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Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene-sequence-similarity-based bioinformatics strategies, the actual access to these NPs for structure elucidation and bioactivity testing remains difficult. Deletion of the gene encoding the RNA chaperone, Hfq, results in strains losing the production of most NPs. By exchanging the native promoter of a desired BGC against an inducible promoter in Δhfq mutants, almost exclusive production of the corresponding NP from the targeted BGC in Photorhabdus, Xenorhabdus and Pseudomonas was observed including the production of several new NPs derived from previously uncharacterized non-ribosomal peptide synthetases (NRPS). This easyPACId approach (easy Promoter Activated Compound Identification) facilitates NP identification due to low interference from other NPs. Moreover, it allows direct bioactivity testing of supernatants containing secreted NPs, without laborious purification.
We present three-particle mixed-harmonic correlations 〈cos(mφa + nφb − (m + n)φc )〉 for harmonics m, n = 1 − 3 for charged particles in √sN N = 200 GeV Au+Au collisions at RHIC. These measurements provide information on the three-dimensional structure of the initial collision zone and are important for constraining models of a subsequent low-viscosity quark–gluon plasma expansion phase. We investigate correlations between the first, second and third harmonics predicted as a consequence of fluctuations in the initial state. The dependence of the correlations on the pseudorapidity separation between particles show hints of a breaking of longitudinal invariance. We compare our results to a number of state-of-the art hydrodynamic calculations with different initial states and temperature dependent viscosities. These measurements provide important steps towards constraining the temperature dependent viscosity and longitudinal structure of the initial state at RHIC.
We present the first measurement of the proton–Ω correlation function in heavy-ion collisions for the central (0–40%) and peripheral (40–80%) Au + Au collisions at √sNN = 200 GeV by the STAR experiment at the Relativistic Heavy-Ion Collider (RHIC). Predictions for the ratio of peripheral collisions to central collisions for the proton–Ω correlation function are sensitive to the presence of a nucleon– bound state. These predictions are based on the proton– interaction extracted from (2 + 1)-flavor lattice QCD calculations at the physical point. The measured ratio of the proton–Ω correlation function between the peripheral (small system) and central (large system) collisions is less than unity for relative momentum smaller than 40 MeV/c. Comparison of our measured correlation ratio with theoretical calculation slightly favors a proton– bound system with a binding energy of ∼ 27 MeV.
J/ψ suppression has long been considered a sensitive signature of the formation of the Quark-Gluon Plasma (QGP) in relativistic heavy-ion collisions. In this letter, we present the first measurement of inclusive J/ψ production at mid-rapidity through the dimuon decay channel in Au+Au collisions at √sNN = 200 GeV with the STAR experiment. These measurements became possible after the installation of the Muon Telescope Detector was completed in 2014. The J/ψ yields are measured in a wide transverse momentum (pT) range of 0.15 GeV/c to 12 GeV/c from central to peripheral collisions. They extend the kinematic reach of previous measurements at RHIC with improved precision. In the 0-10% most central collisions, the J/ψ yield is suppressed by a factor of approximately 3 for pT > 5 GeV/c relative to that in p + p collisions scaled by the number of binary nucleon-nucleon collisions. The J/ψ nuclear modification factor displays little dependence on pT in all centrality bins. Model calculations can qualitatively describe the data, providing further evidence for the color-screening effect experienced by J/ψ mesons in the QGP.
Quark interactions with topological gluon configurations can induce chirality imbalance and local parity violation in quantum chromodynamics. This can lead to electric charge separation along the strong magnetic field in relativistic heavy-ion collisions – the chiral magnetic effect (CME). We report measurements by the STAR collaboration of a CME-sensitive observable in p + Au and d + Au collisions at 200 GeV, where the CME is not expected, using charge-dependent pair correlations relative to a third particle. We observe strong charge-dependent correlations similar to those measured in heavy-ion collisions. This bears important implications for the interpretation of the heavy-ion data.
Objective: Biologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long‐term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long‐term safety with regard to AE of special interest (AESI) was compared between different biologics.
Methods: Patients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose.
Results: A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2‐15, and RR 4.7, 95% CI 1.8‐12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation.
Conclusion: Surveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long‐term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.
Study of the photon strength functions and level density in the gamma decay of the n + 234U reaction
(2019)
The accurate calculations of neutron-induced reaction cross sections are relevant for many nuclear applications. The photon strength functions and nuclear level densities are essential inputs for such calculations. These quantities for 235U are studied using the measurement of the gamma de-excitation cascades in radiative capture on 234U with the Total Absorption Calorimeter at n_TOF at CERN. This segmented 4π gamma calorimeter is designed to detect gamma rays emitted from the nucleus with high efficiency. This experiment provides information on gamma multiplicity and gamma spectra that can be compared with numerical simulations. The code DICEBOXC is used to simulate the gamma cascades while GEANT4 is used for the simulation of the interaction of these gammas with the TAC materials. Available models and their parameters are being tested using the present data. Some preliminary results of this ongoing study are presented and discussed.
Introduction: The Retro-IDEAL (ILUVIEN Implant for chronic DiabEtic MAcuLar edema) study is a retrospective study designed to assess real-world outcomes achieved with the ILUVIEN® (0.19 mg fluocinolone acetonide (FAc)) in patients with chronic diabetic macular edema (DME) in clinical practices in Germany.
Methods: This study was conducted across 16 sites in Germany and involved 81 eyes (63 patients) with persistent or recurrent DME and a prior suboptimal response to a first-line intravitreal therapy (primarily anti-VEGF intravitreal therapies).
Results: Patients were followed-up for 30.8 ± 11.3 months (mean ± standard deviation) and had a mean age of 68.0 ± 10.4 years. Best-recorded visual acuity (BRVA) improved by +5.5 letters at month 9 (P ⩽ 0.005, n=56; from a baseline of 49 letters) and this was maintained through to month 30 (P ⩽ 0.05, n = 42). There was a concurrent improvement in central macular thickness with a reduction from 502 µm at baseline to 338 µm at year 1 (P ⩽ 0.0001, n = 43). This effect was sustained to year 3 (i.e. 318 µm; P ⩽ 0.0001, n = 29). Mean intraocular pressure (IOP) remained constant between baseline and year 3 with a peak change of 1.9 mm Hg occurring at year 1. Elevated IOP was observed in a similar percentage of patients prior to (22.2% of cases) and following (27.2%) treatment with the FAc implant. In the majority of cases, these elevations were managed effectively with IOP medications.
Conclusions: Despite substantial amounts of prior intravitreal treatments – primarily with anti–vascular endothelial growth factor (VEGF) drugs – this real-world study showed that sustained structural and functional improvements can last for up to 3 years with a single FAc implant.
Der UniReport sprach im Institut für Soziologie mit Prof. Thomas Lemke, dem Geschäftsführenden Direktor des Instituts, und den Studierenden Luisa Hecker (Master) und Adam Jendrzejewski (Bachelor) über das Selbstverständnis des Faches, über Studienbedingungen und über die gesellschaftliche Rolle der Soziologie.
Die Studie »Scale-ups in Europe: an untapped potential« ist in Zusammenarbeit der GoetheUniversität mit der Innovationsplattform TechQuartier und der Yi Shi Foundation entstanden. Dr. Thomas Funke, Co-Direktor des TechQuartiers, und Research Manager Dominik Zborek haben die Studie federführend erstellt.