Commissioning of the vacuum system of the KATRIN Main Spectrometer

The KATRIN experiment will probe the neutrino mass by measuring the beta-electron energy spectrum near the endpoint of tritium beta-decay. An integral energy analysis will be performed by an electro-static spectrometer (Main Spectrometer), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240 m^3, and a complex inner electrode system with about 120000 individual parts. The strong magnetic field that guides the beta-electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300{\deg}C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10^{-11} mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016.Comment: submitted for publication in JINST, 39 pages, 15 figure

Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease

Activin-A is a pleiotropic cytokine that participates in developmental, inflammatory, and tissue repair processes. Still, its effects on T helper (Th) cell–mediated immunity, critical for allergic and autoimmune diseases, are elusive. We provide evidence that endogenously produced activin-A suppresses antigen-specific Th2 responses and protects against airway hyperresponsiveness and allergic airway disease in mice. Importantly, we reveal that activin-A exerts suppressive function through induction of antigen-specific regulatory T cells that suppress Th2 responses in vitro and upon transfer in vivo. In fact, activin-A also suppresses Th1-driven responses, pointing to a broader immunoregulatory function. Blockade of interleukin 10 and transforming growth factor β1 reverses activin-A–induced suppression. Remarkably, transfer of activin-A–induced antigen-specific regulatory T cells confers protection against allergic airway disease. This beneficial effect is associated with dramatically decreased maturation of draining lymph node dendritic cells. Therapeutic administration of recombinant activin-A during pulmonary allergen challenge suppresses Th2 responses and protects from allergic disease. Finally, we demonstrate that immune cells infiltrating the lungs from individuals with active allergic asthma, and thus nonregulated inflammatory response, exhibit significantly decreased expression of activin-A's responsive elements. Our results uncover activin-A as a novel suppressive factor for Th immunity and a critical controller of allergic airway disease

Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.

This is the author accepted manuscript.OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10-10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSION: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.German Research CouncilAustrian Science FundFaculty of Medicine, Saarland UniversityResearch Council of LithuaniaSwedish Research CouncilMedical Research Counci

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials

Commissioning of the vacuum system of the KATRIN Main Spectrometer

The KATRIN experiment will probe the neutrino mass by measuring the -electron energy spectrum near the endpoint of tritium -decay. An integral energy analysis will be performed by an electro-static spectrometer (“Main Spectrometer”), an ultra-high vacuum vessel with a length of 23.2 m, a volume of 1240m3, and a complex inner electrode system with about 120 000 individual parts. The strong magnetic field that guides the -electrons is provided by super-conducting solenoids at both ends of the spectrometer. Its influence on turbo-molecular pumps and vacuum gauges had to be considered. A system consisting of 6 turbo-molecular pumps and 3 km of non-evaporable getter strips has been deployed and was tested during the commissioning of the spectrometer. In this paper the configuration, the commissioning with bake-out at 300 C, and the performance of this system are presented in detail. The vacuum system has to maintain a pressure in the 10$^{-11}$ mbar range. It is demonstrated that the performance of the system is already close to these stringent functional requirements for the KATRIN experiment, which will start at the end of 2016

The Effect of a Tax Training Program on Tax Compliance and Business Outcomes of Starting Entrepreneurs: Evidence from a Field Experiment

This paper estimates the long-term impact of a short, partly personalized, mandatory tax training program on tax compliance and business outcomes of first-time entrepreneurs. To this end, we combine survey data, audit data and unique register data from the Netherlands' Tax and Customs Administration with a three year long randomized experiment. The results show that the training affects specific domains of tax compliant behavior. Moreover, it has no impact on business survival, but treated entrepreneurs have significantly higher profits compared to the control group due to lower business costs. These outcomes are partially supportive of our hypotheses developed from theories on tax compliance and mental accounting

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