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Best Miter Saw Stands on the Market in 2018 (Comparison Included) Unless you plan to bolt your miter saw down to the worktable in your shop or garage, you are going to need a rock solid stand to take your miter saw on the go. In order to make precision cuts accurately and safely, your miter saw needs a stable, level base under it to ensure you don’t waste materials or put your own safety at risk while cutting. Choosing the right stand for your saw is a matter of verifying that it can be safely mounted on a potential stand, and knowing that stand will provide years of dependable service. In order to help you make an informed decision, we’ve assembled some miter saw stand product reviews to help you choose the right one for your saw. Take a look at what we have for you: 5 Best Dewalt Miter Saw Stand DeWalt is well known for building high quality, dependable power tools, and their accessories for these power tools are no exception to their outstanding reputation. While they are compatible with other miter saw manufacturer’s products, they work best with DeWalt designed and manufactured miter saws. Check out our reviews of what DeWalt has to offer for your saw. 1. DEWALT DWX726 Rolling Miter Saw Stand When you buy a heavy duty miter saw for doing lots of trim work or finish work with hardwood, timber, or softwood, you need a miter saw stand that can not only support the weight of your heavy duty saw, but also the heavy materials you are going to be cutting. For those heavy duty 12-inch blade sliding compound miter saws that DeWalt makes so well, you definitely want the DWX726 Rolling Miter Saw Stand. The entire stand is made from durable tubular steel that is powdered coated in signature DeWalt Yellow and black. Black rubber wheels provide excellent traction over most job site terrain, and the lift control is easily accessible from the handlebars. Setup is easily achieved by one person thanks to the three-position pneumatically assisted folding mechanism, making it easy for one person to adjust the height of the stand without first needing to unmount and remove the saw. Furthermore this stand supports up to 300 lbs, which can easily accommodate not only your heavy duty miter saw but also boards and sections of molding up to 8 feet in length. Additionally, the DWX726 also has two in feed and out feed work supports that help keep your material stable while you cut even when your materials extend well beyond the base of your miter saw. Overall, this is DeWalt’s top of the line rolling miter saw stand, and is suitable for any kind of portable saw that requires stable and level mounting. 2. DEWALT DWX723 Heavy Duty Miter Saw Stand For the really big jobs, DeWalt makes the DWX723 Miter Saw Stand with extra wide work supports and a 500 pound weight capacity. This model is compatible with any brand of miter saw, and the sliding mounting brackets make it extremely easy to set up and remove your miter saw onsite. Built from lightweight aluminium, the DWX723 collapses down and folds up for superior portability, and the non-marring feet make it easy to achieve a level cutting surface in any setting. Additionally, the 5 ½ inch beam with work supports on each side can extend as much as 8 feet on each side, providing in feed and out feed stability for up to 16 total feet. It also has an integrated carry handle for easier portability when it is folded up and ready to be loaded back on the truck or into storage. Superior portability, weight capacity, and work support design make this an ideal stand for full time contractors and individuals who want a miter saw stand they can depend on without reservation. While it may be more than a hobbyist or DIY user might want or need, it is still an exceptional value that will provide a lifetime of stable support for your miter saw. 3. DEWALT DW7440RS Rolling Saw Stand If the DeWalt DWX726 and DWX723 had a baby, it would look exactly like the DW7440RS Rolling Saw Stand. This lightweight miter saw stand weighs just 33 pounds, and is extremely easy to roll into place and setup by yourself. The quick connect stand brackets make attaching any miter saw fast and easy, and the aluminum legs with non-marring feet keep the whole thing steady while you work. In addition to being light and portable thanks to its hard rubber wheels, the DW7440RS also features quick release levers for the legs so that it can be quickly collapsed and moved with minimal effort. An extendable work support that collapses back into the main assembly also allows you to keep your materials stable during cutting. Overall, the DW7440RS can support up to 200 lbs., and the convenient kickstand allows you to turn the stand on its side and roll it around without removing the miter saw. This can be a major time saver when you need to move the saw around the job site frequently. All in all, this is possibly DeWalt’s best offering for a portable miter saw stand that will work with both heavy duty 12-inch miter saws and lighter 10-inch models, too. If storage space is a factor but you still need portability and strength, this is the miter saw stand for you. What we liked 200 lbs. capacity Extendable work support Kickstand for easy mobility without unmounting your miter saw What we didn't like Work supports are insufficient for extended sections of molding or boards 4. DEWALT DWX724 Compact Miter Saw Stand The DWX726 “little sister”, the DWX724 provides the same rock solid 500 lbs. capacity on a lightweight aluminum frame. It weighs less than its larger counterpart at 29.8 lbs, and it folds up completely into a 40- inch long rectangle that is easy to carry one handed. The folding aluminum legs also have non-marring rubber feet that keep everything steady while you work. Mounting your miter saw is quick and easy thanks too DeWalt’s quick release mounting brackets, and positioning everything properly is just a matter of sliding the brackets where you want your saw to go, then tightening them down. Additionally, the DWX724 features extendable work supports that provide up to a total of 10 feet of infeed and out feed material support for additional stability when you are working with longer sections of molding or lumber. If you are looking for a stable miter saw stand with significant weight capacity, but you don’t need extra long work supports, this is definitely the best choice in terms of features and capability. It’s not rated as “heavy duty”, but it is easily portable, can hold a quarter ton of weight and keeps your miter saw stable while you are cutting. For the home workshop user or DIY enthusiast, what more do you really need? Designed by Delta Power Equipment for use with DeWalt brand and other manufacturer’s miter saws, the 36-267 is an elegant portable miter saw table solution that makes using and transporting your miter saw around the job site fast and easy. One person can move and setup the stand with a single step thanks to the foot actuated pedal, and the 36-267 is rated for up to 350 lbs. Ideal for any make or model miter saw (including 12-inch and 10-inch models), this stand rolls easily over most terrain thanks to its hard rubber wheels, and clamp on miter saw mounts make it easy set your saw down in place and lock it down securely with just a bit of quick tightening. Extendable work supports also make it easy to keep your materials steady while you make your cuts, even if they extend out beyond the base of your miter saw. Thanks to its heavy duty steel tubing construction and easy setup, this is an excellent miter saw stand for contractors or DIY enthusiasts that need a mobile miter saw on a regular basis. It does tend to occupy quite a bit of storage space even when not in use though, so it may not be ideal for use in a home workshop. 1. Hitachi UU240F Heavy-Duty Portable Miter Saw Stand Combining concepts and design features from multiple types of miter saw stands, the UU249F from Hitachi is an exceptional heavy duty miter saw stand that makes light work of any precision cutting job no matter where your work takes you. Just push it to where you need to work, extend the legs, and flip it back into place. Built with heavy duty stainless steel tubing, this saw stand rolls easily on its two hard rubber wheels wherever you need a stable cutting surface for your miter saw. With a weight capacity of up to 400 lbs and quick release mounting brackets, the UU240F can easily accommodate up to a 12-inch sliding compound miter saw. Moreover, the extendable work support arms can hold your materials steady while you make those precision cut, adding to its overall versatility. Another extremely useful feature is that the height can be adjusted as high as 35 inches, allowing users to set the height at their optimal comfort level for easier cutting. All in all, the best thing about the UU240F is that it offers you all of the features of a heavy duty miter saw stand with the versatility of a rolling miter saw stand. There are compromises (such as work support arm length and overall weight capacity), but overall it’s a great choice for both professionals and enthusiastic DIYers alike. 2. POWERTEC MT4000 Deluxe Miter Saw Stand A rolling miter saw stand with a unique innovation, the Tough Built MT4000 from POWERTEC provides many of the features of a heavy duty miter saw stand with the versatility of a rolling miter saw stand. Rated for up to 330 lbs, the MT4000 is constructed of all steel tubing, and can easily accommodate any make or model of 12-inch or 10-inch compound sliding miter saw. What makes this stand unique is the addition of a 110-volt power outlet, simplifying wire management for your miter saw and making your job site safer. After all, the fewer extension cords laying across a work site, the better it is for everyone working there. Additionally, the four legs of the stand are spring loaded and easy to pop into place even if you are setting up or tearing down by yourself. Getting your miter saw securely mounted or safely removed is also a snap thanks to quick-release universal mounting brackets, and extendable work support arms extend on either side to provide a total of 8 feet for keeping your materials stable while you are cutting. Overall, this miter saw stand is a great choice for home workshop or DIY enthusiasts, and provides everything you need to get the most out of your miter saw without permanently mounting it to a worktable. What we liked Innovative 110-volt power outlet Sturdy all steel tubing construction rated to 330 lbs Quick release mounting brackets What we didn't like Support arms are a bit shorter than traditional heavy duty miter saw stands Spring loaded legs can be a little tricky to manipulate when tearing down 3. HICO UWC4000 Compact Folding Miter Saw Stand When storage space is at a premium, but you still need a stable platform for using your miter saw, the HICO UWC4000 is an excellent solution for getting the most out of your miter saw. This stand is rated for use with band saws, planers, and scroll saws as well as up to a 12-inch compound sliding miter saw, and it will support up to 500 lbs of weight. The stand itself is constructed from all-steel tubing with snap pin folding legs for easy setup and teardown. Additionally, the whole stand and accessories folds up into a 4-foot, easy to carry rectangle that takes up very little storage space when not in use. All you have to do after setting up is to drop your miter saw or other bench mounted power tool into the 20 inch quick attach mounting and lock them in place with the quick release knobs. The UWC4000 also has dual extending support arms that add an extra 8 feet of support for your materials, keeping things stable while you make those precision cuts. As bench mount power tool stands go, this model is strong, durable, and easy to store and transport. It is also one of the best value purchases you can make for your home workshop or next DIY project, as its usefulness extends beyond just supporting miter saws when you’re out on the job. What we liked Tough steel tube construction rated up to 500 lbs Accommodates many bench-mounted power tools like band saws and planers 4. Ridgid AC9945 Miter Stand Utility Vehicle Looking to save space in the shop, the work van, or around the job site? The Rigid AC9945 Miter Stand is an excellent choice for anyone that needs a large dedicated work surface to provide stable operation of their miter saw or other portable bench mounted power tools. Rolling on two rubberized wheel and easy to maneuver thanks to multi-grip position handles, the AC9945 can make light work of setting up and tearing down your miter saw work space. The unique innovation of this particular saw stand is that the support leg is housed in the extension arms, allowing you to easily adjust the work surface height without making the overall design cumbersome or bulky. Additionally, the included quick release mounting brackets can be adjusted laterally to position the saw wherever is most convenient for the user while cutting. Furthermore, the work support arms extend outward to keep materials stable and secure while cutting. Length of support arms is also less of an issue with this model since the saw itself can be shifted further or close to either end of the stand. If you are in the market for a heavy duty rolling saw stand that will provide a lifetime of durability despite hard use, this is the miter saw stand for you. It may be somewhat overkill for home users or DIYers, but it is definitely a solid performer with few drawbacks. What we liked Heavy duty steel construction Laterally adjusting quick release mounting brackets Adjustable height What we didn't like Final Verdict Our top pick for the best miter saw stand is without a doubt the HICO UWC4000 Compact Folding Miter Saw Stand. It’s easy to store, easy to carry, can support a quarter ton of weight, and is compatible with other benchmout power tools. It may not have wheels for easier maneuvering around the job site, but it does have the best overall combination of features compared to any other model we’ve reviewed. It’s ideal both for professional job sites and for woodworking shops in the garage or shed out back. Not only is it well built and tough, but it is also easy to setup yourself unassisted, and removing or remounting additional tools onto the stand is exceptionally easy thanks to the snap-pin legs and quick release mounting brackets. If you are looking for a high quality miter saw stand for your workshop or to transport from site to site, the HICO UWC 4000 Compact Folding Miter Saw Stand is our first choice. Definitely check it out before you shop around more. It’s well worth the investment. DrillPressView.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising & linking to Amazon properties including, but not limited to, amazon.com Session expired Please log in again. The login page will open in a new window. After logging in you can close it and return to this page.

Formulation and characterization of microspheres loaded with imatinib for sustained delivery. The aim of this study was the development of imatinib-loaded poly(d,l-lactide-co-glycolide) (PLGA) microspheres with high loading efficiency which can afford continuous release of imatinib over a prolonged period of time. Imatinib mesylate loaded PLGA microspheres with a size of 6-20 μm were prepared by a double emulsion (W1/O/W2) method using dichloromethane as volatile solvent. It was found that the microspheres were spherical with a non-porous surface; imatinib loading efficiency (LE) was highly dependent on the pH of the external water phase (W2). By increasing the pH of W2 phase above the highest pKa of imatinib (pKa 8.1), at which imatinib is mainly uncharged, the LE increased from 10% to 90% (pH 5.0 versus pH 9.0). Conversely, only 4% of its counter ion, mesylate, was retained in the microspheres at the same condition (pH 9.0). Since mesylate is highly water soluble, it is unlikely that it partitions into the organic phase. We demonstrated, using differential scanning calorimetry (DSC), that imatinib was molecularly dispersed in the polymeric matrix at loadings up to 8.0%. At higher drug loading, imatinib partially crystallized in the matrix. Imatinib microspheres released their cargo during three months by a combination of diffusion through the polymer matrix and polymer erosion. In conclusion, we have formulated imatinib microspheres with high LE and LC. Although we started with a double emulsion of imatinib mesylate, the obtained microspheres contained imatinib base which was mainly molecularly dispersed in the polymer matrix. These microspheres release imatinib over a 3-month period which is of interest for local treatment of cancer.

[Optimization of mobilization regimes of blood hemopoietic stem cells in patients with multiple myeloma]. To determine an optimal cyclophosphamide dose in the mobilization scheme providing adequate collection of CD34+ cells in patients with multiple myeloma (MM), to optimize the time of initiation of granulocytic colony-stimulating factor (G-CSF) administration, to study effects of induction therapy schemes on results of mobilization and collection of CD34+ cells. Department of hemoblastoses chemotherapy and bone marrow transplantation of the Russian Hematological Center performed mobilization of autologous blood hemopoietic stem cells (BHSC) in 93 MM patients treated in 2001-2010. This was done with cyclophosphamide and G-CSF. The former was used in 59 cases in a dose 6 g/m2, in 34 cases - 4 g/m2. Myelotoxic agranulocytosis after cyclophosphamide administration developed in all the patients and was observed for 3-10 days (median 5 days). Agranulocytosis ran without documented infections in 51 (54.8%) patients, with febril fever - in 42 (45.2%) patients. Cepticemia, pneumonia, necrotic enteropathy, stomatitis, herpetic lesion of the skin were registered in 9, 4, 11, 14 and 6 cases, respectively. Severe thrombocytopenia (< 30 x 10(9)/l) occurred more frequently in administration of 6 g/m2 cyclophosphamide. It was corrected with 2-5 transfusions of thromboconcentrates, only 1 transfusion was needed after the dose 4 g/m2. Collection of CD34+ cells started in leukocyte level over 3.5 x 10(9)/l on mobilization day 12-20 (median day 15). The day of the first leukocytapheresis did not depend on the day of the first introduction of G-CSF. Duration of G-CSF administration was significantly shorter in the start of its use after leukocyte count decrease under 1.0 x 10(9)/l. Conduction of 1 to S (median 2) leukocytapheresis was needed for collection of BHSC. Sufficient for 2 autotransplantations number of BHSC were stored in 90 of 93 patients. Cyclophosphamide administration in a dose 6 g/m2 allowed collection of cells sufficient for one autotransplantation for the first leukapheresis in 52 (88.1) patients. A total number of CD34+ cells over 4 x 10(6) cells/kg were collected in 56 (94.9%) patients. In administration of cyclophosphamide in a dose 4 g/m2 mobilization was effective in all 34 patients. The first leukapheresis provided sufficient for one autotransplantation number of cells in 29 (85.3%) patients. Administration of high cyclophosphamide doses in combination with G-CSF is an effective and safe method of BHSC mobilization providing collection of adequate number of CD34+ cells for double autotransplantation in 96.8% patients. Cost effective is the start of G-CSF administration in the fall of leukocytes under 1.0 x 10(9)/l. Cyclophosphamide dose 4 g/m2 provides collection of CD34+ cells number sufficient for two autotransplantations in moderate thrombocytopenia and in less number of substitute transfusions in the absence of serious toxic complications.

The presence of oxidative polymeric materials in encapsulated fish oils. Encapsulated health food oils such as fish oils are readily available in health food stores, pharmacies, and supermarkets. They are popular in the United States as well as in the European countries. However, such oils, because of their high degree of unsaturation, are easily oxidized and form complex mixtures of high molecular weight oxidation products. The present work reports the application of high-performance size exclusion chromatography to the determination of these materials in encapsulated fish oils. Of the six samples studied, five showed from 1-10% of dimeric triacylglycerols and one contained 6.3% trimeric triacylglycerols and 3.1% oligomeric triacylglycerols. Further investigation of this sample with silicic acid chromatography indicated that it contained a total of 36.3% polar material.

// // PageTabMenuViewController.swift // PageMenuExample // // Created by Tamanyan on 3/7/17. // Copyright © 2017 Tamanyan. All rights reserved. // import UIKit import SwiftPageMenu class PageTabMenuViewController: PageMenuController { let items: [[String]] let titles: [String] init(items: [[String]], titles: [String], options: PageMenuOptions? = nil) { self.items = items self.titles = titles super.init(options: options) } required init?(coder aDecoder: NSCoder) { fatalError("init(coder:) has not been implemented") } override func viewDidLoad() { super.viewDidLoad() self.edgesForExtendedLayout = [] if options.layout == .layoutGuide && options.tabMenuPosition == .bottom { self.view.backgroundColor = Theme.mainColor } else { self.view.backgroundColor = .white } if self.options.tabMenuPosition == .custom { self.view.addSubview(self.tabMenuView) self.tabMenuView.translatesAutoresizingMaskIntoConstraints = false self.tabMenuView.heightAnchor.constraint(equalToConstant: self.options.menuItemSize.height).isActive = true self.tabMenuView.leftAnchor.constraint(equalTo: self.view.leftAnchor).isActive = true self.tabMenuView.rightAnchor.constraint(equalTo: self.view.rightAnchor).isActive = true if #available(iOS 11.0, *) { self.tabMenuView.bottomAnchor.constraint(equalTo: self.view.safeAreaLayoutGuide.bottomAnchor).isActive = true } else { self.tabMenuView.bottomAnchor.constraint(equalTo: self.view.bottomAnchor).isActive = true } } self.delegate = self self.dataSource = self } } extension PageTabMenuViewController: PageMenuControllerDataSource { func viewControllers(forPageMenuController pageMenuController: PageMenuController) -> [UIViewController] { return self.items.map(ChildViewController.init) } func menuTitles(forPageMenuController pageMenuController: PageMenuController) -> [String] { return self.titles } func defaultPageIndex(forPageMenuController pageMenuController: PageMenuController) -> Int { return 0 } } extension PageTabMenuViewController: PageMenuControllerDelegate { func pageMenuController(_ pageMenuController: PageMenuController, didScrollToPageAtIndex index: Int, direction: PageMenuNavigationDirection) { // The page view controller will begin scrolling to a new page. print("didScrollToPageAtIndex index:\(index)") } func pageMenuController(_ pageMenuController: PageMenuController, willScrollToPageAtIndex index: Int, direction: PageMenuNavigationDirection) { // The page view controller scroll progress between pages. print("willScrollToPageAtIndex index:\(index)") } func pageMenuController(_ pageMenuController: PageMenuController, scrollingProgress progress: CGFloat, direction: PageMenuNavigationDirection) { // The page view controller did complete scroll to a new page. print("scrollingProgress progress: \(progress)") } func pageMenuController(_ pageMenuController: PageMenuController, didSelectMenuItem index: Int, direction: PageMenuNavigationDirection) { print("didSelectMenuItem index: \(index)") } }

Three-dimensional CT angiography in the detection and characterization of intracranial berry aneurysms. To assess the accuracy of three-dimensional CT angiography (CTA) in the detection and characterization of intracranial aneurysms and to help determine its role as a screening test for aneurysms in the asymptomatic population and as an adjunct to angiography in subarachnoid hemorrhages and in the follow-up of untreated aneurysms. In a blinded, prospective study, the 3-D CTA studies in 80 patients with symptomatic aneurysms were analyzed for the presence and morphology of aneurysms. Angiography or surgery acted as the control. Ninety-four aneurysms were found in 63 patients. Negative findings at angiography were noted in 17. Sensitivity and specificity of 3-D CTA for all aneurysms, all patients, and aneurysms 5 mm or smaller were 90.4% and 50%, 98.4% and 82.4%, and 78.8% and 51.9%, respectively. Three-dimensional CTA may have a role in noninvasive screening for asymptomatic aneurysms in the general population, but caution is advocated when data obtained from symptomatic patients are extrapolated to the asymptomatic population who harbor smaller aneurysms. Also, 3-D CTA may be useful as an adjunct to angiography in the characterization of berry aneurysms and in the follow-up of untreated aneurysms.

Naughty Rui En even tried to pull her own prank on him, by throwing a tantrum and storming off when he was late for work. She recalled: ‘But the (Gotcha) producers kept putting a wet blanket on it. They probably have something in store for us.’ We think the real surprise would be if the comely couple were indeed an item. But Rui En scotched such talk, saying: ‘He’s been in this line for a long time, so he knows better than to make things awkward by getting involved. ‘Anyway, he’s quite scared of me, so I don’t think he’d want to!’ But Kui Jien quipped that ‘there is a possibility’.’ We made a pact that when we’re 76, and if we don’t find anybody else, we’re going to hook up.’ Hmm, is that a joke? He’s a really nice, joker/comedian type of guy. And I like his bright, radiant smile … But he thinks I’m one of the most violent girls in Singapore!– Actress-singer Lu Rui En on Gotcha co-host Soo Kui Jien

Connect With Us UCI Starcraft Team Two stormtroopers display the prizes for the 2011 IEEE XTREME lan party. Gamers playing on their own PC's and monitors at the lan party. As the sprites on his screen explode into a flurry of shrapnel, his actions become less calculated and more frantic. Finally, less than a minute after the battle began, he stops typing. He takes a breath, hits enter, and types a parting message to his faceless opponent. “GG.” Good game. He concedes. In the world of competitive video gaming, known within the community as “e-sports,” “StarCraft” has long been the dominant Real-Time Strategy (RTS) game, a genre of game where two or more players make moves against each other in real time. Starting with a small base with a limited amount of units, each player collects more resources using specialized units called “workers” while bulking up their army and fending off harassment from their opponents. As the armies grow, the players maneuver strategically around the terrain, attempting to catch their enemy off guard with their “micro,” short for micro management, and, finally, crush the opposing army. Think of it as chess, except real-time, with pieces continually moving and starting with only pawns. The popularity of the game is so great that, in South Korea, several different leagues and teams were formed. Live matches are televised and crowds fill stadiums to watch. The professional players are true professional athletes, with salaries and sponsorships from large companies such as LG, Samsung and Intel; their lives are nothing but 10-hour training days and tournament competition. ,With the release of the sequel, “StarCraft 2,” new life has been given to the e-sports scene in the West. Though currently not as stable as the Korean organizations, several leagues have been created, such as the North American Starleague (NASL) and the IGN Proleague (IPL). Even MLG, long thought defunct, saw its attendance numbers climb greatly. Combined, the tournaments offer over $100,000 in prize money. The environment is now stable enough that smaller specialized leagues have been able to form, such as those designed specifically for new players, girls and even college students. There are many things one could do on a free Wednesday night during spring quarter. The weather is mild and warm enough to spend time outside but still brisk enough to be able to enjoy a warm drink with a good book. The air is crisp and fresh. The grass and trees are green again. Why then, would someone spend their evening in a room lit by fluorescent bulbs, sitting at table surrounded by two dozen guys and three dozen computers? Nearly every Wednesday of the quarter, the “StarCraft” Club meets in a room on the third floor of CaliT2, in the Henry Samueli School of Engineering. The room is perfect for their purposes. There are rows of desks with power sockets members to plug in their computer. They all face the front of the room, where a podium with projector controls and computer hook ups stands to the left of a large projector screen, allowing the club to screen games on the spot. Timothy Young, co-founder and current operations officer, starts each meeting with a few quick announcements before hooking up his computer and displaying the night’s live games on the provided screen. The members watch the headline matches with deep interest. Once these are finished, the members shift their attentions elsewhere. Almost spontaneously, two players start an impromptu game. They both develop a raucous crowd, who cheer, jeer, or feed the players false information. Other members are off to the side on computers while browsing “StarCraft” community websites, where they read about the newest strategies and biggest tournaments. Others just do their homework. Apart from the tiniest bit of geekiness, members of the “StarCraft” Club are exactly like any other students who maintain interest in particular sports. They are all part friends, part teammates and part rival. With the several dozen members engrossed in their own activities, Young sits apart from the regular membership. Surrounded by team members and club officers, he discusses upcoming events with them. “Among all the events out there is the CSL [Collegiate Starleague]. It was created by Princeton against MIT but has since expanded into something bigger. Originally we would always get forced out of the playoffs by our rivals, San Diego or Davis.” With the introduction with of “StarCraft 2,” however, things have changed for the Irvine team. “[Last season] the UCI “StarCraft” team did exceptionally well, by placing first in their division. In the playoffs, they crushed the first two teams before losing to [eventual champions] the University of British Columbia.” The team’s success is due partly to the new team manager and star player Alex Truong, also known by his online monikers “ShoeMaker” and “Shoey.” At first glance he is a completely normal 22-year-old Asian male, but his nondescript face provides mask for the brain of an honors engineering student, chess player, future doctor and “StarCraft” player. “I’ve always played video games, ever since my uncle gave me his old copy of ‘StarCraft.’ After that, I played games on the Nintendo 64 and the PlayStation 2. I’ve always been involved in competitive games too, whether they were video games like ‘Warcraft 3’ or chess. When ‘StarCraft 2’ came out last year, I started playing immediately. It’s the only game I’ve played since.” Despite his gaming pedigree, Truong hasn’t always been involved in with the “StarCraft” team. He only joined this year, his last at UC Irvine. “I wasn’t serious in ‘StarCraft: Brood War.’ I wish I was but I wasn’t so I didn’t participate in the CSL until this year,” Truong says with a shade of regret. However, his demeanor completely changes when asked at what point he felt accomplished in “StarCraft.” Smiling, Truong recounts the past season. “I was team manager. I helped decide who plays in what lineup. When we had to prepare for a match, I scouted the opponent, and helped devise strategy. I didn’t lose a single match in the CSL either.” With the CSL season over, the team is looking forward to UCI’s annual LAN party, an event run by the campus’s chapter of the Institute of Electrical and Electronics Engineers (IEEE) where players bring their computers to a central area to play. There, Truong will be competing with the best the school has to offer, including many of his own team members. Much like the club’s meeting room, the IEEE LAN party is lit by fluorescent tubes. The tables are also set in rows with electric outlets and Internet cables. There are people huddled around computers, reading and devising strategies before their games. However, as opposed to the small classroom the “StarCraft” Club usually occupies, the LAN party occupies a ballroom in the UCI Student Center, which is capable of holding hundreds of people. “StarCraft” is not the only game on display, though it is still the most popular. On one of the walls, the “StarCraft” tournament bracket is displayed. The top player listed is BonedOUT, an unknown sleeper player who was technically a part of the team but had never played for them. In second, Shoey, Truong’s moniker. Truong, however, does not look disappointed. “The tournament was running out of time. I was supposed to play him for the finals; I came from the loser’s bracket [meaning he had lost a single game earlier] and he came from the winner’s bracket [BonedOUT had yet to drop a match], but they were running late so they just asked if I’d take second. I said yeah. I like the second place prizes more.”Though Truong didn’t get to take home the trophy, he did manage to win an external hard drive and a gaming headset. He valued the prizes slightly more than his opponent’s gaming mouse and mousepad. When asked what his plans for the future were, Truong is surprisingly upbeat. “I originally wanted to compete at MLG Anaheim this summer, but medical school starts before then so I won’t be able to. I’ll continue playing in the CSL at Davis but “StarCraft” is starting to become more of a hobby. Now, I play to relax.” Next year will be a transitional one for the “StarCraft” Club and team. Truong is not the only player leaving. Leaving with him will be Darren Chen, also known as “darrenc,” another co-founder and star player. After a red hot season in the CSL, the next few months will be an uncertain time as new players begin to filter in. Despite the setbacks, Young and the rest of the club and team are ready to face the future. “The interest in competitive “StarCraft 2” doesn’t show any sign of slowing down. The amazing thing about the movement isn’t just the game play or the competition but also the way it’s bringing together people all over the world. The team isn’t going to be disappearing just ‘cause we’re losing a few people. There’s a place for us in e-sports. We’re going to take it.” The UCI “StarCraft” team’s next major event will be MLG Anaheim, July 29 to Aug. 1. Competitor passes are no longer available but spectator tickets are still being sold online and at the door for $25. An online pass is also available for $10 and provides access to HD coverage of the event at mlgpro.com. 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Q: what does it mean in scala val _x and val x_ I'm confused with below the following two declarations : val _x val x_ What does it mean and why we use underscore sometimes for declaring variables and functions? A: Those are just part of the name with no special meaning. You will have to ask the author why he chose to use those names. There are many places where underscore do have special meaning however, take a look at What are all the uses of an underscore in Scala? A: They're nothing special. Underscores are allowed in variable names in Scala (but this is discouraged, as the linked style guide mentions).

Tuesday, January 31, 2017 In the distant past the Vikings came upon a great, hidden and uninhabited island, its verdant lands rich in resources. The Vikings hid the island's location from the rest of the known world, killing all those who stumbled upon it. Soon after, many great clans established settlements across the island. Then the true master of the island revealed himself: Deep below the earth's surface lay Ymir, the powerful Jotunn of old, slumbering since time began. Sensing the Vikings' trespass, the giant awoke enraged and emerged a juggernaut of destruction as he rampaged across the island. Rampaging Jotunn is a competitive fast paced board game for 2 players in which each both players create the island they will be playing on where they will populate it with opposing villages and armies. Each player controls an army of Vikings trying to protect their villages while trying to destroy their opponents villages, at the same time the Jotunn rampages across the island destroying everything in sight. Players use cards to influence the giant and direct him towards your opponents armies and villages. They also use cards to move their armies into battle across the island. The last player with villages on the board wins! Monuments introduces hard to build Monuments to the game. When built, Monuments will bring a lot of Victory Points to your Village, but be sure to keep an eye on the end conditions because someone might end the game before you have a chance to complete your construction! Villages of Valeria is a village-building card game in which players establish resources, construct buildings, and attract adventurers to become the next capital city of Valeria. Take on the role of a Duke in the vast and beautiful kingdom of Valeria and, on your turn, lead the table by selecting an Action - Harvest, Develop, Build, Recruit, or Tax - for everyone to perform while you get a slight advantage for being the Active Player. Villages of Valeria is a stand alone game set in the world of Valeria and takes place just before the hordes of monsters invade the kingdom in Valeria: Card Kingdoms. Friday, January 27, 2017 Release Date: June 2017AWGAW01SWSpoils of War$39.99 SRPSpoils of War is a fast-paced and exciting game of bidding and wagering. Each round, players roll their dice, and then cleverly bluff and bet to out wit their fellow Vikings. The winners claim fantastic treasures, and no one knows who will win until the spoils are counted! 3-5 players60 minute play time Release Date: May 2017AWGDTE02ONX1Onitama Sensei's Path$12.99 SRPOnitama, Sensei's Path is a card expansion for use with Onitama! Included are 16 unique, new, cards that can be used as a standalone set of Move cards instead of those found in the base game. Alternately, these cards can be shuffled with the original 16 cards during Game Setup to create a multitude of new card combinations! $95.76 SRPNPI The walls between dimensions are collapsing and the supreme king of destruction will rise in Maximum Crisis, May's all-new 100-card booster set! Maximum Crisis is the climax of the 2016-2017 Dueling season, introducing three new themes as well as bold new cards for a wide variety of popular Decks. Pendulum Summoning will undergo its final evolution in Maximum Crisis with a pair of Pendulum Monsters with Scales of 0 and 13, opening up the ability to Pendulum Summon monsters of any Level in any Deck! But that's not the only type of Summoning that's evolving. Following up on February's Fusion Enforcers set, Maximum Crisis introduces a new Fusion Summoning Spell Card that lets you keep your Fusion Monster while giving back the monsters you just fused together! Here's a brief overview of what else you can expect in Maximum Crisis: The dawn of the "True Draco" monsters! These monsters can be Tribute Summoned using Continuous Spell/Trap Cards instead of monsters, and their Continuous Spell/Trap Cards have multiple effects depending on whether you just activate them or Tribute them. A brand new way to win a Duel! Even if you can't damage your opponent with this new theme's ace monster, if you can power it up enough, destroying 3 of your opponent's monsters with it will automatically end the Duel! New Winged Beasts that fly over enemy monsters for fast direct attacks and effects that inflict damage. Individually powerful cards to cover a variety of common situations in everyday Dueling. The mastermind behind the global plot has been revealed, and SPYRAL embarks on its final mission to take him down! All is not yet lost! The final battle against the Subterror Behemoths begins… and the Subterror Nemeses receive help from an unlikely source! $79.92 SRPNPITechnology vs. Tyrannos! Take part in the ultimate battle between man-made monstrosities and the greatest predators nature has ever produced with the Machine Reactor Structure Deck and Dinosmasher's Fury Structure Deck. The Machine Reactor Structure Deck uses the popular "Gadget" series of monsters, most recently seen in Movie Pack Gold Edition, to power up gargantuan "Ancient Gear" monsters. You can add your Gold Gadget and Silver Gadget from the Movie Pack to this Deck to help Summon the new Ancient Gear Gadget – a monster that belongs to both themes and turns this Deck's ace monster, Ancient Gear Reactor Dragon, into a 3000 ATK double-attacking, defense-piercing, card destroying behemoth! The Ancient Gear theme first debuted in Yu-Gi-Oh! GX, the animated series that put Fusion Summoning at the forefront, so the Machine Reactor Structure Deck can be enhanced further with "Ancient Gear" Fusion Monsters from Raging Tempest and an upcoming Spell Card from Maximum Crisis that will let you Fusion Summon and Tribute Summon using the same 2 monsters in the same turn! For those of you who prefer natural history over mankind's machinations, the Dinosmasher's Fury Structure Deck provides the ultimate prehistoric Dueling experience! It's survival of the fittest, and only the strongest cards in your Deck will make it. The rest will be food for the apex predator, Ultimate Conductor Tyranno, a 3500 ATK monster that can send all enemy monsters cowering in fear before devouring them all in a single Battle Phase! This Deck is adept at Summoning multiple Dinosaurs of the same Level at the same time, and most of those monsters are Level 4. That makes this Deck a perfect fit for Xyz Summoning! Duelist Saga and Maximum Crisis both have great Rank 4 Xyz Monsters that are perfect fits for this strategy.Please note: The display configuration will be as follows: 5 Dinosmasher's Fury Structure Decks and 3 Machine Reactor Structure Decks per display.Each Machine Reactor Structure Deck contains: Wednesday, January 25, 2017 'Exterminate!' They muttered about their sacred hatred, the On-Coming Storm. Their creator had a plan, a plan to make the Daleks great again. A plan to turn all their defeats into victories. A plan to remove the one variable that has always interfered with the master plan. The Doctor must be erased from time itself! Ever wanted to be the Doctor and travel in time and space to meet companions and have adventures? In Doctor Who Time of the Daleks you do just that, every player picks a Doctor and tries to thwart the Daleks master plan of erasing the Doctor from history. Well done gardener, you have splendidly performed your duties by taking care of the imperial panda. As a reward, the Chinese emperor hands you over a second animal's care and not just any one! You will need to try twice as hard to take care of the couple… and also their babies! The new resident of the bamboo plantation gives you access to new objectives and actions. Miss Panda is a lot less greedy but she can give birth to adorable babies! Brighten up your garden with new plots and create a little paradise on earth for all the members of this little family! A long time ago at the Japanese Imperial Court, the Chinese emperor offered a giant panda bear to the Japanese emperor as a symbol of peace. Now it is your duty to take care of it. This Collector's Edition version has the same components as the original version, but with high-quality deluxe oversized pieces! Just take a look at the "miniatures": you will adore them! Monday, January 23, 2017 $16.00 SRPIn every city you enter, you find inhabited ruins. You hide in them when you need shelter. You search them for food, clothing or valuable stuff. You are a scavenger. The Scavengers State Pack contains 50 new cards,for use with the 51st State: Complete Master Set. The Scavengers expansion introduces new abilities for cards, including the possibility of drawing the topmost card of the discard pile or building ruins and developing your whole strategy around them. This is not a standalone game. You must have the 51st State Complete Master Set to play. Friday, January 20, 2017 $12.99 SRPNPIWordSpiel is a simple yet dynamic card game that everyone enjoys! Use your words wisely and be the first to go out. Word size doesn't matter, but ending with a tricky letter can really challenge your opponents! Each word spins off the last, so the game will never be the same twice! The goal is to get rid of all 10 of your cards by making words. Each turn, simply start your word with the last card played. Just like the name, WordSpiel. Spiel uses the S from WordS. Wednesday, January 18, 2017 $34.99 SRPGather your friends and prepare for adventure in a remote alien planet! Whether you're new to roleplaying games, or just new to FAITH: the Sci-Fi RPG, this Starter Set is the perfect starting point. This box allows you to get started right away, with a learn-as-you go scenario you can read aloud at your table. Crack it open and get started within minutes! Pre-generated character folios keep your character's information right at your fingertips, while the player deck system, and the gear and non-player character cards keep you immersed in the story and allow you to manage your luck. The complete rules will allow you to design your own adventures and continue to play with your characters once you finish your adventures in Ujara. The FAITH: A Garden in Hell Starter Set features a complete campaign for at least 7-12 gaming sessions that will take you to Ujara, an alien planet infested by Ravagers. As a brave member of the Coalition, your task is to not only defeat them, but extract enough information to turn the tides of the battle for the universe. Do you have what it takes? Tuesday, January 17, 2017 The ancient Gates of Antares link or isolate worlds across countless galaxies. The evolved panhuman races wage unending war to control the Gates and the undiscovered systems beyond. Take on the battling forces of the Concord IMTel, the symbiotic Isorians, the bio-adapted Boromites, the twisted Ghar Empire or the warlike Algoryn Prosperate to claim control of the Gates that lead to new planetary systems to trade and colonize. With each faction bringing a unique twist to the otherwise simple rules, roll the Skirmish dice to score victories on your campaign and claim the Gate. Each player’s round represents a military offensive that will give the chance for scoring victories, but be aware of the Fate dice opponents will play against you as they can twist your results and turn a clear victory into a total failure! Monday, January 16, 2017 $20.00 SRPMAE013Masks: A New Generation (Hardcover)$50.00 SRPMasks: A New Generation is a superhero roleplaying game in which a team of young heroes fights villains, saves lives, and tries to figure out who they are. And kick some butt along the way. After all, what's the point of being a hero if you can't fight for the things you believe in? $50.00 SRPUndying is a diceless tabletop roleplaying game about vampirism. Game play revolves around brief periods of intense conflict in which old rivalries and new slights spark a dramatic inferno and long stretches of intrigue in which intricate plots are set in motion by immortal conspirators. RRG940Pyramid Poker$19.99 SRPPyramid Poker is a quick head to head game that takes your ancient Grand- Pharaoh's Poker to whole new levels. Each player takes turns placing blocks to assemble the pyramid. Once it's completed, players begin dismantling the pyramid, taking a block each turn as they attempt to create their best 3 Poker hands. Win 2 of the 3 match-ups to be master of the Pyramid! In this whimsical push your luck dice game, players have three rolls to select a scoring roll. Once all of the scoring options are selected, high score wins! It is an easy way for young players to enjoy rolling dice and making fun decisions to win! The player with the most options completed generally takes home the bacon! Capture the other players' cards by "MimiQ-ing" a variety of facial expressions and collect the most sets of 3 identical cards ! If you don't have the card a player asks you for, stick your tongue out ! Put your memory and your facial muscles to the ultimate test with MimiQ! Share laughs every game! Put your facial muscles and memory to the ultimate test with Farm MimiQ! Share laughs and fun with family and friends, on trips, at parties or on game nights! Capture the other players' cards by "MimiQ-ing" a variety of facial expressions. Collect the most sets of 3 identical cards and win the game! Friday, January 13, 2017 The world of Freeport is a perilous one, as any swab can attest. Sailors face monsters like ocean wyrms and sail dragons, explorers must deal with ghost eaters and harpoon crabs, and city dwellers may be surprised by burnlings and flayed men. You'll find all these creatures and many more in the Freeport Bestiary for the Pathfinder Roleplaying Game! This 160-page full color sourcebook includes a wide variety of threats, from classic Freeport adversaries like serpentmen and fire spectres to new monsters like corsair drakes and witch beasts. It's the perfect complement to Freeport: The City of Adventure and can be used to add spice to any Pathfinder Roleplaying Game campaign. Here there be monsters! Love 2 Hate: Comics brings the world of superheroes and supervillains to the party! This 108 card expansion adds a slew of new sentence Starter and Finisher cards to the game. Mix them in with your standard Love 2 Hate cards or play the expansion on its own for a themed experience. Either way, you'll soon be saying, "I love the way comics make my game super!" GRR5511Mutants & Masterminds: Campaign Settings: Freedom City$19.95 SRPWith the Mutants & Masterminds RPG you have the power to become a hero. Freedom City gives you the world's most renowned city of heroes to rescue from the forces of evil! Called "the greatest superhero setting ever," the award-winning Freedom City is a fully realized and detailed metropolis that can serve as a home base for your heroes or just one of the many places they visit while saving the world of Earth-Prime from disaster. Your heroes can fight the forces of SHADOW, puzzle out the schemes of the Labyrinth, and defeat the alien invaders Syzygy and the Meta-Grue. With dozens of foes and hundreds of locations, Freedom City gives you everything you need to run an exciting Mutants & Masterminds campaign. Use it on its own or in conjunction with Emerald City and the Atlas of Earth-Prime for world-spanning action! The Narrator's Kit is a key accessory for your Blue Rose RPG series. It features a three-panel hardback screen with all the essential game info you need at the table, and a booklet with 7 optimizable pre-generated characters. It also includes 4 quick reference cards that put the stunts and actions at your fingertips, and a combat tracker that you can write on with wet or dry erase markers. The Narrator's Kit is the perfect complement to the Blue Rose RPG and will help you kick off your game with style. About Me Here at ACD we have the products, services, and tools to keep retailers on top of their game. Our warehouses are stocked with thousands of board games, role playing games, dice, cards, fantasy and science fiction miniatures, historical board games and miniatures, modeling tools, and card storage supplies from over 300 of the industry’s top manufacturers!

/* FILE HCRTC_Example.cpp DATE: 23/12/13 VERSION: 0.2 AUTHOR: Andrew Davies This is an example of how to use the Hobby Components RTC library to read and write to and from the DS1307 real time clock 24C32 EEPROM. The library is intended to be used with our RTC clock module (HCMODU0011), but should work fine with any module that uses a DS1307 device. You may copy, alter and reuse this code in any way you like, but please leave reference to HobbyComponents.com in your comments if you redistribute this code. This software may not be used directly for the purpose of selling products that directly compete with Hobby Components Ltd's own range of products. THIS SOFTWARE IS PROVIDED "AS IS". HOBBY COMPONENTS MAKES NO WARRANTIES, WHETHER EXPRESS, IMPLIED OR STATUTORY, INCLUDING, BUT NOT LIMITED TO, IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE, ACCURACY OR LACK OF NEGLIGENCE. HOBBY COMPONENTS SHALL NOT, IN ANY CIRCUMSTANCES, BE LIABLE FOR ANY DAMAGES, INCLUDING, BUT NOT LIMITED TO, SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES FOR ANY REASON WHATSOEVER. */ /* Include the wire library */ #include "Wire.h" /* Include the Hobby Components RTC library */ #include <HCRTC.h> /* The RTC and EEPROM have fixed addresses of 0x68 and 0x50 so define these in software */ #define I2CDS1307Add 0x68 #define I2C24C32Add 0x50 /* Example string to write to EEPROM */ char ExampleString[] = "Hobby Components"; /* Used in example as an index pointer */ byte index; /* Create an instance of HCRTC library */ HCRTC HCRTC; void setup() { Serial.begin(9600); /* Use the RTCWrite library function to set the time and date. Parameters are: I2C address, year, month, date, hour, minute, second, day of week */ HCRTC.RTCWrite(I2CDS1307Add, 13, 4, 24, 14, 21, 0, 3); } void loop() { /************* Example write to EEPROM ***************/ /* Initiate a write sequence. Parameters are: I2C address, EEPROM start location */ HCRTC.EEStartWrite(I2C24C32Add, 32000); for (index = 0; index < sizeof(ExampleString); index++) { /* Sequentially write example data to the EEPROM */ HCRTC.EEWriteByte(ExampleString[index]); } /* End the write sequence */ HCRTC.EEEndWrite(); /* Wait for cached data to finish writing */ delay(10); /************* Example read from EEPROM ***************/ /* Initiate read sequence. Parameters are: I2C address, EEPROM start location */ HCRTC.EEStartRead(I2C24C32Add, 32000); for (index = 0; index < sizeof(ExampleString); index++) { /* Sequentially read data from EEPROM and output it to the UART */ Serial.write(HCRTC.EEReadByte(I2C24C32Add)); } Serial.println(); /* Continuously read the current time and date from the RTC */ while(true) { /* Read the current time from the RTC module */ HCRTC.RTCRead(I2CDS1307Add); /* Output the information to the UART */ Serial.print(HCRTC.GetDay()); Serial.print("/"); Serial.print(HCRTC.GetMonth()); Serial.print("/"); Serial.print(HCRTC.GetYear()); Serial.print(" "); Serial.print(HCRTC.GetHour()); Serial.print(":"); Serial.print(HCRTC.GetMinute()); Serial.print(":"); Serial.print(HCRTC.GetSecond()); Serial.print(" DOW:"); Serial.println(HCRTC.GetWeekday()); /* Now output the same thing but using string functions instead: */ Serial.print(HCRTC.GetDateString()); Serial.print(" "); Serial.println(HCRTC.GetTimeString()); /* Wait a second before reading again */ delay(1000); } } FAQ: What does the SQ pin do? The DS1307 has a feature where you can output a square wave to a pin. This can at fixed frequencies of 1Hz, 4KHz, 8KHz, and 32KHz. You have to configure an internal register to do this but when configured correctly the square wave will appear on the SQ pin. What does the DS pin do? If you take a look at the pictures in this post you'll notice there a unsoldered 3 pads in the top left corner. These allow you to solder an optional DS1820 temperature sensor. If you do this the DS pin provides access to its data out pin. How do I connect this module to an Arduino? The module needs to be connected to your Arduino's I2C interface (SDA & SCL pins). For an Arduino Uno, Nano, or Pro Mini you can connect the module as follows: This is because of the way the print function prints out numbers, rather than anything to do with the RTC library. To pad out the number with an extra zero, a quick and simple way would be to just test if the number is less then 10 and if so, print out an extra zero. For example: I've recently bought a Tiny RTC DS1307 module from your ebay store and I've a problem since the module loses time when I power off Arduino. I've tried with the library (HCRTC) and the example sketch that you have provided and every time I disconnect Arduino from power the time is reset to 1/1/2000. For testing I've uploaded the HCRTC_Example sketch, then I've reuploaded the sketch with line From the information you have given us you don't appear to be doing anything wrong. It really does sound like the DS13072 is not getting power from the battery. The most likely cause is a bad contact in the battery holder but the fact that you can measure the battery voltage at the BAT pin suggests this is not the case. If possible, with the module not powered, could you carefully measure the voltage at pin 3 (VBAT) of the DS13072? This is the 3rd pin down from the pin marked with a dot. Comments made by this poster do not necessarily reflect the views of Hobby Components Ltd. Sorry, I just realised my question could be misinterpreted... Would you be able to measure the voltage on the pin of the IC itself? Its the IC marked DS13072. The pin you are looking for is pin 3 which is the 3rd one down from the pin with a dot next to it. This may be a little fiddly as the pins are very close together. You will also need to do this with no power applied to the module (including IO connections from your Arduino), but with the battery connected. This will tell us if the chip itself is getting power from the battery. Everything you have said suggests that the device is not getting the battery backup. I wouldn't get too hung up about what happens when you remove the 5V supply because if we assume that the device is also not getting the 3V from the battery then it's probably just getting enough leakage current from the data pins on the Arduino, but not enough to keep the clock circuitry running. The battery voltages you measure seem sensible to me. Comments made by this poster do not necessarily reflect the views of Hobby Components Ltd. Yes, I've already measured it on the IC (in the image I've measured voltage between pins highlighted in red) with the module disconnected from any power source (other than the module battery) obtaining 2.94V. Ok, it sounds like you do have a faulty module. I'm going to pull one out of stock and check that nothing has changed to stop the software from working but this is unlikely. I can't find you on our system from your forum details, could you email us either your order number or account number if you bought it via our website, or your eBay user name if you bought it from our eBay shop. The email address is sales@hobbycomponents.com Comments made by this poster do not necessarily reflect the views of Hobby Components Ltd. Thanks for confirming your account. I've pulled one out of stock and it works fine with the library so it does look like you have one with a weird fault. I'm going to contact you via email to arrange a replacement or refund. Comments made by this poster do not necessarily reflect the views of Hobby Components Ltd.

Religion, Feminism, and Freedom of ConscienceEdited by George D. Smith Chapter 8. Tenure as a ToolF. Ross Peterson [p.87]My memory takes me back to May 1970, to the University of Texas at Arlington where I taught history. Shortly after the tragic deaths at Kent State and Jackson State colleges, activist students, black and white, wanted a memorial service. After considerable discussion between administrators and students, they agreed on a program and a main speaker. I was asked to be the speaker. My record on civil rights, the Vietnam War, and student issues was public and fairly dear, so both sides agreed on the choice. The morning before the service, my department chair, E. C. Barksdale, called me into his office. He said, “Do you know what in the hell you are doing?” Barksdale had been fired by a Texas school district in 1937 for organizing teachers. He was crusty, profane, and unforgettable. I responded, “Yes, sir, I do.” He slowly pulled out his tobacco pouch, tore off a sheet of cigarette paper from a small pad, silently and sloppily rolled a cigarette, smashed it a little, then lit it. I waited. Then he said, “Be careful.” I responded, “I’m not worried—I’ve got Academic Freedom.” He squinted, “How long you been here?” He knew. “Two years,” I answered. His eyes lit up, his clenched fist hit the desk, and he growled, “If those students get carried away and the cops get tough—you ain’t got shit!” The memorial service was without incident. As an undergraduate at Utah State University in Logan, I ran into the issue of tenure as it pertained to Brigham Young University. Numerous faculty had previously been BYU instructors. I learned of firings over organic evolution in the early 1900s. Lowry Nelson, [p.88]founder of rural sociology as an academic field, left under duress in the 1920s, and others followed. Closer to my academic lifetime was the disruption caused by President Ernest Wilkinson in the early 1950s and 1960s. J. Golden Taylor, Thorton Y. Booth, Brigham Madsen, and Carlton Culmsee had all navigated to Logan after finding Provo inhospitable. They talked about academic freedom, or lack of it, continually. They blasted the LDS church in their daily classes. George Jensen, Austin Fife, Heber Snell, Venetta Nielsen, and Moyle Q. Rice were all great teachers, but they were harsh, sarcastic, and cynical so far as religious-sponsored education was concerned. Their collective delivery was precise and pointed. George Jensen, a USU German professor, was given to making light of sacred things. Jensen, a returned Mormon missionary to Germany, became disaffected and as he aged evolved toward sacrilege. He loved to give sacred Mormon temple signs while shaking hands and say other things that upset students and faculty. Every so often, the board of trustees wanted him and others like him fired, but tenure provided protection. In his later years Jensen became worried that there might be truth in religion, so he promised after he died to come back and visit a younger colleague, Milton Abrams, in the event that it was true. Years later, Max Peterson rigged a speaker in the ceiling above Abrams’s head and activated a tape that said simply, “Milton! It’s true!” After that when Milton gave up coffee we decided to come dean in case he gave up smoking and came back to church. In graduate school you were taught about tenure, academic freedom, and publish or perish. One of my professors had a memorable cartoon on his wall. The crucified Jesus and the two thieves were depicted in the background and one Roman soldier said, “They say he was a great teacher.” The other responded, “Yeah, but did he publish?” These incidents introduced me to the reality of campus life. There are always problems and difficult decisions, and a thorough analysis reveals that each institution creates its own criteria for retaining teachers. Parochial schools have clear statements about supportive and appropriate behavior. In eight years’ service as a department chair and eight more as an ombudsperson who oversaw due process in tenure and promotion [p.89] meetings, I have seen a variety of challenges to academic freedom. My conclusion is that it is a treasure. It is also threatened. That is why its discussion has profound relevance. Public and private institutions have separate codes, presumably based on the guidelines of the American Association of University Professors (AAUP). However, there are numerous twists on the guidelines. The educator W. T. Couch once wrote Academic Freedom is the principle designed to protect the teacher from hazards that tend to prevent (her) or him from meeting their obligations in the pursuit of truth. The obligations of the teacher are direct to truth, and the teacher who, in order to please anybody, suppresses important information, or says things he knows are not true, or refrains from saying things that need to be said in the interest of truth, betrays his calling and renders himself unworthy to belong in the company of teachers. This is a solid and forthright opinion that deserves careful consideration. Academic freedom as an idea is often considered more important than the ephemeral reality of particular people and circumstances. It is an idea that is gravely threatened in our time. Institutions with specific missions and goals can require unique behavior from their employees. That is not new. The maintenance of academic freedom also implies professional ethical standards of truthful disclosure and reasonable care. It is not nor has it ever been a blank check. As First Amendment scholar William Van Alstyne points out, professors are protected in their “freedom” but not immune “from the power of others to use their authority to restrain its exercise.” Universities or colleges are often faced with the reality of economic and curricular limitations. Consequently, an institution’s decision not to offer a particular subject or not to provide financial means for a particular line of research may be faulted as educationally unenlightened, but such actions would not constitute an abridgment of freedom. However, freedom is abridged when sanctions are threatened against a faculty member because his or her interest pertains to a subject that the institution does not support. If an institution desires to be open and pluralistic, it must avoid any and all forms of censure. But in reality ultimate financial resources of [p.90]almost all institutions of higher learning are beyond the control of the faculty. Only in rare cases do faculty manage resources. Issues of professional integrity are resolved within a given institution. They are ultimately not overseen by extraneous professional groups issuing licenses. Insofar as public universities or cob leges are concerned, the power to force hemlock on a modern Socrates is constrained, and private institutions generally adopt similar procedures as exist in public schools. The original body of oversight is usually a faculty or a faculty committee. Each campus generally has a mechanism whereby charges are filed and hearings are held. This is a well-tried process of peer evaluation. On issues of suspected infringement, an appeal process usually exists that allows a faculty member to seek help from the AAUP or from the administration. Now let me personalize the discussion and bring it closer to home and to the reality that confronts this particular dialogue. That is to illustrate the difference between public and private institutions in Utah. On the surface, the process of academic freedom looks very similar; however, there are distinct differences. On order from the State Board of Regents, Utah institutions have undergone a revision of faculty codes. The Utah State University faculty code states, The University is operated for the common good which depends upon the free search for truth and its free exposition. Academic Freedom is essential to these purposes and applies to teaching, research and service. The University is a community dedicated, through promulgation of thought, truth, and understanding, to teaching, research, and service. It must therefore be a place where innovative ideas, original experiments, creative activities, and independence of thought are not merely tolerated but actively encouraged. Because thought and understanding flourish only in a climate of intellectual freedom, and because the pursuit of truth is fundamentally a personal enterprise, a code statement of faculty responsibility must be strongly anchored to principles of intellectual freedom and personal autonomy. While faculty must abide by a code of standards of professional responsibility, the university must provide and safeguard a climate of intellectual freedom. Relationships within the university should consist of shared confidence, mutual loyalty, [p.91]and trust. Dealing should be conducted with courtesy, civility, decency, and a concern for personal dignity. The code then elaborates: Academic freedom is the right to teach, study, discuss, investigate, discover, create and publish freely. Academic freedom protects the rights of faculty members in teaching and of students in learning. Freedom in research is fundamental to the advancement of truth. The faculty member is entitled to full freedom in teaching, research, and creative activities, subject to the limitations imposed by professional responsibility. Other institutions in the state and region vary. Westminster College has no tenure policy. It operates on three- or five-year renewable contracts. Community college professors are virtually unprotected in many respects. They do not have a national organization like AAUP. Untenured people at any institution clearly have problems. Frankly, private institutions can do what they want. President Rex Lee of BYU said there is more academic freedom at BYU than other universities because people can say positive things about their religion in the classroom. Close examination of Brigham Young University’s annual contract and code illustrates the abandonment of traditional academic freedom. In 1991 the contract was routine and said little about conduct and behavior; however, in 1992 the following statement was added: Brigham Young University is a private university. It has unique goals and aspirations that arise from the mission of its sponsoring institution, The Church of Jesus Christ of Latter-day Saints. By accepting a contract of employment here, faculty members choose to accept, support, and participate in the University’s religiously oriented educational mission, to observe and support the behavior standards of the University, including the Honor Code and Dress and Grooming Standards, and to further the University’s objectives by being role models for a life that combines the quest for intellectual rigor with the quest for spiritual values and personal character. Faculty who are members of BYU’s sponsoring Church also accept the spiritual and temporal expectations of wholehearted Church membership. [p.92]A year later an additional statement was included stipulating that faculty agree to “refrain from behavior or expression that seriously and adversely affects the University mission or the Church.” In addition, “LDS faculty also accept as a condition of employment the standards of conduct consistent with qualifying for temple privileges.” The problem is that this policy takes continuance or tenure away from the hands of the university. If an ecclesiastical leader, a non-academic, revokes a professor’s LDS temple recommend (which verifies personal worthiness in areas of belief and behavior), the individual can be terminated from employment. If a person is terminated for not upholding the mission of a private institution or its sponsoring organization, that is legal. When such political termination is disguised in a charade of academic process, the school’s honesty and morality are jeopardized. When a faculty member’s academic ability is questioned for political, religious, or ideological issues, he or she has cause for redress, according to established academic protocol. In reality, the problems of the Provo campus for LDS church headquarters in Salt Lake City have always existed. In the 1930s the Church Education System drove many talented instructors from their ranks over theological orthodoxy. Included in this group were Obert Tanner, Lynn Bennion, Daryl Chase, and Sterling McMurrin. BYU has always been willing to sacrifice professors and ideas in order to maintain theological orthodoxy. In this respect BYU is no different from any other parochial school which has been less than honest in its academic pretensions. During the winter of Valley Forge, American revolutionary Tom Paine wrote, “These are the times that try men’s souls.” They are also the times that try women’s souls. All concerned must understand the implied as well as written contract between scholars and their employers and the responsibility that accompanies freedom. Students are entitled to more than institutional insecurities about image and longevity. The human spirit deserves more leeway than short-sighted administrators sometimes allow. But they must if BYU is to fulfill a mission at all commensurate with the ideals of a university. And they will if they thoughtfully consider what is best for everyone involved.

952 N.E.2d 733 (2007) 376 Ill. App.3d 1148 PEOPLE v. RAYFIELD. No. 2-06-0513. Appellate Court of Illinois, Second District. November 15, 2007. Affirmed.

Háje (Prague) The Czech village of Háje was founded in 18th century, and became part of Prague in 1968. Now it is its own cadastral area, part of the administrative district Prague 11 (Prague 4). Its area is , its population is 23,528 and its population density is 9,969 inhabitants / km2. Háje was founded in 18th century and historically it was part of Hostivař. Háje became part of Prague 1968. The building of Jižní Město (South Town in English), the biggest housing estate in the Czech republic started in Háje in 1971. Most of old village of Háje was demolished and replaced by panel buildings (paneláky). There is one metro station in Háje, the name of this station is Háje (Line C). References Category:Districts of Prague Category:Prague geography stubs Category:Prague 11 Category:Háje (Prague)

I'm so psyched to have found this stuff. There is a central, publicly accessible repository for all the business conducted by the Green Party US National Committee, a group of just over 100 representatives from various states and party caucuses. ​In Green circles recently, there has been no small amount of hullabaloo surrounding the Green Party National Committee's Proposal 835, amending the platform for adoption of language that opposes capitalism. Much of this hullabaloo ignores the additional language opposing state socialism. Below is the new language added to the platform's Chapter IV on Economic Justice and Sustainability. The Green Party seeks to build an alternative economic system based on ecology and decentralization of power, an alternative that rejects both the capitalist system that maintains private ownership over almost all production as well as the state-socialist system that assumes control over industries without democratic, local decision making. We believe the old models of capitalism (private ownership of production) and state socialism (state ownership of production) are not ecologically sound, socially just, or democratic and that both contain built-in structures that advance injustices. Instead we will build an economy based on large-scale green public works, municipalization, and workplace and community democracy. Some call this decentralized system "ecological socialism," "communalism," or the "cooperative commonwealth," but whatever the terminology, we believe it will help end labor exploitation, environmental exploitation, and racial, gender, and wealth inequality and bring about economic and social justice due to the positive effects of democratic decision making. Production is best for people and planet when democratically owned and operated by those who do the work and those most affected by production decisions. This model of worker and community empowerment will ensure that decisions that greatly affect our lives are made in the interests of our communities, not at the whim of centralized power structures of state administrators or of capitalist CEOs and distant boards of directors. Small, democratically run enterprises, when embedded in and accountable to our communities, will make more ecologically sound decisions in materials sourcing, waste disposal, recycling, reuse, and more. Democratic, diverse ownership of production would decentralize power in the workplace, which would in turn decentralize economic power more broadly. David Cobb, Green nominee for president in 2004, shared the post above on Facebook.​This is incredibly exciting news in more ways than one. Personally, I cheer the Platform Committee for taking this risk. The new language will appear in copies of the Green Party's 2016 platform that will be distributed to delegates and others when they convene in H-Town this August. The decision to reject was not without controversy: Many established Greens objected to it for various reasons. The risk, from the beginning, was not only that mainstream America would accuse the Greens of pining for the good old days of Joe Stalin, but that GPUS might lose a fair number of its long-standing members over its new stance. Among Millennials in particular, but by no means exclusively, "socialism" is no longer a dirty word. It is a rational alternative to an economic system that thrives on exploitation and puts millions in debt peonage. I hope that you read and re-read the quote pictured above with an open mind. The platform also rejects state socialism, while embracing eco-socialism explicitly. I also hope that you will read Naomi Klein'sThis Changes Everything, which illustrates how capitalism is incompatible with protecting the natural environment on which all life—human life included—depends. While the book is thoroughly researched and sourced, it is not such a scholarly work that readers will drown in polysyllables. But even environmentalists who think they've heard it all before may find their heads spinning at the depth and breadth of the climate crisis and the solutions that should have been imposed years ago. Klein is not especially comfortable with state socialism either, but it may be the only way to rescue our world from climate catastrophe. The state won't budge, however, until the people get off their collective arse and make budging politically imperative. DBC Sez... Here you will find political campaign-related entries, as well as some about my literature, Houston underground arts, peace & justice, urban cycling, soccer, alt-religion, and other topics.

--- abstract: 'The role played by the effective residual interaction in the transverse nuclear response for quasi–free electron scattering is discussed. The analysis is done by comparing different calculations performed in the Random–Phase Approximation and Ring Approximation frameworks. The importance of the exchange terms in this energy region is investigated and the changes on the nuclear responses due to the modification of the interaction are evaluated. The calculated quasi–elastic responses show clear indication of their sensibility to the details of the interaction and this imposes the necessity of a more careful study of the role of the different channels of the interaction in this excitation region.' address: - | Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata,\ La Plata, 1900, Argentina. - 'Departamento de Física Moderna, Universidad de Granada, E–18071 Granada, Spain.' author: - 'Eduardo Bauer [@AAAuth]' - 'Antonio M. Lallena' title: 'ON THE ROLE OF THE EFFECTIVE INTERACTION IN QUASI–ELASTIC ELECTRON SCATTERING CALCULATIONS' --- INTRODUCTION ============ An aspect of great importance in nuclear structure calculations at any excitation energy concerns with the role of the effective interaction. At low energies this problem has generated a considerable body of work in the last twenty years. On the contrary, this is a question not studied yet in deep in the literature for higher energies. Giant resonances show an intricate mixture of multipolarities and the study of how the interaction affects it is a difficult task. In the quasi–elastic peak region, the problem of the longitudinal and transverse separation has occupied most of the investigations carried out till now and the discussion of the effects due to changes in the effective interaction have not been considered in detail. As an example, we mention the considerable number of Random–Phase Approximation (RPA) type calculations performed in this energy region, much of them using residual interactions which include basically a zero–range term plus meson–exchange potentials corresponding to $\pi$, $\rho$ and, eventually, other mesons [@al84]–[@gi97]. An important point concerning the interaction refers to the values chosen for the parameters entering in the zero–range piece. However, and to the best of our knowledge, only in Ref. [@gi97] a certain discussion relative to the effects of varying these parameters can be found. In fact, the common practice is to pick an interaction from the literature, which usually corresponds to a parameterization fixed for low energy calculations, and afterwards use it to evaluate quasi–free observables sometimes without taking care of the effective theory in which the interaction was adjusted. It is obvious that, to a certain level, doubtful results are possible because of the known link between effective theory and interaction. In this work we want to address this question and investigate if different parametrizations of the interaction can produce noticeable differences in the results and the extent to which the use of an interaction fixed for a given effective theory affects the results obtained within a different one. In Sec. II we give the details about the effective theories and interactions used to perform the calculations. In Sec. III we show and discuss the results we have obtained. Finally, we present our conclusions in Sec. IV. EFFECTIVE THEORIES AND INTERACTIONS =================================== The first interaction we consider in this work is the so–called Jülich–Stony Brook interaction [@sp80] which is an effective force widely used for calculations in the quasi–elastic peak. It is given as follows: $$\label{int-I} \displaystyle V^{\rm I}_{\rm res} \, = \, V_{\rm LM} \, + \, V_\pi \, + \, \tilde{V}_\rho \, .$$ Here $V_{\rm LM}$ is a zero–range force of Landau–Migdal type, which takes care of the short–range piece of the NN interaction: $$V_{\rm LM} \, = \,C_0 \,[ g_0\, {\mbox{\boldmath $\sigma$}}^1\cdot {\mbox{\boldmath $\sigma$}}^2 +\, g_0^\prime\, {\mbox{\boldmath $\sigma$}}^1\cdot {\mbox{\boldmath $\sigma$}}^2 {\mbox{\boldmath $\tau$}}^1 \cdot {\mbox{\boldmath $\tau$}}^2] \, .$$ On the other hand, a finite–range component generated by the ($\pi$+ $\rho$)–meson exchange potentials is also included. The tilde in $\tilde{V}_\rho$ means that the bare $\rho$–exchange potential is slightly modified in order to take into account the effect of the exchange of more massive mesons. In particular, a factor $r=0.4$ is multiplying the finite–range non–tensor piece of the potential (see Ref. [@sp80] for details). This force was fitted to reproduce low energy magnetic properties in the lead region (specifically, magnetic resonances in $^{208}$Pb and magnetic moments and transition probabilities in the neighboring nuclei). The calculations were performed in the framework of the RPA and Woods–Saxon single–particle wave functions were used in the configuration space. The values $g_0=0.57$ and $g_0^\prime=0.717$ (with $C_0=386.04$ MeV fm$^3$) were found to be adequate to describe the properties studied. As previously stated, this interaction has been considered in different calculations in the quasi–elastic peak (see e.g. [@gi97]). The problem arise because some of them have been done within the Fermi gas (FG) formalism, with local density approximation to describe finite nuclei, in the ring approximation (RA), where the exchange terms are not taken into account, and with the full unmodified $\rho-$exchange potential. Under these circumstances, the possible effects in the nuclear responses due to the inconsistency between the model and the effective interaction could be non–negligible. This is precisely the first aspect we want to investigate. To do that we compare the responses obtained with the Jülich–Stony Brook interaction with those calculated with a second effective force of the form: $$\label{int-II} \displaystyle V^{\rm II}_{\rm res} \, = \, V_{\rm LM} \, + \, V_\pi \, + \, V_\rho \, ,$$ by considering the same values for the zero–range parameters in both cases. The force in Eq. (\[int-II\]) only differs from $V^{\rm I}_{\rm res}$ in the $\rho$-potential which, in this case, does not include any reduction factor. Both RPA and RA effective theories are used to analyze the results. A second question of interest to us is to determine how the change of the zero–range parameters affects the responses calculated within a given theory. This will inform us about the necessity of considering or not in detail the role of these parameters. This aspect is analyzed by considering $V^{\rm II}_{\rm res}$ with parameters $g_0$ and $g_0^\prime$ fixed, as in the case of the Jülich–Stony Brook interaction, to reproduce some low energy properties in the lead region (see details in the next section). It is worth to point out that $V^{\rm II}_{\rm res}$ is precisely the interaction used in practice in much of the calculations mentioned above and that is why we want to use it for this analysis. Our analysis focuses on the transverse response functions in the quasi–elastic peak. We will not consider the longitudinal ones because they are strongly influenced by the spin independent pieces of the interaction (in particular, the $f_0$ and $f_0^\prime$ channels) and these are difficult to fix at low energy because of the role played by the scalar mesons not usually taken into account. RESULTS OF THE CALCULATIONS =========================== The investigation of the various questions we are interested in has been carried out by comparing different calculations of the transverse (e,e’) responses in $^{40}$Ca for three different momentum transfer ($q=300$, 410 and 550 MeV/$c$). (100,180)(35,0) (0,0) [. Transverse nuclear responses for $^{40}$Ca, calculated for the three momentum transfers we have considered in this work. Dotted lines correspond to an RPA calculation with $V^{\rm I}_{\rm res}$, while solid curves represent the RA results for $V^{\rm II}_{\rm res}$. In both cases the values $g_0=0.57$ and $g_0^\prime=0.717$ (with $C_0=386.04$ MeV fm$^3$) have been used. Dashed curves give the free FG responses. In all the calculations a value of $k_{\rm F}=235$ MeV/$c$ has been used.]{} First we have study the effects produced when an effective interaction, which has been determined in a given effective theory (e.g. RPA), is used to calculate (e,e’) transverse responses in a different framework (e.g. RA). By considering the parameterization of Ref. [@sp80] (that is $g_0=0.57$, $g_0^\prime=0.717$ and $C_0=386.04$ MeV fm$^3$), we have carried out two different calculations, the results of which are shown Fig. 1. Therein, solid curves correspond to the calculations performed in the FG approach within the RA and with the interaction $V^{\rm II}_{\rm res}$ in Eq. (\[int-II\]). On the other hand, dotted lines have been obtained within the RPA, also for the FG. The model used in this case is the one developed in Ref. [@ba96], which, contrary to what happens for the RA approach, includes explicitly the exchange terms in the RPA expansion. In this case we have used the interaction $V^{\rm I}_{\rm res}$ in Eq. (\[int-I\]) and we have adopted the factor $r=0.4$, which is consistent with the parameterization used. Also in Fig. 1, we have plotted the free FG responses for comparison (dashed curves). The first comment one can draw from these results is that the use of the interaction, as it was fixed at low energy, leads to transverse responses which are quite different from those obtained in the RA (with $V^{\rm II}_{\rm res}$) calculation, though the differences reduce with increasing momentum transfer. As we can see, the results obtained in the RPA are peaked at lower energies and this is a clear evidence of a more attractive residual interaction. It is straightforward to check this point because the central piece of the $V^{\rm I}_{\rm res}$ is attractive, while the contrary happens for $V^{\rm II}_{\rm res}$, at least for $q\leq 2k_{\rm F}$. On the other hand it is interesting to note how the RA results are more similar to the free response as long as $q$ increases, while the same does not occurs for the RPA responses. Obviously, the reason for the discrepancies between both calculations can be ascribed to the two basic ingredients of the effective theories used in each case: the exchange terms, which are included in the RPA calculations but not in the RA ones, and the reduction factor $r$ modifying the $\rho-$exchange potential. Before going deeper in this question, it is worth to comment on the nuclear wave functions used in the calculations discussed above. As in any FG type calculation, plane–waves have been considered here to describe the single–particle states. The fact that the interaction was fixed in a framework which considered microscopic RPA wave functions, based on Woods–Saxon single–particle states, is an obvious inconsistency. Despite that, it has been shown [@am94; @am96] that, in this energy region, the details concerning the nuclear wave functions are not extremely important and, at least to some extent, the shell–model response can be reasonably described with the FG model, provided an adequate value of the Fermi momentum, $k_{\rm F}$, is used. In the present work, where we study the response in $^{40}$Ca, we have taken $k_{\rm F}=235$ MeV/$c$ which gives a good agreement between FG and finite nuclei calculations [@am94]. We come back to investigate the reasons for the large discrepancy between the RPA and RA calculations presented above. To do that we have done two new calculations: RA with $V^{\rm I}_{\rm res}$ and RPA with $V^{\rm II}_{\rm res}$. These calculations have been compared with the two previous ones by means of the two following quantities: $$\label{relexc} \displaystyle \gamma_{\rm exc}^r(q,\omega) \, = \, \displaystyle \frac{R_T^{{\rm RPA}(r)}(q,\omega) \, - \, R_T^{{\rm RA}(r)}(q,\omega) } {R_T^{{\rm RA}(r)}(q,\omega)}$$ and $$\label{relfac} \displaystyle \gamma_r^{\rm mod}(q,\omega) \, = \, \displaystyle \frac{R_T^{{\rm mod}(r=1.0)}(q,\omega) \, - \, R_T^{{\rm mod}(r=0.4)}(q,\omega) } {R_T^{{\rm mod}(r=0.4)}(q,\omega) } \, .$$ The first one gives us information about the effect of the consideration of the exchange terms in the calculation. The corresponding results have been plotted in Fig. 2 (left panels). The first aspect to be noted is that the exchange terms produce effects considerably larger for $V^{\rm I}_{\rm res}$ (solid lines) than for $V^{\rm II}_{\rm res}$ (dashed curves). These effects reduce with increasing momentum transfer and they are rather small for $V^{\rm II}_{\rm res}$ above $q=410$ MeV/$c$. On the other hand, the effect of the reduction factor $r$ in the $\rho$–exchange potential is measured with the parameter $\gamma_r$. The values of this parameter for the two effective models considered, these are RPA and RA, are shown in Fig. 2 (right panels), with solid and dashed curves respectively. It is apparent that the effects of considering the $r$ factor are much larger than those due to the exchange. In general they are more important for the RA calculations than for the RPA ones, and reduce the higher $q$ is. (100,180)(30,0) (0,0) [. Left panels: $\gamma_{\rm exc}$, in percentage, as defined in Eq. (\[relexc\]). Dashed (solid) curves give the results obtained for $r=1.0 (0.4)$. Right panels: $\gamma_r$, in %, calculated as in Eq. (\[relfac\]), for RPA (solid curves) and RA (dashed curves).]{} The first conclusion to be noted is that when using a given interaction is mandatory to take care of the effective theory where its parameterization was fixed. The change of the framework produces results which could not be under control. The open question in this respect is how different becomes the responses calculated within different effective theories but with an interaction fixed consistently with the theory. This is the second aspect we investigate. To do that we have considered the $V^{\rm II}_{\rm res}$ and have determined the parameters $g_0$ and $g_0^\prime$ of the Landau–Migdal piece in such a way that the energies and B-values of the two $1^+$ states in $^{208}$Pb at 5.85 and 7.30 MeV are reproduced. This has been done both in RPA and RA. The reason for choosing these two states lies in their respective isoscalar and isovector character, what makes them particularly adequate to permit the determination of both parameters almost independently. The values obtained in this procedure are shown in Table I. It is remarkable the small value of $g_0$ needed for the RA calculation. A similar result is found when a pure zero–range Landau–Migdal interaction is adjusted, with the same criterion, in RPA type calculations (see Refs. [@co90; @hi92]). This points out the importance of the exchange, at least at low energy. [ Values of the Landau–Migdal parameters $g_0$ and $g_0^\prime$ obtained in the procedure of fixing the effective interaction $V^{\rm II}_{\rm res}$ (see text). The values quoted “RPA” (“RA”) correspond to calculations performed with (without) the consideration of the exchange terms.]{} Effective theory $g_0$ $g_0^\prime$ ------------------ -- ---------- -------------- RPA $~0.470$ $~0.760$ RA $~0.038$ $~0.717$ With the interaction fixed in this way we have evaluated the transverse responses for the three momentum transfer we are considering throughout this work. The results are shown in Fig. 3 where dotted (solid) curves correspond to the RPA (RA) calculations. Dashed lines represent the free FG responses. As we can see, the differences between the results obtained with the two effective theories are now much smaller than in Fig. 1. (100,180)(35,0) (0,0) [. Transverse nuclear responses for $^{40}$Ca, calculated with the $V^{\rm II}_{\rm res}$ interaction. Dotted lines correspond to an RPA calculation while solid curves represent the RA results. The values of $g_0$ and $g_0^\prime$ in Table I have been used. Dashed curves give the free FG responses. In all the calculations a value of $k_{\rm F}=235$ MeV/$c$ has been used.]{} Two points deserve a comment. First, it is clear that the large differences observed between the RPA calculation here discussed and that shown in Fig. 1 are mainly due to the presence of the reduction factor $r=0.4$ in the $V^{\rm I}_{\rm res}$ interaction. Second, the similitude of the results obtained with the two calculations done now with $V^{\rm II}_{\rm res}$, shows up the relevance of the link between effective theories and interactions. The last aspect we want to analyze is how the responses calculated in a given approach change when the zero–range parameters are modified. In other words, we want to determine what is the role of these parameters. How $g_0^\prime$ affects the responses is a point which has been investigated with a certain detail in different previous works (see e.g., Ref. [@ba96]) and then we focus here in $g_0$. Its influence can be seen in Fig. 4, where we compare the responses plotted in Fig. 3 (solid curves), with those obtained by changing the $g_0$ parameter in order to use values considered by different authors. Dashed–dotted curves correspond to $g_0=0$. Dashed lines represent the responses obtained with $g_0=0.70$ (0.57) for the RPA (RA) calculation. The values of $g_0^\prime$ have not been changed. The first point to be noted is the insensibility of the RA responses to the changes in $g_0$. As we can see, strong changes in $g_0$ produce almost no effect on the RA result. This can be easily understood because in the ring series the $g_0$ contribution is weighted with the magnetic moment $\mu_s^2$ while the $g_0^\prime$ piece appears with $\mu_v^2$. That means, the $g_0$ contribution is $\mu_s^2/\mu_v^2 \, \approx \, 1/28$ of the $g_0^\prime$ contribution. The situation is different in the RPA case, where the $g_0$ contribution is as important as the $g_0^\prime$ one because of the presence of the exchange terms (see Ref. [@ba96]). This makes that some of the RA calculations performed by other authors can be considered as “consistent” in practice, of course despite the fact that these parametrizations are unable to reproduce low energy properties. For example, in Ref. [@gi97], the parameterization of the Jülich–Stony Brook interaction was considered and this coincides with one of those used here ($g_0=0.57$ and $g_0^\prime=0.717$). The results obtained in this work open a series of questions which we consider worth for nuclear calculations in this energy region. In the following we enumerate and comment them: (100,170)(24,0) (0,0) [. $R_T$ responses calculated in the RPA (left panels) and RA (right panels). Solid curves correspond to the parametrizations of Table I. Dashed–dotted curves have been obtained with $g_0=0$, while the dashed ones correspond to $g_0=0.70$ (0.57) for the RPA (RA) calculation, with the same values of $g_0^\prime$ as for the solid curves.]{} 1. It has been shown that the strength of the tensor piece of $V^{\rm I}_{\rm res}$ is too strong to describe low energy properties (see, e.g., Ref. [@co90]) and different mechanisms have been proposed to cure this problem (core–polarization effects [@na85], two–particles two–holes excitations [@dr86], [*in–medium*]{} scaling law [@br91], etc.) The role of the tensor part of the interaction in the quasi-elastic peak should be investigated in order to establish the effective force to be used. 2. The presence of the exchange terms increase the sensitivity of the responses to the details of the interaction. How important can be the interference between these terms and other physical mechanisms basic in this energy region (such as, e.g., meson–exchange currents, final state interactions, short–range correlations, etc.) is a matter of relevance in order to fully understand the nuclear response. The analysis of the possible differences between RA and RPA with respect to these effects is of special interest in view of the fact that RA calculations are the most usual in the quasi–elastic peak. 3. The procedure of fixing the interaction is basic in order to deal with the possibility of having an unique framework to calculate the nuclear response at any momentum transfer and excitation energy. The problem of developing such “unified” model is still unsolved, but the cross analysis of low energy nuclear properties and quasi–elastic peak responses could give valuable hints. CONCLUSIONS =========== In this work we have analyzed the role of the effective interaction in the quasi–elastic peak region by comparing the results obtained with different effective theories and forces previously fixed in order to give a reasonable description of several low energy nuclear properties. Some conclusions can be drawn after our analysis. First, it has been found that the interaction plays a role that, similarly to what happens at low excitation energy, cannot be neglected. The particular point to be noted is the necessity of using effective interactions which have been fixed within an effective theory. Second, the procedure we have followed to perform the calculations, that is to determine the interaction at low energy before calculating at the quasi–elastic peak, seems to be adequate to look for an “unique” framework to calculate the nuclear response in different energy and momentum regimes. The role of the tensor piece of the interaction must be investigated. 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[Cancer lymphangiogenesis and its role in metastasic dissemination]. It is well-known that there are different tumor-type-dependent metastatic patterns. For example, in carcinomas metastatic spread is preferentially via the lymphatic system by which they reach regional lymph nodes through pre-existent afferent lymph vessels and/or newly formed lymph capillaries; while in sarcomas the favored pathway is through bloodvessels. These metastatic patterns have been used for many years by clinicians and surgeons for staging and tumor resection, particularly in the case of breast cancer. Recently this knowledge has been applied to detection and resection of sentinel lymph nodes. The lymphatic system drains the interstitial fluid from tissues and reincorporates it into the blood flow; in addition, it forms part of the host's immune defense and in pathological conditions, induces different types of lymph edema and participates in tumor invasion and metastasis. Although, the study of lymphangiogenesis was stagnated for several decades, it was not until a few years ago that biomolecular mechanisms were discovered and many specific markers are now in use to study the process of tumor dissemination and metastasis. There is a tendency to utilize molecular knowledge in clinical settings for grading and estimating prognostic significance of tumors as well as to develop specific therapeutic strategies.

Q: Nested Loop Unrolling in C I want to optimize my code by using unrolling loop. I tried to apply unrolling but I think I cannot do it and I cannot see my problem. I want to apply unrolling loop to outer loop. This loops do transpose of matrix. This is my loop to apply unrolling loop: void transpose(int dim, int *src, int *dst) { for (i = 0; i < dim; i++) for (j = 0; j < dim; j++) dst[j * dim + i] = src[i * dim + j]; } This is my unrolling loop: void transpose(int dim, int *src, int *dst) { int i = 0, j = 0, dimi = 0, dimj = 0, tempi = 0; for (i = 0; i < dim; i += 8) { for (j = 0; j < dim; j++) { dimj = j * dim + i; dimi = i * dim + j; dst[dimj] = src[dimi]; tempi = i + 1; if (tempi < dim) { dimj = j * dim + tempi; dimi = tempi * dim + j; dst[dimj] = src[dimi]; tempi += 1; if (tempi < dim) { dimj = j * dim + tempi; dimi = tempi * dim + j; dst[dimj] = src[dimi]; tempi += 1; if (tempi < dim) { dimj = j * dim + tempi; dimi = tempi * dim + j; dst[dimj] = src[dimi]; tempi += 1; if (tempi < dim) { dimj = j * dim + tempi; dimi = tempi * dim + j; dst[dimj] = src[dimi]; tempi += 1; if (tempi < dim) { dimj = j * dim + tempi; dimi = tempi * dim + j; dst[dimj] = src[dimi]; tempi += 1; if (tempi < dim) { dimj = j * dim + tempi; dimi = tempi * dim + j; dst[dimj] = src[dimi]; tempi += 1; if (tempi < dim) { dimj = j * dim + tempi; dimi = tempi * dim + j; dst[dimj] = src[dimi]; } } } } } } } } } } A: I'm not sure what the error in your current code is but here is another approach. void transpose(int dim, int *src, int *dst) { int i, j; for (i = 0; i <= dim-8; i += 8) { for (j = 0; j < dim; j++) { dst[j * dim + (i+0)] = src[(i+0) * dim + j]; dst[j * dim + (i+1)] = src[(i+1) * dim + j]; dst[j * dim + (i+2)] = src[(i+2) * dim + j]; dst[j * dim + (i+3)] = src[(i+3) * dim + j]; dst[j * dim + (i+4)] = src[(i+4) * dim + j]; dst[j * dim + (i+5)] = src[(i+5) * dim + j]; dst[j * dim + (i+6)] = src[(i+6) * dim + j]; dst[j * dim + (i+7)] = src[(i+7) * dim + j]; } } // Use the normal loop for any remaining elements for (; i < dim; i++) for (j = 0; j < dim; j++) dst[j * dim + i] = src[i * dim + j]; } Notice: The number of multiplication can be reduced by introducing a variable like: int jdim = j * dim + i; dst[jdim + 0] = ... dst[jdim + 1] = ... ... dst[jdim + 7] = ... and likewise for the RHS.

Prognostic value of thallium-201 exercise scintigraphy in low-risk patients after Q-wave myocardial infarction: comparison with exercise testing and catheterization. In a prospective study of 100 consecutive patients discharged after a Q-wave myocardial infarction, the value of reversible ischemia on thallium-201 scintigraphy to assess the risk of cardiac events (death or reinfarction) during 4 years was compared with variables from exercise testing and cardiac catheterization. Patients with markedly impaired left ventricular function [ejection fraction (EF) < or = 0.30] were excluded. During follow-up there were 20 cardiac events (10 cardiac deaths and 10 reinfarctions). Thallium-201 scintigraphy was significantly better than all exercise test variables and better than an EF < 0.40, with good sensitivity and specificity (75 and 51%, respectively). Exercise-induced reversible ischemia on scintigraphy yielded the same information as the presence of multivessel disease. Exercise test variables were of limited value to assess prognosis. Thus, thallium-201 scintigraphy can be used as the only tool to predict future cardiac events in low-risk patients after a Q-wave myocardial infarction.

Q: Laravel if option value == I need any suggestion how can i do that. Example what i trying todo: I have option value called "Ban reason": Cheating Sample reason If i choose "Cheating" i put reason "Chating" into mysql. That's ok with my code: DB::table('server_bans')->insert(['reason' => Input::get('player_reason') My view: <select id="player_reason" name="player_reason"><option value="" selected="selected">-</option> <option value="Cheating">Cheating</option> <option value="No reason">No reason</option> </select> But i need to add into sql "Ban time" by reason using minutes. Example: If i choose "Cheating" from option value, it goes reason and banlength for 360days by using minutes timer (518400 minutes) Any suggestion how can i do that? Thanks for helping me! A: You just need to switch on the reason and set a variable in your controller method when saving the ban reason. public function banUser (Request $request) { $reason = $request->get('player_reason'); switch ($reason) { case 'Cheating': $banlength = 518400; break; case 'No Reason': $banlength = 1; break; default: $banlength = 0; break; } DB::table('server_bans')->insert(compact('reason', 'banlength')); return back(); }

Tall, well-built, well-spoken, a powerful athlete who was dedicated to the sport, and a wrestler who ran to the ring at the beginning of his matches, then violently shook the ropes to get the fans hyped for his matches. These descriptive words and phrases reflect the legend, Jim Hellwig, better known to wrestling fans as the Ultimate Warrior. Making his debut on WWE television in October 1987, the Warrior was placed in his first major rivalry against another strong man, Hercules. The feud culminated in a match at Wrestlemania 4, which was won by the Warrior. While the victory was a big moment for him, he went on to accomplish something very significant the next year. At the first Summerslam event in August 1988, the Honky Tonk Man was scheduled to defend his Intercontinental title against Brutus “The Barber” Beefcake. But, due to an unfortunate injury, the challenger could not compete. The champion then took the ring announcer’s microphone, and challenged any wrestler to fight him. Familiar music blared over the speakers at Madison Square Garden, which signalled the arrival of the Ultimate Warrior. He ran down the aisle to the ring, bodyslammed, clotheslined and executed his big splash. He then pinned the Honky Tonk Man to win his first major WWE title in around 30 seconds. The fans at MSG were beyond thrilled with this surprise outcome. But, for the Warrior, the best was yet to come. At Wrestlemania 6, on April 1, 1990, the Ultimate Warrior and Hulk Hogan battled with the winner receiving both the Intercontinental and World Titles. Since the event was at the Skydome, in Toronto, I had the pleasure of attending with my family, and what a match it was! Fans went crazy when the Warrior defeated Hogan to become the World Champion. It was also a very classy gesture when Hogan handed the title to the Warrior. The two legends embraced to close the show. Unfortunately, the new champion had to surrender the Intercontinental title, because back then, a wrestler could not hold two singles championships. The new Intercontinental champion was decided in an eight-man tournament, which was won by the late Mr. Perfect, Curt Hennig. As the WWE Champion, The Warrior fought off the challenges of Rick Rude, Haku, Curt Hennig, and Ted Dibiase. But, at the 1991 Royal Rumble event, his luck ran out, when he lost the title to Sgt. Slaughter, with interference by Randy Savage. Later in the year, he was in a feud with the Undertaker. Many great matches were held – there were casket matches (where a wrestler placed his opponent in a casket and closed the lid to win) and body bag matches (where a wrestler fitted his opponent in a body bag and zipped it up to win.) The Warrior quickly learned about the dark side, as Jake “The Snake” Roberts decided to help him. However, it led to Jake turning on the Warrior, and revealing himself to be aligned with the Undertaker. This was supposed to lead to a rivalry between Jake Roberts and the Warrior. But, the Warrior left the company for a while because of a disagreement with Vince McMahon about his contract and money. World Championship Wrestling (WCW) signed the Warrior in 1998, where he spent almost the entire year. A storyline was created where he formed a group called One Warrior Nation (OWN) to counter the New World Order (NWO,) led by Hulk Hogan. The rivalry between the two groups led to a match at the Halloween Havoc event between Hogan and the Warrior. Hogan won through underhanded means, but the match was not as good as the one at Wrestlemania 6, eight years earlier. In a November episode of WCW Monday Nitro, the Disciple (Brutus Beefcake) was attacked by the Hogan-led NWO. But, he was rescued by the Warrior, to the delight of the crowd. Unfortunately, that was the last time fans saw Hellwig in a professional wrestling ring, as he retired from in-ring competition. Over the years, McMahon and Hellwig settled their differences, and the Warrior came back in time for Wrestlemania 30. He was never involved in a match, but the WWE decided that the time was right to induct him into their Hall of Fame, the night before the event, and it was a great moment for him, as well as his family. I am sure the former wrestler felt appreciated. Hellwig made his final appearance in the WWE, on April 7, 2014 – the night after Wrestlemania. He walked to the ring to the cheers and adulation of those in attendance. When he entered the ring, he took out his Warrior mask from his coat pocket and put it on his face, bringing the Ultimate Warrior character back to life one last time. Holding the microphone firmly in hand, he delivered a memorable promo about the wrestlers making their own history, with fans helping them to become either popular or unpopular. He ended by saying “Every man’s heart one day beats its final beat.” It was a very powerful quote, and it seemed to me that he may have known his end was near. It was a tremendous, deep, inspiring and thought-provoking promo. That night was the last time we would see Jim Hellwig in a wrestling ring because the day after his appearance on Monday Night Raw, he passed away at the age of 58. I was away on vacation when I heard the news. Shocked and saddened, I reflected on the Warrior’s wrestling career. The profound, now eerie promo he gave on Raw, the night after Wrestlemania, confirmed to me that he might have known his time was near. I believe he had his signs. The dedicated and charismatic athlete left the wrestling world a hero. Rest in peace – you will always be remembered by wrestling fans worldwide. Leave A Reply Advertisements BloggerNews On The Air We are pleased to announce our latest endeavor, Blogger News is now sponsoring some radio shows on Blog Talk Radio. You can check our full schedule, and listen to previous broadcasts here, and we hope that you will join us on the air in this new venture.

5 comments: Exciting and humbling to hear how God is working. Here is a short video from Francis Chan that you and Mike might find interesting on unanswered prayer and Gods "big plan" that Mike is learning.Cousin Dan.http://alturl.com/2askx

Steven Rigg Steven James Rigg (born 30 June 1992) is an English footballer who plays as striker for Dover Athletic in the National League. Rigg has previously played for Keswick, Penrith, Barrow , Queen of the South and Carlisle United in two spells with the club. Career Rigg began his senior career with Northern League club Penrith. Rigg had previously represented Keswick at youth level. Whilst at Penrith, Rigg was employed as a forester at the National Trust. In July 2014, Rigg signed for League Two club Carlisle United on a one-year professional contract. Rigg signed after a two-week trial period. He debuted in the Football League on 4 October 2014 and also scored in a 3–0 win over Hartlepool United. On 13 November 2014, Rigg signed a new one-year deal keeping him at the club until the summer of 2016. On 26 November 2015, Rigg signed for National League Premier club Barrow until January 2016. Rigg was stretchered off on his debut for Barrow, after coming on as a substitute. Rigg suffered ligament damage which was detected after his injured ankle was x-rayed at Kendal Hospital and his loan spell was subsequently cut short. Rigg was released by Carlisle and signed for Dumfries club Queen of the South of the Scottish Championship when his contract expired at the end of June 2016. Rigg's contract at Queens wasn't renewed during May 2017, so he released after one season. On 12 October 2017, Rigg rejoined the Cumbrians on a short-term contract after being given training facilities with the Brunton Park club to regain his fitness after suffering from a long-term injury whilst playing for the Doonhamers. In June 2019 he moved from Gateshead to Dover Athletic. Career statistics References External links Category:1992 births Category:Living people Category:People from Keswick, Cumbria Category:English footballers Category:Association football midfielders Category:Association football forwards Category:Penrith F.C. players Category:Carlisle United F.C. players Category:Barrow A.F.C. players Category:Queen of the South F.C. players Category:Chorley F.C. players Category:Workington A.F.C. players Category:Gateshead F.C. players Category:Dover Athletic F.C. players Category:Northern Football League players Category:English Football League players Category:National League (English football) players Category:Scottish Professional Football League players

var parse = require('../'); var test = require('tape'); test('dotted alias', function (t) { var argv = parse(['--a.b', '22'], {default: {'a.b': 11}, alias: {'a.b': 'aa.bb'}}); t.equal(argv.a.b, 22); t.equal(argv.aa.bb, 22); t.end(); }); test('dotted default', function (t) { var argv = parse('', {default: {'a.b': 11}, alias: {'a.b': 'aa.bb'}}); t.equal(argv.a.b, 11); t.equal(argv.aa.bb, 11); t.end(); });

The Baltimore Police Department just cannot avoid controversy even amid the implementation of a federal consent decree ordered in the wake of a scathing Department of Justice report detailing BPD’s illegal and discriminatory practices. Marvin McKenstry Jr., an employee at the Mayor’s Office of Employment Development, clashed with a BPD officer who carried out a traffic stop, refusing dozens of requests for his license and registration and implying that the stop was invalid. The fact that McKenstry was then chairman of the Community Oversight Task Force, charged with improving civilian oversight of the police, made the encounter especially interesting. The 50-minute incident, captured on BPD bodyworn camera footage, provides a “real-world” window to view the state of city policing. As a Baltimore public defender, I constantly review police encounters with suspects, witnesses and fellow officers on body cam footage and through other case preparation. Please take a look at the video. Legal, but Arbitrary Was the stop legal? Probably. The bodycam footage doesn’t show us the initial encounter between the officer and McKenstry, who had parked in the middle of an East Baltimore street to let out a passenger following an oversight task force meeting. We don’t know exactly when the passenger got out of the car or how long the officer was sitting at the scene (to create probable cause triggering a legal stop). It was plain to see that McKenstry’s car was in the middle of the road during the encounter, but we don’t get to see what precipitated the officer’s decision to approach the car. Putting on your hazard lights does not permit you to sit in a roadway. That gives an officer the right to stop a vehicle. So does a cracked windshield. Or having no light to illuminate your rear license plate. Or having an inoperable middle third brake light. People are generally unaware that such equipment issues or minor moving violations can get them pulled over. On the flip side, the police have the discretion to not effectuate a stop and can orally warn a driver to correct a minor infraction, like sitting in the street. They can make an allowance for a driver to drop someone off closer to a residence. They could also pull someone over and give a written warning rather than issuing actual tickets, which generate points and fines on driving records. Do as I say, but . . . What’s ironic about McKenstry’s offense of blocking a roadway is that the police themselves do it all the time. Everyone sees it. Cops responding to a crime or an emergency is one thing, but leaving their car in the street to run into court or pick up lunch is another. Parking rules in general seem to be suspended for police. Remember, traffic stops are often not just traffic stops. They double as pretexts to look for evidence of other crimes, most notably drugs and guns. To my dismay, courts have generally deemed pretextual stops as constitutional. Let’s make no bones about it, when we talk pretext, we’re talking about discriminating by race. The DOJ report told us that 26 out of every 27 BPD pedestrian stops yielded no criminal activity, and African Americans are three times more likely to be stopped than others. Let’s make no bones about it, when we talk pretext, we’re talking about discriminating by race. Minor traffic infractions are enforced no differently. Cops note the appearance of an individual, and they look for a violation. The police don’t care if citizens are inconvenienced, nor do they care about the targeting of certain demographics. Noncompliance v. Condescension McKenstry’s stop was on Aisquith Street. It could have easily gone down the same way in Sandtown or Berea, but is much less likely in Roland Park or Locust Point, especially if the driver was white. And that’s the problem that remains unaddressed in our city. Cops are trained on using pretexts – and black people are raised on recognizing them – so the interaction between McKenstry and Sgt. Terrence McGowan should be viewed with an understanding that two subjective mindsets clashed. McKenstry was expressing the distress of a person who’s been stopped or harassed when they feel that their skin color was most likely a factor in the stop. McGowan was audibly frustrated at McKenstry’s noncompliance and that’s understandable, too. But he was also condescending and aggressive for such a minor incident. His tone wasn’t exactly one for the dinner table at grandma’s house. McKenstry’s non-compliance never amounted to danger, either. He was wearing a bow-tie, for crying out loud. Remember the History Did this really have to end with $500 in tickets? Police have a choice in what they charge. There’s no doubt that because of McKenstry’s attitude, every last offense was cited here. The cop essentially called a personal and a technical foul. There’s no doubt that McKenstry got emotionally carried away. But the cop, too, let his emotions and sense of entitlement get the better of him. That’s why there’s a consent decree in place in Baltimore. There’s a history behind this kind of stop – and this type of clash. A better trained officer would have had that history in mind and had kept the situation from escalating. Obviously, McKenstry should have simply handed over his license on demand because, as I advise my clients, you’re never going to win an argument with an officer. Even name dropping and calling supervisors can backfire. The law always has the upper hand. But what makes no sense was how the police further clogged up the street with their own cars. At least three more BPD vehicles pulled up to the scene, obstructing traffic. If the offense itself was extremely minor, enforcement of it was arbitrary and made matters worse. In typical fashion, the Baltimore Fraternal Order of Police demanded an apology from McKenstry and asked for his resignation. (Earlier today, McKenstry did resign as oversight chairman, but will remain on the nine-member panel.) Meanwhile, citizens of this city are still waiting for the police and the FOP to own up to decades of discriminatory practices. More reflection and less knee-jerk posturing on both sides could prevent future incidents like this. ______________________Todd H. Oppenheim is a veteran attorney in the Felony Trial Division of the Office of the Public Defender. His twitter is @Opp4Justice.

Erratum ======= It has come to our attention that we overlooked a previous publication in the course ofdiscussing our work (cited above) on X chromosome inactivation and autoimmunity. Weproposed a model that is very similar to one put forward in 1977 by Richard Kast \[[@B1]\]. Thecentral concept is that X inactivation patterns in a tolerizing compartment, such as thethymus, may differ from those in the periphery, and this may predispose females toadditional risk of autoimmunity. Presumably the loss of tolerance due to this mechanism willbe directed at, or initiated by, polymorphic X-linked autoantigens. Our data neither confirmnor definitively refute this idea, and it will be challenging to develop experimental supportfor this hypothesis. In any case, we apologize for the oversight in not citing Dr Kast\'sprevious publication.

Introduction {#Sec1} ============ "To grow or not to grow" is a very important decision for plant survival. Plants require suitable conditions for growth, in the absence of which growth needs to cease. Thus, they have developed effective systems to control the amount of the growth hormones, gibberellin (GA) and auxin (IAA), by regulating the levels of the corresponding synthetic/inactivation enzymes. In fact, the transcription of GA- and IAA-biosynthesis or breakdown-related genes is strictly regulated by the level of active GA and IAA as a negative feedback or as a positive feedforward mechanism^[@CR1]--[@CR4]^. In 1961, Monod and co-workers^[@CR5]--[@CR9]^ proposed the "allosteric" theory to explain feedback inhibition of bacterial enzymes. The word is composed of two Greek roots that reflect the difference (allo-) and specificity (stereo-) of the two binding sites. The concept of this theory is based on the fact that the activity of proteins is regulated by binding an effector molecule at a site other than the active site, whereby a conformational change occurs, which in turn causes hyperactivation or inactivation. Such allosteric regulation is a natural example of control feedback loops to maintain homeostasis at the post-translational level. However, to our knowledge, there have been no reports to date on the maintenance of homeostasis of phytohormone levels through allosteric regulation, although maintaining phytohormone homeostasis at the post-translational level is surely as important for plant survival as it has been shown to be for the regulation of enzyme activity in bacteria^[@CR10]^. Here, we studied the post-translational regulation of GA and IAA inactivation enzymes from the viewpoint of their allostery and the homeostasis of GA and IAA levels. We performed X-ray structural and functional analyses of GA and IAA inactivation enzymes in rice, GA 2-oxidase 3 (OsGA2ox3) and dioxygenase, for auxin oxidation (OsDAO), respectively. The results revealed that a monomer--multimer switching occurs based on a substrate level, and that the resulting conformational change enhances the activities of these enzymes to maintain phytohormone homeostasis, in full agreement with the allosteric theory by Monod and co-workers^[@CR5]--[@CR9]^. Finally, we also discuss the establishment of homeostatic regulation systems for the two different plant growth hormones from the evolutionary perspective. Results {#Sec2} ======= X-ray structural analysis of OsGA2ox3 complexed with GA~4~ {#Sec3} ---------------------------------------------------------- GA 2-oxidase 3 (GA2ox3) is a member of the 2-oxoglutarate (2OG)- and Fe (II)-dependent dioxygenase (2ODD) enzyme family that requires 2OG and molecular oxygen as co-substrates, and ferrous iron Fe(II) as a co-factor, to inactivate biologically active GA~4~^[@CR11],[@CR12]^. Rice has 10 different *Oryza sativa* GA2oxs (OsGA2oxs) (Supplementary Fig. [1](#MOESM1){ref-type="media"}). Here, we used OsGA2ox3 for studying the molecular mechanism of homeostatic regulation because OsGA2ox3 predominantly functions in rice seedlings^[@CR13]^. We crystallized the enzyme with the co-substrates, 2OG and GA~4~ in the absence Fe(II) to prevent its enzymatic action and determined its structure via X-ray crystallography at a resolution of 2.15 Å (Supplementary Table [1](#MOESM1){ref-type="media"}). The crystallized protein consisted of a homotetramer (see below), whose each subunits with a common core fold in 2ODD enzyme family (red in Fig. [1a](#Fig1){ref-type="fig"}). The overall molecular structure of the OsGA2ox3 subunit was essentially the same as that for other 2ODD enzymes reported^[@CR14],[@CR15]^ (Supplementary Fig. [2a](#MOESM1){ref-type="media"}), including the 2OG-binding active site (yellow in Fig. [1b](#Fig1){ref-type="fig"}, Supplementary Fig. [2b](#MOESM1){ref-type="media"}). In fact, the amino acids interacting with 2OG (R269, S271, and Y183, shown in blue characters in Fig. [1b](#Fig1){ref-type="fig"}) were located in the same manner as in other 2ODD enzymes (Supplementary Figs. [2b](#MOESM1){ref-type="media"} and [3](#MOESM1){ref-type="media"}). As the location of amino acid residues in OsGA2ox3 interacting with Fe(II) are the same as that reported for other 2ODD enzymes, and Fe(II) was absent from crystalized OsGA2ox3, we located Fe(II) at the same position (Fig. [1b](#Fig1){ref-type="fig"}, Supplementary Fig. [2b](#MOESM1){ref-type="media"}). While GA~4~ interacted with non-conserved amino acids, such as Q206, Y312, Y89, Y109, and R179, among 2ODD enzymes (green characters in Fig. [2b](#Fig2){ref-type="fig"} and green closed triangle in Supplementary Fig. [3](#MOESM1){ref-type="media"}). Additionally, GA~4~ also interacted with 2OG located at the bottom of the active-site cavity (Fig. [2b](#Fig2){ref-type="fig"}, Supplementary Fig. [4a](#MOESM1){ref-type="media"}). Interestingly, the opening width of this cavity was too small for the substrate (GA~4~) or for the product (GA~34~) to go in or out (Supplementary Fig. [4b](#MOESM1){ref-type="media"}), indicating that there might be a specific passing mechanism involved in controlling transit in either direction (see below).Fig. 1OsGA2ox3 forms GA-mediated tetramer structure.**a** Crystal structure of OsGA2ox3. The α-helices are shown in blue, the common core fold is shown in red and none core β-strands are in yellow. **b** Close-up view of the active site. Important active site residues 2OG and GA~4~ are shown in yellow and pink with stick form, respectively. Fe(II) is colored in black. The amino acids interacting with 2OG (R269, S271, and Y183 shown in blue characters), with Fe(II) (H202, D204, and H259 shown in orange characters) and with GA~4~ (Q206, Y312, Y89, Y109, and R179 shown in green characters). **c** Overall structure of OsGA2ox3 tetramer composed of four subunits A--D (see details in the text). **d** Close-up view of the interface containing GA~4~ between subunit A and D. The GA~4~ in the interface and active site of subunit A and D are shown in blue and pink, respectively. Amino acids involved in interaction with the interface GA~4~ are highlighted, whereas the hydrogen bonds mediated by two water molecules (red spheres) are also indicated by dashed lines. **e** The gel filtration profile of WT-OsGA2ox3, WT-OsGA2ox6, and their mutation derivatives with or without GA~4~. 3Mu is OsGA2ox3 carrying C194A, K308A, and K313A. T, D, and M indicate the expected elution positions for tetramers, dimers, and monomers of OsGA2oxs. **f** Alignment of amino acids involved in multimerization of GA2oxs from rice and Arabidopsis, 194th, 308th, and 313th. The residue at the position of 308 is always shared by K or R. **g** BiFC analysis of multimer formation of WT-OsGA2ox3, WT-OsGA2ox6, and their mutation derivatives. YFP yellow fluorescent protein, Chl autofluorescence of chloroplasts. Scale bar = 10 μm.Fig. 2Multimerization of OsGA2ox3 enhances its activity in vitro and in planta.**a** Time course of OsGA2ox3 activation by GA~4~. The activity of WT- and 3Mu-OsGA2ox3 is shown by closed and open circles, respectively. **b** Assessment of OsGA2ox3 multimerization by blue-native PAGE. WT- and 3Mu-OsGA2ox3 are indicated with GA~4~ for 0, 8, and 24 h. Monomer (M) and tetramer (T) are indicated. **c** Enzyme analyses of OsGA2ox3, 3Mu, and K308A mutant (*n* = 3 biologically independent samples; central values and error bars represent means ± s.d.). The differences within the same category are indicated. \**P* \< 0.05; NS not significant (*P* \> 0.05); two-tailed paired *t*-tests. **d** Dose response of OsGA2ox3 and 3Mu activation by GA~4~ (*n* = 3 biologically independent samples; central values and error bars represent means ± s.d.). OsGA2ox3 (white bars) and 3Mu (black bars) were incubated for 12 h at various GA~4~ concentrations. **e** *K*~m~ and *V*~max~ of OsGA2ox3 with different multimerization forms (*n* = 3 biologically independent samples). **f** Representative internode elongation pattern shown in **g**. Red arrowheads indicate the position of nodes. Scale bar = 10 cm. **g** Complementation of the culm elongation in *ga2ox3* knockout plants by overexpression of WT- and 3Mu-*OsGA2ox3* cDNA (*n* = 6 biologically independent samples; central values and error bars represent means ± s.d.). Different letters denote significant differences (*P* \< 0.05) based on the Tukey--Kramer test. OsGA2ox3 forms a tetramer structure {#Sec4} ----------------------------------- The crystalized OsGA2ox3 formed a homotetramer (A--D in Fig. [1c](#Fig1){ref-type="fig"}) by disulfide bridges (C194--C194) and hydrogen bonds bridged by the interface GA~4~s in a face-to-face manner (red circles in Fig. [1c](#Fig1){ref-type="fig"}). Figure [1d](#Fig1){ref-type="fig"} shows a close-up view around the interface GA~4~ lying between two subunits, A and D. For their interaction via GA~4~, K308s in both subunit bound to the C-6 carboxyl group of interface GA~4~ via water molecules. K313 in subunit A directly interacted with P87 and F91 in subunit D by a hydrogen bond, and vice versa. We purified OsGA2ox3 in the absence of GA~4~ in an attempt to explain the need for GA~4~ to form the tetramer. A dominant peak of the monomer (M) was observed at a reasonable size with a very weak peak of higher molecular weight (T) in the absence of GA~4~ in a gel filtration profile (GA2ox3−GA~4~ in Fig. [1e](#Fig1){ref-type="fig"} and Supplementary Fig. [5](#MOESM1){ref-type="media"}). In contrast, peak T corresponding to the tetramer appeared in the presence of GA~4~ (GA2ox3 + GA~4~), confirming that tetramerization was induced by the presence of GA~4~. We replaced the amino acids involved in multimerization with Ala and examined its multimerization ability. Single replacement of K308 (GA dependent) or C194 (disulfide bridge), with Ala, drastically impeded tetramer formation (C194A + GA~4~ and K308A + GA~4~). Furthermore, the triple mutant carrying C194A, K308A and K313A (3Mu) did not show a tetramer peak (3Mu + GA~4~). There are two types of GA2oxs, C19- and C20-GA2ox, which specifically act on the C19- and C20-type GAs as substrates^[@CR16]^. Further, OsGA2ox3 is a member of C19-type (Supplementary Fig. [1](#MOESM1){ref-type="media"}). As GA2oxs, including C19- and C20-types, do not always contain Cys for disulfide bridge at the corresponding position (Fig. [1f](#Fig1){ref-type="fig"}, blue box), we also examined multimerization of another C20-type of GA2ox, OsGA2ox6, in the absence of Cys. The presence of GA~4~ induced a new peak of its dimer form (compare GA2ox6 ± GA~4~ in Fig. [1e](#Fig1){ref-type="fig"}), demonstrating that the Cys disulfide bridge is not required for GA-dependent multimerization. Finally, we tested multimerization in planta by BiFC analysis. Co-incubation of the wild-type (WT) OsGA2ox3s fused with N- or C-YFP in rice protoplasts showed a clear signal in the cytosol (Fig. [1g](#Fig1){ref-type="fig"}), whereas 3Mu did not (Fig. [1g](#Fig1){ref-type="fig"}). As before, a single mutation of OsGA2ox6, R332A (Fig. [1f](#Fig1){ref-type="fig"}, red box), caused failure in dimerization (Fig. [1g](#Fig1){ref-type="fig"}), thus confirming that the presence of Lys or Arg corresponding to the position at K308 on OsGA2ox3 is essential for GA-dependent multimerization. Multimerization stimulates GA2oxs enzymatic activity {#Sec5} ---------------------------------------------------- To next address the relationship between multimerization and enzymatic activity, we examined the time course of enzymatic activity upon incubation with GA~4~. We found that a significant level of activation occurred more than 8 h after incubation with GA~4~ (Fig. [2a](#Fig2){ref-type="fig"}), whereas tetramerization was observed to some extent at 8 h and thereafter (Fig. [2b](#Fig2){ref-type="fig"}). In contrast, a single mutation, such as K308A or 3Mu, led to no activation by GA~4~ (Fig. [2a--c](#Fig2){ref-type="fig"}). Additionally, we examined the dose response to GA~4~, and found that the activation started below 10^−6^ M of GA~4~ and saturated at near 10^−4^ M, while no activation of 3Mu occurred at all (Fig. [2d](#Fig2){ref-type="fig"}). We further performed the kinetic study of the various forms of OsGA2ox3 separated by gel filtration (Fig. [2e](#Fig2){ref-type="fig"}, Supplementary Fig.[6](#MOESM1){ref-type="media"}). *K*~m~ for GA~4~ was almost 10-fold lower for the tetramer and dimer than that for the monomers, while, consistently, *V*~max~ of these multimers was more than threefold higher than that corresponding to the monomers. These findings clearly demonstrate that multimerization enhanced OsGA2ox3 activity. Next, we studied the biological significance of the multimerization of GA2ox in planta. We generated overexpressors (*GA2OX3-OV*) driven by the actin promoter and knockout plants (*ga2ox3*) by a CRISPR/Cas9 system. *GA2OX3-OV* showed more severe dwarfism at higher levels of OsGA2ox3 expression (Supplementary Fig. [7a, b](#MOESM1){ref-type="media"}), whereas *ga2ox3* formed elongated internodes and leaves (Supplementary Fig. [7c--g](#MOESM1){ref-type="media"}), indicating that a difference in OsGA2ox3 activity reflected on the morphology of the rice plant. Furthermore, a reporter gene (GUS) controlled by the *OsGA2ox3* promoter was dominantly expressed in elongating internodes and nodes in the culm but was faintly expressed in other tissues (Supplementary Fig. [7h--k](#MOESM1){ref-type="media"}), thus suggesting that internode elongation might be the most suitable system for precise evaluation of changes in enzymatic activity in planta. Next, we examined the effect of WT-OsGA2ox3 cDNA or 3Mu cDNA driven under its own promoter on internode elongation in *ga2ox3* plants (Fig. [2f, g](#Fig2){ref-type="fig"}). At the heading stage, plants carrying WT-cDNA were the shortest in height, with shorter internodes; in contrast, plants carrying 3Mu cDNA showed an intermediate phenotype relative to control plants. This clearly demonstrated that multimerization of OsGA2ox3 changed its enzymatic function in plants growing under natural conditions (see Discussion). Activation mechanism of OsGA2ox by multimerization {#Sec6} -------------------------------------------------- We studied the activation mechanism of OsGA2ox3 using molecular dynamics (MD) simulation based on the tetrameric structure. Note that in the absence of comparative structures for monomers this can only generate a hypothetical mechanism for activation by multimerization. By free-energy analysis, we transferred GA~4~ from the interface to the active sites (shown in purple for interface GA~4~ and in pink for active site in Fig. [3a](#Fig3){ref-type="fig"}), and estimated its relative stability as potential mean force. Our findings agreed with X-ray crystallographic results (Fig. [3b](#Fig3){ref-type="fig"}). The free-energy landscape of GA~4~ revealed the presence of two local free-energy minima around the interface and active sites (indicated with a circle and triangle in Fig. [3b](#Fig3){ref-type="fig"}, respectively), whereas the stability of GA~4~ around the active site (State no.1 in Fig. [3c](#Fig3){ref-type="fig"}) was higher than that of the interface (State no. 25 in Fig. [3c](#Fig3){ref-type="fig"}), with a 2.5 kcal/mol difference (Fig. [3c](#Fig3){ref-type="fig"}). Our results also revealed two possible pathways from the interface to the active sites (red and blue lines in Fig. [3b, c](#Fig3){ref-type="fig"}), with a nearly identical energy barrier of 1.7 kcal/mol, as estimated by the difference between peak height (4.2 kcal/mol) and the base line (2.5 kcal/mol) (Fig. [3c](#Fig3){ref-type="fig"}). These energy barriers are only slightly higher than thermal fluctuation (0.6 kcal/mol at 25 °C), indicating that such barriers can readily be surpassed without assistance from any external force. Consequently, the interface GA~4~ could be readily loaded into the active site. We predicted two possible transition states for these different pathways (Supplementary Fig. [8a](#MOESM1){ref-type="media"}) and identified key interactions to stabilize the intermediate states upon loading of GA~4~ (Supplementary Fig. [8b, c](#MOESM1){ref-type="media"}). In the red and blue pathways, K308 in subunits A and D, respectively, formed a salt bridge with the C-6 carboxyl group of GA~4~; however, an additional hydrogen bond between K308 in subunit A and γ-lactone of GA~4~ occurred only in the blue pathway (Supplementary Fig. [8c](#MOESM1){ref-type="media"}). We predict that K308 is important for moving GA~4~ from the interface to the active site. Because the opening width of the OsGA2ox3 active site is rather small (Supplementary Fig. [4b](#MOESM1){ref-type="media"}), GA~4~ of the active site likely enters and exits by dynamic fluctuations near the entrance. Therefore, we investigated the relative flexibility of various regions by simulating the exit process of GA~4~ from the active site. In addition to the structural change around K308, the root-mean-square fluctuation (RMSF) of Cα atoms indicated that residues 96--106, composed of two β-strands and a loop connecting the strands (Supplementary Fig. [9a--c](#MOESM1){ref-type="media"}), were markedly destabilized as GA exited the active site (Fig. [3d](#Fig3){ref-type="fig"}, Supplementary Fig. [9d](#MOESM1){ref-type="media"}). Next, we determined the structural dynamics of this region in the blue and red pathways over the course of GA~4~ movement by calculating the root-mean-square deviation (RMSD) (Fig. [3e](#Fig3){ref-type="fig"}). In both pathways, the region was opened upon loading GA~4~ into the active center (gate open, Supplementary Fig. [9e](#MOESM1){ref-type="media"}), and was closed when the ligand was fully loaded (gate close, Supplementary Fig. [9e](#MOESM1){ref-type="media"}); we thus termed this loop "gate". This analysis, together with the tetramer structure, suggested that two sets of paired amino acids (R97/F100 and W106/C186) are involved in the stabilization process of the opened gate through interacting with subunits A and D as the hinge of the gate (Supplementary Fig. [9a--c](#MOESM1){ref-type="media"}). We exchanged these residues with Ala and examined the effect on the enzymatic properties (Fig. [3f](#Fig3){ref-type="fig"}). The R97A/F100A-tetramer affected both the *K*~m~ and the *V*~max~ values, whereas the W106A/C186A monomer affected only the *K*~m~. Along with MD and structural analyses, a potential activation mechanism of OsGA2ox3 by multimerization is summarized in Supplementary Fig. [9e](#MOESM1){ref-type="media"}. Together, these findings suggest the importance of the gate region.Fig. 3Free-energy landscape of the GA~4~ loading process.**a** Schematic view of the free-energy analysis. GA~4~ was moved between two binding sites, the interface (purple) and active site (pink). **b** The free-energy landscape of the GA~4~ loading process. Numbers represent the height of the contour in kcal/mol. The horizontal and vertical axes represent the center-of-mass (COM) coordinate of GA~4~. Two GA~4~ sites found in the X-ray crystallographic analysis were plotted as a red circle and a triangle. Broken lines (magenta and orange) represent two possible pathways connecting both sites. **c** The relative stabilities were calculated as a potential of mean force (PMF) for the predicted two pathways in panel **b**. **d** The change in the fluctuation of Cα atoms upon the GA~4~ exiting the active site. In addition to the alpha helices around K308, residues in the gate were destabilized when GA~4~ exited the active site. **e** The root-mean-square deviation (RMSD) of the gate (near residues 96--106) during the simulation (*n* = 8 biologically independent samples; central values and error bars represent means ± s.d.). **f** Kinetic analysis of monomer, dimer and tetramer of WT and mutant OsGA2ox3 (*n* = 3 biologically independent samples). IAA-mediated multimerization of OsDAO triggers its activity {#Sec7} ----------------------------------------------------------- Recent studies have revealed that DAO controls IAA concentration, which is important for modulating auxin homeostasis, since it is dependent on catabolizing IAA. Interestingly, all DAOs listed in Supplementary Fig. [10](#MOESM1){ref-type="media"} share Arg or Lys at residue 308 in OsGA2ox3, which is essential for GA~4~-dependent oligomerization and hyperactivation, as previously mentioned. Thus, we hypothesized that the activity of DAO might also be regulated through multimerization via IAA. We elucidated the crystal structure of OsDAO complexed with its substrate, IAA, at a 2.0-Å resolution (Supplementary Table [1](#MOESM1){ref-type="media"}). As expected, OsDAO had a stereotype structure of 2ODD (Fig. [4a](#Fig4){ref-type="fig"}), and formed a dimer containing two IAA molecules at the interface region (Fig. [4b](#Fig4){ref-type="fig"}). An IAA contacting subunit A (green stick) interacted with R154 and S176 of subunit A and R282 of subunit B via a water molecule, while the other IAA on subunit B (cyan stick) interacted with R281, R290, and S176 of subunit B and R282 of subunit A (Fig. [4b](#Fig4){ref-type="fig"}). These subunits directly interacted with each other through hydrogen bonds at residues D278, D279, R281, and R282 (Fig. [4c](#Fig4){ref-type="fig"}).Fig. 4OsDAO forms an IAA-mediated dimer structure to trigger its enzyme activity.**a** Overall structure of the dimer form of OsDAO. **b**, **c** Detailed interactions at the dimer--dimer interface of the OsDAO bound to IAA (green and cyan stick forms), the residues surrounding the interface are represented by a stick model, shown as pink and yellow sticks. The hydrogen bonds mediated by water molecule (red spheres) are also indicated by dashed lines. **d** A typical elution profile of OsDAO sample under the presence of IAA condition in gel filtration. The proposed conformation of each eluted peak is indicated by M (monomer) and D (dimer). **e** BiFC analysis of dimeric interaction of DAO. Scale bar = 5 μm. **f** Kinetic analysis of monomer and dimer of OsDAO. Comparison of *K*~m~ and *V*~max~ calculated by the corresponding Lineweaver--Burk plots (*n* = 3 biologically independent samples). The elution profile of gel filtration showed that dimer formation of OsDAO occurred in the presence of IAA but not in its absence (Fig. [4d](#Fig4){ref-type="fig"}). OsDAO multimerization in planta was also confirmed by BiFC analysis (Fig. [4e](#Fig4){ref-type="fig"}). *K*~m~ for IAA of the dimer was nearly fivefold lower than that of the monomer, while consistently, *V*~max~ of the dimer was 22-fold higher than that of the monomer (Fig. [4f](#Fig4){ref-type="fig"}, Supplementary Fig. [11](#MOESM1){ref-type="media"}). These observations demonstrated that the activity of an auxin-catabolizing enzyme, DAO, is regulated by the same mechanism that regulates GA2ox; namely, through substrate-mediated multimerization. Phylogenetic analysis of 2ODD enzymes {#Sec8} ------------------------------------- Phylogenetic analysis of 2ODD enzymes from angiosperms (rice, *Arabidopsis thaliana*, and *Amborella trichopoda*), gymnosperms (*Picea abies*), Lycophytes (*Selaginella moellendorffii*), and Bryophytes (*Physcomitrella patens*) revealed that C19 and C20-type GA2oxs and DAO are classified into independent clades (Fig. [5a](#Fig5){ref-type="fig"}, Supplementary Fig. [10](#MOESM1){ref-type="media"}), indicating that these enzymes evolved independently. Phylogeny also suggested that the emergence of the C19-type of GA2ox might have occurred at the time when seed plants first appeared, since *P. abies* contains its homolog but *S. moellendorffii* and *P. patens* do not (Fig. [5b](#Fig5){ref-type="fig"}, Supplementary Fig. [10](#MOESM1){ref-type="media"}). In contrast, the C20-type of GA2ox and DAO may have evolved with angiosperms, because there is no existing homolog within the genome of gymnosperms, although certain homologs have been reported in *A. trichopoda*, the most primitive lineage in the angiosperm clade (Supplementary Fig. [10](#MOESM1){ref-type="media"}). Thus, plants seem to have independently developed essentially identical systems at three distinct time points over the course of evolution to regulate levels of GA~4~ and IAA (Fig. [5b](#Fig5){ref-type="fig"}).Fig. 5Activation model of OsGA2oxs and OsDAO and phylogenetic analysis.**a** Schematic phylogenetic tree of C19- and C20-type GA2oxs and DAOs, including some 2ODD enzymes bearing close resemblance to these enzymes. Each box corresponds to each clade with the same number presented in Supplementary Fig. [10](#MOESM1){ref-type="media"}. Clades containing only 2ODD enzymes with R/K at the 308th position of OsGA2ox3 or not are shown in black or white, whereas clades including both types are shown in gray. Bryophytes, lycophytes, gymnosperms, and angiosperms are shown as B, L, G, and A characters, respectively. **b** The number of gene copies of C19- and C20-type GA2ox and DAO in *P. patens* (Bryophytes), *S. moellendorffii* (Lycophytes), *P. abies* (Gymnosperms), *A. trichopoda* (the most primitive lineage of Angiosperms), *O. sativa* (monocot), and *A. thaliana* (dicot). **c** Under low substrate concentration (GA~4~ or IAA) (left), GA2ox or DAO functions as a monomer with low enzyme activity. At high substrate concentration (right), the interface GA~4~ or IAA causes the formation of multimers by bridging two enzyme molecules, resulting in hyperactivation. Discussion {#Sec9} ========== Here, we determined an X-ray crystal structure and performed functional analyses of two rice 2ODD family enzymes, OsGA2ox3 and OsDAO, which catabolize plant growth hormones GA~4~ and IAA, respectively. Both enzymes formed tetramers for OsGA2ox3, and dimers for OsDAO with the aid of their substrates, thereby enhancing their activity, as schematically summarized in Fig. [5c](#Fig5){ref-type="fig"}. Synchronous structural changes and activity enhancement are typical of allosteric-regulation events, as shown in the model proposed by Monod et al.^[@CR5]--[@CR9]^. Based on this model, triggering of OsGA2ox3 and OsDAO activities can be explained as follows: at a low concentration of GA~4~ or IAA, each enzyme is present as a monomer or protomer (the specific term proposed by Monod) and displays steady-state activity^[@CR8]^. With increasing substrate concentration, the enzyme gradually forms a multimer with the aid of the substrate itself (effecter), thereby resulting in an increase in enzymatic activity and in the active catabolism of GA or IAA to maintain hormonal homeostasis. However, further studies are needed to investigate how multimerization of OsGA2ox3 leads to increase enzyme activity because equivalent simulations on the monomer of OsGA2ox3 have not been performed and thus our proposed mechanism remains hypothetical. Previously, Zhang et al.^[@CR17]^ reported that the inactivation of IAA by AtDAO1 was more than 10,000-fold lower than inactivation by GH3.6, another IAA inactivation enzyme. They speculated that DAO1 might function spatiotemporally to terminate active IAA constitutively during development, in contrast to GH3, which responds quickly to environmental factors that increase cellular IAA levels^[@CR17]^. These studies, combined with our results, provide further insight into the biological implications of the DAO-mediated auxin inactivation system. Indeed, our results showed that OsDAO activity (maximum reaction rate for oxidation of IAA at 54.48 nmol/min/mg protein) was a quarter of that reported for GH3.6 (maximum reaction rate for conjugation of Asp to IAA at 244 nmol/min/mg protein^[@CR18]^), under high concentrations of IAA, to induce DAO-dimer formation. This result confirms the importance of DAO for auxin catabolism relative to GH3, and clarifies differences between these two enzymes in terms of IAA inactivation. *GH3* genes, which mainly work as an emergency-response system against environmental changes experienced by plants^[@CR19]--[@CR22]^, are among the fastest to respond to exogenous auxin and environmental stimuli, with transcript levels increasing by 10-fold within 1 h. In contrast, the DAO inactivation system may primarily be involved in intrinsic biological events/processes, and may modulate activity through an intramolecular mechanism according to substrate level. Effective dual systems are most likely important for plants exposed to diverse environmental conditions under continuous fluctuation. Interestingly, such a dual system was not observed in the case of the GA~4~ catabolic mechanism, suggesting that rapid inactivation may not be essential for GA-regulated biological events. Phylogenetic analysis of 2ODD enzymes revealed that plants seem to have independently developed essentially identical systems at three separate time points over the course of evolution to regulate the level of GA~4~ and IAA (Fig. [5b](#Fig5){ref-type="fig"}). Such independent development of the homeostatic regulation systems described, at the time of seed plant and angiosperm emergence, suggests that systems such as these could be important for plant adaptation to varying environmental conditions and to effectively control levels of growth hormones. Consequently, these elegant systems have no doubt aided plant survival and contributed to better adaptation in fluctuating and challenging environments. Methods {#Sec10} ======= Plasmid construction {#Sec11} -------------------- Sequences of primers used in this study are listed in Supplementary Table [2](#MOESM1){ref-type="media"}. The PCR fragments were sequenced to confirm that no mutations were induced. To construct GST-tagged proteins, the full-length coding regions for the OsGA2ox3, OsGA2ox6, and OsDAO containing appropriate restriction sites were cloned into pGEX6P1 (GE Healthcare) using primer sets (Supplementary Table [2](#MOESM1){ref-type="media"}, No. 1--6). The OsGA2ox3 expression plasmid, in which Cys194, Lys308, Lys313, Trp106, Cys187, Fhe100, and Arg97 residues of OsGA2ox3 were replaced with Ala, was constructed with one set mutagenized primers (Supplementary Table [2](#MOESM1){ref-type="media"}, No. 7--20) corresponding to each mutation and pGEX6P1/OsGA2ox3 as template. To generate constructs of the OsGA2ox3, OsGA2ox6, and OsDAO for the transient protein expression, the full-length cDNA without a stop codon was amplified using appropriate primers (Supplementary Table [2](#MOESM1){ref-type="media"}, No. 21--28) and subcloned into the pENTR-D/TOPO gateway entry vector using the TOPO reaction according to the supplier's directions (Invitrogen). For constructs used in the BiFC experiment, genes from pENTR- D/TOPO clones were transferred to the N-terminal half clone, pGWnY vector and the C-terminal half clone, pGWcY vector by LR Gateway reaction to generate C- and N-terminal fusions to the two YFP fragments. To generate transgenic plants, the Act1 promoter of the pSTARA vector (Kumiai Chemical Industry) located between the gateway cloning site and the acetolactate synthase (ALS) terminator was replaced with a 1.8 kbp genomic DNA of OsGA2ox3 promoter (pOsGA2ox3) using primers with suitable restriction enzyme sites (Supplementary Table [2](#MOESM1){ref-type="media"}, No. 29 and 30). The OsGA2ox3-WT and OsGA2ox3-3Mu cDNA was cloned by LR Gateway reaction into pOsGA2ox3-pSTARA vector. The pOsGA2ox3-pSTARA vector was used as a control for transient transformation. For the promoter-GUS assay, a 2.6 kbp genomic DNA, including the cording region (exon 1 and part of exon 2) and the 5′ promoter region of the OsGA2ox3 was amplified by the primer pair (Supplementary Table [2](#MOESM1){ref-type="media"}, No. 31 and 32) using the Nipponbare genomic DNA as the template and inserted into the *Xba*I and *Sma*I sites of the binary vector pBI/Hm2 to drive the GUS reporter gene expression. For the overexpression of OsGA2x3, the OsGA2ox3 cDNA was amplified by the primer pair (Supplementary Table [2](#MOESM1){ref-type="media"}, No. 33 and 34) and inserted into the *Xba*I and *Sma*I sites of the vector pCAMBIA 1380 to drive CaMV35S promoter. To generate constructs of the OsGA2ox3 for the knockout mutant, the vectors in this study are based on Cas9 cloning vectors (pU6gRNA)^[@CR23]^. The pU6gRNA has two *Bbs*I sites between the OsU6 promoter and the gRNA scaffold sequence. The 20 nt annealed oligonucleotides (Target) (Supplementary Table [2](#MOESM1){ref-type="media"}, No. 35--38) were ligated into this restriction enzyme recognition sites of the pU6gRNA. To connect gRNA expression cassettes, the gRNA expression cassette (OsU6pro- 2pro::gRNA::polyT) was eliminated from pU6gRNA by using *Pac*I and *Asc*I, and inserted into the pZDgRNA_Cas9ver.2_HPT vectors. The all plants were genotyped using primers No. 39--42 (Supplementary Table [2](#MOESM1){ref-type="media"}) by the optimized PCR. Expression and purification of OsGA2ox3 and OsDAO {#Sec12} ------------------------------------------------- OsGA2ox3 and OsDAO/pGEX6P1 constructs were overexpressed in *Escherichia coli* Rosetta (DE3) pLysS (Novagen). Cells were grown at 37 °C to the mid-log phase in Terrific-Broth medium containing 100 μg/ml ampicillin, followed by IPTG induction at 18 °C for 16--18 h. The harvested cells were washed with buffer A \[10 mM Na-phosphate, 150 mM NaCl, 1 mM DTT (pH 7.5)\] containing Complete protease inhibitor (Merck) and 1.5 mM phenylmethylsulfonyl fluoride, and then disrupted by sonication. OsGA2ox3 and OsDAO were obtained from the supernatant fraction. The recombinant protein in the supernatant was purified with Glutathione Sepharose 4B resin (GE Healthcare) equilibrated with Buffer A. The column was washed with 30 bed volumes of buffer A, and eluted with buffer A (plus 20 mM glutathione pH 7.5). To remove the GST-tag, precision protease (GE Healthcare) was added and incubated overnight at 4 °C. The GST and tag-digested OsGA2ox3 and OsDAO were filtered through a 0.22 μm nylon filter and further purified using MONOQ column (GE Healthcare) equilibrated with buffer B \[10 mM Na-phosphate, 1 mM DTT\] with a NaCl gradient (0--1000 mM) in buffer B. The sample was concentrated and dialyzed with buffer C (10 mM sodium phosphate, pH 7.4) using an Amicon Ultra-4 concentrator unit (10 kDa molecular weight cut-off) (Millipore). The protein concentrations of OsGA2ox3 were measured by UV absorbance at 280 nm. The *A*^0.1%^ values at 280 nm (0.90, 0.73 for the OsGA2ox3 and OsDAO, respectively) were calculated from the amino acid composition^[@CR24]^. The amount of OsDAO protein in buffer containing IAA was estimated from intensity of the band in SDS-PAGE gel using Image J. Then all protein samples were run on both a 12% wt/vol SDS gel and a 3--12% wt/vol nondenaturing gel stained and visualized by Coomassie Brilliant Blue R-250 staining. The target proteins were detected by comparison with protein standard markers, and the optimum conditions for in vitro expression were determined. Crystallization {#Sec13} --------------- Screening experiments were performed with several commercial kits. Crystallization was performed by the sitting drop vapor diffusion method at 20 °C with 1 μl protein mixed with 1 μl mother liquid solution. Droplets containing 20 mg/ml OsGA2ox3 dissolved in 5 mM Na-phosphate (pH 7.5), 10 mM 2-oxoglutarate and 2 mM GA~4~ and mother liquor were equilibrated against 50 μl of reservoir solution composed of 0.2 mM ammonium citrate (pH 5.1) and 20% (w/v) PEG3350. The OsDAO was dissolved in 5 mM Na-phosphate (pH 7.5), 10 mM 2-oxoglutarate and 2 mM IAA, and mother liquor comprised 0.1 mM sodium acetate, 0.2 mM ammonium sulfate, and 22% (w/v) PEG 4000. Crystals were flash-frozen in liquid nitrogen with an addition of 30% glycerol in the crystallization of mother liquid as cryoprotectant. X-ray diffraction data were collected on BL26B1 beamline at SPring-8. All data were processed and scaled using HKL2000 (ref. ^[@CR25]^). The crystal data are summarized in Supplementary Table [1](#MOESM1){ref-type="media"}. Structure determination and refinement {#Sec14} -------------------------------------- The crystal of OsGA2ox3 was calculated by a single-wavelength anomalous dispersion (SAD) method using data collection at the peak wavelength of Au. HKL2MAP^[@CR26]^ was used to run the SHELX suite of programs. Au positions were located using SHELXD, then the Au sites were located with SHELXD, and single-wavelength anomalous diffraction phases to 3.0 Å resolution were calculated with SHELXE using the data collected at the X-ray wavelength (1.0 Å) corresponding to the peak of the X-ray fluorescence spectrum. Five gold atom sites in the asymmetric unit were found. Several iterations of model building with WinCoot (version 0.8.9)^[@CR27]^ and restrained refinement with REFMAC5 (ref. ^[@CR28]^) from the CCP4 package (version 7) and PHENIX program (version 1.17.1)^[@CR29]^. After repeated model rebuilding and refinement, the final model was refined using SHELXL at 2.15 Å resolution. The structure of OsDAO was determined by molecular replacement with Molrep using the refined structure and OsGA2ox3 as the search model. Model building and refinement were performed as well as OsGA2ox3. The statistics of the data collection and refinement are shown in Supplementary Table [1](#MOESM1){ref-type="media"}. Molecular graphics (Figs. [1](#Fig1){ref-type="fig"} and [2](#Fig2){ref-type="fig"}, Supplementary Fig. [2](#MOESM1){ref-type="media"}) were illustrated with PyMOL^[@CR30]^ (<http://www.pymol.org>) and UCSF Chimera^[@CR31]^ (Fig. [1](#Fig1){ref-type="fig"}). Gel filtration analysis {#Sec15} ----------------------- Purified monomer OsGA2ox3 and OsGA2ox6 were incubated at 10 mg/ml and 25 °C for 18 h in buffer C (10 mM potassium phosphatase pH 7.4) with 10 mM GA~4~. The incubated sample were fractionated by size exclusion chromatography using a Superdex 200 10/300GL column (GE Healthcare) equilibrated with buffer C and eluted with the same buffer (+1 mM GA~4~) at a flow rate of 0.5 ml/min at 4 °C. Fractions (0.5 ml) were collected, and each peak fraction was analyzed by Blue-Native PAGE. The fractions indicated as in Fig. [2](#Fig2){ref-type="fig"} were used for further experiments. Purified monomer OsDAO was incubated at 10 mg/ml and 4 °C for 18 h in buffer C (10 mM potassium phosphatase pH 7.4) with 10 mM IAA. Size exclusion chromatography was performed as described as for the OsGA2ox3. The fractions indicated as in Fig. [4d](#Fig4){ref-type="fig"} were used for further experiments. Enzyme assay {#Sec16} ------------ The purified OsGA2ox3 and OsDAO were incubated at 30 °C with GA~4~ and IAA (OlChemIm), respectively in 1 ml of 100 mM Tris-HCl (pH 7.9) containing 4 mM ascorbic acid, 4 mM 2-oxoglutaric acid, 0.5 mM FeSO~4~, 4 mM DTT, 2 mg/ml BSA, and 1 mg/ml catalase. The reactions were stopped after 1 h incubation by adding 125 μl of acetic acid. Next, 50 ng of deuterated \[^2^H~2~\] GA~4~ and IAA (OlChemIm) were used as internal standards for the reactions of OsGA2ox3 and OsDAO, respectively. The solution was passed through a 1 ml C18-SD high-performance extraction cartridge (Empore). After the column was washed with 300 μl of water two times, substances retained on the column were eluted with 150 μl of methanol two times. The methanol eluate was evaporated with dry N~2~ gas. After TMSi (trimethylsilyl) ester--TMSi ether derivatization with MSTFA (*N*-methyl-*N*-trimethylsilyl-trifluoroacetamide), the GA~34~ and oxIAA were analyzed by gas chromatography-selected ion monitoring--mass spectrometry. Full-scan GC-MS analysis of GAs was performed using a mass spectrometer (JMS-K9; JEOL) connected to a gas chromatograph (6890N; Agilent Technology). The trimethylsilylated derivatives (TMSi ester--TMSi ether) were injected (285 °C) into an DB-1 column (0.32 mm i.d. × 30 m, 0.25 μm film thickness; Agilent Technology). The column temperature was kept at 120 °C for 2 min, then increased at a rate of 20 °C/min to 260 °C and held for 1 min, and then increased at a rate of 4 °C /min to 320 °C. The flow rate of the carrier He gas was 1.5 ml/min, and mass spectra were acquired by scanning from *m*/*z* 50 to 750 at 70 eV. RNA isolation and quantitative RT-PCR analysis {#Sec17} ---------------------------------------------- Total RNAs were purified from young seedlings using RNeasy Plant Mini Kit according to the manufacturer's guidelines (Qiagen) and treated with RNase-free DNase (Qiagen). Three biological replicates were analyzed using RNAs isolated independently. The first strand of cDNA was synthesized from 1 μg of total RNA using the Omniscript reverse transcription kit (Qiagen). Real- time RT-PCR analysis was performed on a CFX96 real-time PCR detection system (Bio-Rad) with the SYBR Green PCR kit (Qiagen) and appropriate primers. The ubiquitin gene was used as an internal standard for normalizing variations in cDNA concentrations. Production of transgenic rice plants and their growth conditions {#Sec18} ---------------------------------------------------------------- The OsGA2ox3/pBI, OsGA2ox3/pCAMBIA 1380, pOsGA2ox3-WT/pSTARA, pOsGA2ox3-3Mu/pSTARA, pSTARA vector control, and OsGA2ox3 knockout mutant were transferred into *Agrobacterium tumefaciens* stain EHA105 by electroporation. These EHA101 stains were grown for 3 days on the AB medium containing 50 mg/l hygromycin and 50 mg/l kanamycin or 100 mg/l spectinomycin solidified with 1.5 % agar. The bacterial cells were resuspended in AAM medium. The calli (*Oryza sativa* L. cv. Nipponbare) were soaked in this suspension for 2 min and blotted dry, using sterile Kimwipes for removal of excess bacteria. Then these calli were transferred on a piece of filter paper placed on a co-culture medium. A co-culture medium was prepared by spreading 5.35 ml of a liquid medium (2N6-AS medium)^[@CR32],[@CR33]^ on a bottom medium. After co-cultivation, the calli were washed three times with water containing 0.6 mg/l acetosyringone. After washing, the transgenic calli were selected on a medium containing 25 mg/l meropenem (Wako) and antibiotics corresponding to each constructs. Seedlings were established on Murashige and Skoog (MS) medium \[half-strength MS salt mixture (pH 5.7; Wako), B~5~ vitamins, 1% sucrose, and 0.8% gellan gum (Wako)\]. Rice plants, expect when used for protoplast isolation, were grown in a greenhouse at 30 °C under a 16 h light (long-day treatment) and 10 h (short-day treatment). Plants (rice T65) used for protoplast isolation were grown in an incubator at 30 °C for 6 days. β-Glucuronidase (GUS) staining {#Sec19} ------------------------------ The construct of OsGA2ox3::GUS was transformed into *Agrobacterium tumefaciens* stain EHA105. Various organs of transgenic lines were prepared for histochemical GUS staining^[@CR34]^. Transgenic rice was grown in greenhouse, and before and after heading plants were collected and vacuum infiltrated for 10 min with GUS staining buffer (50 mM sodium phosphate, pH 7.0, 1 mM 5-bromo-4-chloro-3-indolyl-β-d-glucuronide and 7% \[v/v\] methanol). After incubation in darkness for 18 h at 37 °C, various tissues were completely cleared with 70% ethanol. Bimolecular fluorescence complementation assay {#Sec20} ---------------------------------------------- Plasmids were extracted using the NucleoBond Xtra Midi Plus according to the manufacturer's instruction (Takara). Leaves (rice T65) were collected from 6-day-old plants grown. The rice T65 mesophyll protoplasts were performed^[@CR35]^ and calculated with the modification that the protoplasts were isolated using the Tape-sandwich method^[@CR36]^. YFP fluorescence was recorded by a LSM 700 confocal microscope (Zeiss). Phylogenetic analysis {#Sec21} --------------------- Alignment analyses on amino acid sequences was accomplished using MAFFT (version 7)^[@CR37]^ with the L-INS-i model, and then manually adjusted to optimize alignments using SeaView (version 4). Bayesian estimation of phylogenetic topology was conducted with MrBayes (version 3.2.6)^[@CR38]^, using the General Time Reversible (GTR) + site-specific rates model (SS) model. Four chains of the Markov chain Monte Carlo (MCMC) analyses were run simultaneously and sampled every 1000 generations for a total of 1,100,000 generations. MD setup {#Sec22} -------- The force field parameters for α-ketoglutalic acid and GA~4~ were constructed using the generalized amber force field (GAFF)^[@CR39]^. Charges of atoms were determined from the restrained electrostatic potential (RESP)^[@CR40],[@CR41]^ calculation using Gaussian09 (ref. ^[@CR42]^). AMBER 14SB force field^[@CR43]^ has been used to model the protein. A tetramer of OsGA2ox3 residue IDs 12--326 was selected for the simulation, where N- and C-termini of each subunit of OsGA2ox3 were capped by acetyl and methyl groups, respectively. Four cysteines at residue 194 were connected by two S--S bonds. All histidines except His182 were protonated at Nε, while His182 residues were protonated at Nδ. The GA~4~ molecule at the A/D subunit intermolecular site was removed from the initial configuration. The system was then solvated in 150 mM sodium chloride solution with the truncated dodecahedron periodic boundary. The periodic boundary was set to ensure at least 10 Å thickness from the protein. In the end, 59,940 molecules of TIP3P water, 202 sodium ions, and 185 chloride ions were placed. The total number of atoms was 199,630. After the model was constructed, MD simulation was performed. Throughout all simulations, long-range interactions were calculated with the smooth particle mesh Ewald method^[@CR44]^ with the real-space cut-off length of 10 Å. The system was first equilibrated in NPT (constant-temperature, constant-pressure condition) for 1 ns with heavy atom restrained to the coordinate from the X-ray crystallographic structure, then the system was further equilibrated with 20 ns NPT run without restraints. The temperature and the pressure were set to 300 K and 1 atm, respectively. The timestep was set to 2 fs with bonds between hydrogens and heavy atoms being constrained. Free-energy analysis of the GA~4~ loading mechanism {#Sec23} --------------------------------------------------- After the equilibration, the GA~4~ inside the subunit "A" was manipulated by the string method^[@CR45]^ using the center-of-mass (COM) coordinate as collective variables. Each COM of the GA~4~ was restrained to the guiding path coordinate by a harmonic restraint of 2.39 kcal/mol/Å^2^ (1000 kJ/mol/nm^2^). There were 48 points in the guiding path conforming one loop; guiding points numbered "0" and "47" were considered to be connected during the string method phase. The guiding points numbered "0" and "24" were fixed to the COM of A/D interface GA~4~ in the X-ray crystallographic structure, and that at the active site in the subunit "A", respectively. The guiding points were optimized with the string method to elucidate a "rough" loading path. After the guiding points were optimized, we performed the replica-exchange umbrella sampling method^[@CR46],[@CR47]^. The combination of the string method and the replica-exchange umbrella sampling method have been shown to be more reliable for the simulation of proteins^[@CR48]^. The simulation used the optimized guiding points as centers of harmonic umbrella potentials with a force constant of 0.48 kcal/mol/Å^2^ (200 kJ/mol/nm^2^). After 2 ns of the equilibration, the production run was performed for 20 ns. We confirmed the convergence by comparing the free-energy landscape at 15 and at 20 ns. Simulations were performed with GROMACS 2016 (ref. ^[@CR49]^) extended with PLUMED2 (ref. ^[@CR50]^). The total simulation time for the production run was thus 960 ns. After the simulation, the free-energy landscape (or the potential of mean force with respect to the GA~4~ coordinates) was constructed using the multistate Bennett acceptance ratio method^[@CR51]^. The loading pathway was then obtained by another round of string method on the obtained 2D free-energy landscape. Energy barrier was simply estimated as the maximum free-energy difference from the interfacial GA~4~ position. The representative structures for the transition states were obtained from the highest energy states along two paths. Structures were extracted using the weighted resampling from the ensemble corresponding to the grid points. For each grid point, 100 structures were randomly resampled with replacement by the reweighting. Additional MD simulation to investigate the role of the gate region {#Sec24} ------------------------------------------------------------------- The structure of OsGA2ox3 tetramer with all six GA~4~-binding sites occupied was constructed (199,660 atoms). The initial structure was equilibrated as described previously. Eight independent 90 ns production runs were then performed from the same coordinate but with different initial velocities with the following biasing potentials. To accelerate the GA~4~ to exit the active site, we added the following artificial bias potential to the simulations:$$\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$V_{{\mathrm{bias}}} = k_{{\mathrm{bias}}}\left( {\min \left( {r - r_0\left( t \right),0} \right)} \right)^2,$$\end{document}$$ $\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$r_0\left( t \right) = r\left( {t = 0} \right) + ct,$$\end{document}$ where *t* is the time from the beginning of the simulation, *r* is the distance between the COM of the active siteGA~4~, and that of the C-α atoms of 61 residues (residue IDs 89--92, 95, 98--105, 110--114, 176--181, 200--210, 242, 243--245, 259--261, 274--278, and 308--321 of subunit A). These residues were selected so that they are within 10 Å from any atoms of GA~4~ in the initial structure. The constants were set to *k*~bias~ = 10 kJ Å^−2^ and *c* = 0.1 Å/ns, respectively. The RMSF (see Supplementary Note 1 for the definition) of all Cα atoms in subunit A was calculated for each 20 ns of the simulation, and averaged over eight independent runs. The time course of RMSD (see Supplemental Note 1) of the gate region from the initial structure was also calculated for subunit A and subunits BCD. Reporting summary {#Sec25} ----------------- Further information on research design is available in the [Nature Research Reporting Summary](#MOESM2){ref-type="media"} linked to this article. Supplementary information ========================= {#Sec26} Supplementary Information Reporting Summary Source Data {#Sec27} =========== Source Data **Peer review information** *Nature Communications* thanks Jutta Ludwig-Müller, Klaus Reuter, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. **Publisher's note** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary information ========================= **Supplementary information** is available for this paper at 10.1038/s41467-020-16068-0. This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas \[grants number, 16H06464 (to M.U.-T.) and 16H06468 (to M.U.-T. and M.M.)\], a Grant-in-Aid for Scientific Research (B) \[Grant number, 16H04907 and 20H03272 (to M.U.-T.)\] and by Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant number, JP19am0101106 (support number 1599). We thank G. Ueno and K. Hasegawa from BL26B1 and BL38B1 in SPring-8 (Harima, Japan) for kind assistance with X-ray diffraction data collection. The computer simulations were performed using supercomputers at ACCMS, Kyoto University, Japan and TSUBAME3.0 supercomputer at Tokyo Institute of Technology, Japan. S.T. and M.U.-T. conceived and designed the project; S.T. performed construct design, purification, crystallization, and structure determinations; H. Yoshimura assisted purification, crystallization, and enzyme assay; B.M., N.W., and T.N. helped to solve and refine the structure; S.S. performed the MD simulation. M.E. cooperated the construction of transgenic Cas9 plant. H. Yoshida helped to analyze the phylogenetic tree. H. Yoshimura. and A.I. took care of the transgenic plant in greenhouse; S.T., S.S., M.M., and M.U.-T. wrote the manuscript. The coordinates are deposited into the Protein Data Bank with accession numbers 6KU3 and 6KUN. All simulation starting models and trajectories are available upon request. The authors declare no competing interests.

Plan Collaboratively Working together to identify shared goals and then to develop an action plan to achieve them is fundamental to successful partnerships. Knowing and incorporating what matters most to the communities shows genuine respect. There are tools available through The Open Standards for the Practice of Conservation that provide a framework for identifying goals and developing clear conservation plans. There is also extensive technical guidance available to help teams define meaningful measures and create practical monitoring and evaluation plans. However, before turning to technical matters, get to the heart of what matters to your partners. When identifying resources for protection and management, give special attention to cultural resources that are vitally important to communities, and look for ways to incorporate them along with natural resources into conservation plans. For example, when selecting indicator species to track ecological health, forego the academic urge to choose an obscure species that has no recognized value to the community. Instead, select species that are socio-culturally relevant. Highlighting the protection of a totem or aumakua species or a species that provides food and livelihoods can easily elicit 100% community support of conservation efforts. In some instances, it also results in richer data. For instance, fishers often possess valuable historic knowledge and ongoing monitoring of relevant species can be integrated into their daily lives. “Deliberately incorporate cultural heritage, which is always priority for communities, to get more bang for your buck. Look to capture biodiversity targets that also show overlap with cultural heritage to increase buy-in for the conservation work. . . . If you get the social and political frameworks for conservation right . . . it’s quite easy to move stuff [protected areas] around afterwards if for any reason your science tells you it’s not an ideal place.”

‘Code Black’ Adds Major Character Code Black has added a new major character for season 2! An actor has not filled the role as of now. Code Black 2.0 continues to take shape. The CBS medical drama — which on Friday announced a major Season 2 cast shake-up that saw two actors promoted and another two fired — is adding a male co-lead opposite Marcia Gay Harden, and TVLine has procured intel on the newbie MD. The character, Colonel David Willis, is a onetime combat doctor who has served three tours in Afghanistan. Described as heroic, blunt, irreverent, and rule-breaking, Willis lands at Angels Memorial to teach the attendings and residents new war-tested techniques. Per the casting notice, he’s a “says-what-he-thinks veteran who doesn’t suffer fools and puts the patient first over all else, including your precious feelings. Possessed with a roguish charm, gallows humor and willingness to take risks, he’s sexy to women and compelling to men.”

LegoOS: a disseminated, distributed OS for hardware resource disaggregation - feross https://blog.acolyer.org/2018/10/22/legoos-a-disseminated-distributed-os-for-hardware-resource-disaggregation/ ====== slazaro I wonder when will they start getting legal trouble from the Lego Company. Using this kind of name seems like it just has potential downsides with no upside. ~~~ webmaven Yeah, I assumed from the name that this had something to do with Mindstorms. If the project gets any real traction, they'll have to rename. The obvious non-infringing name has unfortunate connotations, though. ------ patrickg_zill That is a pretty interesting take on what was called "single system image" in the past: but instead of worrying about all the pieces on a system, they made the system "inside out" and just worry about scheduling processes.

The present attitude toward the biology and technology of limb lengthening. Over the past ten years, many technical innovations and biologic concepts have appeared as they relate to the lengthening of long bones. Each of these has had a substantial influence upon the approach to the treatment of major discrepancies in limb length and angular deformities. It is the purpose of this paper to present these issues as objectively as possible so that the reader can put them into proper perspective, recognizing that there will be some degree of bias in the implementation of some of the technical devices. To appreciate the utility of these techniques, it is necessary to understand the biologic foundation of each method as well as its advantages and disadvantages.

Q: Can't open QImage source file I'm currently building a small project in Qt and wanted to import an icon. I made folder (icons) and put my icon there. Then I made a duplicate of the qml.qrc and changed it, so it contains my resource. <RCC> <qresource> <file>icons/projectfoldericon.png</file> </qresource> </RCC> However, when I set my image as the source of an QImage, it always fails, saying that it can't find the image. The image is loaded properly if I click it in the QtEditor. For the image path, I also tried /icons/projectfoldericon.png, and :/icons/projectfoldericon.png. Any idea what's causing the problem here? A: I would do it this way : <RCC> <qresource prefix="/"> <file alias="projectfoldericon.png">icons/projectfoldericon.png</file> </qresource> </RCC> And in your .qml file : source: "projectfoldericon.png" Don't forget that each time you make changes on your files listed in the QRC file, you need to use qmake on the .qrc file.

Q: How much basic reputation needed to become a moderator on any network site? I think the answer of my question is 10k then, how come this user become moderator of different network sites, including StackOverflow.com? P.S. I read his profile, he's working at StackExchange Inc. Only that reason made him a moderator? A: Community moderation is indeed tied to reputation - you can go to the privileges page (linked from the help center) to find out what each reputation bracket gives you. Things like voting to close/reopen, voting to delete/undelete and so on. Other than that, sites have diamond moderators (with a diamond next to their name) - these are either appointed by Stack Exchange staff (during public beta) and later on are elected by the community. Either way, these are community members. They get more moderation powers than high reputation community members. Stack Exchange employees that need it, get a moderator status (so they can use mod only tags, for example). Arie is one of our iOS developers - as such he responds to bug reports and feature requests for the iOS app, and as such needs moderator access.

Tag: Auckland Super City Council by Jake Quinn Could 2010 be a year of opportunity for the major parties of New Zealand politics or simply more of the same? In a series of posts asking the big questions of the major parties, Life and Politics takes a look at the challenges ahead, beginning with the governing party. National has the chance to cement its place as one of the most popular governments in recent history. Alternatively, it could make some crucial missteps – most likely around its ‘broadening of the tax base’ agenda – while extinguishing much of the political capital it’s been stockpiling since coming to office in 2008. Key has been compared, for some good reason, to Keith Holyoake. Holyoake was PM for a few moments in 1957 and then from 1960 to 1972, before later becoming Governor General. Like Key, Holyoke was renowned for his ‘consensus building’ approach. In plain English this means he was less ideological in his actions than might otherwise have been expected and that he had ‘a great deal of time’ for public opinion. He, so says Historian Barry Gustafson, had a knack for picking the public mood and taking his caucus with it. Mr Key, too, could to be accused of having such a knack. But he hasn’t always won the battles. The story goes that the Māori seats on the Auckland Super Council were never really about the Act Party and their clever little stunt to resign Rodney’s Local Government portfolio if the seats became a reality. But the Battle was always one fought inside the National Party. Key, they say, really did consider the seats an option. He hinted to the news media that they were on the table. He noted the public mood, which while split on the issue, was the closest ever to a majority supporting guaranteed Māori representation – so he thought, why the hell not? But this internal battle he did not win. Why? Well the only issue in recent history that has so united the National Party is that those Māori seats in Parliament should go, so it is unsurprising that his caucus, and more importantly cabinet, weren’t going to have a bar of it – especially not for Auckland, which is seen by most as NZ’s key political battleground. So what are the issues that in 2010 Mr Key will have to battle his colleagues over? Tax reform must be top of the list. Some commentators have suggested that Key, the great currency trader and market man, will want sweeping, revolutionary change. No way. There will be some in his cabinet that will want to reduce overall taxes, they always have. But Key understands that the public appetite for major cuts to public spending that would result from such cuts just isn’t there, so he will resist. Many of his colleagues will oppose the very taxes that would sufficiently broaden the base (freeing up space for cuts to income and corporate rates) such as capital gains taxes, land and plant taxes, inheritance and death taxes and any other tax that targets the wealthy elite, even if the theory backs it creating growth. So Key will have a battle on his hands, but it won’t be with the public. If he’s smart (and wants to hang onto his centrist voter support) he will back some of the above measures for broadening the tax base, but without making the tax burden any heavier on the average or low wage earner. Such changes would see capital flow from unproductive assets like housing to the share market, where it is able to provide the incentives and resources to create new industry and jobs. To do this he must really shake the money tree, and that involves hitting the old money where it hurts. Land, capital gains and pollution taxes must lesson the burden on income and corporate rates, as we must tax that which cannot move. This, bringing his colleagues and the public together on effective tax reform, will be our PM’s biggest challenge for 2010 and his legacy rests on its success. by Jeremy Greenbrook-Held I love listening to Sean Plunkett when he’s playing with his interviewees. It’s the radio equivalent of watching a cat toy with a mouse it’s just caught – it’ll let it go for a bit, but quickly re-catch it. Of course, Plunkett (like the cat) is always in control. To his credit, he takes the same line with the right and the left, which, in my opinion, makes him New Zealand’s top interviewer. Basically, the Citizens and Ratepayers dominated Auckland City Council wanted to limit the opening hours for licenced premises outside of the ‘social’ districts (such as Downtown, Parnell, K Road etc). This drew a quick response from several suburban pubs and bars which said that they’d probably go out of business if they had to close up at 11pm. Respectful, civilised places like the Villager and Gee Gees, where nice, upper-middle class folks go to discuss polo results and how to get their children into Kings, as opposed to the booze-fuelled watering holes at the Viaduct where the early twenties frequent and vomit outside in the wee-small hours. I’m sure Aaron’s a really nice guy when you meet him (in fact, I have it on good authority that he’s a top bloke), but the changes to Auckland suburban liquor licencing were draconian, to say the least, even drawing fire from his National Party mates like David Farrar (although Farrar was very vague about who was responsible for the changes), so to his credit, the changes have been abandoned. In yesterday morning’s interview, Sean Plunkett toyed with Aaron for a full five and a half minutes (Phoebe wanted to turn the car radio off it was so painful, but I insisted that we continue listening). At one point, Plunkett implied that Bhatnagar has been got-at by the hospitality lobby, which Bhatnagar tries to deny: (4:10) Aaron: What we are saying is that there are significant public concerns about this, but just in the hospitality industry, but from the public as well. Sean: How many public submissions did you get on this? Aaron: Sorry? Sean: What, can you just name some of the community groups besides the bar owners and the hospitality industry who were upset at it? Aaron: Oh, absolutely, um, well, we’ve had, um, to name off the top of my head there were, I follow Facebook, and um, online consultation is a great forum for seeing what the mood of the public is, and I think there were something like 4,600 people who had joined a Facebook group to protest, and when you actually see all the people there and the comments they make, it’s actually a very good barometer for… Sean: Do you think that Auckland City should be run by sort of Facebook polls? Aaron: No, I actually think that there are many ways in which politicians can get feedback, and I’m proud that I use online feedback to gauge the public mood. I hardly ever join Facebook groups (I have over 100 outstanding group invites, so stop inviting me) after being let down by a guy proclaiming that he would call his son Batman if a million people joined his group. I have also been invited to fan groups of the ‘Cool Side of the Pillow’, as well one proclaiming that David Bain’s trail-by-media got the wrong verdict (oh the irony). There are so many Facebook groups, and they are so easy to set up (let alone join), that they have lost all effect as a political lobby in my opinion – if they ever had any effect in the first place, that is. While I agree that the changes to the law should have been canned, Bhatnagar really should have built a more solid rationale for his change of heart than “the hopitality lobby were going to be inconvenienced and a group on Facebook convinced me”. Something simple like: “Auckland is a big city, and we’ve come to the realisation that one-size-fits-all doesn’t really work across our diverse communities” or “we’re exploring other avenues for dealing with this problem”. But the way Aaron left this, the perceived problems surrounding inconsistency of liquor licencing laws remain unsolved. Bhatnagar and his Citizens and Ratepayers pals have put this into the ‘too hard’ basket, and defaulted them to the Super City council. Bhatnagar is deluding himself thinking that regulating liquor laws across the Super City going to be any easier. For example, where I live in Waitakere City is under the jurisdiction of the Waitakere and Portage Trusts (more commonly known as ‘The Trusts’), which restrict where alcohol can be sold, and puts the profits back into the community. Aligning Waitakere’s licencing laws with the laissez-faire licencing laws of Rodney District and Auckland City is not going to be easy. Is this what’s going to happen from now until local body elections next year? Anything that’s slightly controversial is going to be palmed off to the new body? I guess this is one of those dead rats that Bhatnagar and his boss, John Banks, probably could do without swallowing, especially if Aaron wants to get the nod from the National Party to be their candidate in Epsom in 2011. by Jeremy Greenbrook-Held The Auckland Local Governance committee has released it’s submission this afternoon. David Farrar has a good summary of the findings here. I made a submission to the committee (it can be seen here if you’re interested). The crux of my submission was: I broadly supported a stronger regional body from the northern boundary of the Rodney District to the southern boundary of the Franklin District. I proposed a London-style local borough model, or, failing that, stronger Community Boards. I was opposed to councilors being elected at-large, and wards retain their current boundaries (within reason). I supported dedicated Maori seats on the Auckland council elected from the Maori electoral roll. I can’t say I’m particularly pleased with the select committee report, nor am I especially disapointed. There’s a few progressive victories (no at-large councillors) but there are a few points that are disappointing (no dedicated Maori seats). And then there is the situation with the Rodney District. I grew up in the Rodney District. My parents still live there. It was a great place to grow up, not so great when you have to commute to Auckland (or, worse, Manukau), and apparently a great place to retire. However, to pretend that the current boundaries reflect community needs and desires would be foolish. Residents in Kumeu and Helensville in the south-west of the district have very little in common with residents in Wellfords and Walkworth in the north or the Hibiscus Coast in the east. Indeed, for a long time there has been an underlying resentment in Western Rodney having to pay rates to a council in Orewa – this came to a head with the lightening consultation regarding the council rezoning a commercial area in Kumeu as industrial. A few years back there was talk of the Western Ward seceding from Rodney and joining Waitakere City, and to be honest, in my opinion it would have been a more comfortable fit. However, I’m not entirely sure what the select committee had in mind when they proposed that the north part of the Rodney District become part of the Dargaville-based Kaipara District and Northland Region. As I stated in my submission, it’s important that the Auckland Council retain it’s rural hinterlands to the north and south. This would allow space for the council to control urban sprawl within their boundaries. This is particularly important in the north where there is almost continuous suburbia from the Harbour Bridge to Orewa. However, the proposed boundaries have put the rural area to the north of Orewa largely in the Kaipara District, and given the chance to develop a natural urban area within their boundaries and within commuting distance of the Auckland central business district, I imagine Kaipara is going to take it. It’s incredibly important that Auckland’s urban sprawl doesn’t go on unabated. The ability of the Auckland Council being able to control this has been delegated to a council based in Dargaville. by Jake Quinn Labour has used its ‘Maori Caucus’ to table an amendment guaranteeing Maori seats on the new Auckland council, based on the model observed in Parliament: The Supplementary Order Paper, lodged by Mita Ririnui, proposes that Maori seats on the council be established in the same way as the Maori seats in Parliament. This means the number of Maori seats on the new council would be allocated according to the number of Maori on the Maori roll, Parekura Horomia said. They draw on the experience of Maori seats in the Bay of Plenty (which are widely seen as effective) as an example: “I introduced a similar piece of legislation in 2001, establishing Maori seats on the Bay of Plenty Regional Council which now has three Maori seats. It was pleasing to see yesterday that the Environment Bay of Plenty Chairman John Cronin said the Maori seats there were working well,” Mita Ririnui says. In other news (and in a swift bout of terrible timing), John Boscawen’s member’s bill has been drawn today. The bill aims to define the level and nature of force which it will be acceptable in ‘correcting’ children. The ballot has displayed an eerie ability to pick extraordinarily relevant (in terms of timing) bills in the last few months. The timing of this one could be pretty serious though, if National decides to go with it. John Key has thus far stared the smackers down by not making any changes to the assault on children legislation, may his principled and rational stance continue. by Jake Quinn And it’s a back down because before last week, the prevailing opinion was that Key would strike a deal with Sharples, based on the overwhelming support at the select committee for having Maori seats, and pull through on some kind of deal that included them for Auckland’s new super council. Key signalled for months that the seats were on thetable. Hide pulls his ‘principled stunt‘ and to be fair to him it does match his principles (the poor bastard would have had to take the very bill through the House that brought the seats into being), and suddenly the game changes. One gets the feeling that Key just couldn’t take cabinet with him. But Key doesn’t need Hide as a minister, he’s got the numbers any way he looks, what’s more, Hide has made it clear he won’t being down the government (not that he could, what this really means is that Hide won’t pull his parties support on confidence and supply thus forcing the Nat’s into the unenviable position of having to rely solely on the Maori Party). So why the change of heart? Key is so far ahead in the polls he doesn’t need to worry about a gap on the right opening up, and in any case they’re are all still votes for a National-led government, so what changed. The only explanation is that his colleagues had let him meander on with his friendliness to the Maori Party, but when push came to shove, Bill and the old school just wouldn’t have a bar of it. New Zealand needs to remember that just because Mr Key is a decent bloke, he’s still surrounded by some pretty conservative old cronies, the same lot who stood by and defended this horrid bloody speech. by Jake Quinn Cabinet is set to make a decision about Maori seats on a new Auckland super city today – likely ruling them out and averting a ministerial resignation… A decision to rule out Maori seats would mean Mr Hide would not have to fulfil a promise made last week to resign over the issue. Putting to one side the incredible level of spin in the above paragraph, for that is worth another post entirely. It is likely that should Key say no to the seats, that this decision is not based on Hide’s resignation threat, but on clear polling data from Pakeha Auckland voters that they have no appetite for them. If that is the case, Hide’s little stunt will work out well as ‘an excuse’ for Key’s decision. It will however have other consequences. It would be the first nail in the coffin of the National-Maori Party governing arrangement. The Maori Party has, as of yet, chosen to play the long game adopting not to sink to Hide’s level. Good on them. National would be wise to do similarly. The sustainability of future National-led minority governments is linked to their relationship with the Maori Party. The Maori Party are likely to become the de facto kingmaker in many future governments and while National currently has the unusual pleasure of choosing its partner on a case by case basis (they can turn to either Act or the Maori Party to command a legislative majority – that is, they don’t need both), this will not always be the case. After the next election it is likely that National will be in a position to form a government. It is also possible that the right (National and Act) will get less total vote share than they did in 2008. If this happens National will need the Maori Party (or some other centre party) to get the numbers on confidence and supply. But will their bridges be burned? Labour needs to do some serious work on its relationship with the Maori Party. Perhaps the silver lining, should Key today adopt for no Maori seats, is that Labour and the Maori Party will have an issue which can unite them. by Jake Quinn A TVNZ Mt Albert by-election poll released yesterday put David Shearer on a staggering %59, Melissa Lee on %21 and Russel Norman on %15. I understand that this is consistent with other private polling. Predictions: Russel will beat Lee on polling day because apathy will see both Nat and Lab voters stay at home (as the result appears to be a foregone conclusion), plus the leftist protest vote will go to Norman instead of Shearer now that they’ve seen the poll result that Shearer is “safe”. Shearer will still win comfortably, but not by anything like this margin. A strong victory for Shearer and Labour in Mt Albert is a strong endorsement of Phil Goff’s leadership of the Labour Party and will see questioning of his leadership off the agenda for sometime. Today’s Herald leads with an Audrey Young piece about the poll capping a bad week for National and explains: “Labour may even increase its majority in the seat this weekend, which would be a big boost to the authority of new leader Phil Goff within the Labour Party.” It was also interesting to hear John Key backtrack on his odd endorsement of John Banks for Super Mayor of Auckland. NZPA reports: “A spokesman from Mr Key’s office said this morning there were no endorsements for any candidates and it was up to the people of Auckland to decide who they wanted as mayor.” This is yet another example of botched political management from John Key and his staff. How could the words “Can I start by acknowledging the mayor – more importantly the Super Mayor of Auckland city – John Banks,” be seen as anything but an endorsement? His “arch-nemesis” (please read inverted commas as an indication of sarcasm) Paul Henry was kind enough not to ask any tough questions about this on Breakfast this morning, rather he ended his piece with “it’s [the tough last week] character building, and you’ve got a good character”. Thank you Paul. Thought for the day:Goff has got John Key and his “Minister for Ethnic Affairs” Richard Worth “by the texties”. by Jake Quinn It is both interesting and encouraging to see the NZ Herald come out strongly in support of Maori seats on the proposed Auckland Super Council. From today’s editorial: The Herald has said previously, both in backing the royal commission’s proposal and in lamenting the Government’s rejection of it, that Maori, as a community of distinctive character and interest, warrant a place around the Auckland Council table. Dedicated seats, equally, are a means of ensuring Maori participation in local government. Oddly, there are no references – at all – to the Treaty in the editorial. The Herald feels John Key has backed himself, somewhat unnecessarily, into a corner: “The Government’s problem, following its thumbs-down for the seats, is how to orchestrate this sort of arrangement without appearing to capitulate.” The editorial concludes: “After due consideration, it must surely find a way to include Maori representation on the Auckland Council.” As has been assumed by many, it would seem inevitable that Key will capitulate and come up with a compromise through his dealings with the Maori Party. The question now is how and when? by Jake Quinn Today thousands of Aucklanders, of different colours, backgrounds and political leanings, are marching against the National-led government because it has failed to act—in respect of the Super City Council structure—“in good faith, fairly, reasonably, and honourably” with the people of Auckland and with Maori in particular. Like it or not our ancestors signed the Treaty of Waitangi. The Treaty gave the Crown the right to make laws in return for the promise to do so, so as to acknowledge and protect the interest of Maori. National and Act, against the recommendations of the Royal Commission on Auckland Governance and without consulting anyone, let alone Maori, chose not to include any Maori seats on the proposed Council. They did this, in principle, because they oppose reserved Maori representation on our governing bodies. While many find their rhetoric rousing; ‘racially divided state’, ‘one person, one vote’, ‘apartheid’ and what have you, one cannot escape that New Zealand is based on a partnership going back to 1840, and that ignoring that inevitably leads to a ‘tyranny of the majority’: a situation where because we have one group that out numbers the rest, pretty much all our elected people would end up representing that group – and that is not democracy. On a cold Sunday morning it was pleasing to see TVNZ Q+A “host” Paul Holmes well out numbered—by his entire panel—on the topic of Maori seats. Sandra Lee, Therese Arseneau and Mayor Tim Shadbolt all differed in their reasons (from ideological to pragmatic, respectively), but all supported Maori seats in Auckland. The word from Espiner yesterday was that Key was feeling “very relaxed” about today’s Hikoi, which could only have meant one thing: A compromise, as this site predicted a month ago, is on the cards. This morning’s news however, that Key said “today’s Hikoi … is unlikely to make a difference, is premature and the wrong forum to raise concerns” shifts the focus back onto the Maori Party. The subtext of Key’s words is not that Maori seats in Auckland are off, but that “the National—Maori Party governing relationship, not the Hikoi, is the context for advancing this discussion.” by Jake Quinn With the monthly political capital meter at an all time low for the Key-led government, it comes as no surprise that Cabinet has delayed yesterday’s announcement about the make of up of the Auckland Transition Agency’s board – what would have been expected not to cause waves just weeks ago, is now going to be the next big test for Key. The Auckland Transition Agency was established by legislation under urgency last week, to oversee the move to the Super City structure by next year. A few weeks back, many observers assumed that the make of the agency’s board would have been relatively uncontroversial as National, under Key, was developing a reputation as being rather centrist and politically risk averse – spotting and following public opinion in a way that was characteristic of Key’s consensus building style. However, coupled with a disaster week in the Mt Albert by-election campaign, where Key’s hand picked candidate Melissa Lee made a series of silly mistakes effectively ruining her party’s chances of winning the unwinnable (and seriously challenging Phil Goff’s position as Labour leader), the Rankin affair has effectively ended the new government’s extended honeymoon – which had been starting to develop into something of a ‘honey-gap-year’. So the now skeptical eyes of the press gallery will be closely focused on the Auckland Transition Agency and its board, expected to be announced in the next week. They will be looking to Key to ‘make right’ and offer up a leadership team that doesn’t stink of divisive (like Rankin) or inexperienced (like Lee). If the headlines read “Rodney Hide’s Mates to Run Auckland” it may well be curtains for Key’s dominated of the polls. I suspect that the government may not have included any Maori seats on Auckland’s proposed new super council simply so that it was in a position to be able to offer up a seat or two after post hikoi “negotiations” with its affable coalition partner. It is also good to see Labour’s Phil Goff moving from just having “an open mind”: PHIL Well that’s the Royal Commission’s argument for it, I’ve got an open mind on that, what I’m saying at this stage is that at least it should have been consulted on, it shouldn’t have been scrapped without any consultation. To actually backing the initiative provided that it is “one person, one vote”. Whilst it would have been stronger to get out in front early with his support, it’s better late than never.

Trade In mid-September, the African Development Bank, the German Federal Ministry for Economic Cooperation and Development and the World Bank will launch Financing Africa: Through the Crisis and Beyond , a comprehensive review documenting current and new trends in Africa’s financial sector and taking into account Africa’s many different experiences. During the coming weeks and leading up to the formal launch of the book in Ethiopia on September 15, we will give a sneak peek of the book’s main findings and recommendations. In this first post, we’ll summarize our main messages. Editor's Note: Murat Seker recently presented the findings of the paper discussed in the following blog post at a session of the FPD Academy. Please see the FPD Academy page on the All About Finance blog for more information on this monthly World Bank event series. Many studies point to the importance of firms that export to economic growth and development. These firms tend to be larger, more productive, and grow faster than non-exporting firms. These findings have focused policymakers’ attention on the importance of international trade for economic growth. From the 1980s to the 2000s traditional trade policies have improved significantly—applied tariff rates across a wide range of countries with varying levels of income have decreased from around 25 percent to 10 percent. However, improvements in trade policies are often not enough to reap the full benefits of international trade. To be fully effective, they require complementary reforms that improve the business environment for firms. In a recent paper on Rigidities in Employment Protection and Exporting, I focus on a particular aspect of the business environment, namely employment protection legislation (EPL), and show how these regulations relate to the decisions of firms to enter export markets.1 Evidence shows that export market entry is associated with significant changes and adjustments in firm performance around the time at which exporting begins. In data collected via the Enterprise Surveys project, the employment levels of firms that subsequently enter export markets ("future-exporters") grow by 13%, four times higher than the growth rate of firms that don’t enter export markets.2 Bernard and Jensen (1999) find that the growth premium for these future-exporters as compared to non-exporters in the U.S. is 1.4% per year for employment and 2.4% for shipments. Foreign direct investment (FDI) can theoretically reduce income gaps between developing and advanced economies. In a neoclassical world, with perfect capital mobility and technology transfer, capital readily flows from rich to poor countries, seeking higher returns in capital-scarce economies. The real world differs starkly from the theory. Even though southern African countries (the Southern African Development Community, SADC hereafter) are poor on average, per capita FDI inflows are a meager 36.6 U.S. dollars per year (in 2000 value), which is about 18 percent of average per capita FDI in non-SADC countries and 58 percent of the average level for similar-income economies. Moreover, within SADC, country differences are huge: FDI per capita ranges from single digits (Malawi, Zimbabwe, Madagascar, Democratic Republic of Congo, and Tanzania) to 10-30 dollars (Mozambique, Zambia, Mauritania, and Swaziland), to 50 to 100 dollars (Lesotho, South Africa, and Angola), and to 167 dollars in the outlier in this region, middle-income Botswana. And even within this region there is a positive relationship between average income and FDI per capita, a pattern that holds for the world as a whole. Thus, any hope of relying on FDI as a supply-side remedy to catapult poor countries onto a development fast track is not likely to materialize soon.

View of the south elevation of the Harem Lounge at 3301 East 1st (First) Avenue in the Cherry Creek neighborhood, Denver, Colorado. The one story building has a corrugated metal and wood facade with a large roof overhang. The name of the bar is painted on the metal along with a bird and a palm tree. A lit sign reading "Harem Lounge" is fixed to the roof. A dancing girl and minarets are on the sign. A MasterCard sign is attached to the overhang. The structure was built around 1950.

Sunday, 22 March 2009 It is mothering sunday today, and I allowed my son to creep into bed with me this morning. He then proceded to wake me by throwing up on his own head and then all over me. Happy Mother's Day! As a sombre twist to Mother's Day, Jade Goody, she of Big Brother fame died this morning. Whether you love her or hate her, you have to shake your head in disbelief at the speed of it. And send hugs to her two little boys. I have sent a couple of queries to magazines, and am chewing over a small business idea. To the future... Wednesday, 18 March 2009 I was over at fwj yesterday, cradling my slack mouthed jaw in disbelief. Certain visitors to the website, when faced with a, in my mind, courteous post explaining a delay in posting leads complained at the unprofessionalism of having other things to do. Whether they realise Deb has a full-time job, a family and other blogs to deal with I don't know, but I'm not sure it matters. If you are getting something for nothing, you are up on the deal- if you (temporarily) get nothing for nothing, you are not hard-done by! Rant over. On another theme of wanting something for nothing, I like to enter fiction competitions, mostly flash or micro fiction, for which there is normally an entry fee. But how much is a reasonable fee? I have heard it said before that paying £10 to enter a competition where the prize is £50 does not make economic sense, but what about different levels of entry fee and prize? Part of me thinks that, by entering a competition, you should be happy that your work is great (I'm sure mine is) and that you stand a good chance of winning, and therefore any entry fee is worthwhile. But the problem with writing is that its appreciation is so subjective- I am aware that Catch 22 is considered a great work, but I just can't get into it. And Brave New World is better than 1984, just not so hyped. Saturday, 14 March 2009 Hi, I have a pretty cool job I’m offering that's pretty easy to do. It’s a great chance to make a little extra money that you can do right from your computer when you run out of stuff to google. I'm looking for writers who can churn out about 500-1000 words per day (around a couple of times a week). The topic on which is being written is everything concerning property management, HOA management, real estate, home repair, Rent collecting, etc. We realize this isn't the most popular subject in the world, so we’d be more than happy to answer any and all of your questions if you have no clue what the heck “property management” is, or anything about real estate, etc. We're really looking for people who like to write or don't mind writing to make some money on the side, so you don't have to be a scholar by any means. If you're a decent writer with pretty good punctuation, you're ok. Please tell us how much you would charge. The quality of the written work has to be good, but not great if great means more expensive. We're looking forward to hearing from you, thank you. We'll be glad to contact you with any and all questions you may have. Thanks again!I suppose at least they are open and honest about what they want. So if there are any good but not great writers who don't mind writing about a boring subject you don't know anything about... Thursday, 12 March 2009 I have been toying with the idea of setting up a site that lists job posting available to UK freelance writers and bloggers, just to save the disappointment of finding a really great gig or writing sitebut not being able to do it because you are not in US/Canada. What do you think? If you stumble past here, let me know if you think it would be useful. This point (specifically re textbroker) came up in some interesting (but highly charged!) discussions we were having in comment threads over at fwj the past couple of days. Check out the arguments and add your tuppence worth here or here. Quotation of the Day Who are you? What's the point? Why do we care? Blogging. This is my second attempt at this blog as, previously, my lack of readers got me down. Surely a blog that no-one else reads is more of a diary?... Anyhow, drawing inspiration from the inspirational Deb Ng over at freelance writing jobs, I thought I'd give it another go. Maybe no one will read it, maybe it doesn't matter. About me, well I write a lot of short fiction, as I enjoy being able to finish a piece. I am also writing a novel (aren't we all), with just the 48,500 words to go. Why do you care? I don't know if you do. But seeing as you are here, please enjoy reading my posts and PLEASE leave me a comment to let me know what you think. All feedback is helpful, good or bad, although good is probably preferred.

--- - name: KubeSphere | Check core components (1) shell: > {{ bin_dir }}/kubectl get deploy -n kubesphere-system ks-account register: check_account failed_when: "check_account.stderr and 'NotFound' not in check_account.stderr" - name: KubeSphere | Check core components (2) shell: > {{ bin_dir }}/kubectl get deploy -n kubesphere-system ks-apigateway register: check_apigateway failed_when: "check_apigateway.stderr and 'NotFound' not in check_apigateway.stderr" - name: KubeSphere | Check core components (3) shell: > {{ bin_dir }}/kubectl get deploy -n kubesphere-system ks-account -o jsonpath='{.spec.replicas}' register: check_account_replicas failed_when: "check_account_replicas.stderr and 'NotFound' not in check_account_replicas.stderr" when: - check_account.rc == 0 - name: KubeSphere | Check core components (4) shell: > {{ bin_dir }}/kubectl get deploy -n kubesphere-system ks-apigateway -o jsonpath='{.spec.replicas}' register: check_apigateway_replicas failed_when: "check_apigateway_replicas.stderr and 'NotFound' not in check_apigateway_replicas.stderr" when: - check_apigateway.rc == 0 - block: - name: KubeSphere | Update ks-core status shell: > {{ bin_dir }}/kubectl patch cc ks-installer --type merge -p '{"status": {"core": {"migration": true}}}' -n kubesphere-system register: import failed_when: "import.stderr and 'Warning' not in import.stderr" until: import is succeeded retries: 5 delay: 3 - set_fact: ks_upgrade: True when: - check_account.rc == 0 - check_apigateway.rc == 0 - check_account_replicas.stdout != "0" - check_apigateway_replicas.stdout != "0" - "'NotFound' not in check_account.stderr" - "'NotFound' not in check_apigateway.stderr" - "'NotFound' not in check_account_replicas.stderr" - "'NotFound' not in check_apigateway_replicas.stderr" - name: KubeSphere | Create KubeSphere dir file: path: "{{ kubesphere_dir }}" state: directory mode: 0755 - name: KubeSphere | Getting installation init files copy: src: "{{ item }}" dest: "{{ kubesphere_dir }}/" loop: - "ks-init" - import_tasks: ks-init.yaml when: ks_upgrade is not defined or (ks_upgrade != True) - name: KubeSphere | Init KubeSphere shell: "{{ bin_dir }}/kubectl apply -f {{ kubesphere_dir }}/ks-init/{{ item }}" loop: - "iam-accounts.yaml" - "webhook-secret.yaml" - "users.iam.kubesphere.io.yaml" register: import failed_when: "import.stderr and 'AlreadyExists' not in import.stderr and 'Warning' not in import.stderr" - name: KubeSphere | Getting controls-system file template: src: "{{ item.file }}.j2" dest: "{{ kubesphere_dir }}/{{ item.file }}" with_items: - { name: kubesphere-controls-system, file: kubesphere-controls-system.yaml } - name: KubeSphere | Installing controls-system command: "{{ bin_dir }}/kubectl apply -f {{ kubesphere_dir }}/kubesphere-controls-system.yaml -n kubesphere-controls-system" register: import failed_when: "import.stderr and 'AlreadyExists' not in import.stderr" # - name: KubeSphere | Create KubeSphere vpa # shell: "{{ bin_dir }}/kubectl apply -f {{ kubesphere_dir }}/ks-init/ks-vpa.yaml" # register: result # until: result is succeeded # retries: 5 # delay: 3 # when: # - vertical_pod_autoscaler_enable == true - name: KubeSphere | Generate kubeconfig-admin shell: > /bin/bash {{ kubesphere_dir }}/ks-init/generate-kubeconfig.sh when: - openpitrix.enabled is defined and openpitrix.enabled # - name: Kubesphere | Checking kubesphere component # shell: > # {{ bin_dir }}/kubectl get deploy -n kubesphere-system # register: kubesphere_component_pod # - name: Kubesphere | Get kubesphere component version # shell: > # {{ bin_dir }}/kubectl get deploy -n kubesphere-system ks-console -o jsonpath='{.metadata.labels.version}' # register: console_version # when: # - kubesphere_component_pod.stdout.find("ks-console") != -1 # - import_tasks: ks-stop.yaml # when: # - console_version.stdout and console_version.stdout != ks_version

Verification of flood damage modelling using insurance data. This paper presents the results of an analysis using insurance data for damage description and risk model verification, based on data from a Danish case. The results show that simple, local statistics of rainfall are not able to describe the variation in individual cost per claim, but are, however, feasible for modelling the overall cost per day. The study also shows that in combining the insurance and regional data it is possible to establish clear relationships between occurrences of claims and hazard maps. In particular, the results indicate that with improvements to data collection and analysis, improved prediction of damage costs will be possible, for example based also on socioeconomic variables. Furthermore, the paper concludes that more collaboration between scientific research and insurance agencies is needed to improve inundation modelling and economic assessments for urban drainage designs.

Q: Store $_POST in Yii2 session I'm having a little trouble with my quiz form. I'm using a page to show a single question that a user answers, from there I was hoping to save the question id and option id (My form is multiple choice, i set the options). My HTML looks like this: <input type="radio" name="question[3]" value="4">My Answer When the form is posted I am doing this if(isset(Yii::$app->session['question'])){ // Get posted array $question = $_POST['question']; Yii::$app->session['question'] = $question; print_r(Yii::$app->session['question']); } So it's saved into my session as: Array ( [3] => 4 ) Which is fine, the problem I'm finding is trying to save the next question without overwriting the previous [question_id] => [option_id]. I understand why the following code just overwrites the existing the session['question'] variable. But I'm struggling to be able to save each question and answer array to my variable. I have tried Yii::$app->session['question'][$i] = $question; and get Indirect modification of overloaded element of yii\web\Session has no effect I've also tried array_push and array_merge to try and combine the previous array of question and chosen option, but have had no luck either. What am I doing wrong here please? A: The correct way to do this is $q = $_POST['question']; Yii::$app->session['question'] = array_merge(Yii::$app->session['question'], [$question]);

Attached is the file to be used for demand invoice verification for December 2001 capacity release transactions. If you have any questions, please feel free to contact me. Thanks, Elizabeth

[On certain topical problems of contemporary industrial medicine]. The article tackles certain problems concerning occupational medicine organization work and methodology of its conceptual apparatus used to characterize individual and populational health of workers, covers suggestions on solving these problems.

Interaction Energies in Complexes of Zn and Amino Acids: A Comparison of Ab Initio and Force Field Based Calculations. Zinc plays important roles in structural stabilization of proteins, enzyme catalysis, and signal transduction. Many Zn binding sites are located at the interface between the protein and the cellular fluid. In aqueous solutions, Zn ions adopt an octahedral coordination, while in proteins zinc can have different coordinations, with a tetrahedral conformation found most frequently. The dynamics of Zn binding to proteins and the formation of complexes that involve Zn are dictated by interactions between Zn and its binding partners. We calculated the interaction energies between Zn and its ligands in complexes that mimic protein binding sites and in Zn complexes of water and one or two amino acid moieties, using quantum mechanics (QM) and molecular mechanics (MM). It was found that MM calculations that neglect or only approximate polarizability did not reproduce even the relative order of the QM interaction energies in these complexes. Interaction energies calculated with the CHARMM-Drude polarizable force field agreed better with the ab initio results, although the deviations between QM and MM were still rather large (40-96 kcal/mol). In order to gain further insight into Zn-ligand interactions, the free energies of interaction were estimated by QM calculations with continuum solvent representation, and we performed energy decomposition analysis calculations to examine the characteristics of the different complexes. The ligand-types were found to have high impact on the relative strength of polarization and electrostatic interactions. Interestingly, ligand-ligand interactions did not play a significant role in the binding of Zn. Finally, analysis of ligand exchange energies suggests that carboxylates could be exchanged with water molecules, which explains the flexibility in Zn binding dynamics. An exchange between carboxylate (Asp/Glu) and imidazole (His) is less likely.

Introduction ============ As we embrace the digital age, the use of serious games has become increasingly popular in many domains, including education, health care, defense, art and culture, religion, corporate training, and advertising \[[@ref1],[@ref2]\]. Serious games are digital games that have a purpose beyond entertaining the player \[[@ref1]\] such as teaching, training, promoting health and well-being, promoting change, and persuading \[[@ref3]\]. Serious games can potentially serve as powerful tools in education because they are motivating and can provide a safe environment for students to learn from their mistakes without having to experience any negative consequences from their actions \[[@ref4]\]. Serious games can also be adapted to different learning styles of learners. By matching the learning environment to the ways in which students process and engage with educational material, serious games can provide a learner-centered approach that can supplement didactic teaching methods \[[@ref5]-[@ref7]\]. There are many examples of how serious games have been used for health care education. By creating different clinical reasoning pathways using virtual environments, serious games have potential to train clinical reasoning skills \[[@ref8]\]. For example, serious games have been used to train medical students in pediatric medicine \[[@ref9]\], insulin management \[[@ref10]\], and surgical skills such as coronary artery bypasses and knee arthroplasties \[[@ref11],[@ref12]\]. Nursing students have used simulation games for training on life support procedures \[[@ref13]\] and emergency medical services \[[@ref14]\]. Both medical and nursing students have shown to be supportive of the use of serious games in their education \[[@ref14]-[@ref16]\]. In pharmacy education, physical quiz-based games, card games, and board games have been used to teach metabolic pathways, pharmacotherapeutics, and pharmacokinetics \[[@ref17]-[@ref19]\]. However, to our knowledge, evidence on the use of serious games for pharmacy education is scarce even though pharmacy students have indicated their desire for serious games to be incorporated in their curriculum \[[@ref20],[@ref21]\]. Although medicine, nursing, and pharmacy are all health care disciplines, existing serious games for medical and nursing students cannot be adopted by pharmacy students because the intricacies of drug compounding and preparation of extemporanous (non-commercially available) products, drug dispensing, medications management, medication labeling and review, and other crucial elements of pharmacy education are not present in serious games for medical and nursing students. Pharmacy education is still largely instructor-centered and based on didactic, knowledge-based teaching \[[@ref22]-[@ref24]\]. At the National University of Singapore, the only provider of pharmacy education in the country \[[@ref25]\], pharmacy undergraduates undergo a 4-year program where content and skills are taught through lectures, tutorials, and practical laboratory sessions. As part of a new theme-based curriculum which includes experiential learning \[[@ref25]\], the Department of Pharmacy intends to develop and incorporate a serious game into the pharmacy practice modules for the incoming batch of undergraduates. From our reviews of published literature, there have been no studies that characterized the gaming preferences of pharmacy students on a pharmacy-related serious game. In order for us to develop such a game for pharmacy education, we needed to determine what aspects of gameplay (eg, settings, storylines, perspectives, and styles) would be interesting and motivating for our students to play as part of their modules. This study aimed to determine the preferences of students on the gaming aspects and type of pharmacy-related serious game they would like to play as part of their pharmacy practice education. The data collected would then serve as guidance for the development of a pharmacy-related serious game catering to the preferences of pharmacy undergraduates at our institution. Methods ======= Questionnaire Design -------------------- The questionnaire consisted of 13 questions split into two main sections. The first obtained demographic information about the participants and whether they had paid for any in-game items before. If they had, they were asked to indicate for which games and how they paid for them (eg, parents' money, own allowance, own income). Their interest in playing a pharmacy-related serious game was also obtained using a 5-point Likert scale indicating their interest (1 being not interested at all and 5 being extremely interested). The second section obtained the preferences of participants regarding various aspects of gameplay for a pharmacy-related serious game, such as their preferred game reward systems, settings, storylines, perspectives, and styles ([Textbox 1](#box1){ref-type="boxed-text"}). These aspects were adapted from classifications defined in the literature \[[@ref26],[@ref27]\] and modified based on input from the game design team. In addition, participants were asked to choose between two hypothetical scenarios conceived for the serious game: scenario A (authentic simulation) and scenario B (post-apocalyptic fantasy). Scenario A was designed in accordance with the principles of the authentic learning environment theory \[[@ref28]-[@ref30]\], whereas scenario B was a fantasy scenario designed for students who prefer a nonauthentic learning environment. The themes for scenario B were inspired based on the popularity of post-apocalypse and vampirism tropes in the media at the time of the study \[[@ref31]-[@ref33]\]. The survey questions were designed by the study team, and the survey was pre-tested on a small group of science students who were not majoring in the pharmacy course. ###### Descriptions of the gameplay aspects obtained from survey respondents. Reward system---how the game provides positive experiences to the player - Score: number used to mark quality of player performance - Experience points: points accumulated during gameplay that reflect effort and time invested into the game. Usually used to mark the growth and development of the player. - Item granting: the acquirement of virtual items that can be used by players. These items can possess useful in-game properties and abilities, collectability value, and/or social comparison value. - Resources: valuables that are collected primarily for practical game use - Achievement system: titles that are given to players upon completing certain stated conditions - Feedback messages: fleeting pictures, sounds, or animations during gameplay that evoke positive emotions - Plot animations and pictures: visually attractive animations and pictures that serve as milestones for player achievement. These usually follow important events in the game. - Unlocking mechanism: access to new game content such as new levels and minigames awarded when certain conditions are fulfilled. The content motivates the player by evoking and maintaining curiosity towards the game. Game setting---environment and background in which the player is immersed - Science fiction: based on futuristic technology, space and time travel, extraterrestrial life, etc. - Historical: based on real historical persons or events - Fantasy/medieval/mythic: based on magic and other supernatural phenomena. Includes magical/mythical creatures such as giants, elves, and dragons. - Modern: setting similar to an authentic, present-day pharmacy Game storyline---plot and overarching theme in the game - War: player is a warrior in a violent, organized conflict involving two or more factions. - Heroic/saving humanity: player must defeat a great evil to save the world. - Spy/secret agent: player must complete missions while remaining covert and discreet. - Adventurer: player explores a largely unknown world. - Authentic pharmacy-related plot: player carries out a role in a workplace that is closely related to an actual pharmacy. Game perspective---planes along which gameplay action occurs - 2D game perspectives: gameplay action occurs along a 2D plane only. - 2D top-down: camera angle displays the player's avatar and the surrounding area from above. - 2D side-scrolling: camera angle is from the side of the player's avatar. - 3D game perspectives: gameplay action occurs in a 3D axis. - 3D first-person: camera angle shows the perspective from the viewpoint of the player's avatar. - 3D third-person: camera angle depicts a view that is slightly behind and above the player's avatar. Game style---interactivity of how the game is played - Competitive: players form strategies and directly oppose other players in the game. - Cooperative: players work together but the benefits from collective efforts are not necessarily shared equally. - Collaborative: players work together while sharing all payoffs and outcomes. Game scenario---hypothetical scenarios for a pharmacy-related serious game - Scenario A (authentic simulation): set in an authentic, modern day pharmacy workplace with a dramatic plot. The goal of the game is to experience the day-to-day operations of a pharmacy. Students will manage contemporary, realistic social issues such as drug addiction, haze, and epidemics. In-game tasks will include activities involving compounding, communication, and pharmaceutical care management. - Scenario B (post-apocalyptic fantasy): set in a post-apocalyptic 3050, where a pandemic has turned the majority of humans into bloodthirsty vampires. To survive, the remaining humans have learned to use herbs to produce synthetic blood to satisfy the vampires' craving for human blood. The goal of the game is to find a remedy to reverse the vampiric mutation and to save mankind. In-game tasks will include activities involving compounding, communication, and pharmaceutical care management. Study Design ------------ This was a cross-sectional census study using a self-administered survey. Pharmacy students from each of the 4 years of undergraduate study were recruited for the study. Emails were sent to the lecturers-in-charge to seek support and permission to conduct the survey post-lecture. A short briefing would be given regarding the background and aims of the study before distributing the questionnaires. Participation was voluntary and submission of the questionnaire would be considered as consent to the survey. Ethics approval was obtained from the university's Institutional Review Board. Data Analysis ------------- Students were divided into groups based on their demographic information and responses to the survey questions. Their year of study was categorized into lower (years 1 and 2) and upper batches (years 3 and 4). Their interest levels in playing a pharmacy-related serious game were categorized as those who were not interested (not interested) or interested (slightly interested, moderately interested, very interested, and extremely interested). Among those who were interested, interest levels were further split into 2 categories: weak interest (slightly interested and moderately interested) and strong interest (very interested and extremely interested). Students were also classified into two groups by their preferred game perspectives: two-dimensional (2D) top-down or side-scrolling and three-dimensional (3D) first-person or third-person perspectives. Students who chose scenarios A and B were known as scenario A students and scenario B students, respectively. Results were analyzed using descriptive statistics. Chi-squared tests were used to determine the associations between preferred gameplay aspects and gender (males and females), year of study (lower and upper batches), and preferred game scenarios (scenario A and scenario B students). Statistical significance was defined as **P*\<.*05. As the questions on gaming preferences were single-choice questions, multiple responses were excluded from analyses. Similarly, missing responses were also excluded from analyses. All analyses were conducted using the Statistical Product and Service Solutions Version 21 (IBM) software. Results ======= Demographics and Preferred Gaming Aspects of Respondents -------------------------------------------------------- Response rate was 72.7% (497/684 students). More than half were females (307/497, 61.8%) ([Table 1](#table1){ref-type="table"}). There were almost equivalent proportions of lower batch (249/497, 50.1%) and upper batch (248/497, 49.9%) students. The majority (450/490, 90.5%) was interested in playing a pharmacy-related serious game, among which 65.1% indicated weak interest and 34.9% indicated strong interest. Over one-fifth (118/497, 23.7%) of students had paid for in-game items before, among which most had used their own allowance (101/118, 85.6%) to pay for the items. The top 2 most popular reward systems were unlocking mechanisms (112/497, 22.5%) and experience points (90/497, 18.1%). Fantasy/medieval/mythic game settings were the most popular (253/497, 50.9%), followed by modern settings (117/497, 23.5%). Almost one-third (147/497, 29.6%) of respondents preferred an adventurer storyline over an authentic pharmacy-related plot (119/497, 23.9%). Three-dimensional game perspectives were more popular than 2D game perspectives (270/497, 54.3% vs 221/497, 44.5%), within which 3D first-person (147/270, 54.4%) and 2D top-down (158/221, 71.5%) views were the more popular ones. A collaborative game style was the most popular (182/497, 36.6%), and scenario B (post-apocalyptic fantasy) was preferred over scenario A (authentic simulation) (287/497, 57.7% vs 209/497, 42.1%). ###### Demographics and preferred gaming aspects of respondents. ----------------------------------------------------------------------------------------------------------------------- Parameters \ \ Total^a^, N=497, n (%) -------------------------------- --------------------------------- --------------------------- ------------------------ **Gender** \ \ \ \ Male \ 187 (37.6) \ Female \ 307 (61.8) **Year of study** \ \ \ \ Year 1 \ 134 (27.0) \ Year 2 \ 115 (23.1) \ Year 3 \ 126 (25.4) \ Year 4 \ 122 (24.5) **Interest in playing** \ \ \ \ Not interested \ 40 (8.0) \ **Interested** \ 450 (90.5) \ \ Weak interest (n=450) 293 (65.1) \ \ Strong interest (n=450) 157 (34.9) **Paid for in-game** **items** \ \ \ \ No \ 379 (76.3) \ **Yes** \ 118 (23.7) \ \ Own allowance (n=118) 101 (85.6) \ \ Own income (n=118) 20 (16.9) \ \ Parents' money (n=118) 13 (11.0) **Reward system** \ \ \ \ Score \ 65 (13.1) \ Experience points \ 90 (18.1) \ Item granting \ 42 (8.5) \ Resources \ 23 (4.6) \ Achievement system \ 60 (12.1) \ Feedback messages \ 5 (1.0) \ Plot animations & pictures \ 38 (7.6) \ Unlocking mechanism \ 112 (22.5) **Game setting** \ \ \ \ Science fiction \ 67 (13.5) \ Historical \ 39 (7.8) \ Fantasy/medieval/mythic \ 253 (50.9) \ Modern \ 117 (23.5) \ Others \ 2 (0.4) **Game storyline** \ \ \ \ War \ 50 (10.1) \ Heroic/saving humanity \ 61 (12.3) \ Spy/secret agent \ 99 (19.9) \ Adventurer \ 147 (29.6) \ Authentic pharmacy-related plot \ 119 (23.9) \ Others \ 5 (1.0) **Game perspective** \ \ \ \ **2D** \ 221 (44.5) \ \ 2D top-down, (n=221) 158 (71.5) \ \ 2D side-scrolling (n=221) 63 (28.5) \ **3D** \ 270 (54.3) \ \ 3D first-person (n=270) 147 (54.4) \ \ 3D third-person (n=270) 123 (45.6) **Game style** \ \ \ \ Competitive \ 147 (29.6) \ Cooperative \ 160 (32.2) \ Collaborative \ 182 (36.6) **Game scenario** \ \ \ \ A (authentic simulation) \ 209 (42.1) \ B (post-apocalyptic fantasy) \ 287 (57.7) ----------------------------------------------------------------------------------------------------------------------- ^a^ Percentages may not add to 100% due to missing data or multiple responses. Analysis by Gender ------------------ Among respondents who were interested in playing a pharmacy-related game, males had a stronger interest than females (77/169, 45.6% vs 79/278, 28.4%, **P*\<.*001) ([Table 2](#table2){ref-type="table"}). Males were also more likely to have paid for in-game items compared to females (59/187, 31.6% vs 59/307, 19.2%, **P*=.*002), and they were more likely to have used their own income to pay for these items (14/58, 24.1% vs 6/59, 10.2%, **P*=.*045). There was a trend in preference for reward systems. Males preferred experience points (31/157, 19.7%) to unlocking mechanisms (29/157, 18.5%); the opposite was true for females, who preferred unlocking mechanisms (83/275, 30.2% vs 59/275, 21.5%). While males were less likely to want unlocking mechanisms for the game (29/159, 18.5% vs 83/275, 30.2%, **P*=.*008), they were more likely to want rewards of item granting (22/157, 14.0% vs 20/275, 7.3%, **P*=.*023) and plot animations and pictures (19/157, 12.1% vs 18/275, 6.5%, **P*=.*047). A fantasy/medieval/mythic game setting with an adventurer storyline was the most popular in both genders, followed by a modern setting with an authentic pharmacy-related plot ([Table 2](#table2){ref-type="table"}). In addition, males preferred storylines with a war component more (38/183, 20.8% vs 11/295, 3.7%, **P*\<.*001) and spy/secret agent settings less (23/183, 12.6% vs 76/295, 25.8%, **P*\<.*001). The perspectives and game styles were similar for both genders, with 2D top-down and 3D first-person views and a collaborative style being the most popular. However, in terms of game perspectives, 3D views were more popular among males than females (126/185, 68.1% vs 142/303, 46.9%, **P*\<.*001). Similarly, while both genders preferred scenario B (post-apocalyptic fantasy) for the pharmacy-related game, males were more likely choose this scenario than females (129/187, 69.0% vs 155/306, 50.7%, **P*\<.*001). ###### Comparison of gaming aspects by gender. ------------------------------------------------------------------------------------------------------------------------------------------------ Gaming aspects \ Male (N=187), n (%) Female (N=307), n (%) *P* values --------------------------------------------------- --------------------------------- --------------------- ----------------------- ------------ **Interest in** **playing** \ \ \ \ \ Not interested 17/186 (9.1) 23/301 (7.6) .558 \ Interested 169/186 (90.9) 278/301 (92.4) **Interest level** **of interested** **students** \ \ \ \ \ Weak interest 92/169 (54.4) 199/278 (71.6) \<.001^b^ \ Strong interest 77/169 (45.6) 79/278 (28.4) **Paid for** **in-game items** \ \ \ \ \ Yes 59/187 (31.6) 59/307 (19.2) .002^b^ \ No 128/187 (68.4) 248/307 (80.8) **Payment** **method for** **in-game items** ^a^ \ \ \ \ \ Own allowance 50/58 (86.2) 51/59 (86.4) .971 \ Own income 14/58 (24.1) 6/59 (10.2) .045^b^ \ Parents' money 6/58 (10.3) 7/59 (11.9) .794 **Reward** **system** \ \ \ \ \ Score 26/157 (16.6) 39/275 (14.2) .506 \ Experience points 31/157 (19.7) 59/275 (21.5) .674 \ Item granting 22/157 (14.0) 20/275 (7.3) .023^b^ \ Resources 7/157 (4.5) 15/275 (5.5) .651 \ Achievement system 23/157 (14.6) 37/275 (13.5) .730 \ Feedback messages 0 (0.0) 4/275 (1.5) .302 \ Plot animations & pictures 19/157 (12.1) 18/275 (6.5) .047^b^ \ Unlocking mechanism 29/157 (18.5) 83/275 (30.2) .008^b^ **Game setting** \ \ \ \ \ Science fiction 30/182 (16.5) 36/293 (12.3) .199 \ Historical 18/182 (9.9) 21/293 (7.2) .293 \ Fantasy/medieval/mythic 98/182 (53.8) 153/293 (52.2) .730 \ Modern 36/182 (19.8) 81/293 (27.6) .053 \ Others 0 (0.0) 2/293 (0.7) \- **Game storyline** \ \ \ \ \ War 38/183 (20.8) 11/295 (3.7) \<.001^b^ \ Heroic/saving humanity 25/183 (13.7) 35/295 (11.9) .564 \ Spy/secret agent 23/183 (12.6) 76/295 (25.8) \<.001^b^ \ Adventurer 54/183 (29.5) 93/295 (31.5) .642 \ Authentic pharmacy-related plot 41/183 (22.4) 77/295 (26.1) .362 \ Others 2/183 (1.1) 3/295 (1.0) \- **Game** **perspective** \ \ \ \ \ 2D 59/185 (31.9) 161/303 (53.1) \<.001^b^ \ 3D 126/185 (68.1) 142/303 (46.9) **2D game** **perspectives** \ \ \ \ \ 2D top-down 48/59 (81.4) 110/161 (68.3) .057 \ 2D side-scrolling 11/59 (18.6) 51/161 (31.7) **3D game perspectives** \ \ \ \ \ 3D first-person 67/126 (53.2) 79/142 (55.6) .687 \ 3D third-person 59/126 (46.8) 63/142 (44.4) **Game style** \ \ \ \ \ Competitive 54/182 (29.7) 93/304 (30.6) .830 \ Cooperative 56/182 (30.8) 101/304 (33.2) .575 \ Collaborative 72/182 (39.6) 110/304 (36.2) .457 **Game scenario** \ \ \ \ \ A (authentic simulation) 58/187 (31.0) 151/306 (49.3) \<.001^b^ \ B (post-apocalyptic fantasy) 129/187 (69.0) 155/306 (50.7) ------------------------------------------------------------------------------------------------------------------------------------------------ ^a^Percentages may not add to 100% due to multiple responses. ^b^Statistical significance was defined as **P*\<.*05. Analysis by Year of Study (Lower and Upper Batches) --------------------------------------------------- Lower batch students were more likely to have paid for in-game items compared to upper batch students (70/245, 28.1% vs 48/245, 19.4%, **P*=.*022) ([Table 3](#table3){ref-type="table"}). However, among those who paid for in-game items, the lower batch was less likely to have used their own income (8/70, 11.4% vs 12/47, 25.5%, **P*=.*047). An experience points reward system (54/214, 25.2%) was more popular for lower batch students compared to unlocking mechanisms (45/214, 21.0%). In contrast, the experience points system was less popular among upper batch students (36/221, 16.3% vs 67/221, 30.3%). Lower batch students were more likely to want an experience points-based reward (54/214, 25.2% vs 36/221, 16.3%, **P*=.*021) than an unlocking mechanism reward (45/214, 21.0% vs 67/221, 30.3%, **P*=.*027). Fantasy/medieval/mythic and modern game settings were the most popular among both lower and upper batch students ([Table 3](#table3){ref-type="table"}). However, lower batch students preferred modern settings less than their upper batch counterparts (47/236, 19.9% vs 70/242, 28.9%, **P*=.*022). The adventurer game storyline was the most popular among lower batch students (75/237, 31.6%), but an authentic pharmacy-related plot was more popular than the adventurer storyline among the upper batch students (77/244, 31.6% vs 72/244, 29.5%). In fact, upper batch students were more likely to prefer the authentic pharmacy-related plot (77/244, 31.6% vs 42/237, 17.7%, **P*\<.*001). On the other hand, lower batch students preferred a spy/secret agent storyline more than their seniors (58/237, 24.5% vs 41/244, 16.8%, **P*=.*038). In terms of game scenario preferences, while scenario B (post-apocalyptic fantasy) was generally more popular for both batches, lower batch students were more open to playing the post-apocalyptic fantasy scenario in the pharmacy-related game (161/248, 64.9% vs 126/248, 50.8%, **P*=.*001). ###### Comparison of gaming aspects by year of study. ---------------------------------------------------------------------------------------------------------------------------------------------------- Gaming aspects \ Lower batch (N=249), n (%) Upper batch (N=248), n (%) *P* values ------------------------------------------- --------------------------------- ---------------------------- ---------------------------- ------------ **Interest in playing** \ \ \ \ \ Not interested 22/245 (9.0) 18/245 (7.3) .509 \ Interested 223/245 (91.0) 227/245 (92.7) **Interest level of interested students** \ Weak interest 139/223 (62.3) 154/227 (67.8) .220 \ Strong interest 84/223 (37.7) 73/227 (32.2) **Paid for in-game items** \ \ \ \ \ Yes 70/245 (28.1) 48/245 (19.4) .022^b^ \ No 179/245 (71.9) 200/245 (80.6) **Payment method for in-game items** ^a^ \ Own allowance 59/70 (84.3) 42/47 (89.4) .433 \ Own income 8/70 (11.4) 12/47 (25.5) .047^b^ \ Parents' money 9/70 (12.9) 4/47 (8.5) .463 **Reward system** \ \ \ \ \ Score 31/214 (14.5) 34/221 (15.4) .793 \ Experience points 54/214 (25.2) 36/221 (16.3) .021^b^ \ Item granting 24/214 (11.2) 18/221 (8.1) .278 \ Resources 10/214 (4.7) 13/221 (5.9) .573 \ Achievement system 28/214 (13.1) 32/221 (14.5) .673 \ Feedback messages 0 (0.0) 5/221 (2.3) .061 \ Plot animations & pictures 22/214 (10.3) 16/221 (7.2) .262 \ Unlocking\ 45/214 (21.0) 67/221 (30.3) .027^b^ mechanism **Game setting** \ \ \ \ \ Science fiction 35/236 (14.8) 32/242 (13.2) .613 \ Historical 18/236 (7.6) 21/242 (8.7) .675 \ Fantasy/medieval/mythic 135/236 (57.2) 118/242 (48.8) .064 \ Modern 47/236 (19.9) 70/242 (28.9) .022^b^ \ Others 1/236 (0.4) 1/242 (0.4) \- **Game storyline** \ \ \ \ \ War 24/237 (10.1) 26/244 (10.7) .849 \ Heroic/saving humanity 35/237 (14.8) 26/244 (10.7) .175 \ Spy/secret agent 58/237 (24.5) 41/244 (16.8) .038^b^ \ Adventurer 75/237 (31.6) 72/244 (29.5) .611 \ Authentic pharmacy-related plot 42/237 (17.7) 77/244 (31.6) \<.001^b^ \ Others 3/237 (1.3) 2/244 (0.8) \- **Game perspective** \ \ \ \ \ 2D 109/245 (44.5) 112/246 (45.5) .817 \ 3D 136/245 (55.5) 134/246 (54.5) **2D game** **perspectives** \ \ \ \ \ 2D top-down 75/109 (68.8) 83/112 (74.1) .383 \ 2D side-scrolling 34/109 (31.2) 29/112 (25.9) **3D game** **perspectives** \ \ \ \ \ 3D first-person 73/136 (53.7) 74/134 (55.2) .799 \ 3D third-person 63/136 (46.3) 60/134 (44.8) \ **Game style** \ \ \ \ \ Competitive 71/243 (29.2) 76/246 (30.9) .686 \ Cooperative 84/243 (34.6) 76/246 (30.9) .387 \ Collaborative 88/243 (36.2) 94/246 (38.2) .648 **Game scenario** \ \ \ \ \ A (authentic simulation) 87/248 (35.1) 122/248 (49.2) .001^b^ \ B (post-apocalyptic fantasy) 161/248 (64.9) 126/248 (50.8) ---------------------------------------------------------------------------------------------------------------------------------------------------- ^a^Percentages may not add to 100% due to multiple responses. ^b^Statistical significance was defined as **P*\<.*05. Analysis by Choice of Game Scenario ----------------------------------- In general, as the students grew in the number of study years, their choices shifted from scenario B (post-apocalyptic fantasy) to scenario A (authentic simulation) ([Table 4](#table4){ref-type="table"}). Students in year 1 of the pharmacy course were more likely to want to play a post-apocalyptic fantasy game (90/287, 31.4% vs 43/209, 20.6%, **P*=.*007), while those who were near graduation preferred to play the authentic simulation game (61/209, 29.2% vs 61/287, 21.3%, **P*=.*043). In terms of rewards, unlocking mechanisms was the most popular choice among scenario A students (57/184, 31.0%), while experience points was the most popular among scenario B students (57/250, 22.8%). Students who chose the authentic simulation scenario (scenario A) were more likely to want an unlocking mechanism reward system for the game compared to those who chose the post-apocalyptic scenario (scenario B) (57/184, 31.0% vs 55/250, 22.0%, **P*=.*035). A modern game setting was preferred by scenario A students (90/201, 44.8% vs 27/276, 9.8%, *P*\<.001), in contrast to a fantasy/medieval/mythic setting, which was the more preferable choice among scenario B students (187/276, 67.8% vs 66/201, 32.8%, **P*\<.*001). An authentic pharmacy-related plot was the most popular among scenario A students (86/201, 42.8%) but the least popular among scenario B students (33/279, 11.8%). Scenario A students were more likely to want an authentic pharmacy-related plot for the game (86/201, 42.8% vs 33/279, 11.8%, **P*\<.*001), while scenario B students were more likely to want war (38/279, 13.6% vs 12/201, 6.0%, **P*=.*007), heroic/saving humanity (44/279, 15.8% vs 17/201, 8.5%, **P*=.*018), or spy/secret agent (67/279, 24.0% vs 31/201, 15.4%, **P*=.*021) storylines. Those who chose authentic simulations (scenario A) preferred the game to be in a 2D perspective (119/207, 57.5%), compared to those who chose the post-apocalyptic fantasy (scenario B), who preferred it in a 3D perspective (182/283, 64.3%, **P*\<.*001). The latter group (scenario B students) were also more likely to want a competitive style (95/281, 33.8% vs 52/207, 25.1%, **P*=.*039) for the game. ###### Comparison of gaming aspects by game scenario choice in the pharmacy-related serious game. -------------------------------------------------------------------------------------------------------------------------------------------------- Gaming aspects \ Scenario A (N=209), n (%) Scenario B (N=287), n (%) *P* values ------------------------------------------- --------------------------------- --------------------------- --------------------------- ------------ **Year of study** \ \ \ \ \ Year 1 43/209 (20.6) 90/287 (31.4) .007^a^ \ Year 2 44/209 (21.1) 71/287 (24.7) .337 \ Year 3 61/209 (29.2) 65/287 (22.6) .099 \ Year 4 61/209 (29.2) 61/287 (21.3) .043^a^ **Interest in playing** \ \ \ \ \ Not interested 20/206 (9.7) 19/283 (6.7) .227 \ Interested 186/206 (90.3) 264/283 (93.3) **Interest level of interested students** \ \ \ Weak interest 126/186 (67.7) 167/264 (63.3) .326 \ Strong interest 60/186 (32.3) 97/264 (36.7) **Paid for in-game items** \ \ \ \ \ Yes 41/209 (19.6) 77/287 (26.8) .063 \ No 168/209 (80.4) 210/287 (73.2) **Payment method for in-game items** \ \ \ \ \ Own allowance 39/40 (97.5) 62/77 (80.5) .010^a^ \ Own income 6/40 (15.0) 14/77 (18.2) .665 \ Parents' money 1/40 (2.5) 12/77 (15.6) .034^a^ **Reward** **system** \ \ \ \ \ Score 31/184 (16.8) 34/250 (13.6) .349 \ Experience points 33/184 (17.9) 57/250 (22.8) .217 \ Item granting 13/184 (7.1) 28/250 (11.2) .146 \ Resources 11/184 (6.0) 12/250 (4.8) .588 \ Achievement system 24/184 (13.0) 36/250 (14.4) .686 \ Feedback messages 3/184 (1.6) 2/250 (0.8) .654 \ Plot animations & pics 12/184 (6.5) 26/250 (10.4) .158 \ Unlocking mechanism 57/184 (31.0) 55/250 (22.0) .035^a^ **Game setting** \ \ \ \ \ Science fiction 23/201 (11.4) 43/276 (15.6) .196 \ Historical 22/201 (10.9) 17/276 (6.2) .060 \ Fantasy/medieval mythic 66/201 (32.8) 187/276 (67.8) \<.001^a^ \ Modern 90/201 (44.8) 27/276 (9.8) \<.001^a^ \ Others 0 (0.0) 2/276 (0.7) \- **Game storyline** \ \ \ \ \ War 12/201 (6.0) 38/279 (13.6) .007^a^ \ Heroic/saving humanity 17/201 (8.5) 44/279 (15.8) .018^a^ \ Spy/secret agent 31/201 (15.4) 67/279 (24.0) .021^a^ \ Adventurer 55/201 (27.4) 92/279 (33.0) .188 \ Authentic pharmacy-related plot 86/201 (42.8) 33/279 (11.8) \<.001^a^ \ Others 0 (0.0) 5/279 (1.8) \- **Game** **perspective** \ \ \ \ \ 2D 119/207 (57.5) 101/283 (35.7) \<.001^a^ \ 3D 88/207 (42.5) 182/283 (64.3) **2D game perspectives** \ \ \ \ \ 2D top-down 87/119 (73.1) 71/101 (70.3) .644 \ 2D side-scrolling 32/119 (26.9) 30/101 (29.7) **3D game perspectives** \ \ \ \ \ 3D first-person 54/88 (61.4) 93/182 (51.1) .112 \ 3D third-person 34/88 (38.6) 89/182 (48.9) **Game style** \ \ \ \ \ Competitive 52/207 (25.1) 95/281 (33.8) .039^a^ \ Cooperative 68/207 (32.9) 91/281 (32.4) .914 \ Collaborative 87/207 (42.0) 95/281 (33.8) .063 -------------------------------------------------------------------------------------------------------------------------------------------------- ^a^Statistical significance was defined as **P*\<.*05. Analysis by Past Payment for In-Game Items ------------------------------------------ Out of the 497 respondents, 118 (23.7%) had previously paid for in-game items. Males were more likely than females to have paid for in-game items (59/187, 31.6% vs 59/307, 19.2%, **P*=.*002) ([Table 2](#table2){ref-type="table"}). Lower batch students were also more likely to have paid for in-game items compared to upper batch students (70/245, 28.1% vs 48/245, 19.4%, **P*=.*022) ([Table 3](#table3){ref-type="table"}). Among the 110 students who indicated the games in which they had made in-game purchases, the most popular game by 57 respondents (51.8%) was MapleStory. A fantasy/medieval/mythic game setting was preferred by students who had paid for in-game items (80/118, 67.8% vs 186/377, 49.3%, **P*\<.*001), in contrast to a modern setting, which was the preferred choice among students who had never paid for in-game items (108/377, 28.6% vs 16/118, 13.6%, **P*=.*001). For game storyline, students with past payment for in-game items preferred war (20/118, 16.9% vs 35/377, 9.3%, **P*=.*021) and adventurer (48/118, 40.7% vs 112/377, 29.7%, **P*=.*026) storylines; authentic storylines were preferred by students who had never paid for in-game items (105/377, 27.9% vs 18/118, 15.3%, **P*=.*006). Discussion ========== Developing a Pharmacy-Related Serious Game Based on Gaming Preferences of Students ---------------------------------------------------------------------------------- The gaming behaviors and preferences of students have been extensively documented in the literature \[[@ref15],[@ref34]-[@ref40]\]. However, these studies have predominantly focused on recreational, not serious, gaming. The focus of serious games is on a purpose other than entertainment, in this case pharmacy education. Although certain recreational gaming preferences can also help explain students' gaming preferences for a serious game, different categorizations of gaming aspects can render direct comparisons between the two types of gameplay difficult. For example, role-playing recreational games can be further split into fantasy/medieval/mythic (eg, World of Warcraft) or science fiction (eg, Eve Online) settings \[[@ref15],[@ref41],[@ref42]\]. In order for us to develop a serious game for pharmacy education, we needed to find out more about the types of gameplay aspects (eg, settings, storylines, perspectives, and styles) that would be relevant. Based on our literature reviews, we could not find any study results that could be directly translated for us to develop such a game. Studies on gaming in medical and nursing education were generally focused on simulations and not role-playing. Furthermore, the gaming preferences of students in different health care fields might differ. To our knowledge, this is the first study that has identified the preferences of students in relation to gaming aspects and the associations between gaming aspects and gender, year of study, and choice of hypothetical game scenarios. In addition, this is the first survey conducted on an Asian population with regards to serious games, and it may help lay the foundation for more studies. In general, the most popular game reward systems and game settings were unlocking mechanisms and fantasy/medieval/mythic settings. Students generally preferred to play an adventurer game in a collaborative mode and from a 3D viewing perspective. Our results suggested that recreational gaming behavior might also explain serious gaming preferences. The most popular game among students who had paid for in-game items was MapleStory, which has a fantasy/medieval/mythic setting and an adventurer storyline \[[@ref43],[@ref44]\]. For the pharmacy-related serious game, these gaming aspects were also preferred by these students compared to their counterparts who had not previously paid for in-game items. Generally, both genders shared the same gaming preferences. The difference in gaming perspectives between males and females, who preferred 3D and 2D perspectives respectively, could be due to the types of gaming platforms used by both genders for recreational gaming. Studies have shown that males were more likely to play games on advanced gaming equipment, such as the Microsoft Xbox and PlayStation gaming consoles \[[@ref15],[@ref34],[@ref35]\]. The recreational gaming preferences of the students could also have played a role in their perceptions of secondary gaming aspects. For example, the higher preference for war storylines by males could be linked to the fact that they played violent video games for recreation more frequently \[[@ref36]\]. The preference of males towards choosing a post-apocalyptic fantasy (scenario B) could also be related to their preference for games that involved fantasy genres \[[@ref40]\]. On the other hand, the preference of females for an authentic simulation (scenario A) game in pharmacy could mimic the fact that they liked games which involved close simulation of real-life activities \[[@ref45]\]. While both the lower and upper batches of students showed similarities in preferences for the gaming aspects, their preferences for the game storyline and setting were quite different. The lower and upper batch students chose the adventurer storyline and authentic pharmacy-related plot respectively, and the upper batch also preferred the intended game to portray a modern setting similar to a present-day pharmacy. Their preferences could be related to the fact that younger players tended to be more motivated by fantasy elements and required more stimulation than older players when playing video games \[[@ref37],[@ref46]\]. However, the shift in choice of scenario B (post-apocalyptic fantasy) to scenario A (authentic simulation) for the pharmacy game among the student batches showed their maturity in attitude as they neared graduation. Their preferences for fantasy elements decreased, and they were more attracted to realistic and authentic elements as they neared the transit from undergraduate study to working life. The differences in preferences among the genders and batches make it a challenge to design a serious game that caters to all pharmacy students. Our results show diversity in gaming preferences, but there are several aspects that can be generalized across the groups. The popularity of realistic and authentic gaming aspects suggests that the final version of the serious game should incorporate elements that mirror that of real-life pharmacy practices. The differences in preferences on reward systems may imply that it is necessary to incorporate an array of reward systems in the final game. In fact, the use of multiple reward systems already exists for current recreational games in the market. For example, Diablo 3 (Blizzard Entertainment) primarily uses an item-granting reward system, where players obtain rare and gameplay-enhancing items by defeating enemies. At the same time, the players can level up their characters by gaining experience points, compete against other players in a leaderboard scoring system, and collect game rewards through achievement and completion of game events. Nevertheless, it will still be a challenge to design a game that caters towards the variety of preferences. While some gaming aspects can be tailored to the player (ie, 3D and 2D perspectives for males and females), other aspects will need to change as the game evolves and caters to a more mature audience (ie, from a fantasy to a more authentic storyline and setting). For our pharmacy game, it will be important to incorporate a variety of reward systems and a mixture of fantasy and authentic elements in order to encourage students to achieve the learning objectives of the module. Limitations ----------- A major limitation in this study is that our results are mainly focused on the gaming aspects that students prefer for a serious game. Taking into consideration that the serious game is intended for educational purposes, other characteristics such as the learning styles of students can affect their gaming preferences. For example, in the Keirsey temperament sorter personality test \[[@ref6]\], students who are Artisans value freedom and spontaneity and therefore may prefer gaming aspects that offer such qualities, such as adventurer storylines. On the other hand, students who are Guardians are traditional and conservative and may prefer gaming aspects that are more grounded in real-life environments, such as having modern settings. However, obtaining such information on our students' learning styles was not feasible in this study due to the limited time in lectures allocated for the survey. Background information such as duration of gaming experience, recreational gaming habits, and technology aversion was not collected, as we were mindful that the increase in the number of questions might predispose the students to survey fatigue and affect the response rate. Obtaining this information is necessary, however, and will be a next step for us in order to cater the game successfully towards its educational purpose. Another limitation is that our results may have limited generalizability to pharmacy students in other countries. However, our university houses the only pharmacy school in the country, and our department produces majority of the country's pharmacy workforce. Therefore, the results of this study are still applicable to the cohorts of students entering pharmacy school in Singapore. Our survey is also valuable as a basic framework that can be used to obtain the perceptions of serious games of other populations of pharmacy students. Future work can obtain quantitative information regarding students' recreational gaming experiences and habits so that more detailed analyses, such as regression models, can be performed to obtain further insights. Conclusion ---------- This is the first study that has attempted to characterize the preferences of pharmacy students on various gaming aspects for a serious game in their education. In general, students want a game with the following combination of gaming aspects: an unlocking mechanism reward system, a fantasy/medieval/mythic setting, an adventurer storyline, a 3D viewing perspective, and a collaborative game style. Students prefer a post-apocalyptic fantasy scenario over an authentic simulation scenario, although this preference shifts as the students mature over the course of their undergraduate years. A balance between real-life environments and fantasy aspects will need to be struck. The authors would like to thank the lecturers (Ms Mui Ling Tan, Dr Zhi Hui Loh, and Dr Chun Wei Yap) for their help and permission to administer the surveys to the pharmacy undergraduates. The printing of surveys was sponsored by the Final Year Project fund in the Department of Pharmacy, Faculty of Science, National University of Singapore. Conflicts of Interest: None declared. 2D : two-dimensional 3D : three-dimensional

Michelin Anakee Adventure Tires Wander wherever the ride takes you with Michelin’s new Anakee Adventure tires. They’re tough all-rounders with an 80/20 focus for pleasant road miles and enough offroad prowess to keep you out of trouble when adventure strikes. The Anakee Adventure tires utilize Michelin’s 2CT and 2CT+ compound for powerful grip in both wet and dry conditions. A range of sizes ensure fitment on most of today’s popular ADV machines, including the BMW R1200GS.

Amadeus The new tourist platform testing. #Travel & Transport #Testing #app Challenge Amadeus provides the technology which keeps the travel sector moving - from initial search to making a booking, from pricing to ticketing, from managing reservations to managing check-in and departure processes. The company was born when Air France, Iberia, Lufthansa and SAS agreed to create a new global distribution system in 1987. Today, Amadeus operates in 195 countries with a worldwide team of more than 11,000 people. Amadeus approach to business is innovation. The company was recognized in December 2014 as the leading European investor in R&D for the travel and tourism sector by the EU Industrial R&D Investment Scoreboard.​ Solution We help the client in testing the new tourism platform. Our main activities: creating test plans, verifying code quality, proceeding and testing activities based on the test plan, covering all major test cases, report all bugs into bug tracking system. References "SolDevelo's experience and knowledge of web applications is a top notch and it will allow us as a company to meet our customers needs. I highly recommend SolDevelo's services to business owners and other companies."

Q: Как задать высоту в TextBox? Как задать нужную высоту в TextBox? A: Высота у однострочного TextBox зависит от размеров шрифта и вычисляется автоматически. В исходниках есть комментарий на тему того, что можно отключить AutoSize и менять высоту, однако согласно исходникам это скрытое публичное свойство, унаследованное от TextBoxBase, которое не отображается ни в автокомплите, ни в редакторе свойств. Если его принудительно выставить в *.Designer.cs (), то это cработает только на время редактирования формы, после запуска дизайнер удалит вашу запись из своего файла все вернется в исходное состояние, хотя в режиме редактирования формы TextBox все еще будет делать вид "послушного мальчика" менять свои размеры, но только во время редактирования. Обходные пути: В визуальном редакторе: Можете попытаться подобрать шрифт нужного размера, но выставить размер с точностью до пикселя не выйдет. Если хочется быстро и наглядно - можно положить TextBox на Panel. Выставить Border = None у TextBox и Border = Fixed3d у Panel. А также заменить цвет фона Panel с дефолтного Control на Window. Получится такой составной контрол, который выглядит как TextBox. Этот вариант также поможет, если нужно выставить позицию ввода текста в положение, отличное от левого верхнего угла. В коде: Можете настроить параметры TextBox, включая скрытое свойство AutoSize полностью в коде, разумеется такой вариант исключает возможность предварительного просмотра в редакторе форм. Можете создать класс унаследованный от TextBox и либо переопределить свойство AutoSize и сделать его видимым (оно виртуальное и скрыто атрибутами см. тут), либо определить конструктор по умолчанию (без параметров) и просто выставить его в конструкторе в false и менять размер как нравится даже в редакторе форм. PS: В формах еще много таких не очевидных сюрпризов, некоторые решаются, некоторые нет.

Fuel systems typically employ multiple fuel injectors to deliver injections of high pressure fuel into an engine for combustion. Each fuel injector typically includes a nozzle assembly having a pressurized chamber configured to contain a volume of pressurized fuel. Each injector further includes a needle valve element that is slidably disposed within the pressurized chamber. In response to a deliberate injection requirement, the needle valve element moves to allow the pressurized fuel to flow from the pressurized chamber into a combustion chamber of the engine. Fuel injectors operate at injection pressures of up to 200 MPa in order to obtain a fine fuel spray for rapid mixing and reduced emissions. Such pressurized fluid systems, however, are susceptible to the phenomenon known as “cavitation.” Cavitation generally refers to the formation of vapor bubbles within a fluid stream when, for example, the fluid's operational pressure drops below the fluid's vapor pressure. As applied to a fuel system, cavitation occurs when the speed or velocity of the flowing fuel increases such that the pressure in the system drops below the vapor pressure of the fuel, resulting in local vaporization of the fuel. The local vaporization, in turn, creates a cavity (i.e., hole) or void within the flowing fuel. This low-pressure cavity generally comprises a swirling mass of fuel droplets and vapor bubbles. Once formed, the low-pressure cavity is generally swept downstream into a region of high pressure, such as, for example, an eddy zone, where it suddenly collapses as the surrounding fluid rushes in to fill the void. As the cavity collapses, each and every vapor bubble within the cavity implodes, releasing a momentary burst of concentrated energy. In instances where a cavity's point of collapse is in contact with a boundary wall, such as, for example, the material surface of the fuel injector nozzle, the concentrated energy released from the bubble implosion locally stresses the wall surface beyond its elastic limit and causes erosion of wall material. Cavitation can be extremely problematic to the performance of fuel injectors. Specifically, cavitation can affect the mass flow and spray quality characteristics of the fuel injector. Moreover, cavitation can lead to structural damage and a shortened life of the injector. It is, therefore, desirable to experimentally study cavitation structures inside of a fuel injector, and more particularly a fuel injector nozzle, to better understand this economically important flow. One method of visualizing cavitation in a diesel fuel injector is discussed by Haiyun Li in an article titled “Visualization of Cavitation in High-Pressure Diesel Fuel Injector Orifices,” in Atomization and Sprays, 2006, 875:886 (“the Li article”). The Li article discloses an apparatus for conducting true-scale, true-pressure visualization of cavitating liquid fuel in a modern diesel fuel injector. Specifically, the Li article discloses an experimental rig consisting of a gaseous nitrogen driver system, a high-pressure flow system, a test section, and a downstream reservoir. The high-pressure flow system includes an intensifier for pressurizing the liquid fuel up to 220 MPa. The intensifier is connected, via a hose, to an optically accessible orifice mount. The orifice mount contains a single acrylic test orifice. The test orifice has a xenon arc lamp on one side as an illumination source, and a camera on the opposing side. In operation, the intensifier pressurizes fuel at a set injection pressure. The fuel then moves from the intensifier to test orifice, where images of both the internal flow and the spray are acquired. Although the Li article discloses an apparatus for visualizing cavitation at an orifice hole of a fuel injector, the apparatus may not be applicable for studying cavitation inside of a fuel injector nozzle as the apparatus does not include a model of, for example, the nozzle sac of the fuel injector. Furthermore, the apparatus described in the Li article may not have the flexibility to control the duration, frequency, and number of fluid injections into the test section and therefore may not capture cavitation under varying operating conditions. The present disclosure is directed to improvements in the existing technology.

Introduction ============ Extracorporeal therapies designed to remove substances from the circulation now include hemodialysis, hemofiltration, hemoadsorption, plasma filtration, cell-based therapies, and combinations of any of these. In recent years there have been considerable advances in our understanding and technical capabilities, but consensus over the optimal way and under what conditions to use these therapies does not exist. In general, these therapies have been adapted to sepsis from nephrology-based therapy (hemodialysis for renal failure) or from hematology-based therapy (plasma exchange for thrombotic thrombocytopenic purpura). Continuous renal replacement therapies ====================================== More than a decade ago, Gotloib and coworkers \[[@B1]\] observed that renal replacement therapy could remove inflammatory mediators from the plasma of septic patients. Subsequently, Stein and coworkers \[[@B2]\] described an improvement in hemodynamics associated with hemofiltration in the pig following administration of intravenous endotoxin. A short time later these findings were confirmed by Grootendorst and coworkers \[[@B3]\], who also found that the ultrafiltrate removed from endotoxemic animals produced hemodynamic instability in healthy animals when it was infused intravenously \[[@B4]\]. At about this time, Lee and coworkers \[[@B5]\] reported a survival benefit associated with hemofiltration in septic pigs and Bellomo and coworkers \[[@B6]\] showed that some of the ILs and tumor necrosis factor (TNF) could be removed from the circulation of humans with sepsis. With these advances, blood purification as a treatment for human septic shock was born. Since that time many technological advances have occurred, along with substantial changes in our basic understanding of sepsis and the inflammatory response. Modifications of existing technology and new approaches have created a vast array of possible therapies to use or investigate. \'Conventional\' continuous renal replacement therapy ----------------------------------------------------- The various modalities of continuous renal replacement therapy (CRRT) differ in the kind of access (arteriovenous versus veno-venous), mechanism of solute transport (convective versus diffusive), and location where the replacement fluid enters the extracorporeal circuit (predilution versus post-dilution). In arteriovenous circuits blood is driven by the patient\'s blood pressure through a filter, via an extracorporeal circuit originating from an artery and terminating in a vein. However, in a veno-venous circuit, blood is driven by a peristaltic pump module (with appropriate air bubble and pressure monitors) through a filter via an extracorporeal circuit originating and terminating in a vein. Arteriovenous circuits carry all of the risks associated with arterial puncture (i.e. thrombosis, bleeding, etc.) and are disadvantageous in that the ultrafiltration and solute clearance are dependent on the patient\'s blood pressure and their efficiency is unpredictable \[[@B7]\]. For these reasons, veno-venous circuits using double-lumen catheters are considered safer, more efficient, and are now widely preferred in the management of renal failure. Given that the system requirements are only greater with immunomodulation, arteriovenous systems have been abandoned in the treatment of sepsis. The term \'diffusion\' describes a type of solute transport across a semipermeable membrane generated by a concentration gradient. The extent of diffusive clearance is determined by the molecular weight of the solute (or more precisely by the Einstein--Stokes radius of the molecule), the concentration gradient across the membrane, temperature, and the membrane surface area, thickness and pore size. Smaller solutes such as urea, creatinine, and electrolytes are cleared efficiently by diffusion, and as a solute\'s molecular weight increases diffusivity decreases. During CRRT the addition of countercurrent dialysate flow accomplishes diffusive clearance by maximizing the concentration gradient between blood and dialysate through the length of the membrane. The term \'convection\' describes a process in which solutes are transported across a semipermeable membrane, along with movement of solvent (ultrafiltration) that occurs in response to a positive transmembrane pressure gradient. Here, the clearance depends on the ultrafiltration rate and sieving characteristics of the membrane and solute, and to a lesser extent on the molecular size of the solute. Dialysis membranes are further classified based on their ultrafiltration coefficients into high-flux and low-flux membranes (i.e. for a given transmembrane pressure gradient, high-flux membranes have a higher filtration rate than do low-flux membranes). There are few data to state convincingly that convective clearance is better than diffusive clearance. However, studies comparing convective clearance and diffusive clearance have shown that middle-molecular-weight substances (peptides) and large molecules such as vancomycin are better removed by convection \[[@B8]-[@B10]\]. Some of the molecules implicated in sepsis and multiple organ dysfunction fall into the middle-molecular-weight range, and hence convective therapy may serve as a useful adjunctive therapy in septic shock \[[@B9]\]. In addition, convective treatments permit isotonic ultrafiltration, whereas in diffusive treatments osmotic changes in plasma may produce unwanted fluid shifts toward the intracellular compartment. The nomenclature of the CRRT modality depends on the type of access (arteriovenous versus veno-venous) and the mechanism of solute clearance used. If the clearance is purely diffusive then the term \'hemodialysis\' is used, and if the clearance is purely convective then the term \'hemofiltration\' is used. When both convective and diffusive clearances are used, the term \'hemodiafiltration\' is applied. Continuous hemodiafiltration -- a combination of convective and diffusive clearance -- is the most efficient CRRT modality. In modalities that involve convective clearance, the ultrafiltrate produced during membrane transit is replaced completely or in part with a replacement solution to achieve volume control and blood purification. Ultrafiltration in excess of replacement results in patient weight loss \[[@B11]\]. The replacement fluid can be infused either before the filter (predilution) or after the filter (postdilution). The efficiency of postdilution CRRT is limited by the maximum acceptable value of filtration fraction and by the maximal blood flow that can be delivered by the access. Conversely, predilution CRRT is not limited by filtration fraction and therefore allows for higher ultrafiltration rates. This, along with increased replacement fluid rate and a more porous membrane, can enhance solute clearance. However, at a given ultrafiltration rate, predilution results in reduced solute clearance as compared with postdilution because of dilution of solutes at blood entry into the filter. Hence, ultrafiltration must be relatively increased to maintain the same efficiency of solute removal as is observed in postdilution mode \[[@B12]-[@B14]\]. Although definitive evidence is lacking, predilution fluid replacement also is believed to enhance filter patency during CRRT and to reduce need for anticoagulation \[[@B15]\]. Along with a surge in proinflammatory mediators, there is a parallel rise in anti-inflammatory substances in sepsis, which creates a state of \'immunoparalysis\' that is characterized by immune effector cell (i.e. monocyte) dysfunction \[[@B16]\]. Both the proinflammatory and anti-inflammatory cascades interact with each other, and form a complex network that is constantly trying to balance and restore immunologic homeostasis \[[@B17]\]. Numerous therapies designed to intervene in the proinflammatory cascade alone have failed to alter the outcome of sepsis in recent years \[[@B18]\]. Hence, the recent focus of immunomodulatory therapy in sepsis has shifted to nonspecifically downregulating the entire inflammatory response without suppressing it, perhaps by using extracorporeal blood purification techniques. The rationale for such a strategy is that it would \'autoregulate\' itself, such that as one component of the response increases, so too would the effect on that component \[[@B19]\]. Most of the immune mediators are water soluble and fall into the middle-molecular-weight category \[[@B20]\] and hence can theoretically be removed by a plasma water purification system such as hemofiltration. Based on the above rationale and observations, several investigators have studied the effects of CRRT in animal models of sepsis and have demonstrated some beneficial effects \[[@B21]\]. Subsequently, Kellum and coworkers \[[@B9]\] demonstrated that, although convective clearance (continuous veno-venous hemofiltration \[CVVH\]) was better than diffusion (continuous veno-venous hemodialysis) in reducing plasma TNF, the mode of clearance did not influence plasma concentrations of IL-6, IL-10, soluble L-selectin, or endotoxin. However, in a small clinical trial of early isovolemic CVVH at 2 l/hour, Cole and coworkers \[[@B22]\] were unable to demonstrate any reduction in the circulating concentrations of several cytokines and anaphylatoxins associated with septic shock, or could they show improved organ dysfunction following severe sepsis. Thus, the relative impact of conventional CRRT on inflammatory molecules is probably small and the impact on clinical outcomes uncertain. Hence, conventional CRRT is currently not recommended as a therapy for sepsis in patients without renal failure \[[@B14]\]. High-volume hemofiltration -------------------------- Wide variation exists in the manner in which CRRT is prescribed worldwide. Although higher effluent flow rates are sometimes prescribed in Europe and Australia, because of the limitations of pump design, effluent flow rates during CRRT in the USA have traditionally been restricted to 2 l/hour or less. Recently, however, Ronco and coworkers \[[@B23]\] showed that higher CRRT doses (35 ml/kg per min) improved patient survival in acute renal failure (ARF) as compared with conventional doses (20 ml/kg per min), whereas further increases in dose to 45 ml/kg per min were not helpful. Because sepsis is a major cause or complicating factor associated with the development of ARF as well as mortality in this population, it is intriguing to speculate that increased inflammatory mediator removal with convection may have played a role in improving survival. Confirmation of this hypothesis awaits further large studies. Although most of the inflammatory mediator molecules fall into the middle-molecular-weight category and can theoretically be removed by hemofiltration, they have very high generation rates relative to uremic toxins. Thus, the intensity of blood purification and the beneficial effects have been relatively modest with the traditionally used effluent flow rates of 1--2 l/hour (as used for management of ARF) \[[@B9],[@B22]\]. Subsequently, investigators seeking to achieve \'adequate blood purification\' in sepsis hypothesized that higher ultrafiltration rates would be necessary. Defined by an ultrafiltration flow rate in excess of 35 ml/kg per hour and often as high as 75--120 ml/kg per hour \[[@B15]\], high-volume hemofiltration (HVHF) may be necessary to achieve \'clinically meaningful\' convective removal of inflammatory mediators. To achieve high-volume hemofiltration (HVHF), it is necessary to use a high permeability membrane with a large surface area and sieving coefficient close to 1 for a wide spectrum of molecular weights. Numerous *in vitro*and animal studies have shown that synthetic filters used in hemofiltration can extract a wide array of substances that are involved in sepsis to a certain degree \[[@B24]\]. Early studies conducted by Grootendorst and coworkers \[[@B3],[@B4]\] using porcine endotoxic models showed a major attenuation of endotoxin-induced hypotension and an improvement in cardiac performance with HVHF. Subsequent animal studies also showed similar beneficial effects with HVHF in endotoxic animal models \[[@B25],[@B26]\]. These animal findings subsequently triggered some interest in the potential benefits of HVHF in human sepsis. HVHF has been shown to improve hemodynamics, decrease vasopressor requirement and perhaps improve survival in septic patients \[[@B27]-[@B30]\]. However, those studies were all done in either small number of patients or were nonrandomized and uncontrolled. Despite these early promising studies, larger trials looking at HVHF as an adjunctive therapy in human sepsis are needed before such therapy can be routinely advocated. Continuous high-flux dialysis ----------------------------- Extending previous work on nomenclature for CRRT, the Definitions Workgroup for the Acute Dialysis Quality Initiative defined continuous high-flux dialysis (CHFD) as a form of CRRT that uses a highly permeable dialyzer with blood and dialysate flowing countercurrent, and in which ultrafiltrate production is controlled by blood pumps whereby there is a balance of filtration and backfiltration, with ultrafiltrate produced in the proximal portion of the fibers and reinfused by backfiltration in the distal portion of the fibers so that replacement fluid is not required \[[@B15]\]. This technique has mainly been developed to optimize the clearance of middle molecules without compromising the clearance of urea nitrogen. Another feature seen in some systems is an addition of a gravimetric pump in the ultrafiltration/dialysate outflow limb. This regulates both the net ultrafiltration rate and the dialysate outflow rate. Once the patient\'s dry weight has been reached, the circuit may operate at zero net filtration using dialysate at varying flow rates to provide back filtration in the distal limb of the circuit equal in amount to the ultrafiltrate generated in the proximal limb. In this mode, convective transport is therefore maintained without any need for replacement fluids \[[@B31]\]. Since this technique combines convective and diffusive clearances, urea clearances of up to 60 l/day and middle molecule clearance (specifically inulin) of up to 36 l/day have been demonstrated. There is very limited data on the use of CHFD as a mode of blood purification in human sepsis. Lonneman and coworkers \[[@B32]\] compared the effects of standard CVVH with CHFD on *ex vivo*induced whole blood production of TNF and inhibitory TNF soluble receptor type I in 12 patients with sepsis and ARF. That study showed an increase in TNF production with time during CHFD as compared with CVVH and a significant increase in soluble receptor concentration in the dialysate during CHFD. Hemo-adsorption =============== Although uncontrolled clinical studies of HVHF suggest that hemodynamic variables and even survival might be improved \[[@B30]\], the optimal flow rate to achieve \'adequate\' clearance of 3 inflammatory mediators has yet to be determined. Furthermore, the application of HVHF routinely in humans raises substantial organizational, technical, and financial issues. Removal rates and clearances of the different inflammatory cytokines (e.g. TNF, IL-1, etc.) are limited by poor membrane passage and may be further reduced over time as the membrane becomes \'fouled\' by plasma proteins. However, there is also evidence that clearance of mediators by hemofiltration may be due more to adsorption of mediators to the membrane, although convective clearance is still partly responsible \[[@B33],[@B34]\]. Hence, in the quest to achieve higher mediator clearance, newer membranes/devices with higher porosity and adsorptive capacity have been tried. \'Hemoperfusion\' is a technique in which a sorbent is placed in direct contact with blood in an extracorporeal circuit. Nonspecific adsorbents, typically charcoal and resins, attract solutes through a variety of forces, including hydrophobic interactions, ionic (or electrostatic) attraction, hydrogen bonding, and van der Waals interactions. By manipulating the porous structure of solid phase sorbents, it is possible to increase the selectivity of nonspecific adsorbents for particular solutes. In this case, solute molecules are separated according to their size and by their ability to penetrate the porous network of the sorbent material \[[@B35]\]. The adsorptive capacity for resins and charcoals is often quite high, in excess of 500 m^2^/g adsorbent. Until recently, poor biocompatibility, as evidenced by thrombocytopenia and neu-tropenia \[[@B36]\], was the major clinical limitation of these materials. Newer resin adsorbents appear to have resolved this issue with the addition of a biocompatible coating \[[@B37]\]. In view of the high-molecular-weight adsorption characteristics of sorbents, it is possible to target larger molecules that exceed the molecular weight cutoff of synthetic high-flux dialysis membranes. This makes sorbents potentially ideal for intervention in sepsis. Sorbents have been applied in different treatment modalities, including hemoperfusion and hemoperfusion coupled with hemodialysis or with plasma filtration. The choice of modality is based mainly on the properties of the sorbent and the technique used. In Gram-negative sepsis, lipopolysaccharide and its fragments are instrumental in the initiation and perpetuation of the inflammatory response. Therefore, earlier extracorporeal devices were designed to remove the inciting stimulus (i.e. endotoxin). Attempts have been made to remove endotoxin from the circulation using polymyxin-B-immobilized fiber and charcoal hemoperfusion. Hemoperfusion with polymyxin-B-bound sepharose, immobilized with fiber, has been shown to have positive effects in an animal model of normotensive sepsis \[[@B38]\]. Subsequently, human studies have demonstrated that treatment with polymyxin-B-immobilized fiber reduces plasma levels of endotoxin, thrombomodulin, TNF release, and endothelin-1 levels in septic shock \[[@B39],[@B40]\]. In a pilot study (*n*= 16), Aoki and coworkers \[[@B41]\] showed that hemoperfusion with polymyxin-B-immobilized fiber significantly decreased endotoxin levels after 2 hours of direct hemoperfusion. Those investigators also showed that the hyperdynamic, high cardiac output state returned to normal levels after treatment, and in patients with arterial systolic pressure below 100 mmHg the pressure increased significantly from the pretreatment level. Fever was also alleviated by this therapy and did not return until the day after treatment. Nonetheless, no randomized controlled studies yet exist to support the effectiveness of this strategy in managing sepsis. Various other sorbents have been designed and used for blood purification, but are currently in the clinical testing phase. One such system is the molecular adsorbent regenerating system device, which employs a polysulfone high-permeability dialyzer with albumin on the dialysate side to aid transfer of protein-bound toxins across the membranes \[[@B42]\]. This system has mainly been used in the treatment of hepatic encephalopathy and fulminant hepatic failure, and good clinical studies in septic patients are lacking at the present time. One of the techniques of hemo-adsorption is to separate the plasma from the blood using a plasma filter and then passing the filtered plasma through a synthetic resin cartridge, ultimately returning it to the blood. A second filter can be added to remove excess fluid and low-molecular-weight toxins. The use of a more open membrane (plasmafilter) coupled with adsorption may increase the adsorptive capacity of the system and achieve higher nonspecific clearance of inflammatory mediators \[[@B43]\]. Tetta and coworkers demonstrated both significant removal of both proinflammatory and anti-inflammatory mediators \[[@B44]\] and improved survival \[[@B45]\] using this technique in an animal model of sepsis. Subsequently, in a recent pilot study Ronco and coworkers \[[@B46]\] documented important physiologic benefits (hemodynamic stability and monocyte responsiveness) using this technique in septic patients. Using hemoperfusion with a different sorbent (CytoSorb™), in a lethal animal model of lipopolysaccharide-induced shock we recently demonstrated improved hemody-namics and survival time, along with significant decreases in plasma IL-6 and IL-10 levels, using hemoadsorption \[[@B47]\]. The above studies support a role for broad-spectrum hemo-adsorption of multiple inflammatory substances to augment the management of sepsis. These therapies offer new promise in the field of immunomodulation because they are both broad-spectrum (removing both proinflammatory and anti-inflammatory substances) and self-regulating (they remove substances in relation to their circulating concentrations) \[[@B48]\]. Broad-spectrum adsorption offers significant advantages over hemofiltration and is simpler to apply than plasmapheresis. Currently, extensive preclinical work is being undertaken to define the duration of therapy with sorbents, the timing of application, and device design \[[@B35]\]. Plasma therapies in critically ill patients =========================================== Although the terms \'plasmapheresis\' and \'plasma exchange\' are commonly used synonymously, the two techniques differ in important ways. Plasmapheresis is a two-step process in which first the separation of blood into its components (cells and plasma) is accomplished, by means of a centrifugal pump or filter. Then, the separated plasma is allowed to flow along column(s) containing different adsorbents, allowing the selective removal of components, and the processed plasma is reinfused back to the patient. Hence, in plasmapheresis no (or minimal) replacement fluids are necessary. By contrast, plasma exchange is a single-step process in which blood is separated into plasma and cells similarly using centrifugation pumps or a filter, and the cells are returned back to the patient while the plasma is replaced with either donor plasma or albumin \[[@B49]\]. Replacing volume lost with fresh frozen plasma is also done to replete any factor(s) (immunoglobu-lins, etc.) necessary to restore homeostasis and often to correct the underlying disorder for which the plasma therapy was done in the first place (e.g. thrombotic thrombocytopenic purpura). Plasma filtration has advantages over centrifugal plasma exchange in that it is less expensive and can be performed with the same machines as are used for CRRT. Like other extracorporeal blood purification techniques, plasma therapies have been tried in the treatment of sepsis. Early animal studies done to evaluate efficacy in altering the inflammatory response have provided conflicting results \[[@B50]-[@B52]\]. In early human studies, plasma exchange has been shown to reduce effectively the plasma concentrations of various sepsis mediators \[[@B53]-[@B55]\]. However, wide variation exists in the pattern of mediator removal. For example, in a study conducted by Gardlund and coworkers \[[@B54]\], plasma exchange therapy in septic patients decreased the plasma levels of TNF but not of other cytokines. In contrast, Reeves and coworkers \[[@B56]\] showed that a wide variety of acute phase proteins and complement fragment C~3~can effectively be removed by plasma exchange therapy in septic patients. However, in that study plasmafiltration did not influence mean concentrations of IL-6, granulocyte colony-stimulating factor, thromboxane B~2~, total white cell count, neutrophil count, or platelet count. There was also no improvement in survival with plasmafiltration in that study. Independent of the specific mediators removed, plasma exchange therapy has been shown to be associated with improvement in hemodynamic variables in some clinical studies \[[@B57]-[@B59]\]. However, all of those studies were limited in that they studied small numbers of patients and were uncontrolled. In septic patients (*n*= 12), Berlot and coworkers \[[@B59]\] showed that the cardiac index improved significantly after plasma exchange therapy (aimed at removing the full volume of plasma). Interestingly, this improvement in cardiac index was not associated with any changes in preload or afterload. However, the improvement in hemodynamic variables was transient and had no effect on the outcome of these patients. Furthermore, patients in the study received plasma replacement, and hence it is difficult to infer whether these changes in hemodynamic variables were due to removal of mediators or due to the replacement substances present in the donor plasma. In patients with septic shock, Ronco and coworkers \[[@B46]\] showed that coupled plasmafiltration-adsorption combined with hemodialysis was associated with improvement in hemodynamics and leukocyte responsiveness as compared with treatment with continuous veno-venous hemodiafiltration. Finally, in a recent retrospective observational study (*n*= 7), Ataman and coworkers \[[@B60]\] failed to demonstrate any significant improvement in cardiovascular parameters (heart rate and mean arterial pressure) during the first 24 hours after plasmapheresis. In a retrospective study looking at outcomes in patients with sepsis treated with plasma exchange therapy, Barzilay and coworkers \[[@B61]\] showed that patients treated with hemodiafiltration associated with plasma exchange had a better survival than did patients treated with conventional hemofiltration or hemodiafiltration without any plasma exchange therapy. Patients who did not receive any blood purification therapy (control group) had the worst outcome. However, that retrospective study has numerous study design limitations (i.e. it was nonrandomized, underpowered, and the different treatment groups were not comparable to each other). Subsequently, in another nonrandomized study, 19 septic patients who underwent CVVH combined with plasmapheresis were compared with 24 patients who had been treated for their sepsis without any blood purification technique \[[@B62]\]. Although in that study the treatment group had an overall lower mortality than did the control group (42.1% versus 45.8%), the primary organ failure rates were higher in the treatment group. Some authors have argued that plasma therapies are most likely to be effective when they are applied after early stabilization of shock and perhaps when targeting thrombotic microangiopathy rather than cytokines \[[@B63]\]. Most recently, Busund and colleagues \[[@B64]\] used partial plasma exchange therapy and showed a tendency toward improve outcome in adult patients with septic shock. Finally, in a preliminary report, Nguyen and colleagues \[[@B65]\] reported that children with thrombocytopenia (platelet count \<100 000/mm^3^)-associated multiple organ failure had reduced or absent von Willi-brand factor cleaving protease activity, along with markedly increased plasminogen activator inhibitor-1 activity, both of which were reversed by plasma exchange therapy. These patients required a median of 11 days of plasma exchange to reverse their multiple organ failure. These findings suggest that prolonged plasma exchange may be required to reverse the thrombotic microangiopathy of thrombocytopenia-associated sepsis as well. Hence, outcomes with plasma exchange therapy may also be related to duration of treatment and the presence of underlying thrombotic microangiopathy. Thus, based on the limited and conflicting data available, it is difficult to know whether plasma exchange will be useful in the management of sepsis, either alone or in combination with other forms of blood purification. These techniques are also more cumbersome and costly than other forms of extracorporeal blood purification (i.e. HVHF and hemo-adsorption). However, the results of recent studies, especially those in patients with sepsis-associated thrombotic microangiopathy, argue in favor of larger clinical trials. Conclusion ========== Although this wider approach to blood purification in sepsis seems logical, promising and opens new perspectives, many questions still remain unanswered, including the timing, duration, and frequency of these therapies in the clinical setting. However, for now one can safely conclude that these techniques are usually well tolerated and are effective in clearing \'mediators\' of sepsis from the plasma, often improving physiologic parameters. Large multicenter trials evaluating their efficacy to improve clinical outcomes (i.e. mortality or organ failure), rather than surrogate markers such as plasma mediator clearance or transient improvement in physiologic variables, are required to define the precise role of these therapies in the management of sepsis. Given the available data to date, we speculate that immunomodulation using either HVHF or hemo-adsorption, or both, will be most useful in the early stages of severe sepsis and septic shock when high levels of inflammatory mediators appear in the circulation, whereas plasma therapies will be most useful later in the course of illness when thrombotic microangiopathy and endothelial injury begin to immerge. The most effective blood purification strategy may be the careful deployment of both of these therapies at right time. Competing interests =================== RV and JK have received research grants from Renaltech International and Gambro. Abbreviations ============= ARF = acute renal failure; CHFD = continuous high-flux dialysis; CRRT = continuous renal replacement therapy; CVVH = continuous veno-venous hemofiltration; HVHF = high-volume hemofiltration; IL = interleukin; TNF = tumor necrosis factor. Acknowledgements ================ As well as the affiliations listed at the top of the article, all authors are also from the \"Clinical Research, Investigation, and Systems Modeling of Acute illness Laboratory\" (CRISMA Laboratory), Pittsburgh, USA.

Scratching the itch: new tools to advance understanding of scabies. Scabies remains a significant public health problem worldwide. Research into aspects of Sarcoptes scabiei biology and host-parasite interactions has been impeded by an inability to maintain mites in vitro and by limited access to parasite material and infected subjects. The generation of comprehensive expressed sequence tag libraries has enabled the initial characterisation of molecules of interest to diagnostics, vaccines, and drug resistance. The recent development and utilisation of animal models, combined with next-generation technologies, is anticipated to lead to new strategies to prevent, diagnose, and treat scabies, ultimately improving skin health in both human and veterinary settings. This article will summarise recent molecular and immunologic advances on scabies, and will address priorities for the exciting 'next chapter' of scabies research.

Regulation of interleukin-11 expression in ovulatory follicles of the rat ovary. The aim of the present study was to examine the regulation of interleukin (IL)-11 expression, as well as the role of IL-11, during ovulation in gonadotropin-primed immature rats. Injection of equine chorionic gonadotropin (eCG), followed by human CG (hCG) to induce superovulation stimulated expression of the Il11 gene in theca cells within 6h, as revealed by northern blot and in situ hybridisation analyses. Real-time reverse transcription-polymerase chain reaction analysis showed that the IL-11 receptor, α subunit gene was expressed in granulosa and theca cells and that injection of hCG had no effect on its expression. IL-11 protein expression was stimulated in theca cells by hCG. LH-stimulated increases in Il11 mRNA levels in cultured preovulatory follicles were inhibited by protein kinase A and mitogen-activated protein kinase kinase inhibitors. Toll-like receptor (TLR) 2 and TLR4 were detected in preovulatory follicles, and the TLR4 ligand lipopolysaccharide, but not the TLR2 ligand Pam3Cys, increased Il11 mRNA levels in theca cells, but not in granulosa cells. Treatment of preovulatory follicles with IL-11 stimulated progesterone production and steroidogenic acute regulatory protein (Star) gene expression. Together, these results indicate that IL-11 in theca cells is stimulated by mitogen-activated protein kinase signalling and TLR4 activation, and increases progesterone production during ovulation.

Q: How to synchronize sound playback in android? I'm writing my first android app, trying to playback two 10min soundfiles synchronously (imagine an instrumental track and an acapella), to be able to change the volume of each track independently). I am using two MediaPlayers for this, since a SoundPool is targeted at shorter audio samples as far as I read. Now my problem is that, when pausing and resuming the playback, sometimes the players are not synchronous anymore, even though I set their positions to the same value before resuming playback. I know that this is kind of inevitable, because they cannot be started at exactly the same moment and they may require different amounts of time for starting playback, but: Is there maybe any other approach to meet my requirements? A: You can take a look at JetPlayer, this may accomplish what you want as far as synchronization. To use it you create audio channels (your instrument channel and vocal channel) as MIDI files in a track and the player can keep them synchronized while allowing you to mute or unmute the different channels as appropriate. The user guide for creating JET resouces can be found here.

Brus - Alojamiento - Hotel - Hostal Homestay Vukovic, Cara Lazara Bb, Brus Offering a terrace and views of the mountain, Homestay Vukovic is located in Brus, 21 km from Kopaonik. Each room has a shared bathroom. Providing free WiFi throughout the property, Homestay Vukovic also offers free private parking. There is a shared kitchen at the property. Vrnjačka Banja is 28 km from Homestay Vukovic, while Kraljevo is 46 km from the property. Constantine the.. más información

Ishida & Asakura is a Japanese comedy manga series written and illustrated by Masao. It was adapted into an anime television series in 2013. Plot Ishida & Asakura focuses on the title characters—the stoic Ishida and the lecherous Asakura—and the bizarre students and teachers that populate their high school. Asakura is obsessed with curvaceous women and dreams of becoming a teacher in order to be surrounded by attractive girls all day. Ishida dreams of running a flower shop together with Asakura after they finish high school, and appears to have strong homosexual feelings for his best friend, although this is always played for laughs. Characters He is the main character of the story, a high school student who dreams of becoming a teacher. However, his motives are far from pure, as Asakura is obsessed with breasts and wishes to become a teacher so he can constantly be surrounded by attractive female students. Asakura has an afro and speaks with a slight stutter. In class, there is constant competition for Asakura's attention between his best friend Ishida and fellow student Yamada. Asakura's best friend is a tall and stoic young man who speaks in a strong, serious tone. He dreams of opening a flower shop with Asakura after they graduate high school, and reacts violently whenever Yamada tries to get Asakura's attention. Because of his constant blushing whenever he speaks to Asakura, it is assumed that he has homosexual feelings for his best friend. Yamada is a classmate of Ishida and Asakura, with the appearance of a stereotypical nerd, wearing thick glasses and having prominent buck-teeth. Yamada dreams of opening a bookstore with Asakura, but Ishida violently "kills" him in a slapstick fashion every time the subject is brought up; Yamada will always appear unharmed in the next episode. He is a mechanical genius and once built a robot version of himself to fight Ishida. Media Manga Anime An anime television series, directed by Pippuya and produced by Dax Production and Hotline, started airing on January 6, 2013 until March 24, 2013, running for a total of 12 episodes. The series had been licensed for simulcast streaming on Crunchyroll. The opening theme is "Doki Doki Doku" by Rayli. Episode list References External links Official website Category:2011 manga Category:2013 anime television series Category:Anime series based on manga Category:Seinen manga Category:Shōnen Gahōsha manga

Nowadays, mobile phones are able to be connected to a network. A user can login a server by entering an ID code and a password on the mobile phone, and obtain music data from the server. In this manner, the user can enjoy a differentiated music service provided by the server. For instance, an ordinary-quality music download service can be provided to ordinary users for free, while a high-quality music download service is provided to users who pay. However, it is a cumbersome operation and inconvenient for the user to login to the server by entering the ID code and the password on the mobile phone every time to obtain the music data. Even though it can be more convenient for the user to automatically login to the server by recording the ID code and the password, the user is still required to reenter the ID code and the password when they use another mobile phone, which leads to a bad user experience.

Joined: 06 Aug 2009Posts: 5951Location: We lived among the people. I think you say "convenience store." We lived above it. Posted: Tue Jan 22, 2013 12:30 pm Post subject: darksymphonies wrote: xyosefx wrote: darksymphonies wrote: xyosefx wrote: When will Dark Descent get their copies in? Should be by the end of this week, and I should have mine by next Tuesday Cool... I placed a huge order with Matt along with this, can't wait to finally have it all in my hands! I am really sorry for the long ass delay on these. They should have been ready by the end of December as planned but the plant closed for the holidays before finishing the ABSU so I kind of got screwed on it. Thankfully they are finally all en route. No worries... I wouldn't hold you responsible for GZ's slacking on this. Should be by the end of this week, and I should have mine by next Tuesday Cool... I placed a huge order with Matt along with this, can't wait to finally have it all in my hands! I am really sorry for the long ass delay on these. They should have been ready by the end of December as planned but the plant closed for the holidays before finishing the ABSU so I kind of got screwed on it. Thankfully they are finally all en route. No worries... I wouldn't hold you responsible for GZ's slacking on this. The Crypt is proud to re-issue the first two albums from Arizona's cult Death metal act, NUCLEAR DEATH, Bride of Insect and Carrion for Worm. Both releases will be luxurious double vinyl sets with new liner notes, classic band photos and original artwork. Bride of Insect will feature the "Wake Me When I'm Dead" 1986 demo and "Welcome to the Minds of the Morbid" 1987 demo. Carrion for worm will feature "A Symphony of Agony" 1987 demo and the "Vultures Feeding" 1988 demo. This ultimate edition will be strictly limited to a one time only pressing of 666 hand-numbered copies - 222 of which will be classic black vinyl, 222 on RADIOACTIVE YELLOW vinyl and 222 on TOXIC GREEN vinyl. These killer slabs of wax come housed in 2 x 350 gram gatefold jackets with UV High Gloss Varnish, featuring the both of the original Wild Rags covers and layouts. Also included will be a 12 page- zine styled booklet with classic flyers, exclusive band photos, classic interviews, new liner notes by Lori Bravo and an introduction by Michele “Mick” Toscan / The Nuclear Abominations rag! Each gatefold will contain a huge poster of each respective original cover artwork.

still waiting on these 2 deals. Kerri Thompson 11/16/2000 04:10 PM To: Kate Symes/PDX/ECT@ECT cc: Subject: apb checkout missing deals jeff r selling williams 20-30th 25 mw sp15 115.00 on peak jeff r buying ees 20-30th 25 mw sp15 114.95 on peak tom a buying koch 20-30 25 mw 114.00 palo on peak

KOLKATA: Taking a lesson from the back to back fire tragedies in the city, office buildings in Sector V, Salt Lake are now making sure that all companies adhere to the standard fire safety norms. "Every year, each building of Sector V has to obtain a no objection certificate (NOC) from the Directorate of Fire and Emergency Services, government of West Bengal. Without the NOC from the said directorate, as a civic authority we do not issue a 'certificate of enlistment' in favour of the organisation(s) for engaging in any kind of business. Besides that, our authority is also in the process of engaging an agency to conduct a fire and safety audit of all the buildings of Sector V," said Badri Narayan Kar executive officer, Nabadiganta Industrial Township Authority (NDITA). Kar also added that a technical committee of this authority also visits different buildings to oversee the arrangement of fire fighting. Any lapses on the part of the building owner have to be rectified immediately. NDITA was also in touch with the fire services department for improving fire-fighting arrangements in the IT hub. Fire safety norms are now a priority for industries in the region. Recently CII, Eastern Region organised a flagship safety initiative of the region, 'Safety Symposium and Exposition', in Kolkata. On the occasion, Janab Javed Ahmed Khan, minister of fire and emergency services, disaster management and civil defense, government of West Bengal said, "We are laying emphasis to ensuring industrial safety in the state. The government has unified the three departments of fire, disaster, and civil defense under one umbrella for better service." He also stated that the government will set up a unified disaster management centre in all districts of the state. At the symposium, he also invited suggestions from the industry for the betterment of the industrial safety scenario in the state. Sometime back, it was the chief minister Mamata Banerjee, who pointed out that several high-rise buildings in Rajarhat and New Town were unplanned. Soon multiple efforts were made to put things on track. Hidco chairman-cum-managing director, Debashis Sen said that Hidco is in the process of appointing an agency to conduct fire audits for high-rises. "An agency will conduct this audit. It will, for instance, check whether dates of fire extinguishers have expired. If any lapse is detected, the developer will be cautioned." He said, in Rajarhat it is mandatory to install fire alarm switches and close circuit cameras in large complexes. "Any complex that is in an area of 1 acre or more has to install them and most of them are complying by the rules." Suparno Moitra, eastern regional head, Nasscom and board member of Nabadiganta Industrial Township Authority (NDITA) said, "All the IT companies in Sector V and Rajarhat -the IT hub of West Bengal - have their safety systems in place. These companies are subject to a security audit from their international clients and so they cannot overlook this." Moitra informed that about six months back Nabadiganta Industrial Township Authority (NDITA) had appointed a task force led by former Inspector General R K Johri. The task force conducted a survey and after studying the fire safety measures in 24 buildings, the team found few lacunae. These companies were then given a time frame to carry forward the recommendations. "It is now time that we re-audit the buildings to check if the recommendations have been carried out." NDITA is also mulling over appointing a security audit firm to take charge of these issues. Ujjwal, assistant vice president, Forum Projects said that the companies are taking pains to ensure that the safety measures are in place. "For the Technopolis building in Sector V just the installation of all the fire safety devices cost us close to Rs 1.3 crore in 2006, which included the water tanks, fire alarms, sprinklers, detectors etc." The reason for this extra caution is only to protect the property. "We lease our property so it is our duty to maintain it as well," said Ujjwal. Dr A K Mathur, president - operations, Infinity Infotech Park in Sector V said, "All companies are complying with the fire safety measures as put down by the ministry. Companies have realised that these requirements cannot be ignored any more. We also have qualified 24x7 fire officers on duty, who are trained to manage such emergencies." Explaining the technology of the fire safety system installed in the buildings, Ujjwal said, "Firstly, fire detectors have been installed on every floor - both on and above the false ceiling. So if a fire breaks out at any point of time, the control room would know the exact source and won't run helter-skelter to detect the source."

Connections between score matching, contrastive divergence, and pseudolikelihood for continuous-valued variables. Score matching (SM) and contrastive divergence (CD) are two recently proposed methods for estimation of nonnormalized statistical methods without computation of the normalization constant (partition function). Although they are based on very different approaches, we show in this letter that they are equivalent in a special case: in the limit of infinitesimal noise in a specific Monte Carlo method. Further, we show how these methods can be interpreted as approximations of pseudolikelihood.

--- abstract: 'In this paper we establish the existence in low dimensions of solutions to the constraint equations in the case of the conformal system recently proposed by David Maxwell [@Max14], with the added presence of a scalar field and under suitable smallness assumptions on its parameters.' author: - 'Caterina Vâlcu[^1]' title: 'The constraint equations in the presence of a scalar field - the case of the conformal method with volumetric drift' --- Introduction ============ The field of general relativity deals with the study of spacetime, an object defined as the equivalence class, up to an isometry, of Lorentzian manifolds $(\tilde{M},\tilde{g})$ of dimension $n+1$ satisfying the Einstein field equations $$Ric_{\alpha\beta}(\tilde{g})-\frac{1}{2}R(\tilde{g})\tilde{g}_{\alpha\beta}=8\pi T_{\alpha\beta},$$ $\alpha,\beta=\overline{1,n+1}$. Here, $R(\tilde{g})$ is the scalar curvature of $\tilde{g}$, $Ric$ the Ricci curvature and $T_{\alpha\beta}$ the stress-energy tensor describing the presence of matter and energy. For example, $T_{\alpha\beta}=0$ describes vacuum. Our interest focuses on the more general case $$T_{\alpha\beta}=\nabla_\alpha\tilde\psi\nabla_\beta\tilde\psi-\left(\frac{1}{2}|\nabla\tilde\psi|^2_{\tilde{g}}+V(\tilde\psi)\right)\tilde{g}_{\alpha\beta},$$ which models the existence within the spacetime of a scalar field $\tilde\psi\in\mathcal{C}^\infty(M)$ having potential $V\in\mathcal{C}^\infty({\mathbb{R}})$. Thus, $\tilde\psi=0$ and $V=\Lambda$ yield the vacuum with cosmological constant $\Lambda$, while $V=\frac{1}{2}m\tilde\psi^2$ corresponds to the Einstein-Klein-Gordon setting. For a globally hyperbolic spacetime, we define its initial data $(M,\hat{g},\hat{K},\hat{\psi},\hat{\pi})$. They consist of an $n$-dimensional Riemannian manifold $(M,\hat{g})$, which models the spacetime at a particular moment in time, a symmetric 2-tensor $\hat{K}$, corresponding to its second fundamental form, the scalar field $\hat{\psi}$ in $M$, and its temporal derivative $\hat{\pi}$. The associated spacetime development takes the form $(M\times {\mathbb{R}},\tilde{g}, \tilde{\psi})$, where $\tilde{g}$ is a Lorentzian metric that verifies $\tilde{g}|_{M}=\hat{g}$ and $\tilde\psi$ is a scalar field such that $\tilde{\psi}|_{M}=\hat{\psi}$ and $\partial_t\tilde{\psi}|_{M}=\hat{\pi}$. Initial data in general relativity may not be freely specified, unlike their Newtonian counterparts. Instead, they must verify the Gauss and Codazzi equations, $$\begin{cases} \displaystyle R(\hat{g})+(tr_{\hat{g}}\hat{K})^2-||\hat{K}||^2_{\hat{g}} &\displaystyle= \hat{\pi}^2+|\hat{\nabla}\hat{\psi}|^2_g+2V(\hat{\psi})\\ \partial_i(tr_{\hat{g}} \hat{K})-\hat{K}_{i,j}^j&\displaystyle= \hat{\pi}\partial_i\hat{\psi}, \end{cases}$$ which are referred to as the *constraint equations*. The work of Choquet-Bruhat [@Cho] establishes, once and for all, that the constraint equations are not only necessary but sufficient conditions for the (local) existence of a solution. Later, Choquet-Bruhat and Geroch [@ChoGer] prove that the maximal development of initial data is unique, up to an isometry. Globally hyperbolic spacetimes may rigorously be studied in the context of mathematical analysis as the result of an evolution problem. The above system is clearly under-determined, which allows for considerable freedom in choosing a solution $(\hat{g},\hat{K},\hat{\psi},\hat{\pi})$. Using the conformal method introduced by Lichnerowicz [@Lic], the constraint equations may be transformed into a determined system of equations by fixing well-chosen quantities (see Choquet-Bruhat, Isenberg and Pollack [@ChoIsePol]). The appeal of such a method lies in that it provides a characterisation of the resulting initial data by fixed quantities. Essentially, it maps a space of parameters to the space of solutions. Given an initial data set $(\hat{g},\hat{K},\hat{\psi},\hat{\pi})$, the classical choice of parameters is $(\mathbf{g},\mathbf{U},\tau,\psi,\pi;\alpha)$: in this case, the conformal class $\mathbf{g}$ is represented by a Riemannian metric $g$, the smooth function $\tau=\hat{g}^{ab}\hat{K}_{ab}$ is a mean curvature and the conformal momentum $\mathbf{U}$ measured by a volume form $\alpha$ (volume gauge) is a 2-tensor that is both trace-free and divergence-free with respect to $g$ (a transverse-traceless tensor). We sometimes prefer to indicate the volume gauge by the densitized lapse $$\tilde{N}_{g,\alpha}:=\frac{\alpha}{dV_g}.$$ Note that this quantity depends on the choice of representative $g$, unlike the volume gauge $\alpha$ which does not. The standard conformal method implicitly fixes $\tilde{N}_{g,\alpha}=2$; in the present paper, we prefer to make use of the freedom of choosing $\tilde{N}_{g,\alpha}$ as needed. We often refer to a parameter set by indicating the representative metric $g$ and the corresponding densitized lapse $\tilde{N}_{g,\alpha}$ instead of giving the conformal class and volume gauge. However, these quantities can immediately be reconstructed from our data. We refer to Maxwell [@Max14] for an introduction to the conformal method in our context. Starting from the parameter set $(g,U,\tau,\psi,\pi;\tilde{N})$, the corresponding (physical) initial data is pinpointed by solving a resulting system, comprising the Lichnerowicz-type equation and the momentum constraints, for a smooth positive function (or conformal factor) $u$ and a smooth vector field $W$ in $M$, $$\begin{cases}\label{syst classical conformal method} \displaystyle \Delta_g u+\mathcal{R}_\psi=&\displaystyle-\mathcal{B}_{\tau,\psi,V}u^{q-1}+\frac{\mathcal{A}_{\pi,U}(W)}{u^{q+1}},\\ \Delta_{g, conf}W=&\displaystyle \frac{n-1}{n}u^{q}\nabla\tau+\pi\nabla\psi, \end{cases}$$ where $$\begin{array}{l} \displaystyle \mathcal{R}_\psi=\frac{n-2}{4(n-1)} \left(R(g)-|\nabla\psi|^2_g\right),\\ \displaystyle \mathcal{B}_{\tau,\psi,V}=\frac{n-2}{4(n-1)}\left(\frac{n-1}{n}\tau^2-2V(\psi)\right),\\ \displaystyle \mathcal{A}_{\pi,U}(W)=\frac{n-2}{4(n-1)}\left(|U+\mathcal{L}_gW|^2_g+\pi^2\right). \end{array}$$ If $(u,W)$ solves the above system, then the initial data we’ve been searching for are $$\hat{g}=u^{q-2}g,\quad \hat{K}=u^{-2}\left(U+\frac{\tilde{N}}{2}\mathcal{L}_g W\right)+\frac{\tau}{n}\hat{g},\quad \hat{\psi}=\psi,\quad\hat{\pi}=u^{-q}\pi.$$ Note also that the solutions generated by $(g,U,\tau;\tilde{N})$ and $$(\varphi^{q-2}g,\varphi^{-2}U,\tau,\psi,\varphi^{-q}\pi; \varphi^q \tilde{N})$$ are the same, where $\varphi$ is a smooth positive function. The notations above are similar to those of Choquet-Bruhat, Isenberg and Pollack ([@ChoIsePol], [@ChoIsePol2]). The following quantities often appear throughout the present paper: $q=\frac{2n}{n-2}$ is the critical Sobolev exponent for the embedding of $H^1$ in Lebesgue spaces, $\Delta_g=-div_g\nabla$ denotes the Laplace-Beltrami operator taken with non-negative eigenvalues, $\Delta_{g,conf}W=div_g(\mathcal{L}_g W)$ is the Lamé operator and $\mathcal{L}_g$ is the conformal Killing operator with respect to $g$, $$\mathcal{L}_g W_{ij}=W_{i,j}+W_{j,i}-\frac{2}{n}div_g W g_{ij}.$$ Conformal Killing fields are defined as vector fields in the kernel of $\mathcal{L}_g.$ The conformal method is particularly successful in finding solutions when the mean curvature $\tau$ is constant as the system (\[syst classical conformal method\]) becomes uncoupled, but it is unclear how well the method functions when the mean curvature is far from being constant: see Maxwell [@Max11] and [@Max14c], where a given set of parameters point to no or to an infinite number of solutions. We emphasize that any failing of the system does not necessarily translate to a singularity in the space of solutions to the constraints system, but may instead derive from a poor choice of mapping. This motivates the study of variations to standard conformal methods. The drift method introduced by Maxwell replaces the mean curvature $\tau$ as a parameter by a pair $(\tau^*,\tilde{V})$, where $\tau^*$ is a unique constant called volumetric momentum and $\tilde{V}$ a vector field related to the drift. They verify an analogue of York splitting, namely $$\label{volumetric momentum} \tau=\tau^*+\tilde{N}_{\hat{g},\alpha}div_{\hat{g}}\tilde{V}=\tau^*+\frac{\tilde{N}_{g,\alpha}}{u^{2q}}div_g(u^q\tilde{V}),$$ the notation $\tilde{V}$ being specific to this paper in order to avoid confusion with the potential $V$. Interestingly, $\tau^*=0$ holds true for all counterexamples found by Maxwell ([@Max11], [@Max14c]). This suggests that the volumetric momentum may play an important role in characterizing the space of initial data. Ideally, we would like to know as soon as we fix a set of parameters $(g,U,\tau,\psi,\pi;\tilde{N})$ if we find ourselves in the case $\tau^*=0$. However, $\tau^*$ cannot be directly calculated by (\[volumetric momentum\]) without first solving (\[syst classical conformal method\]), which somewhat defeats the purpose. This motivates a new choice of parameters, even at the risk of working with an analytically more complicated system. The idea of Maxwell ([@Max11], [@Max14c]) is thus to choose $\tau^*$ as an additional parameter that is to be fixed in the place of $\tau$: the hope is thus to avoid the aforementioned problem. As well as $\tau^*$, Maxwell added $\tilde{N}$ and $\tilde{V}$ as parameters, for geometric and physical reasons. Therefore, instead of fixing $\tau$, we fix $\tau^*$, $\tilde{N}$ and $\tilde{V}$. Intuitively, the drift is a geometric quantity describing infinitesimal motion in the space of metrics modulo the group of diffeomorphisms connected to the identity such that the conformal class and volume are preserved. For any given drift, the choice of a representative vector field $\tilde{V}$ is unique up to conformal Killing fields and vector fields which are divergence-free with respect to the initial metric $\hat{g}$. Given $g$ an arbitrary representative of the conformal class, it is not clear whether two vector fields are indicative of the same drift class defined for $\hat{g}$; this problem is discussed at length in the paper of Mike Holst, David Maxwell and Rafe Mazzeo [@HolMaxMaz] for conformal systems where the critical non-linearity is non-focusing, or negative. Our analysis treats systems with focusing (that is to say positive) non-linearities stemming from the presence of a scalar field with positive potential. The following system corresponds to Problem 12.1 of [@Max14] in the presence of a scalar field, where $g$ admits no non-trivial conformal Killing fields: $$\label{syst of Maxwell} \begin{cases} \Delta_g u+\frac{n-2}{4(n-1)}(R(g)-|\nabla\psi|_g^2)u -\frac{(n-2)|U+\mathcal{L}_g W|^2+\pi^2}{4(n-1)u^{q+1}}\\ \displaystyle\quad-\frac{n-2}{4(n-1)}\left[2V(\psi)-\frac{n-1}{n}\left(\tau^*+\frac{\tilde{N}div_g(u^q\tilde{V})}{u^{2q}}\right)^2\right]u^{q-1}=0\\ \\ div_g\left(\frac{\tilde{N}}{2}\mathcal{L}_g W\right)-\frac{n-1}{n}u^q \mathbf{d} \left(\frac{\tilde{N}div_g(u^{q}\tilde{V})}{2u^{2q}}\right)-\pi\nabla\psi=0. \end{cases}$$ We denote the exterior derivative by $\mathbf{d}$. The unknowns are a smooth positive scalar function $u$ defined on $M$ and a smooth vector field $W$ on $M$. The parameters are $(g,U,\tau^*,\tilde{V},\psi,\pi;\tilde{N})$. Maxwell’s new set of parameters include $\tau^*$, which could not be calculated *a priori* in the classical method. The initial data of the constraint equations verify $$\begin{array}{c} \hat{g}=u^{q-2}g,\quad \hat{K}=u^{-2}\left(U+\frac{\tilde{N}}{2}\mathcal{L}_g W\right)+\frac{1}{n}\left(\tau^*+\frac{\tilde{N}}{u^{2q}}div(u^q\tilde{V})\right)\hat{g},\\ \hat{\psi}=\psi,\quad\hat{\pi}=u^{-q}\pi. \end{array}$$ The following is a more general system than (\[syst of Maxwell\]). The central result of the paper consists in showing that it admits solutions. Let $(M,g)$ be a closed Riemannian manifold of dimension $n\in\{3,4,5\}$, and $g$ has no non-trivial conformal Killing fields. Let $b$, $c$, $d$, $f$, $h$, $\rho_1$, $\rho_2$, $\rho_3$ be smooth functions on $M$ and let $Y$ and $\Psi$ be smooth vector fields defined on $M$. Let $0<\gamma<1$. Assume that $\Delta_g+h$ is coercive, in the sense that its first eigenvalue is positive. Assume that $f>0$, $\rho_1>0$ and $|\nabla \rho_3|<(2C_1)^{-1}$, where $C_1$ is a dimensional constant - see (\[lxest\]). Consider the system $$\label{systemshort} \begin{cases} \displaystyle \Delta_g u+hu &\displaystyle= fu^{q-1}+\frac{\rho_1+|\Psi+\rho_2\mathcal{L}_gW|^2_g}{u^{q+1}}\\ &\displaystyle -\frac{b}{u}-c\langle\nabla u,Y\rangle \left(\frac{d}{u^2}+\frac{1}{u^{q+2}}\right)-\frac{\langle\nabla u,Y\rangle^2}{u^{q+3}}\\ \displaystyle div_g\left(\rho_3\mathcal{L}_g W\right) &\displaystyle =\mathcal{R}(u). \end{cases}$$ Here $\mathcal{R}$ is an operator verifying $$\mathcal{R}(u)\leq C_\mathcal{R}\left(1+\frac{||u||_{\mathcal{C}^2}^2}{(\inf_Mu)^2}\right)$$ for a constant $C_\mathcal{R}>0$. A supersolution of the Lichnerowicz-type equation is a smooth function $u$ verifying that $$\begin{array}{r l} \Delta_g u+hu\geq &fu^{q-1}+\frac{\rho_1+|\Psi+\rho_2\mathcal{L}_gW|^2_g}{u^{q+1}} -\frac{b}{u}\\& -c\langle\nabla u,Y\rangle \left(\frac{d}{u^2}+\frac{1}{u^{q+2}}\right)-\frac{\langle\nabla u,Y\rangle^2}{u^{q+3}}. \end{array}$$ Similarly, a subsolution satisfies an inequality of opposite sign. Whenever the inequality is strict, we say $u$ is a strict subsolution or a strict supersolution respectively. We fix $$\label{th main} \theta=\min(\inf_M\rho_1,\inf_M f),$$ and $$\label{T main} T=\max(||f||_{\mathcal{C}^{1,\gamma}}, ||\rho_1||_{\mathcal{C}^{0,\gamma}}, ||c||_{\mathcal{C}^{0,\gamma}}, ||d||_{\mathcal{C}^{0,\gamma}}, ||h||_{\mathcal{C}^{0,\gamma}}).$$ Here is the main result of our paper: \[thm 1\] There exists a constant $C=C(n,h)$, $C>0$ such that if $\rho_1$ verifies $$||\rho_1||_{L^1(M)}\leq C(n,h)\left(\max_M |f|\right)^{1-n},$$ and there exists a constant $$\delta=\delta(\theta, T )>0$$ such that, if $$||b||_{\mathcal{C}^{0,\gamma}}+ ||Y||_{\mathcal{C}^{0,\gamma}}+ ||\Psi||_{\mathcal{C}^{0,\gamma}}+||\rho_2||_{\mathcal{C}^{0,\gamma}}+ C_\mathcal{R}\leq \delta,$$ then the system (\[systemshort\]) admits a solution. For a slightly more detailed expression of the smallness assumptions, see Section \[theo: system\]. The constant $\displaystyle C(n,h)=\frac{C(n)}{S_h^{n-1}}$ appears explicitly in a paper by Hebey, Pacard and Pollack ([@HebPacPol08], Corollary 3.1). By $S_h$ we understand the Sobolev constant which is defined as the smallest constant $S_h>0$ such that $$\int_M |v|^q\,dv_g\leq S_h\left(\int_M(|\nabla v|^2+hv^2)\,dv_g\right)^\frac{q}{2}$$ for all $v\in H^1(M)$. The following corollary deals with the existence of solutions to the conformal system. It suffices to take $$\begin{cases} h=\frac{n-2}{4(n-1)}\left(\mathcal{R}_g-|\nabla\psi|^2_g\right),\quad f=\frac{n-2}{4(n-1)}\left[2V(\psi)-\frac{n-1}{n}(\tau^*)^2\right],\\ \rho_1=\frac{n-2}{4(n-1)}\left(\pi-\frac{n-1}{n}(\tilde{N})^2div_g(\tilde{V})\right),\quad \rho_2=\sqrt{\frac{n-2}{4(n-1)}}\frac{\tilde{N}}{2}, \quad \Psi=\sqrt{\frac{n-2}{4(n-1)}}U,\\ b=\frac{n-2}{2n}\tau^*\tilde{N}div_g(\tilde{V}),\quad c=2\sqrt{\frac{n-2}{4n}},\quad d=\tau^*\\ Y=\sqrt{\frac{n}{n-2}}\tilde{N}\tilde{V},\quad \rho_3=\ln\tilde{N},\\ \mathcal{R}=\frac{n-1}{n}div_g(\tilde{V})\nabla\ln\tilde{N}+\frac{n-1}{n}\nabla(div_g(\tilde{V}))+\frac{\pi\delta_i\psi}{\tilde{N}}\\\quad+2\langle\tilde{V},\frac{\nabla u}{u}\rangle\nabla\ln\tilde{N}-2\frac{n-1}{n+1}\frac{\langle\tilde{V},\nabla u\rangle\nabla u}{u^2}-\frac{n-1}{n}\langle\tilde{V},\frac{\Delta_g u}{u}\rangle \end{cases}$$ in (\[systemshort\]). It is a direct application of Theorem \[thm 1\]. \[physical result\] Let $\Delta_g + \frac{n-2}{4(n-1)}\left(\mathcal{R}_g-|\nabla\psi|^2_g\right)$ be a coercive operator. Assume that $$2V(\psi)>\frac{n-1}{n}(\tau^*)^2,\quad \pi>\frac{n-1}{n}(\tilde{N})^2div_g(\tilde{V})\quad\text{and}\quad|\nabla \ln\tilde{N}|<C_1^{-1},$$ where $C_1$ depends on $n$ and $g$ (see (\[lxest\]) for more details). Moreover, assume that $$||\pi-\frac{n-1}{n}(\tilde{N})^2div_g(\tilde{V})||_{L^1}\leq C(n,g,h)||2V(\psi)-\frac{n-1}{n}(\tau^*)^2||^{1-n}_{L^\infty}.$$ Then there exists a constant $$\begin{array}{c} \delta=\delta\Big(\inf_M\frac{n-2}{4(n-1)}\left[2V(\psi)-\frac{n-1}{n}(\tau^*)^2\right], \inf_M\frac{n-2}{4(n-1)}\left(\pi-\frac{n-1}{n}(\tilde{N})^2div_g(\tilde{V})\right)\\ \tau^*,||\pi||_{\mathcal{C}^{0,\gamma}}, ||\mathcal{R}_g-|\nabla\psi|^2_g||_{\mathcal{C}^{0;\gamma}},||2V(\psi)||_{\mathcal{C}^{1,\gamma}}\Big)>0 \end{array}$$ such that, if $$||U||_{\mathcal{C}^{0,\gamma}}+||\pi||_{\mathcal{C}^{0,\gamma}}+||\nabla\psi||_{\mathcal{C}^{0,\gamma}}+||\ln \tilde N||_{\mathcal{C}^{1,\gamma}}+||\tilde{V}||_{\mathcal{C}^{1,\gamma}}\leq \delta,$$ then (\[syst of Maxwell\]) admits a solution $(u,W)$, where $u$ is a smooth positive function on $M$ and $W$ a smooth vector field on $M$. A few remarks on the results of the present paper. The classical system of constraint equations obtained by the conformal method (without the modifications proposed by Maxwell [@Max14]) was studied by Bruno Premoselli ([@Pre14], [@Pre14a]) in the presence of a scalar field. Second, the above system is the subject of a paper by Mike Holst, David Maxwell and Rafe Mazzeo [@HolMaxMaz] - in their case, certain conditions are imposed on the presence of the matter field. We treat the separate and delicate case wherein the dominant non linearity is focusing and leads to possible loss of compactness. It is interesting to note that the size of $n$ plays a role; as Premoselli proves in his paper, while his system may be well-behaved in low dimensions ($3\leq n\leq 5$), it most certainly fails to do so in higher dimensions $(n\geq 6)$. Even if our results are similar to those of Premoselli, they are considerably more difficult to obtain. This is mainly due to the presence of a $|\nabla u|^2$ term in the scalar equation, a term which is not compact a priori. **Outline of the paper**. Section 2 is devoted to the study of the first equation in (\[systemshort\]), the so-called Lichnerowicz equation. We prove the existence of stable solutions under suitable assumptions. Section 3 deals with a priori estimates for solutions of the Lichnerowicz equation. A careful blow-up analysis is carried out. As already mentioned, the term $|\nabla u|^2$ poses additional difficulty: blow-up can occur at the $\mathcal{C}^1$ level, even if the solution is bounded in $L^\infty$. Section 4 is devoted to the proof of Theorem \[thm 1\] and Corollary \[physical result\], which relies heavily on the a priori estimates obtained in Section 3. At the end of Section 4, we also explain how to extend Corollary \[physical result\] in the presence of conformal Killing vector fields. **Aknowledgements.** It is a pleasure to express my sincere gratitude to Olivier Druet for many helpful discussions and suggestions. Existence of minimal solutions of the scalar equation ===================================================== We study the Lichnerowicz-type scalar equation in (\[systemshort\]). The following theorem states that, given the existence of supersolutions, one may use an iterative procedure to obtain a sequence which converges in $\mathcal{C}^1$ norm to a solution. We draw the reader’s attention to the fact that this solution is uniquely determined by its construction. The proof contains some similarities with that of Premoselli [@Pre14], but some new difficulties appear. The main difference here comes from the presence of non-linearities containing gradient terms, which force us to further refine the analysis. These gradient terms lead to difficulties in obtaining a priori estimates on solutions of the equation, which in turn lead to problems of stability. The existence result we prove in this section reads as follows: \[theo: existence of sol to Lich type eq\] Let $(M,g)$ be a closed Riemannian manifold. Let $a$, $b$, $c$, $d$, $f$, $h$ be smooth functions on $M$ and $Y$ be a smooth vector field on $M$. Assume that $a>0$ and $f>0$. The equation $$\label{EM} \Delta_g u+ hu-fu^{q-1}-\frac{a}{u^{q+1}}+\frac{b}{u}+\frac{\langle\nabla u, Y\rangle^2}{u^{q+3}}+c\langle\nabla u,Y\rangle\left(\frac{d}{u^2}+\frac{1}{u^{q+2}}\right)=0$$ admits a smooth positive solution $u$ as soon as it admits a supersolution. The solution obtained by the construction below is unique. Moreover, it is stable (see Lemma \[lem weak stability\] at the end of this section.) We begin by fixing a supersolution and a subsolution to serve as upper and lower bounds respectively for the iterative process. Let $\psi$ be a positive supersolution of (\[EM\]). Let $\varepsilon_0>0$ be a small constant such that $$\varepsilon_0<\inf_M\psi,\quad \left(\sup_M h\right)\varepsilon_0^{q+2}<\frac{\inf_M a}{2}\quad \text{and}\quad \left(\sup_M b\right)\varepsilon_0^{q}<\frac{\inf_M a}{2}.$$ The last two bounds ensure that $u_0=\varepsilon_0$ is a strict subsolution of (\[EM\]) since $f>0$. We let $$F(t,x)=-f(x)t^{q-1}-\frac{a(x)}{t^{q+1}}+\frac{b(x)}{t}-Kt$$ for $x\in M$ and $t>0$. We choose $K>0$ large enough such that $$\label{monotonicity of F} \frac{\partial}{\partial t}\left[F(t,x)+\frac{A(x)^2}{t^{q+3}}+c(x)A(x)\left(\frac{d(x)}{t^2}+\frac{1}{t^{q+2}}\right)\right]\leq 0$$ for all $x\in M$ and all $\varepsilon_0\leq t\leq \sup_M\psi$, whatever $A(x)$ is. It is sufficient to take $$\label{K estimate} \begin{array}{c} K\geq \sup_{x\in M, \varepsilon_0\leq t\leq \sup_M\psi}\Big[-(q-1)f(x)t^{q-2}+(q+1)\frac{a(x)}{t^{q+2}}-\frac{b(x)}{t^2}\\ +\frac{c(x)^2\left(\frac{2d(x)}{t^3}+\frac{d+2}{t^{q+3}}\right)^2t^{q+4}}{4(q+3)}\Big]. \end{array}$$ Up to choosing $K$ larger, we may also assume that $h+K>0$ and that $F(t,x)$ is negative for $\varepsilon_0\leq t\leq \sup_M\psi$. We shall now consider a sequence $(u_i)_{i\in\mathbb{N}}$ defined by induction by $u_0\equiv \varepsilon_0$ and $$\label{eq: the Ei eqs} \begin{array}{c} \displaystyle (E_i):\quad \Delta_g u_i+(h+K)u_i+F(u_{i-1}(x),x)+\frac{\langle\nabla u_i, Y\rangle^2}{u_{i-1}^{q+3}}\\ \displaystyle \quad +c\langle \nabla u_{i},Y\rangle\left(\frac{d}{u^2_{i-1}}+\frac{1}{u^{q+2}_{i-1}}\right)=0. \end{array}$$ We prove in Step 1 below that the sequence is well defined. In Step 2, we prove that the sequence if pointwise increasing and uniformly bounded. At last, Step 3 is devoted to the proof that the sequence $(u_i)$ converges to a solution of (\[eq: the Ei eqs\]). **Step 1:** We prove that $(u_i)$ is well defined. We consider the more general equation $$\label{gen eq} \Delta_g u+Hu+\theta_1\langle\nabla u,Z\rangle^2+\theta_2\langle\nabla u,Z\rangle+\theta_3=0,$$ with $H$, $\theta_1$, $\theta_2$, $\theta_3$ smooth functions on $M$ and $Z$ a smooth vector field on $M$ such that $\theta_1>0$, $H>0$, $\theta_3<0$. We claim that (\[gen eq\]) admits a unique smooth positive solution. We shall use the fixed point theorem as stated in Evans [@Eva], Section 9.2.2, Theorem 4. Let us define the operator $T:\mathcal{C}^{1,\gamma}(M)\to\mathcal{C}^{1,\gamma}(M)$ such that $$\Delta_g T(u)+HT(u)+\theta_1\langle\nabla u,Z\rangle^2+\theta_2\langle\nabla u,Z\rangle+\theta_3=0.$$ If we can prove that there exists $C>0$ such that $$\label{fixed point condition} \forall\quad 0\leq \tau\leq 1,\quad w=\tau T(w)\quad\Rightarrow\quad ||w||_{\mathcal{C}^{1,\gamma}(M)}\leq C,$$ then the operator $T$ will have a fixed point, leading to a solution of (\[gen eq\]). Note that this solution will be unique. Indeed, assume that $w_1$ and $w_2$ are two solutions of (\[gen eq\]), then at a point of maximum $x_0$ of $w_1-w_2$, we have that $\nabla w_1(x_0)=\nabla w_2(x_0)$ and $\Delta_g w_1(x_0)\geq \Delta_g w_2(x_0)$ so that (\[gen eq\]) gives $$H(x_0)\left(w_1(x_0)-w_2(x_0)\right)\leq 0.$$ Since $H>0$, this leads to $w_1\leq w_2$. By symmetry, uniqueness is proved. Note that the fixed point of $T$ is smooth and positive by the standard regularity theory and the maximum principle. Thus we are left with the proof of (\[fixed point condition\]). Let $0\leq\sigma_m\leq 1$ and let $w_m\in\mathcal{C}^{1,\gamma}(M)$ be such that $$w_m=\sigma_m T(w_m).$$ Multiplying (\[gen eq\]) by $\sigma_m$, we obtain that $$\Delta_g w_m+Hw_m+\sigma_m\theta_1\langle\nabla w_m,Z\rangle^2+\sigma_m\theta_2\langle\nabla w_m,Z\rangle+\sigma_m\theta_3=0.$$ First, the $L^\infty$ bounds on $w_m$ exist *a priori*. Indeed, consider $x_0\in M$ a minimum of $w_m$. Since $\Delta_g w_m(x_0)\leq 0$ and $\nabla w_m(x_0)=0$, which holds true for all minima, then $Hw_m(x_0)\geq -\sigma_m \theta_3(x_0).$ By applying the same procedure to the study of maxima, we obtain that $$\label{a priori b} \inf_M\frac{-\sigma_m\theta_3}{H}\leq w_m\leq \sup_M\frac{-\sigma_m\theta_3}{H}.$$ Assume now that $||\nabla w_m||_{L^\infty(M)}\to\infty$. Let $$\mu_m:=\frac{1}{||\nabla w_m||_{L^\infty(M)}}\to 0\quad\text{ as }\quad m\to\infty,$$ and $(x_m)_m\subset M$ be such that $$||\nabla w_m||_{L^\infty(M)}=|\nabla w_m(x_m)|.$$ Consider the domains $\displaystyle \Omega_m:=B_{ 0}\left(\frac{i_g (M)}{2\mu_m}\right)$, where $i_g(M)$ is the injectivity radius of $M$, and the rescaled quantities $$v_m(x):=w_m\left(\exp_{x_m}(\mu_m x)\right)\quad\text{and}\quad g_m(x):=\left(\exp_{x_m}^*g\right)(\mu_m x).$$ Clearly, $||\nabla v_m||_{L^\infty}\leq 1$ and $|\nabla v_m(0)|=1$. The $L^\infty$ bounds remain unchanged. In $(\Omega_m)_{m\geq 1}$, we have that $$\begin{array}{c} \Delta_{g_m}v_m+\mu_m^2H\left(\exp_{x_m}(\mu_m\cdot)\right)v_m+\sigma_m\mu_m^2\theta_3\left(\exp_{x_m}(\mu_m\cdot)\right)\\ \\ +\sigma_m\theta_1\left(\exp_{x_m}(\mu_m\cdot)\right)\langle\nabla v_m,Z\left(\exp_{x_m}(\mu_m\cdot)\right)\rangle^2\\ \\ +\mu_m\sigma_m\theta_2\left(\exp_{x_m}(\mu_m\cdot)\right)\langle\nabla v_m, Z\left(\exp_{x_m}(\mu_m\cdot)\right)\rangle=0 \end{array}$$ Note that $g_m\to\xi$ in $\mathcal{C}^2_{loc}({\mathbb{R}}^n).$ By standard elliptic theory, $(v_m)_m$ is bounded in $\mathcal{C}^{1,\eta}_{loc}({\mathbb{R}}^n)$, with $\eta\in (0,1)$. We may extract, up to a subsequence, $v_\infty=\lim_{m\to\infty}v_m$, $x_\infty=\lim_{m\to\infty}x_n$ and $\sigma_\infty:=\lim_{m\to\infty}\sigma_m$. From this is follows that $||\nabla v_\infty||_{L^\infty}=1$ and that the [*a priori* ]{} bounds (\[a priori b\]) become $$\label{bounds on v infinity} \inf_M\frac{-\sigma_{\infty}\theta_3}{H}\leq v_\infty\leq \sup_M\frac{-\sigma_{\infty}\theta_3}{H}.$$ Moreover, $v_\infty$ solves the limit equation $$\Delta v_\infty+\left(\partial_1 v_\infty\right)^2=0$$ in ${\mathbb{R}}^n$, where we have let $$\partial_1 v_\infty:=\sqrt{\sigma_\infty\theta_1(0)}\nabla v_\infty\cdot Z(x_0).$$ If $\sigma_\infty=0$, then $v_\infty$ is a bounded harmonic function, and thus a constant. Let us assume that $\sigma_\infty\not = 0$. Note that, for $\alpha\in{\mathbb{R}}$, $$\begin{array}{r l} \displaystyle \Delta v_\infty^{-\alpha} &\displaystyle =-\frac{\alpha}{v_\infty^{\alpha+1}}\Delta v_\infty-\frac{\alpha(\alpha+1)|\nabla v_\infty|^2}{v_\infty^{\alpha+2}}\\ &\displaystyle \leq\frac{\alpha|\nabla v_\infty|^2}{v_\infty^{\alpha+1}}\left(\sigma_\infty\theta_1(0)|Z(0)|^2-\frac{\alpha+1}{v_\infty}\right). \end{array}$$ This and (\[bounds on v infinity\]) imply that, for $\alpha$ sufficiently large, $v_\infty^{-\alpha}$ is subharmonic. We then apply Lemma \[lem: A1\] (see annex) to get that $v_\infty$ must be constant. Whichever the case, $\nabla v_\infty\equiv 0$ leads to a contradiction. The $\mathcal{C}^{1,\gamma}$ bound follows from an elliptic regularity argument. This ends the proof of Step 1. **Step 2:** We claim that $$\varepsilon_0\leq u_i(x)\leq u_{i+1}(x)\leq \psi(x)$$ for all $x\in M$ and all $i\leq 0$. We proceed by induction. We prove first that $$\label{inductive hyp} \forall\, i\geq 0,\quad u_i \text{ is a subsolution of } (E_{i+1}) \text{ and } u_i\leq \psi.$$ Note that $$\label{induction} (\ref{inductive hyp}) \Rightarrow u_i\leq u_{i+1}.$$ Indeed, let $x_0\in M$ be a maximum point of $u_i-u_{i+1}.$ Then $\nabla u_i(x_0)=\nabla u_{i+1}(x_0)$ and we can use the fact that $u_i$ is a subsolution of $(E_{i+1})$ and $u_{i+1}$ a solution of $(E_{i+1})$ to write that $$\Delta_g(u_i-u_{i+1})(x_0)+(h(x_0)+K)(u_i-u_{i+1})(x_0)\leq 0$$ which implies that $u_i(x_0)\leq u_{i+1}(x_0)$ since $\Delta_g(u_i-u_{i+1})(x_0)\geq 0$ and $h+K>0$. This proves (\[induction\]). We now prove (\[inductive hyp\]) by induction. For $i=0$, it follows from the choice of $\varepsilon_0$ we made. Assume that (\[inductive hyp\]) holds for some $i\geq 0$. We need to prove that $u_{i+1}$ is a subsolution of $(E_{i+2})$. It suffices to show that $$\begin{array}{c} \Delta_g u_{i+2}+(h+K)u_{i+2}+F(u_{i+1}(x),x)+\frac{\langle\nabla u_{i+2}, Y\rangle^2}{u_{i+1}^{q+3}}\\ +c\langle \nabla u_{i+2},Y\rangle\left(\frac{d}{u^2_{i+1}}+\frac{1}{u^{q+2}_{i+1}}\right)\leq \Delta_g u_{i+1}+(h+K)u_{i+1}+F(u_{i+1}(x),x)\\+\frac{\langle\nabla u_{i+1}, Y\rangle^2}{u_{i+1}^{q+3}} +c\langle \nabla u_{i+1},Y\rangle\left(\frac{d}{u^2_{i+1}}+\frac{1}{u^{q+2}_{i+1}}\right), \end{array}$$ since $u_{i+1}$ is defined as a solution of $(E_{i+1})$. This is equivalent to showing that $$\begin{array}{c} F(u_{i+1})+c\langle \nabla u_{i+1},Y\rangle\left(\frac{d}{u_{i+1}^2}+\frac{1}{u_{i+1}^{q+2}}\right)+\frac{\langle\nabla u_{i+1},Y\rangle^2}{u_{i+1}^{q+3}}\\ \leq F(u_{i})+c\langle\nabla u_{i+1},Y\rangle\left(\frac{d}{u_{i}^2}+\frac{1}{u_{i}^{q+2}}\right)+\frac{\langle\nabla u_{i+1},Y\rangle^2}{u_{i}^{q+3}}. \end{array}$$ And this is a consequence of (\[monotonicity of F\]) with $A(x)=\langle\nabla u_{i+1},Y\rangle$, since (\[induction\]) implies that $u_{i+1}\geq u_i$ by induction hypothesis. Thus, $u_{i+1}$ is a subsolution of $(E_{i+2})$. Finally, so as to check the last point, assume there exists $x_0\in M$ such that $u_{i+1}(x_0)>\psi(x_0)$ and that it corresponds to $\max_M\left(u_{i+1}(x)-\psi(x)\right).$ Since $\nabla u_{i+1}(x_0)=\nabla \psi (x_0)$ and $\Delta_g u_{i+1}(x_0)\geq \Delta_g\psi(x_0),$ we obtain that $$\Delta_g(u_{i+1}-\psi)(x_0)+(h+K)(u_{i+1}-\psi)(x_0)>0.$$ But $\psi$ is a supersolution for (\[EM\]), so we get that $$\begin{array}{c} 0<\Delta_g(u_{i+1}-\psi)(x_0)+(h(x_0)+K)(u_{i+1}-\psi)(x_0)\\ \leq F(\psi(x_0),x_0)-F(u_i(x_0),x_0)-\langle\nabla\psi(x_0),Y(x_0)\rangle^2\left(\frac{1}{u_i^{q+3}}-\frac{1}{\psi^{q+3}}\right)(x_0)\\ -\langle\nabla\psi(x_0),Y(x_0)\rangle\left(\frac{d}{u_i^2}-\frac{d}{\psi^2}+\frac{1}{u_i^{q+2}}-\frac{1}{\psi^{q+2}}\right)(x_0). \end{array}$$ Thanks to (\[monotonicity of F\]) with $A(x)=\langle\nabla\psi(x),Y(x)\rangle$ and to the induction hypothesis which says that $u_i\leq\psi$, we obtain a contradiction. This wraps up the induction argument and the proof of Step 2. **Step 3:** The sequence $(u_i)_{i\in\mathbb{N}}$ is uniformly bounded in $\mathcal{C}^1(M)$. Thanks to Step 2, we know that $(u_i)_{i\in\mathbb{N}}$ is an increasing sequence bounded by $\psi$. Thus there exists $u\in\mathcal{C}^0(M)$ such that $u_i\to u_0$ in $\mathcal{C}^0(M).$ Assume by contradiction that exists a subsequence $(u_{\phi(m)})_{m\in N}$ such that $||\nabla u_{\phi(m)}||_{L^\infty}\to\infty.$ Let $$\displaystyle \mu_m:=\frac{1}{||\nabla u_{\phi(m)}||_{L^\infty}}$$ and let $(x_m)_m\subset M$ be such that $$|\nabla u_{\phi(m)}(x_m)|=||\nabla u_{\phi(m)}||_{L^\infty}.$$ Consider the domains $\displaystyle \Omega_m=B_{0}\left(\frac{i_g M}{2\mu_m}\right)$ and the rescaled quantities $$v_m(x):=u_{\phi(m)}\left(\exp_{x_m}(\mu_m x)\right)\quad\text{ and }\quad g_m(x):=\left(\exp_{x_m}^* g\right)(\mu_m x)$$ in $\Omega_m$. We get $$\label{eq: scaling in exist thm} \begin{array}{c} \Delta_{g_m}v_m+\mu_m^2(h\left(\exp_{x_m}(\mu_m \cdot)\right)+K)v_m\left(\exp_{x_m}(\mu_m \cdot)\right)\\ \displaystyle +\mu_m^2F\left(u_{\phi(m)-1}\left(\exp_{x_m}(\mu_m \cdot)\right)\right) \displaystyle +\frac{\langle\nabla v_m,Y\left(\exp_{x_m}(\mu_m \cdot)\right)\rangle^2}{u_{\phi(m)-1}^{q+3}\left(\exp_{x_m}(\mu_m \cdot)\right)}\\ \displaystyle +\mu_m\langle\nabla v_m, Y\left(\exp_{x_m}(\mu_m \cdot)\right)\rangle c\left(\exp_{x_m}(\mu_m \cdot)\right)\Big[\frac{d\left(\exp_{x_m}(\mu_m \cdot)\right)}{u_{\phi(m)-1}^2\left(\exp_{x_m}(\mu_m \cdot)\right)}\\ \displaystyle +\frac{1}{u_{\phi(m)-1}^{q+2}\left(\exp_{x_m}(\mu_m \cdot)\right)}\Big]=0 \end{array}$$ with $(v_m)_{m\in N}$ bounded in $L^\infty$, $||\nabla v_m||_{L^\infty}=1$ and $\varepsilon_0\leq v_m$. By the Sobolev embedding theorem and standard elliptic regularity, there exists a smooth positive limit $v_\infty$ of $(v_m)_{m\in N}$, up to a subsequence. Recall that $(u_i)_{i\in N}$ converges everywhere, so $u_{\phi(m)-1}(\mu_m x)\to v_\infty(x)$ in $M$. By taking $m\to\infty$ in (\[eq: scaling in exist thm\]), $$\Delta v_\infty+\frac{\left(\nabla v_\infty\cdot Y(0)\right)^2}{v_\infty^{q+3}}=0.$$ Note also that $$\Delta v_\infty^{-\alpha}\leq \frac{\alpha|\nabla v_\infty|^2}{v_\infty^{\alpha+2}}\left(\frac{|Y(0)|^2}{v_\infty^{q+2}}-(\alpha+1)\right).$$ For $\alpha$ large enough, $v_\infty^{-\alpha}$ is subharmonic. Using Lemma \[lem: A1\] (see Annex), we find that $v_\infty$ is constant, which contradicts the fact that $||\nabla v_\infty||_{L^\infty}=1.$ This ends the proof of Step 3. Since $(u_i)_{i\in N}$ is uniformly bounded in $\mathcal{C}^1$, we conclude by standard elliptic theory that its limit $u$ is a positive smooth function solving equation (\[EM\]). This ends the proof of the theorem. The solution constructed in the previous proof is uniquely determined as the pointwise limit of $(u_i)_{i\in N}$, where each $u_i$ is the unique solution of (\[eq: the Ei eqs\]). Furthermore, the solution is minimal among all supersolutions (including solutions) of (\[EM\]) with values between $\varepsilon_0$ and $\sup_M\psi$. These bounds were explicitly used in the inductive argument. By construction, $u\leq\psi$, where $\psi$ is the supersolution fixed at the very beginning. Note that the constant $K$ appearing in (\[eq: the Ei eqs\]) depend on $\sup_M\psi$ and $\varepsilon_0$. We would obtain the same iteration were we to use another supersolution $\tilde{\psi}$ and the same $K$, given that $\varepsilon_0<\tilde{\psi}<\sup_M\psi$. Therefore, $u$ is smaller than any supersolution between $\varepsilon_0$ and $\sup_M\psi$. As an immediate consequence of the minimality discussed above, the solutions we found corresponding to different functions $a$ are ordered. Let $0<a<\tilde{a}$ be two functions, and assume that the equation associated to $\tilde{a}$ admits a solution $\tilde{u}$. Then $\tilde{u}$ is a supersolution for (\[EM\]) corresponding to $a$, and by the previous proof we find a solution $u\leq\tilde{u}$. Moreover, given that $\tilde{u}$ may be viewed as a supersolution to all (\[EM\]) with $a\leq\tilde{a}$, we obtain a monotonicity of $u$ in $a$: for $a_1\leq a_2\leq \tilde{a}$, then $u_1\leq u_2\leq \tilde{u}$. Finally, the solution $u$ is stable, as defined in the following lemma. \[lem weak stability\] The operator $L$ resulting from the linearization of (\[EM\]) at the minimal solution $u$ admits a real, simple eigenvalue $\lambda_0\geq 0$ such that $$\begin{array}{c} \displaystyle L\varphi_0=\Delta_g\varphi_0+\Big[h-(q-1)fu^{q-2}+(q+1)au^{-q-2}-bu^{-2}\\ -(q+3)\frac{\langle\nabla u,Y\rangle^2}{u^{q+4}}-c\langle\nabla u,Y\rangle\left(\frac{2d}{u^3}+\frac{q+2}{u^{q+3}}\right)\Big]\varphi_0\\+\langle\nabla\varphi_0,Y\rangle\Big[c\left(\frac{d}{u^2}+\frac{1}{u^{q+2}}\right)+\frac{2\langle\nabla u,Y\rangle}{u^{q+3}}\Big]\\=\lambda_0\varphi_0, \end{array}$$ where $\varphi_0$ is the corresponding positive eigenfunction. Furthermore, if $\lambda\in {\mathbb{C}}$ is any other eigenvalue, then $Re(\lambda)\geq \lambda_0$. Notice that $L$ is nonsymmetric; moreover, one may find a large enough constant $K$ such that $$\begin{array}{c} h-(q-1)fu^{q-2}+(q+1)au^{-q-2}-bu^{-2}-(q+3)\frac{\langle\nabla u,Y\rangle^2}{u^{q+4}}\\ -c\langle\nabla u,Y\rangle\left(\frac{2d}{u^3}+\frac{q+2}{u^{q+3}}\right)+K\geq 0. \end{array}$$ According to ([@Eva], Section 6.5, Theorem 1) there exists a real, positive eigenvalue $\lambda_K>0$ of $L+K$, such that any other complex eigenvalue of $L+K$ has a greater real part. Consequently, the operator $L$ admits a minimal real eigenvalue $\lambda_0>-K$. We now assume that $\lambda_0<0$. Let $u_\delta:=u_0-\delta\varphi_0$, $\delta>0$. By taking $\delta$ small enough, we may ensure that $\varepsilon_0< u_\delta$. Then $$\begin{array}{c} \displaystyle \Delta_g u_\delta+hu_\delta-fu_\delta^{q-1}-\frac{a}{u_\delta^{q+1}}+\frac{b}{u_\delta}+\frac{\langle\nabla u_\delta,Y\rangle^2}{u_\delta^{q+3}}+c\langle\nabla u_\delta, Y\rangle\left(\frac{d}{u_\delta^2}+\frac{1}{u_\delta^{q+2}}\right)\\ \\ \displaystyle =-\delta\lambda_0\varphi_0+o(\delta). \end{array}$$ This implies that $\varepsilon_0< u_\delta<u$ is a supersolution of (\[EM\]), which cannot be the case, as discussed above. Thus, $\lambda_0\geq 0.$ A priori estimates on solutions of the scalar equation in low dimensions ======================================================================== The $\mathcal{C}^1$ estimates obtained in this section will play a crucial role in the proof of Theorem \[thm 1\], which is based on a fixed-point argument. This section is devoted to the proof of the following theorem: \[theo stability eq\] Let $(M,g)$ be a closed Riemannian manifold of dimension $n=3,4,5$. Let $\frac{1}{2}<\eta<1$ and $0<\alpha<1$. Let $a$, $b$, $c$, $d$, $f$, $h$ be smooth functions on $M$, let $Y$ be a smooth vector field on the $M$. For any $0<\theta<T$, there exists $S_{\theta,T}$ such that any smooth positive solution $u$ of (\[EM\]) with parameters within $$\begin{array}{c} \mathcal{E}_{\theta,T}:=\Big\{(f,a,b,c,d,h,Y),\quad f\geq \theta,\quad a\geq \theta, \\ \quad ||f||_{\mathcal{C}^{1,\eta}}\leq T,\quad ||a||_{\mathcal{C}^{0,\alpha}},||b||_{\mathcal{C}^{0,\alpha}}, ||c||_{\mathcal{C}^{0,\alpha}}, ||d||_{\mathcal{C}^{0,\alpha}}, ||h||_{\mathcal{C}^{0,\alpha}}, ||Y||_{\mathcal{C}^{0,\alpha}}\leq T\Big\}, \end{array}$$ satisfies $||u||_{\mathcal{C}^2}\leq S_{\theta,T}$. For the sake of clarity, we’ve taken the bounds on the parameters to be of the form $\theta$ and $T$. They can of course be individually specified. We proceed by contradiction. We assume the existence of a sequence $(u_\alpha)_{\alpha\in{\mathbb{N}}}$ of smooth positive solutions of equations ($EL_\alpha$) $$\label{eq: EL alpha} \begin{array}{c} \Delta_g u_\alpha+ h_\alpha u_\alpha-f_\alpha u_\alpha^{q-1}- \frac{a_\alpha}{u_\alpha^{q+1}}+\frac{b_\alpha}{u_\alpha}+\frac{\langle\nabla u_\alpha, Y_\alpha\rangle^2}{u_\alpha^{q+3}}\\ +c_\alpha\langle\nabla u_\alpha,Y_\alpha\rangle\left[\frac{d_\alpha}{u_\alpha^2}+\frac{1}{u_\alpha^{q+2}}\right]=0 \end{array}$$ with parameters $(a_\alpha, b_\alpha, c_\alpha, d_\alpha, f_\alpha,h_\alpha, Y_\alpha)$ in $\mathcal{E}_{\theta,T}$ such that $$\label{est: explosion} ||u_\alpha||_{\mathcal{C}^1(M)}\to\infty,\quad\text{ as }\alpha\to\infty.$$ A *concentration point* is the limit in $M$ of any sequence $(x_\alpha)_\alpha$ where (\[est: explosion\]) holds. Note that a $\mathcal{C}^1$-bound on $(u_\alpha)_\alpha$ automatically gives a $\mathcal{C}^2$-bound by elliptic theory. Note also that, up to a subsequence, all parameters converge in $\mathcal{C}^0(M).$ Let $m_\alpha=\min_{x\in M}u_\alpha(x)=u_\alpha(x_\alpha)>0.$ Since $\nabla u_\alpha(x_\alpha)=0$ and since $\Delta_g u_\alpha(x_\alpha)\leq 0$, we have thanks to (\[eq: EL alpha\]) that $$h_\alpha(x_\alpha)m_\alpha-f_\alpha(x_\alpha)m_\alpha^{q-1}-\frac{a_\alpha(x_\alpha)}{m_\alpha^{q+1}}+\frac{b_\alpha(x_\alpha)}{m_\alpha}\geq 0.$$ Thanks to the definition of $\mathcal{E}_{\theta,T},$ it follows that $$\frac{\theta}{m_\alpha^{q+1}}\leq T(m_\alpha+\frac{1}{m_\alpha}).$$ Then there exists $\varepsilon=\varepsilon(\theta,T,n)>0$ such that $m_\alpha\geq \varepsilon$, meaning that $$\label{varepsilon} u_\alpha>\varepsilon>0\quad \text{ for all } x\in M \text{ and all } \alpha.$$ The scheme of the proof follows the work of Druet and Hebey [@DruHeb], with the added difficulty consisting in the gradient terms in (\[eq: EL alpha\]). Concentration points -------------------- The first step in finding *a priori* estimates for $(u_\alpha)_\alpha$ is to find all potential concentration points. \[lem: former lemma 2\] There exists $N_\alpha\in {\mathbb{N}}^*$ and $\displaystyle \mathcal{S}_\alpha:=\left(x_{1,\alpha},\dots x_{N_\alpha, \alpha}\right)$ a set of critical points of $(u_\alpha)_\alpha$ such that $$\label{est: 1 of former lemma 1} d_g(x_{i,\alpha},x_{j,\alpha})^{\frac{n-2}{2}}u_\alpha(x_{i,\alpha})\geq 1$$ for all $i,j\in\{1,\dots,N_\alpha\}$, $i\not =j$, and $$\label{est: add fact} \left(\min_{i=1,\dots, N_\alpha}d_g(x_{i,\alpha},x)\right)^{\frac{n-2}{2}}u_\alpha(x)\leq 1$$ for all critical points of $u_\alpha$ and such that there exists $C_1>0$ such that $$\label{est: initial estimate}\left(\min_{i=1,\dots N_\alpha} d_g(x_{i,\alpha},x)\right)^{\frac{n-2}{2}}\left(u_\alpha(x)+\left|\frac{\nabla u_\alpha(x)}{u_\alpha(x)}\right|^{\frac{n-2}{2}}\right)\leq C_1$$ for all $x\in M$ and all $\alpha\in {\mathbb{N}}$. Estimate (\[est: initial estimate\]) implies that any concentration point of $(u_\alpha)_{\alpha\in N}$ calls for the existence of a sequence $(x_\alpha)_\alpha\subset (\mathcal{S}_\alpha)_\alpha$ converging to it. We shall focus our analysis in the neighbourhood of $S_\alpha$ as $\alpha\to\infty$ to find concentration points. In order to choose $(S_\alpha)_\alpha$, we make use of a simple result describing any sufficiently regular function on a compact manifold. \[lem: former lemma 1\] Let $u$ be a positive real-valued $\mathcal{C}^2$ function defined in a compact manifold $M$. Then there exists $N\in {\mathbb{N}}^*$ and $\left(x_1,\, x_2,\dots x_N\right)$ a set of critical points of $u$ such that $$d_g(x_i,x_j)^{\frac{n-2}{2}}u(x_i)\geq 1$$ for all $i,\,j\in\{1, \dots, N\}$, $i\not= j$, and $$\left(\min_{i=1,\dots, N}d_g(x_i,x)\right)^{\frac{n-2}{2}}u(x)\leq 1$$ for all critical points $x$ of $u$. The lemma and its proof may be found in Druet and Hebey’s paper [@DruHeb]. Applying this lemma to $(u_\alpha)$ gives $N_\alpha$ and $\mathcal{S}_\alpha$ as in Lemma \[lem: former lemma 2\] such that (\[est: 1 of former lemma 1\]) and (\[est: add fact\]) hold. We need to prove (\[est: initial estimate\]). Proceeding by contradiction, assume that there exists a sequence $(x_\alpha)_\alpha$ such that $$\label{est: contradiction initial estimate}\left(\min_{i=1,\dots N_\alpha} d_g(x_{i,\alpha},x_\alpha)\right)^{\frac{n-2}{2}}\left(u_\alpha(x_\alpha)+\left|\frac{\nabla u_\alpha(x_\alpha)}{u_\alpha(x_\alpha)}\right|^{\frac{n-2}{2}}\right)\to\infty$$ as $\alpha\to\infty$, where $$\label{contr} \begin{array}{c} \displaystyle \left(\min_{i=1,\dots N_\alpha} d_g(x_{i,\alpha},x_\alpha)\right)^{\frac{n-2}{2}}\left(u_\alpha(x_\alpha)+\left|\frac{\nabla u_\alpha(x_\alpha)}{u_\alpha(x_\alpha)}\right|^{\frac{n-2}{2}}\right)\\ \\ \displaystyle =\sup_{x\in M}\left(\min_{i=1,\dots N_\alpha} d_g(x_{i,\alpha},x)\right)^{\frac{n-2}{2}}\left(u_\alpha(x)+\left|\frac{\nabla u_\alpha(x)}{u_\alpha(x)}\right|^{\frac{n-2}{2}}\right). \end{array}$$ Denote $$\nu_\alpha^{1-\frac{n}{2}}:=u_\alpha(x_\alpha)+\left|\frac{\nabla u_\alpha(x_\alpha)}{u_\alpha(x_\alpha)}\right|^{\frac{n-2}{2}}$$ and see that (\[est: contradiction initial estimate\]) translates to $$\label{est: distance to s alpha} \frac{d_g(x_\alpha, \mathcal{S}_\alpha)}{\nu_\alpha}\to\infty\quad\text{as}\quad \alpha\to\infty.$$ Also, since $M$ is compact, $$\label{nu goes to zero} \nu_\alpha\to 0 \text{ as }\alpha\to\infty.$$ Consider the rescaled quantities $$v_\alpha(x):=\nu_\alpha^{\frac{n-2}{2}}u_\alpha\left(\exp_{x_\alpha}(\nu_\alpha x)\right)\quad\text{and}\quad g_\alpha(x):=\left(\exp_{x_\alpha}^* g\right)(\nu_\alpha x)$$ defined in $\Omega_\alpha:=B_0\left(\frac{\delta}{\nu_\alpha}\right)$, with $ 0<\delta<\frac{1}{2}i_g(M).$ We emphasize that, for any $R>0$, $$\label{est: size of v alpha and co} \limsup_{\alpha\to\infty}\sup_{B_0(R)} \left(v_\alpha+\left|\frac{\nabla v_\alpha}{v_\alpha}\right|^{\frac{n-2}{2}}\right) =1$$ thanks to (\[contr\]) and (\[est: distance to s alpha\]). However, unlike $(u_\alpha)_\alpha$, the sequence $(v_\alpha)_\alpha$ is not necessarily bounded from below by a small positive constant $\varepsilon$. Instead, we deduce from (\[est: size of v alpha and co\]) that $$|\nabla \ln v_\alpha|\leq 1+o(1)\quad\text{ in } B_0(R)$$ for all $R>0$ so that $$\label{size of v alpha} v_\alpha(0)e^{-2|x|}\leq v_\alpha(x)\leq v_\alpha(0)e^{2|x|}\quad\text{ in } B_0(R)$$ for all $R>0$ as soon as $\alpha$ is large enough. We rewrite (\[eq: EL alpha\]) in $\Omega_\alpha$ as $$\label{eq: Ev alpha eqs} \begin{array}{c} \Delta_{g_\alpha}v_\alpha = f_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)v_\alpha^{q-1}+\nu_\alpha^{\frac{n+2}{2}}\frac{a_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}{u_\alpha^{q+1}\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)} \\ -\nu_\alpha^2 h_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)v_\alpha-\nu_\alpha^{\frac{n+2}{2}}\frac{b_\alpha \left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}{u_\alpha \left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}\\ -\frac{\langle\nabla v_\alpha,Y_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)\rangle^2}{v_\alpha}\frac{1}{u_\alpha^{q+2}\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}\\ -\nu_\alpha c_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)\langle\nabla v_\alpha,Y_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)\rangle\Big[\frac{d_\alpha \left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}{u_\alpha^2\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}\\ +\frac{1}{u_\alpha^{q+2}\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}\Big] \end{array}$$ Note that the metrics $g_\alpha\to\xi$ in $\mathcal{C}^2_{loc}$ as $\alpha\to\infty$. Because of (\[varepsilon\]) and (\[est: size of v alpha and co\]), the right hand side is bounded, so by standard elliptic theory there exists up to a subsequence a $\mathcal{C}^1$ limit $U:=\lim_{\alpha\to\infty}v_\alpha$ and $x_0:=\lim_{\alpha\to\infty}x_\alpha$. **First case:** If $u_\alpha(x_\alpha)\to\infty$ as $\alpha\to\infty$, then we can pass to the limit in equation (\[eq: Ev alpha eqs\]) to get $$\Delta U=f(x_0)U^{q-1}$$ in ${\mathbb{R}}^n$. The exact form of these solutions is found in a paper by Caffarelli, Gidas and Spruck [@CaffGidSpr]: $$U(x)=\left(1+\frac{f(x_0)|x-y_0|^2}{n(n-2)}\right)^{1-\frac{n}{2}}$$ with $y_0\in {\mathbb{R}}^n$ the unique maximum point of the function. There exist therefore $(y_\alpha)_\alpha$ local maxima of $(u_\alpha)_\alpha$ such that $$\label{est: blow up analysis, distances} d_g(x_\alpha,y_\alpha)=O(\nu_\alpha)$$ and $$\label{est lim 1} \nu_\alpha^{\frac{n-2}{2}}u_\alpha(y_\alpha)\to 1\quad \text{ as }\quad \alpha\to\infty.$$ Since $(y_\alpha)_\alpha$ are critical points, (\[est: add fact\]) implies that $$d_g(\mathcal{S}_\alpha, y_\alpha)^{\frac{n-2}{2}}u_\alpha(y_\alpha)\leq 1$$ for all $\alpha\in {\mathbb{N}}$, so by (\[est lim 1\]), $\displaystyle d_g(\mathcal{S}_\alpha,y_\alpha)=O(\nu_\alpha)$; together with (\[est: blow up analysis, distances\]), this leads to $\displaystyle d_g(\mathcal{S}_\alpha,x_\alpha)=O(\nu_\alpha)$, which contradicts (\[est: distance to s alpha\]). **Second case:** Assume that, up to a subsequence, $u_\alpha(x_\alpha)\to l<\infty$. From (\[nu goes to zero\]) we deduce that $|\nabla u_\alpha (x_\alpha)|\to\infty$ and that $v_\alpha(0)\to 0$ as $\alpha\to\infty$. Let us set $$w_\alpha(x):=\frac{v_\alpha(x)}{v_\alpha(0)}.$$ These functions are bounded from below, since by (\[varepsilon\]), $$\label{est w} w_\alpha(x)=\frac{u_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}{u_\alpha(x_\alpha)}\geq\frac{\varepsilon}{l}+o(1)$$ in $B_0(R)$ for all $R>0$. Moreover, (\[size of v alpha\]) implies that $$w_\alpha(x)\leq e^{2|x|}$$ in $B_0(R)$ for $\alpha$ large. Multiply (\[eq: Ev alpha eqs\]) by $v_\alpha(0)^{-1}$ to get $$\begin{array}{r l} \displaystyle \Delta_g w_\alpha= &\displaystyle f_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)w_\alpha^{q-1}v_\alpha^{q-2}(0)+\nu_\alpha^2\frac{a\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}{u_\alpha^{q+1}\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)u_\alpha(x_\alpha)} \\ & \displaystyle -\nu_\alpha^2h_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)w_\alpha-\nu_\alpha^2\frac{b_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}{u_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)u_\alpha(x_\alpha)}\\ & \displaystyle-\frac{\langle\nabla w_\alpha,Y_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)\rangle^2}{w_\alpha^{q+2}}\frac{1}{u_\alpha(x_\alpha)^{q+2}}\\ &\displaystyle -\nu_\alpha c_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)\langle\nabla w_\alpha,Y_\alpha\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)\rangle\Big[\frac{d_\alpha \left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}{u_\alpha^2\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}\\ &\displaystyle +\frac{1}{u_\alpha^{q+2}\left(\exp_{x_\alpha}(\nu_\alpha\cdot)\right)}\Big]. \end{array}$$ By standard elliptic theory, we find that there exists $w:=\lim_{\alpha\to\infty}w_\alpha$ in $\mathcal{C}^1$ solving: $$\Delta w=-\frac{1}{l^{q+2}}\frac{\langle\nabla w, Y(x_0)\rangle^2}{w^{q+3}}$$ in ${\mathbb{R}}^n$. Note that, since $w\geq \frac{\varepsilon}{l}$ by (\[est w\]), $$\Delta w^{-\alpha}\leq \alpha\frac{|\nabla w|^2}{w^{\alpha+2}}\left[\frac{|Y(x_0)|^2}{\varepsilon^{q+2}}-(\alpha+1)\right],$$ so $w^{-\alpha}$ is subharmonic for $\alpha$ large. By applying Lemma \[lem: A1\] (see the Annex), we deduce that $w$ is constant, which in turn implies that $U=0$, and so $\nabla U=0$. This implies that $$\lim_{\alpha\to\infty}\nu_\alpha\frac{\nabla u_\alpha(x_\alpha)}{u_\alpha(x_\alpha)}=0,$$ as it contradicts the choice of $\nu_\alpha$ above, which may be rewritten as $$\nu_\alpha^\frac{n-2}{2}\left(u_\alpha(x_\alpha)+\left|\frac{\nabla u_\alpha(x_\alpha)}{u_\alpha(x_\alpha)}\right|\right)=1,$$ since we are in the case where $\nu_\alpha^{\frac{n-2}{2}}u_\alpha(x_\alpha)=v_\alpha(0)\to 0$ as $\alpha\to 0.$ The following is a Harnack-type inequality. It holds whenever an estimate like (\[est: initial estimate\]) is verified, that is when there exists a constant $C_2$ and a sequence $(x_\alpha,\rho_\alpha)_\alpha$ such that $$\label{est: for Harnack} d_g(x_\alpha,x)^{\frac{n-2}{2}}\left[u_\alpha(x)+\left|\frac{\nabla u_\alpha(x)}{u_\alpha(x)}\right|^{\frac{n-2}{2}}\right]\leq C_2,\quad\forall x\in B_{x_\alpha}(7\rho_\alpha).$$ \[lem: former lemma 3\] Let $(x_\alpha, \rho_\alpha)_\alpha$ be a sequence such that (\[est: for Harnack\]) holds. Then there exists a constant $C_3>1$ such that for any sequence $0<s_\alpha\leq\rho_\alpha$, we get $$s_\alpha||\nabla u_\alpha||_{L^\infty(\Omega_\alpha)}\leq C_3\sup_{\Omega_\alpha}u_\alpha\leq C_3^2\inf_{\Omega_\alpha}u_\alpha,$$ where $\Omega_\alpha=B_{x_\alpha}(6s_\alpha)\backslash B_{x_\alpha}(\frac{1}{6}s_\alpha).$ Estimate (\[est: for Harnack\]) implies that $$\label{e1} \left|\frac{\nabla u_\alpha(x)}{u_\alpha(x)}\right|\leq C_2 d_g(x_\alpha,x)^{-1}$$ in $\Omega_\alpha,$ and therefore $$\label{e2} s_\alpha|\nabla\ln u_\alpha(x)|\leq 6C_2$$ in $\Omega_\alpha$. Taking $C_3\geq 6C_2$, we get the first inequality from (\[e1\]). Then, from (\[e2\]) and from the fact that the domain is an annulus $\Omega_\alpha=B_{x_\alpha}(6s_\alpha)\backslash B_{x_\alpha}(\frac{1}{6}s_\alpha)$, we estimate that $$\sup_{\Omega_\alpha}\ln u_\alpha- \inf_{\Omega_\alpha}\ln u_\alpha\leq l_\alpha(\Omega_\alpha)||\nabla \ln u_\alpha||_{L^\infty(\Omega_\alpha)}\leq 42C_2,$$ where $l_\alpha(\Omega_\alpha)$ is the infimum of the length of a curve in $\Omega_\alpha$ drawn between a maximum and a minimum of $u_\alpha$. Equivalently $$\sup_{\Omega_\alpha} u_\alpha\leq e^{42C_2}\inf_{\Omega_\alpha} u_\alpha,$$ so it suffices to take $C_3=e^{42C_2}$. Local blow-up analysis ---------------------- In order to show that $u_\alpha$ is bounded in $\mathcal{C}^1$, we define a *blow-up sequence* $(x_\alpha)_\alpha$ with $(\rho_\alpha)_\alpha$ as follows: let $(x_\alpha)_\alpha$ be critical points of $(u_\alpha)_\alpha$ and $(\rho_\alpha)_\alpha$ positive numbers such that they verify the following three conditions: $$\label{est: blow up no 1} 0<\rho_\alpha<\frac{1}{7}i_g(M),$$ $$\label{est: blow up no 2} \rho_\alpha^{\frac{n-2}{2}}\sup_{B_{x_\alpha}(6\rho_\alpha)}u_\alpha\to\infty,$$ and $$\label{est: blow up no 3} d_g(x_\alpha,x)^{\frac{n-2}{2}}\left[u_\alpha(x)+\left|\frac{\nabla u_\alpha(x)}{u_\alpha(x)}\right|^{\frac{n-2}{2}}\right]\leq C_2\quad\forall x\in B_{x_\alpha}(7\rho_\alpha),$$ where $C_2$ is a constant. In the rest of the section, we denote $$\mu_\alpha^{1-\frac{n}{2}}:=u_\alpha(x_\alpha).$$ The limit as $\alpha\to \infty$ of a blow-up sequence is a concentration point, as seen from (\[est: blow up no 2\]). Any sequence $(x_\alpha)_\alpha\subset (S_\alpha)_\alpha$ qualifies as a blow-up sequence as soon as (\[est: blow up no 2\]) is verified. In this case, $(\rho_\alpha)_\alpha$ can be chosen as $$\rho_\alpha:=\min\left(\frac{1}{7}i_g(M),\frac{1}{2}\min_{1\leq i<j\leq N_\alpha}d_g(x_{i,\alpha},x_{j,\alpha})\right)$$ and $C_2=C_1$. Given any blow-up sequence, the following proposition gathers the central results of our local analysis for the reader’s convenience: namely, it states the exact asymptotic profile of $(u_\alpha)_\alpha$ at distance $(\rho_\alpha)_\alpha$ of $(x_\alpha)_\alpha$ and it gives sharp pointwise asymptotic estimates on balls of radius $\rho_\alpha$. This is the result we shall point to whenever we want to describe the local asymptotic behaviour of $(u_\alpha)_\alpha$ around a concentration point corresponding to local maximum points $x_\alpha$. Note that in this case $\nabla u_\alpha(x_\alpha)=0$. \[prop\] Let $(x_\alpha)_\alpha$ and $(\rho_\alpha)_\alpha$ be a blow-up sequence. Then there exists $C_4>0$ such that $$u_\alpha(x)+d_g(x_\alpha,x)|\nabla u_\alpha(x)|\leq C_4\mu^{\frac{n-2}{2}}_\alpha d_g(x_\alpha,x)^{2-n}$$ for all $x\in B_{x_\alpha}(6\rho_\alpha)\backslash\{x_\alpha\}.$ Moreover, we see that up to a subsequence, the asymptotic profile of $(u_\alpha)_\alpha$ is $$u_\alpha(x_\alpha)\rho^{n-2}_\alpha u_\alpha(\exp_\alpha(\rho_\alpha x))\to\frac{R_0^{n-2}}{|x|^{n-2}}+H(x)$$ in $C^2_{loc}(B_0(5)\backslash\{0\})$, where $H$ is some harmonic function in $B_0(5)$ satisfying $H(0)=0.$ Here $R_0^2=\frac{n(n-2)}{f(x_0)}$ where $x_0=\lim_{\alpha\to\infty} x_\alpha$. The proof of this proposition is the subject of this section. It will follow from Lemma \[lem: former lemma 6\] and Lemma \[lem: former lemma 7\] below. We first describe the asymptotic profile at distance $(\mu_\alpha)_\alpha$ of $(x_\alpha)_\alpha$ as $\alpha\to\infty$ of any blow-up sequence. \[lem: former lemma 4\] Let $(x_\alpha)_\alpha$ with $(\rho_\alpha)_\alpha$ be a blow-up sequence. We have $$\label{est: estimate of old lemma 4} \mu_\alpha^{\frac{n-2}{2}}u_\alpha\left(\exp_{x_\alpha}(\mu_\alpha x)\right)\to\left(1+\frac{f(x_0)|x|^2}{n(n-2)}\right)^{1-\frac{n}{2}}$$ in $\mathcal{C}^1_{loc}({\mathbb{R}}^n)$ as $\alpha\to\infty$, with $\mu^{1-\frac{n}{2}}_\alpha:=u_\alpha(x_\alpha)$ and $x_0:=\lim_{\alpha\to\infty}x_\alpha$, up to a subsequence. The proof involves similar arguments to the ones used for Lemma $\ref{lem: former lemma 2}$. Let $y_\alpha\in B_{x_\alpha}(6\rho_\alpha)$ be such that $$u_\alpha(y_\alpha)+\left|\frac{\nabla u_\alpha(y_\alpha)}{u_\alpha(y_\alpha)}\right|^{\frac{n-2}{2}}=\sup_{B_{x_\alpha}(6\rho_\alpha)}\left(u_\alpha(x)+\left|\frac{\nabla u_\alpha(x)}{u_\alpha(x)}\right|^{\frac{n-2}{2}}\right)$$ and let $$\nu_\alpha^{1-\frac{n}{2}}:=u_\alpha(y_\alpha)+\left|\frac{\nabla u_\alpha(y_\alpha)}{u_\alpha(y_\alpha)}\right|^{\frac{n-2}{2}}.$$ Conditions (\[est: blow up no 2\]) and (\[est: blow up no 3\]) imply that $$\frac{\rho_\alpha}{\nu_\alpha}\to \infty$$ and $$d_g(x_\alpha,y_\alpha)\leq C_2^{\frac{2}{n-2}}\nu_\alpha.$$ It follows that the coordinates of $y_\alpha$ in the exponential chart around $x_\alpha$ defined as $\tilde{y}_\alpha:=\nu^{-1}\exp^{-1}_{x_\alpha}(y_\alpha)$ are bounded by $C_2^{\frac{2}{n-2}}$. Up to a subsequence, we may choose a finite limit $\tilde{y}_0:=\lim_{\alpha\to\infty}\tilde{y}_\alpha$. We denote $$v_\alpha(x)=\nu_\alpha^{\frac{n-2}{2}}u_\alpha\left(\exp_{x_\alpha}(\nu_\alpha x)\right)\quad\text{ and}\quad g_\alpha(x)=\left(\exp^*_{x_\alpha}g\right)\left(\exp_{x_\alpha}(\nu_\alpha x)\right)$$ for $\displaystyle x\in\Omega_\alpha:=B_0\left(\frac{\rho_\alpha}{\nu_\alpha}\right).$ As before, $g_\alpha\to\xi$ in $\mathcal{C}^2_{loc},$ $v_\alpha=O(1),$ and $\left|\frac{\nabla v_\alpha}{v_\alpha}\right|=O(1)$. By applying the same analysis as in the proof of Lemma $\ref{lem: former lemma 2}$, we get that, up to passing to a subsequence, there exists $U:=\lim_{\alpha\to\infty}v_\alpha$ in $\mathcal{C}^1_{loc}({\mathbb{R}}^n)$, with $x_0:=\lim_{\alpha\to\infty}x_\alpha$, $$\Delta U= f(x_0) U^{q-1}.$$ where $$U(x)=\left(1+\frac{f(x_0)|x-\tilde{y_0}|^2}{n(n-2)}\right)^{1-\frac{n}{2}}.$$ We know that $x_\alpha$ are local maxima for $u_\alpha$, so both $0$ and $\tilde{y}_0$ are maxima of $U$. However, since $U$ admits a unique maximum, we conclude that $\tilde{y}_0=0$. We recall the aim of this section is to show that concentration points do not exist for the system (\[systemshort\]). So far, we have obtained a pointwise estimate (\[est: initial estimate\]) that holds everywhere on $M$ and an asymptotic profile in the neighbourhood of $x_\alpha$, a blow-up sequence; we aim to also find estimates around $x_\alpha$. We defined $(\rho_\alpha)_\alpha$ as the quantity describing the sphere of dominance of the blow-up sequence $(x_\alpha)_\alpha$. However, the influence of other blow-up sequences may be felt earlier. Let $\varphi_\alpha : (0, \rho_\alpha)\to {\mathbb{R}}^+$ be the average of $u_\alpha$ defined as $$\varphi_\alpha(r) :=\frac{1}{|\partial B_{x_\alpha}(r)|_g}\int_{\partial B_{x_\alpha}(r)} u_\alpha d\sigma_g.$$ It follows from Lemma \[lem: former lemma 4\] that $$\label{est: former lemma 4 but for averages} (\mu_\alpha r)^{\frac{n-2}{2}}\varphi_\alpha(\mu_\alpha r)\to r^{\frac{n-2}{2}}\left(1+\frac{f(x_0) r^2}{n(n-2)}\right)^{1-\frac{n}{2}}$$ in $\mathcal{C}^1_{loc}([0,+\infty))$. We define $$\label{def: r alpha} r_\alpha:=\sup_{r\in(2R_0\mu_\alpha,\rho_\alpha)}\left\{s^{\frac{n-2}{2}}\varphi_\alpha(s)\text{ is non-increasing in } (2R_0\mu_\alpha, r)\right\}$$ with $$R_0^2:=\frac{n(n-2)}{f(x_0)}.$$ Note that $$\text{ if }r_\alpha<\rho_\alpha, \quad\text{ then } \left(r^{\frac{n-2}{2}}\varphi_\alpha(r)\right)'(r_\alpha)=0.$$ Since $r^{\frac{n-2}{2}}U$ is non-increasing in $[2R_0,\infty)$, then (\[est: former lemma 4 but for averages\]) implies $$\label{ess: between r alpha and mu alpha} \frac{r_\alpha}{\mu_\alpha}\to\infty.$$ so $\mu_\alpha=o(r_\alpha)$. Considering that the asymptotic profile of blow-up sequences $(x_\alpha)_\alpha$, which is a bump function with a unique maximum, the quantity $r_\alpha$ is an indicator of the beginning of the influence of neighbouring blow-up sequences within the sphere of dominance, as the average of $u_\alpha$ is no longer decreasing. Let $$\label{def: eta} \eta_\alpha:=\sup_{B_{x_\alpha}(6r_\alpha)\backslash B_{x_\alpha}(\frac{1}{6}r_\alpha)}u_\alpha.$$ Note that, by Lemma \[lem: former lemma 3\], $$\frac{1}{C_3}\sup_{B_{x_\alpha}(6s_\alpha)\backslash B_{x_\alpha}\left(\frac{1}{6}s_\alpha\right)}u_\alpha\leq\varphi_\alpha(s_\alpha)\leq C_3\inf_{B_{x_\alpha}(6s_\alpha)\backslash B_{x_\alpha}\left(\frac{1}{6}s_\alpha\right)}u_\alpha$$ for $0<s_\alpha\leq r_\alpha$ and all $\alpha$. By (\[est: former lemma 4 but for averages\]), we obtain the estimate $$\label{est: using the harnack} \lim_{R\to\infty}\limsup_{\alpha\to\infty}\sup_{B_{x_\alpha}(6r_\alpha)\backslash B_{x_\alpha}(R\mu_\alpha)}d_g(x_\alpha,x)^{\frac{n-2}{2}}u_\alpha=0.$$ Thus, $$\label{est: rel size to max} r_\alpha^2\eta^{q-2}_\alpha\to 0$$ as $\alpha\to\infty.$ It is important to note that this implies that $$\label{ess: ok for former lemma 5} r_\alpha\to 0$$ as $\alpha\to\infty$ since $u_\alpha\geq\varepsilon$ by (\[varepsilon\]). We now prove a pointwise asymptotic estimate for $u_\alpha$ in $B_{x_\alpha}(6r_\alpha)\backslash\{x_\alpha\}.$ \[lem: former lemma 5\] Let $(x_\alpha)_\alpha$ with $(\rho_\alpha)_\alpha$ be a blow-up sequence. Then, for any $0<\varepsilon<\frac{1}{2},$ there exists $C_\varepsilon>0$ such that $$u_\alpha(x)\leq C_\varepsilon\left(\mu_\alpha^{\frac{n-2}{2}(1-2\varepsilon)}d_g(x_\alpha,x)^{(n-2)(1-\varepsilon)}+\eta_\alpha\left(\frac{r_\alpha}{d_g(x_\alpha,x)}\right)^{(n-2)\varepsilon}\right)$$ for all $x\in B_{x_\alpha}(6r_\alpha)\backslash\{x_\alpha\}.$ Let $G$ be a Green function for the Laplace operator $\Delta_g$ on $M$ with $G> 0$. Recall the following estimates, that can be found in Aubin [@Au]: $$\label{ess: G on M} \begin{array}{c} \left|d_g(x_\alpha,y)^{n-2}G(x,y)-\frac{1}{(n-2)\omega_{n-1}}\right|\leq\tau\left(d_g(x,y)\right)\\ \left|d_g(x_\alpha,y)^{n-1}|\nabla G(x,y)|-\frac{1}{\omega_{n-1}}\right|\leq\tau\left(d_g(x,y)\right) \end{array}$$ where $\tau:{\mathbb{R}}^+\to {\mathbb{R}}^+$ is a continuous function satisfying $\tau(0)=0$. For a fixed $\varepsilon$, let $$\label{def: uhm monster function i don't know it's late} \Phi^{\varepsilon}_\alpha(x):=\mu_\alpha^{\frac{n-2}{2}(1-2\varepsilon)}G(x_\alpha,x)^{1-\epsilon}+\eta_\alpha r_\alpha^{(n-2)\varepsilon}G(x_\alpha,x)^\varepsilon$$ and let $y_\alpha\in\overline{B_{x_\alpha}(6 r_\alpha)}\backslash\{x_\alpha\}$ be such that $$\label{def of y} \sup_{B_{x_\alpha}(6r_\alpha)}\frac{u_\alpha}{\Phi_\alpha^{\varepsilon}}=\frac{u_\alpha(y_\alpha)}{\Phi_\alpha^\varepsilon(y_\alpha)},$$ We continue by studying the following two cases, separately. **First case:** Assume that the relative size of $d_g(x_\alpha,y_\alpha)$ with respect to $\mu_\alpha$ is $$\label{ess: position of y} R:=\lim_{\alpha\to\infty}\frac{d_g(x_\alpha,y_\alpha)}{\mu_\alpha}\quad\text{with }R\in[0,\infty).$$ Thanks to Lemma \[lem: former lemma 4\], $$\mu_\alpha^{\frac{n-2}{2}}u_\alpha(y_\alpha)=\left(1+\frac{R^2}{R_0^2}\right)^{1-\frac{n}{2}}+o(1),$$ so that, whenever $R\in[0,\infty)$, using (\[ess: between r alpha and mu alpha\]), (\[ess: G on M\]) and (\[ess: position of y\]), it is easily shown that $$\frac{u_\alpha(y_\alpha)}{\Phi_\alpha^\varepsilon(y_\alpha)}\to((n-2)\omega_{n-1})^{1-\varepsilon}R^{(n-2)(1-\varepsilon)}\left(1+\frac{R^2}{R_0^2}\right)^{1-\frac{n}{2}}$$ as $\alpha\to\infty.$ **Second case:** It remains to study the case $$\lim_{\alpha\to\infty}\frac{d_g(x_\alpha,y_\alpha)}{\mu_\alpha}\to\infty\quad\text{ as }\alpha\to\infty.$$ If $(y_\alpha)_\alpha$ sits on the outer boundary $\partial B_{x_\alpha}(6r_\alpha)$, then by (\[ess: ok for former lemma 5\]), (\[ess: G on M\]), and (\[def: uhm monster function i don’t know it’s late\]), $$\frac{u_\alpha(y_\alpha)}{\Phi^{\varepsilon}_\alpha(y_\alpha)}\leq \left(6^{n-2}(n-2)\omega_{n-1}\right)^\varepsilon + o(1).$$ Otherwise, if up to a subsequence $y_\alpha\in B_{x_\alpha}(6r_\alpha)$, then $$\frac{\Delta_{g}u_\alpha(y_\alpha)}{u_\alpha(y_\alpha)}\geq\frac{\Delta_g\Phi^\varepsilon_\alpha(y_\alpha)}{\Phi_\alpha^{\varepsilon}(y_\alpha)}$$ as a consequence of the fact that $y_\alpha$ is the maximum of $\displaystyle\frac{u_\alpha}{\Phi_\alpha^\varepsilon}$. On the other hand, taking note of the sign of the dominant gradient term in equations (\[eq: EL alpha\]), we see that $$\label{because of the gradient sign} \begin{array}{r l} \Delta_g u_\alpha&= -h_\alpha u_\alpha+f_\alpha u_\alpha^{q-1}+ \frac{a_\alpha}{u_\alpha^{q+1}}-\frac{b_\alpha}{u_\alpha}-\frac{\langle\nabla u_\alpha, Y_\alpha\rangle^2}{u_\alpha^{q+3}}\\ &\quad-c_\alpha\langle\nabla u_\alpha,Y_\alpha\rangle\left[\frac{d_\alpha}{u_\alpha^2}+\frac{1}{u_\alpha^{q+2}}\right]\\ &\leq C u_\alpha^{q-1}, \end{array}$$ where $C$ is a constant depending on $\theta$ and $T$. Here we used (\[varepsilon\]). Finally, thanks to (\[est: using the harnack\]), $$d_g(x_\alpha,y_\alpha)^2\frac{\Delta_g u_\alpha(y_\alpha)}{u_\alpha(y_\alpha)}\leq C d_g(x_\alpha,y_\alpha)^2 u^{q-2}_\alpha(y_\alpha)\to 0.$$ To conclude, (\[ess: ok for former lemma 5\]) and (\[ess: G on M\]) imply that $$d_g(x_\alpha,y_\alpha)^2\frac{\Delta_g \Phi^\varepsilon_\alpha(y_\alpha)}{\Phi^\varepsilon_\alpha(y_\alpha)}=\varepsilon(1-\varepsilon)(n-2)^2+o(1).$$ We deduce that $u_\alpha(y_\alpha)=O(\Phi^\varepsilon_\alpha(y_\alpha)).$ The study of the previous two cases ends the proof of the lemma. The following lemma improves the estimate we’ve just obtained and gives a very important bound on the size of $r_\alpha$. \[lem: former lemma 6\] Let $(x_\alpha)_\alpha$ with $(\rho_\alpha)_\alpha$ be a blow-up sequence. Then there exists $C_4>0$ such that $$\label{est: for former lemma 6} u_\alpha(x)+d_g(x_\alpha,x)|\nabla u_\alpha(x)|\leq C_4\mu^{\frac{n-2}{2}}_\alpha \left(d_g(x_\alpha,x)+\mu_\alpha\right)^{2-n}$$ for all $x\in B_{x_\alpha}(6r_\alpha)\backslash\{x_\alpha\}.$ Moreover, $r_\alpha^2=O(\mu_\alpha)$. It suffices to prove the estimate for $u_\alpha$; the rest follows as an immediate consequence of Lemma \[lem: former lemma 3\]. We start by showing that for any sequence $z_\alpha\in \overline{B_{x_\alpha}(6r_\alpha)}\backslash\{x_\alpha\}$, there holds $$\label{est: form lem 6 most of the work} u_\alpha(z_\alpha)=O\left(\mu_\alpha^{\frac{n-2}{2}}d_g(x_\alpha,z_\alpha)^{2-n}+\eta_\alpha\right).$$ First, if $d_g(x_\alpha,z_\alpha)=O(\mu_\alpha)$, it falls within the range described in Lemma \[lem: former lemma 4\]. On the other hand, when $r_\alpha=O\left(d_g(x_\alpha,z_\alpha)\right),$ we use Lemma \[lem: former lemma 3\] together with (\[def: eta\]). It remains to consider the intermediary case: $$\frac{d_g(x_\alpha,z_\alpha)}{\mu_\alpha}\to\infty\quad\text{ and }\quad\frac{d_g(x_\alpha,z_\alpha)}{r_\alpha}\to 0\quad\text{ at }\alpha\to\infty.$$ According to the Green representation formula, $$u_\alpha(z_\alpha)=O\left(\int_{B_{x_\alpha}(6r_\alpha)}d_g(z_\alpha,x)^{2-n}\Delta_g u_\alpha(x)\,dv_g\right)+O(\eta_\alpha),$$ where the second term corresponds to the boundary element. Recall that $$\Delta_g u_\alpha\leq C u_\alpha^{q-1}$$ because of the sign of the dominant gradient term, see (\[because of the gradient sign\]). Using (\[varepsilon\]), (\[est: rel size to max\]) and Lemma \[lem: former lemma 5\], we can write that $$\begin{array}{l} \int_{B_{x_\alpha}(6r_\alpha)}d_g(z_\alpha,x)^{2-n}u_\alpha^{q-1}(x)\,dv_g\\ \displaystyle =O\left(\mu_\alpha^{\frac{n}{2}-1}d_g(x_\alpha,z_\alpha)^{2-n}\right)\\ +O\left(\mu_\alpha^{\frac{n+2}{2}(1-2\varepsilon)}\int_{B_{x_\alpha}(6r_\alpha)\backslash B_{x_\alpha}(\mu_\alpha)}d_g(z_\alpha,x)^{2-n}d_g(x_\alpha,x)^{-(n+2)(1-\varepsilon)}\,dv_g\right)\\ +O\left(\eta_\alpha^{q-1}r_\alpha^{(n+2)\varepsilon}\int_{B_{x_\alpha}(6r_\alpha)\backslash B_{x_\alpha}(\mu_\alpha)}d_g(z_\alpha,x)^{2-n}d_g(x_\alpha,x)^{-(n+2)\varepsilon}\,dv_g\right)\\ = O\left(\mu^{\frac{n}{2}-1}_\alpha d_g(x_\alpha,z_\alpha)^{2-n}\right)+O\left(\eta_\alpha^{q-1}r_\alpha^2\right)\\ = O\left(\mu^{\frac{n}{2}-1}_\alpha d_g(x_\alpha,z_\alpha)^{2-n}\right)+O\left(\eta_\alpha\right). \end{array}$$ In order to get estimate (\[est: for former lemma 6\]), it suffices to show that $$\label{est: of eta} \eta_\alpha=O\left(\mu_\alpha^{\frac{n-2}{2}}r_\alpha^{2-n}\right).$$ For any fixed $0<\delta<1$, taking $\alpha$ large enough, then the monotonicity of $r^{\frac{n-2}{2}}\varphi_\alpha(r)$ expressed in the definition of $r_\alpha$, see (\[def: r alpha\]), and the fact that $\mu_\alpha=o(r_\alpha)$, see (\[ess: between r alpha and mu alpha\]), imply that $$r_\alpha^{\frac{n-2}{2}}\varphi_\alpha(r_\alpha)\leq (\delta r_\alpha)^{\frac{n-2}{2}}\varphi_\alpha(\delta r_\alpha)\quad\text{ for all }0<\delta<1,$$ so by Lemma \[lem: former lemma 3\], $$\frac{1}{C_3}\eta_\alpha\leq \delta^{\frac{n-2}{2}}\sup_{\partial B_{x_\alpha}(\delta r_\alpha)}u_\alpha.$$ According to estimate (\[est: form lem 6 most of the work\]), this leads to $$\eta_\alpha\leq C\left(\mu_\alpha^{\frac{n-2}{2}}\delta^{2-n}r_\alpha^{2-n}+\eta_\alpha\right)\delta^{\frac{n-2}{2}},$$ where $C$ is independent of $\delta$ and $\alpha$. Choosing $\delta$ small enough leads to (\[est: of eta\]). Estimates (\[varepsilon\]) and (\[est: of eta\]) imply that $$\label{size of r alpha} r_\alpha^2= O(\mu_\alpha).$$ This ends the proof of the lemma. Given a blow-up sequence $(x_\alpha)_\alpha$ with $(\rho_\alpha)_\alpha$, the following lemma gives the exact asymptotic profile of $(u_\alpha)_\alpha$ at distance $(\rho_\alpha)_\alpha$ of $(x_\alpha)_\alpha$. \[lem: former lemma 7\] Let $(x_\alpha)_\alpha$ and $(\rho_\alpha)_\alpha$ be a blow-up sequence. Then we have that $r_\alpha=\rho_\alpha$, where $r_\alpha$ is as in (\[def: r alpha\]). Up to a subsequence, we have $$\label{est final profile in r alpha} u_\alpha(x_\alpha)\rho^{n-2}_\alpha u_\alpha(\exp_\alpha(\rho_\alpha x))\to\frac{R_0^{n-2}}{|x|^{n-2}}+H(x)$$ in $C^2_{loc}(B_0(5)\backslash\{0\})$, where $H$ is some harmonic function in $B_0(5)$ satisfying $H(0)=0.$ First, we prove that, up to a subsequence, $$\label{prefinal profile} u_\alpha(x_\alpha)r^{n-2}_\alpha u_\alpha(\exp_\alpha(r_\alpha x))\to\frac{R_0^{n-2}}{|x|^{n-2}}+H(x).$$ Let us define the following rescaled quantities: $$\hat{u}_\alpha(x)=\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n-2}u_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)\text{ and }\hat{g}_\alpha(x)=\exp_{x_\alpha}^*g\left(\exp_{x_\alpha}(r_\alpha x)\right).$$ Then $$\Delta_{\hat{g}_\alpha}\hat{u}_\alpha=\hat{F}_\alpha,$$ in $B_0(\delta r_\alpha^{-1})$ for some $\delta>0$ small enough, with $$\label{eq: form lemma 7's hat F} \begin{array}{r l} \hat{F}_\alpha=& \displaystyle -\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n}h_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)u_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right) \\ & +\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n}f_\alpha \left(\exp_{x_\alpha}(r_\alpha x)\right)u_\alpha^{q-1}\left(\exp_{x_\alpha}(r_\alpha x)\right) \\ & +\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n}\frac{a_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)}{u^{q+1}_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)} -\mu_\alpha^{1-\frac{n}{2}}r_\alpha^n\frac{b_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)}{u_\alpha \left(\exp_{x_\alpha}(r_\alpha x)\right)}\\ & -\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n} \frac{\langle\nabla u_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right), Y_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)\rangle^2}{u_\alpha^{q+3}\left(\exp_{x_\alpha}(r_\alpha x)\right)}\\ & -\mu_\alpha^{1-\frac{n}{2}}r_\alpha^n c_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)\langle\nabla u_\alpha,Y_\alpha\rangle\left(\exp_{x_\alpha}(r_\alpha x)\right) \Big[ \frac{d_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)}{u_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)^2}\\ & + \frac{1}{u_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)^{q+2}}\Big]\\ \end{array}$$ Thanks to Lemma \[lem: former lemma 6\], we know that $|\hat{u}_\alpha|\leq C_K$ and $|\hat{F}_\alpha|=O(1)$ on any compact $K\subset B_0(5)\backslash\{0\}$. By standard elliptic theory, up to a subsequence, $$\hat{u}_\alpha\to\hat{U}\text{ in }\mathcal{C}^1_{loc}(B_0(5)\backslash\{0\})$$ with $$\Delta_\xi\hat{U}=0\text{ in }B_0(5)\backslash\{0\}.$$ Separate $\hat{U}$ into the sum of a regular harmonic function and a singular part $$\hat{U}=\frac{\lambda}{|x|^{n-2}}+H(x),$$ where $\lambda\geq 0.$ To get (\[prefinal profile\]), it remains to show that $\lambda=R_0^{n-2}.$ For any $\delta>0$: $$\label{eq: lemma 7 minutia} \int_{B_0(\delta)}\hat{F}_\alpha\,dv_{\hat{g}_\alpha}=-\int_{\partial B_0(\delta)}\partial_\nu\hat{u}_\alpha\,d\sigma_{\hat{g}_\alpha}.$$ Using the equation (\[eq: form lemma 7’s hat F\]), we estimate the left hand side of (\[eq: lemma 7 minutia\]). In particular, $$\begin{array}{c} \displaystyle \int_{B_0(\delta)}f_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n}u_\alpha^{q-1}\left(\exp_{x_\alpha}(r_\alpha x)\right)\,dx \\ \\ \displaystyle =\int_{B_0(\delta\frac{r_\alpha}{\mu_\alpha})}f_\alpha\left(\exp_{x_\alpha}(\mu_\alpha z)\right)\mu_\alpha^{\frac{n+2}{2}}u_\alpha^{q-1}\left(\exp_{x_\alpha}(\mu_\alpha z)\right)\,dz \end{array}$$ where $\displaystyle z=\frac{r_\alpha}{\mu_\alpha}x$, and by Lemma \[lem: former lemma 4\] and Lemma \[lem: former lemma 6\], $$\begin{array}{c} \displaystyle \lim_{\alpha\to\infty}\int_{B_0(\delta)}f_\alpha\left(\exp_{x_\alpha}(r_\alpha x)\right)\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n}u_\alpha^{q-1}\left(\exp_{x_\alpha}(r_\alpha x)\right)\,dx \\ \\ \displaystyle =f(x_0)\int_{R^n}\left(1+\frac{|x|^2}{R_0^2}\right)^{-1-\frac{n}{2}}\,dx. \end{array}$$ The gradient terms are controlled with the estimate (\[est: initial estimate\]), and together with (\[varepsilon\]), we obtain that the dominant gradient term of (\[eq: form lemma 7’s hat F\]) verifies $$\label{es 1} \begin{array}{r l} \displaystyle \int_{B_0(\delta)}\frac{|\nabla u_\alpha|^2}{u_\alpha^{q+3}}\left(\exp_{x_\alpha}(r_\alpha x)\right)\mu_\alpha^{1-\frac{n}{2}}r_\alpha^n\,dx\leq & \displaystyle C \mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n-2}\int_{B_0(\delta)}|x|^{-2}\,dx \\ \\ & \leq \displaystyle C\omega_{n-1} \mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n-2}\delta^{n-2}. \end{array}$$ As $\mu_\alpha^{1-\frac{n}{2}}r_\alpha^{n-2}=O(1),$ the integral does not vanish as $\alpha\to\infty$; its size depends on $\delta$. The remaining terms in (\[eq: form lemma 7’s hat F\]) are negligible. Thus $$\int_{B_0(\delta)}\hat{F}_\alpha\, dv_{\hat{g}_\alpha}= f(x_0)\int_{R^n}\left(1+\frac{|x|^2}{R_0^2}\right)^{-1-\frac{n}{2}}\,dx+o(1)+O(\delta^{n-2})$$ for any $\delta>0$. It follows that $$f(x_0)\int_{{\mathbb{R}}^n}\left(1+\frac{|x|^2}{R_0^2}\right)^{-1-\frac{n}{2}}\,dx=(n-2)\omega_{n-1}R_0^{n-2}.$$ Note also that the right hand side of (\[eq: lemma 7 minutia\]) verifies $$\begin{array}{r l} -\int_{\partial B_0(\delta)}\partial_\nu \hat{u}_\alpha\,d\sigma_{\check{g}_\alpha}&=-\int_{\partial B_0(\delta)}\partial_\nu\hat{U}+o(1)\\ &=\lambda(n-2)\omega_{n-1}+o(1). \end{array}$$ since $H$ is smooth and harmonic. Since $$\lambda(n-2)\omega_{n-1}=R^{n-2}_0(n-2)\omega_{n-1}+O(\delta^{n-2})+o(1),$$ for any $\delta>0$, we get that $\lambda=R_0^{n-2}.$ Finally, let us prove that $H(0)=0.$ The equation’s dominant terms are invariant by rescaling, which leads us to use a Pohozaev identity to obtain new estimates for the remaining terms. Let $\Omega_\alpha$ correspond to $B_0(\delta r_\alpha)$ in the exponential chart at $x_\alpha\in M$ and let $X_\alpha=\frac{1}{2}\nabla d_g(x_\alpha,x)^2$ be the vector field of coordinates. Using integration by parts, $$\begin{array}{r l} \int_{\Omega_\alpha}\nabla u_\alpha(X_\alpha)\Delta_gu_\alpha\,dv_g=& \int_{\Omega_\alpha}\langle\nabla \left(\nabla u_\alpha(X_\alpha)\right),\nabla u_\alpha\rangle\, dv_g\\ & - \int_{\partial \Omega_\alpha}\nabla u_\alpha(X_\alpha)\partial_{\nu}u_\alpha\,d\sigma_g\\ = & \int_{\Omega_\alpha}\nabla^\#\nabla u_\alpha( X_\alpha, \nabla u_\alpha) + \nabla^\# X_\alpha\left(\nabla u_\alpha, \nabla u_\alpha\right)\,dv_g\\ & - \int_{\partial \Omega_\alpha}\nabla u_\alpha(X_\alpha)\partial_{\nu}u_\alpha\,d\sigma_g, \end{array}$$ where $(\nabla^\# X_\alpha)=(\nabla^i X_\alpha)^j$. Since $$\begin{array}{c} \int_{\Omega_\alpha}|\nabla u_\alpha|^2div_g X_\alpha\,dv_g+\int_{\Omega_\alpha}\langle\nabla\left(|\nabla u_\alpha|^2\right),X_\alpha\rangle\,dv_g\\ =\int_{\partial \Omega_\alpha}|\nabla u_\alpha|^2 \langle X_\alpha, \nu\rangle \,d\sigma_g, \end{array}$$ we can write that $$\label{eq: Pohozaev} \begin{array}{r l} \int_{\Omega_\alpha} &\displaystyle\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)\Delta_g u_\alpha\,dv_g \\ & =\int_{\Omega_\alpha}\left(\nabla^\# X_\alpha\left(\nabla u_\alpha, \nabla u_\alpha\right)-\frac{1}{2}\left(div_g X_\alpha\right)|\nabla u_\alpha|^2\right)\,dv_g\\ & + \int_{\partial\Omega_g}\left(\frac{1}{2}\langle X_\alpha,\nu\rangle |\nabla u_\alpha|^2-\nabla u_\alpha(X_\alpha)\partial_\nu u_\alpha-\frac{n-2}{2}u_\alpha\partial_\nu u_\alpha\right)\,d\sigma_g. \end{array}$$ We begin by analyzing the right-hand side of (\[eq: Pohozaev\]). By our choice of $X_\alpha$, $(\nabla^\# X_\alpha)^{ij}=g^{ij}+O(d_g(x_\alpha,x)^2),$ and consequently $$\begin{array}{rl} \int_{\Omega_\alpha} &\displaystyle \left(\nabla^\# X_\alpha\left(\nabla u_\alpha, \nabla u_\alpha\right)-\frac{1}{2}\left(div_g X_\alpha\right)|\nabla u_\alpha|^2\right)\,dv_g \\ & =O\left(\int_{\Omega_\alpha}d_g(x_\alpha,x)^2|\nabla u_\alpha|^2dv_g\right). \end{array}$$ According to (\[est: for former lemma 6\]), $$\begin{array}{c} \displaystyle \int_{\Omega_\alpha}d_g(x_\alpha,x)^2|\nabla u_\alpha|^2\,dv_g\leq C\int_{\Omega_\alpha}\mu_\alpha^{n-2}\left(d_g(x_\alpha,x)+\mu_\alpha\right)^{4-2n}\,dv_g, \end{array}$$ so $$\displaystyle \int_{\Omega_\alpha}d_g(x_\alpha,x)^2|\nabla u_\alpha|^2\,dv_g \leq\left\{ \begin{array}{l c} \displaystyle O(\mu_\alpha r_\alpha) & \displaystyle \text{ if }n=3 \\ \\ \displaystyle O\left(\mu_\alpha^2\ln\frac{1}{\mu_\alpha}\right) & \displaystyle \text{ if }n=4 \\ \\ \displaystyle O\left(\mu_\alpha^2\right) & \displaystyle \text{ if }n=5 \end{array}\right.$$ In all these three cases, thanks to (\[size of r alpha\]), the integral is of the order $o(\mu_\alpha^{n-2} r_\alpha^{2-n})$. From (\[est final profile in r alpha\]), $$\begin{array}{r l} \displaystyle \int_{\partial\Omega_\alpha} & \displaystyle \left(\frac{1}{2}\langle X_\alpha,\nu\rangle |\nabla u_\alpha|^2-\nabla u_\alpha(X_\alpha)\partial_\nu u_\alpha-\frac{n-2}{2}u_\alpha\partial_\nu u_\alpha\right)\,d\sigma_g \\ &=\left(\frac{(n-2)^2}{2}\omega_{n-1}R_0^{n-2}H(0)+o(1)\right)\mu_\alpha^{n-2}r_\alpha^{2-n}. \end{array}$$ Note that the boundary term does not depend on $\delta$, and as a result $$\label{eq: pohozaev id 1 in lem 7 former} \begin{array}{r l} \int_{\Omega_\alpha}&\displaystyle\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)\Delta_g u_\alpha\,dv_g \\ & =\left(\frac{(n-2)^2}{2}\omega_{n-1}R_0^{n-2}H(0)+o(1)\right)\mu_\alpha^{n-2}r_\alpha^{2-n} \end{array}$$ We now analyse the right hand side of (\[eq: Pohozaev\]) by using (\[eq: EL alpha\]): $$\label{eq: from the eq} \begin{array}{r l} \int_{\Omega_\alpha} &\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)\Delta_g u_\alpha\,dv_g \\ =& \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)f_\alpha u_\alpha^{q-1}\,dv_g\\ & - \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)\langle\nabla u_\alpha, Y_\alpha\rangle^2 u_\alpha^{-q-3}\,dv_g\\ & - \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)c_\alpha\langle\nabla u_\alpha, Y_\alpha\rangle(d_\alpha u_\alpha^{-2}+u_\alpha^{-q-2})\,dv_g\\ & + \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)\left(a_\alpha u_\alpha^{-q-1}-b_\alpha u_\alpha^{-1}- h_\alpha u_\alpha\right)\,dv_g \end{array}$$ and we look at each term in turn. By the estimates (\[varepsilon\]) and (\[est: initial estimate\]), we get $$\label{for dominant nabla term} \begin{array}{r l} \left|\int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)\langle\nabla u_\alpha,Y_\alpha\rangle^2 u_\alpha^{-q-3}\,dv_g \right| & \leq C\int_{\Omega_\alpha}d_g(x_\alpha,x)^{-2}dv_g\\ & \leq C(\delta r_\alpha)^{n-2} \end{array}$$ and, similarly, $$\label{for nondominant nabla term} \begin{array}{c} \left|\int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)c_\alpha\langle\nabla u_\alpha, Y_\alpha\rangle(d_\alpha u_\alpha^{-2}+u_\alpha^{-q-2})\,dv_g\right|\\ \leq C(\delta r_\alpha)^{n-1}. \end{array}$$ We also have that $$\label{for a and b} \left|\int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)\left(a_\alpha u_\alpha^{-q-1}-b_\alpha u_\alpha^{-1}\right)\right|\leq Cr_\alpha^n.$$ From (\[est: for former lemma 6\]), we obtain that $$\label{for h} \begin{array}{c} \left|\int_{\Omega_\alpha}h_\alpha\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)u_\alpha\,dv_g\right|\\=O\left(\int_{\Omega_\alpha}\mu_\alpha^{n-2}(\mu_\alpha+d_g(x_\alpha,x))^{4-2n}\,dx\right)\\ =o(\mu_\alpha^{n-2}r_\alpha^{2-n}) \end{array}$$ for $3\leq n\leq 5.$ Using integration by parts, $$\begin{array}{r l} \int_{\Omega_\alpha}\nabla u_\alpha(X_\alpha)f_\alpha u_\alpha^{q-1}\,dv_g=&\frac{1}{q} \int_{\partial \Omega_\alpha}f_\alpha r_\alpha u_\alpha^q\,d\sigma_g\\ & -\frac{1}{q}\int_{\Omega_\alpha}div_g X_\alpha f_\alpha u_\alpha^q\, dv_g \\ &- \frac{1}{q}\int_{\Omega_\alpha}\nabla f_\alpha(X_\alpha)u_\alpha^q\,dv_g. \end{array}$$ Thus we can write that $$\begin{array}{r l} \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)f_\alpha u_\alpha^{q-1}\,dv_g&=\frac{1}{q}r_\alpha\int_{\partial \Omega_\alpha}f_\alpha u_\alpha^q\,d\sigma_g\\ &\,+\int_{\Omega_\alpha}\left(-\frac{1}{q}div_g(X_\alpha)+\frac{n-2}{2}\right)f_\alpha u_\alpha^q\,dv_g\\ &\,-\frac{1}{q}\int_{\Omega_\alpha}\nabla f_\alpha(X_\alpha)u_\alpha^q\,dv_g. \end{array}$$ Since $div_g(X_\alpha)=n+O\left(d_g(x_\alpha,x)^2\right)$, this leads to $$\begin{array}{r l} \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)f_\alpha u_\alpha^{q-1}\,dv_g&=\frac{1}{q}r_\alpha\int_{\partial \Omega_\alpha}f_\alpha u_\alpha^q\,d\sigma_g\\ &\,+O\left(\int_{\Omega_\alpha} d_g(x_\alpha,x)^2 u_\alpha^q\,dv_g\right)\\ &\,-\frac{1}{q}\int_{\Omega_\alpha}\nabla f_\alpha(X_\alpha)u_\alpha^q\,dv_g. \end{array}$$ Using lemmas \[lem: former lemma 4\] and \[lem: former lemma 6\], this leads to $$\begin{array}{r l} \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)f_\alpha u_\alpha^{q-1}\,dv_g&= O\left(\mu_\alpha^n r_\alpha^{-n}\right)+O(\mu_\alpha^2)\\ &-\frac{1}{q}\int_{\Omega_\alpha}\nabla f_\alpha(X_\alpha)u_\alpha ^q\,dv_g \end{array}$$ so that, thanks to (\[size of r alpha\]), $$\label{for f} \begin{array}{c} \int_{\Omega_\alpha}\left(\nabla u_\alpha(X_\alpha)+\frac{n-2}{2}u_\alpha\right)f_\alpha u_\alpha^{q-1}\,dv_g=o\left(\mu_\alpha^{n-2}r_\alpha^{2-n}\right)\\-\frac{1}{q}\int_{\Omega_\alpha}\nabla f_\alpha(X_\alpha)u_\alpha^q\,dv_g \end{array}$$ if $3\leq n\leq 5.$ We claim that $$\label{for nabla f} \int_{\Omega_\alpha}\nabla f_\alpha (X_\alpha)u_\alpha^q\,dv_g=o\left(\mu_\alpha^{n-2}r_\alpha^{2-n}\right).$$ Thanks to (\[eq: pohozaev id 1 in lem 7 former\]), (\[for dominant nabla term\]), (\[for nondominant nabla term\]), (\[for a and b\]), (\[for h\]), (\[for f\]) and (\[for nabla f\]), we see that $$\label{Hdelta} H(0)=o(1)+\delta^4$$ for any $\delta>0$, so by taking $\delta\to 0$ wee see that $H(0)=0$. In order to prove (\[for nabla f\]), we can first use Lemma \[lem: former lemma 6\] to write that $$\int_{\Omega_\alpha}\nabla f_\alpha(X_\alpha)u_\alpha^q\,dv_g=O(\mu_\alpha)$$ which leads to (\[for nabla f\]) if $n=3,4$ thanks to (\[size of r alpha\]), but is not enough for $n=5$. In order to improve the estimate in the case $n=5$, note that $$\begin{array}{r l} \displaystyle \int_{\Omega_\alpha}\nabla f_\alpha(X_\alpha)u_\alpha^q\,dv_g &\displaystyle =\partial_i f(x_\alpha)\int_{\Omega_\alpha}x^iu_\alpha^q\,dv_g\\ \\ &\displaystyle\quad +O\left(\int_{\Omega_\alpha}d_g(x_\alpha,x)^{1+\eta}u_\alpha^q\,dv_g\right)\\ \\ &\displaystyle =o\left(\mu_\alpha|\nabla f_\alpha(x_\alpha)|\right)+ O\left(\mu_\alpha^{1+\eta}\right)\\ \\ &\displaystyle =o\left(\mu_\alpha|\nabla f_\alpha(x_\alpha)|\right)+ o\left(\mu_\alpha^{3}r_\alpha^{-3}\right). \end{array}$$ with $\eta>\frac{1}{2}.$ Thus it remains to prove that $$\label{est: gjgjhvj} |\nabla f_\alpha(x_\alpha)|=O\left(\mu_\alpha^2 r_\alpha^{-3}\right).$$ As before, we use a Pohozaev-type identity. We make use of the equation’s symmetry by translation, with $Z=Z^i$ a constant vector field in the exponential chart of $x_\alpha$. We can write that $$\label{newpoz} \int_{\Omega_\alpha}\nabla u_\alpha(Z_\alpha)\Delta_g u_\alpha\,dv_g=O\left(\int_{\Omega_\alpha}d_g(x_\alpha,x)|\nabla u_\alpha|^2\,dv_g +\int_{\partial \Omega_\alpha}|\nabla u_\alpha|^2\,d\sigma_g\right),$$ which is $o(\mu_\alpha^2 r_\alpha^{-3})$. On the left-hand side, we use (\[eq: EL alpha\]). Lemma \[lem: former lemma 3\] and (\[varepsilon\]) imply that $$\label{newpoz1} \begin{array}{r l} \displaystyle \int_{\Omega_\alpha}\nabla u_\alpha(Z_\alpha)\frac{\langle\nabla u_\alpha,Y_\alpha\rangle^2}{u_\alpha^{q+3}} \,dv_g &\displaystyle \leq \frac{1}{\varepsilon^q}\int_{\Omega_\alpha}\left|\frac{\nabla u_\alpha}{u_\alpha}\right|^3\,dv_g\\ \\ &\displaystyle \leq \frac{1}{\varepsilon^q}\int_{\Omega_\alpha}d_g(x_\alpha,x)^{-3}\,dv_g\\ \\ &\displaystyle =O(r^2_\alpha)=o(\mu_\alpha^2r_\alpha^{-3}). \end{array}$$ We see that $$\label{newpoz2} \int_{\Omega_\alpha}\nabla u_\alpha(Z_\alpha)c_\alpha\langle\nabla u_\alpha, Y_\alpha\rangle\left(\frac{d_\alpha}{u_\alpha^2}+\frac{1}{u_\alpha^{q+2}}\right) \,dv_g=O(r^2_\alpha)=o(\mu_\alpha^2r_\alpha^{-3}),$$ and that the same holds for the terms corresponding to $h_\alpha$, $b_\alpha$ and $c_\alpha$. So (\[newpoz\]), (\[newpoz1\]) and (\[newpoz2\]) imply that $$\int_{\Omega_\alpha}\nabla u_\alpha(Z_\alpha)f_\alpha u_\alpha^{q-1}\,dv_g=o(\mu_\alpha^2 r_\alpha^{-3}).$$ Furthermore, $$\begin{array}{r l} \displaystyle \int_{\Omega_\alpha}\nabla u_\alpha(Z_\alpha)f_\alpha u_\alpha^{q-1}\,dv_g= &\displaystyle O\left(\int_{\partial\Omega_\alpha}u_\alpha^q\,d\sigma_g\right)\\ \\ &\displaystyle-\frac{1}{q}\int_{\Omega_\alpha}div_g(Z_\alpha)f_\alpha u_\alpha^q\,dv_g\\ \\ &\displaystyle -\frac{1}{q}\nabla f_\alpha(Z_\alpha)\int_{\Omega_\alpha}u_\alpha^q\,dv_g, \end{array}$$ which leads us to conclude the claim in (\[for nabla f\]). Note that $$div_g(Z_\alpha)=O\left(d_g(x_\alpha,x)^\eta\right)$$ and $$\int_{\Omega_\alpha}u_\alpha^q\,dv_g\rightarrow\int_{R^n}\left(1+\frac{|x|^2}{R_0^2}\right)^{-5}\,dx<\infty.$$ Finally, we are in the position to remark that $\rho_\alpha=r_\alpha.$ Remember that $$\varphi(r)=\frac{1}{\omega_{n-1}r^{n-1}}\int_{\partial B_0(r)}\hat{U}=\left(\frac{R_0}{r}\right)^{n-2}+H(0)$$ and that $\left(r^{\frac{n-2}{2}}\varphi(r)\right)'(1)=0$, so if $r_\alpha<\rho_\alpha$, then $H(0)=R_0^{n-2}$, which contradicts (\[Hdelta\]). Thus (\[prefinal profile\]) implies (\[est final profile in r alpha\]), and this wraps up the proof of the lemma. Moreover, $\rho_\alpha=r_\alpha$ means that $\rho_\alpha\to 0$ because $r_\alpha=O\left(\mu_\alpha^\frac{1}{2}\right)$ thanks to (\[size of r alpha\]). As an important consequence, there do not exist any isolated bubbles. Otherwise, if a bubble were isolated, then we could choose a blow-up sequence with $0<\delta<\rho_\alpha$, contradicting the previous result. Proof of the stability theorem ------------------------------ We are now in the position to prove Theorem \[theo stability eq\]. Let $$\delta_\alpha:=\min_{1\leq i<j\leq N_\alpha}d_g(x_{i,\alpha}, x_{j,\alpha}).$$ For any $R>0$, let $1\leq M_{R,\alpha}$ be such that $$d_g(x_{1,\alpha}, x_{i_\alpha,\alpha})\leq R\delta_\alpha\quad\text{ for }\quad i_\alpha\in\{1,\dots,M_{R,\alpha}\}, \text{ and}$$ $$d_g(x_{1,\alpha}, x_{j_\alpha,\alpha})> R\delta_\alpha \quad\text{ for }\quad j_\alpha\in\{M_{R,\alpha}+1,\dots, N_\alpha\}.$$ We consider the rescaled quantities $$\check{u}_\alpha(x):=\delta_\alpha^{\frac{n-2}{2}}u_\alpha(\exp_{x_{1,\alpha}}(\delta_\alpha x))\quad\text{ and }\quad \check{g}_\alpha(x):=\left(\exp^*_{x_{1,\alpha}}g\right)(\delta_\alpha x)$$ and the coordinates $\check{x}_{i,\alpha}:=\delta_\alpha^{-1}\exp_{x_{1,\alpha}}^{-1}(x_{i,\alpha})$ in the exponential chart. It’s obvious that $|\check{x}_{2,\alpha}|=1$ and $|\check{x}_{i,\alpha}|\geq 1$. The following lemma is a direct consequence of Lemma \[lem: former lemma 3\]. \[lem former lemma 9\] For all $R>0$, there exists $C_R>0$ such that the Harnack-type inequality $$||\nabla \check{u}_\alpha||_{L^\infty(\Omega_R)}\leq C_R \sup_{\Omega_R}\check{u}_\alpha\leq C_R^2\inf_{\Omega_R}\check{u}_\alpha$$ holds, where $\Omega_R=B_0(R)\backslash\bigcup^{M_{2R,\alpha}}_{i=1}B_{\check{x}_{i,\alpha}}\left(\frac{1}{R}\right).$ Note that, for $1\leq i<j\leq M_{R,\alpha}$, $B_{x_{i,\alpha}}\left(\frac{\delta_\alpha}{4}\right)$ and $B_{x_{j,\alpha}}\left(\frac{\delta_\alpha}{4}\right)$ are disjoint, which is equivalent to saying that $B_{\check{x}_{i,\alpha}}\left(\frac{1}{4}\right)$ and $B_{\check{x}_{j,\alpha}}\left(\frac{1}{4}\right)$ are also disjoint. At this point, we are finally able to prove Theorem \[theo stability eq\], which we stated at the very beginning of this section. We define two possible types of concentration points, according to how $\check{u}_\alpha$ explodes. We prove that, within a cluster, we can only find one type or the other, but never both. Finally, we see that the existence of either type leads to contradictions, which implies that $\check{u}_\alpha$ admits no concentration points whatsoever. Consider the cluster around $(x_{1,\alpha})_\alpha$, for some $R>0$. There are two possible cases. The first type of concentration point corresponds to $$\label{first case concentration point} \sup_{B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)}\left(\check{u}_\alpha(x)+\left|\frac{\nabla\check{u}_\alpha(x)}{\check{u}_\alpha(x)}\right|^{\frac{n-2}{2}}\right)=O(1).$$ In this case, note that $(\check{u}_\alpha)_\alpha$ is uniformly bounded in $\mathcal{C}^1_{loc}$. Moreover, we find a lower bound, as by (\[est: 1 of former lemma 1\]) from Lemma \[lem: former lemma 2\], $$|\check{x}_{i,\alpha}|^{\frac{n-2}{2}}\check{u}_\alpha(\check{x}_{i,\alpha})\geq 1.$$ There exists $\delta_i>0$ such that $$\inf_{B_{\check{x}_{i,\alpha}}(\delta_i)}\check{u}_\alpha\geq \frac{1}{2}|\check{x}_{i,\alpha}|^{1-\frac{n}{2}},$$ which leads to the existence of $\delta_0>0$ where $$\label{lower bound} \inf_{B_{\check{x}_{i,\alpha}}(\delta_0)}\check{u}_\alpha\geq \frac{1}{2}.$$ The second type is defined by $$\label{second case concentration point} \sup_{B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)}\left(\check{u}_\alpha(x)+\left|\frac{\nabla\check{u}_\alpha(x)}{\check{u}_\alpha(x)}\right|^{\frac{n-2}{2}}\right)\to\infty.$$ In this case, either $$\label{nabla explodes} \sup_{B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)}\check{u}_\alpha(x)\leq M\quad \text{ and }\quad \sup_{B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)}|\nabla\check{u}_\alpha(x)|\to\infty,$$ or $$\label{l infty explodes} \sup_{B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)}\check{u}_\alpha(x)\to\infty.$$ We show (\[nabla explodes\]) is not actually possible. Assume it holds true. Then there exist $(\check{x}_\alpha)_\alpha\subset (B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right))_\alpha$ and $(\check{\nu}_\alpha)_\alpha$ such that $$\check{\nu}_\alpha^{1-\frac{n}{2}}:= \check{u}_\alpha(\check{x}_\alpha)+\left|\frac{\nabla \check{u}_\alpha(\check{x}_\alpha)}{\check{u}_\alpha(\check{x}_\alpha)}\right|^{\frac{n-2}{2}}=\sup_{x\in B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)}\left(\check{u}_\alpha(x)+\left|\frac{\nabla \check{u}_\alpha(x)}{\check{u}_\alpha(x)}\right|^{\frac{n-2}{2}}\right)$$ with $$\check{\nu}_\alpha\to 0.$$ We define the rescaled quantities $$\check{v}_\alpha(x):=\check{\nu}_\alpha^{\frac{n-2}{2}}\check{u}_\alpha\left(\exp_{\check{x}_\alpha}(\check{\nu}_\alpha x)\right)\quad\text{and}\quad \check{h}_\alpha(x):=\left(\exp_{\check{x}_\alpha}^* \check{g}\right)(\check{\nu}_\alpha x)$$ respectively, defined in $\Omega_\alpha:=B_0\left(\frac{1}{2\check{\nu}_\alpha}\right)$. For any $R>0$ and $\alpha$ large enough so that $R<\frac{1}{2\check{\nu}_\alpha}$, $$\limsup_{\alpha\to\infty}\sup_{B_0(R)} \left(\check{v}_\alpha+\left|\frac{\nabla \check{v}_\alpha}{\check{v}_\alpha}\right|\right)=1.$$ Thus $$|\nabla \ln \check{v}_\alpha|\leq 1$$ and $$\check{v}_\alpha(0)e^{-x}\leq \check{v}_\alpha(x)\leq \check{v}_\alpha(0)e^{x}.$$ Note that the metrics $\check{h}_\alpha\to\xi$ in $\mathcal{C}^2_{loc}$ as $\alpha\to\infty$. Assume that, up to a subsequence, $u_\alpha(\check{x}_\alpha)\to l<\infty$. We also deduce that $\check{v}_\alpha(0)\to 0.$ Let $\check{x}_0:=\lim_{\alpha\to\infty}\check{x}_\alpha$ and let us denote $$\check{w}_\alpha(x):=\frac{\check{v}_\alpha(x)}{\check{v}_\alpha(0)}.$$ These functions are bounded from below, $$\label{est w again} \check{w}_\alpha(x)\geq\frac{\varepsilon}{l}+o(1)>0.$$ Moreover, $$\check{w}_\alpha(x)\leq e^{|x|}.$$ By standard elliptic theory, we find that there exists $\check{w}:=\lim_{\alpha\to\infty}\check{w}_\alpha$ in $\mathcal{C}^1$ solving: $$\Delta \check{w}=-\frac{1}{l^{q+2}}\frac{\langle\nabla \check{w}, Y(\check{x}_0)\rangle^2}{\check{w}^{q+3}}.$$ Note that $$\Delta \check{w}^{-\alpha}\leq \alpha\frac{|\nabla \check{w}|^2}{\check{w}^{\alpha+2}}\left[\frac{||Y(\check{x}_0)||_{L^\infty}^2}{\varepsilon^{q+2}}-(\alpha+1)\right],$$ so $\check{w}^{-\alpha}$ is subharmonic for $\alpha$ large, and so Lemma \[lem: A1\] (see the Annex) implies that $\check{w}$ is constant, which in turn implies that $\check{U}=0$ and $\nabla \check{U}=0$, which is false (see proof of Lemma \[lem: former lemma 1\]). Therefore, the second subcase cannot be true. This essentially means that when a concentration point is of the second type, then $$\sup_{B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)}\check{u}_\alpha(x)\to\infty$$ and so $$\check{u}_\alpha(\check{x}_{i,\alpha})\to\infty.$$ Let us denote $\check{x}_i:=\lim_{\alpha\to\infty}\check{x}_{i,\alpha}$ up to a subsequence. According to Proposition \[prop\], $$\label{sectype} \check{u}_\alpha(\check{x}_{i,\alpha})\check{u}_\alpha(x)\mapsto\frac{\lambda_i}{|x-\check{x}_i|^{n-2}}+H_i(x)$$ in $\mathcal{C}^1$ in $B_{\check{x}_i}\left(\frac{1}{2}\right)\backslash \{\check{x_i}\}$, with $\lambda_i>0$, where $H_i$ is a harmonic function in $B_{\check{x}_{i,\alpha}}\left(\frac{1}{2}\right)$, $H(\check{x}_i)=0$. Let $U$ be a connected open set of ${\mathbb{R}}^n$, $U_R\subset B_0(R+1)$, containing no other point of the cluster apart from $\check{x}_i$ and $\check{x}_j$. For any $0<r<\frac{1}{8}$, we set $$V_{r,R}=U_R\backslash\left(\overline{B_{\check{x_i}}(r)\bigcup B_{\check{x_j}}(r)}\right).$$ For a fixed $x\in B_{\check{x}_i}\left(\frac{1}{4}\right)\backslash V_{r,R}$, (\[sectype\]) implies that $\check{u}_\alpha(x)\to 0$ as $\alpha\to\infty$. It follows from Lemma \[lem former lemma 9\] and (\[lower bound\]) that all points of a cluster must be of the same type. Assuming all points in the cluster are of the first type, then $$\check{u}_\alpha(0)+\left|\frac{\nabla\check{u}_\alpha(0)}{\check{u}_\alpha(0)}\right|^{\frac{n-2}{2}}=O(1),$$ then by standard elliptic theory there exists $\check{u}:=\lim_{\alpha\to\infty}\check{u}_\alpha$ in $\mathcal{C}^1(B_0(R))$, $R>0$. Repeating the reasoning of Lemma \[lem: former lemma 2\] or Lemma \[lem: former lemma 4\], we know that $$\Delta_\xi \check{u}=f(x_1)\check{u}^{q-1}.$$ However, $\check{u}$ must have at least two separate maxima, at 0 and $\check{x}_2$, which leads to a contradiction by the classification result of Caffarelli, Gidas and Spruck [@CaffGidSpr]. Therefore $\check{u}_\alpha(\check{x}_{i,\alpha})\to\infty$, for any $i=\overline{1,M_{2R,\alpha}}$. Up to a subsequence $$\frac{\check{u}_\alpha(\check{x}_{i,\alpha})}{\check{u}_\alpha(0)}\to\mu_i>0\quad\text{as}\quad\alpha\to\infty.$$ We fix $R>0$ and assume, without loss of generality, that $(M_{2R,\alpha})_\alpha$ is a constant denoted by $M_{2R}$. Using Lemma \[lem former lemma 9\] and standard elliptic theory, we pass to a subsequence and get $$\check{u}_\alpha(0)\check{u}_\alpha(x)\to\check{G}(x)$$ in $\mathcal{C}^1_{loc}\left(B_0(R)\backslash\{\check{x}_i\}_{i=\overline{1,N_{2R}}}\right)$ for $\alpha\to\infty$, with $$\begin{array}{r l} \check{G}(x)&=\sum_{i=1}^{p}\frac{\lambda_i}{\mu_i|x-\check{x}_i|^{n-2}}+\check{H}(x)\\&=\frac{\lambda_1}{|x|^{n-2}}+\left(\sum_{i=2}^{p}\frac{\lambda_i}{\mu_i|x-\check{x}_i|^{n-2}}+\check{H}(x)\right) \end{array}$$ Here, $\check{H}$ is harmonic on $B_0(R)$, and $2\leq p\leq M_{2R}$ such that $|\check{x}_p|\leq R$ as $|\check{x}_{p+1}|>R$. If we apply Proposition \[prop\] to the blow-up sequence $x_\alpha=x_{1,\alpha}$ with $\rho_\alpha=\frac{1}{16}d_\alpha$, we obtain $$\hat{H}(0):=\sum_{i=2}^{p}\frac{\lambda_i}{\mu_i|\check{x}_i|^{n-2}}+\check{H}(0)=0$$ Since $\hat{H}(x)-\frac{\lambda_2}{\mu_2|x-\check{x}_{2}|}=\check{G}(x)-\frac{\lambda_1}{|x|^{n-2}}-\frac{\lambda_2}{\mu_2|x-\check{x}_2|^{n-2}}$ is harmonic in the ball $B_0(R)\backslash\{\check{x}_i\}_{i\in\overline{2,N_{2R}}}$ and $\check{G}\geq 0$, then as a consequence of the maximum principle, by considering a minimum on $\partial B_0(R),$ we see that $$\hat{H}(0)\geq\frac{\lambda_2}{\mu_2}-\frac{\lambda_1}{R^{n-2}}-\frac{\lambda_2}{\mu_2(R-1)^{n-2}}.$$ Choosing $R>0$ large enough, we ensure that $\hat{H}>0,$ which contradicts Theorem \[lem: former lemma 7\]. Consequently, $u_\alpha$ admits no concentration points and is therefore uniformly bounded in $\mathcal{C}^1$. \[lem strong stability\] Assuming equation (\[EM\]) associated to $\tilde{a}$ admits a supersolution and that $\Delta_g+h$ is coercive, then for any $0<T<\inf_M\tilde{a}$ and any equation with parameters in $\mathcal{E}_{\theta,T}$ (as in Theorem \[theo stability eq\]), there exists a constant $C_{\theta,T}=C(n,\theta,T)>0$ such that, for any $||Y||_{L^\infty}\leq C_{\theta,T}$ and $||b||_{L^\infty}\leq C_{\theta,T}$, we may find a smallest real eigenvalue $\lambda_0>0$, where $\lambda_0$ is as in Lemma \[lem weak stability\]. Given any parameters $(f,a,b,c,d,h,Y)$ in $\mathcal{E}_{\theta,T}$ and additionally asking for $Y$ and $b$ to be sufficiently small in $L^\infty$ norm with respect to $\theta$ and $T$, we aim to prove that minimal solutions to the Lichnerowicz-type equation change continuously with their parameters. In order to do this, we study the sign of the smallest real eigenvalue associated to the linearisation around a minimal solution and show that it is positive by comparing it to the smallest real eigenvalue at $b=0$ and $Y=0$. Indeed, let $s>0$ a real number and $E_s$ the equation $$\label{eq theta} \begin{array}{c} E_s(u_s):=\Delta_g u_s+hu_s-fu_s^{q-1}-\frac{a}{u_s^{q+1}}+\frac{s b}{u_s}+c\langle\nabla u_s,s Y\rangle\left(\frac{d}{u_s^2}+\frac{1}{u_s^{q+2}}\right)\\+\frac{\langle\nabla u_s,s Y\rangle^2}{u_s^{q+3}}=0, \end{array}$$ with $u_s$ its minimal solution. Let $L_s$ be the linearisation of $E_s$ around $u_s$, $$\begin{array}{c}\label{eq varphi} \Delta_g\varphi_s+\Big[h-(q-1)fu_s^{q-2}+(q+1)\frac{a}{u_s^{q+2}}-\frac{s b}{u_s}-c\langle\nabla u_s,s Y\rangle\left(\frac{2d}{u_s^3}+\frac{q+2}{u_s^{q+3}}\right)\\-(q+3)\frac{\langle\nabla u_s,s Y\rangle^2}{u_s^{q+4}}\Big]\varphi_s+\langle\nabla\varphi_s,s Y \rangle\Big[c\left(\frac{d}{u_s^2}+\frac{1}{u_s^{q+2}}\right)+\frac{2\langle\nabla u_s,s Y\rangle}{u_s^{q+3}}\Big]=\lambda_s\varphi_s, \end{array}$$ with $\lambda_s\geq 0$ the smallest real eigenvalue, $\varphi_s>0$ the associated eigenfunction, normalised such that $||\varphi_s||_{L^2}=1.$ Note that the linear equations $L_s$ are stable, in the sense that $\varphi_s$ is *a priori* uniformly bounded in $\mathcal{C}^1$. This follows from the fact that the $u_s$ is uniformly bounded. We may also suppose that $\lambda_s$ is uniformly bounded, because if $\lambda_s\to\infty$, then it is clear that $\lambda_s>0$. As Premoselli proved by way of a variational argument [@Pre14], the equation $E_0$ is strictly stable, in the sense that its corresponding smallest real eigenvalue is positive. It uses the coerciveness of $\Delta_g+h$. We emphasize that his argument makes use of the fact that $E_0$ is symmetric, which is not the case for our more general equations. The strict stability implies continuity, *i.e.* that $u_s\to u_0$, with $u_0$ the minimal value. Indeed, let $u_s\to \tilde{u}$ another solution of $E_0$. Clearly, $\tilde{u}>u_0$. Let $\tilde{u}_\delta=u_0+\delta\varphi_0$. Note that $$\begin{array}{r l} E_s(\tilde{u}_\delta)&=E_0(\tilde{u}_\delta)+\frac{s b}{u_\delta}+c\langle\nabla u_\delta,s Y\rangle\left(\frac{d}{u_\delta^2}+\frac{1}{u_\delta^{q+2}}\right)+\frac{\langle\nabla u_\delta,s Y\rangle^2}{u_\delta^{q+3}}\\ &=E_0(u_0)+\lambda_0\delta\varphi_0+o(\delta)+\frac{s b}{u_\delta}+s c\langle\nabla u_\delta, Y\rangle\left(\frac{d}{u_\delta^2}+\frac{1}{u_\delta^{q+2}}\right)\\ &\quad +s^2\frac{\langle\nabla u_\delta, Y\rangle^2}{u_\delta^{q+3}} \end{array}$$ If we fix $\delta>0$ sufficiently small, the error terms $|o(\delta)|\leq \frac{\lambda_0\delta\varphi_0}{3}$ and $\tilde{u}_\delta<\tilde{u}\leq u_s$, $\forall s$. Then, by taking $s$ sufficiently close to $0$, we get that the rest of the terms are also smaller in absolute size than $\frac{\lambda_0\delta\varphi_0}{3}$. Consequently, $E_s(\tilde{u}_\delta)>0$, so $\tilde{u}_\delta$ is a supersolution of $E_s$ that is smaller than the minimal solution $u_s$. Since $u_s\to u_0$, we also get that $\lambda_s\to\lambda_0$, so for $s$ small, the first eigenvalue $\lambda_s>0$. We would like to obtain that there exists $s_{\theta,T}>0$ such that, for any $0\leq s<s_{\theta,T}$, the minimal eigenvalue corresponding to $L_s$ is positive, where $(a,b,c,d,f,h,Y)\in\mathcal{E}_{\theta,T}$. In other words, we attempt to set a size for $Y$ and $b$, depending on $\theta$ and $T$ (and $n$), such that the resulting equations are strictly stable. First, there exists $\delta_{\theta,T}>0$ such that if $Y=0$, $b=0$ and the equation’s parameters are found in $\mathcal{E}_{\theta,T}$, then $\lambda_0>\delta_{\theta,T}.$ We let $u_s=u_0+\varepsilon_s v_s$ such that $||v_s||_{L^2}=1$, $\varepsilon_s\in{\mathbb{R}}$. Note that $\varepsilon_s\to 0$ as $s\to 0$. We begin by analyzing the difference in size between $\varepsilon_s$ and $s$, or equivalently between $||u_s-u_0||_{L^\infty}$ and $s$. Let $$E_s=E_0+s M_s,$$ where $$M_s(u_s)=\frac{b}{u_s}+c\langle\nabla u_s, Y\rangle\left(\frac{d}{u_s^2}+\frac{1}{u_s^{q+2}}\right)+s\frac{\langle\nabla u_s, Y\rangle^2}{u_s^{q+3}}.$$ Recall that $$\label{Eq theta develop} E_0(u_s)=-s M_s(u_s)$$ where $$E_0(u_s)=L_0(u_s-u_0)+O(|u_s-u_0|^2).$$ Since $u_0$ is a solution of $E_0$ and the operator $L_0$ is coercive, with minimal eigenvalue $\lambda_0$, then by testing (\[Eq theta develop\]) against $(u_s-u_0)$, we see that $$\lambda_0\left(1+o(1)\right)||u_s-u_0||_{L^2}^2\leq -s \int_M M_s(u_s)(u_s-u_0)\leq s||M_s(u_s)||_{L^2}||u_s-u_0||_{L^2}.$$ The size of $M_s(u_s)$ is determined by a constant depending on $\theta$ and $T$. Therefore, we may write $$(1+o(1))\varepsilon_s =(1+o(1))||u_s-u_0||_{L^2}\leq s \frac{C}{\lambda_0}$$ Finally, in order to compare $\lambda_s$ to $\lambda_0$, extract the terms of order $s$ from the quantity $\int_M \varphi_0L_s(\varphi_s)-\varphi_s L_0(\varphi_0)$, $$\label{eq L theta order varepsilon theta} \begin{array}{c} -\int_M\frac{s b}{u_0}\varphi_0\varphi_s-\int_Mc\langle\nabla u_0,s Y\rangle\left(\frac{2d}{u_0^3}+\frac{q+3}{u_0^{q+3}}\right)\varphi_s\varphi_0-\int_M(q+3)\frac{\langle\nabla u_s,s Y\rangle^2}{u_s^{q+4}}\varphi_s\varphi_0\\ \varepsilon_s\int_M\left[(q-1)(q-2)fu_0^{q-3}-(q+1)(q+2)\frac{a}{u_0^{q+3}}\right]v_s \varphi_s\varphi_0\\ +O(s^2)=(\lambda_\theta-\lambda_0)\int_M\varphi_s\varphi_0, \end{array}$$ so there exists a constant $C$ depending on $\theta$ and $T$ such that $$|\lambda_s-\lambda_0|\leq s C\left(\int_M\varphi_s\varphi_0\right)^{-1}.$$ As $\varphi_s=\varphi_0+o(1)$ and the $L^2$ norm of $\varphi_0$ is $1$, we may choose $s$ small enough so that $|\lambda_s-\lambda_0|\geq \frac{\delta_{\theta,T}}{2}$, and thus $\lambda_s>0$. Existence of solutions to the system {#theo: system} ==================================== The proof of the main theorem ----------------------------- The following is a useful estimate we can find in [@IseMur]; it plays a crucial role in ensuring the necessary compacity of the sequence $W_\alpha$ in the main theorem. \[prop isemur\] Let $(M,g)$ be a closed Riemannian manifold of dimension $n\geq 3$ such that $g$ has no conformal Killing fields. Let $X$ be a smooth vector field in $M$. Then there exists a unique solution $W$ of $$\Delta_{g, conf}W=X.$$ Also, for $0<\gamma<1$, there exists a constant $C_0>0$ that depends only on $n$ and $g$ such that $$||W||_{\mathcal{C}^{1,\gamma}}\leq C_0||X||_\infty.$$ As a consequence, there exists a constant $C_1=C_1(n,g)$ such that $$\label{lxest} ||\mathcal{L}_g W||_{\mathcal{C}^{0,\gamma}}\leq C_1||X||_\infty$$ Let $(M,g)$ be a closed Riemannian manifold of dimension $n\in\{3,4,5\}$ such that $g$ has no conformal Killing fields. Let $b$, $c$, $d$, $f$, $h$, $\rho_1$, $\rho_2$, $\rho_3$ be smooth functions on $M$ and let $Y$ and $\Psi$ be smooth vector fields defined on $M$. Let $0<\gamma<1$. Assume that $\Delta_g+h$ is coercive. Assume that $f>0$, $\rho_1>0$ and $|\nabla \rho_3|<(2C_1)^{-1}$, where $C_1$ is defined in (\[lxest\]). Consider the coupled system $$\label{system in proof} \begin{cases} \displaystyle \Delta_g u+hu &\displaystyle= fu^{q-1}+\frac{\rho_1+|\Psi+\rho_2\mathcal{L}_gW|^2_g}{u^{q+1}}\\ &\displaystyle -\frac{b}{u}-c\langle\nabla u,Y\rangle \left(\frac{d}{u^2}+\frac{1}{u^{q+2}}\right)-\frac{\langle\nabla u,Y\rangle^2}{u^{q+3}}\\ \displaystyle div_{g}\left(\rho_3\mathcal{L}_g W\right) &\displaystyle =\mathcal{R}(u), \end{cases}$$ where $\mathcal{R}$ is an operator verifying $$\label{CR} \mathcal{R}(u)\leq C_\mathcal{R}\left(1+\frac{||u||_{\mathcal{C}^2}^2}{(\inf_Mu)^2}\right)$$ for a constant $C_\mathcal{R}>0$. We fix $$\label{theta} \theta=\min(\inf_M\rho_1,\inf_M f),$$ and $$\label{T2} T=\max(||f||_{\mathcal{C}^{1,\eta}}, ||\rho_1||_{\mathcal{C}^{0,\gamma}}, ||c||_{\mathcal{C}^{0,\gamma}}, ||d||_{\mathcal{C}^{0,\gamma}}, ||h||_{\mathcal{C}^{0,\gamma}}).$$ Let $$\label{bound m} M=\ln S_{\theta,2T},$$ with $S_{\theta,2T}$ a constant as in Theorem \[theo stability eq\]. The following theorem is the main result of the present paper. \[thm plus 1\] Assume there exists a smooth positive function $\tilde{a}$ for which $$\label{licheq} \Delta_g \tilde{u}+ h\tilde{u}=f\tilde{u}^{q-1}+\frac{\tilde{a}}{\tilde{u}^{q+1}}$$ admits a positive supersolution $\tilde{u}$. Assume that $\rho_1<\tilde{a}$ and let $\omega=\inf_M(\tilde{a}-\rho_1)$. Then there exists $$\delta=\delta(\omega,\theta,T)>0$$ such that if $$||b||_{\mathcal{C}^{0,\gamma}}+ ||Y||_{\mathcal{C}^{0,\gamma}}+ ||\Psi||_{\mathcal{C}^{0,\gamma}}+||\rho_2||_{\mathcal{C}^{0,\gamma}}+ C_\mathcal{R}\leq \delta,$$ the system (\[system in proof\]) admits a solution $(u,W)$, with $u$ a smooth positive function and $W$ a smooth vector field. We can use a result by Hebey, Pacard and Pollack ([@HebPacPol08], Corollary 3.1) in order to ensure the existence of a supersolution $\tilde{u}$. There exists a constant $C=C(n,h)$, $C>0$ such that if $\tilde{a}$ is a smooth positive function verifying $$||\tilde{a}||_{L^1(M)}\leq C(n,h)\left(\max_M |f|\right)^{1-n},$$ then (\[licheq\]) accepts a smooth positive solution. The proof of the theorem consists of a fixed-point argument. Formally, we define the operator $$\Phi:\varphi\to\ln u\left(\mathcal{L}_gW(e^\varphi)\right),$$ where $W(e^\varphi)$ solves the second equation of (\[system in proof\]) for a fixed $u=e^\varphi$ and where $u\left(\mathcal{L}_gW(e^\varphi)\right)$ is the solution of the scalar equation of (\[system in proof\]) constructed in Section 2 for a fixed $W(e^\varphi)$. In order to apply Schauder’s fixed point theorem, we show that $\Phi:B_M\to B_M$, $B_M:=\{\varphi\in\mathcal{C}^2(M), ||\varphi||_{\mathcal{C}^2}\leq M\}$, where $M$ is defined as in (\[bound m\]), and that $\Phi$ is continuous and compact. We first want to prove that $$\label{smaller than a tilde} \rho_1+|\Psi+\rho_2\mathcal{L}_gW(e^\varphi)|^2_g<\tilde{a}$$ to ensure that $\Phi(\varphi)$ is well defined, with $\tilde{u}$ from (\[licheq\]) a supersolution. By (\[lxest\]), we have $$\label{l c gamma} ||\mathcal{L}_g W(e^\varphi)||_{\mathcal{C}^{0,\gamma}}\leq C_1\left(||\nabla\rho_3||_{L^\infty}||\mathcal{L}_g W(e^\varphi)||_{L^\infty}+||\mathcal{R}(e^\varphi)||_{L^\infty}\right)$$ and thanks to (\[CR\]) we see that $$\begin{array}{c} \rho_1+|\Psi+\rho_2\mathcal{L}_gW(e^\varphi)|^2_g\leq \rho_1+ 2||\Psi||_{L^\infty}^2\\ +2\left(\frac{C_1 C_{\mathcal{R}}||\rho_2||_{L^\infty}}{1-C_1||\nabla \rho_3||_{L^\infty}}\right)^2 \left(1+\frac{M^2e^{2M}}{e^{2\varepsilon}}\right)^2, \end{array}$$ where $\varepsilon$ is the lower bound of any solution corresponding to $\mathcal{E}_{\theta,2T}$ from Theorem \[theo stability eq\]. There exists $$\label{delta1} \delta_1=\delta_1(\omega,\theta,T)>0$$ such that if $$||\Psi||_{\mathcal{C}^{0,\gamma}}+||\rho_2||_{\mathcal{C}^{0,\gamma}}+C_{\mathcal{R}}\leq \delta_1,$$ then (\[smaller than a tilde\]) holds. In order to use the *a priori* estimate of Section 3 to see that $\Phi:B_M\to B_M$, we need to prove that $$\label{ee} \theta\leq \rho_1+|\Psi+\rho_2\mathcal{L}_gW(e^\varphi)|^2_g \quad\text{ and }\quad ||\rho_1+|\Psi+\rho_2\mathcal{L}_gW(e^\varphi)|^2_g||_{\mathcal{C}^{0,\gamma}}\leq 2T.$$ From (\[theta\]) we deduce that $$\label{ee1} \theta\leq \rho_1+|\Psi+\rho_2\mathcal{L}_gW(e^\varphi)|^2_g.$$ and thanks to (\[l c gamma\]) we see that $$\begin{array}{c} ||\rho_1+|\Psi+\rho_2\mathcal{L}_gW(e^\varphi)|^2_g||_{\mathcal{C}^{0,\gamma}}\leq ||\rho_1||_{\mathcal{C}^{0,\gamma}}+ 2||\Psi||_{\mathcal{C}^{0,\gamma}}^2\\ +2\left(\frac{C_1 C_{\mathcal{R}}||\rho_2||_{\mathcal{C}^{0,\gamma}}}{1-C_1||\nabla \rho_3||_{L^\infty}}\right)^2 \left(1+\frac{M^2e^{2M}}{e^{2\varepsilon}}\right)^2. \end{array}$$ There exists $$\label{delta2} \delta_2=\delta_2(\omega,\theta, T)>0$$ such that if $$||\Psi||_{\mathcal{C}^{0,\gamma}}+||\rho_2||_{\mathcal{C}^{0,\gamma}}+C_{\mathcal{R}}\leq \delta_2,$$ then $$\label{ee2} ||\rho_1+|\Psi+\rho_2\mathcal{L}_gW(e^\varphi)|^2_g||_{\mathcal{C}^{0,\gamma}}\leq 2T.$$ Thanks to (\[ee1\]) and (\[ee2\]), the *a priori* estimates in Section 3 imply that $$||u\left(\mathcal{L}_gW(e^\varphi)\right)||_{\mathcal{C}^2}\leq S_{\theta,2T},$$ so $$\Phi(\varphi)\leq M,$$ where $M$ is as in (\[bound m\]). We have thus proved that $\Phi$ is well-defined and that $\Phi:B_M\to B_M$. In order to show that $\Phi$ is continuous, we want to check that it holds true for $a\mapsto u(a)$, where $u(a)$ is the minimal solution constructed in Section 2. For all $a<\tilde{a}$, we’ve established monotony, which ensures that the minimal solutions exist. For $t>0$ small, let us denote by $u_t$ the solutions corresponding to $a(1+t)<\tilde{a}$. Let $u_0$ be the limit of $u_t$ as $t\to 0$; it is also a solution of the Lichnerowicz-type equation associated to $a$. If $u_0\not=u,$ then $u<u_0$. According to Section 3, there exists $C_{\theta,2T}>0$ such that $$||b||_{\mathcal{C}^{0,\gamma}}+||Y||_{\mathcal{C}^{0,\gamma}}\leq C_{\theta,2T}$$ implies that $u$ is strictly stable. We ask that $$\delta\leq\min\left( \delta_1, \delta_2, C_{\theta,2T}\right)$$ where $\delta_1$ is defined in (\[delta1\]) and $\delta_2$ is defined in (\[delta2\]). We choose $\mu>0$ small enough such that $u< \hat{u}_\mu< u_0$, where $\hat{u}_\mu:=u+\mu\psi$, $\psi$ a positive eigenfunction at $u$ corresponding to the smallest real eigenvalue. But $\hat{u}_\mu$ is a supersolution for $a(1+\epsilon)$, $\epsilon>0$ small, which contradicts the monotonicity. Therefore, $\Phi$ is continuous. Lastly, $B_M$ being a closed convex set in $\mathcal{C}^2$, it remains to show that $\Phi(B_M)$ is compact to conclude. From the previous discussion, $\Phi(B_M)\subset B_M$, and is thus bounded in $\mathcal{C}^2$. By standard elliptic theory, we conclude the proof of Theorem \[thm 1\]. The case of a metric with conformal Killing fields -------------------------------------------------- Let us consider the case of a metric $g$ with non-trivial conformal Killing fields associated to it. For $\tilde{V}$ a representative of the drift, the equation $$div_{\bar{g}}\left(\frac{\tilde{N}}{2}\mathcal{L}_{g}W\right)=\frac{n-1}{n}u^q\mathbf{d}\left(u^{-2q}\tilde{N}div_{g}(u^q\tilde{V})\right)+\pi\nabla\psi$$ admits a solution $W$ if and only if $$\frac{n-1}{n}\int_Mu^{-2q}\tilde{N}div_{g}(u^q\tilde{V})div_{g}(u^q P)=\int_M\langle\pi\nabla\psi,P\rangle$$ for all $P$ conformal Killing fields. Moreover, the solution $W$ is unique up to the addition of a conformal Killing field. Note that the drift is defined modulo conformal Killing fields, so $\tilde{V}$ and $\tilde{V}+P$ are representatives of the same drift for all $P$ conformal Killing fields. We claim that given a vector field $\tilde{V}$ there exists a conformal Killing field $\tilde{Q}$ which is unique up to a true Killing field and such that $$\label{Q eq} \frac{n-1}{n}\int_M u^{-2q}\tilde{N}div_{g}\left(u^q(\tilde{V}+\tilde{Q})\right)div_{g} (u^qP)=\int_M\langle\pi\nabla\psi,P\rangle.$$ By analyzing the homogeneous operator associated to the equation above, $$\int_Mu^{-2q}\tilde{N}div_{g}\left(u^q(\tilde{V}+\tilde{Q}')\right)div_{g}(u^q P)=0,$$ we check that it is positive definite, thus invertible. Consider the functional $$F(P)=\int_Mu^{-2q}\tilde{N}div_{g}\left(u^q(\tilde{V}+P)\right)^2\,dv_{g}$$ on the finite-dimensional space of conformal Killing fields and note that $\tilde{Q}'$ is stationary for $F$. Since $F$ is quadratic and non-negative definite, stationary points are associated to minimizers. If $\bar{g}$ does not admit any nontrivial true Killing fields, then every conformal Killing field $P$ satisfies $div P\not = 0$ and the quadratic term of $F$ is positive definite. On the other hand, if $g$ admits proper Killing fields, then $F$ descends to a functional on the quotient space and its quadratic order term is again positive definite. So the minimum of $F$ is unique up to a true Killing field. The conformal system proposed by Maxwell [@Max14] becomes in this framework $$\label{syst of Maxwell - with CKF} \begin{cases} \Delta_g u+\frac{n-2}{4(n-1)}(R(g)-|\nabla\psi|_g^2)u -\frac{(n-2)}{4(n-1)}\frac{|U+\mathcal{L}_g W|^2+\pi^2}{u^{q+1}}\\ \displaystyle\quad-\frac{n-2}{4(n-1)}\left[2V(\psi)-\frac{n-1}{n}\left(\tau^*+\frac{\tilde{N}div_g\left(u^q(\tilde{V}+\tilde{Q})\right)}{u^{2q}}\right)^2\right]u^{q-1}=0\\ \\ div_g\left(\frac{\tilde{N}}{2}\mathcal{L}_g W\right)=\frac{n-1}{n}u^q \mathbf{d} \left(\frac{\tilde{N}div_g(u^q\left(\tilde{V}+\tilde{Q}\right))}{2u^{2q}}\right)+\pi\nabla\psi, \end{cases}$$ whose solution $(u,W,\tilde{Q})$ is a smooth positive function $u$, a smooth vector field $W$, defined up to a conformal Killing field, and $\tilde{Q}$ a conformal Killing field defined up to a true Killing field. The existence of solutions to (\[syst of Maxwell - with CKF\]) follows from Theorem \[thm 1\] and is similar to Corollary \[physical result\], with slight modifications. Here, $$\begin{array}{c} \rho_1=\frac{n-2}{4(n-1)}\left[\pi-\frac{n-1}{n}\tilde{N}^2 div_g(\tilde{Q}+\tilde{V})\right],\quad b=-\tau^*\tilde{N}div_g(\tilde{V}+\tilde{Q}),\\ Y=\sqrt{\frac{n}{n-2}}\tilde{N}(\tilde{V}+\tilde{Q}) \end{array}$$ and $$C_\mathcal{R}=C_\mathcal{R}(||\tilde{Q}||_{\mathcal{C}^2}).$$ Moreover, we define $\theta$ and $T$ as in (\[th main\]) and (\[T main\]) respectively, but without the dependency on $\rho_1=\rho_1(\tilde{Q})$, *i.e.* $$\theta=\min(\inf_M f),$$ and $$T=\max(||f||_{\mathcal{C}^{1,\eta}}, ||c||_{\mathcal{C}^{0,\gamma}}, ||d||_{\mathcal{C}^{0,\gamma}}, ||h||_{\mathcal{C}^{0,\gamma}}).$$ First of all, the stability of the first equation still holds, as in Lemma \[lem weak stability\] and Lemma \[lem strong stability\]. In order to apply the last theorem, we need to check that: $\rho_1(\tilde{Q})>\theta$, $||\rho_1(\tilde{Q})||_{\mathcal{C}^{0,\gamma}}<2T$, $||b||_{\mathcal{C}^{0,\gamma}}\leq C_{\theta,2T}$ and $||Y||_{\mathcal{C}^{0,\gamma}}\leq C_{\theta, 2T}$. This translates to $$div_g\tilde{Q}<\left(\frac{n-2}{4(n-1)}\pi-\theta\right)\frac{n}{n-1}\tilde{N}^{-2}-div_g\tilde{V},$$ $$\frac{n-2}{4(n-1)}||\pi||_{\mathcal{C}^{0,\gamma}}+\frac{n-1}{n}||\tilde{N}div_g(\tilde{V}+\tilde{Q})||_{\mathcal{C}^{0,\gamma}}\leq 2T,$$ $$||\tau^*\tilde{N}div_g(\tilde{V}+\tilde{Q})||_{\mathcal{C}^{0,\gamma}}\leq C_{\theta,2T},$$ and $$\sqrt{\frac{n}{n-2}}||\tilde{N}(\tilde{V}+\tilde{Q})||\leq C_{\theta,2T}.$$ We find bounds on $\tilde{Q}$ depending on $\pi$, $\psi$, $\tilde{N}$, $\tilde{V}$ from (\[Q eq\]), thereby proving the necessary compactness. Finally, the continuity $(a,b,Y)\to u_{a,b,Y}$ doesn’t pose any problem, and the proof mirrors our previous argument for the continuty of $a\to u(a).$ This shows the existence of solutions $(u,W,\tilde{Q})$. Annex ===== We used the following result repeatedly throughout the paper. \[lem: A1\] Let $u$ be a bounded subharmonic function defined on ${\mathbb{R}}^n$. If there exists $0<\varepsilon\leq u$ which bounds $u$ from below and $\alpha>0$ such that $u^{-\alpha}$ is a subharmonic function, then $u$ is a constant. Let us denote $$\bar{u}_{x}(R):=\frac{1}{\omega_{n-1}R^{n-1}}\int_{\partial B_{x}(R)}u(y)\,dy$$ the average of a smooth function $u$ over the sphere $\partial B_{x}(R)$. We will sometimes use the simplified notation $\bar{u}(R)$. Recall that, given any subharmonic function $u$, $x\in{\mathbb{R}}^n$ and for any two radii $R\leq\tilde{R}$, then $$\label{decreasing averages} \bar{u}_{x}(R)\leq \bar{u}_x(\tilde{R}).$$ This follows from $$r^{n-1}\bar{u}'(r)=\frac{1}{\omega_{n-1}}\int_{\partial B_x{(r)}}\partial_\nu u(y)\,dy=-\frac{1}{\omega_{n-1}}\int_{B_x{(r)}}\Delta u(y)\,dy\geq 0$$ where $r>0$ and $\nu$ is the exterior normal. Note that $u^{-\alpha}\leq \varepsilon^{-\alpha}$ implies that the average of $u^{-\alpha}$ on arbitrary subsets is uniformly bounded. Let us fix $x\in{\mathbb{R}}^n$. Since $u^{-\alpha}$ is bounded, there exists a constant $M>0$ and a sequence of radii $R_i\to\infty$ as $i\to\infty$ such that $$\label{def M} M^{-\alpha}:=\lim_{i\to\infty}\overline{u^{-\alpha}}_{x}(R_i).$$ In fact, because the averages are decreasing (\[decreasing averages\]), any sequence $R\to\infty$ around any point in ${\mathbb{R}}^n$ leads to the same limit $M$, since one may always find a subsequence of $R_i$ such that $B_x(R_i)$ includes the new sequence. As $u^{-\alpha}$ is subharmonic, $$u^{-\alpha}(x)\leq \overline{u^{-\alpha}}_x(R)$$ and therefore $u^{-\alpha}(x)\leq M^{-\alpha}$, or equivalently $$\label{M smaller than u x} M\leq u(x).$$ For $z\in {\mathbb{R}}^n$, let $R:=|z-x|$ and $\tilde{R}>R$. By Green’s representation theorem, we get $$\label{est: from the annex} \begin{array}{r l} \displaystyle u(z) &\displaystyle \leq \int_{\partial B_x(\tilde{R})}u(y)\frac{\tilde{R}^2-R^2}{\omega_{n-1}\tilde{R}|z-y|^n}\, dy\\ \\ &\displaystyle\leq \frac{(\tilde{R}+R)\tilde{R}^{n-2}}{(\tilde{R}-R)^{n-1}}\overline{u}_x(\tilde{R}). \end{array}$$ For $\delta>0,$ we denote $$\Omega_{\delta,R}:=\{z\in\partial B_x(R), u(z)\geq M+\delta\}$$ a subset of $\partial B_x(R)$ and let $$\theta_{\delta, R}:=\frac{|\Omega_{\delta, R}|}{|\partial B_x(R)|}\in[0,1]$$ be the corresponding relative size of its volume. Note that $\theta_{\delta,R}\to 0$ as $R\to\infty$. Otherwise, if there exists $\varepsilon\in(0,1]$ such that $$\limsup_{R\to\infty}\frac{|\{z\in\partial B_x(R), u(z)\geq M+\delta\}|}{|\partial B_x(R)|}=\varepsilon$$ then $$\limsup_{R\to\infty}\overline{u^{-\alpha}}_x(R) \leq \varepsilon(M+\delta)^{-\alpha}+(1-\varepsilon)M^{-\alpha}<M^{-\alpha}$$ which contradicts our definition (\[def M\]) of $M$. By choosing $R$ large, $\theta_{\delta,R}\leq \delta$. Let $$\lambda_{\delta,i}:=\bar{u}_x(2^iR)$$ Note that, by (\[est: from the annex\]), $\lambda_{\delta,i}\leq 3\times 2^{n-2}\lambda_{\delta, i+1}.$ Since $$u(x)\leq\lambda_{\delta,i}\leq(M+\delta)(1-\theta_{\delta,2^iR})+\lambda_{\delta,i+1}\times\theta_{\delta,2^iR}$$ then, by induction, $$u(x)\leq (M+\delta)\frac{1-\delta^l}{1-\delta}+\lambda_l\delta^l$$ for all $l\in {\mathbb{N}}$. As we take $l\to\infty$, $$u(x)\leq(M+\delta)\frac{1}{1-\delta}$$ for any $\delta>0$, and therefore $u(x)\leq M.$ By (\[M smaller than u x\]), $u(x)\equiv M.$ We may apply the same argument to any other $\tilde{x}\in{\mathbb{R}}^n$ and obtain the same value $u(\tilde{x})=M$. Indeed, assuming that $$\tilde{M}^{-\alpha}:=\lim_{\tilde{R}\to\infty}\overline{u^{-\alpha}}_{\tilde{x}}(\tilde{R})$$ so that $\tilde{M}^{-\alpha}\geq M^{-\alpha}$, then for $\tilde{R}$ large, $\overline{u^{-\alpha}}_{\tilde{x}}(\tilde{R})\geq M^{-\alpha}$. But, at the same time, given any fixed $\tilde{R}$, then for $R$ sufficiently large, by (\[est: from the annex\]), $\overline{u^{-\alpha}}_{\tilde{x}}(\tilde{R})\leq \overline{u^{-\alpha}}_{x}(R)$. Thus we obtain that $u\equiv M$ in ${\mathbb{R}}^n$. [99]{} Aubin, T., *Nonlinear analysis on manifolds. Monge-Amp[è]{}re equations. Grundlehren der Mathematischen Wissenschaften*, vol. 252. 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Evans, *Partial Differential Equations*, 2nd edition, GSM19, *American Mathematical Society* (2010). Y. Four[è]{}s-Bruhat, *Th[é]{}or[è]{}me d’existence pour certains syst[è]{}mes d’[é]{}quations aux d[é]{}riv[é]{}es partielles non lin[é]{}aires*, Acta Math. 88 (1952), 141–225. MR 0053338 (14,756g) Emmanuel Hebey, Frank Pacard, Daniel Pollack, *A Variational Analysis Of Einstein–Scalar Field Lichnerowicz Equations On Compact Riemannian Manifolds* arXiv:gr-qc/0702031, Commun.Math.Phys.278:117-132,2008 Michael Holst, Gabriel Nagy, and Gantumur Tsogtgerel, *Rough Solutions of the Einstein Constraints on Closed Manifolds without Near-CMC Conditions*, Comm. Math. Phys. 288 (2009), no. 2, 547–613. 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Bruno Premoselli, *The Einstein-Scalar Field Constraint System in the Positive Case*, *Communications in Mathematical Physics* **326** (2014), no. 2, 543-557. Bruno Premoselli, *Effective multiplicity for the Einstein-scalar field Lichnerowicz equation* *Calculus of Variations and Partial Differential Equations*, (2014), 10.1007/s00526-014-0740-y. [^1]: Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69100 Villeurbanne, `valcu@math.univ-lyon1.fr`

Factors Influencing Cane Use for the Management of Knee Osteoarthritis: A Cross-Sectional Survey. To investigate demographic, symptom-related, and cognitive determinants of cane use for knee osteoarthritis (OA) and prioritize the factors that could facilitate cane use in people with no previous cane use. A survey of people ages ≥45 years with a clinical diagnosis of knee OA was conducted. The survey consisted of the following two sections: 1) demographic and cognitive determinants of cane use assessed via subscales of the Cane Cognitive Mediator Scale, and 2) 19 statements, underpinned by the Behaviour Change Wheel theoretical framework, relating to factors that could facilitate regular cane use. Logistic regression was used to examine determinants of cane use, while a priority pairwise ranking activity (1000minds software) determined the rank order of the 19 statements that could facilitate cane use. A total of 529 people completed Part 1 (80% females; 35% cane users) and 231 people completed Part 2. Age (odds ratio [OR] 1.06, 95% confidence interval [95% CI] 1.03- 1.09), body mass index (BMI) (OR 1.03, 95% CI 1.01-1.06), knee pain ≥3 years (OR 2.62, 95% CI 1.63-4.21) and numeric rating scale pain level while walking (OR 1.19, 95% CI 1.09-1.30) were significant independent determinants of cane use. In people who had never used a cane, statements relating to cane-use technique, fitting, knowledge of benefits, and motivation were ranked highest overall. Independent determinants of cane use include older age, higher BMI, greater pain duration, and greater severity of knee pain. Strategies targeting an individual's capability and motivation to use a cane may increase cane use among people with knee OA.

Q: Turning vector of shared_ptr into vector of shared_ptr to const Let class A { std::vector<std::shared_ptr<int>> v_; }; Now I'd like to add access to v_ using two public member functions std::vector<std::shared_ptr<int>> const & v() { return v_; } and std::vector<std::shared_ptr<int const> const & v() const { TODO } I cannot replace TODO with return v_; though. One option would be to not return a reference but a copy. Apart from the obvious performance penalty, this would also make the interface somewhat less desirable. Another option is to make TODO equal to return reinterpret_cast<std::vector<std::shared_ptr<int const>> const &>(v_); My question is, is this undefined behavior? Or, alternatively, is there a better option, preferably without using reinterpret_cast? A: A way to avoid copying the container is to provide transform iterators that transform the element on dereference: #include <vector> #include <memory> #include <boost/iterator/transform_iterator.hpp> class A { std::vector<std::shared_ptr<int> > v_; struct Transform { template<class T> std::shared_ptr<T const> operator()(std::shared_ptr<T> const& p) const { return p; } }; public: A() : v_{std::make_shared<int>(1), std::make_shared<int>(2)} {} using Iterator = boost::transform_iterator<Transform, std::vector<std::shared_ptr<int> >::const_iterator>; Iterator begin() const { return Iterator{v_.begin()}; } Iterator end() const { return Iterator{v_.end()}; } }; int main() { A a; // Range access. for(auto const& x : a) std::cout << *x << '\n'; // Indexed access. auto iterator_to_second_element = a.begin() + 1; std::cout << **iterator_to_second_element << '\n'; } A: Putting aside the discussion of whether or not you should return a reference to a member... std::vector already propagates its own const qualifier to the references, pointee's and iterators it returns. The only hurdle is making it propagate further to the pointee type of the std::shared_ptr. You can use a class like std::experimental::propagate_const (that will hopefully be standardized) to facilitate that. It will do as its name implies, for any pointer or pointer-like object it wraps. class A { using ptr_type = std::experimental::propagate_const<std::shared_ptr<int>>; std::vector<ptr_type> v_; }; Thus TODO can become return v_;, and any access to the pointees (like in the range-based for you wish to support) will preserve const-ness. Only caveat is that it's a moveable only type, so copying out an element of the vector will require a bit more work (for instance, by calling std::experimental::get_underlying) with the element type of the vector itself.

to paraphrase the great Paul Rand, I strive to add value and meaning; to illuminate, clarify and simplify; to dignify, dramatize, and sometimes even to amuse. Irene is an award-winning graphic designer creating meaningful brands and communications, adding value to businesses worldwide. Her clients range from larger organizations and institutions to startups and entrepreneurs. She has lived in the USA, the United Kingdom and Slovenia, and this experience of other cultures inspires her work which is described as clean, idea-driven and engaging. "There are many great things I could say about Irene. She’s dependable, thoughtful, talented, knowledgeable, creative, and passionate about design and typography. But more than that, she’s a good collaborator. I recently hired her to complete the design of my latest book—160 pages of customized typography, Photoshopped images, and complex charts and diagrams. We worked side by side on this demanding project, and what I found was that Irene actually “thinks” about the work as she’s doing it. She questions every detail. She finds ways to improve it. She catches discrepancies in the text that would normally be the author’s responsibility. What many people don’t realize—even in the design profession—is that good design requires proficiency with language. Images don’t stand alone. They’re bound up with words and cultural norms. Working with Irene, you sense how much she’s learned from other cultures, including the UK and Slovenia. She’s more than a designer. She’s a true communicator." Member of the Preliminary Interactive Jury of the Cresta International Advertising AwardsDesign & Media Assets Chair for the Fork&Cork Classic, Foodbank of Santa Barbara CountyBrand Consultant for WEV Santa Barbara (Women's Economic Ventures)Former Marketing Director of AIGA Santa Barbara, the professional association for designFormer Brand Manager/Board Member of Utu, a grassroots non-profit fighting the spread of HIV/AIDS in sub-Saharan Africa EDUCATION MA Advertising (Distinction), 2006 Bucks New University, UK. Dissertation: The Relentless Drive Towards Participatory Media (mentors: Dr Paul Springer, Bruce Sinclair and Steve Walls).BTECs in Creative Typography and Graphic Design, London College of Printing (now the London College of Communication), London, UK (mentors: Paul Eckersley and Jerry Gull).BA in English (Language & Literature) and Art History,* Faculty of Social Sciences, University of Ljubljana, Slovenia (*3 years, uncompleted)Secondary School of Visual Merchandising, Ljubljana, SloveniaSecondary School of Design and Photography, Ljubljana, Slovenia (2 years)

Pages About Me I'm a simple Scottish girl with an unusual name and a strange obsession for nail polish! My aim is to capture what the eye sees, with a camera! Too much nail polish and never enough time. Welcome to my little world :-) Tuesday, 15 May 2012 Nails Inc Garrick Street My first Nails Inc post! Yah. This is an iridescent lovely. Mr Posh doesn't understand what my obsession with iridescence is. I'm the same when I see cars! How cool. This is purple and blue and amazing. Artificial light. All natural light. All above are 2 coats. Tried my best to capture the change in colour. This is easy to use, easy to apply and has a good brush. It's also quick drying which is always a winner. It's gorgeous and got some really nice comments from peeps. It looks quite sparkly in the sunshine as well. Didn't last well, once it got chipped it was very flaky and keep coming off. So need to use a top coat with it for sure. It's hot and lovely!

[FR] Feature Request threads I've decided to try to start a new trend. Many users have asked about a separate Feature Request forum, it's not been created & users also seem frustrated trying to find if a specific feature request has been made already. I propose the following for the sanity of the users: 1. Put all Feature Requests in the Questions forum & don't, instead or also, put them in the ticketing system - leave that for bug reports. 2. One Feature Request per thread! 3. Use [FR] at the beginning of the thread title 4. Make the rest of the thread title succinct yet descriptive 5. Users look for/search on [FR] to find all Feature Requests first to avoid creating duplicates. 6. Users particpate in the thread discussion of how they would want said feature to work & give an indication of how important that feature is to them personally. 7. Jake & crew can easily see what Features we users are interested in but are obviously under no obligation to implement any of them or in any particular order. Jake has been clear that much of their motivation derives from having the freedom to work on the features they want. He's also been very clear that, for numerous reasons, he does not want to have an official public list of planned features so don't ask for it! I'm proposing this so we can cut down on our frustration, reduce duplication that may be distracting the developers, & encourage free flow of ideas on feature design & how it would work. Ideally, we'll be happier, TD will have less stuff to keep track of so they can spend time developing & any ideas that are proposed will get fleshed out enough that the devs have good info on what that feature would look like if they decide to implement it! PS. For this to work, you'll need to create threads in this format for those requests you've already put in but have not been implemented...especially since some requests have been out there a long time & may stay that way. Maybe you can use it as a good time to consider if you really still want that feature or not & how it would work if you got it. Sorry but I don't know a better way to consolidate the open requests so they're easily findable. Suggestions are welcome!

Q: How to exclude multiple line patterns using diff? I want to do a diff over two xml files but ignore 2-3 line patterns. eg: Say I want to ignore availability & price while comparing the xml format below. Here is what I have so far: diff -I '^<PRICE>*' 1.xml 2.xml <CATALOG> <PLANT> <COMMON>Bloodroot</COMMON> <BOTANICAL>Sanguinaria canadensis</BOTANICAL> <ZONE>4</ZONE> <LIGHT>Mostly Shady</LIGHT> <PRICE>$2.44</PRICE> <AVAILABILITY>031599</AVAILABILITY> </PLANT> </CATALOG> Using the above diff, it skips the price but how do I add availability to this regex? A: Did you try using -I again? This works for me: diff -I 'PRICE' -I 'AVAILABILITY' 1.xml 2.xml A: Run the files through grep -v to remove the lines you don't need and then diff them as shown below: diff <(grep -vE "^(<PRICE>|<AVAILABILITY>)" 1.xml) <(grep -vE "^(<PRICE>|<AVAILABILITY>)" 2.xml) <(...) syntax is called Process Substitution. If your shell does not support it, you will have to use temporary files, like this: $ grep -vE "^(<PRICE>|<AVAILABILITY>)" 1.xml > 1.new.xml $ grep -vE "^(<PRICE>|<AVAILABILITY>)" 2.xml > 2.new.xml $ diff 1.new.xml 2.new.xml I don't think diff -I can be used with multiple patterns.

In order to transmit maximum allowable power, broadcast antennas should be placed at the highest possible location, as for example, on top of a hill or a tower. Such towers may be up to 2,000 feet in height in order to give the best line-of-sight to distant viewers. The transmitter which produces the high-power broadcast signal is a large structure and is necessarily located on the ground. The high-power signal must be carried from the transmitter up the tower to the feed point at the base of the antenna. VHF (54-88 MHz and 174-216 MHz) and UHF (470-890 MHz) broadcast television signals are ordinarily carried by transmission lines, which are signal conductors designed to minimize signal losses between a source and a load. At UHF frequencies, waveguides are used for carrying the signal from the transmitter to the antenna since a waveguide is particularly well suited to handle the relatively high-power signals associated with television broadcasting with a minimum of signal attenuation. At present, for high power UHF-TV applications there are only two types of waveguides to choose from, i.e., either hollow circular waveguide or rectangular waveguide. Rectangular waveguide is advantageous since it offers a relatively wide bandwidth for the dominant mode of signal propagation and substantially no propagation of the cross-polarized dominant modes. Thus, video signal distortion due to the appearance of cross-polarized modes is minimal. However, due to the flat exterior sides of rectangular waveguide, very high lateral forces are presented to the antenna tower due to windloading, thereby requiring a more sturdy, and therefore more costly, antenna tower. On the other hand, hollow circular waveguide has an exterior which is optimum for minimizing the effect of windloading on the antenna tower. However, unavoidable flexing and asymmetries in circular waveguide due to windloading on the waveguide itself lead to the generation of undesirable cross-polarized mode propagation and resulting video signal distortion. Cross-polarized modes effectively swing the principal plane of polarization, i.e., the dominant mode of the electromagnetic energy propagating through the waveguide, from the desired plane to a plane intermediate the desired plane and the plane of the cross-polarized mode. If an electric probe or magnetic loop is used for coupling energy from the end of the waveguide to the antenna, rotation of the polarization plane results in reduction of the power available to the antenna and also results in reflection of the remainder of the power back to the transmitter. The latter can result in undesirable picture distortion. Thus, a broadcast system is needed in which an antenna on a tower is fed by a waveguide which has relatively low windloading while displaying stable polarization characteristics under conditions of stress and flexure.

Q: MATLAB using 2D Array i want to use a 2D array to store all the values of img1, img2 and the compared vlaue of img1 and img2, I want to achive the algorithm likes: % read in the images from a folder one by one: somefolder = 'folder'; filelist = dir([somefolder '/*.jpg']); s=numel(filelist); C = cell(length(filelist), 1); for k=1:s C{k}=imread([somefolder filelist(k).name]); end %choose any of the two images to compare for t=1:(s-1) for r=(t+1):s img1=C{r}; img2=C{t}; ssim_value[num][1]=img1; % first img ssim_value[num][2]=img2; % second img ssim_value[num][3]=mssim; % ssim value of these two images end end So, there is error about using the 2D array (ssim_value) that I used, what is the correct way of initialization it, and how to achieve the purpose that save the values that I want to store. Could someone help me. Thanks in advance. A: I'm assuming that "num" is a number that you will supply, like 5 or something. You cannot mix types in arrays as you do in Python. Also, as @Schorsch pointed out, you use parenthesis to index arrays in Matlab. The two-dimensional array you are trying to form needs to be a 2-D cell array. For example: a = {{"a",3},{"two",[1,2,3]}; In this case, a{1,2} = 3, and a{2,1} = "two". You may not know in advance how many files are in the directory, so pre-initializing the cell array may not be possible in advance. In any case, Matlab arrays only need to be pre-initialized for performance reasons, and you can easily find information on initializing arrays in Matlab. In light of this, I'm pretty sure what you are trying to accomplish is: %choose any of the two images to compare ssim_value = {}; for t=1:(s-1) for r=(t+1):s img1=C{r}; img2=C{t}; ssim_value{num,1}=img1; % first img ssim_value{num,2}=img2; % second img ssim_value{num,3}=mssim; % ssim value of these two images end end

Associations of obesity, physical activity and diet with benign prostatic hyperplasia and lower urinary tract symptoms. Epidemiological and clinical data indicate that modifiable lifestyle factors - including obesity, physical activity, and diet - significantly influence the risks of symptomatic benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). Modifiable factors associated with significantly increased risks of symptomatic BPH and LUTS include obesity and consumption of meat and fat. Factors associated with decreased risks include increased physical activity, vegetable consumption, and moderate alcohol intake. Obesity potentially attenuates the clinical efficacy of 5α-reductase inhibitors (5-ARI). Randomized clinical trials of lifestyle alterations - such as weight loss, exercise, and diet - for the prevention or treatment of BPH and LUTS have yet to be performed. Obesity, physical activity, and diet substantially alter the risks of symptomatic BPH and LUTS. 5-ARIs exhibit diminished efficacy in obese patients. Although clinical trials of lifestyle modifications have yet to be undertaken, it is reasonable to promote weight loss, exercise, and healthy diet within the context of standard treatments for symptomatic BPH and LUTS.

383 F.3d 558 Emanuel ADEYEMO,* Petitioner,v.John D. ASHCROFT, Respondent. No. 03-2640. United States Court of Appeals, Seventh Circuit. Argued April 21, 2004. Decided September 2, 2004. Petition for review from the Board of Immigration Appeals. Mark S. Kocol (argued), Chicago, IL, for Petitioner. George P. Katsivalis, Department of Homeland Security, Office of the District Counsel, Chicago, IL, Larry P. Cote (argued), Department of Justice, Civil Division, Immigration Litigation, Washington, DC, for Respondent. Before COFFEY, MANION, and KANNE, Circuit Judges. KANNE, Circuit Judge. 1 The petitioner in this immigration case, Emanuel Adeyemo, claims that he did not receive notice of his deportation hearing. The government sent the initial Order to Show Cause by certified mail to the correct address, but Adeyemo has presented evidence that the signature on the return receipt is not his. He suggests that some other resident of his 187-unit apartment building may have signed for the certified letter but failed to pass it along to him. Because the government has not adequately shown that the notice was properly delivered, we grant Adeyemo's petition for review. 2 The case hinges on the distinction between Orders to Show Cause and Notices of Hearing. Under the pre-1996 version of the Immigration and Nationality Act (INA), an alien's initial notice of deportation proceedings was provided in an Order to Show Cause, which had to be delivered in person or by certified mail. See INA § 242B(a)(1), 8 U.S.C. § 1252b(a)(1), repealed by Illegal Immigration Reform and Immigrant Responsibility Act of 1996 (IIRIRA), § 308(b)(6), Pub.L. 104-208, 110 Stat. 3009 (Sept. 30, 1996). Besides informing the alien of the nature of the charges against him, the Order to Show Cause directed him to provide the government with a current address to which further notices could be sent. These included the Notice of Hearing, informing the alien of the time and place at which proceedings would be held. See INA § 242B(a)(2), 8 U.S.C. § 1252b(a)(2) (repealed 1996).1 3 The distinction between these two forms of notice is important because of the differing consequences of nondelivery. In Matter of Huete, 20 I. & N. Dec. 250, 253 (BIA 1991), the Board of Immigration Appeals held that when certified mail is used to deliver an Order to Show Cause, "the certified mail receipt [must] be signed by the respondent or a responsible person at the respondent's address and returned to effect personal service." In contrast, the BIA has held that no such proof of delivery is required for a Notice of Hearing, but only proof of attempted delivery. See Matter of Grijalva, 21 I. & N. Dec. 27, 33 (BIA 1995). 4 In Adeyemo's case, the Immigration and Naturalization Service issued an Order to Show Cause in February 1994. A certified mail receipt, signed on March 8, was returned to the agency, but the signature on the receipt was illegible. A later Notice of Hearing was returned as undeliverable. The hearing was held in February 1995, and when Adeyemo did not appear, he was ordered deported in absentia. 5 Seven years later, when Adeyemo found out about this deportation order, he moved to reopen his deportation proceedings for lack of notice. He claimed that he did not receive either the Order to Show Cause or the Notice of Hearing. The immigration judge denied the motion, declaring that it did not matter whether the documents were received, so long as there was proof of attempted delivery. 6 This was, of course, a mistake. The IJ explicitly relied on the BIA's decision in Grijalva, not recognizing that the reasoning of that case is limited to Notices of Hearing, and does not apply to Orders to Show Cause. See Grijalva, 21 I. & N. Dec. at 32; see also Tapia v. Ashcroft, 351 F.3d 795, 798 n. 5 (7th Cir.2003). Adeyemo pointed out this error on appeal to the BIA, and presented contemporary examples of signatures from himself and from his ex-wife Casandra to show that the signature on the return receipt was neither his nor that of any responsible person at his address. 7 The BIA acknowledged the IJ's mistake, but nevertheless concluded that the government had presented sufficient proof of proper delivery. The Board placed the burden of proving nonreceipt squarely on Adeyemo: 8 We do not read the statute or Matter of Huete ... as imposing on the Service the burden of establishing that the postal service had the return receipt signed by either the respondent himself or a responsible person. To hold otherwise would allow an alien to thwart effective service by altering his or her signature on the return receipt or by disclaiming knowledge of the signatory of the return receipt. 9 Finding "no indication on the face of the [return receipt] that the person who signed [it] suffered from a legal infirmity due to either age or mental incompetence," the BIA charged Adeyemo with receipt of the Order to Show Cause. As for the later Notice of Hearing (which had been returned as undeliverable) the BIA found there was proof of attempted delivery, which is sufficient under Grijalva for such notices. The BIA therefore dismissed Adeyemo's appeal. 10 Adeyemo now argues that the BIA wrongly considered the illegible signature on the certified return receipt to be adequate proof under Huete that the Order to Show Cause was properly delivered, and contends that the Board's refusal to reopen his deportation proceedings was therefore an abuse of discretion. The government argues in response that it is appropriate to presume that the post office carries out its duties properly — specifically, that the post office would not deliver the certified mail to an unauthorized person — and Adeyemo's evidence that the signature on the receipt was neither his nor his ex-wife's is not enough to overcome this presumption. 11 Under the former § 242B(c)(1) of the INA, 8 U.S.C. § 1252b(c)(1) (repealed 1996), when an alien fails to appear at a deportation hearing, the government must establish "by clear, unequivocal, and convincing evidence" that proper notice was given. The BIA determined in Huete (and reaffirmed in Grijalva) that when the initial notice in the Order to Show Cause is sent by certified mail, proper delivery must be demonstrated by a certified mail receipt "signed by the respondent or a responsible person at the respondent's address." The BIA noted that "[a]bsent such a requirement, there is no meaningful distinction between service by certified mail and service by regular mail." Huete, 20 I. & N. Dec. at 253; see also Grijalva, 21 I. & N. Dec. at 32 (reaffirming Huete's holding that a certified mail receipt must be signed by the respondent or a responsible person at the respondent's address to accomplish personal service of an Order to Show Cause). 12 In this case, the certified mail receipt was returned with a signature. The question is whether the government must show that the signature belonged to Adeyemo or some responsible person at his address. We recently analyzed a similar situation in Tapia v. Ashcroft, 351 F.3d 795. In that case, the government sent an Order to Show Cause by certified mail to Tapia's last known address. The return receipt appeared to bear the signature of Tapia's adult sister, who lived with him at that address. Tapia argued that the government had not shown that the person who signed the receipt was "responsible." He did not, however, have his sister testify that the signature was not hers, nor did he argue or present evidence that his sister was not in fact a "responsible person." We concluded that the government had met its burden of showing delivery. Tapia, 351 F.3d at 798. 13 This case differs from Tapia in two respects. First, in Tapia there was evidence that the signature belonged to Tapia's adult sister; in this case, the signature is almost completely illegible and does not resemble any of the signature exemplars provided by Adeyemo and his ex-wife. Second, Tapia presented no evidence to rebut the government's claim that the signature was his sister's or that his sister was a "responsible person"; Adeyemo, in contrast, has presented evidence that the signature was neither his nor his ex-wife's and that there was no other responsible person living at his address at the time. 14 The government suggests that Adeyemo's evidence of nonreceipt is inadequate. It cites Grijalva for the propositions that "a bald and unsupported denial of receipt of certified mail notices is not sufficient to support a motion to reopen" and that the presumption of proper delivery can only be rebutted by "substantial and probative evidence ... showing that there was improper delivery." See Grijalva, 21 I. & N. Dec. at 37. But again, this passage from Grijalva concerns only Notices of Hearing, to which the return-receipt requirement does not apply. See id. at 34 (when a Notice of Hearing is provided by certified mail, "[t]here is no requirement that the return receipt be signed by the alien or a responsible person at his address to effect service") (emphasis added). In contrast, there is such a requirement in the context of delivering an Order to Show Cause. See id. at 32 (when an Order to Show Cause is sent by certified mail, "the certified mail receipt [must] be signed by the respondent or a responsible person at the respondent's address"). 15 The illegible signature on the return receipt in this case is not enough to create a presumption of actual delivery to Adeyemo or a responsible person at his address. We therefore GRANT the petition for review and REMAND the case for further proceedings. Notes: * The petitioner's last name is spelled "Adeeyemoh" in the decisions of the Immigration Judge and the Board of Immigration Appeals. We follow the spelling used in the briefs and throughout most of the administrative record 1 These two forms of notice have since been consolidated into a single "Notice to Appear," for which the use of certified mail is no longer requiredSee INA § 239(a)(1), 8 U.S.C. § 1229(a)(1).

Utility meters may be configured to perform wireless transmission of meter readings. For example, an Encoder Receiver Transmitter (“ERT”) may be implemented within a utility meter in order to encode and transmit data utilizing radio-based communications. Utility meters configured to report meter readings in this way are commercially available and increasingly being installed in homes, businesses, and the like. At installation or subsequently, a utility service provider may register and begin obtaining meter readings using a collection system such as fixed network, mobile collection unit, etc. Transmissions of meter readings are typically encoded as “packetized” data. In the present application, the term “packet” is intended to encompass packets, frames, cells or any other method used to encapsulate data for transmission between remote devices. As understood in the art, packets typically maintain a plurality of fields as well as a preamble and trailer to identify the beginning and end of the packet. For example, existing packet formats typically include a time stamp field identifying the time maintained by the “clock” of a utility meter. To extend the operating life of a battery or other power source, techniques and devices that minimize power consumption are utilized. As a result, a low-power clock having at least some tendency to “drift” from an actual time may be employed by utility meters. Unfortunately, existing packet formats and related systems are not readily able to measure inaccuracies in the time maintained by utility meters. A collection system employed by a utility service provider may include Cell Control Units (“CCU”) that receive meter readings within a geographic coverage area. To provide fault-tolerance and ensure that meter readings are collected, CCUs will typically maintain overlapping coverage areas. As a result, meter readings originating from a utility meter may be received by multiple CCUs with each being forwarded to a utility service provider. During normal operations, this fault tolerance may result in excessive network resources being consumed since the same data is forwarded by multiple CCUs.

Paged media (e.g., paper, transparencies, pages that are displayed on computer screens, etc.) differ from continuous media in that the content of the document is split into one or more discrete pages. CSS 2.1 has three properties that indicate where the user agent may or should break pages, and on what page (left or right) the subsequent content should resume. Each page break ends layout in the current page and causes remaining pieces of the document tree to be laid out on a new page. Force one or two page breaks before (after) the generated box so that the next page is formatted as a left page. right Force one or two page breaks before (after) the generated box so that the next page is formatted as a right page. Whether the first page of a document is a left page or a right page is not defined in this specification. A conforming user agent may interpret the values 'left' and 'right' as 'always'. A potential page break location is typically under the influence of the parent element's 'page-break-inside' property, the 'page-break-after' property of the preceding element, and the 'page-break-before' property of the following element. When these properties have values other than 'auto', the values 'always', 'left', and 'right' take precedence over 'avoid'. These properties only apply to non-floating block-level elements. Also, page breaks cannot be forced to occur inside table cells, absolutely positioned boxes, and fixed positioned boxes. Page breaks set before, inside, or after such elements must be ignored. Rule A: Breaking at (1) is allowed only if the 'page-break-after' and 'page-break-before' properties of all the elements generating boxes that meet at this margin allow it, which is when at least one of them has the value 'always', 'left', or 'right', or when all of them are 'auto'. Rule B: However, if all of them are 'auto' and the nearest common ancestor of all the elements has a 'page-break-inside' value of 'avoid', then breaking here is not allowed. If the above rules do not provide enough break points to keep content from overflowing the page boxes, then rules B and C are dropped in order to find additional breakpoints. If that still does not lead to sufficient break points, rule A is dropped as well. A page break must occur at (1) if, among the 'page-break-after' and 'page-break-before' properties of all the elements generating boxes that meet at this margin, there is at least one with the value 'always', 'left', or 'right'. CSS 2.1 does not define which of a set of allowed page breaks must be used; CSS 2.1 does not forbid a user agent from breaking at every possible break point, or not to break at all. But CSS 2.1 does recommend that user agents observe the following heuristics (while recognizing that they are sometimes contradictory): Break as few times as possible. Make all pages that don't end with a forced break appear to have about the same height.

THE STATE OF SOUTH CAROLINA In The Court of Appeals Joey Lemmons d/b/a Rugs International, Appellant, v. Macedonia Water Works, Inc., Respondent. Appellate Case No. 2017-002171 Appeal From Cherokee County R. Keith Kelly, Circuit Court Judge Opinion No. 5747 Submitted June 1, 2020 – Filed July 22, 2020 AFFIRMED Christopher David Kennedy and N. Douglas Brannon, both of Kennedy & Brannon, P.A., of Spartanburg; and J. Falkner Wilkes, of Greenville, for Appellant. Joseph L. Mathis and Joseph L.V. Johnson, both of Saint- Amand Thompson & Mathis, LLC, of Gaffney; and Lawrence Emile Flynn, III, of Pope Flynn, LLC, of Columbia, for Respondent. GEATHERS, J.: Appellant Joey Lemmons, d/b/a Rugs International (Customer) seeks review of the circuit court's order granting summary judgment to Respondent Macedonia Water Works, Inc. (Utility) in Customer's action seeking a refund. Customer argues the circuit court erred in declining to enforce section 58-5-390 of the South Carolina Code (2015), which limits the fee a utility may charge for the installation and maintenance of a fire sprinkler system. Utility seeks a dismissal of this appeal on the ground that Customer did not timely serve the notice of appeal. We deny the motion to dismiss and affirm the circuit court's order. FACTS/PROCEDURAL HISTORY In 1999, Customer purchased a commercial building in Cherokee County, near Gaffney, for his business, Rugs International.1 At that time, a single tap onto Utility's water main supplied the water for the building's dual-purpose service line to a potable water system and a fire sprinkler system. The eight-inch line was accompanied by a four-inch bypass line to accommodate the variance in the volume of water flow—when the flow was low, a valve within the service line's compound meter assembly closed to force all of the water to flow through the assembly's four- inch meter, and when the flow increased to a certain point, the valve opened to allow the water to flow through the assembly's eight-inch meter. This assembly increased the accuracy of metering—a low flow could not be measured accurately by a large meter; therefore, the meter assembly compounded the readings between the eight- inch meter and the four-inch bypass meter. Utility has billed its customers a certain monthly minimum charge based primarily on the size of the customer's water meter. The minimum charge has covered water usage up to 2,000 gallons, and a volumetric charge has been added for usage exceeding 2,000 gallons. Utility's water rate schedule (effective January 1, 2001) indicates that the minimum charge for an eight-inch meter is $650. Utility determined this amount to be the actual cost of providing an eight-inch line, explaining that this amount includes the cost of increased capacity in the event that a customer "decides to make maximum use of the volumes of water that are available to him at any time." On the other hand, the monthly charge for a service line that is dedicated exclusively to a fire sprinkler system is a flat rate of $50. These accounts 1 In his affidavit, Customer references one building. However, in an exhibit attached to the affidavit, specifically, a letter from Utility to Customer, Utility contends, "In the case of the Rugs International facility, there are multiple facilities, services, and buildings [that] are supplied water service from a single water meter and tap." Nonetheless, we need not resolve this discrepancy for purposes of deciding the issues on appeal. are charged much less than other accounts because "consumption virtually never occurs . . . unless there is a fire."2 In 2012, Customer became aware of section 58-5-390 of the South Carolina Code, which limits the fee a utility may charge for the installation and maintenance of a fire sprinkler system.3 Customer believed that the statute applied to his water line and sought a refund of amounts he claimed Utility had overbilled him. Utility took the position that it had not overbilled Customer because his building did not have a service line dedicated exclusively to a fire sprinkler system. In March 2014, Customer added a new one-inch meter to his building to accommodate the potable 2 Jeffrey Walker, Customer's expert witness and general manager for a nearby water district that bills in the same manner that Utility bills its customers, made this statement in his August 10, 2016 letter to Utility's counsel. 3 The legislation creating section 58-5-390 was passed in 2008. See Act No. 357, 2008 S.C. Acts 3601, effective June 25, 2008. This act was amended in 2010 to add subsection (C) to section 58-5-390. Section 58-5-390 states, (A) A publicly or privately owned utility may not impose a tap fee, other fee, or a recurring maintenance fee of any nature or however described for the installation and maintenance of a fire sprinkler system that exceeds the actual costs associated with the water line to the system. (B) For purposes of this section, actual costs include direct labor, direct material, the necessity of increased capacity, and other direct charges associated with the separate fire sprinkler line. The direct costs must be documented by either an invoice or work order that specifically assigns the costs to the separate fire sprinkler line. Nothing in this section may be construed as requiring a utility to provide service to support a private fire protection system. (C) Nothing in this section shall give the commission or the regulatory staff any power to regulate or interfere with public utilities owned or operated by or on behalf of any municipality, county, or regional transportation authority as defined in Chapter 25 of this title or their agencies. (emphases added). water system and dedicated the eight-inch meter to the fire sprinkler system. From that point forward, Utility charged Customer $50 per month for the line dedicated to the fire sprinkler system and a monthly minimum of $20 for the one-inch line to the potable water system. On November 24, 2014, Customer filed this action seeking a refund based on section 58-5-390. In his complaint, Customer alleged that his former compound meter had included an eight-inch meter and a two-inch meter and regular water usage had flowed through the two-inch meter. Customer also alleged that the higher volume of water had flowed through the eight-inch meter only when a fire activated the sprinkler system and only fifteen gallons had passed through the eight-inch meter since it had been installed. After filing an answer to Customer's complaint, Utility filed a motion for summary judgment, and the circuit court conducted a hearing on the motion on January 6, 2017. In its order granting summary judgment to Utility, the circuit court concluded that section 58-5-390 did not apply to Customer's former dual-purpose line because it was not dedicated exclusively to a fire sprinkler system as contemplated by the statute. The circuit court later denied Customer's Rule 59(e) motion. This appeal followed. Utility did not file a separate motion to dismiss this appeal, but rather raised the issue of appellate jurisdiction for the first time in its appellate brief. ISSUES ON APPEAL 1. Does this court have appellate jurisdiction over this action? 2. Did the circuit court err by interpreting section 58-5-390 to apply to only those lines dedicated exclusively to a fire sprinkler system? 3. Did Customer have a separate fire sprinkler line for purposes of section 58-5-390 during the period for which he seeks a refund? STANDARD OF REVIEW This court reviews the grant of a summary judgment motion under the same standard applied by the trial court pursuant to Rule 56(c), SCRCP. Jackson v. Bermuda Sands, Inc., 383 S.C. 11, 14 n.2, 677 S.E.2d 612, 614 n.2 (Ct. App. 2009). Rule 56(c), SCRCP, provides that summary judgment shall be granted when "the pleadings, depositions, answers to interrogatories, and admissions on file, together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law." Further, when a circuit court grants summary judgment on a question of law, such as statutory interpretation, the appellate court must review the ruling de novo. Wright v. PRG Real Estate Mgmt., Inc., 426 S.C. 202, 212, 826 S.E.2d 285, 290 (2019); see Lightner v. Hampton Hall Club, Inc., 419 S.C. 357, 363, 798 S.E.2d 555, 558 (2017) ("An issue regarding statutory interpretation is a question of law." (quoting Univ. of S. Cal. v. Moran, 365 S.C. 270, 274, 617 S.E.2d 135, 137 (Ct. App. 2005))). LAW/ANALYSIS I. Appellate Jurisdiction Utility asserts that this appeal should be dismissed for lack of jurisdiction because Customer did not timely serve the notice of appeal.4 See Rule 203(b)(1), SCACR ("A notice of appeal shall be served on all respondents within thirty (30) days after receipt of written notice of entry of the order or judgment. When a timely motion for judgment n.o.v. (Rule 50, SCRCP), motion to alter or amend the judgment (Rules 52 and 59, SCRCP), or a motion for a new trial (Rule 59, SCRCP) has been made, the time for appeal for all parties shall be stayed and shall run from receipt of written notice of entry of the order granting or denying such motion."); Camp v. Camp, 386 S.C. 571, 574–75, 689 S.E.2d 634, 636 (2010) ("Service of the notice of appeal is a 'jurisdictional requirement, and this [c]ourt has no authority to extend or expand the time in which the notice of intent to appeal must be served.'" (quoting Mears v. Mears, 287 S.C. 168, 169, 337 S.E.2d 206, 207 (1985))). Specifically, Utility contends that Customer's Rule 59(e) motion did not stay the time for serving the notice of appeal because the motion was not served until after the ten-day deadline. See Rule 59(e), SCRCP ("A motion to alter or amend the judgment shall be served not later than 10 days after receipt of written notice of the entry of the order."); Rule 203(b)(1), SCACR (indicating that when a timely post-trial or post-hearing motion has been made, "the time for appeal for all parties shall be stayed and shall run from receipt of written notice of entry of the order granting or denying such motion"); see also Rule 59(f), SCRCP ("The time for appeal for all parties shall be stayed by a timely motion under this Rule and shall run 4 Utility actually employs the term "subject matter jurisdiction." However, late service of the notice of appeal deprives this court of appellate jurisdiction rather than subject matter jurisdiction. See State v. Brown, 358 S.C. 382, 387, 596 S.E.2d 39, 41 (2004) (holding that the failure to comply with the procedural requirements for an appeal divests a court of appellate jurisdiction but not of subject matter jurisdiction). from the receipt of written notice of entry of the order granting or denying such motions." (emphasis added)). Utility bases its argument on the premise that the time-stamp on the circuit court's e-mail providing the parties notice of the entry of its summary judgment order was the starting point for calculating the ten-day deadline, relying on Wells Fargo Bank, N.A. v. Fallon Props. S.C., LLC, 422 S.C. 211, 217, 810 S.E.2d 856, 859 (2018). In Wells Fargo, our supreme court discussed the thirty-day deadline for filing a notice of appeal and stated, "[A]n email providing written notice of entry of an order or judgment for purposes of Rule 203(b)(1), SCACR[,] triggers the time to appeal as long as the email is received from the court, an attorney of record, or a party." 422 S.C. at 217, 810 S.E.2d at 859. The court explained that the notice of entry of the order being appealed does not have to be formally served by the court or an opposing party but rather "[a]ll that is required to trigger the time to appeal is that the parties receive such notice." Id. at 215–16, 810 S.E.2d at 858. Notably, the date the appellants in Wells Fargo received the e-mail from the circuit court's administrative assistant was not in dispute. Rather, the appellants argued that their receipt of notice by e-mail rather than by regular mail or hand delivery could not trigger the time within which to file the notice of appeal. Id. at 215, 810 S.E.2d at 858. However, in the instant case, Customer challenges the date of receipt of the e-mail because there was no record created before the circuit court as to that critical date. Customer maintains that the time-stamp on the e-mail is not always the starting point because the time-stamp does not conclusively determine the date a party receives the e-mail and the date of receipt determines the starting point for calculating the ten-day deadline. See Rule 59(e), SCRCP ("A motion to alter or amend the judgment shall be served not later than 10 days after receipt of written notice of the entry of the order." (emphasis added)). Customer credibly asserts, "Emails, although commonly used, are nonetheless subject to unpredictable and unexplainable travels[ and] delayed and sometimes failed delivery, just as are letters mailed through the postal system." See S.C. Code Ann. § 26-6-150(B) (2007) ("Unless otherwise agreed between a sender and the recipient, an electronic record is received when it: (1) enters an information processing system that the recipient has designated or uses for the purpose of receiving electronic records or information of the type sent and from which the recipient is able to retrieve the electronic record; and (2) is in a form capable of being processed by that system." (emphasis added));5 5 Section 26-6-150 was enacted in 2004. Act No. 279, 2004 S.C. Acts 2804. S.C. Code Ann. § 26-6-150(G) (2007) ("If a person is aware that an electronic record purportedly sent pursuant to subsection (A), or purportedly received pursuant to subsection (B), was not actually sent or received, the legal effect of the sending or receipt is determined by other applicable law." (emphasis added)). Customer also maintains that when the circuit court was considering his Rule 59(e) motion, he did not have an opportunity to submit evidence of the date he actually received written notice of the entry of the summary judgment order because at that time, Utility presented neither an argument that the Rule 59(e) motion was late nor the AIS document on which it now relies to show when the circuit court's e-mail was sent.6 The question of whether the e-mail's time-stamp can be presumed to be the date of a party's receipt of the notice has not yet been addressed by our appellate courts. In the absence of our supreme court's pronouncement of such a presumption, this court must look to the Record on Appeal to determine the date of receipt of the circuit court's e-mail notice according to the standards of section 26-6-150(B). See § 26-6-150(B) ("Unless otherwise agreed between a sender and the recipient, an electronic record is received when it: (1) enters an information processing system that the recipient has designated or uses for the purpose of receiving electronic records or information of the type sent and from which the recipient is able to retrieve the electronic record; and (2) is in a form capable of being processed by that system." (emphases added)). Because Utility failed to present to the circuit court its argument that Customer's Rule 59(e) motion was late, the parties did not create a record establishing either the date that the circuit court's e-mail notice entered counsel's e-mail server or whether the e-mail notice was "in a form capable of being processed by" counsel's server. Therefore, we reject Utility's argument that Customer did not timely invoke this court's appellate jurisdiction. II. Interpretation of section 58-5-390 Customer maintains the circuit court erred by interpreting section 58-5-390 to apply to only those lines dedicated exclusively to a fire sprinkler system. He argues 6 In its brief, Utility asserts that the order granting summary judgment was sent to the attorneys of record via the Attorney Information System (AIS) at 12:00 p.m. on March 23, 2017. Utility also asserts that Customer served his Rule 59(e) motion on Utility via AIS on April 4, 2017. that the legislative intent underlying section 58-5-390 was for the statute to apply to all fire sprinkler systems "without exception, even if the tap supplies other water uses." We disagree. Section 58-5-390 states, (A) A publicly or privately owned utility may not impose a tap fee, other fee, or a recurring maintenance fee of any nature or however described for the installation and maintenance of a fire sprinkler system that exceeds the actual costs associated with the water line to the system. (B) For purposes of this section, actual costs include direct labor, direct material, the necessity of increased capacity, and other direct charges associated with the separate fire sprinkler line. The direct costs must be documented by either an invoice or work order that specifically assigns the costs to the separate fire sprinkler line. Nothing in this section may be construed as requiring a utility to provide service to support a private fire protection system. (C) Nothing in this section shall give the commission or the regulatory staff any power to regulate or interfere with public utilities owned or operated by or on behalf of any municipality, county, or regional transportation authority as defined in Chapter 25 of this title or their agencies. (emphases added). "In interpreting statutes, the [c]ourt looks to the plain meaning of the statute and the intent of the Legislature." Gay v. Ariail, 381 S.C. 341, 344, 673 S.E.2d 418, 420 (2009). "All rules of statutory construction are subservient to the maxim that legislative intent must prevail if it can be reasonably discovered in the language used." Id. Therefore, "[i]n interpreting a statute, the court will give words their plain and ordinary meaning[] and will not resort to forced construction that would limit or expand the statute." State v. Johnson, 396 S.C. 182, 188, 720 S.E.2d 516, 520 (Ct. App. 2011). Under the plain meaning rule, it is not the province of the court to change the meaning of a clear and unambiguous  statute. Where the statute's language is plain, unambiguous,7 and conveys a clear, definite meaning, the rules of statutory interpretation are not needed and the court has no right to impose another meaning. S.C. Energy Users Comm. v. S.C. Pub. Serv. Comm'n, 388 S.C. 486, 491, 697 S.E.2d 587, 590 (2010) (citation omitted). Further, "[t]he intention of the legislature must be gleaned from the entire section and not simply clauses taken out of context." Singletary v. S.C. Dep't of Educ., 316 S.C. 153, 162, 447 S.E.2d 231, 236 (Ct. App. 1994). First, the plain language of the statute as a whole reflects the legislature's intent to isolate the costs "associated with" a line to a fire sprinkler system to a separate line dedicated to only that system. Subsection (A) limits the utility's fee to "the actual costs associated with the water line to the system." Next, subsection (B) fleshes out the terms "actual costs" and "associated with" by not only itemizing those costs but also requiring utilities to document costs and to do so in a manner that assigns them to a line dedicated solely to the fire sprinkler system: "The direct costs must be documented by either an invoice or work order that specifically assigns the costs to the separate fire sprinkler line." § 58-5-390(B) (emphases added); see Collins v. Doe, 352 S.C. 462, 470, 574 S.E.2d 739, 743 (2002) ("[U]se of words such as 'shall' or 'must' indicates the legislature's intent to enact a mandatory requirement."). The use of this mandatory language rules out the possibility that the legislature simply left unaddressed the question of how costs could be calculated on dual-purpose lines to existing fire sprinkler systems, which would have created a latent ambiguity in the statute. See Barth v. Barth, 293 S.C. 305, 309, 360 S.E.2d 309, 311 (1987) ("The ascertainment of intention may be the least of a judge's troubles in ascribing meaning to a statute. 'The fact is . . . that the difficulties of so-called interpretation arise when the legislature has had no meaning at all; when the question [that] is raised on the statute never occurred to it; when what the judges have to do is, not to determine what the legislature did mean on a point [that] was present to its mind, but to guess what it would have intended on a point not present to its mind, if the point had been present.'" (quoting Benjamin N. Cardozo, The Nature of the Judicial Process 14–14 (Yale University Press 1921))). 7 "If a statute is susceptible to two reasonable interpretations, it is ambiguous." S.C. Dep't of Soc. Servs. v. Lisa C., 380 S.C. 406, 416, 669 S.E.2d 647, 652 (Ct. App. 2008).  Nonetheless, even if the statute may be reasonably interpreted in more than one way so as to render it ambiguous, applying the rules of statutory construction to section 58-5-390 underscores the reality that it is not feasible to determine all of the "actual" costs associated with a line to a fire sprinkler system if the line is also used for other purposes. The only way to stay true to the requirement to charge only the actual costs is to isolate those costs through the separation of the line to the fire sprinkler system from any water line serving other building systems. If the legislature had deemed it sufficient for a utility to extrapolate the costs of a water line to a fire sprinkler system from the costs of a dual-purpose line, it would not have included the word "actual" in subsections (A) and (B) or the word "separate" in subsection (B). See CFRE, LLC v. Greenville Cty. Assessor, 395 S.C. 67, 74, 716 S.E.2d 877, 881 (2011) ("[W]e read the statute as a whole and in a manner consonant and in harmony with its purpose." (emphasis added)); id. ("In that vein, we must read the statute so 'that no word, clause, sentence, provision or part shall be rendered surplusage, or superfluous,' for '[t]he General Assembly obviously intended [the statute] to have some efficacy, or the legislature would not have enacted it into law.'" (emphases added) (citation omitted) (alterations in original) (quoting State v. Sweat, 379 S.C. 367, 377, 382, 665 S.E.2d 645, 651, 654 (Ct. App. 2008) ("Sweat I"), aff'd as modified on other grounds, 386 S.C. 339, 688 S.E.2d 569 (2010) ("Sweat II"))); Sweat I, 379 S.C. at 376, 665 S.E.2d at 650 ("A statute as a whole must receive a practical, reasonable, and fair interpretation consonant with the purpose, design, and policy of the lawmakers." (emphasis added)); Sweat II, 386 S.C. at 351, 688 S.E.2d at 575 ("Courts will reject a statutory interpretation [that] would lead to a result so plainly absurd that it could not have been intended by the Legislature or would defeat the plain legislative intention."); id. ("Any ambiguity in a statute should be resolved in favor of a just, equitable, and beneficial operation of the law." (quoting Bennett v. Sullivan's Island Bd. of Adjustment, 313 S.C. 455, 458, 438 S.E.2d 273, 274 (Ct. App. 1993))). Customer relies on the language stating the statute's purpose, i.e., "[I]t is the purpose of this act to create meaningful incentives for the installation of fire sprinkler systems,"8 to support his argument that the legislature intended for the statute to apply to all fire sprinkler systems. However, the statute's purpose contemplates the installation of new fire sprinkler systems into buildings that did not already have them on the statute's effective date and provides fair notice to utilities that they must document actual costs only by installing a separate line dedicated exclusively to a fire sprinkler system. See CFRE, 395 S.C. at 74, 716 S.E.2d at 881 ("[W]e read the 8 Act No. 357, Preamble, 2008 S.C. Acts 3602, effective June 25, 2008. statute as a whole and in a manner consonant and in harmony with its purpose." (emphasis added)); Sweat I, 379 S.C. at 376, 665 S.E.2d at 650 ("A statute as a whole must receive a practical, reasonable, and fair interpretation consonant with the purpose, design, and policy of the lawmakers." (emphasis added)); cf. Gatewood v. S.C. Dep't of Corr., 416 S.C. 304, 321, 785 S.E.2d 600, 609 (Ct. App. 2016) ("[A]bsent a specific provision or clear legislative intent to the contrary, statutes are to be construed prospectively rather than retroactively, unless the statute is remedial or procedural in nature." (quoting Edwards v. State Law Enf't Div., 395 S.C. 571, 579, 720 S.E.2d 462, 466 (2011))).9 The owners of buildings with fire sprinkler systems already in place when section 58-5-390 was enacted did not need the incentive created by the statute. Therefore, the statute's incentive-creating purpose was not fulfilled by existing fire sprinkler systems. Hence, we see no incongruity in excluding from the class of the statute's beneficiaries those owners of fire sprinkler systems that were already existing on the statute's effective date and were served by a dual-purpose line. Further, we note that Act No. 357 also created or amended several other statutes to serve the purpose of creating incentives for installing fire sprinkler systems. For example, section 2 of the Act added section 12-6-3622 to the South Carolina Code. Act No. 357, 2008 S.C. Acts 3603–04; S.C. Code Ann. § 12-6-3622 (2014 & Supp. 2019). Section 12-6-3622 allows a property tax credit, under certain conditions, for the installation of a fire sprinkler system in a business or residence. Further, section 3 of the Act amended section 12-37-3130 of the South Carolina Code (2014) to exclude the voluntary installation of a fire sprinkler system from the definition of "additions" or "improvements" in determining the fair market value of real property for tax purposes, provided the utility and function of the structure remains unchanged. Act No. 357, 2008 S.C. Acts 3604–05. Moreover, section 5 of the Act amended section 12-37-220 of the South Carolina Code (2014 & Supp. 2019) to add a property tax exemption for fire sprinkler system equipment until the building in which the system is installed undergoes an "assessable transfer of interest." Act No. 357, 2008 S.C. Acts 3605. In light of these additional incentives, we do not believe that limiting the fire sprinkler systems governed by section 58-5- 390 to those that have a separate connection to a utility's main significantly detracts from the Act's purpose of creating incentives for the installation of these systems. 9 Id. ("A statute is remedial whe[n] it creates new remedies for existing rights unless it violates a contractual obligation, creates a new right, or divests a vested right." (quoting Se. Site Prep, LLC v. Atl. Coast Builders & Contractors, LLC, 394 S.C. 97, 106, 713 S.E.2d 650, 655 (Ct. App. 2011))); id. ("[A] statute that limits a right is generally not procedural." (quoting Edwards, 395 S.C. at 580, 720 S.E.2d at 467)).  Based on the foregoing, we affirm the circuit court's conclusion that section 58-5-390 applies to only those lines dedicated exclusively to a fire sprinkler system. III. Separate Line Customer argues that he presented at least a scintilla of evidence that his building had a separate fire sprinkler line for purposes of section 58-8-390 before he added his one-inch line and, therefore, summary judgment was inappropriate. See Hancock v. Mid-S. Mgmt. Co., 381 S.C. 326, 330, 673 S.E.2d 801, 803 (2009) ("[I]n cases applying the preponderance of the evidence burden of proof, the non-moving party is only required to submit a mere scintilla of evidence in order to withstand a motion for summary judgment."). Customer contends that the circuit court improperly weighed the evidence because "[a] simple examination of the two meters along with [Customer's] testimony was more than sufficient to require the court to deny summary judgment in this case." See S.C. Prop. & Cas. Guar. Ass'n v. Yensen, 345 S.C. 512, 518, 548 S.E.2d 880, 883 (Ct. App. 2001) ("At the summary judgment stage of litigation, the court does not weigh conflicting evidence with respect to a disputed material fact."). Customer also argues that the circuit court failed to view the evidence in the light most favorable to him. See Hendricks v. Clemson Univ., 353 S.C. 449, 455–56, 578 S.E.2d 711, 714 (2003) ("In determining whether any triable issues of fact exist, the evidence and all reasonable inferences must be viewed in the light most favorable to the nonmoving party."). We disagree. "[A] scintilla of evidence is any material evidence which, taken as true, would tend to establish the issue in the mind of a reasonable juror." Crosby v. Seaboard Air Line Ry., 81 S.C. 24, 31, 61 S.E. 1064, 1067 (1908) (emphasis added). "[A]ny evidence, even a scintilla, that is useful to withstand a summary judgment motion must meet the prerequisite of being probative." Bass v. Gopal, Inc., 384 S.C. 238, 246 n.6, 680 S.E.2d 917, 921 n.6 (Ct. App. 2009), aff'd, 395 S.C. 129, 716 S.E.2d 910 (2011). The circuit court "is not required to single out some one morsel of evidence and attach to it great significance when patently the evidence is introduced solely in a vain attempt to create an issue of fact that is not genuine." Main v. Corley, 281 S.C. 525, 527, 316 S.E.2d 406, 407 (1984). "Once the moving party carries its initial burden, the opposing party must come forward with specific facts that show there is a genuine issue of fact remaining for trial." Sims v. Amisub of S.C., Inc., 408 S.C. 202, 208, 758 S.E.2d 187, 190–91 (Ct. App. 2014), aff'd, 414 S.C. 109, 777 S.E.2d 379 (2015) (emphasis added) (quoting Sides v. Greenville Hosp. Sys., 362 S.C. 250, 255, 607 S.E.2d 362, 364 (Ct. App. 2004)).  Here, Customer asserts that an examination of his meter assembly shows two separate lines running to two separate meters. However, in determining whether a factual issue is genuine, a true understanding of certain evidence requires the court to move beyond a cursory examination to acknowledge existing expertise on the matter. See Crosby, 81 S.C. at 31, 61 S.E. at 1067 ("[A] scintilla of evidence is any material evidence which, taken as true, would tend to establish the issue in the mind of a reasonable juror." (emphasis added)); Main, 281 S.C. at 527, 316 S.E.2d at 407 (stating that the circuit court "is not required to single out some one morsel of evidence and attach to it great significance when patently the evidence is introduced solely in a vain attempt to create an issue of fact that is not genuine"). Further, viewing the evidence in the light most favorable to the party opposing summary judgment does not change this reality. Turning to the opinions of both parties' experts in the present case, a reasonable juror could not escape the conclusion that during the period for which Customer seeks a refund, the building did not have a separate line dedicated to the fire sprinkler system. After examining these opinions, we agree with Utility's assessment that during the period for which Customer seeks a refund, the eight-inch line was not limited to fire service only as it served the entire building and water capacity was available to Customer at any time and for any purpose. Utility's engineering expert, William H. Bingham, Jr., prepared a report to formalize the findings he made during his site visit on November 1, 2013, and to provide the basis for his opinion regarding the service to the Rugs International facility.10 Bingham described Customer's water meter as an eight-inch compound water meter with a four-inch bypass meter. Bingham explained the nature of this meter in the following manner: Since this style of water meter is used on both separate fire lines and dual purpose service lines, a determination of the type of water service for a given customer cannot be made simply by observing whether the meter assembly is comprised of a single meter or a compound meter. The use of two meters in the compound meter assembly is purely for improvement in the measurement of flow in the system and has no bearing on whether the water is used for fire sprinklers or other water consumption. Compound 10 Mr. Bingham conducted a subsequent site visit on May 12, 2015, to collect additional information needed for his report.  meters on dual-purpose service lines have no capability to differentiate between the volume of water consumed by the commercial usage of a facility from the volume of water consumed by the fire sprinkler system. There can be no assumption that the smaller meter reads the commercial water consumption and the larger diameter meter only reads the fire sprinkler consumption. (emphases added). Additionally, in his August 10, 2016 letter to Utility's counsel, Customer's own expert, Jeffrey Walker, General Manager for the Inman-Campobello Water District (ICWD), gave the following opinion after reviewing the report of Utility's expert: [S]ince all of the water for this customer flowed through this meter assembly and therefore, this was not a connection dedicated to fire protection only, the ICWD would not consider this a private fire protection line. At the ICWD, a private fire protection line is solely dedicated to fire protection and consumption virtually never occurs with these types of connections, unless there is a fire. For this reason, accounts of this type are charged much less than accounts that are not solely dedicated to fire protection. Therefore, given the same meter and the same or a similar industry, the ICWD would bill the customer the minimum bill for an 8-inch meter plus any consumption that exceeded the amount that is included in the minimum charge. Even though the meter assembly is comprised of two meters, it is still considered an 8-inch meter. The smaller meter is in place to capture lower flows that the 8- inch meter cannot detect. (emphasis added).11 11 Walker acknowledged that the ICWD bills in the same manner that Utility bills its customers.  Based on the foregoing, the circuit court properly granted summary judgment to Utility. See Rule 56(c), SCRCP (providing that summary judgment shall be granted when "the pleadings, depositions, answers to interrogatories, and admissions on file, together with the affidavits, if any, show that there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law."); Wright, 426 S.C. at 211, 826 S.E.2d at 290 ("The purpose of summary judgment is to expedite disposition of cases [that] do not require the services of a fact finder." (quoting George v. Fabri, 345 S.C. 440, 452, 548 S.E.2d 868, 874 (2001))). CONCLUSION Accordingly, we deny the motion to dismiss and affirm the circuit court's order. AFFIRMED.12 LOCKEMY, C.J., and HEWITT, J., concur. 12 We decide this case without oral argument pursuant to Rule 215, SCACR. 

1. Field of the Invention The present invention relates to a slider for a slide fastener having an automatic stop function and more particularly to a slider for a slide fastener with an automatic stopper which enables to simplify a structure of a slider body and also enables a pull to be easily installed on the slider body. 2. Description of Related Art Conventionally, there has been often used a slider for a slide fastener having an automatic stop function in which by operating a pull to a slider body which couples/uncouples a zip teeth row of a fastener chain, a stop pawl of a stop pawl body is engaged with a part of the zip teeth row of the fastener chain so as to stop the slider body from moving (see for example, Japanese Utility Model Publication No. 4-32974). In a slider 100 described in Japanese Utility Model Publication No. 4-32974, as shown in FIGS. 17 and 18, a downward concave pull holding body 102 is fixed firmly on a slider body 101 from a shoulder side of an upper blade piece to a rear opening side. The base end portion of a stop pawl body 103 is mounted near the shoulder side of the same pull holding body 102 such that it is capable of moving vertically. An engaging pawl 105 projecting to a zip teeth row position on a fastener chain through an engagement window 104 formed in the upper blade piece of the slider body 101 such that it goes through vertically and an operation concave portion 107 which is opened to a rear opening side of the upper blade piece for accommodating the mounting shaft portion of a pull 106 are formed at a front end of the stop pawl body 103. A bottom face of the base end portion of the stop pawl body 103 is always urged by a spring force of a compression coil spring placed in a small hole formed in the upper blade piece as shown in FIG. 18 so as to project the engaging pawl 105 of the stop pawl body 103 to the zip teeth row position on the fastener chain through the engagement window 104. As shown in FIG. 18, a gap portion 108 formed between an end portion on the side of the rear opening of the pull holding body 102 and the upper blade piece of the slider body 101 serves as a gap used for inserting the mounting shaft portion of the pull 106. A closing member 109 for closing an insertion gap is disposed in this gap portion 108 so that it is capable of sliding between a gap closing position near the rear opening side and a gap opening position near a shoulder side. The closing member 109 is always urged toward the gap closing position. The closing member 109 is formed in a substantially U shape as seen in its plan view as shown in FIG. 17. At its two-branched arm portion, there are formed a first closing portion 110 for closing the gap portion 108 for a mounting shaft portion of the pull 106 not to be able to pass through the gap position and a second closing portion 114 for closing a continuous edge portion 113 which is continuous between a clearance 111 formed near the rear opening in right and left wall portions of the pull holding body 102 and an accommodating space 112 formed near a shoulder for the mounting shaft portion of the pull 106 not to be able to pass through. Both first and second closing portions 110, 114 project upwardly. For the slider 100 having the above-described structure, as shown in FIGS. 18 to 20, the stop pawl body 103, the closing member 109 and the pull holding body 102 are assembled on the slider body 101 except the pull 106 as a slider assembly product and then, the pull 106 is installed on the slider assembly product. Upon installation of the pull 106 onto the slider body 101, as shown in FIGS. 18 and 19, the mounting shaft portion of the pull 106 is pressed into the gap portion 108 in the slider body 101 as a first step. If an outside end of the first closing portion 110 of the closing member 109 is pressed with the mounting shaft portion of the pull 106, the first closing portion 110 leaves an end on the rear opening side of the pull holding body 102 as shown in FIG. 19 so that the gap portion 108 is opened widely for the mounting shaft portion of the pull 106 to be able to pass through. After the mounting shaft portion is moved from the gap portion 108 into the clearance 111 in the pull holding body 102, the closing member 109 returns to its original gap closing position by a restoration force of the spring as shown in FIG. 20. Next, as shown in FIG. 20, the mounting shaft portion of the pull 106 is moved from the clearance 111 in the pull holding body 102 into a concave portion formed between the first and second closing portions 110 and 114 of the closing member 109 as a second step. If the mounting shaft portion of the pull 106 is pressed into the gap portion 108 again as a third step, the second closing portion 114 looses out of a position of the continuous edge portion 113 in the pull holding body 102 as shown in FIG. 19. The mounting shaft portion of the pull 106 passes the bottom end of the continuous edge portion 113 in a condition in which it is accommodated in the concave portion and moves to the bottom end of the accommodating space 112 in the pull holding body 102. At the same time, the mounting shaft portion of the pull 106 moves into an operation concave portion 107 in the stop pawl body 103 as indicated with a broken line in FIG. 19. As a fourth step, if the pull 106 is moved upward so as to move the mounting shaft portion of the pull 106 into the accommodating space 112 in the pull holding body 102, an interference between the mounting shaft portion and the second closing portion 114 of the closing member 109 is eliminated. Consequently, the closing member 109 returns to the gap closing position due to a spring force and then, the installation of the pull 106 is completed. Then, if the closing member 109 returns to the gap closing position, the pull 106 is prevented from escaping out. After the installation of the pull 106, if it is intended to remove the pull 106 out from the slider body 101, the closing member 109 is moved to the gap opening position against an elastic force and with the closing member 109 held at the gap opening position, a reverse operation for the pull 106 to the above-mentioned operation is carried out. Consequently, the existing pull 106 can be removed out from the slider body 101 and a new pull can be installed instead of the existing pull 106. As for an operation with the pull 106 installed in this way, if the pull 106 is pulled obliquely upward or in a sliding direction of the slider, the stop pawl body 103 is brought up against an elastic force through the operation concave portion 107 in the stop pawl body 103 by the mounting shaft portion of the pull 106, so that the engaging pawl 105 of the stop pawl body 103 leaves the zip teeth row on the fastener chain. In this condition, the slider body 101 can be moved freely so as to mesh the zip teeth row on the fastener chain with each other. When the pull 106 is released from a hand, the stop pawl body 103 is urged by a spring so that the engaging pawl 105 is automatically inserted into the zip teeth row on the fastener chain through the engagement window 104 in the upper blade piece, thereby stopping the motion of the slider. Meanwhile the technology on the slider for the slide fastener with the automatic stopper disclosed in Japanese Utility Model Publication No. 4-32974 was previously proposed by the present inventor. Manufacturers of clothing, bags and the like have been demanded to prepare slider bodies and various types of pulls separately so as to install the diversified types of pulls each having a different color and shape onto the slider body corresponding to a request and desire of a customer. As a result, after an order on a slider corresponding to a request or desire of customer is received, the necessity of requesting a part manufacturer, who manufactures and sells fixing devices such as fasteners for, for example, bags, sport wears and other clothes to develop and manufacture a slider which fits to the request or desire of the customers again is eliminated, so that the manufacturers of clothing, bags and the like can meet such request or desire of the customer quickly. According to the related art described in Japanese Utility Model Publication No. 4-32974, the pull 106 can be installed on a slider assembly product detachably in the above-described manner. However, upon installing the stop pawl body 103 and the pull holding body 102 on the slider body 101 of the conventional slider 100, it is necessary to form a shaft hole in each of a pair of mounting pieces, right and left, erected on the side of the shoulder of the slider body 101 and support the front end of the stop pawl body 103 between the respective mounting pieces so as to be vertically rotatable via a pin inserted into each shaft hole. Next, exposed end portions on both sides of the aforementioned pin are inserted into the shaft holes formed in the right and left side wall portions of the pull holding body 102 and the pull holding body 102 should be fixed on each mounting piece so that it is immobile by crimping each exposed end of the pin with respect to the right and left side wall portions of the pull holding body 102. For the reason, the mounting structures of the stop pawl body 103 and the pull holding body 102 onto the slider body 101 become complicated. In case where the stop pawl body 103 and the pull holding body 102 are assembled on the slider body 101 using an automatic assembly machine, diversified apparatuses accompanied by that automatic assembly work are required thereby boosting its equipment cost and accompanied by an increase in the equipment cost, management cost and the like possibly increase. Further, because the mounting structures of the stop pawl body 103 and the pull holding body 102 to the slider body 101 become complicated, manufacturing cost of the slider increases, thereby making it impossible to produce at a low cost. According to the related art described in Japanese Utility Model Publication No. 4-32974, when the closing member 109 is pressed to the gap closing position of the slider body 101 as described above, the gap portion 108 formed between an end portion on the rear opening side of the pull holding body 102 and the upper blade piece of the slider body 101 is opened. Then, the mounting shaft portion of the pull 106 is inserted through the opening portion of this gap portion 108 to below the rear face of the pull holding body 102 and further inserted into the operation concave portion 107 in the stop pawl body 103. Then, the installation of the pull 106 is completed. However, when engaging the pull 106 with the operation concave portion 107 in the stop pawl body 103, it is necessary to move the pull 106 by amounts that allow it to go beyond top ends of sliding faces of the first and second closing portions 110, 114 of the closing member 109 while moving the closing member 109 by the pull 106 with resisting an elastic force. As a result, if the pull holding body 102 is set large, necessarily, the size of the closing member 109 increases, so that an excessive pressing force for that closing member 109 is necessary. Because such a strong pressing force is applied directly to the first and second closing members 110, 114 of the closing member 109 and the stop pawl body 103, damage, deformation and the like are likely to occur in the closing member 109, the stop pawl body 103 and the pull 106, thereby worsening the assembly performance for the pull 106 and the slider body 101. On the other hand, when removing an existing pull 106 from the slider assembly product, it is necessary to move the closing member 109 to a gap opening position resisting an elastic force so as to release an engagement between the pull 106 and the operation concave portion 107 in the stop pawl body 103. By executing a reverse operation to the operation for engaging the pull 106 with the operation concave portion 107 in the stop pawl body 103 with the closing member 109 held at the gap opening position resisting an elastic force of the closing member 109, it is necessary to pull out the pull 106 while moving it by the amounts which allows it to go beyond the top faces of the respective sliding faces of the first and second closing portions 110, 114. For the reason, the mounting work for the pull 106 becomes complicated like a case where the pull 106 is engaged with the operation concave portion 107 in the stop pawl body 103. The slider for the slide fastener with the automatic stopper described in Japanese Utility Model Publication No. 4-32974 is so constructed that its pull 106 can be replaced with a new pull different in color or shape by pulling out the pull 106 from the slider assembly product. Thus, the slider structure is complicated as described above and there is a limit in installing the pull on the slider assembly product accurately and thus, the installation work of the pull has been demanded to be facilitated. If such a demand can be satisfied, the pull can be installed on the slider body reasonably.

Oz The Great And Powerful To Start Shooting In June 2011 It’s been an Oz filled year of news already and we’re not going to stop hearing about the ever-growing franchise for a while to come. With no less than four projects on the horizon involving the magical land (Dorothy of Oz, Oz The Great and Powerful, Wicked, and the rumored remake Oz from the Polish brothers), the property is surely getting a lot of attention and all eyes are on them as we wait anxiously to see what each of them brings to the table. According to the ever-active Production Weekly Twitter, the prequel, Oz The Great and Powerful, is set to begin filming next June with a recently attached Robert Downey Jr. Having set a start date, one has to wonder just who they have on board that will be ready in that amount of time to direct the film, the most likely choice being Sam Raimi. After being unceremoniously booted from the Spider-Man franchise, Raimi was first believed to be jumping right into World of Warcraft, but instead his involvement with Oz The Great and Powerful seemed to increase until he recently reported that he wasn’t yet tied to the film, but that he would like to be. The announcement is sure to get the internet buzzing about who will actually helm the film, be it Sam Raimi or someone else (Timur Bekmambetov and Sam Mendes have both at one point been rumored). So let the producers have their fun making us wait and in time they will reveal what seems to be secret info about the crew.

JEN (charity) JEN, formerly named Japan Emergency NGOs, was established in January 1994 as the first federation of Japanese NGOs. History By working and pulling together the expertise of human and financial resources across several NGOs, it became feasible to carry out a project which otherwise could have been difficult by a single NGO. It also aimed for a more collaborative form of humanitarian assistance with the cooperation of Japanese government and UN organisations. Since May 1994, 14 offices were established in different areas in Serbia, Croatia, Bosnia & Herzegovina and Montenegro with international staff delegated to each office to start the refugee and internally displaced persons assistance activities. The activity of JEN in the former Yugoslavia, which has once started as a half-year project, grew from emergency relief to rehabilitation over the years. In 2004, all directly implemented projects ended in the former Yugoslavia and were handed over to local NGOs. After the 2011 Tōhoku earthquake and tsunami, JEN's teams of volunteers spread out in Ishinomaki to dig out houses and people from the debris. They also worked on rebuilding houses. In 2012, the company Uniqlo invested $300 million in a group of 5 NGOs, including JEN, to support their projects. In March 2016, JEN received the authorization to operate in Pakistan. In October 2017, in collaboration with the Ford Foundation, JEN launched three agricultural projects in Sri Lanka to reboot the local economy after the Civil War. Projects At present, JEN works in seven countries including Afghanistan, Pakistan, Sri Lanka, Iraq, Sudan, Myanmar, and Niigata, Japan and our projects differ ranging from providing rehabilitation of schools in Iraq and Afghanistan from livelihood programme in Sri Lanka. JEN worked for the victims of 2005 earthquake in District Bagh, Kashmir, Pakistan References External links Category:Development charities based in Japan Category:Organizations established in 1994 Category:1994 establishments in Japan

The object of the invention is a pixel element for a three-dimensional screen. The pixel element of the invention comprises means for generating multiple substantially collimated, controllable light beams. These light beams are emitted in multiple directions, so that each light beam is associated to a predetermined viewing direction. Various methods and devices have been suggested to achieve a true three-dimensional image (3D image). The underlying principle of all true 3D methods is the same. If a planexe2x80x94two-dimensionalxe2x80x94image is displayed on a surface, then every point of the surface emits or reflects light with approximately same intensity (and colour) in all directions. This is the working principle of a traditional picture, like a postcard (reflection) or a traditional TV-image (light emission). In the case when a three-dimensional image is presented, the emitted light has a different intensity (and colour) in the different directions, even if it is emitted from the same point. We may regard in this way a window pane or a hologram as a display. Hence, in order to display a three-dimensional image, there is needed a light emitting surface where the intensity (and colour) of the light emitted from a single image point (pixel) may be controlled as the function of the emission angle (exit angle), with other words, the intensity of the light emitted in the different directions may be controlled. In order to produce true or realistic three-dimensional images, two technical problems must be solved. Firstly, a large number of light beams must be projected in the different directions in space, with the appropriate intensity/colour, which allow the viewer to see different perspectives from different viewpoints. Secondly, means must be provided to allow the feeding of the necessary data to the light sources generating the light beams. This second problem involves difficulties when video images (i.e. moving images) must be displayed, because large amounts of data (kB/s) must be forwarded into each (!) image point or pixel. Obviously, a true 3D video image providing n different viewing directions require n times the data amount of a normal video image. There are many known technical solutions that addresses the problem of the directed light beams. The Hungarian Patent application published under No. T/63 503 discloses two methods for the presentation of three-dimensional images. In a first version, a modulated laser beam is subjected to deflection which is controlled in time. The deflection is performed before the image pixels, according to the directions defining the viewing range. In this manner the modulated laser beam enters the image pixel deflected with an angle, the beam is parallel translated. From the image pixel the laser beam propagates with an optical deflection corresponding to the view range, or propagates further in different directions within the viewing range without further deflection. A disadvantage of this solution is that the laser beam must be focused and positioned very precisely, because the entry point of the laser beam within the image pixel defines the direction of the exiting laser beam. In the second version, the modulated laser beam enters an image pixel in the same entry point, without deflection, and it is deflected towards the different viewing angles within the image pixel, with the help of a controllable active optical element positioned in the image pixel. The deflection of light beam with the angle-dependent intensity is performed by the active optical element. The advantage of the solution is that the positioning and focusing of the beam need not be very exact, but the active optical elements make the device extremely expensive. Also, the problem of the feeding of the data to the active pixels is not discussed. In other known methods, in order to display true 3D images, two surfaces are used, where the first front surface is a surface with a controllable light transmission, and the second back surface is an illuminating surface comprising light sources. One point of the back surface and one point of the front surface defines unequivocally a direction. With a possible embodiment, the image is created on the back surface by controlling the intensity and/or colour of the light sources, while on the first surface only masking is performed according to the selected viewing directions, by switching the image pixels on and off. With an other possible embodiment, the light sources on the back surface are continuously on, or they are only switched on or off, while the controlling according to the image information is made on the first surface. The first surface comprising the image pixels with controllable light transmission is preferably an LCD display. Such solutions utilising an LCD display are disclosed, among others, in the documents EP 0 316 465 and U.S. Pat. No. 5,132,839. Here, illuminated strips are used behind an LCD screen, and the light of the strips are either transmitted or blocked by the controlled image pixels of the LCD screen. In the solution disclosed in EP 0 316 465, there is an illuminated line behind every pair of LCD-pixel columns, and the light of the line passes through either one column or the other, corresponding to the control of the LCD pixels. This arrangement allows the display of a stereoscopic image with two viewing directions, but the resolution of the LCD-display is low, because two LCD-pixels are needed for an image point. The description suggest to increase the number of LCD-pixels associated to one illuminating line, in order to increase the number of viewing directions, but this leads to a further lowering of the resolution. There is no teaching how the data must be fed to the LCD-pixels. With another possible embodiment, it is suggested to use one illuminating line (light source) behind each LCD-pixel column. In this case every pixel is illuminated by multiple light sources, which results in several viewing directions, having independently controllable light emissions in the same image point. Such a display is described in the publication xe2x80x9cA prototype flat panel hologram-like display that produces multiple perspective views at full resolutionxe2x80x9d, by J. Eichenlaub, in: Proceedings of the SPIE Vol. 2409, pp. 102-112. Here, the number of the light sources is essentially equal to the number of the image pixels in a line. Therefore, in order to produce an image with an acceptable resolution, a large number of very small light sources are needed. These light sources are extremely expensive, due to their small size and the large quantity needed. The light sources may be manufactured by optical methods (e.g. cylindrical lens matrix, disclosed in WO 94/06249), but this requires again a very precise and costly technology, and the illumination angle is also limited. A further disadvantage of this approach is the limited intensity which may be achieved. The application of this system for moving images is clearly limited by the addressing speed of the LCD screen, and the switching speed of the light sources. The need to provide several emitting directions from one image point is also recognised in the solution described in U.S. Pat. No. 5,521,724 (Shires). In this solution a simple electronic display is presented, which produces 3D images by binocular parallax. The effect is produced by the pixels of a traditional 2D display, which are spatially multiplexed by holographic elements. The problem of the data speed is not discussed. There are also disclosed various forms of lenticular lens systems, which provide outgoing light beams according to different viewing directions. Such a solution used to create an autostereoscopic display is described in EP 0 786 912 A2. Again, in this document there is no teaching how the large amount of data may be fed into the subpixels of the image pixels (essentially, the pixels of an SLM, see FIG. 11.), which then produce the different images in different directions through the lenticular lenses. In the field of laser printers, LED arrays arranged in a line are already known. These arrays contain individually adressable light sources. However, it has not been suggested to use such a LED array to produce light beams which are radiating in different directions, and thereby achieving 3D images. Accordingly, it is an object of the present invention to provide a pixel element which simultaneously solves the optical problem of the multiple directed light beams and the problem of the data transfer to the light sources. It is a further object to provide a pixel element that is relatively easy to manufacture, replaceable, and require simple supporting systems, both in mechanical, optical, and electronic terms. The above objectives are reached by a pixel element for a 3D screen, comprising means for generating multiple substantially collimated, controllable light beams emitted in multiple directions, so that each light beam is associated to a predetermined viewing direction. According to the invention, the pixel element comprises at least one set of substantially point source type, individually addressable light sources arranged in a line, and optical imaging means for imaging the light of each light sources in a collimated light beam and for deflecting each collimated light beam in a predetermined individual deflection direction, and further comprising means for serially addressing the light sources. Especially, it is foreseen that the addressing means comprises a serial input shift register and/or a multiplexer for distributing the information from the input shift register to the individual light sources. It is also suggested to use three sets of light sources radiating in the RGB colours, where each set is arranged in a line parallel with the other sets. Alternatively, one set of light sources may be arranged in multiple parallel lines. One line of light sources may be imaged by a lenticular matrix and/or an objective lens, which is associated to the line of the light sources. In a particular embodiment, the addressing means comprises memory means for storing the input information of several operation cycles. It is also foreseen that the addressing means comprises means for evaluating the state of the light sources radiating in the neighbouring deflection directions. The invention also includes a novel 3D display comprising pixel elements according to the invention. Essentially, there is provided a novel light emitting pixel element, particularly for 3D screen applications. The main feature of such a pixel element is the ability to generate several independent light beams within a single unit, and without the use of expensive and bulky active optical elements. These light beams are emitted in several independent directions, so that each light beam is associated to a predetermined viewing direction. The different light beams are practically collimated, in order not to interfere with the neighbouring viewing directions. To achieve a true 3D effect, each independent light beam must be controllable on its own. The light beams are realised in the form of miniature diode lasers or LEDs, which function as substantially point source type, individually addressable light sources. The light sources are arranged in a line, which facilitates their deflection with a common optical projection system. Colour screens are created with three lines of light sources radiating in the RGB colours. The coloured lines of the light sources are positioned sufficiently close to each other, so the light beams appear to be emitted from one source. This optical projection system includes means for imaging the light of each light sources in a collimated light beam, preferably a matrix of miniature lenses. The generated set of the parallel, collimated light beams are deflected in predetermined individual deflection directions, which corresponds to the viewing directions. This deflection is effected with a common objective lens. To keep the wiring and addressing within feasible limits, the pixel elements are provided with appropriate means for serially addressing the light sources. E.g. a serial input buffer or shift register, and/or a multiplexer could be integrated on the same chip or at least on the same ceramic plate which carries the light sources and their driver circuits. The suggested pixel element is currently limited to provide 3D image along one axis (co-ordinate) only. To increase the viewing angle along the other axis, it is foreseen to apply a holographic plate or a cylindrical lens system as a means for establishing a divergence (diffusion) of the light beams perpendicular to the plane of deflection. To achieve a continuous image, when moving from one viewing angle to another, it is also suggested to apply some sort of diffusor to establish a divergence of the light beams in the plane of deflection. This divergence should be sufficient to cause an overlap of the edges of neighbouring light beams at least in a distance from the pixel element. The divergence or diffusion of the light beams could be done with the same holographic element, both in the perpendicular and the parallel direction. It is fully feasible to provide the addressing logic of the pixel elements with intelligent features, like a firmware-type microprogram for evaluating the state of the light sources in neighbouring pixel elements. In this manner the whole screen of the pixel elements could act as a distributed processing unit, and e.g. certain functions of the data compression and decompression algorithms could be assigned to the microprograms in the pixels. However, the greatest advantage of such a pixel element is the inherent simplicity of the device, which fully substitutes the functions of complicated and sensitive optical arrangements for producing a true 3D image. The pixel elements according to the present invention may be used to produce 3D screens in various sizes and resolution, using the same basic unit. The pixel element itself is relatively low-cost, if produced in large quantities. The necessary technologies to produce the different parts of the pixel element are all available and already tested in practice. The pixel element of the invention allows the realisation of a very powerful and sophisticated, and at the same time mass-produced and low-cost 3D screen.

All relevant data are within the paper. Introduction {#sec001} ============ The world population of humans is forecast to exceed 9 billion by 2050 \[[@pone.0127846.ref001]\]. Most growth is expected in developing countries alongside a trend for increased wealth and urbanisation, leading to unprecedented consumer demand for foods of animal origin \[[@pone.0127846.ref001]\]. However, livestock are responsible for around 18% of anthropogenic greenhouse gas emissions worldwide \[[@pone.0127846.ref002]\], and increased agricultural production must be sustainable against a background of climate change and limitations on land availability \[[@pone.0127846.ref003]\]. Without complete reliance on potentially human-edible food, dairy production can be energetically efficient compared to farming non-ruminants \[[@pone.0127846.ref004]\]. However microbial ruminal fermentation of cellulosic feeds releases methane, a greenhouse gas with at least 25 times the global warming potential of carbon dioxide \[[@pone.0127846.ref005]\]. Methane has been identified as an important target for short term climate change mitigation strategies, and thus dairy producers will be required to reduce emissions \[[@pone.0127846.ref006]\]. However this must occur alongside an increase in productivity and economic efficiency. Oestrus detection efficacy is a common limiting factor in dairy herd reproductive management, and synchronisation programmes allowing pre-set (fixed time) artificial insemination have become popular, particularly for large herds with limited labour \[[@pone.0127846.ref007]\]. However routine use of hormonal therapy has been highlighted as an ethical dilemma, and some veterinarians may be reluctant to recommend this approach \[[@pone.0127846.ref008]\]. As demand for dairy products on the world market increases, milk prices tend to become more volatile \[[@pone.0127846.ref009]\]. To remain profitable and competitive, farmers may need to both adopt new technologies, and make optimal use of existing ones to reduce the cost of producing milk. Importantly, this should also be achieved with minimal adverse environmental impact. Using simulations or statistical models to predict herd scenarios is useful to inform decisions around the most appropriate management strategy to adopt \[[@pone.0127846.ref010], [@pone.0127846.ref011]\], particularly where this may be controversial. Existing analyses of hormonal synchronisation programmes in dairy herds have focused on the input of deterministic parameter values, and hence generate the average financial value in a particular case \[[@pone.0127846.ref012]--[@pone.0127846.ref014]\]. Manual sensitivity analysis is then required to evaluate the impact of changes in uncertain parameters, and this may fail to identify situations that could alter decisions. With stochastic simulation, the importance of variation in input values is explicitly explored \[[@pone.0127846.ref015]\]. As farming develops in the face of future demands, it is important that common practices can be justified to all interested parties. Despite potentially adverse public perception, hormonal interventions for dairy herds could have benefits to society through reduction in methane emissions in addition to financial benefit for the farmer, and this has not previously been considered. The aim of this study was to predict the magnitude and between herd variation of changes in methane emissions and production efficiency associated with 3 simple hormonal interventions to improve dairy herd reproductive efficiency. Materials and Methods {#sec002} ===================== A logistic regression model describing the risk of pregnancy in cows over time after calving was replicated using data from 312 herds ([Table 1](#pone.0127846.t001){ref-type="table"} \[[@pone.0127846.ref016]\]). This model was combined with a forward simulation of time series data, as described below, to predict the occurrence of pregnancy following insemination over the course of a cow's lactation. A 3-level stochastic simulation model was developed using the software R version 3.0.2 \[[@pone.0127846.ref017]\]. At the highest level, herd data were specified, and used to simulate cow level data. The trajectory of individual cows in each herd was then simulated over 2 years. The model had 4 branches that used the same inputs but varied the approach to reproductive management; a baseline scenario, and 3 potential interventions, such that trajectories for exactly the same simulated cows could be compared under different management programmes. 10.1371/journal.pone.0127846.t001 ###### Final logistic regression model for the occurrence of pregnancy in cows inseminated at different times. {#pone.0127846.t001g} Fixed effects Mean coefficient Standard error ---------------------------------------------------------- ------------------ ---------------- Intercept[^1^](#t001fn001){ref-type="table-fn"} -0.517 0.041 Parity = 1 (reference) Parity = 2 -0.0136 0.0112 Parity = 3 -0.0209 0.0125 Parity = 4 -0.081 0.014 Parity \> = 5 -0.284 0.0122 Days in milk (DIM) 0.0177 0.000875 DIM^\^^2 -0.0000994 0.00000616 DIM\^3 0.000000177 0.000000013 305 day milk yield[^2^](#t001fn002){ref-type="table-fn"} -0.0695 0.00246 Season: October to May (reference) Season: June to September -0.0861 0.0091 Random effect variance Herd level 0.065 0.006 Cow level 0.135 0.005 ^1^Parity 1 cow at calving with milk yield of 0 kg. ^2^Estimated cumulative milk yield in 305 days (thousand kg). Herd simulation {#sec003} --------------- Measures of production and reproductive efficiency in dairy herds vary, and this could influence the response to management changes. In order to incorporate this variation, independent uniform distributions for herd characteristics were specified where possible based on observed ranges in a dataset of 312 United Kingdom dairy herds ([Table 2](#pone.0127846.t002){ref-type="table"} \[[@pone.0127846.ref016]\]). Ten thousand herds were simulated by taking random draws from these distributions to fully explore the parameter space for all joint distributions of herd characteristics. 10.1371/journal.pone.0127846.t002 ###### Herd level inputs for simulation model. {#pone.0127846.t002g} Parameter Distribution ------------------------------------------------------------------ --------------------- Submission risk[^1^](#t002fn001){ref-type="table-fn"} Uniform(0.1, 0.65) Pregnancy risk[^2^](#t002fn002){ref-type="table-fn"} Uniform(0.1, 0.65) Milk yield[^3^](#t002fn003){ref-type="table-fn"} Uniform(3, 10) Heifers[^4^](#t002fn004){ref-type="table-fn"} Uniform (0.05, 0.5) Calving index cost (£/day)[^5^](#t002fn005){ref-type="table-fn"} Uniform (2, 5) Cull cost[^6^](#t002fn006){ref-type="table-fn"} Uniform(700, 1500) Serve cost[^7^](#t002fn007){ref-type="table-fn"} Uniform(0, 25) VWP[^8^](#t002fn008){ref-type="table-fn"} Uniform(30, 70) Time to first cycle (days) Uniform(20, 30) Cycle length[^9^](#t002fn009){ref-type="table-fn"} Uniform(20.5, 22.5) Forage ME[^10^](#t002fn010){ref-type="table-fn"} Uniform(9.5, 11.5) Milk margin (£/L) Uniform(0.1, 0.2) ^1^Proportion of eligible cows that are served prior to intervention. ^2^Proportion of served cows that conceive prior to intervention. ^3^Cumulative 305 day milk yield (thousand kg). ^4^Proportion of heifers in the herd. ^5^Cost of changing the interval between subsequent calvings. ^6^Depreciation cost of culling a cow and replacing with a heifer (£). ^7^Cost of each artificial insemination (£). ^8^Voluntary waiting period (days) from calving to first service. ^9^Length of oestrous cycle (days). ^10^Metabolisable energy (MJ/kg dry matter). Cow simulation {#sec004} -------------- Distributions of cow characteristics depend on the characteristics of the herd they are in. Therefore, data for 200 cows in each herd were generated by taking random draws from the distributions in [Table 2](#pone.0127846.t002){ref-type="table"}. The parity of cows varied according to the observed age structure in a previous dataset, and this influenced cumulative milk yield over a standardised 305 day lactation \[[@pone.0127846.ref016]\]. Beta distributions were used to simulate physiological variation in length of post-partum anoestrus (mode = herd average, minimum = 10, maximum = 80), and oestrous cycle length in days (mode = herd average, minimum = 18, maximum = 27 \[[@pone.0127846.ref018]\]). Lactation simulation {#sec005} -------------------- Cows cycle between productive periods of lactation and non-productive (dry) periods in late pregnancy, dependent on the timing of re-breeding. In this study individual cows were followed up over 730 days commencing with the birth of a calf (calving) and a period of lactation. Repeated days of lactation for each cow were represented as lines in an array, the initial calving was equally likely to occur on any day of the year. At the start of lactation, cows' ovaries are inactive for a variable time before cycles commence (post-partum anoestrus). Oestrus refers to a sexually receptive stage of the ovarian cycle characterised by physiological and behavioural changes \[[@pone.0127846.ref019]\]. Therefore day of the ovarian cycle was determined based on a period of post-partum anoestrus followed by the recurrence of regular length cycles (both based on random draws from input distributions). Cows were deemed to be in oestrus on day 1 of the cycle, and an insemination event was simulated at random according to the distribution of risk that the cow was observed in oestrus and inseminated (submission risk), provided that the designated voluntary post parturient non-breeding period (voluntary waiting period) for the herd had elapsed. The outcome of insemination (pregnant or not pregnant) was determined by a random draw from a distribution based on the mean predicted probability of conception on that day ([Table 1](#pone.0127846.t001){ref-type="table"}). Breeding continued until the occurrence of pregnancy or day 300 of lactation. Daily milk yield was calculated based on stage of lactation, time of year and pregnancy status using a previously reported method \[[@pone.0127846.ref020]\]. Pregnant cows were deemed to have a physiologically normal gestation length of 280 days and milking ceased 60 days before their expected calving date. Cows not pregnant by day 300 were culled and replaced by a young cow (heifer) after a lag time of 60 days. Methane emissions arise from the ruminal fermentation of cellulose which is relatively more important in late lactation when forage feeds (such as grass silage) make up a higher proportion of the cows' diet. It was assumed that forage alone provided energy for maintenance and up to 10 L of milk production per day. To support higher milk yields, concentrate was assumed to be fed at 0.4 kg per L and this was 90 per cent dry matter. Daily dry matter intake was calculated from the stage of lactation and milk yield as reported previously \[[@pone.0127846.ref021]\]. Methane emissions were mainly determined by daily forage dry matter intake (total dry matter intake minus concentrate dry matter intake), forage quality, and replacement risk \[[@pone.0127846.ref022]\]. The proportion of herd methane emissions produced by replacement heifers was estimated to be 27% under commercial conditions \[[@pone.0127846.ref022]\]. Methane production from concentrate feeds occurred, but this was 150 times lower than for forage feeds on a dry matter basis \[[@pone.0127846.ref022]\]. This baseline scenario (Group 1) was compared directly to simulations that incorporated one of three hormonal interventions that altered the timing of first insemination, submission and pregnancy risk. These calculations were made in parallel with the baseline scenario using the same theoretical cows and are described below. Group 2: Ovsynch {#sec006} ---------------- The Ovsynch protocol involves 2 injections with gonadotrophin releasing hormone analogues given 9 days apart, and a prostaglandin injection on day 7. This protocol is used to ensure all cows receive a first insemination at a fixed time (16 to 24 hours after the completion of the protocol), which eases and automates reproductive management of dairy herds \[[@pone.0127846.ref007], [@pone.0127846.ref023], [@pone.0127846.ref024]\]. The programme of injections was assumed to be applied in order to schedule a fixed time insemination from day 50 of lactation (50 DIM). In practice, it is preferable to administer routine treatments to groups of eligible cows rather than individuals. It was therefore assumed that treatments took place every 2 weeks, and cows were therefore inseminated between 50 and 64 DIM, and day of the oestrus cycle was set to 1 on the treatment day. This change was made regardless of the herd voluntary waiting period, and all cows were served (submission risk = 1). Probability of becoming pregnant at insemination (conception risk) was altered by a factor drawn from a beta distribution (mode = 0.8, minimum = 0.4, maximum = 1.7) obtained from a previous study \[[@pone.0127846.ref025]\]. Cows that did not become pregnant to first insemination continued regular oestrous cycles and repeated inseminations as with the baseline scenario until the occurrence of pregnancy or 300 DIM. Cows that were still in the postpartum anoestrus period by 64 DIM, having not resumed regular cycles were assumed to be infertile and could not conceive despite treatment and insemination. Group 3: Ovsynch with progesterone {#sec007} ---------------------------------- This regime was similar to the Ovsynch protocol above but progesterone was also administered to all cows, via a controlled intravaginal drug releasing device for a 7 day period commencing at the start of the protocol. This therapy was investigated as it has been associated with beneficial influences on subsequent fertility in anoestrus cows compared to Ovsynch alone \[[@pone.0127846.ref026]--[@pone.0127846.ref030]\]. Specifically, this was summarised as a 5% increase in the risk of resumption of cyclicity by 64 DIM for multiparous cows that had not commenced regular cyclicity in the baseline scenario, based on reported research with metrics suitable for inclusion \[[@pone.0127846.ref029]\]. First insemination submission risk was 1 (as for Ovsynch), and the baseline pregnancy risk was altered by a factor drawn from a beta distribution (mode = 0.96, minimum = 0.96, maximum = 1.02) obtained from a previous study \[[@pone.0127846.ref030]\]. Cows that did not become pregnant to first insemination continued regular oestrous cycles and repeat inseminations as for the baseline scenario until the occurrence of pregnancy or 300 DIM. Group 4: Double prostaglandin {#sec008} ----------------------------- In this scenario, hormonal (prostaglandin) injections were only administered to cows that had not already been inseminated by a specified time after calving. Eligible cows were treated in batches every 2 weeks such that oestrus could occur from 50 DIM, assuming regular ovarian cycles had resumed. The probability that prostaglandin treatment resulted in oestrus was taken to be 0.8 \[[@pone.0127846.ref031]\]. Following successful treatments, cows were simulated as being observed in oestrus according to the herd submission risk and were then simulated as being inseminated. Otherwise a second injection was administered 2 weeks later, and the process was repeated. Pregnancy risk given prostaglandin treatment, oestrus observation, and insemination was altered by a factor drawn from a uniform distribution (minimum = 0.9, maximum = 1.1) based on summary results from 2 contradictory studies \[[@pone.0127846.ref031], [@pone.0127846.ref032]\]. Cows that did not become pregnant, or which underwent the double prostaglandin regime without being inseminated were then handled as described for the baseline situation. Herd summary {#sec009} ------------ The absolute differences between mean parameter values were determined by subtracting the mean estimate calculated for each intervention scenario from the mean estimate calculated for the baseline scenario. This was used to determine the mean change in non-tangible costs based on the mean change in milk yield, mean change in the number of cows served, and differences in the proportions of cows culled, multiplied by the respective unit costs ([Table 2](#pone.0127846.t002){ref-type="table"}). The change in costs modelled did not include the costs of implementing the programme as drug costs would be known by the farmer. For comparison, drug costs per cow were taken as: Ovsynch; £9, Ovsynch with progesterone; £19, double prostaglandin; £5. The proportion of cows in each herd predicted to have not resumed regular oestrous cycles by the end of the herd voluntary waiting period was recorded. Associations between inputs and outputs {#sec010} --------------------------------------- Scatter plots were used to visualise relationships between input parameters and the change in cost (based on changes in milk production, culling, and insemination costs) or methane emissions with each intervention. Multivariate analyses were then applied; 6 linear regression models were developed (2 for each intervention) with difference in cost /cow per year or herd methane emissions (g per L milk produced) as outcomes and herd as random effects. Models were built in MLwiN version 2.29 \[[@pone.0127846.ref033]\]. Mean coefficient values were generated with the iterative generalised least squares algorithm. All parameters in [Table 2](#pone.0127846.t002){ref-type="table"} were investigated for inclusion in the model as polynomials. Parameters were removed from a saturated model if their mean effect size was ≤ the standard error (Wald test; *P* ≤ 0.05). Biologically plausible interactions between remaining parameters were investigated. Model fit assessment was by inspection of the residuals \[[@pone.0127846.ref033]\] Results {#sec011} ======= Multivariate analyses of change in methane emissions {#sec012} ---------------------------------------------------- The major factors that determined changes in methane emissions are shown in the final models in [Table 3](#pone.0127846.t003){ref-type="table"}. These models explained 36%, 41%, and 4% of the null model variance for the Ovsynch, Ovsynch with progesterone, and double prostaglandin programmes respectively; residuals were distributed normally ([Table 3](#pone.0127846.t003){ref-type="table"}). The impact of comparable changes in model input parameters (from the mean to the upper quartile) on change in methane emissions per L of milk with other inputs held at the mean is shown in [Table 4](#pone.0127846.t004){ref-type="table"}; the Ovsynch based programmes (Groups 2 and 3) were most beneficial in herds with low submission risk, pregnancy risk, and voluntary waiting period. However the models included quadratic terms and interactions ([Table 3](#pone.0127846.t003){ref-type="table"}) meaning the largest reductions in methane emissions per L of milk produced occurred in herds with the lowest submission risks, but otherwise good reproductive efficiency (voluntary waiting period \< 50 days and high pregnancy risk; [Fig 1](#pone.0127846.g001){ref-type="fig"}). Further reductions in methane occurred through supplementing the Ovsynch programme (Group 2) with progesterone (Group 3) that increased with increasing pregnancy risk and decreasing submission risk ([Fig 2](#pone.0127846.g002){ref-type="fig"}). A similar trend was observed for the reduction in methane emissions associated with the double prostaglandin treatment ([Fig 3](#pone.0127846.g003){ref-type="fig"}), although the absolute reduction in methane was less than for the other programmes. {ref-type="table"}). Methane emissions per cow were estimated from daily forage dry matter intake, forage quality, and replacement risk. Cumulative milk yield per cow was estimated based on parity, stage of lactation, and stage of gestation. Methane emissions in the baseline scenario were subtracted to give the expected change in methane per L milk produced. Negative values indicate reductions. Associations with input parameters were evaluated in a linear model ([Table 3](#pone.0127846.t003){ref-type="table"}); mean values were used to generate predictions.](pone.0127846.g001){#pone.0127846.g001} {ref-type="table"}). Methane emissions per cow were estimated from daily forage dry matter intake, forage quality, and replacement risk. Cumulative milk yield per cow was estimated based on parity, stage of lactation, and stage of gestation. Associations with input parameters were evaluated in a linear model ([Table 3](#pone.0127846.t003){ref-type="table"}). Mean predicted methane emissions in the Ovsynch scenario were subtracted from that for use of Ovsynch with supplementary progesterone to give the expected change in methane per L milk produced. Negative values indicate reductions.](pone.0127846.g002){#pone.0127846.g002} {ref-type="table"}). Methane emissions per cow were estimated from daily forage dry matter intake, forage quality, and replacement risk. Cumulative milk yield per cow was estimated based on parity, stage of lactation, and stage of gestation. Methane emissions in the baseline scenario were subtracted to give the expected change in methane per L milk produced. Negative values indicate reductions. Associations with input parameters were evaluated in a linear model ([Table 3](#pone.0127846.t003){ref-type="table"}); mean values were used to generate predictions.](pone.0127846.g003){#pone.0127846.g003} 10.1371/journal.pone.0127846.t003 ###### Final models for the difference in methane emissions (g) per litre of milk produced following the implementation of 3 reproductive management programmes in dairy herds compared to a baseline[^1^](#t003fn001){ref-type="table-fn"} scenario. {#pone.0127846.t003g} Group 2: Ovsynch[^2^](#t003fn002){ref-type="table-fn"} Group 3: Ovsynch with progesterone[^3^](#t003fn003){ref-type="table-fn"} Group 4: Double prostaglandin[^4^](#t003fn004){ref-type="table-fn"} --------------------------------------------------------- -------------------------------------------------------- -------------------------------------------------------------------------- --------------------------------------------------------------------- ----- ---------- ----- **Fixed effects** Mean SE[^5^](#t003fn005){ref-type="table-fn"} Mean SE Mean SE Intercept -0.5 0.0 -0.5 0.0 -0.2 0.0 (Submission risk)[^6^](#t003fn006){ref-type="table-fn"} 2.4 0.0 2.7 0.0 0.3 0.0 (Submission risk).(Submission risk) -5.2 0.3 -5.8 0.3 0.7 0.2 (Pregnancy risk)[^7^](#t003fn007){ref-type="table-fn"} 0.5 0.1 0.6 0.1 -0.2 0.0 (Pregnancy risk).(Pregnancy risk) 2.0 0.3 2.2 0.3 0.8 0.2 (Milk yield)[^8^](#t003fn008){ref-type="table-fn"} 0.0 0.0 0.0 0.0 (VWP)[^9^](#t003fn009){ref-type="table-fn"} 0.0 0.0 0.0 0.0 0.0 0.0 (Submission risk).(VWP) 0.0 0.0 0.0 0.0 (Submission risk).(Submission risk).(VWP) 0.0 0.0 0.1 0.0 (Pregnancy risk).(VWP) 0.0 0.0 0.0 0.0 (Pregnancy risk).(Pregnancy risk).(VWP) 0.1 0.0 0.1 0.0 (Pregnancy risk).(Submission risk) 4.59 0.2 5.5 0.2 0.7 0.2 (Pregnancy risk).(Submission risk)\^2 -19.5 1.6 -21.1 1.6 **Random effects** Variance SE Variance SE Variance SE Herd 0.3 0.0 0.3 0.0 0.2 0.0 ^1^ Cows submitted for service based on observation of oestrus only (Group 1). ^2^ All cows treated with gonadotropin releasing hormone and prostaglandin such that they all receive a first service between 50 and 64 days in milk regardless of oestrous detection. Repeat services based on observation of oestrous. ^3^ All cows treated with gonadotrophin releasing hormone, progesterone, and prostaglandin such that all cows can receive a first service between 50 and 64 days in milk. Repeat services based on observation of oestrus. ^4^ Cows not observed in oestrous treated up to 2 times with prostaglandin to increase the probability of oestrus between 50 and 64 days in milk. All services based on observation of oestrus. ^5^ Standard error. ^6^ Proportion of eligible cows that are served prior to intervention (centred on the mean). Polynomial term. ^7^ Proportion of served cows that conceive prior to intervention (centred on the mean). Polynomial term. ^8^ Cumulative 305 day milk yield (thousand kg; centred on the mean). ^9^ Voluntary waiting period (days) from calving to first service (centred on the mean). 10.1371/journal.pone.0127846.t004 ###### Model predictions; impact of a change in input values from the mean to the upper quartile at mean values of other parameters, on the difference in methane emissions (g /litre of milk produced) following the implementation of 3 reproductive management programmes in dairy herds compared to a baseline[^1^](#t004fn001){ref-type="table-fn"} scenario; negative values indicate reductions. {#pone.0127846.t004g} Size of change (mean to upper quartile) Group 2: Ovsynch[^2^](#t004fn002){ref-type="table-fn"} Group 3: Ovsynch with progesterone[^3^](#t004fn003){ref-type="table-fn"} Group 4: Double prostaglandin[^4^](#t004fn004){ref-type="table-fn"} --------------------------------------------------------- ----------------------------------------- -------------------------------------------------------- -------------------------------------------------------------------------- --------------------------------------------------------------------- (Submission risk)[^5^](#t004fn005){ref-type="table-fn"} 0.37 to 0.51 0.23 0.23 0.06 (Pregnancy risk)[^6^](#t004fn006){ref-type="table-fn"} 0.37 to 0.51 0.11 0.13 -0.01 (Milk yield)[^7^](#t004fn007){ref-type="table-fn"} 6.5 to 8.3 0.01 0.01 (VWP)[^8^](#t004fn008){ref-type="table-fn"} 50 to 60 0.06 0.06 0.03 ^1^Cows submitted for service based on observation of oestrus only (Group 1). ^2^ All cows treated with gonadotropin releasing hormone and prostaglandin such that they all receive a first service between 50 and 64 days in milk regardless of oestrous detection. Repeat services based on observation of oestrus. ^3^ All cows treated with gonadotrophin releasing hormone, progesterone, and prostaglandin such that all cows can receive a first service between 50 and 64 days in milk. Repeat services based on observation of oestrus. ^4^ Cows not observed in oestrus treated up to 2 times with prostaglandin to increase the probability of a heat between 50 and 64 days in milk. All services based on observation of oestrus. ^5^ Proportion of eligible cows that are served prior to intervention (centred on the mean). Polynomial term. ^6^ Proportion of served cows that conceive prior to intervention (centred on the mean). Polynomial term. ^7^ Cumulative 305 day milk yield (thousand kg; centred on the mean). ^8^ Voluntary waiting period (days) from calving to first service (centred on the mean). Multivariate analyses of change in costs {#sec013} ---------------------------------------- The major factors that determined changes in cost are shown in the final models in [Table 5](#pone.0127846.t005){ref-type="table"}. These models explained 65%, 68%, and 8% of the null model variance for the Ovsynch, Ovsynch with progesterone, and double prostaglandin programmes respectively; residuals were distributed normally ([Table 5](#pone.0127846.t005){ref-type="table"}). The impact of comparable changes in model input parameters (from the mean to the upper quartile) on change in costs with other inputs held at the mean is shown in [Table 6](#pone.0127846.t006){ref-type="table"}. The hormonal interventions were all most financially beneficial if herd voluntary waiting period exceeded 50 days. For the Ovsynch based programmes (Groups 2 and 3; [Table 6](#pone.0127846.t006){ref-type="table"}), comparable changes in submission and pregnancy risk, at mean values of other inputs were associated with similar magnitude of change in cost but in opposing directions, indicating that these approaches would be economically beneficial in herds with low submission risk, but relatively high pregnancy risk. Ovsynch programmes were more economically beneficial when the depreciation cost of cull cows increased ([Table 6](#pone.0127846.t006){ref-type="table"}). Cost savings through the Ovsynch programme (Group 2) exceeded drug costs except if submission risk exceeded 0.5 ([Fig 4](#pone.0127846.g004){ref-type="fig"}). Results for supplementing the Ovsynch programme with progesterone (Group 3) were similar to use of Ovsynch alone (Group 2); therefore the marginal benefit of progesterone supplementation is shown in [Fig 5](#pone.0127846.g005){ref-type="fig"}. With other inputs held at the mean, cost savings through progesterone supplementation failed to exceed the marginal cost of treatment for herds with pregnancy risk \< 0.2, or submission risks \> 0.5, otherwise the decision would depend on the balance of voluntary waiting period and submission risk ([Fig 5](#pone.0127846.g005){ref-type="fig"}). Comparable multivariate plots for the double prostaglandin programme confirm that cost savings may fail to exceed drug costs unless the herd voluntary waiting period is reduced ([Fig 6](#pone.0127846.g006){ref-type="fig"}). {ref-type="table"}). The cost /cow per year was determined from the proportion of cows that were culled due to failure to conceive by 300 days in milk, the number of inseminations required, and the difference in cumulative milk yield per cow. Cost of the baseline scenario was subtracted to give the expected change in costs. Negative values indicate financial gain. Associations with input parameters were evaluated in a linear model ([Table 5](#pone.0127846.t005){ref-type="table"}); mean values were used to generate predictions.](pone.0127846.g004){#pone.0127846.g004} {ref-type="table"}). The cost of each programme /cow per year was determined from the proportion of cows that were culled due to failure to conceive by 300 days in milk, the number of inseminations required, and the difference in cumulative milk yield per cow. Associations with input parameters were evaluated in a linear model ([Table 5](#pone.0127846.t005){ref-type="table"}). The mean predicted cost of the Ovsynch scenario was subtracted from that for use of Ovsynch with supplementary progesterone to give the expected marginal change in costs. Negative values indicate financial gain.](pone.0127846.g005){#pone.0127846.g005} {ref-type="table"}). The cost /cow per year was determined in each scenario from the proportion of cows that were culled due to failure to conceive by 300 days in milk, the number of inseminations required, and the difference in cumulative milk yield per cow. Cost of the baseline scenario was subtracted to give the expected change in costs. Negative values indicate financial gain. Associations with input parameters were evaluated in a linear model ([Table 5](#pone.0127846.t005){ref-type="table"}); mean values were used to generate predictions.](pone.0127846.g006){#pone.0127846.g006} 10.1371/journal.pone.0127846.t005 ###### Final models for the difference in cost per cow (£ /year; based on change in milk production, culling risk, and number of services) following the implementation of 3 reproductive management programmes in dairy herds compared to a baseline[^1^](#t005fn001){ref-type="table-fn"} scenario. {#pone.0127846.t005g} Group 2: Ovsynch[^2^](#t005fn002){ref-type="table-fn"} Group 3: Ovsynch with progesterone[^3^](#t005fn003){ref-type="table-fn"} Group 4: Double prostaglandin[^4^](#t005fn004){ref-type="table-fn"} --------------------------------------------------------- -------------------------------------------------------- -------------------------------------------------------------------------- --------------------------------------------------------------------- ------ ---------- ----- **Fixed effects** Mean SE[^5^](#t005fn005){ref-type="table-fn"} Mean SE Mean SE Intercept -64.7 0.6 -78.0 0.6 -5.5 0.4 (Submission risk)[^6^](#t005fn006){ref-type="table-fn"} 134.3 2.0 142.8 2.0 11.6 1.3 (Submission risk).(Submission risk) -103.3 13.8 -106.3 14.1 44.5 9.0 (Pregnancy risk)[^7^](#t005fn007){ref-type="table-fn"} -128.7 3.0 -155.5 3.0 -5.9 1.3 (Pregnancy risk).(Pregnancy risk) 112.3 13.9 120.0 14.2 29.2 9.1 (Milk yield)[^8^](#t005fn008){ref-type="table-fn"} -1.2 0.2 -1.4 0.2 (VWP)[^9^](#t005fn009){ref-type="table-fn"} -1.9 0.1 -1.9 0.1 0.0 0.0 (Cull cost)[^10^](#t005fn010){ref-type="table-fn"} -0.1 0.0 -0.1 0.0 (Serve cost)[^11^](#t005fn011){ref-type="table-fn"} 0.4 0.0 0.3 0.0 (Submission risk).(VWP) -3.1 0.2 -3.2 0.2 -0.4 0.1 (Submission risk).(Submission risk).(VWP) 4.6 1.2 4.7 1.2 (Pregnancy risk).(VWP) -3.9 0.2 -3.8 0.2 -1.3 0.1 (Pregnancy risk).(Pregnancy risk).(VWP) 7.2 1.2 7.6 1.2 2.5 0.8 (Pregnancy risk).(Submission risk) 404.4 12.4 446.0 12.4 46.1 8.0 (Pregnancy risk).(Submission risk)\^2 -810.3 88.5 -825.2 88.5 **Random effects** Variance SE Variance SE Variance SE Herd 976.8 13.8 1023.3 14.5 420.9 6.0 ^1^ Cows submitted for service based on observation of oestrus only (Group 1). ^2^ All cows treated with gonadotropin releasing hormone and prostaglandin such that they all receive a first service between 50 and 64 days in milk regardless of oestrous detection. Repeat services based on observation of oestrus. ^3^ All cows treated with gonadotrophin releasing hormone, progesterone, and prostaglandin such that all cows can receive a first service between 50 and 64 days in milk. Repeat services based on observation of oestrus. ^4^ Cows not observed in oestrous treated up to 2 times with prostaglandin to increase the probability of a heat between 50 and 64 days in milk. All services based on observation of oestrus. ^5^ Standard error. ^6^ Proportion of eligible cows that are served prior to intervention (centred on the mean). Polynomial term. ^7^ Proportion of served cows that conceive prior to intervention (centred on the mean). Polynomial term. ^8^ Cumulative 305 day milk yield (thousand kg; centred on the mean). ^9^ Voluntary waiting period (days) from calving to first service (centred on the mean). ^10^ Cost of culling a cow and replacing with a heifer (£; centred on the mean). ^11^ Cost of each artificial insemination (£; centred on the mean). 10.1371/journal.pone.0127846.t006 ###### Model predictions; impact of a change in input values from the mean to the upper quartile at mean values of other parameters, on the difference in cost per cow (£ /year; based on change in milk production, culling risk, and number of services) following the implementation of 3 reproductive management programmes in dairy herds compared to a baseline[^1^](#t006fn001){ref-type="table-fn"} scenario; negative values indicate financial gain. {#pone.0127846.t006g} Size of change (mean to upper quartile) Group 2: Ovsynch[^2^](#t006fn002){ref-type="table-fn"} Group 3: Ovsynch with progesterone[^3^](#t006fn003){ref-type="table-fn"} Group 4: Double prostaglandin[^4^](#t006fn004){ref-type="table-fn"} --------------------------------------------------------- ----------------------------------------- -------------------------------------------------------- -------------------------------------------------------------------------- --------------------------------------------------------------------- (Submission risk)[^5^](#t006fn005){ref-type="table-fn"} 0.37 to 0.51 16.2 17.3 2.4 (Pregnancy risk)[^6^](#t006fn006){ref-type="table-fn"} 0.37 to 0.51 -15.3 -18.8 -0.3 (Milk yield)[^7^](#t006fn007){ref-type="table-fn"} 6.5 to 8.3 -2.1 -2.4 (VWP)[^8^](#t006fn008){ref-type="table-fn"} 50 to 60 -18.8 -19.4 -4.4 (Cull cost)[^9^](#t006fn009){ref-type="table-fn"} 1100 to 1300 -12.3 -14.2 -1.8 (Serve cost)[^10^](#t006fn010){ref-type="table-fn"} 12 to 19 2.5 2.1 ^1^ Cows submitted for service based on observation of oestrus only (Group 1). ^2^ All cows treated with gonadotropin releasing hormone and prostaglandin such that they all receive a first service between 50 and 64 days in milk regardless of oestrus detection. Repeat services based on observation of oestrus. ^3^ All cows treated with gonadotrophin releasing hormone, progesterone, and prostaglandin such that all cows can receive a first service between 50 and 64 days in milk. Repeat services based on observation of oestrus. ^4^ Cows not observed in oestrous treated up to 2 times with prostaglandin to increase the probability of a heat between 50 and 64 days in milk. All services based on observation of oestrus. ^5^ Proportion of eligible cows that are served prior to intervention (centred on the mean). Polynomial term. ^6^ Proportion of served cows that conceive prior to intervention (centred on the mean). Polynomial term. ^7^ Cumulative 305 day milk yield (thousand kg; centred on the mean). ^8^ Voluntary waiting period (days) from calving to first service (centred on the mean). ^9^ Cost of culling a cow and replacing with a heifer (£; centred on the mean). ^10^ Cost of each artificial insemination (£; centred on the mean). Discussion {#sec014} ========== Across a wide range of herd scenarios, use of hormonal therapy to aid reproductive management of dairy cows can lead to economic and environmental benefits. However the scale of variability between herds in these outcomes emphasises that decisions around changing reproductive management require careful consideration. Where controversy over interventions exists it is important that use is justified to be in the public interest, in addition to being economically beneficial to the farmer. From this study, society could benefit through judicious application of hormonal programmes to specific herds through availability of affordable milk, and a relative reduction in methane emissions. These issues are increasingly important due to expected population growth, and the challenge for the dairy industry will be to engage positively with consumers to maintain support for development. Average UK herd size and annual milk yield per cow are 126 and 7,353 L respectively (with increasing trends \[[@pone.0127846.ref034]\]). If such a herd also had average input values ([Table 2](#pone.0127846.t002){ref-type="table"}), the 3.6% annual reduction in methane (0.4 g per L of milk) if an Ovsynch programme was used prior to first insemination compared with breeding to observed oestrus, would be roughly equivalent to the annual global warming potential of 2 cars, a family home, or 21 barrels of oil \[[@pone.0127846.ref005], [@pone.0127846.ref035]\]. The synchronisation programmes tested could be put in place quickly, with benefits after 1 year. This is consistent with targeting of methane for short term greenhouse gas emission reductions that may be attractive for policy makers \[[@pone.0127846.ref006]\]. Changing farm management depends on the compliance of the farmer which could be facilitated by an understanding of the costs involved; a gain of £50 per cow after deduction of drug costs for the average case described. This saving could ultimately also benefit society if milk is more available or becomes cheaper as a result. However, it is not clear how to quantify the opinion of society on use of routine hormone therapy to balance against change in methane emissions and costs. This problem has also occurred in human medicine, where quality adjusted life years are used as units in cost effectiveness analyses; however an arbitrary monetary value must still be assigned to these units for comparison with treatment costs \[[@pone.0127846.ref036]\]. The synchronisation programmes tested were not always associated with clear benefits for all interested parties. This emphasises the benefit of using stochastic simulation for predictions to investigate all feasible scenarios. For example, if a herd with upper quartile submission risk, pregnancy risk and voluntary waiting period, but otherwise average performance applied an Ovsynch programme, there would be no decrease in methane emissions per L of milk produced ([Fig 1](#pone.0127846.g001){ref-type="fig"}), yet the farmer would be better off ([Fig 4](#pone.0127846.g004){ref-type="fig"}). In this situation, routine hormone therapy may not be accepted by society. Conversely, an Ovsynch programme could reduce methane emissions per L of milk for a herd with high submission risk and a short voluntary waiting period despite no direct financial benefit to the farmer ([Fig 1](#pone.0127846.g001){ref-type="fig"}; [Fig 4](#pone.0127846.g004){ref-type="fig"}). This could occur if reproductive efficiency improved to such an extent that the number of cows that were dry per day of the study increased, meaning less milk was sold. Prompt breeding and short lactations imply that forage intake and hence methane emissions per L of milk would decline. We assumed that inputs and outputs for individual herds were known. With the exception of the double prostaglandin programme that was most similar to the baseline scenario, linear models explained most variation between herds; the remainder was due to the complex manner in which uncertainty in parameters was propagated through the simulation models \[[@pone.0127846.ref015]\]. However in reality there is likely to be both epistemic uncertainty in input values (which can also vary over time), and aleatory uncertainty in outcomes that have yet to occur at the point of making the decision. In practice, it is therefore important to make calculations for specific farms rather than rely on generalisations to inform decision making around management programmes using hormonal therapy. These should also be tailored to specific situations. From the farmers' point of view, it is simplistic to assume that it is acceptable to at least break even, and some decision makers may expect a higher level of return to compete with other investments. The impact of the attitude to risk and willingness to pay of decision makers has been used to set budgets for interventions to control mastitis \[[@pone.0127846.ref010]\], but not to aid decisions around reproductive management, which are potentially of greater economic importance. It is therefore useful to present the likely impact of interventions and demonstrate the potential scale of effects to producers, and indicate how likely it is that these will occur. This is particularly important for marginal benefits such as for supplementing the Ovsynch programme with progesterone. A similar approach could be applied to reduction in methane emissions to justify use of hormone treatments to society, although it is not clear what level of reduction would be sufficient. Despite simulation of a positive influence of Ovsynch with progesterone on chance of resumption of cyclicity in acyclic cows \[[@pone.0127846.ref029], [@pone.0127846.ref030]\], associations of the proportion of anoestrous cows by the end of the voluntary waiting period for each herd with the outcomes were not significant in this study. Beneficial influences of progesterone supplementation have been shown elsewhere \[[@pone.0127846.ref026]--[@pone.0127846.ref028]\], but the metrics presented could not be applied to the parameter values used in our simulation. Any simulation of a biological system must have boundaries, and we restrict our analyses to the farm level, consistent with the major source of greenhouse gas emissions associated with dairy production \[[@pone.0127846.ref037]\]. In summary, this paper emphasises the importance of being able to predict economic and environmental outcomes in order to facilitate decision making, and justify controversial management practices for society. However we emphasise the importance of simulating specific herd scenarios when making these predictions. This project was funded by Zoetis. We are grateful for access to the University of Nottingham High Performance Computing Facility. [^1]: **Competing Interests:**The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: SCA CDH MJG. Performed the experiments: SCA. Analyzed the data: SCA MJG. Contributed reagents/materials/analysis tools: SCA CDH. Wrote the paper: SCA CDH MJG.

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(http://www.magentocommerce.com) * @license http://opensource.org/licenses/osl-3.0.php Open Software License (OSL 3.0) */ /* @var $installer Mage_Core_Model_Resource_Setup */ $installer = $this; $installer->startSetup(); /** * Drop foreign keys */ $installer->getConnection()->dropForeignKey( $installer->getTable('api/rule'), 'FK_API_RULE' ); $installer->getConnection()->dropForeignKey( $installer->getTable('api/session'), 'FK_API_SESSION_USER' ); /** * Drop indexes */ $installer->getConnection()->dropIndex( $installer->getTable('api/role'), 'PARENT_ID' ); $installer->getConnection()->dropIndex( $installer->getTable('api/role'), 'TREE_LEVEL' ); $installer->getConnection()->dropIndex( $installer->getTable('api/rule'), 'RESOURCE' ); $installer->getConnection()->dropIndex( $installer->getTable('api/rule'), 'ROLE_ID' ); $installer->getConnection()->dropIndex( $installer->getTable('api/session'), 'API_SESSION_USER' ); $installer->getConnection()->dropIndex( $installer->getTable('api/session'), 'API_SESSION_SESSID' ); /* * Change columns */ $tables = array( $installer->getTable('api/assert') => array( 'columns' => array( 'assert_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'identity' => true, 'unsigned' => true, 'nullable' => false, 'primary' => true, 'comment' => 'Assert id' ), 'assert_type' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 20, 'comment' => 'Assert type' ), 'assert_data' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => '64K', 'comment' => 'Assert additional data' ) ), 'comment' => 'Api ACL Asserts' ), $installer->getTable('api/role') => array( 'columns' => array( 'role_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'identity' => true, 'unsigned' => true, 'nullable' => false, 'primary' => true, 'comment' => 'Role id' ), 'parent_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'Parent role id' ), 'tree_level' => array( 'type' => Varien_Db_Ddl_Table::TYPE_SMALLINT, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'Role level in tree' ), 'sort_order' => array( 'type' => Varien_Db_Ddl_Table::TYPE_SMALLINT, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'Sort order to display on admin area' ), 'role_type' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 1, 'nullable' => false, 'default' => '0', 'comment' => 'Role type' ), 'user_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'User id' ), 'role_name' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 50, 'comment' => 'Role name' ) ), 'comment' => 'Api ACL Roles' ), $installer->getTable('api/rule') => array( 'columns' => array( 'rule_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'identity' => true, 'unsigned' => true, 'nullable' => false, 'primary' => true, 'comment' => 'Api rule Id' ), 'role_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'Api role Id' ), 'resource_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 255, 'comment' => 'Module code' ), 'assert_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'Assert id' ), 'role_type' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 1, 'comment' => 'Role type' ) ), 'comment' => 'Api ACL Rules' ), $installer->getTable('api/user') => array( 'columns' => array( 'user_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'identity' => true, 'unsigned' => true, 'nullable' => false, 'primary' => true, 'comment' => 'User id' ), 'firstname' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 32, 'comment' => 'First name' ), 'lastname' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 32, 'comment' => 'Last name' ), 'email' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 128, 'comment' => 'Email' ), 'username' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 40, 'comment' => 'Nickname' ), 'api_key' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 40, 'comment' => 'Api key' ), 'created' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TIMESTAMP, 'nullable' => false, 'comment' => 'User record create date' ), 'modified' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TIMESTAMP, 'comment' => 'User record modify date' ), 'lognum' => array( 'type' => Varien_Db_Ddl_Table::TYPE_SMALLINT, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'Quantity of log ins' ), 'reload_acl_flag' => array( 'type' => Varien_Db_Ddl_Table::TYPE_SMALLINT, 'nullable' => false, 'default' => '0', 'comment' => 'Refresh ACL flag' ), 'is_active' => array( 'type' => Varien_Db_Ddl_Table::TYPE_SMALLINT, 'nullable' => false, 'default' => '1', 'comment' => 'Account status' ) ), 'comment' => 'Api Users' ), $installer->getTable('api/session') => array( 'columns' => array( 'user_id' => array( 'type' => Varien_Db_Ddl_Table::TYPE_INTEGER, 'unsigned' => true, 'nullable' => false, 'default' => '0', 'comment' => 'User id' ), 'logdate' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TIMESTAMP, 'nullable' => false, 'comment' => 'Login date' ), 'sessid' => array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 40, 'comment' => 'Sessioin id' ) ), 'comment' => 'Api Sessions' ) ); $installer->getConnection()->modifyTables($tables); $installer->getConnection()->changeColumn( $installer->getTable('api/rule'), 'privileges', 'api_privileges', array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 20, 'comment' => 'Privileges' ) ); $installer->getConnection()->changeColumn( $installer->getTable('api/rule'), 'permission', 'api_permission', array( 'type' => Varien_Db_Ddl_Table::TYPE_TEXT, 'length' => 10, 'comment' => 'Permission' ) ); /** * Add indexes */ $installer->getConnection()->addIndex( $installer->getTable('api/rule'), $installer->getIdxName('api/rule', array('resource_id', 'role_id')), array('resource_id', 'role_id'), Varien_Db_Adapter_Interface::INDEX_TYPE_INDEX ); $installer->getConnection()->addIndex( $installer->getTable('api/rule'), $installer->getIdxName('api/rule', array('role_id', 'resource_id')), array('role_id', 'resource_id'), Varien_Db_Adapter_Interface::INDEX_TYPE_INDEX ); $installer->getConnection()->addIndex( $installer->getTable('api/session'), $installer->getIdxName('api/session', array('user_id')), array('user_id'), Varien_Db_Adapter_Interface::INDEX_TYPE_INDEX ); $installer->getConnection()->addIndex( $installer->getTable('api/session'), $installer->getIdxName('api/session', array('sessid')), array('sessid'), Varien_Db_Adapter_Interface::INDEX_TYPE_INDEX ); $installer->getConnection()->addIndex( $installer->getTable('api/role'), $installer->getIdxName('api/role', array('parent_id', 'sort_order')), array('parent_id', 'sort_order'), Varien_Db_Adapter_Interface::INDEX_TYPE_INDEX ); $installer->getConnection()->addIndex( $installer->getTable('api/role'), $installer->getIdxName('api/role', array('tree_level')), array('tree_level'), Varien_Db_Adapter_Interface::INDEX_TYPE_INDEX ); /** * Add foreign keys */ $installer->getConnection()->addForeignKey( $installer->getFkName('api/rule', 'role_id', 'api/role', 'role_id'), $installer->getTable('api/rule'), 'role_id', $installer->getTable('api/role'), 'role_id' ); $installer->getConnection()->addForeignKey( $installer->getFkName('api/session', 'user_id', 'api/user', 'user_id'), $installer->getTable('api/session'), 'user_id', $installer->getTable('api/user'), 'user_id' ); $installer->endSetup();

Q: Detect windows service failure Is it possible for one windows service to detect whether one of the other running windows services have stopped? For some reason, 3rd party services are sometimes stopping, and I have to manually start them again. I need a service to automate this annoying process. A: I would strongly advise you target your efforts on correcting the issues diagnosed instead of fire-fighting the symptoms. Find out why the third party services are stopping / failing and nip the issues in the bud. However, if you must implement something in the time being, take a look at ServiceController, with information found at this MSDN link. This will allow you to query services, their states, and further control them, as in calling Start, as required, for your particular case. Assuming (maybe against better judgement) that your'e using .NET, and, due to my affinity to it, C# as the language, consider the following for a quick off-the-cuff example: //Add a reference to System.ServiceProcess using System.ServiceProcess; var services = ServiceController.GetServices(); foreach (var service in services) { if (service.ServiceName == myServiceName && service.Status == ServiceControllerStatus.Stopped) { service.Start(); } }

As mobile telephones have received increasing amounts of computing power in successive generations, the mobile telephones have been termed “smart phones”. Along with increasing amounts of computing power, such smart phones have seen increases in storage capacity and, consequently, increased utility. Beyond telephone functions, smart phones may now send and receive digital messages, be they formatted to use e-mail standards, Short Messaging Service (SMS) standards, Instant Messaging standards and proprietary messaging systems. Smart phones may also store, read, edit and create documents, spreadsheets and presentations. Accordingly, there have been increasing demands for smart phones with enhanced authentication functions.

/* This file is part of the KDE project SPDX-FileCopyrightText: 2010 Thomas Fjellstrom <thomas@fjellstrom.ca> SPDX-License-Identifier: LGPL-2.0-or-later */ #ifndef KATE_FILETREE_PLUGIN_H #define KATE_FILETREE_PLUGIN_H #include <QIcon> #include <KTextEditor/Command> #include <KTextEditor/Plugin> #include <ktexteditor/document.h> #include <ktexteditor/editor.h> #include <ktexteditor/mainwindow.h> #include <ktexteditor/sessionconfiginterface.h> #include "katefiletreepluginsettings.h" #include <KXMLGUIClient> class KToolBar; class KateFileTree; class KateFileTreeModel; class KateFileTreeProxyModel; class KateFileTreeConfigPage; class KateFileTreePluginView; class KateFileTreePlugin : public KTextEditor::Plugin { Q_OBJECT public: explicit KateFileTreePlugin(QObject *parent = nullptr, const QList<QVariant> & = QList<QVariant>()); ~KateFileTreePlugin() override; QObject *createView(KTextEditor::MainWindow *mainWindow) override; int configPages() const override; KTextEditor::ConfigPage *configPage(int number = 0, QWidget *parent = nullptr) override; const KateFileTreePluginSettings &settings(); void applyConfig(bool shadingEnabled, const QColor &viewShade, const QColor &editShade, bool listMode, int sortRole, bool showFulPath); public Q_SLOTS: void viewDestroyed(QObject *view); private: QList<KateFileTreePluginView *> m_views; KateFileTreeConfigPage *m_confPage = nullptr; KateFileTreePluginSettings m_settings; }; class KateFileTreePluginView : public QObject, public KXMLGUIClient, public KTextEditor::SessionConfigInterface { Q_OBJECT Q_INTERFACES(KTextEditor::SessionConfigInterface) public: /** * Constructor. */ KateFileTreePluginView(KTextEditor::MainWindow *mainWindow, KateFileTreePlugin *plug); /** * Virtual destructor. */ ~KateFileTreePluginView() override; void readSessionConfig(const KConfigGroup &config) override; void writeSessionConfig(KConfigGroup &config) override; /** * The file tree model. * @return the file tree model */ KateFileTreeModel *model(); /** * The file tree proxy model. * @return the file tree proxy model */ KateFileTreeProxyModel *proxy(); /** * The file tree. * @return the file tree */ KateFileTree *tree(); void setListMode(bool listMode); bool hasLocalPrefs(); void setHasLocalPrefs(bool); protected: void setupActions(); private: QWidget *m_toolView; KToolBar *m_toolbar; KateFileTree *m_fileTree; KateFileTreeProxyModel *m_proxyModel; KateFileTreeModel *m_documentModel; bool m_hasLocalPrefs = false; bool m_loadingDocuments; KateFileTreePlugin *m_plug; KTextEditor::MainWindow *m_mainWindow; private Q_SLOTS: void showToolView(); void hideToolView(); void showActiveDocument(); void activateDocument(KTextEditor::Document *); void viewChanged(KTextEditor::View * = nullptr); void documentOpened(KTextEditor::Document *); void documentClosed(KTextEditor::Document *); void viewModeChanged(bool); void sortRoleChanged(int); void slotAboutToCreateDocuments(); void slotDocumentsCreated(const QList<KTextEditor::Document *> &); void slotDocumentSave(); void slotDocumentSaveAs(); }; #endif // KATE_FILETREE_PLUGIN_H

// (C) Copyright John Maddock 2005. // Use, modification and distribution are subject to the Boost Software License, // Version 1.0. (See accompanying file LICENSE_1_0.txt or copy at // http://www.boost.org/LICENSE_1_0.txt). // // See http://www.boost.org/libs/type_traits for most recent version including documentation. #ifndef BOOST_TT_HAS_VIRTUAL_DESTRUCTOR_HPP_INCLUDED #define BOOST_TT_HAS_VIRTUAL_DESTRUCTOR_HPP_INCLUDED #include <boost/type_traits/intrinsics.hpp> #include <boost/type_traits/integral_constant.hpp> namespace boost { #ifdef BOOST_HAS_VIRTUAL_DESTRUCTOR template <class T> struct has_virtual_destructor : public integral_constant<bool, BOOST_HAS_VIRTUAL_DESTRUCTOR(T)>{}; #else template <class T> struct has_virtual_destructor : public integral_constant<bool, false>{}; #endif } // namespace boost #endif // BOOST_TT_IS_MEMBER_FUNCTION_POINTER_HPP_INCLUDED

Phosphorylation of AfsR by multiple serine/threonine kinases in Streptomyces coelicolor A3(2). AfsK, a protein serine/threonine kinase, autophosphorylates on serine and threonine residues and phosphorylates serine and threonine residues of AfsR, a transcriptional activator for afsS involved in secondary metabolism in Streptomyces coelicolor A3(2). pkaG encoding a 592-amino-acid protein and SCD10.09 (named afsL) encoding a 580-amino-acid protein, both of which encode an AfsK-like protein, were transcribed throughout growth. PkaG with a histidine-tag and the kinase catalytic domain of PkaG, produced in Escherichia coli, autophosphorylated dominantly on threonine and slightly on serine residues. In addition, these proteins phosphorylated AfsR on threonine and serine residues. The catalytic domain of AfsL also autophosphorylated and phosphorylated AfsR, on threonine and serine residues in both cases. AfsR was thus found to be phosphorylated by multiple kinases. Disruption of the chromosomal pkaG gene resulted in slightly reduced production of the pigmented antibiotic actinorhodin. These findings, together with the presence of about 40 AfsK homologues and at least five AfsR homologues in S. coelicolor A3(2), suggest that the regulatory networks via eukaryotic-type protein phosphorylation are more diverse and versatile than we have expected.

Helen Novikov Helen Novikov (born November 26, 1976) is an Estonian architect and former Olympic luger. She represented Estonia at the 1994 and 1998 Winter Olympics. Biography Novikov was born in Tallinn and grew up in Tõrva. She attended the Estonian Academy of Arts in architecture. Following the 1988 Olympics, she got her Bachelor of Applied Science degree at the Tallinn University of Applied Sciences. Novikov began luging in 1987. She trained in Sigulda, Latvia with coaches Viljo Grauding and Peter Kirdi. She is currently an architect for Ritsu AS, a company that designs and produces wooden houses. Winter Olympics Novikov made her Olympic debut in the 1994 Winter Olympics in Lillehammer, Norway. She was the sole Estonian luger at the games. She participated in the women's singles event finishing 19th overall. Novikov returned in 1998 to the following Winter Olympics in Nagano, Japan. She came in 20th in the women's singles. References Category:Living people Category:1976 births Category:Estonian female lugers Category:Olympic lugers of Estonia Category:Lugers at the 1994 Winter Olympics Category:Lugers at the 1998 Winter Olympics Category:Sportspeople from Tallinn

INTRODUCTION {#s1} ============ The immunophenotypic analysis of acute leukemia by multiparameter flow cytometry is a powerful tool for proper identification of lymphoid or myeloid lineage and is indispensable in modern diagnosis and management of acute leukemia \[[@R1]\]. CD45/side scatter (SS) gating for isolating blasts by flow cytometry was first proposed by Borowitz and Stelzer \[[@R2], [@R3]\] and is now widely used. Blasts in the classic "blast gate" (cBG) show CD45^dim^ in CD45/SS gating. However, other cells contaminate the cBG \[[@R4]\], and blasts may also occur in other gates. Mouse models have been widely used for medical research for more than 100 years and are indispensable for leukemic research. We and others \[[@R5]--[@R9]\] have suggested similar proposals for diagnosis of murine acute leukemia, including cytologic, histologic, and immunophenotypic analyses. In mouse models expressing transgene and/or marker genes such as enhanced green fluorescent protein (EGFP) in hematopoietic cells, leukemic cells may be easily isolated by flow cytometry \[[@R5], [@R10]--[@R13]\]. However, in many situations, for example in transgenic mice in which no marker gene was introduced into hematopoietic cells, blast cells may be difficult to distinguish from other cell types. So far, immunophenotypic analysis of murine leukemia was not always performed in published studies, and blast gating for isolation of blasts was shown only in very few studies. No systemic characterization of all types of murine acute leukemia in large cohorts by flow cytometry has been reported. In the present study, we analyze murine acute leukemia by flow cytometry in a large cohort of mice. We show that murine T-lymphoblastic leukemia/lymphoma (T-ALL) demonstrates a distinctive "blast gate" by CD45/SS gating. Our gating strategy for immunophenotypic analysis can be used for leukemogenesis and preclinical gene therapy studies in mouse models and may improve the quality of such analyses. RESULTS {#s2} ======= Murine T-ALL demonstrates a distinctive "blast gate" by CD45/SS gating {#s2_1} ---------------------------------------------------------------------- We performed experiments for leukemogenesis and preclinical gene therapy studies in more than 3,000 mice, including transplantation of retrovirally modified hematopoietic cells into C57Bl/6J and C3H/HeJ mice, serial transplantation of murine leukemic cells, and studies of transgenic and knock-in mice \[[@R5], [@R10]--[@R17]\]. At least 500 animals developed acute leukemia. A diagnosis of leukemia was established generally based on cytologic, histologic, and/or immunophenotypic findings. Consistent with clustering of human bone marrow cells in CD45/SS gating (Figure [1A](#F1){ref-type="fig"}), bone marrow cells from healthy mice and mice without hematological malignancies showed similar distribution of cell populations (Figure [1B](#F1){ref-type="fig"}), except for the location of some B lymphocytes in the CD45^dim^ cBG in most analyzed cases (n = 22) (Figures [1C](#F1){ref-type="fig"} and [Supplementary Figure 1](#SD1){ref-type="supplementary-material"}). Contamination of non-blast cells in the cBG has been reported in patients without acute myeloid leukemia (AML) \[[@R4]\]. Blasts from mice with AML (non-monocytic) (n = 31) and B-lymphoblastic leukemia (n = 8) were in the same location in the cBG as blasts from patients with acute leukemia (Figures [1D-1L](#F1){ref-type="fig"}). Cytological assessment confirmed the presence of acute leukemia in these mice and patients (Figures [1M-1P](#F1){ref-type="fig"}). While the cBG for human AML and B-lymphoblastic leukemia was clearly separated from granulocytes and monocytes (Figures [1F](#F1){ref-type="fig"} and [1K](#F1){ref-type="fig"}), the cBG for murine AML and B-lymphoblastic leukemia was sometimes difficult to set because of the close proximity of granulocytes and monocytes (Figure [1B](#F1){ref-type="fig"}). Interestingly, blasts from murine T-ALL were located in a gate with the highest CD45 fluorescence intensity (CD45^bright^) (Figures [2A-2P](#F2){ref-type="fig"}), whereas blasts from patients with T-ALL were exclusively present in the cBG (Figures [2C](#F2){ref-type="fig"} and [2D](#F2){ref-type="fig"}). This distinctive "blast gate" (CD45^bright^) (Figure [2A](#F2){ref-type="fig"}) was reproducibly seen for T-ALL in all analyzed mice (n = 74) from different experiments addressing the role of several genes in the leukemogenesis, for example, ΔTRKA \[[@R15]\], TRKA/NGF \[[@R13]\], TRKB/BDNF \[[@R12]\], and p53 (in p53 knock-out and p53/FLT3 double transgenic mice). This blast gate was consistent for T-ALL cells from thymus, spleen, liver, and bone marrow, and for T-ALL with different phenotyping (e.g. CD4/CD8 double positive, CD4 or CD8 single positive, and CD4/CD8 double negative) (data not shown). We proposed this distinctive "blast gate" of T-ALL as an alternative "blast gate" (aBG). Interestingly, this blast region was also seen in Pten-null T-ALL \[[@R18]\]. Moreover, normal T precursor cells isolated from thymus of wild type (WT) mice (n = 2) and one mouse without hematological malignancies were also located in this aBG as T-ALL ([Supplementary Figure 1](#SD1){ref-type="supplementary-material"}). Importantly, infiltration of T-ALL and AML cells was observed in the bone marrow of some mice, demonstrating different locations of myeloblasts and lymphoblasts in the same sample (Figures [2E-2H](#F2){ref-type="fig"}). Moreover, we mixed T-ALL cells with AML cells and other cell populations from different mice, and flow cytometric analysis confirmed the same clustering of T-ALL cells ([Supplementary Figure 2](#SD1){ref-type="supplementary-material"} and data not shown). Of note, none of the human T-ALL blasts were located in the aBG in a cohort of patients with acute leukemia (n \> 200) including ALL (n = 21), but we observed monoblasts in the aBG from some patients with AML M4/5 (Figures [2I-2L](#F2){ref-type="fig"}) or in the monocyte gate (Figures [1F](#F1){ref-type="fig"} and [1H](#F1){ref-type="fig"}) as reported by Gorczyca \[[@R19]\]. Acute monocytic leukemia is rare in mice. Blasts from the mouse with acute monocytic leukemia in our cohort \[[@R16]\] were also found in the aBG ([Supplementary Figure 4](#SD1){ref-type="supplementary-material"}). {#F1} {ref-type="supplementary-material"}).](oncotarget-09-2320-g002){#F2} T-ALL development in FLT3-ITD knock-in mice {#s2_2} ------------------------------------------- Using this gating strategy, we performed immunophenotypic analysis in selected FLT3-ITD knock-in mice, in which an 18-bp ITD mutation was inserted into the juxtamembrane domain of the FLT3 gene \[[@R20]\]. This allows physiological expression of FLT3-ITD from its endogenous promoter and better understanding of the role of FLT3-ITD in leukemogenesis. Homozygous FLT3-ITD/ITD (ITD/ITD) mice develop myeloproliferative disease after a long latency \[[@R20], [@R21]\]. We found T-ALL in 7 out of 30 (23%) ITD/ITD mice (Figures [3A-3D](#F3){ref-type="fig"}), in which infiltration of tumor cells was observed in different organs. Other mice developed a (Chronic myelomonocytic leukemia=CMML)-like disease or AML (n=1) as reported (Figures [3E](#F3){ref-type="fig"} and [3F](#F3){ref-type="fig"}) \[[@R20], [@R21]\]. To the best of our knowledge, our report is the first report of T-ALL in FLT3-ITD knock-in mice. Together with an early report showing ALL development in FLT3-ITD transgenic mice \[[@R22]\], our data suggest a potential role of FLT3-ITD in the pathogenesis of T-ALL. Accordingly, FLT3 mutations have been reported in patients with T-ALL and B-lymphoblastic leukemia \[[@R23]\], particularly among children with ALL (incidence: up to 25%) \[[@R24], [@R25]\]. Moreover, leukemic cells from mice with T-ALL were sensitive to FLT3 inhibition (Figure [3G](#F3){ref-type="fig"}). Crenolanib and midostaurin almost completely killed the cells at 500 nM and 200 nM concentrations, respectively, similar to the concentration (crenolanib) or well below the concentration (midostaurin) safely achieved in humans \[[@R26]--[@R28]\]. Our data indicate that crenolanib and midostaurin might be effective in treating the subset of T-ALL patients with FLT3-ITD. {#F3} DISCUSSION {#s3} ========== Mouse models facilitate our understanding of the molecular mechanisms for leukemia development. However, immunophenotypic analysis of leukemic cells is not well investigated, and blast cell gating for isolation of blasts has been performed so far only in very few studies. Guo et al. \[[@R18], [@R29]\] described the blast gating for T-ALL in an early study. However, they analyzed only leukemia in *Pten*-mutant mice, and no murine B-lymphoblastic leukemia was characterized. No report has confirmed their finding. Whether the blast cell gating can be applied to other murine leukemias is not clear. In the present study of a large cohort of mice, we extended the finding of Guo et al., and confirmed the same blast gating for T-ALL in different models. Moreover, we analyzed other types of murine malignancies, including B-lymphoblastic leukemia, monocytic leukemia, and lymphoblastic lymphoma, that were not addressed by Guo et al. We demonstrate a distinctive "blast gate" (aBG, CD45^bright^) of murine T-ALL derived from different mouse models that is different from the blast gate of human T-ALL, whereas other murine leukemia (AML and B-lymphoblastic leukemia) show the same blast region as human leukemia. Use of cBG (CD45^dim^) for immunophenotypic analysis in cases of murine T-ALL can lead to a wrong diagnosis, particularly in mice without enlargement of the thymus. With the use of blast gating (i.e. aBG), we found T-ALL development in FLT3-ITD knock-in mice (incidence: 23%) that was not reported before in the same models, probably due to the use of different gating. Without the correct blast gating, we would have also overlooked some cases of T-ALL in our model. Pitfalls in the use of the cBG for blast analysis have been also reported in patients without AML \[[@R4]\]. The reason for this aBG of murine T-ALL is unknown and needs to be determined. CD45 is shown to regulate phosphorylation of kinases such as SRC and JAK family kinases and might have a tumor suppressor role in T-ALL \[[@R30], [@R31]\]. However, high CD45 expression on leukemic blasts was associated with a poor prognosis in children with precursor B-cell and T-cell ALL, mainly due to a higher cumulative incidence of relapse \[[@R32]\]. In our cohort, mice with T-ALL seemed to have shorter survival than mice without T-ALL. However, in some instances an enlarged thymus might also have contributed to shorter survival of some mice. FLT3 plays a critical role in the maintenance of hematopoietic homeostasis. In humans, FLT3 is expressed on hematopoietic stem cells, and FLT3 signaling prevents apoptosis in stem cells and progenitors and induces proliferation and maintenance of stem/progenitor cells \[[@R33]\]. Mutated FLT3 has been identified in approximately 30% of AML patients, making it one of the most common mutations with prognostic implications observed in this disease. Frequently, the mutation is an in-frame internal tandem duplication (ITD) in the juxtamembrane region or a point mutation in tyrosine kinase domain-1 that results in constitutive activation of FLT3. A recently published trial that included 717 patients with previously untreated FLT3+ AML demonstrated a statistically significant improvement in overall survival (OS) for patients treated with midostaurin (targeting FLT3-ITD) compared with those on the placebo-containing arm (HR 0.77, *P* = 0.016) \[[@R34]\]. This led to recent FDA approval of midostaurin as frontline therapy for adult patients with newly diagnosed AML. In this study, our data suggest a potential role of FLT3-ITD in the development of T-ALL. We showed that murine T-ALL induced by FLT3-ITD is highly sensitive to treatment with FLT3 inhibitors, including midostaurin. Early studies demonstrated that ALL samples from patients with FLT3 mutations or high level of FLT3 expression were selectively killed by FLT3 inhibition \[[@R24]\]. These data suggest that targeting FLT3-ITD might be a treatment option for ALL patients with FLT3 mutations or high FLT3 expression. In conclusion, our study is the first comprehensive study that characterizes all common types of murine acute leukemia in a large cohort of mice by flow cytometry. Careful immunophenotypic analysis of leukemic cells with the right blast gating may improve the quality of mouse experiments. Because both murine and human blasts can be in both blast gates (cBG with CD45^dim^ and the aBG with CD45^bright^), our data highlight careful isolation of blasts in acute leukemia by flow cytometry, and the proposed aBG is thus helpful for making appropriate diagnoses of T-ALL in mouse models. Moreover, for clinical diagnosis and management of patients with acute leukemia, it should be aware that leukemic blasts can be also isolated from the aBG with CD45^bright^. MATERIALS AND METHODS {#s4} ===================== *In vivo* tumorigenesis assays {#s4_1} ------------------------------ Retroviral transductions of murine hematopoietic cells and *in vivo* tumorigenesis assays have been described \[[@R5], [@R10]--[@R16], [@R35]\]. We purchased FLT3-ITD knock-in (KI) mice from the Jackson Laboratory, in which an 18-bp ITD mutation was inserted into the juxtamembrane domain of the FLT3 gene. The mice with C57BL/6 background were originally established in the Gilliland´s laboratory \[[@R20]\]. Upon arrival at the Jackson Laboratory, the mice were crossed to C57BL/6J mice at least once to establish the colony. After arrival at our animal facility, the mice were crossed to C57BL/6J at least three times in order to obtain a high C57BL/6J background. FLT3-ITD mice were crossed to p53 knock-out mice to generate double transgenic mice. Animal experiments were approved by the local ethical committee and performed according to their guidelines. Tumor phenotyping {#s4_2} ----------------- At the end point analysis, mice were macroscopically examined for pathological abnormalities during dissection. Enlarged organs were weighed. Bone marrow, spleen, liver, skin, gut, kidney, lung, brain and thymus were fixed in a buffered 4% formalin solution and embedded in Paraplast Plus (Kendall, Mansfield, MA, USA). Sections were routinely stained with hematoxylin and eosin. Blood cell counts were measured by an automatic analyzer (ABC Counter, Scil, Viernheim, Germany). Cytological and histological examinations were performed as previously described \[[@R12]\]. Flow cytometric analyses {#s4_3} ------------------------ Flow cytometric analyses were performed by use of whole murine bone marrow/spleen cells and patient samples after Ficoll separation (thus lower erythrocytes and debris in patient samples; see e.g. Figure [1A](#F1){ref-type="fig"}). Murine cells were stained with fluorescein isothiocyanate (FITC)-conjugated, R-phycoerythrin (PE)-conjugated, allophycocyanin (APC)-conjugated, APC-eFluor 780-conjugated, Percp-cy5.5-conjugated, or PE-Cy7-conjugated antibodies, including CD45, CD34, CD117, CD11b, Gr-1, Ter119, CD71, F4/80, CD4, CD8a, CD3, CD19, B220, CD44, and CD25 (from eBioscience or Biolegend). Human cells were stained with fluorescein isothiocyanate (FITC)-conjugated, R-phycoerythrin (PE)-conjugated, allophycocyanin (APC)-conjugated, APC-H7-conjugated, Percp-cy5.5-conjugated, or PE-Cy7-conjugated antibodies, including CD45, CD34, CD117, myeloperoxidase, CD13, CD14, CD15, CD33, CD61, CD235a (glycophorin A), HLA-DR, CD3, CD4, CD8, CD1a, CD2, CD5, CD7, CD8, Tdt, TCR α/β, TCR γ/δ, CD19, CD10, CD20, CD20, CD79a, kappa, lamda, and IgM (from BD Biosciences or Biolegend). Intracellular staining was performed using an IntraPrep Permeabilization Reagent Kit according to the manufacturer\'s protocol (Beckman Coulter, Marseille, France). The cells stained with antibodies were analyzed by flow cytometry either on an FACSCalibure or FCASCanto (BD Bioscience). Generally, atleast 10,000 cells per tube were measured and analyzed. Leukemic blasts were analyzed on CD45/SSC plots as previously described \[[@R2], [@R3]\]. Apoptosis assay {#s4_4} --------------- Leukemic cells were cultured in the presence of inhibitors for 48 hours before apoptosis analysis. Cell viability was analyzed using the Annexin-V assay (BD Pharmingen, Heidelberg, Germany) on an FCASCanto. We generally measured and analyzed at least 10,000 cells per tube. Annexin V^+^/PI^-^ and Annexin V^+^/PI^+^ cells are considered cells in the early stage of apoptosis and the late-stage of apoptosis, respectively. The inhibitors crenolanib and midostaurin were purchased from Selleckchem (Houston, TX). SUPPLEMENTARY MATERIALS FIGURES {#s5} =============================== We are very grateful to Jolanta Adolf, Christine Garen, Ellen Hebold, and Kerstin Schantl for technical assistance. We thank Matthias Gaestel and Karl Lenhard Rudolph for providing p53 knock-out mice. **CONFLICTS OF INTEREST** The authors do not declare any competing financial interest. **GRANT SUPPORT** This work was supported by the Deutsche Forschungsgemeinschaft (DFG grant: Li 1608/2-1), Deutsche José Carreras Leukämie-Stiftung (grant: 13/22), and Alfred & Angelika Gutermuth-Stiftung (projects 16/3 and 17/3). ZP and KH were supported by the China Scholarship Council (201406100008 and 2011638024). GB and SG were supported by the DFG excellence cluster REBIRTH. **Authorship** ZP and MY performed research and collected, analyzed, and interpreted data. KH and SG performed research. GB performed histological analysis. AG performed cytological analysis and provided administrative support. ZL conceived the concept, performed research, collected, analyzed, and interpreted data, and wrote the manuscript.

Cycle to work during National Bike Month May is National Bike Month. Experts say any individual, from beginner to someone with years of experience, can reap the benefits of cycling. Stronger, more toned legs and a healthier heart, and not paying for gas are a few of the benefits. A person also saves time not searching for a parking space in an overcrowded parking lot or trying to parallel park on the street. As much as this pastime is able to improve an individual’s health, additionally, cycling provides great benefits for the environment. If just one person chooses biking over driving a car as their mode of transportation, they are greatly lessening the amount of pollutants being emitted into the air Friday, May 20, is National Bike to Work Day. People throughout the United States will participate. Take part in the American Lung Association’s Trek Across Maine Friday, June 17, to Sunday, June 19, from Sunday River to Belfast, and enjoy picturesque views. The trek is open to cyclists of all skill levels, and participants are encouraged to go at their own pace. Accommodations are provided along with food, beverages, medical staff and entertainment. The registration fee for the ride is $55 along with a $500 fundraising minimum to participate. Proceeds will help the American Lung Association promote lung health and fight lung disease. For more information, or to register for the trek, visit http://www.biketreknewengland.org/ or call 888-241-6566, ext. 0312.

Q: How do I map a network drive so that any user that logs in the PC could see it in Windows 7? I have a PC here that needs to connect to a network drive to receive data. Multiple users will log in with their own accounts to do research with the data from that same network drive. I want to know if there is a way that i could map the network drive one time so that everybody who logs in will see the drive and won't have to map it themselves. The PC is Windows 7 pro. thank you A: You mentioned that the accounts are on the domain, and you are the domain admin, and so this article goes over what you're asking. It shows you multiple ways of determining which users should have access to the network drive, if you don't want to map it for all your users. Basically you have to setup a security group in AD with the users for which you want to map the network drive. There are other ways to map network drives, such as running a script on startup, if you need more complex logic, but typically doing it by security group is the easiest way to do it.

On Jun 9, 2011, at 9:42 AM, "Tab Atkins Jr." <jackalmage@gmail.com> wrote: >> You are saying that marker placement is the result of a new value of 'position' that causes it to ignore all other ways of selecting it (in the case of an explicit 'position:marker'), and only be styled by the new pseudo-class only, meanwhile causing it to change from 'display: inline' into 'display: inline-block'. That sounds pretty magical to me already, and we have to still nail down how the magic works. And what happens if I have '::marker { display:block; position:static; }'? I still haven't seen an answer to that one. Does it jump back into an inside position? Does it keep the 'display' value from ::marker, or does it now ignore ::marker and revert to only looking at normal (non-pseudo) selection rules? > > Hmm, it looks like there was some major miscommunication here. Also, > the spec is in a somewhat inconsistent state at the moment, so you > can't look to it for guidance until I correct it (which I'll do > today). I would say lack of clarity in communication, not miscommunication. You seem to have a different mental model than I do, which has not been clear to me (in parts) from the spec or your subsequent emails, and I've been trying to understand the parts that I find confusing, while making suggestions for ways to avoid confusion via alteration to the way it works. > There are two values for list-style-position: 'inside' and 'outside'. > Their primary effect is changing where the ::marker is placed in the > element-tree. I'm with you so far. > 'outside' also tweaks the default value Do you mean computed value? > of a few > properties on ::marker, > including making it "position:marker". OK. That bit of magic wasn't clear to me before. I had thought "position:marker" was just to move arbitrary elements into marker position. > "position:marker" is just a new positioning scheme based on how > markers are typically positioned. > > You can also use "position:marker" on arbitrary elements, which does > the expected thing of just making the element positioned. > > My point about avoiding magical behavior is that, given the concept of > "position:marker" (which I like), ::marker should act almost exactly > like an extra ::before I agree ::marker should be similar to an extra ::before in most ways. > that list-items happen to possess (modulo the > few places where 'outside' tweaks default property values). This > seems elegant and minimally invasive, which hopefully means that it > should be easy to understand too. OK so at least I understand you better now. However, "new positioning scheme based on how markers are typically positioned" doesn't sound significantly less magical than "outside marker content has a containment block that is the box where markers are typically positioned".

{#sp1 .353} {#sp2 .354} {#sp3 .355} {#sp4 .356} {#sp5 .357} {#sp6 .358}

The Immunology Core I was originally established as the Molecular Immunology Core with three subcores focused on humoral immunity, cellular immunity, and flow-based assays. The mission of this Core is to develop, refine, and provide by training and technology-transfer state-of-the-art immunological assays to evaluate and quantify humoral and cellular responses to support NIH-sponsored AIDS research and training. The assays, reagents, and training offered by the Core are designed to support basic, clinical, and translational research in the prevention, detection, and treatment of HIV infection and AIDS. During the last five years, this Immunology Core has significantly increased its user base, with an overall 3.9-fold increase in total users from 21 to 82, and a 5.4-fold increase in support of local users (60% of total) and a 2.8-fold increase in non-local users (40% of total). Since 2002, the Immunology Core has continuously worked to expand its impact by focusing on the training of investigators in the use of the Core's technologies. As an example of these activities, we developed a hands-on workshop entitled "Research ELISA Assays: The Practical Guide" in Nairobi, Kenya, February 14-25, 2005. Highlights of research progress during the last five years have included studies on HIV Envelope tropism, Envelope variation and its relationship to the development of neutralizing antibodies (NAbs), the role of antibodies in perinatal transmission in nonhuman primates, examination of the role of IgG with ADCC activity in newborn macaques, hepatitis C-specific T cell responses and phenotypic analysis of liver NK T cells, gamma-delta T cell involvement in the viral immune control of chronic human herpesvirus-8 (HHV8) infection, epitope-specific T cell proliferation in HIV-infected subjects with long-term nonprogression, detailed examination of T cell responses to HIV-2, novel scaffold approaches to present HIV Envelope epitopes as vaccines, and support of translational studies. Over the next five years, we propose: (1) continuous development of state-of-the art assays within a more streamlined organization with two cores located in two, rather than three, locations;(2) the inclusion of a new Core Manager;(3) a redistributed budget to support a higher level of personnel to provide expanded services to a wider group of users;(4) linkages to a new Protein Core at the Seattle Biomedical Research Institute to obtain materials in a more cost-effective manner;and (5) a stronger focus on outreach, with training sessions for individual investigators and technical workshops for groups requesting services to transfer technology and reagents.

Aqueous Two-Phase System Rehydration of Antibody-Polymer Microarrays Enables Convenient Compartmentalized Multiplex Immunoassays. Multiplex immunoassays are rapidly increasing in popularity due to the offered advantages of increased throughput and decreased sample volume requirements. However, a major weakness inherent to multiplex enzyme-linked immunosorbent assays (ELISA) is generation of false signals through reagent-driven cross-talk. Typically, multiplex platforms necessitate bath application of antibody cocktails, increasing probability of nonspecific antibody binding, especially when multiplexing large numbers of analytes. Aqueous two-phase systems (ATPS) exploiting the phase-separating polymers poly(ethylene) glycol (PEG) and dextran (DEX) have been used to compartmentalize antibodies and prevent cross-talk in multliplex, plate-based ELISA. However, the resulting protocol is tedious and lengthy, and requires too many user steps to be practical for widespread use. Here, we report an improved, user-friendly, cross-talk-free multiplex ELISA method in which dehydrated arrays of colocalized capture and detection antibodies in DEX are prepared on multiwell plates. Addition of a PEG-based sample buffer rehydrates antibody/DEX droplets for analysis. In this report, we demonstrate rehydrated ATPS components for multiplex ELISA retain the ability to compartmentalize antibodies and prevent cross-talk, while analytes in sample buffer partition into rehydrated DEX droplets for analysis. Utility of this method was demonstrated through successful quantitative analysis of five inflammatory cytokines in lipopolysaccharide-stimulated ThP-1 cell culture supernatant.

liwen MAO: this project finds potential geometries that arise within a swarm intelligence system. such bottom up systems can not only create global complex phenomena but also unexpected smaller scale forms and gives the designer more localized control within the system. the project uses curves negotiate between the hierarchies of ornament and structure based on local rules. the advantage of this methodology of form finding is that it can break the limit of human imagination and create unlimited yet reasonable forms by changing specific parameters. shown here are examples of final products: one gold and the other crystal. the gold one focuses on how the geometry interacts with external conditions, while the crystal one focuses on how different local rules can influence form. sP: what or who influenced this project? lM: my instructor roland snooks sP: what were you reading/listening to/watching while developing this project? lM: by steven r johnson is a fundamental theory book for bottom-up system. by the way, muse’s music is good for thinking while writing script.

Balatonszárszó Balatonszárszó is a village along the southern shore of Lake Balaton in Somogy county, Hungary. The settlement is part of the Balatonboglár wine region. Gallery Notable residents Attila József (1905-1937), Hungarian poet Gyula J. Obádovics (born 1927), Hungarian mathematician, Dr. Techn., Dr. Rer. nat., professor emeritus Tivadar Farkasházy (born 1945), Hungarian humorist, author, and journalist External links Street map (Hungarian) Street map (Google) References Category:Populated places in Somogy County

Q: Applying for a new doctoral program after expulsion I am not prepared to give many details in a public forum - as such this posting will contain intentional generalizations that may be of interest to academia.se's research higher studies community help, in particular senior faculty members, if any. I would like to ask for help in figuring out if there would be a pathway to return to the pursuit of a terminal degree sometime 2020++ in a field related to my accumulated research work and career credentials with publications and products. At present I have a major blemish in my overall academic record at my last institution based upon an off-campus incident several years ago which ended in a sentence in a felony case. At the time of my projected return as a doctoral candidate, the faculty committee recommended suspension, and the admin decided on termination after it became clear I had failed to report it per student policy. Elsewhere on Stack Exch. I have already described the good that came out of that research, and that chapter of my life is now finished. Can I ask the community if there is any practical chance of pursuing a doctoral program again? If so, When could I approach that, and at what stage should I broach the subject to a new institution? Thank you. Added: This is a US academic industry question, but I would think my research area would be useful for academic institutions of major space faring nations. My felony is for a offense not related to any workplace or academic setting. I was in the middle of my doctoral program when the inquiry began. Over a year I was encouraged to continue by the judge(s) to try to conclude the program as fast as possible. I continued work for the institution throughout (I tried to quit after some discussion but was asked to remain while trial was underway and the outcome not known). A sentence was imposed with reduction of all charges save a single one, based upon the admissions I made and material I surrendered. After completing my sentence, When I attempted to return, I was found to have violated policy for the crime conducted away from campus but while a student, and also that I violated another policy as I had signed a form for a leave of absence using a made up reason to explain my projected absence, the day before I left to begin my short sentence. The ruling was split: faculty recommended suspension and admin recommended expulsion. A: I don't think your goal is impossible, but it will be difficult to achieve. I assume that your past infraction was serious or you wouldn't be in the state you are in. You can do one thing now, and you must do another thing later, however. Now, you can find ways to behave in a way that shows you learned from your experience, have paid for your sins, recognize them for what they are, ameliorate the bad effects they caused, and that it can never happen again. This is harder (even) than it sounds, as some acts might not be repeated, but an underlying attitude might lead a person to do other things, not exactly the same, but also quite bad. Narcissism, for example, can often lead to a lot of bad behavior of various kinds. Also, thing things you do should leave some visible record that clearly shows a change. Even better if other people can attest to your good character now and in the future. The thing you must do later is to be completely honest with any institution that you apply to. It won't be enough for you to promise to behave better. But the things you have done in the interim should speak for your change without your comment. Even then, of course, there are many who won't believe in your change. You need to make it real change, both for your future chances and for yourself generally. Good luck. Note that I mention narcissism as an example only. Lack of empathy is another. But I'm not trying to attribute either to you. A: The felony itself shouldn't be a big problem. While university will often have rules that basically allow them to kick out students that commit crimes while in school, to my knowledge it is not common to ask incoming students about crimes they committed before starting school. To meaningfully screen for felons the university would need to require a criminal background check as part of the application, which is rarely asked for. Now some sources of financial aid may require that applicants have a clean record, but then again, some might not. In any case, you are asking about studying, not funding. Your former institution specifically might be committed to cut ties with you, so if you re-apply there perhaps they would not accept, but this is hardly an issue when there are hundreds of other universities you can go to. However, wherever you end up applying, you will probably have to mention your past work. Whether you will be able to get away with only discussing your research work, and simply state that you were forced to abandon the program due to "personal issues", and if forced to elaborate, whether the committee there will be sympathetic to your situation, is impossible to predict. You will just have to try and see.

p? 4 Suppose p = 2 - 0. Suppose -10 - p = 3*t. What is the units digit of -2*(-7)/t*-2? 7 Let w(g) = g**3 - 9*g**2 + 20*g - 20. What is the hundreds digit of w(11)? 4 Let c = -3 - 6. Let g = c - -59. What is the units digit of g? 0 Suppose -5*v + 3*c + 10 = 0, 0*v = -5*v - 3*c + 10. Suppose v*g - 31 = 115. What is the units digit of g? 3 Suppose 4*v - 3*v = -5*d - 11, -3*d = 4*v - 7. What is the tens digit of -3 + (-1436)/(-16) + 1/v? 8 Let r(m) = -6*m - 39. Let o be r(-7). Suppose -4*w = -i - 692, o*i = -w - i + 156. What is the tens digit of w? 7 What is the hundreds digit of (448/400*20)/((-4)/(-70))? 3 Let g(n) = -2*n**3 + 18*n**2 + 15*n - 15. What is the hundreds digit of g(-7)? 4 Let k = 66 + -31. Suppose 0 = 10*x - 3*x - k. Suppose -x*l + 4*u + 74 = -8, 3*l - 5*u - 44 = 0. What is the units digit of l? 8 Let v(x) = 1470*x**2 - 3*x - 1. What is the units digit of v(-1)? 2 Let u be (-3 + 1 + 3)*2. Let p be (1 - -3 - -119) + -1. Suppose 5*h = u*t - 110, 0 = -2*t - h - 0*h + p. What is the units digit of t? 0 Suppose i + 3*d - 1623 = 1271, 2*d - 8696 = -3*i. What is the thousands digit of i? 2 Suppose -67*f + 183818 = -38354. What is the tens digit of f? 1 Suppose 5*o - 5*t - 4388 = 7107, -4610 = -2*o - 4*t. What is the tens digit of o? 0 Suppose -111*d = -146*d + 119805. What is the tens digit of d? 2 Let l(j) = j**2 - 2*j - 7. Let u be l(3). What is the units digit of (u/(-20))/((-1)/(-205))? 1 Suppose -19*o = -10*o - 981. What is the tens digit of o? 0 Let w(d) = -d**3 - 15*d**2 + 3*d + 19. Let q be w(-15). Let v = q + 33. Suppose v + 22 = f. What is the units digit of f? 9 Let z(w) = w**2 - 23*w + 65. Let m be z(-28). Suppose 7*s - 530 = m. What is the tens digit of s? 8 Let h be (-24)/(-36)*(1 + 2). Suppose 2*p - 2*w = 3*w + 25, h*p - 20 = 4*w. Suppose p = 4*v - 5*b - 190, 5*b + 96 = 2*v + 2*b. What is the units digit of v? 5 Suppose 7*s - 1 = 8*s, -v = 3*s - 2195. What is the thousands digit of v? 2 Let i(k) be the second derivative of -k**4/12 - 3*k**3/2 + 2*k**2 + 7*k. Let u = -10 - -1. What is the units digit of i(u)? 4 Let y = 3988 - 2276. What is the thousands digit of y? 1 Suppose 3*n = -5*d - 0*n - 313, -d = -n + 69. Let v = -22 - d. What is the tens digit of v? 4 Let h be (-35)/7 + 6/1. What is the tens digit of 0 - ((-1)/h)/((-5)/(-250))? 5 Suppose -12*l + 108 = -6*l. Let q be ((-81)/l)/(6/8). What is the units digit of 30 + q + (-12)/3? 0 Let w(b) = b - 105. Let t(o) = -o**2 + o + 1. Let v(d) = -t(d) - w(d). What is the units digit of v(0)? 4 Suppose -8 = 2*d - 18. Suppose -d*m + 6 = -34. Let z(n) = -n**2 + 9*n + 6. What is the units digit of z(m)? 4 Let n(w) = w**2 + 5*w + 43. Let k be n(0). Suppose -3*u = -5*s - 7*u + k, 2*u = -3*s + 25. What is the units digit of s? 7 Suppose 30*f - 20110 + 880 = 0. What is the tens digit of f? 4 Suppose 11*v - 5703 = 952. What is the tens digit of v? 0 What is the units digit of 3/(-10) + (39543/10)/1? 4 Let f(n) be the third derivative of n**6/120 - n**5/5 + 13*n**4/24 + 7*n**3/6 - n**2. What is the units digit of f(11)? 9 Let x = -1 - 3. Let c(z) = z**2 + 5*z + 9. What is the units digit of c(x)? 5 Let w(l) = l**3 - 6*l**2 - 6*l - 3. Let y be w(7). Suppose y*f + 1 = 13. Suppose 42 = -j + f*j. What is the tens digit of j? 2 Let v = -249 - -366. What is the hundreds digit of v? 1 Let s = 878 - 179. What is the hundreds digit of s? 6 What is the hundreds digit of -15 + (-54)/(-4) + 2170/4? 5 Suppose -2*u - 428 = 712. Let r = -404 - u. What is the hundreds digit of r? 1 Let b be 4*-1 - (-8 + 6). Let h(n) = 2*n**3 + 3*n**2 - n - 2. Let j be h(b). What is the units digit of (j - -2)*(-123)/6? 1 Suppose -3*b - 3332 = -5*b - 2*m, 3*b - 5*m = 5030. What is the thousands digit of b? 1 What is the tens digit of (-60)/(-105) - 71304/(-21)? 9 Let q(n) = 10*n + 2. Let z be q(3). Let u = z + 247. What is the hundreds digit of u? 2 Let d be 71/(-3)*36/(-12). Suppose -11 + 5 = -2*n. Suppose -174 = -n*s - 2*k + 37, -k + d = s. What is the units digit of s? 9 What is the tens digit of (1*-1)/(20/(-1500))? 7 Let k be 294/8 - (-4)/16. Suppose -c - 5 = -k. What is the tens digit of c? 3 Let h = -587 + 2243. What is the units digit of h? 6 Suppose -b = -16 + 12. Suppose 0*s - b*s = 20, -5*c = 2*s - 280. What is the units digit of c? 8 Let m(u) = 36*u**2 - 5*u - 8. Let f(v) = -v**3 + 7*v**2 + 9*v - 11. Let x be f(8). What is the hundreds digit of m(x)? 3 Let h(a) = 4*a + 45. Let w be h(-10). Suppose -w*n + 3*c + 1233 = 0, 0*c = -n - c + 245. What is the tens digit of n? 4 Let n = -10 - -5. Let b(f) = -9*f + 4. What is the units digit of b(n)? 9 Let c = 333 - 193. What is the tens digit of c? 4 Suppose 4*v - 86 = 2*r, -5*v + 5*r = -62 - 33. Suppose 0 = 16*m + v - 712. What is the units digit of m? 3 Let u be -190 + (1 - 2) - (-9 - -10). Let n = -98 - u. What is the units digit of n? 4 Let v(y) = y**2 - 5. Let r be v(-6). Suppose -102 = 28*d - r*d. What is the tens digit of d? 3 Let d = -22 - -18. Let a be d/(-10)*1*-5. Let y = 10 + a. What is the units digit of y? 8 Let k(w) = w + 20. Let c be k(-4). Suppose -3*g + c*g = 65. What is the units digit of g? 5 Let n(q) = -q**3 + 5*q**2 + 6*q + 5. Let s be n(6). Suppose 3*d - 36 = -o, d + d = -s*o + 37. Suppose -10*v + d*v - 12 = 0. What is the units digit of v? 2 Let f = -80 + 523. What is the tens digit of f? 4 Let k(a) = 5*a**2 + 40*a + 10. Let t be k(-8). What is the units digit of ((-15)/t)/(4/(-536))? 1 Let b = 785 - 101. What is the units digit of b? 4 Let g = -42 + 785. Suppose 3*w - g = -2*r, 0 = -4*w + 6*r - r + 1006. What is the units digit of w? 9 Suppose 0 = 3*k - d - 7739, 8*k - 10*k = 3*d - 5174. What is the thousands digit of k? 2 Let v(r) = 8*r - 9. Suppose 0 = 2*x - 180 + 140. What is the units digit of v(x)? 1 What is the tens digit of (2/8 - 483/(-36))*6? 8 Let u be (-1 - -2)/(1/(-948)*-2). What is the hundreds digit of ((-3)/(-6))/(1/u)? 2 Let v(h) = 3*h + 28. Let m be v(-7). Let s = -16 + 5. Let n = m - s. What is the units digit of n? 8 Suppose 0 = -i - 3, -3*j - 3*i = -0*i - 174. What is the units digit of j + 3/2*(6 - 8)? 8 Let m(f) = -f**3 - 17*f**2 + 22*f - 21. Let q be m(-18). Let s = 236 + q. Suppose 176 = 4*t + 4*c, -27 = -4*t - 2*c + s. What is the tens digit of t? 4 Let w be (-180)/(-99) - 2/(-11). Suppose w*p - 1 = 1. What is the units digit of (0/(-1) + p)*30? 0 Suppose -31 = -6*d + 53. Let b(f) be the second derivative of -f**5/20 + 13*f**4/12 + 5*f**3/2 + 4*f**2 - f. What is the units digit of b(d)? 2 Suppose 3468 = b - m, -6*b = -4*b - 3*m - 6940. What is the tens digit of b? 6 Suppose t - 16 = -3*t. Suppose 4*q = t + 20. Let k(j) = j**2 - 3. What is the tens digit of k(q)? 3 Let r = -16 - -23. Suppose 3*c = r*c - 332. What is the tens digit of c? 8 Suppose 80*t = 89*t - 9153. What is the thousands digit of t? 1 Suppose 6 = 3*l - 3*h - 201, 139 = 2*l - h. What is the units digit of l/4 - (-2)/(-4)? 7 Suppose 46 + 44 = 2*q. Let d = q - 24. What is the tens digit of d? 2 Suppose -198 = -4*b + 2*u + 3*u, -b + 2*u = -48. Suppose 22*i = 19*i + 12. Suppose i*w - 64 = b. What is the tens digit of w? 2 Suppose 530 + 3230 = -5*k. Let y be 26/39 + k/(-6). Suppose -y = -9*a + 6*a. What is the units digit of a? 2 Let i be -5*12*(0 + 8/10). Let u = i + 84. What is the tens digit of u? 3 Suppose 3*v + 2473 = -2*v + 4*d, -5*d + 10 = 0. Let a = -237 - v. What is the units digit of a? 6 Let c = 2155 - 983. What is the hundreds digit of c? 1 Suppose t + 353 = 4054. What is the tens digit of t? 0 Suppose 2*i - 2*x = -5*x + 3507, 5*i - 8770 = -5*x. What is the hundreds digit of i? 7 Let v(y) = -y**3 + 16*y**2 - 14*y - 7. Let t be (-4)/(-2)*15/2. Let q be v(t). Suppose -5*c = -3*b + q, b + 2*b = 4*c + 7. What is the units digit of b? 1 Suppose -3 = -j - 0, -3*d + 4*j + 21 = 0. Let z(u) = u + 26. What is the tens digit of z(d)? 3 Suppose 4*u = -3*z + 10926, 2*z - 5 = -1. What is the thousands digit of u? 2 Let g(c) = 2*c**3 - c**3 + 9*c**2 + 7*c + 3 + 0*c**3. Let l(w) = 7*w + 51. Let d be l(-8). What is the tens digit of g(d)? 6 What is the hundreds digit of (5 + 0)/(-10)*(3 - 617)? 3 Let m = 160 + 1931. What is the units digit of m? 1 What is the tens digit of 437 + -8 + 14 + 0? 4 Let j(y) = -y**3 - y**2 - 13*y - 90. What is the tens digit of j

Thomas Zwijsen Thomas Zwijsen is a Dutch/Belgian (Flemish) classical acoustic and Heavy Metal guitarist. He is known for his arrangements of Iron Maiden (and a selection of other artists') songs for classical guitar both on YouTube since 2007 and with his 2013 and 2014 albums "Nylon Maiden", "Nylonized" and "Nylon Maiden II". Since 2011, he has worked closely with ex Iron Maiden & Wolfsbane frontman Blaze Bayley, co-composing Bayley's 2012 album The King of Metal and 2013 released Russian Holiday E.P. In 2015 he released an album in Flamenco/fusion style consisting entirely of his own compositions, entitled "Divide & Unite". He has toured extensively both with Blaze, as a solo performer and since 2013 with the Master Guitar Tour, bringing him across Europe, South America and to Dubai. Thomas is particularly popular on YouTube, having reached more than 17 million views and 70.000+ subscribers as of 2017. This is a significant amount of traffic, considering his genre. Biography Thomas Zwijsen started taking music lessons at age 9. During his teens he studied Classical Guitar at several conservatories in Belgium and the Netherlands. He also played in a local band called Sarcadia. From 2007, Zwijsen began creating YouTube videos. His main focus was making arrangements of Iron Maiden songs for classical guitar. He also made arrangements of Dream Theater and Deep Purple songs, to name a few. These videos gained in popularity, leading to over 6 million hits and 27,000 subscribers as of March 2015. Due to his online popularity, Thomas was inspired to create a solo album with 11 of his Iron Maiden arrangements, called Nylon Maiden. He collaborated closely with drummer Nathanael Taekema and Edgetip Studio in Arnhem, Netherlands. Later, he attracted interest from former Iron Maiden and Wolfsbane frontman Blaze Bayley, who performed guest vocals on "The Clansman". This co-operation led to Thomas joining Blaze during his composition and production process for the 2012 album The King of Metal, and its subsequent tour. Additional musicians on the Nylon Maiden album were Anne Bakker (violin), Nathanael Taekema (drums) and Tony Newton (Voodoo Six, bass). The King of Metal tour with Blaze Bayley took him across Europe and further cemented an ongoing musical relationship with the singer. This led to a subsequent European acoustic tour featuring only Blaze and Thomas, later developing into a world tour for 2013 in which Zwijsen would open with a Nylon Maiden set list, followed by a full acoustic Blaze show afterwards. Anne Bakker (violinist) was also present for the Brazilian leg of the tour. Supporting his 2012/2013 album release, Zwijsen also toured with Maiden uniteD, the all-acoustic Maiden tribute project featuring singer Damian Wilson (Threshold) and guitarist Ruud Jolie (Within Temptation), on most of their European dates in November and December 2012. During 2013, Thomas Zwijsen continued his world tour with Blaze, taking him to South America, Europe and Dubai. In spring 2013, his Nylon Maiden album was released in Japan including 3 bonus tracks under the Japanese record label King Records. Spring 2013 also saw the release of a collaborative E.P. by Blaze Bayley & Thomas Zwijsen, called Russian Holiday. In early 2014, Zwijsen released Nylonized, a 12 track album featuring an eclectic mix of song arrangements (ranging from The Who to Adele), original compositions and guest artists. Among the twelve guest musicians on the album are: Kee Marcello (Europe - guitar), Derek Sherinian (Dream Theater, Black Country Communion - piano), David Readman (Pink Cream 69 - vocals), Damian Wilson (Threshold, Headspace – vocals), and Blaze Bayley (Iron Maiden – vocals). 3 original compositions are featured on the album, co-written with drummer Nathanael Taekema, including a 9minute flamenco-metal opera called "Perfect Storm". In 2014, Thomas Zwijsen released Nylon Maiden II, the sequel to his first album. Featuring a new selection of popular Iron Maiden songs (and "Doctor Doctor" by UFO) arranged for classical guitar, he also showcased a couple of original compositions: "Nylon Madness" and "The Dream Is True". Zwijsen released his first album entirely of original work on October 3, 2015. Divide & Unite contains 11 original compositions in a flamenco fusion style, supported on Drums and co-composed by Nathanael Taekema for six of the tracks. Other musicians appearing on the album are Anne Bakker (Violin, Viola), Rosie Taekema (Cello), Raoul Soentken (Percussion, mixing and mastering) and a guest appearance by American flamenco guitarist (and Master Guitar tour co-artist) Ben Woods. The songs display Thomas' classical background, as well as subtle influences of (progressive) rock and metal. An Extended Production by the name of "Treasure Island" was released simultaneously containing 4 tracks plus hidden bonus of various rock arrangements for classical guitar and trio. Guitar Technique Thomas studied classical and flamenco guitar at music conservatoire. This has influenced his playing style, which is a unique mix of classical elements and his Heavy/Progressive Metal roots. Thomas' technique reflects an interesting and often technical fusion between these influences. Endorsements Thomas Zwijsen is currently (2013) endorsed by: Ortega Guitars, The Guitar Villa and Griffin Allstar. Discography Studio albums References External links http://www.thomaszwijsen.com Category:1988 births Category:Living people Category:Dutch guitarists Category:Male guitarists Category:Belgian guitarists Category:People from Antwerp Category:Belgian classical musicians Category:Belgian jazz Category:Belgian classical guitarists Category:21st-century guitarists Category:21st-century male musicians

is 7/2 of a litre in millilitres? 3500 What is 13/8 of a milligram in micrograms? 1625 Convert 17.56586 micrometers to centimeters. 0.001756586 What is 0.997032 years in months? 11.964384 How many litres are there in 39.05038ml? 0.03905038 Convert 191.4088 millilitres to litres. 0.1914088 What is 716311.35 minutes in days? 497.4384375 How many nanograms are there in 10.69712 kilograms? 10697120000000 What is thirty-two fifths of a kilometer in meters? 6400 What is 6/5 of a kilogram in grams? 1200 How many millilitres are there in 7.994393 litres? 7994.393 What is sixty-four fifths of a decade in years? 128 How many microseconds are there in 333060.1ms? 333060100 What is 9247.608 months in millennia? 0.770634 What is 1071.702 months in centuries? 0.893085 How many decades are there in 26.9416 millennia? 2694.16 How many nanograms are there in 2/125 of a microgram? 16 Convert 36173.6 weeks to microseconds. 21877793280000000 How many microseconds are there in 21/4 of a millisecond? 5250 What is 75.20114 seconds in nanoseconds? 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Rafik Schami’s Swallow Editions Aims to Help Arab Authors Take Flight Syria’s Rafik Shami is one of the world’s leading Arab writers. He’s now launched a new press to bring new Arabic voices to the attention of English-language readers. By Olivia Snaije Rafik Schami: "The new generation of Arab writers have been freed by the Internet." Syrian writer Rafik Schami has been in political exile in Germany for 40 years. Best known in the English-language world for two recently translated novels, The Dark Side of Love, dubbed “the Great Arab novel” by The Independent, and The Calligrapher’s Secret, Schami has written his numerous novels and plays in German. He began writing in German, he said, because “for a long time I thought I could write for an Arab publisher, but most were affiliated with a political regime and they knew I was in exile so I wouldn’t get published.” Ultimately, writing in German became something positive for Schami: “It freed me from self-censorship — the type of thing where you don’t write about family or the government. In German there were no red lines for me and it’s been very productive.” Now Schami has founded Swallow Editions, with the aim of finding and helping young writers from the Arab world to get published in English. Swallow is structured as a not-for-profit organization and is run by London-based Arabia Books and Haus Publishing. Schami and Barbara Schwepke, Haus and Arabia’s founder, provided the start-up capital and they are hoping for UK Arts Council Funding. Profits from book sales and rights will go to Swallow, which is ring-fenced by Arabia and Haus (watch our video interview Barbara Schwepke). Schami has been thinking about such a project for 20 years, and now with the advent of the Arab Spring and the collaboration of Haus’ publisher, Barbara Schwepcke, who brings out Schami’s books in English, everything fell into place. Swallow Editions first novel, Sarmada, by Syrian journalist Fadi Azzam, was published last Friday. The novel follows the life of three women in a Druze village through the political changes of the 20th century. Schami has not yet met Azzam, whose writings he found on the Internet. Schami said he read over 50 manuscripts before he chose Azzam’s and that his intention is to be a reader who ferrets out manuscripts for his publishing house with a Western eye. “My secret plan is not to talk to any of the writers, I only want to read them,” he said. “I don’t want to be introduced to them either. If you speak to an author and they start to say, ‘I was in prison’, or ‘I have four children to feed,’ then you feel bad if you reject their work. I can’t be like Amnesty International, I’m interested in literature.” Swallow Editions will publish two to three books a year in order to be able to devote a maximum amount of attention to each manuscript. Schami works on the Arabic version, which is then translated into English. Barbara Schwepke explained the process: “In the case of Fadi Azzam’s Sarmada, the translator Adam Talib worked very closely with the author, as some of the book was full of Syrian colloquialisms — so in a way, Adam became the second editor. We then engaged a bilingual editor who worked on the translation, making sure that it was as close as possible to the Arabic original and as free as necessary to make it a good English text — the usual challenge for a translation.” Schami said collaborating with Azzam was symbolic of a whole new generation of Arab writers: “It was like a revelation, it was such a pleasure to work with him, he is highly intelligent . . . this new generation is able to resist; the internet liberated it. The [Arab] governments underestimated how clued in this generation is, it smells freedom through the Internet. They were afraid at first but when they learned that they could be quicker than the secret service they lost their fear, and when people lose their fear then it is dangerous for a government.” Should the Syrian regime fall, Schami will make his first trip back to Damascus since 1971. (He wasn’t allowed to return for his mother’s funeral.) “I will go back,” he said, “but as a visitor.” About the Author Olivia Snaije Olivia Snaije is a journalist and editor based in Paris who writes about the Middle East, multiculturalism, translation, literature, and graphic novels. She is a contributor to newspapers and magazines including The Guardian, Harper’s Bazaar Art, The Global Post, The New York Times and CNN.