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During a 4-week run in October–November 2006, a pilot experiment was performed at the CERN Proton Synchrotron in preparation for the Cosmics Leaving OUtdoor Droplets (CLOUD) experiment, whose aim is to study the possible influence of cosmic rays on clouds. The purpose of the pilot experiment was firstly to carry out exploratory measurements of the effect of ionising particle radiation on aerosol formation from trace H2SO4 vapour and secondly to provide technical input for the CLOUD design. A total of 44 nucleation bursts were produced and recorded, with formation rates of particles above the 3 nm detection threshold of between 0.1 and 100 cm -3 s -1, and growth rates between 2 and 37 nm h -1. The corresponding H2O concentrations were typically around 106 cm -3 or less. The experimentally-measured formation rates and htwosofour concentrations are comparable to those found in the atmosphere, supporting the idea that sulphuric acid is involved in the nucleation of atmospheric aerosols. However, sulphuric acid alone is not able to explain the observed rapid growth rates, which suggests the presence of additional trace vapours in the aerosol chamber, whose identity is unknown. By analysing the charged fraction, a few of the aerosol bursts appear to have a contribution from ion-induced nucleation and ion-ion recombination to form neutral clusters. Some indications were also found for the accelerator beam timing and intensity to influence the aerosol particle formation rate at the highest experimental SO2 concentrations of 6 ppb, although none was found at lower concentrations. Overall, the exploratory measurements provide suggestive evidence for ion-induced nucleation or ion-ion recombination as sources of aerosol particles. However in order to quantify the conditions under which ion processes become significant, improvements are needed in controlling the experimental variables and in the reproducibility of the experiments. Finally, concerning technical aspects, the most important lessons for the CLOUD design include the stringent requirement of internal cleanliness of the aerosol chamber, as well as maintenance of extremely stable temperatures (variations below 0.1 °C)
Elliptic flow from nuclear collisions is a hadronic observable sensitive to the early stages of system evolution. We report first results on elliptic flow of charged particles at midrapidity in Au+Au collisions at sqrt(s_NN)=130 GeV using the STAR TPC at RHIC. The elliptic flow signal, v_2, averaged over transverse momentum, reaches values of about 6% for relatively peripheral collisions and decreases for the more central collisions. This can be interpreted as the observation of a higher degree of thermalization than at lower collision energies. Pseudorapidity and transverse momentum dependence of elliptic flow are also presented.
Background: Patients with liver cirrhosis have a highly elevated risk of developing bacterial infections that significantly decrease survival rates. One of the most relevant infections is spontaneous bacterial peritonitis (SBP). Recently, NOD2 germline variants were found to be potential predictors of the development of infectious complications and mortality in patients with cirrhosis. The aim of the INCA (Impact of NOD2 genotype-guided antibiotic prevention on survival in patients with liver Cirrhosis and Ascites) trial is to investigate whether survival of this genetically defined high-risk group of patients with cirrhosis defined by the presence of NOD2 variants is improved by primary antibiotic prophylaxis of SBP.
Methods/Design: The INCA trial is a double-blind, placebo-controlled clinical trial with two parallel treatment arms (arm 1: norfloxacin 400 mg once daily; arm 2: placebo once daily; 12-month treatment and observational period). Balanced randomization of 186 eligible patients with stratification for the protein content of the ascites (<15 versus ≥15 g/L) and the study site is planned. In this multicenter national study, patients are recruited in at least 13 centers throughout Germany. The key inclusion criterion is the presence of a NOD2 risk variant in patients with decompensated liver cirrhosis. The most important exclusion criteria are current SBP or previous history of SBP and any long-term antibiotic prophylaxis. The primary endpoint is overall survival after 12 months of treatment. Secondary objectives are to evaluate whether the frequencies of SBP and other clinically relevant infections necessitating antibiotic treatment, as well as the total duration of unplanned hospitalization due to cirrhosis, differ in both study arms. Recruitment started in February 2014.
Discussion: Preventive strategies are required to avoid life-threatening infections in patients with liver cirrhosis, but unselected use of antibiotics can trigger resistant bacteria and worsen outcome. Thus, individualized approaches that direct intervention only to patients with the highest risk are urgently needed. This trial meets this need by suggesting stratified prevention based on genetic risk assessment. To our knowledge, the INCA trial is first in the field of hepatology aimed at rapidly transferring and validating information on individual genetic risk into clinical decision algorithms.
Trial registrations: German Clinical Trials Register DRKS00005616. Registered 22 January 2014. EU Clinical Trials Register EudraCT 2013-001626-26. Registered 26 January 2015.
Overconsumption of carbohydrates and lipids are well known to cause nonalcoholic fatty liver disease (NAFLD), while the role of nutritional protein intake is less clear. In Western diet, meat and other animal products are the main protein source, with varying concentrations of specific amino acids. Whether the amount or composition of protein intake is associated with a higher risk for disease severity has not yet been examined. In this study, we investigated associations of dietary components with histological disease activity by analyzing detailed 14‐day food records in a cohort of 61 patients with biopsy‐proven NAFLD. Furthermore, we used 16S ribosomal RNA gene sequencing to detect associations with different abundances of the gut microbiota with dietary patterns. Patients with definite nonalcoholic steatohepatitis (NAFLD activity score of 5‐8 on liver biopsy) had a significantly higher daily relative intake of protein compared with patients with a NAFLD activity score of 0‐4 (18.0% vs. 15.8% of daily protein‐based calories, P = 0.018). After adjustment for several potentially confounding factors, a higher protein intake (≥17.3% of daily protein‐based calories) remained associated with definite nonalcoholic steatohepatitis, with an odds ratio of 5.09 (95% confidence interval 1.22‐21.25, P = 0.026). This association was driven primarily by serine, glycine, arginine, proline, phenylalanine, and methionine. A higher protein intake correlated with a lower Bacteroides abundance and an altered abundance of several other bacterial taxa. Conclusion: A high protein intake was independently associated with more active and severe histological disease activity in patients with NAFLD. Further studies are needed to investigate the potential harmful role of dietary amino acids on NAFLD, with special attention to meat as their major source.
Latent transforming growth factor beta binding protein 4 (LTBP4) belongs to the fibrillin/LTBP family of proteins and plays an important role as a structural component of extracellular matrix (ECM) and local regulator of TGFβ signaling. We have previously reported that Ltbp4S knock out mice (Ltbp4S −/−) develop centrilobular emphysema reminiscent of late stage COPD, which could be partially rescued by inactivating the antioxidant protein Sestrin 2 (Sesn2). More recent studies showed that Sesn2 knock out mice upregulate Pdgfrβ-controlled alveolar maintenance programs that protect against cigarette smoke induced pulmonary emphysema. Based on this, we hypothesized that the emphysema of Ltbp4S −/− mice is primarily caused by defective Pdgfrβ signaling. Here we show that LTBP4 induces Pdgfrβ signaling by inhibiting the antioxidant Nrf2/Keap1 pathway in a TGFβ-dependent manner. Overall, our data identified Ltbp4 as a major player in lung remodeling and injury repair.
Using e+e− collision data collected with the BESIII detector operating at the BEPCII collider, the Born cross sections of e+e−→Λ+cΛ¯c(2595)−+c.c. and e+e−→Λ+cΛ¯c(2625)−+c.c. are measured for the first time at center-of-mass energies of s√=4918.0 and 4950.9 MeV. Non-zero cross sections are observed very close to the production threshold. The measured Born cross sections of e+e−→Λ+cΛ¯c(2625)−+c.c. are about 2∼3 times greater than those of e+e−→Λ+cΛ¯c(2595)−+c.c., thereby indicating that the exotic structure potentially exists in the excited charmed baryons. The Born cross sections are 15.6±3.1±0.9 pb and 29.4±3.7±2.7 pb for e+e−→Λ+cΛ¯c(2595)−+c.c., and are 43.4±4.0±4.1 pb and 76.8±6.5±4.2 pb for e+e−→Λ+cΛ¯c(2625)−+c.c. at s√=4918.0 and 4950.9 MeV, respectively. Based on the polar angle distributions of the Λ¯c(2625)− and Λc(2625)+, the form-factor ratios |GE|2+3|GM|2−−−−−−−−−−−−√/|GC| are determined for e+e−→Λ+cΛ¯c(2625)−+c.c. for the first time, which are 5.95±4.07±0.15 and 0.94±0.32±0.02 at s√=4918.0 and 4950.9 MeV, respectively. All of these first uncertainties are statistical and second systematic.
Using a sample of (10087±44)×106 J/ψ events, which is about fifty times larger than that was previously analyzed, a further investigation on the J/ψ→γ3(π+π−) decay is performed. A significant distortion at 1.84 GeV/c2 in the line-shape of the 3(π+π−) invariant mass spectrum is observed for the first time, which is analogous to the behavior of X(1835) and could be resolved by two overlapping resonant structures, X(1840) and X(1880). The new state X(1880) is observed with a statistical significance of 14.7σ. The mass and width of X(1880) are determined to be 1882.1±1.7±0.7 MeV/c2 and 30.7±5.5±2.4 MeV, respectively, which indicates the existence of a pp¯ bound state.
Using a sample of (10087±44)×106 J/ψ events, which is about 45 times larger than that was previously analyzed, a further investigation on the J/ψ→γ3(π+π−) decay is performed. A significant distortion at 1.84 GeV/c2 in the line-shape of the 3(π+π−) invariant mass spectrum is observed for the first time, which could be resolved by two overlapping resonant structures, X(1840) and X(1880). The new state X(1880) is observed with a statistical significance larger than 10σ. The mass and width of X(1880) are determined to be 1882.1±1.7±0.7 MeV/c2 and 30.7±5.5±2.4 MeV, respectively, which indicates the existence of a pp¯ bound state.
Using e+e− collision data collected with the BESIII detector operating at the BEPCII collider, the Born cross sections of e+e−→Λ+cΛ¯c(2595)−+c.c. and e+e−→Λ+cΛ¯c(2625)−+c.c. are measured for the first time at center-of-mass energies of s√=4918.0 and 4950.9 MeV. Non-zero cross sections are observed very close to the production threshold. The measured Born cross sections of e+e−→Λ+cΛ¯c(2625)−+c.c. are about 2∼3 times greater than those of e+e−→Λ+cΛ¯c(2595)−+c.c., thereby indicating that the exotic structure potentially exists in the excited charmed baryons. The Born cross sections are 15.6±3.1±0.9 pb and 29.4±3.7±2.7 pb for e+e−→Λ+cΛ¯c(2595)−+c.c., and are 43.4±4.0±4.1 pb and 76.8±6.5±4.2 pb for e+e−→Λ+cΛ¯c(2625)−+c.c. at s√=4918.0 and 4950.9 MeV, respectively. Based on the polar angle distributions of the Λ¯c(2625)− and Λc(2625)+, the form-factor ratios |GE|2+3|GM|2−−−−−−−−−−−−√/|GC| are determined for e+e−→Λ+cΛ¯c(2625)−+c.c. for the first time, which are 5.95±4.07±0.15 and 0.94±0.32±0.02 at s√=4918.0 and 4950.9 MeV, respectively. All of these first uncertainties are statistical and second systematic.
We search for the semi-leptonic decays Λ + c → Λπ+π−e+νe and Λ + c → pK0 Sπ−e+νe in a sample of 4.5 fb−1 of e+e− annihilation data collected in the center-of-mass energy region between 4.600 GeV and 4.699 GeV by the BESIII detector at the BEPCII. No significant signals are observed, and the upper limits on the decay branching fractions are set to be B(Λ+c → Λπ+π−e+νe ) < 3.9 × 10−4 and B(Λ + c → pK0Sπ−e+νe ) < 3.3 × 10−4 at the 90% confidence level, respectively.