The contribution of electrostatic interactions to the collapse of oligoglycine in water

Protein solubility and conformational stability are a result of a balance of interactions both within a protein and between protein and solvent. The electrostatic solvation free energy of oligoglycines, models for the peptide backbone, becomes more favorable with an increasing length, yet longer peptides collapse due to the formation of favorable intrapeptide interactions between CO dipoles, in some cases without hydrogen bonds. The strongly repulsive solvent cavity formation is balanced by van der Waals attractions and electrostatic contributions. In order to investigate the competition between solvent exclusion and charge interactions we simulate the collapse of a long oligoglycine comprised of 15 residues while scaling the charges on the peptide from zero to fully charged. We examine the effect this has on the conformational properties of the peptide. We also describe the approximate thermodynamic changes that occur during the scaling both in terms of intrapeptide potentials and peptide-water potentials, and estimate the electrostatic solvation free energy of the system.Comment: 10 pages, 7 figure

An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed

Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population

Monitoring interval-training responses for swimming using the 3-min all-out exercise test.

International Journal of Exercise Science 9(5): 545-553, 2016. The purpose of this study was to determine whether the 3-min all-out exercise test (3MT) could be applied to create an off-season high intensity, interval training (HIIT) program to improve performance, specifically critical velocity (CV), in the sport of swimming. We tested a group of competitive female swimmers (age = 19 ± 1 yrs, height = 169 ± 7 cm, body mass = 69 ± 9 kg) to determine their swimming CV and finite energy capacity \u3eCV (D’), and created a four week (2 d∙wk-1) personalized interval training program. Participants were divided in to two groups, a 150yd interval group (n =11) and a 250yd interval group (n =6). Each group completed a series of intervals designed to deplete a given percentage of D’ at velocities exceeding CV. A 3MT following the training period was administered to assess for any changes in CV, D’, average velocity during the first 150s of the test (V150s) and total distance traveled (D). Both groups improved their CV (+0.04 m∙s-1), V150s (+0.03 m∙s-1) and D (+8.64 m) (p \u3c 0.05), however, significant interactions for D’ between groups was not observed (p \u3e 0.05). We conclude that HIIT prescriptions based on a 3MT can improve swim performance over a four-week period. Future research on the fidelity of measuring CV and D’ using a swimming 3MT is needed to help aid practitioners in interpreting true training adaptations

A Novel Genome-Wide Association Study Approach Using Genotyping by Exome Sequencing Leads to the Identification of a Primary Open Angle Glaucoma Associated Inversion Disrupting ADAMTS17

Closed breeding populations in the dog in conjunction with advances in gene mapping and sequencing techniques facilitate mapping of autosomal recessive diseases and identification of novel disease-causing variants, often using unorthodox experimental designs. In our investigation we demonstrate successful mapping of the locus for primary open angle glaucoma in the Petit Basset Griffon Vendéen dog breed with 12 cases and 12 controls, using a novel genotyping by exome sequencing approach. The resulting genome-wide association signal was followed up by genome sequencing of an individual case, leading to the identification of an inversion with a breakpoint disrupting the ADAMTS17 gene. Genotyping of additional controls and expression analysis provide strong evidence that the inversion is disease causing. Evidence of cryptic splicing resulting in novel exon transcription as a consequence of the inversion in ADAMTS17 is identified through RNAseq experiments. This investigation demonstrates how a novel genotyping by exome sequencing approach can be used to map an autosomal recessive disorder in the dog, with the use of genome sequencing to facilitate identification of a disease-associated variant

A procedure for the change point problem in parametric models based on phi-divergence test-statistics

This paper studies the change point problem for a general parametric, univariate or multivariate family of distributions. An information theoretic procedure is developed which is based on general divergence measures for testing the hypothesis of the existence of a change. For comparing the accuracy of the new test-statistic a simulation study is performed for the special case of a univariate discrete model. Finally, the procedure proposed in this paper is illustrated through a classical change-point example

Robert L. Bailey\u27s Disciplined Creativity Process for Engineers Compared to the Creative Problem-solving Process

emerging from this process with a piece of literature that I have always dreamed o

Physico-chemical foundations underpinning microarray and next-generation sequencing experiments

Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next-generation sequencing (NGS). A physical understanding of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concentrations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinformatics and biostatistics, to theoretical and experimental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present knowledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico-chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized

Searching for New Physics Through AMO Precision Measurements

We briefly review recent experiments in atomic, molecular, and optical physics using precision measurements to search for physics beyond the Standard Model. We consider three main categories of experiments: searches for changes in fundamental constants, measurements of the anomalous magnetic moment of the electron, and searches for an electric dipole moment of the electron.Comment: Prepared for Comments on AMO Physics at Physica Script