Expanding the scope of integral equation-based solvation theory

Implizite Lösungsmittelmodelle werden verwendet, um die Eigenschaften von Lösungen mit realisierbarem Rechenaufwand vorauszusagen und zu verstehen. Viele dieser impliziten Lösungsmittelmodelle ignorieren jedoch die Granularität des Lösungsmittels und scheitern an der Beschreibung wichtiger gerichteter Wechselwirkungen, wie z. B. Wasserstoffbrücken. Einen Weg zur Beschreibung verschiedenster Lösungsmitteleigenschaften, der die Merkmale der Lösungsmittelmoleküle nicht vernachlässigt, ermöglicht das Reference Interaction Site Model (RISM). Hierbei wird das Lösungsmittel über seine Paarverteilungsfunktion charakterisiert. Diese stellt ein Maß für die Nahordnung der Lösungsmittelteilchen dar und ist im Rahmen des RISM-Ansatzes verbunden mit der freien Solvatationsenergie. Eine Kombination des RISM-Modells mit quantenmechanischer Präzision für die gelöste Substanz führt zu dem so genannten Embedded Cluster Reference Interaction Site Model, EC-RISM. Diese Kombination wird durch die Anwendung eines selbstkonsistenten Ansatzes, bei dem die Wechselwirkung zwischen dem Solvens und der gelösten Substanz durch eingebettete Punktladungen beschrieben wird, erreicht. Bisher wurde die EC-RISM-Methodik nur für Studien von freien Energien und verwandten Größen von dipolaren, hauptsächlich wässrigen Lösungen, verwendet. Die Anwendbarkeit von EC-RISM auf andere Eigenschaften von Lösungen sowie für nicht dipolare Lösungsmittel wurde bisher nicht sichergestellt. Daher stehen im Folgenden zwei Aspekte im Fokus der Arbeit. Einerseits werden chemische NMR-Verschiebungen berechnet, mit denen getestet wird, ob der Einfluss des Solvens auf die Wellenfunktion des gelösten Teilchens geeignet beschrieben wird und um die Wellenfunktion selbst zu überprüfen. Andererseits werden Benzol- und Hexafluorbenzolmodelle entwickelt um zu erforschen, ob diese komplexen, aber ähnlichen Lösungsmittel mit Hilfe von Integralgleichungsmethoden wie RISM unterscheidbar sind. Anschließend werden diese Modelle verwendet, um eine chemische Reaktion zu untersuchen, bei der eine Steigerung der Stereoselektivität durch den Einsatz von Hexafluorbenzol im Vergleich mit Benzol ausgelöst wird. Die Ergebnisse der Untersuchungen zeigen, dass die Anwendung von EC-RISM die chemische Verschiebung in wässriger Lösung systematisch verbessert und somit auch eine plausible Wellenfunktion wiedergibt. Weiterhin wird bestätigt, dass sich Lösungen in Benzol und Hexafluorbenzol adäquat beschreiben lassen und sogar Stereoselektivitätsvoraussagen in Übereinstimmung mit Experimenten möglich sind. Hierbei können verschiedenste Lösungsmitteleinflüsse separiert und analysiert sowie betrachtet und diskutiert werden, wobei die Bedeutung sowohl dispersiver als auch multipolarer Wechselwirkungsanteile verdeutlicht wird.Implicit solvation models are used to predict and to understand various properties of solutions within feasible time scales. But common implicit approaches ignore the granularity of the solvent and fail to describe substantial directional interactions like hydrogen bonds. A different way to calculate various properties of solvents without that retains this features is presented in this work, the reference interaction site model (RISM). Thereby the solvent is characterized by its pair distribution function, which is a measure for the near-order of the solvent particles. Furthermore the pair distribution functions are connected within the RISM approach with the free energy of solvation. Combining the RISM approach with quantummechanical precision for the solute leads to the so-called embedded cluster reference interaction site model, EC-RISM. This is achieved by application of a self-consistent approach for both parts that are connected with a cluster of embedded point charges, which describes the solvent-solute interaction. By now the EC-RISM methodology was only applied for studies of free energies and related subjects of dipolar, mostly aqueous solutions. The applicability of EC-RISM for different properties of solutions as well as for nondipolar solvents was so far not ensured in the past. Here, two important aspects are in the focus; on the one hand, NMR chemical shifts are calculated to test whether the EC-RISM approach properly describes the solvent influence on the wave function of the solute and to test the wave function itself. On the other hand benzene and hexafluorobenzene models are developed to research if these complex and very similar solvents are distinguishable with integral equation theories like RISM. Furthermore these models are applied for the investigation of a chemical reaction that shows a stereoselectivity enhancement that is caused by the application of hexafluorobenzene compared to benzene. These investigations show that EC-RISM systematically improves the chemical shifts in aqueous solutions and therefore displays the adequacy of the corresponding wave function. Additionally it is confirmed that benzene and hexafluorobenzene are properly described and that even the stereoselectivity of the previously mentioned chemical reaction is correctly predicted. Thereby the different solvent influences are separated, analyzed, considered and discussed, whereas the relevance of dispersive and multipolar parts is elucidated

Causal inference methods for intergenerational research using observational data

Identifying early causal factors leading to the development of poor mental health and behavioral outcomes is essential to design efficient preventive interventions. The substantial associations observed between parental risk factors (e.g., maternal stress in pregnancy, parental education, parental psychopathology, parent-child relationship) and child outcomes point toward the importance of parents in shaping child outcomes. However, such associations may also reflect confounding, including genetic transmission-that is, the child inherits genetic risk common to the parental risk factor and the child outcome. This can generate associations in the absence of a causal effect. As randomized trials and experiments are often not feasible or ethical, observational studies can help to infer causality under specific assumptions. This review aims to provide a comprehensive summary of current causal inference methods using observational data in intergenerational settings. We present the rich causal inference toolbox currently available to researchers, including genetically informed and analytical methods, and discuss their application to child mental health and related outcomes. We outline promising research areas and discuss how existing approaches can be combined or extended to probe the causal nature of intergenerational effects. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Validation of a German Version of the Stress Overload Scale and Comparison of Different Time Frames in the Instructions

Abstract: Introduction: The Stress Overload Scale (SOS; Amirkhan, 2012 , 2018 ) was introduced as a two-factorial self-report measure of stress to overcome limitations of other scales. Methods: We developed a German translation of the SOS and validated it in addition to a short version and an extra-short version. Furthermore, we tested whether manipulating the time frame introduced as retention interval in the instructions affected its psychometric properties. Results: Using two independent age-heterogeneous convenience samples ( Ntotal = 1,239), we found good psychometric properties for a modified German short version of the SOS-S (SOS-S-G) and a new extra-short version (SOS-XS-G), but not for the German long version of the SOS. Moreover, manipulating the time frame of the SOS did not affect its psychometric quality. Discussion The SOS enriches the repertoire of self-report measures of stress as it captures the nonpathological core facets of stress in line with theoretical stress conceptualizations

Das ILZNAWI-Modell: Inklusive Lernzugänge im naturwissenschaftlichen Unterricht. Zur Planbarkeit von Individualisierung und Kooperation am Gemeinsamen Gegenstand

Der Beitrag stellt das im Rahmen des Projekts „Reckahner Modelle zur inklusiven Unterrichtsplanung“ (REMI) entwickelte ILZNAWI-Modell („Inklusive Lernzugänge im naturwissenschaftlichen Unterricht“) vor. Es dient dazu, den Gemeinsamen Gegenstand im naturwissenschaftlichen Unterricht inklusionsförderlich und heterogenitätssensibel auszudifferenzieren und bildet auf Grundlage eines weiten Inklusionsverständnisses gestufte Lernzugänge und Abstraktionsgrade ab. Der Artikel gibt einen Überblick über diesbezüglich bestehende Forschungsprojekte und Unterrichtskonzepte, leitet hieraus die Notwendigkeit für das Modell ab und anschließend dessen Entwicklung theoretisch her. Anhand ausgewählter Stufenmodelle für die Fächer Biologie, Physik und Chemie wird die Planungsanwendung konkretisiert. In einer Unterrichtssequenz zur Evolution des Menschen werden Möglichkeiten zur Verbindung von Individualisierung und Kooperation aufgezeigt. Weitere Umsetzungsideen der Fächer Chemie und Physik verdeutlichen die Bandbreite an Nutzungsmöglichkeiten des Modells. (DIPF/Orig.

No long-term effects of antenatal synthetic glucocorticoid exposure on epigenetic regulation of stress-related genes

Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis “functioning”. The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning

Resting heart rate and antisocial behaviour: a Mendelian randomisation study

Observational studies frequently report phenotypic associations between low resting heart rate (RHR) and higher levels of antisocial behaviour (ASB), although it remains unclear whether this relationship reflects causality. To triangulate evidence, we conducted two-sample univariable Mendelian randomisation (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses. Genetic data were accessed from published genome-wide association studies (GWAS) for RHR (n = 458,835) and ASB (n = 85,359) for the univariable analyses, along with a third GWAS for heart rate variability (HRV; n = 53,174) for all other analyses. Genome-wide significant (p < 5 × 10-8) single-nucleotide polymorphisms associated with RHR (n = 278) were selected as instrumental variables and the outcome was a composite measure of ASB. No causal association was observed between RHR and ASB (BIVW =  - 0.0004, p = 0.841). The multivariable MR analyses including RHR and HRV also suggested no causal associations (BIVW = 0.016, p = 0.914) and no genetic correlations between the heart rate measures and ASB were observed using LDSC (rg = 0.057, p = 0.169). Sensitivity analyses suggested that our results are not likely to be affected by heterogeneity, pleiotropic effects, or reverse causation. These findings suggest that individual differences in autonomic nervous system functioning indexed by RHR are not likely to directly contribute to the development of ASB. Therefore, previously observed associations between RHR and ASB may arise from confounding, reverse causation, and/or additional study characteristics. Further causally informative longitudinal research is required to confirm our findings, and caution should be applied when using measures of RHR in interventions targeting ASB

High-rate low-temperature dc pulsed magnetron sputtering of photocatalytic TiO2films: the effect of repetition frequency

The article reports on low-temperature high-rate sputtering of hydrophilic transparent TiO2thin films using dc dual magnetron (DM) sputtering in Ar + O2mixture on unheated glass substrates. The DM was operated in a bipolar asymmetric mode and was equipped with Ti(99.5) targets of 50 mm in diameter. The substrate surface temperature Tsurfmeasured by a thermostrip was less than 180 °C for all experiments. The effect of the repetition frequency frwas investigated in detail. It was found that the increase of frfrom 100 to 350 kHz leads to (a) an improvement of the efficiency of the deposition process that results in a significant increase of the deposition rate aDof sputtered TiO2films and (b) a decrease of peak pulse voltage and sustaining of the magnetron discharge at higher target power densities. It was demonstrated that several hundreds nm thick hydrophilic TiO2films can be sputtered on unheated glass substrates at aD = 80 nm/min, Tsurf < 180 °C when high value of fr = 350 kHz was used. Properties of a thin hydrophilic TiO2film deposited on a polycarbonate substrate are given

The DNA methylation landscape of the human oxytocin receptor gene (OXTR): data-driven clusters and their relation to gene expression and childhood adversity

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers reporting childhood maltreatment (CM). OXTR DNA methylation was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated in mothers. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, substantial mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study makes an important contribution to the mapping of the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to facilitate the choice of CpG sites