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Background: Patients with acutely decompensated cirrhosis (AD) may or may not develop acute-on-chronic liver failure (ACLF). ACLF is characterized by high-grade systemic inflammation, organ failures (OF) and high short-term mortality. Although patients with AD cirrhosis exhibit distinct clinical phenotypes at baseline, they have low short-term mortality, unless ACLF develops during follow-up. Because little is known about the association of profile of systemic inflammation with clinical phenotypes of patients with AD cirrhosis, we aimed to investigate a battery of markers of systemic inflammation in these patients.
Methods: Upon hospital admission baseline plasma levels of 15 markers (cytokines, chemokines, and oxidized albumin) were measured in 40 healthy controls, 39 compensated cirrhosis, 342 AD cirrhosis, and 161 ACLF. According to EASL-CLIF criteria, AD cirrhosis was divided into three distinct clinical phenotypes (AD-1: Creatinine<1.5, no HE, no OF; AD-2: creatinine 1.5–2, and or HE grade I/II, no OF; AD-3: Creatinine<1.5, no HE, non-renal OF).
Results: Most markers were slightly abnormal in compensated cirrhosis, but markedly increased in AD. Patients with ACLF exhibited the largest number of abnormal markers, indicating “full-blown” systemic inflammation (all markers). AD-patients exhibited distinct systemic inflammation profiles across three different clinical phenotypes. In each phenotype, activation of systemic inflammation was only partial (30% of the markers). Mortality related to each clinical AD-phenotype was significantly lower than mortality associated with ACLF (p < 0.0001 by gray test). Among AD-patients baseline systemic inflammation (especially IL-8, IL-6, IL-1ra, HNA2 independently associated) was more intense in those who had poor 28-day outcomes (ACLF, death) than those who did not experience these outcomes.
Conclusions: Although AD-patients exhibit distinct profiles of systemic inflammation depending on their clinical phenotypes, all these patients have only partial activation of systemic inflammation. However, those with the most extended baseline systemic inflammation had the highest the risk of ACLF development and death.
Adhesion of human pathogenic bacteria to endothelial cells is facilitated by fibronectin interaction
(2023)
Human pathogenic bacteria circulating in the bloodstream need to find a way to interact with endothelial cells (ECs) lining the blood vessels to infect and colonise the host. The extracellular matrix (ECM) of ECs might represent an attractive initial target for bacterial interaction, as many bacterial adhesins have reported affinities to ECM proteins, in particular to fibronectin (Fn). Here, we analysed the general role of EC-expressed Fn for bacterial adhesion. For this, we evaluated the expression levels of ECM coding genes in different ECs, revealing that Fn is the highest expressed gene and thereby, it is highly abundant in the ECM environment of ECs. The role of Fn as a mediator in bacterial cell-host adhesion was evaluated in adhesion assays of Acinetobacter baumannii, Bartonella henselae, Borrelia burgdorferi, and Staphylococcus aureus to ECs. The assays demonstrated that bacteria colocalised with Fn fibres, as observed by confocal laser scanning microscopy. Fn removal from the ECM environment (FN1 knockout ECs) diminished bacterial adherence to ECs in both static and dynamic adhesion assays to varying extents, as evaluated via absolute quantification using qPCR. Interactions between adhesins and Fn might represent the crucial step for the adhesion of human-pathogenic Gram-negative and Gram-positive bacteria targeting the ECs as a niche of infection.
Accurate measurement of the standard 235U(n,f) cross section from thermal to 170 keV neutron energy
(2020)
An accurate measurement of the 235U(n,f) cross section from thermal to 170 keV of neutron energy has recently been performed at n_TOF facility at CERN using 6Li(n,t)4He and 10B(n,α)7Li as references. This measurement has been carried out in order to investigate a possible overestimation of the 235U fission cross section evaluation provided by most recent libraries between 10 and 30 keV. A custom experimental apparatus based on in-beam silicon detectors has been used, and a Monte Carlo simulation in GEANT4 has been employed to characterize the setup and calculate detectors efficiency. The results evidenced the presence of an overestimation in the interval between 9 and 18 keV and the new data may be used to decrease the uncertainty of 235U(n,f) cross section in the keV region.
233U is the fissile nuclei in the Th-U fuel cycle with a particularily small neutron capture cross setion which is on average about one order of magnitude lower than its fission cross section. Hence, the measurement of the 233U(n, γ) cross section relies on a method to accurately distinguish between capture and fission γ-rays. A measurement of the 233U α-ratio has been performed at the n_TOF facility at CERN using a so-called fission tagging setup, coupling n_TOF 's Total Absorption Calorimeter with a novel fission chamber to tag the fission γ-rays. The experimental setup is described and essential parts of the analysis are discussed. Finally, a preliminary 233U α-ratio is presented.
233U is of key importance among the fissile nuclei in the Th-U fuel cycle. A particularity of 233U is its small neutron capture cross-section, which is on average about one order of magnitude lower than the fission cross-section. The accuracy in the measurement of the 233U capture cross-section depends crucially on an efficient capture-fission discrimination, thus a combined set-up of fission and γ-detectors is needed. A measurement of the 233U capture cross-section and capture-to-fission ratio was performed at the CERN n_TOF facility. The Total Absorption Calorimeter (TAC) of n_TOF was employed as γ-detector coupled with a novel compact ionization chamber as fission detector. A brief description of the experimental set-up will be given, and essential parts of the analysis procedure as well as the preliminary response of the set-up to capture are presented and discussed.
Neutron-induced fission cross sections of isotopes involved in the nuclear fuel cycle are vital for the design and safe operation of advanced nuclear systems. Such experimental data can also provide additional constraints for the adjustment of nuclear model parameters used in the evaluation process, resulting in the further development of fission models. In the present work, the 237Np(n,f) cross section was studied at the EAR2 vertical beam-line at CERN's n_TOF facility, over a wide range of neutron energies, from meV to MeV, using the time-of-flight technique and a set-up based on Micromegas detectors, in an attempt to provide accurate experimental data. Preliminary results in the 200 keV – 14 MeV neutron energy range as well as the experimental procedure, including a description of the facility and the data handling and analysis, will be presented.
The design and operation of innovative nuclear systems requires a better knowledge of the capture and fission cross sections of the Pu isotopes. For the case of capture on 242Pu, a reduction of the uncertainty in the fast region down to 8-12% is required. Moreover, aiming at improving the evaluation of the fast energy range in terms of average parameters, the OECD NEA High Priority Request List (HPRL) requests high-resolution capture measurements with improved accuracy below 2 keV. The current uncertainties also affect the thermal point, where previous experiments deviate from each other by 20%. A fruitful collaboration betwen JGU Mainz and HZ Dresden-Rossendorf within the EC CHANDA project resulted in a 242Pu sample consisting of a stack of seven fission-like targets making a total of 95(4) mg of 242Pu electrodeposited on thin (11.5 μm) aluminum backings. This contribution presents the results of a set of measurements of the 242Pu(n, γ) cross section from thermal to 500 keV combining different neutron beams and techniques. The thermal point was determined at the Budapest Research Reactor by means of Neutron Activation Analysis and Prompt Gamma Analysis, and the resolved (1 eV - 4 keV) and unresolved (1 - 500 keV) resonance regions were measured using a set of four Total Energy detectors at the CERN n_TOF-EAR1.
The experimental area 2 (EAR-2) at CERNs neutron time-of-flight facility (n_TOF), which is operational since 2014, is designed and built as a short-distance complement to the experimental area 1 (EAR-1). The Parallel Plate Avalanche Counter (PPAC) monitor experiment was performed to characterize the beam pro↓le and the shape of the neutron 'ux at EAR-2. The prompt γ-flash which is used for calibrating the time-of-flight at EAR-1 is not seen by PPAC at EAR-2, shedding light on the physical origin of this γ-flash.
Monte Carlo (MC) simulations are an essential tool to determine fundamental features of a neutron beam, such as the neutron flux or the γ-ray background, that sometimes can not be measured or at least not in every position or energy range. Until recently, the most widely used MC codes in this field had been MCNPX and FLUKA. However, the Geant4 toolkit has also become a competitive code for the transport of neutrons after the development of the native Geant4 format for neutron data libraries, G4NDL. In this context, we present the Geant4 simulations of the neutron spallation target of the n_TOF facility at CERN, done with version 10.1.1 of the toolkit. The first goal was the validation of the intra-nuclear cascade models implemented in the code using, as benchmark, the characteristics of the neutron beam measured at the first experimental area (EAR1), especially the neutron flux and energy distribution, and the time distribution of neutrons of equal kinetic energy, the so-called Resolution Function. The second goal was the development of a Monte Carlo tool aimed to provide useful calculations for both the analysis and planning of the upcoming measurements at the new experimental area (EAR2) of the facility.
An important experimental program on Nuclear Astrophysics is being carried out at the n_TOF since several years, in order to address the still open issues in stellar and primordial nucleosynthesis. Several neutron capture reactions relevant to s-process nucleosynthesis have been measured so far, some of which on important branching point radioisotopes. Furthermore, the construction of a second experimental area has recently opened the way to challenging measurements of (n, charged particle) reactions on isotopes of short half-life. The Nuclear Astrophysics program of the n_TOF Collaboration is here described, with emphasis on recent results relevant for stellar nucleosynthesis, stellar neutron sources and primordial nucleosynthesis.
he study of the resonant structures in neutron-nucleus cross-sections, and therefore of the compound-nucleus reaction mechanism, requires spectroscopic measurements to determine with high accuracy the energy of the neutron interacting with the material under study.
To this purpose, the neutron time-of-flight facility n_TOF has been operating since 2001 at CERN. Its characteristics, such as the high intensity instantaneous neutron flux, the wide energy range from thermal to few GeV, and the very good energy resolution, are perfectly suited to perform high-quality measurements of neutron-induced reaction cross sections. The precise and accurate knowledge of these cross sections plays a fundamental role in nuclear technologies, nuclear astrophysics and nuclear physics.
Two different measuring stations are available at the n_TOF facility, called EAR1 and EAR2, with different characteristics of intensity of the neutron flux and energy resolution. These experimental areas, combined with advanced detection systems lead to a great flexibility in performing challenging measurement of high precision and accuracy, and allow the investigation isotopes with very low cross sections, or available only in small quantities, or with very high specific activity.
The characteristics and performances of the two experimental areas of the n_TOF facility will be presented, together with the most important measurements performed to date and their physics case. In addition, the significant upcoming measurements will be introduced.
The change in allele frequencies within a population over time represents a fundamental process of evolution. By monitoring allele frequencies, we can analyze the effects of natural selection and genetic drift on populations. To efficiently track time-resolved genetic change, large experimental or wild populations can be sequenced as pools of individuals sampled over time using high-throughput genome sequencing (called the Evolve & Resequence approach, E&R). Here, we present a set of experiments using hundreds of natural genotypes of the model plant Arabidopsis thaliana to showcase the power of this approach to study rapid evolution at large scale. First, we validate that sequencing DNA directly extracted from pools of flowers from multiple plants -- organs that are relatively consistent in size and easy to sample -- produces comparable results to other, more expensive state-of-the-art approaches such as sampling and sequencing of individual leaves. Sequencing pools of flowers from 25-50 individuals at ∼40X coverage recovers genome-wide frequencies in diverse populations with accuracy r > 0.95. Secondly, to enable analyses of evolutionary adaptation using E&R approaches of plants in highly replicated environments, we provide open source tools that streamline sequencing data curation and calculate various population genetic statistics two orders of magnitude faster than current software. To directly demonstrate the usefulness of our method, we conducted a two-year outdoor evolution experiment with A. thaliana to show signals of rapid evolution in multiple genomic regions. We demonstrate how these laboratory and computational Pool-seq-based methods can be scaled to study hundreds of populations across many climates.
The slow neutron capture process (s-process) is responsible for producing about half of the elemental abundances heavier than iron in the universe. Neutron capture cross sections on stable isotopes are a key nuclear physics input for s-process studies. The 72Ge(n, γ) cross section has an important influence on production of isotopes between Ge and Zr during s-process in massive stars and therefore experimental data are urgently required. 72Ge(n, γ) was measured at the neutron time-of-flight facility n_TOF (CERN) for the first time at stellar energies. The measurement was performed using an enriched 72GeO2 sample at a flight path of 185m with a set of liquid scintillation detectors (C6D6). The motivation, experiment and current status of the data analysis are reported.
Teleconnections of the Quasi-Biennial Oscillation in a multi-model ensemble of QBO-resolving models
(2021)
The Quasi-biennial Oscillation (QBO) dominates the interannual variability of the tropical stratosphere and influences other regions of the atmosphere. The high predictability of the QBO implies that its teleconnections could lead to increased skill of seasonal and decadal forecasts provided the relevant mechanisms are accurately represented in models. Here modelling and sampling uncertainties of QBO teleconnections are examined using a multi-model ensemble of QBO-resolving atmospheric general circulation models that have carried out a set of coordinated experiments as part of the Stratosphere-troposphere Processes And their Role in Climate (SPARC) QBO initiative (QBOi). During Northern Hemisphere winter, the stratospheric polar vortex in most of these models strengthens when the QBO near 50 hPa is westerly and weakens when it is easterly, consistent with, but weaker than, the observed response. These weak responses are likely due to model errors, such as systematically weak QBO amplitudes near 50 hPa, affecting the teleconnection. The teleconnection to the North Atlantic Oscillation is less well captured overall, but of similar strength to the observed signal in the few models that do show it. The models do not show clear evidence of a QBO teleconnection to the Northern Hemisphere Pacific-sector subtropical jet.
Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R3B/LAND setup with incident beam energies in the range of 300–450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type AO(p,2p)A−1N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.