Detailed measurements of the electron densities, temperatures, and ionization states of compressed CH shells approaching pressures of 50 Mbar are achieved with spectrally resolved x-ray scattering. ...Laser-produced 9 keV x-rays probe the plasma during the transient state of three-shock coalescence. High signal-to-noise x-ray scattering spectra show direct evidence of continuum depression in highly degenerate warm dense matter states with electron densities ne>1024 cm-3. The measured densities and temperatures agree well with radiation-hydrodynamic modeling when accounting for continuum lowering in calculations that employ detailed configuration accounting.
The state and evolution of planets, brown dwarfs and neutron star crusts is determined by the properties of dense and compressed matter. Due to the inherent difficulties in modelling strongly coupled ...plasmas, however, current predictions of transport coefficients differ by orders of magnitude. Collective modes are a prominent feature, whose spectra may serve as an important tool to validate theoretical predictions for dense matter. With recent advances in free electron laser technology, X-rays with small enough bandwidth have become available, allowing the investigation of the low-frequency ion modes in dense matter. Here, we present numerical predictions for these ion modes and demonstrate significant changes to their strength and dispersion if dissipative processes are included by Langevin dynamics. Notably, a strong diffusive mode around zero frequency arises, which is not present, or much weaker, in standard simulations. Our results have profound consequences in the interpretation of transport coefficients in dense plasmas.
Central to inflammatory bowel disease (IBD) pathogenesis is loss of mucosal barrier function. Emerging evidence implicates extracellular adenosine signaling in attenuating mucosal inflammation. We ...hypothesized that adenosine-mediated protection from intestinal barrier dysfunction involves tissue-specific signaling through the A2B adenosine receptor (Adora2b) at the intestinal mucosal surface. To address this hypothesis, we combined pharmacologic studies and studies in mice with global or tissue-specific deletion of the Adora2b receptor. Adora2b(-/-) mice experienced a significantly heightened severity of colitis, associated with a more acute onset of disease and loss of intestinal epithelial barrier function. Comparison of mice with Adora2b deletion on vascular endothelial cells (Adora2b(fl/fl)VeCadCre(+)) or intestinal epithelia (Adora2b(fl/fl)VillinCre(+)) revealed a selective role for epithelial Adora2b signaling in attenuating colonic inflammation. In vitro studies with Adora2b knockdown in intestinal epithelial cultures or pharmacologic studies highlighted Adora2b-driven phosphorylation of vasodilator-stimulated phosphoprotein (VASP) as a specific barrier repair response. Similarly, in vivo studies in genetic mouse models or treatment studies with an Adora2b agonist (BAY 60-6583) recapitulate these findings. Taken together, our results suggest that intestinal epithelial Adora2b signaling provides protection during intestinal inflammation via enhancing mucosal barrier responses.
We present a method to determine the bulk temperature of a single crystal diamond sample at an X-Ray free electron laser using inelastic X-ray scattering. The experiment was performed at the high ...energy density instrument at the European XFEL GmbH, Germany. The technique, based on inelastic X-ray scattering and the principle of detailed balance, was demonstrated to give accurate temperature measurements, within Formula: see text for both room temperature diamond and heated diamond to 500 K. Here, the temperature was increased in a controlled way using a resistive heater to test theoretical predictions of the scaling of the signal with temperature. The method was tested by validating the energy of the phonon modes with previous measurements made at room temperature using inelastic X-ray scattering and neutron scattering techniques. This technique could be used to determine the bulk temperature in transient systems with a temporal resolution of 50 fs and for which accurate measurements of thermodynamic properties are vital to build accurate equation of state and transport models.
High‐resolution inelastic X‐ray scattering is an established technique in the synchrotron community, used to investigate collective low‐frequency responses of materials. When fielded at hard X‐ray ...free‐electron lasers (XFELs) and combined with high‐intensity laser drivers, it becomes a promising technique for investigating matter at high temperatures and high pressures. This technique gives access to important thermodynamic properties of matter at extreme conditions, such as temperature, material sound speed, and viscosity. The successful realization of this method requires the acquisition of many identical laser‐pump/X‐ray‐probe shots, allowing the collection of a sufficient number of photons necessary to perform quantitative analyses. Here, a 2.5‐fold improvement in the energy resolution of the instrument relative to previous works at the Matter in Extreme Conditions (MEC) endstation, Linac Coherent Light Source (LCLS), and the High Energy Density (HED) instrument, European XFEL, is presented. Some aspects of the experimental design that are essential for improving the number of photons detected in each X‐ray shot, making such measurements feasible, are discussed. A careful choice of the energy resolution, the X‐ray beam mode provided by the XFEL, and the position of the analysers used in such experiments can provide a more than ten‐fold improvement in the photometrics. The discussion is supported by experimental data on 10 µm‐thick iron and 50 nm‐thick gold samples collected at the MEC endstation at the LCLS, and by complementary ray‐tracing simulations coupled with thermal diffuse scattering calculations.
High‐resolution inelastic X‐ray scattering measurements at hard X‐ray free‐electron lasers coupled with energetic laser drivers have shown a 2.5‐fold improved energy resolution compared with previous experiments at similar XFEL instruments. Aspects of the experimental design that can be adjusted to improve the number of recorded photons on the detector are discussed.
PAX8-PPARγ1 Fusion in Oncogene Human Thyroid Carcinoma Kroll, Todd G.; Sarraf, Pasha; Pecciarini, Lorenza ...
Science (American Association for the Advancement of Science),
08/2000, Letnik:
289, Številka:
5483
Journal Article
Recenzirano
Chromosomal translocations that encode fusion oncoproteins have been observed consistently in leukemias/lymphomas and sarcomas but not in carcinomas, the most common human cancers. Here, we report ...that t(2;3)(q13;p25), a translocation identified in a subset of human thyroid follicular carcinomas, results in fusion of the DNA binding domains of the thyroid transcription factor PAX8 to domains A to F of the peroxisome proliferator-activated receptor (PPAR) γ1. PAX8-PPARγ1 mRNA and protein were detected in 5 of 8 thyroid follicular carcinomas but not in 20 follicular adenomas, 10 papillary carcinomas, or 10 multinodular hyperplasias. PAX8-PPARγ1 inhibited thiazolidinedione-induced transactivation by PPARγ1 in a dominant negative manner. The experiments demonstrate an oncogenic role for PPARγ and suggest that PAX8-PPARγ1 may be useful in the diagnosis and treatment of thyroid carcinoma.
In higher plants there are two forms of ferredoxin NADP+ oxidoreductase (FNR), a photosynthetic pFNR primarily required for the photoreduction of NADP+, and a heterotrophic hFNR which generates ...reduced ferredoxin by utilizing electrons from NADPH produced during carbohydrate oxidation. The aim of this study was to investigate the presence of multiple forms of FNR in wheat leaves and the capacity of FNR isoforms to respond to changes in reductant demand through varied expression and N-terminal processing. Two forms of pFNR mRNA (pFNRI and pFNRII) were expressed in a similar pattern along the 12 cm developing primary wheat leaf, with the highest levels observed in plants grown continuously in the dark in the presence (pFNRI) or absence (pFNRII) of nitrate respectively. pFNR protein increased from the leaf base to tip. hFNR mRNA and protein was in the basal part of the leaf in plants grown in the presence of nitrate. FNR activity in plants grown in a light/dark cycle without nitrate was mainly due to pFNR, whilst hFNR contributed significantly in nitrate-fed plants. The potential role of distinct forms of FNR in meeting the changing metabolic capacity and reductant demands along the linear gradient of developing cells of the leaf are discussed. Furthermore, evidence for alternative N-terminal cleavage sites of pFNR acting as a means of discriminating between ferredoxins and the implications of this in providing a more effective flow of electrons through a particular pathway in vivo is considered.
PDF
