Cyclic di-guanosine monophosphate (di-GMP) is a circular RNA dinucleotide that functions as a second messenger in diverse species of bacteria to trigger wide-ranging physiological changes, including ...cell differentiation, conversion between motile and biofilm lifestyles, and virulence gene expression. However, the mechanisms by which cyclic di-GMP regulates gene expression have remained a mystery. We found that cyclic di-GMP in many bacterial species is sensed by a riboswitch class in messenger RNA that controls the expression of genes involved in numerous fundamental cellular processes. A variety of cyclic di-GMP regulons are revealed, including some riboswitches associated with virulence gene expression, pilus formation, and flagellum biosynthesis. In addition, sequences matching the consensus for cyclic di-GMP riboswitches are present in the genome of a bacteriophage.
KASCADE and KASCADE-Grande were multi-detector installations to measure individual air showers of cosmic rays at ultra-high energy. Based on data sets measured by KASCADE and KASCADE-Grande, 90% C.L. ...upper limits to the flux of gamma-rays in the primary cosmic ray flux are determined in an energy range of eV. The analysis is performed by selecting air showers with a low muon content as expected for gamma-ray-induced showers compared to air showers induced by energetic nuclei. The best upper limit of the fraction of gamma-rays to the total cosmic ray flux is obtained at eV with . Translated to an absolute gamma-ray flux this sets constraints on some fundamental astrophysical models, such as the distance of sources for at least one of the IceCube neutrino excess models.
LOPES, the LOFAR prototype station, was an antenna array for cosmic-ray air showers operating from 2003 to 2013 within the KASCADE-Grande experiment. Meanwhile, the analysis is finished and the data ...of air-shower events measured by LOPES are available with open access in the KASCADE Cosmic Ray Data Center (KCDC). This article intends to provide a summary of the achievements, results, and lessons learned from LOPES. By digital, interferometric beamforming the detection of air showers became possible in the radio-loud environment of the Karlsruhe Institute of Technology (KIT). As a prototype experiment, LOPES tested several antenna types, array configurations and calibration techniques, and pioneered analysis methods for the reconstruction of the most important shower parameters, i.e., the arrival direction, the energy, and mass-dependent observables such as the position of the shower maximum. In addition to a review and update of previously published results, we also present new results based on end-to-end simulations including all known instrumental properties. For this, we applied the detector response to radio signals simulated with the CoREAS extension of CORSIKA, and analyzed them in the same way as measured data. Thus, we were able to study the detector performance more accurately than before, including some previously inaccessible features such as the impact of noise on the interferometric cross-correlation beam. These results led to several improvements, which are documented in this paper and can provide useful input for the design of future cosmic-ray experiments based on the digital radio-detection technique.
We present the results of the search for large-scale anisotropies in the arrival directions of cosmic rays performed with the KASCADE-Grande experiment at energies higher than eV. To eliminate ...spurious anisotropies due to atmospheric or instrumental effects we apply the east-west method. We show, using the solar time distribution of the number of counts, that this technique allow us to remove correctly the count variations not associated to real anisotropies. By applying the east-west method we obtain the distribution of number of counts in intervals of 20 minutes of sidereal time. This distribution is then analyzed by searching for a dipole component; the significance of the amplitude of the first harmonic is 3.5 , therefore, we derive its upper limit. The phase of the first harmonic is determined with an error of a few hours and is in agreement with the measurements obtained in the 1014 < E < 2 × 1015 eV energy range by the EAS-TOP, IceCube, and IceTop experiments. This supports the hypothesis of a change of the phase of the first harmonic at energies greater than ∼2 × 1014 eV.
The KASCADE-Grande air shower experiment 1 consists of, among others, a large scintillator array for measurements of charged particles, Nch, and of an array of shielded scintillation counters used ...for muon counting, Nμ. KASCADE-Grande is optimized for cosmic ray measurements in the energy range 10PeV to about 2000PeV, where exploring the composition is of fundamental importance for understanding the transition from galactic to extragalactic origin of cosmic rays. Following earlier studies of the all-particle and the elemental spectra reconstructed in the knee energy range from KASCADE data 2, we have now extended these measurements to beyond 200PeV. By analysing the two-dimensional shower size spectrum Nch vs. Nμ for nearly vertical events, we reconstruct the energy spectra of different mass groups by means of unfolding methods over an energy range where the detector is fully efficient. The procedure and its results, which are derived based on the hadronic interaction model QGSJET-II-02 and which yield a strong indication for a dominance of heavy mass groups in the covered energy range and for a knee-like structure in the iron spectrum at around 80PeV, are presented. This confirms and further refines the results obtained by other analyses of KASCADE-Grande data, which already gave evidence for a knee-like structure in the heavy component of cosmic rays at about 80PeV 3.
Summary
Background
Treatment of chronic hepatitis C genotype 3 (GT3) is more challenging compared with other genotypes. Since 2014, several new treatment regimens have been approved but sometimes ...based on limited data.
Aim
To validate the use, effectiveness and safety of anti‐viral treatment in chronic hepatitis C genotype 3 infection under real‐word conditions.
Methods
The German Hepatitis C‐Registry is a large national non‐interventional real‐world study for patients with chronic hepatitis C. A total of 1322 GT3 patients were enrolled (211 untreated and 1111 treated patients).
Results
Between February 2014 and September 2015, five different treatment strategies have been used (PegIFN+RBV, PegIFN+RBV+SOF, SOF+RBV, DCV+SOF±RBV, LDV/SOF±RBV). Treatment uptake and use of treatment concepts changed markedly and rapidly during the study influenced by new approvals, guideline recommendations, and label updates. PegIFN‐based therapies constantly declined while DCV‐based therapies increased with one interruption after the approval of LDV/SOF, which was frequently used until new guidelines recommended not using this combination for GT3. Per‐protocol SVR ranged from 80.9% in the PegIFN+RBV group to 96.1% in PegIFN+RBV+SOF treated patients. Treatment‐experienced patients with cirrhosis showed a suboptimal SVR of 68% for SOF+RBV but a high SVR of 90–95% for DCV+SOF±RBV. The safety analysis showed more adverse events and a stronger decline of haemoglobin for RBV containing regimens.
Conclusions
Real‐world data can validate the effectiveness and safety for treatment regimens that had previously been approved with limited data, in particular for specific subgroups of patients. The present study demonstrates how rapid new scientific data, new treatment guidelines, new drug approvals and label changes are implemented into routine clinical practice today.
Linked ContentThis article is linked to Bruno et al paper. To view this article visit https://doi.org/10.1111/apt.14042.
•The effective muon attenuation and absorption lengths of air showers are investigated.•Air shower data of the KASCADE-Grande observatory is analyzed.•Predictions of the models SIBYLL 2.1, EPOS-LHC, ...QGSJET-II-02 and -04 are tested.•The studied models fail to describe consistently the attenuation of the muon data.
The evolution of the muon content of very high energy air showers (EAS) in the atmosphere is investigated with data of the KASCADE-Grande observatory. For this purpose, the muon attenuation length in the atmosphere is obtained to Λμ=1256±85−232+229(syst)g/cm2 from the experimental data for shower energies between 1016.3 and 1017.0 eV. Comparison of this quantity with predictions of the high-energy hadronic interaction models QGSJET-II-02, SIBYLL 2.1, QGSJET-II-04 and EPOS-LHC reveals that the attenuation of the muon content of measured EAS in the atmosphere is lower than predicted. Deviations are, however, less significant with the post-LHC models. The presence of such deviations seems to be related to a difference between the simulated and the measured zenith angle evolutions of the lateral muon density distributions of EAS, which also causes a discrepancy between the measured absorption lengths of the density of shower muons and the predicted ones at large distances from the EAS core. The studied deficiencies show that all four considered hadronic interaction models fail to describe consistently the zenith angle evolution of the muon content of EAS in the aforesaid energy regime.
► All-particle energy spectrum of cosmic rays between knee and ankle is not a single power law. ► Just above 1016eV the spectrum exhibits a hardening. ► Around 8×1016eV there is a knee-like feature ...in the spectrum.
The energy spectrum of cosmic rays between 1016eV and 1018eV, derived from measurements of the shower size (total number of charged particles) and the total muon number of extensive air showers by the KASCADE-Grande experiment, is described. The resulting all-particle energy spectrum exhibits strong hints for a hardening of the spectrum at approximately 2·1016eV and a significant steepening at ≈8·1016eV. These observations challenge the view that the spectrum is a single power law between knee and ankle. Possible scenarios generating such features are discussed in terms of astrophysical processes that may explain the transition region from galactic to extragalactic origin of cosmic rays.
The KASCADE-Grande experiment Apel, W.D.; Arteaga, J.C.; Badea, A.F. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
08/2010, Letnik:
620, Številka:
2
Journal Article
Recenzirano
Odprti dostop
KASCADE-Grande is the enlargement of the KASCADE extensive air shower detector, realized to expand the cosmic ray studies from the previous 10
14–10
17
eV primary energy range to 10
18
eV. This is ...performed by extending the area covered by the KASCADE electromagnetic array from 200×200 to 700×700
m
2 by means of 37 scintillator detector stations of 10
m
2 area each. This new array is named Grande and provides measurements of the all-charged particle component of extensive air showers (
N
ch
), while the original KASCADE array particularly provides information on the muon content
(
N
μ
)
. Additional dense compact detector set-ups being sensitive to energetic hadrons and muons are used for data consistency checks and calibration purposes. The performance of the Grande array and its integration into the entire experimental complex is discussed. It is demonstrated that the overall observable resolutions are adequate to meet the physical requirements of the measurements, i.e. primary energy spectrum and elemental composition studies in the primary cosmic ray energy range of 10
16–10
18
eV.
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