Constraints on elastic neutrino nucleus scattering in the fully coherent regime from the CONUS experiment

We report the best limit on coherent elastic scattering of electron antineutrinos emitted from a nuclear reactor off germanium nuclei. The measurement was performed with the CONUS detectors positioned at 17.1m from the 3.9GWth reactor core of the nuclear power plant in Brokdorf, Germany. The antineutrino energies of less than 10 MeV assure interactions in the fully coherent regime. The analyzed dataset includes 248.7 kgd with the reactor turned on and background data of 58.8 kgd with the reactor off. With a quenching parameter of k = 0.18 for germanium, we determined an upper limit on the number of neutrino events of 85 in the region of interest at 90% confidence level. This new CONUS dataset disfavors quenching parameters above k = 0.27, under the assumption of standard-model-like coherent scattering of the reactor antineutrinos

Direct measurement of the ionization quenching factor of nuclear recoils in germanium in the keV energy range

This article reports the measurement of the ionization quenching factor in germanium for nuclear recoil energies between 0.4 and 6.3 keV$_{nr}$. Precise knowledge of this factor in this energy range is relevant for coherent elastic neutrino-nucleus scattering and low mass dark matter searches with germanium-based detectors. Nuclear recoils were produced in a thin high-purity germanium target with a very low energy threshold via irradiation with monoenergetic neutron beams. The energy dependence of the ionization quenching factor was directly measured via kinematically constrained coincidences with surrounding liquid scintillator based neutron detectors. The systematic uncertainties of the measurements are discussed in detail. With measured quenching factors between 0.16 and 0.23 in the [0.4, 6.3] keV$_{nr}$ energy range, the data are compatible with the Lindhard theory with a parameter $k$ of 0.162 $\pm$ 0.004 (stat+sys)

Full background decomposition of the CONUS experiment

The CONUS experiment is searching for coherent elastic neutrino nucleus scattering of reactor anti-neutrinos with four low energy threshold point-contact high-purity germanium spectrometers. An excellent background suppression within the region of interest below 1keV (ionization energy) is absolutely necessary to enable a signal detection. The collected data also make it possible to set limits on various models regarding beyond the standard model physics. These analyses benefit as well from the low background level of ~10d$^{-1}$kg$^{-1}$below 1keV and at higher energies. The low background level is achieved by employing a compact shell-like shield, that was adapted to the most relevant background sources at the shallow depth location of the experiment: environmental gamma-radiation and muon-induced secondaries. Overall, the compact CONUS shield including the active anti-coincidence muon-veto reduces the background by more than four orders of magnitude. The remaining background is described with validated Monte Carlo simulations which include the detector response. It is the first time that a full background decomposition in germanium operated at reactor-site has been achieved. Next to remaining muon-induced background, $^{210}$Pb within the shield and cryostat end caps, cosmogenic activation and air-borne radon are the most relevant background sources. The reactor-correlated background is negligible within the shield. The validated background model together with the parameterization of the noise are used as input to the likelihood analyses of the various physics cases

First upper limits on neutrino electromagnetic properties from the CONUS experiment

We report first constraints on neutrino electromagnetic properties from neutrino-electron scattering using data obtained from the CONUS germanium detectors, i.e. an upper limit on the effective neutrino magnetic moment and an upper limit on the effective neutrino millicharge. The electron antineutrinos are emitted from the 3.9 GW$_\mathrm{th}$ reactor core of the Brokdorf nuclear power plant in Germany. The CONUS low background detectors are positioned at 17.1 m distance from the reactor core center. The analyzed data set includes 689.1 kg$\cdot$d collected during reactor ON periods and 131.0 kg$\cdot$d collected during reactor OFF periods in the energy range of 2 to 8 keV. With the current statistics, we are able to determine an upper limit on the effective neutrino magnetic moment $\mu_\nu < 7.5\cdot10^{-11}\,\mu_B$ at 90% confidence level. From this first magnetic moment limit we can derive an upper bound on the neutrino millicharge of $\vert$q$_{\nu}\vert < 3.3\cdot10^{-12}\,e_0$

Large-size sub-keV sensitive germanium detectors for the CONUS experiment

Intense fluxes of reactor antineutrinos offer a unique possibility to probe the fully coherent character of elastic neutrino scattering off atomic nuclei. In this regard, detectors face the challenge to register tiny recoil energies of a few keV at the maximum. The CONUS experiment was installed in 17.1 m distance from the reactor core of the nuclear power plant in Brokdorf, Germany, and was designed to detect this neutrino interaction channel by using four 1 kg-sized point contact germanium detectors with sub-keV energy thresholds. This report describes the unique specifications addressed to the design, the research and development, and the final production of these detectors. It demonstrates their excellent electronic performance obtained during commissioning under laboratory conditions as well as during the first two years of operation at the reactor site which started on April 1, 2018. It highlights the long-term stability of different detector parameters and the achieved background levels of the germanium detectors inside the CONUS shield setup.Comment: (18 pages, 12 figures

Pneumococcal polysaccharide vaccination in adults undergoing immunosuppressive treatment for inflammatory diseases - a longitudinal study.

INTRODUCTION: Patients undergoing immunosuppressive therapy are at increased risk of infection. Community-acquired pneumonia and invasive pneumococcal disease account for substantial morbidity and mortality in this population and may be prevented by vaccination. Ideally, immunization to pneumococcal antigens should take place before the start of immunosuppressive treatment. Often, however, the treatment cannot be delayed. Little is known about the efficacy of pneumococcal vaccines during immunosuppressive treatment. The objectives of this study were to determine the percentage of vaccine-naïve, immunosuppressed adults with inflammatory diseases seroprotected against Streptococcus pneumoniae and to assess factors associated with the immunogenicity, clinical impact and safety of 23-valent pneumococcal polysaccharide vaccine (PPV) in seronegative subjects. METHODS: This observational study included patients 18 years of age and older who were receiving prednisone ≥20 mg/day or other immunosuppressive drugs. Exclusion criteria were PPV administration in the previous 5 years, intravenous immunoglobulins and pregnancy. Serum immunoglobulin G (IgG) antibody levels against six pneumococcal serotypes were measured. Seropositivity was defined as IgG of 0.5 μg/ml or greater for at least four of six serotypes. Seronegative patients received PPV, and seropositive patients were included as a comparison group. Vaccine response and tolerance were assessed after 4-8 weeks. Disease activity was evaluated on the basis of the Physician Global Assessment scores. Serology was repeated after 1 year, and information on any kind of infection needing medical attention was collected. Outcomes were the proportion of seropositivity and infections between vaccinated and unvaccinated patients. RESULTS: Of 201 included patients, 35 received high-dose corticosteroids and 181 were given immunosuppressive drugs. Baseline seronegativity in 60 (30 %) patients was associated with corticotherapy and lower total IgG. After PPV, disease activity remained unchanged or decreased in 81 % of patients, and 87 % became seropositive. After 1 year, 67 % of vaccinated compared with 90 % of observed patients were seropositive (p &lt; 0.001), whereas the rate of infections did not differ between groups. Those still taking prednisone ≥10 mg/day tended to have poorer serological responses and had significantly more infections. CONCLUSIONS: PPV was safe and moderately effective based on serological response. Seropositivity to pneumococcal antigens significantly reduced the risk of infections. Sustained high-dose corticosteroids were associated with poor vaccine response and more infections

A Meta-Analysis of the Existing Knowledge of Immunoreactivity against Hepatitis C Virus (HCV)

Approximately 3% of the world population is infected by HCV, which represents a major global health challenge. Almost 400 different scientific reports present immunological data related to T cell and antibody epitopes derived from HCV literature. Analysis of all HCV-related epitope hosted in the Immune Epitope Database (IEDB), a repository of freely accessible immune epitope data, revealed more than 1500 and 1900 distinct T cell and antibody epitopes, respectively. The inventory of all data revealed specific trends in terms of the host and the HCV genotypes from which sequences were derived. Upon further analysis we found that this large number of epitopes reflects overlapping structures, and homologous sequences derived from different HCV isolates. To access and visualize this information we developed a novel strategy that assembles large sets of epitope data, maps them onto reference genomes and displays the frequency of positive responses. Compilation of the HCV immune reactivity from hundreds of different studies, revealed a complex and thorough picture of HCV immune epitope data to date. The results pinpoint areas of more intense reactivity or research activities at the level of antibody, CD4 and CD8 responses for each of the individual HCV proteins. In general, the areas targeted by the different effector immune functions were distinct and antibody reactivity was positively correlated with hydrophilicity, while T cell reactivity correlated with hydrophobicity. At the sequence level, epitopes frequently recognized by both T cell and B cell correlated with low variability, and our analysis thus highlighted areas of potential interest for practical applications. The human reactivity was further analyzed to pinpoint differential patterns of reactivity associated with acute versus chronic infection, to reveal the apparent impact of glycosylation on T cell, but not antibody responses, and to highlight a paucity of studies involved antibody epitopes associated with virus neutralization

Interactions Between Laminin Receptor and the Cytoskeleton During Translation and Cell Motility

Human laminin receptor acts as both a component of the 40S ribosomal subunit to mediate cellular translation and as a cell surface receptor that interacts with components of the extracellular matrix. Due to its role as the cell surface receptor for several viruses and its overexpression in several types of cancer, laminin receptor is a pathologically significant protein. Previous studies have determined that ribosomes are associated with components of the cytoskeleton, however the specific ribosomal component(s) responsible has not been determined. Our studies show that laminin receptor binds directly to tubulin. Through the use of siRNA and cytoskeletal inhibitors we demonstrate that laminin receptor acts as a tethering protein, holding the ribosome to tubulin, which is integral to cellular translation. Our studies also show that laminin receptor is capable of binding directly to actin. Through the use of siRNA and cytoskeletal inhibitors we have shown that this laminin receptor-actin interaction is critical for cell migration. These data indicate that interactions between laminin receptor and the cytoskeleton are vital in mediating two processes that are intimately linked to cancer, cellular translation and migration

Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future

There are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes, while inappropriate antibiotic therapy increases antibiotic resistance. A growing body of evidence supports the use of procalcitonin (PCT) to improve diagnosis of bacterial infections and to guide antibiotic therapy. For patients with upper and lower respiratory tract infection, post-operative infections and for severe sepsis patients in the intensive care unit, randomized-controlled trials have shown a benefit of using PCT algorithms to guide decisions about initiation and/or discontinuation of antibiotic therapy. For some other types of infections, observational studies have shown promising first results, but further intervention studies are needed before use of PCT in clinical routine can be recommended. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and discuss the reliability of this marker when used with validated diagnostic algorithms