CONSTRUCTION OF COMPUTATIONAL 3D STRUCTURES OF PROTEIN DRUG TARGETS OF MYCOBACTERIUM TUBERCULOSIS

Objective: This study aims in constructing a three-dimensional modeled protein structure of potential drug targets in Mycobacterium tuberculosis bacteria. Methods: The protein models were constructed using SWISS-Model online tool. The constructed protein models were submitted in online database called Protein Model Database (PMDB) for public access to the structures. Results: A total of 100 protein sequences of M. tuberculosis were retrieved from UniProt database and were subjected for sequence similarity search and homology model construction. The constructed models were subjected for Ramachandran plot analysis to validate the quality of the structures. A total of 69 structures were considered to be of significant quality and were submitted to the online database PMDB. Conclusion: These predicted structures would help greatly in identification and drug design to various strains of M. tuberculosis that are sensitive and resistant to different antibiotics. This would greatly help in drug development and personalized drug treatment against different strains of the pathogen. This database would significantly support the structure-based computational drug design applications toward personalized medicine in regard to differences in the various strains of the pathogen

Computational algebraic methods in efficient estimation

A strong link between information geometry and algebraic statistics is made by investigating statistical manifolds which are algebraic varieties. In particular it it shown how first and second order efficient estimators can be constructed, such as bias corrected Maximum Likelihood and more general estimators, and for which the estimating equations are purely algebraic. In addition it is shown how Gr\"obner basis technology, which is at the heart of algebraic statistics, can be used to reduce the degrees of the terms in the estimating equations. This points the way to the feasible use, to find the estimators, of special methods for solving polynomial equations, such as homotopy continuation methods. Simple examples are given showing both equations and computations. *** The proof of Theorem 2 was corrected by the latest version. Some minor errors were also corrected.Comment: 21 pages, 5 figure

Development and presentation of an objective risk stratification tool for healthcare workers when dealing with the COVID-19 pandemic in the UK: risk modelling based on hospitalisation and mortality statistics compared with epidemiological data

This paper presents a tool for objective risk stratification of doctors and healthcare professionals during the COVID-19 pandemic, without requiring disclosure of information that an individual may not wish to share during the risk assessment process. This tool is freely available through the British Medical Association website and is widely used in the National Health Service and other external organisation

Application of collapsing methods for continuous traits to the Genetic Analysis Workshop 17 exome sequence data

Genetic Analysis Workshop 17 used real sequence data from the 1000 Genomes Project and simulated phenotypes influenced by a large number of rare variants. Our aim is to evaluate the performance of various collapsing methods that were developed for analysis of multiple rare variants. We apply collapsing methods to continuous phenotypes Q1 and Q2 for all 200 replicates of the unrelated individuals data. Within each gene, we collapse (1) all SNPs, (2) all SNPs with minor allele frequency (MAF) < 0.05, and (3) nonsynonymous SNPs with MAF < 0.05. We consider two tests when collapsing variants: using the proportion of variants and using the presence/absence of any variant. We also compare our results to a single-marker analysis using PLINK. For phenotype Q1, the proportion test for collapsing rare nonsynonymous SNPs often performed the best. Two genes (FLT1 and KDR) had statistically significant results. A single-marker analysis using PLINK also provided statistically significant results for some SNPs within these two genes. For phenotype Q2, collapsing rare nonsynonymous SNPs performed the best, with almost no difference between proportion and presence tests. However, neither collapsing methods nor a single-marker analysis provided statistically significant results at the true genes for Q2. We also found that a large number of noncausal genes had high correlations with causal genes for Q1 and Q2, which may account for inflated false positives

Modern Privacy Threats and Privacy Preservation Techniques in Data Analytics

Today we are living in a digital rich and technology driven world where extremely large amounts of data get generated every hour in the public domain, which also includes personal data. Applications like social media, e-commerce, smartphone apps, etc. collect a lot of personal data which can harm individual privacy if leaked, and hence ethical code of conduct is required to ensure data privacy. Some of the privacy threats include Digital profiling, cyberstalking, recommendation systems, etc. leading to the disclosure of sensitive data and sharing of data without the consent of the data owner. Data Privacy has gained significant importance in the recent times and it is evident from the privacy legislation passed in more than 100 countries. Firms dealing with data-sensitive applications need to abide by the privacy legislation of respective territorial regions. To overcome these privacy challenges by incorporating privacy regulations, we have designed guidelines for application development, incorporating key features of privacy regulations along with the implementation strategies which will help in developing data-sensitive applications which can offer strong and coherent privacy protection of personal data

Hemangiopericytoma of the Greater Omentum

A 41-year-old Chinese woman was admitted to our hospital with epigastric pain. Computed tomography detected a heterogeneous enhancement tumor fed by the left gastroepiploic artery in the left lower quadrant and cholelithiasis. Excision of the tumor in the greater omentum and cholecystectomy were performed laparoscopically. Histological findings confirmed a diagnosis of hemangiopericytoma with low-grade malignancy. To our knowledge, hemangiopericytoma of the greater omentum is very rare, and only 12 cases were reported in English literature. We report a case of hemangiopericytoma arising in the greater omentum and review the literature

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Two-dimensional amine and hydroxy functionalized fused aromatic covalent organic framework

Ordered two-dimensional covalent organic frameworks (COFs) have generally been synthesized using reversible reactions. It has been difficult to synthesize a similar degree of ordered COFs using irreversible reactions. Developing COFs with a fused aromatic ring system via an irreversible reaction is highly desirable but has remained a significant challenge. Here we demonstrate a COF that can be synthesized from organic building blocks via irreversible condensation (aromatization). The as-synthesized robust fused aromatic COF (F-COF) exhibits high crystallinity. Its lattice structure is characterized by scanning tunneling microscopy and X-ray diffraction pattern. Because of its fused aromatic ring system, the F-COF structure possesses high physiochemical stability, due to the absence of hydrolysable weak covalent bonds

A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis

The use of architectural and morphological characteristics of cells for establishing prognostic indicators by which individual pathologies are assigned grade and stage is a well-accepted practice. Advances in automated micro- and macroscopic image acquisition and digital image analysis have created new opportunities in the field of prognostic assessment; but, one area in experimental pathology, animal models for colon cancer, has not taken advantage of these opportunities. This situation is primarily due to the methods available to evaluate the colon of the rodent for the presence of premalignant and malignant pathologies. We report a new method for the excision and processing of the entire colon of the rat and illustrate how this procedure permitted the quantitative assessment of aberrant crypt foci (ACF), a premalignant colon pathology, for characteristics consistent with progression to malignancy. ACF were detected by methylene blue staining and subjected to quantitative morphometric analysis. Colons were then restained with high iron diamine–alcian blue for assessment of mucin depletion using an image overlay to associate morphometric data with mucin depletion. The subsequent evaluation of ACF for beta-catenin staining is also demonstrated. The methods described are particularly relevant to the screening of compounds for cancer chemopreventive activity