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2019年10月14日 14:07:29来源:康泰面诊

  • Science and Technology Creutzfeldt-Jakob disease Breaking down the barrier科技 克雅氏病 攻破屏障A glimmer of hope for a drug that treats disease caused by prions药物治疗朊病毒感染疾病的一线希望THE epidemic of mad-cow disease in people that some forecast in the 1990s has not, fortunately, come to pass.时至今日,疯牛病没有像上世纪90年代的某些预言说的那样在人群中流行,真是幸运。But Creutzfeldt-Jakob disease (CJD), to give its proper name, is still a nasty illness that humanity would be better off without.这种严重损害人类性情的疾病的准确名称叫克雅氏病(CJD),治疗起来仍然棘手。It is also a strange illness.克雅氏病是一种奇怪的疾病。CJD and a handful of similar neurological conditions are caused by the misfolding of a particular protein that is found in the membranes of certain nerve cells.该病以及类似的一些神经症状是由于某种神经细胞的细胞膜上的一个特殊蛋白发生错误折叠所致。The strangeness is that the misfolded protein, known as a prion, somehow catalyses other molecules of the protein to misfold in the same way. The result is a chain reaction in which more and more protein ends up as prions.这种错误折叠的蛋白称为朊病毒,令人奇怪的是它可以催化其他蛋白分子发生相同的错误折叠,这个链式反应使越来越多的蛋白质变成朊病毒。Nerve cells containing the prions stop working. The sufferer endures memory loss, personality changes and spontaneous, jerky bodily movements.含有朊病毒的神经细胞失去正常功能,罹患者出现记忆减退、人格改变和自发的躯体急速抽动等症状,最后患者死亡。Eventually, the disease kills him.所以,能够治疗CJD的药物将大受青睐。A drug to treat CJD would therefore be welcome. And chemicals that seem either to prevent the misfolding, or to help the body clear away misfolded molecules, do, indeed, exist. The problem is turning at least one of those chemicals into an effective medicine.能阻止分子错误折叠或帮助机体清除错误折叠分子的化学药品似乎确实存在,困难在于如何用至少一种这样的化学药品进行有效治疗。Adam Renslo of the University of California, San Francisco, and his colleagues (who include Stanley Prusiner, the Nobel laureate who discovered prions) have been trying to do so.旧金山加利福尼亚大学的Adam Renslo与其同事(包括因发现朊病毒获得诺贝尔奖的Stanley Prusiner)一直在进行将化学药品用于治疗CJD的尝试,The chemicals they have lighted on are called aminothiazoles. These are quite effective in reducing the prion levels of cultured nerve cells.他们感兴趣的化学药品叫做氨噻唑,它能有效降低体外培养的神经细胞内的朊病毒水平。Testing aminothiazoles in Petri dishes is, however, rather different from testing them on living animals.但是,检验发现氨噻唑在活动物体内的作用与在体外培养细胞中的作用大不相同。A natural barrier exists between the bloodstream and the brain, to protect it from harmful chemicals. This barrier interprets many putative drugs, including aminothiazoles, as harmful, and thus keeps them out.生理状态下,血流与脑之间存在着一个屏障,使脑避免接触有害物质,可能有效的许多药物包括氨噻唑也被这个屏障当作有害物质阻挡在脑外。And if a molecule cannot cross the barrier, it will not make an effective neurological treatment.不能通过屏障进入脑的分子当然就无法完成有效的神经治疗。Dr Renslo and his colleagues have therefore been analysing and modifying the chemical structure of aminothiazoles to see if this can enable them to cross the blood-brain barrier.为此,Renslo士与其同事已经在分析并尝试修饰氨噻唑的分子结构,以使之能通过血脑屏障。As they report in the Journal of Medicinal Chemistry, they think they have now pulled off the trick.根据他们在药物化学杂志的报道,他们已经找到了突破口。They did it by removing groups of atoms called hydrogen-bond donors from the original molecules and adding a ring of carbon and hydrogen atoms.他们移除氨噻唑分子上一组提供氢键的原子,并加上一个碳氢环。That made the aminothiazoles look more like cholesterol—which despite its malign everyday reputation is an important component of brains and routinely crosses the blood-brain barrier.修饰后的氨噻唑分子看起来更像胆固醇分子。尽管胆固醇整天被认为是个对人体有害的物质,但它却是脑的重要成分,是通过血脑屏障的常客。It worked. When Dr Renslo fed mice a diet containing the improved aminothiazoles, he found that the most promising of them accumulated in the brain in concentrations nearly 25 times higher than those required to clear prions from cultured cells.成功了!Renslo士给小鼠喂食含有改进后的氨噻唑的饮食后,发现这些最有希望的分子在小鼠的脑内聚集,其浓度达到清除体外培养细胞内朊病毒所需浓度的25倍。The molecular changes did not, though, seem to change the aminothiazoles prion-killing attributes.氨噻唑分子的改变似乎并没有改变其杀灭朊病毒的特性。When tested in Petri dishes, the new molecules were as good as their precursors.在培养皿实验中,修饰后的分子与其前体一样有效。More importantly, preliminary results suggest they are effective at extending the lives of prion-infected mice. Such mice lived for 100 days longer when treated with the new molecules than they did when untreated.更重要的是,初步的实验结果提示这些分子能有效延长朊病毒感染小鼠的寿命,用这些新分子治疗的小鼠比不治疗的小鼠多存活100天。That is a significant fraction of the two to three years a healthy laboratory mouse might be expected to survive if it is not experimented on.考虑到实验室中未受试的健康小鼠的预期寿命是2到3年,染毒小鼠获得延长的这部分存活期显得很显著了。Trials in mice are, of course, just the beginning.当然,用小鼠进行的试验只是个开始。But breaching the blood-brain barrier in this way is a crucial step, and one that might be generalised to potential treatments for other brain diseases—Alzheimers, for example.但药物以这种方式突破血脑屏障确实是个关键步骤,在此基础上,人们还可能找到治疗阿尔茨海默尔病这样的其他脑部疾病的良方。If that came to pass, this small step on the journey of drug discovery might come to be seen, in retrospect, as a giant leap.在达到那些目标之后,回过头来看,实现药物通过屏障的这一小步将被视为一个巨大的跨步 /201301/218113。
  • The site was once a spring-fed pond, full of water.这片区域过去是泉水供养的池塘,有充足的水源。Mammoths were tempted in to drink.猛犸象就曾经尝试过到此饮水。But when they tried to climb back out, the banks were steep and slippery.但当它往回爬的时候,河堤又陡又滑。Just like the short-faced bear imprisoned underground, some became trapped.像被困在地下的短面熊一样,有些猛犸象也被困住了。Scavengers would have been attracted by the mammoths plight.这会吸引食腐动物(来吃)。The bones of wolf, coyote, and the short-faced bear have also been recovered from the dried-up sediment.河水干涸的时候狼,郊狼和短面熊的尸体会露出来。The search for food was probably their death pool,too.池塘成了他们到河边觅食的死亡地。These prairie ponds are like time capsules. And they store another kind of data, showing how the plains have changed across millennia.这些大草原池塘就像时间胶囊一样。它们也留存了另一样数据,即记录了大草原几千年来是怎样变化的。Each spring, pollen from nearby plants is blown into the water.每年春天,附近的花粉被风吹入池塘。It sinks and settles layer upon layer on the bottom, building into a data bank of local plant life that we can still today.它们在池塘底部落了一层又一层,形成了本地植物的数据库,使我们今天仍能品读研究。And grass pollens aren’t the only clue still sandwiched in the sediment.然而,这些沉积物中的植物花粉并不是寻找古植物痕迹的唯一线索。There are a wide variety of tree pollens, too, from aspens, spruce and other trees, both coniferous and deciduous.沉积物种还有很多其他植物的种子,比如白杨,云杉和其他针叶科和落叶科树木。201304/232545。
  • The debate over gun control in America has been ongoing and intense for many years — with proponents seeking to reduce gun—related injuries and curtail criminal activity, and opponents sighting second—amendment rights and the need to defend themselves. Despite the complexities of differing opinions, sometimes theres been enough agreement for legislation to pass Congress.在美国械管制一直是多年来备受争议的话题。持者力图减少造成的受伤事件以及残忍的犯罪活动,而反对者则照准第二修正法案的权力,以及防身的需要。尽管意见不同,情况复杂,但有时还是有足够的协议让国会通过立法。The first major gun control act was passed by Congress in 1934, regulating the sale of fully—automatic fire arms, like machine guns, after an assassination attempt on President-elect Franklin Roosevelt and a series of organized crime killings. In 1938, a further restriction required licenses for gun dealers, and prohibited gun sales to people who had committed a violent felony.1934年,在企图暗杀总统当选人富兰克林·罗斯福以及一系列有组织杀人事件之后,国会通过了第一项重大的械管控法案,这条法案规范了全自动武器,比如说机关的销售。1938年进行了更进一步的限制,即要求经销商持照经营,并禁止向有过犯罪记录的人的售卖。The 1963 assassination of President John Kennedy — which was committed with a mail—order rifle — and the subsequent assassinations of Martin Luther King and Senator Robert Kenndey in 1968, led Congress to pass additional legislation. The Gun Control Act of 1968 added many restrictions on who could import, buy, and sell guns, and established harsher penalties for those using a gun in the commission of a federal crime. The debate on gun control remains an intense one across the country today — making this a particularly difficult issue to tackle.1963年约翰·肯尼迪总统刺杀事件——事后实凶器是邮购步——1968年马丁·路德金和参议员罗伯特·肯尼迪被刺,促使国会通过新的立法。1968年的械管制法令对进口,购买,售卖又进行了多项限制,并且对使用进行联邦犯罪的人处以更严厉的惩罚。如今,管控仍然是全美人民备受争议的话题,这使问题变得尤为棘手。原文译文属!201210/204654。
  • Books and Arts; America and the politics of recovery;文艺;美国与复苏政治学;The big promise;What did Barack Obamas stimulus package really achieve?高飞的承诺;巴拉克·奥巴马的刺激计划究竟有何成就?The New New Deal: The Hidden Story of Change in the Obama Era. By Michael Grunwald.《新“新政”:奥巴马时代隐藏的变革史》,迈克尔·格伦沃尔德著。The word “boondoggle”, Michael Grunwald points out, was coined back in the days of the original New Deal, to describe “make-work” bits of arts and craft paid for by the government at a price that was out of all proportion to their actual value.迈克尔·格伦沃尔德指出:政府常常以与实际价值完全不成比例的价格来为一些无用的奢侈品买单,其中就包括“为扩大就业而安排的工作岗位”——早在罗斯福新政时代,人们就创造了“无效投资”一词来描述这一概念。This is not necessarily a bad thing. In times of economic woe, when normal patterns of consumption and investment are frozen, prodigal government spending can sometimes be the only way to break the vicious circle of declining demand and shrinking employment. Value for money, paradoxically, can sometimes be an unaffordable luxury. To sum up John Maynard Keynes, it can even make sense to bury money in bottles, so that miners, and the suppliers of their pickaxes and overalls, and those who sell food and materials to those suppliers can, in turn, benefit from the circulation of money that they dig up. Mr Grunwalds newbook is the story of what was arguably the greatest boondoggle in history and the politics that surrounded it, both before and since.这并不一定是什么坏事。在经济困难时期,常规的消费和投资模式会陷入僵局,慷慨的政府开有时候可能是打破需求下滑、失业率上升这个恶性循环的唯一途径。很矛盾的是,现金价值有时候奢侈得难以承受。将凯恩斯的观点简单概括一下:甚至连把钱放在瓶子里埋起来都是有意义的——这样矿工就能把这笔钱挖出来,从而用于流通;于是矿工本人、矿工的鹤嘴镐和工装裤的供应商、以及向这些供应商销售食物和材料的人都可以依次从这种流通中获益。格伦沃尔德这本新书介绍的可能是史上最大的一笔无效投资,以及这笔投资前后的政治背景。Barack Obamas 7 billion stimulus package, enacted within a month of his taking office in January , amounted to about 4% of Americas GDP. In the Depression of the 1930s, the biggest stimulus in any year of Franklin Roosevelts New Deal amounted to only about 1.5% of GDP. The American Recovery and Reinvestment Act, as Mr Obamas bill was formally named, was a tale that grew in the telling. In the months running up to the election in November 2008, the economy entered virtual free-fall. The severity of the downturn surprised the participants, but long before he was elected, Mr Obama knew that he faced a crisis of 1930s proportions.巴拉克·奥巴马于年1月上任后的一个月内通过了7870亿美元的刺激计划,这笔资金约占美国 GDP 的4%。而20世纪30年代的大萧条时期,在富兰克林·罗斯福的“新政”年间,最大的一笔刺激方案也只占当时 GDP 的约1.5%。奥巴马法案的正式名称为《美国复苏与再投资法案》,它的规模越来越大了。在2008年11月大选前的几个月,美国经济几乎直线下滑。衰退的严重性让各位候选人感到吃惊。但奥巴马在当选以前很早就意识到了他将面临像20世纪30年代那样严重的危机。Mr Grunwalds book does a meticulous job, casting much new light on the advance thinking of Mr Obamas team, both before the election and, especially, during the long transition. In the last quarter of 2008, the final three months of the Bush era, the American economy contracted by an astonishing 8.9%. By early job losses hit 800,000 a month. The size of the policy response grew too. An early plan, calculated at 0 billion, grew, long before inauguration day, to around 0 billion. And that, as Mr Grunwald makes clear, was very much at the low end of what Mr Obamas economists thought was required.格伦沃尔德的这本书做了细致入微的研究,让人们对当年选举前、特别是在漫长的过渡时期中的奥巴马团队先进思想有了更多的了解。在2008年最后一个季度,布什时代最后的三个月里,美国经济萎缩了8.9%,令人惊讶。截至年早期,失业人数达到每月80万人。政府也加大了应对政策的力度。早在奥巴马就职日之前,预估价值为3000亿美元的早期计划就提高到了约8000亿美元。格伦沃尔德表明,甚至连这个数目都大大低于奥巴马经济学家的预期。One thing that may surprise ers not fully acquainted with the grisly nature of political sausage-making is the degree of cynicism that surrounded the passing of the Recovery Act. It was naive of Mr Obama to expect the Republicans to play ball. But because he needed to win at least a couple of their votes in the Senate to break the threat of a filibuster, he tried hard to court them. Mr Grunwald lays out in shocking detail how the Republican leadership decided early and wholeheartedly not to co-operate with the new president. So deep was their opposition that they even opposed things that they supposedly supported, such as the Recovery Acts deep tax cuts and its emphasis on infrastructure.有些读者对于政治“裹香肠”那可憎的特性并不完全了解。他们可能会感到惊奇——针对《复苏法案》的通过,政界存在严重的犬儒主义。如果奥巴马期待能与共和党合作,他就太天真了。但他需要在参议院赢得至少部分共和党的选票,以避免自己的议案遭到阻挠。因此,他极力取悦共和党人。格伦沃尔德清楚地提及了共和党领导层是如何早早决定完全不与新总统合作的,细节所到令人震惊。共和党的反对情绪极为强烈,以至于本应持的观点,他们都加以反对——如《复苏法案》所主张的深度减税、强调基础设施等等。As cynical as this may have been, it made political sense. If the stimulus succeeded, Mr Obama would get all the credit. If it failed, the Republicans could portray themselves as having been on the side of fiscal prudence. Since then, the economy has stubbornly refused to grow at anything beyond an an . Many Republican economists, such as the respected Mark Zandi, who advised John McCain in his contest with Mr Obama, agree that without it, things would have been even worse. But the problem is that it did not work well enough. As a result, the Republicans triumphed at the mid-term vote and Mr Obamas ratings are now uncomfortably low as he struggles for re-election.尽管共和党的这种态度可能有些愤世嫉俗了,但它在政治上是说得通的。如果刺激成功了,奥巴马将得到各方的赞扬;如果刺激失败了,共和党人会表示他们可是一直都持稳健的财政方针的。自从那时起,美国经济一直衰弱无力,顽固地拒绝增长。许多共和党经济学家(比如受人尊敬的马克·赞迪,他是约翰·麦凯恩同奥巴马争夺总统宝座时的谋士)同意,如果没有奥巴马的刺激计划,情况将变得更糟。但问题在于该计划的成效并不是十分显著。于是,共和党在中期选举投票中获胜了;而奥巴马力争连任,得票率却低的可怜。Mr Grunwalds heart plainly beats on the left, and it is clear that he admires Mr Obama, with his “hyper-rational side”. At the same time, the author does make some effort to explain the Republican point of view. The whole point of an economic stimulus is that it is supposed to stimulate. It needs to move money out of the door fast, get it quickly to where it can do most good and not carry with it a tail of long-term spending commitments. But Mr Obamas agenda was always much bigger than that, and it is in explaining this that Mr Grunwalds book is at its best.可以看出,格伦沃尔德倾向于左派;他有“过于理性的一面”,显然比较赞赏奥巴马。然而,他的确也做了一些努力来阐述共和党的观点。经济刺激的全部意义就在于它应当去进行刺激。它需要让资金涌出闸门,迅速把这笔钱送到能带来最多效益的地方,而不是拖着长期开投入的尾巴。但奥巴马的胃口总是远不止如此,而格伦沃尔德这本书最擅长的就是解释这一点。Much of the meat involves parsing the issues that riled the Republicans: how the stimulus bill was to be used as a tool to transform American society. Right from the start, Mr Obama wanted his Recovery Act to spend money on a low-carbon future, on radical school reform, on health reform and on creating jobs. All of these, Mr Grunwald thinks, are laudable aims. Many ers would agree. But Republicans in Washington have other views. New energy projects, like job creation, should be left to the market, not picked by bureaucrats; school and health reform should be a matter for individual states. What they saw was an attempt to use the crisis to push the political economy of America in a more statist and Washington-centric direction. Mr Grunwald does not attempt to deny that; it is simply that he has no problem with it.本书的主要部分大多都在剖析共和党感到恼怒的几个问题:如何将刺激法案用作转化美国社会的工具。从一开始,奥巴马就要求《复苏法案》在以下几个方面进行投资:向低碳社会的转变、彻底的学校改革、卫生改革以及创造就业岗位。格伦沃尔德认为所有这些目标都是值得赞赏的。许多读者也会认同这一点。但华盛顿的共和党并不这么想。他们认为新能源项目和创造就业岗位应当交给市场去引导,而不是由当局来推动;学校改革和卫生改革应当根据各个州的具体情况进行。他们认为奥巴马在试图利用危机把美国的政治经济推向一个以华盛顿为中心、中央集权度更高的方向。格伦沃尔德并未试图否认这一点;他对此完全没有异议。The most interesting part of the book is the part that leaves most questions open. What will be the legacy of all Mr Obamas greening and rebuilding? Mr Grunwald waxes on about the cleverness of Steven Chu, the presidents energy secretary,and all the amazing things that his scientists think they can do with their oodles of new cash. But there have also, as he admits, been many failures. Mr Grunwalds instinct is to praise the splashing around of government money for untested new technologies which, when exposed to life without the government teat, may quickly wither. Governments make bad venture capitalists, as the book es Larry Summers, a key member of the presidents original team, as saying.本书最有趣的部分在于它将大多数问题留给了读者思考。奥巴马的众多环保和重建措施将给美国留下什么样的遗产?格伦沃尔德描述了奥巴马的能源部长——朱棣文的机智,也描述了这位总统手下的科学家——他们认为利用大笔新有资金可以做一些惊人的事情。但格伦沃尔德承认,奥巴马政府也存在不少失败之处。有些政府资金经过种种周转,用于未经检验的新技术,格伦沃尔德本能地对此加以赞扬。但当这些新技术离开政府的怀抱以后,可能很快就夭折了。本书引述了奥巴马早期团队重要成员劳伦斯·萨默斯的言论:政府并不是好的风险投资家。The truth is that no one really knows yet how well spent the longer-term parts of the immense Recovery and Reinvestment Act will turn out to have been. But no writer has yet gone this far, at least in unravelling where the money has gone. “The New New Deal” is the most interesting book that has been published about the Obama administration. Even Republicans should it.事实上,《复苏与再投资法案》篇幅很长,其中的长期部分最终能否妥善付诸实施,还没有人真正清楚。但还没有任何作家进行过如此深入的探究,至少还没有人阐明这笔资金的去向。在关于奥巴马政府的出版物中,《新“新政”》是最有趣的一本书。即使是共和党人都应该拿来读一读。 /201210/202799。
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