Changes in Binding of [(123)I]CLINDE, a High-Affinity Translocator Protein 18 kDa (TSPO) Selective Radioligand in a Rat Model of Traumatic Brain Injury

After traumatic brain injury (TBI), secondary injuries develop, including neuroinflammatory processes that contribute to long-lasting impairments. These secondary injuries represent potential targets for treatment and diagnostics. The translocator protein 18 kDa (TSPO) is expressed in activated microglia cells and upregulated in response to brain injury and therefore a potential biomarker of the neuroinflammatory processes. Second-generation radioligands of TSPO, such as [123I]CLINDE, have a higher signal-to-noise ratio as the prototype ligand PK11195. [123I]CLINDE has been employed in human studies using single-photon emission computed tomography to image the neuroinflammatory response after stroke. In this study, we used the same tracer in a rat model of TBI to determine changes in TSPO expression. Adult Sprague– Dawley rats were subjected to moderate controlled cortical impact injury and sacrificed at 6, 24, 72 h and 28 days post surgery. TSPO expression was assessed in brain sections employing [123I]CLINDE in vitro autoradiography. From 24 h to 28 days post surgery, injured animals exhibited a marked and time-dependent increase in [123I]CLINDE binding in the ipsilateral motor, somatosensory and parietal cortex, as well as in the hippocampus and thalamus. Interestingly, binding was also significantly elevated in the contralateral M1 motor cortex following TBI. Craniotomy without TBI caused a less marked increase in [123I] CLINDE binding, restricted to the ipsilateral hemisphere. Radioligand binding was consistent with an increase in TSPO mRNA expression and CD11b immunoreactivity at the contusion site. This study demonstrates the applicability of [123I]CLINDE for detailed regional and quantitative assessment of glial activity in experimental models of TBI

The effect of skin fatty acids on Staphylococcus aureus

Staphylococcus aureus is a commensal of the human nose and skin. Human skin fatty acids, in particular cis-6-hexadecenoic acid (C-6-H), have high antistaphylococcal activity and can inhibit virulence determinant production. Here, we show that sub-MIC levels of C-6-H result in induction of increased resistance. The mechanism(s) of C-6-H activity was investigated by combined transcriptome and proteome analyses. Proteome analysis demonstrated a pleiotropic effect of C-6-H on virulence determinant production. In response to C-6-H, transcriptomics revealed altered expression of over 500 genes, involved in many aspects of virulence and cellular physiology. The expression of toxins (hla, hlb,hlgBC) was reduced, whereas that of host defence evasion components (cap, sspAB, katA) was increased. In particular, members of the SaeRS regulon had highly reduced expression, and the use of specific mutants revealed that the effect on toxin production is likely mediated via SaeRS

Associations between <i>paratuberculosis</i> status and milk production traits in Holstein cattle under consideration of interaction effects between test result and farm and lactation number

One of the most important factors for economic losses as result of infection with Mycobacterium avium ssp. paratuberculosis (MAP) is the decrease in milk yield. Different phenotyping methods for MAP lead to an inconsistent impact of MAP infection on milk parameters. It was the aim of the study to analyse the effect of the MAP status on milk yield, milk fat and milk protein (in kilograms), as well as on the calving interval and milk kilograms per day of life in German Holstein cattle. A dataset of 9&thinsp;367 faecal culture tested animals from 14 farms in Thuringia (Germany) were available. The MAP status of the animals affected milk yield and the milk parameters. Beside the effects of farm, lactation number and MAP status, the interaction between MAP status and farm on the milk parameters was significant. The latter result is a possible explanation for the inconsistent results from recent studies. For milk kg per day of life, the interaction between lactation number and MAP status also showed significance

Relativistic hydrodynamics on spacelike and null surfaces: Formalism and computations of spherically symmetric spacetimes

We introduce a formulation of Eulerian general relativistic hydrodynamics which is applicable for (perfect) fluid data prescribed on either spacelike or null hypersurfaces. Simple explicit expressions for the characteristic speeds and fields are derived in the general case. A complete implementation of the formalism is developed in the case of spherical symmetry. The algorithm is tested in a number of different situations, predisposing for a range of possible applications. We consider the Riemann problem for a polytropic gas, with initial data given on a retarded/advanced time slice of Minkowski spacetime. We compute perfect fluid accretion onto a Schwarzschild black hole spacetime using ingoing null Eddington-Finkelstein coordinates. Tests of fluid evolution on dynamic background include constant density and TOV stars sliced along the radial null cones. Finally, we consider the accretion of self-gravitating matter onto a central black hole and the ensuing increase in the mass of the black hole horizon.Comment: 23 pages, 13 figures, submitted to Phys. Rev.

Numerical simulation of small perturbation on an accretion disk due to the collision of a star with the disk near the black hole

In this paper, perturbations of an accretion disk by a star orbiting around a black hole are studied. We report on a numerical experiment, which has been carried out by using a parallel-machine code originally developed by D\"{o}nmez (2004). An initially steady state accretion disk near a non-rotating (Schwarzschild) black hole interacts with a "star", modeled as an initially circular region of increased density. Part of the disk is affected by the interaction. In some cases, a gap develops and shock wave propagates through the disk. We follow the evolution for order of one dynamical period and we show how the non-axisymetric density perturbation further evolves and moves downwards where the material of the disk and the star become eventually accreted onto the central body. When the star perturbs the steady state accretion disk, the disk around the black hole is destroyed by the effect of perturbation. The perturbed accretion disk creates a shock wave during the evolution and it loses angular momentum when the gas hits on the shock waves. Colliding gas with the shock wave is the one of the basic mechanism of emitting the $X-$rays in the accretion disk. The series of supernovae occurring in the inner disk could entirely destroy the disk in that region which leaves a more massive black hole behind, at the center of galaxies.Comment: 20pages, 8 figures, accepted for publication in Astrophysics and Space Scienc

Projections of global warming-induced impacts on winter storm losses in the German private household sector

We present projections of winter storm-induced insured losses in the German residential building sector for the 21st century. With this aim, two structurally most independent downscaling methods and one hybrid downscaling method are applied to a 3-member ensemble of ECHAM5/MPI-OM1 A1B scenario simulations. One method uses dynamical downscaling of intense winter storm events in the global model, and a transfer function to relate regional wind speeds to losses. The second method is based on a reshuffling of present day weather situations and sequences taking into account the change of their frequencies according to the linear temperature trends of the global runs. The third method uses statistical-dynamical downscaling, considering frequency changes of the occurrence of storm-prone weather patterns, and translation into loss by using empirical statistical distributions. The A1B scenario ensemble was downscaled by all three methods until 2070, and by the (statistical-) dynamical methods until 2100. Furthermore, all methods assume a constant statistical relationship between meteorology and insured losses and no developments other than climate change, such as in constructions or claims management. The study utilizes data provided by the German Insurance Association encompassing 24 years and with district-scale resolution. Compared to 1971–2000, the downscaling methods indicate an increase of 10-year return values (i.e. loss ratios per return period) of 6–35 % for 2011–2040, of 20–30 % for 2041–2070, and of 40–55 % for 2071–2100, respectively. Convolving various sources of uncertainty in one confidence statement (data-, loss model-, storm realization-, and Pareto fit-uncertainty), the return-level confidence interval for a return period of 15 years expands by more than a factor of two. Finally, we suggest how practitioners can deal with alternative scenarios or possible natural excursions of observed losses

Double-detonation supernovae of sub-Chandrasekhar mass white dwarfs

In the "double-detonation sub-Chandrasekhar" model for type Ia supernovae, a carbon-oxygen (C + O) white dwarf accumulates sufficient amounts of helium such that a detonation ignites in that layer before the Chandrasekhar mass is reached. This detonation is thought to trigger a secondary detonation in the C + O core. By means of one- and two-dimensional hydrodynamic simulations, we investigate the robustness of this explosion mechanism for generic 1-M_sun models and analyze its observable predictions. Also a resolution dependence in numerical simulations is analyzed. The propagation of thermonuclear detonation fronts, both in helium and in the carbon-oxygen mixture, is computed by means of both a level-set function and a simplified description for nuclear reactions. The decision whether a secondary detonation is triggered in the white dwarf's core or not is made based on criteria given in the literature. In a parameter study involving different initial flame geometries for He-shell masses of 0.2 and 0.1 M_sun, we find that a secondary detonation ignition is a very robust process. Converging shock waves originating from the detonation in the He shell generate the conditions for a detonation near the center of the white dwarf in most of the cases considered. Finally, we follow the complete evolution of three selected models with 0.2 M_sun of He through the C/O-detonation phase and obtain nickel-masses of about 0.40 to 0.45 M_sun. Although we have not done a complete scan of the possible parameter space, our results show that sub-Chandrasekhar models are not good candidates for normal or sub-luminous type Ia supernovae. The chemical composition of the ejecta features significant amounts of nickel in the outer layers at high expansion velocities, which is inconsistent with near-maximum spectra. (abbreviated)Comment: 11 pages, 10 figures, PDFLaTeX, accepted for publication in A&

Determinantal Characterization of Canonical Curves and Combinatorial Theta Identities

We characterize genus g canonical curves by the vanishing of combinatorial products of g+1 determinants of Brill-Noether matrices. This also implies the characterization of canonical curves in terms of (g-2)(g-3)/2 theta identities. A remarkable mechanism, based on a basis of H^0(K_C) expressed in terms of Szego kernels, reduces such identities to a simple rank condition for matrices whose entries are logarithmic derivatives of theta functions. Such a basis, together with the Fay trisecant identity, also leads to the solution of the question of expressing the determinant of Brill-Noether matrices in terms of theta functions, without using the problematic Klein-Fay section sigma.Comment: 35 pages. New results, presentation improved, clarifications added. Accepted for publication in Math. An

Three Dimensional Numerical General Relativistic Hydrodynamics I: Formulations, Methods, and Code Tests

This is the first in a series of papers on the construction and validation of a three-dimensional code for general relativistic hydrodynamics, and its application to general relativistic astrophysics. This paper studies the consistency and convergence of our general relativistic hydrodynamic treatment and its coupling to the spacetime evolutions described by the full set of Einstein equations with a perfect fluid source. The numerical treatment of the general relativistic hydrodynamic equations is based on high resolution shock capturing schemes. These schemes rely on the characteristic information of the system. A spectral decomposition for general relativistic hydrodynamics suitable for a general spacetime metric is presented. Evolutions based on three different approximate Riemann solvers coupled to four different discretizations of the Einstein equations are studied and compared. The coupling between the hydrodynamics and the spacetime (the right and left hand side of the Einstein equations) is carried out in a treatment which is second order accurate in {\it both} space and time. Convergence tests for all twelve combinations with a variety of test beds are studied, showing consistency with the differential equations and correct convergence properties. The test-beds examined include shocktubes, Friedmann-Robertson-Walker cosmology tests, evolutions of self-gravitating compact (TOV) stars, and evolutions of relativistically boosted TOV stars. Special attention is paid to the numerical evolution of strongly gravitating objects, e.g., neutron stars, in the full theory of general relativity, including a simple, yet effective treatment for the surface region of the star (where the rest mass density is abruptly dropping to zero).Comment: 45 pages RevTeX, 34 figure