An Investigation of Process Variables Influencing Fatigue Properties of Components Produced by Direct Metal Laser Sintering

Direct Metal Laser Sintering (DMLS) is one of the methods in layered manufacturing technologies by which metal powder can be directly used to produce both prototype and production tools. Fatigue strength is one of the important mechanical properties for the functional application of DMLS parts. This study was carried out to determine the optimum process parameters influencing the fatigue cycles to failure of DMLS components. Sintering speed, scan spacing, post-contouring speed, infiltration and hatch type are the process parameters taken up for the study. Statistical design of experiments using Taguchi’s orthogonal array was employed for this study. Experimental data obtained were analysed using analysis of variance (ANOVA). From the results, it is found that one of the process parameters, sintering speed affects the fatigue properties of parts produced by this technology to a significant exten

Sympathovagal Imbalance in Prehypertensive Offspring of Two Parents versus One Parent Hypertensive

Objective. Though prehypertension has strong familial predisposition, difference in pathophysiological mechanisms in its genesis in offspring of both parents and single parent hypertensive have not been elucidated. Methods. Body mass index (BMI), waist-hip ratio (WHR), basal heart rate (BHR), blood pressure (BP), HR and BP response to standing, deep breathing difference, BP response to handgrip and spectral indices of heart rate variability (HRV) were analyzed in normotensive offspring of two parents hypertensive (Group I), normotensive offspring of one parent hypertensive (Group II), prehypertensive offspring of two parents hypertensive (Group III) and prehypertensive offspring of one parent hypertensive (Group IV). Results. Sympathovagal imbalance (SVI) in prehypertensive offspring was observed due to increased sympathetic and decreased vagal activity. In group III, SVI was more prominent with greater contribution by vagal withdrawal. LF-HF ratio, the marker of SVI was correlated more with diastolic pressure, 30 : 15 ratio and E : I ratio in prehypertensives and the degree of correlation was more in group III prehypertensives. Conclusion. Vagal withdrawal plays a critical role in development of SVI in prehypertensive offspring of hypertensive parents. The intensity of SVI was more in offspring of two parents hypertensive compared to single parent hypertensive

Frequency of polymorphic variants in corticotropin releasing hormone receptor 1, glucocorticoid induced 1 and Fc fragment of IgE receptor II genes in healthy and asthmatic Tamilian population

Background: Asthma is a chronic airway inflammatory disease characterized by increased hyper-responsiveness and recurrent episodes of reversible obstructions. Asthma pharmacogenomic studies report significant association of single nucleotide polymorphisms (SNPs) in genes corticotropin releasing hormone receptor 1 (CRHR1), Fc fragment of IgE receptor II (FCER2) and glucocorticoid induced 1 (GLCCI1) with inhaled corticosteroid (ICS) response. The present study was aimed to establish the allelic and genotypic frequencies of polymorphisms rs242941, rs28364072 & rs37972 in CRHR1, FCER2 and GLCCI1 genes, respectively in Tamilian healthy population and asthma patients and to compare with established frequencies of global populations.Methods: The study groups consisted of healthy volunteers and persistent asthma patients who were drug naïve or without ICS treatment in the last ≥2 months, attending JIPMER hospital (n=111 and 78, respectively). SNP genotyping was done using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and real time-PCR methods.Results: Allelic and genotypic frequencies for all the studied variants found to be in hardy-weinberg equilibrium with minor allele frequencies (MAF) of rs 242941, rs 28364072 and rs 37972 at 0.51, 0.33 and 0.38, respectively, in healthy population. No significant difference in gene frequencies was obtained between healthy control and asthma patient groups. Significant difference in allele frequencies was observed between Tamilian healthy and specific global populations. West African frequency was found to be significantly different for all 3 SNPs (p<0.0001).Conclusions: MAF of rs 242941, rs 28364072 and rs 37972 were 0.51, 0.33 and 0.38, respectively in Tamilian population which were significantly different from various global populations. The frequency distribution found helps to further with ICS response association studies in larger cohorts of asthma patients

Global text mining and development of pharmacogenomic knowledge resource for precision medicine

Understanding patients' genomic variations and their effect in protecting or predisposing them to drug response phenotypes is important for providing personalized healthcare. Several studies have manually curated such genotype-phenotype relationships into organized databases from clinical trial data or published literature. However, there are no text mining tools available to extract high-accuracy information from such existing knowledge. In this work, we used a semiautomated text mining approach to retrieve a complete pharmacogenomic (PGx) resource integrating disease-drug-gene-polymorphism relationships to derive a global perspective for ease in therapeutic approaches. We used an R package, pubmed.mineR, to automatically retrieve PGx-related literature. We identified 1,753 disease types, and 666 drugs, associated with 4,132 genes and 33,942 polymorphisms collated from 180,088 publications. With further manual curation, we obtained a total of 2,304 PGx relationships. We evaluated our approach by performance (precision = 0.806) with benchmark datasets like Pharmacogenomic Knowledgebase (PharmGKB) (0.904), Online Mendelian Inheritance in Man (OMIM) (0.600), and The Comparative Toxicogenomics Database (CTD) (0.729). We validated our study by comparing our results with 362 commercially used the US- Food and drug administration (FDA)-approved drug labeling biomarkers. Of the 2,304 PGx relationships identified, 127 belonged to the FDA list of 362 approved pharmacogenomic markers, indicating that our semiautomated text mining approach may reveal significant PGx information with markers for drug response prediction. In addition, it is a scalable and state-of-art approach in curation for PGx clinical utility

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network.Comment: White paper submitted to the Astro2020 Decadal Surve

Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population

<p>Abstract</p> <p>Background</p> <p>Genetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (<it>CYP) 2C8</it>, <it>CYP2C9</it>, and <it>CYP2C19 </it>variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies.</p> <p>Methods</p> <p>RFLP assays were used to genotype <it>CYP2C8 </it>(<it>*2</it>, <it>*3</it>, <it>*4</it>) variant alleles in 204 unrelated Ghanaians. <it>CYP2C9*2 </it>and <it>CYP2C19 </it>(<it>*2 </it>and <it>*3</it>) variants were determined by single-tube tetra-primer assays while <it>CYP2C9 </it>(<it>*3, *4, *5 </it>and <it>*11</it>) variants were assessed by direct sequencing.</p> <p>Results</p> <p>Allelic frequencies were obtained for <it>CYP2C8*2 </it>(17%), <it>CYP2C8*3 </it>(0%), <it>CYP2C8*4 </it>(0%), <it>CYP2C9*2 </it>(0%), <it>CYP2C9*3 </it>(0%), <it>CYP2C9*4 </it>(0%), <it>CYP2C9</it>*5 (0%), <it>CYP2C9*11 </it>(2%), <it>CYP2C19*2 </it>(6%) and <it>CYP2C19*3 </it>(0%).</p> <p>Conclusion</p> <p>Allele frequency distributions for <it>CYP2C8</it>, <it>CYP2C9 </it>and <it>CYP2C19 </it>among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for <it>CYP2C9 </it>and <it>CYP2C19 </it>are reported for the first time among indigenous Ghanaian population.</p

Multi-Messenger Astronomy with Extremely Large Telescopes

The field of time-domain astrophysics has entered the era of Multi-messenger Astronomy (MMA). One key science goal for the next decade (and beyond) will be to characterize gravitational wave (GW) and neutrino sources using the next generation of Extremely Large Telescopes (ELTs). These studies will have a broad impact across astrophysics, informing our knowledge of the production and enrichment history of the heaviest chemical elements, constrain the dense matter equation of state, provide independent constraints on cosmology, increase our understanding of particle acceleration in shocks and jets, and study the lives of black holes in the universe. Future GW detectors will greatly improve their sensitivity during the coming decade, as will near-infrared telescopes capable of independently finding kilonovae from neutron star mergers. However, the electromagnetic counterparts to high-frequency (LIGO/Virgo band) GW sources will be distant and faint and thus demand ELT capabilities for characterization. ELTs will be important and necessary contributors to an advanced and complete multi-messenger network