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  • 1
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    A public resource for clinical use of genomes [Genetics] (2012)
    National Academy of Sciences
    Details
    Publication Date: 2012-07-25
    Description: Rapid advances in DNA sequencing promise to enable new diagnostics and individualized therapies. Achieving personalized medicine, however, will require extensive research on highly reidentifiable, integrated datasets of genomic and health information. To assist with this, participants in the Personal Genome Project choose to forgo privacy via our institutional review board- approved “open consent” process. The contribution of public data and samples facilitates both scientific discovery and standardization of methods. We present our findings after enrollment of more than 1,800 participants, including whole-genome sequencing of 10 pilot participant genomes (the PGP-10). We introduce the Genome-Environment-Trait Evidence (GET-Evidence) system. This tool automatically processes genomes and prioritizes both published and novel variants for interpretation. In the process of reviewing the presumed healthy PGP-10 genomes, we find numerous literature references implying serious disease. Although it is sometimes impossible to rule out a late-onset effect, stringent evidence requirements can address the high rate of incidental findings. To that end we develop a peer production system for recording and organizing variant evaluations according to standard evidence guidelines, creating a public forum for reaching consensus on interpretation of clinically relevant variants. Genome analysis becomes a two-step process: using a prioritized list to record variant evaluations, then automatically sorting reviewed variants using these annotations. Genome data, health and trait information, participant samples, and variant interpretations are all shared in the public domain—we invite others to review our results using our participant samples and contribute to our interpretations. We offer our public resource and methods to further personalized medical research.
    Keywords: Inaugural Articles
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Cambrian animal radiation [Earth, Atmospheric, and Planetary Sciences] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-08-14
    Description: The Proterozoic-Cambrian transition records the appearance of essentially all animal body plans (phyla), yet to date no single hypothesis adequately explains both the timing of the event and the evident increase in diversity and disparity. Ecological triggers focused on escalatory predator–prey “arms races” can explain the evolutionary pattern but not...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 3
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    Agronomic improvements can make future cereal systems in South Asia far more productive and result in a lower environmental footprint (2015)
    Wiley
    Details
    Publication Date: 2015-11-04
    Description: South Asian countries will have to double their food production by 2050 while using resources more efficiently and minimizing environmental problems. Transformative management approaches and technology solutions will be required in the major grain-producing areas that provide the basis for future food and nutrition security. This study was conducted in four locations representing major food production systems of densely populated regions of South Asia. Novel production-scale research platforms were established to assess and optimize three futuristic cropping systems and management scenarios (S2, S3, S4) in comparison with current management (S1). With best agronomic management practices (BMPs), including conservation agriculture (CA) and cropping system diversification, the productivity of rice- and wheat-based cropping systems of South Asia increased substantially whereas the global warming potential intensity decreased. Positive economic returns and less use of water, labor, nitrogen, and fossil fuel energy per unit food produced were achieved. In comparison to S1, S4, in which BMPs, CA and crop diversification were implemented in the most integrated manner, achieved 54% higher grain energy yield with a 104% increase in economic returns, 35% lower total water input, and a 43% lower global warming potential intensity. Conservation agriculture practices were most suitable for intensifying as well as diversifying wheat-rice rotations, but less so for rice-rice systems. This finding also highlights the need for characterizing areas suitable for CA and subsequent technology targeting. A comprehensive baseline dataset generated in the present study will allow the prediction of extending benefits to a larger scale. This article is protected by copyright. All rights reserved.
    Print ISSN: 1354-1013
    Electronic ISSN: 1365-2486
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Published by Wiley
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  • 4
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    Coordinative Supramolecular Assembly of Electrochromic Films Based on Metal Ion Complexes of Polyiminofluorene with Terpyridine Substituent Groups (2009)
    American Chemical Society
    Details
    Publication Date: 2009-05-26
    Print ISSN: 0897-4756
    Electronic ISSN: 1520-5002
    Topics: Chemistry and Pharmacology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by American Chemical Society
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  • 5
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    Tf modulates leaf and shoot architecture [Plant Biology] (2013)
    National Academy of Sciences
    Details
    Publication Date: 2013-02-06
    Description: Leaf morphology and the pattern of shoot branching determine to a large extent the growth habit of seed plants. Until recently, the developmental processes that led to the establishment of these morphological structures seemed unrelated. Here, we show that the tomato Trifoliate (Tf) gene plays a crucial role in both...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Critical assessment of genome-scale metabolic networks: the need for a unified standard (2015)
    Oxford University Press
    Details
    Publication Date: 2015-11-20
    Description: Genome-scale metabolic networks have been reconstructed for several organisms. These metabolic networks provide detailed information about the metabolism inside the cells, coupled with the genomic, proteomic and thermodynamic information. These networks are widely simulated using ‘constraint-based’ modelling techniques and find applications ranging from strain improvement for metabolic engineering to prediction of drug targets in pathogenic organisms. Components of these metabolic networks are represented in multiple file formats and also using different markup languages, with varying levels of annotations; this leads to inconsistencies and increases the complexities in comparing and analysing reconstructions on multiple platforms. In this work, we critically examine nearly 100 published genome-scale metabolic networks and their corresponding constraint-based models and discuss various issues with respect to model quality. One of the major concerns is the lack of annotations using standard identifiers that can uniquely describe several components such as metabolites, genes, proteins and reactions. We also find that many models do not have complete information regarding constraints on reactions fluxes and objective functions for carrying out simulations. Overall, our analysis highlights the need for a widely acceptable standard for representing constraint-based models. A rigorous standard can help in streamlining the process of reconstruction and improve the quality of reconstructed metabolic models.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
    Published by Oxford University Press
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  • 7
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    Enhanced efficiency in the excitation of higher modes for atomic force microscopy and mechanical sensors operated in liquids (2014)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2014-10-28
    Description: Recent developments in dynamic Atomic Force Microscopy where several eigenmodes are simultaneously excited in liquid media are proving to be an excellent tool in biological studies. Despite its relevance, the search for a reliable, efficient, and strong cantilever excitation method is still in progress. Herein, we present a theoretical modeling and experimental results of different actuation methods compatible with the operation of Atomic Force Microscopy in liquid environments: ideal acoustic, homogeneously distributed force, distributed applied torque (MAC Mode™), photothermal and magnetostrictive excitation. From the analysis of the results, it can be concluded that magnetostriction is the strongest and most efficient technique for higher eigenmode excitation when using soft cantilevers in liquid media.
    Print ISSN: 0003-6951
    Electronic ISSN: 1077-3118
    Topics: Physics
    Published by American Institute of Physics (AIP)
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  • 8
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    A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-09-18
    Description: Antiviral responses must be tightly regulated to defend rapidly against infection while minimizing inflammatory damage. Type 1 interferons (IFN-I) are crucial mediators of antiviral responses and their transcription is regulated by a variety of transcription factors; principal among these is the family of interferon regulatory factors (IRFs). The IRF gene regulatory networks are complex and contain multiple feedback loops. The tools of systems biology are well suited to elucidate the complex interactions that give rise to precise coordination of the interferon response. Here we have used an unbiased systems approach to predict that a member of the forkhead family of transcription factors, FOXO3, is a negative regulator of a subset of antiviral genes. This prediction was validated using macrophages isolated from Foxo3-null mice. Genome-wide location analysis combined with gene deletion studies identified the Irf7 gene as a critical target of FOXO3. FOXO3 was identified as a negative regulator of Irf7 transcription and we have further demonstrated that FOXO3, IRF7 and IFN-I form a coherent feed-forward regulatory circuit. Our data suggest that the FOXO3-IRF7 regulatory circuit represents a novel mechanism for establishing the requisite set points in the interferon pathway that balances the beneficial effects and deleterious sequelae of the antiviral response.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Litvak, Vladimir -- Ratushny, Alexander V -- Lampano, Aaron E -- Schmitz, Frank -- Huang, Albert C -- Raman, Ayush -- Rust, Alistair G -- Bergthaler, Andreas -- Aitchison, John D -- Aderem, Alan -- HHSN272200700038C/AI/NIAID NIH HHS/ -- HHSN272200700038C/PHS HHS/ -- HHSN272200800058C/AI/NIAID NIH HHS/ -- HSN272200800058C/PHS HHS/ -- R01 AI025032/AI/NIAID NIH HHS/ -- R01 AI032972/AI/NIAID NIH HHS/ -- R01AI025032/AI/NIAID NIH HHS/ -- R01AI032972/AI/NIAID NIH HHS/ -- U19 AI100627/AI/NIAID NIH HHS/ -- U54 GM103511/GM/NIGMS NIH HHS/ -- U54 RR022220/RR/NCRR NIH HHS/ -- U54GM103511/GM/NIGMS NIH HHS/ -- England -- Nature. 2012 Oct 18;490(7420):421-5. doi: 10.1038/nature11428. Epub 2012 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, Washington 98109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22982991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Forkhead Transcription Factors/deficiency/genetics/*metabolism ; Gene Deletion ; Gene Expression Regulation/*immunology ; Inflammation/genetics/*immunology/*pathology ; Interferon Regulatory Factor-7/deficiency/genetics/*metabolism ; Interferon Type I/immunology ; Lung/immunology/pathology/virology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Reproducibility of Results ; Vesiculovirus/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 9
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    The spatial architecture of protein function and adaptation (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-10-09
    Description: Statistical analysis of protein evolution suggests a design for natural proteins in which sparse networks of coevolving amino acids (termed sectors) comprise the essence of three-dimensional structure and function. However, proteins are also subject to pressures deriving from the dynamics of the evolutionary process itself--the ability to tolerate mutation and to be adaptive to changing selection pressures. To understand the relationship of the sector architecture to these properties, we developed a high-throughput quantitative method for a comprehensive single-mutation study in which every position is substituted individually to every other amino acid. Using a PDZ domain (PSD95(pdz3)) model system, we show that sector positions are functionally sensitive to mutation, whereas non-sector positions are more tolerant to substitution. In addition, we find that adaptation to a new binding specificity initiates exclusively through variation within sector residues. A combination of just two sector mutations located near and away from the ligand-binding site suffices to switch the binding specificity of PSD95(pdz3) quantitatively towards a class-switching ligand. The localization of functional constraint and adaptive variation within the sector has important implications for understanding and engineering proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991786/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991786/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McLaughlin, Richard N Jr -- Poelwijk, Frank J -- Raman, Arjun -- Gosal, Walraj S -- Ranganathan, Rama -- R01 EY018720/EY/NEI NIH HHS/ -- R01EY018720-05/EY/NEI NIH HHS/ -- England -- Nature. 2012 Nov 1;491(7422):138-42. doi: 10.1038/nature11500. Epub 2012 Oct 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23041932" target="_blank"〉PubMed〈/a〉
    Keywords: *Adaptation, Physiological/genetics/physiology ; Amino Acid Sequence ; *Amino Acid Substitution ; Binding Sites/genetics ; Evolution, Molecular ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Mutant Proteins/*chemistry/genetics/metabolism ; Mutation ; PDZ Domains/*genetics/*physiology ; Proteins/*chemistry/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 10
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    Performance of Fluidized bed Fenton process in Degrading Acid Blue 113 (2017)
    Institute of Physics (IOP)
    Details
    Publication Date: 2017-06-27
    Description: The performance of a fluidized bed Fenton process in degrading Acid Blue 113 (AB 113) was investigated. Fluidized bed Fenton process is a modification of conventional Fenton oxidation, aimed at reducing sludge generation and improving process performance. Response surface methodology was used to study the effects of operational parameter on the color removal from the dye. Dimensionless factors, Dye/Fe 2+ , H 2 O 2 /Fe 2+ and pH were used as the independent variables in Box-Behnken Design (BDD). Reduced quadratic model was developed to predict the color removal. The process could remove up to 99 % of the initial color. The most significant factor for color removal was found to be Dye/Fe 2+ , followed by H 2 O 2 /Fe 2+ . Unlike conventional Fenton, the initial pH of the solution does not have a significant effect on the color removal.
    Print ISSN: 1757-8981
    Electronic ISSN: 1757-899X
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Institute of Physics (IOP)
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