2018年01月17日 21:19:39|来源:国际在线|编辑:飞度永州新闻
Pfizer plans to test a combination of three novel cancer drugs in humans next year, as the US drugmaker seeks to make up lost ground in the race to develop a new generation of “immunotherapy” medicines that turn the body into a weapon against tumours.辉瑞(Pfizer)计划明年在人体上测试综合使用三种新型抗癌药的疗效。这家美国药企正寻求在研发新一代“免疫疗法”药物的竞赛中收复失地,这类药物能把人体变成对抗肿瘤的武器。The “triplet” trial will be one of the first to test three immunotherapies at the same time, and will involve giving a small group of patients a cocktail of drugs to determine whether the combination is safe, and whether it can shrink tumours in those suffering from solid cancers.这一“三药合一”试验,将成为首批同时考察三种免疫疗法药物效果的试验之一,几名患者将下三种药物的混合物,以判定这一混合物是否安全、以及是否能让那些患有实体癌的人体内的肿瘤变小。Pfizer has fallen behind rivals such as Bristol-Myers Squibb and US Merck, which have aly launched the first wave of immunotherapies, known as checkpoint inhibitors. These drugs remove brakes in the body’s immune system that stop it from attacking tumours, and have shown they can extend the lives of patients with very poor prognoses.辉瑞已落在百时美施贵宝(BMS)和美国默克(Merck)等竞争对手后面,后两者已推出第一波免疫疗法药物——检查点抑制剂(checkpoint inhibitor)。这些药物会移除人体免疫系统中的“制动器”(“制动器”会阻止免疫系统攻击肿瘤),并已明能够延长预后很差的患者的生命。However, the existing therapies only work in about a third of patients, prompting rival drugmakers to find ways of augmenting their effect然而,现有疗法仅对约三分之一患者有效,这促使其他药企想方设法增强这些疗法的效果。Pfizer believes it can gain an edge by developing combination treatments, including a therapy that adds Avelumab, a checkpoint inhibitor it is developing with Merck of Germany, to two further drugs — Utomilumab and another code-named OX40.辉瑞认为,自己可以通过研发综合疗法——包括一种将其与德国默克(Merck)联合研发的检查点抑制剂Avelumab同另两种药物Utomilumab和OX40混合到一起的疗法——来获得优势。While Avelumab is designed to remove the brakes in the immune system, Pfizer thinks the other two drugs will speed up the body’s response, likening their effects to the “gas” or “oil” needed to run a well-functioning engine.Avelumab旨在移除免疫系统中的“制动器”,辉瑞认为,另两种药物将加快人体的反应,它把它们的效果比作让一个功能良好的引擎运转所需的“气”或“油”。The arrival of immunotherapies has been heralded as the most important development in cancer treatment in generations. Whereas new cancer drugs used to be deemed successful if they could stall tumour growth for a number of weeks, these newer medicines can keep patients alive for many months and, in some cases, years.一些人宣称,免疫疗法的出现是几代人以来癌症治疗领域的最重要进展。过去,新的抗癌药物如果能让肿瘤生长停止几周,就会被认为是成功的,而这些更新的药物能让患者多活许多个月,在某些情况下可以多活好几年。 /201605/442971An eye is for seeing, a nose is for smelling. Many aspects of the human body have obvious purposes.眼睛是用来看东西的,鼻子是用来闻气味的。人体的很多方面都有明显的用途。But some defy easy explanation. For biologists, few phenomena are as mysterious as the female orgasm.但有些地方令人费解。对生物学家来说,几乎没有什么现象能像女性性高潮那么神秘。While orgasms have an important role in a woman’s intimate relationships, the evolutionary roots of the experience — a combination of muscle contractions, hormone release, and intense pleasure — have been difficult to uncover.尽管性高潮在女性的亲密关系中发挥着重要作用,但这种经历——同时出现肌肉收缩、荷尔蒙分泌和强烈的快感——的进化根源却难觅踪迹。For decades, researchers have put forward theories, but none are widely accepted. Now two evolutionary biologists have joined the fray, offering a new way of thinking about the female orgasm based on a reconstruction of its ancient history.几十年来,研究人员提出了各种理论,但没有一种理论得到广泛的认可。现在,又有两名进化生物学家加入争论,提出了一种新的思考女性性高潮的方式,它的基础是再现其古老的历史。On Monday, in The Journal of Experimental Zoology, the authors conclude that the response originated in mammals more than 150 million years ago as a way to release eggs to be fertilized after sex.周一,两名作者在《实验动物学杂志》(The Journal of Experimental Zoology)上推断,女性性高潮这种反应起源于逾1.5亿年前的哺乳动物,当时是为了排出卵子,让其在性行为结束后受精。Until now, few scientists have investigated the biology of distantly related animals for clues to the mystery.此前,几乎没有科学家通过研究属于人类远亲的那些动物的生物学,来寻找解开这个谜团的线索。“For orgasms, we kept it reserved for humans and primates,” said Mihaela Pavlicev, an evolutionary biologist at University of Cincinnati College of Medicine and an author of the new paper. “We didn’t look to other species to dig deeper and look for the origin.”“对于性高潮,我们过去认为它仅限于人类和灵长目动物,”辛辛那提大学医学院(University of Cincinnati College of Medicine)进化生物学家、新发表的那篇论文的作者之一米哈埃拉#8226;帕夫利塞夫(Mihaela Pavlicev)说。“我们没有为了更深入地挖掘和寻找起源而研究其他物种。”The male orgasm has never caused much of a stir among evolutionary biologists. The pleasure is precisely linked to ejaculation, the most important step in passing on a male’s genes to the next generation. That pleasure encourages men to deliver more sperm, which is evolutionarily advantageous.男性的性高潮从未在进化生物学家中引起这么大的波澜。这种快感被精确地和射精联系在了一起。射精是将男性的基因传递给下一代的过程中最重要的一步。这种快感鼓励男性分泌更多,从进化的角度来说这是有好处的。For women, the evolutionary path is harder to figure out. The muscle contractions that occur during an orgasm are not essential for a woman to become pregnant. And while most men can experience an orgasm during sex, it’s less reliable for women.对女性来说,相关进化过程更难厘清。性高潮过程中发生的肌肉收缩,并不是女性怀必不可少的。并且尽管大部分男性都能在性交期间体验一次性高潮,性高潮对女性来说却没那么可靠。In a 2010 survey, 35.6 percent of women said that they hadn’t had an orgasm the most recent time they had sex. Part of the reason for this is anatomy: the clitoris is physically separated from the vagina.在2010年的一项调查中,35.6%的女性称在上一次性生活中未达到性高潮。造成这种现象的部分原因在于人体结构:阴蒂和阴道在位置上是分开的。Still, a number of scientists suspect that the female orgasm serves some biological function favored by natural selection. They just need to figure out what it is.但仍有大量科学家怀疑,女性性高潮具有某种生物学功能,该功能得到了自然选择的青睐。他们只需要找出是什么功能。“My gut instinct is that something that matters so much at an emotional level — the intense pleasure of orgasm — would seem to have reproductive consequences,” said David A. Puts, an evolutionary anthropologist at Pennsylvania State University.“我的直觉是,在情感层面上——高潮的强烈快感——这么重要的一件事,似乎应该产生繁衍的后果,”宾夕法尼亚州立大学(Pennsylvania State University)的进化人类学家戴维#8226;A#8226;普茨(David A. Puts)说。Many hypotheses have been put forward. Dr. Puts and his colleagues have carried out studies to test the possibility that orgasms increase the odds that a woman’s eggs are fertilized by a genetically attractive male.已有许多假说涌现出来。普茨士及其同事进行了研究,目的是检验一种可能性:高潮会增加基因出色的男性让女性卵子受精的几率。Elisabeth A. Lloyd, a philosopher at Indiana University, isn’t buying it. In 2005, she published a book called “The Case of the Female Orgasm,” in which she reviewed 18 published theories about its function.这并没有说印第安纳大学(Indiana University)的哲学教授伊丽莎白#8226;A#8226;劳埃德(Elisabeth A. Lloyd)。在2005年,她出版了一本书,名为《女性性高潮的问题》(The Case of the Female Orgasm),其中对已发表的有关性高潮功能的18种理论进行了综述。None had strong evidence in its favor, she concluded, and many were undermined by other findings about human sexuality. Years of further research have only strengthened her skepticism.她得出的结论是,没有一种理论提供了有力的据,其中不少还遭到了有关人类性行为的其他一些研究成果的削弱。多年的进一步研究让她的疑虑有增无减。Dr. Lloyd thinks the best explanation for the female orgasm is that it hasn’t served any evolutionary purpose at all. It’s nothing more than the byproduct of the development of the male orgasm. The orgasm is to women, she believes, as nipples are to men.劳埃德士认为,对女性性高潮的最佳解释是,它并没有任何进化上的意义,不过是男性性高潮的发展的副产品。她相信,性高潮之于女性就好比乳头之于男性。But now Dr. Pavlicev and her colleague, Gu#776;nter P. Wagner of Yale University, are making the case that the human female orgasm has a deep evolutionary history that reaches back to early mammals.不过,帕夫利塞夫士与耶鲁大学的京特#8226;P#8226;瓦格纳(Gu#776;nter P. Wagner)现在提出,人类女性的性高潮拥有可以追溯到原始哺乳动物的悠久进化史。They began by getting better acquainted with the sex lives of other animals, poring through obscure old journals to gather information on species ranging from aardvarks to koalas.他们首先更好地了解了其他动物的性行为,从不知名的旧期刊里梳理各物种的信息,范围覆盖了从非洲食蚁兽到考拉等各种动物。They noted that many female mammals release oxytocin and prolactin during sex — the hormones released by women during orgasms. What’s more, in many of those species, females use a radically different kind of reproduction.他们注意到,许多雌性哺乳动物会在性交过程中释放催产素和催乳素,也就是人类女性高潮过程中释放的荷尔蒙。此外,在这类物种里,有不少物种的雌性采用与人类截然不同的繁衍方式。While women release an egg each month, other female mammals, such as rabbits and camels, release an egg only after mating with a male.人类女性每个月排一次卵,其他一些雌性哺乳动物则是与男性交配后才会排卵,比如兔子和骆驼。Ovulatory cycles evolved in only a few lineages of mammals, including our own, Dr. Pavlicev and Dr. Wagner found. Before then, our ancient mammal ancestors originally relied on ovulation triggered by sex with a male.帕夫利塞夫士与瓦格纳士发现,只有少数哺乳动物种群进化出了排卵周期,包括我们人类。在那之前,我们古老的哺乳动物祖先起初是依赖与雄性交配来激发排卵的。Those early mammals developed a clitoris inside the vagina. Only in mammals that evolved ovulatory cycles did the clitoris move away. Based on these findings, Dr. Pavlicev and Dr. Wagner argue that the female orgasm first evolved as a reflex to help females become pregnant.这些原始哺乳动物身上出现了位于阴道内的阴蒂。只有进化出了排卵周期的哺乳动物,阴蒂才移去了别处。在这些发现的基础上,帕夫利塞夫与瓦格纳提出,人类女性性高潮起初进化出来,是作为帮助女性怀的一种条件反射。When early mammals mated, the clitoris could send signals to the brain, triggering hormones that released an egg. Once the egg became fertilized, the hormones may have helped ensure it became implanted in the uterus.原始哺乳动物交配时,阴蒂可以向大脑发送信号,释放出激发排卵的荷尔蒙。一旦卵子受精,这些荷尔蒙或许有助于保它在子宫里着床。This arrangement has worked well for mammals that rarely encounter males. It helps females make the most of each mating.这种安排对于很少遇见雄性的哺乳动物来说是不错的。它帮助雌性最大限度地利用每次交配的机会。But eventually some mammals, including primates like us, started spending their lives in social groups. Females had access to regular sex with males, and orgasm as an ovulatory mechanism was no longer so useful. Our female forebears instead evolved a new system: releasing eggs in a regular cycle.不过,后来有一部分哺乳动物,包括我们这样的灵长目,开始以社群的形式生活。雌性有了与雄性频繁性交的机会,高潮作为排卵机制的作用就不那么重要了。我们的雌性祖先于是进化出了一种新机制:按照周期规律地排卵。As the original purpose of the orgasm was lost, the clitoris moved away from its original position. Dr. Wagner speculated that this shift was part of evolution’s dismantling of a sensor system: “You don’t want to have the old signal sending noise at the wrong time,” he said.随着性高潮的初始意义丧失,阴蒂就离开了原来的位置。瓦格纳猜测,这种移位相当于进化在废除一个感官系统:“你不想要古老的信号系统在错误的时间发出噪音,”他说。“Basically, we don’t know why this happened,” he added. But across mammalian species, “it’s just a very strong evolutionary pattern.”“基本上,我们并不知道其中的原因,”他还说。不过在哺乳动物种群中,“这的确是一种非常明显的进化模式。”Dr. Lloyd and Dr. Puts welcomed the new study as a provocative addition to the debate over the female orgasms.劳埃德与普茨对这项新研究表示欢迎,认为它加入了有关女性性高潮的辩论,能够激发探讨。“I’m pretty excited that it’s being published,” Dr. Lloyd said, “because people are going to start talking about female orgasms and getting a fresh look at how much we don’t know about female orgasms, and thinking hard about what we need to know.”“它的发表让我很兴奋,”劳埃德说,“因为大家会开始谈论女性的性高潮,重新审视我们在这方面有多么大的认知空白,努力思考我们需要了解些什么。”The new theory may shed light on how the human female orgasm first evolved, but Dr. Pavlicev and Dr. Wagner said that it doesn’t settle the debate about its current role in women. “All directions are open,” Dr. Wagner said.这项新理论或许有助于揭示人类女性性高潮起初如何进化而来,不过帕夫利塞夫与瓦格纳表示,这并不能平息有关它对女性今时今日起到的作用的讨论。“所有方向都有可能,”瓦格纳说。Dr. Wagner said that deciphering the history of the female orgasm might improve reproductive medicine.瓦格纳认为,解开女性性高潮历史的谜团,也许能推进生殖医学的发展。“I think you’re looking at the whole woman’s reproductive system a little differently when you have a model for how it might have evolved,” he said.“我想,当你有了女性生殖系统可能怎样进化而来的模型,就会对这整套系统有不太一样的认识,”他说。 /201608/458413

To see if wrinkled primate fingers had similar features to river basins, Changizi and his team analysed photos of 28 human fingers. They found that wrinkled fingers had the exact inverse formation as river drainages, with a raised, interconnected “tree” of bumpy skin, punctuated by diverging, disconnected sunken channels. 为了确定灵长类手指起皱是否与江河流域有共同点,尚依兹和他的团队分析了28个人类手指的照片。他们发现起皱的手指恰好是逆向的河流排水系统,鼓起的皮肤形成了凸起的相互连通的“树状”结构,而分叉的、互不连通的、下沉的渠道加强了这一结构。The ridges aren’t haphazardly placed; that inverted pattern actually makes sense. Rivers combine water, while the channels on a wrinkled finger and meant to force water away. “The act of pressing a fingertip down on a wet surface squeezes the fluid out from under the finger through the channels, and upon completion of this single pulsatile flow the entire finger’s skin contacts the surface,” write the researchers.凸起的纹路是有章可循的;逆向的结构是有根据的。尽管河流将水汇聚起来,但起皱的手指上的沟渠是以排水为目的。“把指尖按压在潮湿的表面上,手指上沟壑中的水就被挤出,完成这样的一次脉动后,手指的皮肤就完全贴住表面了,”研究者写道。And then there’s this: wrinkles don’t appear until around five minutes of constant exposure to water, meaning that incidental contact isn’t enough to result in wrinkling, the response only becomes useful in rainy or dewy conditions. And it occurs far more quickly in response to freshwater than seawater, which could reflect the circumstances in which it may have originally evolved in primates.另外,皱纹会在持续接触水五分钟后出现。也就是说,偶然碰到水并不足以导致皮肤起皱,这种反应只在有雨水或露水的环境下才会发挥作用。而在淡水中出现这一反应的速度比在海水中快很多,这说明这一反应可能原本就是灵长类进化的结果。Even if the wet-wrinkling response didn’t explicitly evolve to aid in gripping, it could still be that it remains useful for the task. Indeed, a 2013 study conducted by British neuroscientists uncovered evidence that wrinkled fingers aided people in manipulating wet objects. 尽管没有清晰的据明泡水起皱反应就是为了增强抓握力而进化出来的,但是它仍然有利于人类完成这类任务。2013年英国神经科学家发现据,明起皱的手指有助于人操控潮湿的物体。In the experiment, 20 people had to transfer 45 objects of different sizes – all marbles and fishing weights – from one container into another. In some cases, the objects were dry while the participants’ fingers were either smooth or wrinkled. In other cases, the objects were submerged. They found that wrinkled fingers allowed the participants to more quickly transfer the objects when submerged, though they made no difference for dry objects.在实验中,20个人将45个不同大小的物品——所有都是大理石和钓鱼用的沉子——从一个容器取出,放到另一个容器中。一些情况下,物品是干的,而被试者有的手指是平滑的,有的是起皱的。在另一些情况下,物品泡在水里。他们发现,起皱的手指能让被试者更快地搬运水中的物品,但是对干的物品没有作用。However, a similar 2014 study conducted by German researchers found the opposite. In that study, the researchers had 40 people transfer 52 marbles and dice of different sizes and weights from one container into another. They found, however, no significant differences in the participants’ ability to manipulate the objects, no matter whether their fingers were smooth or wrinkled, and the objects dry or submerged.不过,2014年德国研究者进行的一个类似的研究产生了相反的结论。在该研究中,研究者让40个人在两个容器之间搬运52枚不同大小的大理石和骰子。但是结果发现,不论手指是光滑的还是皱的,也不论物品是干的或是湿的,被试者操控这些物品的能力都没有变化。Likewise, a group of Taiwanese researchers conducted a series of experiments aided by a 24-year-old male volunteer. They assessed the friction applied to a smooth surface by his smooth or wrinkled fingertips, for example, and how much force his hands applied when sliding across a bar. They also measured his ability to force two ends of a spring together. Rather than finding no differences, however, they actually found that wet-wrinkles resulted in decreased performance for each test. 台湾的一些研究者也有类似的发现。在一名24岁男性志愿者的帮助下,他们进行了一系列的实验。比如,他们让志愿者用光滑或起皱的手指接触一块光滑的表面,根据他的手抚摸时的力量计算擦力。他们还测量了志愿者挤压弹簧两端直到合拢的能力。然而,他们不仅没有发现任何变化,还发现在每项测试中起皱手指的表现较差。Of course, if the wet-wrinkling response did evolve as an adaptation, it was certainly not for the highly contrived laboratory conditions in which these experiments were run.当然,假如泡水起皱反应真的是适应环境进化的结果,那它当然不适用于这些精心设计的实验环境。Changizi thinks that the wet-wrinkling response is useful for supporting one’s own body weight, not for fine-motor manipulations of small objects. “If you#39;re really going to do a behavioural test where it matters, [it should be] gripping onto trees or heavier things, not little marbles,” he says. “You’re not at a risk of hydroplaning in any way,” he points out, when your task is to transfer marbles between buckets. The key is to assess the impact of wrinkled skin on locomotion, rather than on dexterity.尚依兹认为泡水起皱反应有利于撑人体的重量,但不利于对小物品的精细操作。“如果你真的打算进行行为测试,那应该测试抓住树枝或其他较重的东西,而不是小块的大理石。”他说。当说到把小块大理石从一个水桶搬到另一个水桶时,他说:“无论如何,你没有轮胎打滑那样的风险。”关键是评估皮肤起皱对运动的作用,而不是对灵敏度的作用。His ideal experiment? Recruiting parkour experts to show off their urban acrobatics while either wrinkled or non-wrinkled, and in wet or dry conditions. “In some kind of safe way,” he adds.他理想的实验是什么?招募跑酷达人,在潮湿和干燥的时候和在皮肤起皱和不起皱的情况下,展现他们在城市中的杂技。“以某种安全的形式。”他补充道。 /201606/450858

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