On the generalized process capability under simple and mixture models

<div><p>Process capability (PC) indices measure the ability of a process of interest to meet the desired specifications under certain restrictions. There are a variety of capability indices available in literature for different interest variables such as weights, lengths, thickness, and the life time of items among many others. The goal of this article is to study the generalized capability indices from the Bayesian view point under different symmetric and asymmetric loss functions for the simple and mixture of generalized lifetime models. For our study purposes, we have covered a simple and two component mixture of Maxwell distribution as a special case of the generalized class of models. A comparative discussion of the PC with the mixture models under Laplace and inverse Rayleigh are also included. Bayesian point estimation of maintenance performance of the system is also part of the study (considering the Maxwell failure lifetime model and the repair time model). A real-life example is also included to illustrate the procedural details of the proposed method.</p></div

A comparison of single- and double-threshold ROC plots for mixture distributions

The receiver operating characteristics (ROC) analysis is commonly used in clinical settings to check the performance of a single threshold for distinguishing population-wise bimodal-distributed test results. However, for population-wise three-modal distributed test results, a single threshold ROC (stROC) analysis showed poor discriminative performance. The purpose of this study is to use a double-threshold ROC analysis for the three-modal distributed test results to provide better discriminative performance than the stROC analysis. A double-threshold receiver operating characteristic plot (dtROC) is constructed by replacing the single threshold with a double threshold. The sensitivity and specificity coordinates are chosen to maximize sensitivity for a given specificity value. Besides a simulation study assuming a mixture of lognormal, Poisson, and Weibull distributions, a clinical application is examined by a secondary data analysis of palpation test results of the C7 spinous process using the modified thorax–rib static technique. For the assumed mixture models, the discrimination performance of dtROC analysis outperforms the stROC analysis (area under ROC (AUROC) increased from 0.436 to 0.983 for lognormal distributed test results, 0.676 to 0.752 for the Poisson distribution, and 0.674 to 0.804 for Weibull distribution).</p

Identification of new benzamide inhibitor against <i>α</i>-subunit of tryptophan synthase from <i>Mycobacterium tuberculosis</i> through structure-based virtual screening, anti-tuberculosis activity and molecular dynamics simulations

<p>Multi-drug-resistant tuberculosis and extensively drug-resistant tuberculosis has emerged as global health threat, causing millions of deaths worldwide. Identification of new drug candidates for tuberculosis (TB) by targeting novel and less explored protein targets will be invaluable for antituberculosis drug discovery. We performed structure-based virtual screening of eMolecules database against a homology model of relatively unexplored protein target: the <i>α</i>-subunit of tryptophan synthase (<i>α</i>-TRPS) from <i>Mycobacterium tuberculosis</i> essential for bacterial survival. Based on physiochemical properties analysis and molecular docking, the seven candidate compounds were selected and evaluated through whole cell-based activity against the H37Rv strain of <i>M. tuberculosis</i>. A new Benzamide inhibitor against <i>α</i>-subunit of tryptophan synthase (<i>α</i>-TRPS) from <i>M. tuberculosis</i> has been identified causing 100% growth inhibition at 25 μg/ml and visible bactericidal activity at 6 μg/ml. This benzamide inhibitor displayed a good predicted binding score (−48.24 kcal/mol) with the <i>α</i>-TRPS binding pocket and has logP value (2.95) comparable to Rifampicin. Further refinement of docking results and evaluation of inhibitor-protein complex stability were investigated through Molecular dynamic (MD) simulations studies. Following MD simulations, Root mean square deviation, Root mean square fluctuation and secondary structure analysis confirmed that protein did not unfold and ligand stayed inside the active pocket of protein during the explored time scale. This identified benzamide inhibitor against the <i>α</i>-subunit of TRPS from <i>M. tuberculosis</i> could be considered as candidate for drug discovery against TB and will be further evaluated for enzyme-based inhibition in future studies.</p

High Genetic Diversity in the Himalayan Common Bean (Phaseolus vulgaris) Germplasm with Divergence from Its Center of Origin in the Mesoamerica and Andes

The common bean is found in the Himalayan region of Pakistan with substantial morphological variability. Genetic diversity within any crop species is a precursor for genetic improvement; however, little is known about common bean genetic diversity in this region. We explored the genetic diversity in the common bean from the Himalayan region (Khyber Pakhtunkhwa, Gilgit–Baltistan, Kashmir) of Pakistan. Microsatellite genotyping was carried out for 147 samples with 40 simple sequence repeat (SSR) markers. The results revealed a clear divergence of the Pakistani population from the primary gene pool (with FST values of 0.2 with Andes and 0.27 with Mesoamerica). However, within the Himalayan germplasm, no clear evidence of spatial structure was observed (with the maximum FST values of only 0.025), probably due to the dispersal of seeds by human activity within the region. This was further elucidated by the discriminant analyses of principal components. Considering the diversity parameters, high genotypic diversity was observed for the indigenous lines (0.990), comparable to the primary gene pool (0.976 for Mesoamerica and 0.976 for Andes populations). A high genotypic diversity was observed within the Himalayan population (ranging from 0.500 for Upper Dir to 0.952 for Mansehra). Gene diversity across loci varied between 0.28 for Chitral to 0.38 for Kurram. Our results suggested a divergent and independent evolution of the Himalayan population, which might have led to the diversification of the common bean germplasm in the region postintroduction into the region. The diversity observed could also be exploited in future breeding programs for the development and introduction of climate-resilient varieties

Ancestral relationship among worldwide PST populations as inferred from the analyses of Approximate Bayesian Computations.

<p>Ancestral relationship among worldwide PST populations as inferred from the analyses of Approximate Bayesian Computations.</p

Expected (He) and observed (Ho) heterozygosity for clone-corrected data based on 20 polymorphic microsatellite loci for PST isolates sampled from diverse geographical regions.

<p>Expected (He) and observed (Ho) heterozygosity for clone-corrected data based on 20 polymorphic microsatellite loci for PST isolates sampled from diverse geographical regions.</p

Preparation, Characterization, and Evaluation of Physcion Nanoparticles for Enhanced Oral Bioavailability: An Attempt to Improve Its Antioxidant and Anticancer Potential

This study aims to enhance the dissolution rate of a poorly water-soluble drug physcion by producing its nanoparticles (NPs) using an antisolvent precipitation with a syringe pump (APSP) method and to assess its antioxidant and cytotoxic potential. The NPs were prepared using a simple and cost-effective APSP method and subsequently characterized by different analytical techniques including dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray powder diffractometry (XRD). They were also subjected to solubility and dissolution studies, and different parameters such as dissolution efficiency (DE), mean dissolution time (MDT), and difference (f1) and similarity factors (f2) were determined. Furthermore, physcion and its NPs were investigated for antioxidant and cytotoxic effects using various in vitro assays. SEM and DLS analysis indicated that the average size of physcion NPs was 110 and 195 ± 5.6 nm, respectively. The average ζ-potential and polydispersibility index (PDI) of the prepared NPs were −22.5 mV and 0.18, respectively, showing excellent dispersibility. XRD confirmed the amorphous nature of physcion NPs. The solubility and dissolution rates of NPs were significantly higher than those of the original powder. The antioxidant potential studied by the (DPPH), FRAP, and H2O2 assays was greater for physcion NPs than that for the raw powder. The IC50 values of physcion NPs against the aforementioned models were 57.56, 22.30, and 22.68 μg/mL, respectively. Likewise, the cytotoxic potential investigated through the MTT assay showed that physcion NPs were more cytotoxic to cancer cell lines A549 (IC50 4.12 μg/mL), HepG2 (IC50 2.84 μg/mL), and MDA-MB-231 (IC50 2.97 μg/mL), while it had less effect on HPAEpiC (IC50 8.68 μg/mL) and HRPTEpiC (IC50 10.71 μg/mL) normal human epithelial cells. These findings have proved that the APSP method successfully produced physcion NPs with enhanced solubility, dissolution rate, and antioxidant and cytotoxic activities

Discriminant analysis of principal components (DAPC) analysis of worldwide PST populations sampled from different geographical regions.

<p>The Eigen values of the analysis suggest that the first two components explained the maximum genetic structure of the dataset (A). The Bayesian information criteria (BIC) supported six distinct genetic groups (B). Scatter-plot of the worldwide distribution of PST isolates into six genetic groups (C).</p

Estimates of F_ST (upper diagonal) and its significance (lower diagonal) based on 20 microsetillite loci for 386 PST isolates representing worldwide geographically spaced populations.

<p>The lower two lines shows F_ST and its p-value for isolates representing the post-2000 emerged strains. Non-significant <i>F_ST</i> values (>0.01) are shown in bold.</p

Clustering of 409 PST isolates representing worldwide geographical regions to genetic groups for the optimal K-value (K = 6) in the DAPC analysis.

<p>PstS1 and PstS2 refers to the two closely related aggressive strains, while PstS3 refers to the older aggressive isolates regularly reported in Southern Europe.</p