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  • 1
    Publication Date: 2013-04-10
    Description: Author(s): Paul R. Shapiro, Yi Mao, Ilian T. Iliev, Garrelt Mellema, Kanan K. Datta, Kyungjin Ahn, and Jun Koda The 21 cm background from the epoch of reionization is a promising cosmological probe: line-of-sight velocity fluctuations distort redshift, so brightness fluctuations in Fourier space depend upon angle, which linear theory shows can separate cosmological from astrophysical information. Nonlinear fl... [Phys. Rev. Lett. 110, 151301] Published Tue Apr 09, 2013
    Keywords: Gravitation and Astrophysics
    Print ISSN: 0031-9007
    Electronic ISSN: 1079-7114
    Topics: Physics
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  • 2
    Publication Date: 2015-05-06
    Description: Author(s): Yi Mao, Anson D’Aloisio, Benjamin D. Wandelt, Jun Zhang, and Paul R. Shapiro The linear perturbation theory of inhomogeneous reionization (LPTR) has been developed as an analytical tool for predicting the global ionized fraction and large-scale power spectrum of ionized density fluctuations during reionization. In the original formulation of the LPTR, the ionization balance ... [Phys. Rev. D 91, 083015] Published Thu Apr 30, 2015
    Keywords: Astrophysics
    Print ISSN: 0556-2821
    Electronic ISSN: 1089-4918
    Topics: Physics
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  • 3
    Publication Date: 2019
    Description: Wake models play an integral role in wind farm layout optimization and operations where associated design and control decisions are only as good as the underlying wake model upon which they are based. However, the desired model fidelity must be counterbalanced by the need for simplicity and computational efficiency. As a result, efficient engineering models that accurately capture the relevant physics—such as wake expansion and wake interactions for design problems and wake advection and turbulent fluctuations for control problems—are needed to advance the field of wind farm optimization. In this paper, we discuss a computationally-efficient continuous-time one-dimensional dynamic wake model that includes several features derived from fundamental physics, making it less ad-hoc than prevailing approaches. We first apply the steady-state solution of the model to predict the wake expansion coefficients commonly used in design problems. We demonstrate that more realistic results can be attained by linking the wake expansion rate to a top-down model of the atmospheric boundary layer, using a super-Gaussian wake profile that smoothly transitions between a top-hat and Gaussian distribution as well as linearly-superposing wake interactions. We then apply the dynamic model to predict trajectories of wind farm power output during start-up and highlight the improved accuracy of non-linear advection over linear advection. Finally, we apply the dynamic model to the control-oriented application of predicting power output of an irregularly-arranged farm during continuous operation. In this application, model fidelity is improved through state and parameter estimation accounting for spanwise inflow inhomogeneities and turbulent fluctuations. The proposed approach thus provides a modeling paradigm with the flexibility to enable designers to trade-off between accuracy and computational speed for a wide range of wind farm design and control applications.
    Electronic ISSN: 1996-1073
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by MDPI
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  • 4
    Publication Date: 2012-04-24
    Description: The brain is a large and complex network of neurons. Specific neuronal connectivity is thought to be based on the combinatorial expression of the 52 protocadherins ( Pcdh ) membrane adhesion proteins, whereby each neuron expresses only a specific subset. Pcdh genes are arranged in tandem, in a cluster of three families: Pcdhα , Pcdhβ and Pcdh . The expression of each Pcdh gene is regulated by a promoter that has a regulatory conserved sequence element (CSE), common to all 52 genes. The mechanism and factors controlling individual Pcdh gene expression are currently unknown. Here we show that the promoter of each Pcdh gene contains a gene-specific conserved control region, termed specific sequence element (SSE), located adjacent and upstream to the CSE and activates transcription together with the CSE. We purified the complex that specifically binds the SSE–CSE region and identified the CCTC binding-factor (CTCF) as a key molecule that binds and activates Pcdh promoters. Our findings point to CTCF as a factor essential for Pcdh expression and probably governing neuronal connectivity.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2013-10-24
    Description: Author(s): Yi Mao, Anson D’Aloisio, Jun Zhang, and Paul R. Shapiro Measuring the small primordial non-Gaussianity (PNG) predicted by cosmic inflation theories may help diagnose them. The detectability of PNG by its imprint on the 21 cm power spectrum from the epoch of reionization is reassessed here in terms of f NL , the local nonlinearity parameter. We find that an... [Phys. Rev. D 88, 081303] Published Wed Oct 23, 2013
    Keywords: Astrophysics & Cosmology
    Print ISSN: 0556-2821
    Electronic ISSN: 1089-4918
    Topics: Physics
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  • 6
    Publication Date: 2014-05-01
    Description: Author(s): Bohua Li, Tanja Rindler-Daller, and Paul R. Shapiro Despite the great successes of the cold dark matter (CDM) model in explaining a wide range of observations of the global evolution and the formation of galaxies and large-scale structure in the Universe, the origin and microscopic nature of dark matter is still unknown. The most common form of CDM c... [Phys. Rev. D 89, 083536] Published Wed Apr 30, 2014
    Keywords: Cosmology
    Print ISSN: 0556-2821
    Electronic ISSN: 1089-4918
    Topics: Physics
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  • 7
    Publication Date: 2009-02-27
    Description: The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from 〉2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P 〈 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3148020/" 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/PMC3148020/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawashima, Yuka -- Pfafferott, Katja -- Frater, John -- Matthews, Philippa -- Payne, Rebecca -- Addo, Marylyn -- Gatanaga, Hiroyuki -- Fujiwara, Mamoru -- Hachiya, Atsuko -- Koizumi, Hirokazu -- Kuse, Nozomi -- Oka, Shinichi -- Duda, Anna -- Prendergast, Andrew -- Crawford, Hayley -- Leslie, Alasdair -- Brumme, Zabrina -- Brumme, Chanson -- Allen, Todd -- Brander, Christian -- Kaslow, Richard -- Tang, James -- Hunter, Eric -- Allen, Susan -- Mulenga, Joseph -- Branch, Songee -- Roach, Tim -- John, Mina -- Mallal, Simon -- Ogwu, Anthony -- Shapiro, Roger -- Prado, Julia G -- Fidler, Sarah -- Weber, Jonathan -- Pybus, Oliver G -- Klenerman, Paul -- Ndung'u, Thumbi -- Phillips, Rodney -- Heckerman, David -- Harrigan, P Richard -- Walker, Bruce D -- Takiguchi, Masafumi -- Goulder, Philip -- 1 R01 AI067073/AI/NIAID NIH HHS/ -- G0500384/Medical Research Council/United Kingdom -- G0501777/Medical Research Council/United Kingdom -- G108/626/Medical Research Council/United Kingdom -- R01 AI046995/AI/NIAID NIH HHS/ -- R01 AI046995-10/AI/NIAID NIH HHS/ -- R01 AI060460/AI/NIAID NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI064060-06A1/AI/NIAID NIH HHS/ -- R01AI46995/AI/NIAID NIH HHS/ -- R01AI64060/AI/NIAID NIH HHS/ -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Apr 2;458(7238):641-5. doi: 10.1038/nature07746. Epub 2009 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral Immunology, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242411" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; CD8-Positive T-Lymphocytes/immunology ; Cohort Studies ; Epitopes, T-Lymphocyte/chemistry/genetics/immunology ; HIV Antigens/chemistry/genetics/immunology ; HIV-1/genetics/*immunology/physiology ; HLA-B Antigens/genetics/*immunology ; Humans ; Internationality ; Leukocytes/*immunology ; Polymorphism, Genetic ; gag Gene Products, Human Immunodeficiency Virus/chemistry/genetics/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2009-12-17
    Description: Mistranslation arising from confusion of serine for alanine by alanyl-tRNA synthetases (AlaRSs) has profound functional consequences. Throughout evolution, two editing checkpoints prevent disease-causing mistranslation from confusing glycine or serine for alanine at the active site of AlaRS. In both bacteria and mice, Ser poses a bigger challenge than Gly. One checkpoint is the AlaRS editing centre, and the other is from widely distributed AlaXps-free-standing, genome-encoded editing proteins that clear Ser-tRNA(Ala). The paradox of misincorporating both a smaller (glycine) and a larger (serine) amino acid suggests a deep conflict for nature-designed AlaRS. Here we show the chemical basis for this conflict. Nine crystal structures, together with kinetic and mutational analysis, provided snapshots of adenylate formation for each amino acid. An inherent dilemma is posed by constraints of a structural design that pins down the alpha-amino group of the bound amino acid by using an acidic residue. This design, dating back more than 3 billion years, creates a serendipitous interaction with the serine OH that is difficult to avoid. Apparently because no better architecture for the recognition of alanine could be found, the serine misactivation problem was solved through free-standing AlaXps, which appeared contemporaneously with early AlaRSs. The results reveal unconventional problems and solutions arising from the historical design of the protein synthesis machinery.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799227/" 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/PMC2799227/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Min -- Chong, Yeeting E -- Shapiro, Ryan -- Beebe, Kirk -- Yang, Xiang-Lei -- Schimmel, Paul -- GM 15539/GM/NIGMS NIH HHS/ -- R01 GM015539/GM/NIGMS NIH HHS/ -- R01 GM015539-43/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 10;462(7274):808-12. doi: 10.1038/nature08612.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010690" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine/*metabolism ; Alanine-tRNA Ligase/chemistry/genetics/*metabolism ; Aspartic Acid/genetics/metabolism ; Catalytic Domain ; Crystallization ; Escherichia coli/*enzymology ; Kinetics ; Models, Molecular ; Mutation ; *Protein Biosynthesis ; Protein Conformation ; RNA, Transfer, Ala/metabolism ; Serine/*metabolism ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2014-07-12
    Description: Heterosexual transmission of HIV-1 typically results in one genetic variant establishing systemic infection. We compared, for 137 linked transmission pairs, the amino acid sequences encoded by non-envelope genes of viruses in both partners and demonstrate a selection bias for transmission of residues that are predicted to confer increased in vivo fitness on viruses in the newly infected, immunologically naive recipient. Although tempered by transmission risk factors, such as donor viral load, genital inflammation, and recipient gender, this selection bias provides an overall transmission advantage for viral quasispecies that are dominated by viruses with high in vivo fitness. Thus, preventative or therapeutic approaches that even marginally reduce viral fitness may lower the overall transmission rates and offer long-term benefits even upon successful transmission.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289910/" 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/PMC4289910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carlson, Jonathan M -- Schaefer, Malinda -- Monaco, Daniela C -- Batorsky, Rebecca -- Claiborne, Daniel T -- Prince, Jessica -- Deymier, Martin J -- Ende, Zachary S -- Klatt, Nichole R -- DeZiel, Charles E -- Lin, Tien-Ho -- Peng, Jian -- Seese, Aaron M -- Shapiro, Roger -- Frater, John -- Ndung'u, Thumbi -- Tang, Jianming -- Goepfert, Paul -- Gilmour, Jill -- Price, Matt A -- Kilembe, William -- Heckerman, David -- Goulder, Philip J R -- Allen, Todd M -- Allen, Susan -- Hunter, Eric -- 2P51RR000165-51/RR/NCRR NIH HHS/ -- G108/626/Medical Research Council/United Kingdom -- OD P51OD11132/OD/NIH HHS/ -- P01-AI074415/AI/NIAID NIH HHS/ -- P30 AI050409/AI/NIAID NIH HHS/ -- P51 OD010425/OD/NIH HHS/ -- P51 OD011132/OD/NIH HHS/ -- P51RR165/RR/NCRR NIH HHS/ -- R01 AI064060/AI/NIAID NIH HHS/ -- R01 AI64060/AI/NIAID NIH HHS/ -- R37 AI051231/AI/NIAID NIH HHS/ -- R37 AI51231/AI/NIAID NIH HHS/ -- T32 AI007387/AI/NIAID NIH HHS/ -- T32-AI007387/AI/NIAID NIH HHS/ -- U01 AI 66454/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Jul 11;345(6193):1254031. doi: 10.1126/science.1254031. Epub 2014 Jul 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Microsoft Research, Redmond, WA 98052, USA. carlson@microsoft.com ehunte4@emory.edu. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. ; Microsoft Research, Redmond, WA 98052, USA. ; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX1 7BN, UK. National Institute of Health Research, Oxford Biomedical Research Centre, Oxford OX3 7LE, UK. Oxford Martin School, University of Oxford, Oxford OX1 3BD, UK. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02114, USA. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa. Max Planck Institute for Infection Biology, D-10117 Berlin, Germany. ; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. ; International AIDS Vaccine Initiative, London SW10 9NH, UK. Imperial College of Science Technology and Medicine, London SW10 9NH, UK. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA 94105, USA. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. ; Microsoft Research, Los Angeles, CA 98117, USA. ; HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4013, South Africa. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. ; International AIDS Vaccine Initiative, San Francisco, CA 94105, USA. Microsoft Research, Los Angeles, CA 98117, USA. Department of Paediatrics, University of Oxford, Oxford OX1 3SY, UK. ; Emory Vaccine Center at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. Rwanda-Zambia HIV Research Group: Zambia-Emory HIV Research Project, Lusaka, Zambia. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. carlson@microsoft.com ehunte4@emory.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25013080" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Consensus Sequence ; DNA Mutational Analysis ; Disease Transmission, Infectious/statistics & numerical data ; Female ; HIV Infections/*transmission ; HIV-1/*genetics ; *Heterosexuality ; High-Throughput Nucleotide Sequencing ; Human Immunodeficiency Virus Proteins/genetics ; Humans ; Male ; Models, Statistical ; Molecular Sequence Data ; Point Mutation ; Risk Factors ; *Selection, Genetic ; Viral Load
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2009-08-08
    Description: Protein synthesis involves the accurate attachment of amino acids to their matching transfer RNA (tRNA) molecules. Mistranslating the amino acids serine or glycine for alanine is prevented by the function of independent but collaborative aminoacylation and editing domains of alanyl-tRNA synthetases (AlaRSs). We show that the C-Ala domain plays a key role in AlaRS function. The C-Ala domain is universally tethered to the editing domain both in AlaRS and in many homologous free-standing editing proteins. Crystal structure and functional analyses showed that C-Ala forms an ancient single-stranded nucleic acid binding motif that promotes cooperative binding of both aminoacylation and editing domains to tRNA(Ala). In addition, C-Ala may have played an essential role in the evolution of AlaRSs by coupling aminoacylation to editing to prevent mistranslation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559334/" 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/PMC4559334/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guo, Min -- Chong, Yeeting E -- Beebe, Kirk -- Shapiro, Ryan -- Yang, Xiang-Lei -- Schimmel, Paul -- GM 15539/GM/NIGMS NIH HHS/ -- R01 GM015539/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2009 Aug 7;325(5941):744-7. doi: 10.1126/science.1174343.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661429" target="_blank"〉PubMed〈/a〉
    Keywords: Alanine-tRNA Ligase/*chemistry/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Bacteria/enzymology ; Base Sequence ; Crystallography, X-Ray ; Escherichia coli Proteins/chemistry/metabolism ; Evolution, Molecular ; Models, Molecular ; Molecular Sequence Data ; Nucleic Acid Conformation ; Phylogeny ; Protein Structure, Secondary ; Protein Structure, Tertiary ; RNA, Bacterial/chemistry/metabolism ; RNA, Transfer, Ala/*chemistry/*metabolism ; RNA, Transfer, Amino Acyl/chemistry/metabolism ; *Transfer RNA Aminoacylation
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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