Detection of Interacting Variables for Generalized Linear Models via Neural Networks

The quality of generalized linear models (GLMs), frequently used by insurance companies, depends on the choice of interacting variables. The search for interactions is time-consuming, especially for data sets with a large number of variables, depends much on expert judgement of actuaries, and often relies on visual performance indicators. Therefore, we present an approach to automating the process of finding interactions that should be added to GLMs to improve their predictive power. Our approach relies on neural networks and a model-specific interaction detection method, which is computationally faster than the traditionally used methods like Friedman H-Statistic or SHAP values. In numerical studies, we provide the results of our approach on different data sets: open-source data, artificial data, and proprietary data.Comment: 35 pages, 10 Figure

Etablierung verschiedener Modelle zur Testung der Wirkung von Zytostatika auf Tumorzellen sowie ihrer Nebenwirkungen auf die humane Plazenta

Die humane Plazenta ist in Hinblick auf toxikologische Fragestellungen ein vielversprechendes Untersuchungsobjekt. Sie enthält eine Vielzahl verschiedener Zelltypen, bspw. Trophoblast-, Immun- und Endothelzellen, und steht nach der Geburt als Gewebe humanen Ursprungs relativ leicht für Forschungszwecke zur Verfügung. Aufgrund ihrer hohen Artspezifität ist im Besonderen auf dem Gebiet der Plazentaforschung die Übertragung Tiermodell-basierter Daten auf den menschlichen Organismus kritisch zu hinterfragen. Häufig konnten klinische Studien über potentielle Wirkstoffe die vermuteten Effekte aus der Grundlagenforschung nicht bestätigen und verliefen z. T. mit katastrophalem Ausmaß (Thalidomid, TGN1412, Sildenafil etc.). In der vorliegenden Arbeit sollte das Potenzial der humanen Plazenta als Forschungsgegenstand für toxikologische Testreihen untersucht werden. Dazu wurden unterschiedliche, auf plazentastämmige Zellen und Gewebe basierte Modellsysteme charakterisiert und methodische Schwachstellen herausgearbeitet. Die beiden immortalisierten Trophoblast-Zelllinien HTR8/SVneo und JEG-3 wurden im Monolayer sowie in Form von Sphäroiden kultiviert, da 3D-Modelle in vivo-Bedingungen meist besser simulieren können. Des Weiteren wurden villöse Plazenta-Explantate aus Terminplazenta unkomplizierter Schwangerschaften in die Untersuchungen eingeschlossen

Adenine Nucleotide Translocase 1 Expression is Coupled to the HSP27-Mediated TLR4 Signaling in Cardiomyocytes

The cardiac-specific overexpression of the adenine nucleotide translocase 1 (ANT1) has cardioprotective effects in various experimental heart disease models. Here, we analyzed the link between ANT1 expression and heat shock protein 27 (HSP27)-mediated toll-like receptor 4 (TLR4) signaling, which represents a novel communication pathway between mitochondria and the extracellular environment. The interaction between ANT1 and HSP27 was identified by co-immunoprecipitation from neonatal rat cardiomyocytes. ANT1 transgenic (ANT1-TG) cardiomyocytes demonstrated elevated HSP27 expression levels. Increased levels of HSP27 were released from the ANT1-TG cardiomyocytes under both normoxic and hypoxic conditions. Extracellular HSP27 stimulated TLR4 signaling via protein kinase B (AKT). The HSP27-mediated activation of the TLR4 pathway was more pronounced in ANT1-TG cardiomyocytes than in wild-type (WT) cardiomyocytes. HSP27-specific antibodies inhibited TLR4 activation and the expression of HSP27. Inhibition of the HSP27-mediated TLR4 signaling pathway with the TLR4 inhibitor oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) reduced the mitochondrial membrane potential (∆ψm) and increased caspase 3/7 activity, which are both markers for cell stress. Conversely, treating cardiomyocytes with recombinant HSP27 protein stimulated TLR4 signaling, induced HSP27 and ANT1 expression, and stabilized the mitochondrial membrane potential. The activation of HSP27 signaling was verified in ischemic ANT1-TG heart tissue, where it correlated with ANT1 expression and the tightness of the inner mitochondrial membrane. Our study shows a new mechanism by which ANT1 is part of the cardioprotective HSP27-mediated TLR4 signaling

The Power of Related Articles – Improving Fake News Detection on Social Media Platforms

Social media is increasingly used as a platform for news consumption, but it has also become a breeding ground for fake news. This serious threat poses significant challenges to social media providers, society, and science. Several studies have investigated automated approaches to fighting fake news, but little has been done to improve fake news detection on the users’ side. A simple but promising approach could be to broaden users\u27 knowledge to improve the perceptual process, which will improve detection behavior. This study evaluates the impact of a digital nudging approach which aims to fight fake news with the help of related articles. 322 participants took part in an online experiment simulating the Facebook Newsfeed. In addition to a control group, three treatment groups were exposed to different combinations of related articles. Results indicate that the presence of controversial related articles has a positive influence on the detection of fake news

Hepatitis B virus core protein phosphorylation: Identification of the SRPK1 target sites and impact of their occupancy on RNA binding and capsid structure

International audienceHepatitis B virus (HBV) replicates its 3 kb DNA genome through capsid-internal reverse transcription, initiated by assembly of 120 core protein (HBc) dimers around a complex of viral pregenomic (pg) RNA and polymerase. Following synthesis of relaxed circular (RC) DNA capsids can be enveloped and secreted as stable virions. Upon infection of a new cell, however, the capsid disintegrates to release the RC-DNA into the nucleus for conversion into covalently closed circular (ccc) DNA. HBc´s interactions with nucleic acids are mediated by an arginine-rich C terminal domain (CTD) with intrinsically strong non-specific RNA binding activity. Adaptation to the changing demands for nucleic acid binding during the viral life cycle is thought to involve dynamic phosphorylation / dephosphorylation events. However, neither the relevant enzymes nor their target sites in HBc are firmly established. Here we developed a bacterial coexpression system enabling access to definably phosphorylated HBc. Combining Phos-tag gel electrophoresis, mass spectrometry and mutagenesis we identified seven of the eight hydroxy amino acids in the CTD as target sites for serine-argi-nine rich protein kinase 1 (SRPK1); fewer sites were phosphorylated by PKA and PKC. Phosphorylation of all seven sites reduced nonspecific RNA encapsidation as drastically as deletion of the entire CTD and altered CTD surface accessibility, without major structure changes in the capsid shell. The bulk of capsids from human hepatoma cells was similarly highly, yet non-identically, phosphorylated as by SRPK1. While not proving SRPK1 as the infection-relevant HBc kinase the data suggest a mechanism whereby high-level HBc phos-phorylation principally suppresses RNA binding whereas one or few strategic dephosphory-lation events enable selective packaging of the pgRNA/polymerase complex. The tools developed in this study should greatly facilitate the further deciphering of the role of HBc phosphorylation in HBV infection and its evaluation as a potential new therapeutic target. PLOS Pathogens | https://doi.org/10.1371/journal.ppat

Microscale <i>In Vitro</i> Assays for the Investigation of Neutral Red Retention and Ethoxyresorufin-<i>O</i>-Deethylase of Biofuels and Fossil Fuels

<div><p>Only few information on the potential toxic effectiveness of biofuels are available. Due to increasing worldwide demand for energy and fuels during the past decades, biofuels are considered as a promising alternative for fossil fuels in the transport sector. Hence, more information on their hazard potentials are required to understand the toxicological impact of biofuels on the environment. In the German Cluster of Excellence “Tailor-made Fuels from Biomass” design processes for economical, sustainable and environmentally friendly biofuels are investigated. In an unique and interdisciplinary approach, ecotoxicological methods are applied to gain information on potential adverse environmental effects of biofuels at an early phase of their development. In the present study, three potential biofuels, ethyl levulinate, 2-methyltetrahydrofuran and 2-methylfuran were tested. Furthermore, we investigated a fossil gasoline fuel, a fossil diesel fuel and an established biodiesel. Two <i>in vitro</i> bioassays, one for assessing cytotoxicity and one for aryl hydrocarbon receptor agonism, so called dioxin-like activity, as measured by Ethoxyresorufin-<i>O</i>-Deethylase, were applied using the permanent fish liver cell line RTL-W1 (<i>Oncorhynchus mykiss</i>). The special properties of these fuel samples required modifications of the test design. Points that had to be addressed were high substance volatility, material compatibility and low solubility. For testing of gasoline, diesel and biodiesel, water accommodated fractions and a passive dosing approach were tested to address the high hydrophobicity and low solubility of these complex mixtures. Further work has to focus on an improvement of the chemical analyses of the fuel samples to allow a better comparison of any effects of fossil fuels and biofuels.</p></div

The genome of Romanomermis culicivorax:revealing fundamental changes in the core developmental genetic toolkit in Nematoda

Background: The genetics of development in the nematode Caenorhabditis elegans has been described in exquisite detail. The phylum Nematoda has two classes: Chromadorea (which includes C. elegans) and the Enoplea. While the development of many chromadorean species resembles closely that of C. elegans, enoplean nematodes show markedly different patterns of early cell division and cell fate assignment. Embryogenesis of the enoplean Romanomermis culicivorax has been studied in detail, but the genetic circuitry underpinning development in this species has not been explored. Results: We generated a draft genome for R. culicivorax and compared its gene content with that of C. elegans, a second enoplean, the vertebrate parasite Trichinella spiralis, and a representative arthropod, Tribolium castaneum. This comparison revealed that R. culicivorax has retained components of the conserved ecdysozoan developmental gene toolkit lost in C. elegans. T. spiralis has independently lost even more of this toolkit than has C. elegans. However, the C. elegans toolkit is not simply depauperate, as many novel genes essential for embryogenesis in C. elegans are not found in, or have only extremely divergent homologues in R. culicivorax and T. spiralis. Our data imply fundamental differences in the genetic programmes not only for early cell specification but also others such as vulva formation and sex determination. Conclusions: Despite the apparent morphological conservatism, major differences in the molecular logic of development have evolved within the phylum Nematoda. R. culicivorax serves as a tractable system to contrast C. elegans and understand how divergent genomic and thus regulatory backgrounds nevertheless generate a conserved phenotype. The R. culicivorax draft genome will promote use of this species as a research model

Further Results from the Galactic O-Star Spectroscopic Survey: Rapidly Rotating Late ON Giants

With new data from the Galactic O-Star Spectroscopic Survey, we confirm and expand the ONn category of late-O, nitrogen-enriched (N), rapidly rotating (n) giants. In particular, we have discovered two "clones" (HD 102415 and HD 117490) of one of the most rapidly rotating O stars previously known (HD 191423, "Howarth's Star"). We compare the locations of these objects in the theoretical HR Diagram to those of slowly rotating ON dwarfs and supergiants. All ON giants known to date are rapid rotators, whereas no ON dwarf or supergiant is; but all ON stars are small fractions of their respective spectral-type/luminosity-class/rotational subcategories. The ONn giants, displaying both substantial processed material and high rotation at an intermediate evolutionary stage, may provide significant information about the development of those properties. They may have preserved high initial rotational velocities or been spun up by TAMS core contraction; but alternatively and perhaps more likely, they may be products of binary mass transfer. At least some of them are also runaway stars.Comment: 18 pages, 2 figures, 2 tables; accepted for publication in the November 2011 issue of The Astronomical Journa

The genome of a songbird

The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chickenthe only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat- based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour. © 2010 Macmillan Publishers Limited. All rights reserved