Institution
Stony Brook University
Education•Stony Brook, New York, United States•
About: Stony Brook University is a education organization based out in Stony Brook, New York, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 32534 authors who have published 68218 publications receiving 3035131 citations. The organization is also known as: State University of New York at Stony Brook & SUNY Stony Brook.
Papers published on a yearly basis
Papers
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Cold Spring Harbor Laboratory1, Stony Brook University2, Watson School of Biological Sciences3, Medical University of Vienna4, Johns Hopkins University School of Medicine5, Harvard University6, Cincinnati Children's Hospital Medical Center7, University of California, San Francisco8, Howard Hughes Medical Institute9
TL;DR: The results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention.
Abstract: Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs. Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention.
1,737 citations
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29 Sep 2014TL;DR: The survey has been conducted for more than 50 years and has been used by the Census Bureau for the Bureau of Labor Statistics (BLS) as discussed by the authors to estimate employment, unemployment, earnings, hours of work, and other indicators.
Abstract: The CPS is a monthly survey of about 50,000 households conducted by the Bureau of the Census for the Bureau of Labor Statistics. The survey has been conducted for more than 50 years. This is all about employment. Estimates obtained from the CPS include employment, unemployment, earnings, hours of work, and other indicators. They are available by a variety of demographic characteristics including age, sex, race, marital status, and educational attainment. They are also available by occupation, industry, and class of worker. Supplemental questions to produce estimates on a variety of topics including school enrollment, income, previous work experience, health, employee benefits, and work schedules are also often added to the regular CPS questionnaire.
1,713 citations
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University of California, Los Angeles1, Wayne State University2, University of California, San Diego3, Stanford University4, University of Cincinnati5, Stony Brook University6, Fred Hutchinson Cancer Research Center7, Medical College of Wisconsin8, Brown University9, NorthShore University HealthSystem10, University of Hawaii at Manoa11
TL;DR: Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms, a pattern which continued for the study duration.
Abstract: ContextThe Women's Health Initiative trial of combined estrogen plus progestin
was stopped early when overall health risks, including invasive breast cancer,
exceeded benefits. Outstanding issues not previously addressed include characteristics
of breast cancers observed among women using hormones and whether diagnosis
may be influenced by hormone effects on mammography.ObjectiveTo determine the relationship among estrogen plus progestin use, breast
cancer characteristics, and mammography recommendations.Design, Setting, and ParticipantsFollowing a comprehensive breast cancer risk assessment, 16 608
postmenopausal women aged 50 to 79 years with an intact uterus were randomly
assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus
medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40
clinical centers. Screening mammography and clinical breast examinations were
performed at baseline and yearly thereafter.Main Outcome MeasuresBreast cancer number and characteristics, and frequency of abnormal
mammograms by estrogen plus progestin exposure.ResultsIn intent-to-treat analyses, estrogen plus progestin increased total
(245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001)
and invasive (199 vs 150 cases; HR, 1.24; weighted P =
.003) breast cancers compared with placebo. The invasive breast cancers diagnosed
in the estrogen plus progestin group were similar in histology and grade but
were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic
25.4% vs 16.0%, respectively; P = .04) compared with
those diagnosed in the placebo group. After 1 year, the percentage of women
with abnormal mammograms was substantially greater in the estrogen plus progestin
group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.ConclusionsRelatively short-term combined estrogen plus progestin use increases
incident breast cancers, which are diagnosed at a more advanced stage compared
with placebo use, and also substantially increases the percentage of women
with abnormal mammograms. These results suggest estrogen plus progestin may
stimulate breast cancer growth and hinder breast cancer diagnosis.
1,707 citations
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TL;DR: This protocol describes the use of the various options, the construction of auxiliary restraints files, the selection of the energy parameters, and the analysis of the results of the ClusPro server.
Abstract: The ClusPro server (https://cluspro.org) is a widely used tool for protein-protein docking. The server provides a simple home page for basic use, requiring only two files in Protein Data Bank (PDB) format. However, ClusPro also offers a number of advanced options to modify the search; these include the removal of unstructured protein regions, application of attraction or repulsion, accounting for pairwise distance restraints, construction of homo-multimers, consideration of small-angle X-ray scattering (SAXS) data, and location of heparin-binding sites. Six different energy functions can be used, depending on the type of protein. Docking with each energy parameter set results in ten models defined by centers of highly populated clusters of low-energy docked structures. This protocol describes the use of the various options, the construction of auxiliary restraints files, the selection of the energy parameters, and the analysis of the results. Although the server is heavily used, runs are generally completed in <4 h.
1,699 citations
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TL;DR: The results suggest that compounds that exploit the distinctive inactivation mechanisms of individual protein kinases can achieve both high affinity and high specificity.
Abstract: The inadvertent activation of the Abelson tyrosine kinase (Abl) causes chronic myelogenous leukemia (CML). A small-molecule inhibitor of Abl (STI-571) is effective in the treatment of CML. We report the crystal structure of the catalytic domain of Abl, complexed to a variant of STI-571. Critical to the binding of STI-571 is the adoption by the kinase of an inactive conformation, in which a centrally located "activation loop" is not phosphorylated. The conformation of this loop is distinct from that in active protein kinases, as well as in the inactive form of the closely related Src kinases. These results suggest that compounds that exploit the distinctive inactivation mechanisms of individual protein kinases can achieve both high affinity and high specificity.
1,694 citations
Authors
Showing all 32829 results
Name | H-index | Papers | Citations |
---|---|---|---|
Zhong Lin Wang | 245 | 2529 | 259003 |
Dennis W. Dickson | 191 | 1243 | 148488 |
Hyun-Chul Kim | 176 | 4076 | 183227 |
David Baker | 173 | 1226 | 109377 |
J. N. Butler | 172 | 2525 | 175561 |
Roderick T. Bronson | 169 | 679 | 107702 |
Nora D. Volkow | 165 | 958 | 107463 |
Jovan Milosevic | 152 | 1433 | 106802 |
Thomas E. Starzl | 150 | 1625 | 91704 |
Paolo Boffetta | 148 | 1455 | 93876 |
Jacques Banchereau | 143 | 634 | 99261 |
Larry R. Squire | 143 | 472 | 85306 |
John D. E. Gabrieli | 142 | 480 | 68254 |
Alexander Milov | 142 | 1143 | 93374 |
Meenakshi Narain | 142 | 1805 | 147741 |