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This research was carried out to study how shouts, shinai (bamboo kendo sword) contact, and fumikomi(step-in foot-stamping) sounds accompanying shinai strikes are perceived by collegiate-level kendo fencers both when fencing and when refereeing. As part of this study, a questionnaire survey was administered to individuals involved in collegiate-level kendo, with survey questions distinguishing between perceptions of such sounds both when fencing and when refereeing. Our survey results revealed the following findings: (1) In referee evaluations of ki-ken-tai-icchi, sounds are perceived as being equal in importance to the visual aspects of a fencer's physical movements. (2) Sounds created during the execution of a shinai strike are considered important by fencers while competing in a match. (3) Sounds created during the execution of a shinai strike are considered even more important when refereeing other fencers' matches than during one's own match. (4) Foot-stamping sounds during step-in probably influence referee scoring of shinai strikes. [ABSTRACT FROM AUTHOR]

Background: Estrogen receptors alpha (ER) are implicated in many types of female cancers, and are the common target for anti-cancer therapy using selective estrogen receptor modulators (SERMs, such as tamoxifen). However, cell-type specific and patient-to-patient variability in response to SERMs (from suppression to stimulation of cancer growth), as well as frequent emergence of drug resistance, represents a serious problem. The molecular processes behind mixed effects of SERMs remain poorly understood, and this strongly motivates application of systems approaches. In this work, we aimed to establish a mathematical model of ER-dependent gene expression to explore potential mechanisms underlying the variable actions of SERMs. Results: We developed an equilibrium model of ER binding with 17β-estradiol, tamoxifen and DNA, and linked it to a simple ODE model of ER-induced gene expression. The model was parameterised on the broad range of literature available experimental data, and provided a plausible mechanistic explanation for the dual agonism/antagonism action of tamoxifen in the reference cell line used for model calibration. To extend our conclusions to other cell types we ran global sensitivity analysis and explored model behaviour in the wide range of biologically plausible parameter values, including those found in cancer cells. Our findings suggest that transcriptional response to tamoxifen is controlled in a complex non-linear way by several key parameters, including ER expression level, hormone concentration, amount of ER-responsive genes and the capacity of ER-tamoxifen complexes to stimulate transcription (e.g. by recruiting co-regulators of transcription). The model revealed non-monotonic dependence of ER-induced transcriptional response on the expression level of ER, that was confirmed experimentally in four variants of the MCF-7 breast cancer cell line. Conclusions: We established a minimal mechanistic model of ER-dependent gene expression, that predicts complex non-linear effects in transcriptional response to tamoxifen in the broad range of biologically plausible parameter values. Our findings suggest that the outcome of a SERM's action is defined by several key components of cellular microenvironment, that may contribute to cell-type-specific effects of SERMs and justify the need for the development of combinatorial biomarkers for more accurate prediction of the efficacy of SERMs in specific cell types. [ABSTRACT FROM AUTHOR]

L-2-haloacid dehalogenase (L-DEX) catalyzes the hydrolytic dehalogenation of L-2-haloalkanoic acids to produce the corresponding D-2-hydroxyalkanoic acids. This enzyme is expected to be applicable to the bioremediation of environments contaminated with halogenated organic compounds. We analyzed the reaction mechanism of L-DEX from Pseudomonas sp. YL (L-DEX YL) by using molecular modeling. The complexes of wild-type L-DEX YL and its K151A and D180A mutants with its typical substrate, L-2-chloropropionate, were constructed by docking simulation. Subsequently, molecular dynamics (MD) and ab initio fragment molecular orbital (FMO) calculations of the complexes were performed. The ab initio FMO method was applied at the MP2/6-31G level to estimate interfragment interaction energies. K151 and D180, which are experimentally shown to be important for enzyme activity, interact particularly strongly with L-2-chloropropionate, catalytic water, nucleophile (D10), and with each other. Our calculations suggest that K151 stabilizes substrate orientation and balances the charge around the active site, while D180 stabilizes the rotation of the nucleophile D10, fixes catalytic water around D10, and prevents K151 from approaching D10. Further, D180 may activate catalytic water on its own or with K151, S175, and N177. These roles are consistent with the previous results. Thus, MD and ab initio FMO calculations are powerful tools for the elucidation of the mechanism of enzymatic reaction at the molecular level and can be applied to other catalytically important residues. The results obtained here will play an important role in elucidating the reaction mechanism and rational design of L-DEX YL with improved enzymatic activity or substrate specificity. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009 [ABSTRACT FROM AUTHOR]