260 research outputs found
Roughening improves hydrogen embrittlement resistance of Ti-6Al-4V
Polished surfaces of Ti-6Al-4V, the most commonly used titanium alloy, were observed to suffer from hydride growth and associated embrittlement during hydrogen charging, whereas rough surfaces suffered no such susceptibility. Direct microscopic analyses of recombined hydrogen bubbles and thermal desorption spectroscopy (TDS) revealed that the surface roughening promotes recombination of atomic hydrogen to molecular hydrogen, in turn, reducing the relative amount of atomic hydrogen uptake. Subsurface time-of-flight secondary-ion mass spectrometry (ToF-SIMS) further revealed that the high defect density underneath the roughened surface impedes hydrogen diffusion into the bulk. These combined effects mean that, unexpectedly, roughening significantly reduces hydrogen uptake into Ti-6Al-4V and enhances its resistance against hydrogen embrittlement – all resulting from a simple surface treatment
Prioritizing causal disease genes using unbiased genomic features
Background: Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits. Results: To aid in localizing causal genes, we develop a machine learning approach, Objective Prioritization for Enhanced Novelty (OPEN), which quantitatively prioritizes gene-disease associations based on a diverse group of genomic features. This approach uses only unbiased predictive features and thus is not hampered by a preference towards previously well-characterized genes. We demonstrate success in identifying genetic determinants for CVD-related traits, including cholesterol levels, blood pressure, and conduction system and cardiomyopathy phenotypes. Using OPEN, we prioritize genes, including FLNC, for association with increased left ventricular diameter, which is a defining feature of a prevalent cardiovascular disorder, dilated cardiomyopathy or DCM. Using a zebrafish model, we experimentally validate FLNC and identify a novel FLNC splice-site mutation in a patient with severe DCM. Conclusion: Our approach stands to assist interpretation of large-scale genetic studies without compromising their fundamentally unbiased nature. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0534-8) contains supplementary material, which is available to authorized users
Anxiolytic Effects of the MCH1R Antagonist TPI 1361-17
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that acts on the MCH1 receptor. MCH1R is expressed widely throughout the brain, particularly in regions thought to be involved in the regulation of stress and emotional response. The role of MCH in anxiety has been controversial, however. Central administration of MCH has been reported to promote or reduce anxiety-like behaviors. The anxiolytic activity of several MCH1R antagonists has also been debated. To address this issue, we have tested whether TPI 1361-17, a highly specific and high affinity MCH1R antagonist, exerts anxiolytic effects in two commonly used models of anxiety, the elevated plus maze and the light–dark transition test. We show that this MCH1R antagonist exerts potent anxiolytic effects in both assays. Our study therefore supports previous studies indicating that MCH1R antagonists may be useful in the treatment of anxiety
Deformation-induced microstructural banding in TRIP steels
Microstructure inhomogeneities can strongly influence the mechanical properties of advanced high-strength steels in a detrimental manner. This study of a transformation-induced plasticity (TRIP) steel investigates the effect of pre-existing contiguous grain boundary networks (CGBNs) of hard second-phases and shows how these develop into bands during tensile testing using in situ observations in conjunction with digital image correlation (DIC). The bands form by the lateral contraction of the soft ferrite matrix, which rotates and displaces the CGBNs of second-phases and the individual features within them to become aligned with the loading direction. The more extensive pre-existing CGBNs that were before the deformation already aligned with the loading direction are the most critical microstructural feature for damage initiation and propagation. They induce micro-void formation between the hard second-phases along them, which coalesce and develop into long macroscopic fissures. The hard phases, retained austenite and martensite, were not differentiated as it was found that the individual phases do not play a role in the formation of these bands. It is suggested that minimizing the presence of CGBNs of hard second-phases in the initial microstructure will increase the formability
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Stratification of candidate genes for Parkinson’s disease using weighted protein interaction network analysis
Genome wide association studies (GWAS) have helped identify large numbers of genetic loci that significantly associate with increased risk of developing diseases. However, translating genetic knowledge into understanding of the molecular mechanisms underpinning disease (i.e. disease-specific impacted biological processes) has to date proved to be a major challenge. This is primarily due to difficulties in confidently defining candidate genes at GWAS-risk loci. The goal of this study was to better characterize candidate genes within GWAS loci using a protein interactome based approach and with Parkinson's disease (PD) data as a test case.We applied a recently developed Weighted Protein-Protein Interaction Network Analysis (WPPINA) pipeline as a means to define impacted biological processes, risk pathways and therein key functional players. We used previously established Mendelian forms of PD to identify seed proteins, and to construct a protein network for genetic Parkinson's and carried out functional enrichment analyses. We isolated PD-specific processes indicating 'mitochondria stressors mediated cell death', 'immune response and signaling', and 'waste disposal' mediated through 'autophagy'. Merging the resulting protein network with data from Parkinson's GWAS we confirmed 10 candidate genes previously selected by pure proximity and were able to nominate 17 novel candidate genes for sporadic PD.With this study, we were able to better characterize the underlying genetic and functional architecture of idiopathic PD, thus validating WPPINA as a robust pipeline for the in silico genetic and functional dissection of complex disorders
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