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Microsoft Research Connections Blog

The Microsoft Research Connections blog shares stories of collaborations with computer scientists at academic and scientific institutions to advance technical innovations in computing, as well as related events, scholarships, and fellowships.

  • Microsoft Research Connections Blog

    Universities Partner with Scholarships for Aspirations Award Winners

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    There is a significant dearth of women working in—or even entering—the computer science field. According to the National Center for Women & Information Technology (NCWIT), only 18 percent of computer science degrees in 2008 were awarded to women. That was a dramatic drop from 37 percent in 1985. With those totals, it's not surprising that only 16 percent of Fortune 500 technology companies have female executives. Of greater concern is the small number of women who are applying for technology jobs, even during the economic downturn when jobs are scarce. NCWIT is working to reverse that trend.

    Winners at the event held at the Microsoft New England Research & Development Center in Cambridge, MA

    Winners at the event held at the Microsoft New England Research & Development Center in Cambridge, MA

    We are proud to be the primary financial supporter of the NCWIT Award for Aspirations in Computing, which honors young women at the high-school level for their computer-related achievements and interests. NCWIT offers both national and local "affiliate" competitions to generate support and visibility for women's participation in communities nationwide.

    National Award winners receive a US$500 cash prize; a laptop computer provided by Bank of America; a trip to attend the Bank of America Technology Showcase and Awards Ceremony in Charlotte, North Carolina; and an engraved award for both the student and the student's school. Affiliate Award winners receive an engraved award for their home and school, plus additional prizes from local sponsors.

    I'm pleased to announce that the academic community stepped up this year to offer scholarships to this year's NCWIT winners as well. There will be 19 Affiliate Award programs serving 20 states and U.S. territories in the 2010/2011 round. Schools expected to connect with our winners include:

    The NCWIT Award for Aspirations in Computing is a promising avenue for reaching out to and encouraging young women with a budding interest in computer science. By nurturing this interest early, we are increasing the likelihood that these young women will pursue computer science degrees and one day join us as the next generation of world-class computer scientists.

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    —Jane Prey, Senior Research Program Manager, Microsoft Research Connections division of Microsoft Research

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    Coevolution of Viruses and the Immune System Study Featured in Journal of Virology

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    Mosquito larvaeResearchers believe that pathogens are evolving to evade detection from the human immune system. I recently co-published a paper that discussed research into the ongoing evolutionary struggle between the immune system and pathogens. In this study, we sought to identify possible commonalities in HLA (human leukocyte antigen) binding preferences that would reveal patterns of optimization of this component of the immune system in response to the variation in pathogens.

     

    I worked with post-doctoral student Tomer Hertz (now with Fred Hutchinson Cancer Research Lab) and a distinguished group of colleagues from the Institute for Immunology and Infectious Diseases, Royal Perth Hospital, and Murdoch University (Western Australia); the School of Anatomy and Human Biology, Centre for Forensic Science, University of Western Australia (Western Australia); and Fundacion Ciencia para la Vida (Chile).

    Our paper, "Mapping the Landscape of Host-Pathogen Coevolution: HLA Class I Binding and Its Relationship with Evolutionary Conservation in Human and Viral Proteins," appeared in the American Society for Microbiology's Journal of Virology in February 2011. I'd like to share some highlights from the study with you.

    Identifying Possible Commonalities in HLA Binding Preference

    The majority of the cells in our bodies express something called HLA molecules, whose role is to sample cellular proteins and present them on the cellular surface for external surveillance by the specialized cells of our immune systems. This action forces all cells to reveal imprints of their inner workings.

    When something out of the ordinary is detected—for example, the presence of an unusual mutation or a gene expression—the type and quality of the presented samples can spur the immune system's specialized killer cells into action. By sending kill signals to "odd" cells, the immune system can stop diseases such as cancer or viral infections. (Viruses bring their own genetic material to the cell and use the cellular resources to propagate.)

    However, this scrutiny of the immune system creates evolutionary pressure on viruses, which often mutate to evade detection. Since the system of HLA molecules is highly selective in its sampling of protein segments, the mutational patterns in viruses are not entirely random: mutations tend to occur within the segments that HLA molecules are most likely to present.

    On the other hand, over many generations, the distribution of thousands of HLA variants present in human populations may change. Additionally, in different geographic regions, we find significant variation in frequencies of different HLA molecules. This sets up an evolutionary game between the viruses on the one side and our immune systems on the other.

    Targeting Efficiency

    In order to analyze the results of the evolutionary processes that are driven by the interaction of HLA molecules with a wide diversity of viral intruders, we quantified the HLA binding preferences by using a novel measure called "targeting efficiency."

    Targeting efficiency entails capturing the correlation between HLA-peptide binding affinities with the genetic conservation in the targeted proteomic regions. If HLA molecules possessed such targeting efficiency, this would (presumably) prove beneficial to humans. In theory, HLA molecules would draw attention to protein segments that are shared across related viral species as functionally important and thus immutable sections of their proteins. Individual invading viruses would find it more difficult to evade surveillance by mutating, because mutation within these segments would ruin the protein function. Targeting efficiency could even allow the immune system to generalize across related viral species.

    Our analysis of targeting efficiencies for 95 HLA Class I alleles over thousands of human proteins and 52 human viruses indicate that HLA molecules do indeed prefer to target conserved regions in these proteomes! However, the arboviral Flaviviridae (for example, Dengue virus) proved a notable exception in which non-conserved regions were the preferred target of most alleles.

    HLA molecules are encoded in three separate parts of the human genome: A, B, and C. During our study, we discovered that the oldest versions of our HLA molecules—namely the HLA-A alleles and several HLA-B alleles that had maintained a close sequence identity with chimpanzee homologues—were targeting conserved human proteins and DNA viruses (for example, Herpesviridae and Adenoviridae) most efficiently.

    By contrast, the HLA-B alleles were targeting RNA viruses efficiently. This is reminiscent of predator-prey patterns that have been identified in evolutionary theory. For example, we know the following factors to be true:

    • The different HLA families can evolve separately because they are encoded separately.
    • The different HLA families can act on the same targets in the same cells.

    Based on this information, we can extrapolate that evolution is going to drive their binding properties in different directions, thus splitting their targets, as in the established Lotka-Volterra (predator-prey) model of different types of foxes and rabbits inhabiting the same forest. In addition, we identified various patterns of host/pathogen specialization that are consistent with co-evolutionary selection and were also functionally relevant in specific cases. For example, preferential HLA targeting of conserved proteomic regions is associated with improved outcomes in HIV infections as well as protection against Dengue Hemorrhagic Fever.

    I have just scratched the surface of the study in this blog. For complete study details, including a complete presentation of our methodology and findings, please follow the links below.

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    —Nebojsa Jojic, Principal Researcher, Microsoft Research eScience Group

     

  • Microsoft Research Connections Blog

    Project Hawaii Students Get More Done in the Cloud: Announcing Speech to Text Service

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    Project HawaiiBack in January, I blogged about Project Hawaii, a research and academic outreach program sponsored by Microsoft Research in cooperation with 20 universities worldwide. Approximately 300 students at those universities are developing applications for Windows Phone 7 this semester as part of the program. These students have already come up with new and innovative scenarios by using our previously released Relay and Rendezvous services. Beginning today, they will have another cloud service in their development arsenal: a Speech to Text Service.

    This new cloud service will enable Project Hawaii participants to expand their applications with options such as diction, transcription, and voice commands. Students will also be able to use the new service to integrate other complex applications, such as Microsoft Translator, into their development projects. There is one limitation: Speech to Text currently supports English only. There are no plans to expand into other languages at this time.

    In addition to making this service available to our Project Hawaii students, we are also releasing sample code from an application for Windows Phone 7 as part of the software development kit (SDK). This sample will allow users to speak into a phone and get transcribed text of their words in return. Plus, we'll be releasing an Optical Character Recognition (OCR) service for our Hawaii participants to use in the near future.

    —Arjmand Samuel, Research Project Manager with the Microsoft Research Connections division of Microsoft Research

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