From His Eyes Only

As promised, Here I give you the movie "From His Eyes Only"!

It was made for Marc's 60th birthday on 2003. At that time, the K lab was still in cell biology department where Marc was the chair. Many events in it were not made up but based on real things happened before, at least that is what I was told.

You will see some big names in it, including cross dressed Tim dancing around. Both Marc and Tim speak in very unique ways. Mimicking those two speaking to each other is always a fun and popular activity in our department, as shown in the frog room in the movie.

I have thought about sharing this funny movie for a while, but the concern on drawing "close" people here keeps me from doing it. So, if you "really" like to show this movie to someone, you can use the link to Google video instead.

http://video.google.com/videoplay?docid=5781157539807455730&hl=en

Enjoy and have a nice weekend!

From His Eyes Only

In case you are confused, the woman who helped Marc for everything is Marc's sectary.

Bitch Is the New Black !

Awesome clip from Tina Fey in SNL!

Tina Fey was the head writer and also the first female one of SNL.

Bitch is the new black

Tina Fey:

And maybe what bothers me the most is that people say that Hillary is a bitch. And let me say something about that: yeah, she is, and so am I. And so is this one (pointing at Amy Poehler). And you know what, bitches get stuff done. That’s why Catholic schools use nuns as teachers and not priests. Those nuns are mean old clams, and they sleep on cots and are allowed to hit you. And at the end of the school year, you hated those bitches, but you knew the capital of Vermont. So, I’m saying it’s not too late Texas and Ohio. Get on board. Bitch is the new black!

SNL also addressed the obvious biased treatment from press given to Obama and Clinton.

BioNumber Show

The new projecting work in our department, from the BioNumber which is established by people in our department.

Biking

這幾天又下雪了，沒法出去玩，帶著凡凡到地下室活動活動。

車牽出來，得先把輪子的氣打足，凡凡又想自己來了。


擺個姿勢拍張照，可惜現在的腿還不夠長，只能擺擺樣子，得要人在後面推才能前進。

Mitchisonisms

Someone wrote and put this on our intranet.

Mitchisonisms
=============

I prefer knowledge independent of approaches, because I lack knowledge.

90% of the literature is crap anyway.

Oh xxxx... How is the paper going?

Fluorescein? I take that back, this is a horrible experiment.

Duplication of small GTPases is not rate limiting for evolution.

You can't build a career on cytoplasm.

Robust Design and Biology

Friday, the day for lunch with theories.

Today we had another speaker from MIT. Different to the one last week, Gerald Jay Sussman gave a very good presentation.

Gerald is an expert in computer science. His talk was to explain how people make artificial systems robust, and what is different compared with biological systems.

"Robust" is a hot term in systems biology. Gerald started from its definition in computer science - when you are building a system, "robustness" means you won't get any unpredictable result; thus you have a robust system.

In order to make the system robust, programmers usually discards many information which could be valuable. Sometimes it leads to a totally wrong result. Using "floating-point calculation" as an exmaple.

Asking a floating-point processor to average 0.998 and 0.996.

If the processor can only handle 3 digits, it will work like this:

0.998 -> 998 x 10^(-3) ==> 3 digids

0.996 -> 998 x 10^(-3) ==> 3 digits

0.998+0.996 = 1.994 x 10^(-3) ==> 4 digits,

floating point to 1.99 x 10^(-3) ==> 3 digits

(1.99 x 10^(-3)) / 2 = 0.995 ==> 3 digits

Now you get the average 0.995 which is not even between 0.998 and 0.996.

This seemed to be a classic joke in computer science, because a small population of people always responded these kind of joke immediately by first few words.

What surprised me most, is Gerald really knows biology, amazing. He thinks the artificial system still have its robustness in a very different way to biology systems, i.e. removing anything it cannot handle or explain. Thus the user-end feels fine without knowing anything inside the box.

I feel it's like the old modeling question, basically you need several assumptions to elimate factors which could bring you troubles. By doing that, it is in a risk moving one step further away from the real.

--

Robust design and biology
22 February 2008

Gerald Jay Sussman
Computer Science and Artificial Intelligence Laboratory
MIT

Abstract
It is hard to build robust systems: systems that have acceptable behavior over a larger class of situations than was anticipated by their designers. The most robust systems are evolvable: they can be easily adapted to new situations with only minor modification. How can we design systems that are flexible in this way?

Observations of biological systems tell us a great deal about how to make robust and evolvable systems. Techniques originally developed in support of symbolic Artificial Intelligence can be viewed as ways of enhancing robustness and evolvability in programs and other engineered systems. By contrast, the common practice of computer science actively discourages the construction of robust systems.

Robust designs are built on an additive infrastructure: there are exposed interfaces for attaching new functionality without serious disruption of preexisting mechanisms. Indeed, the ability to harmlessly duplicate a mechanism and then modify the copy to supply useful new functionality is one of the principal ploys appearing in natural evolution. What are the preconditions that support such augmentation? Can we engineers arrange our systems to be extensible in this way? Are there exploitable analogies between the techniques that we have created to make extensible artifacts and the mechanisms that we find in biological systems?

I will try to address these and related issues.

Lab Reagent Helping List

Someone in our department just came out a very good idea, called laphelp mailing list. Just thought maybe someone will be interested doing similar things in his/her own institutes.

--

Dear all!

Everyone knows how frustrating it is when you are halfway through your experiment, and you find out that one of the (common) reagents is out. Or you're looking for someone who has experience with a technique that you want to set up. Or you're looking to get that particular vector that is crazy expensive from Invitrogen, and not available from the common stocks, but that you really would like to have.

For these purposes I have set up the mailing list "labhelp". Anyone who is a member of this list can email the list with questions about reagents, techniques or other lab-related business. These emails will be sent to all your colleagues in the list throughout the department (for the time being). If the system works well, I plan to expand it to more departments.

The advantages are obvious:

- You get your reagents quickly
- It will improve interaction between the different groups (and departments)
- It will save loads of money
- It will improve your experiments
- Etc etc.

The only action YOU have to take for all these advantages is to send your email address to me, so that I can add you to this list. Only people on this list can email to and receive email from this list!

I hope you'll like this initiative and want to be part of it! Please let me know if you have suggestions to exchange lab-related knowledge within the department and between other departments.

--

On the Process of Becoming a Great Scientist

Days ago I read a correspondence from a PLoS journal which talked about how to become a great sceintist. I know its title is a cliche. But I really like this one and feel it is the best one among tons of similar articles.

On the Process of Becoming a Great Scientist
[PDF file]

Richard Hamming's talk in Bell Lab - "You and Your Research", probably is the best known and most famous one under this category. However, I feel it is too long and a little bit out of date. I think this one in PLoS is more close to the real situation nowadays and more helpful, too.

Here are several points mentioned in it:
1. Don't worry about age, worry about being exposed to new ideas
2. Tinker
3. Take risks
4. Enjoy your work
5. Learn to say "No!"
6. Learn to enjoy the process of writing and presenting
7. See the big picture and keep in mind

Point #4 is a no brainer. My personal feeling is point #2, #3, and #7 are especially helpful and important for students and any beginner in sciences.

I'll recommend students (especially in TW) read this article and really try to follow it on own researches.

Naughty Chair

Naughty chair，從電視節目 Super Nanny 看來的，簡單講這是外國人替待體罰的方式，找個固定的角落或位子，一旦小孩不聽話犯了錯，就要他們坐在那個地方十分鐘，如果小孩子中途離開，就抓回去重新計時一次。節目裡面一堆調皮搗蛋的小孩子，只要 super nanny 一聲令下要他們去坐 naughty chair，每一個都嚇得屁滾尿流乖得跟甚麼一樣。


昨天凡凡又把他的故事書從書架上全部翻了下來，凡凡的媽媽看到了便要凡凡去坐 naughty chair！

凡凡聽到也很帥氣，乖乖地走到我們幫他選好的小角落，一屁股坐了下去，吭都沒吭。好像很有效喔？



凡凡很聽話，一直到最後凡凡媽媽要他起來才離開，沒有中間就跑走。不過好像情況好像完全不是像電視上那麼回事。凡凡坐著不但沒有嚇得屁滾尿流，表示再也不敢了，反而樂在其中，頭手腳還跟著電臺音樂打起拍子來，跟電視上演的完全不一樣嘛！以後再也不看 supernanny or nanny 911 了。

Movie List

It's been a long time I didn't update my movie list.

While several movies were crossed on my list, I felt many other good ones (from my point of view) I had were missed on that non-updating movie list.

Therefore, I decided to list my watched movies here, no matter it is on the list or not. I won't discuss it in details, but only say I like it or not.

I spent lots of time on movies this weekend.

1. 投名狀 (The Warlords)
It is good, my version is the mainlad version; heard the TW/HK version is better and more complete.

趙二虎's personality addressing is the weakest link in the movie.

2. Surf's Up
Not good at all, even FanFan who loves to watch cartoon didn't want to watch this one and went away in the middle.

3. In the Land of Women
Three reasons I watched this movie:
1. Kristen Stewart
2. Kristen Stewart
3. Kristen Stewart

4. Superbad
A good one, funny but full of F words.

5. Thank You for Smoking
A very good one. I like this movie and the way it addresses the anti-smoking issue in real life.

6. Jeux d'enfants (Love Me If You Dare)
I love this French movie a lot. It might be a follower to the success of Amelie, but I really think it came with its own style in the movie.

It was the #1 blockbuster in France at 2003. Surprisingly many U.S. critists gave it very bad comments, but feedbacks from COMMON people in real world were good acturally. I love this movie and will recommend it to my friends anyway.

English Trailer


The movie is about two childhood friends Julien and Sophie who have a seriously troubled relationship because they keep daring each other to do more and more outrageous things, especially to get back at each other. The phrase "cap ou pas cap ?" came up a million times. "Cap, pas cap" is a game in France, played by kids. Kids dare each other saying "Cap, pas cap", and you answer cap, you must do it.

French Trailer - I think this one is better edited than the English one.

It's Never Too Early to Study Systems Biology !

家裡有幾本關於 systems biology 的書(見「Books I'm Reading」)，這本紅皮的其實還不錯，只是原作是日文，翻成英文之後讀起來有點痛苦。

凡凡大概一堆有趣又色彩豐富的童書看煩了，決定改看些「無趣」許多的書，選擇了這本紅皮的 "Life - An Intriducion to Complex Systems Biology"，看得有模有樣地。


過了一陣子，果然發現電腦空著，心想上 PTT 比較有趣，就把書本拋下改做鄉民。很可以理解的決定。

打保齡球

凡凡有一套保齡球玩具，最近越來越感興趣，每次只要一拿出來玩，就不肯讓人收好放回去。

凡凡現在「打」保齡球的方法大概是介於保齡球跟棒球之間，拿球去砸球瓶。雖然凡凡知道可以用滾的，也會滾球，但還是喜歡用丟的。

FYI，凡凡嘴裡一直講的是「球球」。


不只保齡球，甚麼東西凡凡都可以拿來玩。

How T cells 'see' antigen

It is Friday, the theory lunch time. I chatted with several people before the talk. Found we all liked the talk given by the Pfizer guy last week.

Today's speaker, Professor Arup Chakraborty, is coming from our dearest one-way rivalry neighbor, MIT. He wanted to talk about how the selection between APC and T cells can work as digitalized behavior, that is, bistability, either on or off; and models control the bistable senstivity threshold.

The topic is interesting, I will say. However, the speaker presented it with a less interesting way spending more than half of the time "teaching" the related mechansims which probably most of the people in the room had it learnt from the textbook already.

He found the Sos proteins might be the key protein to control such bistable behavior and did some simulations to confirm it. I don't know, maybe this piece of information is interesting to some people in similar fields. The talk then came to a point which I cannot stand anymore, so I left the room early.

(at least I had my stomach fulled!)

--

How T cells 'see' antigen
15 February 2008

Arup Chakraborty
Laboratory for Computational Immunology
Departments of Chemistry, Chemical and Biological Engineering
MIT

Abstract
The orchestrators of adaptive immunity are a class of cells called T lymphocytes(T cells). They express T cell receptor (TCR) molecules on their surface, which recognize molecular signatures of pathogens. Each T cell expresses a distinct TCR, which can bind to short peptides (p) derived from pathogenic proteins associated with products of the major histocompatibility (MHC) genes; these pMHC molecules are expressed on antigen presenting cells. Sufficiently strong TCR-pMHC binding results in T cell activation. TCR bind weakly to endogenous pMHC molecules, thereby preventing frequent autoimmune responses. After briefly outlining how T cells detect minute numbers of pathogen-derived pMHC molecules, I will focus on how the specific, diverse, and self-tolerant T cell repertoire is designed in the thymus. I will detail how an approach that brings together theoretical and computational studies (rooted in statistical physics) with genetic, biochemical, and imaging experiments has allowed us to shed light on the pertinent mechanistic principles.

--

剪頭髮

凡凡的頭髮又長了，年前沒有時間理，趁過年休息的時候把凡凡的頭髮給剪一剪。

凡凡坐在 high chair 上，專心地看著他的湯馬士小火車，一點兒都不吵鬧，令人意外的合作，十分順利。


不過等到換成要用電剪的時候，凡凡就開始會怕了，不時回頭看；跟凡凡的爸爸一樣，凡凡爸爸小時候也是一直不敢給人用電動剪刀理髮，一直到國中。


成果，小瓜呆髮型。

馬‧凡凡

凡凡現在可以爬上爬下，家裡已經沒有多少地方是絕對安全凡凡搆不著的了。我們怕危險把角落的櫃子移開，新換的櫃子較矮，凡凡爬得更高興，三不五時站在上面，沙發與櫃子間的空隙也毫無問題跨來跨去，如履平地。



凡凡很喜歡牆上掛著的照片，那是凡凡滿三個月的時候拍的 (2006/07/13)；先唸出「馬」，一臉得意狀，然後再指出裡面的人是凡凡。


不過凡凡現在大概還不是很清楚，可能以為所有四隻腳的動物都叫作馬的樣子。因為只要是在水裡的動物，就算是螃蟹凡凡也會說那是「魚」，天上飛的，除了飛機和雲他知道不是動物，叫得出來之外，幾乎都叫做「鴨鴨」。

畫重點

凡凡現在喜歡畫圖，或許是常看到凡凡的爸爸在家裡拿著紅筆對著 paper 畫呀畫的，凡凡現在最愛把 paper 翻出來然後如擬拿著紅筆也在上面東畫西畫。弄到最後現在幾乎每一份凡凡爸爸的 paper 上面都有凡凡幫忙「畫過的重點」。

凡凡似乎這陣子也畫出了小小心得，手對筆的運用越來越好，本來想說姿勢不是很好，會把眼睛弄壞，後來才發現是沒有椅子的關係，給凡凡個小板凳，姿勢就一百分了。

眨眼睛

禮拜六大年初三，初一早初二早初三睏到飽，媽媽還在補眠，凡凡就自己爬起床到客廳活動了。

溫了杯牛奶給凡凡當早餐，凡凡就自顧自地吃了起來。大概吃得開心，最後還跑到相機前特寫，表演媽媽教的眨眼睛。

Is the pharmaceutical industry ready for systems biology?

Okay, it is time to move on, to out of the blue. New semester has begun, so does the theory lunch.

I really like this talk; someone from the industry telling you what it is in the real world, the systems biology.

The introduction -
--

Is the pharmaceutical industry ready for systems biology?
8 February 2008

Bruce Gomes
Systems Biology Group
Pfizer Inc.

Abstract
When reading reviews of systems biology it would seem that this method should be immediately adopted as the new paradigm for drug discovery in the pharmaceutical industry. This methodology promises to pick the best approach for amelioration of disease pathology by choosing the optimal target for drug design; identify co-drugging strategies; find the most discriminating biomarkers; stratify patients for clinical trials; militate against toxic outcomes; and overall, reduce drug discovery attrition. Yet, the adoption of systems biology methods in the industry is cautious and slow. This talk will discuss what the limitations of systems biology are that slow its adoption. These limitations are the starting points for the generation of new approaches that are a fertile area for the interface between academic labs and the pharmaceutical industry.

Even without the large scale adoption of systems biology methodologies in the industry, these methods are being used to some extent. This talk will highlight one area of systems biology that is currently being used very successfully, namely the small to moderate sized models created to predict the behavior and properties of biotherapeutics.

--

講者是 Pfizer 裡的人，從他口中大概可以理解到在真實世界中，所謂 Systems Biology 目前的可行性及應用度到底在哪裡，的確，與在象牙塔裡學術圈子想的大不相同。

通常 Systems Biology 常被質疑的就是到底有沒有可能掌握「系統」裡所有的變因 (parameters)，這個問題通常問學術圈子裡的人，答案多是持保留態度的。但就藥廠的立場，只要謹慎地選擇「標靶」，這個目標是可以達到的。

Bruce 給了幾個數據，目前市面上 FDA 共核准了 1480 種不同的藥物販售，可是這些藥物的標靶基因總數約只有 300，也就是說儘管是來自不同藥廠的藥物，許多都是 targeting 相同的基因。

這現象是許多原因加總的結果，其中一項是成本，一個新藥從一開始的評估到 phase I，平均的花費大約是 $1 billion，就算好不容易通過上市，到 Phase IV 後仍有大約 70% 的機會這個藥競爭不過市場上同質性的藥物，never got description。正因如此再一開始選擇標靶的時候，基本上是極端保守風險取向的。藥廠只會選擇 small systems，在這種情況下，所有系統的 parameters 可以全部掌握，系統中的每個成員的貢獻或影響程度可以被計算及實驗出來。

在後半段，Bruce 也表示 Systems Biology 距完全發揮應用還有一段很長的距離，實務上仍存在著許多 holes，其中 text mining 是最大的問題，業界的各大生技公司花了非常多的心力在這一部分，但很明顯的 auto-paper-reading robot 仍是遙不可及的夢，進展十分有限。其它許多臨床上的問題，像不同個體間臨床反應不同的情況，也造成了系統解析上很大的困難。

整場 talk 的感覺，業界重實務的文化確實點到了許多學術界不會考慮的問題，對整個 systems biology 的發展評估感覺也比象牙塔裡搞 systems biology 的人自己說來得準切真實多了。

SysBio in Allston

It is known that my school is going to expand the campus to the Allston area. Due to the man and space demanding, our department is going to relocate to the Allston campus. The whole project should be done in 20 years (yeah, TWO ZERO, it is not a typo), but the SysBio plans to move from 2011.

During today's happy hour, under the direction of Associate Professor Mark Goulthorpe and Visiting Professor Jeannette Kuo, this design studio at MIT’s Department of Architecture is working on generating more specific solutions to Stefan Behnisch’s master plan on the proposed Allston Campus for the Department of Systems Biology, yet still articulating a range of technical and environmental concerns that need to be addressed in addition to the basic technical requirements of a wet-lab building type.

Here are their posters and designs - (clicks on pictures to see details)



I have to say, most the buildings are really weird, and lots of people in our lab seem having no taste to appreciate such great designs (including me...)

Anyway, if nothing will happen before 2011, hopefully there should be none my bussiness then.

Good Signs

We had a good party last night, hanging around with friends. It recovered my mood from the blue somehow.

We had rains in the Chinese New Year's Eve. Today it snows! Both are very good signs for the superstitious me.

It will be a great start, at least for people in Massachusetts...


I took this video from my seat. Besides the snow, you can also see dentists working hard in the dental school.

Happy Chinese New Year !

We are gonna have a party in house with other Taiwanese students tonight. We trained FanFan to say "恭喜" but he was reluctant to say it and gave you a cute facial expression instead.


Happy Chinese New Year my friends!

Wish everything is going to be great next year, for me, and you too.

Don't It Make My Brown Eyes Blue

I used to love this song. I had this song on a CD which was a gift from EDWIN jeans.

I searched and found its MV last Friday for the article about the identification of blue eye genes (listed in the leftside A-log). Now it turns to be a very sad song for me who happen to have brown eyes in a deep blue.

Now I don't like it anymore.



Crystal Gayle - Don't It Make My Brown Eyes Blue

I don't know when I've been so blue \ Don't know what's come over you \ You've found someone new \ And don't it make my brown eyes blue

I'll be fine when you're gone \ I'll just cry all night long \ Say it isn't true \ And don't it make my brown eyes blue

Tell me no secrets, tell me some lies \ Give me no reasons, give me alibis \ Tell me you love me and don't let me cry \ Say anything but don't say goodbye

I didn't mean to treat you bad \ Didn't know just what I had \ But honey now I do \ And don't it make my brown eyes \ Don't it make my brown eyes \ Don't it make my brown eyes blue

Tell me no secrets, tell me some lies \ Give me no reasons, give me alibis \ Tell me you love me and don't let me cry \ Say anything but don't say goodbye

I didn't mean to treat you bad \ Didn't know just what I had \ But honey now I do
And don't it make my brown eyes \ Don't it make my brown eyes \ Don't it make my brown eyes blue

The Biggest Upset

Sigh... What an upset, an imperfect season.

I am sad. But the very weird part is, I had a dream last Tuesday about this Superbowl game, and the socres were exactly the same as I dreamed 17-14, NYG.

It made me double sad, especially after Randy Moss' TD which gave NE an 14-10 lead with 2 minutes to go. At that moment, I knew my dream WAS gonna happen. It made me double sad.

I told my dream to labmates on the next day. All of them thought the scores are unlikely low, so we seen it as a joke. Now this...

Congrats to Giants and Eli. As I said I like Eli and thought he is better than his brother. I just don't want anyone to screw Patriots and Tom Brady's this perfect season. What frustrated me the most is,usually you tell yourself that "it is alright, there will be another season", but this time, it is not; there is no other chance like this to write done the history.

Nothing but deep deep sadness. (well, at least I am not the ones who purchased $17,000 tickets to witness such kind of historical game.

Live goes on.

Warm-Up for THE Game

Have some warm-up before Sunday's game?

Randy Moss Top 10 catches


How can you not love Brady-Moss combo after watching this clip?

New England Patriots have -
Tom Brady, the best QB in NFL,
Randy Moss, the best WR in NFL, and
Bill Belichick, the best coach in NFL.

You can count the odds that Giants win this superbowl...

Impact Factors of Impact Factors

前陣子看到的 JCB editorial，繼上次對 HHMI 開幹後，這次罵的是搞 impact factor 的 Thomson Scientific 公司。

剛登出來的時候，我們幾個人在 lab 裡也有討論過這些問題，很值得來講一講。

不過，因為 Superbowl 在即，沒時間，先貼出來大家有空可以看看，等 Pats 拿下冠軍後再找時間慢慢說。


1. JCB Editorial
Show me the data

2. Thomson Scientific 的回應
Article Titled “Show me the Data”, Journal of Cell Biology, Vol. 179, No. 6, 1091-1092, 17 December 2007 is Misleading and Inaccurate

3. JCB Editors 對 Thomson Scientific 回應的回應
Irreproducible results: a response to Thomson Scientific

--
Enjoy & Have a good weekend,

And don't miss the historical moment this Sunday!

Go Patriots! Go Brady!