Free Convection Boundary Layer Flow and Heat Transfer of a Nano Fluid over a Moving Plate with Internal Heat Generation

This paper presents considers the extended Blasius Flow problem and Heat transfer characteristics in Nano fluid with internal heat generation by considering free stream parallel to a moving plat plate which has much practical significance. The total transport model employed here includes the effect of Blasius motion and internal heat generation in energy transfer. It is also assumed that the plate moves in same or opposite direction to the free stream. Using the Similarity transformations, the transport equations followed by their Numerical computations. The governing system of highly non-linear ordinary differential equations are solved for three kinds of nanoparticals namely Cooper(Cu), Alumina() and Titania() in the water base fluid with the value of Prandtl Number Pr=6.2 numerically. Initially by the similarity analysis the governing partial differential equations are converted into system of non linear ordinary differential equations. The governing p.d.e’s are converted into system of first order o.d.e’s and are solved numerically using MATLAB ode45 solver. The effect of various Physical parameters encountered in the problem such as solid volume fraction of three types of nano particles on velocity transfer and Energy transfer are analysed and studied by representing through graphs. The results are compared with earlier published results and are well in agreement. Keywords: Nano fluid, moving plate, heat transfer, ode solver, solid volume fractio

Structure Prediction and Active Site Analysis of New H1N1 Neuraminidase:Target for Antiviral Drug Design

Abstract: The H1N1 viral envelope protein neuraminidase encoded by NA gene plays a key role in the pathogenesis of swine flu. The active site of the neuraminidase protein is targeted by presently available antiviral drugs. The influenza virus often proves to be resistant to currently available drugs, due single amino acid substitutions conferred by the mutations in the gene coding for neuraminidase protein. The latest Influenza A virus A/Perth/262/2009(H1N1) sequence with accession number ADJ67981 was selected from NCBI. The BLAST program was used to identify the best template structure, which was found to be 3NSS_A. Sequence alignment was carried out with the template and query sequence, the identity and similarity was found to be 81.9% and 82.6% respectively. Homology modeling was performed using Accelrys Discovery Studio 3.5 software, the model with the lowest energy was then assessed for stereochemical quality and side-chain environment. The PDF energy and DOPE score of the best modeled structure was 2090.1682 and -43752.3632 respectively. Further active site optimization of the modeled protein was performed by molecular dynamics. The key active site residues which are crucial for further docking studies were ascertained

Structural correlations between brain magnetic resonance image‐derived phenotypes and retinal neuroanatomy

Background and purpose: The eye is a well‐established model of brain structure and function, yet region‐specific structural correlations between the retina and the brain remain underexplored. Therefore, we aim to explore and describe the relationships between the retinal layer thicknesses and brain magnetic resonance image (MRI)‐derived phenotypes in UK Biobank. Methods: Participants with both quality‐controlled optical coherence tomography (OCT) and brain MRI were included in this study. Retinal sublayer thicknesses and total macular thickness were derived from OCT scans. Brain image‐derived phenotypes (IDPs) of 153 cortical and subcortical regions were processed from MRI scans. We utilized multivariable linear regression models to examine the association between retinal thickness and brain regional volumes. All analyses were corrected for multiple testing and adjusted for confounders. Results: Data from 6446 participants were included in this study. We identified significant associations between volumetric brain MRI measures of subregions in the occipital lobe (intracalcarine cortex), parietal lobe (postcentral gyrus), cerebellum (lobules VI, VIIb, VIIIa, VIIIb, and IX), and deep brain structures (thalamus, hippocampus, caudate, putamen, pallidum, and accumbens) and the thickness of the innermost retinal sublayers and total macular thickness (all p < 3.3 × 10−5). We did not observe statistically significant associations between brain IDPs and the thickness of the outer retinal sublayers. Conclusions: Thinner inner and total retinal thicknesses are associated with smaller volumes of specific brain regions. Notably, these relationships extend beyond anatomically established retina–brain connections

The association of alcohol consumption with glaucoma and related traits: findings from the UK Biobank

PURPOSE: To examine the associations of alcohol consumption with glaucoma and related traits; to assess whether a genetic predisposition to glaucoma modified these associations; and to perform Mendelian randomization (MR) experiments to probe causal effects. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. PARTICIPANTS: UK Biobank participants with data on intraocular pressure (IOP) (n=109 097), OCT derived macular inner retinal layer thickness measures (n=46 236) and glaucoma status (n=173 407). METHODS: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a two-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers), before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic and restricted cubic spline (RCS) regression, adjusted for key sociodemographic, medical, anthropometric and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multi-trait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. MAIN OUTCOME MEASURES: IOP, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. RESULTS: Compared to infrequent drinkers, regular drinkers had higher IOP (+0.17mmHg; P<0.001) and thinner mGCIPL (-0.17μm; P=0.049); while former drinkers had a higher prevalence of glaucoma (OR 1.53; P=0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P<0.001). RCS regression analyses suggested non-linear associations, with apparent threshold effects at approximately 50g (∼6 UK or 4 US alcoholic units)/week, for mRNFL and mGCIPL thickness. Significantly stronger alcohol-IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction<0.001). MR analyses provided evidence for a causal association with mGCIPL thickness. CONCLUSIONS: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current UK (<112g/week) and US (women: <98g/week; men: <196g/week) guidelines. While we cannot infer causality definitively, these results will be of interest to people with, or at risk of, glaucoma and their advising physicians

The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank.

PurposeTo examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects.DesignCross-sectional observational and gene-environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia.ParticipantsUK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407).MethodsParticipants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses.Main outcome measuresIntraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma.ResultsCompared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P interaction ConclusionsAlcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (Financial disclosure(s)Proprietary or commercial disclosure may be found after the references

The association of urinary sodium excretion with glaucoma and related traits in a large United Kingdom population

Purpose: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease. Design: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. Participants: Up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data. Methods: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. Main Outcome Measures: Corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. Results: In maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12–0.17; P < 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07–1.14; P < 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36–0.53, P < 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17–1.45; P < 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score. Conclusions: Urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking

The association of urinary sodium excretion with glaucoma and related traits in a large United Kingdom population

Purpose: excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and determine whether this relationship is modified by genetic susceptibility to disease.Design: cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study.Participants: up to 103 634 individuals (mean age: 57 years; 51% women) with complete urinary, ocular, and covariable data.Methods: urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination, and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score comprising 2673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions.Main outcome measures: corneal-compensated IOP, OCT derived macular retinal nerve fiber layer and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma.Results: in maximally adjusted regression models, a 1 standard deviation increase in UNa:Cr was associated with higher IOP (0.14 mmHg; 95% confidence interval [CI], 0.12–0.17; P &lt; 0.001) and greater prevalence of glaucoma (odds ratio, 1.11; 95% CI, 1.07–1.14; P &lt; 0.001) but not macular retinal nerve fiber layer or ganglion cell-inner plexiform layer thickness. Compared with those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45 mmHg; 95% CI, 0.36–0.53, P &lt; 0.001) and prevalence of glaucoma (odds ratio, 1.30; 95% CI, 1.17–1.45; P &lt; 0.001). Stronger associations with glaucoma (P interaction = 0.001) were noted in participants with a higher glaucoma polygenic risk score.Conclusions: urinary sodium excretion, a biomarker of dietary intake, may represent an important modifiable risk factor for glaucoma, especially in individuals at high underlying genetic risk. These findings warrant further investigation because they may have important clinical and public health implications

The association of alcohol consumption with glaucoma and related traits: Findings from the UK Biobank

Purpose: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. Design: Cross-sectional observational and gene–environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. Participants: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). Methods: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. Results: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P &lt; 0.001) and thinner mGCIPL (-0.17 μm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P &lt; 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol–IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction &lt; 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. Conclusions: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (&lt; 112 g/week) and United States (women, &lt; 98 g/week; men, &lt; 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.</p