Elite Influence? Religion, Economics, and the Rise of the Nazis

Adolf Hitler's seizure of power was one of the most consequential events of the twentieth century. Yet, our understanding of which factors fueled the astonishing rise of the Nazis remains highly incomplete. This paper shows that religion played an important role in the Nazi party's electoral success -- dwarfing all available socioeconomic variables. To obtain the first causal estimates we exploit plausibly exogenous variation in the geographic distribution of Catholics and Protestants due to a peace treaty in the sixteenth century. Even after allowing for sizeable violations of the exclusion restriction, the evidence indicates that Catholics were significantly less likely to vote for the Nazi Party than Protestants. Consistent with the historical record, our results are most naturally rationalized by a model in which the Catholic Church leaned on believers to vote for the democratic Zentrum Party, whereas the Protestant Church remained politically neutral

ne–xt facades: Proceedings of the COST Action TU1403 Adaptive Facades Network Mid-term Conference

The ne-xt facades conference is the official International Mid-term Conference of the European COST Action TU1403 ‘Adaptive Facades Network’, an international scientific cooperation with the aim to harmonise, share and disseminate technological knowledge on adaptive facades on the European level. During the mid-term conference first results are presented to stakeholders from industry and design and to the public. The goal is to share knowledge and discuss novel facade concepts, effective evaluation tools and design methods for adaptive facades. Alongside the contributions from members of the COST Action, the conference received many contributions from external researchers and the industry. This added to the interesting debate about adaptive facades we believe it was an excellent stage to test the first results of the COST Action

Podocytes maintain high basal levels of autophagy independent of mTOR signaling

While constant basal levels of macroautophagy/autophagy are a prerequisite to preserve long-lived podocytes at the filtration barrier, MTOR regulates at the same time podocyte size and compensatory hypertrophy. Since MTOR is known to generally suppress autophagy, the apparently independent regulation of these two key pathways of glomerular maintenance remained puzzling. We now report that long-term genetic manipulation of MTOR activity does in fact not influence high basal levels of autophagy in podocytes either in vitro or in vivo. Instead we present data showing that autophagy in podocytes is mainly controlled by AMP-activated protein kinase (AMPK) and ULK1 (unc-51 like kinase 1). Pharmacological inhibition of MTOR further shows that the uncoupling of MTOR activity and autophagy is time dependent. Together, our data reveal a novel and unexpected cell-specific mechanism, which permits concurrent MTOR activity as well as high basal autophagy rates in podocytes. Thus, these data indicate manipulation of the AMPK-ULK1 axis rather than inhibition of MTOR as a promising therapeutic intervention to enhance autophagy and preserve podocyte homeostasis in glomerular diseases

Building an Aerial-Ground Robotics System for Precision Farming: An Adaptable Solution

The application of autonomous robots in agriculture is gaining increasing popularity thanks to the high impact it may have on food security, sustainability, resource use efficiency, reduction of chemical treatments, and the optimization of human effort and yield. With this vision, the Flourish research project aimed to develop an adaptable robotic solution for precision farming that combines the aerial survey capabilities of small autonomous unmanned aerial vehicles (UAVs) with targeted intervention performed by multi-purpose unmanned ground vehicles (UGVs). This paper presents an overview of the scientific and technological advances and outcomes obtained in the project. We introduce multi-spectral perception algorithms and aerial and ground-based systems developed for monitoring crop density, weed pressure, crop nitrogen nutrition status, and to accurately classify and locate weeds. We then introduce the navigation and mapping systems tailored to our robots in the agricultural environment, as well as the modules for collaborative mapping. We finally present the ground intervention hardware, software solutions, and interfaces we implemented and tested in different field conditions and with different crops. We describe a real use case in which a UAV collaborates with a UGV to monitor the field and to perform selective spraying without human intervention.Comment: Published in IEEE Robotics & Automation Magazine, vol. 28, no. 3, pp. 29-49, Sept. 202

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial

Introduction: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. Methods and analysis: This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-angstrom sberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12. Ethics and dissemination: This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut fur Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences

Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life

The human gut microbiome matures towards the adult composition during the first years of life and is implicated in early immune development. Here, we investigate the effects of microbial genomic diversity on gut microbiome development using integrated early childhood data sets collected in the DIABIMMUNE study in Finland, Estonia and Russian Karelia. We show that gut microbial diversity is associated with household location and linear growth of children. Single nucleotide polymorphism- and metagenomic assembly-based strain tracking revealed large and highly dynamic microbial pangenomes, especially in the genus Bacteroides, in which we identified evidence of variability deriving from Bacteroides-targeting bacteriophages. Our analyses revealed functional consequences of strain diversity; only 10% of Finnish infants harboured Bifidobacterium longum subsp. infantis, a subspecies specialized in human milk metabolism, whereas Russian infants commonly maintained a probiotic Bifidobacterium bifidum strain in infancy. Groups of bacteria contributing to diverse, characterized metabolic pathways converged to highly subject-specific configurations over the first two years of life. This longitudinal study extends the current view of early gut microbial community assembly based on strain-level genomic variation.Peer reviewe

AZASPIRACIDS – Toxicological Evaluation, Test Methods and Identifcation of the Source Organisms (ASTOX II)

Since the Irish monitoring program was set up in 2001 azaspiracids (AZAs) have been detected in shellfish above the regulatory limit every year with the exception of 2004. The south west coast of Ireland is especially prone to the onsets of AZA events. Over this period a number of poisoning incidents associated with this toxin group have occurred, all related to Irish shellfish. In 2003 the Marine Institute was awarded funding for a research project named ASTOX. This project was very successful in producing a range of reference materials (RMs, which are essential for accurate detection and monitoring, and which up to this point were unavailable. The project also examined the toxicity of AZAs, primarily using in vitro cell assays but some in vivo studies were also performed. The overall aims of the ASTOX 2 project were to strengthen knowledge on the causative organism and toxicity of AZAs. The project aims were grouped into three areas: ecology, chemical support and toxicology.Marine Institute Marine Research Sub Programme (NDP 2007 - 2013), co financed under the European Regional Development Fund

Common clonal origin of conventional T cells and induced regulatory T cells in breast cancer patients

Regulatory CD4+ T cells (Treg) prevent tumor clearance by conventional T cells (Tconv) comprising a major obstacle of cancer immune-surveillance. Hitherto, the mechanisms of Treg repertoire formation in human cancers remain largely unclear. Here, we analyze Treg clonal origin in breast cancer patients using T-Cell Receptor and single-cell transcriptome sequencing. While Treg in peripheral blood and breast tumors are clonally distinct, Tconv clones, including tumor-antigen reactive effectors (Teff), are detected in both compartments. Tumor-infiltrating CD4+ cells accumulate into distinct transcriptome clusters, including early activated Tconv, uncommitted Teff, Th1 Teff, suppressive Treg and pro-tumorigenic Treg. Trajectory analysis suggests early activated Tconv differentiation either into Th1 Teff or into suppressive and pro-tumorigenic Treg. Importantly, Tconv, activated Tconv and Treg share highly-expanded clones contributing up to 65% of intratumoral Treg. Here we show that Treg in human breast cancer may considerably stem from antigen-experienced Tconv converting into secondary induced Treg through intratumoral activation

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes