On partial local smoothing rules for curve estimation

We compare the performances of local and global rules for smoothingparameter choice, in terms of asymptotic mean squared errorsof the resulting estimators. In some instances there is surprisinglylittle to choose between local and global approaches; our analysisidentifies contexts where the differences are small or large.This work motivates development of smoothing rules that forma ‘half-way house’ between local and global smoothing.There, interpolation provides a basis for partial local smoothing.A key result shows that interpolation on even a coarse gridcan produce a very good approximation to full local smoothing.Our theoretical and numerical results lead us to suggest linearinterpolation of a bandwidth obtained by integral approximationson discrete intervals.     

Saroglitazar is noninferior to fenofibrate in reducing triglyceride levels in hypertriglyceridemic patients in a randomized clinical trial

Saroglitazar, being a dual PPAR-α/γ agonist, has shown beneficial effect in diabetic dyslipidemia and hypertriglyceridemia. Fibrates are commonly used to treat severe hypertriglyceridemia. However, the effect of saroglitazar in patients with moderate to severe hypertriglyceridemia was not evaluated. We conducted a study to compare the efficacy and safety of saroglitazar (4 mg) with fenofibrate (160 mg) in patients with moderate to severe hypertriglyceridemia. This was a multicenter, randomized, double-blinded, double-dummy, active-control, and noninferiority trial in adult patients with fasting triglyceride (TG) levels of 500–1,500 mg/dl. The patients were randomized in a 1:1 ratio to receive daily dose of saroglitazar or fenofibrate for 12 weeks. The primary efficacy end point was the percent change in TG levels at week 12 relative to baseline. The study comprised of 41 patients in the saroglitazar group and 41 patients in the fenofibrate group. We found that the percent reduction from baseline in TG levels at week 12 was significantly higher in the saroglitazar group (least square mean = ?55.3%; SE = 4.9) compared with the fenofibrate group (least square mean = ?41.1%; SE = 4.9; P = 0.048). Overall, 37 treatment-emergent adverse events (AEs) were reported in 24 patients (saroglitazar: 13; fenofibrate: 11). No serious AEs were reported, and no patient discontinued the study because of AEs. We conclude that saroglitazar (4 mg) is noninferior to fenofibrate (160 mg) in reducing TG levels after 12 weeks of treatment, was safe, and well tolerated.     

Reductive Biotransformation of Benzaldehyde Derivatives by Baker's Yeast in Non-Conventional Media: Effect of Substrate Hydrophobicity on the Biocatalytic Reaction

The reduction of six derivatives of benzaldehyde, α,α,α-trifluorotolualdehyde, nitrobenzaldehyde, anisaldehyde, fluorobenzaldehyde, tolualdehyde, chlorobenzaldehyde, each of which was substituted in the ortho-, meta- and para-positions, was investigated in whole cell yeast biotransformations conducted in non-conventional media. Correlation between hydrophobic (π) and electronic (σ) parameters of the substituent of the substrate and biocatalytic activity in organic solvent media (hexane containing 2% v/v water) was evaluated. While catalytic activity in general decreased as the substituent hydrophobicity (π) increased, the trend was more pronounced for ortho- substituents compared to meta- and para-. When the electronic parameters (σ) of the meta- and para- substituents were correlated with the catalytic activity, the opposite was observed, namely the catalytic activity increased as the electronic parameter of the substituent increased. This observation was similar for meta- and para- substituents.

Preliminary studies on the relationships between solvent and substrate polarity on the one hand and catalytic activity on the other are also presented and discussed.     

Sequential polypeptides: 5. Statistical mechanical analysis of helix-coil transition in sequential polypeptides

A statistical mechanical theory of the helix-coil transition in sequential polypeptides is developed assuming that the statistical weights of the Zimm-Bragg parameters of a given residue depend on the type of adjacent residues. In the case of a sequential polypeptide consisting of two kinds of residues, the theory describes the helix- coil transition of the polypeptide in terms of the Zimm-Bragg parameters associated with the corresponding residues. The theory is then used to determine this parameter, as a function of temperature, from experimental data for transition temperature as a function of solvent composition, for a series of sequential polypeptides consisting of Glu(OBzl) and Lys(Chz) residues in mixtures of dichloroacetic acid and 1,2-dichlorethane. This parameter is then combined with the Zimm-Bragg parameters for the parent homopolypeptides, and the theory used to predict helix coil transition curves which are in good agreement with the experimental ones for the sequential polypeptides studied.     

On Some Nuisance Parameter Free Uniformly Most Powerful Tests

TAKEUCHI (1969) provides a uniformly most powerful (UMP) one side test for testing the location parameter of the two parameters exponential model when the scale parameter is unknown. The power of his similar size α test depends, however, on the unknown scale parameter. In this case and in more general situations when there exists a sufficient statistic for the nuisance parameter, the theory of generalized THOMPSON's distributions, more specifically, the Thompsonization of a test statistic, LAURENT (1959, 1972) provides a UMP test whose power does not depend on the nuisance parameter. Examples of application of the general nuisance parameter free test procedure include here the truncated exponential, the inverse Gaussian, and the geometric distributions.     

Validation of density–elasticity relationships for finite element modeling of human pelvic bone by modal analysis

In total hip arthroplasty and particularly in revision surgery, computer assisted pre-operative prediction of the best possible anchorage strategy for implant fixation would be a great help to the surgeon. Computer simulation relies on validated numerical models. In the current study, three density–elasticity relationships (No. 1–3) from the literature for inhomogeneous material parameter assignment from CT data in automated finite element (FE) modeling of long bones were evaluated for their suitability for FE modeling of human pelvic bone. Numerical modal analysis was conducted on 10 FE models of hemipelvic bone specimens and compared to the gold standard provided by experimental modal analysis results from a previous in-vitro study on the same specimens. Overall, calculated resonance frequencies came out lower than measured values. Magnitude of mean relative deviation of numerical resonance frequencies with regard to measured values is lowest for the density–elasticity relationship No. 3 (−15.9%) and considerably higher for both density–elasticity relationships No. 1 (−41.1%) and No. 2 (−45.0%). Mean MAC values over all specimens amount to 77.8% (No. 1), 78.5% (No. 2), and 83.0% (No. 3). MAC results show, that mode shapes are only slightly influenced by material distribution. Calculated resonance frequencies are generally lower than measured values, which indicates, that numerical models lack stiffness. Even when using the best suited (No. 3) out of three investigated density–elasticity relationships, in FE modeling of pelvic bone a considerable underestimation of model stiffness has to be taken into account.     

An Efficient Timer and Sizer of Biomacromolecular Motions

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Inference of Multisite Phosphorylation Rate Constants and Their Modulation by Pathogenic Mutations

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