Refine
Year of publication
Language
- English (26)
Is part of the Bibliography
- yes (26)
Keywords
Institute
- Institut für Physik und Astronomie (17)
- Department Psychologie (2)
- Institut für Biochemie und Biologie (2)
- Hasso-Plattner-Institut für Digital Engineering GmbH (1)
- Hasso-Plattner-Institut für Digital Engineering gGmbH (1)
- Institut für Geowissenschaften (1)
- Mathematisch-Naturwissenschaftliche Fakultät (1)
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
The origin of Galactic cosmic rays is a century-long puzzle. Indirect evidence points to their acceleration by supernova shockwaves, but we know little of their escape from the shock and their evolution through the turbulent medium surrounding massive stars. Gamma rays can probe their spreading through the ambient gas and radiation fields. The Fermi Large Area Telescope (LAT) has observed the star-forming region of Cygnus X. The 1- to 100-gigaelectronvolt images reveal a 50-parsec-wide cocoon of freshly accelerated cosmic rays that flood the cavities carved by the stellar winds and ionization fronts from young stellar clusters. It provides an example to study the youth of cosmic rays in a superbubble environment before they merge into the older Galactic population.
Observations of radio halos and relics in galaxy clusters indicate efficient electron acceleration. Protons should likewise be accelerated and, on account of weak energy losses, can accumulate, suggesting that clusters may also be sources of very high energy (VHE; E > 100 GeV) gamma-ray emission. We report here on VHE gamma-ray observations of the Coma galaxy cluster with the VERITAS array of imaging Cerenkov telescopes, with complementing Fermi Large Area Telescope observations at GeV energies. No significant gamma-ray emission from the Coma Cluster was detected. Integral flux upper limits at the 99% confidence level were measured to be on the order of (2-5) x 10(-8) photonsm(-2) s(-1) (VERITAS, >220 GeV) and similar to 2 x 10(-6) photonsm(-2) s(-1) (Fermi, 1-3GeV), respectively. We use the gamma-ray upper limits to constrain cosmic rays (CRs) and magnetic fields in Coma. Using an analytical approach, the CR-to-thermal pressure ratio is constrained to be < 16% from VERITAS data and <1.7% from Fermi data (averaged within the virial radius). These upper limits are starting to constrain the CR physics in self-consistent cosmological cluster simulations and cap the maximum CR acceleration efficiency at structure formation shocks to be <50%. Alternatively, this may argue for non-negligible CR transport processes such as CR streaming and diffusion into the outer cluster regions. Assuming that the radio-emitting electrons of the Coma halo result from hadronic CR interactions, the observations imply a lower limit on the central magnetic field in Coma of similar to(2-5.5) mu G, depending on the radial magnetic field profile and on the gamma-ray spectral index. Since these values are below those inferred by Faraday rotation measurements in Coma (for most of the parameter space), this renders the hadronic model a very plausible explanation of the Coma radio halo. Finally, since galaxy clusters are dark matter (DM) dominated, the VERITAS upper limits have been used to place constraints on the thermally averaged product of the total self-annihilation cross section and the relative velocity of the DM particles, <sigma nu >.
Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
We report the discovery of TeV gamma-ray emission coincident with the shell-type radio supernova remnant (SNR) CTA 1 using the VERITAS gamma-ray observatory. The source, VER J0006+729, was detected as a 6.5 standard deviation excess over background and shows an extended morphology, approximated by a two-dimensional Gaussian of semimajor (semiminor) axis 0.degrees 30 (0.degrees 24) and a centroid 5’ from the Fermi gamma-ray pulsar PSR J0007+7303 and its X-ray pulsar wind nebula (PWN). The photon spectrum is well described by a power-law dN/dE = N-0(E/3 TeV)(-Gamma), with a differential spectral index of Gamma = 2.2 +/- 0.2(stat) +/- 0.3(sys), and normalization N-0 = (9.1 +/- 1.3(stat) +/- 1.7(sys)) x 10(-14) cm(-2) s(-1) TeV-1. The integral flux, F-gamma = 4.0 x 10(-12) erg cm(-2) s(-1) above 1 TeV, corresponds to 0.2% of the pulsar spin-down power at 1.4 kpc. The energetics, colocation with the SNR, and the relatively small extent of the TeV emission strongly argue for the PWN origin of the TeV photons. We consider the origin of the TeV emission in CTA 1.
We report the discovery of an unidentified, extended source of very-high-energy gamma-ray emission, VER J2019+407, within the radio shell of the supernova remnant SNR G78.2+2.1, using 21.4 hr of data taken by the VERITAS gamma-ray observatory in 2009. These data confirm the preliminary indications of gamma-ray emission previously seen in a two-year (2007-2009) blind survey of the Cygnus region by VERITAS. VER J2019+407, which is detected at a post-trials significance of 7.5 standard deviations in the 2009 data, is localized to the northwestern rim of the remnant in a region of enhanced radio and X-ray emission. It has an intrinsic extent of 0 degrees.23 +/- 0 degrees.03(stat-0 degrees.02sys)(+0 degrees.04) and its spectrum is well-characterized by a differential power law (dN/dE = N-0 x (E/TeV)-Gamma) with a photon index of Gamma = 2.37 +/- 0.14(stat) +/- 0.20(sys) and a flux normalization of N-0 = 1.5 +/- 0.2(stat) +/- 0.4(sys) x 10(-12) photon TeV-1 cm(-2) s(-1). This yields an integral flux of 5.2 +/- 0.8(stat) +/- 1.4(sys) x 10(-12) photon cm(-2) s(-1) above 320 GeV, corresponding to 3.7% of the Crab Nebula flux. We consider the relationship of the TeV gamma-ray emission with the GeV gamma-ray emission seen from SNR G78.2+2.1 as well as that seen from a nearby cocoon of freshly accelerated cosmic rays. Multiple scenarios are considered as possible origins for the TeV gamma-ray emission, including hadronic particle acceleration at the SNR shock.
We report on the discovery of high-energy (HE; E > 0.1 GeV) and very high energy (VHE; E > 100 GeV) gamma-ray emission from the high-frequency-peaked BL Lac object RBS 0413. VERITAS, a ground-based gamma-ray observatory, detected VHE. rays from RBS 0413 with a statistical significance of 5.5 standard deviations (sigma) and a gamma-ray flux of (1.5 +/- 0.6(stat) +/- 0.7(syst)) x 10(-8) photons m(-2) s(-1) (similar to 1% of the Crab Nebula flux) above 250 GeV. The observed spectrum can be described by a power law with a photon index of 3.18 +/- 0.68(stat) +/- 0.30(syst). Contemporaneous observations with the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope detected HE gamma rays from RBS 0413 with a (stat)istical significance of more than 9 sigma, a power-law photon index of 1.57 +/- 0.12(stat-0.12sys')(+0.11) and a gamma-ray flux between 300 MeV and 300 GeV of (1.64 +/- 0.43(stat-0.22sys)(+ 0.31)) x 10(-5) photons m(-2) s(-1). We present the results from Fermi-LAT and VERITAS, including a spectral energy distribution modeling of the gamma-ray, quasi-simultaneous X-ray (Swift-XRT), ultraviolet (Swift-UVOT), and R-band optical (MDM) data. We find that, if conditions close to equipartition are required, both the combined synchrotron self-Compton/external-Compton and the lepto-hadronic models are preferred over a pure synchrotron self-Compton model.
Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
We present varve chronologies for sediments from two maar lakes in the Valle de Santiago region (Central Mexico): Hoya La Alberca (AD 1852-1973) and Hoya Rincn de Parangueo (AD 1839-1943). These are the first varve chronologies for Mexican lakes. The varved sections were anchored with tephras from Colima (1913) and Paricutin (1943/1944) and (210)Pb ages. We compare the sequences using the thickness of seasonal laminae and element counts (Al, Si, S, Cl, K, Ti, Mn, Fe, and Sr) determined by micro X-ray fluorescence spectrometry. The formation of the varve sublaminae is attributed to the strongly seasonal climate regime. Limited rainfall and high evaporation rates in winter and spring induce precipitation of carbonates (high Ca, Sr) enriched in (13)C and (18)O, whereas rainfall in summer increases organic and clastic input (plagioclase, quartz) with high counts of lithogenic elements (K, Al, Ti, and Si). Eolian input of Ti occurs also in the dry season. Moving correlations (5-yr windows) of the Ca and Ti counts show similar development in both sequences until the 1930s. Positive correlations indicate mixing of allochthonous Ti and autochthonous Ca, while negative correlations indicate their separation in sublaminae. Negative excursions in the correlations correspond with historic and reconstructed droughts, El Nio events, and positive SST anomalies. Based on our data, droughts (3-7 year duration) were severe and centred around the following years: the early 1850s, 1865, 1880, 1895, 1905, 1915 and the late 1920s with continuation into the 1930s. The latter dry period brought both lake systems into a critical state making them susceptible to further drying. Groundwater overexploitation due to the expansion of irrigation agriculture in the region after 1940 induced the transition from calcite to aragonite precipitation in Alberca and halite infiltration in Rincn. The proxy data indicate a faster response to increased evaporation for Rincn, the lake with the larger maar dimensions, solar radiation receipt and higher conductivity, whereas the smaller, steeper Alberca maar responded rapidly to increased precipitation.
We present varve chronologies for sediments from two maar lakes in the Valle de Santiago region (Central Mexico): Hoya La Alberca (AD 1852-1973) and Hoya Rincn de Parangueo (AD 1839-1943). These are the first varve chronologies for Mexican lakes. The varved sections were anchored with tephras from Colima (1913) and Paricutin (1943/ 1944) and Pb-210 ages. We compare the sequences using the thickness of seasonal laminae and element counts (Al, Si, S, Cl, K, Ti, Mn, Fe, and Sr) determined by micro X-ray fluorescence spectrometry. The formation of the varve sublaminae is attributed to the strongly seasonal climate regime. Limited rainfall and high evaporation rates in winter and spring induce precipitation of carbonates (high Ca, Sr) enriched in C-13 and O-18, whereas rainfall in summer increases organic and clastic input (plagioclase, quartz) with high counts of lithogenic elements (K, Al, Ti, and Si). Eolian input of Ti occurs also in the dry season. Moving correlations (5-yr windows) of the Ca and Ti counts show similar development in both sequences until the 1930s. Positive correlations indicate mixing of allochthonous Ti and autochthonous Ca, while negative correlations indicate their separation in sublaminae. Negative excursions in the correlations correspond with historic and reconstructed droughts, El Nio events, and positive SST anomalies. Based on our data, droughts (3-7 year duration) were severe and centred around the following years: the early 1850s, 1865, 1880, 1895, 1905, 1915 and the late 1920s with continuation into the 1930s. The latter dry period brought both lake systems into a critical state making them susceptible to further drying. Groundwater overexploitation due to the expansion of irrigation agriculture in the region after 1940 induced the transition from calcite to aragonite precipitation in Alberca and halite infiltration in Rincn. The proxy data indicate a faster response to increased evaporation for Rincn, the lake with the larger maar dimensions, solar radiation receipt and higher conductivity, whereas the smaller, steeper Alberca maar responded rapidly to increased precipitation.