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发表于 2017-3-22 11:49:52 | 显示全部楼层
OpenZika Researchers Continue Calculations and Prepare for Next Stage
By: The OpenZika research team
21 三月 2017          

摘要
The OpenZika researchers are continuing to screen millions of chemical compounds as they look for potential treatments for the Zika virus. In this update, they report on the status of their calculations and their continuing work to spread the word about the project.

Project Background

While the Zika virus may not be getting the continuous press coverage that it received in 2015 and 2016, it is still a threat to the health of people across the globe. New infections continue to be reported in both South America and North America, and medical workers are just beginning to assess the effects of the virus on young children whose mothers were infected while pregnant.

The search for effective treatments is crucial to stemming the tide of the virus. In addition to the OpenZika project, several other labs are doing cell-based screens with drugs already approved by the US Food and Drug Administration (FDA) agency, but few to none of the “hit” compounds that have been identified thus far are both potent enough against Zika virus and also safe for pregnant women.

Also, there are a number of efforts underway to develop a vaccine against the Zika virus. However, vaccines do not help people who already have the infection. It will be several years before they are proven effective and safe, and before enough doses can be mass produced and distributed. And even after approved vaccines are available and distributed to the public, not all people will be vaccinated. Consequently, in the meantime and in the future, cures for Zika infections are needed.

Progress on choosing compounds for lab testing
https://www.youtube.com/embed/QixgaZFkFms


ZIKV NS3 helicase bound to RNA with the predicted binding modes of five approved drugs (from our second set of candidates) selected by virtual screening. These candidates are shown as surfaces with different shades of green. The identification of these candidates and the video were made by Dr. Alexander L. Perryman.

We began the analysis phase of the project by focusing on the results against the apo NS3 helicase crystal structure (apo means that the protein was not bound to anything else, such as a cofactor, inhibitor, or nucleic acid) to select our first set of candidates, which are currently being assayed by our collaborator at University of California San Diego, Dr. Jair L. Siqueira-Neto, using cell-based assays. The NS3 helicase is a component of the Zika virus that is required for it to replicate itself.

In the second set of screening results that we recently examined, we used the new crystal structure of NS3 helicase bound to RNA as the target (see the images / animation above). Similar to the first set of candidates, we docked approximately 7,600 compounds in a composite library composed of the US Food and Drug Administration-approved drugs, the drugs approved in the European Union, and the US National Institutes of Health clinical collection library against the new RNA-bound structure of the helicase. Below are the results of this second screening:

232 compounds passed the larger collection of different energetic and interaction-based docking filters, and their predicted binding modes were inspected and measured in detail.
Of the compounds that were inspected in detail, 19 unique compounds passed this visual inspection stage of their docked modes.
From the compounds that passed the visual inspection, 9 passed subsequent medicinal chemistry-based inspection and will be ordered soon.
Status of the calculations

In total, we have submitted 2.56 billion docking jobs, which involved the virtual screening of 6 million compounds versus 427 different target sites. We have already received approximately 1.9 billion of these results on our server. (There is some lag time between when the calculations are performed on your volunteered machines and when we get the results, since all of the results per “package” of approximately 10,000 different docking jobs need to be returned to World Community Grid, re-organized, and then compressed before sending them to our server.)

Except for a few stragglers, we have received all of the results for our experiments that involve docking 6 million compounds versus the proteins NS1, NS3 helicase (both the RNA binding site and the ATP site), and NS5 (both the RNA polymerase and the methyltransferase domains).  We are currently receiving the results from our most recent experiments against the NS2B / NS3 protease.

A new stage of the project

We just finished preparing and testing the docking input files that will be used for the second stage of this project. Instead of docking 6 million compounds, we will soon be able to start screening 30.2 million compounds against these targets. This new, massive library was originally obtained in a different type of format from the ZINC15 server. It represents almost all of “commercially available chemical space” (that is, almost all of the “small molecule” drug-like and hit-like compounds that can be purchased from reputable chemical vendors).

The ZINC15 server provided these files as “multi-molecule mol2” files (that is, many different compounds were contained in each “mol2” formatted file). These files had to be re-formatted (we used the Raccoon program from Dr. Stefano Forli, who is part of the FightAIDS@Home team) by splitting them into individual mol2 files (1 compound per file) and then converting them into the “pdbqt” docking input format.

We then ran a quick quality control test to make sure that the software used for the project, called AutoDock Vina, could properly use each pdbqt file as an input. Many compounds had to be rejected, because they had types of atoms that cause Vina to crash (such as silicon or boron), and we obviously don’t want to waste the computer time that you donate by submitting calculations that will crash.

By splitting, reformatting, and testing hundreds of thousands of compounds per day, day after day, after approximately six months this massive new library of compounds is ready to be used in our OpenZika calculations. Without the tremendous resources that World Community Grid volunteers provide for this project, we would not even dream of trying to dock over 30 million compounds against many different targets from the Zika virus. Thank you all very much!!!

For more information about these experiments, please visit our website.

Publications and Collaborations

Our PLoS Neglected Tropical Diseases paper, "OpenZika: An IBM World Community Grid Project to Accelerate Zika Virus Drug Discovery," was published on October 20, and it has already been viewed over 4,000 times. Anyone can access and read this paper for free. Another research paper “Illustrating and homology modeling the proteins of the Zika virus” has been accepted by F1000Research and viewed > 3800 times.

A group from Brazil, coordinated by Prof. Glaucius Oliva, has contacted us because of our PLoS Neglected Tropical Diseases paper to discuss a new collaboration to test the selected candidate compounds directly on enzymatic assays with the NS5 protein of Zika virus. They have solved two high-resolution crystal structures of ZIKV NS5, which have been recently released on the PDB (Protein Data Bank) (PDB ID: 5TIT and 5U04).

Our paper entitled “Molecular Dynamics simulations of Zika Virus NS3 helicase: Insights into RNA binding site activity” was just accepted for publication in a special issue on Flaviviruses for the journal Biochemical and Biophysical Research Communications. This study of the NS3 helicase system helped us learn more about this promising target for blocking Zika replication. The results will help guide how we analyze the virtual screens that we already performed against NS3 helicase, and the molecular dynamics simulations generated new conformations of this protein that we will use as input targets in new virtual screens that we perform as part of OpenZika.

These articles are helping to bring additional attention to the project and to encourage the formation of new collaborations.

Additional News

We have applied and been accepted to present “OpenZika: Opening the Discovery of New Antiviral candidates against Zika Virus and Insights into Dynamic behavior of NS3 Helicase” to the 46th World Chemistry Congress. The conference will be held in Sao Paulo, Brazil, on July 7-14.

Dr. Sean Ekins has hired a postdoc and a master level scientist who will get involved with the OpenZika project. We have also started to collate literature inhibitors from Zika papers.

Also, Drs. Sean Ekins and Carolina Andrade have offered to buy some of the candidate compounds that we identified in the virtual screens from OpenZika, so that they can be assayed in the next round of tests.  

Fundraising


Dr. Alex Perryman models an OpenZika shirt. Profits from the sale of OpenZika merchandise go to purchasing compounds for lab testing. (Photo by Keith Bratcher, courtesy of Rutgers University)
Thank you to anyone who has visited our store on Zazzle to check out OpenZika merchandise such as T-shirts, polo shirts, mugs, buttons, mouse pads, and phone cases. All profits from the sale of this merchandise will go toward buying compounds for lab testing. Drs. Alex Perryman and Sean Ekins have bought OpenZika shirts for themselves. Alex likes the polo style version the best, and he recommends getting the white or gray shirts. But avoid the red shirts, since the OpenZika logo does not stand out as well, especially after it is washed (Alex learned this the hard way).

The OpenZika team is working on grants from the National Institutes of Health, CNPq (a Brazilian funding agency), and other organizations to try raise funds for purchasing and testing compounds.

Outreach

We have been working hard to promote the project, and we continue to look for additional opportunities. Below is a list of our most recent outreach efforts.

Dr. Carolina Horta Andrade gave one invited lecture at the 27th annual Institute of Biology Week, at Federal University of Goias, Brazil, to biology and pharmacy students and to the general public regarding the “Design and discovery of new drug candidates for the Zika and Dengue Viruses and OpenZika” (November, 2016).
Dr. Carolina Horta Andrade has been elected as an Affiliated Member of the Brazilian Academy of Sciences. She also gave a talk at the Federal University of Minas Gerais, Brazil, to researchers from many different fields of science and to authorities, in which she discussed OpenZika (October 2016).
Dr. Melina Mottin, one of the OpenZika team members, presented a poster and gave an oral presentation, titled “OpenZika: an open science collaboration project to discover drug candidates against Zika virus,” at the 8th Brazilian Symposium on Medicinal Chemistry, held in Búzios, Rio de Janeiro, Brazil, from November 27-30, 2016.
Dr. Melina Mottin also gave an invited lecture at the Federal University of Rio Grande do Sul, Brazil, at the Post-Graduation Program in Chemistry, to chemistry and pharmacy Ph.D. students and to the general public regarding “[url=http://quimicabiologica.wixsite.com/ciclodepalestras/programacao-1]Identification of Drug Candidates for Zika virus using Virtual Screening and Molecular Dynamics Simulations,[/ur]” in which she discussed the OpenZika project (December 2016).
Dr. Sean Ekins attended the National Institutes of Health (NIH) “Rare disease day” (February 27, 2017) and also the Gordon Research Conference on Tropical Infectious Diseases (March 12-17 2017).

We are very grateful for all of the volunteers who are donating their unused computing time to this project!  Thank you very much!!
大意:
OpenZika项目近况
OpenZika一期总共有25.6亿个任务,目前已经完成19亿个。
二期任务目前还整理准备中,大概6个月后就可以上传了。

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发表于 2017-3-29 09:44:37 | 显示全部楼层
Clean Energy Project Researchers Sharing Results and Planning for the Future
By: The Clean Energy Project team
Harvard University
28 三月 2017          

摘要
The Clean Energy Project team is working on publicizing their results to-date. They have wrapped up the second phase of the project, and are also making decisions about their future work with World Community Grid.

Remember this video from a couple of years ago about the goals of the Clean Energy Project? Thanks to the many volunteers who supported this study, the researchers were able to collect an enormous amount of data, which they are now analyzing and getting ready to publish.
https://www.youtube.com/embed/VNuOcbWeL90

The Clean Energy Project research team at Harvard would like to thank the volunteers who supported us through two phases of the project! Currently, we are getting ready to share our findings in at least one publication and a conference. We are also weighing different options for further work with World Community Grid, which might include new types of calculations on solar cells or perhaps a study with a much larger scope.

Publishing Our Results

We have completed our screening of non-fullerene acceptor materials for new organic photovoltaic devices. The findings were quite interesting and have kept us very busy! We describe our results in a manuscript that was submitted to the high-impact journal Energy & Environmental Science.  

Steven Lopez will travel to San Francisco to present this work at the American Chemical Society national meeting in April 2017. Alán has presented the results of the Clean Energy Project in several forums and they have helped inform the screening for other materials, such as organic flow batteries, in his research group.

Considering our findings, we are working hard to continue developing what we have learned with this initial study. Our work may have led to the discovery of a new class of non-fullerene acceptors, with excellent properties including low production costs! We will reveal the chemical identities of these exciting derivatives when the paper is published.

How Scientific Papers Get Published

The process of peer-review scientific publishing is not so straightforward and can take many months, or even years in some cases.

First, the manuscript of a paper is sent to an editor, which decides whether the work will be reviewed at all. Depending on the journal, this can be just one out of every five manuscripts received. Then, three to five experts in the field independently assess the manuscripts that are accepted for review. Each reviewer must certify that the researchers’ approach and results are novel and worth publishing.

If the panel decides that a manuscript should be published, they will put forth suggestions and concerns that the manuscript’s authors respond to. Typically, after these concerns and edits have been addressed, the publishing agency will recommend that a paper be published. If it is to be published online, it usually become available in 1-2 weeks.

Future Work with World Community Grid

We have not been able to submit work units for volunteer calculation because we had been working to expand the number of molecules we will test by using a low-cost computational method to evaluate the properties of potential photovoltaic materials. With our efficient calibration scheme, this would allow us to screen 10-100 times as many candidates in the same amount of time. If this process can be fully optimized, we could begin generating these work units for volunteers. Benjamin Sanchez-Lengeling has pushed this aspect of the project forward; keep an eye on this rising star!

However, it is also possible that we may go in a different direction altogether. Another idea we are considering is to use these efficient computational methods to catalog the properties of molecules that benefit humanity and have applications beyond clean energy. Molecular Space is vast and full of useful molecules for the world.

We appreciate everyone’s patience while we take stock of the resources and personnel available in our lab, and make decisions about the best scientific use of the generous donations of computing time provided by World Community Grid volunteers.

Thanks again to everyone for your support of this project over the years,

Alán Aspuru-Guzik and Steven Lopez
On Behalf of the CEP Team
大意:
CEP2项目近况
研究论文已经提交同行评审了。
目前在优化算法,计算效率大概能提升10-100倍。
同时我们也计划将来用我们算法研究分子的其他一些对人类来说有用的特性(不仅仅是光伏发电)

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发表于 2017-4-7 13:49:23 | 显示全部楼层
Mapping Cancer Markers Team Analyzes Lung Cancer Data
By: The Mapping Cancer Markers research team
6 四月 2017          

摘要
In this project update, the Mapping Cancer Markers team describes how they are analyzing 45 million of the most promising lung cancer data results, and how they have begun to disseminate their early findings.

The Mapping Cancer Markers (MCM) project continues to process work units for the Ovarian Cancer dataset. As we accumulate these results, we continue to analyze MCM results from the previous Lung Cancer dataset. Below, we discuss one direction in which we are pursuing the analysis.

Patterns of gene-family signatures in lung cancer

In cancer, and human biology in general, multiple biomarkers (genes, proteins, microRNAs, etc.) can have similar patterns of activity. This may be because the genes serve redundant roles, or because the genes (or other molecules) participate together in a group to serve a biological function. A cancer signature composed of a set of specific genes may appear different than another signature composed of different, specific genes, and yet perform equivalently because the genes in each are functionally related. With this problem in mind, post-doctorate fellow Anne-Christin Hauschild is leading a study of frequently-occurring patterns (or motifs) of genes present in high-performing lung cancer gene signatures.

(Click to see an enlarged version.)

Illustration 1: Summary of the analysis workflow

This project looked at the first phase results from the Lung Cancer MCM analysis, which was a systematic exploration of the entire space of potential fixed-length signatures. We began by selecting 45 million high-performing signatures derived from World-Community-Grid-computed MCM results. These are the signatures evaluated to carry the most information for lung cancer diagnosis.

Next, we divided all genes in the lung cancer dataset into 180 clusters (gene families), where genes in each family show similar activity in the lung cancer dataset. We then labelled those top signatures with the gene families into which the genes were assigned. This gave us a set of high-performing signatures expressed as gene families instead of genes. This allowed us to treat two different gene signatures as the same gene-family signature, as long as the corresponding genes in each signature are members of the same family.

To help understand the gene-families themselves, we can visualize each one with word clouds that describe the functions of the genes they contain, or the biological pathways they represent. We draw this information from databases such as Gene Ontology, pathDIP, or other sources.

From there, we looked for patterns in these gene-family signatures: which families appear unusually frequently (or rarely) in high-performing signatures, or families that tend to appear multiple times in the same signature. We used Frequent-Itemset mining algorithm to discover specific patterns that occur unusually frequently in good signatures.


Illustration 2: Some gene families occur multiple times in a single signature with surprising frequency (high or low). Family 109 rarely appears multiple times. Family 12 appears surprisingly often in 9x multiples.

(Click to see an enlarged version.)

Illustration 3: Several important gene families, characterized by word clouds describing the genes’ molecular function annotations from the Gene Ontology database. Circles group families into common patterns found in high-performing signatures. Patterns often overlap, as in this example: one pattern containing families 3, 5, and 18 intersects with another containing families 12, 18, and 57.
Using databases such as IID or pathDIP, we can take these patterns and examine the relationships between the gene-families they contain, so we can start to understand why certain combinations of such families carry so much information about lung cancer. We use NAViGaTOR to visualize and explore these complex sets of relationships.

(Click to see an enlarged version.)

Illustration 4: Relationship between 11 significant gene families (large circles) within a protein interaction network. Only the most important genes (dots, colour-coded by biological function) in each family are shown.


Early project results presented at Personalizing Cancer Medicine 2017

We presented the preliminary results of this project to Canadian and international cancer researchers this February, in a poster at the Personalizing Cancer Medicine Conference 2017 in Toronto, Ontario. We gained many insights and ideas from discussing this early work, and we continue developing them further.

Some of the additional, related results have been presented in other publications, including:

Pinheiro, M., Drigo, S.A., Tonhosolo, R., Andrade, S.C.S., Marchi, F.A., Jurisica, I., Kowalski, L.P., Achatz, M.I., Rogatto, S.R., HABP2 p.G534E variant in patients with family history of thyroid and breast cancer, Oncotarget, In press.
Citron, F., Armenia, J., Barzan, L., Franchin, G., Polesel, J., Talamini, R., Sulfaro, S., Croce, C.M., Klement, W., Pastrello, C., Jurisica, I., Vecchione, A., Belletti, B., Baldassarre, G., A microRNA signature identifies SP1 and TGFbeta pathways as potential mediators of local recurrences in head and neck squamous carcinomas, Clin Cancer Res, In press.
Sokolina K, Kittanakom S, Snider J, Kotlyar M, Maurice P, Gandía J, Benleulmi-Chaachoua A, Tadagaki K, Wong V, Malty RH, Deineko V, Aoki H, Amin S, Riley L, Yao Z, Morató X, Otasek D, Kobayashi H, Menendez J, Auerbach D, Angers S, Pržulj N, Bouvier M, Babu M, Ciruela F, Jockers R, Jurisica I, and Stagljar I. Systematic protein-protein interaction mapping for clinically-relevant human GPCRs, Mol Sys Biol, In press.
Yao Z, Darowski K, St-Denis N, Wong V, Offensperger F, Villedieu A, Amin S, Malty R, Aoki H, Guo H, Xu Y, Iorio C, Kotlyar M, Emili A, Jurisica I, Babu M, Neel B, Gingras AC, and Stagljar I, A global analysis of the protein phosphatase interactome, Mol Cell, in press.
Petschnigg J, Kotlyar M, Blair L, Jurisica I, Stagljar I, and Ketteler R, Systematic identification of oncogenic EGFR interaction partners, J Mol Biol, in press.
Rahmati, S., Abovsky, M., Pastrello, C., Jurisica, I. pathDIP: An annotated resource for known and predicted human gene-pathway associations and pathway enrichment analysis. Nucl Acids Res, 45(D1): D419-D426, 2016.
Chehade, R., R. Pettapiece-Phillips, Salmena, L., Kotlyar, M., Jurisica, I., Narod, S. A., Akbari, M. R., Kotsopoulos, J. Reduced BRCA1 transcript levels in freshly isolated blood leukocytes from BRCA1 mutation carriers is mutation specific, Breast Cancer Res, 18(1): 87, 2016.
Cierna, Z., Mego, M., Jurisica, I., Machalekova, K., Chovanec, M., Miskovska, V., Svetlovska, D., Hainova, K., Kajo, K., Mardiak, J., Babal, P. Fibrillin-1 (FBN-1) a new marker of germ cell neoplasia in situ, BMC Cancer, 16: 597, 2016.
Thank you to members

This work would not be possible without the participation of World Community Grid Members. Thank you for generously contributing CPU cycles, and for your interest in this and other World Community Grid projects.
大意:
MCM项目近况
MCM项目当前正在计算卵巢癌数据,继续分析已经上传的肺癌数据。
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发表于 2017-4-25 09:48:31 | 显示全部楼层
World Community Grid Moves to IBM Cloud
24 四月 2017          

摘要
On May 15, World Community Grid will begin migrating to IBM Cloud, as part of an effort to modernize and enhance our infrastructure capabilities. Our system will be unavailable for approximately 48 hours while the migration takes place, but otherwise the move will not affect most volunteers.


We're happy to announce that World Community Grid is moving to IBM Cloud. Through this migration, we are leveraging more scalable and powerful hosting capabilities, as well as IBM and open source automation tools that make our development and deployment processes more efficient. This allows us to identify, diagnose and address major technical issues more quickly. Most significantly, IBM Cloud's global footprint of more than 50 data centers across 19 countries allows us to expand more easily and prepares us for years of growth.

The migration will begin on May 15 and is expected to last approximately 48 hours, during which World Community Grid will be unavailable. This means that volunteers will not be able to access the website, fetch new research or return completed work during that time.

No action is required by most volunteers, as our systems will resume sending and receiving research tasks once the migration is complete. However, for individuals or organizations who have restricted firewall rules, you may need to update those rules in order to continue contributing, by allowing connections to our new IP address (169.47.63.74).

Anyone with questions about this migration can post in this forum thread. We appreciate everyone's support during this migration, which will provide a modern hosting environment for volunteers and researchers for years to come.
大意:
WCG计划于5月15日整体迁移至IBM云平台,预计需要48小时,请大家做好准备。
迁移后平台服务容量将大增。迁移后服务器ip地址将变为169.47.63.74,安装了防火墙的用户,请将该地址加入白名单。

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发表于 2017-4-26 16:35:50 | 显示全部楼层
vmzy大佬原来已经默默的更新过新闻了。。最近真是疏于工作。。
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发表于 2017-8-2 13:36:06 | 显示全部楼层
Potential New Treatments for Leishmaniasis Tested in Lab
By: Dr. Carlos Muskus López
Coordinator, Molecular Biology and Computational Unit, PECET University of Antioquia
1 八月 2017          

摘要
The Drug Search for Leishmaniasis team has begun lab testing potential treatments for this serious—yet neglected—tropical disease. In this update, Dr. Carlos Muskus discusses the results of topical (on the skin) testing of four compounds.


Sandflies, such as the P. papatasi shown above, are responsible for the spread of leishmaniasis.
Background

Leishmaniasis is one of the most neglected tropical diseases in the world, infecting more than two million people in 98 countries. One form of the disease, caused by Leishmania infantum in America, mainly affects children, who can die if adequate treatment is not provided promptly. The classical treatments for all forms of Leishmaniasis can cause severe side effects, including death. Furthermore, drug resistant parasites are causing major problems in many endemic countries. For these reasons, there is an urgent need for new, safe, and inexpensive drug compounds.

Identifying Potential Compounds

After analyzing many compounds with the best docking score based on the data from the project on World Community Grid and our further testing, 10 compounds were finally selected to test in vitro. The in vitro evaluation involved cytotoxicity analysis against human-derived cell lines. (As part of the process of drug discovery, we do testing to ensure that the promising compounds do not affect human cells, thus decreasing the chance of side effects.) In addition, we evaluate the effectiveness of each compound against Leishmania, the parasites that cause leishmaniasis. The best compounds are those that kill the parasites at a low dose and do not affect the human cells even at higher doses.

Lab Testing of Potential Compounds

After in vitro testing, four compounds were selected. to evaluate in vivo in hamsters. Hamsters and humans have similar reactions to leishmaniasis, so we can use hamsters to evaluate potential compounds.

Each compound was prepared as a topical formulation and applied daily for 10 days on the hamster's lesions. The hamsters were followed for two months. Groups of five hamsters per compound were used, and a summary of the compound, dose, and an outcome is presented in the table below. The different dosages used for each compound were selected based on the previous in vitro assays.


Compound
Dose mg /day
Results (%)
1107818
0,14 / 10
Improvement of the lesion between 11,1 - 15,7%  
20287460
1,3 / 10
Cure in 2 out 5 hamsters and improvement between 18,9-44,2%
20312719
2,8 / 10
Improvement in 35,7%
20325767
0,6 / 10
Improvement between 18,9-66%







Improvement: Percentage of reduction of the lesion size.
Cure: Complete re-epithelization of the lesion.

For the four compounds, different degrees of improvement were observed. The compound Amb 20287460 induced an almost complete curing of the lesions in two out of five hamsters. The compound 20312719 decreased the size of the lesions to various degrees. The remaining two compounds only induced small decreases in lesion size.

Next Steps

We still have a small remaining quantity of one of the compounds that produced some of the best result in the in vitro assay, but unfortunately the company that provided it did not synthesize it in sufficient quantity.  We plan to contact another company to order more of this compound.

In addition, we are planning to re-test the compound that induced a complete cure in two of five hamsters. In future tests, we will probably change the method of administration to injection or oral, and closely monitor the outcomes.

Thank you to everyone who supported this project. We will keep you updated on our progress.
大意:
利什曼是一种没有得到重视的热带寄生虫,在98个热带国家大约有2百万感染者。他会导致婴儿利什曼病,造成夭折。目前的治疗方法有很大副作用,而且由于抗药性的原因,药效每况愈下。所以研发新药变得更加迫在眉睫。
根据DSFL子项目的计算结果我选了10中最有潜在效果的化合物,进行了实验室试管毒理验证,保证这些化合物对正常的细胞没有毒性。
随后我们根据实验结果,我们选出了4种化合物,在仓鼠(和人类细胞一样可以感染利什曼寄生虫)身上进行活体测试。具体实验结果数据见表格。
其中20287460化合物完全治愈了两只,20312719化合物平均治愈率最高。
由于前一个公司提供的化合物合成量不足,无法进行进一步测试,接下来我们会找其他公司合成更多的药物,继续对药物进行研究。

译注:其实上个月还有个我朝c4cw项目的新闻,但是内容太有天朝特色(空话连篇,又开始新一年论文了,你懂的),就不翻译了,有兴趣的自己到wcg官网看吧

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发表于 2017-8-28 11:02:28 | 显示全部楼层
The Bacteria Inside Us: Gaining a New Understanding of Human Disease
By: The Microbiome Immunity Project research team
23 八月 2017

摘要
What if you could help researchers learn more about how the bacteria in and on our bodies play a role in diseases such as Type 1 diabetes? We're proud to announce our latest project, which will be the first of its kind, large-scale, comprehensive study of the human microbiome.

https://www.youtube.com/embed/3AdM6Cmpd58

What's the microbiome, and why is it important?

The human microbiome is a collection of all of the bacteria that live inside our bodies and all of the genes that they have. Scientists have found that we each have as many as 30 trillion bacteria in our own microbiome, and most of them live in our gut.  

The bacteria in the microbiome are usually beneficial to humans. They can even be essential to our health. However, some are linked to diseases such as Type 1 diabetes, Crohn's disease, and ulcerative colitis. These diseases are becoming more common all over the world.

What's the microbiome's role in various diseases?

The short answer: scientists don't know exactly how the microbiome influences the beginning and development of disease, but they know that it plays an important role. That's why our group–consisting of researchers from the Broad Institute of MIT and Harvard, Massachusetts General Hospital, University of California San Diego, and the Simons Foundation's Flatiron Institute–is partnering with World Community Grid on the Microbiome Immunity Project. The project's goal is to study all the proteins (the building blocks of organisms) of the human microbiome, so that we and other researchers have a strong foundation to address these diseases.

In order to uncover the microbiome's role in the development of diseases, we need to first study the proteins produced by the bacteria in the microbiome. Learning about these proteins is important because proteins perform cell functions– they can interact with each other to form larger structures, they can carry out chemical reactions, bind on to other macromolecules in the cell, transport smaller molecules, or carry out a host of other roles within cells.

So far, there has not been a study of the human microbiome on this scale. Researchers have studied individual bacteria and specific proteins in the microbiome, but never all the proteins that are made by all the different bacteria. When you have trillions of bacteria to study in the gut alone, this becomes a monumental task.

We, like most research organizations, don't have anywhere near the amount of computing power needed to take on such a task.

You can help!

We're enlisting the help of volunteers like you from all over the world to support the Microbiome Immunity Project. Together, World Community Grid volunteers provide researchers like us with the enormous computing power we need to carry out studies that would not otherwise be possible.

"Without World Community Grid, we wouldn't have even contemplated this project."

Rob Knight, PhD
Professor, Departments of Pediatrics
and Computer Science & Engineering
Director, Center for Microbiome Innovation
Co-Principal Investigator, Microbiome Immunity Project

Here's how it works: As a World Community Grid volunteer, you download a secure software program to your computer. And when your computer has any unused processing power, it will run a simulated experiment for us in the background. As we receive the results of these simulations, we'll analyze the data to find the most likely structure for each of the proteins in the microbiome. This will help us understand the role of these proteins and therefore allow us to unlock new strategies for treating diseases impacted by the microbiome.

With thousands of volunteers running millions of simulations, we can get this crucial work done in just a few years, instead of decades. And in keeping with World Community Grid's open data policy, we're committed to making the data publicly available to other scientists, which will help accelerate the advancement of scientific knowledge in this important area of research.

The more volunteers we have for this project, the more quickly we can get this done! Thanks for joining us!

To contribute to the Microbiome Immunity Project, join World Community Grid, or if you are already a volunteer, make sure the project is selected on your My Projects page.
大意:
微生物群免疫(MIP)新项目启动
微生物群是生活在我们体内的细菌,一个普通人体内大概有30万亿的细菌,其中大部分生活在肠道内。他们一般都是益生菌,但也有些细菌也会导致1型糖尿病、克罗恩病、肠溃疡,这些疾病在全世界发病率越来越高。
但是科学家目前对细菌如何引发这些疾病还知之甚少。所以我们发起了这个新项目,对细菌的相关蛋白进行研究。
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发表于 2017-9-27 10:53:34 | 显示全部楼层
The Road Ahead for Help Fight Childhood Cancer
By: Dr. Akira Nakagawara, MD, PhD
CEO of the Saga Medical Center KOSEIKAN and President Emeritus, Chiba Cancer Center
26 九月 2017          

摘要
The Help Fight Childhood Cancer researchers discuss how they’re moving forward with data analysis and continuing their search for pharmaceutical partners.

Background

The Help Fight Childhood Cancer (HFCC) project was created to look for better treatments for neuroblastoma, which is refractory among childhood cancers (meaning that it is resistant to treatment). The project’s goal was to target certain cell proteins regulating cancer cell growth—such as TrkB tyrosine kinase receptor, ALK tyrosine kinase receptor, N - CYM protein and others—with the help of World Community Grid’s enormous computing power, which is donated by an international community of volunteers.

Our research team conducted in-silico (computer simulation-based) drug discovery screening using World Community Grid to search through a library of three million small molecular compounds. We discovered a small molecule compound which competitively binds to the TrkB protein pocket to which BDNF (a specific growth factor) binds. The discovered molecule can thus prevent BDNF from binding to the TrkB protein and diminish cancer cell growth. This could lead to a new and improved treatment for neuroblastoma.

Subsequently, the anti-tumor effect of the compound was examined using cultured cancer cells, or human neuroblastoma transplanted into mice, and this laboratory research confirmed that this small molecular compound and possibly some others could be candidates for anticancer drugs targeting TrkB. We announced this breakthrough and published our findings in the peer-reviewed, English language journal, Cancer Medicine, in 2014.

Current Research

Currently, we are conducting research to develop even more potent inhibitors by synthesizing small molecular compounds similar in structure to the compounds found using the screening. The road to developing commercial, approved new drugs is a tough task. We must find a pharmaceutical company that will conduct joint research and development and create a patentable compound so that this expensive effort is profitable. If any of you have contacts with a pharmaceutical company that may be interested in pursuing this venture, please introduce us.

Additionally, using World Community Grid to screen drug candidates, we found other small molecular compounds showing the ability to inhibit the ligand BDNF. These results were presented it in another English language journal (Neurochem International, 2016, abstract here). These compounds also look promising as a remedy for depression and dementia, and similarly, we are seeking a pharmaceutical company to cooperate in research and development of these.

The N-CYM is a new protein we discovered which is implicated in neuroblastoma. A published paper about this can be found here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879166/. Before we can screen for drug candidates, we must determine this protein's three-dimensional structure. Therefore, we are currently working on the difficult task of crystallizing the N-CYM protein so that we can perform X-ray analysis to determine the protein’s three-dimensional structure. Once the three-dimensional structure of the protein is determined, we will screen to find inhibiting compounds in the Smash Childhood Cancer project, which is building on the work from this project.

Regarding the development of ALK inhibitors (see article https://www.ncbi.nlm.nih.gov/pubmed/15972965), candidate compounds as inhibitors were found in the in-silico screening, and analysis on cultured cancer cells was completed. Because of the lack of research personnel, unfortunately preclinical tests have not yet progressed.

We thank all volunteers who supported this project, and look forward to keeping you updated on the progress of this project as well as the Smash Childhood Cancer project.
大意:
HFCC项目的主要目标是找到治疗神经母细胞瘤的药物
利用之前HFCC项目中大家计算的结果我们找到了一种小分子,它在试管和小鼠实验中都非常有效。现在我们诚征愿意冒险的制药公司来合作研制专利药品(译注:药品研发费时费钱,风险较大,一旦无法通过临床测试,前期投入几乎全打水漂)。
其次,在之前的计算结果中我们还发现了其他一些分子,有治疗抑郁或痴呆的潜在可能,我们同求有意向的制药公司进行合作研究。
N-CYM是神经母细胞瘤中一种新抑制剂蛋白。我们现在在对其做x射线3D构型,一旦完成,我们将在SCC项目中对其进行药物筛查。
至于ALK抑制剂,计算结果经实验室验证基本无效,囧rz
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发表于 2017-9-28 11:28:10 | 显示全部楼层
vmzy 发表于 2017-9-26 19:53
The Road Ahead for Help Fight Childhood Cancer
By: Dr. Akira Nakagawara, MD, PhD
CEO of the Saga Me ...

没事,实验室验证无效根本没事。一方面来说计算得出的结果就应该经受实验的检验。这个结果无效还有下一个潜在的可通过计算得到的结果可供验证。答案终将被发现。另一方面,如果每一个计算得到的结果都能通过验证那就太可怕了,人类的计算科学水平该有多高啊。所以平常心就好,且对未来抱有希望,这就是志愿计算的意义。
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发表于 2017-12-1 10:01:36 | 显示全部楼层
New Facility and Expanded Plans for the Mapping Cancer Markers Research Team
By: Dr. Igor Jurisica
Krembil Research Institute, University Health Network, Toronto
30 十一月 2017          

摘要
The Mapping Cancer Markers researchers recently moved to a new institute, but continues analyzing results, planning for expanded research, and creating new work units throughout the transition. Learn about their plans in this article.


The Mapping Cancer Markers project is currently processing data to identify biomarkers for ovarian cancer, one of the deadliest cancers for women.

Background

The Mapping Cancer Markers (MCM) project continues to process data to identify biomarkers for ovarian cancer. We are also in the process of analyzing MCM results from the lung cancer dataset, and we are finalizing preparation of the new work units for sarcoma, a type of malignant tumor. We will devote more space in the next project update to this work. Below we provide details about an exciting new development in the team.

The Move

After more than 17 years at Ontario Cancer Institute (now Princess Margaret Cancer Centre), we got an opportunity to join Krembil Research Institute (KRI) to work on a more complex approach to chronic diseases, where we moved in mid-November. KRI is still part of the University Health Network in Toronto, but focuses also on arthritis, neuroscience, and vision. The research and translational clinical research interests focus not only on diagnosis and improved treatment, but importantly on prevention, which aligns with my group’s interest over the last few years.

Thus, MCM has not been negatively affected—the physical move was smooth, and our severs stayed in the original server rooms, reducing the risk of any hiccup for World Community Grid work units and results. We will not only continue, but will expand on our research.

New Computational Biology Platform

Importantly, we are in the finalizing stages of paperwork to embark on a newly-funded research by the Ontario Government: The Next Generation Signalling Biology Platform. This will provide us funds to create a software infrastructure for the comprehensive, integrative computational biology analyses workflows, in collaboration with translational research and clinical trials groups. Our partners are Princess Margaret Cancer Centre, Krembil Research Institute, University of Toronto, University of Montreal, BC Cancer Agency, Cancer Clinical Trials Group, Queen’s University, and European Bioinformatics Institute (IMEx Consortium). Besides focusing on cancer, this is our first large osteo-arthritis research project.

Thank you to everyone for your support, and we look forward to providing additional updates as our work progresses.
大意:
MCM当前正在计算卵巢癌数据,正在分析肺癌数据,同时我们开始准备扩展项目,增加恶性肉瘤的新任务。

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发表于 2017-12-7 09:35:29 | 显示全部楼层
Planned Maintenance on Saturday, December 9
6 十二月 2017          

摘要
We are upgrading the software on multiple parts of the system on Saturday, December 9, beginning at 2:00 UTC.

We will be doing maintenance on multiple parts of our system on Saturday, December 9, beginning at 2:00 UTC. We anticipate that the work will take approximately four hours.

During this time, volunteers will not be able to upload or download new work, and the website will not be accessible. No action is required by you, as your devices will automatically retry their connections after the maintenance work is completed.

We appreciate your patience, and your participation in World Community Grid.
大意:
计划于9号(本周六)上午10点对系统软件进行升级,预计耗时4小时,届时全站下线,不能上传/下载任务。

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发表于 2017-12-15 09:38:27 | 显示全部楼层
2017-12-14: World Community Grid, Sustainable Water Data Available to Interested Scientists

Dr. Gerry Learmonth, the principal investigator for the Computing for Sustainable Water project, gives an update on the primary findings of the project as well as how other scientists can access the data.


-----------------
2017.12.14 可持续水资源(Sustainable Water)子项目的计算数据对科学家开放

该项目的负责人Gerry Learmonth 博士更新了项目的主要研究成果,并且对其他科学家开放了成果数据访问权限。

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发表于 2018-1-5 10:41:03 | 显示全部楼层
Planned Maintenance on Saturday, January 6
4 一月 2018          

摘要
We are updating the operating system on our servers on Saturday, January 6, beginning at 2:00 UTC.

We will be applying an important operating system update to our servers on Saturday, January 6, beginning at 2:00 UTC. We anticipate that the work will take approximately four hours.

During this time, volunteers will not be able to upload or download new work. The website will not be accessible during this time. No action is required by volunteers, as devices will automatically retry their connections after the maintenance work is completed.

We appreciate your patience and participation.
大意:
计划于1月6日(周六)早10点开始进行操作系统升级,预计耗时4小时,届时全站离线,不能上传/下载任务。

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发表于 2018-1-23 12:52:23 | 显示全部楼层
Computing for Clean Water Results Inspire Further Study
By: The Computing for Clean Water team
22 一月 2018
An international team of researchers was inspired by the Computing for Clean Water project to do a series of further simulations, using a slightly different model and studying the diffusion of oxygen molecules as well as water molecules. Learn about their results, which validated the work done on World Community Grid, in this article.

清水计算结果启发了二次研究
一个国际研究团队受到清水计划项目结果启发,使用了略微不同的模型研究氧分子以及水分子的扩散效应。
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发表于 2018-2-9 10:02:13 | 显示全部楼层
Planned Maintenance on Monday, February 12
8 二月 2018          

摘要
We are updating the operating system on our servers on Monday, February 12 beginning at 15:00 UTC.

We will be applying an important operating system update to our servers on Monday, February 12, beginning at 15:00 UTC. We anticipate that the work will take approximately four hours.

During this time, volunteers will not be able to upload or download new work, and the website will not be accessible. No action is required by you, as your devices will automatically retry their connections after the maintenance work is completed.

We appreciate your patience and participation.
大意:
计划于2月12号(下周一)晚上11点对操作系统进行升级,预计耗时4小时,届时全站下线,不能上传/下载任务。

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金鹏 + 20 辛苦了!

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