2020年10月27日 星期二

錢學森 Qian Xuesen 1911~2009

 


学森(せん がくしん、拼音 Qián Xuésēn、ウェード式 Tsien Hsue-shen、1911年12月11日 - 2009年10月31日)は、中華人民共和国の航空力学研究者、中国科学院・中国工程院研究員。五代十国時代の呉越国王銭鏐から数えて33代目の子孫 ...


BBC Future


He helped two superpowers into outer space, but his story is only remembered by one.



BBC.CO.UK
Qian Xuesen: The man the US deported - who then helped China into space
A Chinese rocket scientist helped two superpowers reach the moon, but his story is remembered in only one of them.


2020年10月22日 星期四

張上淳:日本入境的新冠抗原快篩真陽性僅有73%?









台灣輸出日本新冠確診10例?日本抗原快篩的偽陽性有多高?
分類:2019新型冠狀病毒» 疫情災情報導 @2020-10-15 | 22,791 瀏覽數



截至十月十四日,台灣境外檢驗陽性46例,除了檢驗烏龍的菲律賓之外,日本至少驗出10例,但後續PCR檢測多為陰性,指揮中心認為,日方抗原檢查可能有誤差,偽陽性機率高。但不會因為可能是偽陽性而都不管它,這些病例一樣都會做疫調,該隔離該檢調的都會做,有些時間比較長的還會做血清檢測。

新冠病毒診斷的標準檢查是用核酸檢測PCR。但有價錢較貴,需要特殊實驗室還有訓練有素的人員,一直有檢驗量能限制的問題。快篩的好處就是可以在一小時內出來結果,便宜,不需要特別技術還有實驗室,就像驗孕棒一般可以很方便的做出結果來。日本目前入境是都要做採檢的,日本機場也已經從七月開始採用唾液的抗原快篩檢查。但快篩當然也有很多限制,比方說要知道是在檢測抗原還是抗體(採檢時機不同),且快篩品質參差不齊,不同商品有不同的敏感性(sensitivity),在疾病盛行率低的時候會有比較嚴重的偽陽性問題。

這篇就來整理一下日本快篩的種種消息吧!


2020.10.21更新:
日本入境的抗原快篩真陽性僅有73%?
今天的防疫記者會上,張上淳老師有提出前幾天我有提過的日本入境抗原快篩準確度的問題。現在來說清楚一些。

張P:連續看到日本抗原檢測陽性,後續5~7天再驗PCR是陰性的狀況。今天的三例有兩例在出境前有驗PCR陰性。

指揮中心已透過管道拿到日本抗原快篩檢測試劑說明書,內容提到被日本允許使用前的臨床試驗中,以此快篩檢測出的30例陽性個案,經由PCR核酸檢測僅22例陽性,有8個是陰性。代表檢測陽性是真陽性的機率只有73%左右,確實還有很高檢測陽性但不是真陽性的狀況。今日通報新的三例台灣出境前檢驗陰性,到日本卻檢出陽性,可能是偽陽性。

04b解讀:
1.張P說的臨床試驗是總共有325個臨床檢體,拿去做抗原快篩也去做PCR,以PCR當作診斷的黃金標準來看此檢查的準確度。結果如下:

敏感性(sensitivity): 91.4%(22/24 例)將有病者判定為陽性的比率
特異性(specificity): 97.3%(293/301 例)將健康者判定為陰性的比率
偽陽性(false positive rate):2.7% (8/301 例),將健康者判定為陽性的比率,1-特異性
偽陰性(false negative rate):8.6% (2/24 例),將有病者判定為陰性的比率,1-敏感性
陽性預測值(positive predictive value,PPV): 73.3%(22/30 例)判定為陽性中有病者的比率
陰性預測值(negative predictive value,NPV): 99.3%(293/295 例)判定為陰性中健康者的比率

每次遇到這個都很怕還給老師了,要查查書才確定自己沒算錯@@

2.張P今天提的是”檢測陽性是真陽性的機率只有73%左右”。就是上面所說的:陽性預測值PPV。但我們臨床上在描述一個檢驗的精確度通常會用的是敏感性還有特異性,因為這兩個數字不會變化。但是陽性預測值還有陰性預測值會隨著測試母群體的盛行率而有變化,在盛行率很低的時候,測出很多偽陽性,大於真的陽性,會讓你的陽性預測值變低。在盛行率很高的時候,陽性預測值會變高。

3.這325個臨床檢體中PCR陽性是24例,陰性是301例。也就是盛行率是7.4%,這其實算高了。一般從機場入境盛行率大概不會這麼高的場合,那陽性預測值PPV可能會比73.3%還低。

4.不過以快篩試劑而言,敏感性91.4%還有特異性97.3%已經算是很不錯了!很多流感的快篩敏感性可能只有五到七成。









LINSHIBI.PROS.IS
張上淳:日本入境的新冠抗原快篩真陽性僅有73%?
截至十月十四日,台灣境外檢驗陽性46例,除了檢驗烏龍的菲律賓之外,

2020年10月21日 星期三

Nikon、Canon 日系光刻機為何被後起之秀 ASML 超越?



產業的了解也容易或很難。昨天讀了朋友轉的李家同教授談中國半導體業的往下紮根......他拿到中國一張製程的關鍵因素和世界領導廠商圖......其實,這些是半導體產業的幼稚園水準知識......







Technews 科技新報

當今世界光刻機三大製造商是:日本 Nikon、Canon 和荷蘭 ASML,如今 ASML 聲勢更勝其他兩者。
一起看看後發制人的 ASML 是如何邁向成功?



TECHNEWS.TW | 作者:TECHNEWS 科技新報
Nikon、Canon 日系光刻機為何被後起之秀 ASML 超越?
當今世界光刻機三大製造商是:日本 Nikon、Canon 和荷蘭 ASML,日本 Niko

2020年10月18日 星期日

Unmanned boats and drones could repair offshore wind farms and clean up plastic in the sea

 


A team of scientists from the University of Bristol and French-based engineering and science firm Thales are testing technology that will eventually remove the need for humans to carry out the dangerous role

2020年10月8日 星期四

Sir Roger Penrose.Nobel Prize. MOSAIC SOPHISTICATION

When a massive star collapses under its own gravity, it forms a black hole that is so heavy that it captures everything that passes its event horizon. Not even light can escape. At the event horizon, time replaces space and points only forward. The flow of time carries everything towards a singularity furthest inside the black hole, where density is infinite and time ends (see figure).
Roger Penrose – awarded the 2020 Nobel Prize in Physics – invented ingenious mathematical methods to explore Albert Einstein’s general theory of relativity. He showed that the theory leads to the formation of black holes, those monsters in time and space that capture everything that enters them.
Not even Albert Einstein, the father of general relativity, thought that black holes could actually exist. However, ten years after Einstein’s death, the British theorist Roger Penrose demonstrated that black holes can form and described their properties. At their heart, black holes hide a singularity, a boundary at which all the known laws of nature break down.
To prove that black hole formation is a stable process, Penrose needed to expand the methods used to study the theory of relativity – tackling the theory’s problems with new mathematical concepts. Penrose’s ground-breaking article was published in January 1965 and is still regarded as the most important contribution to the general theory of relativity since Einstein.
The 2020 Nobel Prize in Physics has been awarded with one half to Roger Penrose “for the discovery that black hole formation is a robust prediction of the general theory of relativity” and the other half jointly to Reinhard Genzel and Andrea Ghez “for the discovery of a supermassive compact object at the centre of our galaxy.”
Press release: https://bit.ly/309oZqF
Popular information: https://bit.ly/3jjZSJk
Advanced information: https://bit.ly/3kEwwFI
圖像裡可能有顯示的文字是「 Cross section of a black hole When massive collapses under black hati everything passes escape. points forward. singularity inside density is inhnite and time nds. own gravity, captures OBSERVER morizon replaces and erything black hole, where SINGULARITY EVENT HORIZON TIME SINGULARITY SPACE TIME EVENT HORIZON TIME SPACE MATTER FUTURE COLLAPSING STAR PRESENT The cone shows paths backward When horizon PAST horizon, they ©Johan Jarnestad/T forward and black black event toward singularity. outside light event ee further In. nudge No Royal Swedish Academy Sciences 」







羅傑·潘洛斯爵士,OMFRS(英語:Sir Roger Penrose,1931年8月8日),英國數學物理學家牛津大學數學系W. W. Rouse Ball名譽教授。他在數學物理方面的工作擁有高度評價,特別是對廣義相對論宇宙學方面的貢獻。他也是娛樂數學家與具爭議性的哲學家。羅傑·潘洛斯是科學家理昂內·潘洛斯瑪格麗特·雷瑟斯的兒子,為數學家奧利佛·潘洛斯西洋棋大師強納森·潘洛斯的兄弟。

他於2020年獲得諾貝爾物理學獎,因為他發現黑洞的形成有力預測了廣義相對論


Hanching Chung

3人中只知道此君。連我這外行人都買過:Popular publications
The Emperor's New Mind: Concerning Computers, Minds, and The Laws of Physics (1989) 可能有中譯


羅傑·潘洛斯以其於1974年發現潘洛斯鋪磚法著稱,能以兩種磚片非週期性地鋪滿整個平面。於1984年,類似特徵被發現在類晶體中的原子排列。他最重要的貢獻可能是他在1971年發明了自旋網路,爾後在迴圈量子重力理論中成為構成時空幾何的基礎。他在推廣通稱為潘洛斯圖因果圖頗具影響力。


西方藝術中的幾何多半著重空間與比例,但是在其他文化,特別是伊斯蘭、中國和日本,平面幾何藝術則是較為繁盛,尤其是嵌合、拼貼和織錦藝術,通常都會利用緊密複雜的重複圖形,製造精細美麗的視覺效果。

幾何藝術其實就是點、線、面的規律組成,經過幾百年的發展後,「面」與「界」的應用產生了各種繁雜而循環的樣式,有些後來甚至為數學法則證明。一九七四年之前,大家深信嵌合組成的基本樣式只有一、二、三、四、六角對稱,直到牛津大學的數學家羅傑‧潘若斯(Roger Penrose)發現了五角對稱的樣式,才把這種迷思推翻。組成這種樣式的主要成分有二,「菱形」和兩組角各為七十二度和一百四十四度的「鳶形」。鳶形中兩條對角線的比例正好是黃金比例。

潘若斯用這兩種胖「菱形」與瘦「鳶形」的磁磚拼湊出五角對稱,但是儘管看起來很像,事實上五角對稱的圖樣,並不會如同其他對稱那般不斷規律重複,而是會一直變化。

伯斯的西澳大利亞大學的分子化學大樓,中庭地板就巧妙地運用潘若斯的五角對稱概念(見下圖上半部)鋪設地磚。這起先是凱普(David Kepert)、林肯(Frank Lincoln)還有化學學院院長共同的主意,建築師佛格森(Guz Ferguson)則是負責磁磚設計。結果鋪排的圖形從天井中央的五芒星開始,介於電梯和樓梯之間(五芒星在古文明有深遠的意涵)。佛格森用了兩種當地產的水泥磚,分別是瘦長鳶形和菱形。

佛格森用簡單的兩種形狀,舖絮出了奇異而複雜的網狀線條,也讓人見識到幾何世界不可思議的無盡可能性。如此奧秘而複雜的結構,給人的震撼是一般對稱圖形所遠遠不能及的。

盯著這種繁複的圖案一段時間之後,一般都會產生錯覺,覺得自己看到了什麼圖案,像是五芒星、對稱多面體、彎彎曲曲的長條之類。立體感錯覺也常常在這時候介入搗亂,讓人覺得看見了凹凸立體的形狀,但事實上圖形的表面是完全平坦的,就像是瑞士結晶學家奈克(Necker)一八三二年著名的凹凸方塊為例。

早期拼磚藝術家們多半會利用這種錯覺,以顏色、質料不同的磚瓦製造立體效果,並在其間留下空隙作為勾邊。早在一五二四年德國藝術家杜赫(Albrecht Dürer)讓人困惑的作品中,就可以看到這種傾向。把某些區塊塗黑之後,帶有立體感的圖形看起來順眼多了,因為它們看起來就是像立體方塊。儘管原本的作品上並沒有標明陰影,但是我們看到的時候就是忍不住會「覺得」那是立體的。

同樣地,西澳大利亞大學的拼磚也沒有任何呈現立體感的深淺著色,因為那樣做會把視覺效果變得太明顯而讓人不舒服。不過就算沒有深淺色差,看到的人還是忍不住會覺得它是立體的,抗拒這種錯覺反而比較困難。



K. Dudley and M. Elliff

MOSAIC SOPHISTICATION A quasi-crystalline Penrose pattern at the Darb-i Imam shrine in Isfahan, Iran.

Published: February 27, 2007

In the beauty and geometric complexity of tile mosaics on walls of medieval Islamic buildings, scientists have recognized patterns suggesting that the designers had made a conceptual breakthrough in mathematics beginning as early as the 13th century.

Science

A piece from a mausoleum in Turkey.

W. B. Denny

A pattern taken from a Turkish mosque.

A new study shows that the Islamic pattern-making process, far more intricate than the laying of one's bathroom floor, appears to have involved an advanced math of quasi crystals, which was not understood by modern scientists until three decades ago.

The findings, reported in the current issue of the journal Science, are a reminder of the sophistication of art, architecture and science long ago in the Islamic culture. They also challenge the assumption that the designers somehow created these elaborate patterns with only a ruler and a compass. Instead, experts say, they may have had other tools and concepts.

Two years ago, Peter J. Lu, a doctoral student in physics at Harvard University, was transfixed by the geometric pattern on a wall in Uzbekistan. It reminded him of what mathematicians call quasi-crystalline designs. These were demonstrated in the early 1970s by Roger Penrose, a mathematician and cosmologist at the University of Oxford.

Mr. Lu set about examining pictures of other tile mosaics from Afghanistan, Iran, Iraq and Turkey, working with Paul J. Steinhardt, a Princeton cosmologist who is an authority on quasi crystals and had been Mr. Lu's undergraduate adviser. The research was a bit like trying to figure out the design principle of a jigsaw puzzle, Mr. Lu said in an interview.

In their journal report, Mr. Lu and Dr. Steinhardt concluded that by the 15th century, Islamic designers and artisans had developed techniques "to construct nearly perfect quasi-crystalline Penrose patterns, five centuries before discovery in the West."

Some of the most complex patterns, called "girih" in Persian, consist of sets of contiguous polygons fitted together with little distortion and no gaps. Running through each polygon (a decagon, pentagon, diamond, bowtie or hexagon) is a decorative line. Mr. Lu found that the interlocking tiles were arranged in predictable ways to create a pattern that never repeats — that is, quasi crystals.

"Again and again, girih tiles provide logical explanations for complicated designs," Mr. Lu said in a news release from Harvard.

He and Dr. Steinhardt recognized that the artisans in the 13th century had begun creating mosaic patterns in this way. The geometric star-and-polygon girihs, as quasi crystals, can be rotated a certain number of degrees, say one-fifth of a circle, to positions from which other tiles are fitted. As such, this makes possible a pattern that is infinitely big and yet the pattern never repeats itself, unlike the tiles on the typical floor.

This was, the scientists wrote, "an important breakthrough in Islamic mathematics and design."

Dr. Steinhardt said in an interview that it was not clear how well the Islamic designers understood all the elements they were applying to the construction of these patterns. "I can just say what's on the walls," he said.

Mr. Lu said that it would be "incredible if it were all coincidence."

"At the very least," he said, "it shows us a culture that we often don't credit enough was far more advanced than we ever thought before."

From a study of a few hundred examples, Mr. Lu and Dr. Steinhardt determined that the technique was fully developed two centuries later in mosques, palaces, shrines and other buildings. They noted that "a nearly perfect quasi-crystalline Penrose pattern" is found on the Darb-i Imam shrine in Isfahan, Iran, which was built in 1453. The researchers described how the architects there had created overlapping patterns with girih tiles at two sizes to produce nearly perfect quasi-crystalline patterns.

In the report, Mr. Lu and Dr. Steinhardt said the examples they had studied so far "fall just short of being perfect quasi crystals; there may be more interesting examples yet to be discovered."

In a separate article in Science, some experts in the math of crystals questioned if the findings were an entirely new insight. In particular, Emil Makovicky of the University of Copenhagen in Denmark said the new report failed to give sufficient credit to an analysis he published in 1992 of mosaic patterns on a tomb in Iran.

Mr. Lu and Dr. Steinhardt said they regretted what they called a misunderstanding. They pointed out that the length of their report was strictly enforced by journal editors, but it did include two footnotes to Dr. Makovicky's research. None of the referees or editors who reviewed the paper, Dr. Steinhardt said, asked for more attention to the previous research.

Although their work had some elements in common with Dr. Makovicky's, Dr. Steinhardt said in an interview that their research dealt with not one but a "whole sweep of tilings" interpreted through a few hundred examples.

The article quoted two other experts, Dov Levine and Joshua Socolar, physicists at the Israel Institute of Technology in Haifa and Duke University, respectively, as agreeing that Dr. Makovicky deserved more credit. But, the article noted, they said the Lu-Steinhardt research had "generated interesting and testable hypotheses."



2020年10月5日 星期一

The unsung mapmakers behind the Johns Hopkins COVID-19 dashboard








Johns Hopkins University

Behind the scenes of our renowned #COVID19 dashboard are teams working around the clock to support it. Here's their story.



HUB.JHU.EDU
The unsung mapmakers behind the Johns Hopkins COVID-19 dashboard
The Johns Hopkins COVID-19 dashboard requires an array of behind-










THE UNSUNG MAPMAKERS
The Johns Hopkins COVID-19 dashboard requires an array of behind-the-scenes expertise from staff at multiple divisions, selflessly working at all hours. Here's their story.


ByKatie Pearce / Published 13 hours ago

In the early days of managing the Johns Hopkins COVID-19 dashboard, experts at the university and those at Esri, the company providing the mapping software for the real-time pandemic tracker, had a friendly rivalry.

"They would tell us, 'Oh, your COVID map is big, but not as big as our Pokémon Go map,' which was their most in demand," says Reina Murray, an application administrator at JHU's Sheridan Libraries.

By March, the volume of web traffic to the Hopkins map effectively shut down that conversation—the Hopkins dashboard now holds the record as Esri's highest-used service of all time, drawing hundreds of millions of feature requests every day. At a peak in March, the dashboard saw 4.56 billion feature requests.

For Johns Hopkins, the dashboard has been a groundbreaking endeavor, pooling the collaborative energy of specialists across the university—software developers, systems engineers, data scientists, mapping experts, digital curators—who may never have crossed paths otherwise but now coordinate shifts around the clock and keep in touch constantly through Zoom and Slack.

"We're all one big happy Blue Jay family, working together to answer a set of key questions, globally and domestically, around the progression of this virus," says Aaron Katz, supervisor of the large-scale analytic systems group at the Applied Physics Laboratory.

 Katz's team at APL typically works with complex datasets for large government projects, in areas like global health security. The team from Sheridan Libraries supports data-intensive scholarship: collecting, sharing, visualizing, and preserving digital research and collections, spanning areas from humanities to engineering. For the COVID-19 project, many of these experts have rearranged their work—if not entirely tilted their careers—around the shared behemoth, gathering coronavirus data from across the globe and presenting it to the public.

The larger project also now includes a U.S. map following the pandemic down to the county level, and an array of data visualizations from JHU's Centers for Civic Impact, tracing trends like racial disparities and policy impacts from the virus. The project is supported by funding from the Bloomberg Philanthropies and the Stavros Niarchos Foundation.

"If you want to produce something of this kind of high quality and integrity, it really does take a lot of people," says Sayeed Choudhury, associate dean for research data management at the Sheridan Libraries, which supports software logistics for the dashboard.



Image caption:In March, when this photo was taken, the team's map was the only global resource for tracking the spread of the pandemic in real time

IMAGE CREDIT: WILL KIRK / JOHNS HOPKINS UNIVERSITY

The original global map—developed by Lauren Gardner and PhD student Ensheng "Frank" Dong of JHU's Center for Systems Science and Engineering—went viral almost as soon as it launched on Jan. 22. Dong constructed the dashboard using Esri's ArcGIS mapping platform, at first entering data manually. That quickly proved unsustainable as coronavirus cases spilled out of mainland China onto every continent.

The APL team came on board to streamline the data-entry process. "We've built an automated infrastructure that goes out and pulls the coronavirus data from around the globe," Katz says.

APL's system now collects confirmed reports of coronavirus cases and deaths from nearly 200 data sources, including the World Health Organization and international and local health agencies. For the U.S. map, the system draws from state- and county-level reports, and sometimes local news outlets that supply machine-readable data.

A number of team members from the different divisions vet those data sources before they're integrated into the system. "A lot of time and energy goes into finding the right data sources, assessing their validity, and creating ways to harmonize them with our system and present them to the public," Choudhury says.



Image caption:Ensheng "Frank" Dong

IMAGE CREDIT: WILL KIRK / JOHNS HOPKINS UNIVERSITY

APL's software platform processes the data in near real time, as soon as sources post it on their own websites. Anomalies do arise, but the system is designed to catch them. "We're able to spot large discrepancies," says Tamara Goyea, an APL senior data scientist. "For example, if a state reports 20 deaths one day and the next day two deaths, our system flags that and we look into it."

A small team at the Sheridan Libraries, including Murray and Choudhury, works to support this massive data infrastructure, which includes managing the ongoing relationship with Esri. Hopkins researchers have used the company's ArcGIS tools for years for a range of internal projects—tracking everything from Baltimore food deserts to Frederick Douglass' travels—but the COVID-19 dashboard brought the software into a public realm of unprecedented scale.

While absorbed with time-consuming minutiae behind the scenes of the dashboard, the team members never lose sight of their larger mission: providing a critical public service during a global health crisis, one that informs research, policymaking, and individual decisions. The Hopkins dashboard has become a ubiquitous and trusted reference point, cited by U.S. federal agencies and major news sources including The Washington Post and The Wall Street Journal. The National Science Foundation awarded $200,000 to the effort in April, and recently Esri honored the project with its "Making a Difference" award. For her role, Gardner was named one of the 100 most influential people in the world by TIME magazine.

"This is the most impactful work that I've participated in to date," Goyea says. "That's what drives the team—we're trying to provide information about a pandemic that's affecting so many people in so many areas. For us to contribute some kind of understanding, and help with some kind of decision making, that's our whole objective."

Everyone involved acknowledges that the dashboard numbers provide a partial picture of the pandemic's true reach, given unknowns from cases that are asymptomatic, unreported, or untested.

"We can't tell you exactly how many cases there are in the state of Maryland right now, but we can tell exactly you what the state of Maryland is reporting," Katz says. "We are bound by the accuracy of our reporting sources, and we do our absolute best to vet those sources and do quality control."

Ten years from now, Katz imagines, "we'll see all the reports and retrospectives that will tell us exactly what happened and where" with the pandemic. But for now, he says, "we're trying to solve this problem of situational awareness in the present moment."


評李開復先生的一次談話Time100 Talks With Kai-Fu Lee

 

Time100 Talks With Kai-Fu Lee | TIME

hc:

實際上,此番沒多少新意。他說Superpower 一書出版二年來的中美產業重點之分,是虛的,也非重點。樂觀的只是應用,而這方面,各國政府/人民願接受的風險/不完美,而非技術的突破,例如自動駕駛,美國可能領先,但其政府/人民的安全要求相對中國高.....。


李開復及許多人認為 data 越多越好,原則如此,然而這是迷思,我不相信12000萬和20000萬的用戶一定約1.2 比2的AI 學習效能,重點是AI 被後的學習理論,學習的質,而非量。



Ben Chen


四個月前, 李開復在北京的訪談



YOUTUBE.COM
Time100 Talks With Kai-Fu Lee | TIME
AI expert Kai-Fu Lee said the U.S. has started to catch up to China on the adoption of Artificial Intelligence technology. Speaking at TIME100 Talks event, h...

Harvey J. Alter,Michael Houghton和Charles M. Rice 2020年諾貝爾生理學或醫學獎 發現丙型肝炎病毒

 2020年諾貝爾生理學或醫學獎

共同

Harvey J. Alter,Michael Houghton和Charles M. Rice

用於發現丙型肝炎病毒

概要

今年的諾貝爾獎授予了三位科學家,他們在與血源性肝炎的鬥爭中做出了決定性的貢獻。血源性肝炎是導致世界各地人們肝硬化和肝癌的主要全球性健康問題。

Harvey J. Alter,Michael Houghton和Charles M. Rice做出了開創性發現,從而鑑定出一種新型病毒,即丙型肝炎病毒。在開展工作之前,發現甲型和乙型肝炎病毒是向前邁出的關鍵步驟,但大多數血源性肝炎病例仍無法解釋。丙型肝炎病毒的發現揭示了剩餘的慢性肝炎病例的病因,並使血液檢測和新藥成為可能,挽救了數百萬人的生命。

肝炎–對人類健康的全球威脅

肝炎或肝炎,是希臘語中“肝和炎症”的組合詞,主要是由病毒感染引起的,儘管酗酒,環境毒素和自身免疫性疾病也是重要的原因。在1940年代,很明顯有兩種主要類型的傳染性肝炎。第一種稱為甲型肝炎,是通過污水或食物傳播的,通常對患者幾乎沒有長期影響。第二種是通過血液和體液傳播的,它代表著更為嚴重的威脅,因為它會導致慢性疾病,並發展為肝硬化和肝癌(圖1)。)。這種形式的肝炎是隱性的,因為否則健康個體可以在嚴重並發症出現之前靜默感染多年。血源性肝炎與高發病率和高死亡率相關,每年在世界範圍內造成超過一百萬的死亡,因此使其成為與HIV感染和結核病相當的全球性健康問題。

病毒性肝炎

圖1肝炎有兩種主要形式。一種形式是由甲型肝炎病毒引起的急性疾病,這種病毒是由受污染的水或食物傳播的。另一種形式是由乙型肝炎病毒或丙型肝炎病毒引起的(今年的諾貝爾獎)。這種形式的血源性肝炎通常是一種慢性疾病,可能會發展為肝硬化和肝細胞癌。

未知的傳染源

成功干預傳染病的關鍵是確定病原體。在1960年代,Baruch Blumberg確定一種形式的血源性肝炎是由一種被稱為乙型肝炎病毒的病毒引起的,這一發現導致了診斷測試和有效疫苗的發展。由於這一發現,布倫伯格被授予1976年諾貝爾生理學或醫學獎。

當時,美國國立衛生研究院的Harvey J. Alter研究了接受輸血的患者中肝炎的發生情況。儘管對新發現的乙型肝炎病毒進行的血液檢查減少了與輸血有關的肝炎的病例數,但Alter及其同事令人擔憂地證明仍有大量病例存在。大約在這段時間也進行了甲型肝炎病毒感染的檢測,很明顯,甲型肝炎不是這些原因不明的原因。

令人擔憂的是,大量輸血者由於未知的傳染原而患上了慢性肝炎。Alter和他的同事表明,這些肝炎患者的血液可以將疾病傳播給黑猩猩,這是人類之外唯一的易感宿主。隨後的研究還表明,未知的傳染原具有病毒的特徵。Alter的方法研究以這種方式定義了一種新型的,獨特形式的慢性病毒性肝炎。這種神秘的疾病被稱為“非甲,非乙”肝炎。

丙型肝炎病毒的鑑定

現在,鑑定新型病毒是當務之急。儘管使用了所有傳統的病毒搜尋技術,但儘管如此,病毒仍無法隔離已有十多年的歷史。在Chiron製藥公司工作的Michael Houghton進行了分離病毒遺傳序列所需的艱鉅工作。霍頓和他的同事們從感染黑猩猩血液中發現的核酸中提取了DNA片段。這些片段大部分來自黑猩猩本身的基因組,但研究人員預測,其中一些片段將來自未知病毒。假設從肝炎患者的血液中會存在針對病毒的抗體,研究人員使用患者血清來鑑定克隆的編碼病毒蛋白的病毒DNA片段。經過全面搜索,發現了一個陽性克隆。進一步的工作表明,該克隆源自一種新型的RNA病毒,屬於黃病毒家族,它被命名為丙型肝炎病毒。慢性肝炎患者中抗體的存在強烈暗示了這種病毒是缺少的因素。

發現摘要

圖2本年度諾貝爾獎授予的發現摘要。Harvey J. Alter進行的輸血相關性肝炎的方法研究表明,未知病毒是導致慢性肝炎的常見原因。邁克爾·霍頓(Michael Houghton)使用未經測試的策略來分離名為丙型肝炎病毒的新病毒的基因組。查爾斯·賴斯(Charles M. Rice)提供了最後證據,證明僅丙型肝炎病毒即可引起肝炎。

丙型肝炎病毒的發現具有決定性意義。但是,這個難題的一個基本要素卻沒有得到解決:僅病毒本身就能引起肝炎嗎?為了回答這個問題,科學家不得不研究克隆的病毒是否能夠複製並引起疾病。聖路易斯華盛頓大學的研究員查爾斯·賴斯(Charles M. Rice)以及其他研究RNA病毒的小組指出,丙型肝炎病毒基因組末端的一個先前未知的區域,他們懷疑這可能對病毒複製很重要。賴斯還觀察到分離出的病毒樣本中的遺傳變異,並假設其中一些可能會阻礙病毒複製。通過基因工程,賴斯產生了丙型肝炎病毒的RNA變異體,其中包括病毒基因組的新定義區域,並且沒有失活的遺傳變異。將這種RNA注射到黑猩猩的肝臟中後,在血液中檢測到病毒,並觀察到與慢性病患者相似的病理變化。這是僅丙型肝炎病毒可能導致無法解釋的輸血介導的肝炎病例的最終證據。

這一獲得諾貝爾獎的發現的意義

諾貝爾獎獲得者發現丙型肝炎病毒是正在進行的與病毒性疾病鬥爭的里程碑式成就(圖2)。由於他們的發現,現在可以對該病毒進行高度敏感的血液檢查,並且這些檢查基本上已經消除了世界許多地方的輸血後肝炎,從而大大改善了全球健康狀況。他們的發現還使針對丙型肝炎的抗病毒藥物得以快速發展。歷史上首次可以治愈該病,這為從世界人口中根除丙型肝炎病毒帶來了希望。為了實現這一目標,將需要國際努力以促進血液測試和在全球範圍內提供抗病毒藥物(圖3)。

圖3三位諾貝爾獎獲得者的發現允許設計敏感的血液測試,從而消除了世界上大部分地區通過輸血傳播的肝炎的風險。這一突破也使開發可以治愈該疾病的抗病毒藥物成為可能。丙型肝炎仍然是全球主要的健康問題,但是現在存在消除這種疾病的機會。

 

重點出版物

Alter HJ,Holland PV,Purcell RH,Lander JJ,Feinstone SM,Morrow AG,Schmidt PJ。排除商業和乙型肝炎抗原陽性供體後的輸血後肝炎。安實習生1972年;77:691-699。

Feinstone SM,Kapikian AZ,Purcell RH,Alter HJ和Holland PV。與輸血相關的肝炎不是由於A型或B型病毒性肝炎引起的。N Engl J Med1975年;292:767-770。

Alter HJ,Holland PV,Morrow AG,Purcell RH,Feinstone SM,Moritsugu Y.與輸血相關的肝炎的臨床和血清學分析。柳葉刀1975年;2:838-841。

Alter HJ,Purcell RH,Holland PV,PopperH。非甲非乙型肝炎的可傳播藥物。柳葉刀。1978年;1:459-463。

Choo QL,Kou G,Weiner AJ,Overby LR,Bradley DW,HoughtonM分離源自血源性非A,非B病毒性肝炎基因組的cDNA克隆。科學1989年;244:359-362。

Kuo G.,Choo QL,Alter HJ,Gitnick GL,Redeker AG,Purcell RH,Miyamura T,Dienstag JL,Alter CE,Stevens CE,Tegtmeier GE,Bonino F,Colombo M,Lee WS,Kuo C.,Berger K, Shuster JR,Overby LR,Bradley DW,HoughtonM一種針對人非甲非乙型肝炎主要病原性病毒的循環抗體的測定方法。科學。1989年;244:362-364。

Kolykhalov AA,Agapov EV,Blight KJ,Mihalik K,Feinstone SM,Rice CM通過肝內接種轉錄的RNA傳播丙型肝炎。科學1997; 277:570-574。

 

Harvey J. Alter於1935年出生於紐約。他在羅切斯特大學醫學院獲得醫學學位,並在斯特朗紀念醫院和西雅圖大學醫院接受內科醫學培訓。1961年,他加入國立衛生研究院(NIH),擔任臨床助理。他在喬治敦大學(Georgetown University)工作了幾年,然後於1969年返回NIH,加入了臨床中心輸血醫學系,擔任高級研究員。

邁克爾·霍頓Michael Houghton)出生於英國。他於1977年從倫敦國王學院獲得博士學位。他於1982年加入GD Searle&Company,之後於1982年移居加利福尼亞州埃默里維爾的Chiron公司。他於2010年移居艾伯塔大學,目前是加拿大傑出病毒學研究主席和李嘉誠病毒學教授,在艾伯塔大學任教。他還是李嘉誠應用病毒學研究所所長。

查爾斯·賴斯Charles M. Rice)於1952年出生在薩克拉曼多。他於1981年在加州理工學院獲得博士學位,並於1981年至1985年期間接受了博士後培訓。他於1986年在聖路易斯華盛頓大學醫學院成立了研究小組,並於1995年成為正式教授。自2001年以來,他一直擔任紐約洛克菲勒大學的教授。在2001年至2018年期間,他一直是洛克菲勒大學丙型肝炎研究中心的科學與執行主任,並一直活躍在該中心。

 

插圖:©諾貝爾生理學或醫學委員會。插圖畫家:MattiasKarlén


-itis
Pronunciation: /ˈʌɪtɪs/

Definition of -itis in English:

suffix

1Forming names of inflammatory diseases:cystitishepatitis
音節
  
hep • a • ti • tis
  
発音
  
hèpətáitis
  
レベル
  
社会人必須
  1. [名][U]《病理(学)》肝臓炎,肝炎
    • hepatitis A [B]
    • A[B]型肝炎.

The 2020 Medicine Laureates
2020年諾貝爾醫學獎桂冠得主
獲獎因由:"... for the discovery of Hepatitis C virus"
2020年的諾貝爾生醫獎頒給了 Harvey J. Alter,Michael Houghton 和 Charles M. Rice,表彰他們發現了 C 型肝炎病毒。