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OBJECTIVE:
Recent publications describing lingual movement strategies within the oral cavity of brass players have established the existence of efficient and predictable movement patterns in healthy performers for a variety of performance tasks. In this study we extend the research to include the playing of large interval slurs in horn players.
METHODS:
Real-time MRI films at 40-msec resolution were simultaneously obtained in the sagittal
and coronal planes in 9 professional horn players as they performed 2 repetitions each of 3 slur sequences spanning 1 octave, 1 octave + 3rd, and 1 octave + 5th at a mezzo forte dynamic level. Nine profile lines were overlaid on the images allowing the measurement of dorsal tongue edge movement using a customized MATLAB toolkit. Movement along lines representing the anterior, middle, and posterior oral cavity in the sagittal plane, as well as the vertical height of an air channel observed in the coronal plane, are reported.
RESULTS:
Both sagittal and coronal views demonstrate patterned tongue movements that narrow and widen the air channel during ascending and descending slurs, respectively. The magnitude of these movements is greater during larger intervals, though not perfectly consistent within each slur sequence. Additionally, the tongue position during notes
tends to drift in the direction of the subsequent note in each sequence. We suggest that the observed movements may help to modulate air speed through the lips, possible attenuating embouchure muscle tension changes by assisting changes in lip vibration frequency.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
The unidentified very-high-energy (VHE; E > 0.1 TeV) gamma -ray source, HESS J1826-130, was discovered with the High Energy Stereoscopic System (HESS) in the Galactic plane. The analysis of 215 h of HESS data has revealed a steady gamma -ray flux from HESS J1826-130, which appears extended with a half-width of 0.21 degrees +/- 0.02 <br /> (stat)degrees <br /> stat degrees +/- 0.05 <br /> (sys)degrees sys degrees . The source spectrum is best fit with either a power-law function with a spectral index Gamma = 1.78 +/- 0.10(stat) +/- 0.20(sys) and an exponential cut-off at 15.2 <br /> (+5.5)(-3.2) -3.2+5.5 TeV, or a broken power-law with Gamma (1) = 1.96 +/- 0.06(stat) +/- 0.20(sys), Gamma (2) = 3.59 +/- 0.69(stat) +/- 0.20(sys) for energies below and above E-br = 11.2 +/- 2.7 TeV, respectively. The VHE flux from HESS J1826-130 is contaminated by the extended emission of the bright, nearby pulsar wind nebula, HESS J1825-137, particularly at the low end of the energy spectrum. Leptonic scenarios for the origin of HESS J1826-130 VHE emission related to PSR J1826-1256 are confronted by our spectral and morphological analysis. In a hadronic framework, taking into account the properties of dense gas regions surrounding HESS J1826-130, the source spectrum would imply an astrophysical object capable of accelerating the parent particle population up to greater than or similar to 200 TeV. Our results are also discussed in a multiwavelength context, accounting for both the presence of nearby supernova remnants, molecular clouds, and counterparts detected in radio, X-rays, and TeV energies.
Context. On 27 April 2015, when comet 67P/Churyumov-Gerasimenko was at 1.76 au from the Sun and moving toward perihelion, the OSIRIS and VIRTIS-M instruments on board the Rosetta spacecraft simultaneously observed the evolving dust and gas coma during a complete rotation of the comet. Aims. We aim to characterize the spatial distribution of dust, H2O, and CO2 gas in the inner coma. To do this, we performed a quantitative analysis of the release of dust and gas and compared the observed H2O production rate with the rate we calculated using a thermophysical model. Methods. For this study we selected OSIRIS WAC images at 612 nm (dust) and VIRTIS-M image cubes at 612 nm, 2700 nm (H2O emission band), and 4200 nm (CO2 emission band). We measured the average signal in a circular annulus to study the spatial variation around the comet, and in a sector of the annulus to study temporal variation in the sunward direction with comet rotation, both at a fixed distance of 3.1 km from the comet center. Results. The spatial correlation between dust and water, both coming from the sunlit side of the comet, shows that water is the main driver of dust activity in this time period. The spatial distribution of CO2 is not correlated with water and dust. There is no strong temporal correlation between the dust brightness and water production rate as the comet rotates. The dust brightness shows a peak at 0 degrees subsolar longitude, which is not pronounced in the water production. At the same epoch, there is also a maximum in CO2 production. An excess of measured water production with respect to the value calculated using a simple thermophysical model is observed when the head lobe and regions of the southern hemisphere with strong seasonal variations are illuminated (subsolar longitude 270 degrees-50 degrees). A drastic decrease in dust production when the water production (both measured and from the model) displays a maximum occurs when typical northern consolidated regions are illuminated and the southern hemisphere regions with strong seasonal variations are instead in shadow (subsolar longitude 50 degrees-90 degrees). Possible explanations of these observations are presented and discussed.
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia
(2019)
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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 flat spectrum radio quasar 3C 279 is known to exhibit pronounced variability in the high-energy (100MeV < E < 100 GeV) gamma-ray band, which is continuously monitored with Fermi-LAT. During two periods of high activity in April 2014 and June 2015 target-of-opportunity observations were undertaken with the High Energy Stereoscopic System (H.E.S.S.) in the very-high-energy (VHE, E > 100 GeV) gamma-ray domain. While the observation in 2014 provides an upper limit, the observation in 2015 results in a signal with 8 : 7 sigma significance above an energy threshold of 66 GeV. No VHE variability was detected during the 2015 observations. The VHE photon spectrum is soft and described by a power-law index of 4.2 +/- 0.3. The H.E.S.S. data along with a detailed and contemporaneous multiwavelength data set provide constraints on the physical parameters of the emission region. The minimum distance of the emission region from the central black hole was estimated using two plausible geometries of the broad-line region and three potential intrinsic spectra. The emission region is confidently placed at r greater than or similar to 1 : 7 X 1017 cm from the black hole, that is beyond the assumed distance of the broad-line region. Time-dependent leptonic and lepto-hadronic one-zone models were used to describe the evolution of the 2015 flare. Neither model can fully reproduce the observations, despite testing various parameter sets. Furthermore, the H.E.S.S. data were used to derive constraints on Lorentz invariance violation given the large redshift of 3C 279.
Context. We present a detailed view of the pulsar wind nebula (PWN) HESS J1825-137. We aim to constrain the mechanisms dominating the particle transport within the nebula, accounting for its anomalously large size and spectral characteristics. Aims. The nebula was studied using a deep exposure from over 12 years of H.E.S.S. I operation, together with data from H.E.S.S. II that improve the low-energy sensitivity. Enhanced energy-dependent morphological and spatially resolved spectral analyses probe the very high energy (VHE, E > 0.1 TeV) gamma-ray properties of the nebula. Methods. The nebula emission is revealed to extend out to 1.5 degrees from the pulsar, similar to 1.5 times farther than previously seen, making HESS J1825-137, with an intrinsic diameter of similar to 100 pc, potentially the largest gamma-ray PWN currently known. Characterising the strongly energy-dependent morphology of the nebula enables us to constrain the particle transport mechanisms. A dependence of the nebula extent with energy of R proportional to E alpha with alpha = -0.29 +/- 0.04(stat) +/- 0.05(sys) disfavours a pure diffusion scenario for particle transport within the nebula. The total gamma-ray flux of the nebula above 1 TeV is found to be (1.12 +/- 0.03(stat) +/- 0.25(sys)) +/- 10(-11) cm(-2) s(-1), corresponding to similar to 64% of the flux of the Crab nebula. Results. HESS J1825-137 is a PWN with clearly energy-dependent morphology at VHE gamma-ray energies. This source is used as a laboratory to investigate particle transport within intermediate-age PWNe. Based on deep observations of this highly spatially extended PWN, we produce a spectral map of the region that provides insights into the spectral variation within the nebula.
Gamma-ray bursts (GRBs) are brief flashes of gamma-rays and are considered to be the most energetic explosive phenomena in the Universe(1). The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed(2). GRBs typically emit most of their energy via.-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments(3). However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive(4). Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and gamma-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.