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31.
Stochastic search variable selection (SSVS) is a Bayesian variable selection method that employs covariate‐specific discrete indicator variables to select which covariates (e.g., molecular markers) are included in or excluded from the model. We present a new variant of SSVS where, instead of discrete indicator variables, we use continuous‐scale weighting variables (which take also values between zero and one) to select covariates into the model. The improved model performance is shown and compared to standard SSVS using simulated and real quantitative trait locus mapping datasets. The decision making to decide phenotype‐genotype associations in our SSVS variant is based on median of posterior distribution or using Bayes factors. We also show here that by using continuous‐scale weighting variables it is possible to improve mixing properties of Markov chain Monte Carlo sampling substantially compared to standard SSVS. Also, the separation of association signals and nonsignals (control of noise level) seems to be more efficient compared to the standard SSVS. Thus, the novel method provides efficient new framework for SSVS analysis that additionally provides whole posterior distribution for pseudo‐indicators which means more information and may help in decision making.  相似文献   
32.
The mechanism of action of a potent peptidic inhibitor fasciculin 2 (Fas2) on electric eel acetylcholinesterase (eleelAChE) has been examined in a three-level analysis. Classical steps included equilibration experiments for the evaluation of high affinity binding constant and the existence of residual hydrolytic activity in a solution of completely Fas2 saturated enzyme. The two rate constants for the association (k(on)) and the dissociation (k(off)) of Fas2 with free enzyme were determined by the time course of residual enzyme activity measurements. In the third step, with a nonclassical progress curve analysis, we found that the Fas2-enzyme complex exhibited hydrolytic activity in a butyrylcholinesterase-like kinetics. The switch appears to be a consequence of steric obstruction, but also the consequence of subtle rapid conformational changes around catalytic site, upon slow single-step binding of large Fas2 molecule at the peripheral site. An unusual unilateral effect of bound Fas2 is reflected by acylation-independent association and dissociation rates and might indeed be due to inability of small acylation agent to influence the binding of a large opponent.  相似文献   
33.

Background

Although recent studies report on the benefits of blended learning in improving medical student education, there is still no empirical evidence on the relative effectiveness of blended over traditional learning approaches in medical statistics. We implemented blended along with on-site (i.e. face-to-face) learning to further assess the potential value of web-based learning in medical statistics.

Methods

This was a prospective study conducted with third year medical undergraduate students attending the Faculty of Medicine, University of Belgrade, who passed (440 of 545) the final exam of the obligatory introductory statistics course during 2013–14. Student statistics achievements were stratified based on the two methods of education delivery: blended learning and on-site learning. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course.

Results

Mean exam scores for the blended learning student group were higher than for the on-site student group for both final statistics score (89.36±6.60 vs. 86.06±8.48; p = 0.001) and knowledge test score (7.88±1.30 vs. 7.51±1.36; p = 0.023) with a medium effect size. There were no differences in sex or study duration between the groups. Current grade point average (GPA) was higher in the blended group. In a multivariable regression model, current GPA and knowledge test scores were associated with the final statistics score after adjusting for study duration and learning modality (p<0.001).

Conclusion

This study provides empirical evidence to support educator decisions to implement different learning environments for teaching medical statistics to undergraduate medical students. Blended and on-site training formats led to similar knowledge acquisition; however, students with higher GPA preferred the technology assisted learning format. Implementation of blended learning approaches can be considered an attractive, cost-effective, and efficient alternative to traditional classroom training in medical statistics.  相似文献   
34.
Fibroblast growth factors (FGFs) are key regulators of tissue development, homeostasis and repair, and abnormal FGF signalling is associated with various human diseases. In human and murine epidermis, FGF receptor 3 (FGFR3) activation causes benign skin tumours, but the consequences of FGFR3 deficiency in this tissue have not been determined. Here, we show that FGFR3 in keratinocytes is dispensable for mouse skin development, homeostasis and wound repair. However, the defect in the epidermal barrier and the resulting inflammatory skin disease that develops in mice lacking FGFR1 and FGFR2 in keratinocytes were further aggravated upon additional loss of FGFR3. This caused fibroblast activation and fibrosis in the FGFR1/FGFR2 double‐knockout mice and even more in mice lacking all three FGFRs, revealing functional redundancy of FGFR3 with FGFR1 and FGFR2 for maintaining the epidermal barrier. Taken together, our study demonstrates that FGFR1, FGFR2 and FGFR3 act together to maintain epidermal integrity and cutaneous homeostasis, with FGFR2 being the dominant receptor.  相似文献   
35.
Interorgan lipid transport occurs via lipoproteins, and altered lipoprotein levels correlate with metabolic disease. However, precisely how lipoproteins affect tissue lipid composition has not been comprehensively analyzed. Here, we identify the major lipoproteins of Drosophila melanogaster and use genetics and mass spectrometry to study their assembly, interorgan trafficking, and influence on tissue lipids. The apoB-family lipoprotein Lipophorin (Lpp) is the major hemolymph lipid carrier. It is produced as a phospholipid-rich particle by the fat body, and its secretion requires Microsomal Triglyceride Transfer Protein (MTP). Lpp acquires sterols and most diacylglycerol (DAG) at the gut via Lipid Transfer Particle (LTP), another fat body-derived apoB-family lipoprotein. The gut, like the fat body, is a lipogenic organ, incorporating both de novo-synthesized and dietary fatty acids into DAG for export. We identify distinct requirements for LTP and Lpp-dependent lipid mobilization in contributing to the neutral and polar lipid composition of the brain and wing imaginal disc. These studies define major routes of interorgan lipid transport in Drosophila and uncover surprising tissue-specific differences in lipoprotein lipid utilization.  相似文献   
36.
To establish the use of Metaphire posthuma as a sensitive model for ecotoxicological studies, the comparative effects of five metals on the hatching profiles of the cocoons of the earthworms, Metaphire posthuma, Eisenia foetida and Perionyx excavatus, were studied. The cocoons of the three species of earthworms were exposed to copper, chromium (III), chromium (VI), lead and zinc at 1.25, 2.5, 5.0 and 10.0 ppm. Viable cocoons were incubated at 20 +/- degrees C by using the immersion method. The results indicated that the inhibition of cocoon hatching was concentration dependent. The normal hatching, delayed hatching and non-viability of cocoons were recorded. At a concentration of 1.25 ppm, there was almost no effect on the hatching of the cocoons of all three species of earthworms, except when exposed to chromium (VI), but higher concentrations (2.5 and 5.0 ppm) caused severe effects. It was concluded that M. posthuma was more sensitive than the other two species, and that it is a suitable model for use in ecotoxicity testing.  相似文献   
37.
38.
Protease activity is tightly regulated in both normal and disease conditions. However, it is often difficult to monitor the dynamic nature of this regulation in the context of a live cell or whole organism. To address this limitation, we developed a series of quenched activity-based probes (qABPs) that become fluorescent upon activity-dependent covalent modification of a protease target. These reagents freely penetrate cells and allow direct imaging of protease activity in living cells. Targeted proteases are directly identified and monitored biochemically by virtue of the resulting covalent tag, thereby allowing unambiguous assignment of protease activities observed in imaging studies. We report here the design and synthesis of a selective, cell-permeable qABP for the study of papain-family cysteine proteases. This probe is used to monitor real-time protease activity in live human cells with fluorescence microscopy techniques as well as standard biochemical methods.  相似文献   
39.
The purpose of this paper is to evaluate the incidence of denture repairs in different districts of Croatia through the year of 2002. and to analyse the percentage of different repairs (relinings, simple repairs up to 2 elements and complicated repairs-more than 2 elements) in relation to prosthodontic teams. Data on the number of dentures, and the number and types of denture repairs delivered in the Croatian regions of Zagreb, Rijeka, Split and Karlovac were obtained from the Croatian Institute for Health Insurance for the whole of the year 2002. Information of the number of prosthodontic teams operating in those regions was also obtained. Proportionally more denture repairs were carried out in Karlovac (18%) than Split (5%). The smallest percantage of dentures that required relining was registered in Split and the highest in Rijeka (chi2 = 36.7, p < 0.01). The smallest percentage of simple repairs was registered in Rijeka and the highest in Split (chi2 = 24.3, p < 0.01). The smallest percentage of complicated repairs was registered in Split and the highest in Karlovac. In each region the proportion of denture repairs and types of repairs were correlated with a number of prosthodontic teams in that region. Karlovac had the smallest percentage of specialistic prosthodontic teams and the highest rate of denture repairs.  相似文献   
40.
Apitol®, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister chromatid exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol® (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35 ± 0.18%, 8.31 ± 0.20% and 12.33 ± 0.25%, respectively), the proliferative index (PI = 1.83 ± 0.01, 1.84 ± 0.01 and 1.88 ± 0.02, respectively) and the frequency of sister chromatid exchange (SCE = 8.19 ± 1.81, 8.78 ± 1.80 and 13.46 ± 1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential.  相似文献   
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