Release of Enzymatically Active Deubiquitinating Enzymes upon Reversible Capture by Disulfide Ubiquitin Reagents

Chemical Immunolog

Immobilisation versus immediate mobilisation after intrauterine insemination: randomised controlled trial

Objective To evaluate the effectiveness of 15 minutes of immobilisation versus immediate mobilisation after intrauterine insemination

Minor surgery in general practice and effects on referrals to hospital care: Observational study

<p>Abstract</p> <p>Background</p> <p>Strengthening primary care is the focus of many countries, as national healthcare systems with a strong primary care sector tend to have lower healthcare costs. However, it is unknown to what extent general practitioners (GPs) that perform more services generate fewer hospital referrals. The objective of this study was to examine the association between the number of surgical interventions and hospital referrals.</p> <p>Methods</p> <p>Data were derived from electronic medical records of 48 practices that participated in the Netherlands Information Network of General Practice (LINH) in 2006-2007. For each care-episode of benign neoplasm skin/nevus, sebaceous cyst or laceration/cut it was determined whether the patient was referred to a medical specialist and/or minor surgery was performed. Multilevel multinomial regression analyses were used to determine the relation between minor surgery and hospital referrals on the level of the GP-practice.</p> <p>Results</p> <p>Referral rates differed between diagnoses, with 1.0% of referrals for a laceration/cut, 8.2% for a sebaceous cyst and 10.2% for benign neoplasm skin/nevus. The GP practices performed minor surgery for a laceration/cut in 8.9% (SD:14.6) of the care-episodes, for a benign neoplasm skin/nevus in 27.4% (SD:14.4) of cases and for a sebaceous cyst in 26.4% (SD:13.8). GP practices that performed more minor surgery interventions had a lower referral rate for patients with a laceration/cut (-0.38; 95%CI:-0.60- -0.11) and those with a sebaceous cyst (-0.42; 95%CI:-0.63- -0.16), but not for people with benign neoplasm skin/nevus (-0.26; 95%CI:-0.51-0.03). However, the absolute difference in referral rate appeared to be relevant only for sebaceous cysts.</p> <p>Conclusions</p> <p>The effects of minor surgery vary between diagnoses. Minor surgery in general practice appears to be a substitute for specialist medical care only in relation to sebaceous cysts. Measures to stimulate minor surgery for sebaceous cysts may induce substitution.</p

Enzymatic Blockade of the Ubiquitin-Proteasome Pathway

Ubiquitin-dependent processes control much of cellular physiology. We show that expression of a highly active, Epstein-Barr virus-derived deubiquitylating enzyme (EBV-DUB) blocks proteasomal degradation of cytosolic and ER-derived proteins by preemptive removal of ubiquitin from proteasome substrates, a treatment less toxic than the use of proteasome inhibitors. Recognition of misfolded proteins in the ER lumen, their dislocation to the cytosol, and degradation are usually tightly coupled but can be uncoupled by the EBV-DUB: a misfolded glycoprotein that originates in the ER accumulates in association with cytosolic chaperones as a deglycosylated intermediate. Our data underscore the necessity of a DUB activity for completion of the dislocation reaction and provide a new means of inhibition of proteasomal proteolysis with reduced cytotoxicity.National Institutes of Health (U.S.)EMBO (long term Fellowship 2008-379)Boehringer Ingelheim Fond

First Dark Matter Search with Nuclear Recoils from the XENONnT Experiment

We report on the first search for nuclear recoils from dark matter in the form of weakly interacting massive particles (WIMPs) with the XENONnT experiment, which is based on a two-phase time projection chamber with a sensitive liquid xenon mass of 5.9 ton. During the (1.09±0.03)  ton yr exposure used for this search, the intrinsic $^{85}$Kr and $^{222}$Rn concentrations in the liquid target are reduced to unprecedentedly low levels, giving an electronic recoil background rate of (15.8±1.3)  events/ton yr keV in the region of interest. A blind analysis of nuclear recoil events with energies between 3.3 and 60.5 keV finds no significant excess. This leads to a minimum upper limit on the spin-independent WIMP-nucleon cross section of 2.58×10$^{47}$  cm$^2$ for a WIMP mass of 28  GeV/c$^2$ at 90% confidence level. Limits for spin-dependent interactions are also provided. Both the limit and the sensitivity for the full range of WIMP masses analyzed here improve on previous results obtained with the XENON1T experiment for the same exposure

Detector signal characterization with a Bayesian network in XENONnT

We developed a detector signal characterization model based on a Bayesian network trained on the waveform attributes generated by a dual-phase xenon time projection chamber. By performing inference on the model, we produced a quantitative metric of signal characterization and demonstrate that this metric can be used to determine whether a detector signal is sourced from a scintillation or an ionization process. We describe the method and its performance on electronic-recoil (ER) data taken during the first science run of the XENONnT dark matter experiment. We demonstrate the first use of a Bayesian network in a waveform-based analysis of detector signals. This method resulted in a 3% increase in ER event-selection efficiency with a simultaneously effective rejection of events outside of the region of interest. The findings of this analysis are consistent with the previous analysis from XENONnT, namely a background-only fit of the ER data

Searching for Heavy Dark Matter near the Planck Mass with XENON1T

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This Letter places strong constraints on spin-independent interactions of dark matter particles with a mass between 1×10$^{12}$ and 2×10$^{17}$  GeV/c$^2$. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross sections for dark matter particles with masses close to the Planck scale

Search for events in XENON1T associated with Gravitational Waves

We perform a blind search for particle signals in the XENON1T dark matter detector that occur close in time to gravitational wave signals in the LIGO and Virgo observatories. No particle signal is observed in the nuclear recoil, electronic recoil, CE$\nu$NS, and S2-only channels within $\pm$ 500 seconds of observations of the gravitational wave signals GW170104, GW170729, GW170817, GW170818, and GW170823. We use this null result to constrain mono-energetic neutrinos and Beyond Standard Model particles emitted in the closest coalescence GW170817, a binary neutron star merger. We set new upper limits on the fluence (time-integrated flux) of coincident neutrinos down to 17 keV at 90% confidence level. Furthermore, we constrain the product of coincident fluence and cross section of Beyond Standard Model particles to be less than $10^{-29}$ cm$^2$/cm$^2$ in the [5.5-210] keV energy range at 90% confidence level

Cosmogenic background simulations for neutrinoless double beta decay with the DARWIN observatory at various underground sites

Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With 40t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay (0 ν β β), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We present here the results of simulations performed to determine the production rate of 137 Xe, the most crucial isotope in the search for 0 ν β β of 136 Xe. Additionally, we explore the contribution that other muon-induced spallation products, such as other unstable xenon isotopes and tritium, may have on the cosmogenic background

Cosmogenic background simulations for the DARWIN observatory at different underground locations

Xenon dual-phase time projections chambers (TPCs) have proven to be a successful technology in studying physical phenomena that require low-background conditions. With 40t of liquid xenon (LXe) in the TPC baseline design, DARWIN will have a high sensitivity for the detection of particle dark matter, neutrinoless double beta decay ($0\nu\beta\beta$), and axion-like particles (ALPs). Although cosmic muons are a source of background that cannot be entirely eliminated, they may be greatly diminished by placing the detector deep underground. In this study, we used Monte Carlo simulations to model the cosmogenic background expected for the DARWIN observatory at four underground laboratories: Laboratori Nazionali del Gran Sasso (LNGS), Sanford Underground Research Facility (SURF), Laboratoire Souterrain de Modane (LSM) and SNOLAB. We determine the production rates of unstable xenon isotopes and tritium due to muon-included neutron fluxes and muon-induced spallation. These are expected to represent the dominant contributions to cosmogenic backgrounds and thus the most relevant for site selection