Evolutionary Multi-Objective Design of SARS-CoV-2 Protease Inhibitor Candidates

Computational drug design based on artificial intelligence is an emerging research area. At the time of writing this paper, the world suffers from an outbreak of the coronavirus SARS-CoV-2. A promising way to stop the virus replication is via protease inhibition. We propose an evolutionary multi-objective algorithm (EMOA) to design potential protease inhibitors for SARS-CoV-2's main protease. Based on the SELFIES representation the EMOA maximizes the binding of candidate ligands to the protein using the docking tool QuickVina 2, while at the same time taking into account further objectives like drug-likeliness or the fulfillment of filter constraints. The experimental part analyzes the evolutionary process and discusses the inhibitor candidates.Comment: 15 pages, 7 figures, submitted to PPSN 202

The diagnosis of clinically significant oesophageal Candida infections: a reappraisal of clinicopathological findings

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154961/1/his14063_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154961/2/his14063.pd

A peptide cross-linked polyacrylamide hydrogel for the detection of human neutrophil elastase

The authors are grateful to the Malaysian government, EPSRC, BBSRC and Heptagon for providing funding for this projec

Preserving Madagascar's Natural Heritage: The Importance of Keeping the Island's Vertebrate Fossils in the Public Domain

No Abstrac

Measurement batch differences and between-batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values

Introduction: Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. Methods: A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland-Altman plot, paired t test, Pitman-Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches. Results: We found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R2 except for converting P-tau between batches 1 and 3. Discussion: Between-batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers

Constraints from orbital motions around the Earth of the environmental fifth-force hypothesis for the OPERA superluminal neutrino phenomenology

It has been recently suggested by Dvali and Vikman that the superluminal neutrino phenomenology of the OPERA experiment may be due to an environmental feature of the Earth, naturally yielding a long-range fifth force of gravitational origin whose coupling with the neutrino is set by the scale M_*, in units of reduced Planck mass. Its characteristic length lambda should not be smaller than one Earth's radius R_e, while its upper bound is expected to be slightly smaller than the Earth-Moon distance (60 R_e). We analytically work out some orbital effects of a Yukawa-type fifth force for a test particle moving in the modified field of a central body. Our results are quite general since they are not restricted to any particular size of lambda; moreover, they are valid for an arbitrary orbital configuration of the particle, i.e. for any value of its eccentricity $e$. We find that the dimensionless strength coupling parameter alpha is constrained to |alpha| <= 1 10^-10-4 10^-9 for 1 R_e <= lambda <= 10 R_e by the laser data of the Earth's artificial satellite LAGEOS II, corresponding to M_* >= 4 10^9 -1.6 10^10. The Moon perigee allows to obtain |alpha| <= 3 10^-11 for the Earth-Moon pair in the range 15 R_e <= lambda = 3 10^10 - 4.5 10^10. Our results are neither necessarily limited to the superluminal OPERA scenario nor to the Dvali-Vikman model, in which it is M_* = 10^-6 at lambda = 1 R_e, in contrast with our bounds: they generally extend to any theoretical scenario implying a fifth-force of Yukawa-type.Comment: LaTex2e, 18 pages, 4 figures, 1 table, 81 reference

Is a history of work-related low back injury associated with prevalent low back pain and depression in the general population?

<p>Abstract</p> <p>Background</p> <p>Little is known about the role of prior occupational low back injury in future episodes of low back pain and disability in the general population. We conducted a study to determine if a lifetime history of work-related low back injury is associated with prevalent severity-graded low back pain, depressive symptoms, or both, in the general population.</p> <p>Methods</p> <p>We used data from the Saskatchewan Health and Back Pain Survey – a population-based cross-sectional survey mailed to a random, stratified sample of 2,184 Saskatchewan adults 20 to 69 years of age in 1995. Information on the main independent variable was gathered by asking respondents whether they had ever injured their low back at work. Our outcomes, the 6-month period prevalence of severity-graded low back pain and depressive symptoms during the past week, were measured with valid and reliable questionnaires. The associations between prior work-related low back injury and our outcomes were estimated through multinomial and binary multivariable logistic regression with adjustment for age, gender, and other important covariates.</p> <p>Results</p> <p>Fifty-five percent of the eligible population participated. Of the 1,086 participants who responded to the question about the main independent variable, 38.0% reported a history of work-related low back injury. A history of work-related low back injury was positively associated with low intensity/low disability low back pain (OR, 3.66; 95%CI, 2.48–5.42), with high intensity/low disability low back pain (OR, 4.03; 95%CI, 2.41–6.76), and with high disability low back pain (OR, 6.76; 95%CI, 3.80–12.01). No association was found between a history of work-related low back injury and depression (OR, 0.85; 95%CI, 0.55–1.30).</p> <p>Conclusion</p> <p>Our analysis shows an association between past occupational low back injury and increasing severity of prevalent low back pain, but not depression. These results suggest that past work-related low back injury may be an important risk factor for future episodes of low back pain and disability in the general population.</p