Matrix Gla protein (MGP), a natural inhibitor of calcification, strongly correlates with the extent of coronary calcification. Vitamin K is the essential cofactor for the activation of MGP. The ...nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP) reflects the status of this vitamin. We investigated whether there is an association between dp-ucMGP and stiffness of elastic and muscular-type large arteries in a random sample from the general population. In a cross-sectional design, we analyzed 1087 subjects from the Czech post-MONICA study. Aortic and femoro-popliteal pulse wave velocities (PWVs) were measured using a Sphygmocor device. Dp-ucMGP concentrations were assessed in freshly frozen samples by enzyme-linked immunosorbent assay methods using the InaKtif MGP iSYS pre-commercial kit developed by IDS and VitaK. Aortic PWV significantly (P<0.0001) increased across the dp-ucMGP quartiles. After adjustment for all potential confounders, aortic PWV independently correlated with dp-ucMGP (with beta coefficient (s.d.) 11.61 (5.38) and P-value=0.031). In a categorized manner, subjects in the top quartile of dp-ucMGP (⩾ 671 pmol l(-1)) had a higher risk of elevated aortic PWV, with corresponding adjusted odds ratio (95% confidence interval) 1.73 (1.17-2.5). In contrast, no relation between dp-ucMGP and femoro-popliteal PWV was found. In conclusion, increased dp-ucMGP, which is a circulating biomarker of vitamin K status and vascular calcification, is independently associated with aortic stiffness, but not with stiffness of distal muscular-type arteries.
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.
Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to ...identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4(+) T-cell subsets, regulatory T cells, CD8(+) T cells, B cells, and monocytes. We find that ∼90% of causal variants are non-coding, with ∼60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10-20% directly alter recognizable transcription factor binding motifs. Rather, most non-coding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The ‘KASCADE Cosmic ray Data Centre’ is a web portal (
https://kcdc.ikp.kit.edu
), where the data of the astroparticle physics experiment KASCADE-Grande are made available for the interested public. ...The KASCADE experiment was a large-area detector for the measurement of high-energy cosmic rays via the detection of extensive air showers. The multi-detector installations KASCADE and its extension KASCADE-Grande stopped the active data acquisition in 2013 after more than 20 years of data taking. In several updates since our first release in 2013 with KCDC we provide the public measured and reconstructed parameters of more than 433 million air showers. In addition, KCDC provides meta data information and documentation to enable a user outside the community of experts to perform their own data analysis. Simulation data from three different high energy interaction models have been made available as well as a compilation of measured and published spectra from various experiments. In addition, detailed educational examples shall encourage high-school students and early stage researchers to learn about astroparticle physics, cosmic radiation as well as the handling of Big Data and about the sustainable and public provision of scientific data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
► 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.
A composition analysis of KASCADE air shower data is performed by means of unfolding the two-dimensional frequency spectrum of electron and muon numbers. Aim of the analysis is the determination of ...energy spectra for elemental groups representing the chemical composition of primary cosmic rays. Since such an analysis depends crucially on simulations of air showers the two different hadronic interaction models QGSJet and SIBYLL are used for their generation. The resulting primary energy spectra show that the knee in the all particle spectrum is due to a steepening of the spectra of light elements but, also, that neither of the two simulation sets is able to describe the measured data consistently over the whole energy range with discrepancies appearing in different energy regions.
Although many phenotypes have been associated with variants in human leukocyte antigen (HLA) genes, the full phenotypic impact of HLA variants across all diseases is unknown. We imputed HLA genomic ...variation from two populations of 28,839 and 8431 European ancestry individuals and tested association of HLA variation with 1368 phenotypes. A total of 104 four-digit and 92 two-digit HLA allele phenotype associations were significant in both discovery and replication cohorts, the strongest being
and type 1 diabetes. Four previously unidentified associations were identified across the spectrum of disease with two- and four-digit HLA alleles and 10 with nonsynonymous variants. Some conditions associated with multiple HLA variants and stronger associations with more severe disease manifestations were identified. A comprehensive, publicly available catalog of clinical phenotypes associated with HLA variation is provided. Examining HLA variant disease associations in this large data set allows comprehensive definition of disease associations to drive further mechanistic insights.
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.
The phase II J003 (N = 169) and phase III RECOURSE (N = 800) trials demonstrated a significant improvement in survival with trifluridine (FTD)/tipiracil (TPI) versus placebo in patients with ...refractory metastatic colorectal cancer. This post hoc analysis investigated pharmacokinetic data of FTD/TPI exposure and pharmacodynamic markers, such as chemotherapy-induced neutropenia (CIN) and clinical outcomes.
A total of 210 patients from RECOURSE were enrolled in this substudy. A limited sampling approach was used, with three pharmacokinetic samples drawn on day 12 of cycle 1. Patients were categorized as being above or below the median area under the plasma concentration–time curve (AUC) for FTD and TPI. We conducted a post hoc analysis using the entire RECOURSE population to determine the correlations between CIN and clinical outcome. We then carried out a similar analysis on the J003 trial to validate the results.
In the RECOURSE subset, patients in the high FTD AUC group had a significantly increased CIN risk. Analyses of the entire population demonstrated that FTD/TPI-treated patients with CIN of any grade in cycles 1 and 2 had significantly longer median overall survival (OS) and progression-free survival (PFS) than patients who did not develop CIN and patients in the placebo group. Patients who required an FTD/TPI treatment delay had increased OS and PFS versus those in the placebo group and those who did not develop CIN. Similar results were obtained in the J003 cohort.
In RECOURSE, patients with higher FTD drug exposure had an increased CIN risk. FTD/TPI-treated patients who developed CIN had improved OS and PFS versus those in the placebo group and those who did not develop CIN. Similar findings were reported in the J003 cohort, thus validating the RECOURSE results. The occurrence of CIN may be a useful predictor of treatment outcomes for FTD/TPI-treated patients.
NCT01607957 (RECOURSE).
JapicCTI-090880 (J003).
•Patients with higher FTD exposure had a significantly increased risk of CIN.•In RECOURSE, FTD/TPI-treated patients who developed CIN had improved OS and PFS compared with placebo and those with no CIN.•Similar results from J003 validated the RECOURSE results.
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