Walker Jr. – acoustic guitar Curtis Young – background vocals Reggie Young – electric guitar Chart positions Album – Billboard (North America) Singles – Billboard (North America) References Category:1988 albums Category:Loretta Lynn albums Category:MCA Records albums Category:Albums produced by Jimmy Bowen
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Wikipedia (en)
Conversion from cyclosporine to FK506 in adult liver transplant recipients: a combined North American and European experience. Although cyclosporine (CsA) made clinical liver transplantation possible, side effects and development of rejection have limited its use. In some patients, conversion to tacrolimus has been necessary to abrogate side effects and to preserve allograft function. The results of conversion from CsA to tacrolimus were studied retrospectively in 94 liver allograft recipients from a North American and a European transplant center (Duke University Medical Center, Durham, NC, and Hopital Beaujon, Clichy, France). Forty-seven of 94 patients (50%) were converted for steroid-resistant acute rejection. Conversion was successful in 91% of these patients, whereas 9% of patients developed chronic rejection. A further nine patients were converted for chronic allograft rejection with positive results in eight of nine grafts. Mean serum bilirubin in these nine patients was 8.7 mg/dl before conversion and 2.1 mg/dl 6 months after conversion (P=0.02). Nine patients were converted due to inability to wean steroid. Of these, six patients remains steroid free 1 year after conversion. Twenty-three patients (24%) were converted for nephrotoxicity with a reduction in serum creatinine from 167+/-36 mmol/L to 119+/-28 mmol/L 1 year after conversion (P=0.006). Eight of 11 patients converted for neurotoxicity improved after conversion. Conversion to tacrolimus had no effect on seizure frequency or memory loss. These results suggest that conversion to tacrolimus from CsA is an appropriate paradigm for graft rescue and treatment of a variety of side effects after liver transplant. However, some situations such as memory loss and hypertension may require other strategies.
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PubMed Abstracts
Last Saturday and Sunday, Seattle's Myrtle Edwards Park, a mile-long strip of land fronting Puget Sound just north of downtown, once again played host to the Seattle Hempfest. And once again, the Hempfest lived up to its reputation as the world's largest marijuana "protestival." With a core staff of around a hundred, led by the indefatigable Vivian McPeak, and about a thousand volunteers who worked to set up the event, keep it running smoothly, and tear it all down at the end of the weekend, Hempfest is not only a celebration of cannabis culture but also the living embodiment of the grassroots cooperative activism that has flourished for years in Seattle. From its beginnings as a small pro-hemp event 17 years ago, Hempfest has become the coming out party for America's cannabis nation, which in Seattle includes not only youthful stoners, wizened hippies, and Mr. Bong Head (a guy wearing a working bong contraption on his head), but punks, Goths, ravers, uncostumed twenty- and thirty-somethings, families with children in strollers, and -- the biggest cannabis celebrity in town -- travel writer Rick Steves. Steves once again called for the US to follow the lead of Europe in relaxing marijuana laws. Over the event's two-day span, an estimated 150,000+ people showed up to see and be seen, listen to four stages worth of live music, peruse the hundreds of vendors' stands for the newest technologies and best buys on glass pipes, t-shirts, hemp items, and other pot-related accoutrements and accessories. And to get high in public with their comrades. Seattle police have for years now had an accommodation with Hempfest, even more so since the city's voters told law enforcement very clearly in 2003 that marijuana should be the city's lowest law enforcement priority. Police were on the scene, patrolling the park's sidewalks in pairs, but appeared oblivious to the open pot-smoking going on all over the place. In effect, Hempfest is not only the largest marijuana protestival in the world, it is also a massive act of civil disobedience. Even though Seattle has its lowest priority policy and Washington state has decriminalized pot possession, marijuana use and possession is still against the law. As one speaker addressed the crowd, pointing out this fact and telling listeners that despite all the progress they had made, they were still criminals, the crowd responded with an enormous cheer. The only real tension at Hempfest occurred when a small group of sign-holding fundamentalist preachers berated the passing crowds, telling them they were going to hell for their sins. That sparked occasional heated discussions. At one point Saturday, Hempfest organizers were heard threatening to send a squad of transgender people to scare off the fanatics. Some Hempfest attendees took a break from browsing, shopping, and listening to music to actually listen to between-band speeches by activists calling for further marijuana law reform. While decriminalization and legalization were predictably common themes, this year's Hempfest emphasized two other issues: The promotion of hemp and the battle over Washington state's medical marijuana law, especially the ongoing fight over what are appropriate quantities of marijuana allowable for patients. The state is currently tangling with patients and advocates over what constitutes a minimum 60-day supply of their medicine. An earlier proposal called for 35 ounces of marijuana, but Gov. Christine Gregoire sought a review of that, and the state is now recommending a 24-ounce limit. Besides between-band speeches, political activism also took place throughout Hempfest at the Hemposium tent, although in an indication of the role politics played in the larger festival, crowds in the tent numbered in the dozens, as opposed to the tens of thousands listening to music. "Every single patient I know will not be in compliance with the 60-day rule. It's not going to work. It's driven by law enforcement, not science," said Douglas Hiatt, a lawyer who represents medical-marijuana users, as he spoke at one of the Hemposium sessions. Hiatt was among the activists calling on patients and supporters to come out for an August 25 action in support of higher limits. But for most Hempfest attendees, the event was a party, a celebration, not a political seminar. While that may be a disappointment to activists, it is also a demonstration of the breadth and scope of Pacific Northwest cannabis culture. It has gone mainstream, with all the apolitical apathy abundant in the broader culture. And if Hempfest was a little too mellow for your taste, you could always check out Methfest, not a celebration of amphetamine culture but a scary rock music show put on in nearby Belltown.
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Two hundred faeces sample were collected from cattle with different age and sex in Al- Diwaniyah Province. The study was conducted in the period between November 2016 and November 2017. Salmonella typhimurium bacteria identified by routine methods such as culturing on selective media, biochemical test and agglutination test using monovalent and multivalent antisera. PCR was can detection type-1 fimbriae gene coding for fimC of Salmonella typhimurium. Results showed that Salmonella isolates were 14.5% in the bovine fecal samples. Also, the serotyping of isolates by using monovalent and polyvalent antisera revealed that all Salmonella isolates in cows were S. typhimurium. The PCR technique was used for detection of type-1 fimbriae coding gene by specific primer for fimC gene. All S. typhimurium isolates in cows appeared to be contained this gene show one distinct band MW.289 bp when electrophoresed on agarose gel. The results of this score indicated that the PCR technique potentate a loud specify in the disclosing of S. typhimurium especially the serotype that encoded to fimC gene type-1 fimbriae isolated from cows in comparison to other routine diagnostic tests.
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With the Saturday arrest of Jeffrey Epstein – who is reportedly offering to name elite pedophiles in exchange for leniency, a leaked copy of the billionaire sex predator’s “little black book” may provide some insight into some very rich individuals who should be nervous right about now. The book was smuggled out of Epstein’s residence by his former house manager, Alfredo Rodriguez, who was busted trying to sell it in 2009 for $50,000 – only to get caught, charged with obstruction of justice, and die in prison after 18 months from a ‘long illness.’ According to an FBI affidavit, Rodriguez described the address book and the information contained within it as the “Holy Grail” or “Golden Nugget” to unraveling Epstein’s sprawling child-sex network. But despite having been subpoenaed for everything he had on his former boss, Rodriguez didn’t share it with the FBI or Palm Beach Police Department detectives investigating Epstein. Instead, he tried to make a $50,000 score by covertly peddling the black book to one of the attorneys launching lawsuits at Epstein on behalf of his victims. –Gawker Jeffrey Epsteins Little Bla… by on Scribd According to a 2015 Gawker article, Epstein’s little black book contains hundreds of names that a hobnobbing socialite billionaire might keep on hand, however around 50 of the entries were circled by Rodriguez – “including those of many of Epstein’s suspected victims and accomplices,” according to the report. – READ MORE
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Q: How to change reply-to and return-path header with gmail smtp in django I am using gmail smtp in my django website. I have a contact form where user put email and message then I send a mail to the admin with : email = EmailMessage('email subject', 'email message', settings.EMAIL_HOST_USER, ['[email protected]'], headers = {'Reply-To': '[email protected]', 'Sender': '[email protected]','from': '[email protected]','Return-Path': '[email protected]'}) email.send(fail_silently=False) email is sent/received correctly but when admin client select reply in gmail, it always reply to the settings.EMAIL_HOST_USER and not the user address. On the email original header the From and Return-path are set with the setting.EMAIL_HOST_USER A: Google violates the RFPs defining the expected operation of an SMTP server, rewriting the headers. This may be the root cause of your problem: http://lee-phillips.org/gmailRewriting/
tomekkorbak/pile-curse-small
StackExchange
HBO's "Real Time" returned Friday night after a month hiatus. Host Bill Maher came back from vacation to find the country in bigger disarray than he could have imagined. One new phenomenon that popped up last week was the emergence of QAnon in the national discourse. QAnon is a running conspiracy theory made popular by an anonymous online figure named Q. According to The Daily Beast, Q began posting on anonymous internet forums 4Chan and 8Chan in late 2017. The person or group behind the Q persona claim to have top-level security clearance in the federal government. Q has surfaced, supposedly, to whistleblow a monstrous worldwide criminal conspiracy that portrays high-profile Democrats as pedophiles and President Donald Trump the liberator of vulnerable children. Advertisement: To no surprise, Trump fans latched onto the conspiracy and have used the narrative to justify their distrust in the media. People who've attended Trump's recent rallies have shown up with signs and t-shirts that promote Q and "The Great Awakening," a nod to the rising awareness of pedophile rings orchestrated by Hollywood celebrities. Maher attempted to explain all this to his studio audience in Los Angeles on Friday. “This is a big movement on the right. See, we don’t hear about these things because we’re not crazy,” Maher said near the end of his monologue. “Q is a person—a member of the ‘deep state,’ way high up in the ‘deep state’—but now he’s turning on them, and he’s revealing that the world is run by a giant pedophile ring. Really. Every president since Reagan has been part of it." Advertisement: "You know who’s a pedophile? Tom Hanks. Steven Spielberg," Maher revealed. "And who’s gonna stop this? Trump. Because who’s more qualified to stop pedophilia than the creep who used to walk in on Miss Teen USA pageants?” "He wasn't being a creep. He was looking for pedophiles," Maher joked. Maher's reference to QAnon wasn't lost on the people who believe in the conspiracy. The Reddit channel r/greatawakening shared the video of Maher's monologue and subsequently chastised his ignorance on the subject. Advertisement: "This is why it's really hard to feel sympathy for the sheep who follow the media/Hollywood," one reddit user wrote. "How can they laugh at this shit? What the fuck is wrong with them? This makes me not want to console them at all when the truth comes out but rub it in their faces." "It's amazing how well-crafted their lies are," another reddit user said. "People buy into this shit and we have to fight even harder because people are too stupid to actually look into and understand things for themselves. How frustrating." Advertisement: You can watch Maher's Friday monologue below:
tomekkorbak/pile-curse-small
OpenWebText2
Explaining level inversion of the La and Lb States of indole and indole derivatives in polar solvents. Quantum chemical methods are used to study the solvent effects on the spectra of indole and a series of methyl-substituted indoles. We focus on the low-lying L(a) and L(b) states and study their interplay. We find that the solvent mainly affects emission from the L(a) state, by stabilizing its energy in its excited-state geometry. The stabilization of the L(a) state increases with increasing solvent polarity, which accounts for the large fluorescence shift observed in indoles and leads to an inversion in the nature of the lowest emitting state, from L(b) in vacuum to L(a) in water. To the best of our knowledge, this is the first theoretical evidence for level inversion done for a series of indoles. The underlying mechanism of level inversion is analyzed in detail. The usual interpretation of level inversion in terms of their static dipole moment is criticized and an improved predictive measurement is suggested.
tomekkorbak/pile-curse-small
PubMed Abstracts
Introduction ============ Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity, accounting for \>90% of all oral cancer cases ([@b1-etm-0-0-6493]--[@b3-etm-0-0-6493]). Although substantial advances have been made in the treatment of OSCC, including surgical resection combined with chemotherapy and radiotherapy, the prognosis of patients with advanced OSCC is unsatisfactory ([@b4-etm-0-0-6493],[@b5-etm-0-0-6493]). Therefore, it is necessary to explore underlying mechanisms of OSCC tumourigenesis, which may be helpful in the development of novel therapeutic targets. Long non-coding RNAs (lncRNAs) are a group of small and single-stranded non-coding RNAs that are \>200 nt in size and evolutionarily conserved ([@b6-etm-0-0-6493],[@b7-etm-0-0-6493]). Although lncRNAs exhibit no protein-coding capacity, they are key regulators of gene expression and serve important roles in various biological processes, including cell growth, migration, invasion and tumourigenesis ([@b8-etm-0-0-6493],[@b9-etm-0-0-6493]). In recent years, evidence has suggested that lncRNAs serve promoting or tumour suppressive roles in the development and malignant progression of OSCC ([@b10-etm-0-0-6493],[@b11-etm-0-0-6493]). For instance, lncRNA taurine upregulated gene 1 promotes progression of OSCC through upregulation of formin-like 2 by acting as molecular sponges for microRNA (miR)-219 ([@b12-etm-0-0-6493]). LncRNA maternally expressed 3 inhibits proliferation and metastasis of OSCC via regulation of the WNT/β-catenin signalling pathway ([@b13-etm-0-0-6493]). Recently, lncRNA nuclear enriched abundant transcript 1 (NEAT1) has been observed to be upregulated in several human cancer types and studies have revealed its oncogenic role ([@b14-etm-0-0-6493]--[@b16-etm-0-0-6493]). For example, NEAT1 is regulated by the epidermal growth factor receptor signalling pathway and contributes to glioblastoma progression through the WNT/β-catenin pathway by serving as a scaffold for enhancer of zeste homolog 2 ([@b15-etm-0-0-6493]). NEAT1 contributes to paclitaxel resistance in ovarian cancer cells through regulation of zinc finger E-box-binding homeobox 1 expression via miR-194 ([@b16-etm-0-0-6493]). However, to the best of our knowledge, the function of NEAT1 in OSCC has not yet been reported. miRs are a class of small non-coding RNAs that are composed of \~22--25 nt and have been demonstrated to regulate gene expression via binding to the 3′-untranslated region (3′-UTR) of their target mRNAs, which results in mRNA degradation or translation repression ([@b17-etm-0-0-6493],[@b18-etm-0-0-6493]). Similar to lncRNAs, miRs are also involved in development and progression of tumours, including OSCC ([@b2-etm-0-0-6493],[@b3-etm-0-0-6493],[@b17-etm-0-0-6493]--[@b19-etm-0-0-6493]). Recently, miR-365 has been reported to serve a general tumour-suppressive role in multiple human cancer types; for instance, inhibiting ovarian cancer progression by targeting Wnt5a ([@b20-etm-0-0-6493]). Additionally, miR-365 inhibits proliferation, migration and invasiveness of glioma cells by targeting phosphoinositide-3-kinase regulatory subunit 3 ([@b21-etm-0-0-6493]). However, to the best of our knowledge, the exact role of miR-365 in OSCC has not been reported. In addition, matrix metalloproteinase (MMP)2 and MMP9 are two key enzymes involved in tumour cell invasiveness ([@b22-etm-0-0-6493]). Whether these enzymes are involved in the function of NEAT1 and miR-365 in OSCC still remains unclear. The present study aimed to investigate NEAT1 and miR-365 expression levels and functions in OSCC, as well as their underlying molecular mechanism *in vitro*. Materials and methods ===================== ### Clinical tissues The current study was approved by the Research Ethics Committee of the Stomatological Hospital of Jinan City (Jinan, China). A total of 58 OSCC and adjacent non-tumour tissues were collected from patients with primary OSCC at the Stomatological Hospital of Jinan City between March 2010 and April 2012. No patient received chemotherapy or radiotherapy before surgical resection. The clinicopathological characteristics of the patients are summarized in [Table I](#tI-etm-0-0-6493){ref-type="table"}. Written informed consent was obtained from all patients. Tissues were immediately snap-frozen in liquid nitrogen and stored at −80°C until use. ### Cell culture and transfection Human OSCC cell lines HN4, Tca-8113, UM-SCC-1, Cal-27, SCC-25 and SCCKN, and the normal human oral keratinocyte cell line hNOK were purchased from the Cell Bank of the Chinese Academy of Sciences (Shanghai, China). All cell lines were cultured in Dulbecco\'s modified Eagle\'s medium (DMEM; Thermo Fisher Scientific, Inc., Waltham, MA, USA) supplemented with 10% fetal bovine serum (FBS; Thermo Fisher Scientific, Inc.) at 37°C in humidified atmosphere with 5% CO~2~. Lipofectamine 2000 (Thermo Fisher Scientific, Inc.) was used to transfect HN4 and Tca-8113 cells with 100 nM of non-specific short interfering RNA (NC siRNA; Am10301; Amspring, Changsha, China), NEAT1-specific siRNA (NEAT1 siRNA; Am10542; Amspring), pcDNA3.1 vector (Am00013; Amspring), pcDNA-NEAT1 expression plasmid (Am02051; Amspring), miR-365 inhibitor (HmiR-AN0451-SN-10; Guangzhou Fulengen Co., Ltd., Guangzhou, China) and negative control (NC) inhibitor (CmiR-AN0001-SN; Guangzhou Fulengen Co., Ltd.) according to the manufacturer\'s instructions. Subsequent experiments were performed 48 h following transfection. ### Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) Total RNA was extracted from tissues and cells using TRIzol reagent (Thermo Fisher Scientific, Inc.), while genomic DNA was removed by treatment with DNase (Thermo Fisher Scientific, Inc.) according to the manufacturer\'s instructions. Total RNA (1 µg) was reverse transcribed using a RevertAid First Stand cDNA Synthesis kit (Thermo Fisher Scientific, Inc.) according to the manufacturer\'s instructions. Reverse transcription was performed at 16°C for 30 min, followed by incubation at 42°C for 30 min and enzyme inactivation at 85°C for 5 min. The expression of miR-365 was detected using miScript SYBR Green PCR kit (Qiagen, Inc., Valencia, CA, USA) on an ABI 7500 PCR machine (Thermo Fisher Scientific, Inc.). U6 was used as the internal reference. To detect NEAT1 expression, qPCR was performed using Power SYBR Green PCR Master mix (Thermo Fisher Scientific, Inc.). GAPDH was used as the internal reference. The reaction conditions for all qPCR experiments were as follows: 95°C for 5 min, followed by 40 cycles of 95°C for 10 sec, 60°C for 30 sec and 72°C for 30 sec. The relative expression was determined using the 2^−∆∆Cq^ method ([@b23-etm-0-0-6493]). The following primers were used: U6, forward 5′-CTCGCTTCGGCAGCACATATACT-3′ and reverse 5′-CGCTTCACGAATTTGCGTGT-3′; GAPDH, forward 5′-GGAGCGAGATCCCTCCAAAAT-3′ and reverse 5′-GGCTGTTGTCATACTTCTCATGG-3′. miR-365 primers were purchased from Guangzhou Fulengen Co., Ltd. ### Bioinformatics analysis Target genes for NEAT1 and miR-365 were predicted using RNAhybrid 2.12 (<http://bibiserv.techfak.uni-bielefeld.de/rnahybrid/>). ### Luciferase reporter gene assay Fragments of NEAT1 containing wild-type (WT) or mutant type (MT) miR-365 binding sites were cloned into pmirGLO Dual-luciferase Target Expression Vector (Promega Corporation, Madison, WI, USA), which generated WT or MT NEAT1 plasmids. HN4 and Tca-8113 cells were co-transfected with miR-365 mimic, scramble miR mimic (miR-NC), WT or MT NEAT1 plasmid using Lipofectamine 2000. Following 48 h of transfection, luciferase reporter gene assays were performed using the Dual-Luciferase Reporter Assay System (Promega Corporation). The firefly luciferase activity was normalized against *Renilla* luciferase activity. ### Wound-healing assay Wound-healing assays were conducted to determine the migratory capacity of cells. HN4 and Tca-8113 cells were cultured to full confluence, wounds of \~1 mm in width were generated with a plastic scriber and cells were washed with PBS. Cells were then cultured at 37°C with 5% CO~2~ for 48 h and assessed with an inverted microscope (magnification, ×40). ### Transwell assay HN4 and Tca-8113 cells (10,000/well) in DMEM were added to the upper chamber of Transwell inserts, pre-coated with Matrigel (BD Biosciences, Franklin Lakes, NJ, USA) and DMEM supplemented with 10% FBS was added to the lower chamber. HN4 and Tca-8113 cells were then incubated at 37°C for 24 h. HN4 and Tca-8113 cells that had not migrated through the membrane of the insert were removed using a cotton-tipped swab, while the cells on the lower surface of the membrane were stained with gentian violet (Sigma-Aldrich; Merck KGaA, Darmstadt, Germany) at room temperature for 10 min and counted under an inverted microscope (magnification, ×400). ### Western blotting Tissues and cells were lysed in cold radioimmunoprecipitation assay buffer (Thermo Fisher Scientific, Inc.) and the protein concentration was determined using a Bicinchoninic Acid Protein Assay kit (Thermo Fisher Scientific, Inc.). Proteins (50 µg) were separated on 10% SDS-PAGE gels and transferred to a polyvinylidene difluoride membrane (Thermo Fisher Scientific, Inc.). The membrane was blocked in 5% non-fat milk in PBS containing 0.1% Tween-20 (Sigma-Aldrich; Merck KGaA) at room temperature for 3 h. It was then incubated with rabbit polyclonal anti-human MMP2 (1:200; ab37150; Abcam, Cambridge, MA, USA), rabbit polyclonal anti-human MMP9 (1:200; ab38898; Abcam) or rabbit polyclonal anti-human GAPDH (1:100; ab9485; Abcam) at room temperature for 3 h. This was followed by incubation with the horseradish peroxidase-conjugated goat anti-rabbit secondary IgG antibody (1:5,000; ab6721; Abcam) at room temperature for 1 h. Enhanced chemiluminescence (Thermo Fisher Scientific, Inc.) was used to examine protein expression, which was analysed using Image-Pro Plus software 6.0 (Media Cybernetics, Inc., Rockville, MD, USA) according to the manufacturer\'s protocol. ### Statistical analysis All data are presented as the mean ± standard deviation. SPSS 18.0 (SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Student\'s t-test was used for comparisons between two groups, while one-way analysis of variance followed by Tukey\'s post hoc test was used for comparisons of \>2 groups. The associations between NEAT1 expression and the clinicopathological characteristics of OSCC were examined using the χ^2^ test. The Kaplan-Meier method was applied to analyse overall survival of patients with OSCC. Pearson\'s correlation was used to analyze the correlation between NEAT1 and miR-365 expression in OSCC tissues. P\<0.05 was considered to indicate a statistically significant difference. Results ======= ### NEAT1 is upregulated in OSCC In the present study, NEAT1 expression in OSCC and adjacent non-tumour tissue was evaluated. RT-qPCR assay data indicated that NEAT1 was significantly upregulated in OSCC tissue compared with adjacent non-tumour tissue ([Fig. 1A](#f1-etm-0-0-6493){ref-type="fig"}). Based on the mean expression value of NEAT1 as cut-off value (5.54), these patients with OSCC were divided into high and low expression groups. Further investigation indicated that increased NEAT1 expression was significantly associated with positive lymph node metastasis and advanced clinical stage ([Table I](#tI-etm-0-0-6493){ref-type="table"}). NEAT1 was significantly upregulated in OSCC cell lines compared with hNOK cells ([Fig. 1B](#f1-etm-0-0-6493){ref-type="fig"}). Additionally, patients with OSCC and high NEAT1 expression exhibited a shorter survival time compared with patients with low NEAT1 expression ([Fig. 1C](#f1-etm-0-0-6493){ref-type="fig"}). ### MiR-365 is downregulated in OSCC Potential target miRs of NEAT1 in OSCC cells were evaluated. A bioinformatics analysis revealed that miR-365 was predicted to bind to NEAT1 ([Fig. 2A](#f2-etm-0-0-6493){ref-type="fig"}). To examine the association between NEAT1 and miR-365 in OSCC, miR-365 levels in OSCC tissue and cell lines were determined. As indicated in [Fig. 2B](#f2-etm-0-0-6493){ref-type="fig"}, RT-qPCR assay data demonstrated that miR-365 expression was significantly lower in OSCC tissue compared with adjacent non-tumour tissue. In addition, miR-365 expression was significantly reduced in OSCC cell lines compared with hNOK cells ([Fig. 2C](#f2-etm-0-0-6493){ref-type="fig"}). It was demonstrated that miR-365 was downregulated in OSCC. In addition, the present study revealed an inverse correlation between NEAT1 and miR-365 expression in OSCC tissue ([Fig. 2D](#f2-etm-0-0-6493){ref-type="fig"}), which suggests that reduced miR-365 expression may be involved in OSCC development. ### NEAT1 downregulates miR-365 expression via sponging in OSCC cells As HN4 and Tca-8113 cells exhibited the highest expression levels of NEAT1 among the tested OSCC cell lines, these cell lines were selected for *in vitro* experiments. To further clarify the association between miR-365 and NEAT1 in HN4 and Tca-8113 cells, a luciferase reporter plasmid containing WT or MT miR-365 binding sites of NEAT1 was constructed in the present study ([Fig. 3A](#f3-etm-0-0-6493){ref-type="fig"}). A luciferase reporter gene assay was then performed. The data revealed that transfection with an miR-365 mimic significantly inhibited luciferase activity of WT NEAT1 in OSCC cells but did not affect luciferase activity of MT NEAT1 ([Fig. 3B and C](#f3-etm-0-0-6493){ref-type="fig"}). These findings suggest that NEAT1 may be able to sponge miR-365 in OSCC cells. ### Effects of NEAT1 on miR-365 expression of in OSCC cells were evaluated HN4 and Tca-8113 cells were transfected with NEAT1 siRNA to knock down NEAT1 levels or cells were transfected with NEAT1 plasmid to upregulate its expression. Following transfection, NEAT1 expression was significantly decreased in cells transfected with NEAT1 siRNA compared with the NC siRNA group and was significantly increased in the NEAT1 group compared with the blank control group ([Fig. 3D and E](#f3-etm-0-0-6493){ref-type="fig"}). The current study demonstrated that knockdown of NEAT1 enhanced miR-365 expression in OSCC cells and NEAT1 overexpression significantly inhibited miR-365 expression ([Fig. 3F and G](#f3-etm-0-0-6493){ref-type="fig"}). These findings indicated that NEAT1 downregulates miR-365 expression via sponging in OSCC cells. ### Knockdown of NEAT1 inhibits OSCC cell invasion To further study the function of NEAT1 in OSCC cells, wound-healing assays were performed to examine effects of NEAT1 downregulation on OSCC cell migration. As presented in [Fig. 4A](#f4-etm-0-0-6493){ref-type="fig"}, migratory capacity of HN4 and Tca-8113 cells was significantly reduced in the NEAT1 siRNA group compared with the NC siRNA group. Transwell assays were performed to evaluate cell invasion. As presented in [Fig. 4B](#f4-etm-0-0-6493){ref-type="fig"}, invasiveness of HN4 and Tca-8113 cells in the NEAT1 siRNA group was significantly reduced following inhibition of NEAT1 expression. Consistently, western blot data indicated that protein expression of MMP2 and MMP9, two key enzymes involved in tumour cell invasiveness ([@b22-etm-0-0-6493]), was significantly reduced in the NEAT1 siRNA group compared with the NC siRNA group ([Fig. 4C](#f4-etm-0-0-6493){ref-type="fig"}). These findings indicate that knockdown of NEAT1 expression inhibits OSCC cell migration and invasion. ### Inhibition of NEAT1 suppresses OSCC cell migration and invasion by sponging miR-365 Based on the aforementioned findings, it was speculated that NEAT1 may regulate migration and invasiveness of OSCC cells by sponging miR-365. To clarify this, NEAT1 siRNA-transfected OSCC cells were co-transfected with NC inhibitor or miR-365 inhibitor. Following co-transfection, miR-365 levels were significantly reduced in the NEAT1 siRNA+miR-365 inhibitor group compared with the NEAT1 siRNA+NC inhibitor group ([Fig. 5A](#f5-etm-0-0-6493){ref-type="fig"}). Further investigation indicated that migration ability and invasiveness of OSCC cells was increased in the NEAT1 siRNA+miR-365 inhibitor group compared with the NEAT1 siRNA+NC inhibitor group ([Fig. 5B and C](#f5-etm-0-0-6493){ref-type="fig"}). Consistently, suppressive effects of NEAT1 inhibition on MMP2 and MMP9 protein expression were reversed following co-transfection with miR-365 inhibitor ([Fig. 5D](#f5-etm-0-0-6493){ref-type="fig"}). These findings demonstrated that inhibition of NEAT1 suppressed OSCC migration and invasiveness via inhibition of miR-365 sponging. Discussion ========== To the best of our knowledge, the function and regulatory mechanism of NEAT1 in OSCC has not been reported previously. The present study revealed that NEAT1 was significantly upregulated in OSCC tissue and cell lines and that its upregulation was significantly associated with advanced clinical stage and shorter survival time of patients with OSCC. Data from luciferase reporter gene assays confirmed an interaction between miR-365 and NEAT1 and demonstrated that NEAT1 negatively regulated miR-365 expression in two OSCC cell lines. Furthermore, inhibition of NEAT1 expression led to a significant decrease in OSCC cell migration and invasion, whereas inhibition of miR-365 eliminated NEAT1 knockdown-induced suppressive effects on OSCC cell migration and invasion. In addition, miR-365 was significantly downregulated in OSCC tissue and cell lines and an inverse correlation was observed between miR-365 and NEAT1 expression in OSCC tissue. Previous studies have demonstrated that NEAT1 functions as an oncogene in multiple types of human cancer ([@b24-etm-0-0-6493],[@b25-etm-0-0-6493]). For instance, NEAT1 promotes laryngeal squamous cell cancer through regulation of the miR-107/CDK6 signalling pathway ([@b24-etm-0-0-6493]). NEAT1 is an unfavourable prognostic factor in gastric cancer, as it promotes tumour cell migration and invasion ([@b25-etm-0-0-6493]). However, the role of NEAT1 in OSCC remains unclear. In the present study, it was demonstrated that NEAT1 expression was significantly higher in OSCC tissue and cell lines compared with adjacent non-tumour tissue and normal oral keratinocytes, respectively. Additionally, upregulation of NEAT1 may be associated with lymph node metastasis, advanced clinical stage and poor prognosis of patients with OSCC. Similarly, increased NEAT1 expression was further associated with unfavourable clinical characteristics and poor prognosis in ovarian cancer ([@b26-etm-0-0-6493]), oesophageal squamous cell carcinoma ([@b27-etm-0-0-6493]), gastric cancer ([@b28-etm-0-0-6493]) and liver cancer ([@b29-etm-0-0-6493]). The present study investigated underlying regulatory mechanisms of NEAT1 in OSCC metastasis. A bioinformatics analysis predicted that miR-365 is a potential target of NEAT1. Luciferase reporter gene assays revealed that transfection with a miR-365 mimic significantly inhibited luciferase activity of WT NEAT1 in OSCC cells but did not affect luciferase activity of MT NEAT1, which indicates that NEAT1 may sponge miR-365 in OSCC cells. To further study the relationship between miR-365 and NEAT1 in OSCC, experiments that demonstrated that miR-365 was significantly downregulated in OSCC tissue and cell lines were performed. The current study observed an inverse correlation between miR-365 and NEAT1 in OSCC tissue. The function of NEAT1 in OSCC metastasis was examined *in vitro* and it was revealed that knockdown of NEAT1 reduced OSCC cell migration and invasion. As miR-365 expression was downregulated by NEAT1 in OSCC cells, it was speculated that miR-365 may be involved in NEAT1-mediated OSCC cell migration and invasion. Experimental data confirmed suppressive effects of NEAT1 inhibition on OSCC cell migration and invasion, as well as downregulation of MMP2 and MMP9 protein expression. To the best of our knowledge, this is the first study to report that NEAT1 promotes migration and invasiveness of OSCC cells by sponging miR-365. Therefore, the current study suggests that NEAT1 may be used as a novel therapeutic target when treating patients with OSCC. Not applicable. Funding ======= No funding was received. Availability of data and materials ================================== All data generated or analyzed during this study are included in this published article. Authors\' contributions ======================= XL wrote the manuscript and performed the experiments. WS collected clinical samples and performed the statistical analysis. FZ designed the present study and revised the manuscript. All authors read and approved the final manuscript. Ethics approval and consent to participate ========================================== The present study was approved by the Medical Ethics Committee of Stomatological Hospital of Jinan City (Jinan, China). All patients provided written informed consent. Patient consent for publication =============================== Not applicable. Competing interests =================== The authors declare that they have no competing interests. ![NEAT1 is upregulated in OSCC. (A) RT-qPCR analysis performed to examine NEAT1 levels in OSCC tissue compared with adjacent non-tumor tissue. \*\*P\<0.01 vs. adjacent non-tumor tissue. (B) RT-qPCR performed to examine NEAT1 levels in numerous OSCC cell lines compared with hNOK cells. \*\*P\<0.01 vs. hNOK cells. (C) Patients with OSCC and high NEAT1 expression demonstrated shorter survival time compared with low NEAT1 expression. RT-qPCR, reverse transcription-quantitative polymerase chain reaction; NEAT1, nuclear enriched abundant transcript 1; OSCC, oral squamous cell carcinoma.](etm-16-03-2243-g00){#f1-etm-0-0-6493} ![miR-365 is downregulated in OSCC. (A) miR-365 was predicted to bind to NEAT1. (B) RT-qPCR performed to examine miR-365 levels in OSCC tissue compared with adjacent non-tumor tissue. \*\*P\<0.01 vs. adjacent non-tumor tissue. (C) RT-qPCR was performed to examine miR-365 levels in various OSCC cell lines compared with hNOK cells. \*\*P\<0.01 vs. hNOK cells. (D) Inverse correlation between NEAT1 and miR-365 expression in OSCC tissue. miR-365, microRNA-365; NEAT1, nuclear enriched abundant transcript 1; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; OSCC, oral squamous cell carcinoma; hNOK, human normal oral keratinocytes.](etm-16-03-2243-g01){#f2-etm-0-0-6493} ![NEAT1 downregulates miR-365 expression via sponging in OSCC cells. (A) Constructed luciferase reporter plasmids containing WT or MT miR-365 binding sites in NEAT1. Luciferase reporter gene assay conducted in (B) HN4 and (C) Tca-8113 cells. Transfection with miR-365 mimic significantly inhibited luciferase activity of WT NEAT1 in OSCC cells, but did not affect the luciferase activity of MT NEAT1. \*\*P\<0.01 vs. Control. HN4 and Tca-8113 cells transfected with (D) NEAT1 siRNA to knock down NEAT1 levels or (E) NEAT1 plasmid to upregulate its expression. (F) NEAT1 overexpression significantly inhibited expression of miR-365 and (G) knock down of NEAT1 enhanced miR-365 expression in HN4 and Tca-8113 cells. \*\*P\<0.01 vs. NC siRNA or Blank. WT, wild-type; MT, mutant type; miR-365, microRNA-365; NEAT1, nuclear enriched abundant transcript 1; OSCC, oral squamous cell carcinoma; siRNA, short interfering RNA; NC, negative control.](etm-16-03-2243-g02){#f3-etm-0-0-6493} ![Knockdown of NEAT1 inhibits OSCC cell invasion. (A) Wound healing (magnification, ×40) and (B) Transwell assays performed to study effects of NEAT1 downregulation on HN4 and Tca-8113 cell migration and invasion (magnification, ×400). (C) Western blot assay to examine MMP2 and MMP9 protein expression. \*\*P\<0.01 vs. NC siRNA. NEAT1, nuclear enriched abundant transcript 1; siRNA, short interfering RNA; MMP, matrix metalloproteinase; NC, negative control.](etm-16-03-2243-g03){#f4-etm-0-0-6493} ![Inhibition of NEAT1 suppresses OSCC cell migration and invasion by sponging miR-365. NEAT1 siRNA transfected OSCC cells co-transfected with NC or miR-365 inhibitor. (A) Reverse transcription-quantitative polymerase chain reaction analysis of miR-365 levels. (B) Wound healing (magnification, ×40) and (C) Transwell assay performed to examine cell migration and invasion (magnification, ×400). (D) Western blot analysis of MMP2 and MMP9 protein expression. \*\*P\<0.01 vs. siNEAT1+NCin. NEAT1, nuclear enriched abundant transcript 1; siRNA, short interfering RNA; OSCC, oral squamous cell carcinoma; NC, negative control; miR-365, microRNA-365; MMP, matrix metalloproteinase; NC, negative control; in, inhibitor.](etm-16-03-2243-g04){#f5-etm-0-0-6493} ###### Association between NEAT1 expression and clinicopathological characteristics in patients with oral squamous cell carcinoma. NEAT1 expression ---------------------------------- ---- ------------------ ---- ------- Age (years) 0.791   ≤55 24 14 10   \>55 34 18 16 Sex 0.183   Male 35 22 13   Female 23 10 13 Differentiation grade 0.213   Well and moderately 45 27 18   Poor 13 5 8 Lymph node metastasis 0.009   Present 18 5 13   Absent 40 27 13 Tumor, node and metastasis stage 0.007   I--II 36 25 11   III--IV 22 7 15 NEAT1, nuclear enriched abundant transcript 1.
tomekkorbak/pile-curse-small
PubMed Central
Odoo: The new OpenERP - seyz https://www.odoo.com/ ====== jamesmcintyre If you look around there is no "beautiful ERP" solution out there and the status quo is "you can make a very capable ERP or a "pretty" ERP but not both". I understand the the difficulty of striking that balance but I think by applying the right kind of modularity to the app design (sort of like openERP but even more granular and forgiving) you can arrive at a solution which invites businesses of all-sizes but can grow with the company into very complex processes. There is HUGE opportunity in this market and I believe one big reason is that a new generation of userbase will expect and demand a better UX than any current offering. In fact, I suggest a great startup idea would be a to take the openerp codebase and wrap a new UI/UX around it starting with one vertical ("niche") market and working out from there. (i.e. "A beautiful ERP for medium-sized businesses focusing on your growing warehouse, sales and purchasing needs built on the solid foundation of openERP."). Not saying it would be easy, but just worthwhile. I have a feeling the Odoo rebranding points to an effort for a UI overhaul which acknowledges the opportunity of a great UX. ~~~ kfk This is nonsense. An ERP has to run your business and operations. It has to be extremely reliable. Users couldn't care less about it's UX, in fact, the standard ERP solution, SAP, looks terrible, but it is also quite ok to use. In a big company an ERP error/fault can generate millions worth of damage, are you still thinking a prettier UI is a great start up idea for an ERP? Finally, you forget that IT departments in big companies are just a tad above trained monkeys and your software solution has to take that into account, in fact, it's the first piece of your service: it has to be easy to maintain. It's probably here where you want to focus on to compete... ~~~ UVB-76 _> This is nonsense. An ERP has to run your business and operations. It has to be extremely reliable. Users couldn't care less about it's UX [...]_ Indeed. When a person's livelihood depends on using your software, they have a pretty strong incentive to learn how to use it effectively, and put up with all its imperfections. I'm sure some employees actually revel in how backwards and difficult to use their business software is. If everything were automated, effortless, and required no expertise, they'd be out of a job. ------ icebraining By the way, the core and base modules (and in theory, all community modules, since they're derived works) of Odoo are Free Software (APGL) and available on Github: [https://github.com/odoo/odoo](https://github.com/odoo/odoo) Disclaimer: I work for a company that implements solutions based on Odoo for small and large companies. So yeah, it's possible to make a living working on FOSS, if anyone still doubted it :) ~~~ ddorian43 they still use their custom-own-built orm ? ~~~ codeape I cannot understand why anyone would not use SQLAlchemy if they're building a database-backed Python application. ~~~ jlnthws True today, but not 10 years ago :) Plus Odoo ORM and SQLAlchemy have different purposes. ------ davidbrent OpenERP could've really benefited from some usability expertise, and if this site is any indication, Odoo may suffer the same fate. If you're going to put this much time/money into a new brand, how could you miss so badly? In my experience with OpenERP, the end users always took a back seat to the developers. Granted, ERP software is inherently complicated, but with each new version you could tell they made an attempt at a simplified interface and never hit the mark. ~~~ paulyg OpenERP is still leagues above the million dollar paid apps of Oracle and SAP. I'm not saying you are wrong. Just how bad this particular segment of software is. It is wripe for disruption. ~~~ UK-AL ERP software is huge, simply because there so many different ways businesses works, all the regulations you have to comply with etc etc It would be very hard for a startup to build it from scratch. ------ kepano Not sure the rebrand is what will attract new customers to OpenERP. A couple months ago, I evaluated ERPs for our business. OpenERP was one of the main contenders but ultimately the manufacturing module failed to meet our requirements and custom development would have been too costly. I was also shocked to get a glimpse at OpenERP's internal corporate structure. Despite the open source nature of the project, their business model puts them on track to become yet another big, slow, expensive ERP company pushing massive service fees. Unfortunately there's just no great solution in the ERP world. Requirements for this category are so complex that by the time a system becomes adequately feature rich, improvements in software technology make it feel obsolete. I wonder if someone will crack that nut. ~~~ thematt Exactly. Every company's business process has it's own uniqueness, so if you try to evolve it into a mass-market tool (as opposed to designing for it up- front), you end up with a Frankenstein system that is enormous and complicated. Then your company starts morphing to match what you're selling. If some YC'ers want to make some serious cash, go build the JIRA of ERP. Make the system: pluggable, VERY configurable, give it a sexy UI and don't require an army of consultants to implement. Want some reasons? Pretty much all your potential customers hate their existing ERP system. Your competition is staffed by sleazy salespeople that sell nothing but snakeoil. Your market is filled with companies of all sizes who will literally throw cash at you to make them more efficient. ------ ritonlajoie What are the alternatives to OpenERP today ? (I mean, free and open sources ones, with acceptable UI) ~~~ naringas There is [http://tryton.org/](http://tryton.org/) however I don't know what you mean by "acceptable" UI ~~~ ritonlajoie For me, an acceptable UI in an ERP means this ERP can be used to do basic tasks by someone not having any PhD ni ERP Usage :) ------ joshmlewis Icons! As a designer, I've probably never seen so many icons on a page. ------ pnathan I've considered working with OpenERP and looking at becoming a consultant in it (ERP is $$$ and very useful), but last I checked the OpenERP site (2? years ago?), the demo site was half broken. Glad to see it's gotten a refresh and a genuinely web 2.0 name. ;) Apparently the devs have churned it into a SaaS offering, which is also very cool. ~~~ UK-AL is OpenERP contractor fees that large? I know SAP and Oracle Fees are high, simply because its quite hard to get opportunity to work on it, and all the certifications. So there aren't that many people around. ~~~ pnathan Well, I'm not sure what the rate is. But I know that it supplies a _very valuable service_ , and other things in the space are very lucrative. I imagine that part of the lucrativity is the value that it provides to businesses. ~~~ UK-AL Salary does't always mean value provided. Salary = Supply/Demand. ------ gaunab They also discovered how to succeed as a tech company: Better use at least three 'O's in your brand name. "Choosing the right name is hard. To find the perfect name, we analysed the names of top internet companies. We discovered a direct correlation between the company valuation and the number of 'O' in its name. The graph below shows the average valuation of the top 10 internet companies according to the number of 'O' in their names. With three 'O' in its name, 'Odoo' is in phase with our ambitions."
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HackerNews
Q: Running SonarQube on internal Web Server I am trying to make Sonarqube working on a virtual machine, IP 192.168.0.150, running on a production server (Win Server 2012 R2). I need also to access it from the Internet. Thus, I created a new website in IIS on the Physical server enabling the reverse proxy and redirecting everything to 192.168.0.150. This apparently works: I can access successfully the dashboard from any remote pc. The problem is: when i try to login, sonarqube redirects to 192.168.0.150. As you can easily imagine this blows up everything from a remote pc. I tried everything in sonar.web.host and sonar.host.url but nothing. I tried an Outbound rule in IIS to overwrite 192.168.0.150 with my website address but it doesn't work with gzip compression. What can I do? Thanks A: Resolved. I had to check "Reverse rewrite host in response headers" option in IIS -> Machine -> Application Request Routing Cache -> Server Proxy Settings.
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StackExchange
Share this: Related Comments I love both outfits so much! you are so great at doing little adjustments and tailoring the outfits exactly right. I'm always inspired to go through my pile of clothes that don't fit correctly and fix them after I read your blog 🙂 Your email address will not be published. Required fields are marked * Comment Name * Email * Website Notify me of follow-up comments by email. Notify me of new posts by email. Hello! My name is Sarah and I am so happy to have you here! Here you'll find DIY sewing, DIY home building & decor, honest and vulnerable posts of motherhood and snippets of my family. We are building our dream house and will update you regularly on our whole process from start to finish and I am also starting a mother-daughter sewing series. So I hope you stay awhile!
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question is Blake whether he ran the wrong route or did tony get mixed up on the plays? i think witten ran the right route, based on what it looked like, witten was concentrating too much on getting free from his defender instead of the ball. Quote: Originally Posted by gonzo In the post game interview Tony said it was his fault for the loss. Witten acted like it was his fault at the end of the game, but that is just the kind of player he is. i could blame any number of people, but it doesn't change the fact that we lost. romo made too many mistakes, so i'd probably have to put the biggest amount of blame on him. if he didn't throw that pick that sealed the game for the steelers, we wouldn't be bitching right now. Quote: Originally Posted by Couch Everyone can say what they want about the Texans, but that was a great game overall by both the Packers and Texans. so what's going to be the redskins excuse when they fail to make the playoffs again? Again? We've been to the playoffs two out of the past three years... and we've WON a playoff game. More than the Cowboys can say. You guys should be thinking of drafting a quarterback who doesn't cost you the big games and getting rid of T.O. who can't catch and just cries every time he doesn't get thrown to. You have a future with Felix Jones though once he gets healthy. Again? We've been to the playoffs two out of the past three years... and we've WON a playoff game. More than the Cowboys can say. You guys should be thinking of drafting a quarterback who doesn't cost you the big games and getting rid of T.O. who can't catch and just cries every time he doesn't get thrown to. You have a future with Felix Jones though once he gets healthy. you must have water on the brain. the only reason you want to piss and moan about TO, romo, and anyone else is because your jealous your busted ass team doesn't have such weapons. that's the only reason why anyone ever pisses and moans about the cowboys. people are jealous of our swagger when it's there, it's something that other teams loath for. enjoy mediocrity bitches, i'll take all the weapons in the world. sorry, that was a little harsh. honestly, i wish the texans all the best of luck. i'd like to see them become a great team, and as previously stated in this thread, i would love an annual cowboys/texans regular season game. it's a shame schaub got hurt, i think the texans would be right in the wild card race if he didn't have that knee injury. another thing that doesn't really help the texans is being in the same division as tennessee and indy. sorry, that was a little harsh. honestly, i wish the texans all the best of luck. i'd like to see them become a great team, and as previously stated in this thread, i would love an annual cowboys/texans regular season game. it's a shame schaub got hurt, i think the texans would be right in the wild card race if he didn't have that knee injury. another thing that doesn't really help the texans is being in the same division as tennessee and indy. You don't have to appologize. It is what is. We're all sports fans and love our teams. People can knock my team(s) all they want. I still pull for them, and still see tremendous potential in the making for the Texans. It's been a fun season to watch, even with all the problems and mistakes. I agree, a yearly Cowboy/Texan match up would be awesome. We'll see yall next season. you must have water on the brain. the only reason you want to piss and moan about TO, romo, and anyone else is because your jealous your busted ass team doesn't have such weapons. that's the only reason why anyone ever pisses and moans about the cowboys. people are jealous of our swagger when it's there, it's something that other teams loath for. enjoy mediocrity bitches, i'll take all the weapons in the world. Of all people I would think a Cowboys fan would be tired of Romo and T.O. I have respect for each and every team (except Detroit). Your team should have went to the Super Bowl last year AND the year before that. You're right, you have ALL the weapons but what do you do with them? Absolutely nothing. So that makes you guys no better than the Redskins. And if you think the Redskins don't have weapons, you need to start watching more of our games. Clinton Portis, arguably the best running back in the league this season. Santana Moss, Chris Cooley, Jon Jansen, Chris Samuels, Jason Taylor, London Fletcher, our WHOLE secondary. Yeah, I'm really jealous of the Cowboys. Just like you should, I get frustrated when we underachieve. You can have all the weapons in the world, but what use are they if you don't win it all? Of all people I would think a Cowboys fan would be tired of Romo and T.O. I have respect for each and every team (except Detroit). Your team should have went to the Super Bowl last year AND the year before that. You're right, you have ALL the weapons but what do you do with them? Absolutely nothing. So that makes you guys no better than the Redskins. And if you think the Redskins don't have weapons, you need to start watching more of our games. Clinton Portis, arguably the best running back in the league this season. Santana Moss, Chris Cooley, Jon Jansen, Chris Samuels, Jason Taylor, London Fletcher, our WHOLE secondary. Yeah, I'm really jealous of the Cowboys. Just like you should, I get frustrated when we underachieve. You can have all the weapons in the world, but what use are they if you don't win it all? The Redskins have weapons, but no QB! If the Cowboys would have made it to the SB 2 years ago...they would have lost to the Colts! Won't be before W. Phillips gets kicked out. Anyone ever think that the cowboys play book maybe to damn complicated for the players and thats why Tony throws so many interceptions and no one ever knows where to line up! I can't believe that Jason Garrett has integrated this system of the so called "Cowboys live and die by the big play" Since when have the cowboys lived and died by the big play? WTF happened to the 4-5 yard plays and wearing down the defense while running all over them the entire game! My opinion, if we don't have a big run in the playoffs then not only will Wade Phillips be gone next year, but so will Jason Garrett, and I doubt TO is going anywhere. Won't be before W. Phillips gets kicked out. Anyone ever think that the cowboys play book maybe to damn complicated for the players and thats why Tony throws so many interceptions and no one ever knows where to line up! I can't believe that Jason Garrett has integrated this system of the so called "Cowboys live and die by the big play" Since when have the cowboys lived and died by the big play? WTF happened to the 4-5 yard plays and wearing down the defense while running all over them the entire game! My opinion, if we don't have a big run in the playoffs then not only will Wade Phillips be gone next year, but so will Jason Garrett, and I doubt TO is going anywhere. Okay /Rant I do agree with a lot of what you said. The only problem is you are assuming the Cowboys are making the playoffs. I still think TO is a cancer, though. I do agree with a lot of what you said. The only problem is you are assuming the Cowboys are making the playoffs. I still think TO is a cancer, though. I'm not assuming their going to make the playoffs, what I was trying to say is they not only have to make the playoffs this year but they need to get deep into the playoffs. Also I don't think TO is the cancer to the team, I think losing is the cancer, because any good player hates losing. Take for example Clinton Portis in Washington, or Roy Williams in Detriot, Jason Taylor with Miami last year, etc. etc. It's human nature to start complaining when your good at something and you continue to fail at it which in this case is TO is a above average reciever with a more then above average team but yet they we continue to lose. i think this, and pretty much all the TO controversies this year, are OVERLY INFLATED by ESPN and the sports media to garner ratings. i'm so sick of espn, they're like nazi germany when it comes to propaganda. i can't even stand to watch that crap anymore. if someone drops a pen in the cowboys locker room, espn claims the cowboys are falling apart, which then perpetuates throughout the entire rest of the media. it's fucking ridiculous. cowboys players and assistant coaches should not even be allowed to talk to the media, then this shit wouldn't happen. most true cowboys fans, like myself, aren't worried about TO ruining our team, because most true cowboys fans don't see it like the rest of the world sees it. everyone wants us to fail so bad because we've got all these big egos. here in dallas, we don't give a shit what you guys think. all these EXTERIOR influences are trying to tear the team apart. i don't think there is much going on inside the team that is too significant...it's the media that gets it and blows the shit way out of proportion. /end rant oh and playoffs, if we don't make it, i've already accepted that. injuries have absolutely decimated us this year, can't avoid that. everyone can say we choked, but we have not had a lot of the key pieces in place all year long consistently. romo being out that long for some really easy games that were almost automatics killed us. oh well. i think this, and pretty much all the TO controversies this year, are OVERLY INFLATED by ESPN and the sports media to garner ratings. i'm so sick of espn, they're like nazi germany when it comes to propaganda. i can't even stand to watch that crap anymore. if someone drops a pen in the cowboys locker room, espn claims the cowboys are falling apart, which then perpetuates throughout the entire rest of the media. it's fucking ridiculous. cowboys players and assistant coaches should not even be allowed to talk to the media, then this shit wouldn't happen. most true cowboys fans, like myself, aren't worried about TO ruining our team, because most true cowboys fans don't see it like the rest of the world sees it. everyone wants us to fail so bad because we've got all these big egos. here in dallas, we don't give a shit what you guys think. all these EXTERIOR influences are trying to tear the team apart. i don't think there is much going on inside the team that is too significant...it's the media that gets it and blows the shit way out of proportion. /end rant That is true obviously to an extent but no locker room is 100 percent okay. When I played football in highschool and college, anytime we lost we all felt like someone had to be blamed. Whether it was the coaches, players, etc. there was always drama. I do agree with you that it's blown out of proportion in the media because we would get over it the next practice but thats what the media does, entertain people with bullshit stories right? Nonetheless the cowboys have to start winning or major changes are going to occur regardless of what the media says. Jerry nor the fans (including myself and the insane blake!) are going to put up with this much talent and this many heartbreaking losses year after year. oh and playoffs, if we don't make it, i've already accepted that. injuries have absolutely decimated us this year, can't avoid that. everyone can say we choked, but we have not had a lot of the key pieces in place all year long consistently. romo being out that long for some really easy games that were almost automatics killed us. oh well. The shitty back ups is the Cowboys fault. WTF is Brad going to do in place of Romo, lol. If someone sneezes on him he goes down. We should of been better prepared for injuries IMO. Look at our defense, if Ware goes down we have someone else to step up. Newman went down, and we had a rookie step up and do a decent job. Now the rookie is down but we got Newman back That is true obviously to an extent but no locker room is 100 percent okay. When I played football in highschool and college, anytime we lost we all felt like someone had to be blamed. Whether it was the coaches, players, etc. there was always drama. I do agree with you that it's blown out of proportion in the media because we would get over it the next practice but thats what the media does, entertain people with bullshit stories right? Nonetheless the cowboys have to start winning or major changes are going to occur regardless of what the media says. Jerry nor the fans (including myself and the insane blake!) are going to put up with this much talent and this many heartbreaking losses year after year. i would give a kidney to just start the season over today with a healthy roster.
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Thanks so much to the Desirabelles for inviting me to blog with you this week. And hello to all my old pals from the Diamonds blog. I am excited to announce the release of my sixth book for Silhouette Desire. Friday Night Mistress began life around Christmas 2007 when for some inexplicable reason, I began to hear Strauss waltzes in my head from morning to night. I have two very old CDs of Strauss’s Famous Viennese waltzes, but suddenly, I couldn’t get the music out of my head so I figured I was meant to write a ball story. My first idea didn’t fly but we eventually wrangled something from the ashes, which turned into two books about Kiwi brothers, Nick and Adam Thorne. I did stage a ball in Friday Night Mistress but as it turned out, the real ball bonanza was relegated to the second story, Adam’s book, which is set in England and Vienna. Friday Night Mistress takes place mostly in Wellington, New Zealand, a pretty city at the bottom of the North Island. Nick and his love interest, Jordan, also take a trip on a chartered boat to the Marlborough Sounds, one of the loveliest parts of the country in my opinion. Nick Thorne is a financier, a serious, rather conservative man. I fell in love with the Venezuelan supermodel, Enrique Palacios, when I saw him on the Armani Code ad. A little more delving delivered a wonderful You Tube clip of him in many poses. This is one of my favourites (left) – and there actually was a steamy stairwell scene in the book…Gorgeous, intense, purposeful, he clearly needs a shake-up. Who better than the flashy, flighty heiress, Jordan Lake, who just happens to be the daughter of Nick’s father’s most hated enemy? That’s Mischa Barton of OC fame (right). Aside from the problems that arise between their families, Jordan has exactly the right amount of flair, notoriety and vulnerability to rock Nick’s ordered and organised world. Nick prides himself on his sense of honour and duty. So much more responsible than his playboy brother, Adam, whom we meet in Friday Night Mistress, and who has Nick shaking his head over the relentless pursuit of his prim and proper PA… You’ll be happy to know that since I finished writing Adam’s story – which was THE BEST to research – the Strauss music has subsided to an occasional treat. Now a little story. My neighbor has told me she got goose bumps when she heard Strauss blaring from my house. Apparently the couple who built this house fifty years ago were keen ballroom dancers. We have a lovely big, long lounge with a huge curved window. They used to have dancing afternoons where their friends would come around and they would move the furniture back and waltz around the room. I like that! I always love hearing about different eras in a house’s life. One of our houses was built in 1848 and had a most interesting history – including a suicide – but even Google can’t help me with this place. I was going to kick off the comments with a question pertaining to family feuds but let’s have some fun. ::Shines torch under your chin:: Do you have a snippet of fascinating history from a house you’ve lived in? It can be as creepy, crazy or cuckoo as you like. And if you raise the hairs on the back of my neck or tickle my funny bone, or even just dazzle me with the truth, I have two copies of Friday Night Mistress to give away. Good luck!
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Lorens' Cloud Modular Table is a Friendly and Practical Design The hexagonal shapes of the Cloud Modular Table may not actually bring to mind those fluffy white shapes up in that big blue sky; instead, it happens to look more like the honeycombs in bee hives. Yet whatever it may look like, despite its name, it would definitely be a happy and handy piece of furniture to have in one's home. Designed by Anna and Mark of Lorens, the Cloud Modular Table allows the owner to arrange it however he or she sees fit in regards to the space they are working with. It also boasts shallow storage that can hide away home and office knickknacks easily and conveniently.
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But in this nondescript office block, as commuters rushed by outside, they would speak at last. And, finally, after all those years, these adults, who were once children in Scotland’s care homes, would tell their stories. Stories of neglect, of cruelty, of abuse and of murder. The Scottish Child Abuse Inquiry started its second phase in Edinburgh last week as judge Lady Smith, pictured, turned her attention to Smyllum Park children’s home in Lanarkshire, the orphanage where, as we revealed in September, up to 400 children are buried in an unmarked grave. The hearings were harrowing for those who gave evidence and those who heard it. It was often heart-breaking. Some in the seats open to the public wept as former child residents – most are now pensioners – described growing up in Smyllum. The children’s home – ran by a Catholic order of nuns called the Daughters of Charity of St Vincent De Paul from 1864 to 1981 – is one of more than 60 institutes being looked at by the inquiry. But it’s the first to come under scrutiny by the inquiry which is examining cases of abuse from the 1930s onwards. Until Christmas, dozens of former residents will give evidence and statements alongside former residents of another home called Bellvue Home in Rutherglen, which was run by the same order of nuns. Previously, the inquiry heard apologies from groups who ran some of the institutes who said they “deplored that physical sexual abuses could occur” in the homes they ran. Now, it was time to drag those allegations into the light. Smyllum orphanage In the long, white-walled hearing room of Rosebury House, near Haymarket Station in the city’s west end, the first witnesses came forward to speak openly about their lives at Smyllum Park. For some it was the first time they had ever spoken of their ordeal there. In June, the head of the Daughters of Charity, Sister Ellen Flynn, described allegations of abuse at Smyllum Park as a “mystery” and said there was “no evidence” of abuse happening there. Last week, her words rang hollow as witness after witness remembered their lives in the orphanage. Within minutes of the inquiry restarting, the order’s lawyer, Gregor Rolfe, admitted for the first time that a worker at Smyllum Park in the mid-70s may have sexually abused two brothers. He described how earlier this year, a member of staff came forward to tell how she told a nun in the 1970s that Brian Dailey, a former care worker jailed in June for the predatory abuse of children in residential homes, had abused two Smyllum Park boys on a holiday. Former residents – some of whom only came forward after The Sunday Post published our reports into Smyllum Park earlier this year – soon began. Wiping away tears while delivering his testimony, David – not his real name – was the first to speak about the suffering he endured at Smyllum Park. The “rage” he’d been left with would scar his adult life and relationships, he told Lady Smith. By the age of just 10, David said he had suffered both physical and sexual abuse at the hands of nuns. But he’d also seen much worse happen to those close to him. Visibly upset, he recalled how he’d helplessly watched six-year-old best friend Sammy Carr suffer a frenzied kicking by a nun. Tragic Sammy died days later, David claimed. A police investigation earlier this year into David’s allegations confirmed that Carr had indeed died of a brain haemorrhage despite the family saying they were given a different account by the nuns at the time. However, authorities have found no evidence in the post-mortem to suggest it was linked to an assault. Instead, Carr may have had a fungal brain infection, potentially brought on by malnutrition. It wasn’t the only death the inquiry would touch on last week. On Wednesday, another former resident, going by the name Chief, told how he heard a four-year-old boy called David repeatedly slapped by a nun behind a curtain before he died. “We heard slap, slap, slap, and ‘shut up’, ‘shut up’. It was one of the nuns,” he told the inquiry. “The next day the boy didn’t show up. We all cheered because we thought he had got a family and he was away.” But there was no happy ending for the young boy. David, whose full name was David Carberry, died in July 1955 aged just four. In September, our joint investigation with the BBC revealed how he was one of more than 400 deaths linked to the home – a death rate at odds with national averages. His death certificate says he died from bronchial pneumonia. But like Sammy Carr, his family have told the Sunday Post how nuns offered a different explanation for his death at the time. Speaking from Australia last week, David’s older brother Leon, a former police officer and Smyllum Park resident, said he felt “upset, anger and rage” at hearing fresh allegations about physical abuse suffered by David before his death. For Chief – who says he himself suffered nearly a decade of physical abuse at the home – our revelations that David Carberry had passed away was just as shocking as the beatings he says he suffered at the hands of the nuns decades ago. “It wasn’t until I saw The Sunday Post that I found out he died, or he was killed,” he told the inquiry. For some the wait to appear proved too long. Frank Docherty and Jim Kane – firm friends who passed away earlier this year within weeks of each other – had campaigned for an inquiry to hear what had happened to them at Smyllum Park for years. Last week, they were finally vindicated. Their posthumous statements – salted with their trademark language and humour – took an hour each to read aloud. In death, they finally achieved what they had fought for in life. Frank’s widow Janet, who has taken over her husband’s campaigning role with the charity In Care Abuse Survivors (INCAS), looked on determinedly from the public gallery as the inquiry heard from Frank from beyond the grave. Evidence is expected to continue to be heard about Smyllum Park into 2018 and after that it will move on to other care institutes. Lady Smith will not report on her findings until October 2019 at the earliest. For the former residents of Scottish care homes it can’t come soon enough. And it’s not for the compensation one former nun cruelly told the inquiry earlier this year she suspected they were after. Rather it is for redress. As prominent QC John Scott – acting for INCAS – told the inquiry on Tuesday, “This inquiry has seen how much more there is to survivors than any legitimate demand for money. “Prevention, acknowledgment, apology and accountability are what drives them.”
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Bad experience, good birthing: Dutch low-risk pregnant women with a history of sexual abuse. The long-term effects on women in childbirth with a history of sexual abuse have only been studied to a limited degree. We estimated the prevalence of lifetime experience among low-risk pregnant women (non-clinical) in The Netherlands as well as the association with (1) psycho-social outcomes, and (2) the birth process. Study of 625 randomly selected low-risk pregnant women. At 20-24 weeks gestation, participants completed a questionnaire covering socio-demographic variables, sexual attitude, and psychological determinants. Midwives recorded details of the birth process. Nearly one-in-nine (11.2%) women had experienced sexual abuse. They were on average younger, more likely to smoke, and had lower household income. They reported more conflicting feelings about sex than women who did not report a history of abuse (p = 0.02). Multiparous women with a history of sexual abuse reported more emotional distress (p = 0.037), more internal beliefs concerning health (p = 0.004), and they were also more likely to suffer pelvic pain (p = 0.045). Sexually-abused women reported higher levels of autonomy (p = < 0.001). Referral rates to secondary care were equal. Sexually-abused women were less likely to receive episiotomies (p < 0.005). Little difference was observed in major birth-related technical interventions between women with and without a history of sexual abuse.
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PubMed Abstracts
Blogs Movement The Most Overlooked Area for Women Mark VerstegenJanuary 12, 2010 Dave Cruz Hip stability might be the number one issue facing women when it comes to injuries and ailments. Injuries of the anterior cruciate ligament (ACL) of the knee have reached epidemic proportions among young women, and not just athletes. Nobody can pinpoint a reason, with theories ranging from the increased physical nature of women’s sports to biomechanical issues to a possible tie-in to menstrual cycles. ACL injuries lead to other knee problems, along with shin splints, stress fractures and other injuries. ACL injuries often are related to a lack of stability and mobility in the hips; the knee moves to compensate for the hip. The hip cuff is the control unit for your lower body. It governs the thigh, which interacts with your knee and affects your foot position. The centrality of the hip cuff is why tremendous attention must be paid to strengthening the muscles in and around the area, as they are critical in controlling everything below your hips, and everything above as well. The hip cuff consists of more than 40 muscles in and around your lower pelvis that are responsible for much of your lower body movement. Even if you think you already have the ultimate hip-and-glute workout routine, I assure you that you haven’t come close to addressing this key area. Hips are the most overlooked area when it comes to decreasing the potential for injury. Most back and hip problems occur because of improper mobility and stability and faulty utilization of the hips. Most people are locked down or unstable in their hips. If one of your hip capsules is locked down, it’s as if one of your thighbones is welded to your pelvis—imagine wearing a permanent cast on your hip. To get anything to move, you would have to use excessive motion in your knees and back to make up for your hip’s immobility. The lower and middle back share some common responsibilities with your hips, but they were meant to be secondary, not primary, initiators of movement. By maximizing efficiency in and around the hip cuff through improved mobility, stability, and strength, you will discover the engine that will propel you throughout daily life, to say nothing of creating “buns of steel.” We want to focus on becoming glute dominant instead of quad dominant. This is a key concept. Most women move from their knee joints as opposed to their hip joints; they’re “quad dominant.” Their knees move first, stimulating the quadriceps muscles to fire at the onset of movement. This is a dangerous thing because the hub of your wheel is your pelvic area—not the quads. You want to absorb force through the more powerful center of your body toward your glutes, which will enable the limbs to work together to produce force. To try to absorb this much force in the quads alone is to invite ACL and other leg injuries. Imagine if you slip on a patch of ice. If your knees and quads move first, you’re probably going to fall, likely resulting in a knee injury. But if you can absorb that force through the center of your body and your glutes, you’re less likely to tumble and if you do, it’s less likely to produce a knee injury. The reason women tend to be quad dominant is that they have a larger “Q angle,” the angle at which the femur (upper leg bone) meets the tibia (lower leg bone). Women’s hips are slightly wider relative to their knees and often a woman’s knees fall more toward the midline of the body, creating a greater angle from the knee to the hip. This is the price women have to pay for being able to produce the miracle of childbirth. There’s nothing we can do to change this, obviously. But what you can do is be aware of it so that when you look in the mirror or watch your workout routine, your knees are not coming together and definitely not rubbing together. The Core Performance program will help you develop more femoral control by focusing not on your knees but in your hip cuff, which is the control center for both your knees and lower legs. We’ll spend lots of time on movements that challenge the hip rotators. These exercises might feel like butt busters but are actually knee and back protectors, giving your body the ability to control the angles and better disperse force into your muscular system.
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Pile-CC
Boston police and firefighters suspended the search around 3:30 a.m. last night for a naked woman who reportedly jumped into Jamaica Pond and disappeared. According to a Boston police spokesperson, witnesses at the scene said they saw a woman who entered the pond, but then lost sight of her. By 11 p.m., firefighters cleared the scene, leaving police to continue the search. Witnesses told police they saw the woman enter the pond from the side closest to Brookline. There were dive teams, police boats and approximately 20 emergency response vehicles at the scene, but the divers had not entered the water as of 10:30 p.m.. A lighting truck circled the pond along a walkway to illuminate the water for searchers. Quincy Police also responded to the scene with a dive team and sonar equipment, according to the Boston Fire Department. Searchers requested helicopters from the Massachusetts State Police and Coast Guard, but the evening’s severe weather kept them grounded, according to police. Formed by a glacier, the 60-acre Jamaica Pond reaches a depth of 53 feet, making dives and searches difficult. Despite the depth of the water, drownings are relatively rare in Jamaica Pond. In 2007, a Roxbury woman drowned in the pond while her horrified son watched from the shore. In 2005, a walker spotted a fully clothed man struggling in the water and crying for help. His body was later found by first responders at the scene. In 1990, a Jamaica Plain man drowned in the water after suffering an undisclosed medical problem.
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OpenWebText2
Q: Catalan number problem I have a dynamic formula to calculate numbers of the Catalan sequence length-N, the formula: $$f_{i, j} = f_{i - 1, j - 1} + f_{i - 1, j + 1}, f_{0, 0} = 1$$ in that: $i$ is the current length, $j$ is the value of the catalan number at position $i$ How can I calculate the number $f_{i, j}$ faster ? Is there any formula for that ? A: When faced with questions like this, it's always worth generating a few terms and searching OEIS. Searching for the $n=8$ row $$\begin{matrix}14 & 0 & 28 & 0 & 20 & 0 & 7 & 0 & 1\end{matrix}$$ I find A053121 which includes such notes as $a(n, m) = a(n-1, m-1) + a(n-1, m+1)$ if $n > 0$ and $m \ge 0$, $a(0, 0)=1$, $a(0, m)=0$ if $m > 0$, $a(n, m)=0$ if $m < 0$. - Henry Bottomley, Jan 25 2001 (so it's the right sequence) and $$a(n, m) = \begin{cases} 0 & \textrm{if } n<m \textrm{ or } n-m \textrm{ odd} \\ \frac{m+1}{n+1} \binom{n+1}{\frac12(n-m)} & \textrm{otherwise}\end{cases}$$
tomekkorbak/pile-curse-small
StackExchange
Far out Friday: 20 of the lamest sick day excuses by WP | 25 Oct 2013 One of the benefits of being self-employed is that you don’t have to fake a feeble 'pneumonia voice' to your boss on the phone whenever the surf’s up. On the other hand, you don’t have the luxury of getting some other poor sod to do your job when you really do eat some dodgy poultry and come down with a sudden, debilitating bout of ‘chickenpox’ as a result. Either way, employers in every industry get their fair share of ‘sick’ day excuses from people who really just want some quality time with their golf clubs. And as a recent study conducted by recruitment website CareerBuilder.com found out, those excuses can sometimes be pretty hilarious. Below, we’ve compiled some of the more bizarre anecdotes on the list, as well as a few other numbers from various far-flung corners of the internet. All are reportedly real-life scenarios (number five was even used by someone at our own company). If you've got another example to add to the list, make sure to write it in the comment box below: Top 20 lamest sick day excuses ever: 20. Employee's dog was having a nervous breakdown 19. Employee's dead grandmother was being exhumed for a police investigation 18. Employee was bitten by a bird 17. Employee was upset after watching The Hunger Games 16. Employee got sick from reading too much 15. Employee's hair turned orange from dying her hair at home 14. Employee dropped a tin of baked beans on his toe 13. Employee swam too fast and knocked his head on the poolside 12. Employee’s hamster died 11. Employee was hallucinating 10. Employee’s new girlfriend bit him in a ‘delicate’ place 9. Employee’s toe was trapped in the bathtub tap 8. Employee drank too much and fell asleep on a stranger’s floor: ‘I don’t know where I am’ 7. Employee had a sore finger 6. Employee’s trousers split on the way to work 5. Employee electrocuted herself with a hair straightener 4. Employee’s dog ate his shoes 3. Employee's fish wasn't feeling well 2. Employee forgot he had been hired for the job 1. Employee's mum had died (this was the second time the employee had used this excuse)
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Pile-CC
39 Cal.App.3d 772 (1974) 114 Cal. Rptr. 663 THE PEOPLE, Plaintiff and Respondent, v. CHESTER C. FEAGLEY, Defendant and Appellant. Docket No. 12323. Court of Appeals of California, First District, Division Three. June 12, 1974. *773 COUNSEL Stephen L. Katz for Defendant and Appellant. Evelle J. Younger, Attorney General, Jack R. Winkler, Chief Assistant Attorney General, Robert R. Granucci and W. Eric Collins, Deputy Attorneys General, for Plaintiff and Respondent. OPINION DRAPER, P.J. Appellant is described in a probation report as a "rather pathetic, guarded, defensive man who has an obsessional ritualistic pattern of snipping hair" from the heads of young girls. The report shows a number *774 of prior convictions for offenses stemming from his hair fetishism. He was charged in this case with two counts of child molesting (Pen. Code, § 647, subd. (a)), and pleaded guilty to one count of misdemeanor battery (Pen. Code, § 242), agreed to be a lesser included offense. Appellant was found to be a mentally disordered sex offender and was committed to the department of mental hygiene. After some 1,000 days of such hospitalization, he was returned to the court as one who would not benefit from further treatment but was not a menace to the health and safety of others. The criminal proceeding was resumed, imposition of sentence was suspended and he was admitted to probation for five years, upon condition that he refrain from use of intoxicating liquor, from association with any minor under the age of 18, and participate in a treatment program recommended by the probation officer. Treating the order admitting him to probation as a judgment (Pen. Code, § 1237), Feagley appeals. (1) The issue is whether the court had power to impose probation upon appellant on a criminal charge under these circumstances. By statute, "the time ... spent under indeterminate commitment as a mentally disordered sex offender shall be credited in fixing his term of sentence." (Welf. & Inst. Code, § 6325.) But the maximum penalty for battery, the crime of which appellant stands convicted, is imprisonment in the county jail for six months, a fine of $1,000, or both (Pen. Code, § 243). It is apparent that if appellant had been sentenced to the maximum six months' jail term, with execution of that sentence suspended, the order would be void because the credit against the sentence was far more than its duration. (People v. Berry, 257 Cal. App.2d 731, 738-739 [65 Cal. Rptr. 125].)[1] Here, however, no sentence was imposed. Rather, imposition of sentence was suspended for the period of probation. It is apparent that, insofar as incarceration is concerned, the probation order is completely toothless. If appellant is found to have violated the conditions of probation, the credit to which he is entitled will bar any sentence to jail. But the maximum penalty for battery permits a fine of not to exceed $1,000. No time credit due appellant bars imposition of a fine if probation terms be violated (see People v. Harvath, 1 Cal. App.3d 521, 526-527 [82 Cal. Rptr. 48]). Thus probation does serve the purpose of reserving *775 to the court the right to impose a penalty, albeit wholly financial, in the event of a probation violation. We recognize, as will the trial court, that appellant cannot be imprisoned for failure to pay the fine if payment is financially impossible for him (Williams v. Illinois, 399 U.S. 235 [26 L.Ed.2d 586, 90 S.Ct. 2018]; In re Antazo, 3 Cal.3d 100 [89 Cal. Rptr. 255, 473 P.2d 999]). Appellant apparently had established indigency at the time this prosecution was initiated, since he was represented throughout by court-appointed counsel. Whether this condition will continue through the probation period is uncertain. But measures alternative to incarceration are available to collect fines (see In re Antazo, supra, at p. 114), and the threat of such a penalty may serve, in some degree, to decrease the chances of probation violation. We conclude that the trial court has power to prescribe probation with the foregoing limitation of sanctions. (2) The five-year term of probation is, however, overlong. The maximum term of probation on a misdemeanor conviction is three years (Pen. Code, § 1203a; Witkin, Cal. Crimes, pp. 1010-1011). Respondent relies on the statute (Welf. & Inst. Code, § 6325) governing probation for a mentally disordered sex offender returned to the court as not cured but not a menace. It provides that the court "may place the person on probation for a period of not less than five years if the criminal charge permits such probation and the person is otherwise eligible for probation." (Italics added.) Respondent argues that the section mandates a minimum five-year period of probation, whatever the maximum period would otherwise be. Neither party cites, and we are unable to find, any decision upon the point. But to adopt respondent's construction would be to ignore the word "such" in the clause italicized in the above quotation. This clause immediately follows the words "probation for a period of not less than five years." If the word "such" is to be given any meaning, it qualifies the five-year requirement by directing it only when the criminal charge "permits" so long a probation period. A cardinal rule of construction requires that we give effect to all language of a statute. Hence we hold that the maximum period of probation which may be imposed upon appellant is that provided by section 1203a — three years. There is another question as to the term of probation, although not raised by the parties (see People v. Harvath, supra, 1 Cal. App.3d 521). Harvath was convicted of contributing to the delinquency of a minor, committed to a hospital as a mentally disordered sex offender, and, after more than the maximum term for his offense, returned to court as no longer a menace to others. He was placed on probation for a term of *776 three years, and appealed. The decision recognized the bar to incarceration, but relied upon the availability of fine to give some sanction to the probation order. It affirmed the order granting probation, stating that "If revocation of probation should occur, the trial court will be aware of the law which gives credit for the prior confinement." (P. 527.) The Supreme Court granted hearing, retransferred the cause to the Court of Appeal and, by minute order dated October 22, 1969, directed it to hold that "the order granting probation is reversed and the cause is remanded to the trial court with directions to reconsider the matter of appellant's probation and, as to the term of any probation granted, to allow ... full credit for time served by him under the invalid commitment orders...." (1 Cal. App.3d at p. 528.) The Supreme Court order might be construed to mean that the period of probation should be shortened by the credit allowed under section 6325. The more reasonable interpretation, however, is that the high court intended only to have the probation order make clear that, because of this credit, no incarceration could be imposed in the event of revocation of probation. Unquestionably, the Supreme Court recognized the propriety of probation, even though a fine was the only penalty which could be imposed upon revocation. The order granting probation, treated as a judgment, is reversed and the cause is remanded to the trial court with direction to admit appellant to probation for a term of not to exceed three years, but making clear that the credit for hospital time exceeds the maximum criminal penalty, and that no incarceration may be ordered if probation terms be violated. Brown (H.C.), J., and Devine, J.,[*] concurred. Appellant's petition for a hearing by the Supreme Court was denied September 12, 1974. NOTES [1] In a separate appeal, defendant has challenged the validity of his indeterminate commitment as a mentally disordered sex offender. But the result of that appeal will not affect this appeal, since he was entitled to credit under section 6325 even if the commitment were invalid. (People v. Foster, 67 Cal.2d 604, 609 [63 Cal. Rptr. 288, 432 P.2d 976]; People v. Berry, supra, at p. 738.) [*] Retired Presiding Justice of the Court of Appeal sitting under assignment by the Chairman of the Judicial Council.
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FreeLaw
Tarset Castle Tarset Castle is a ruin near Tarset in Northumberland. History A licence to crenellate was granted to John Comyn in 1267, and the castle was built half a mile south-west of the present village of Tarset. The castle, which had four square corner turrets, was destroyed by the Scots shortly after the Battle of Bannockburn in June 1314. All that remains now is some stone foundations on top of a mound. The route of the former Border Counties Railway cut through the site in 1861. The remains of the castle are a Grade II* listed structure. References Category:Castles in Northumberland Category:1314 in England Category:Grade II* listed buildings in Northumberland Category:Clan Comyn
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Wikipedia (en)
In active use of edge-emitting lasers, in recent years, interest in the vertical cavity surface emitting laser (VCSEL) has been increasing. The VCSEL is a semiconductor laser that emits a laser in a vertical direction on an upper surface and has advantages in that it is easy to mass produce because of its simple manufacturing process and it is able to be manufactured in a small size because of its high degree of integration. The VCSEL has mostly been applied to the telecommunications field, but recently, attempts to apply the VCSEL to the optical system have been vigorously made. Particularly, with autonomous-driving vehicles being in the spotlight, attempts to apply the VCSEL to a light detection and ranging (LiDAR) device have been vigorously made.
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USPTO Backgrounds
How Id built Wolfenstein 3D using Commander Keen tech - Impossible https://www.gamasutra.com/view/news/344672/How_id_built_Wolfenstein_3D_using_Commander_Keen_tech.php ====== Jayschwa Hovertank and Catacomb, the games between Keen and Wolfenstein, are both open- sourced: [https://github.com/FlatRockSoft/Hovertank3D](https://github.com/FlatRockSoft/Hovertank3D) [https://github.com/CatacombGames/Catacomb3D](https://github.com/CatacombGames/Catacomb3D) I'm the current owner of the Catacomb games, and have been working on improving and porting them in my spare time (not publicly available yet, but will be When It's Done). Fabien's Game Engine Black Book has been an invaluable resource for me. I highly recommend it! ~~~ abeisgreat How did you become the current owner? I'm very curious about how you went about obtaining the rights. ~~~ Jayschwa The original publisher, Softdisk sold many of its assets to Flat Rock Software in the 2000s. Flat Rock sold off bits and pieces over the years, and the Catacomb games were one of the last things it held [1]. In 2017, I wrote a toy implementation of Catacomb 3D in WebGL [2]. Since the project used art that was under copyright, I contacted Richard at Flat Rock to ask permission to use it. That conversation eventually led to me deciding to buy the overall game ownership from him [3]. [1]: [https://web.archive.org/web/20150101022225/http://www.flatro...](https://web.archive.org/web/20150101022225/http://www.flatrocksoft.com/) [2]: [https://github.com/jayschwa/CatacombWebGL](https://github.com/jayschwa/CatacombWebGL) [3]: [https://web.archive.org/web/20170623155041/http://www.flatro...](https://web.archive.org/web/20170623155041/http://www.flatrocksoft.com/) ~~~ jackpirate Wow! Mind if I ask what the price is to the rights of an old game like Catacomb? ~~~ mysterydip I was looking into buying that IP a few years ago, and the asking price was affordable (I just didn't have the $ at the time so I went onto other projects). Glad to see someone doing something with it, I think it's perfect for a remake. ~~~ theresistor Would you be willing to share an order of magnitude? ~~~ mysterydip It was high four figures ------ leshokunin It can’t be understated how much impact Wolfenstein 3D and Doom had. Commander Keen was already quite the tech demo, with scrolling on a PC without dedicated hardware; the most advanced platforming you’d see at the time would be Price of Persia. Wolf 3D felt like a next gen tech demo out of time. It was great fun, it was violent, it looked unlike anything else (besides Ultima Underworld). Of course, that monumental achievement looks insignificant when compared with Doom, which single-handedly added stairs, different floors, multiplayer (!) and modding. Most of us here work in software. To see software so casually come in, introduce never seen before concepts, it’s so impressive to me. I don’t think That I know of something having quite this impact in other aspects of software. ~~~ BurningFrog I've played much "better" games than Doom in many ways, but never one so revolutionary for its time, and I've never been so genuinely _afraid_ when playing. But seriously: Overstated! You mean overstated! ~~~ hnzix _> so genuinely afraid_ As a little tyke I used to actually duck left of my monitor when an imp threw a fireball with my heart thumping. Replaying as an adult I'm like wtf that's just a lumpy mass of pixels, how could I have been so scared? ~~~ ygra I remember watching my father play Descent and that was pretty much the first real 3D game I've seen (Germany, so there was a bit of trouble with Doom and Wolfenstein). And I was constantly trying to peek around corners by moving my head. ~~~ monster99 You should all check out overload by the original descent developers. [https://store.steampowered.com/app/448850/Overload/](https://store.steampowered.com/app/448850/Overload/) ------ doomlaser Impressive id went through development of Quake 3 with no version control. When I was interning at Apple back in the day I had a side project of porting wolf3d to OS X, and it was the first occasion I had where I came to admire John Carmack's code directly. His game source code is something I recommend checking out to coders interested in gamedev. Also, I have fond memories of poking around making DOS experiments in Borland C++ as a teen. But speaking of version control — I guess that's just how things were done in the 90s. I read recently that not only was Final Fantasy 7 developed and shipped without it, but Squaresoft contemporaneously lost the final PlayStation source code and art assets. The studio contracted to port it to PC was supplied with a mishmash of non-final code and assets. ~~~ mr_toad Version control software was a lot more primitive and less fun to use in the 90s. On Unix you had CVS, on Windows just VSS. SVN, Mercurial and Git all came post 2000. ~~~ hinkley And it took SVN a couple extra years to be performant on Windows, which at the time was still the dominant development environment in many places. Maybe my second SVN project, we had a monorepo, Windows, and a virus scanner (multiply pull time by five). I'd come in in the morning, log in, do an svn up, go get coffee and say hi to the people I was collaborating with, and be back to my desk all before it finished. Many days I only synced to head twice because it was a pain in the ass, and the SVN maintainers were not at all sympathetic. A new contributor consolidated the config files and cut the number of file open operations by a couple orders of magnitude. I don't think we ever properly thanked that guy. ~~~ dev_dull > _A new contributor consolidated the config files and cut the number of file > open operations by a couple orders of magnitude. I don 't think we ever > properly thanked that guy._ Unspoken benefit of “new person” — eventually someone not desensitized to the crap will throw up their hands and fix it. ~~~ vidarh Sometimes it's so tiny too, but requires you to look at code that nobody else has a reason to look at any more. I once increased performance of a CMS by 30 percent my first day in the job because I happened to spot a handful of lines of unnecessary string copying while trying to figure out how the thing worked. Everyone else could have, but none of them had any reason to look at that part of the code because it worked. ------ cgrealy "We didn’t have a version control system. Surprisingly, we went all the way to Quake 3 without one, then we started using Visual Source Safe." That is both impressive and terrifying. I'm old enough to remember when I first started using VSS, and being amazed at how awesome source control was :D These days, it's hard to look back at SourceSafe with anything other than horror.... ~~~ alain94040 There was a transition from the 80s to late 90s: until you had some kind of network, the important thing was to backup your machine. Daily if you can. Even if you had been running a local revision control on your local machine, you wouldn't be protected enough, so backups were more important. Once networking and servers became more prevalent, it slowly made sense that backups turned into revision control. If your machine crashes, there is a remote repo you can connect to and get back to where you were. ------ bluedino >> Everybody was working witht he best PC money could buy, a high end 386DX/33MHz with 4MB of RAM According to a May 15, 1990 issue of PC Magazine, that was a $3,500-4,000 USD machine back then. Used to develop Wolf3D, but only good for about 8fps when Doom (ID's next hit) came out. ~~~ rhacker Interestingly that's the exact PC my dad bought us when we were kids. I loved how computers back then had a turbo button, but I could never figure out why anyone would turn off turbo! :P ~~~ spion I believe it was due to programs (mainly games) that relied on clock speed to work. If you ran some of them with turbo, they were so fast they were unplayable. ------ snvsn "Masters of Doom: How Two Guys Created an Empire and Transformed Pop Culture" has an excellent account of how Romero and Carmack built these games. ~~~ abraae I've tried using that book to explain to people how "real" software development works. How the inception of the real cool shit, the stuff that spawns a company, is almost always 2, 3 or a small handful of people working late, night after night, living on pizzas and cola, churning code. And how that apparent anarchy is a more productive environment that ten pointy headed bosses plugging away at their gantt charts and a hundred 9 to 5 developers carrying out their orders. ~~~ untog Not that I want to be seen defending pointy headed bosses, but I think there's a fair amount of survivorship bias in your statement. How many groups of 2-3 people have worked late, lived on pizza and coke and produced absolute garbage? Quite a few, but you never hear about them because they aren't notable. You don't have to get into pointy headed boss territory to be a successful programmer _and_ leave the office at a respectable time every day. ~~~ SmellyGeekBoy Are many successful game programmers in corporate environments leaving the office at a respectable time every day? I definitely don't get that impression at all. At least in a 2/3 man team surviving on pizza and Coke you're not lining someone else's pockets with millions of dollars only to be thrown out onto the street at the end of the process. ------ bitwize A version of Keen's tile editor was used to create maps for games as recent as _Rise of the Triad_ , which was itself built on a modified Wolfenstein engine. ~~~ jonny_eh > as recent as Rise of the Triad Released December 21, 1994 ~~~ gmueckl That game got a remake a couple of years ago. I don't know if they were referring to that. ~~~ SketchySeaBeast If they were still using the Keen Tile Editor that'd be amazing. ~~~ bitwize I was referring to the original -- which was still released after _Doom_ came out. ------ filereaper John Romero mentions this in his talk - "The Early Days of Id Software" [https://www.youtube.com/watch?v=KFziBfvAFnM](https://www.youtube.com/watch?v=KFziBfvAFnM) ~~~ filereaper John talks about Id's Software Principles, one of the YouTube commenters (Sean Ramey) summarized them below: 1\. No prototypes. Just make the game. Polish as you go. Don't depend on polish happening later. Always maintain constantly shippable code. (Large teams require more planning though.) 2\. It's incredibly important that your game can always be run by your team. Bulletproof your engine by providing defaults (for input data) upon load failure. 3\. Keep your code absolutely simple. Keep looking at your functions and figure out how you can simplify further. 4\. Great tools help make great games. Spend as much time on tools as possible. 5\. We are our own best testing team and should never allow anyone else to experience bugs or see the game crash. Don't waste others' time. Test thoroughly before checking in your code. 6\. As soon as you see a bug, you fix it. Do not continue on. If you don't fix your bugs your new code will be built on a buggy codebase and ensure an unstable foundation. 7\. Use a development system that is superior to your target. 8\. Write your code for this game only - not for a future game. You're going to be writing new code later because you'll be smarter. 9\. Encapsulate functionality to ensure design consistency. This minimizes mistakes and saves design time. 10\. Try to code transparently. Tell your lead and peers exactly how you are going to solve your current task and get feedback and advice. Do not treat game programming like each coder is a black box. The project could go off the rails and cause delays. 11\. Programming is a creative art form based in logic. Every programmer is different and will code differently. It's the output that matters. Extra advice: 1\. Only program for a few minutes and test code immediately. Try not to code for even as long as 30 minutes. This is will help to avoid debugging because you will catch bugs sooner, and won't have as wide an area of code to look through for the bug. ------ LocalH Interesting how they make sure to mention the use of 320x200 during graphic editing to maintain proper aspect ratio, then display screenshots from the game in improper aspect ratio ------ bcheung Wow, those screenshots bring back memories. Used that same exact IDE to make games when I was a kid. It was an amazing time to be programming. ------ scarface74 And notice that they used an IDE. So that kind of gives credence to the idea and the HN meme that “10x developers don’t use IDE’s” is BS.... ~~~ bonzini You are not making an equal comparison. DOS at the time didn't have multiple windows or multitasking. People that don't use IDEs these days still use multiple terminals or windows. Using the Borland C++ IDE in 1991 is way more similar to using Emacs these days, than Visual Studio Code. ~~~ scarface74 The source code for Doom 3 (circa 2004) was released on Github - it was a Visual Studio solution. [http://fabiensanglard.net/doom3/](http://fabiensanglard.net/doom3/) ------ QuadrupleA Great article - cool to get an inside look at tools, IDE environments, art sketches etc. Such an exciting time for PC games, with ID way out at the forefront - highly recommend the Masters of Doom book mentioned in the article too, it's a deep dive into the making and eventual impact of Doom. Great snapshot of the ID guys and of that time period. ------ m12k For anyone curious about the technical details, there's a decent description of how Adaptive Tile Refresh works in the wikipedia article: [https://en.wikipedia.org/wiki/Adaptive_tile_refresh](https://en.wikipedia.org/wiki/Adaptive_tile_refresh) ------ btilly I remember playing Wolfenstein 3D for many hours back in grad school. Then Doom came out, and I found out the hard way that I get motion sickness from playing immersive games with good graphics. :-( I've not been able to play first person shooters since. But I sure loved Wolfenstein 3D. ~~~ lostmyoldone Used to get severe motion sickness too until I figured out it went away at high FPS. At least for well made games with low input latency. With a good 1000Hz wired mouse and games I where I get _at least_ 100fps, preferably >144fps, I don't feel anything at all when I play. Still can't watch others play though. ~~~ btilly My curiosity is not sufficient to test whether the same is true for me. Particularly not since if I get immersed in the game, by the time I realize it is happening it is too late. The potential upside just isn't there to make it worthwhile. However I've also found that 3-D systems that everyone else oohs over whose operators promise don't cause motion sickness any more, always do. Really fast. So I'm apparently on the sensitive end of motion sickness from computer systems. ------ mobilemidget These two titles in one sentence, make me wonder how a 3d shooter version of Commander Keen would be with current day graphics..... ------ acjohnson55 My dad brought copies of both of these games home on floppy disk, which is what got me into computers. ------ x3ro Shameless plug: this reminds me of how I once spent an afternoon compiling the open sourced version of Keen Dreams using Borland C++ 3.1 :D [http://x3ro.de/2014/09/18/keen-dreams- dosbox.html](http://x3ro.de/2014/09/18/keen-dreams-dosbox.html) ------ Yajirobe What is the blue-yellow IDE/editor called? ~~~ pjmlp It is quite clear on the figure captions, Borland C++ 3.1. ~~~ gmueckl You could even license the UI library from Borland for use in your own programs. And Turbo Pascal had the exact same look. Later, there was a near clone of the Borland IDE called RHIDE which wrapped DJGPP, a GCC port for DOS/DPMS. I had some fun times with that. ~~~ antod _> You could even license the UI library from Borland for use in your own programs. And Turbo Pascal had the exact same look._ Turbo Vision? ~~~ dfox They even released the C++ version as public domain. Free Pascal uses it's own Free Vision which is back port of the TUI support into Graphics Vision[1] (which in turn is LGPL's reimplementation of Turbo Vision API in graphical mode) [1] [https://www.math.ucdavis.edu/~mkoeppe/mkm/mkmeng.html](https://www.math.ucdavis.edu/~mkoeppe/mkm/mkmeng.html) ------ Endy I miss Keen. ------ m3kw9 Now that’s a flex!
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HackerNews
1. Field of the Invention The present invention relates to a multi-row crop header attachable to a forage harvester and, more particularly, it is directed to an improvement in such crop headers to enable the same to be used in harvesting down and tangled row crops, such as corn which is sometimes blown down by windstorms and the like and is sometimes difficult to harvest with conventional forage harvesters. 2. Description of the Prior Art Headers for forage harvesters adapted to handle down and tangled row crops have been devised heretofore. These have been developed to assist particularly in the harvesting of corn where some of the corn stalks are down and bent over, extending across and entangled with stalks of an adjacent row, for example. The forwardly extending dividers of crop headers, such as those similar to corn harvesters, move between the rows and the stalks of corn which are down become draped over and along the dividers as the stalks are conveyed rearwardly along the passageways between such dividers as the stalks are positively engaged by gathering chains which have longitudinal segments thereof extending respectively along opposite sides of the passageways, said chains gripping the lower portions of the stalks after they have been cut by a cutting disk or the like, at the forward end of each passageway and the lower portions of said stalks are fed into a harvester, butt end first. When the dividers encounter down or draped-over stalks, said stalks tend to wrap around the dividers and bunch up, particularly adjacent the rear ends of the passageways of the outermost dividers which results in jamming, thereby requiring greater amounts of power than ordinarily to overcome such jamming, as well as producing an uneven feeding of the stalks to the harvester. It is not uncommon that an appreciable amount of a crop of this type is lost or damaged, as well as producing unnecessary wear upon the harvesting equipment. One of the principal difficulties occurring in the harvesting of down and tangled crops comprises the handling of draped stalks, such as corn stalks, extending across and downward from the aforementioned dividers into configurations which is sometimes referred to as "hairpinning". In particular, the difficulty is accentuated when stalks extend in hairpin fashion across the outermost divider in a multi-row crop header because one end of such stalk engages the sides of the housing of the header and becomes bound and tangled adjacent the same. One expedient for handling this type of problem is to provide rotatable rollers, especially in the vicinity of the outer end of the frame of a header for purposes of engaging the hairpin stalks and tending to feed them toward the discharge area of the header and normally into a harvester of some type, especially those including feed rolls for forcefully feeding the crop material to a cutting and chopping head of various types. A typical example of a prior device in which rollers of the aforementioned type are employed is shown in U.S. Pat. No. 4,048,792, to Shriver, dated Sept. 20, 1977, the roller being associated with dividers that are not adjustable laterally as to spacing between adjacent pairs of dividers for purposes of adapting same to different row spacings of crops. Additional patents which have attempted to alleviate the above-described difficulty comprise U.S. Pat. No. 3,338,538 to Markham, dated June 18, 1968, and U.S. Pat. No. 3,791,117 to Lawrence, dated Feb. 12, 1974. In both of these patents, however, the feed assist rollers, which are not movable in concert with the outer divider, are mounted substantially vertically and extend through the upwardly and rearwardly extending inclined shield surfaces of the outermost divider, thereby producing situations where pinching of the crop material between the edges of the openings in the shields and the ribs on the rollers can occur. Still another patent having the same difficulty as the two patents set forth immediately above comprises U.S. Pat. No. 3,803,820 to Knapp, dated Apr. 16, 1974, in which a ribbed feed assist roller extends downwardly through an opening in the shield of the outermost dividers of a row crop harvester, thus providing such possibilities of pinching crop stalks between the edges of the openings and the ribs of the rollers. The present invention, while utilizing rotatably-mounted feed assist rollers to overcome the difficulties previously encountered with hairpinning of stalks, nevertheless, obviates any pinching of crop material incident to utilizing such rollers and also includes other distinct advantages set forth in detail hereinafter.
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USPTO Backgrounds
This application claims priority to Japanese Patent Application No. JP2001-239352, filed on Aug. 7, 2001, which is incorporated herein in its entirety. This disclosure relates to polyphenylene ether group resin composite containing recovered polystyrene group resin. The polyphenylene ether (PPE) group resin composite is widely known as the resin having excellent anti-thermal characteristic, mechanical properties as well as electrical properties. It is being widely used as denatured polyphenylene ether group resin composite having its processability reformed by compounding it with polystyrene, rubber modified polystyrene (high impact polystyrene), etc. Such PPE group resin composites are being widely used in the fields of automobile parts, electric parts, office devices, etc., due to their excellent properties mentioned above. As regards the polystyrene resin that is compounded with the polyphenylene ether group resin, virgin resin material was used. In the case of polystyrene group resin used in plastic parts, foaming styrol, etc., when a certain durability period is exceeded in the market, it is usually discarded, and replaced it with a new product. The end products of molding that get generated at the time of carrying out molding, or the inferior molded product that can be recycled, etc., are treated as the so-called recycled products in the factory. However, the number of products receiving such a treatment is insignificant if seen from the point of the total number of such products. If the polystyrene group resin is recovered from the market after it has completed its useful life, there would be an effective use of resources. The authors carried out an earnest research on the use of such polystyrene group resin recovered from the market. They showed that if the recovered polystyrene group resin was used instead of virgin polystyrene group resin in the polyphenylene ether group resin composite and moreover, if flame retardation reagent was used jointly with it, then a composite having properties similar to that of polyphenylene ether group resin composite of the past can be obtained. This disclosure is directed to polyphenylene ether group resin composites in which recovered polystyrene group resin, which has been discarded in the past, is effectively used, and articles made from embodiments of the polyphenylene ether group resin composite. In one embodiment, a polyphenylene ether group resin composite can comprise: polyphenylene ether group resin, flame retardation reagent, and recovered polystyrene group resin. The recovered polystyrene group resin can be recovered using limonene or thermal shrinkage recovery, and can comprises polystyrene that has been recovered from a product or a part of a product that has been used by an end customer for a period of time. One embodiment of a method for making an article comprises: dissolving a polystyrene group resin product that has been used as a product by an end customer for a period of time in a terpene group material, recovering polystyrene group resin from the polystyrene group resin product, melt blending the recovered polystyrene with polyphenylene ether group resin, flame retardation reagent, and additive, wherein the parts by weight are based upon a total of 100 parts by weight of polyphenylene ether group resin, recovered polystyrene group resin and any virgin polystyrene group resin, extruding the blend, and molding the extruded blend to form an article. Another embodiment of a method for making an article comprises: employing thermal fusion to reduce a volume of a polystyrene group resin in a polystyrene group resin product that has been used as a product by an end customer for a period of time, recovering the polystyrene group resin from the polystyrene group resin product, melt blending the recovered polystyrene with polyphenylene ether group resin, and flame retardation reagent, extruding the blend, and molding the extruded blend to form an article. The above described and other features are exemplified by the following detailed description.
tomekkorbak/pile-curse-small
USPTO Backgrounds
These tweets with 5 likes are really selling this to me! Reply Thread Link Just because they have a smaller fanbase doesn't mean there isn't merit to the comparisons. I've listened to Paramore for years but as a ionnalee fan it's hard not to see the inspiration between it all imo. Reply Parent Thread Link the aesthetic is not that original anyway Reply Thread Link for real. Reply Parent Thread Link Mte like. At least 5 film students have done something like this in a project they turned in this week. Reply Parent Thread Link Agreed. Although, Hayley made it really fucking cool. Reply Parent Thread Link feels like a reach to me. lots of videos use that ultra white lighting to give it a hazy, almost foggy and otherworldly feel. their interlude pieces especially, are entirely different. do they both need to go back to annie lennox and give credit for the use of lighting? when your fav is known only to you and 5 other people, so you try and start some shit with a name to get some press. Reply Thread Link Pretty sure they didn't originate this style either sooooooooo Reply Thread Link Nothing is original anymore. Good artists borrow, great artists steal. The first thing I thought of when I looked at these is 'Bad Romance'. Reply Thread Link i just wished Hayley's songs were catchier. I love a good depressing song but these just kinda meander and go nowhere. Reply Thread Link mte I like her voice so much but these songs are duds Reply Parent Thread Link I thought I was the only one who thought this, thank you. Everyone always says how good her solo music and "After Laughter" are but they are so boring and bleh. Reply Parent Thread Link Her tens of fans sound pissed. Reply Thread Link Some of it is similar but it's not identical. This aesthetic has been around for a long time. Anyways I really like fountain and play Reply Thread Link There is no originality left in everything. Reply Thread Link Similar, but not identical imo. And this aesthetic has been around forever. Reply Thread Link it was such an exciting time when those first iamamiwhoami videos started dropping and she's been delivering for 10 years now... love her Reply Thread Link Thinking back on it, how the hell did we ever think it could really be Xtina? Lol Reply Parent Thread Link when she started releasing songs with one letter titles and people though it was spelling out BIONIC lol Reply Parent Thread Link i think people just really wanted xtina to rise as an alternative artsy musician, especially after the comparisons with lady gaga and bionic having a ~different sound Reply Parent Thread Link Lmao those posts were so fucking fun! Reply Parent Thread Link Learn more about LiveJournal Ratings in Hello! Your entry got to top-25 of the most popular entries in LiveJournal!Learn more about LiveJournal Ratings in FAQ Reply Thread Link the first two hw solo music vids made me think of bjork tbh. did she just release cinnamon? i think it's my favorite of the solo songs i've heard so far, kinda reminds me of kimbra. Reply Thread Link Yeah I actually enjoy Cinnamon a lot better than the other songs. Reply Parent Thread Link yeah she dropped cinnamon and 2 other songs today. i think she's releasing them as 2 eps. Reply Parent Thread Link i looked it up after i commented, haven't listened to it yet though. i'm kinda over all these artists releasing eps (or 6mil singles) instead of full-lengths, but i guess it's just how it is now. /shrug Reply Parent Thread Link lmao i was going to say they look like budget matthew barney visuals aka bjork’s ex lol Reply Parent Thread Expand Link literally thought "oh is that that girl we hoped was pre-bionic christina aguilera" when I saw the Hayley stuff on my timeline so... those tweets might only have a few likes, but I cosign LOL Reply Thread Link Oh man I remember those posts, lol. But that was back when a lot of ONTD hated Christina. I distinctly remember so many comments like “nah, Christina is not smart enough to pull off something like this.” Reply Parent Thread Link
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award-winning As we celebrate our 10 year Anniversary in February 2020 its all change for Sinead Kelly London. Moving into 2020 the salon’s reputation has gone from strength to strength as we pave the way to being one of London’s go-to salons. Now is the time that salon owners and power couple Sinead and Andy decided to give the salon a modern and luxurious look. No expense was spared in the quarter of a million pound refit as Sinead and Andy worked tirelessly with builders, light engineers and furniture suppliers to create a space that truly represented the brand and the new direction SKL are going in. From the moment you walk into the salon you are greeted by one of the members of the SKL family at the modern reception area, directly behind is a bespoke shelving unit displaying the trophies and awards the salon has won; the latest of which being the coveted L’Oreal Colour Trophy. Sinead and Vas (the resident colour specialist) nabbed the trophy in June 2019 in a record breaking win, Vas being the only colourist to ever win the award twice. We are very excited to announce that Sinead and Vas will be showcasing their winning look on the world stage when they venture to Milan in March 2020 for the International Colour Trophy. The trophy takes pride of place, showcasing the in-salon talent you can expect when visiting. Next to this is a private consultation table for new clients who wish to discuss hair colour, cut and style options as well as existing clients who might want a more in-depth consultation prior to their appointment if looking for a change. You are then guided through to an impeccably designed salon floor; pendant lights and soft furnishings from West Elm bring warmth to an ultra chic and modern space. The lighting ranges from track lighting that runs across the ceiling, reminiscent of Hollywood film sets, to golden pendant globes above sections and on the walls to mirror backlighting all carefully selected to create the correct ambience. The main lighting is flattering to the client and ensures your colour tone is exactly as it should be. A ‘community’ table stretches along the central part of the salon, designed by Sinead and made reality by the fine Italian brand Maletti. This table means clients and stylists can work opposite each other promoting a social and community feel. The mirrors that divide each section can be removed in order to hold meetings with staff or creative discussions to ensure the team are always at the forefront of fashion and new trends. All seating is also Maletti and made of beautiful Italian leather to ensure the utmost comfort during your visit. Sinead and Andy worked alongside L’OrealProfessionel and Kerastase to create a hair bathing area luxurious in treatments and products, exquisite in design and most importantly an environment of relaxation, tranquillity and indulgence. Massage chairs with rising footrests mean you can choose exactly how you prefer to enjoy this integral part of your salon visit. Sonos is installed throughout the salon and calming, dulcet spa music fills the hair bathing area in contrast to the upbeat deep house sounds that brings vibrancy and fun to the main salon. Every tiny but important detail has been thought through to ensure Sinead Kelly London remains at the forefront of excellent service as well as fashion. It provides a high-end and lavish experience very rarely found outside central London salons, showcasing why they are the go-to salon for colour and current national winners of one of the biggest awards in the country. The team are more like a family and this will be instantly noticeable when visiting as a warm and friendly environment is integral to the salon’s success. 2020 is a very exciting year for Sinead Kelly London. Sinead and her highly trained team look forward to welcoming you into this new space of creativity, fashion and design in order to give you the highest level of service and care in London hairdressing. As we raise a toast to a fantastic decade of SKL we also raise a toast to the next, making sure we continue to go from strength to strength and keep our reputation of excellence in one of the world’s most fashion forward and thrilling cities. Don’t miss out and make sure you get your Christmas appointment booked in with one of our fabulous team members by either call 0208392244 or email [email protected] Check out our work on instagram @sineadkellyldn Our Christmas opening hours mean we are closed on the 24th December and reopen on the 2nd January As the weather turns cooler things are hotting up in the world of hair colour. Here I talk you through two of the biggest colour trends this season. Antique Hair 2019 lets platinum blonde take a back seat and introduces one of the hottest trends right now: Antique Hair. To achieve this look successfully aim for soft golden hues, hints of rose gold and a blonde that reflects light for a glow-like shine. It harks back to the soft focus and romantic lighting reminiscent of 70’s photography and film and adds a touch of glamour to both light and dark blondes. The key to achieving this new trend is to do a combination of warm and cool tones when colouring the hair; muted gold, champagne and beige. This is a colour which will suit most blonde clients, however assess the natural tones in the hair; if on a warmer natural base inject cooler tones by making the primary tone ashen and if the natural base is cooler then a warm primary tone followed by a secondary cool tone will work better. Dependent on how adventurous your client is you can either go for an all over sepia look by toning prelightened hair or if they prefer a more subtle nod to the trend use your more golden colours in highlights. It’s a great way to warm up skin tones and adds a healthy shine which makes the look much more appealing to blonde clients of all ages and hair lengths. Ensure you keep your locks super healthy by doing an intense conditioning treatment after colouring in-salon and using home products advised by your stylist to maintain shine and the integrity of the hair between services. Spice Rack Things are heating up even further this year with inspiration from the rich, sumptuous tones found in spices from around the world. Colour is becoming bolder with Turmeric yellows, luxurious paprika reds and deep clove brunettes. It’s a trend redheads, blondes and brunettes can embrace equally which makes it accessible to all. For maximum impact and for your more adventurous clients go for an all over gloss and for clients who might want a touch of spice, use more freehand techniques like balayage and slices to add a taste of colour. Earthy in nature, this trend is reflective of what is currently happening socially with people becoming much more environmentally conscious and looking after our planet. To get maximum results ensure the hair is well looked after and in optimum condition to avoid colour fade and pre-colour hair that requires more attention to create the desired depth and tone. For lighter clients take inspiration from softer hues like that found in cinnamon and for real impact on blondes who want to make a statement look to stronger shades such as saffron. Layer glosses to draw on the complexity and depth found in the colour of spices. This is a trend you can really have fun with but make sure clients are aware that without the right after care it will fade quicker. Let’s rewind back to 2016, the first time I entered the L’Oreal Colour Trophy with Sara Bergantini under the mentorship of salon owner Sinead Johnson. I admit I did not know much about the Colour Trophy or what it entailed in terms of kudos in the industry and sheer amount of work and dedication to not only represent ourselves as colourists and stylists but also as a salon aesthetic. We went on to win the competition with a denim blue bob. Little did I know how important this would be, not only in my own career but as a creative. Our beautiful model Natasha Underwoodembodied everything we felt represented the modern London woman, the colour; a bold, strong statement with an expertly cut bob by Sara to make the look unconventional yet timeless. Gladiator heels were added to the Maje umbrella dress to indicate a fierce, industrial warrior going into battle on the National hairdressing stage of L’Oreal. Now, here we are again. Three years on and with a new challenge ahead of us. How has fashion evolved? How has our interpretation of the London woman evolved? And how do we create yet another iconic look that embodies the aesthetic and ideals of Sinead Kelly London as a salon? Myself and Sinead go into battle again, armed with a new warrior; new in terms of style but recognisable in terms of bringing out our finest muse; Natasha. As we have evolved, so has our model, embodying a new representation of style. The challenge is great but one I and Sinead fervently take on. Both of us complete perfectionists to the point of obsessive. So where do we start? Colour Trophy isn’t simply a hair competition. L’Oreal Colour Trophy is the longest running live hairdressing competition and has also evolved in its 64 years from only 300 attendees in 1954 to thousands of the industry’s greatest talents. This is serious business in the world of hairdressing and the cup is greatly coveted. In terms of colour, it was brought to my attention by one of my best friends Emer (who also trained as a hairdresser originally) that mustard hair was an exciting new trend hitting social media. It certainly caught my attention yet something was lacking. As beautiful a colour as it can be…mustard to me represents something matte, dense and simplistic. I wanted to take this concept of mustard hair and elevate it. Create a colour not yet seen in a single tube. I didn’t want it ‘yellow’ or ‘orange’; I wanted something luxurious, beautiful, and complex. Something that also embodied the ideals of L’Oreal and its preference for shiny, beautiful hair. Then it hit me, Sienna. Sienna represents a colour which is classic in its use but multi-faceted and luxuriant. But how do you make it? After several failed attempts on multiple swatches, like some mad scientist, my thoughts go to my sister Elizabeth Mikellides, a master of fine art with a wealth of education behind her with a Masters from the Slade School of Art under her belt and a creative analytical thought process. Surely if I follow the laws of fine art painting I can adapt those to the laws of hair colour? I got straight on the phone to her. This is when it clicked, a trichological eureka moment. Elizabeth explained to me that Sienna is translucent, whereas yellow ochre (a colour similar to mustard) is opaque. There are various tones in Sienna: orange, yellow, blue. Tones that contradict each other on the colour wheel but when layered on top of each other and kept translucent can create a stunning colour with multiple reflects. I won’t bore you with the exact measurements of each tone but it was armed with this information that I created our final colour. We had our colour but now we needed our ‘look’. What does our muse represent? How is this relevant for today’s woman? There is a mutual respect between myself and Sinead. We work well together and hold no punches. We are honest about what we think from the outset and it is with this that our most achieved looks are created. Every length and style of hair was considered. Long, short, sharp, straight, curly. With Sinead as the stylist and with a penchant for giving a woman the most complimentary length and style it was decided that a long sharp bob was the canvas to our colour, the style a meticulously symmetrical yet elegant soft wave. A true representation of the 2019 woman; strong and bold yet soft and with a French classic twist (it is L’Oreal after all). A contemporary yet chic look, I would describe the colour as a rich and glossy Sienna, multi-faceted and complex in its composition, the style; a soft yet perfectly symmetrical waved sharp long-bob. It is a combination of contradictory messages, challenging the expectation of femininity. Not sticking to current trends, it was our goal to produce a look with our own interpretation of the 2019 London woman, resilient yet feminine, gentle, earthy and natural. Recognition of what is going on culturally with climate change and ethical obligations to preserving our environment. This was further represented by our beautiful burnt orange dress by Self Portrait, with its classic 1940s cut but modern high neckline and the fierce Zara ankle sock boot with a killer heel and beaded flower brooches to add softness and pay homage to classic ideals of femininity. The make-up was executed by Cristiana Maxim, the same make-up artist who worked her magic on 2016’s final look. A fresh, dewy complexion with freckles and muted nude lip, complemented by a stronger brow and Natasha’s hazel eyes. The colour palette; from the hair to the make-up to the clothing all marries together to create a fluid, earthy interpretation of the London woman with a nod to French style and class. Off we send our Amazonian beauty into battle, having already beaten hundreds of salons nationwide to get to the highly anticipated final. A glitzy affair in Battersea, where we again compete to lift that sought after trophy. This time a little wiser and happy in the knowledge that win or lose, we have yet again represented ourselves and the salon as a force to be reckoned with. Even more importantly, I and Sinead are content in our ability as colourist and stylist and thrilled to showcase our collaborative work as Natasha sashays down that catwalk once more. And that truly is triumph enough. We’re famous for our colour and style transformations and as we welcome two new, extremely talented members to our already wonderful Sinéad Kelly London team it’s time you met the award-winning experts behind some of South London’s best hairstyles. Sara Sara, our resident London Fashion Week stylist, qualified under Sinéad’s training at just 17. Showing natural talent and flare, Sara’s haircutting skills are outstanding and her sought after up styling, make Sara our go-to girl for wedding hair. Ellie Ellie is now a fully qualified stylist under the training of Sinéad and Natasha. She has an abundance of natural talent and the eye for the latest styles and trends. Sarah New to the team, Sarah is a highly skilled colour and styling specialist with over 10 years experience in the industry. Her A-Z product knowledge is exceptional, giving the valuable advice on treatments and styles for each of her clients. Vas Our most recent addition to the team is Vas, a qualified L’Oreal Colour Specialist consultant. Having worked alongside the likes of Beverley Corbella in Selfridges, Vas is paving the way in beautiful colour transformations. From the loudest reds to the brightest blondes, Vas has the expert eye to advise your next colour change. Natasha Our award-winning executive stylist Natasha has a host of celebrity clients on her books. Working with Sinéad from when the salon first opened, Natasha has previously won the L’Oreal Colour Trophy and is well-known for her first-class consultations. Technically, Natasha’s hair colouring and styling skills are unmatched, with clients from all over London travelling miles for an appointment. Sinéad Kelly Johnson Founder of The Sinéad Kelly Salon, Sinéad has been working in the industry for over 18 years, scooping numerous awards and recently becoming a L’Oreal Paris European consultant. After graduating in 2003 with a degree in colour, Sinéad has worked on numerous national campaigns and hasn’t seen the end of her waiting list since. Her clients include the likes of ITV’s Holly Willoughby, the face of Garnier Nutrisse Pearly Blondes. Whether you’re looking for a total refresh, a style update or a colour transformation, book a consultation and let the expert Sinéad Kelly London colourists and stylists revamp your look.
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Pile-CC
Where the dead act as mentors By FOONG PEK YEE, The Star, May 21, 2006 Taipei, Taiwan -- It was after a good lunch and rest when our guide announced that our next stop was a “visit to our silent mentors”. << CARING HOSPITAL: The Tzu Chi Buddhist General Hospital is among four hospitals set up by the Tzu Chi Foundation in Taiwan, and is also the teaching hospital for the Tzu Chi University. --Picture by FOONG PEK YEE “Who are they and how many are there?” I asked Chad Liu the guide as he took us up the stairs leading to the silent mentors' office. This was part of our visit to the Tzu Chi Buddhist General Hospital in Hualien, Taiwan in early spring this year. “We will find out very soon,” he said, flashing a smile. As we reached the office, Liu pointed towards a door, and said: “They are waiting for their students inside.” Noting that there was not a sound to be heard from inside the room and that it was freezing cold, the visitors cast puzzled glances at him. “Silent mentors are corpses,” he finally explained. The silent mentors are actually cadavers of people who had pledged their bodies to be used in anatomy classes by medical students. Usually unclaimed bodies and mannequins are used for such purposes. “It is a very noble act, and that is why we gave them the title ‘silent mentors’,” he said. In Tzu Chi University, four medical students share a cadaver, and this is made possible by the silent mentors. The ratio in many universities around the world is eight students to one body. “Even the United States has a ratio of between four and six students to one body,” Liu said. “Our lower ratio helps to enhance the quality of our education,” Liu said, before inviting me to join him inside the room to count the number of silent mentors. I sheepishly declined, knowing fullly well that it was not a very journalistic act. Liu: ‘It is a noble act, that is why we call them silent mentors’ >> Without any hesitation, he strolled into the room and reappeared shortly, saying that there were 32 of them. Opened in 1986, The Tzu Chi Buddhist General Hospital is also the teaching hospital for the Tzu Chi University. It is among the four hospitals in Taiwan set up by the Tzu Chi Foundation, a charity body founded in 1966 by Master Cheng Yen, a world-renowned Buddhist nun. Liu who is with the foundation's secretarial services department in Hualien, said bu jiang hua de lao xi (silent mentors in Chinese) commanded high respect, recognition and love from their students. My curiosity having somehow got the better of me, I peeped through the door. To my surprise, the room was actually one of two rooms within a larger room. Separated by a passageway, the other room is a mini columbarium with niches (where the urns containing ashes of the deceased are placed ) for the silent mentors who had “completed their mission”. Liu said the families of the silent mentors would be asked to give up some of the ashes in remembrance of their contribution. He said the medical students also become part of their silent mentor's family, inviting them to attend their graduation ceremony and visiting each other during festive seasons. Asked how the grieving families of the silent mentors felt about the delayed burial, Liu said they felt it was a noble act fulfilling the wishes of their loved ones.
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Murray Frum Murray Frum (September 3, 1931 – May 28, 2013) was a Canadian real estate developer and philanthropist. Biography Frum was born to a poor Jewish family on September 3, 1931, the only child of Saul and Rivka Frum, who had immigrated from Poland the year before. Most of their family who stayed in Poland died in the Holocaust. His parents operated a grocery store in Toronto. Frum attended the King Edward elementary school and in 1950, graduated from the Harbord Collegiate Institute. In 1956, he graduated with a degree in dentistry from the University of Toronto. In 1970 he left dentistry to become a real estate developer (the Frum Development Group) and made his fortune developing suburban strip malls. Frum was a collector of African art and donated over 80 pieces to the Art Gallery of Ontario, one of the largest in North America; and along with his son-in-law, Howard Sokolowski, built the gallery in which the collection is housed. He later expanded into Renaissance art. In 2007, he donated Bernini's 17th-century bronze of the crucifixion to the Art Gallery of Ontario which he bought while its origin was uncertain (it was later appraised at $50 million). Frum served on the boards of the Stratford Festival, the Canadian Centre for Advanced Film Study, and the Art Gallery of Ontario. Personal life Frum married twice. In 1957, he married 19-year-old Barbara Rosberg who would later become a CBC broadcaster; she died of leukemia in 1992. The couple had three children: David Frum, a journalist and a former speechwriter for U.S. president George W. Bush; Linda Frum, a Canadian senator who is married to Howard Sokolowski; and Matthew Frum. His second marriage was to Nancy Lockhart. He died on May 28, 2013 at his home in Toronto of lung cancer despite being a non-smoker. References Category:1932 births Category:2013 deaths Category:Canadian Jews Category:Canadian philanthropists Category:Canadian real estate businesspeople
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You are using an out-of-date version of the Internet Explorer web browser. For a better experience on our website, please use a different web browser or update your Internet Explorer to version 8 or higher. Click here for more information. Few cities have been at both the forefront of American history and at the pulse of a nation like Richmond, Virginia. Architecture designed by Thomas Jefferson intertwines with modern universities, while landmarks of the Civil War mingle with museums, residential neighborhoods and businesses. Discover Richmond as experts offer their insight into the Revolutionary and Civil War eras, and learn about the thriving Jackson Ward neighborhood during a field trip to the Maggie Walker National Historic Site. Study art and architecture as you explore historical homes, attend a performance at a local theater and much more! Highlights • Take a field trip to the State House — designed by Thomas Jefferson — and St. John’s Church where Patrick Henry famously declared, “Give me liberty or give me death!” • Study Civil War history during a field trip to the Museum of the Confederacy and its restored Confederate White House. • View the statues along Monument Avenue and stop to take in the impressive collection of American art at the Virginia Museum of Fine Arts. Activity Notes Walking up to one mile; standing during museum explorations.Coordinated by Virginia Commonwealth University. Need Help? The latest in light, portable, easy-to-use QUIETVOX listening devices are available on Road Scholar programs.* Whether you are outdoors, in a crowd or in a museum environment where speaking loudly is discouraged, a listening device makes it feel like our experts are speaking clearly and directly to you. Hear for yourself on a Road Scholar adventure! *Please note that due to the nature of some programs, the remote location or government regulations, listening devices may not be available. If you’d like to know for sure if your program will offer listening devices, just call and ask an Advisor!
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Warren Ellis bibliography Warren Ellis is an English author of comics, novels, and television, well known for sociocultural commentary, both through his online presence and his writing, which covers transhumanist themes (most notably nanotechnology, cryonics, uploading, and human enhancement). He is a resident of Southend-on-Sea, England. Comics UK publishers Titles published by various British publishers include: Deadline #24: "United We Fall" (with Nigel Dobbyn, Deadline Publications, 1990) Judge Dredd Megazine vol. 1 #7: "Judge Edwina's Strange Cases: Feed Me" (with Sean Phillips, Fleetway, 1991) Atomeka: Lazarus Churchyard (tpb, 120 pages, 1993, ) collects: Blast! #1–7 (with D'Israeli, John Brown Publishing, 1991) Lazarus Churchyard #1–3 (with various artists, Tundra Publishing, 1992) A1 #6: "Harlequin Bones: Dada 331" (with Phil Winslade, 1992) Ammo Armageddon: "Harlequin Bones: Kil 4/11/44" (with Phil Winslade, anthology graphic novel, 1993) Sugarvirus (with Martin Chaplin, one-shot, 1993) Damage #1–6 (with David Gordon, self-published, 1993–1994) SVK (with D'Israeli, one-shot, BERG, 2011) Marvel Comics Titles published by Marvel include: Hellstorm: Prince of Lies #12–21 (with Leonardo Manco, Peter Gross, Derek Yaniger and Martin Chaplin, 1994) Marvel 2099: 2099 Unlimited: "Metalscream 2009" (with D'Israeli, in No. 4, 1994) "Old Red-Eyes is Back" (with D'Israeli, in No. 7, 1994) "Steel Rain" (with Gary Erskine, in No. 9, 1995) Doom 2099: "Island of Lost Souls" (with John Francis Moore and Pat Broderick, in No. 24, 1994) "Fables of the Deconstruction" (with John Francis Moore and Pat Broderick, in No. 25, 1995) "Ramparts, Barricades, Borderlines" (with Pat Broderick, in #26–28, 1995) "One Nation Under Doom" (with Pat Broderick, David G. Klein, John Royle and Steve Pugh, in #29–35, 1995) "Shockriding" (with Steve Pugh and Ashley Wood, in #36–38, 1995–1996) "May the Circle Be Unbroken" (with John Buscema, in No. 39, 1996) 2099 A.D. Apocalypse: "Midnight in Hell!" (with Mark Buckingham, one-shot, 1995) 2099 A.D. Genesis: "Mid Day Sun" (with Dale Eaglesham, one-shot, 1996) X-Men: Excalibur: Excalibur Visionaries: Warren Ellis Volume 1 (tpb, 216 pages, 2010, ) collects: "Soul Sword" (with Terry Dodson, Dærick Gröss Sr. and Ken Lashley, in #83–85, 1994–1995) "Back to Life" (with Ken Lashley, in #86–87, 1995) "Dream Nails" (with Ken Lashley, Derick Gross, Jeffrey Moy, Larry Stroman, David A. Williams and Carlos Pacheco, in #88–90, 1995) Excalibur Visionaries: Warren Ellis Volume 2 (tpb, 232 pages, 2010, ) collects: Starjammers #1–4 (with Carlos Pacheco, 1995–1996) "Baby I Love You" (with Mike S. Miller, Mike Wieringo, Jeffrey Moy and David A. Williams, in No. 91, 1994–1995) "I Want You" (with Casey Jones, in No. 92, 1995) "The Spire" (with Casey Jones, in No. 93, 1996) "Days of Future Tense" (with Casey Jones, in No. 94, 1996) "Amplified Heart" (with Carlos Pacheco, in No. 95, 1996) Excalibur Visionaries: Warren Ellis Volume 3 (tpb, 272 pages, 2010, ) collects: "Fireback" (with Carlos Pacheco, in #96, 1996) "Counterfire" (with Casey Jones, in #97, 1996) "Fireflies" (with Carlos Pacheco, in #98, 1996) "Fire with Fire" (with Casey Jones, in #99, 1996) "London's Burning" (with Randy Green, Rob Haynes and Casey Jones, in No. 100, 1996) "Quiet" (with Casey Jones, in No. 101, 1996) "After the Bomb" (with Casey Jones, in No. 102, 1996) "Bend Sinister Reprise" (with Carlos Pacheco, in No. 103, 1996) Pryde and Wisdom #1–3 (with Terry Dodson, Karl Story and Aaron Lopresti, 1996) X-Calibre #1–4 (with Ken Lashley, 1995) collected in X-Men: The Complete Age of Apocalypse Volume 2 (tpb, 376 pages, 2006, ) Storm #1–4 (with Terry Dodson, 1996) X-Men/WildC.A.T.s: The Dark Age (with Mat Broome, one-shot, 1998) collected in tpb, 194 pages, Image, 1998, Wolverine #119–122 (with Leinil Francis Yu, 1997–1998) collected as Wolverine: Not Dead Yet (tpb, 96 pages, 1998, ; hc, 2009, ) X-Force (with Ian Edginton and Whilce Portacio): Counter-X Volume 1 (tpb, 192 pages, 2008, ) collects: "Games without Frontiers" (in #102–105, 2000) "Murder Ballads" (with Lan Medina, Ariel Olivetti and Enrique Breccia, in #106–109, 2000) Generation X (with Brian Wood and Steve Pugh): Counter-X Volume 2 (tpb, 192 pages, 2008, ) collects: "Correction" (in #63–66, 2000) "Come on Die Young" (with Ron Lim and Alan Evans, in #67–70, 2000) X-Man (with Steven Grant and Ariel Olivetti): Counter-X Volume 3 (tpb, 192 pages, 2008, ) collects: "No Direction Home" (in #63–66, 2000) "Infinities of Evil" (in #67–70, 2000) "Fearful Symmetries, Part One" (in #71, 2001) Astonishing X-Men: Ghost Box (hc, 184 pages, 2009, ; tpb, 2009, ) collects: "Ghost Box" (with Simone Bianchi, in #25–30, 2008–2009) Astonishing X-Men: Ghost Boxes #1–2 (with Alan Davis, Adi Granov, Clayton Crain and Kaare Andrews, 2008–2009) Exogenetic (hc, 136 pages, 2010, ; tpb, 2011, ) collects: "Exogenetic" (with Phil Jimenez, in #31–35, 2009–2010) Xenogenesis (hc, 160 pages, 2010, ; tpb, 2011, ) collects: Astonishing X-Men: Xenogenesis #1–5 (with Kaare Andrews, 2010) Ghost Rider: "Skin Games" (with Salvador Larroca, in No. 55, 1994) "Wish for Pain" (with Javier Saltares, in Annual No. 2, 1994) Marvel/Top Cow: The Crossover Collection (tpb, 304 pages, 2005, ) includes: Ghost Rider/Ballistic: "Kill Everyone We See" (with Billy Tan, one-shot, 1997) Druid #1–4 (with Leonardo Manco, 1995) Daredevil #343: "Recross" (with Arvell Jones and Keith Pollard, 1995) Dr. Strange, Sorcerer Supreme #80–82: "Earthquake Logic" (with Todd Dezago, Evan Skolnick, Mark Buckingham and Gary Frank, 1995) Ruins #1–2 (with Cliff Nielsen, Terese Nielsen and Christopher Moeller, 1995) What If #77: "What If... Legion Had Killed Magneto?" (with Benny R. Powell and Hector Gomez, 1995) Thor #491–494 (with Mike Deodato, Jr., 1995–1996) collected as Thor: Worldengine (tpb, 96 pages, 1996, ; hc, 2011, ) Akira #38: "Candy Flower Napalm" (with Terry Shoemaker, Epic, 1996) Carnage: Mind Bomb (with Kyle Hotz, one-shot, 1996) Ultimate Fantastic Four: Volume 1 (hc, 320 pages, 2005, ) includes: "Doom" (with Stuart Immonen, in #7–12, 2004) Volume 2 (hc, 240 pages, 2006, ) includes: "N-Zone" (with Adam Kubert, in #13–18, 2005) Ultimate Galactus Trilogy (hc, 368 pages, 2007, ; tpb, 2009, ) collects: Ultimate Nightmare #1–5 (with Trevor Hairsine and Steve Epting, 2004–2005) also collected as U-Nightmare (tpb, 120 pages, 2005, ) Ultimate Secret #1–4 (with Steve McNiven and Tom Raney, 2005) also collected as U-Secret (tpb, 96 pages, 2006, ) Ultimate Extinction #1–5 (with Brandon Peterson, 2006) also collected as U-Extinction (tpb, 120 pages, 2006, ) Iron Man v4 #1–6 (with Adi Granov 2005–2006) collected as Iron Man: Extremis (hc, 160 pages, 2006, ; tpb, 2007, ) Nextwave: Agents of H.A.T.E. (with Stuart Immonen, 2006–2007) collected as: This is What They Want (hc, 144 pages, 2006, ; tpb, 2007, ) I Kick Your Face (hc, 144 pages, 2007, ; tpb, 2008, ) Ultimate Collection (tpb, 304 pages, 2010, ) newuniversal: newuniversal #1–6 (with Salvador Larroca, 2007) collected as Volume 1 (hc, 152 pages, 2007, ; tpb, 2008, ) newuniversal: Shockfront #1–2 (with Steve Kurth, 2008) Thunderbolts (with Mike Deodato, Jr., 2007–2008) collected as: Faith in Monsters (includes #110–115 and the Civil War: The Initiative one-shot, hc, 192 pages, 2007, ; tpb, 2008, ) Caged Angels (collects #116–121, hc, 144 pages, 2008, ; tpb, 2008, ) Ultimate Collection (tpb, 296 pages, 2011, ) Ultimate Human #1–4 (with Cary Nord, 2008) collected as U-Human (hc, 104 pages, 2008, ; tpb, 2008, ) Ultimate Comics: Armor Wars #1–4 (with Steve Kurth, 2009–2010) collected as UC-AW (hc, 112 pages, 2010, ; tpb, 2010, ) Osborn #1: "The Prime of Miss June Covington" (with Jamie McKelvie, 2010) collected in O: Evil Incarcerated (hc, 120 pages, 2011, ) Secret Avengers #16–21 (with Jamie McKelvie, Kev Walker, David Aja, Michael Lark and Alex Maleev, 2011–2012) collected as Secret Avengers: Run the Mission, Don't Get Caught, Save the World (hc, 144 pages, 2012, ) Avengers: Endless Wartime (with Mike McKone) (Marvel Original Graphic Novel, 120 pages, 2013, ) Avengers Assemble #21, #22.INH-23.INH, #24–25 (with Kelly Sue DeConnick and Matteo Buffagni, 2013–2014) collected as Avengers Assemble: The Forgeries of Jealousy (tpb, 112 pages, 2014, ) Moon Knight #1–6 (with Declan Shalvey, 2014) collected as Moon Knight Vol. 1: From the Dead (tpb, 136 pages, 2014, ) Captain Marvel #12–13 (with Kelly Sue DeConnick and David Lopez, 2015) collected in Captain Marvel Vol. 3: Alis, Volat, Propriis (tpb, 96 pages, 2015, ) Karnak #1–6 (with Gerardo Zaffino, 2015–2016) DC Comics/Vertigo Titles published by DC Comics and its Vertigo imprint include: Batman: Legends of the Dark Knight #83–84: "Infected" (with John McCrea, 1996) collected in Monsters (tpb, 192 pages, 2009, ) Gotham Knights #1: "To Become the Bat" (with Jim Lee, 2000) collected in Black & White Volume 2 (tpb, 176 pages, 2003, ) Batman: Detective Comics #1000 (with Becky Cloonan and others) 2019 Transmetropolitan (with Darick Robertson and various artists, 1997–2001) collected as: Back on the Street (collects #1–6, tpb, 144 pages, 2009, ) Lust for Life (collects #7–12, tpb, 144 pages, 2009, ) Year of the Bastard (collects #13–18, tpb, 144 pages, 2009, ) The New Scum (collects #19–24 and short stories from Winter's Edge #2–3, tpb, 160 pages, 2009, ) Lonely City (collects #25–30, tpb, 144 pages, 2009, ) Gouge Away (collects #31–36, tpb, 144 pages, 2010, ) Spider's Thrash (collects #37–42, tpb, 144 pages, 2010, ) Dirge (collects #43–48, tpb, 144 pages, 2010, ) The Cure (collects #49–54, tpb, 144 pages, 2011, ) One More Time (collects #55–60, I Hate It Here and Filth of the City, tpb, 256 pages, 2011, ) Hellblazer: Haunted (tpb, 144 pages, 2003, ) collects: "Haunted" (with John Higgins, in #134–139, 1999) Setting Sun (tpb, 96 pages, 2004, ) collects: "Locked" (with Frank Teran, in No. 140, 1999) "The Crib" (with Tim Bradstreet, in No. 141, 1999) "Setting Sun" (with Javier Pulido, in No. 142, 1999) "Telling Tales" (with Marcelo Frusin, in No. 143, 1999) Orbiter (with Colleen Doran, graphic novel, hc, 104 pages, 2003, ) JLA Classified #10–15 (with Butch Guice, 2005–2006) collected as JLA Classified: New Maps of Hell (tpb, 136 pages, 2006, ) Jack Cross #1–4: "Love Will Get You Killed" (with Gary Erskine, 2005–2006) Stealth Tribes (with Colleen Doran, graphic novel, forthcoming) Image Comics Titles published by Image include: Celestine #1–2 (with Pat Lee, Extreme Studios, 1996) Jinx: Buried Treasures (with Brian Michael Bendis, one-shot, 1998) collected in Total Sell Out (tpb, 184 pages, 2003, ) City of Silence #1–3 (with Gary Erskine, 2000) collected as City of Silence (tpb, 104 pages, 2004, ) Ministry of Space #1–3 (with Chris Weston, 2001–2004) collected as MoS (hc, 96 pages, 2005, ; tpb, 2006, ) Fell (with Ben Templesmith, 2005–...) collected as: Feral City (collects #1–8, hc, 128 pages, 2007, ; tpb, 2007, ) Trees #1- (with Jason Howard, 2014–) "In Shadow" (#1–8, collected as Trees Volume 1: In Shadow, tpb, 2015, 160 pages, ) "Two Forests" (#9–14, collected as Trees Volume 2: Two Forests, tpb, 2016, 128 pages, ) Supreme: Blue Rose #1–7 (with Tula Lotay, 2014–2015) Injection #1- (with Declan Shalvey, 2015–) Volume 1 (Collects #1–5, tpb, 2015, 120 pages, ) Cemetery Beach #1-#7 (with Jason Howard, 2018–2019) Wildstorm Titles published by Wildstorm include: Sword of Damocles #1–2 (with Randy Green, 1996) DV8: DV8: Rave (with Humberto Ramos, one-shot, 1996) DV8: Neighborhood Threat (tpb, 176 pages, 2002, ) collects: "Lust for Life" (with Humberto Ramos, in #1, 1996) "Some Weird Sin" (with Humberto Ramos, in #2, 1996) "Neighborhood Threat" (with Michael Lopez, in No. 3, 1996) "Miss Drugstore" (with Humberto Ramos, in No. 4, 1996) "Cigarettes & Alcohol" (with Juvaun Kirby, in #1/2, 1997) "Isolation" (with Humberto Ramos, in No. 5, 1997) "Tonight" (with Humberto Ramos and Kevin J. West, in No. 6, 1997) "Shades" (with Shon C. Bury, Humberto Ramos, Jason Johnson and Al Rio, in No. 7, 1997) "Three" (with Shon C. Bury, Michael Lopez and Juvaun Kirby, in No. 8, 1997) Stormwatch (with Tom Raney, Pete Woods, Michael Ryan, Jim Lee, Oscar Jimenez, Bryan Hitch and Chris Sprouse, 1996–1998) collected as: Force of Nature (collects v1 #37–42, tpb, 160 pages, 2000, ) Lighting Strikes (collects v1 #43–47, tpb, 144 pages, 2000, ) Change or Die (collects v1 #48–50 and v2 #1–3, tpb, 176 pages, 1999, ) A Finer World (collects v2 #4–9, tpb, 144 pages, 1999, ) Final Orbit (collects v2 #10–11 and WildC.A.T.s/Aliens one-shot, tpb, 96 pages, 2001, ) Gen¹³: "London's Brilliant" (with Steve Dillon, in Annual No. 1, 1997) "New York Confidential" (with Steve Dillon, in Bootleg Annual No. 1, 1998) Planetary (with John Cassaday, 1999–2009) collected as: All Over the World and Other Stories (collects #1–6, hc, 160 pages, 2001, ; tpb, 2000, ) The Fourth Man (collects #7–12, hc, 144 pages, 2001, ; tpb, 2001, ) Leaving the 20th Century (collects #13–18, hc, 192 pages, 2004, ; tpb, 2005, ) Spacetime Archaeology (collects #19–27, hc, 224 pages, 2010, ; tpb, 2010, ) Crossing Worlds (tpb, 192 pages, 2004, ) collects: Planetary/The Authority: Ruling the World (with Phil Jimenez, one-shot, 2000) Planetary/JLA: Terra Occulta (with Jerry Ordway, one-shot, 2002) Planetary/Batman: Night On Earth (with John Cassaday, one-shot, 2003) Absolute Edition Volume 1 (collects #1–12, hc, 320 pages, 2010, ) Absolute Edition Volume 2 (collects #13–27, hc, 384 pages, 2010, ) The Authority (with Bryan Hitch, 1999–2000) collected as: Relentless (collects #1–8, tpb, 192 pages, 2000, ) Under New Management (includes #9–12, tpb, 192 pages, 2000, ) Earth Inferno and Other Stories (tpb, 192 pages, 2002, ) includes: "Orbital" (with Cully Hamner, in Wildstorm Summer Special one-shot, 2001) Absolute Edition Volume 1 (collects #1–12, hc, 320 pages, 2002, ) Global Frequency: Planet Ablaze (tpb, 144 pages, 2004, ) collects: "Bombhead" (with Garry Leach, in No. 1, 2002) "Big Wheel" (with Glenn Fabry, in No. 2, 2003) "Invasive" (with Steve Dillon, in No. 3, 2003) "Hundred" (with Roy Allan Martinez, in No. 4, 2003) "Big Sky" (with Jon J. Muth, in No. 5, 2003) "The Run" (with David Lloyd, in No. 6, 2003) Detonation Radio (tpb, 144 pages, 2004, ) collects: "Detonation" (with Simon Bisley, in No. 7, 2002) "Untitled" (with Chris Sprouse, in No. 8, 2003) "Untitled" (with Lee Bermejo, in No. 9, 2003) "Superviolence" (with Tomm Coker, in No. 10, 2003) "Aleph" (with Jason Pearson, in No. 11, 2004) "Harpoon" (with Gene Ha, in No. 12, 2004) Reload/Mek (tpb, 144 pages, 2004, ) collects: Mek #1–3 (with Steve Rolston, 2003) Reload #1–3 (with Paul Gulacy, Homage, 2003) Red/Tokyo Storm Warning (tpb, 144 pages, 2004, ) collects: Tokyo Storm Warning #1–3 (with James Raiz, Cliffhanger, 2003) Red #1–3 (with Cully Hamner, Homage, 2003) Two-Step #1–3 (with Amanda Conner, 2003) collected as Two-Step (tpb, 128 pages, 2010, ) Ocean #1–6 (with Chris Sprouse, 2004–2005) collected as Ocean (tpb, 160 pages, 2005, ) Desolation Jones: Made in England (tpb, 144 pages, 2006, ) collects: "Made in England" (with J. H. Williams III, in #1–6, 2005–2006) "To Be in England" (with Danijel Žeželj, in #7–8, 2006–2007) Avatar Press Titles published by Avatar include: Gravel: Gravel: Never a Dull Day (hc, 576 pages, 2008, ) collects: Strange Kiss #1–3 (with Mike Wolfer, 1999–2000) Stranger Kisses #1–3 (with Mike Wolfer, 2001) Strange Killings #1–3 (with Mike Wolfer, 2002) Strange Killings: Body Orchard #1–6 (with Mike Wolfer, 2002–2003) Strange Killings: Strong Medicine #1–3 (with Mike Wolfer, 2003) Strange Killings: Necromancer #1–6 (with Mike Wolfer, 2004) Gravel (with Mike Wolfer, Raulo Cáceres and Oscar Jimenez, 2007–2010) collected as: Bloody Liars (collects #0–7, hc, 192 pages, 2009, ; tpb, 2009, ) The Major Seven (collects #8–14, hc, 176 pages, 2009, ; tpb, 2009, ) The Last King of England (collects #15–21, hc, 176 pages, 2010, ; tpb, 2010, ) Threshold #25–30: "Dark Blue" (with Jacen Burrows, 2000) collected as Dark Blue (tpb, 72 pages, 2001, ) Bad World #1–3 (with Jacen Burrows, 2001) collected as Bad World (tpb, 80 pages, 2002, ) Scars #1–6 (with Jacen Burrows, 2002–2003) collected as Scars (tpb, 164 pages, 2004, ) Bad Signal (with Jacen Burrows, 1999–2000): Volume 1 (tpb, 64 pages, 1999, ) Volume 2 (tpb, 64 pages, 2000, ) Blackgas (hc, 144 pages, 2007, ; tpb, 2007, ) collects: Blackgas #1–3 (with Max Fiumara, 2006) Blackgas 2 #1–3 (with Max Fiumara and Ryan Waterhouse, 2006–2007) Wolfskin: Volume 1 (hc, 120 pages, 2009, ; tpb, 2009, ) collects: Wolfskin #1–3 (with Juan Jose Ryp, 2006–2007) Wolfskin Annual No. 1 (with Mike Wolfer and Gianluca Pagliarani, 2008) Volume 2 (hc, 160 pages, 2012, ; tpb, 2012, ) collects: Wolfskin: Hundredth Dream #1–6 (with Mike Wolfer and Gianluca Pagliarani, 2010–2011) Black Summer #0–7 (with Juan Jose Ryp, 2007–2008) collected as BS (hc, 192 pages, 2008, ; tpb, 2008, ) Doktor Sleepless (with Ivan Rodriguez, 2007–...) collected as: Engines of Desire (collects #1–8, hc, 216 pages, 2008, ; tpb, 2008, ) FreakAngels (with Paul Duffield, webcomic, 2008–2011) collected as: Volume 1 (collects episodes #1–24, hc, 144 pages, 2008, ; tpb, 2008, ) Volume 2 (collects episodes #25–48, hc, 144 pages, 2009, ; tpb, 2009, ) Volume 3 (collects episodes #49–72, hc, 144 pages, 2009, ; tpb, 2009, ) Volume 4 (collects episodes #73–96, hc, 144 pages, 2009, ; tpb, 2009, ) Volume 5 (collects episodes #97–120, hc, 144 pages, 2011, ; tpb, 2011, ) Volume 6 (collects episodes #121–144, hc, 144 pages, 2011, ; tpb, 2011, ) Anna Mercury: Anna Mercury #1–5 (with Facundo Percio, 2008) collected as AM: The Cutter (hc, 144 pages, 2009, ; tpb, 2009, ) Anna Mercury 2 #1–3 (with Facundo Percio, 2009) No Hero #0–7 (with Juan Jose Ryp, 2008–2009) collected as No Hero (hc, 192 pages, 2010, ; tpb, 2010, ) Ignition City #1–5 (with Gianluca Pagliarani, 2009) collected as IC Volume 1 (hc, 144 pages, 2010, ; tpb, 2010, ) Supergod #1–5 (with Garrie Gastony, 2009–2010) collected as Supergod (hc, 128 pages, 2011, ; tpb, 2011, ) Captain Swing and the Electrical Pirates of Cindery Island #1–4 (with Raulo Cáceres, 2010) collected as Captain Swing and the Electrical Pirates of Cindery Island (hc, 128 pages, 2011, ; tpb, 2011, ) Apparat Titles published by Avatar's Apparat imprint include: Warren Ellis' Apparat: The Singles Collection Volume 1 (tpb, 112 pages, 2005, ) collects: Warren Ellis' Frank Ironwine (with Carla Speed McNeil, one-shot, 2004) Warren Ellis' Quit City (with Laurenn McCubbin, one-shot, 2004) Warren Ellis' Simon Spector (with Jacen Burrows, one-shot, 2004) Warren Ellis' Angel Stomp Future (with Juan Jose Ryp, one-shot, 2004) Crécy (with Raulo Cáceres, graphic novel, tpb, 48 pages, 2007, ) Aetheric Mechanics (with Gianluca Pagliarani, graphic novel, tpb, 48 pages, 2008, ) Frankenstein's Womb (with Marek Oleksicki, graphic novel, hc, 48 pages, 2009, ; tpb, 2009, 1-5929-1059-9) Other US publishers Titles published by various American publishers include: Malibu: The All-New Exiles #1: "Wave of Mutilation" (with Steven D. Butler, 1995) Ultraforce: "Burnt Offerings" (with Ian Edginton and John Royle, in #∞, 1995) "Wave of Mutilation" (with Steven D. Butler, in #1–3, 1995) "Becoming More Like God" (with George Pérez and Larry Welch, in Ultraforce/Avengers one-shot, 1995) "Smoke and Bone" (with Ian Edginton, Darick Robertson, Jeff Johnson, Scott Kolins, Brandon McKinney and Christopher Schenck, in #5–7, 1996) Caliber: Calibrations #1–5: "Atmospherics" (with Ken Meyer, Jr., 1996) collected as Atmospherics (tpb, 48 pages, Avatar, 2002, ) Negative Burn #37: "Better Living Through Chemistry" (with Brian Michael Bendis, 1996) Sherlock Holmes: The Sussex Vampire One shot. (with Craig Gilmore, 1996) Vampirella Lives (Harris): The Ellis Collection (tpb, 112 pages, 2010, ) collects: "The Movement of Blood" (with Amanda Conner, in Vampirella 25th Anniversary Special, 1996) "Vampirella Lives" (with Amanda Conner, in #1–3, 1996–1997)) "Necromance" (with Mark Beachum, in Vampirella/Dracula: The Centennial, 1997) Vampirella/Shi: "Nine Kinds of Dirt" (with Louis Small, Jr., one-shot, 1997) Shi/Vampirella: "In Rashomon" (with Kevin Lau, one-shot, Crusade Comics, 1997) Starship Troopers: Insect Touch #1–3 (with Gordon Rennie, Davide Fabbri and Paolo Parente, Dark Horse, 1997) collected in Starship Troopers (tpb, 152 pages, 1998, ) Solar, Man of the Atom (with Darick Robertson, one-shot, Acclaim, 1997) Down and Top Cow's Best of Warren Ellis (tpb, 176 pages, Top Cow, 2006, ) collects: Tales of the Witchblade #3–4 (with Brian Ching and Billy Tan, 1997–1998) Down #1–4 (with Tony Harris and Cully Hamner, 2005–2006) No Justice/No Piece #2: "Manifesto" (with Robert James Luedke, Head Press, 1998) Oni Press Color Special '02: "The Operation: Friday I'm in Love" (with Phil Hester, Oni Press, 2002) Switchblade Honey (with Brandon McKinney, graphic novel, tpb, 72 pages, AiT/Planet Lar, 2003, ) Hotwire: Requiem for the Dead #1–4 (with Steve Pugh, Radical, 2009) collected as H:RftD (tpb, 128 pages, 2010, ) James Bond 007 with Jason Masters, Dynamite Entertainment, 2015–2016) collects: James Bond 007 Volume 1: VARGR (collects #1–6, HC, 176 pages, 2016, ) James Bond 007 Volume 2: Eidolon (collects #7–12, HC, 152 pages, 2017, ) Shipwreck (comics) – After-Shock Comics – (2016 to current) NovelsCrooked Little Vein (William Morrow, 2007) Gun Machine (Mulholland Books, 2013)Amazon book's profile. Retrieved 16 August 2012.Normal (novella) (2016) Short fiction "At the zoo", Nature no. 408 (16 November 2000) "Lich-House", An Aura of Familiarity: Visions from the Coming Age of Networked Matter (2013) Dead Pig Collector (July 2013) "The Shipping Forecast" Twelve Tomorrows, ed. Bruce Sterling (2014) Elektrograd: Rusted Blood (2015) "Headcold", Terraform (2016) Nonfiction Second Life Sketches, a weekly column about Second Life Works on Ellis Meaney, Patrick (director). Warren Ellis: Captured Ghosts. Respect! Films and Sequart, 2011. Documentary film. Walker, Cody (ed.). Keeping the World Strange: A Planetary Guide. Sequart, 2011. Thurman, Kevin and Julian Darius. Voyage in Noise: Warren Ellis and the Demise of Western Civilization. Sequart, 2013. Nevett, Chad (ed.). Shot in the Face: A Savage Journey to the Heart of Transmetropolitan. Sequart, 2013. Meaney, Patrick and Kevin Thurman. Warren Ellis: The Captured Ghosts Interviews. Sequart, 2013. Appearances in others' work He makes a lengthy cameo appearance in Powers'' volume 1 issue No. 7, in which much of his dialogue consists of actual quotations from Ellis' writings. References External links The Complete Warren Ellis bibliography Warren Ellis on Marvel.com Warren Ellis at 2000 AD online Warren Ellis at whitechapel Category:Bibliographies of British writers Category:Science fiction bibliographies Category:Bibliographies by writer Category:Lists of comics by creator
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Dating tv show audience members 06-Jan-2018 19:14 Sex cam sean poole If you would like to join us at Media City, Manchester for some heart-pounding tension at this brilliant game show during September & October, then apply now! To take it home, they must hold their nerve by placing their money on the trap doors containing the correct answers.Laugh - including at some exclusive, not-for-broadcast, ad-break-only comedy from the Project team. No catches, no asterisks, no hidden fees or monthly payments. Just email [email protected] and let us know what date you’d like to come. Don’t just be a face in the crowd – be a voice on the soundtrack as well!See - what happens in the ad breaks, including some comedy that we would never be able to broadcast. All we ask is that you book in advance, turn up on time, and if you can’t make it, to let us know as soon as possible so we can reallocate your seats. And remember: The Project is currently the only news program in the world with a live audience (all the other news shows use canned laughter – even 60 Minutes.) With guests James Smith & Madeleine West, and guest hosts Rachel Corbett & Tommy Little, plus stories on man spread fines, firefighter snags, airline mood food, anti vax doctors and Carrie's good news.Conor Pope’s Consumer 999 is a brand new investigative consumer series. wow hangs on updating blizzard launcher Conor Pope will use all of his expertise and experience to confront companies who are misleading, mistreating and defrauding their customers, in an effort to bring positive closure to distressing consumer ordeals. Maybe you hired someone to work on your house and it turned out to be a disaster?
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Perkins quits after harassment charges JUNEAU (AP) -- Facing harassment charges over allegations that he inappropriately touched two women, Gov. Tony Knowles' new legislative director has stepped down after less than a month on the job. Dwight Perkins withdrew his acceptance of the job in a memo to Jim Ayers, Knowles' chief of staff, that was released Tuesday by the governor's office. ''The time needed to respond to these personal matters may pose an impediment to my ability to accomplish the legislative goals that the governor has established for Alaska's families and children,'' Perkins wrote. Bob King, Knowles' press secretary, said the decision that Perkins should step aside was mutual. ''We both concluded that given these circumstances Dwight would be unable to fully commit the time that's necessary,'' King said. ''He needs to focus more time on his personal matters.'' In the memo, Perkins said he had been offered a job as an assistant to Labor and Workforce Development Commissioner Ed Flanagan. Perkins was the department's deputy commissioner until he was named to replace Pat Pourchot as legislative director last month. Perkins, 47, pleaded innocent in Juneau District Court last week to two charges of harassment, a misdemeanor. He was ordered not to have contact with his accusers, whose names are confidential under state law. Perkins served two terms on the Juneau Assembly and is a former deputy commissioner for the Department of Labor. Perkins has declined to address the substance of the allegations against him, citing the advice of his attorney, but called them ''shocking to me.'' According to the complaint, Perkins made an unwanted physical advance toward a woman Oct. 1 while they were opening a building for a meeting. After the woman commented that she was leaving the organization she was with, Perkins said he hated to see her leave and asked her for a hug, according to the complaint. The woman said he hugged for so long that she felt uncomfortable and stepped back. She told police that Perkins then stepped close, rubbed his body against her, fondled her breast and said he wanted to have sex with her, according to the complaint. Police later obtained a search warrant and recorded a conversation between Perkins and the woman in which he admitted saying he wanted to have sex with her but said he did not recall fondling her breast, according to the complaint. The complaint also cites a second woman who said Perkins improperly touched her between July 1999 and March. Perkins has said he doesn't know if he will fight the charges at a trial. His next scheduled court appearance is Jan. 2. The maximum penalty for one count of harassment is 90 days in jail and a $1,000 fine.
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The U.S. Securities and Exchange Commission in Washington, D.C. The U.S. Securities and Exchange Commission on Friday said it settled a lawsuit against two former ITT Educational Services executives accused of hiding the defunct for-profit college operator's actual financial condition from investors. The settlements with former Chief Executive Officer Kevin Modany and former Chief Financial Officer Daniel Fitzpatrick came ahead of a trial scheduled for Monday in federal court in Indianapolis, Indiana. The deal came after the SEC's commissioners took the rare step last year of rejecting an earlier proposed settlement negotiated between the defendants and the agency's staff. Under Friday's settlements, both men agreed to be barred from serving as officers and directors of publicly-traded companies for five years. Modany and Fitzpatrick will also pay penalties of $200,000 and $100,000, respectively. Modany and Fitzpatrick settled the lawsuit without admitting or denying the SEC's claims that they acted as so-called "control persons" for ITT's securities violations. David Miller, Modany's lawyer, and Fredric Firestone, Fitzpatrick's lawyer, said both men were pleased to put the case behind them. In 2015, the SEC sued Carmel, Indiana-based ITT, Modany and Fitzpatrick and accused them of fraudulently concealing from its investors potentially huge losses in two student loan programs that the for-profit college operator had guaranteed. The SEC said that by 2012, the loans made through those programs were performing abysmally, with high default rates. But instead of disclosing that it expected to owe hundreds of millions of dollars because its guarantee obligations had been triggered, ITT and its management took steps to make its exposure to the programs appear limited, the SEC said. In 2016, the U.S. Department of Education banned ITT from enrolling new students who receive federal aid. ITT subsequently announced it would shut its 137 technical college campuses in 39 states, which affected about 35,000 students. It filed for bankruptcy in September 2016. The SEC settled its case against ITT in July 2017, after reaching agreements-in-principle two months earlier to resolve the charges against Modany and Fitzpatrick. But in August 2017, SEC attorneys informed the court that the agency's commissioners had rejected the proposed settlements with Modany and Fitzpatrick. Democratic Senators Dick Durbin of Illinois and Sherrod Brown of Ohio wrote to SEC Chairman Jay Clayton in June 2017 urging the SEC to permanently bar Modany from acting as an officer of a publicly traded company and to seek tough penalties against him and Fitzpatrick. The case is SEC v. ITT Educational Services Inc et al, U.S. District Court, Southern District of Indiana, No. 15-00758.
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OpenWebText2
Introduction ============ Reviews of evidence consistently highlight management as either an enabler or barrier to successful implementation of integrated care \[[@B1][@B2][@B3][@B4][@B54]\]. This includes management at both strategic and operational levels \[[@B5]\]. Leadership was traditionally conceptualised as primarily focussed on those in senior positions but more recent thinking emphasises distributed leadership across multiple management levels \[[@B6][@B7]\], and indeed the contribution of other stakeholders such as clinicians and those with lived experience \[[@B8][@B54][@B55]\]. Supportive and engaged leadership by managers is seen to make a positive contribution but neglect or resistance by leaders present major risks to the achievement of successful outcomes \[[@B1][@B4][@B9][@B10][@B11][@B12][@B13][@B54]\]. Evaluations of individual programmes also reflect the importance of proactive management to successful implementation \[e.g. [@B14][@B15][@B16][@B17]\]. Contributions of strategic managers that have been identified to date are bringing together stakeholders, mobilizing action within organisations by emotionally connecting individuals with their vision, securing internal and external resources for implementation including to support learning, fostering a culture of innovation, and prioritising involvement of communities within strategic developments \[[@B12][@B13][@B15][@B17][@B54]\]. Operational managers' contribution includes generating confidence within frontline staff of their ability to implement, communicating the overall vision in a version that is understandable by the frontline, quantifying tangible benefits for service recipients, and practical coordination of activities and resources \[[@B1][@B4][@B16]\]. In addition to specific management functions, many of the general enablers of integrated care fall wholly or largely under the remit of managers. These include shared patient records, pooling of budgets, team-based processes, co-location, partnership governance, opportunities for development, person-centric quality improvement, and introduction of new roles \[[@B4][@B10][@B16][@B17][@B18][@B19]\]. Such enablers commonly require both strategic and operational management within specific management functions such as finance, human resources, information technology. Whilst its importance is clear, the nuances of what 'good' management for integrated care involves is less understood. Much research essentially describes supportive local contexts in which those in key management roles are willing to commit personal and other resources to facilitate more integrated care, and are able to trust that colleagues in other agencies will not behave opportunistically. The behaviours that support such contexts, and how it can be encouraged and developed in areas which are not fortunate to have established a positive collaboration are however unclear. The extent to which strategic and operational management of integrated care is different to management of "traditional care", and if existing approaches to developing competences amongst managers is sufficient, are similarly unknown. This then creates an 'Achilles heel' for those embarking on the long journey to more integrated care -- with the right management capacity, competence and commitment the connected challenges can be overcome, but all too often these are not in place leading to a well conceived programme not being well implemented and sustained beyond an initial pilot phase. Similarly, attempts to diffuse innovations beyond the areas with the initial champions for change flounder when they fail to find receptive and competent management contexts. This exploratory study seeks to respond to these important gaps in our knowledge about the management of integrated care. It is based on interviews with those with extensive experience of developing and implementing collaborative approaches within clinical, strategic, operational and/or policy roles at a regional, national and international level. Those with direct experience of providing or facilitating the voice of those who have accessed health and care services are also included. It considers three main questions -- is strategic and operational management of integrated care different to that of traditional care, what competences are connected with the management of integrated care, and how can we support the development of such competences in practice. At the outset, the study specifically addressed management, purposefully excluding the term leadership, as it was the intention to focus on those who have to make integrated care work on a daily basis. Methodology and Theory ====================== Theoretical background ---------------------- The question of what makes a good manager has interested philosophers and statesmen throughout the ages. Whilst there is recognition that the demands made on a manager will vary dependant on the context and their particular role, considerable work has been done to clarify what competences are required by managers within healthcare settings \[[@B13][@B18][@B28][@B30][@B31][@B49][@B56]\]. Pihlainen et al (2016)'s \[[@B57]\] systematic review suggests that competences related to the healthcare context have social, organisational, and financial dimensions, and that these should be demonsrated alongside operational (i.e. quality improvement, credibility with professionals, and staff development) and general management (i.e. strategic mindset, interpersonal skills and time management). Likewise the question of what constitutes the difference between management and leadership. "Scientific" management theories started to be developed at the beginning of the 20th century, the most famous of the early works being Fredrerick Winslow Taylor's "The Principles of Scientific Management" \[[@B20]\]. Other notable works include McLelland's Human Motivation Theory \[e.g. [@B21][@B22]\] or Kotter's leadership versus management challenge \[e.g. [@B23] and later\]. In the field of integrated care however, this discussion has only recently emerged, as a result of the questions on how to scale, transfer and sustain change in a complex environment. Whilst frameworks underline the importance of the management function in integrated care \[e.g. [@B18][@B24]\], these do not specify the elements of what constitutes good management for integrated care \[e.g. [@B25][@B54][@B55]\]. There is emerging evidence of how difficult it is to manage both the change process and a resultant integrated care system \[[@B26][@B27][@B55]\]. Leadership, and in particular 'systems leadership', is often portrayed as the dynamic solution to overcome long-standing barriers, with management being relegated to the less appealing role of administering what leaders have achieved \[[@B7]\]. That said, there is no consensus even on whether leadership and management in integrated care are two distinct concepts, or merely two sides of the same coin \[[@B28]\]. For the purposes of this study and to answer the research questions outlined above, Mintzberg's distinction between strategic (Strategic Apex) and operational management (Middle Line) was selected as the basis for discussion during the interviews and the analysis of the results \[[@B29][@B30]\]. This approach was selected, because this study aimed at understanding management better, and Mintzberg does not classify leadership as an opposing or separate concept to management. Indeed, Mintzberg went on to say, that "\[I\]n place of heroic leaders who don't manage, health care needs engaged managers who lead." \[[@B31]\] The description of the two levels of management were thus adapted to suit the needs of the interviews \[based on [@B29][@B30][@B32]\]: > **Strategic Managers** -- decision makers, interaction with environment, setting policies, goals & frameworks, supervision of operational managers. > > **Operational Managers** -- implementers, mediators between strategic and core, limited interaction with environment related to their delivery areas, departmental strategies within strategic framework. Managers responsible for integrated care may be doing so within the boundaries of a single organization, in a distinct partnership role connected with two or more organisations, or of hybrid roles that incorporate both single and partnership responsibilities. All of these were included in the study as they all require managers to introduce new ways of working, to deploy resources differently, and to achieve person centred outcomes in order to provide more integrated care. In the results and the discussion sections, the appropriateness of this approach as well as the necessity to distinguish between management and leadership will be explored in more detail. Methodology ----------- In order to understand what makes a good manager of integrated care, and answer the research questions, an exploratory, qualitative approach was chosen in form of in-depth interviews. A purposive sample of managers and reseachers of integrated care was put together, covering North America, Europe and Australasia. Interviewees were selected based on their long-standing experience on both levels and in various roles (policy, practice, person/caregiver, research) over at least 10 years in the integrated care field. Overall 50 people were invited to take part in the study, 25 of whom accepted the invitation, and two declined. Ultimately, 22 interviews were conducted by RM and VS, lasting between 25 and 74 minutes. The interview guidance can be found in Appendix 1. The interviewees represented 13 different countries from four continents, and four supra-national or international organisations (see Table [1](#T1){ref-type="table"}). There was parity of gender amongst participants. The interviews were conducted either online or in person by one of the study authors, and were recorded and transcribed by a professional verbatim. ###### Characteristics of participants by roles/stakeholder group. ---------------- ------------- --------------- -------- ------------------------ -------------------------- -------- ---------- ------------------ ---------- Female/male North America Europe Western Pacific Region Internal organisations\* Policy Practice Person/Caregiver Research Interviewee 1 F ✓ ✓ ✓ ✓ ✓ Interviewee 2 M ✓ ✓ ✓ ✓ Interviewee 3 M ✓ ✓ ✓ Interviewee 4 M ✓ ✓ ✓ ✓ Interviewee 5 M ✓ ✓ ✓ ✓ Interviewee 6 M ✓ ✓ ✓ Interviewee 7 F ✓ ✓ ✓ Interviewee 8 M ✓ ✓ ✓ ✓ Interviewee 9 F ✓ ✓ ✓ ✓ ✓ Interviewee 10 F ✓ ✓ ✓ ✓ Interviewee 11 F ✓ ✓ Interviewee 12 F ✓ ✓ ✓ ✓ ✓ Interviewee 13 F ✓ ✓ Interviewee 14 M ✓ ✓ ✓ Interviewee 15 M ✓ ✓ Interviewee 16 M ✓ ✓ Interviewee 17 M ✓ ✓ ✓ ✓ Interviewee 18 M ✓ ✓ ✓ ✓ Interviewee 19 F ✓ ✓ ✓ Interviewee 20 M ✓ ✓ Interviewee 21 F ✓ ✓ Interviewee 22 M ✓ ✓ ✓ ---------------- ------------- --------------- -------- ------------------------ -------------------------- -------- ---------- ------------------ ---------- \* International organisations encompass UN agencies, Bretton Woods Institutes, European Union, and transnational NGOs. Many respondents represented more than one perspective, which reflected their long-standing and diverse careers in integrated care. Geographic representation was skewed towards Europe, because most known, published and internationally active experts still work there. While the authors of the study are well aware that there are many experts and initiatives in Latin America and Africa, who would have been equally qualified, accessibility, time and language restrictions were the main barrier to inclusion. The transcripts were analysed and coded separately by each study author. The codes were then discussed and consensus was reached as to the final coding framework \[[@B33]\]. The coding was performed on the full text statements and only fill words or repetitions were left out. The coding framework is described in Table [2](#T2){ref-type="table"}. Initial codes were derived directly from the interview questions, and were subsequently altered, deleted or renamed, where it was found necessary and after discussion between the two study authors. A paucity in quotes did not automatically lead to a deletion of the code, as it was seen as an interesting outcome in itself. The originator of quotes within the findings are identified through a number relating to Table [1](#T1){ref-type="table"}. ###### Coding framework. -------------------------------------------------- -------------------- ----------------------------------- Code name References overall No of interviews referencing code Developing competences 111 18 Strategic competences 59 15 Operational competences 23 13 Context 53 15 Culture 41 11 Personal commitment and resilience 17 12 Community perspective and holistic understanding 22 9 Doctors and management 29 9 Management vs leadership 27 10 Other issues 48 11 Good examples 20 10 Bad examples 9 4 Stakeholders 4 4 -------------------------------------------------- -------------------- ----------------------------------- Ethics approval was granted by the Humanities and Social Sciences Ethical Review Committee at the University of Birmingham (ERN_18-1347). Findings ======== Management of Integrated Care ----------------------------- Participants expressed varied opinions as to the extent to which management of integrated care was different. For some, it was essentially standard practice deployed in a particular context. Unsuccessful implementation was due to a lack of commitment by operational and/or strategic managers or that they were not competent managers of usual or integrated care. Most participants however did see management of integration as requiring different ways of understanding and behaving as a strategic or operational manager compared to 'traditional care'. These include an ability to focus on societal not just organisational value, to work towards holistic and not just financial performance targets, to be comfortable with distributed and not solely hierarchical and linear approaches, a willingness to challenge and not be comfortable with the status quo, and meaningful not tokenistic public involvement. In addition, there was general agreement that the need for an understanding of the wider system was crucial, but rarely found in managers. > And first I thought maybe there's no big difference, so you have to fight your same battles if you are normal manager in a hospital and ...but the difference is that you are more on a change management role and you really have to have the skills of a change manager...and endurance to knock on every door again and again and again and at the tenth time it will maybe open a little bit. (Interviewee 3) The Mintzberg distinction between operational and strategic was seen as helpful although the roles were often re-labeled as 'senior' (strategic) and 'middle' (operational) management. Leadership was interpreted by some participants as primarily being the responsibility of those in more senior, strategic positions but most reflected Mintzberg's perspective \[[@B30][@B31][@B32]\] that integrated care requires leadership to be demonstrated at all levels as part of management responsibilities. The emphasis on distribution of such influence was articulated by one participant as a move from 'leader*ship* roles' to 'leader*ful* systems' \[[@B34]\]. There was also a noticeable tendency for inspirational individuals to being singled out as a main catalyst of integrated care becoming a local or national priority and reality. This did not go as far or as gendered as stating that the development was due to a 'great man' but did suggest that one outstanding person had been central to generating momentum within the local context. Strategic managers were described as crucial to new visions of integrated care being developed and structural legitimacy being gained through formal governance structures within providers, funders and government. Strategic managers engaging directly with people and communities made symbolic and practical differences. Practical in that their views were seen more likely to have influence if it had been heard in the first person, and symbolic in that it demonstrated to others within organisations that this was seen as a valuable contribution. Furthermore experiencing authentic listening and responsive action by strategic managers encouraged public representatives to continue their involvement > You see her \[vice-president\] everywhere. If you saw her in the waiting room, she might be sitting with someone, you might think she's a care giver or she's a patient herself, but she wants to get to know her clients and there's a genuineness about her that people really relate to and she's very, very caring. I see her with her subordinates who are not maybe pulling their weight and she really encourages them to do that more with a carrot rather than with a stick. I imagine that she wouldn't put up with someone who is not doing that for very long. (Interviewee 13) Once the vision is set, operational managers are instrumental to the hard work of implementation including overcoming active resistance to the connected changes and general inertia to any form of transformation. Strategic managers supported through providing 'permission' for operational managers to be entrepreneurial in their recognition of opportunities and mobilising the necessary resources to unlock the connected value. Culture was mentioned by many participants as the historical partnership context in which integration was being introduced and a relational dynamic which required active intervention. Both levels had responsibility to role model new practices and constantly emphasise the rationale and vision of integrated care. Operational managers maintained implementation momentum using influence, inspiration and more directive means to ensure professionals and others adopt the expected behaviours: > They follow up and monitor or they push, they fight, they push again, they require from their staff or the supervisors, so that the overall management role is very important because there is always a need for somebody to actually push forward for the change. (Interviewee 18) The dynamic between managers and clinicians is well recognised as an enabler or barrier of quality in health care. According to participants clinicians, and in particular doctors, appeared something of a mixed blessing to achieving more integrated care. All recognised the influence of the medical professional regarding implementation with several particpants reporting the major contribution that an inspirational doctor had made to progressing more person-centred care. Using the credibility based on their expertise and contact with patients, they had challenged the status quo maintained by managers to encourage or force it to be more flexible and responsive. > Whereas the people who've been instrumental in leading the change initially have been clinical leaders locally and yet they wouldn't necessarily perceive to be...to have a management role per se. (Interviewee 17) Others had experienced a less positive contribution in which clinicians were not open to major changes being made by managers to traditional arrangements in which they felt comfortable professionally and personally. This resulted in clinicians, and in particular doctors, acting as principle resistors to a more integrated care. There was similar polarisation of views as to the ability of doctors to take on management roles -- with some believing that their professional paradigms and skills precluded them from being competent managers, whils others reporting that hybrids who could combine clinical competence and credibility with management were the most influential and impactful: > Clinical people are good at individual one on one: diagnosis, treatment, coaching, encouraging and so forth. Management have to think across boundaries at scale about systems. It's an almost exactly opposite skillset. And healthcare is full of management people who used to be clinical people. In our system we pretty much have outlawed that. (Interviewee 12) > > So I think then to call it out clearly, the doctors are probably the group that are struggling most with the idea of integrated care, because they have to give away. (Interviewee 8) > > I would argue that there shouldn't be a rule that you don't appoint clinicians. I have a left-hand, right-hand law. What we are good at is the right hand, what we are bad at is the left hand, but many doctors use both hands. (Interviewee 18) Most supported the powerful impact of doctors, and indeed other clinicians and practitioners, working collaboratively with managers to achieve shared leadership within an organisation or system. > the contribution of both in terms of mutually reinforcing dynamic is really important I think. And one cannot function without the other in my experience on that journey. (Interviewee 17) Competences for management -------------------------- Competences are comprised of "K(nowledge), S(kills)s, A(ttitudes) \[which\] are the abilities and characteristics that enable a job holder to accomplish the activities described in a task statement that describes what the job holder does." In other words, it's about "what I do, what I can do and how, and why I do it." \[[@B35]\] While teaching knowledge and skills is straight forward and widely practiced, attitudes cannot be tought directly, but are influenced by teachers, superiors, mentors and peers \[[@B36]\]. There was general agreement amongst participants that in order to be a successful manager of integrated care, both aspects, learned behaviour and innate personality, were important, thus echoing the discussions in more recent management theory that both intrinsic and extrinsic factors make good managers \[[@B56][@B58]\]. Whilst some managers had a more natural leaning towards integrated care, it was thought that all could develop the necessary competences with personal commitment and a supportive environment. Furthermore, even those with more innate abilities benefitted from formal and informal development opportunities. > I think the personality traits are largely intrinsic, but I think some of the technical skills around pushing the boundaries are teachable because we get them from experience, so through our experiential learning and through our apprenticeship in the system.... And we would need to give consideration to how we support those attributes emerge and develop, because I think it is developing them rather than building them from scratch. (Interviewee 2) Using the knowledge, skills and attitudes concept of competences as a basis, the interviews were analysed to extract which competencies were identified as crucial for integrated care managers to be successful. A summary of the identified competences with a description and illustrative quote can be found in Table [3](#T3){ref-type="table"}. Participants were not able to articulate specific differences in the competences of operational and strategic managers so they are presented as a 'generic' set. This is further supported by the general agreement that the competences themselves wouldn't necessarily change, rather the scale and scope as well as the personal ability to perform grew over time and with changing roles. ###### Knowledge, Skills and Attitudes for Managers of Integrated Care. -------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Explanation Quote **Knowledge** *Technical knowledge* This includes professional knowledge; management theory and theories of innovation; understanding of the workings of the overall system (and not just their own organization or sector); being able to understand social determinants of health; and being able to apply knowledge in the context of integrated care. "the knowledge that she had from the actual needs and the actual how things operate was probably critical to navigate the landscape and then ... she had knowledge of the political setting and how policy works and she managed to play very well between those two fields and make something that is a compromise that fits both sides." (Interviewee 19) **Skills** *Taking a people-centred approach* Involving patients, people and communities in every step of the way; using their perspective as the guiding principle in the design, implementation and evaluation of care; challenging existing power bases which could diminish the importance of lived experiences; engaging communities whose voice is often unheard due to disadvantage and exclusion "a the fundamental rethink is they're the managers. They manage their care, they coordinate the team, not that a patient or family has to do all those but we have to flip on its head the notion of who we work for. And we work for people and their families." (Interviewee 9) *Communication* Communicating through alternative means and formats, including social media in order to engage a broader range of stakeholders; framing opportunities in paradigms and language that will be relevant to different professional and sectorial groups; ability of listening actively, being present during a conversation; creating the time to go out and listen to people. "you have to check in so many times to make sure that what you have either said or communicated has been received in the way that you thought it was being communicated, because I have found that most of the time it's not and I have been completely gobsmacked by how differently people have -- even from what I have said and what I have communicated -- they have received something completely different, a completely different message than the one that I was sending out and I find that absolutely fascinating." (Interviewee 1) *Building and maintaining relationships* Bringing people together who previously had little contact and/or experienced tensions; fostering a supportive and trusting environment; creating the space for new solutions to emerge; building networks; understanding relationship management as an integral and ongoing task. "...because I've realised that you could have all the intellectual prowess you want but if you don't know how to help people and teams and integrated teams and cross-organisations and systems thrive, you can't integrate care. It's all relational. So I think it has to be taught in every aspect of every curriculum." (Interviewee 9) *Distributive leadership and collaborative approach to management* Being able to let go; trusting your team; creating the conditions; managing by shared outcomes; managing teams across professions and organisations; giving permission to innovate and be flexible. "...something requiring tolerance, ambiguity, organic iterative and allowing people latitude to be able to do stuff and one of the things that's emerged strongly is the tension between central control and command at the centre of organisations, ... just as letting go of that control and trusting to people who know their business and empowering them to do stuff and when you do that, that tends to work out well." (Interviewee 17) *Being a coach and a mentor* Developing and implementing inter-disciplinary CPD programmes; giving constructive feedback; understanding management as a coaching role rather than a 'command and control' role. "So I think that issue about how do we invest, not just in the formation but actually in the development. And I think that's about giving people opportunities to learn, to share, to innovate, to fail and to hopefully move on and do things better." (Interviewee 5) *Managing culture change* Identifying culture as a key topic to be managed; understanding different cultures and culture change; managing culture as a continuous work in progress. "This is a big culture change and you don't find people and you don't change people easily to a completely different culture than the one that they signed up for in the first place... you tend to revert to the average or revert to the norm if you don't continue, to continually renew the new reality and that's hard work, because we're trying to do something that's not just a little bit different but something that's significantly different from the norm." (Interviewee 12) **Attitudes** Resilience Being able to weather the storm; be persistent; withstand constant resistance; being able to cope with loneliness. "you really have to have the skills of a change manager and you need I think a lot of resilience and endurance to knock on every door again and again and again and a tenth time it will maybe open a little bit." (Interviewee 16) Courage Standing up against the norm; addressing uncomfortable truths; approaching people and organisations, which are opposing the change. "I think that's a really important part of encouraging people to be brave in integrated care, so if you think of the characteristics of a good chief executive, you know, there's all of that high EQ stuff, there's all of the competencies that come with leadership, but one of those competencies is bravery and bravery is not just about being stuck on your idea, it's about being brave enough to fail and to learn the lessons of those failures..., so that characteristic of teaching flexibility ...is something that can be taught and that comes through in that experiential learning." (Interviewee 2) Humility Accepting mistakes and learning from them; helping others to thrive; taking another persons' perspective; being able to see the big picture. "And the ones that I'm attracted to in terms of a role are the people who are reflective about the failure and can understand the multidimensional aspects of that and, most importantly, understand their role in that failure. So did they listen enough, did they codesign enough, did they stay in the problem long enough. How did they deal with it when it was all going wrong, did they offer the resignation or did they go and say 'mea culpa' and then what was their response." (Interviewee 2) -------------------------------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ Technical knowledge was considered as the basis for any good manager. Building on the individuals' professional background, an in-depth knowledge of integrated care theories, frameworks, models and tools was considered a given, along with knowledge of management, leadership, innovation and systems. An interesting element of learning was highlighted by one interviewee stating that professionals had already a lot of knowledge, but did not know how to apply it in the new context or how to connect the dots. Many interviewees acknowledged that they had never really received any training and some even mentioned that they only found out afterwards, that what they were trying to do actually had a name. The skills necessary to manage integrated care successfully all relate to people and relationship management in essence. As one interviewee put it: "*Soft skills are actually the hard skills*." All participants agreed that communication was one crucial skill for success. There was general recognition that communication was hard work, did not receive enough attention and had to be targeted towards different audiences and different levels. Taking a people-centred approach was identified as a skill, rather than an attitude, as it reinforced and underpinned many management tasks related to integrated care. This categorisation also emphasised the conviction of the participants, that a people-centred approach was teachable and needed to be implemented actively. Integrated care is a means to overcome sectoral barriers and break down professional prejudices, so being able to reach out across professions and organisations to establish and maintain a strong network of providers, include the target population or community, and create trusted relationships was identified as essential for sustainable change. The skill of distributive leadership and having a collaborative approach to management reflects the difficulty of participants to clearly distinguish between management and leadership. It was clearly identified as a skill, however, as it was considered teachable, especially through continuous development programmes and action learning. The importance of continuous learning was emphasised throughout the interviews and reflected in the need for a manager to be a coach and teacher, supporting the professional and personal development of staff and colleagues. Managing culture (and culture change) was unanimously considered a vital and separate skill, which many managers tend to ignore in the beginning of their endeavours, to often detrimental effect. In an organisational context, individual attitudes translate into collective professional and organisational cultures -- if personal attitudes and the culture of the environment don't overlap, a conflict will arise. As integrated care usually challenges established cultures, managing this conflict was identified as a key competence. Several participants also emphasised the importance of personal adjectives such as being brave, stubborn, persistant, resilient, and having a fire or passion burning inside. It was acknowledged that not everyone was cut out to be a manager for integrated care, as it meant dealing with a lot of stress, pressure and uncertainty, as well as being attacked from the 'top' (e.g. policy makers and funders) and from the 'bottom' (e.g. operational staff and clinicians) if expectations were not met in short timescales and anxieties were running high due to changes in established practices and cultures. The right attitude included representing core values, embracing the community and patients as key partners on a daily basis, being approachable, accessible and being seen. Other issues raised were around the ethics of integrated care, legal requirements, the lack of integration between research and practice towards a more improvement-based management approach or the size of organisations. Development of competences -------------------------- The respondents had a very diverse background, many having filled different roles and worked in various sectors over time, and none of them had straight forward career paths (see also Table [1](#T1){ref-type="table"}). The majority had previous experience in service delivery, and had then moved on to management positions within organisations and/or the public sector. A combination of academia and practice was not unusual, nor was the involvement in policymaking and private enterprises. This also meant that most interviewees had changed organisations several times, often citing the search for more meaningful and impactful ways of changing the system, personal development and curiosity of learning the "other sides' viewpoint" as the reason. Questioned about their background in management and integrated care, they reveiled a piecemeal education and training experience, some of them seeking very specific training through MBA programmes, others preferring a learning by doing approach. But all agreed that current programmes were not enough, and that there were not sufficient opportunities to hone the competences outlined above. There was also consensus that while making one's own mistakes was necessary, many of the pitfalls, which lead to failure or stalling of an integrated care initiative, could and should be avoided through better education, training and preparation of managers. General agreement was also found in the conviction that integrated care principles should be part of every training programme, and not limited to health and social care or a specialist MBA course. In regard to preparing for the future and proactively identifying managers for integrated care, these competences should also be included in Continuing Professional Development (CPD) programmes. Another key message was the call for recognising management of integrated care as a job or role in and of itself, which needed to be rewarded appropriately. It was not something one could do on top of a day job or on the fly, as so often happens in practice. By giving such responsibilities proper recognition in relation to capacity and status, it would also make it easier to connect with peers and build a peer network. There was a desire to create such a network for support, peer learning, mentoring and feedback, as a means to deal with the stress and pressure mentioned throughout the interviews. This was found to be especially necessary as managing integrated care often meant a dual role within ones' own organisation and as part of a wider integrated care network. Conflicts arising through split loyalities and accountibilities added to the existing pressure, especially when the role within the integrated care initiative did not match executive power in one's own organisation. While this might seem a challenge on the senior level, it was actually reported on all levels, e.g. managing a care team across different sectors and organisations, or facilitating the steering committee of an integrated care alliance. The set of comptences to deal with this conflict reinforced previous statements around role clarity, communication and networking skills, as well as resilience. Many interviewees would have wished to have a peer support network at hand to reach out to for advice and support. Putting these two elements, structured training programmes combined with peer learning, together, the ideal approach to developing the competencies necessary to manage integrated care should include a strong focus on case-based learning with the possibility of learning on the job. Ultimately, the goal of managing integrated care should be to design a learning organisation, which can not only react and adapt to the continuously changing environment, but influence and co-design it, together with its partners. As a manager, this requires a skillset around how to build and maintain learning environments, how to use monitoring and evaluation as a positive influencer to reinforce the necessity for change, how to establish a continuous professional development programme within the organisation, and how to reassure and empower professionals in the face of these changes. > \[integrated care programmes\] are innovative and they require from all staff, from low level staff to highest managers and policy makers even, to think about service delivery or their role in what they do differently. Managers set the tone, set the directions, support and strengthen the changes which are not always easy. Make sure that those changes are actually happening so they follow up and monitor or they push, they fight, they push again, they require from their staff or the supervisors. (Interviewee 18) Discussion ========== The question of whether there was a clear difference between competencies for operational and strategic managers was not answered conclusively as many found it difficult to differentiate between the two. While some participants acknowledged that they were useful concepts to structure thinking and discussion, others challenged the whole notion as being set in the current hierharchical system and thinking, and that it needed new technical terms as well as new concepts to describe these roles of the future. One participant went so far as to call for a new language to describe integrated care to capture the innate difference to the status quo. There was also a definitive tendency to see these roles in the context of the system the managers were working in, and as part of a learning journey for managers who gradually progress from more junior to senior roles. Inherently the distinction was made between for example team managers, who would have the oversight of several teams and have a more operational role of implementation, and the system managers, who were seen to have a distinctive policy role, reaching out to stakeholders and providing the vision and framework for integrated care. There was agreement that the competences remained the same, and the question was more around the degree and maturity of the knowledge, skills and attitudes acquired, which made the difference. This ambiguity is reflected in the literature, where management usually is not recognised as a task in itself, but implicated in other activities, which lead to successful integration like change management, quality improvement, communication, organisational culture and leadership, or managing teams \[[@B13][@B24][@B37][@B38][@B39][@B40][@B41][@B54]\]. Similary, Stein (2016) identified the necessity of building competences on all levels of the system as a building block for sustainable integrated care \[[@B42]\]. There were interesting parallels with research regarding the management of networks. In some ways this is inevitable, as networks are a recognised approach to achieving more integrated care \[[@B59][@B60]\]. Indeed, local integration often begins through voluntary networks in which clinicians, people with lived experience and/or managers come together to respond to the needs of a particular geographic or other community \[[@B61]\]. Such networks can be instrumental to governments deciding to form integrated care policies through highlighting the inequalities of access, outcomes and experience caused by fragmentation, and/or to local services delivering practical solutions to improve care within their locality \[[@B62]\]. A challenge for government is often how to replicate the benefits of local voluntary networks in areas in which they have not emerged informally, as mandation can stifle the reciprocity and intrinsic motivations that contribute to the original progress \[[@B63]\]. Network managers are crucial to the success of voluntary and mandated networks but have to encourage engagement and coordinate activity of members with little of the traditional power bases available to them \[[@B64]\]. Success is instead reliant on their ability to develop a shared identity and purpose, to demonstrate that the network will respond to existing incentives and challenges experienced by partners, and to facilitate opportunities for building relationships and trust \[[@B65]\]. Such management work has been termed 'orchestration' and been described as the 11^th^ management role to the ten roles initially outlined by Mintzerg \[[@B66][@B67]\]. The emphasis on 'soft skills', distributing responsibilities, effective communication, and ability to cope with emerging flexibilities mirror the competences which were connected with integrated care managers \[[@B68][@B69]\]. The integrated care manager has to become a boundary spanner \[[@B65]\], who has the power and comptences to overcome conflict, create shared values and collective accountability, and drive disruptive innovation. The importance of leadership in developing initial support and common vision for integrated care, and inspiring professionals and managers to work more collaboratively is again confirmed \[[@B8][@B43]\]. The issue of who is best placed to provide this leadership, particularly in localities in which it does not emerge through existing individuals or networks, remains unresolved. Professionals and managers working together to lead integrated care should present as a powerful coalition as they bring different expertise and legitimacies, but there remains the potential for turf-wars over who should be the most influential ('*the* leader') and a danger that those with less influence, such as people with lived experience and in low paid roles, are excluded from such allegiances \[[@B44][@B45]\]. Furthermore managers have to learn how to engage with new sets of 'professional' leaders who may have different perspectives and incentives to those with a health setting. Work to articulate the competences or characteristics of 'leaders' within integrated care systems reflects what was found in this study for managers \[eg [@B43][@B46]\] -- this potentially suggests that development opportunities for managers in relation to integrated care could usefully be extended to those within other roles. An acknowledgement that the process of integration is collaborative, recursive and ongoing, and requires managers to contiuously work on establishing, revising and reinforcing the purpose, relationships, and trust between all partners reflects findings in network theory \[[@B70]\]. Also confirmed is the need for managers to implement the vision of leaders through undertaking 'the graft' that accompanies any transformation programme \[[@B47]\]. Systems and organisations need to move towards a networked, learning environment, which emphasises co-design, shared responsibilities and an active and continuous approach to learning on the job. So rather than distinguishing between strategic and operational, or manager and leader, the emphasis should be to understand the competences for integrated care and then teaching and living them as part of the culture and vision for integrated care. With experience, these competences are reinforced and thus enable people to move to different levels and roles. So far, no competency framework for integrated care exists, let alone one for managers of integrated care. However, Langins and Borgermans (2015) \[[@B48]\] made a significant first attempt and identified five competency clusters for the health workforce in integrated care. These encompassed patient advocacy, effective communication, team work, people-centred care, and continuous learning -- all of which were reflected in the competences identified in the current study. The "Leadership Competencies for Healthcare Services Managers" \[[@B49]\] blow in a similar horn with communication and relationship management, professional and social responsibility, health and healthcare environment, business, and leadership as the five domains of competences for managers. The significant impact of a strategic and coordinated approach to continuous education and training of all involved was also recognised by extending the Triple Aim and adding the improvement of the work-life balance of staff to the concept \[[@B50]\]. The present exploratory study synthesises all these different frameworks and experiences to identify key competences for managers of integrated care. There is another underlying challenge buried in this discussion and that is the realisation that we are trying to capture new concepts with old technical terms. There is a conflict between the call for shared decisionmaking, shared outcomes and shared accountability, which are then to be implemented and managed by medical directors for integrated care or chief executive officers. The struggle to maintain change and build sustainable integrated care systems is also a struggle between the old and the new power, where the former is held by a few and represented by hierarchies and the latter is held by many and represented by networked organisations \[[@B51]\]. The solution to this struggle may be a recognition that both hierarchy and networks will be required to ensure that dynamic innovations can emerge, but there is sufficient stability and order for these to be implemented consistently \[[@B70]\]. This will however require a common set of values to be adopted, in which those with structural power are willing to concede existing arrangements to new ideas \[[@B52][@B53]\]. Managers will undoubtedly have an important role in achieving such synergies. Limitations =========== There are several limitations to this study, which reflect its exploratory nature. First of all, while there was every effort made to have a balanced representation of all stakeholders and geographic regions, the respondents primarily reflect the clinical-managerial tradition of North America, Europe, Australia and New Zealand. This was partly due to the reach of the network, but also to language and time restrictions. All interviews were conducted in English, which required not only a high level of command of the language, but also the confidence to express oneself in technical terms. Some respondents, specifically from civil society organisations and non-English native speakers, did not consider themselves capable or 'expert enough' to participate in the interviews. Secondly, due to the time consuming nature of the study, not all initially scheduled interviews could be conducted and the number of interviews was limited. This may have lead to the omission of competences or aspects of managing integrated care, which could have shed more light on the complex nature of the task at hand. Thirdly, there has not been triangulation to provide validity that the perspectives of participants regarding their own management reflects the reality experienced by others. Finally, the findings have not been validated yet, but preliminary findings were presented to a workshop at the 19th International Confernce for Integrated Care in San Sebastian, and the feedback informed the finalisation of the study. Conclusion ========== In the myth of Achilles, the baby is dipped in the river Styx to make him invulnerable, but is held by the heel which is therefore not protected. Whilst integrated care programmes contain many vulnerabilities, this research supports our contention that management, and a lack of recognition of and investment in appropriate skills and capacity, remains a consistent weakness. The role has so far received little attention in theory or practice having rather been taken for granted. Internationally there is a common failure to articulate what is different about such management, to actively prepare people to undertake such roles, and to recognise the unique challenges that they face. Further research is needed to understand what is required in general for those managing integrated care, and if there is variation connected to practice contexts, stages of implementation, forms of integration and regional location. The current gaps in knowledge present a considerable vulnerability to the mainstreaming of integrated care as managers are central to embedding new cultures, processes and alliances. There is an urgent need to actively identify, support and train future managers, and to ensure that those already in such roles have time for reflection and learning. A competency framework for integrated care management would help to guide development opportunities, and have potential value within recruitment processes. This should form part of a wider organisational and cultural shift towards the development of learning environments, which build upon the strengths of individuals and foster personal and professional development. Such a movement would also support the necessary shift towards more distributed and equitable management, which is inclusive of individuals, communities and "auxiliary" professions. Above and beyond a conducive systems and organisational context, this study has brought to light that resilience, humility and "an inner fire" are paramount for managers of integrated care to weather the storms and persevere in their endeavours to change not only one organisation, but systems, cultures, and attitudes. It is time to acknowledge their crucial role in taking integrated care to the next level and giving the support necessary to make this change happen. Additional File =============== The additional file for this article can be found as follows: 10.5334/ijic.5440.s1 ###### Management and leadership competency interview guide. The authors are greatly indebted to the participants of the study, and would like to express their appreciation for the willingness to give a significant amount of their valuable time to answer the authors' questions. We also thank the International Foundation for Integrated Care for covering the transcription costs, without which this study would not have been possible. Reviewers ========= Ewan Ferlie, Professor of Public Services Management, King's College London, UK. Professor Henk Nies, PhD, Director of Strategy & Development, Vilans, Utrecht, The Netherlands. Competing Interests =================== The authors have no competing interests to declare.
tomekkorbak/pile-curse-small
PubMed Central
John Alexander McDougall (artist) John Alexander McDougall (c.1810–1894) was an American painter and photographer, known for his portrait miniatures. Born in Livingston, New Jersey, he studied at the National Academy of Design in New York City, and lived for much of his life in Newark, New Jersey. McDougall was good friends with painters George Inness and Asher B. Durand, as well as writers Washington Irving and Edgar Allan Poe, whom he painted. His miniatures, some of which were unusually small, are found in the permanent collections of the Metropolitan Museum of Art and the Smithsonian American Art Museum. He died in Newark on July 29, 1894. He had a daughter and five sons, including the cartoonist Walt McDougall, the artist John A. McDougall Jr. (also a miniaturist), and Harry C. McDougall, proprietor of the Newark Sunday Call. Notes References Category:Year of birth uncertain Category:1894 deaths Category:Artists from Newark, New Jersey Category:People from Livingston, New Jersey Category:American portrait painters Category:Portrait miniaturists Category:19th-century American painters Category:American male painters Category:Painters from New Jersey Category:National Academy of Design alumni
tomekkorbak/pile-curse-small
Wikipedia (en)
Cleanflight best flight controllers As Cleanflight firmware is getting popular among the multirotor pilots, I wanted to make a summary of the flight controllers that can use it. The question is not anymore “Naze32 vs. CC3D”. At the end of 2015 there are more powerful flight controllers with additional features. All supported flight controllers use STM 32bit processors. Most of them, including the Naze32 and CC3D, use the STM32 F103. But there are flight controllers with F3 and F4 processor series. Some of them have integrated OSD (On Screen Display) or PDB (Power Distribution Board). First I will list the F1 controllers, than F3 and at the end the F4 flight controllers. I will put my comments to the boards, that have some additional features, but this is just my personal opinion. Flip32 Series. Sadly there are so many different Flip32 controllers on ReadyToFlyQuads website, that I simply lost my self. I should mention at least the Flip32 AIO, that have additional OSD, PDB, BEC and current sensor on board. I am not sure if it is a good idea to have all the current passing through your flight controller board, but can’t comment this further as I haven’t tested it yet. It is good to have such a good choice of flight controllers, but it is also hard to choose the right one for you. I like the F1 flight controllers with the integrated OSD and will review the Illuminati 32 as soon as it arrives. The OZE32 seems to be a great all-in-one package too. Beside that, my favorite F1 flight controller is still the CC3D. F3 flight controllers have a bit advantage over F1: the STM32 F3 MCU has integrated FPU (floating point unit) and because of this a better performance. I ordered a SPRacingF3 clone, as the price is one third of the official board. Note that Banggood is not giving a single penny to Dominic Clifton and his work on the Cleanflight firmware. So if you decide to order a board not from a official retailer, definitely make a donation to him. F4 boards have some more processing power and will be good for feature firmware development. Both Sparky2 and OpenPilot Revo have great specifications. As far as I know, the OpenPilot Revo is hard to find on the official webstore and the project is shut down. Overall the Sparky2 seems to be the best flight controller for Cleanflight at the moment. Update 05.11.2016: The new Airbot /Flip F4 flight controller is based on the Revo design and can be powered directly from the LiPo battery without additional BEC, which makes it my favourite at the moment. Also on all F4 based flight controllers you are now able to install rapidly evolving new forks of Cleanflight, like Betaflight and Raceflight. If you have tested any of the flight controllers and want to share your experience, leave your comment. Let me know in case I forgot a flight controller or a feature. Update 10.2017: As of October 2017 the most popular flight controller firmware is Betaflight. This firmware based on the previous Cleanflight code got more and more developed and have a lot of new futures. Check out the current Top 5 flight controllers for it. Thank you for reading! Follow DroneHiTech on Facebook and stay tuned for more drone news, reviews and tutorials. Sergey I’m about to try an F3 next. I was looking around at the more full featured flight controllers to play with the autopilot programming. I’m checking out the HKPilot Mega and the Px4Pilot 32Bit. There was a cheap skyline, but I believe no black box. Any thoughts on which board to play with autopilot for the first time? I’m not really sure the cheapest solution, but a working solution is probably a better one 😉 I’ll stop back by and share my thoughts on the f3 😎 Sergey Hi Joshua, the F3 flight controller with Betaflight/Cleanflight is great for FPV Racing or line of sight flights. If you need a FC with AutoPilot functions there are two great flight controllers: DJI Naza or the newest DJI N3, or Pixhawk based board like the HKPilot32. Best wishes, Sergey
tomekkorbak/pile-curse-small
Pile-CC
click "dopal" as in "dope opal" not "do your pal" I draw whenever im not having an anxiety attack Requests & commissions closed There will be spoilers & nsfw content, but both are tagged.
tomekkorbak/pile-curse-small
OpenWebText2
When *not* to sign an e-mail message? - PGP This is a discussion on When *not* to sign an e-mail message? - PGP ; Anne &amp; Lynn Wheeler writes: > there are all sort of short-comings if you believe that digital > signatures translate straight-forward to the same as human signatures. Well, they do, legally. They reduce to exactly the same thing in court: ... Re: When *not* to sign an e-mail message? Anne & Lynn Wheeler writes: > there are all sort of short-comings if you believe that digital > signatures translate straight-forward to the same as human signatures. Well, they do, legally. They reduce to exactly the same thing in court: one party says "he agreed to this," and the other party says "no, I didn't." The actual method of authentication is often irrelevant, since the forgery is often out-of-band. Thus, the handwritten signature may pass the authentication test, but the forger simply manages this by carefully copying an authentic signature. And the digital signature may be impossible to forge without a key, but the forger manages by simply stealing the key. -- Transpose mxsmanic and gmail to reach me by e-mail. Re: When *not* to sign an e-mail message? Mxsmanic wrote: > Andrew Swallow writes: > > >>It is equivalent to a company using a rubber stamp to sign cheques. >>Where there are a thousand people on the pay roll it is quite common for >>the clerks to be given such rubber stamps. It saves the boss a lot of >>writing. > > > In practice, it's a check-signing machine, but your point still > applies; indeed, with a check-signing machine, it resembles digital > signatures even more. Thank you. Yes signing using rubber stamps is a little Victorian. Andrew Swallow Re: When *not* to sign an e-mail message? Mxsmanic wrote in news:[email protected]: >> No, in any western system of law, the person relying on the signature >> (usually the recipient or beneficiary) must prove its validity (e.g., >> a bank relying on my signature on a cheque must validate it against >> its sample signature). If it is contested and goes to court it is >> the bank's burden (to use my example) to satisfy the court that the >> signatures match. > > Which is trivially easy to do, if the bank did indeed look at the > signatures--it is sufficient to show the two signatures in court. No, it is highly inlikely that that would be sufficient for any serious matter. In all likelihood there would be expert witnesses (including specialists in handwriting, forensics, counterfeiting, ink, paper, and on and on) from the bank and a number of other parties involved. > Yes, you do. If the signature matches the model the bank used for > validation, you have to find a way to prove that it's not your > signature, even though it looks the same. See above. It is inconceivable that the standard in any sensible court regarding a handwriting aspect that rises above the trivial or incidental would be your dismissive "looks the same." >> With electronic signatures I have taken on additional burdens that do >> not apply with traditional signatures. For instance, I now carry a >> burden not to be negligent in my keeping the keys safe. And, if the >> signature is disputed, it would fall on *me* to show that they had >> somehow leaked or been compromised (e.g., I might have to show >> Verisign has a corrupt employee). I have taken on (or rather had >> imposed on me) additional responsibility and the need for a wider net >> of trust - things I don't have to do the old-fashioned way. > Still, it is trivially easy to forge a handwritten signature, whereas > it is not feasible to forge a digital signature. It is actually rather difficult to forge a handwritten signature so that it will pass detailed forensic examination rather than a mere quick, casual visual inspection. It is not by accident that signatures have been relied on for many hundreds of years for matters great and small. Moreover it can be easy to forge a digital signature. True, one method, brute forcing the key, is currently computationally infeasible, but that hardly exhausts the possibilities. There are any number of methods of stealing the key, compromising the security (e.g., having the signer foolishly sign a document presented to him), electronically switching which document is presented and which is actually signed, and on and on. Regards, Re: When *not* to sign an e-mail message? Mxsmanic wrote in news:[email protected]: >> No reversal, just harder to lie. > > Exactly. And the consequences are more severe if one is careless. I don't want to adopt a signing system that imposes a severe duty of care regarding keys. As I pointed out before, that is equivalent to having to guard a chequebook in which I have already signed every blank cheque. If you were to propose to someone that he should manage his chequebook that way he'd laugh in your face. It would be seen as not just imprudent but as utterly reckless. And yet that is what you equivalently would impose on me to support your digital signing system. No, I'd much rather have a system where the only requirement was for a single constructive act on my part - a handwritten signature - with no onerous additional obligations before or after. Regards, Re: When *not* to sign an e-mail message? nemo_outis writes: > I don't want to adopt a signing system that imposes a severe duty of care > regarding keys. You prefer a signing system that makes forgery so easy that it's essentially dependent on the honor system? > No, I'd much rather have a system where the only requirement was for a > single constructive act on my part - a handwritten signature - with no > onerous additional obligations before or after. And anyone can write that handwritten signature--you need not even be present. -- Transpose mxsmanic and gmail to reach me by e-mail. Re: When *not* to sign an e-mail message? nemo_outis writes: > No, it is highly inlikely that that would be sufficient for any serious > matter. In all likelihood there would be expert witnesses (including > specialists in handwriting, forensics, counterfeiting, ink, paper, and on > and on) from the bank and a number of other parties involved. The reality is that it's easy to forge handwritten signatures, no matter how much forensic effort you put into checking them. They are fundamentally insecure. > See above. It is inconceivable that the standard in any sensible court > regarding a handwriting aspect that rises above the trivial or incidental > would be your dismissive "looks the same." That's the whole basis of handwritten signatures. If they look the same, they pass. > It is actually rather difficult to forge a handwritten signature so that > it will pass detailed forensic examination rather than a mere quick, > casual visual inspection. Examples? > It is not by accident that signatures have > been relied on for many hundreds of years for matters great and small. It has been relied upon because there has never been anything else. > Moreover it can be easy to forge a digital signature. True, one method, > brute forcing the key, is currently computationally infeasible, but that > hardly exhausts the possibilities. There are any number of methods of > stealing the key, compromising the security (e.g., having the signer > foolishly sign a document presented to him), electronically switching > which document is presented and which is actually signed, and on and on. Re: When *not* to sign an e-mail message? And many Asians continue to use the chop system rather than signatures. But we were discussing handwritten versus digital signatures. Regards, Re: When *not* to sign an e-mail message? Mxsmanic wrote in news:[email protected]: > nemo_outis writes: > >> Handwritten and digital signatures are not equivalent - the reference >> to both as "signatures" is at best an analogy, at worst a deception. > > Legally, they are identical. No, they are not legally identical. As just one blatant difference digital signatures are not recognized as valid in many jurisdictions. >> PPS A different signature on my cheques than my contracts? ...or >> on my credit cards? ...or on my letters? ...or on my...? Gimme a >> break! I do not have a quiver of signatures, nor do most people. >> Why don't we talk about this universe rather than the parallel one >> you might prefer? > > Why don't you refrain from personal attacks in your arguments? The ad > hominem undermines your credibility. What personal attack? I asked him to speak of the universe in which we currently reside. You know, the universe in which virtually no one uses multiple handwritten signatures. It is he with his nonsense who has indicted himself as a fool - he needed no help from me. But speaking more broadly, yes, I do infer that a man who says foolish things is a fool. It's called proceeding on the evidence. However, my initial judgment is graciously open to appeals from him pleading he was hasty, thoughtless, or careless rather than a fool. Regards, Re: When *not* to sign an e-mail message? nemo_outis wrote: > "Non scrivetemi" wrote in > news:[email protected] tonsmith.info: > >> Hi, >> >> I'm wondering if there are any hypothetical situations where one would >> NOT want to sign an email message they are sending to another party. >> In my opinion, there are no valid reasons not to sign a message. >> >> Can anyone point out a situation to me where *not* signing would be >> advantageous (excluding off course that the message may be smaller if >> it's not signed)? >> >> TIA >> > > > > The whole question of digital signing and non-repudiation is fatally > flawed. > > Why? Because it reverses the burden of proof. > > With existing handwritten signatures the burden of verifying the signature > falls on the recipient (e.g., banks re a cheque). With digital signatures > the sender must prove he didn't send it (e.g., he might argue his key had > been stolen). > > The traditional basis of signatures is that the burden lies on the fellow > relying on them; digital signatures reverse 1000 years of legal and > commercial practice. While arguments can be advanced why such a reversal > might be desirable they have to overcome this "who proves" hurdle and > cannot rely solely on their "gee-whiz" gimcrackery as sufficient > justification. > > Regards, > The legal standing of digital signatures in different nations is documented in Dr. Simone van der Hof's "Digital Signature Law Survey" at. Re: When *not* to sign an e-mail message? > The reality is that it's easy to forge handwritten signatures, no > matter how much forensic effort you put into checking them. They are > fundamentally insecure. Well then, why don't you pen a series of letters ostensibly from George Washington and sell them at immense profit? >> It is not by accident that signatures have >> been relied on for many hundreds of years for matters great and >> small. > It has been relied upon because there has never been anything else. While every system has limitations and deficiencies, written signatures have worked well for a very long time, across numerous cultures and legal systems, for a very wide range of purposes from casual letters to multi- billion dollar deals and international treaties. Moreover, the practices and principles of a number of important institutions and social and economic practices have been refined to work on an integrated basis with such handwritten signatures. Despite the enthusiasm of technophiles, it remains to be shown whether digital signatures can attain anything like such widespread and longterm utility. >> Moreover it can be easy to forge a digital signature. True, one >> method, brute forcing the key, is currently computationally >> infeasible, but that hardly exhausts the possibilities. There are >> any number of methods of stealing the key, compromising the security >> (e.g., having the signer foolishly sign a document presented to him), >> electronically switching which document is presented and which is >> actually signed, and on and on. > > These are out-of-band compromises of the system. I don't give a fig about the modality of compromise (except as the most incidental of trivia). I care about whether and to what degree digital signature systems are susceptible to any form of compromise, what mitigative measures are necessary to prevent such compromise, on whom the burdens (technical, legal, ecopnomic, or whatever) fall, and to what extent such problems diminish the social utility of such signature systems. If digital signatures are susceptible to compromise it matters little to me (or anyone else I suspect) whether their failures are attributable to factoring large numbers or putting a keylogger on someone's computer. Regards, PS For instance, one mitigative measure to preserve ANY utility in digital signatures, potentially a very onerous one, is the need to keep the key secret - possibly for decades! Re: When *not* to sign an e-mail message? nemo_outis wrote: > Andrew Swallow wrote in > news:[email protected]: > > >>Thank you. Yes signing using rubber stamps is a little Victorian. >> >>Andrew Swallow > > > > And many Asians continue to use the chop system rather than signatures. > > But we were discussing handwritten versus digital signatures. Governments and corporations use seals rather than signatures on important documents and have done for centuries. The British kings even had different seals for personal and state use.http://www.battle1066.com/g223.shtml You continue to require digital signature to supply a level of security millions of times higher than handwritten signatures. When we point this out you discard this information and reply with insults. You then cheat and chose the weakest form of signing of the grounds that it is stronger. Andrew Swallow Re: When *not* to sign an e-mail message? Mxsmanic wrote in news:[email protected]: > nemo_outis writes: > >> I don't want to adopt a signing system that imposes a severe duty of >> care regarding keys. > > You prefer a signing system that makes forgery so easy that it's > essentially dependent on the honor system? No, it is not "essentially dependent on the honour system." In your eagerness to make a point you have crossed over into transparent intellectual dishonesty. Five hundred years and more of social, legal and commercial practice says handwritten signatures are adequate to the task. Actually, to many tasks. Yes, there are deficiencies and weaknesses in the handwriting system - as with any system - but it has been, on the whole, satisfactory. Now that doesn't mean one should close one's mind to alternatives. Indeed, in time, we may decide that the digital alternatives are superior. More likely we will find that they are superior for some uses and inferior for others. However, digital signatures are in their infancy - it would be not just premature but rash to say they should supplant handwritten signatures. >> No, I'd much rather have a system where the only requirement was for >> a single constructive act on my part - a handwritten signature - with >> no onerous additional obligations before or after. > > And anyone can write that handwritten signature--you need not even be > present. Once again, in your eagerness you have grossly misstated your case. No, only *I* can write *my* signature. Others can only produce simulacra which approximate it to a greater or lesser degree. You are confusing and conflating the verification and validation of handwritten signatures with their production. But whatever deficiencies handwritten signatures may have, digital signatures are even worse - they can be counterfeited *perfectly* rather than approximately by someone who manages to get the key (which would be a very significant risk for many in the real world). Regards, Re: When *not* to sign an e-mail message? Andrew Swallow writes: > You continue to require digital signature to supply a level of > security millions of times higher than handwritten signatures. When > we point this out you discard this information and reply with insults. > You then cheat and chose the weakest form of signing of the grounds > that it is stronger. it turns out that the issue of digital signatures with integrity and authentication is different than the issue of human signatures with intent. one might be tempted to use an example of comparing the color orange in oranges with the color red in apples (except they have closer relationship being both colors and both involve fruit). in any case, there was the whole attempt to try and establish the non-repudiation flag in digital certificate standards ... which eventually fell into much disrepute, in large part because the issue of integrity and authentication (associated with digital signatures) is unrelated to intent (associated with human signatures). Re: When *not* to sign an e-mail message? Andrew Swallow wrote: >> But we were discussing handwritten versus digital signatures. > > Governments and corporations use seals rather than signatures on > important documents and have done for centuries. The British kings even > had different seals for personal and state use. And the signature of Karl the Great (or Charlemagne, as the French call him) was actually just a little line that he added to the official seal... Re: When *not* to sign an e-mail message? "nemo_outis" wrote: >> The reality is that it's easy to forge handwritten signatures, no >> matter how much forensic effort you put into checking them. They are >> fundamentally insecure. > > Well then, why don't you pen a series of letters ostensibly from > George Washington and sell them at immense profit? Because he can't get the right (old enough) paper? ;-) Juergen Nieveler -- Modesty is a vastly overrated virtue Re: When *not* to sign an e-mail message? > You continue to require digital signature to supply a level of security > millions of times higher than handwritten signatures. When we point > this out you discard this information and reply with insults. You then > cheat and chose the weakest form of signing of the grounds that it is > stronger. > > Andrew Swallow There is no evidence that digital signatures provide security "millions of times higher." You have focussed on one narrow aspect of their use: the difficulty of computationally breaking the key. However, the breaking of the key is only one potential failure mode for a digital signature system. Signature systems must operate in a far broader legal, social and economic milieu than that with respect to all their functions, including security. It is the end-to-end security, and social utility generally, which must be considered, rather than merely one aspect of calculating the key. And, as I have pointed out, the digital signature system can impose a number of burdens on users, such as the requirement to keep keys secret for a very long time, or to extend trust to third parties (e.g., Verisign). It is an open question whether many people can successfully bear such burdens, for if they are not sustainable generally in ordinary human intercourse then the application of digital signatures will be reduced to a narrow niche. Regards, Re: When *not* to sign an e-mail message? Andrew Swallow wrote in news:dui7ql$6se$1 @nwrdmz01.dmz.ncs.ea.ibs-infra.bt.com: > nemo_outis wrote: > >> Andrew Swallow wrote in >> news:[email protected]: >> >> >>>Thank you. Yes signing using rubber stamps is a little Victorian. >>> >>>Andrew Swallow >> >> >> >> And many Asians continue to use the chop system rather than signatures. >> >> But we were discussing handwritten versus digital signatures. > > Governments and corporations use seals rather than signatures on > important documents and have done for centuries. The British kings even > had different seals for personal and state use. > http://www.battle1066.com/g223.shtml > > You continue to require digital signature to supply a level of security > millions of times higher than handwritten signatures. When we point > this out you discard this information and reply with insults. You then > cheat and chose the weakest form of signing of the grounds that it is > stronger. > > Andrew Swallow There is no evidence that digital signatures provide security "millions of times higher." You have focussed on one narrow aspect of their use: the difficulty of computationally breaking the key. However, the breaking of the key is only one potential failure mode for a digital signature system. Signature systems must operate in a very broad legal, social and economic milieu with respect to all their functions, including security. It is the *end-to-end security,* and the social utility generally, which must be considered, rather than merely the one aspect of calculating the key. And, as I have pointed out, the digital signature system can impose a number of burdens on users, such as the requirement to keep keys secret for a very long time, or to extend trust to third parties (e.g., Verisign). It is an open question whether many people can do this successfully, for if these additional requirements are not sustainable generally in ordinary human intercourse, then the utility of digital signatures will be largely vitiated and their application reduced to a narrow niche. In short, while digital signaturs are strong in one aspect, they are tediously and burdensomely deficient in other aspects. Moreover, they differ from handwritten signatures in yet other ways which invites confusion, abuse and exploitation of the public which is not aware of such lurking dangers. Regards, PS That encrypted email has never achieved even modest acceptance is strongly suggestive of how unenthusiastic the general public is likely to remain regarding digital signatures. Re: When *not* to sign an e-mail message? Juergen Nieveler wrote in news:[email protected]: > "nemo_outis" wrote: > >>> The reality is that it's easy to forge handwritten signatures, no >>> matter how much forensic effort you put into checking them. They are >>> fundamentally insecure. >> >> Well then, why don't you pen a series of letters ostensibly from >> George Washington and sell them at immense profit? > > Because he can't get the right (old enough) paper? ;-) > > Juergen Nieveler Absolutely correct. Real handwritten signatures do not "hang in the air" but exist in a physical context. That physical context (the ink used, the paper, writing pressure and speed, the other printing or writing on the page, etc.) can play a role in verification of a handwritten signature and distinguishing it from a counterfeit. Regards, Re: When *not* to sign an e-mail message? nemo_outis writes: > No, they are not legally identical. As just one blatant difference digital > signatures are not recognized as valid in many jurisdictions. That's a local determination, not a global principle. -- Transpose mxsmanic and gmail to reach me by e-mail. Re: When *not* to sign an e-mail message? Mxsmanic wrote in news:[email protected]: > nemo_outis writes: > >> No, they are not legally identical. As just one blatant difference >> digital signatures are not recognized as valid in many jurisdictions. > > That's a local determination, not a global principle. I have no idea what your quibbling and weaseling is intended to convey. And neither, I suspect, do you. You stated that digital and handwritten signatures were legally identical. You made a statement of [alleged] fact, an absolute and unqualified statement. And that statement is patently false!
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Pile-CC
Nissan Maxima Fuel and Fuel System Questions Hi! I just bought my first maxima today. It's a 95 GXE automatic. unfortunately it didn't come with the owner's manual, I'll have to buy one online I guess. I just read something that said some models need premium grade gasoline, does anyone know if this is true for the one I drive? thanks! I have a 2000 maxima 6cyl auto. Sometimes when I go some place, park it for a while and then come out and start it up it misfires. When I get home and park it in the garage it has a smell of rotten eggs. The next day it runs perfect. Could it be a fuel injector not working correctly? I think I read in a mechanic magazine that the gasoline sometimes coats the fuel injectors. Has anyone heard this or knows what the problem might be?? thanks in advance for your answer. Paul G I have a 91 maxima, low miles for the age (abour 110). One day it just started running very rough, like a cylinder wasn't firing. I don't know enough to diagnose it though. Mechanic said one piston wasn't firing due to clogged fuel injector. Naturally, it's like a million dollars to replace it (and the rest, might as well based on the age). I tried some fuel injector cleaner off the shelf, but it didn't work. The car isn't worth but $1200 so I don't want to spend much to get it running smoothly - any ideas? Thanks! Hi Ovey...... I will be willing to bet your having trouble with one of the ignition coils !!!! To my susprise I discovered that there are six ignition coils... one for each spark plug. With 85.000 miles on my car I decided to replace all my spark plugs thinking at the same time I might be able to find out which cylinder was misfiring by looking at each plug. Only one was a little bit darker than the other five so I decided to replace the coil ot this cylinder. Presto ! Problem was solved. My car has been running great ever since. Hope this helps you. Replaceing the plugs and the coil is really easy if your just a little bit mechanically inclined. The coil only cost $69.99 at Auto Zone. I can only imagine how much it would have cost me at a Nissan dealer. Paul i wanted to know if it was ok to put regular gasoline (not premium) in my 2007 nissan maxima. i consulted the owner's manual and on page 9-3, they say that they recommend 91 AKI, which is equivalent to 96 octane. i have never seen octane higher than 93....so i dont know what they expect there. the manual goes on to say that i can use "regular"....but their definition of regular is 87 AKI, which is octane 91 according to the manual. every gas station i go to has "regular" defined as 87 octane....and you dont see any thing about AKI. furthermore.....i never see "91 octane" anyway...its all 87, 89, and 93. What Gives!! can i use regular or not?? and where the %&*% do they expect me to find 96 octane?? i assume the drop in performance that the manual speaks about would be unnoticeable to teh average driver, am i correct? I just bought an 08 Maxima with same engine as your 07 and they say you can run regular fuel but car is more efficient if premium is used. My son has same engine and he runs reg. most of the time and a tank of premium every third fill up. The manual and a mechanic I trust told me not to use any fuel additives in the tank since it will effect the computer that regulates fuel system. Your engine may 'ping' some with reg. but it won't hurt it......good luck right...and I just made a short trip of 700 miles and I ran 87 octane first tank and the mid fuel, i think 89 in the second tank(just filled ) Got just at 27.5 mpg.....on regular. I will let you know if 89 gets any better milage. You will not see any difference until you get several tanks as it will be mixed. 87 and 89 are too close to see any difference. 87 and 93 you at most will see a 1-2 mpg difference. Then again it will depend on your driving and road conditions. I've noticed that on occasion the day after I fill the gas tank, turn the gas cap three times after filling up the Service Engine light will go on and stay on until I have it cleared by a tech. It seems that when I do a fill up it happens. Not when the tank is at 3/4-1/2-1/4. Anyone out there experience the same problem? Is there a possibility that I may need a new gas cap where air is getting through the seal causing this to happen? Or does anyone have a solution ? Other than that there's been no operating problems with the light staying on. Only a nuisance.Thanks in advance to those who may be able to help me with this. I have a 2000 Maxima SE 4-speed automatic with 120K miles and when I am waiting at a traffic light or stuck in traffic, the car will stay "on" and then after about 20 seconds or so the idle speed kinda goes down from 750 rpm to near 500 rpm and then the car shuts off. This has been happening for the last couple of weeks on a regular basis. I turn the car back on without difficulty and press the gas hard to make sure it stays and then quickly put it into D. It doesn't happen on the highway when I am cruising at 60 mph. I went to the local Midas and they thought that if the "check engine" light was on that would lead them to figuring out the problem. No such luck, the light is not on. The mechanic thinks it may be a problem with the Throttle Position Sensor or some other acronyms; basically he thought there was some sort of intermittent communication error between the engine and the computer that is causing this. He didn't think it was the fuel injectors or the fuel pump. If anyone has idea what might be causing this, I would appreciate it. Thanks. I actually did take it to the dealer last year and they told me that the MAF required replacement. Well, I had it replaced for about $300ish and it has been fine since. Well...then now yesterday, the engine was idling a little rough when I first started (I guess I didn't give it enough time to warm up) and now the "Service Engine Soon" lamp glows so now I have to get it checked out (again) with the OBD tool. Thinking about going back to the dealer...will see. The car runs fine and doesn't cause any stalling/rough idling. Maybe it was a one time thing...but at some point I'll have find out what the code is for and clear it and hopefully it won't return. If you even still have the car it may be the idle flow controller up by air filter area. My '01 Maxima recently started doing the exact same thing & turned out to be just that. First time this car has been in the shop since I got it 10 years ago! I have a 08 Maxima 3.5. I live in the upper midwest with cold weather the norm. I was idling through a 2 hour display of holiday lights, which weren't that great. I lowered the window and smelled coolant. Next day I was at the drive-up bank and waited about 10 minutes and smelled it again. I don't seem to be loosing coolant since the level is staying at the same point. Has anyone else had this or a similar problem? My 1996 Nissan Maxima will not start unless the fuel pump fuse (15A) is removed. Once removed the car will start and the fuse is put back in. The Nissan dealership said it was the oxygen sensors and the starter. The parts replaced include the fuel pump and fuel pump relay sensor, MAF and MAP sensor, fuel injector, crankshaft sensors. Any ideal if the dealer could be correct?
tomekkorbak/pile-curse-small
Pile-CC
Risk of post-transplantation diabetes mellitus is greater in South Asian versus Caucasian kidney allograft recipients. South Asians have increased risk for type 2 diabetes mellitus compared with Caucasians in the general population, but data for the development of post-transplantation diabetes mellitus (PTDM) is scarce. In this retrospective analysis, data was extracted from electronic patient records at a single centre (2004-2014). Caucasians were more likely to be male, with higher age and BMI than South Asians. Case-control matching was therefore undertaken to remove this bias, resulting in 102 recipient pairs. Median follow-up was 50 months (range 4-127 months). Matched groups had similar baseline characteristics, although South Asians compared with Caucasians received more deceased-donor kidneys (74% vs. 43%, respectively, P < 0.001) and were more likely to be CMV positive (77% vs. 43%, respectively, P < 0.001). PTDM incidence was significantly higher in South Asians versus Caucasians (35% vs. 10%, respectively, subhazard ratio 4.2 [95% CI: 2.1-8.5, P < 0.001]). Donor type had significant interaction with ethnicity, with the observed difference in PTDM rates between ethnicities most visible with receipt of deceased-donor kidneys. No significant difference was detected in allograft function, rejection episodes, adverse cardiovascular events or patient/graft survival. South Asians have increased risk of PTDM, especially recipients of deceased kidneys, and recognition of this allows appropriate patient counselling and development of targeted strategies.
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PubMed Abstracts
Right now, the three leading candidates for the Democrat presidential nomination are all septuagenarians. On Election Day next year, Bernie Sanders will be 79, Joe Biden will be 78, and Liz Warren will be 71. It may be over for the two oldest. Bolshevik Bernie just suffered a heart attack and had two stents inserted. (Now he's Bionic Bernie.) Joe, often fumbling for words, has appeared "frail" from the get-go. And we shouldn't forget the appearance of influence-peddling in Ukraine and China. That leaves Liz, who by comparison to the other two is a spring chicken. But Senator Warren has her own issues. On October 7, Fox News's Tucker Carlson aired a montage of Warren on the campaign trail where she repeatedly asserts that she was "visibly pregnant" and that her employer "wished me luck" and then "hired someone else." Watch the video montage and notice how similar her deliveries are. At each venue, she retells her story with the same well rehearsed inflections and mannerisms. These canned performances are all the more embarrassing because they repeat a lie. Earlier on October 7, the Free Beacon ran "County Records Contradict Warren's Claim She Was Fired over Pregnancy" by Collin Anderson. The article included the 12 pages of the minutes of the school board meeting in an easy-to-navigate SCRIBD box where the parts concerning Warren are circled: Minutes of an April 21, 1971, Riverdale Board of Education meeting obtained by the Washington Free Beacon show that the board voted unanimously on a motion to extend Warren a "2nd year" contract for a two-days-per-week teaching job. That job is similar to the one she held the previous year, her first year of teaching. Minutes from a board meeting held two months later, on June 16, 1971, indicate that Warren's resignation was "accepted with regret." Also on October 7, the Media Research Center's NewsBusters ran "Nets Ignore Warren's Tall Tale She Was Fired from Job over Pregnancy" by Kristine Marsh: Just like in 2016, the networks have done their best to ignore Democrat presidential candidate scandals and lies while harping on everything surrounding Donald Trump. After capitalizing on her grossly exaggerated Native American ancestry, frontrunner Elizabeth Warren has been caught in another lie, by her own words from twelve years ago. However, you wouldn't know this if you only watched ABC, NBC and CBS. ... Only Fox News has been covering the story, thus far. On October 8, the Media Research Center ran "Warren Doubles Down on Claims She Was Fired in '71 for Being Pregnant" by Brittany M. Hughes. The article embeds two tweets Warren made on Oct. 8 where she sticks to her story. Hughes writes: "Now, it seems she's again grasping at anecdotal evidence for why she was allegedly fired from her teaching job, suggesting she simply assumed she was let go for being pregnant (despite previously indicating she'd left of her own accord)." On October 9, Legal Insurrection ran "Elizabeth Warren's Pregnancy Discrimination Fib Uncovered by Bernie-Supporting Socialist, Not 'Right Wing' as Warren Claims" by William A. Jacobson, professor of law at Cornell, who reported that the genesis of this latest "fib" of Warren's was Meaghan Day, writer for the socialist magazine Jacobin. The controversy seems to have started on October 1 with a Twitter war. On October 10, National Review ran "The Media Scramble the Jets for Elizabeth Warren's Lies" by Kyle Smith, who gives a rundown of how the establishment media have been covering for Liz's latest lie: "The more the media behave like the DNC's propaganda arm, the more Americans will dismiss them as such." Maybe Liz is suffering from some memory issues. After all, she's old. Or maybe she's just a chronic and habitual liar. Indeed, maybe she engages in compulsive or pathological lying. Regardless of the etiology for Lyin' Liz's stories, we need to get a better idea of what kind of character and temperament this woman has and whether she's fit to be president. That's why Tucker's video montage (above) is so damned damning: Liz is quite the little actress. It's depressing that so many Americans buy Warren's kind of politicking. She sashays on stage like some celebrity, waving to those assembled, and then embraces some supporter, some local stooge whom I doubt she knows. Campaigns should be more like job interviews than fan fests. Folks need to develop a better "sense" about others, especially our celebrity politicians. So who is the real Liz Warren? Maybe she's like that leopard up on Mt. Kilimanjaro. No one knows what it was doing up there; maybe it was up to no good. On January 30, Bloomberg aired "Sen. Elizabeth Warren Says Capitalism without Rules Is Theft," a video interview conducted by Joe Weisenthal, who asks the senator about her wealth tax, which she had unveiled six days earlier. Warren displays her usual antics as she explains her new tax and tries to justify grabbing trillions of dollars from the tiniest sliver of Americans. As a former special needs teacher, perhaps Liz thinks Weisenthal has a disability, because she's rather condescending, talking about the "tippy top" paying their "fair share." In March of 2018, the Mises Institute ran "Another Reminder that Elizabeth Warren Is a Fraud" by Tho Bishop: Elizabeth Warren's entire career has been based on a lie. I speak, of course, of the notion that she's some sort of expert on the financial sector. Not only is the Senator from Massachusetts bad on basic economics ... but she is ignorant of basic facts that played out during the financial crisis. Now we're getting to Liz's "Big Lie" — that Warren is an expert on finance, business, and the economy. But what business has Warren ever run, much less created? Warren wants to "break up Big Tech," but what does she know about technology? Warren is a lawyer, and as an affirmative action hire at Harvard Law, we might wonder just how good of a lawyer she really is. On October 9, the Wall Street Journal ran "Elizabeth Warren Vows to Remake Capitalism. Businesses Are Bracing" by Greg Ip and eight other writers. You see, Warren has lots of plans for "remaking" American capitalism. Warren doesn't want to fine-tune and improve our system; she wants to replace it. Liz is more concerned about social justice, equality, redistribution, the damned climate, and expanding the size and scope of the central government than she is with the production of the goods and services that private enterprises work to provide. Liz seems nothing less than a wrinkled older version of Alexandria Ocasio-Cortez. But although she is on board with all the socialist programs of the other Democrat candidates, Warren has nonetheless repeatedly assured us, "I am a capitalist to my bones." Right, but why on Earth would anyone believe her? Jon N. Hall of ULTRACON OPINION is a programmer from Kansas City. Image: Edward Kimmel via Flickr.
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OpenWebText2
A network meta-analysis of progression free survival and overall survival in first-line treatment of chronic lymphocytic leukemia. A limited evidence exists regarding comparisons of clinical effectiveness of available therapies for first-line treatment of chronic lymphocytic leukemia (CLL). We compared available therapies for treatment-naïve, symptomatic CLL regarding progression free survival (PFS) and overall survival (OS) in all the identified random control trials and in subgroups composed of younger/fit and older/unfit patients, using a Bayesian network meta-analysis. In younger/fit patients we obtained median of projected mean PFS of: 19, 26, 31, 43, 51 and 75months for chlorambucil, fludarabine, alemtuzumab, fludarabine with cyclophosphamide (FC), bendamustine and fludarabine with cyclophosphamide and rituximab (FCR), respectively. We noted median OS of: 59, 66, 66, 70months for FC, chlorambucil, FCR and fludarabine, respectively. In older/unfit patients we noted PFS of: 16, 17, 24, 30, 60months for chlorambucil, fludarabine and chlorambucil with ofatumumab (OClb) or rituximab (RClb) or obinutuzumab (GClb), respectively. We obtained median OS of: 44, 58, 59 and 90months for fludarabine, RClb, chlorambucil and GClb, respectively. Our results suggest that: (1) FCR has higher potential of preventing CLL progression in younger/fit patients over four therapy options, which were subject of previous meta-analysis but also over bendamustine; (2) in these patients FCR does not entail prolonging of OS in comparison with chlorambucil and it is outperformed by fludarabine; (3) in older/unfit patients GClb demonstrates longer projected PFS than all assessed comparators; (4) in this group GClb has also the highest potential of increasing OS.
tomekkorbak/pile-curse-small
PubMed Abstracts
Story highlights Further tests on George Michael's body needed, police say Star died on Christmas Day at age 53 (CNN) An autopsy on the body of pop star George Michael proved inconclusive and further tests will be needed, UK police said Friday. The Grammy-award winning star, who was 53, was found dead at his home in Oxfordshire, England, on Christmas Day. Thames Valley police, the local force, said a postmortem examination was carried out on Thursday, "The cause of death is inconclusive and further tests will now be carried out.," the statement said. "The results of these tests are unlikely to be known for several weeks." In a statement shortly after his death, his manager Michael Lippman said he believed the singer suffered heart failure. His partner, Fadi Fawaz, said he found him dead in bed alone when he came to the house on December 24. Thames Valley police said a file would be prepared for the Oxfordshire coroner. Read More
tomekkorbak/pile-curse-small
OpenWebText2
JAKARTA, Indonesia — The party had the feel of 1960s America, almost. A group of women, thrilled to get a break from the daily routine of hanging laundry and shuttling their children to and from school, sat in a circle, listening to a friend hawk plastic storage bowls in a dizzying array of pastels. Some shushed babies on their laps; others occasionally leaned in for juicy pieces of news. The women were, in fact, at a modern-day Tupperware party in the company’s biggest market. The twist? That market is halfway around the world from the product’s Massachusetts birthplace — in Indonesia. Once a fixture in middle-class American kitchens, Tupperware has become a bit of an afterthought in its home country even as its popularity has risen abroad. (Germany was the top marketplace until Indonesia slid past it two years ago.) Indonesia is, in many ways, in Tupperware’s sweet spot. As the economy has taken off in recent years, an expanding middle class now has more disposable income for containers of all shapes and sizes that are sturdier than those found in local markets. And, as in 1960s America, many women stay at home to keep house and raise their children, creating a captive audience for parties run by saleswomen who have begun to sidle past conservative social mores and into the work force.
tomekkorbak/pile-curse-small
OpenWebText2
Assessment of erectile dysfunction in diabetic patients. Erectile dysfunction (ED) aetiology is multifactorial, including endocrine, neurological, vascular, systemic disease, local penile disorders, nutrition, psychogenic factors, and drug-related. This study was performed to compare the relevant comprehensive biochemical parameters as well as the clinical characteristics in diabetic ED and healthy control subjects and to assess the occurrence of penile neuropathy in diabetic patients and thus the relationship between ED and diabetes. A total of 56 patients accepted to undergo assessment for penile vasculature using intracavernosal injection and colour Doppler ultrasonography. Of the 56 diabetic patients, 38 patients were found with normal blood flow and thus they were considered as the diabetic-ED group, whereas, ED diabetic patients with an arteriogenic component were excluded. These patients with an age range between 17 and 58 years, complaining of ED, with duration of diabetic illness ranging from 2 to 15 years. The Control group comprised of 30 healthy subject aged between 19 and 55 years. Peripheral venous levels of testosterone, prolactin, follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), malondialdehyde and glycosylated haemoglobin (HbA(1)c) were obtained in all subjects. Valsalva manoeuvre and neurophysiological tests were also determined. Testosterone, prolactine, FSH, LH, and TSH hormones of the diabetic patients were not significantly different from those of the control group. Diabetic patients with ED have higher HbA(1)c and oxidative stress levels while the R-R ratio was significantly decreased. Bulbocavernosus reflex latency was significantly prolonged, whereas its amplitude, the conduction velocity and amplitude of dorsal nerve of penis were significantly reduced in the diabetic patients. We concluded that although ED is a multifactorial disorder, yet, the present study revealed that in ED patients without arteriogenic ED a neurogenic component is present. Furthermore, the complex effect of the Valsalva manoeuvre on cardiovascular function is the basis of its usefulness as a measure of autonomic function. Thus, it can be of value in the diagnosis of ED although these hypotheses require follow-up in a large study cohort.
tomekkorbak/pile-curse-small
PubMed Abstracts
Electric lanterns have been proposed with selectively directional bulb and reflector combinations. Such a lantern is shown in U.S. Pat. No. 4,447,863 to Fenne. In this patent, however, the rotation of the bulb and reflector is accomplished manually. Fenne does not provide for oscillation of the bulb/reflector combination by selectively activated means within the lantern. Similarly, the patent of Dunbar (U.S. Pat. No. 4,129,899) provides a flashlight with a rotatable lamp holder. Again the lamp holder, reflector and bulb combination are articulated manually. Dunbar does not provide means for selectively oscillating the reflector/bulb combination. U.S. Pat. No. 1,991,753 to Kurlander shows an adjustable light diffuser in a electric lantern. The light diffuser is manually adjustable and moves along the axis of the lamp/reflector combination to adjust the beam of light from a tight beam to a broad flood. Oscillating movement is not disclosed. The patent to Schwartz (U.S. Pat. No. 3,603,783) shows magnetic lamp focussing and switching. A motor drive is not provided, nor is there oscillating movement of the bulb and reflector. The movement of the switch of Schwartz indicates the direction of movement of the bulb. Oscillation is not provided for as the bulb moves only in a single direction when the switch is activated. The patent to Webber (U.S. Pat. No. 762,215) is directed to the field of searchlights, not hand held lanterns or flashlights.
tomekkorbak/pile-curse-small
USPTO Backgrounds
BDSM Katy Kiss, Dee Williams and Matt Williams part 3 Happy Halloween! Today we offer the amazing Katy Kiss for your sexual destruction on this most awesome holiday. Bound on her back with her arms securely bound in a brutal strappado position, Kati is about to get the throat fucking of her life. Dee and Matt bring the cock and soon our tiny red head is struggling to breath as we stuff inch after inch of cock down her helpless throat. Kati is fucked and fucked hard from both sides. She cums and cums while struggling to get air from the cock that fill her face hole.
tomekkorbak/pile-curse-small
Pile-CC
Prosecutors say three men accused of conspiring to bomb a Kansas mosque and an apartment complex housing Somali refugees also discussed killing the refugees' white landlord because he rented to Muslims. The allegations are included in new court filings ahead of a Wednesday hearing to determine if one of the men, Gavin Wright, should be freed pending his trial. Wright and co-defendants Curtis Allen and Patrick Stein were arrested in October 2016. The three men face charges of conspiring to detonate truck bombs at the apartment complex where Somali immigrants live. Wright's attorney says Wright wasn't aware that his co-defendants intended to actually carry out the attack and portrays him as a lonely man desperate to find friends after moving to Liberal in southwestern Kansas. But prosecutors submitted transcripts of profanity-laden recordings of the men discussing their plans that paint a more damning picture of Wright. The court filings say the group's plans for violent action "became more specific and more advanced." The filings say during regular meetings in August and September 2016 at Wright's business the group, called the Crusaders, selected a target, purchased equipment and gathered chemicals and other materials to start making homemade explosives. The filings say during interactions with an undercover FBI employee, Stein said the Crusaders planned to attack Muslims in southwest Kansas. "Stein explained that the purpose of the attack was "to take them [the Muslims] out...,'" the court filings say. The filings say FBI agents arrested Stein on Oct. 14, 2016, during a third meeting with the undercover FBI employee, "shortly after (Stein) delivered approximately 300 pounds of urea to the undercover employee for use in assembling an explosive device. Wright was arrested later on the day of Oct. 14. Allen was already in custody, having been arrested three days earlier for domestic violence. The court filings provide further insight into the case against Wright, Allen and Stein, including background information on anti-Muslim statements they're accused of making and the transcripts of conversations where they discussed plans to carry out the bomb plot.
tomekkorbak/pile-curse-small
OpenWebText2
Diet drinks not 'diet' after all - Mz http://www.medicalnewstoday.com/articles/315101.php ====== life2hack It is just 'diet' on the label, nothing more than that. As far as i understand it is a marketing stunt performed by big companies to lure more customers. personally i do not take that diet sh*t.
tomekkorbak/pile-curse-small
HackerNews
Q: In Angular, can I bind the emited output of a component directly to a property? My main application component interacts with sub components through @Output decorated properties on the subcomponent. The output properties use and EventEmitter<>(). Often the property emits a simple boolean or number. I would like to bind this output directly to properties in the main application. But am failing to do so. What I am doing at the moment is: //In my sub component: @Output() subProperty = new EventEmitter<boolean>(); //In my main template: <sub-component (subProperty)="setPropertyValue($event)"></subcomponent> //In my main component (this I would like to avoid): setPropertyValue(event) { this.mainProperty = event; } What I wanted to do was avoid the function in my main component and bind directly to my property, but the below code doesn't work: //In my sub component: @Output() subProperty = new EventEmitter<boolean>(); //In my main template: <sub-component (subProperty)="mainProperty"></subcomponent> Is there anyway I can avoid the additional function in my main component? A: I believe the best you can do is this: (subProperty)="mainProperty = $event"
tomekkorbak/pile-curse-small
StackExchange
**What's Known** Allergy is a growing burden worldwide. Tree pollens are considered as one the most important sources of allergy. Pollens lead to rhinitis and asthma, especially in cities with ornamental trees in public areas. **What's New** The commonest tree pollens among the 23 studied countries in the Middle East have been reported. Introduction {#sec1-1} ============ Allergy is the hypersensitive reaction of the immune system of the body to an unknown substance. It follows with symptoms such as itching, allergic rhinitis, red eyes, eczema, hives, or even an asthma attack. The reaction of the immune system to normally harmless materials in the environment is the production of IgE by basophils and mast cells. Among the four types of hypersensitivity, allergy is categorized as type I (immediate) hypersensitivity.^[@ref1],[@ref2]^ The spectrum of manifestations in this inflammatory reaction can range from mildly uncomfortable to dangerous phenomenon,^[@ref3]^ such as sensitization to aeroallergens of plants that may be associated with serious morbidity.^[@ref4]^ There are two general categories of risk factors for allergy, namely patient characteristics and environmental factors. Genetic makeup, age, sex, and race are the most significant factors of patient characteristics. Among environmental factors, exposure to infectious disease during the newborn period and early childhood, and pollutants in the environment are the most important causes.^[@ref5]^ However, pollens play a major role in the onset of allergies.^[@ref6]^ It is approximated that about 40% of allergic patients have been affected by pollens.^[@ref7]^ On the other hand, global climate change occurs around the world, including the Middle East. A number of studies have shown a significant impact of climate fluctuation on the status of plants of each area and also on aeroallergens and their public and clinical healths.^[@ref8]^ This reality urges the need for an up-to-date, frequency, and distribution of allergenic tree pollens in each region. Pollen is a fine powder-like substance released by weeds, scrubs, shrubs, grass, and trees. Wind is one of the main sources of pollen dispersal. Plants pollinated by animals are more frequent. However, in terms of allergy, people are more exposed to pollen dispersed by the wind. Usually, flowers that have brightly colored petals and sugary scents (to attract insects) are less allergic, while the pollens of flowers with drab colors and small flowers without an obvious scent (mainly dispersed by the wind) mostly cause hay fever or allergies. Specific selection of aeroallergens for the skin prick test by allergists is not always evidence-based.^[@ref9],[@ref10]^ In the medical literature, there is no comprehensive report that describes the global status of allergenic pollens of trees in the Middle East (e.g. plants, distribution and allergenicity of pollen grains, or other plant attributes). The current literature review is aimed to cover the gap and present a checklist on the status of trees and pollens in the region. Herein, we report the allergenic pollens of trees in 23 Middle Eastern countries, including Afghanistan, Azerbaijan, Bahrain, Cyprus, Djibouti, Egypt, Eritrea, Ethiopia, Kuwait, Iran, Iraq, Libya, Oman, Palestine, Israel, Pakistan, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Turkmenistan, United Arab Emirates, and Yemen. It is intended to provide recommendations on aeroallergens of pollens in the Middle Eastern countries to allergists who are often required to give advice to patients that plan traveling to the region. We trust that the included information (e.g. distribution map of allergenic trees and pollens) would be helpful to allergists, health authorities, research scientists, and patients concerned with tree pollen allergies. The search strategy was developed based on the guidelines of the NHS center for reviews and dissemination (CRD) (<https://www.york.ac.uk/crd/>).^[@ref11]-[@ref14]^ The frequency of reported allergenic tree pollens varied from an adequate number of reports (17 from Iran, 12 from Turkey) to no reports from some countries (Afghanistan and Azerbaijan). A summary of the reported surveys is described below. *Iran* {#sec1-4} ------ To identify all related published studies, Persian and English databases such as SID, IranMedex, PubMed, Scopus, and ScienceDirect were searched. In total, 17 articles on allergenic tree pollens were identified. Among the 31 provinces in Iran, only 16 (51.6%) provinces covered the topic. Furthermore, some of the reports provided information on a province over different time periods.^[@ref15]-[@ref31]^ Positive reaction to tree mix was reported in Mazandaran (50%), Tehran (26%), Fars (data not cited), Sistan and Balouchestan (41.2%), Khorasan-Razavi (24.8%), East Azerbaijan (11.3%), Kermanshah (18.9%), and Karaj (50%). As shown in [table 1](#T1){ref-type="table"}, the most common allergic pollens were Mesquite, Ash, Acacia, Eucalyptus, Cedar, Sycamore, Maple, Fraxinus excelsior, Pinus, Birch, Hazel, Alder, Pine, Elm, Plane tree, Olive, Botrytis, Salicaceae, Frene, Salix babylonica, and Ailanthus altissima. For convenience, common and scientific names of the relevant trees are provided in [table 2](#T2){ref-type="table"}. ###### The list of published papers on tree pollens aeroallergens based on the prick test in Iran with relevant details before November 2015 Authors Year of publication Year of study Sample size Province Reported allergic pollens (%) -------------------------- --------------------- --------------- ------------- --------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------ Ahmadiafshar^[@ref15]^ 2008 2003-2005 164 Zanjan Olive (22%), Salicacea (13.5%), Ash (20%) Hedayat^[@ref16]^ 2000 1998 1,077 Isfahan Salix babylonica (37%), Fraxinus excelsior (26%), Platanus orientalis (23%), Ailanthus altissima (14%) Assarehzadegan^[@ref17]^ 2013 2010-2011 299 Ahwaz Mesquite (Prosopis Juliflora) (65.9%), Acacia (Acacia longifolia) (48.2%), Eucalyptus (Eucalyptus globulus) (21.7%), White Ash (Fraxinus Americana) (52.5%) Behmanesh^[@ref18]^ 2010 2008-2009 133 Mashhad Tree mix (24.8%) Bonyadi^[@ref19]^ 2014 2010-2012 150 Tabriz Street trees (11.33%) Farhoudi^[@ref20]^ 2005 2002-2003 226 Karaj Tree mix (50%), Ash (40%), Cedar (27%), Sycamore (57%) Fereidouni^[@ref21]^ 2009 2006 356 Khorasan Razavi Fraxinus americana (53.5%), Pine (9.6%) Fouladseresht^[@ref22]^ 2014 2007-2010 157 Kerman Salicaceae (8.3%), Fagaceae (3.8%), Oleaceae (9.6%), Betulaceae (7.6%) Ghaffari^[@ref23]^ 2010 2006-2007 375 Mazandaran Maple (3%), Oak (1%), Fraxinus excelsior (6%), Birch (4%), Ulmus (3%), Pine (1%), Platanus orientalis (1%) Ghaffari^[@ref24]^ 2012 2006-2009 375 Sari Tree mix (3%), Platanus orientalis (1%), Oak (1%), Maple (3%), Hazel (Alnus serrulata) (5%), Fraxinus excelsior (6%), Ulmus ulmaceae (3%), Pine (1%), Birch (4%) Hosseini^[@ref25]^ 2014 2006-2009 313 Tehran Tree mix (26%) Kashef^[@ref26]^ 2003 2001-2002 212 Shiraz Acacia, Ash, Birch, Hazel, Oak, Elm, Pine, Plane tree Nabavizadeh^[@ref27]^ 2013 2011-2014 184 Yasouj Oak (16.3%), Tree mix (18.9%) Shakurnia^[@ref28]^ 2012 2010 354 Ahwaz Prosopis juliflora (65.1%), Eucalyptus (21%) Khazaei^[@ref29]^ 2003 1996-2003 1,286 Sistan-Balouchestan Tree mix (41.2%) Mohammadi^[@ref30]^ 2008 2005-2007 206 Tehran Tree mix Pazouki^[@ref31]^ 2008 2008 19 Mashhad Platanus orientalis (43%) ###### The common and scientific names of reported trees with allergen pollens in the Middle East Common name Binomial name ----------------------------- ------------------------ Mesquite Prosopis juliflora Acaci Acacia longifolia Eucalyptus Eucalyptus globulus White ash Fraxinus Americana Cedar Cupressus sempervirens Sycamore Platanus orientalis Oak Quercus robur Maple or Acer Acer pseudoplatanus Hazel Alnus serrulata Elm Ulmus ulmaceae Pinus Pinus pinacaea Birch Betula betulaceae Olive Olea europaea Willow Salicaceae Beach Fagaceae European ash Fraxinus excelsior Tree of heaven Ailanthus altissima Weeping willow Salix babylonica Cajeput tree Melaleuca cajuputi White mulberry Morus alba Queen palm or cocos palm Syagrus romanzoffiana Pecan Carya illinoensis Alder Alnus glutinosa Pussy willow or goat willow Salix caprea Horse chest Aesculus x carnea The review of reported aeroallergens of pollens shows that most current studies from Iran were during 2003 to 2014. Although the geographical distribution of reports does not show a certain pattern, most are related to the western provinces of Iran ([figure 1](#IJMS-44-87-g001.tif){ref-type="fig"}). The most commonly studied trees were 8 reports on White or European Ash (Fraxinus Americana and excelsior); 5 reports on Sycamore (Platanus orientalis); 4 reports on Birch (Betula betulaceae), Oak (Quercus robur), and Pinus (Pinus pinaceae); 3 reports on Elam (Ulmus ulmaceae) and Olive (Oleaceae); 2 reports on Maple (Acer pseudoplatanus), Willow (Salicaceae), Mesquite (Prosopis julifera), Eucalyptus (Eucalyptus globulus), and Hazel (Alnus serrulata); and 1 report on Weeping willow (Salix babylonica), Beach (Fagaceae), and Cedar (Cupressus sempervirens). ![A schematic map illustrating various provinces of Iran with and without a report of aeroallergen pollens with common type in each region before January 2015.](IJMS-44-87-g001){#IJMS-44-87-g001.tif} A synthesis of reported contributions showed that the most allergenic tree pollens according to the current reports were White or European Ash (min. 6%, max. 53.5%, mean 29.1%), Sycamore (min. 1%, max. 57%, mean 25%), Birch (min. 4%, max. 7.6%, mean 5.2%), Oak (min. 1%, max. 16.3%, mean 6.1%), Pine (min. 1%, max. 9.6%, mean 3.8%), Elm (min. 3%, max. 3%, mean 3%), Maple (3%), Willow (min. 8.3%, max. 13.5%, mean 10.9%), Olive (min. 9.6%, max. 22%, mean 15.8%), Mesquite (min. 65.1%, max. 65.9%, mean 65.5%), Eucalyptus (min. 21%, max. 21.7%, mean 21.3%), Hazel (5%), Weeping (37%), Beach (3.8%), and Cedar (27%). The cited percentages for each tree depict the frequency of allergy to tree pollens among the studied groups. *Other Middle Eastern Countries* {#sec1-5} -------------------------------- As shown in [figure 2](#IJMS-44-87-g002.tif){ref-type="fig"}, among the 23 Middle Eastern countries, 8,071 article titles were observed, 181 abstracts read, 87 full-text articles studied, and eventually, 36 articles were selected. The distribution of the selected articles per country in terms of the number of reports, the most important allergenic tree pollens, and frequency of their allergenicity is described below. ![The Middle Eastern countries tagged with the number(s) of reported reference(s) of allergenic pollens. NR: Not reported.](IJMS-44-87-g002){#IJMS-44-87-g002.tif} - Cyprus: 2 reports; Acacia (29.4%) and Olive (23.7%).^[@ref32],[@ref33]^ - Egypt: 1 report, Olive (12.5%).^[@ref34]^ - Kuwait: 1 report; Eucalyptus (42.9%), Cajuput (53.5%), and Palm (39.6%).^[@ref35]^ - Oman: 2 reports; Prosopis juliflora (10.4%), Queen palm and Cupressus (7%), and Willow (0.5%).^[@ref36],[@ref37]^ - Pakistan: 2 reports; Morus alba (7%), Qatar the Beach (0.4%), Birch (1.1%), White mulberry (1.4%), Cypress (0.4%), and Olive (1.4%).^[@ref38],[@ref39]^ - Palestine and Israel: 8 reports; Olive (37.2%), Pistacia (29%), Cedar (29.4%), and Pecan (30.3%).^[@ref40],[@ref47]^ - Qatar: 1 report; Fagaceae (0.4%), Betulaceae (1.1%), Mulberry white tree (1.4%), Cypress (0.4%), Oleaceae (1.4%), Salicaceae (0.5%), and Tree mix (2.1%).^[@ref48]^ - Saudi Arabia: 6 reports; Mesquite (42.3%), Palm (40%), Olive (35.8%), and Acacia (17%).^[@ref49],[@ref54]^ - Turkey: 12 reports; Birch (23.4%), Beach (22.5%), Olive (30.2%), Acer (14.2%), Sycamore (20.3%), Oak (19.9%), Pine (8.2%), Pussy willow (16%), Elm (18%), Alder (19.1%), White mulberry (19.8%), Hazel (19.5%) and Horse chestnut (57.4%).^[@ref55],[@ref67]^ - United Arab Emirates: 2 reports; Ricinus communis (6.3%)53 and (23.5%),67 Prosopis juliflora (12.6%)53 and (12%).^[@ref67]^ As indicated in [table 3](#T3){ref-type="table"}, there were no reports from Afghanistan, Azerbaijan, Bahrain, Djibouti, Eritrea, Ethiopia, Iraq, Libyan, Somalia, Sudan, Syrian, Turkmenistan, and Yemen. ###### The list of published papers on pollens of trees in countries located in the Middle East based on prick test before November 2015 Authors Year of publication Year of study Sample size Country province Reported allergic pollens (%) ----------------------------------- --------------------- --------------- -------------------- ----------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Dalkan et al.^[@ref37]^ 2014 2010 97 Cyprus Nicosia Acasia dealbata (29.4%), Olea europaea (23.7%) Priftis et al.^[@ref38]^ 2007 1996-1999 1,038 Cyprus Maroussi, Aliartos Olea europaea (N) Elshabrawy et al.^[@ref39]^ 2014 2012 96 Egypt Qassim Olea europaea (12.5%) Ezeamuzie et al.^[@ref40]^ 2000 1997-1998 553 Kuwait Cajuput tree (53.5%), Eucalyptus tree (42.9%), Phoenix dactylijera 39.6% Al-Tamemi^[@ref41]^ 2008 2004-2006 384 Oman Prosopis juliflora (10.4%) Al-Amiri et al.^[@ref42]^ 2002 N 71 Oman Queen palm and Cupressus trees (7%) Ahmad et al.^[@ref43]^ 2011 N 650,067 Pakistan Sensitive to pollens has been reported only (58.9%) Abbas et al.^[@ref44]^ 2012 2005-2007 1,000 Pakistan Morus alba (7%) Sharif EI et al.^[@ref45]^ 2003 2000-2001 273 Palestine Olea europaea, Betula verrucosa, Alnus glutinosa, Corylus avellana trees (N%) Keynan et al.^[@ref46]^ 1997 N 216 Israel Pistacia vera (31.5%), Pistacia atlantic (29.9%), Pistacia lentiscus (30.3%), Pistacia Plastina (24.6%) Geller-Bernstein et al.^[@ref47]^ 1996 N 1,573 Jews 90 Arab Israel Sardinia Olea europaea (40% in Jews and 16% in Arab) Bibi et al.^[@ref48]^ 2002 1998 448 Israel Ash, kelo Olea europaea (28.1%), Cupressus sempervirens (28.1%) Geller-Bernstein et al.^[@ref49]^ 2002 N 86 Israel Shearam Olea europaea (21%) Tamir et al.^[@ref50]^ 1991 N 19 Israel Olea europaea (100%)[\*](#t3f1){ref-type="table-fn"} Graif et al.^[@ref51]^ 2006 N 127 Israel Olea europaea, Cttpressus sctnpervirctis, Carya illinocsis (49%)[\*\*](#t3f2){ref-type="table-fn"} Rachmihl et al.^[@ref52]^ 1996 N 395 Israel Netzer, Tzireni Carya illinocsis (11.6%), Cupressus sempervirctis (11.1%), Phoenix dactylijera (6.3%), Olea europaea (6.3%) Sattar et al.^[@ref53]^ 2003 2001-2003 1,106 Qatar Doha Fagaceae (0.4%), Betulaceae (1.1%), Mulberry white tree (1.4%), Cypress (0.4%), Oleaceae (1.4%), Salicaceae (0.5%), Tree mix (2.1%) Almogren^[@ref54]^ 2009 2003-2004 139 Saudi Arabia Riyadh Prosopis juliflora (72.1%), Phoenix dactylijera (23%) Harfi et al.^[@ref55]^ 1992 N 60 Saudi Arabia Phoenix dactylifera (25%) Al-Frayeh et al.^[@ref56]^ 1999 1995-1996 420 Saudi Arabia Abha, Qassim, Hofuf, Gizan Prosopis juliflora (38.8%), Olea europaea (35.8%), Suliaman et al.^[@ref57]^ 1997 1992-1994 806 Saudi Arabia Mesquite 46%, Acacia 29% Hasnain et al.^[@ref58]^ 2012 N 492 Saudi Arabia, United Arab Emirates, Sudan Ricinus communis (6.3%), Prosopis juliflora (12.6%), Phoenix dactylifera (12%) Al-Frayh et al.^[@ref59]^ 1992 N 240 Saudi Arabia Riyadh, Mecca Acacia SP (5% and 17%), Salix caprea (5% and 9%) Geçer et al.^[@ref60]^ 2012 N 100 Turkey Betulecea (alder, birch, hazel, hornbeam) N%, Salicacea (poplar, willow) N% Aydin et al.^[@ref61]^ 2009 2002-2006 1,552 Turkey Istanbul Betulaceae (23.5%), Fagaceae (19.4%) Can IH et al.^[@ref62]^ 2010 2007-2008 43 Turkey Acer (3%), Betulaceae (18.1%), Oleaceae (4.5%), Salicaceae (3%), Fagaceae (25.7%) Senol M et al.^[@ref63]^ 2006 N 246 Turkey Tree mix-1 (13%), Tree mix-2 (12%)≤ Gokmen et al.^[@ref64]^ 2012 N 437 Turkey Olea europaea (48.5%) Sin et al.^[@ref65]^ 2008 2003-2004 455 Turkey Cupressus sempervirens (14.3%) Dursun et al.^[@ref66]^ 2008 2004 54 Turkey Ankara Olea oleaceae (olive) (59.2%), Pinaceae (14.5%), Acer (25.5%), Populus (21.5%), Oak quercus (14.5%), Betula (18.2%), Salix (16.4%), Fraxinus (20%), Ulmus (18.2%), Aesculus (horse chestnut) (57.4%), Tilia (linden) (42.5%), Platanus (plane) (29.6%) Tezcan et al.^[@ref67]^ 2003 1994-2001 5,055 Turkey Izmir Alnus glutinosa, Corylus avellana, Populus alba, Ulmus scabra, Salix caprea, (overall 14%) Yazicioglu et al.^[@ref68]^ 2004 2000-2002 539 Turkey Trakya Olea europaea (8.9%), Corylus avellana (8.3%), Fraxinus excelsior (8.3%), Salix caprea (7.2%), Alnus glutinosa (5.9%), Populus alba (5.8%), Quercus robur (3.8%), Juglans regia (5%), Ulmus campestris (3.5%), Pinus sylvestris (2%), Platanus vulgaris (3.8%), Tilia platyphyllos (2.8%) Erkara et al.^[@ref69]^ 2009 2000-2001 130 Turkey Alnus glutinosa (32.3%), Corylus avellana (30.8%), Populus alba (32.3%), Ulmus scabra (32.3%), Salix caprea (24.6%), Betula verrucosa (33.8%), Fagus sylvatica (26.2%), Quercus robur (41.5%), Platanus orientalis (27.7%) Misirlioğlu et al.^[@ref70]^ 2007 1995-2000 539 Turkey Ankara Betulacae, Moist zone frees, Park tree pollens, Fagaceae, Eastern trees, Mediterranean trees (overall 16.5%) Cavkaytar et al.^[@ref71]^ 2015 2013 318 Turkey Robinia pseudoacacia (9.7%), Cupressus arizonica (7.5%), Tilia platyphyllos (6.3%), Alnus glutinosa (0.3%) Lestringant et al.^[@ref72]^ 1999 N 263 United Arab Emirates Prosopis juliflora (23.5%) ^N^Not determined, Skin prick test has been done on selected community and has not been done on the general population, Positive skin prick test for at least one tree pollen, £Tree mix-1: Willow, beech, maple, black mulberry, lime-tree, juniper, pine. Tree mix-2: Betula pendula, olive tree, poplar, peanut, oat, black alder, white ash. Cypress: Cupressus sempervirens, Olive: Olea europaea, Palm: Phoenix dactylijera, Pecan: Carya illinocsis, Mesqquite tree: Prosopis juliflora, Castor bean: Ricinus communis Discussion {#sec1-2} ========== Awareness of airborne pollens in each country and region can be regarded a necessity due to increasing mobility for leisure time and business activities.^[@ref68]^ On the other hand, it is becoming clear that allergenic tree species may be considered as a problem within subtropical climate zones.^[@ref68]^ It has been shown that in some types of trees, pollen grains can exacerbate respiratory symptoms in allergic patients and result in hospitalization.^[@ref69],[@ref70]^ Commercially, there are about more than 200 pollen grains, extracts of allergens for trees, grass, and weeds that are distributed by vendors worldwide.^[@ref71]^ These extracts of allergens are used in the diagnosis of allergic disorders in prick tests and immunotherapy.^[@ref70]^ A selection of extracts for the skin prick test is done according to clinical data, regional distribution of plants, inter alia, season, regional distribution, and flowering cycles. Awareness of common aeroallergens of pollens in each area can assist allergists in choosing the most suitable allergens for the prick test and immunotherapy, as well as to address the source of the patient's allergy better. In addition, prevention and better treatment options can reduce the financial burden allergies placed on the healthcare services. In central, north, west, and Eastern Europe, birch (Betula) has been reported as the most allergenic tree pollen grains in the months of June and July. While in central Alpine regions, pollen grains of Alnus virdis are common in the months of May and June.^[@ref71]^ The Middle East is a transcontinental region centered in Western Asia and Northeast Africa ([figure 2](#IJMS-44-87-g002.tif){ref-type="fig"}), where that climate is dry in summers and mild in the winters. This fact has caused special vegetation with various types of allergenic pollen that are different from allergenic pollens in Europe.^[@ref68]^ The largest ethnic populations in the region include Arabs, Azeri, Persians, Kurds, and Turks. The climate of the Middle East is usually dry, although winters are mild with rain. According to the current literature review, we could not find any reports for allergic pollens of trees for 13 countries in the Middle East (56.5%). This may be due to our unfamiliarity with the local languages such as Arabic and Turkish and/or because such articles have only been published in domestic journals in local languages. Moreover, it seems that countries with lower economic status have few publications in the field of allergens whereas more contributions are found in PubMed from countries with a better economic ranking. The coverage of domestic trees varies in each area of the Middle East while palm and mesquite trees are common in countries located in the Persian Gulf area, olive is common in Palestine, Israel, and Turkey, and sycamore in Iran. The diversity of reported allergenic pollens in different areas of some countries should be taken into consideration and creating a panel of allergen extracts for the skin prick test that is decision-based according to locally reported allergic pollens can be more effective in the treatment of type I allergies. Furthermore, it is particularly notable that with an increasingly common practice of planting imported ornamental trees in public parks, highways, and streets, special attention should be paid to these new sources of pollens. Iran is a large territory situated between the Persian Gulf and the Caspian Sea in western Asia, and its 1,648,195 km^2^ area has a changeable climate. According to FAO reports, about 7% of the country is covered by forests. The forest slopes rising from the Caspian Sea are mostly covered with ash, oak, elm, and cypress, and at the same time, the central and western parts of the country are predominately covered with oak. However, the country has mostly semi-desert areas.^[@ref72]^ This pattern of vegetation coverage emphasizes the necessity of separately identifying domestic pollen grains aeroallergens in each region. The current review has shown that there are different types of allergic pollens in many Iranian provinces and areas; this needs to be investigated thoroughly. Although the reported allergic pollens in some provinces are vague and need to be addressed in detail ([figure 1](#IJMS-44-87-g001.tif){ref-type="fig"}), we should keep in mind that due to the special types of trees that are growing in specific climates, reported common allergic pollens of neighboring areas in the country may not accurately represent the adjacent geographical area. The present literature review has shown that a severe allergy to tree pollens fluctuate from 1% to 65.9% ([Table 1](#T1){ref-type="table"}). These findings emphasize the importance of pollens in causing allergic reactions in the inhabitants of the relevant regions of the country. Although mild symptoms of allergic reactions do not lead to hospitalization or absence from work, they may influence the sufferer's quality of life and bother individuals to such an extent that drug intervention may be needed. Hence, the main step in the management of allergy sufferers is to avoid sources of allergic pollens. This requires a vast survey to identify the type of pollen grains aeroallergens and severity of the allergic reaction. A major concern about the published contributions in Iran is that the investigators have not indicated the ingredients of pollens used in the mixes extracts of tree allergens that they used for the skin prick tests. This information is important because pollen grains and extracts that are used in prick tests are supplied commercially and imported from other countries, hence they may not completely cover local pollens. In such cases, the skin prick test may not be a reliable tool for identifying allergies in patients. Conclusion {#sec1-3} ========== Although it was attempted to map a complete picture of allergenic pollens in the Middle East, this review showed that the available data are still fragmentary. Hence, it is still difficult to draw a clear and perfect map of allergenic pollen grains of the trees across the region. Owing to the span of countries and the various species of flowers grown on trees in each region, it seems that allergists who are trained in identifying and managing allergic sensitivities should be aware, not only of the history of the patients but also be aware of the common allergenic pollens in each area and their seasonal air dispersion. The potential of climate changes in the distribution of allergenic tree species should be noticed by allergists. Furthermore, distribution and frequency of various allergens of pollen grains of newly imported trees need to be given more consideration and included in future studies. The present study was supported by a grant (number: 931396) from the Vice Chancellor of Research at Mashhad University of Medical Sciences, Mashhad, Iran. **Conflict of Interest:**None declared.
tomekkorbak/pile-curse-small
PubMed Central
Q: How do short lived certificates increase security? After reading a blog post about the new Roughtime protocol, I am not convinced of the original premise that shorter certificate lifetimes increase security. The claim is that a shorter time somehow reduces the exposure if a secret key is compromised. But how realistic is that scenario? If the crypto protocol is weak and that’s how the key was compromised, changing the key for a new equally weak one is meaningless. Conversely, if the protocol is good, an attacker will only be able to compromise the secret key from breaching the system (or by exploiting weak people.) And we know from long experience with breaches that the first thing any attacker does is to open a back door in order to retain access if their originally exploited vulnerability is closed. The amount of time between a breach and the back-dooring process is usually measured in seconds or minutes, which a rotation policy likely won’t help. We’ve finally begun to accept with passwords that frequent rotation is pointless (and risky). The NIST recommendations are evidence of that shift. Believing in frequent rotations for certificates seems like a superstitious holdover from the 1980s ideas of security. So I’m asking for evidence. Have there been any studies on the efficacy of short-lived certificates as a security measure? Is there any proof that frequent certificate rotations improve security instead of simply causing frustrating inconveniences (and significant downtime as certificates expire) for all concerned? Another way to ask the question is what are the actual benefits a short certificate rotation period provides? A: One document I can't resist from showing you here is draft-nir-saag-star by Yoav Nir (the chair of ACME working group) and the subsequent discussion across the saag mailing list. An important issue Yoav rises there is that neither OCSP responders nor CRL distribution points are widely recognized as reliable network parties. I mean, there's obviously no evidence they are constantly down either, but, given the soft-fail approach currently in use, there's no need for a current certificate authority infrastructure to be available and monitored 24/7, which makes the transition to hard-fail (with the likes of Must-Staple, etc.) much harder. And, anyway, CRL and OCSP both constitute an additional single point of failure, while a today's Internet service tries its best to avoid those at all. As a matter of fact, a short-lived certificate is only good if the rotation is automated; however, for a sufficiently scalable network service, deployed across tens to hundreds to thousands physical and/or virtual instances, this holds true. Also a few quick remarks on the rest of the question, Conversely, if the protocol is good, an attacker will only be able to compromise the secret key from breaching the system — But not necessarily the system where the certificate and the private key are deployed in order to handle the production traffic. Might as well be the central Ansible server, or its network storage, or a server used for certificate renewal, or anything else. Might also be just a small portion of the production servers, not even in use (e.g. when a network service is deployed over a few cloud providers and one of those has allowed for a breach). In some (more outdated?) threat models it might have also been a (stolen) personal laptop of an employee responsible for certificate renewal. In all the above cases there won't be any immediate benefit to an attacker for installing a backdoor, while they can still easily go away with the private key and use it for MitM, etc. We’ve finally begun to accept with passwords that frequent rotation is pointless (and risky) Well, not exactly. E.g. NIST SP 800-63B suggests that "verifiers SHOULD NOT require memorized secrets to be changed arbitrarily (e.g., periodically)", where a memorized secret is "a type of authenticator comprised of a character string intended to be memorized or memorable by the subscriber, permitting the subscriber to demonstrate something they know as part of an authentication process". However, this doesn't apply to a private key which is never ever expected to be memorized or memorable in any sane contemporary usage scenario. As a matter of fact, there are also drawbacks of a frequent certificate rotation (such as the need to properly automate things), but those are not even close to the disadvantages of a frequent memorable passwords' rotation.
tomekkorbak/pile-curse-small
StackExchange
Giving a voice to the Voiceless We dedicate our lives to improving the circumstance of those who have been harmed and wronged by the greed and thoughtless acts of others. Whether you’ve been seriously injured through no fault of your own, we are here to help. Lawsuit: Waitress Fired for Complaining of Harassment NEW YORK – A cocktail waitress fired from the Penthouse Executive Club is suing the jiggle joint, claiming male and female bosses sexually harassed her. Lourdes Garcia says she was one of the top servers at the club but was booted when she rebuffed the sexual advances and then complained. “It’s disgusting,” Garcia, 34, said after filing a suit against the club in Manhattan Federal Court Thursday. She alleges that club general manager Kelly Gerald-Hughes made remarks about the size of Garcia’s breasts in front of customers and stroked her leg in a VIP room, promising that the customer would give her a big tip if the two women kissed. “That’s when I had it. I couldn’t take any more,” the Peekskill, N.Y., woman said. She said she complained to owner Robert Gans, who dismissed her concerns “like it was no big deal – I work at Penthouse,” she said. She said bar manager John Loukas repeatedly told her, “You do something for me, I’ll do something for you.” Garcia says that when she confronted the frisky GM about the hostile work environment, she was fired two weeks before Christmas on trumped-up charges that she stole a few bucks. “They couldn’t look me in the eye,” she said. “I was loyal to them, and this is how they treat me.” At the W. 45th St. club, a woman who identified herself as the general manager but said her name was Kelly Skillen, sounded surprised to hear of Garcia’s specific allegations. “Oh, is that what she’s saying?” she said. “We appreciate the opportunity to comment, but I cannot comment,” she added.
tomekkorbak/pile-curse-small
Pile-CC
Nuñez FJ, Johnstone TB, Corpuz ML, et al. Glucocorticoids rapidly activate cAMP production via G~αs~ to initiate non‐genomic signaling that contributes to one‐third of their canonical genomic effects. The FASEB Journal. 2020;34:2882--2895. 10.1096/fj.201902521R 31908022 Francisco J. Nuñez and Timothy B. Johnstone contributed equally to this work. ßAR : ß‐adrenergic receptor cAMP : 3′,5′‐cyclic adenosine monophosphate CS : connectivity score Fsk : forskolin GPCR : G protein‐coupled receptor GPER : G protein estrogen receptor GR : glucocorticoid receptor GRE : glucocorticoid response element HASM : airway smooth muscle IBMX : 3‐isobutyl‐1‐methylxanthine Iso : isoproterenol mGR : membrane‐bound glucocorticoid receptor PDE : phosphodiesterase 1. INTRODUCTION {#fsb220198-sec-0001} =============== Glucocorticoids are used in the treatment of a wide array of diseases, including rheumatoid arthritis, autoimmune disorders, allergy, cancer, and respiratory syndromes. The occurrence of side effects and glucocorticoid resistance, particularly with systemic use, greatly hamper their use.[1](#fsb220198-bib-0001){ref-type="ref"} The combination of glucocorticoids ß‐agonists has long been considered the most effective means for controlling asthma and chronic obstructive pulmonary disease, even more than using either alone.[2](#fsb220198-bib-0002){ref-type="ref"}, [3](#fsb220198-bib-0003){ref-type="ref"}, [4](#fsb220198-bib-0004){ref-type="ref"}, [5](#fsb220198-bib-0005){ref-type="ref"} While the mechanisms underlying glucocorticoid genomic effects on enhancing the clinical efficacy of ß‐agonist have been previously studied,[6](#fsb220198-bib-0006){ref-type="ref"} the possibility that non‐genomic signaling by glucocorticoids enhance the clinical efficacy of ß‐agonists has not been investigated due to the limited tools to measure real time kinetics of intracellular changes in 3′,5′‐cyclic adenosine monophosphate (cAMP) concentration. Conventional thought suggests that glucocorticoids alter the cell function through changes in the gene expression that occur via activation of ubiquitously expressed intracellular glucocorticoid receptors (GR).[7](#fsb220198-bib-0007){ref-type="ref"} In the absence of glucocorticoid, the GR resides in the cytoplasm then translocates to the cell nucleus upon binding of ligand. Nuclear GR then interacts with glucocorticoid response elements (GREs) to alter the gene expression. Various reports, some published over 25 years ago, suggest that glucocorticoids also induce rapid alterations in various signaling processes that appear to be non‐genomic in nature.[5](#fsb220198-bib-0005){ref-type="ref"}, [8](#fsb220198-bib-0008){ref-type="ref"}, [9](#fsb220198-bib-0009){ref-type="ref"} The human skin blanching assay (often called the vasoconstrictor assay) has been used for nearly 50 years as a means of qualitatively assessing the topical availability and potency of glucocorticoids.[10](#fsb220198-bib-0010){ref-type="ref"} This test characterizes the potency of glucocorticoids through non‐genomic effects on vasoconstriction. Some of these non‐genomic effects may require specific interactions with membrane‐bound versions of GR (mGR) or other undefined membrane components.[5](#fsb220198-bib-0005){ref-type="ref"} Short duration treatment of various cell types with glucocorticoid affect many different signaling events, including agonist‐induced calcium release, reactive oxygen species, and arachidonic acid release.[11](#fsb220198-bib-0011){ref-type="ref"}, [12](#fsb220198-bib-0012){ref-type="ref"}, [13](#fsb220198-bib-0013){ref-type="ref"}, [14](#fsb220198-bib-0014){ref-type="ref"}, [15](#fsb220198-bib-0015){ref-type="ref"}, [16](#fsb220198-bib-0016){ref-type="ref"} BSA‐conjugated cortisol, a steroid unable to cross the cell membrane, has been used as a tool to differentiate plasma membrane GR effects from those of the cytosolic GR. For instance, the effects of short (5 to 90 minutes) exposure of BSA‐cortisol on leukemia cells was studied using proteomic tools and 128 unique proteins were found to be specifically upregulated.[17](#fsb220198-bib-0017){ref-type="ref"} Interestingly, the putative mGR may interact with the NMDA receptor or may directly activate a G protein‐coupled receptor (GPCR) coupled to G~αs~ and/or G~q/11~.[18](#fsb220198-bib-0018){ref-type="ref"} While these and other studies support the idea that glucocorticoids possess the ability to modulate rapid, non‐genomic signaling, none reveal the specific signaling pathways or receptor(s) responsible. Our studies demonstrate that glucocorticoids rapidly increase the cAMP levels in a variety of cell types. In human airway smooth muscle (HASM) glucocorticoids trigger this non‐genomic signaling via binding to an extracellular site and activating the stimulatory G protein, G~αs~. While a GPCR might be involved, our data suggest that the G protein estrogen receptor (GPER) does not mediate this response. Removal of this rapid, non‐genomic signal via siRNA knockdown of G~αs~ modifies the transcriptomic response to the glucocorticoid, budesonide. Out of a 140 gene budesonide signature, the alteration of 48 of these genes was dependent upon the G~αs~‐cAMP signal. Thus, of all the canonical changes in gene transcription by glucocorticoid, a full one‐third of them require this rapid, non‐genomic signal. 2. MATERIALS AND METHODS {#fsb220198-sec-0002} ======================== 2.1. Materials {#fsb220198-sec-0003} -------------- Forskolin (Fsk) was purchased from LC Laboratories. Cell culture media and components were purchased from Thermo Fisher. Fetal bovine serum was purchased from Atlanta Biologicals. siRNA construct for silencing GNAS were obtained from Dharmacon. The sense sequence used was CGAUGUGACUGCCAUCAUCUU. Secondary antibodies were obtained from Santa Cruz Biotechnology. All other drugs and chemicals were purchased from Sigma‐Aldrich unless otherwise noted. 2.2. Cell culture {#fsb220198-sec-0004} ----------------- HASM cells were isolated from deceased, de‐identified lung donors by enzymatic dissociation in accordance with Institutional Review Board approval and as described previously.[19](#fsb220198-bib-0019){ref-type="ref"} HASM cells were grown in Ham\'s F‐12 media (Thermo Fisher Scientific) supplemented with 10% fetal bovine serum, pen/strep, 25 mM HEPES, 1.7 mM CaCl~2~, and [l]{.smallcaps}‐glutamine. Cells were kept at 5% CO~2~ and 37°C. Experiments were performed on cells from passage 3‐7 using cells from 10 different donors in total, and at least three different donors for each study. Patient demographics are described in Table [1](#fsb220198-tbl-0001){ref-type="table"}. Human fetal lung (HFL‐1) fibroblasts (American Type Culture Collection) were grown in Ham\'s F12 medium with 10% fetal bovine serum and 1% antibiotic‐antimycotic solution. HEK‐293 cells (American Type Culture Collection) were cultured in Dulbecco\'s modified Eagle\'s medium (Thermo Fisher Scientific) supplemented with 10% fetal bovine serum. All cells were kept in a humidified incubator with 5% CO~2~ at 37°C. ###### HASM cell patient demographics Designation Age Sex Race ------------- ----- ----- ----------- N100217 39 M Black N041717 19 M Caucasian N021014 54 M Caucasian N101317K 54 F Hispanic N012317 29 F Caucasian N012414 20 F Black N030116 69 M Caucasian N062017 47 M Hispanic N080817 23 M Black N012518K 18 M Caucasian N112017K 53 M Asian N011118K 14 M Caucasian HASM cells were derived from the following patients who had no history of asthma or chronic illness. RNA‐seq analysis was performed using the cell lines from the first six rows. John Wiley & Sons, Ltd 2.3. Transfection {#fsb220198-sec-0005} ----------------- To transfect HASM cells with siRNA, 250 000 cells were incubated with 100 nM siRNA (target or scrambled) for 30 minutes at room temperature using HiPerFect transfection reagent (Qiagen) following the manufacturer\'s instructions. Cells were then transferred to 6‐well plates. After 5 hours incubation at 37°C with 5% CO~2~, HASM growth media containing 5% fetal bovine serum was added for 48 hours. Media was replaced with serum‐free media for 24 hours prior to drug treatment or assay. 2.4. cADDis cAMP assays {#fsb220198-sec-0006} ----------------------- We performed kinetic measurements of cAMP production in live cells using the green cAMP difference detector in situ (cADDis) cAMP sensor (Montana Molecular, Bozeman, MT) as described previously.[20](#fsb220198-bib-0020){ref-type="ref"} Briefly, sub‐confluent HASM, HFL‐1, or HEK‐293 cells were plated on a black‐walled, clear flat bottom 96‐well plates along with recombinant BacMam virus expressing the cADDis sensor and 1 µM trichostatin‐A. Cells were grown overnight at 5% CO~2~ and 37°C. Media was aspirated and replaced with 180 µL per well of 1X Dulbecco\'s Phosphate Buffered Saline Solution without calcium and magnesium. The 96‐well plate was covered with aluminum foil and incubated at room temperature for 30 minutes. Cell fluorescence was read from the plate bottom using excitation/emission wavelengths of 494 and 522 nm, respectively, using a SpectraMax M5 plate reader (Molecular Devices). A 5 minutes kinetic read on unstimulated cells was monitored until the variability in each well\'s fluorescence was ≤5%. Cells were then stimulated with the indicated drug and fluorescence changes in each well were read at 30 seconds intervals for 30 minutes. Data were transformed to the change in fluorescence over the initial fluorescence (Δ*F*/*F* ~0~) then plotted and fit to a single site decay model using GraphPad Prism 8.0 (GraphPad Software). The K value (slope) and the plateau from this one‐site decay fit are reported. To create a concentration‐response curve, the K was multiplied by the plateau for each drug concentration and plotted on a log scale. 2.5. Immunoblot analysis {#fsb220198-sec-0007} ------------------------ Whole cell lysates were obtained by scraping cells in modified RIPA lysis buffer (50 mM Tris--HCl, pH 7.5, 150 mM NaCl, 1% Igepal CA‐630, plus mammalian protease inhibitor cocktail). Whole cell lysates were separated on 10% SDS‐polyacrylamide gels by electrophoresis before being transferred to PVDF membranes (Millipore) by electroblotting. ß‐actin (Santa Cruz Biotechnology sc‐47778, 1:1000 dilution) and G~αs~ (Santa Cruz Biotechnology sc‐135914, 1:500 dilution) antibodies were simultaneously incubated overnight at 4°C following block in nonfat milk. The appropriate secondary antibodies with conjugated horseradish peroxidase were purchased from Santa Cruz Biotechnology. Images were captured using a BioRad Gel Doc system then the alignment, exposure, and contrast of each image was optimized using Adobe Photoshop CS4. Immunoreactive bands were analyzed by densitometric analysis using the volume plus density method and normalized to ß‐actin, as described previously.[21](#fsb220198-bib-0021){ref-type="ref"} 2.6. RNA‐Seq {#fsb220198-sec-0008} ------------ Control or G~αs~‐knockdown HASM cells (see transfection procedure above) from six different donors (see Table [1](#fsb220198-tbl-0001){ref-type="table"}) at the same passage number were treated with either vehicle or 1 µM budesonide for 24 hours. Total RNA was extracted using the miRNAeasy mini kit (Qiagen). Approximately 1 µg of RNA from each sample was used to generate RNA‐Seq cDNA libraries for sequencing using the TruSeq RNA Sample Prep Kit v2 (Illumina, Inc). Sequencing of 100 bp single‐end reads was performed with an Illumina HiSeq 4000 instrument at the University of California, Irvine Genomics High‐Throughput Facility. 2.7. Data analysis and statistics {#fsb220198-sec-0009} --------------------------------- *Data analysis and statistics*: Standard curves were fit and unknown values were extrapolated using GraphPad Prism 8.0. Data were presented as the mean ± SEM. Statistical comparisons (*t* tests and one‐way analysis of variance) were performed and graphics were generated using GraphPad Prism 8.0.*RNA‐Seq alignment and quantification:* RNA‐Seq data quality was checked using *FastQC* and all samples had high quality score (Phred score \>28) for all nucleotides sequenced. *FastQC* analysis showed Illumina TrueSeq adapters were overrepresented in two samples. *Cutadapt* software was used to remove the identified adapters and reads were filtered for a minimum length of 20 bp. The *Rsubread* R package (version v1.30.6; Liao et al[22](#fsb220198-bib-0022){ref-type="ref"}) was used to align the reads and to produce the gene‐level summarized values using hg38 annotation from the *Rsubread* package. Integer‐based gene counts were generated using the *featureCounts* function in the *Rsubread* package.[22](#fsb220198-bib-0022){ref-type="ref"}, [23](#fsb220198-bib-0023){ref-type="ref"} *limma* [24](#fsb220198-bib-0024){ref-type="ref"} and *edgeR* (version v3.22.3) [25](#fsb220198-bib-0025){ref-type="ref"}, [26](#fsb220198-bib-0026){ref-type="ref"} ) packages were used to calculate FPKM values[27](#fsb220198-bib-0027){ref-type="ref"} and a custom script to convert FPKM to TPM values.[28](#fsb220198-bib-0028){ref-type="ref"} Ensembl Genome Reference Consortium Human Build 38 patch 12 (GRCh38.p12) database was used to convert gene IDs to Hugo Gene Nomenclature Commitee (HGNC) HCNC gene symbols.[29](#fsb220198-bib-0029){ref-type="ref"} RNA‐Seq data was available in GEO under accession number <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130715>. <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94335>, an independent dataset including 34 samples from fatal‐asthma and non‐asthma donors treated with control and budesonide,[40](#fsb220198-bib-0040){ref-type="ref"} was also processed with the same alignment and quantification pipeline to minimize technical and analytical bias.*Differential gene expression and pathway analysis*: Genes with less than 100 counts in 50% of our samples were filtered out prior to any analysis. Principal Component Analysis (PCA) was used to investigate interpatient variability compared to treatment‐specific variability. The *prcromp* function from the *stats* R package was used to compute PCAs. Plotting of first two PCAs showed intended treatment‐specific variability was more dominant than interpatient variability. Therefore, no adjustment was necessary.*DESeq2* R package was used to generate differential gene‐lists between various treatment conditions: (a) vehicle‐treated and G~αs~‐knockdown vehicle‐treated HASM cells, (b) budesonide‐treated and G~αs~‐knockdown budesonide‐treated HASM cells, (c) vehicle‐treated and budesonide‐treated HASM cells, and (d) G~αs~‐knockdown vehicle‐treated and G~αs~‐knockdown budesonide‐treated HASM cells. Gene‐lists from (a) and (b) were used for in silico validation of G~αs~ (GNAS gene) knockdown. Differential gene‐lists from (c) and (d) represent the budesonide induced transcriptional activity in control (genomic + non‐genomic) and G~αs~‐knockdown (genomic only) HASM cells, respectively. (c) and (d) were compared to previously published budesonide‐associated differentially expressed genes by Himes et al[30](#fsb220198-bib-0030){ref-type="ref"} for validation of our budesonide signature (Figure [S1](#fsb220198-sup-0001){ref-type="supplementary-material"}). Overlap analysis of signature gene‐lists was performed using a Venn diagram. Then, ASSIGN, a pathway profiling toolkit, was used to evaluate the gene‐lists (c) and (d) in predicting budesonide‐induced transcriptional activity in HASM.[31](#fsb220198-bib-0031){ref-type="ref"} (c) and (d) gene‐lists were budesonide signatures due to G~αs~‐independent and ‐dependent transcriptional changes due to 24‐hour post‐budesonide treatment, respectively. An independent HASM dataset, GSE94335,[40](#fsb220198-bib-0040){ref-type="ref"} was used to validate both budesonide signatures. Predicted budesonide activity was correlated using Pearson's correlation to evaluate budesonide and budesonide‐G~αs~ knockdown signatures.*Gene set enrichment analysis*: Using *fgsea* function, a gene set enrichment analyses were performed against KEGG molecular pathways and gene ontology gene annotations for both budesonide signatures. Cutoff values of *P* \< .05 and a false discovery rate (FDR) \< 0.05 were used to assess significant enrichment.Analysis of budesonide transcriptional activity in publicly available data: Connectivity scores (CSs) were assessed using the gene‐list that was unique to differentially expressed gene‐ list (3) using a ConnectivityMap (CMAP) query to identify most similar and dissimilar perturbagen signatures in a publicly available database.[32](#fsb220198-bib-0032){ref-type="ref"} All RNA‐Seq data analyses except the CMAP query were performed in R version 3.6.0 and Bioconductor version 3.7[33](#fsb220198-bib-0033){ref-type="ref"} (R Core Team, 2014; <http://www.R-project.org/>). All codes are available at <https://github.com/mumtahena/gluc_HASMs>. 3. RESULTS {#fsb220198-sec-0010} ========== 3.1. Rapid effect of glucocorticoids on cellular production of cAMP {#fsb220198-sec-0011} ------------------------------------------------------------------- Since glucocorticoids have been found to rapidly activate different signaling pathways in neurons,[9](#fsb220198-bib-0009){ref-type="ref"}, [18](#fsb220198-bib-0018){ref-type="ref"} we hypothesized that glucocorticoids stimulate the cAMP production in mammalian cells. Using a highly sensitive cAMP biosensor capable of displaying rapid cAMP kinetics in live HEK‐293 cells (cADDis, Montana Molecular), we examined responses to two commonly prescribed glucocorticoids. As shown in Figure [1](#fsb220198-fig-0001){ref-type="fig"}A, the addition of 10 µM fluticasone increased cAMP levels (reflected as a decay in cADDis fluorescence) within 30‐60 seconds of drug exposure. This cAMP response reached a plateau at approximately 12 minutes and the maximal effect was nearly as efficacious as the response to a maximal concentration of the direct adenylyl cyclase activator, Fsk (10 µM, Figure [1](#fsb220198-fig-0001){ref-type="fig"}A). A 10‐fold lower concentration of fluticasone (1 µM) also stimulated the cAMP levels, but at a somewhat slower rate of decay and smaller plateau. Fluticasone concentrations lower than 1 µM induced responses that were not statistically significant when compared to vehicle control (0.1 µM fluticasone is shown). The addition of budesonide (0.1, 1, or 10 µM) elicited responses similar to fluticasone (Figure [1](#fsb220198-fig-0001){ref-type="fig"}B). We also expressed the cADDis sensor in HFL‐1 cells, a human fetal lung fibroblast cell line, and measured cAMP responses to glucocorticoids. Both budesonide and fluticasone induced rapid increases in cAMP levels in HFL‐1 cells that were similar to that seen in HEK‐293 cells (10 µM budesonide plateau was −0.251 in HFL‐1 cells compared to −0.395 in HEK‐293 cells; 10 µM fluticasone plateau was −0.341 in HFL‐1 cells compared −0.457 in HEK‐293 cells). Thus, two different glucocorticoids induce rapid increases in cAMP levels in two different cell lines (HEK‐293 and HFL‐1 cells) and these responses were large enough to observe without the presence of phosphodiesterase (PDE) inhibitors. ![Glucocorticoids stimulate rapid cAMP responses in HEK‐293 cells. Cells were incubated with recombinant BacMam virus expressing the cADDis cAMP sensor. After establishing baseline, fluorescence decay was monitored for 30 minutes after addition of drug. cADDis sensor fluorescent decay curves elicited by 1 or 10 µM fluticasone (A) 1 or 10 µM budesonide (B) are shown. Fluorescence decay curves elicited by vehicle and 10 µM forskolin are shown as reference to the minimal and maximal responses. Each point represents the mean ± SEM of n = 5 experiments and lines represent the fit by one‐phase decay non‐linear regression analysis. \* denotes *P* \< .05 for the 1 µM glucocorticoid conditions at the indicated time points, \# denotes *P* \< .05 for the 10 µM glucocorticoid conditions at the indicated time points compared to vehicle using multiple *t* tests and the Holm‐Sidak method for correction of multiple comparisons. The 0.1 µM glucocorticoid conditions were not significantly different than vehicle](FSB2-34-2882-g001){#fsb220198-fig-0001} When primary cultured HASM cells obtained from several donors were treated with various glucocorticoids, a rapid production of cAMP was again observed. Prednisone (Figure [2](#fsb220198-fig-0002){ref-type="fig"}A), fluticasone (Figure [2](#fsb220198-fig-0002){ref-type="fig"}C), and budesonide (Figure [2](#fsb220198-fig-0002){ref-type="fig"}D) elicited cAMP responses in HASM within minutes of drug addition. Prednisone induced smaller responses than fluticasone or budesonide, but significantly increased cAMP within 8 minutes of treatment. We also examined other steroids and found that progesterone (Figure [2](#fsb220198-fig-0002){ref-type="fig"}B) stimulated the cAMP production in HASM cells. Estradiol did not stimulate the cAMP responses that were significantly different than vehicle (Figure [4](#fsb220198-fig-0004){ref-type="fig"}A). To determine if glucocorticoids increase cAMP via inhibition of PDEs, we preincubated HASM with a broad‐spectrum PDE inhibitor, 3‐isobutyl‐1‐methylxanthine (IBMX). Fluticasone retained cAMP stimulating activity in the presence of 10 µM IBMX (Figure [2](#fsb220198-fig-0002){ref-type="fig"}E). IBMX stimulated cADDis responses on its own, so once the baseline was set following IBMX addition, the maximal response to Fsk was diminished as compared to control (shown in Figure [2](#fsb220198-fig-0002){ref-type="fig"}C). All these responses occurred within minutes of drug addition, indicating a non‐genomic mode of action. ![Glucocorticoids stimulate rapid cAMP responses in HASM. Primary HASM cells were incubated with recombinant BacMam virus expressing the cADDis cAMP sensor. After establishing baseline, fluorescence decay was monitored for 30 minutes after addition of drug. cADDis sensor fluorescent decay curves elicited by 1 or 10 µM prednisone (A), 1 or 10 µM progesterone (B), 1 or 10 µM fluticasone (C), 1 or 10 µM budesonide (D), and 1 or 10 µM fluticasone in cell preincubated with 10 µM IBMX (E). Fluorescence decay curves elicited by 10 µM forskolin are shown in each panel as reference to the maximal response. Fluorescence decay by cADDis was monitored for 30 minutes after addition of either vehicle, 1 µM forskolin, 10 µM cortisol, or 10 µM cortisol‐BSA (F). A different Y axis scale is used on panel E to better visualize these responses. Each point represents the mean ± SEM of n = 4‐6 donors and lines represent the fit by one‐phase decay non‐linear regression analysis. \* denotes *P* \< .05, \*\* denotes *P* \< .01 of each time point compared to vehicle using multiple *t* tests and the Holm‐Sidak method for correction of multiple comparisons](FSB2-34-2882-g002){#fsb220198-fig-0002} We have recently observed that this non‐genomic action of glucocorticoids in HASM is blocked by RU486 but not altered by knockdown of GRα.[34](#fsb220198-bib-0034){ref-type="ref"} Therefore, we posited that this rapid stimulation of cAMP levels involves glucocorticoid binding to a plasma membrane receptor. Addition of 10 µM cortisol or 10 µM cortisol‐BSA conjugate (the latter drug is unable to cross cell membranes) elicited identical cAMP responses in HASM (Figure [2](#fsb220198-fig-0002){ref-type="fig"}F). Cortisol and cortisol‐BSA induced significant reductions in cADDis fluorescence within 4 minutes (as compared to vehicle) and reached a maximal response that was about half of that induced by a near‐maximal concentration of Fsk (1 µM). These data were consistent with the idea that glucocorticoids activate a membrane‐bound receptor via an outward‐facing binding site to stimulate cAMP production. 3.2. Role of G~αs~ in mediating glucocorticoid effects on production of cAMP {#fsb220198-sec-0012} ---------------------------------------------------------------------------- Since the stimulation of cAMP by glucocorticoids is rapid and plasma membrane delimited, we hypothesized that the response involves the direct activation of the stimulatory G protein, G~αs~. To this end, we used siRNA strategy to knockdown the expression of G~αs~ in HASM cells. HASM cells were transfected with validated siRNA sequences specific for *GNAS* or scrambled siRNA.[35](#fsb220198-bib-0035){ref-type="ref"} As shown in Figure [3](#fsb220198-fig-0003){ref-type="fig"}A, immunoblot analysis indicated a reduction in expression of both the long and short forms of G~αs~ in siRNA transfected HASM as compared to scrambled control. We consistently observed a reduction in the cADDis sensor expression levels following the transfection procedure, which resulted in the maximal cADDis responses being reduced by about 50% (comparing the response to 10 µM Fsk in Figure [2](#fsb220198-fig-0002){ref-type="fig"} vs Figure [3](#fsb220198-fig-0003){ref-type="fig"}). cAMP responses to vehicle or Fsk (10 µM) were unaffected by G~αs~ knockdown, indicating that adenylyl cyclase expression and total activity were unaffected (Figure [3](#fsb220198-fig-0003){ref-type="fig"}B). In contrast, cAMP responses to 100 nM formoterol (a long‐acting ß~2~‐adrenoceptor agonist approved for the treatment of asthma) were significantly reduced in G~αs~‐knockdown HASM as compared to control, consistent with ß‐adrenoceptors stimulating cAMP production via activation of G~αs~ (Figure [3](#fsb220198-fig-0003){ref-type="fig"}C). cAMP responses to budesonide (10 µM, Figure [3](#fsb220198-fig-0003){ref-type="fig"}D) or fluticasone (10 µM, Figure [3](#fsb220198-fig-0003){ref-type="fig"}E) were also significantly diminished in cells with G~αs~ knockdown. Taken together, these results indicate that glucocorticoids activate a rapid, non‐genomic signaling pathway that stimulates G~αs~ and the production of cAMP. ![Glucocorticoid stimulation of cAMP depends upon G~αs~ expression. A, HASM were transfected with siRNA specific for GNAS or scrambled control for 48 hours and lysates analyzed by SDS‐PAGE and immunoblotting simultaneously with antibodies specific for G~αs~ and ß‐actin. Image is representative of n = 3 experiments on separate donor cells. RNA sequencing revealed GNAS transcript was reduced 6.07 ± 0.35 fold (n = 6) following transfection with siRNA. B‐E, cADDis sensor was expressed in control or G~αs~‐knockdown HASM using a recombinant BacMam virus then responses to vehicle, forskolin (C), formoterol (C), budesonide (D), or fluticasone (E) were measured. Each point represents the mean ± SEM of n = 4‐5 donors. \* denotes *P* \< .05, \*\* denotes *P* \< .01 of each time point](FSB2-34-2882-g003){#fsb220198-fig-0003} 3.3. Role of GPER in mediating glucocorticoid effects on production of cAMP {#fsb220198-sec-0013} --------------------------------------------------------------------------- Given that glucocorticoids act via an extracellular binding site and depend upon G~αs~, we hypothesize that a GPCR is involved. The GPER is a known GPCR that is activated by specific steroids and has been reported to couple to G~αs~ in certain cells.[36](#fsb220198-bib-0036){ref-type="ref"}, [37](#fsb220198-bib-0037){ref-type="ref"}, [38](#fsb220198-bib-0038){ref-type="ref"}, [39](#fsb220198-bib-0039){ref-type="ref"} 1 and 10 µM estradiol stimulated small cAMP responses that were not significantly different than vehicle (Figure [4](#fsb220198-fig-0004){ref-type="fig"}A). GPER mRNA is detected in a wide array of cell types, including HEK‐293, HFL‐1, and HASM cells (GEO accession numbers <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE128076>, <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73555>, and <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52778>). We examined budesonide cAMP responses in cells preincubated with selective GPER antagonists to determine if glucocorticoids stimulated cAMP via activation of GPER. In HASM cells, the addition of 1 µM G36 had no effect on fluticasone stimulation of cAMP responses (Figure [4](#fsb220198-fig-0004){ref-type="fig"}B). Another GPER antagonist, G15 (1 µM), also had no effect on fluticasone responses (Figure [4](#fsb220198-fig-0004){ref-type="fig"}C). These results are consistent with the idea that the GPER is not involved in mediating the rapid cAMP signaling stimulated by glucocorticoids. ![GPER antagonists do not block glucocorticoid‐stimulated cAMP responses. Primary HASM cells were incubated with recombinant BacMam virus expressing the cADDis cAMP sensor. After establishing baseline, fluorescence decay was monitored for 30 minutes after addition of drug. cADDis sensor fluorescent decay curves elicited by 1 or 10 µM estradiol (A) or 10 µM fluticasone (C). A different Y axis scale is used on panel A to better visualize these responses. Each point represents the mean ± SEM of n = 5 donors and lines represent the fit by one‐phase decay non‐linear regression analysis. No significant differences are seen comparing fluticasone alone to either condition where a GPER antagonist (G15 or G36) was included at any time point using multiple *t* tests and the Holm‐Sidak method for correction of multiple comparisons](FSB2-34-2882-g004){#fsb220198-fig-0004} 3.4. Transcriptional effects of glucocorticoid non‐genomic signaling through G~αs~ {#fsb220198-sec-0014} ---------------------------------------------------------------------------------- Glucocorticoid effects on cells are attributed to their genomic actions, so the role that this rapid, non‐genomic signal plays in regulating cell function is relatively under studied.[5](#fsb220198-bib-0005){ref-type="ref"} To investigate the transcriptional effects of the non‐genomic signaling through G~αs~, we performed an RNA‐Seq analysis from HASM cells treated with 1 µM budesonide, comparing transcripts from control and G~αs~‐knockdown samples 24 hours post‐treatment. We used HASM cell lines isolated from six different donors at the same passage. Each donor cell line was subjected to four conditions: scrambled siRNA treated with vehicle, scrambled siRNA treated with 1 µM budesonide, GNAS siRNA treated with vehicle, GNAS siRNA treated with 1 µM budesonide. We chose a 24‐hour drug treatment duration in order to capture the classical genomic effects of glucocorticoids. We chose to use 1 µM budesonide since this concentration elicited a sub‐maximal cAMP response that could be completely abolished by G~αs~ knockdown. In addition, this lower concentration is more consistent with other studies of the genomic effects of glucocorticoid treatment. With this approach, any observed differences in the budesonide transcriptomes between control and G~αs~‐knockdown cells would reflect the role of the non‐genomic glucocorticoid signaling. We performed quantitative analysis of the transcripts that were altered by budesonide acting through both genomic and non‐genomic signaling (control) or acting through only genomic signaling (G~αs~ knockdown). We began our analysis with the hypothesis that the non‐genomic transcriptional activities are due to signaling via G~αs~. Two novel budesonide signatures were generated using the differential gene expression lists: (a) a 140‐gene genomic and non‐genomic signature of budesonide effect in control cells, and (b) a 121‐gene genomic only signature of budesonide in G~αs~‐knockdown cells (Figure [5](#fsb220198-fig-0005){ref-type="fig"}; Supplemental Tables [S1](#fsb220198-sup-0001){ref-type="supplementary-material"} and [S2](#fsb220198-sup-0001){ref-type="supplementary-material"}). ASSIGN, a pathway analysis toolkit, was used to assess the predictive ability of these gene‐sets in determining budesonide induced transcriptional activity. As an internal validation, we used the signatures to predict budesonide activity in all 24 HASM samples using ASSIGN. Predictions show that both signatures were able to correctly identify budesonide induced transcriptional activity in all 24 HASM samples (Pearson\'s correlation 0.9977; *P* \< .0001; Supplemental Figure [S4](#fsb220198-sup-0001){ref-type="supplementary-material"}). To validate these signatures further, we applied these two signatures to a previously published independent dataset of 34 HASM samples derived from asthma and non‐asthma donors with either control or budesonide treatment[40](#fsb220198-bib-0040){ref-type="ref"} (GEO dataset accession <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94335>). Since there are variation in budesonide concentration and duration for the treatment conditions between the datasets (100 nM for 1 hour vs 1 µM for 24 hours of budesonide treatment), we used ASSIGN's background adaptive feature. Thus, the background gene expression differences between our signature (training) and <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE94335> (test) samples were adjusted to provide more accurate prediction. Despite the slight difference in predicted genomic + non‐genomic and genomic only budesonide activity, both signatures accurately estimated high budesonide activity in budesonide‐treated HASMs derived from both asthma and non‐asthma donors (Pearson\'s correlation 0.9995; *P*  \< .0001, Supplemental Table [S1](#fsb220198-sup-0001){ref-type="supplementary-material"}).[40](#fsb220198-bib-0040){ref-type="ref"} This similarity in predicted budesonide activity validates the robustness of both types of budesonide signatures in capturing transcriptional activity regardless of G~αs~ status 24 hours post‐budesonide treatment. Although genes within each signature are different, the ubiquitous effects of the canonical genomic signaling pathway activated by budesonide, along with a large number of genes in the signatures, maintains the robustness of the predictive ability. ![The transcriptional activity due to budesonide treatment in HASM. A, 140 gene budesonide signature representing the transcriptional activity (genomic + non‐genomic) variation between control and budesonide treated HASM. B, 121 gene budesonide G~αs~ knockdown signature showing the transcriptional activity (genomic only) variation between G~αs~ knockdown‐control and budesonide‐treated HASM. For both (A) and (B), each row represents a gene, and each column represents a sample. The red cell color represents level of overexpression and the blue cell color represents levels of low expression. Brighter the red, higher the gene expression and darker the blue, lower the expression. C, Comparison of genes from each budesonide signatures show 94 genes were shared between budesonide (out of 140 genes) and budesonide‐G~αs~ knockdown (out of 121 genes) signatures. 48 genes unique to budesonide signature represent G~αs~ dependent activity](FSB2-34-2882-g005){#fsb220198-fig-0005} To evaluate the roles of these signature genes in known cellular processes, a gene set enrichment analysis was performed with databases, particularly, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) annotations.[41](#fsb220198-bib-0041){ref-type="ref"} These databases provide curated gene‐sets for understanding the functions and utilities of biological systems, cellular components, and molecular functions of a given test gene‐set. There was no significant enrichment of any KEGG or GO gene‐sets for the budesonide signature gene‐lists after adjusting the p‐value for multiple comparisons. This implies that these budesonide signatures present unique transcriptional activity not represented by the gene‐sets in these databases. Next, we analyzed the overlapping genes from the two budesonide signatures to evaluate the genomic and non‐genomic interplay of these signature genes. There were 92 genes shared between budesonide and budesonide G~αs~‐knockdown signatures (Figure [5](#fsb220198-fig-0005){ref-type="fig"}C). Forty‐eight genes were unique to the budesonide signature, indicating these genes (26 upregulated and 22 downregulated) are dependent on G~αs~‐dependent budesonide transcriptional activity (Table [2](#fsb220198-tbl-0002){ref-type="table"},Supplemental Figure [S2](#fsb220198-sup-0001){ref-type="supplementary-material"}). We then used an unsupervised hierarchical clustering method to investigate how the transcriptional activity attributed to this non‐genomic signature affected the HASM without knowing the treatment conditions. Essentially, we evaluated these 48 genes in their ability to differentiate the treatment conditions. The hierarchical clustering clearly differentiates the two budesonide treatment conditions (Table [2](#fsb220198-tbl-0002){ref-type="table"}, Figure [S2](#fsb220198-sup-0001){ref-type="supplementary-material"}). The clustering also shows two distinct sub‐clusters that identify the non‐genomic signature. ###### List of 48 genes representing the non‐genomic budesonide transcriptional activity in HASM cells Gene symbols Gene name -------------- ---------------------------------------------------------------------------------------- ADARB1 adenosine deaminase, RNA‐specific, B1 ADH1B alcohol dehydrogenase 1B (class I), beta polypeptide ANGPTL1 angiopoietin‐like 1 APBB2 amyloid beta (A4) precursor protein‐binding, family B, member 2 ARID5A AT rich interactive domain 5A (MRF1‐like) ARMC8 armadillo repeat containing 8 ARNTL aryl hydrocarbon receptor nuclear translocator‐like CCDC102B coiled‐coil domain containing 102B CCND3 cyclin D3 CHST7 carbohydrate (N‐acetylglucosamine 6‐O) sulfotransferase 7 CIART Circadian Associated Repressor of Transcription FADS1 fatty acid desaturase 1 FSTL3 follistatin‐like 3 (secreted glycoprotein) GAL galanin prepropeptide GPR1 G protein‐coupled receptor 1 HMGA1 high mobility group AT‐hook 1 IER5L immediate early response 5‐like IL16 interleukin 16 LY96 lymphocyte antigen 96 MAP3K7CL NAMAP3K7 C‐Terminal Like MEX3B mex‐3 homolog B (C. elegans) MMD monocyte to macrophage differentiation‐associated NNMT nicotinamide N‐methyltransferase NR1D1 nuclear receptor subfamily 1, group D, member 1 NR1D2 nuclear receptor subfamily 1, group D, member 2 NRG1 neuregulin 1 PDE5A phosphodiesterase 5A, cGMP‐specific PDLIM1 PDZ and LIM domain 1 PER1 period homolog 1 (Drosophila) PKDCC protein kinase domain containing, cytoplasmic homolog (mouse) PLA2G4A phospholipase A2, group IVA (cytosolic, calcium‐dependent) PLXNA2 plexin A2 PRRX1 paired related homeobox 1 PTPRG protein tyrosine phosphatase, receptor type, G PTX3 pentraxin 3, long RAB7B RAB7B, member RAS oncogene family RGMB RGM domain family, member B SEMA3A sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A SH3PXD2B SH3 and PX domains 2B SHISAL1 Shisa Like 1 SLC19A2 solute carrier family 19 (thiamine transporter), member 2 SQOR Sulfide Quinone Oxidoreductase SSX2IP synovial sarcoma, X breakpoint 2 interacting protein STOM stomatin SYNJ2 synaptojanin 2 TEF thyrotrophic embryonic factor TMEM158 transmembrane protein 158 (gene/pseudogene) ZBTB16 zinc finger and BTB domain containing 16 John Wiley & Sons, Ltd To find similar patterns of non‐genomic transcriptional activity in existing data sets, a gene expression query was performed using these 48 genes in the CMAP database. CMAP is a publicly available independent dataset housing over one million differential gene expression signatures. A CMAP query is used to find similarities and dissimilarities across the curated expression profiles of various perturbations, including compounds, overexpressions, and knockdowns.[32](#fsb220198-bib-0032){ref-type="ref"} CS is a quantitative score between a query gene‐list and a perturbagen that ranges from −100 (opposing signature) to 100 (same signature). CS from a query with 48 G~αs~‐dependent budesonide induced gene‐list across the CMAP database was the highest (98.97) for "GR agonist" among the 171 pharmacologic classes available in the CMAP database. CSs for GR agonists including budesonide investigated in different cell lines including prostate (PC3), melanoma (A375), lung (A549), and hepatocellular cancer (HA1E, HCC515) show high similarity (CSs\>90) (Supplemental Figure [S3](#fsb220198-sup-0001){ref-type="supplementary-material"}, Table [S2](#fsb220198-sup-0001){ref-type="supplementary-material"}). This high similarity across various cell lines and glucocorticoid agonists indicates that the non‐genomic budesonide signature, as represented by these 48 genes, extends beyond HASM and is significantly associated with the GR agonists including, but not limited to, budesonide. 4. DISCUSSION {#fsb220198-sec-0015} ============= A number of glucocorticoids cause rapid increases in cAMP levels in multiple cell types (Figures [1](#fsb220198-fig-0001){ref-type="fig"} and [2](#fsb220198-fig-0002){ref-type="fig"}). These responses appear to be mediated by a plasma membrane‐associated receptor with an outward facing binding site since albumin‐conjugated cortisol, which can\'t cross the plasma membrane, retains activity (Figure [2](#fsb220198-fig-0002){ref-type="fig"}F). The increase in cAMP levels requires stimulation of G~αs~, as knockdown of *GNAS* via siRNA drastically reduces cAMP signaling by glucocorticoids. Since our cAMP assays are performed in the absence of PDE inhibitors there is a possibility that glucocorticoids could work via inhibition of PDE activity. However, inclusion of a broad spectrum PDE inhibitor did not impinge upon fluticasone responses, implying that the glucocorticoid works independently of PDE inhibition. Glucocorticoids can also inhibit uptake of ß‐adrenergic receptor (ßAR) agonists by cells[42](#fsb220198-bib-0042){ref-type="ref"} but our assays are performed in cultured cells with no other drugs or serum present. In these conditions, glucocorticoids would not increase cAMP within seconds via inhibition of uptake of other drugs, even if the cells were producing autocrine‐acting agonists. Glucocorticoids are also known to increase expression of ßAR[43](#fsb220198-bib-0043){ref-type="ref"} but this occurs via genomic action so also can\'t explain our observations. Based on these findings we speculate that these glucocorticoids activate a GPCR of unknown identity. This mechanism appears to be highly conserved through evolution since both insect and amphibian genomes appear to contain GPCRs that respond to glucocorticoids.[9](#fsb220198-bib-0009){ref-type="ref"}, [44](#fsb220198-bib-0044){ref-type="ref"} The canonical nuclear GR appears to be dispensable for the response as its knockdown via siRNA had little effect on these responses.[34](#fsb220198-bib-0034){ref-type="ref"} RU‐486, a progesterone and GR antagonist, blocks the non‐genomic signaling but this chemical likely has the structural elements needed to antagonize glucocorticoid action at non‐GR binding sites.[34](#fsb220198-bib-0034){ref-type="ref"} RU‐486 can also stimulate GR responses so this chemical can act as both an antagonist and an agonist of GR.[45](#fsb220198-bib-0045){ref-type="ref"}, [46](#fsb220198-bib-0046){ref-type="ref"} GR has been shown to exist in the plasma membrane of various cells.[17](#fsb220198-bib-0017){ref-type="ref"} Plasma membrane GR could directly activate G~αs~ or may do so via transactivation of a GPCR. However, the concentrations required to activate cAMP signaling are much higher than those that activate genomic signaling, implying that these occur via different binding sites. It does not appear that glucocorticoids work through binding to GPER since two different antagonists had no effect on glucocorticoid cAMP responses (Figure [4](#fsb220198-fig-0004){ref-type="fig"}). More work is needed to thoroughly understand the receptor mechanism involved in glucocorticoid stimulation of cAMP. A number of investigators have reported rapid actions of glucocorticoids in various cells and tissues. These effects include modulation of basal and stimulated intracellular calcium levels, increases in reactive oxygen species and reactive nitrogen species, increased inflammatory and apoptotic pathways and reduced skeletal and smooth muscle tone (recently reviewed in [5](#fsb220198-bib-0005){ref-type="ref"}). G~αs~‐cAMP signaling has numerous and diverse effects in all cells so many of these prior observations of rapid glucocorticoid signaling may be mediated via increased cAMP. Efforts to understand the non‐genomic effects of glucocorticoids have focused on using the membrane‐impermeable cortisol‐BSA conjugate.[17](#fsb220198-bib-0017){ref-type="ref"}, [18](#fsb220198-bib-0018){ref-type="ref"} However, this agent is a weak activator of cAMP signaling (Figure [2](#fsb220198-fig-0002){ref-type="fig"}F) so this is not an optimal approach. G~αs~ knockdown is a more specific and effective intervention that will be a more powerful means for understanding this non‐genomic signaling. This approach will be useful for understanding the divergent actions of glucocorticoids in other cells and tissues (at least until the membrane receptor involved is identified). Other work demonstrates the physiological relevance of this non‐genomic signaling by glucocorticoids. We demonstrate that budesonide‐stimulated cAMP augments formoterol‐induced bronchodilation in human small airways when combined with formoterol, a long‐acting ßAR agonist.[34](#fsb220198-bib-0034){ref-type="ref"} It is interesting to note that in the present study the glucocorticoids most efficacious at stimulating cAMP production were budesonide and fluticasone, two drugs developed for inhaled use in asthma. The clinical utility of these inhaled glucocorticoids is clearly enhanced by this unappreciated non‐genomic signaling that enhances bronchodilation. While success of these important drugs may have been aided by this additional activity, a complete understanding of this alternate signaling paradigm may inform future development of new drugs. Can drugs be designed with different mixtures of genomic and non‐genomic actions for specific clinical applications? Some side effects of glucocorticoids may be dependent on one signaling pathway or another, allowing improved drug design. Finally, a novel membrane receptor capable of augmenting bronchodilation in small airways could provide a much‐needed alternative drug target to existing ßAR agonists, which suffer from issues with tachyphylaxis and potential maladaptive responses after long‐term use. Confirmation that glucocorticoids act via both rapid, non‐genomic, and canonical genomic signaling mechanisms led us to ask what the role of each might be in context of the known effects of these drugs on the gene transcription. We hypothesized that the cAMP signal serves as a primer to subsequent genomic effects, shaping the size, and/or direction of the transcription of particular genes. Using RNA‐seq and comparing the budesonide treatment transcriptomes from control cells and cells with G~αs~ knockdown allowed identification of the effects of both the genomic and non‐genomic signals. Comparing our data to existing data sets demonstrate that the gene expression changes we observe are highly reproducible across other cell types and other glucocorticoids. We identified a panel of 140 differentially expressed genes that characterize the effects of budesonide in HASM. Of these, 94 genes were shared between the control and G~αs~ knockdown conditions and 48 were unique to the control. These 48 genes (Table [2](#fsb220198-tbl-0002){ref-type="table"}) depend upon the non‐genomic cAMP signal for their differential expression since they were not significantly altered by budesonide treatment in cells lacking G~αs~. Thus, one‐third of the genes altered by budesonide treatment depended upon the non‐genomic signal in some way. These results show the importance of this alternate signaling mechanism and force a rethinking of how glucocorticoids act to alter cell function. We propose that this non‐genomic site of action is not an off‐target effect, but rather an integral part of canonical glucocorticoid action. Our study does have some limitations that require further research. In particular, we chose a 24 hours time point to study the transcriptional effects of budesonide in order to capture the classical genomic effects. A rapid increase in cAMP upon adding glucocorticoid to HASMs suggests that the non‐genomic signaling could begin to alter the transcriptional activity soon after (within an hour or two) glucocorticoid application. Therefore, the transcriptional activity we observe at the 24 hours time point may be too late to capture the full effect of the non‐genomic signaling events. Additional studies are needed to capture RNA‐Seq datapoints from early glucocorticoid treatments to better understand non‐genomic activity attributed to glucocorticoids. Even with this limitation, our data makes clear that the non‐genomic signaling via G~αs~ and cAMP contributes substantially to the regulation of certain glucocorticoid‐responsive genes. We imagine that the non‐genomic signal integrates with the genomic signal via the convergence of transcription factors regulated by cAMP, including but not limited to CREB, with classical GRE at the promotor of certain genes (Figure [6](#fsb220198-fig-0006){ref-type="fig"}). More research is needed to understand how these very different signaling modalities integrate at the level of the gene transcription. ![Schematic diagram of proposed signaling by a putative membrane glucocorticoid receptor (mGR). We propose two signaling pathways mediated by glucocorticoids, the canonical cytosolic GRα receptor mediating direct genomic effects via GRE and a second, non‐genomic activation of G~αs~ and cAMP signaling (illustrated here as signaling via CREB for simplicity, but other transcription factors are likely involved). The latter can have both rapid effects and effects that contribute to the genomic actions of glucocorticoids](FSB2-34-2882-g006){#fsb220198-fig-0006} Our study is also limited to a few cell types (just HASM in the case of RNA‐seq) so broad conclusions about the relevance non‐genomic cAMP signaling by glucocorticoids won\'t be appreciated until other cell types can be studied. However, our analysis of the 48 gene non‐genomic signature in the existing gene expression datasets indicate that many cell types contain this signature. It will be of particular importance to understand how immune cells, major targets of glucocorticoid therapy, respond in terms of both genomic, and non‐genomic signaling. The concentrations required for glucocorticoids to induce cAMP signaling are higher than those associated with activation of nuclear glucocorticoid receptors. While this highlights that a different receptor may be involved, one might question the clinical relevance of the glucocorticoid concentrations we use. While local tissue concentrations of budesonide following inhalation dosing are difficult to determine, plasma concentrations of glucocorticoid following oral dosing of 80 mg in humans reaches peaks of nearly 4 µM.[47](#fsb220198-bib-0047){ref-type="ref"} Thus, the responses we observe are relevant to therapeutic uses of glucocorticoids. Our study identifies a rapid, non‐genomic signaling mechanism by glucocorticoids that contributes to the known gene expression changes induced by these drugs. By acting on a membrane receptor and stimulating G~αs~, glucocorticoids increase the cAMP levels in cells within seconds. We hypothesize that these signals get integrated into the networks that alter the expression of many genes along with the canonical genomic signaling by nuclear GR. This non‐genomic signal can also contribute to rapid effects such a smooth muscle relaxation and likely many others. These findings help explain the clinical utility of inhaled glucocorticoids on an acute basis but also provide a specific mechanism that can be leveraged for the development of future glucocorticoid analogs. CONFLICT OF INTEREST {#fsb220198-sec-0020} ==================== None of the authors have any conflicts of interest to report. AUTHOR CONTRIBUTIONS {#fsb220198-sec-0017} ==================== T.B. Johnstone, C. Koziol‐White, R.A. Panettieri, R.S. Ostrom conception and design; F.J. Nuñez, T.B. Johnstone, M.L. Corpuz, A.G. Kazarian, N.N. Mohajer conducted experiments; F.J. Nuñez, T.B. Johnstone, O. Tliba, R.A. Panettieri, C. Koziol‐White, M.R. Roosan, R.S. Ostrom analysis and interpretation; F.J. Nuñez, T.B. Johnstone, O. Tliba, R.A. Panettieri, C. Koziol‐White, M.R. Roosan, R.S. Ostrom drafting the manuscript for important intellectual content; all authors approved the final version. Supporting information ====================== ######   ###### Click here for additional data file. The authors thank Drs. Raymond Penn and Tonio Pera, Thomas Jefferson University, and Dr Gaoyuan Cao and Brian Deeney, Rutgers University, for isolating and providing HASM cells. This work was made possible, in part, through access to the Genomics High Throughput Facility Shared Resource of the Cancer Center Support Grant (P30CA‐062203) at the University of California, Irvine and NIH shared instrumentation grants 1S10RR025496‐01, 1S10OD010794‐01, and 1S10OD021718‐01.
tomekkorbak/pile-curse-small
PubMed Central
Mr. Satan is challenged to a fight by an old rival, and he is taken to an island where the fight is to be held. Accompanying him are Android 18, who is making sure he doesn't skip town before paying the money he owes her for letting him win the World Martial Arts Tournament, and Trunks and Gote... When a worker at King Yemma's spiritual check-in station is accidentally covered in spiritual waste, he is transformed into a powerful monster named Janemba, who destroys the barrier between the real world and Other World, allowing the dead to walk the Earth. As the living Z Fighters fend off t... Dr. Raichi, a survivor of the Tuffle race that was eliminated from Planet Vegeta by the Saiyans, is trying to take revenge on the surviving Saiyans by killing them and Earth's population. Goku, Gohan, Piccolo, Trunks, and Vegeta must find and destroy generators emitting deadly Destron Gas befor... A teenage boy (Ryohei) lands his dream job working for Poteto Boy magazine - a popular playboy style magazine. He becomes infatuated with both his attractive female editor and star reporter Aki. Ryohei's enthusiasm and perverse nature leads to some unusual and amusing situations. A traveler is confronted by spirits in an abandoned shrine; a story of honor and firefighting in ancient Japan; a white bear defends the royal family from a monstrous red demon; ragtag soldiers battle a robotic force in futuristic Japan. The death of Dr. Gero at the hands of Androids 17 and 18 prompts the activation of Androids 13, 14, and 15. They try to kill Goku, who fights them with the help of Trunks, Piccolo, Vegeta, Krillin, and Gohan. You are searching for a site to watch movies and TV series online for free? MovieWatcher. to is the right place - streaming videos was never easier! Our website privides real streaming links from external video hosters where you will be able to watch all movies and most popular TV series online. MovieWatcher crawls external sites for streaming links and exctracts videos into emded player. You can stream movies by imported player or visiting the video hosters. Our portal is absolutely free and requires no registration. Our highest priority is to crawl movie links in best quality: AVI, MPEG or High Defintion formats. You are welcome to browse movies by genres, rating, actors, release date or by name. If you love movies you will love Moviewatcher!
tomekkorbak/pile-curse-small
Pile-CC
Trouble logging in?If you can't remember your password or are having trouble logging in, you will have to reset your password. If you have trouble resetting your password (for example, if you lost access to the original email address), please do not start posting with a new account, as this is against the forum rules. If you create a temporary account, please contact us right away via Forum Support, and send us any information you can about your original account, such as the account name and any email address that may have been associated with it. Aside from her being a level 5, she probably gets away with all the destruction because it's Academy City. It's a city of people with powers, property destruction is probably the least of their concerns. Heck, with amount of ability users running around (around 736k if the 60% Level 0 stat is to be believe), it's probably expected and they probably have it allocated in their budget. Academy City seems to have a lot of money to throw around anyway, if the have a lot of useless security robots (that cost 1.2 million per unit) running all over the place. If it's create a network I don't think so... unless Misaki's clones stayed in a relatively close range with each other. I think the electric waves have a way higher range than Misaki's telepathy, probably. If it's to create an army for Accelerator to fight they would probably would not present enough challenge in the first place, whatever their numbers were. EDIT: Then again, I hadn't thought about it, but the Sister's electric waves should not be able to connect to each other all across the world without relays... so how do they pull that off? do they use public satellites? do they connect through the internet? ... Now I'm confused. well guys, this chapter does sort of imply that mikoto's friends "dont" really need to have their memories restored, they can be convinced through pics and stuff. so the theory that kuruko and co. not remembering, and kuruko falling in love all over again, is not obsolete. Then again, I hadn't thought about it, but the Sister's electric waves should not be able to connect to each other all across the world without relays... so how do they pull that off? do they use public satellites? do they connect through the internet? ... Now I'm confused. Shortwave radios, which in their case can be fine-tuned for maximum reception. Shortwave radios, which in their case can be fine-tuned for maximum reception. Right, how dumb of me, it's not called Radio Noise for nothing. Most likely high frequency (maybe up to GHz with their power) encoded single sideband messages over AM radio. They are sure to be making a lot of "noise" for other radio users. When Mikoto started having problems on the arc I thought that some major character (Touma, Accelerator, Mugino) or potential (Gunha) would be placed in a situation that ended up helping her, but it looks like the girls in your school who will this. Well, see Kongou being beaten really gives the feeling that I'm watching the show right. When Mikoto started having problems on the arc I thought that some major character (Touma, Accelerator, Mugino) or potential (Gunha) would be placed in a situation that ended up helping her, but it looks like the girls in your school who will this. You might not remember this, but Touma showing up 'frequently' at the end the Sisters Arc had some fans up-in-arms about him 'stealing the spotlight', never mind that it's part of the established canon. Well, never again! Back to the side-character you ! Gunha is a good guess, but my gut feeling says he would have more to do with Misaki than Mikoto... Or maybe zero involvement The other Tokiwadai girls have been foreshadowed earlier on so their involvement now doesn't come as a surprise. Quote: Originally Posted by Acer Well, see Kongou being beaten really gives the feeling that I'm watching the show right. Lol, call it a series tradition to always have a girl getting beat up and tortured almost every arc Higurashi: Its a bit like watching a trainwreck, except you keep getting to see different trains wrecking with roughly the same passengers, into a variety of different objects. Also, the trains are driven by monkeys. On LSD. click to play
tomekkorbak/pile-curse-small
Pile-CC
The present invention relates to a car stereo generally provided on the dashboard of a motor vehicle, more particularly to a car stereo having a detachable grille. With an increase in the use of sophisticated car stereo in recent years, there have been more and more theft concerning car stereo. Such theft are supposed to have happened due to a clear appearance of a grille having various operation pushbuttons which enables a thief to quickly recognize the existence of a car stereo. In order to prevent theft of a car stereo from increasing, a car stereo having a detachable grille has been developed and become commercially available. If a car driver releases the grille from the stereo body when leaving his car, the theft may be prevented since it is difficult to know there is a car stereo provided on the dashboard. FIG. 9 shows the above-mentioned conventional car stereo wherein a grille 20 having various operating pushbuttons is detachable from a stereo body 10. As shown in FIG. 9, the stereo body 10 has a recess 11 into which the grille 20 is mounted. The recess 11 is provided with a connector member 12 on the right hand side thereof, an elongated cassette opening 14 on nearly central portion thereof, and a detecting switch 15 on the left side of the opening 14. The detecting switch 15 is provided to detect whether or not the grille 20 is mounted on the stereo body 10. Also, as shown in FIG. 9, the grille 20 has, on the front face thereof, a series of operating pushbuttons 22, display 23 for indicating various information such as time and a radio receiving frequency. On the upper portion of the front face of the grille 20, there is provided an elongated cassette opening 24 corresponding to and communicating with the elongated opening 14 formed on the recess 11 of the stereo body 10. FIG. 10 shows an inner structures of the grille 20 and the stereo body 10 respectively and an electrical relationship between these two. As shown in FIG. 10, the connector member 12 is provided with various contacts including a contact 12a for obtaining 5 V electric power supply, a contact 12b for data input and output, a contact 12c for obtaining 8 V electric power supply, and an earth contact 12d. The contact 12a is connected to 5 V electric power supply circuit 17, and the contact 12c is connected to 8 V electric power supply circuit 18. The contact 12b is connected to a micro-computer 19. Also, as shown in FIG. 11, on the rear face of the grille 20 is provided a plug member 21 which is to be connected with the connector member 12 provided on the stereo body 10. The plug member 21 has a contact 21a corresponding to the contact 12a for obtaining 5 V electric power supply, a contact 2lb corresponding to the contact 12b for data input and output, a contact 21c corresponding to the contact 12c for obtaining 8 V electric power supply, and an earth contact 21d corresponding to the earth contact 12d provided on the connector member 12. The contact 21a and contact 2lb are connected to another micro-computer 25 which, in accordance with operating modes of the various pushbuttons 22, produces control signals for indicating various information such as time and a radio receiving frequency. Further, a display driver 26 controls the operation of the display 23 in accordance with a control signal fed from the micro-computer 25. In addition, an illuminating lamp 27 is connected to the contact 21c. The grille 20 may be attached to the stereo body 10 by first pushing the rear left end portion of the grille 20 into the left side portion of the recess 11 of the stereo body 10, and then pushing the rear right end portion of the grille 20 into the right side portion of the stereo body 10. Meanwhile, the detecting switch 15 is abutted by the rear left end portion of the grille 20 so as to become in ON state, thereby detecting the attachment of the grille 20. Then, the micro-computer 19 feeds control data through the data output contact 12b to the grille 20. After the attachment of the grille 20 to the stereo body 10, the connector member 12 provided on the stereo body 10 becomes engaged with the plug member 21, so that an electric power of 5 V is supplied through the contacts 21a and 12a to the micro-computer 25. After the micro-computer 25 performs a reset operation, the micro-computer 25 receives a control data which is fed through the contacts 12b and 2lb from the micro-computer 19, thereby enabling the display driver 26 to perform proper operations in accordance with the control data fed thereto. On the other hand, upon detachment of the grille 20 from the stereo body 10, the detecting switch 15 returns to OFF state. This OFF state is detected by the micro-computer 19 which at once stops feeding of the data to the contact 12b. However, in a conventional car stereo having a detachable grille, the connector member 12 provided on the stereo body 10 and the plug member 21 provided on the grille 20 are constructed as shown in FIG. 11 which cause some problems as discussed hereinafter. First, it is seen from FIG. 11 that said contacts 12a-12d are all in an exposed state. Since these contacts are formed of a kind of torsion spring, they have a low resistance to torsion and are easy to suffer from a deformation due to an external force in their lateral direction. Second, since the connector member 12 is engaged with the plug member 21 only when the grille 20 is attached to the recess 11 of the stereo body 10, if the attachment is performed in an inappropriate manner, an aberration is apt to occur while the contacts 12a-12d of the connector member 12 are being engaged with the corresponding contacts 21a-21d of the plug member 21. And, if an external force is unduly applied to the contacts 12a-12d on the connector member 12, the contacts 12a-12d will be deformed, hence causing an imperfect contact between the contacts 12a-12d of the connector member 12 and the contacts 21a-21d of the plug member 21. Moreover, as shown in FIG. 3, since the contacts 12a-12d are in an exposed state after the grille 20 is released from the stereo body 10, some insulant substances such as oil is apt to be depositted onto the surfaces of the contacts due to an accidental touching. This also causes an imperfect contact between the contacts 12a-12d of the connector member 12 and the contacts 21a-21d of the plug member 21. In addition, since the contacts 21a-21d of the plug member 21 are pressure-contacted by the contacts 12a-12d of the connector member 12, the vibration of a travelling motor vehicle will produce an external force applied on to the contacts, causing an aberration in the pressure-contact relationship and hence resulting in a deformation of the contacts which leads to a similar imperfect contact.
tomekkorbak/pile-curse-small
USPTO Backgrounds