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Institution

Research Triangle Park

NonprofitDurham, North Carolina, United States
About: Research Triangle Park is a nonprofit organization based out in Durham, North Carolina, United States. It is known for research contribution in the topics: Population & Environmental exposure. The organization has 24961 authors who have published 35800 publications receiving 1684504 citations. The organization is also known as: RTP.


Papers
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Journal ArticleDOI
TL;DR: A new procedure to take the product of only those P‐values less than some specified cut‐off value and to evaluate the probability of such a product, or a smaller value, under the overall hypothesis that all L hypotheses are true is presented.
Abstract: We present a new procedure for combining P-values from a set of L hypothesis tests. Our procedure is to take the product of only those P-values less than some specified cut-off value and to evaluate the probability of such a product, or a smaller value, under the overall hypothesis that all L hypotheses are true. We give an explicit formulation for this P-value, and find by simulation that it can provide high power for detecting departures from the overall hypothesis. We extend the procedure to situations when tests are not independent. We present both real and simulated examples where the method is especially useful. These include exploratory analyses when L is large, such as genome-wide scans for marker-trait associations and meta-analytic applications that combine information from published studies, with potential for dealing with the "publication bias" phenomenon. Once the overall hypothesis is rejected, an adjustment procedure with strong family-wise error protection is available for smaller subsets of hypotheses, down to the individual tests.

521 citations

Journal ArticleDOI
TL;DR: Characterization of the TK-/- mutants suggests that two mutagenic mechanisms contribute to their final yield, and is consistent with the induction of slow-growing specific locus mutants by a chromosomal mechanism and their subsequent dilution during this long expression time.
Abstract: The current status of the L5178Y/TK+/- leads to TK-/- mouse-lymphoma mutagenicity assay is described. Dose-survival-mutagenic response data are shown for 43 chemicals. Mutagenicity and cytotoxicity in the presence or absence of non-induced and/or Aroclor-induced rat-liver S-9 are compared for most of these chemicals, 25 of these for which usuable carcinogenicity data exist have been used to construct an approximately linear relationship between oncogenic potency in vivo and mutagenic potency in this system in vitro; linearity between these two endpoints extends over a greater than 100,000-fold range in potencies. Several carcinogens which are negative or difficult to detect in the standard Ames assay are mutagenic in this mammalian cell system. These include natulan, sodium saccharin (lot S-1022), p,p'-DDE (metabolite of DDT), dimethylnitrosamine, diethylnitrosamine and diethylstilbestrol. Characterization of the TK-/- mutants suggests that two mutagenic mechanisms contribute to their final yield. Large-colony TK-/- mutants probably represent point or gene mutations affecting the TK locus. In addition, a class of small-colony TK(/- mutants are described and characterized as being heritably growth-deficient; this and other properties suggest that these small-colony TK-/- mutants originate by a heritable and viable chromosomal aberration. Most carcinogens and mutagens tested produce both classes of TK-/- mutants in this system; the relative proportions of small- and large-colony mutants are both mutagen- and dose-dependent. Comparative studies have been done at the rapidly-expressing TK locus and the slowly-expressing HGPRT locus in these cells. Several carcinogens detected at the TK locus are non- or very weakly mutagenic at the HGPRT locus. This findings is consistent with the induction of slow-growing specific locus mutants by a chromosomal mechanism and their subsequent dilution during this long expression time.

521 citations

Journal ArticleDOI
01 Jan 1999-Neuron
TL;DR: PICK1 (protein interacting with C kinase), a PDZ domain-containing protein, interacts with the C termini of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors in vitro and in vivo and suggests that PICK1 may play an important role in the modulation of synaptic transmission by regulating the synaptic targeting of AMPA receptors.

520 citations

Journal ArticleDOI
01 Apr 1999-Chest
TL;DR: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.

518 citations


Authors

Showing all 25006 results

NameH-indexPapersCitations
Douglas G. Altman2531001680344
Lewis C. Cantley196748169037
Ronald Klein1941305149140
Daniel J. Jacob16265676530
Christopher P. Cannon1511118108906
James B. Meigs147574115899
Lawrence Corey14677378105
Jeremy K. Nicholson14177380275
Paul M. Matthews14061788802
Herbert Y. Meltzer137114881371
Charles J. Yeo13667276424
Benjamin F. Cravatt13166661932
Timothy R. Billiar13183866133
Peter Brown12990868853
King K. Holmes12460656192
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202317
202277
2021988
20201,001
20191,035
20181,051