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Large axial-radial bearings are widely used as means of attachment of slewing mechanisms of cranes and heavy machinery. In case of an inadequate support structure these loadings can hinder proper functioning of the slewing bearing or even lead to its terminal failure. In the paper support of a large-radial bearing mounted on an overhead type manipulator was optimized with the goal of minimization of the peaks of the reaction forces acting between the bearing ring and the bearing support and of increase of the uniformity of the reaction forces. A finite element model of the overhead travelling manipulator was established and the support structure reinforcement configuration was successively optimized. In the final solution maximum tensile and compressive reaction forces were reduced by 13 % in comparison to the initial solution. Also the uniformity of tensile and compressive maximal reaction forces was improved by 74 % and 70 % respectively.

Reports on the formation of single- and two-phase glasses from rare-earth oxide-alumina materials. Transition of the liquids with rare-earth oxide-alumina materials; Reason for the formation of the two glasses; Effect of the addition of lanthanum; Discussion of the results in the context of polyamorphism and formation of single-phase glass.

The paper presents an overview of different types of defects at friction stir welding. In order to explain the reasons for their occurrence a short theoretical background of the process is given first. The main emphasis is on the parameters that influence the process. An energy supply based division of defects into three disjoint groups was used. The occurring defects are demonstrated on various materials. [ABSTRACT FROM AUTHOR]

In the paper a possible scenario for the occurrence of the local buckling of the wall of the thin walled aluminium mast is analyzed. It is assumed that the hook of the auxiliary crane of the rubber-tired marine crane buckled to the lateral mast-supporting wire rope during the retrieval motion from the pier. The consequences of an unintended crane action on the mast of the sailing boat are studied using combination of analytical calculations and FEM. The complexity of the mast - mast wires system, the big displacements and nonlinear material characteristics are taken into account. The properties of the tempered aluminium alloy are included as well as properties in the heat affected zone in the vicinity of the welds. On the basis of the calculated internal forces and moments in the mast and wire-ropes, the possibility of occurrence of different types of failure are studied. The estimated possible damages are compared with actual damages.

Background: It has been suggested that outcomes of antidepressant treatment for major depressive disorder could be significantly improved if treatment choice is informed by genetic data. This study aims to test the hypothesis that common genetic variants can predict response to antidepressants in a clinically meaningful way.Methods and Findings: The NEWMEDS consortium, an academia-industry partnership, assembled a database of over 2,000 European-ancestry individuals with major depressive disorder, prospectively measured treatment outcomes with serotonin reuptake inhibiting or noradrenaline reuptake inhibiting antidepressants and available genetic samples from five studies (three randomized controlled trials, one part-randomized controlled trial, and one treatment cohort study). After quality control, a dataset of 1,790 individuals with high-quality genome-wide genotyping provided adequate power to test the hypotheses that antidepressant response or a clinically significant differential response to the two classes of antidepressants could be predicted from a single common genetic polymorphism. None of the more than half million genetic markers significantly predicted response to antidepressants overall, serotonin reuptake inhibitors, or noradrenaline reuptake inhibitors, or differential response to the two types of antidepressants (genome-wide significance p<5×10(-8)). No biological pathways were significantly overrepresented in the results. No significant associations (genome-wide significance p<5×10(-8)) were detected in a meta-analysis of NEWMEDS and another large sample (STAR*D), with 2,897 individuals in total. Polygenic scoring found no convergence among multiple associations in NEWMEDS and STAR*D.Conclusions: No single common genetic variant was associated with antidepressant response at a clinically relevant level in a European-ancestry cohort. Effects specific to particular antidepressant drugs could not be investigated in the current study. Please see later in the article for the Editors' Summary. [ABSTRACT FROM AUTHOR]

Rock wool insulation slabs are produced in special curing ovens, where molten rock wool fibres coated with binder are compressed between two slat conveyors and blown with hot air for vitrification. Often, the cross-section of the final slabs is slightly convex, which is undesirable. The degree of convexity depends on the deformation of the steel crossbars of the slat conveyors, which are subjected to combined pressure and nonlinear temperature loadings. Due to this complex loading state, it is difficult to determine the contribution of individual load to the total deformation. The main aim of the study was to determine these contributions. Temperature and stress measurements of the crossbars were performed during rock wool production. Upon collecting these measurements, a finite element (FE) model of a crossbar was established for the identification of the pressure loading acting on the crossbars, and finally for determination of their deformations. As a main result of the study, an inverse problem-based methodology for the identification of the deflection of a structure due to unknown temperature and pressure loadings was established and applied on the specific case. The deviations between the deformations of the FE crossbars and the final shape of the rock wool slabs were below 10%, which validates the novel methodology.

The altitude differential of the specific mechanical energy, diff e mech , is used to evaluate skiing performance. It is defined as the negative differential between the skier's total specific mechanical energy ( e mech ) and the altitude of the skier's center of mass (COM). Till now, e mech was obtained upon a mass-point (MP) model of the skier's COM, which neither considered the segmental energies of their relative movements to the COM, nor their rotational kinetic energies. The aims of the study were therefore: (a) to examine the deviations in diff e mech between the MP and a more complex linked segment (LS) skier model consisting of 15 rigid bodies, which encountered the aforementioned defectiveness, (b) to compare the energy fluctuations of the two skier models, and (c) to investigate the influence of the gate setup on (a) and (b) in giant slalom. Three-dimensional whole-body kinematics of nine skiers was measured using a global navigation satellite system and an inertial motion capture system while skiing on a predefined course divided into a turny and open gate setup. Mechanical energies including their altitude differentials were calculated for the LS and MP models. There were no significant differences in e mech and diff e mech ski turn averages, as in individual data points, between both skier models for both analyzed gate setups. The energies additionally considered by the LS model presented a negligible part regardless of the gate setup. In conclusion, the MP skier model is sufficiently accurate for the evaluation of the skiing performance with diff e mech ., (© 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait., Methods: Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy; 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole sample or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756)., Results: No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in individual studies or a meta-analysis. Stratifying by antidepressant did not alter the results., Discussion: We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Antidepressant drugs are used as first-line treatment in depression, but response has been shown to be highly heterogeneous, with drugs often failing to have the desired therapeutic effect. We report on an integrative analysis from the Genome-Based Therapeutic Drugs for Depression (GENDEP) study using gene expression from mice to inform prioritization in a human pharmacogenetic study., Methods: The same two antidepressants were used in mice and humans: escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor). The animal study used four inbred strains of mice (129S1/SvlmJ, C57LB/6J, DBA/2J, and FVB/NJ). Hippocampus mRNA levels were measured in 144 animals using the Affymetrix MOE 430 v2 chip., Results: Based on gene-expression analysis of strain-by-drug interactions, 17 genes differentially expressed with nortriptyline or escitalopram versus saline were prioritized in the human pharmacogenetic analysis. Single nucleotide polymorphisms tagging common sequence variation in human orthologs of these genes were tested for association with response to antidepressants in 706 participants of the GENDEP human pharmacogenetic study, treated with escitalopram or nortriptyline for 12 weeks, with available high-quality Illumina 610 quad array genotyping. Several polymorphisms in the protein phosphatase 1A gene (PPM1A) remained significantly associated with response to nortriptyline in humans after correction for multiple comparisons within the gene. PPM1A encodes a phosphatase involved in mitogen-activated protein kinase signaling and cell stress response., Conclusions: Convergent evidence from mice and humans suggests a role of the PPM1A in response to noradrenergic but not serotonergic antidepressants., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Secreted group X phospholipase A2 (sPLA2-X) is one of the most effective mammalian PLA2 enzymes at hydrolyzing plasma lipoproteins and phospholipids in the membranes of intact cells, due in particular to its relatively high binding affinity to zwitterionic phospholipid substrates, such as phosphatidylcholine. The products of its enzymatic activity, lysophospholipids and free fatty acids, especially arachidonic acid, are involved in various physiological and pathological processes and currently being studied intensively. In spite of numerous studies, the biological roles of sPLA2-X have not been completely elucidated. With the aims of studying various cellular functions and designing effective enzyme inhibitors, we prepared a high amount of recombinant human sPLA2-X. Here we describe an effective Escherichia coli expression system, together with an in vitro refolding and simple purification procedure, that yields up to 10 mg of mature human sPLA2-X from a litre of culture. In contrast to the natural protein, the recombinant enzyme was produced in bacterial cells without the N-terminal propeptide, i.e. as a mature protein, and was not N-glycosylated. It however retained all the enzymatic properties for hydrolysis of vesicular substrates composed of either phosphatidylglycerol or phosphatidylcholine.

Objective: The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment. The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs., Method: High-quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram (N=394) or nortriptyline (N=312) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression (GENDEP) project, a partially randomized open-label pharmacogenetic trial., Results: Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association. Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline. Response to escitalopram was best predicted by a marker in the interleukin-11 (IL11) gene. A set of 72 a priori-selected candidate genes did not show pharmacogenetic associations above a chance level, but an association with response to escitalopram was detected in the interleukin-6 gene, which is a close homologue of IL11., Conclusions: While limited statistical power means that a number of true associations may have been missed, these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional candidates. Genome-wide studies, if properly replicated, may thus be important steps in the elucidation of the genetic basis of pharmacological response.

Osmotic coefficients, phi, and apparent molar volumes, PhiV, of aqueous solutions of isotactic, syndiotactic, and atactic poly(methacrylic acid), i-PMA, s-PMA, and a-PMA, respectively, were measured at 298 K in dependence on polymer concentration and on degree of neutralization, alphaN, of carboxyl groups. The solutions of i-PMA have lower phi values than those of a-PMA and s-PMA in the whole region of alphaN. Molecular dynamics simulation studies of the isotactic and the syndiotactic PMA 101-mer have shown that lower phi is a consequence of a shorter distance between charges, which leads to a greater charge density of the isotactic polymer and thus to stronger binding of counterions. The experimental phi data were analyzed using a cylindrical cell model. Good agreement between theory and experiment was achieved when charges on the polyion were distributed periodically along the z-axis of the polyion in accordance with the simulation results. The alphaN dependence of the PhiV data pointed out that all PMA isomers bind an appreciable amount of water in the elementary dissociation process (electrostriction). For a- and s-PMA, the PhiV values decrease linearly with increasing alphaN, whereas they show a marked nonlinear dependence in the case of i-PMA for alphaN < 0.6. The latter finding was ascribed to a very high intermolecular association tendency of the isotactic polymer. This association tendency of PMA chains was confirmed by light scattering measurements. It is present in both i- and a-PMA solutions but is much more pronounced in the i-PMA case.

Association of a cationic surfactant cetylpyridinium chloride, CPC, with isotactic and atactic poly(methacrylic acid), i-PMA and a-PMA, respectively, in aqueous 0.01 M NaCl solutions was studied by pH and fluorescence measurements in conjunction with potentiometric studies using a surfactant-sensitive membrane electrode. pH measurements have demonstrated that the presence of an oppositely charged surfactant increases ionization of carboxyl groups on PMA at low degrees of neutralization. The increase is more pronounced in the case of i-PMA. The isotactic form of PMA is not soluble in water at zero degrees of neutralization but can be rendered soluble by the addition of CPC at the surfactant to a polyion molar ratio of around 0.4. In the solubilized complex, the positive charge of the CPC molecule is facing the polar solvent, whereas surfactant tails are oriented toward the i-PMA compact coil. Binding isotherms and cooperativity parameters show that chain tacticity has an important influence on the interaction of cetylpyridinium cation with polymethacrylate anion. At the onset of cooperative binding, the association is stronger with i-PMA than with the atactic form, as demonstrated by lower CAC values and higher values of the cooperativity parameters. In contrast, more surfactant is bound by a-PMA in the region where polyion becomes saturated with surfactant ions. Results are interpreted by taking into account local chain conformations as obtained from quantum mechanical semiempirical molecular orbital calculations. Greater hydrophobicity and possibly higher charge density of i-PMA on one hand and more flexibility of the a-PMA chain on the other are held responsible for these observations.

Antibiotics that interfere with DNA replication, as well as cell wall synthesis, induce the SOS response. In this report, we show that ciprofloxacin induces synthesis of colicins, narrow-spectrum antibiotics frequently produced by Escherichia coli strains, in an SOS-dependent manner.