November 28, 2008
Donor Question: Why do certain servers go down more easily?
I'll start posting replies that I make in the forum (http://foldingforum.org) when I think it would be of broad interest.Here's one regarding server downtime.
Is there a reason, that this particular server seems to have an exceptional amount of down time?
Physically, the server is fine. However, when it gets overloaded, it just fails to continue and the binary must be killed.This is a software issue, likely in the low-level HTTP code/library.
And what can be done, on a long term basis ...
We have been looking into solutions for the past two years. Two years ago, we refactored the server code to clean up elements and try to isolate the problem (creating the v4 branch of the server code from v3). That did help, but not enough. One feature of the v4 code is that it can detect when it has this problem and restart itself, but we don't want it falsely restarting itself (that can lead to other problems), so the timeout is somewhat long.
About a year ago, we took a radically different approach and worked with an outside programming company (Joseph Coffland from Cauldron) to rewrite the server code from scratch. That new server code (v5) is now under beta testing. Project 3798 are run on the new server platform. We are rolling it out gradually to avoid any sort of disaster, but so far so good; beta testing has found bugs in the v5 code which Joe has fixed and it looks like the code is ready for a bigger rollout (which is underway). I expect that it will see its first duty in production projects (i.e. not server test projects) in early 2009 (likely January 2009) and a more complete roll out throughout the year.
The SMP and GPU servers will get it last, since they need additional code to bring the v5 code path up to spec with what the GPU and SMP needs. However, we expect this won't be too onerous to get done.
大意：
为了解决服务器频繁宕机问题，我们改进了服务器代码。现在正在测试。
09年初我们会正式发布。
SMP 和 GPU由于机制不同，可能要晚些时候才能上。
Collection Server (CS) overhaul
We've made some changes to the Collection Servers (CS) which seems to be making a big difference.We've migrated them to a new network (the old net had many issues, as discussed in previous posts) and recently made some configuration tweaks.The two new CS's (171.67.108.17 and 171.67.108.25) seem to be doing reasonably well right now.
Hopefully, this will help donors get WUs in faster and allow the FAH team some leeway when a server goes down, knowing the CS is there as a backup.We'll continue to monitor the CS issue, since this is such a critical part of FAH.
大意：
我们对CS服务器进行了检修，并转到了新网络里（老网络有很多问题）。
Overuse of fah-web.stanford.edu web pages
Please note that one should not access the cgi pages from the fah-web.stanford.edu web pages too frequently, since that means that other people are blocked out of their stats.We have seen numerous people accessing these pages hundreds to thousands of times per day (most likely by running a script).
We have blocked the worst offenders for now.If you find yourself blocked, please see what was causing this (eg turn off your script) and post a message in our forum (http://foldingforum.org) to get unblocked.
One can access our "fast" team pages by scripts.For example, for the Pande Lab team (team 1), the cgi-bin url is this
http://fah-web.stanford.edu/cgi-bin/main.py?qtype=teampage&teamnum=1
this would be an example of a bad url to access frequently.
However, if you look at that page, you will see this
Pande Lab
Date of last work unit 2008-11-28 06:53:43
Active CPUs within 50 days 3682
Team Id 1
Grand Score 141820948 (certificate)
Work Unit Count 472377 (certificate)
Team Ranking (incl. aggregate) 30 of 148437
Home Page http://www.stanford.edu/group/pandegroup/index.html
Fast Teampage URL http://fah-web.stanford.edu/teamstats/team1.html
Note the "Fast Teampage URL" line at the end.This url (http://fah-web.stanford.edu/teamstats/team1.html) is designed to be loadable quickly.The top 2500 teams have a fast teampage URL, so it's likely that your team is one of them.
Another alternative is the 3rd party stats.They are very slightly less up to date (since they parse a file we send out less frequently), but they help balance the load.See http://fahwiki.net/index.php/Third_Party_Contributions for a list of 3rd party stats systems.
Please do not use scripts or only use scripts on the fast teampages or 3rd party stats.By overloading the stats by using automatic scripts, it blocks out others and makes the stats slow or unreachable for everyone.
大意：
由于统计服务器访问压力过大（大部分是由于签名脚本造成的），我们把前2500名小组的统计信息静态化了。为了减少服务器压力，我们屏蔽了部分脚本服务器。请大家尽快修改签名统计脚本，访问新的静态化页面吧。
December 02, 2008
Long term vision for FAH: Science, clients, etc
It's been a while since I've posted on this topic, so I thought it would be a good time to talk about the long term vision for FAH.In the first few years, we have done a lot to build up methodology (novel distributed computing algorithms, tests of methods), especially in the last years working to bring GPU's, PS3's, and tightly coupled SMP calculations to a distributed computing platform.While all of this has been going on, there has been a lot of work which would have a direct impact to disease and human health, and donors should see more results (i.e. papers) coming out in this direction soon.In particular, results on Alzheimer's Disease, Huntington's Disease, and some other surprises in the works (sorry, some details are best left until peer review is done).
In terms of a long term vision for the FAH software, our short term goals is to shore up the SMP client.Just as there was a big improvement from the GPU1 -> GPU2 client, we have been working steadily on an SMP2 client -- a version which is much easier to use, requires less donor effort, and scales much better.This really is a combination of a modified client and (especially) new cores.This effort has been going on for about a year and it's far enough along that I'm starting to talk about it publicly.
In the previous post, I also mentioned about some of our work behind the scenes in revamping the backened of FAH, i.e. a whole new set of server codes.We have code for the workserver and collection servers, but in time we expect the full backend to be cleanly rewritten from scratch.
Longer term, with a more solid GPU2 and SMP2 clients done, we can then move on to other areas.Our goal is to be bleeding edge in the nature of our science, but get back to the simplicity and stability found in the classic client.We still have a ways to go, but I am excited that projects that were started some time ago are now looking like they will see the light of day.
大意：
项目展望
这几年我们大幅改进了计算方法，发布了如GPU，PS3，SMP等高性能客户端。发布了许多研究成果。特别是Alzheimer和Huntington氏症，还有其它的一些方面（抱歉，内容正在审查，所以不能透露太多信息）。
接下来我们将致力于SMP2客户端的研究。努力使它更快更好，实现犹如GPU1 -> GPU2那样质的飞跃。
虽然我们已经对服务器代码进行了不少改进，不过我们打算重写服务器端代码。
今后，等GPU2和SMP2客户端完工，我们还会研究更多的计算领域。
译者注：官方今后不会真要研究手机客户端吧，呵呵！
原帖由 vmzy 于 2008-11-29 14:18 发表 http://www.equn.com/forum/images/common/back.gif
November 28, 2008
由于统计服务器访问压力过大（大部分是由于签名脚本造成的），我们把前2500名小组的统计信息静态化了。为了减少服务器压力，我们屏蔽了部分脚本服务器。请大家尽快修改签名统计脚本，访问新的静态化页面吧。
是不是意味着以后论坛里使用的签名图片不能更新了？新的静态化页面什么样子？
December 08, 2008
Folding@home Alzheimer's Simulation work published
I am very happy to announce that a first key work (paper #58 at http://folding.stanford.edu/English/Papers) from the Folding@home project on Alzheimer's Disease (AD) was just publishedSimulating oligomerization at experimental concentrations and long timescales: A Markov state model approach, by Nicholas W. Kelley, V. Vishal, Grant A. Krafft, and Vijay S. Pande. J. Chem. Phys. 129, 214707 (2008); DOI:10.1063/1.3010881
url:http://link.aip.org/link/?JCP/129/214707
Abeta misfolding and aggregation is believed to be the cause of Alzheimer's Disease. Simulations, like Folding@home, are a natural way to understand this process. However, there are several key challenges for simulating the key step -- oligomerization. This work represents a new way to simulate Abeta oligomerization, with a key advance of being able to simulate experimentally relevant timescales and concentrations, using a novel method. We use this new method and the power provided by Folding@home donors to simulate oligomerization in all-atom detail. This has lead to specific predictions about the process, which we are now testing experimentally.
In many ways, this paper is the "tip of the iceberg" for the Folding@home activities in AD, with a lot more interesting results to come, especially in terms of experimental tests of our predictions and interesting new possibilities for new drugs and AD therapeutics.So, while we're excited that this result is now past peer review, we're even more excited for what's coming down the pipeline, waiting peer review.We'll keep you posted as more results become public, hopefully with some even bigger announcements in 2009.
UPDATE:
It was asked which clients participated.This work started several years ago and took some time to analyze and then publish.So, it ran exclusively on classic clients.For the follow up simulations, we are using a mixture of GPU, SMP, and classic clients.Due to the large number of classic clients, they allow us to calculations not possible on the other platforms.However, the raw speed (but smaller number) of the GPU and SMP clients allow us to get a good rough idea quickly, refining later with classic clients.
大意：
公布Alzheimer模拟结果。
更新：
有人问，是哪些客户端参与了此次计算。
主要是cpu标准版客户端，后期有少量GPU 和SMP 客户端参与，不过主要还是cpu标准版客户端。
[ 本帖最后由 vmzy 于 2008-12-10 09:21 编辑 ]
原帖由 vmzy 于 2008-12-9 11:46 发表
公布Alzheimer模拟结果。
终于有实质性进展了
December 09, 2008
New paper #59: Ribosome gateWe have another paper (paper #59 at http://folding.stanford.edu/English/Papers)
Side-chain recognition and gating in the ribosome exit tunnelby Paula M. Petrone, Christopher D. Snow, Del Lucent, and Vijay S. Pande.Proceedings of the National Academy of Sciences, USA 2008
which recently was published, representing a major step for FAH.
This one deals with the ribosome. The ribosome is a fascinating molecular machine, responsible for the synthesis of proteins. For this reason it is of fundamental importance to protein folding (as the last step in the central dogma of biology) as well as to human health (since the ribosome is the target of a very large fraction of antibiotics). One of the questions revolving around ribosome function is why is there a large tunnel inside the ribosome, through which proteins exit after being synthesized. In this paper, we used "bigWU" classic clients (clients which allow larger systems to run) since the ribosome is so huge that it would not run on regular classic clients.
The primary goal of this paper was to analyze the surface of the ribosome tunnel. Understanding the nature of this surface would be useful for both understanding the fundamental nature of protein synthesis as well as how key antibiotics interact with the ribosome. An interesting related discovery was the identification of a potential "ribosome gate" which can open and close selectively, based on what is interacting with the gate. This suggests novel hypotheses for several aspects of ribosome function as well as interesting new directions for work on studying the ribosome and for new routes for antibiotics.
大意：
公布有关核糖体的论文。
核糖体跟绝大部分的蛋白质及抗生素合成有密切关系。研究了核糖体内管道的作用。提出了，合成抗生素的新方法。
因为核糖体很复杂，所以只有开启了bigWU功能的cpu客户端参与了相关计算。
译者注：强烈建议内存上G的用户开启bigWU选项。
[ 本帖最后由 vmzy 于 2008-12-10 09:52 编辑 ]
December 11, 2008
New paper #60: PS3 paperWe have another paper that came out recently (paper #60 at http://folding.stanford.edu/English/Papers).This one describes the PS3 client in FAH:
]%20edgar%20luttmann,%20daniel%20l.%20ensign,%20vishal%20vaidyanathan,%20mike%20houston,%20noam%20rimon,%20jeppe%20Øland,%20guha%20jayachandran,%20mark%20friedrichs,%20vijay%20s.%20pande.%20]Accelerating Molecular Dynamic Simulation on the Cell processor and PlayStation 3
by Edgar Luttmann, Daniel L. Ensign, Vishal Vaidyanathan, Mike Houston, Noam Rimon, Jeppe Øland, Guha Jayachandran, Mark Friedrichs, Vijay S. Pande.
'In this paper, we detail how we were able to get great speed increases for Folding@home (and actually certain molecular dynamics calculations in general) on the PS3. This is our first paper using the PS3, laying out the "how does it work," with a follow up paper in the works describing the results obtained in FAH from PS3 clients.
It is also worth noting that this paper is a collaboration between FAH team members (Luttmann, Ensign, Vaidyanathan, Houston , Jayachandran, Friedrichs, and Pande) with developers at Sony (Rimon and Øland and their coworkers).
Here's the more technical abstract as well:
Implementation of molecular dynamics (MD) calculations on novel architectures will vastly increase its power to calculate the physical properties of complex systems. Herein, we detail algorithmic advances developed to accelerate MD simulations on the Cell processor, a commodity processor found in PlayStation 3 (PS3). In particular, we discuss issues regarding memory access versus computation and the types of calculations which are best suited for streaming processors such as the Cell, focusing on implicit solvation models. We conclude with a comparison of improved performance on the PS3's Cell processor over more traditional processors.
大意：
发布有关利用ps3做蛋白质模拟的文章。
December 16, 2008
Strongly suggested update client update: new ATI GPU client 6.23
We have made several bug fixes and speed improvements wrapped into a new ATI GPU client (version 6.23).We strongly suggest that everyone upgrade.While current (and new cores, especially ATI GPU core version 1.22) should work with other clients, we are seeing some possible issues which the new client fixes.
As always, we suggest that one backup their machine before upgrading software, especially in case you would like to go back to the previous version.You can download the new client at
http://folding.stanford.edu/English/DownloadATI
and as always, please post comments in the forum (http://foldingforum.org).
PS For those with NVIDIA GPUs, you could also consider upgrading to client version 6.23 (from http://folding.stanford.edu/English/DownloadWinOther ) as it also fixes some issues.However, this is less of a critical at the moment for NVIDIA than ATI.
大意：
强烈建议A卡用户升级到新6.23版客户端（计算内核是1.22版），修正了一些bug，大幅提高了计算速度。
升级前最好做好备份工作。遇到问题请到论坛发帖。
注：N卡的客户端也更新了，不过相对A卡而言变动不大。大家可以试试。
December 17, 2008
Planned maintenance for Stanford network over the next 2 weeks
During the next two weeks (December 20 - January 4), the Backbone Networking group plans to schedule a backbone maintenance window every morning from 4-8am pacific time to implement improvements in the network, as they did last year. In most cases, the changes should not affect the connectivity of the networks used by Folding@home. In cases where they might, any interruption in service should be under 5 minutes.
大意：
从12月20日~1月4日，对斯坦福主干网进行为期2周的例行维护（北京时间每天下午4点~晚上8点），期间网络可能会断掉，不过理论上断网时间不会超过5分钟。
December 18, 2008
New FAH results on possible new Alzheimer's drug presented
This is very preliminary news, but something I'm very, very excited about, so I'll give some advance news.On Tuesday, we presented our results regarding new possible drugs (small molecule leads) to fight Alzheimer's Disease at a recent meeting at Stanford.This meeting was part of the NIH Roadmap Nanomedicine center (http://proteinfoldingcenter.org/) retreat and was supported by NIH grants to Folding@home.
It's very early (so we are not publicly talking about the details until this has passed peer review), but we are very excited that it looks like we may have multiple small molecules which appear to inhibit toxicity of Abeta, the protein which is the toxic element in Alzheimer's Disease.
This is exciting in many ways.It's been a long road for FAH to get to this point, but we are starting to see the possibility of seeing these results published easily before our 10th birthday (October 2010).Considering all the technology development that had to be done in the first five years, these results have come very quickly (in the last 3 years), which is exciting.In particular, we are now looking to apply these methods to other protein misfolding diseases (we have pilot projects for Huntington's Disease underway).
Finally, I should stress that while we're very excited about this, it's still early and a lot can go wrong between where we are and having a drug that doctors can prescribe.Over the holidays, we will be double checking the experimental data, crossing t's and dotting i's to make sure there is nothing missed before we think about submitting this for peer reviewed publication.Also, there is still a long way from an interesting possible drug (where we are now) to something which has passed FDA clinical trials (where we'd love to be), and a lot can go wrong in clinical trials in particular.
Thus, this is an important milestone for FAH and we are very grateful to all who have contributed.Happy holidays to all!
大意：
我们关于Alzheimer氏症的研究结果可能催生新型抗Alzheimer药物。不过我们还有很长的路要走，希望能在10周年的时候（2010年10月）找到可用的药物。
同时我们开始集中精力研究Huntington氏症。
译者注：FAHer们可以准备庆功酒了吧。
有成果，不管有多大，总是值得庆祝的。希望我能坚持到2010年
原帖由 vmzy 于 2008-12-19 10:09 发表 大意：
我们关于Alzheimer氏症的研究结果可能催生新型抗Alzheimer药物。不过我们还有很长的路要走，希望能在10周年的时候（2010年10月）找到可用的药物。
同时我们开始集中精力研究Huntington氏症。
译者注：FAHer们可以准备庆功酒了吧。
庆祝啊！哈哈
January 02, 2009
New paper #61: Computational screen to identify important mutations in influenza
We're happy to announce a new Pande Group paper (paper #61 at http://folding.stanford.edu/English/Papers).This paper describes a new computational screen to identify important mutations in influenza:
Combining Mutual Information with Structural Analysis to Screen for Functionally Important Residues in Influenza Hemagglutinin.
Peter M. Kasson and Vijay S. Pande. Pacific Symposium on Biocomputing 14:492-503(2009).
Download URL: http://psb.stanford.edu/psb-online/proceedings/psb09/kasson.pdf
The influenza hemagglutinin protein performs several important functions, including attaching the virus to cells it will infect and releasing the viral genome into the interior of the cell. Most protective antibodies against influenza also bind to the hemagglutinin protein. We wish to understand how mutations to hemagglutinin affect viral function, including what keeps avian influenza ("bird flu") from being readily transmissible between humans. In this paper, we have applied a technique from information theory known as mutual information to genetic sequence data to predict important mutation sites on the hemagglutinin protein. In follow-up work, we are combining this technique with other methods to refine these predictions and test some of them using Folding@Home.
PS For those curious out in more details, check out the paper (see link above) or the technical abstract:
Influenza hemagglutinin mediates both cell-surface binding and cell entry by the virus. Mutations to hemagglutinin are thus critical in determining host species specificity and viral infectivity. Previous approaches have primarily considered point mutations and sequence conservation; here we develop a complementary approach using mutual information to examine concerted mutations. For hemagglutinin, several overlapping selective pressures can cause such concerted mutations, including the host immune response, ligand recognition and host specificity, and functional requirements for pH-induced activation and membrane fusion. Using sequence mutual information as a metric, we extracted clusters of concerted mutation sites and analyzed them in the context of crystallographic data. Comparison of influenza isolates from two subtypes—human H3N2 strains and human and avian H5N1 strains—yielded substantial differences in spatial localization of the clustered residues. We hypothesize that the clusters on the globular head of H3N2 hemagglutinin may relate to antibody recognition (as many protective antibodies are known to bind in that region), while the clusters in common to H3N2 and H5N1 hemagglutinin may indicate shared functional roles. We propose that these shared sites may be particularly fruitful for mutagenesis studies in understanding the infectivity of this common human pathogen. The combination of sequence mutual information and structural analysis thus helps generate novel functional hypotheses that would not be apparent via either method alone.
大意：
第61号论文：利用计算筛选确定流感红血球凝集素蛋白质重要变异
流感红血球凝集素蛋白质的主要作用是绑定目标细胞，并破坏细胞膜将病毒基因注入目标细胞。我们主要研究了流感红血球凝集素蛋白质变异对病毒功能的影响，以及禽流感为何可以传染给人类。
满满看 学习了
任重而道远啊。。。。。
