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Context. About 40% of the observation time of the High Energy Stereoscopic System (H.E.S.S.) is dedicated to studying active galactic nuclei (AGN), with the aim of increasing the sample of known extragalactic very-high-energy (VHE, E > 100 GeV) sources and constraining the physical processes at play in potential emitters.
Aims. H.E.S.S. observations of AGN, spanning a period from April 2004 to December 2011, are investigated to constrain their gamma-ray fluxes. Only the 47 sources without significant excess detected at the position of the targets are presented.
Methods. Upper limits on VHE fluxes of the targets were computed and a search for variability was performed on the nightly time scale.
Results. For 41 objects, the flux upper limits we derived are the most constraining reported to date. These constraints at VHE are compared with the flux level expected from extrapolations of Fermi-LAT measurements in the two-year catalog of AGN. The H.E.S.S. upper limits are at least a factor of two lower than the extrapolated Fermi-LAT fluxes for 11 objects Taking into account the attenuation by the extragalactic background light reduces the tension for all but two of them, suggesting intrinsic curvature in the high-energy spectra of these two AGN.
Conclusions. Compilation efforts led by current VHE instruments are of critical importance for target-selection strategies before the advent of the Cherenkov Telescope Array (CTA).
Context. On March 4, 2013 the Fermi-EAT and AGILE reported a flare from the direction of the Crab nebula in which the high-energy (HE; E > 100 MeV) flux was six times above its quiescent level. Simultaneous observations in other energy bands give us hints about the emission processes during the flare episode and the physics of pulsar wind nebulae in general.
Aims. We search for variability in the emission of the Crab nebula at very-high energies (VHF,; E > 100 GeV), using contemporaneous data taken with the H.E.S.S. array of Cherenkov telescopes.
Methods. Observational data taken with the H.E.S.S. instrument on five consecutive days during the flare were analysed for the flux and spectral shape of the emission from the Crab nebula. Night-wise light curves are presented with energy thresholds of 1 TeV and 5 TeV.
Results. The observations conducted with H.E.S.S. on March 6 to March 10, 2013 show no significant changes in the flux. They limit the variation in the integral flux above 1 TeV to less than 63% and the integral flux above 5 TeV to less than 78% at a 95% confidence level.
Discovery of very high energy gamma-ray emission from the BL Lacertae
object PKS0301-243 with HESS
(2013)
The active galactic nucleus PKS 0301-243 (z = 0.266) is a high-synchrotron-peaked BL Lac object that is detected at high energies (HE, 100 MeV < E < 100 GeV) by Fermi/LAT. This paper reports on the discovery of PKS 0301-243 at very high energies (E > 100 GeV) by the High Energy Stereoscopic System (H.E.S.S.) from observations between September 2009 and December 2011 for a total live time of 34.9 h. Gamma rays above 200 GeV are detected at a significance of 9.4 sigma. A hint of variability at the 2.5 sigma level is found. An integral flux I(E > 200GeV) = (3.3 +/- 1.1(stat) +/- 0.7(syst)) x 10(-12) ph cm(-2) s(-1) and a photon index Gamma = 4.6 +/- 0.7(stat) +/- 0.2(syst) are measured. Multi-wavelength light curves in HE, X-ray and optical bands show strong variability, and a minimal variability timescale of eight days is estimated from the optical light curve. A single-zone leptonic synchrotron self-Compton scenario satisfactorily reproduces the multi-wavelength data. In this model, the emitting region is out of equipartition and the jet is particle dominated. Because of its high redshift compared to other sources observed at TeV energies, the very high energy emission from PKS 0301-243 is attenuated by the extragalactic background light (EBL) and the measured spectrum is used to derive an upper limit on the opacity of the EBL.
Composite supernova remnants (SNRs) constitute a small subclass of the remnants of massive stellar explosions where non-thermal radiation is observed from both the expanding shell-like shock front and from a pulsar wind nebula (PWN) located inside of the SNR. These systems represent a unique evolutionary phase of SNRs where observations in the radio, X-ray, and gamma-ray regimes allow the study of the co-evolution of both these energetic phenomena. In this article, we report results from observations of the shell-type SNR G15.4+0.1 performed with the High Energy Stereoscopic System (H. E. S. S.) and XMM-Newton. A compact TeV gamma-ray source, HESS J1818-154, located in the center and contained within the shell of G15.4+0.1 is detected by H. E. S. S. and featurs a spectrum best represented by a power-law model with a spectral index of -2.3 +/- 0.3(stat) +/- 0.2(sys) and an integral flux of F(>0.42 TeV) = (0.9 +/- 0.3(stat) +/- 0.2(sys)) x 10(-12) cm(-2) s(-1). Furthermore, a recent observation with XMM-Newton reveals extended X-ray emission strongly peaked in the center of G15.4+0.1. The X-ray source shows indications of an energy-dependent morphology featuring a compact core at energies above 4 keV and more extended emission that fills the entire region within the SNR at lower energies. Together, the X-ray and VHE gamma-ray emission provide strong evidence of a PWN located inside the shell of G15.4+0.1 and this SNR can therefore be classified as a composite based on these observations. The radio, X-ray, and gamma-ray emission from the PWN is compatible with a one-zone leptonic model that requires a low average magnetic field inside the emission region. An unambiguous counterpart to the putative pulsar, which is thought to power the PWN, has been detected neither in radio nor in X-ray observations of G15.4+0.1.
TeV gamma-ray observations of the young synchrotron-dominated SNRs G1.9+0.3 and G330.2+1.0 with HESS
(2014)
The non-thermal nature of the X-ray emission from the shell-type supernova remnants (SNRs) G1.9+0.3 and G330.2+1.0 is an indication of intense particle acceleration in the shock fronts of both objects. This suggests that the SNRs are prime candidates for very-high-energy (VHE; E > 0.1 TeV) gamma-ray observations. G1.9+0.3, recently established as the youngest known SNR in the Galaxy, also offers a unique opportunity to study the earliest stages of SNR evolution in the VHE domain. The purpose of this work is to probe the level of VHE gamma-ray emission from both SNRs and use this to constrain their physical properties. Observations were conducted with the H. E. S. S. (High Energy Stereoscopic System) Cherenkov Telescope Array over a more than six-year period spanning 2004-2010. The obtained data have effective livetimes of 67 h for G1.9+0.3 and 16 h for G330.2+1.0. The data are analysed in the context of the multiwavelength observations currently available and in the framework of both leptonic and hadronic particle acceleration scenarios. No significant gamma-ray signal from G1.9+0.3 or G330.2+1.0 was detected. Upper limits (99 per cent confidence level) to the TeV flux from G1.9+0.3 and G330.2+1.0 for the assumed spectral index Gamma = 2.5 were set at 5.6 x 10(-1)3 cm(-2) s(-1) above 0.26 TeV and 3.2 x 10(-12) cm(-2) s(-1) above 0.38 TeV, respectively. In a one-zone leptonic scenario, these upper limits imply lower limits on the interior magnetic field to B-G1.9 greater than or similar to 12 mu G for G1.9+0.3 and to B-G330 greater than or similar to 8 mu G for G330.2+1.0. In a hadronic scenario, the low ambient densities and the large distances to the SNRs result in very low predicted fluxes, for which the H.E.S.S. upper limits are not constraining.
In this paper we report on the analysis of all the available optical and very high-energy gamma-ray (> 200 GeV) data for the BL Lac object PKS 2155-304, collected simultaneously with the ATOM and H.E.S.S. telescopes from 2007 until 2009. This study also includes X-ray (RXTE, Swift) and high-energy gamma-ray (Fermi-LAT) data. During the period analysed, the source was transitioning from its flaring to quiescent optical states, and was characterized by only moderate flux changes at different wavelengths on the timescales of days and months. A flattening of the optical continuum with an increasing optical flux can be noted in the collected dataset, but only occasionally and only at higher flux levels. We did not find any universal relation between the very high-energy gamma-ray and optical flux changes on the timescales from days and weeks up to several years. On the other hand, we noted that at higher flux levels the source can follow two distinct tracks in the optical flux-colour diagrams, which seem to be related to distinct gamma-ray states of the blazar. The obtained results therefore indicate a complex scaling between the optical and gamma-ray emission of PKS 2155 304, with different correlation patterns holding at different epochs, and a gamma-ray flux depending on the combination of an optical flux and colour rather than a flux alone.
An annihilation signal of dark matter is searched for from the central region of the Milky Way. Data acquired in dedicated on-off observations of the Galactic center region with H.E.S.S. are analyzed for this purpose. No significant signal is found in a total of similar to 9 h of on-off observations. Upper limits on the velocity averaged cross section, <sigma upsilon >, for the annihilation of dark matter particles with masses in the range of similar to 300 GeV to similar to 10 TeV are derived. In contrast to previous constraints derived from observations of the Galactic center region, the constraints that are derived here apply also under the assumption of a central core of constant dark matter density around the center of the Galaxy. Values of <sigma upsilon > that are larger than 3 x 10(-24) cm(3)/s are excluded for dark matter particles with masses between similar to 1 and similar to 4 TeV at 95% C.L. if the radius of the central dark matter density core does not exceed 500 pc. This is the strongest constraint that is derived on <sigma upsilon > for annihilating TeV mass dark matter without the assumption of a centrally cusped dark matter density distribution in the search region.
The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of 100 billion electron volts for a deep exposure of 210 hours. Three sources of different types were detected: the pulsar wind nebula of the most energetic pulsar known, N 157B; the radio-loud supernova remnant N 132D; and the largest nonthermal x-ray shell, the superbubble 30 Dor C. The unique object SN 1987A is, unexpectedly, not detected, which constrains the theoretical framework of particle acceleration in very young supernova remnants. These detections reveal the most energetic tip of a g-ray source population in an external galaxy and provide via 30 Dor C the unambiguous detection of g-ray emission from a superbubble.
Re-observations with the HESS telescope array of the very high-energy (VHE) source HESS J1018-589A that is coincident with the Fermi-LAT gamma-ray binary 1FGL J1018.6-5856 have resulted in a source detection significance of more than 9 sigma and the detection of variability (chi(2)/nu of 238.3/155) in the emitted gamma-ray flux. This variability confirms the association of HESS J1018-589A with the high-energy gamma-ray binary detected Fermi-LAT and also confirms the point-like source as a new VHE binary system. The spectrum of HESS J1018-589A is best fit with a power-law function with photon index Gamma = 2.20 +/- 0.14(stat) +/- 0.2(sys). Emission is detected up to similar to 20 TeV. The mean differential flux level is (2.9 +/- 0.4) x 10(-13) TeV-1 cm(-2) s(-1) at 1 TeV, equivalent to similar to 1% of the flux from the Crab Nebula at the same energy. Variability is clearly detected the night-by-night light curve. When folded on the orbital period of 16.58 days, the rebinned light curve peaks in phase with the observed X-ray high-energy phaseograms. The fit of the HESS phaseogram to a constant flux provides evidence of periodicity at the level of N-sigma > 3 sigma. The of the VHE phaseogram and measured spectrum suggest a low-inclination, low-eccentricity system with a modest impact from VHE gamma-ray due to pair production (tau less than or similar to 1 at 300 GeV).
Context. Very-high-energy (VHE; E > 100 GeV) gamma-ray emission from blazars inevitably gives rise to electron-positron pair production through the interaction of these gamma-rays with the extragalactic background light (EBL). Depending on the magnetic fields in the proximity of the source, the cascade initiated from pair production can result in either an isotropic halo around an initially- beamed source or a magnetically- broadened cascade :aux.
Aims. Both extended pair-halo (PH) and magnetically broadened cascade (MBC) emission from regions surrounding the blazars 1ES 1101-232, IRS 0229+200, and PKS 2155-304 were searched for using VHE y-ray data taken with the High Energy Stereoscopic System (HESS.) and high-energy (HE; 100 MeV < E < 100 GeV) gamma-ray data with the Fermi Large Area Telescope (LAT).
Methods. By comparing the angular distributions of the reconstructed gamma-ray events to the angular profiles calculated from detailed theoretical models, the presence of PH and MBC was investigated.
Results. Upper limits on the extended emission around lES 1101-232, lES 0229+200, and PKS 2155-304 are found to be at a level of a few per cent of the Crab nebula flux above 1 TeV, depending on the assumed photon index of the cascade emission. Assuming strong extra-Galactic magnetic field (EGME) values, >10(-12) G, this limits the production of pair haloes developing from electromagnetic cascades. For weaker magnetic fields, in which electromagnetic cascades would result in MBCs. EGMF strengths in the range (0.3-3) x 10(-15) G were excluded for PKS 2155-304 at the 99% confidence level, under the assumption of a 1 Mpc coherence length.
Very high energy (VHE, E > 100 GeV)gamma-ray flaring activity of the high-frequency peaked BL Lac object PG 1553 + 113 has been detected by the H.E.S.S. telescopes. The flux of the source increased by a factor of 3 during the nights of 2012 April 26 and 27 with respect to the archival measurements with a hint of intra-night variability. No counterpart of this event has been detected in the Fermi-Large Area Telescope data. This pattern is consistent with VHE gamma(-)ray flaring being caused by the injection of ultrarelativistic particles, emitting.-rays at the highest energies. The dataset offers a unique opportunity to constrain the redshift of this source at z = 0.49 +/- 0.04 using a novel method based on Bayesian statistics. The indication of intra-night variability is used to introduce a novel method to probe for a possible Lorentz invariance violation (LIV), and to set limits on the energy scale at which Quantum Gravity (QG) effects causing LIV may arise. For the subluminal case, the derived limits are E-QG,E- 1 > 4.10 x 10(17) GeV and E-QG,E- 2 > 2.10 x 10(10) GeV for linear and quadratic LIV effects, respectively.
Diffuse gamma-ray emission is the most prominent observable signature of celestial cosmic-ray interactions at high energies. While already being investigated at GeVenergies over several decades, assessments of diffuse gamma-ray emission at TeVenergies remain sparse. After completion of the systematic survey of the inner Galaxy, the H.E.S.S. experiment is in a prime position to observe large-scale diffuse emission at TeVenergies. Data of the H.E.S.S. Galactic Plane Survey are investigated in regions off known gamma-ray sources. Corresponding gamma-ray flux measurements were made over an extensive grid of celestial locations. Longitudinal and latitudinal profiles of the observed gamma-ray fluxes show characteristic excess emission not attributable to known gamma-ray sources. For the first time large-scale gamma-ray emission along the Galactic plane using imaging atmospheric Cherenkov telescopes has been observed. While the background subtraction technique limits the ability to recover modest variation on the scale of the H.E.S.S. field of view or larger, which is characteristic of the inverse Compton scatter-induced Galactic diffuse emission, contributions of neutral pion decay as well as emission from unresolved gamma-ray sources can be recovered in the observed signal to a large fraction. Calculations show that the minimum gamma-ray emission from pi(0) decay represents a significant contribution to the total signal. This detection is interpreted as a mix of diffuse Galactic gamma-ray emission and unresolved sources.
Context. Puppis A is an interesting similar to 4 kyr-old supernova remnant (SNR) that shows strong evidence of interaction between the forward shock and a molecular cloud. It has been studied in detail from radio frequencies to high-energy (HE, 0.1-100 GeV) gamma-rays. An analysis of the Fermi-LAT data has shown extended HE gamma-ray emission with a 0.2-100 GeV spectrum exhibiting no significant deviation from a power law, unlike most of the GeV-emitting SNRs known to be interacting with molecular clouds. This makes it a promising target for imaging atmospheric Cherenkov telescopes (IACTs) to probe the gamma-ray emission above 100 GeV.
Aims. Very-high-energy (VHE, E >= 0.1 TeV) gamma-ray emission from Puppis A has been, for the first time, searched for with the High Energy Stereoscopic System (HESS.).
Methods. Stereoscopic imaging of Cherenkov radiation from extensive air showers is used to reconstruct the direction and energy of the incident gamma-rays in order to produce sky images and source spectra. The profile likelihood method is applied to find constraints on the existence of a potential break or cutoff in the photon spectrum.
Results. The analysis of the HESS. data does not reveal any significant emission towards Puppis A. The derived upper limits on the differential photon flux imply that its broadband gamma-ray spectrum must exhibit a spectral break or cutoff. By combining Fermi-LAT and HESS. measurements, the 99% confidence-level upper limits on such a cutoff are found to be 450 and 280 GeV, assuming a power law with a simple exponential and a sub-exponential cutoff, respectively. It is concluded that none of the standard limitations (age, size, radiative losses) on the particle acceleration mechanism, assumed to be continuing at present, can explain the lack of VHE signal. The scenario in which particle acceleration has ceased some time ago is considered as an alternative explanation. The HE/VHE spectrum of Puppis A could then exhibit a break of non-radiative origin (as observed in several other interacting SNRs, albeit at somewhat higher energies), owing to the interaction with dense and neutral material, in particular towards the NE region.
Axionlike particles (ALPs) are hypothetical light (sub-eV) bosons predicted in some extensions of the Standard Model of particle physics. In astrophysical environments comprising high-energy gamma rays and turbulent magnetic fields, the existence of ALPs can modify the energy spectrum of the gamma rays for a sufficiently large coupling between ALPs and photons. This modification would take the form of an irregular behavior of the energy spectrum in a limited energy range. Data from the H. E. S. S. observations of the distant BL Lac object PKS 2155 - 304 (z = 0.116) are used to derive upper limits at the 95% C. L. on the strength of the ALP coupling to photons, g(gamma a) < 2.1 x 10(-11) GeV-1 for an ALP mass between 15 and 60 neV. The results depend on assumptions on the magnetic field around the source, which are chosen conservatively. The derived constraints apply to both light pseudoscalar and scalar bosons that couple to the electromagnetic field.
Context. Pulsar wind nebulae (PWNe) represent the most prominent population of Galactic very-high-energy gamma-ray sources and are thought to be an efficient source of leptonic cosmic rays. Vela X is a nearby middle-aged PWN, which shows bright X-ray and TeV gamma-ray emission towards an elongated structure called the cocoon. Aims. Since TeV emission is likely inverse-Compton emission of electrons, predominantly from interactions with the cosmic microwave background, while X-ray emission is synchrotron radiation of the same electrons, we aim to derive the properties of the relativistic particles and of magnetic fields with minimal modelling. Methods. We used data from the Suzaku XIS to derive the spectra from three compact regions in Vela X covering distances from 0.3 to 4 pc from the pulsar along the cocoon. We obtained gamma-ray spectra of the same regions from H.E.S.S. observations and fitted a radiative model to the multi-wavelength spectra. Results. The TeV electron spectra and magnetic field strengths are consistent within the uncertainties for the three regions, with energy densities of the order 10(-12) erg cm(-3). The data indicate the presence of a cutoff in the electron spectrum at energies of similar to 100 TeV and a magnetic field strength of similar to 6 mu G. Constraints on the presence of turbulent magnetic fields are weak. Conclusions. The pressure of TeV electrons and magnetic fields in the cocoon is dynamically negligible, requiring the presence of another dominant pressure component to balance the pulsar wind at the termination shock. Sub-TeV electrons cannot completely account for the missing pressure, which may be provided either by relativistic ions or from mixing of the ejecta with the pulsar wind. The electron spectra are consistent with expectations from transport scenarios dominated either by advection via the reverse shock or by diffusion, but for the latter the role of radiative losses near the termination shock needs to be further investigated in the light of the measured cutoff energies. Constraints on turbulent magnetic fields and the shape of the electron cutoff can be improved by spectral measurements in the energy range greater than or similar to 10 keV.
G349.7+0.2 is a young Galactic supernova remnant (SNR) located at the distance of 11.5 kpc and observed across the entire electromagnetic spectrum from radio to high energy (HE; 0.1 GeV < E < 100 GeV) gamma-rays. Radio and infrared observations indicate that the remnant is interacting with a molecular cloud. In this paper, the detection of very high energy (VHE, E > 100 GeV) gamma-ray emission coincident with this SNR with the High Energy Stereoscopic System (HESS.) is reported. This makes it one of the farthest Galactic SNR ever detected in this domain. An integral flux F(E > 400 GeV) = (6.5 +/- 1.1(stat) +/- 1.3(syst)) x 10-11 ph cm(-2) s(-1) corresponding to similar to 0.7% of that of the Crab Nebula and to a luminosity of similar to 10(34) erg s(-1) above the same energy threshold, and a steep photon index Gamma(VHE) = 2.8 +/- 0.27(stat) +/- 0.20(syst) are measured. The analysis of more than 5 yr of Fermi-LAT data towards this source shows a power-law like spectrum with a best-fit photon index Gamma(HE) = 2.2 +/- 0.04.2(stat-0.31sys)(+0.13), The combined gamma-ray spectrum of 0349.7+0.2 can be described by either a broken power law (I3PL) or a power law with exponential (or sub exponential) cutoff (PLC). In the former case, the photon break energy is found at E-br,E-gamma = 551(-30)(+70) GeV, slightly higher than what is usually observed in the HE/VHE gamma-ray emitting middle-aged SNRs known to be interacting with molecular clouds. In the latter case. the exponential (respectively sub-exponential) cutoff energy is measured at E-cat,E-gamma = 1.4(-0.55)(+1.6) (respectively 0.35(-0.21)(+0.75)) TeV. A pion decay process resulting from the interaction of the accelerated protons and nuclei with the dense surrounding medium is clearly the preferred scenario to explain the gamma-ray emission. The BPL with a spectral steepening of 0.5-1 and the PLC provide equally good fits to the data. The product or the average gas density and the total energy content of accelerated protons and nuclei amounts to nu W-p similar to 5 x 10(51) erg cm(-3)
Search for TeV Gamma-ray emission from GRB 100621A, an extremely bright GRB in X-rays, with HESS
(2014)
The long gamma-ray burst (GRB) 100621A, at the time the brightest X-ray transient ever detected by Swift-XRT in the 0.3-10 keV range, has been observed with the H.E.S.S. imaging air Cherenkov telescope array, sensitive to gamma radiation in the very-high-energy (VHE, >100 GeV) regime. Due to its relatively small redshift of z similar to 0.5, the favourable position in the southern sky and the relatively short follow-up time (<700 s after the satellite trigger) of the H.E.S.S. observations, this GRB could be within the sensitivity reach of the HESS. instrument. The analysis of the HESS. data shows no indication of emission and yields an integral flux upper limit above similar to 380 GeV of 4.2 x 10(-12) cm(-2) s(-1) s (95% confidence level), assuming a simple Band function extension model. A comparison to a spectral-temporal model, normalised to the prompt flux at sub-MeV energies, constraints the existence of a temporally extended and strong additional hard power law, as has been observed in the other bright X-ray GRB 130427A. A comparison between the HESS. upper limit and the contemporaneous energy output in X-rays constrains the ratio between the X-ray and VHE gamma-ray fluxes to be greater than 0.4. This value is an important quantity for modelling the afterglow and can constrain leptonic emission scenarios, where leptons are responsible for the X-ray emission and might produce VHE gamma rays.
Galactic cosmic rays reach energies of at least a few petaelectronvolts (of the order of 1015 electronvolts). This implies that our Galaxy contains petaelectronvolt accelerators (‘PeVatrons’), but all proposed models of Galactic cosmic-ray accelerators encounter difficulties at exactly these energies. Dozens of Galactic accelerators capable of accelerating particles to energies of tens of teraelectronvolts (of the order of 1013 electronvolts) were inferred from recent γ-ray observations3. However, none of the currently known accelerators—not even the handful of shell-type supernova remnants commonly believed to supply most Galactic cosmic rays—has shown the characteristic tracers of petaelectronvolt particles, namely, power-law spectra of γ-rays extending without a cut-off or a spectral break to tens of teraelectronvolts4. Here we report deep γ-ray observations with arcminute angular resolution of the region surrounding the Galactic Centre, which show the expected tracer of the presence of petaelectronvolt protons within the central 10 parsecs of the Galaxy. We propose that the supermassive black hole Sagittarius A* is linked to this PeVatron. Sagittarius A* went through active phases in the past, as demonstrated by X-ray outbursts5and an outflow from the Galactic Centre6. Although its current rate of particle acceleration is not sufficient to provide a substantial contribution to Galactic cosmic rays, Sagittarius A* could have plausibly been more active over the last 106–107 years, and therefore should be considered as a viable alternative to supernova remnants as a source of petaelectronvolt Galactic cosmic rays.
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
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.
X-ray free-electron lasers have, over the past decade, opened up the possibility of understanding the ultrafast response of matter to intense X-ray pulses. In earlier research on atoms and small molecules, new aspects of this response were uncovered, such as rapid sequences of inner-shell photoionization and Auger ionization. Here, we studied a larger molecule, buckminsterfullerene (C-60), exposed to 640 eV X-rays, and examined the role of chemical effects, such as chemical bonds and charge transfer, on the fragmentation following multiple ionization of the molecule. To provide time resolution, we performed femtosecond-resolved X-ray pump/X-ray probe measurements, which were accompanied by advanced simulations. The simulations and experiment reveal that despite substantial ionization induced by the ultrashort (20 fs) X-ray pump pulse, the fragmentation of C-60 is considerably delayed. This work uncovers the persistence of the molecular structure of C-60, which hinders fragmentation over a timescale of hundreds of femtoseconds. Furthermore, we demonstrate that a substantial fraction of the ejected fragments are neutral carbon atoms. These findings provide insights into X-ray free-electron laser-induced radiation damage in large molecules, including biomolecules.
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 selaginella genome identifies genetic changes associated with the evolution of vascular plants
(2011)
Vascular plants appeared similar to 410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
The Great Nebula in Carina provides an exceptional view into the violent massive star formation and feedback that typifies giant H II regions and starburst galaxies. We have mapped the Carina star-forming complex in X-rays, using archival Chandra data and a mosaic of 20 new 60 ks pointings using the Chandra X-ray Observatory's Advanced CCD Imaging Spectrometer, as a testbed for understanding recent and ongoing star formation and to probe Carina's regions of bright diffuse X-ray emission. This study has yielded a catalog of properties of > 14,000 X-ray point sources;> 9800 of them have multiwavelength counterparts. Using Chandra's unsurpassed X-ray spatial resolution, we have separated these point sources from the extensive, spatially-complex diffuse emission that pervades the region; X-ray properties of this diffuse emission suggest that it traces feedback from Carina's massive stars. In this introductory paper, we motivate the survey design, describe the Chandra observations, and present some simple results, providing a foundation for the 15 papers that follow in this special issue and that present detailed catalogs, methods, and science results.
Das 10. Herbsttreffen Patholinguistik mit dem Schwerpunktthema »Panorama Patholinguistik: Sprachwissenschaft trifft Sprachtherapie« fand am 19.11.2016 in Potsdam statt. Das Herbsttreffen wird seit 2007 jährlich vom Verband für Patholinguistik e.V. (vpl) durchgeführt. Der vorliegende Tagungsband beinhaltet die vier Hauptvorträge zum Schwerpunktthema sowie Beiträge zu den Kurzvorträgen »Patholinguistik im Fokus« und der Posterpräsentationen zu weiteren Themen aus der sprachtherapeutischen Forschung und Praxis.
Terrestrial mud volcanoes (TMVs) represent geochemically diverse habitats with varying sulfur sources and yet sulfur cycling in these environments remains largely unexplored. Here we characterized the sulfur-metabolizing microorganisms and activity in four TMVs in Azerbaijan. A combination of geochemical analyses, biological rate measurements and molecular diversity surveys (targeting metabolic genes aprA and dsrA and SSU ribosomal RNA) supported the presence of active sulfur-oxidizing and sulfate-reducing guilds in all four TMVs across a range of physiochemical conditions, with diversity of these guilds being unique to each TMV. The TMVs varied in potential sulfate reduction rates (SRR) by up to four orders of magnitude with highest SRR observed in sediments where in situ sulfate concentrations were highest. Maximum temperatures at which SRR were measured was 60 degrees C in two TMVs. Corresponding with these trends in SRR, members of the potentially thermophilic, spore-forming, Desulfotomaculum were detected in these TMVs by targeted 16S rRNA analysis. Additional sulfate-reducing bacterial lineages included members of the Desulfobacteraceae and Desulfobulbaceae detected by aprA and dsrA analyses and likely contributing to the mesophilic SRR measured. Phylotypes affiliated with sulfide-oxidizing Gamma- and Betaproteobacteria were abundant in aprA libraries from low sulfate TMVs, while the highest sulfate TMV harboured 16S rRNA phylotypes associated with sulfur-oxidizing Epsilonproteobacteria. Altogether, the biogeochemical and microbiological data indicate these unique terrestrial habitats support diverse active sulfur-cycling microorganisms reflecting the in situ geochemical environment.
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.
Signaling trough p53is a major cellular stress response mechanism and increases upon nutrient stresses such as starvation. Here, we show in a human hepatoma cell line that starvation leads to robust nuclear p53 stabilization. Using BioID, we determine the cytoplasmic p53 interaction network within the immediate-early starvation response and show that p53 is dissociated from several metabolic enzymes and the kinase PAK2 for which direct binding with the p53 DNA-binding domain was confirmed with NMR studies. Furthermore, proteomics after p53 immunoprecipitation (RIME) uncovered the nuclear interactome under prolonged starvation, where we confirmed the novel p53 interactors SORBS1 (insulin receptor signaling) and UGP2 (glycogen synthesis). Finally, transcriptomics after p53 re-expression revealed a distinct starvation-specific transcriptome response and suggested previously unknown nutrient-dependent p53 target genes. Together, our complementary approaches delineate several nodes of the p53 signaling cascade upon starvation, shedding new light on the mechanisms of p53 as nutrient stress sensor. Given the central role of p53 in cancer biology and the beneficial effects of fasting in cancer treatment, the identified interaction partners and networks could pinpoint novel pharmacologic targets to fine-tune p53 activity.
Androgens and estrogens are transported bound to the sex hormone binding globulin (SHBG). SHBG is believed to keep sex steroids inactive and to control the amount of free hormones that enter cells by passive diffusion. Contrary to the free hormone hypothesis, we demonstrate that megalin, an endocytic receptor in reproductive tissues, acts as a pathway for cellular uptake of biologically active androgens and estrogens bound to SHBG. In line with this function, lack of receptor expression in megalin knockout mice results in impaired descent of the testes into the scrotum in males and blockade of vagina opening in females. Both processes are critically dependent on sex-steroid signaling, and similar defects are seen in animals treated with androgen- or estrogen-receptor antagonists. Thus, our findings uncover the existence of endocytic pathways for protein bound androgens and estrogens and their crucial role in development of the reproductive organs
OBJECTIVE - We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (S-I), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference. RESEARCH DESIGN AND METHODS - Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992-1994) were analyzed. Usual dietary intake was assessed via a 114- item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. S-I and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying S-I with AIR. Multiple linear regression modeling was employed. RESULTS - No association was observed between glycemic index and S-I fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with S-I insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with S-I and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR. CONCLUSION - Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects. on insulin sensitivity and adiposity, but also on pancreatic functionality
We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals
Adipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which therefore belongs to the group of ciliopathies. The cilium is a hair-like organelle involved in cellular signal transduction. The BBSome, a supercomplex of several Bbs gene products, localizes to the basal body of cilia and is thought to be involved in protein sorting to and from the ciliary membrane. The effects of a functional BBSome on energy metabolism and lipid mobilization in brown and white adipocytes were tested in whole-body Bbs4 knockout mice that were subjected to metabolic challenges. Chronic cold exposure reveals cold-intolerance of knockout mice but also ameliorates the markers of metabolic pathology detected in knockouts prior to cold. Hepatic triglyceride content is markedly reduced in knockout mice while circulating lipids are elevated, altogether suggesting that defective lipid metabolism in adipose tissue creates increased demand for systemic lipid mobilization to meet energetic demands of reduced body temperatures. These findings taken together suggest that Bbs4 is essential for the regulation of adipose tissue lipid metabolism, representing a potential target to treat metabolic disorders.
Study of crosslinking process in fluorinated poly(imide-amide)s containing pendant cyano groups
(1994)
Study of crosslinking process in fluorinated poly(imide-amide)s containing pendant cyano groups
(1994)
A unified understanding of the relationship between disturbance and biodiversity is needed to predict biotic responses to global change. Recent advances have identified the need to deconstruct traditional models of disturbance into intensity and frequency to reconcile empirical studies that appear to generate contradictory associations between species diversity and disturbance. We integrate results from theoretical simulation modelling, field-based surveys of 5176 vegetation plots from 48 transects across 6 sites, and experimental pot-based manipulations of flooding to identify how disturbance drives species diversity within ephemeral wetlands in South Island, New Zealand. We find empirical, hump-shaped and positive relationships between species diversity and both disturbance intensity and frequency, mirroring patterns from a simulation model in which species differed in their demographic responses to disturbance. More generally, our simulations show that the relationships between diversity and disturbance shift from positive to hump-shaped to negative as species that are favored at low disturbance because of their resistance strategies, defined by low mortality and recruitment, decline within communities relative to resilient species. Resilient species with higher mortality and recruitment rates are instead favored as disturbance intensity and frequency intensify. Our theoretical findings suggest that sites must also have a third group of unique species with intermediate resilience and resistance. Analyses of community composition along our disturbance gradients support this prediction, emphasizing that shifts in community-level resistance and resilience drive empirical associations between diversity and disturbance. Overall, terrestrial plants may be unable to resist intense and frequent flooding, even with specialized traits. Only fast-growing species with high regeneration from seed may respond once flooding subsides and dominate community composition in these situations, especially on nutrient-rich soils. However, different strategies can co-occur at intermediate disturbance, ultimately increasing species richness. As disturbances become more pervasive globally, our results suggest that differences in the niches of species, rather than demographic stochasticity, drive biodiversity patterns. These niche-based processes may especially prevail, without accompanying losses in species richness, where sites are initially dominated by resistant taxa or life history strategies that balance resistance and resilience.
Arsenic-containing hydrocarbons (AsHC) constitute one group of arsenolipids that have been identified in seafood. In this first in vivo toxicity study for AsHCs, we show that AsHCs exert toxic effects in Drosophila melanogaster in a concentration range similar to that of arsenite. In contrast to arsenite, however, AsHCs cause developmental toxicity in the late developmental stages of Drosophila melanogaster. This work illustrates the need for a full characterisation of the toxicity of AsHCs in experimental animals to finally assess the risk to human health related to the presence of arsenolipids in seafood.
Effective recognition of enzymatically active tetrameric acetylcholinesterase (AChE) is accomplished by a hybrid nanofilm composed of a propidium-terminated self-assembled monolayer (Prop-SAM) which binds AChE via its peripheral anionic site (PAS) and an ultrathin electrosynthesized molecularly imprinted polymer (MIP) cover layer of a novel carboxylate-modified derivative of 3,4-propylenedioxythiophene. The rebinding of the AChE to the MIP/Prop-SAM nanofilm covered electrode is detected by measuring in situ the enzymatic activity. The oxidative current of the released thiocholine is dependent on the AChE concentration from approximate to 0.04 x 10(-6) to 0.4 x 10(-6)m. An imprinting factor of 9.9 is obtained for the hybrid MIP, which is among the best values reported for protein imprinting. The dissociation constant characterizing the strength of the MIP-AChE binding is 4.2 x 10(-7)m indicating the dominant role of the PAS-Prop-SAM interaction, while the benefit of the MIP nanofilm covering the Prop-SAM layer is the effective suppression of the cross-reactivity toward competing proteins as compared with the Prop-SAM. The threefold selectivity gain provided by i) the shape-specific MIP filter, ii) the propidium-SAM, iii) signal generation only by the AChE bound to the nanofilm shows promise for assessing AChE activity levels in cerebrospinal fluid.
Questions: Which are the factors that influence forest and shrubland loss and regeneration and their underlying drivers?
Location: Central Chile, a world biodiversity hotspot.
Methods: Using land-cover data from the years 1975, 1985, 1999 and 2008, we fitted classification trees and multiple logistic regression models to account for the relationship between different trajectories of vegetation change and a range of biophysical and socio-economic factors.
Results: The variables that most consistently showed significant effects on vegetation change across all time-intervals were slope and distance to primary roads. We found that forest and shrubland loss on one side and regeneration on the other often displayed opposite patterns in relation to the different explanatory variables. Deforestation was positively related to distance to primary roads and to distance within forest edges and was favoured by a low insolation and a low slope. In turn, forest regeneration was negatively related to the distance to primary roads and positively to the distance to the nearest forest patch, insolation and slope. Shrubland loss was positively influenced by slope and distance to cities and primary roads and negatively influenced by distance to rivers. Conversely, shrubland regeneration was negatively related to slope, distance to cities and distance to primary roads and positively related to distance from existing forest patches and distance to rivers.
Conclusions: This article reveals how biophysical and socioeconomic factors influence vegetation cover change and the underlying social, political and economical drivers. This assessment provides a basis for management decisions, considering the crucial role of perennial vegetation cover for sustaining biodiversity and ecosystem services.
As WR 6 is a putatively single WN4 star, and is relatively bright (V = 6.9), it is an ideal case for studying the wind mechanisms in these extremely luminous stars. To obtain higher resolution spectra at higher energy (above 1 keV) than previously obtained with the XMM/Newton RGS, we have observed WR 6 with the Chandra High Energy Transmission Grating Spectrometer for 450 ks. We have resolved emission lines of S, Si, Mg, Ne, and Fe, which all show a “fin"-shaped prole, characteristic of a self-absorbed uniformly expanding shell. Steep blue edges gives robust maximal expansion velocities of about 2000 km/s, somewhat larger than the 1700km/s derived from UV lines. The He-like lines all indicate that X-ray emitting plasmas are far from the photosphere – even at the higher energies where opacity is lowest { as was also the case for the longer wavelength lines observed with XMM-Newton/RGS. Abundances determined from X-ray spectral modeling indicate enhancements consistent with nucleosynthesis. The star was also variable in X-rays and in simultaneous optical photometry obtained with Chandra aspect camera, but not coherently with the optically known period of 3.765 days.
We present an analysis of a 78 ks Chandra high-energy transmission gratings observation of the B0I star QV Nor, the massive donor of the wind-accreting pulsar 4U1538-52. The neutron star (NS) orbits its companion in a very close orbit (r < 1.4R(*), in units of the stellar radii), thereby allowing probing of the innermost wind regions. The flux of the Fe K alpha line during eclipse reduces to only similar to 30% of the flux measured out of eclipse. This indicates that the majority of Fe fluorescence must be produced in regions close to the NS, at distances smaller than 1R(*) from its surface. The fact that the flux of the continuum decreases to only similar to 3% during eclipse allows for a high contrast of the Fe Ka line fluorescence during eclipse. The line is not resolved and centered at lambda = 1.9368(-0.0018)(+0.0032) angstrom. From the inferred plasma speed limit of v < c Delta lambda/lambda < 800 km s(-1) and range of ionization parameters of log xi =[-1, 2], together with the stellar density profile, we constrain the location of the cold, dense material in the stellar wind of QV Nor using simple geometrical considerations. We then use the Fe K alpha line fluorescence as a tracer of wind clumps and determine that these clumps in the stellar wind of QV Nor (B0I) must already be present at radii r < 1.25R(*), close to the photosphere of the star.
Farber disease (FD) is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments are clinically available and affected patients have a severely shortened lifespan. Due to the low incidence, the pathogenesis of FD is still poorly understood. Here, we report a novel acid ceramidase mutant mouse model that enables the study of pathogenic mechanisms of FD and ceramide accumulation. Asah1(tmEx1) mice were generated by deletion of the acid ceramidase signal peptide sequence. The effects on lysosomal targeting and activity of the enzyme were assessed. Ceramide and sphingomyelin levels were quantified by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and disease manifestations in several organ systems were analyzed by histology and biochemistry. We show that deletion of the signal peptide sequence disrupts lysosomal targeting and enzyme activity, resulting in ceramide and sphingomyelin accumulation. The affected mice fail to thrive and die early. Histiocytic infiltrations were observed in many tissues, as well as lung inflammation, liver fibrosis, muscular disease manifestations and mild kidney injury. Our new mouse model mirrors human FD and thus offers further insights into the pathogenesis of this disease. In the future, it may also facilitate the development of urgently needed therapies.
With a deep Chandra/HETGS exposure of WR 6, we have resolved emission lines whose profiles show that the X-rays originate from a uniformly expanding spherical wind of high X-ray-continuum optical depth. The presence of strong helium-like forbidden lines places the source of X-ray emission at tens to hundreds of stellar radii from the photosphere. Variability was present in X-rays and simultaneous optical photometry, but neither were correlated with the known period of the system or with each other. An enhanced abundance of sodium revealed nuclear-processed material, a quantity related to the evolutionary state of the star. The characterization of the extent and nature of the hot plasma in WR 6 will help to pave the way to a more fundamental theoretical understanding of the winds and evolution of massive stars.
Time-resolved crystallography reveals allosteric communication aligned with molecular breathing
(2019)
A comprehensive understanding of protein function demands correlating structure and dynamic changes. Using time-resolved serial synchrotron crystallography, we visualized half-of-the-sites reactivity and correlated molecular-breathing motions in the enzyme fluoroacetate dehalogenase. Eighteen time points from 30 milliseconds to 30 seconds cover four turnover cycles of the irreversible reaction. They reveal sequential substrate binding, covalent-intermediate formation, setup of a hydrolytic water molecule, and product release. Small structural changes of the protein mold and variations in the number and placement of water molecules accompany the various chemical steps of catalysis. Triggered by enzyme-ligand interactions, these repetitive changes in the protein framework’s dynamics and entropy constitute crucial components of the catalytic machinery.
We present a ‘hit-and-return’ (HARE) method for time-resolved serial synchrotron crystallography with time resolution from milliseconds to seconds or longer. Timing delays are set mechanically, using the regular pattern in fixed-target crystallography chips and a translation stage system. Optical pump-probe experiments to capture intermediate structures of fluoroacetate dehalogenase binding to its ligand demonstrated that data can be collected at short (30 ms), medium (752 ms) and long (2,052 ms) intervals.