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At least 469 records · Page 26Linked to original sources
PubMed2004

A general framework for development and data analysis of competitive high-throughput screens for small-molecule inhibitors of protein-protein interactions by fluorescence polarization.

Equilibrium binding experiments are widely used for the accurate characterization of binding and competitive binding behavior in biological systems. Modern high-throughput discovery efforts in chemical biology rely heavily upon this principle. Here, we derive exact analytical expressions for general competitive binding models which can also explain a commonly encountered phenomenon in these types of experiments, anticooperative incomplete displacement. We explore the effects of nonspecific binding behavior and parameter misestimation. All expressions are derived in terms of total concentrations determined a priori. We discuss a general framework for high-throughput screening assays based on fluorescence polarization and strategies for assay development, sensitivity regimes, data quality control, analysis, and ranking. Theoretical findings are visualized by simulations using realistic parameter sets. Our results are the basis for the discovery of small-molecule inhibitors of the protein-protein interaction between human calcineurin and NFAT transcription factors, as discussed in the subsequent paper (31).

Computer Simulation↗
PubMed2004

Noncontingent reinforcement, alternative reinforcement, and the matching law: a laboratory demonstration.

Basic researchers, but not most applied researchers, have assumed that the behavior-decelerating effects of noncontingent reinforcement result at least partly from adventitious reinforcement of competing behaviors. The literature contains only sketchy evidence of these effects because few noncontingent reinforcement studies measure alternative behaviors. A laboratory model is presented in which concurrent schedules of contingent reinforcement were used to establish a "target" and an "alternative" behavior. Imposing noncontingent reinforcement decreased target behavior rates and increased alternative behavior rates, outcomes that were well described by the standard quantitative account of alternative reinforcement, the generalized matching law. These results suggest that adventitious reinforcement of alternative behaviors can occur during noncontingent reinforcement interventions, although the range of conditions under which this occurs remains to be determined in future studies. As an adjunct to applied studies, laboratory models permit easy measurement of alternative behaviors and parametric manipulations needed to answer many research questions.

Competitive Behavior↗
PubMed1992

The behavior of multihospital chains in increasingly competitive California hospital markets: pro- or anti-competitive?

In previous literature, no evidence of competitive advantage has been found from hospital affiliation with chains. In this paper, the role of chains in hospital adaptation to a more competitive environment is examined further. Two dimensions of hospital behavior are examined: the propensity to engage in contractual arrangements with insurers, and the effect of a changed competitive environment on preferred acquisition targets by chains. We find evidence that chains behave pro-competitively in the short run, and discuss policy implications of the observed market restructuring in the longer run.

California↗
PubMed1987

[Effect of competitive sports on the menstrual cycle and sexuality--results of a survey of the West German team for the Olympic games in Los Angeles].

The present investigation attempts to analyse exact data on the menstruation cycle, contraception and the sexual behavior of competitive sportswomen. Since the West German participants at the Olympic Games of 1984 in Los Angeles were chosen for this investigation, the patients are unquestionably highly selected. For this reason, the results cannot claim to be representative in all respects. The objective of this study was primarily to register and to analyse the gynecological aspects of women's competitive sport, to reveal interrelationships and if appropriate to point out disadvantageous tendencies. The Olympics participants were subdivided into five different groups on the basis of the type of sport: I. take-off power/speed II. anaerobic endurance III. aerobic endurance IV. technique/dexterity V. team games. A control group was formed of middle-distance and long-distance runners. The data were analysed with regard to competitive sport and age, number of days of training and training minutes per week, menarche, duration and length as well as intensity of menstrual bleeding, menstruation symptoms, influence of menstrual bleeding on sport performance, dependence of peak performance on the menstruation cycle, sexual behavior, contraception behavior.

Adult↗
PubMed1993

All together now.

Integrated health plans, in which doctors, hospitals and insurers join forces to manage care, are a cornerstone of the "managed competition" approach to health care reform. But it's not clear that these longtime adversaries are ready to work together--or that consumers will be happy if they do.

Choice Behavior↗
PubMed1979

Machines as organisms: an exploration of the relevance of recent results.

The capacity of machines to exhibit organism-like behavior is examined. Some known results on machine description, self-description, construction and self-construction, are reviewed. The basic mechanism of machines and the ways in which they can be combined to form more complex biological-like systems are put forth as a source of explanatory mechanisms in biology. The proven properties can be employed in the design of machines which can repair themselves, and can exhibit a behavior distinguishing between machines which are or are not structurally similar to themselves. It is then argued that in an appropriate setting of variation and competition, such behavior would arise without explicit design.

Automation↗
PubMed2005

Competition between intercellular adhesion molecule-1 and a small-molecule antagonist for a common binding site on the alphal subunit of lymphocyte function-associated antigen-1.

The lymphocyte function-associated antigen-1 (LFA-1) binding of a unique class of small-molecule antagonists as represented by compound 3 was analyzed in comparison to that of soluble intercellular adhesion molecule-1 (sICAM-1) and A-286982, which respectively define direct and allosteric competitive binding sites within LFA-1's inserted (I) domain. All three molecules antagonized LFA-1 binding to ICAM-1-Immunoglobulin G fusion (ICAM-1-Ig) in a competition ELISA, but only compound 3 and sICAM-1 inhibited the binding of a fluorescein-labeled analog of compound 3 to LFA-1. Compound 3 and sICAM-1 displayed classical direct competitive binding behavior with ICAM-1. Their antagonism of LFA-1 was surmountable by both ICAM-1-Ig and a fluorescein-labeled compound 3 analog. The competition of both sICAM-1 and compound 3 with ICAM-1-Ig for LFA-1 resulted in equivalent and linear Schild plots with slopes of 1.24 and 1.26, respectively. Cross-linking studies with a photoactivated analog of compound 3 localized the high-affinity small-molecule binding site to the N-terminal 507 amino acid segment of the alpha chain of LFA-1, a region that includes the I domain. In addition, cells transfected with a variant of LFA-1 lacking this I domain showed no significant binding of a fluorescein-labeled analog of compound 3 or ICAM-1-Ig. These results demonstrate that compound 3 inhibits the LFA-1/ICAM-1 binding interaction in a directly competitive manner by binding to a high-affinity site on LFA-1. This binding site overlaps with the ICAM-1 binding site on the alpha subunit of LFA-1, which has previously been localized to the I domain.

Allosteric Regulation↗