Research Triangle Park

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.

Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma.

Abstract: The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-dependent transcription factor that is important in adipocyte differentiation and glucose homeostasis and which depends on interactions with co-activators, including steroid receptor co-activating factor-1 (SRC-1). Here we present the X-ray crystal structure of the human apo-PPAR-gamma ligand-binding domain (LBD), at 2.2 A resolution; this structure reveals a large binding pocket, which may explain the diversity of ligands for PPAR-gamma. We also describe the ternary complex containing the PPAR-gamma LBD, the antidiabetic ligand rosiglitazone (BRL49653), and 88 amino acids of human SRC-1 at 2.3 A resolution. Glutamate and lysine residues that are highly conserved in LBDs of nuclear receptors form a 'charge clamp' that contacts backbone atoms of the LXXLL helices of SRC-1. These results, together with the observation that two consecutive LXXLL motifs of SRC-1 make identical contacts with both subunits of a PPAR-gamma homodimer, suggest a general mechanism for the assembly of nuclear receptors with co-activators.

The Importance of Being Earnest: Validation is the Absolute Essential for Successful Application and Interpretation of QSPR Models

Abstract: This paper emphasizes the importance of rigorous validation as a crucial, integral component of Quantitative Structure Property Relationship (QSPR) model development. We consider some examples of published QSPR models, which in spite of their high fitted accuracy for the training sets and apparent mechanistic appeal, fail rigorous validation tests, and, thus, may lack practical utility as reliable screening tools. We present a set of simple guidelines for developing validated and predictive QSPR models. To this end, we discuss several validation strategies including (1) randomization of the modelled property, also called Y-scrambling, (2) multiple leave-many-out cross-validations, and (3) external validation using rational division of a dataset into training and test sets. We also highlight the need to establish the domain of model applicability in the chemical space to flag molecules for which predictions may be unreliable, and discuss some algorithms that can be used for this purpose. We advocate the broad use of these guidelines in the development of predictive QSPR models.

American Cancer Society guidelines for the early detection of cancer.

Abstract: Each year the American Cancer Society publishes a summary of existing recommendations for early cancer detection, including updates, and/or emerging issues that are relevant to screening for cancer. In last year's article, the guidelines regarding screening for the early detection of prostate, colorectal, and endometrial cancers were updated, as was the narrative pertaining to testing for early lung cancer detection. Although none of the ACS's guidelines were updated in 2001, work is proceeding on an update of screening recommendations for breast and cervical cancer and an update of these guidelines will be announced in the January/February 2003 issue of CA. As in previous issues, we review recommendations for the "cancer-related check-up," in which clinical encounters provide case-finding and health counseling opportunities. Finally, we provide an update of the most recent data pertaining to participation rates in cancer screening by age, gender, and ethnicity from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS) and National Health Interview Survey (NHIS).