3,831 research outputs found
The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology
Background/Aims: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on the ARDS etiology and the dose. Methods: C57/BL6 mice were divided to be pre-treated with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage. Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups. ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h. Results: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β in ARDSp. The higher dose of dasatinib caused no changes in lung mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6, vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp. In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology, but careful dose monitoring is required. © 2015 S. Karger AG, Basel
Influence of apical oxygen on the extent of in-plane exchange interaction in cuprate superconductors
In high Tc superconductors the magnetic and electronic properties are
determined by the probability that valence electrons virtually jump from site
to site in the CuO2 planes, a mechanism opposed by on-site Coulomb repulsion
and favored by hopping integrals. The spatial extent of the latter is related
to transport properties, including superconductivity, and to the dispersion
relation of spin excitations (magnons). Here, for three antiferromagnetic
parent compounds (single-layer Bi2Sr0.99La1.1CuO6+delta, double-layer
Nd1.2Ba1.8Cu3O6 and infinite-layer CaCuO2) differing by the number of apical
atoms, we compare the magnetic spectra measured by resonant inelastic x-ray
scattering over a significant portion of the reciprocal space and with
unprecedented accuracy. We observe that the absence of apical oxygens increases
the in-plane hopping range and, in CaCuO2, it leads to a genuine 3D
exchange-bond network. These results establish a corresponding relation between
the exchange interactions and the crystal structure, and provide fresh insight
into the materials dependence of the superconducting transition temperature.Comment: 9 pages, 4 figures, 1 Table, 42 reference
Two-Centered Magical Charge Orbits
We determine the two-centered generic charge orbits of magical N = 2 and
maximal N = 8 supergravity theories in four dimensions. These orbits are
classified by seven U-duality invariant polynomials, which group together into
four invariants under the horizontal symmetry group SL(2,R). These latter are
expected to disentangle different physical properties of the two-centered
black-hole system. The invariant with the lowest degree in charges is the
symplectic product (Q1,Q2), known to control the mutual non-locality of the two
centers.Comment: 1+17 pages, 1 Table; v2: Eq. (3.23) corrected; v3: various
refinements in text and formulae, caption of Table 1 expanded, Footnote and
Refs. added. To appear on JHE
Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease
Background
Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes.
Methods
We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants.
Results
Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects.
Conclusions
Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application
Stringy effects in black hole decay
We compute the low energy decay rates of near-extremal three(four) charge
black holes in five(four) dimensional N=4 string theory to sub-leading order in
the large charge approximation. This involves studying stringy corrections to
scattering amplitudes of a scalar field off a black hole. We adapt and use
recently developed techniques to compute such amplitudes as near-horizon
quantities. We then compare this with the corresponding calculation in the
microscopic configuration carrying the same charges as the black hole. We find
perfect agreement between the microscopic and macroscopic calculations; in the
cases we study, the zero energy limit of the scattering cross section is equal
to four times the Wald entropy of the black hole.Comment: 32 page
First-order flows and stabilisation equations for non-BPS extremal black holes
We derive a generalised form of flow equations for extremal static and
rotating non-BPS black holes in four-dimensional ungauged N = 2 supergravity
coupled to vector multiplets. For particular charge vectors, we give
stabilisation equations for the scalars, analogous to the BPS case, describing
full known solutions. Based on this, we propose a generic ansatz for the
stabilisation equations, which surprisingly includes ratios of harmonic
functions.Comment: 27 pages; v2: presentation improved and references added as in the
published versio
Black holes and black strings of N=2, d=5 supergravity in the H-FGK formalism
We study general classes and properties of extremal and non-extremal static
black-hole solutions of N=2, d=5 supergravity coupled to vector multiplets
using the recently proposed H-FGK formalism, which we also extend to static
black strings. We explain how to determine the integration constants and
physical parameters of the black-hole and black-string solutions. We derive
some model-independent statements, including the transformation of non-extremal
flow equations to the form of those for the extremal flow. We apply our methods
to the construction of example solutions (among others a new extremal string
solution of heterotic string theory on K_3 \times S^1). In the cases where we
have calculated it explicitly, the product of areas of the inner and outer
horizon of a non-extremal solution coincides with the square of the
moduli-independent area of the horizon of the extremal solution with the same
charges.Comment: 33 pages. Revised version: references added. No other change
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