Toward a structural understanding of turbulent drag reduction: nonlinear coherent states in viscoelastic shear flows

Nontrivial steady flows have recently been found that capture the main structures of the turbulent buffer layer. We study the effects of polymer addition on these "exact coherent states" (ECS) in plane Couette flow. Despite the simplicity of the ECS flows, these effects closely mirror those observed experimentally: Structures shift to larger length scales, wall-normal fluctuations are suppressed while streamwise ones are enhanced, and drag is reduced. The mechanism underlying these effects is elucidated. These results suggest that the ECS are closely related to buffer layer turbulence.Comment: 5 pages, 3 figures, published version, Phys. Rev. Lett. 89, 208301 (2002

Associations of NINJ2 sequence variants with incident ischemic stroke in the Cohorts for Heart and Aging in Genomic Epidemiology (CHARGE) consortium

Background<p></p> Stroke, the leading neurologic cause of death and disability, has a substantial genetic component. We previously conducted a genome-wide association study (GWAS) in four prospective studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and demonstrated that sequence variants near the NINJ2 gene are associated with incident ischemic stroke. Here, we sought to fine-map functional variants in the region and evaluate the contribution of rare variants to ischemic stroke risk.<p></p> Methods and Results<p></p> We sequenced 196 kb around NINJ2 on chromosome 12p13 among 3,986 European ancestry participants, including 475 ischemic stroke cases, from the Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, and Framingham Heart Study. Meta-analyses of single-variant tests for 425 common variants (minor allele frequency [MAF] ≥ 1%) confirmed the original GWAS results and identified an independent intronic variant, rs34166160 (MAF = 0.012), most significantly associated with incident ischemic stroke (HR = 1.80, p = 0.0003). Aggregating 278 putatively-functional variants with MAF≤ 1% using count statistics, we observed a nominally statistically significant association, with the burden of rare NINJ2 variants contributing to decreased ischemic stroke incidence (HR = 0.81; p = 0.026).<p></p> Conclusion<p></p> Common and rare variants in the NINJ2 region were nominally associated with incident ischemic stroke among a subset of CHARGE participants. Allelic heterogeneity at this locus, caused by multiple rare, low frequency, and common variants with disparate effects on risk, may explain the difficulties in replicating the original GWAS results. Additional studies that take into account the complex allelic architecture at this locus are needed to confirm these findings

An analytical Micro CT methodology for quantifying inorganic dentine debris following internal tooth preparation

AbstractObjectivesMicroCT allows the complex canal network of teeth to be mapped but does not readily distinguish between structural tissue (dentine) and the debris generated during cleaning. The aim was to introduce a validated approach for identifying debris following routine instrumentation and disinfection.MethodsThe mesial canals of 12 mandibular molars were instrumented, and irrigated with EDTA and NaOCl. MicroCT images before and after instrumentation and images were assessed qualitatively and quantitatively.ResultsDebris in the canal space was identified through morphological image analysis and superimposition of the images before and after instrumentation. This revealed that the removal of debris is prohibited by protrusions and micro-canals within the tooth creating areas which are inaccessible to the irrigant. Although the results arising from the analytical methodology did provide measurements of debris produced, biological differences in the canals resulted in variances. Both irrigants reduced debris compared to the control which decreased with EDTA and further with NaOCl. However, anatomical variation did not allow definitive conclusions on which irrigant was best to use although both reduced debris build up.ConclusionsThis work presents a new approach for distinguishing between debris and structural inorganic tissue in root canals of teeth. The application may prove useful in other calcified tissue shape determination.Clinical significanceRemaining debris may contain bacteria and obstruct the flow of irrigating solutions into lateral canal anatomy. This new approach for detecting the amount of remaining debris in canal systems following instrumentation provides a clearer methodology of the identification of such debris

Adam Smith’s Green Thumb and Malthus’ Three Horsemen: Cautionary tales from classical political economy

This essay identifies a contradiction between the flourishing interest in the environmental economics of the classical period and a lack of critical parsing of the works of its leading representatives. Its focus is the work of Adam Smith and Thomas Malthus. It offers a critical analysis of their contribution to environmental thought and surveys the work of their contemporary devotees. It scrutinizes Smith's contribution to what Karl Polanyi termed the "economistic fallacy," as well as his defenses of class hierarchy, the "growth imperative" and consumerism. It subjects to critical appraisal Malthus's enthusiasm for private property and the market system, and his opposition to market regulation. While Malthus's principal attraction to ecological economists lies in his having allegedly broadened the scope of economics, and in his narrative of scarcity, this article shows that he, in fact, narrowed the scope of the discipline and conceptualized scarcity in a reified and pseudo-scientific way

Hierarchical modelling and X-ray analysis of human dentine and enamel

Human teeth consist of enamel, dentine and cementum, hierarchical mineralised tissues with a two-level composite structure. The understanding of the mechanical behaviour of dentine and enamel in terms of their micro- and nano-scale structure has been somewhat limited. Here we present an overview of our recent work aimed at improving the understanding of the internal lattice strain response of the mineral crystallites of different orientations under external in situ loading. A range of experimental techniques was employed for the purpose of this analysis. Small- and Wide- Angle X-ray Scattering (SAXS/WAXS) were used to determine the internal lattice strain and orientational distribution of HAp crystals, while quantitative stress distribution evaluation in the birefringent mounting epoxy surrounding the sample was carried out in parallel using photoelasticity. Finite element analysis and advanced multi-scale Eshelby inclusion modelling were used to interpret the data. The satisfactory agreement achieved between the model and the experimental data, in terms of the values of multi-directional strain components under the action of differently orientated loads, demonstrates that our multi-scale approach captures successfully the structure-property relationships between the hierarchical architecture of human dental tissues and their response to the applied forces. Our systematic approach can be used to improve the insight into the mechanical properties of dentine and enamel, and of textured hierarchical biomaterials (such as bones) in general.</p

rephrasing an established mechanistic model?’

okpublishersversionepub_ahead_of_prin

Metabolic Syndrome features and risk of neural tube defects

Research articl

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response

The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports

Background: The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies. Methods: Adult participants (n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests. Results: The participants were white of European descent and from the FHS Original and Offspring Cohorts (examination 1 Offspring mean age 32 ± 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency ≥ 10%, genotype call rate ≥ 80%, Hardy-Weinberg equilibrium p-value ≥ 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at http:// www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication.Molecular and Cellular Biolog

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention