Separation of a thin rigid inclusion under cyclic loading with the assumption of the plane thermoelasticity problem

Separation of a rigid thin inclusion heated up to the set temperature is investigated in conditions of a plane problem thermoelasticity. Development of localized zones of prefracture (the weakened contact) precedes inclusions separation in a vicinities of its ends. They can correspond to regions of damages, plastic deformation, partial break of connection and another precedes. The analytical solution of the problem is obtained and its numerical analysis is made

Shape Shifting Leads to Small-Molecule Allosteric Drug Discovery

SummaryEnzymes that regulate their activity by modulating an equilibrium of alternate, nonadditive, functionally distinct oligomeric assemblies (morpheeins) constitute a recently described mode of allostery. The oligomeric equilibrium for porphobilinogen synthase (PBGS) consists of high-activity octamers, low-activity hexamers, and two dimer conformations. A phylogenetically diverse allosteric site specific to hexamers is proposed as an inhibitor binding site. Inhibitor binding is predicted to draw the oligomeric equilibrium toward the low-activity hexamer. In silico docking enriched a selection from a small-molecule library for compounds predicted to bind to this allosteric site. In vitro testing of selected compounds identified one compound whose inhibition mechanism is species-specific conversion of PBGS octamers to hexamers. We propose that this strategy for inhibitor discovery can be applied to other proteins that use the morpheein model for allosteric regulation

First Results from the TOTEM Experiment

The first physics results from the TOTEM experiment are here reported, concerning the measurements of the total, differential elastic, elastic and inelastic pp cross-section at the LHC energy of $\sqrt{s}$ = 7 TeV, obtained using the luminosity measurement from CMS. A preliminary measurement of the forward charged particle $\eta$ distribution is also shown.Comment: Conference Proceeding. MPI@LHC 2010: 2nd International Workshop on Multiple Partonic Interactions at the LHC. Glasgow (UK), 29th of November to the 3rd of December 201

Site-specific protein modification using immobilized sortase in batch and continuous-flow systems

Transpeptidation catalyzed by ​sortase A allows the preparation of proteins that are site-specifically and homogeneously modified with a wide variety of functional groups, such as fluorophores, PEG moieties, lipids, glycans, bio-orthogonal reactive groups and affinity handles. This protocol describes immobilization of ​sortase A on a solid support (Sepharose beads). Immobilization of ​sortase A simplifies downstream purification of a protein of interest after labeling of its N or C terminus. Smaller batch and larger-scale continuous-flow reactions require only a limited amount of enzyme. The immobilized enzyme can be reused for multiple cycles of protein modification reactions. The described protocol also works with a Ca²⁺-independent variant of ​sortase A with increased catalytic activity. This heptamutant variant of ​sortase A (7M) was generated by combining previously published mutations, and this immobilized enzyme can be used for the modification of calcium-senstive substrates or in instances in which low temperatures are needed. Preparation of immobilized ​sortase A takes 1–2 d. Batch reactions take 3–12 h and flow reactions proceed at 0.5 ml h⁻¹, depending on the geometry of the reactor used.United States. National Institutes of Health (RO1 AI087879

Dietary Supplements and Sports Performance: Herbals

This is the fourth in a series of six articles to discuss the major classes of dietary supplements (vitamins; minerals; amino acids; herbs or botanicals; metabolites, constituents/extracts, or combinations). The major focus is on efficacy of such dietary supplements to enhance exercise or sport performance

Measurement of elastic pp scattering at √ s = 8 TeV in the Coulomb-nuclear interference region : determination of the rho-parameter and the total cross-section

The TOTEM experiment at the CERN LHC has measured elastic proton-proton scattering at the centre-of-mass energy root s = 8 TeV and four-momentum transfers squared, vertical bar t vertical bar, from 6 x 10(-4) to 0.2GeV(2). Near the lower end of the t-interval the differential cross-section is sensitive to the interference between the hadronic and the electromagnetic scattering amplitudes. This article presents the elastic cross-section measurement and the constraints it imposes on the functional forms of the modulus and phase of the hadronic elastic amplitude. The data exclude the traditional Simplified West and Yennie interference formula that requires a constant phase and a purely exponential modulus of the hadronic amplitude. For parametrisations of the hadronic modulus with second-or third-order polynomials in the exponent, the data are compatible with hadronic phase functions giving either central or peripheral behaviour in the impact parameter picture of elastic scattering. In both cases, the.-parameter is found to be 0.12 +/- 0.03. The results for the total hadronic cross-section are sigma(tot) = (102.9 +/- 2.3) mb and (103.0 +/- 2.3) mb for central and peripheral phase formulations, respectively. Both are consistent with previous TOTEM measurements.Peer reviewe

Haploinsufficiency of the E3 Ubiquitin Ligase C-Terminus of Heat Shock Cognate 70 Interacting Protein (CHIP) Produces Specific Behavioral Impairments

The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET) mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and cellular stress

Diamond detectors for the TOTEM timing upgrade

This paper describes the design and the performance of the timing detector developed by the TOTEM Collaboration for the Roman Pots (RPs) to measure the Time-Of-Flight (TOF) of the protons produced in central diffractive interactions at the LHC. The measurement of the TOF of the protons allows the determination of the longitudinal position of the proton interaction vertex and its association with one of the vertices reconstructed by the CMS detectors. The TOF detector is based on single crystal Chemical Vapor Deposition (scCVD) diamond plates and is designed to measure the protons TOF with about 50 ps time precision. This upgrade to the TOTEM apparatus will be used in the LHC run 2 and will tag the central diffractive events up to an interaction pileup of about 1. A dedicated fast and low noise electronics for the signal amplification has been developed. The digitization of the diamond signal is performed by sampling the waveform. After introducing the physics studies that will most profit from the addition of these new detectors, we discuss in detail the optimization and the performance of the first TOF detector installed in the LHC in November 2015.Peer reviewe