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Valid Interpretation (valid + interpretation)

Distribution by Scientific Domains

Chemistry	50%

Selected Abstracts

Protein flexibility: coordinate uncertainties and interpretation of structural differences

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 11 2009
Alexander A. Rashin
Valid interpretations of conformational movements in protein structures determined by X-ray crystallography require that the movement magnitudes exceed their uncertainty threshold. Here, it is shown that such thresholds can be obtained from the distance difference matrices (DDMs) of 1014 pairs of independently determined structures of bovine ribonuclease A and sperm whale myoglobin, with no explanations provided for reportedly minor coordinate differences. The smallest magnitudes of reportedly functional motions are just above these thresholds. Uncertainty thresholds can provide objective criteria that distinguish between true conformational changes and apparent `noise', showing that some previous interpretations of protein coordinate changes attributed to external conditions or mutations may be doubtful or erroneous. The use of uncertainty thresholds, DDMs, the newly introduced CDDMs (contact distance difference matrices) and a novel simple rotation algorithm allows a more meaningful classification and description of protein motions, distinguishing between various rigid-fragment motions and nonrigid conformational deformations. It is also shown that half of 75 pairs of identical molecules, each from the same asymmetric crystallographic cell, exhibit coordinate differences that range from just outside the coordinate uncertainty threshold to the full magnitude of large functional movements. Thus, crystallization might often induce protein conformational changes that are comparable to those related to or induced by the protein function. [source]

TICL , a web tool for network-based interpretation of compound lists inferred by high-throughput metabolomics

FEBS JOURNAL, Issue 7 2009
Alexey V. Antonov
High-throughput metabolomics is a dynamically developing technology that enables the mass separation of complex mixtures at very high resolution. Metabolic profiling has begun to be widely used in clinical research to study the molecular mechanisms of complex cell disorders. Similar to transcriptomics, which is capable of detecting genes at differential states, metabolomics is able to deliver a list of compounds differentially present between explored cell physiological conditions. The bioinformatics challenge lies in a statistically valid interpretation of the functional context for identified sets of metabolites. Here, we present TICL, a web tool for the automatic interpretation of lists of compounds. The major advance of TICL is that it not only provides a model of possible compound transformations related to the input list, but also implements a robust statistical framework to estimate the significance of the inferred model. The TICL web tool is freely accessible at http://mips.helmholtz-muenchen.de/proj/cmp. [source]

Chain graph models and their causal interpretations,

JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 3 2002
Steffen L. Lauritzen
Chain graphs are a natural generalization of directed acyclic graphs and undirected graphs. However, the apparent simplicity of chain graphs belies the subtlety of the conditional independence hypotheses that they represent. There are many simple and apparently plausible, but ultimately fallacious, interpretations of chain graphs that are often invoked, implicitly or explicitly. These interpretations also lead to flawed methods for applying background knowledge to model selection. We present a valid interpretation by showing how the distribution corresponding to a chain graph may be generated from the equilibrium distributions of dynamic models with feed-back. These dynamic interpretations lead to a simple theory of intervention, extending the theory developed for directed acyclic graphs. Finally, we contrast chain graph models under this interpretation with simultaneous equation models which have traditionally been used to model feed-back in econometrics. [source]

The Effect of Comorbidity and Socioeconomic Status on Sexual and Urinary Function and on General Health-Related Quality of Life in Men Treated with Radical Prostatectomy for Localized Prostate Cancer

THE JOURNAL OF SEXUAL MEDICINE, Issue 4 2008
Pierre I. Karakiewicz MD
ABSTRACT Introduction., Different treatments for localized prostate cancer (PCa) may be associated with similar overall survival but may demonstrate important differences in health-related quality of life (HRQOL). Therefore, valid interpretation of cancer control outcomes requires adjustment for HRQOL. Aim., To assess the effect of comorbidity and socioeconomic status (SES) on sexual and urinary function as well as general HRQOL in men treated with radical prostatectomy (RP) for PCa. Methods., We sent a self-addressed mail survey, composed of the research and development short form 36-item health survey, the PCa-specific University of California at Los Angeles (UCLA) Prostate Cancer Index (PCI), as well as a battery of items addressing SES and lifetime prevalence of comorbidity, to 4,546 men treated with RP in Quebec between 1988 and 1996. Main Outcome Measures., The association between comorbidity, SES, and HRQOL was tested and quantified using univariable and multivariable linear regression models. Results., Survey responses from 2,415 participants demonstrated that comorbidity and SES are strongly related to sexual, urinary, and general HRQOL in univariable and multivariable analyses. In multivariable models, the presence of comorbid conditions was associated with significantly worse HRQOL, as evidenced by lower scale scores by as much as 17/100 points in general domains, and by as much as 10/100 points in PCa-specific domains. Favorable SES characteristics were related to higher general (up to 9/100 points) and higher PCa-specific (up to 8/100 points) HRQOL scale scores. Conclusions., Comorbidity and SES are strongly associated with sexual, urinary and general HRQOL. Karakiewicz PI, Bhojani N, Neugut A, Shariat SF, Jeldres C, Graefen M, Perrotte P, Peloquin F, and Kattan MW. The effect of comorbidity and socioeconomic status on sexual and urinary function and on general health-related quality of life in men treated with radical prostatectomy for localized prostate cancer. J Sex Med 2008;5:919,927. [source]