Mean-field density functional theory of ananoconfined classical, three-dimensional Heisenberg fluid. I. The role of molecularanchoring

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in J. Chem. Phys. 144, 194704 (2016) and may be found at https://doi.org/10.1063/1.4949330.In this work, we employ classical density functional theory (DFT) to investigate for the first time equilibrium properties of a Heisenberg fluid confined to nanoscopic slit pores of variable width. Within DFT pair correlations are treated at modified mean-field level. We consider three types of walls: hard ones, where the fluid-wall potential becomes infinite upon molecular contact but vanishes otherwise, and hard walls with superimposed short-range attraction with and without explicit orientation dependence. To model the distance dependence of the attractions, we employ a Yukawa potential. The orientation dependence is realized through anchoring of molecules at the substrates, i.e., an energetic discrimination of specific molecular orientations. If the walls are hard or attractive without specific anchoring, the results are “quasi-bulk”-like in that they can be linked to a confinement-induced reduction of the bulk mean field. In these cases, the precise nature of the walls is completely irrelevant at coexistence. Only for specific anchoring nontrivial features arise, because then the fluid-wall interaction potential affects the orientation distribution function in a nontrivial way and thus appears explicitly in the Euler-Lagrange equations to be solved for minima of the grand potential of coexisting phases.DFG, 65143814, GRK 1524: Self-Assembled Soft-Matter Nanostructures at Interface

Artificial neural network surrogate modeling for uncertainty quantification and structural optimization of reinforced concrete structures

Optimization approaches are important to design sustainable structures. In structural mechanics, different design objectives can be defined, for example, to minimize the required construction material or to maximize the structural durability. In this paper, the durability of a reinforced concrete (RC) structure is assessed by advanced finite element (FE) models to simulate the cracking behavior and the chloride transport process. The corrosion initiation time is used as durability measure to be maximized within an optimization approach, where the concrete cover is defined as design variable. The variability of structural loads and material parameters and unavoidable construction imprecision leads to a probabilistic reliability and durability assessment, where aleatory as well as epistemic uncertainties are quantified by random variables, intervals and probability-boxes. The FE simulation models cannot directly be applied to structural analyses and optimizations with polymorphic uncertain parameters and design variables because of the high computational demand of the multi-loop algorithm (Monte Carlo simulation, interval analysis, global optimization). In this paper, a new surrogate modeling strategy is presented, where artificial neural networks are trained sequentially to speed-up the coupled mechanical and transport simulation FE models. The new approach is applied to the uncertainty quantification and the structural durability optimization of a RC structure

Anwendungsmodalitäten und Qualität von Online-Befragungen in der Kommunikationswissenschaft

Seit Mitte der 90er Jahre ergänzt die Online-Befragung das Repertoire der sozialwissenschaftlichen Befragungsinstrumente. Sie hat sich seither sowohl in der kommerziellen Marktforschung als auch in den empirischen Sozialwissenschaften etabliert. Auch im wissenschaftlichen Bereich erfreuen sich internetgestützte Befragungen wachsender Beliebtheit. Die wachsende Popularität der Online-Befragung kann man jedoch nicht nur an ihrer zunehmenden Anwendungshäufigkeit ablesen, auch weichere Indikatoren, wie entsprechende Kapitel in Methodenlehrbüchern, lassen erkennen, dass sie mittlerweile einen festen Platz im Kanon des sozialwissenschaftlichen Methodeninstrumentariums einnimmt. Die Gründe für diesen Zuwachs liegen in den zahlreichen Vorteilen der Methode, insbesondere ihren geringen Kosten, ihrer Schnelligkeit und Flexibilität. Der durchschlagende Erfolg der Online-Befragung wurde in der wissenschaftlichen Sphäre von einer intensiven Qualitätsdiskussion begleitet, in deren Mittelpunkt vor allem die offensichtlichen Schwächen dieses Befragungsmodus standen

Relationship Between High-Sensitivity Cardiac Troponin I and Blood Pressure Among Young and Healthy Adults

BACKGROUND The aim of this study was to evaluate the relationship of cardiac troponin (cTn) levels with conventional and ambulatory blood pressure (BP) in young and healthy adults. METHODS We performed a population based cross-sectional analysis among 2,072 young and healthy adults aged 25-41 years free of cardiovascular disease and diabetes mellitus. cTnI was measured using a highly sensitive (hs) assay. The relationships of high sensitivity cardiac tropononin I (hs-cTnI) with office and 24-hour BP were assessed using multivariable regression analyses. RESULTS Median age was 37 years and 975 (47%) participants were male. hs-cTnI levels were detectable in 2,061 (99.5%) individuals. Median (interquartile range) hs-cTnI levels were 0.98 (0.71; 1.64) ng/L among men and 0.48 (0.33; 0.71) ng/L among women. Systolic BP, but not diastolic BP, gradually increased across hs-cTnI quartiles (118, 120, 121, and 122 mm Hg for conventional BP; P = 0.0002; 122, 123, 124, and 124 mm Hg for 24-hour BP, P = 0.0001). In multivariable linear regression analyses, the β estimates for systolic BP per 1-unit increase in log transformed hs-cTnI were 2.52 for conventional BP (P = 0.0001); 2.75 for 24-hour BP (P < 0.0001); 2.71 and 2.41 (P < 0.0001 and P = 0.0002) for day and nighttime BP, respectively. There was a significant relationship between hs-cTnI and the Sokolow-Lyon Index (odds ratio (95% confidence interval): 2.09 (1.37; 3.18), P < 0.001). CONCLUSION Using a hs assay, hs-cTnI was detectable in virtually all participants of a young and healthy population. hs-cTnI was independently associated with systolic BP and left ventricular hypertroph

Subclinical sleep apnoea and plasma levels of endothelin-1 among young and healthy adults.

OBJECTIVE Obstructive sleep apnoea (OSA) is a risk factor for vascular disease and other adverse outcomes. These associations may be at least partly due to early endothelin-1 (ET-1)-mediated endothelial dysfunction (ED). Therefore, we assessed the relationships between subclinical sleep apnoea and plasma levels of ET-1. METHODS We performed a population-based study among 1255 young and healthy adults aged 25-41 years. Cardiovascular disease, diabetes or a body mass index >35 kg/mwere exclusion criteria. Plasma levels of ET-1 were measured using a high-sensitivity, single-molecule counting technology. The relationships between subclinical sleep apnoea (OSA indices: respiratory event index (REI), oxygen desaturation index (ODI), mean night-time blood oxygen saturation (SpO)) and ET-1 levels were assessed by multivariable linear regression analysis. RESULTS Median age of the cohort was 35 years. Median ET-1 levels were 2.9 (IQR 2.4-3.6) and 2.5 pg/mL (IQR 2.1-3.0) among patients with (n=105; 8%) and without subclinical sleep apnoea (REI 5-14), respectively. After multivariable adjustment, subclinical sleep apnoea remained significantly associated with plasma levels of ET-1 (β=0.13 (95% CI 0.06 to 0.20) p=0.0002 for a REI 5-14; β=0.10 (95% CI 0.03 to 0.16) p=0.003 for an ODI≥5). Every 1% decrease in mean night-time SpOincreased ET-1 levels by 0.1 pg/mL, an association that remained significant after multivariable adjustment (β=0.02 (95% CI 0.003 to 0.033) p=0.02). CONCLUSIONS In this study of young and healthy adults, we found that participants with subclinical sleep apnoea had elevated plasma ET-1 levels, an association that was due to night-time hypoxaemia. Our results suggest that ED may already be an important consequence of subclinical sleep apnoea

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

Novel Common Genetic Susceptibility Loci for Colorectal Cancer

BACKGROUND: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. METHODS: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. RESULTS: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. CONCLUSIONS: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screenin