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We report on simultaneous broadband observations of the TeV-emitting blazar Markarian 501 between 2013 April 1 and August 10, including the first detailed characterization of the synchrotron peak with Swift and NuSTAR. During the campaign, the nearby BL Lac object was observed in both a quiescent and an elevated state. The broadband campaign includes observations with NuSTAR, MAGIC, VERITAS, the Fermi Large Area Telescope, Swift X-ray Telescope and UV Optical Telescope, various ground-based optical instruments, including the GASP-WEBT program, as well as radio observations by OVRO, Metsahovi, and the F-Gamma consortium. Some of the MAGIC observations were affected by a sand layer from the Saharan desert, and had to be corrected using event-by-event corrections derived with a Light Detection and Ranging (LIDAR) facility. This is the first time that LIDAR information is used to produce a physics result with Cherenkov Telescope data taken during adverse atmospheric conditions, and hence sets a precedent for the current and future ground-based gamma-ray instruments. The NuSTAR instrument provides unprecedented sensitivity in hard X-rays, showing the source to display a spectral energy distribution (SED) between 3 and 79 keV consistent with a log-parabolic spectrum and hard X-ray variability on hour timescales. None (of the four extended NuSTAR observations) show evidence of the onset of inverse-Compton emission at hard X-ray energies. We apply a single-zone equilibrium synchrotron self-Compton (SSC) model to five simultaneous broadband SEDs. We find that the SSC model can reproduce the observed broadband states through a decrease in the magnetic field strength coinciding with an increase in the luminosity and hardness of the relativistic leptons responsible for the high-energy emission.
Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
Novel nanogels that possess the capacity to change their physico-chemical properties in response to external stimuli are promising drug-delivery candidates for the treatment of severe skin diseases. As thermoresponsive nanogels (tNGs) are capable of enhancing penetration through biological barriers such as the stratum corneum and are taken up by keratinocytes of human skin, potential adverse consequences of their exposure must be elucidated. In this study, tNGs were synthesized from dendritic polyglycerol (dPG) and two thermoresponsive polymers. tNG_dPG_tPG are the combination of dPG with poly(glycidyl methyl ether-co-ethyl glycidyl ether) (p(GME-co-EGE)) and tNG_dPG_pNIPAM the one with poly(N-isopropylacrylamide) (pNIPAM). Both thermoresponsive nanogels are able to incorporate high amounts of dexamethasone and tacrolimus, drugs used in the treatment of severe skin diseases. Cellular uptake, intracellular localization and the toxicological properties of the tNGs were comprehensively characterized in primary normal human keratinocytes (NHK) and in spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (HaCaT). Laser scanning confocal microscopy revealed fluorescently labeled tNGs entered into the cells and localized predominantly within lysosomal compartments. MTT assay, comet assay and carboxy-H2DCFDA assay, demonstrated neither cytotoxic or genotoxic effects, nor any induction of reactive oxygen species of the tNGs in keratinocytes. In addition, both tNGs were devoid of eye irritation potential as shown by bovine corneal opacity and permeability (BCOP) test and red blood cell (RBC) hemolysis assay. Therefore, our study provides evidence that tNGs are locally well tolerated and underlines their potential for cutaneous drug delivery.
The implementation of a high-transmission, angular-resolved time-of-Right electron spectrometer with a 1.25 MHz pulse selector at the PM4 soft X-ray dipole beamline of the synchrotron BESSY II creates unique capabilities to inquire electronic structure via photoelectron spectroscopy with a minimum of radiation dose. Solid-state samples can be prepared and characterized with standard UHV techniques and rapidly transferred from various preparation chambers to a 4-axis temperature-controlled measurement stage. A synchronized MHz laser system enables excited-state characterization and dynamical studies starting from the picosecond timescale. This article introduces the principal characteristics of the PM4 beamline and LowDosePES end-station. Recent results from graphene, an organic hole transport material for solar cells and the transition metal dichalcogenide MoS2 are presented to demonstrate the instrument performances.
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.
Aim: Fossil pollen spectra from lake sediments on the Tibetan Plateau have been used for qualitative climate reconstruction, but no modern pollen-climate calibration set based on lake sediments is available to infer past climate quantitatively. This study aims to develop such a dataset and apply it to fossil data. Location: The Tibetan Plateau, between 30 and 40 degrees N and 87 and 103 degrees E. Methods: We collected surface sediments from 112 lakes and analysed them palynologically. The lakes span a wide range of mean annual precipitation (P-ann; 31-1022 mm), mean annual temperature (T-ann; -6.5 to 1 degrees C), and mean July temperature (T-July; 2.6-19.7 degrees C). Redundancy analysis showed that the modern pollen spectra are characteristic of their respective vegetation types and local climate. Transfer functions for P-ann, T-ann and T-July were developed with weighted averaging partial least squares. Model performance was assessed by leave-one-out cross-validation. Results: The root mean square errors of prediction (RMSEP) were 104 mm (P-ann), 1.18 degrees C (T-ann) and 1.17 degrees C (T-July). The RMSEPs, when expressed as percentages of the gradient sampled, were 10.6% (P-ann), 15.7% (T-ann) and 11.9% (T-July). These low values indicate the good performance of our models. An application of the models to fossil pollen spectra covering the last c. 50 kyr yielded realistic results for Luanhaizi Lake in the Qilian Mountains on the north-eastern Tibetan Plateau (modern P-ann 480 mm; T-ann-1 degrees C). T-ann and P-ann values similar to present ones were reconstructed for late Marine Isotope Stage 3, with minimum values for the Last Glacial Maximum (c. 300 mm and 2 degrees C below present), and maximum values for the early Holocene (c. 70 mm and 0.5 degrees C greater than present). Main conclusions: The modern pollen-climate calibration set will potentially be useful for quantitative climate reconstructions from lake-sediment pollen spectra from the Tibetan Plateau, an area of considerable climatic and biogeographical importance.
We utilized femtosecond time-resolved resonant inelastic X-ray scattering and ab initio theory to study the transient electronic structure and the photoinduced molecular dynamics of a model metal carbonyl photocatalyst Fe(CO)(5) in ethanol solution. We propose mechanistic explanation for the parallel ultrafast intra-molecular spin crossover and ligation of the Fe(CO)(4) which are observed following a charge transfer photoexcitation of Fe(CO)(5) as reported in our previous study [ Wernet et al., Nature 520, 78 (2015)]. We find that branching of the reaction pathway likely happens in the (1)A(1) state of Fe(CO)(4). A sub-picosecond time constant of the spin crossover from B-1(2) to B-3(2) is rationalized by the proposed B-1(2) -> (1)A(1) -> B-3(2) mechanism. Ultrafast ligation of the B-1(2) Fe(CO)(4) state is significantly faster than the spin-forbidden and diffusion limited ligation process occurring from the B-3(2) Fe(CO)(4) ground state that has been observed in the previous studies. We propose that the ultrafast ligation occurs via B-1(2) -> (1)A(1) -> (1)A'Fe(CO)(4)EtOH pathway and the time scale of the (1)A(1) Fe(CO)(4) state ligation is governed by the solute-solvent collision frequency. Our study emphasizes the importance of understanding the interaction of molecular excited states with the surrounding environment to explain the relaxation pathways of photoexcited metal carbonyls in solution. (C) 2016 Author(s).
Recent PIC simulations of relativistic electron-positron (electron-ion) jets injected into a stationary medium show that particle acceleration occurs in the shocked regions. Simulations show that the Weibel instability is responsible for generating and amplifying highly nonuniform, small-scale magnetic fields and for particle acceleration. These magnetic fields contribute to the electron’s transverse eflection behind the shock. The “jitter” radiation from deflected electrons in turbulent magnetic fields has properties different from synchrotron radiation calculated in a uniform magnetic field. This jitter radiation may be important for understanding the complex time evolution and/or spectral structure of gamma-ray bursts, relativistic jets in general, and supernova remnants. In order to calculate radiation from first principles and go beyond the standard synchrotron model, we have used PIC simulations. We present synthetic spectra to compare with the spectra obtained from Fermi observations.
Magnetic agnetic field generation in core-sheath jets via the kinetic Kelvin-Helmholtz instability
(2014)
We have investigated magnetic field generation in velocity shears via the kinetic Kelvin-Helmholtz instability (kKHI) using a relativistic plasma jet core and stationary plasma sheath. Our three-dimensional particle-in-cell simulations consider plasma jet cores with Lorentz factors of 1.5, 5, and 15 for both electron-proton and electron-positron plasmas. For electron-proton plasmas, we find generation of strong large-scale DC currents and magnetic fields that extend over the entire shear surface and reach thicknesses of a few tens of electron skin depths. For electron-positron plasmas, we find generation of alternating currents and magnetic fields. Jet and sheath plasmas are accelerated across the shear surface in the strong magnetic fields generated by the kKHI. The mixing of jet and sheath plasmas generates a transverse structure similar to that produced by the Weibel instability.