Numerische Behandlung von Kaskadengleichungen zur schnellen Simulation höchstenergetischer Luftschauer

Von Teilchen der kosmischen Strahlung ausgelöste Luftschauer können mit Kaskadengleichungen beschrieben werden. Dies sind Systeme gekoppelter partieller Differentialgleichungen. In der vorliegenden Arbeit wird ein numerisches Lösungsverfahren für die elektromagnetische Kaskadengleichung entwickelt. Ziel ist die Beschleunigung der Berechnung der elektromagnetischen Schauerkomponente in Hybrid-Luftschauersimulationen. Die Ergebnisse werden mit parallel dazu entwickelten Monte-Carlo-Simulationen und der historischen Approximation A und B verifiziert. Das Monte-Carlo- und das numerische Verfahren werden dann in einem Hybrid-Verfahren miteinander kombiniert. Die numerischen Lösungen werden abschließend mit CORSIKA-Simulationsrechnungen und Auger-Daten verglichen, und es wird eine Rechenzeitanalyse der verschiedenen Methoden durchgeführt

Numerische Behandlung von Kaskadengleichungen zur schnellen Simulation höchstenergetischer Luftschauer

Von Teilchen der kosmischen Strahlung ausgelöste Luftschauer können mit Kaskadengleichungen beschrieben werden. Dies sind Systeme gekoppelter partieller Differentialgleichungen. In der vorliegenden Arbeit wird ein numerisches Lösungsverfahren für die elektromagnetische Kaskadengleichung entwickelt. Ziel ist die Beschleunigung der Berechnung der elektromagnetischen Schauerkomponente in Hybrid-Luftschauersimulationen. Die Ergebnisse werden mit parallel dazu entwickelten Monte-Carlo-Simulationen und der historischen Approximation A und B verifiziert. Das Monte-Carlo- und das numerische Verfahren werden dann in einem Hybrid-Verfahren miteinander kombiniert. Die numerischen Lösungen werden abschließend mit CORSIKA-Simulationsrechnungen und Auger-Daten verglichen, und es wird eine Rechenzeitanalyse der verschiedenen Methoden durchgeführt

A Time-Saving Approach to Parameter Studies in Microwave-Assisted Freeze Drying

Microwave-assisted freeze drying (MFD) is particularly suited for drying heat-sensitive materials. However, optimizing process parameters is time-consuming due to lengthy individual experiments. This study investigates the feasibility of partial MFD for parameter studies, with the process being terminated after removing 20 wt% of the water contained. The proposed approach reduces the time required for parameter evaluation by 92.0% compared to complete MFD. It also enables the evaluation of the samples’ drying homogeneity. A subsequent parameter study based on partial MFD was then conducted to evaluate the effects of chamber pressure, microwave power, and microwave frequencies on the drying kinetics and drying homogeneity. Lowering the average chamber pressure from 0.87 mbar to 0.19 mbar reduced the process duration by 18.8%. An increase in the dissipated specific microwave power from 0.048 W/g to 0.143 W/g reduced the duration by 46.7%. The targeted application of frequencies increased the average energy efficiency to as high as 92.4%, contributing to a shortened process duration of up to 51.2%. Only the application of multiple frequencies caused a notable increase in drying homogeneity. In summary, this study demonstrates the feasibility and time-saving benefits of partial drying for parameter studies in MFD and potentially different types of drying processes

Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field