2013年10月31日 星期四

Computer-Controlled Anesthesia Could Be Safer for Patients

大概15年前黃醫師告訴我們"採用病人自助式麻醉方式"更好
現在美國mit的Tecnology Review的這篇說由電腦程式偵腦來決定比專更安全
 

Computer-Controlled Anesthesia Could Be Safer for Patients

Computer-controlled sedation could lighten the load for intensive-care staff and make the process safer for patients.
By tracking brain activity through electroencephalography, or EEG, software may be able to maintain a patient in a medically induced coma more safely than a human expert can.
Anesthesiologists use EEG to monitor a patient’s level of sedation through sensors placed on the scalp. When a patient is deeply sedated in a medical coma—a technique sometimes used to reduce brain swelling after a traumatic injury or to treat uncontrolled seizures—a nurse or doctor must currently monitor the patient’s brain activity and adjust the rate of anesthetic delivery around the clock, sometimes for days.
Emery Brown, an MIT neuroscientist and an anesthesiologist at Massachusetts General Hospital, thinks the computer-controlled anesthetic system he has developed could do a better job. In a study published on Thursday in PLoS Computational Biology, Brown and colleagues demonstrate the technology in rats as a step toward developing it for human patients.
The potential for computer-assisted sedation stems from extensive work researchers have done to understand and control brain states during anesthesia. In recent years, brain monitoring technologies such as EEG and MRI have helped begin to unravel the differences between conscious and unconscious brains, says Martin Monti, a cognitive psychologist at the University of California, Los Angeles, who was not involved in the new study. Such work could help answer basic questions such as whether multiple brain functions are necessary to produce consciousness and whether loss of consciousness after severe injury is similar to unconsciousness during sedation or sleep, he says.
Brown’s group has been studying the anesthetized brain both to further scientific understanding of consciousness and to make anesthesia safer and more effective (see “The Mystery Behind Anesthesia”). The pattern of brain activity that doctors monitor to control sedation is well defined and can be recognized by a computer, says Brown. In fact, he says, the computer can be more accurate than the human eye at spotting how a patient’s activity pattern differs from the one that’s ideal for sedation, and it can make adjustments without under- or over-shooting the amount of drug required to maintain the sedated state. That could help ensure that patients aren’t given more anesthetic than they need.
The system could potentially be adapted to target the well-defined EEG signatures associated with levels of sedation used during surgery or in other situations, he says.
Other groups are exploring the possibility of computer-assisted sedation as well. Johnson & Johnson has developed a system to automate partial sedation of patients being screened for colon cancer. Sedasys was approved by the FDA in May, and J&J says it will begin selling the system in early 2014.
Automated sedation could be helpful to anesthesiologists or intensive-care nurses, says Mark Newman, an anesthesiologist at Duke University. However, he notes that monitoring a patient in a medically induced coma requires much more than EEG—heart activity and kidney activity, for instance, must also be tracked. So the technology could improve the precision of sedation, but it couldn’t automate it entirely.
 

2013年10月26日 星期六

The 3-D Printed Electric Motorcycle/Masks...... 混凝土......

The 3-D Printed Electric Motorcycle

 

 混凝土

提到替代方案:玻璃太貴/3D列印其實也太緲茫/砂土銀行也難行/唯一成功個案似乎是移山造關西機場

2013年10月18日 星期五

Modern scientists are doing too much trusting and not enough verifying



A simple idea underpins science: "trust, but verify". That powerful idea has generated a vast body of knowledge. Since its birth in the 17th century, modern science has changed the world beyond recognition, and overwhelmingly for the better. But success can breed complacency. Modern scientists are doing too much trusting and not enough verifying http://econ.st/H6jqxA


Problems with scientific research
How science goes wrong
Scientific research has changed the world. Now it needs to change itself
Oct 19th 2013 |From the print edition










A SIMPLE idea underpins science: “trust, but verify”. Results should always be subject to challenge from experiment. That simple but powerful idea has generated a vast body of knowledge. Since its birth in the 17th century, modern science has changed the world beyond recognition, and overwhelmingly for the better.

But success can breed complacency. Modern scientists are doing too much trusting and not enough verifying—to the detriment of the whole of science, and of humanity.
In this section


Too many of the findings that fill the academic ether are the result of shoddy experiments or poor analysis (see article). A rule of thumb among biotechnology venture-capitalists is that half of published research cannot be replicated. Even that may be optimistic. Last year researchers at one biotech firm, Amgen, found they could reproduce just six of 53 “landmark” studies in cancer research. Earlier, a group at Bayer, a drug company, managed to repeat just a quarter of 67 similarly important papers. A leading computer scientist frets that three-quarters of papers in his subfield are bunk. In 2000-10 roughly 80,000 patients took part in clinical trials based on research that was later retracted because of mistakes or improprieties.

What a load of rubbish

Even when flawed research does not put people’s lives at risk—and much of it is too far from the market to do so—it squanders money and the efforts of some of the world’s best minds. The opportunity costs of stymied progress are hard to quantify, but they are likely to be vast. And they could be rising.

One reason is the competitiveness of science. In the 1950s, when modern academic research took shape after its successes in the second world war, it was still a rarefied pastime. The entire club of scientists numbered a few hundred thousand. As their ranks have swelled, to 6m-7m active researchers on the latest reckoning, scientists have lost their taste for self-policing and quality control. The obligation to “publish or perish” has come to rule over academic life. Competition for jobs is cut-throat. Full professors in America earned on average $135,000 in 2012—more than judges did. Every year six freshly minted PhDs vie for every academic post. Nowadays verification (the replication of other people’s results) does little to advance a researcher’s career. And without verification, dubious findings live on to mislead.

Careerism also encourages exaggeration and the cherry-picking of results. In order to safeguard their exclusivity, the leading journals impose high rejection rates: in excess of 90% of submitted manuscripts. The most striking findings have the greatest chance of making it onto the page. Little wonder that one in three researchers knows of a colleague who has pepped up a paper by, say, excluding inconvenient data from results “based on a gut feeling”. And as more research teams around the world work on a problem, the odds shorten that at least one will fall prey to an honest confusion between the sweet signal of a genuine discovery and a freak of the statistical noise. Such spurious correlations are often recorded in journals eager for startling papers. If they touch on drinking wine, going senile or letting children play video games, they may well command the front pages of newspapers, too.

Conversely, failures to prove a hypothesis are rarely even offered for publication, let alone accepted. “Negative results” now account for only 14% of published papers, down from 30% in 1990. Yet knowing what is false is as important to science as knowing what is true. The failure to report failures means that researchers waste money and effort exploring blind alleys already investigated by other scientists.

The hallowed process of peer review is not all it is cracked up to be, either. When a prominent medical journal ran research past other experts in the field, it found that most of the reviewers failed to spot mistakes it had deliberately inserted into papers, even after being told they were being tested.

If it’s broke, fix it

All this makes a shaky foundation for an enterprise dedicated to discovering the truth about the world. What might be done to shore it up? One priority should be for all disciplines to follow the example of those that have done most to tighten standards. A start would be getting to grips with statistics, especially in the growing number of fields that sift through untold oodles of data looking for patterns. Geneticists have done this, and turned an early torrent of specious results from genome sequencing into a trickle of truly significant ones.

Ideally, research protocols should be registered in advance and monitored in virtual notebooks. This would curb the temptation to fiddle with the experiment’s design midstream so as to make the results look more substantial than they are. (It is already meant to happen in clinical trials of drugs, but compliance is patchy.) Where possible, trial data also should be open for other researchers to inspect and test.

The most enlightened journals are already becoming less averse to humdrum papers. Some government funding agencies, including America’s National Institutes of Health, which dish out $30 billion on research each year, are working out how best to encourage replication. And growing numbers of scientists, especially young ones, understand statistics. But these trends need to go much further. Journals should allocate space for “uninteresting” work, and grant-givers should set aside money to pay for it. Peer review should be tightened—or perhaps dispensed with altogether, in favour of post-publication evaluation in the form of appended comments. That system has worked well in recent years in physics and mathematics. Lastly, policymakers should ensure that institutions using public money also respect the rules.

Science still commands enormous—if sometimes bemused—respect. But its privileged status is founded on the capacity to be right most of the time and to correct its mistakes when it gets things wrong. And it is not as if the universe is short of genuine mysteries to keep generations of scientists hard at work. The false trails laid down by shoddy research are an unforgivable barrier to understanding.

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2013年10月9日 星期三

Nobel prize in chemistry, 2013

Computers have allowed modellers to incorporate ever more factors into their equations. There are, however, limits to the mathematical prowess even of computers. This year's Nobel prize in chemistry was awarded to a trio of researchers who came up with a clever way of circumventing some of them http://econ.st/19jFH5r


40年前洞燭機先
〔編 譯管淑平/綜合報導〕三名美國籍學者卡普拉斯(Martin Karplus)、李維特(Michael Levitt)和瓦歇爾(Arieh Warshel)以電腦為複雜的化學系統建立多尺度模型,模擬化學反應過程,共同獲得今年的諾貝爾化學獎。瑞典皇家科學院指出,三人的研究讓人們能在電腦 上預測和了解微妙難解的化學過程,實際上是把化學帶入電腦,加速了從製藥到太陽能應用等多領域的進展。
為電腦模擬化學過程奠基
瑞 典皇家科學院說,化學反應一閃即逝,難以用肉眼觀察,也幾乎不可能用實驗描繪化學過程中的每一細節,過去化學家用塑膠球、塑膠棍模擬化學分子結構,現在用 電腦;對今日的化學家而言,電腦的重要性不下於試管,反映真實狀態的電腦模型已是現今大多數化學領域進展的關鍵,而卡普拉斯等三人在一九七○年代的研究, 則為電腦模擬化學過程奠定基礎。
計算生命化學的通用程序
以製藥為例,借助電腦模型計算原子間的互動,研究人員得以了解實驗性藥物與體內特定蛋白質會有什麼反應,工業應用如太陽能板設計、汽車觸媒轉化器的催化機制等。頌詞說,三人發展出的電腦模擬方法具通用性,「能用於研究從生命體分子結構到工業化學等所有類型的化學過程」。
卡普拉斯 核磁共振方程式開發人
現年八十三歲的化學家卡普拉斯,在奧地利出生,擁有美、奧地利國籍,現為法國史特拉斯堡大學、美國哈佛大學教授,他也開發用於核磁共振的「卡普拉斯方程式」。
六十六歲生物物理學家李維特具美、英籍,任教史丹福大學。他說,知道得獎時「心快跳出來」,好像喝下「三倍義式濃縮咖啡」,而得獎研究基本上是他二十歲撰寫的電腦程式,「我想我的程式真的寫得很好」。
七 十二歲的化學家瓦歇爾是以色列、美國雙國籍,任教南加州大學。瓦歇爾說,獲獎令他「極為高興」,他說,「簡單來說,我們開發的就是用電腦了解蛋白質結構的 方式,然後最終了解其如何發揮其作用」,你能用來設計藥物。從一九七五年以來,瓦歇爾一直堅定認為電腦科技是研究的未來,但每篇文章都曾遭拒絕,曾感嘆 「不知道能不能活到證明我是對的那天」。
結合古典物理和量子物理
過去科學家在電腦上模擬化學分子結構,需選擇使用以古典物理學或者量子物理學為基礎建構的軟體。卡普拉斯等三人的研究擷取兩者長處,發展出能並用古典物理學以及量子物理學研究化學過程的方法。
卡 普拉斯七○年代在哈佛大學建立用量子物理模擬化學反應的電腦程式。瓦歇爾和李維特則在以色列魏茲曼科學研究所建立以古典物理理論為基礎的電腦程式。一九七 ○年瓦歇爾到美國加入卡普拉斯的實驗室,後來回到以色列又與李維特合作,讓古典、量子物理能更順暢地並用於模擬蛋白質化學反應過程。

2013年10月8日 星期二

希格斯場和希格斯粒子的存在/"沒有物理學家是孤島" François Englert and Peter Higgs Win Nobel Prize in Physics


紐約時報有篇"沒有物理學家是孤島" ---他們都必須充分合作來研究  所以諾貝爾獎等的頒發給某些人   而他們是否能反映某創新當時的真正情況 頗令人懷疑的ˊ
Op-Ed: No Physicist Is an Island
Science is an intensely collaborative pursuit, and prizes to individuals are rarely able to capture the full nuance of the historical reality. 


 諾貝爾物理獎 "上帝粒子"學者獲殊榮
2013年的諾貝爾物理學獎,8號由瑞典皇家學院宣佈,頒給發現所謂「上帝粒子」的兩位科學家。他們是英國愛丁堡大學的希格斯,以及比利時布魯塞爾自由大學的英格勒。

==聲音來源 諾貝爾物理獎得主 英格勒==
我非常非常開心,可以獲得這樣的認可與殊榮。

另一位得主希格斯,則是透過愛丁堡大學發表書面聲明,對於得獎表示相當的驚喜。

早在1964年,英格勒和希格斯跟其他4位學者,就先後提出理論,認為宇宙中存在一種機制,是讓粒子有質量的根源,而粒子和這種機制交互作用,必然會產生玻色子。為了表示對希格斯等人的尊崇,這種玻色子被命名為希格斯粒子,而讓粒子產生質量的機制,被稱為希格斯場。

歐洲核能研究所設在瑞士與法國交界的大型強子對撞機LHC,經過多年的延宕以及3年的實驗,在去年證實了希格斯粒子的存在,也就是證實希格斯等人提出的理論。

==歐洲核能研究所所長 霍耶爾==
是你們的努力才有這個獎,所以你們也該給自己鼓鼓掌!

學術界認為,希格斯場和希格斯粒子的存在,讓粒子構成宇宙物質有了明確的理論基礎,因此希格斯粒子又被媒體戲稱為上帝粒子。至於實驗證實希格斯粒子存在的 大型強子對撞機,在去年11月完成階段性任務後,已經從今年2月情人節當天開始停機,展開維修與升級,預計2015年重新運轉。

記者徐家仁報導
(2013-10-09 12:00)  中晝新聞

François Englert and Peter Higgs Win Nobel Prize in Physics

Scientists' Theory Confirmed by Detection of Higgs Boson Particle


Francois Englert and Peter Higgs received the 2013 Nobel Prize in physics for their work on the so-called Higgs mechanism. Gordon Kane, professor of physics at the University of Michigan, explains why their work is so important to our understanding of the universe. Photo: AP
Peter Higgs and François Englert shared the Nobel Prize in physics for independently proposing a particle, now known as the Higgs boson, that confers mass to all other particles and whose recent discovery stands as one of the seminal moments of modern science.
Nearly a half-century after predicting the existence of the particle, the pair's work was confirmed last year, in a nail-biting experiment undertaken at the atom-smashing machine built by the European particle physics laboratory at CERN in Switzerland. That July day, in a packed hall in Geneva, Drs. Higgs and Englert met for the first time.
After further analysis, physicists at the Geneva laboratory said earlier this year they are confident that the particle they had discovered was in fact the one Mr. Higgs and his colleagues had predicted.
François Englert and Peter Higgs won the 2013 Nobel Prize in physics. They received the award for their work on the "Higgs mechanism," which was proposed in 1964 as a theory to explain how mass is conferred to elementary particles.
Though widely expected, the Nobel award is also a controversial one, partly because several other scientists—and CERN itself—can claim significant credit for work done on the boson. A Nobel Prize can be shared by a maximum of three people and isn't granted posthumously.
Dr. Englert, a Belgian who is 80 years old, published his landmark 1964 paper with colleague Robert Brout, who died in 2011. Other strong contenders were three scientists—Carl Hagen of the University of Rochester, Tom Kibble of Imperial College and Gerald Guralnik of Brown University—who published a very similar theory just a month after Dr. Higgs of the U.K. published his paper, which affixed his name to the fabled particle for posterity.
"I'd be lying if I said it doesn't sting a little" not to share in the prize, Dr. Guralnik, 77, said in a phone interview. "No matter what, [the Nobel committee] had a difficult time" in choosing the winners. But, he added, "we are amazed and delighted that our mathematical exercise turned out to play a huge part in describing how nature works."

Nobel Prize Winners

In a statement, Dr. Higgs, of the University of Edinburgh, congratulated "all those who have contributed to the discovery of this new particle."
The Higgs boson explains a big puzzle about matter concerning why some objects in the universe such as the quark, a constituent of protons, possess mass, while others, such as the photon, a constituent of light, have only energy and zip around the universe unhindered.
Until this enigma was resolved, physicists couldn't properly explain why many things in the universe exist, from stars and planets to germs and people.

Nobel Science Winners

See which countries and academic institutions have had the most Nobel laureates.
Dr. Higgs and others explained away the problem by proposing a ghostlike field that pervades the universe—space, after all, is already filled with other invisible fields, such as the gravitational field and electromagnetic field.
The scientists' notion was that particles acquire mass only in contact with this field, which would become known as the Higgs field. How much mass they acquire depends on the type of particles they are. Some, like the photon, seem to ignore the field and don't acquire mass at all.
By contrast, electrons interact with the field. If the field were to disappear, the suddenly massless electrons would zoom away at the speed of light—and all matter would collapse.
"The Higgs field is always there," said Dr. Guralnik. "It slows down the particles and induces a mass to them."
The Higgs boson and its associated field neatly filled a potentially embarrassing hole in one of the most successful theories of physics, known as the standard model. But it was only a theory. It took half a century for the physicists' bold theoretical leap to be confirmed by experimental science.
Last year, hundreds of scientists assembled at CERN, and others tuned in to a live webcast, to hear a report on the latest data from the Large Hadron Collider. The quest for the elusive Higgs had involved some 6,000 scientists, cost millions of dollars and required billions of particle collisions. "I think we have it," said Rolf-Dieter Heur, CERN's director general.Dr. Higgs, now 84, received a round of applause when he entered the auditorium, and shed a tear on hearing the news. He was heartened that his main finding had been so concretely and dramatically confirmed.
Agence France-Presse/Getty Images
François Englert, left, spoke with Peter Higgs at a news conference on July 4, 2012, at European Organization for Nuclear Research offices in Meyrin near Geneva.
"It is an incredible thing that it has happened in my lifetime," he said.
"The miracle of the standard model is that it works so well," said Dr. Guralnik. "But we have many, many open questions, such as [the mystery] of how gravitational interactions occur."
The Nobel Prize in physics is seen as the most prestigious award of its kind, and comes with an 8 million Swedish kronor ($1.25 million) cash award. The winner is selected by the Royal Swedish Academy of Sciences, after a process in which thousands of scientists world-wide are invited to name contenders.
—Niclas Rolander in Stockholm contributed to this article. Write to Gautam Naik at gautam.naik@wsj.com

2013年10月7日 星期一

James E. Rothman, Randy W. Schekman and Thomas C. Südhof: The 2013 Nobel Prize in Physiology or Medicine




2013諾貝爾生理學與醫學獎授予3名美德科學家
北京新浪網 (2013-10-07 19:39)

2013諾貝爾生理學或醫學獎得主

  新浪科技訊 北京時間107日消息,據諾貝爾獎官方網站報導,2013諾貝爾生理學或醫學獎今日公布,得主為James E. Rothman, Randy W. Schekman & Thomas C. S?dhof,得獎原因為他們發現了細胞內的運輸機制之謎。

翻譯: 原文參考附文

    生物體內每一個細胞都是一個生產和輸出分子的工廠。比如,胰島素在這裏被製造出來並釋放進入血液當中,神經傳遞素從一個神經細胞傳導至另一個細胞。這些分子在細胞內都是以「小包」的形式傳遞的,這就是「細胞囊泡」。這三位獲獎科學家發現了這些「小包」是如何被在正確的時間輸運至正確地點的分子機制。

  Randy Schekman發現了一系列與細胞囊泡輸運機制有關的基因;James Rothman發現了讓這些囊泡得以與其目標相融合的蛋白質機制,從而可以實現對所運「貨物」的傳遞;Thomas S?dhof則揭示了信號是如何實現對囊泡的控制,使其得以精確分配其所載「貨物」。

  在這項發現過程中,三位科學家:Rothman, Schekman S?dhof揭示了細胞內輸運體系的精細結構和控制機制。這一系統的失穩將導致有害結果,如神經系統疾病,糖尿病或免疫系統紊亂。

  細胞內物質輸運是如何實現的?

  正如在一個繁忙的大型港口,你必須要有一套體系來確保你的貨物會在規定的時間被配送到規定的位置,細胞也是一樣。細胞內有各種複雜的細胞器,它們面臨的問題是相似的:細胞會產生出各種不同的分子,如荷爾蒙,神經傳遞素,細胞活素以及?,它們必須被傳遞至細胞內不同的位置上,或者需要被精確地在正確的時間轉運至細胞外部。在這一過程中,時間和地點的正確是最關鍵的。這就要依賴於囊泡的作用,這是一些微小的小泡結構,外部有膜包裹,它們負責在各細胞器之間運輸細胞內部的「貨物」,或是通過與細胞膜的融合從而向細胞外部釋放細胞內產生的物質。這一機制至關重要,如它控制著神經傳遞素的傳遞,後者是激發生物體神經系統反應的觸發開關;又或者在新陳代謝方面,它控制著荷爾蒙的分配傳遞。那麼這些囊泡結構究竟是如何能確保運輸的時間和地點正確性的呢?

  交通堵塞背後的基因控制機制

  早在上世紀的1970年代,Randy Schekman便被細胞如何調節其內部輸運機制深深吸引並投身此項研究,並試圖利用酵母菌作為模型樣本來研究其背後的基因機制。在基因篩選中,他找到一些顯示出輸運機制缺陷的酵母菌細胞,其表現就像是一個缺乏指揮協調而一片混亂的公共交通系統,其內部囊泡堆積在細胞內的部分區域。他發現造成這種囊泡發生「交通堵塞」的原因是基因層面的,並據此順藤摸瓜找到了其背後的基因機制。他找到了3組不同的基因對這一細胞運輸機制產生作用,從而改變並大大加深了我們對細胞如何規範其內部輸運系統的認識。

  精確對接

  James Rothman同樣對細胞輸運機制感到好奇。在上世界80~90年代期間,Rothman正開展對哺乳動物細胞囊泡輸運機制的研究,他發現一種蛋白質可以讓囊泡實現與其目標細胞膜的對接和融合。在融合過程中,囊泡上的蛋白質和細胞膜上的蛋白質相互結合,就像分開的拉鏈相互咬合一樣。這類蛋白質有很多種,並且只有當合適的配對出現時才會發生融合,這就確保了「貨物」只會被運輸到設定的位置上而不會出現錯誤。這一機制不管是在內部細胞器之間的運輸,還是向外的運輸過程中都會起作用。

  隨後的研究發現,Schekman在酵母菌細胞內所發現的部分基因正是產生Rothman在哺乳動物細胞內發現的蛋白質的背後機制,這揭示了一項細胞輸運體系內古老的進化起源。至此,這兩位科學家的研究工作描繪了細胞輸運體系的關鍵環節。

  時間就是一切

  Thomas S?dhof對大腦內神經細胞是如何相互之間進行溝通感興趣。這種傳遞信息的物質被稱為神經傳遞素,這種特殊分子正是由囊泡負責運輸至神經細胞的細胞膜上並藉助融合機制向外釋放的。這正是Rothman Schekman所發現的機制。然而這些囊泡只有在其所在的神經細胞向其「鄰居」發送信號之後才會被允許釋放它們運載的「貨物」。這種精確的時機把握究竟是如何實現的?

  科學家們此前便已經知道鈣離子參与了這一過程,在上世紀90年代,S?dhof便開始在神經細胞中尋找對鈣離子敏感的蛋白質。最終他識別出一種分子機制,其會對注入的鈣離子做出反應,並控制鄰近的蛋白質迅速讓囊泡與神經細胞的外部細胞膜相結合。於是「拉鏈」打開了,信號物質被釋放出去。S?dhof的發現解釋了這種細胞傳輸的時間精確性是如何實現的,以及囊泡中的物質是如何實現受控地釋放。

  囊泡輸運機制與疾病過程

  今年的3位諾獎獲獎科學家發現了細胞生理學過程中的一項關鍵過程。他們的工作揭示了細胞內部和外部的輸運體系是如何達成時間與位置上的精確性的。在細胞中,不管是酵母菌還是人類,不管高等生物還是低等生物,它們體內的囊泡輸運以及細胞膜融合機制都遵循相同的基本原理。這一體系對於一系列的生理過程而言都至關重要,從大腦信號的傳遞,到荷爾蒙的釋放,再到免疫細胞活素。但當發生疾病時,細胞內的囊泡輸運機制會出現問題,這當中包括一些神經系統和免疫系統疾病。離開這一堪稱完美的控制機制,細胞將陷於混亂。

  獲獎科學家簡歷:

  James E. Rothman1950年出生於美國馬薩諸塞州Haverhill,他於1976年在哈佛大學醫學院獲得博士學位,隨後在麻省理工學院做博士后研究工作。1978Rothman前往加州的斯坦福大學,並在那裡開始進行針對細胞囊泡的研究工作。Rothman還曾經在普林斯頓大學以及紀念斯隆-凱特林癌症研究所和哥倫比亞大學工作過。2008年,他開始在耶魯大學任職,目前是耶魯大學細胞生物學繫系主任和教授。

  Randy W. Schekman1948年生於美國明尼蘇達州St Paul,曾先後在加州大學洛杉磯分校以及斯坦福大學求學,並於1974年獲得博士學位,指導老師為Arthur Kornberg,後者是1959年度諾貝爾獎獲得者。1976年,Schekman前往加州大學伯克利分校任職,目前他仍然是該校分子與細胞生物學系教授。同時Schekman也是霍華德休斯醫學研究所研究員。

  Thomas C. S?dhof1955年生於德國哥廷根。他在哥廷根大學求學並於1982年獲得碩士學位,同年獲得該校神經化學博士學位。1983年他前往美國達拉斯的德州大學西南醫學研究中心開展博士后研究,其導師是Michael BrownJoseph GOLdstein,他們是1985年度諾貝爾生理學與醫學獎得主。S?dhof1991年成為霍華德休斯醫學研究所研究員,並在2008年開始擔任斯坦福大學分子與細胞生理學教授。(晨風)

  原文:http://www.nobelprize.org/nobel_prizes/medicine/laureates/2013/press.html


Press Release

2013-10-07
The Nobel Assembly at Karolinska Institutet has today decided to award

The 2013 Nobel Prize in Physiology or Medicine
jointly to
James E. Rothman, Randy W. Schekman
and Thomas C. Südhof
for their discoveries of machinery regulating vesicle traffic,
a major transport system in our cells


Summary

The 2013 Nobel Prize honours three scientists who have solved the mystery of how the cell organizes its transport system. Each cell is a factory that produces and exports molecules. For instance, insulin is manufactured and released into the blood and chemical signals called neurotransmitters are sent from one nerve cell to another. These molecules are transported around the cell in small packages called vesicles. The three Nobel Laureates have discovered the molecular principles that govern how this cargo is delivered to the right place at the right time in the cell.
Randy Schekman discovered a set of genes that were required for vesicle traffic. James Rothman  unravelled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. Thomas Südhof revealed how signals instruct vesicles to release their cargo with precision.
Through their discoveries, Rothman, Schekman and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders.

How cargo is transported in the cell

In a large and busy port, systems are required to ensure that the correct cargo is shipped to the correct destination at the right time. The cell, with its different compartments called organelles, faces a similar problem: cells produce molecules such as hormones, neurotransmitters, cytokines and enzymes that have to be delivered to other places inside the cell, or exported out of the cell, at exactly the right moment. Timing and location are everything. Miniature bubble-like vesicles, surrounded by membranes, shuttle the cargo between organelles or fuse with the outer membrane of the cell and release their cargo to the outside. This is of major importance, as it triggers nerve activation in the case of transmitter substances, or controls metabolism in the case of hormones. How do these vesicles know where and when to deliver their cargo?

Traffic congestion reveals genetic controllers

Randy Schekman was fascinated by how the cell organizes its transport system and in the 1970s decided to study its genetic basis by using yeast as a model system. In a genetic screen, he identified yeast cells with defective transport machinery, giving rise to a situation resembling a poorly planned public transport system. Vesicles piled up in certain parts of the cell. He found that the cause of this congestion was genetic and went on to identify the mutated genes. Schekman identified three classes of genes that control different facets of the cell´s transport system, thereby providing new insights into the tightly regulated machinery that mediates vesicle transport in the cell.

Docking with precision

James Rothman was also intrigued by the nature of the cell´s transport system. When studying vesicle transport in mammalian cells in the 1980s and 1990s, Rothman discovered that a protein complex enables vesicles to dock and fuse with their target membranes. In the fusion process, proteins on the vesicles and target membranes bind to each other like the two sides of a zipper. The fact that there are many such proteins and that they bind only in specific combinations ensures that cargo is delivered to a precise location. The same principle operates inside the cell and when a vesicle binds to the cell´s outer membrane to release its contents.
It turned out that some of the genes Schekman had discovered in yeast coded for proteins corresponding to those Rothman identified in mammals, revealing an ancient evolutionary origin of the transport system. Collectively, they mapped critical components of the cell´s transport machinery.

Timing is everything

Thomas Südhof was interested in how nerve cells communicate with one another in the brain. The signalling molecules, neurotransmitters, are released from vesicles that fuse with the outer membrane of nerve cells by using the machinery discovered by Rothman and Schekman. But these vesicles are only allowed to release their contents when the nerve cell signals to its neighbours. How is this release controlled in such a precise manner? Calcium ions were known to be involved in this process and in the 1990s, Südhof searched for calcium sensitive proteins in nerve cells. He identified molecular machinery that responds to an influx of calcium ions and directs neighbour proteins rapidly to bind vesicles to the outer membrane of the nerve cell. The zipper opens up and signal substances are released. Südhof´s discovery explained how temporal precision is achieved and how vesicles´ contents can be released on command.

Vesicle transport gives insight into disease processes

The three Nobel Laureates have discovered a fundamental process in cell physiology. These discoveries have had a major impact on our understanding of how cargo is delivered with timing and precision within and outside the cell.  Vesicle transport and fusion operate, with the same general principles, in organisms as different as yeast and man. The system is critical for a variety of physiological processes in which vesicle fusion must be controlled, ranging from signalling in the brain to release of hormones and immune cytokines. Defective vesicle transport occurs in a variety of diseases including a number of neurological and immunological disorders, as well as in diabetes. Without this wonderfully precise organization, the cell would lapse into chaos.

James E. Rothman was born 1950 in Haverhill, Massachusetts, USA. He received his PhD from Harvard Medical School in 1976, was a postdoctoral fellow at Massachusetts Institute of Technology, and moved in 1978 to Stanford University in California, where he started his research on the vesicles of the cell. Rothman has also worked at Princeton University, Memorial Sloan-Kettering Cancer Institute and Columbia University. In 2008, he joined the faculty of Yale University in New Haven, Connecticut, USA, where he is currently Professor and Chairman in the Department of Cell Biology.
Randy W. Schekman was born 1948 in St Paul, Minnesota, USA, studied at the University of California in Los Angeles and at Stanford University, where he obtained his PhD in 1974 under the supervision of Arthur Kornberg (Nobel Prize 1959) and in the same department that Rothman joined a few years later. In 1976, Schekman joined the faculty of the University of California at Berkeley, where he is currently Professor in the Department of Molecular and Cell biology. Schekman is also an investigator of Howard Hughes Medical Institute.
Thomas C. Südhof was born in 1955 in Göttingen, Germany. He studied at the Georg-August-Universität in Göttingen, where he received an MD in 1982 and a Doctorate in neurochemistry the same year. In 1983, he moved to the University of Texas Southwestern Medical Center in Dallas, Texas, USA, as a postdoctoral fellow with Michael Brown and Joseph Goldstein (who shared the 1985 Nobel Prize in Physiology or Medicine). Südhof became an investigator of Howard Hughes Medical Institute in 1991 and was appointed Professor of Molecular and Cellular Physiology at Stanford University in 2008.

Key publications:

Novick P, Schekman R: Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1979; 76:1858-1862.
Balch WE, Dunphy WG, Braell WA, Rothman JE: Reconstitution of the transport of protein between successive compartments of the Golgi measured by the coupled incorporation of N-acetylglucosamine. Cell 1984; 39:405-416.
Kaiser CA, Schekman R: Distinct sets of SEC genes govern transport vesicle formation and fusion early in the secretory pathway. Cell 1990; 61:723-733.
Perin MS, Fried VA, Mignery GA, Jahn R, Südhof TC: Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature 1990; 345:260-263.
Sollner T, Whiteheart W, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE: SNAP receptor implicated in vesicle targeting and fusion. Nature 1993;
362:318-324.
Hata Y, Slaughter CA, Südhof TC: Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. Nature 1993; 366:347-351.

2013年10月6日 星期日

「大人の科学マガジン」《大人的科學雜誌》




「大人の科学マガジン」、大人気で中国語版創刊!=台湾メディア







学研教育出版より発売されている、付録つきの人気雑誌「大人の科学マガジン」。中国語版での展開が決まり、台湾では10月8日に発売されるとのこと。現地メディアが報道した。
  日刊紙「中國時報(チャイナ・タイムス)」によると、日本で好評だったタイトルの中国語版ができるそうで、「まずは“35ミリ二眼レフカメラ” と“卓上ロボット掃除機”を、10月に発売。日本から輸入されるキットももれなく付いてくる」そうだ。「例えば“35ミリ二眼レフカメラ”は、カメラの原 理や歴史の紹介に始まり、カメラマンとモデルを招き実際にキットで撮影させるなどしている」と、解説から学んで実践結果も知ることができると内容を紹介し た。
  また8月には西村編集長が台湾を訪問していたことを報告し、「この雑誌のFacebook上のファンの半数が台湾人。数にすると7000人近い のです」というコメントも載せた。特にデザイナーなど、クリエイティブな職業の人々に人気らしい。中國時報は「これまで約40種類が発行され、200万冊 以上の売上げを記録している」と、日本での人気も強調した。
  日本の「大人の科学マガジン」1号の付録は、ポンポン船ジェットボートで2003年4月に発売。それ以前には「大人の科学製品版」として発売し た、からくり人形や電子ブロックが注目され人気を集めた。その後科学キットが付いた雑誌スタイルでの発売が定着しているようだ。学びながら、科学に関連し た品を自分の手で作ることができる楽しさが魅力だ。そして1957年から2010年3月まで発売されていた、小学生向けの学習誌「科学」の大人版という位 置づけで製作されている面もあり、懐かしくて「大人の科学マガジン」を手に取る人もいるだろう。
  台湾ではすでに多くの「大人の科学マガジン」ファンがいるようだが、中国語版で発売されると広く認識され、ファンの拡大が見込める。台湾の一般 の書店に並ぶのか、それともジュンク堂や紀伊國屋といった日系書店に置かれるのかなど、販売方法も気になるところだ。(編集担当:饒波貴子・黄珮君)
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    2013-10-03 01:28
    中國時報
    【林欣誼/台北報導】

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