Comparison of porcine thorax to gelatine blocks for wound

Published online first in International Journal of Legal Medicine. The support of EPSRC and The Home Office are recognised. Open Access, this article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:/ /creativecommons.org/licenses/by/4.0/)Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 × 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 × 45 Federal Premium® Tactical® Bonded®) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations,though greater debris was produced in the thoraxes.The support of EPSRC and The Home Office are recognised

Cerebellar Abiotrophy in Two Related Lion-tailed Macaques (Macaca silenus)

Cerebellar abiotrophy is a degenerative condition characterized by either early or late onset of severe neurological deficits caused by the marked depletion of Purkinje cells and granule cell neurons of the cerebellar cortex. The condition has been reported in numerous species with a proposed genetic basis of transmission. Here we present the anatomopathological investigation of two closely related lion-tailed macaques. Both cases, a 9-month-old male and a 4-month-old female, shared a long history of progressively worsening ataxia, incoordination and delayed body growth. Based on the characteristic findings, diagnoses of cerebellar abiotrophy were made. The relatedness of the two cases strongly supports an inherited mode of transmission. To the authors’ knowledge, this is the first report of cerebellar abiotrophy in a macaque species

The protective performance of selected UK police body armor challenged by M75 grenades

UK Police ‘soft’ body armor is designed to provide protection from sharp-weapons and low-velocity pistol ammunition; if ‘hard’ armor plates are fitted then high-velocity rifle protection is provided. Several different levels of protection for both soft and hard armor are available and these are tailored to the individual police officers’ role. The level of protection offered by these types of armor from fragmentation threats is not known as fragmentation is not typically considered a threat to UK Police Officers. However, fragmentation from devices such as grenades may be a threat to certain specialized units and during terrorist incidents. In this work, neither the soft nor hard UK Police body armor (HG2 and RF1 respectively) investigated were perforated when challenged by M75 Yugoslavian grenades at a distance of 1 m from the point of detonation. The effect due to blast was not considered. The work has provided confidence regarding the performance of selected police body armor against fragmentation from a selected grenade threat

Reconstructing the massive black hole cosmic history through gravitational waves

The massive black holes we observe in galaxies today are the natural end-product of a complex evolutionary path, in which black holes seeded in proto-galaxies at high redshift grow through cosmic history via a sequence of mergers and accretion episodes. Electromagnetic observations probe a small subset of the population of massive black holes (namely, those that are active or those that are very close to us), but planned space-based gravitational-wave observatories such as the Laser Interferometer Space Antenna (LISA) can measure the parameters of ``electromagnetically invisible'' massive black holes out to high redshift. In this paper we introduce a Bayesian framework to analyze the information that can be gathered from a set of such measurements. Our goal is to connect a set of massive black hole binary merger observations to the underlying model of massive black hole formation. In other words, given a set of observed massive black hole coalescences, we assess what information can be extracted about the underlying massive black hole population model. For concreteness we consider ten specific models of massive black hole formation, chosen to probe four important (and largely unconstrained) aspects of the input physics used in structure formation simulations: seed formation, metallicity ``feedback'', accretion efficiency and accretion geometry. For the first time we allow for the possibility of ``model mixing'', by drawing the observed population from some combination of the ``pure'' models that have been simulated. A Bayesian analysis allows us to recover a posterior probability distribution for the ``mixing parameters'' that characterize the fractions of each model represented in the observed distribution. Our work shows that LISA has enormous potential to probe the underlying physics of structure formation.Comment: 24 pages, 16 figures, submitted to Phys. Rev.

Direct cosmological simulations of the growth of black holes and galaxies

We investigate the coupled formation and evolution of galaxies and their embedded supermassive black holes using state-of-the-art hydrodynamic simulations of cosmological structure formation. For the first time, we self-consistently follow the dark matter dynamics, radiative gas cooling, star formation, as well as black hole growth and associated feedback processes, starting directly from initial conditions appropriate for the LambdaCDM cosmology. Our modeling of the black hole physics is based on an approach we have developed in simulations of isolated galaxy mergers. Here we examine: (i) the predicted global history of black hole mass assembly (ii) the evolution of the local black hole-host mass correlations and (iii) the conditions that allow rapid growth of the first quasars, and the properties of their hosts and descendants today. We find a total black hole mass density in good agreement with observational estimates. The black hole accretion rate density peaks at lower redshift and evolves more strongly at high redshift than the star formation rate density, but the ratio of black hole to stellar mass densities shows only a moderate evolution at low redshifts. We find strong correlations between black hole masses and properties of the stellar systems, agreeing well with the measured local M_BH-sigma and M_BH -M_* relationships, but also suggesting (dependent on the mass range) a weak evolution with redshift in the normalization and the slope. Our simulations also produce massive black holes at high redshift, due to extended periods of exponential growth in regions that collapse early and exhibit strong gas inflows. These first supermassive BH systems however are not necessarily the most massive ones today, since they are often overtaken in growth by quasars that form later. (abridged)Comment: 22 pages, 17 figures, submitted to Ap

Toward precise constraints on growth of massive black holes

Growth of massive black holes (MBHs) in galactic centers comes mainly from gas accretion during their QSO/AGN phases. In this paper we apply an extended Soltan argument, connecting the local MBH mass function with the time-integral of the QSO luminosity function, to the demography of MBHs and QSOs from recent optical and X-ray surveys, and obtain robust constraints on the luminosity evolution (or mass growth history) of individual QSOs (or MBHs). We find that the luminosity evolution probably involves two phases: an initial exponentially increasing phase set by the Eddington limit and a following phase in which the luminosity declines with time as a power law (with a slope of -1.2--1.3) set by a self-similar long-term evolution of disk accretion. Neither an evolution involving only the increasing phase with a single Eddington ratio nor an exponentially declining pattern in the second phase is likely. The period of a QSO radiating at a luminosity higher than 10% of its peak value is about (2-3)x10^8 yr, during which the MBH obtains ~80% of its mass. The mass-to-energy conversion efficiency is $0.16\pm0.04 ^{+0.05}_{-0}$, with the latter error accounting for the maximum uncertainty due to Compton-thick AGNs. The expected Eddington ratios in QSOs from the constrained luminosity evolution cluster around a single value close to 0.5-1 for high-luminosity QSOs and extend to a wide range of lower values for low-luminosity ones. The Eddington ratios for high luminosity QSOs appear to conflict with those estimated from observations (~0.25) by using some virial mass estimators for MBHs in QSOs unless the estimators systematically over-estimate MBH masses by a factor of 2-4. We also infer the fraction of optically obscured QSOs ~60-80%. Further applications of the luminosity evolution of individual QSOs are also discussed.Comment: 25 pages, 13 figures, ApJ in pres

Gravitational waves from resolvable massive black hole binary systems and observations with Pulsar Timing Arrays

Massive black holes are key components of the assembly and evolution of cosmic structures and a number of surveys are currently on-going or planned to probe the demographics of these objects and to gain insight into the relevant physical processes. Pulsar Timing Arrays (PTAs) currently provide the only means to observe gravitational radiation from massive black hole binary systems with masses >10^7 solar masses. The whole cosmic population produces a stochastic background that could be detectable with upcoming Pulsar Timing Arrays. Sources sufficiently close and/or massive generate gravitational radiation that significantly exceeds the level of the background and could be individually resolved. We consider a wide range of massive black hole binary assembly scenarios, we investigate the distribution of the main physical parameters of the sources, such as masses and redshift, and explore the consequences for Pulsar Timing Arrays observations. Depending on the specific massive black hole population model, we estimate that on average at least one resolvable source produces timing residuals in the range ~5-50 ns. Pulsar Timing Arrays, and in particular the future Square Kilometre Array (SKA), can plausibly detect these unique systems, although the events are likely to be rare. These observations would naturally complement on the high-mass end of the massive black hole distribution function future surveys carried out by the Laser Interferometer Space Antenna (LISA)Comment: 12 pages, 10 figures, accepted for publication in MNRAS. Results revised (differences within a factor of two) after a bug in the code for generating the timing residuals has been fixe

Reciprocal regulation of PKA and rac signaling

Activated G protein-coupled receptors (GPCRs) and receptor tyrosine kinases relay extracellular signals through spatial and temporal controlled kinase and GTPase entities. These enzymes are coordinated by multifunctional scaffolding proteins for precise intracellular signal processing. The cAMP-dependent protein kinase A (PKA) is the prime example for compartmentalized signal transmission downstream of distinct GPCRs. A-kinase anchoring proteins tether PKA to specific intracellular sites to ensure precision and directionality of PKA phosphorylation events. Here, we show that the Rho-GTPase Rac contains A-kinase anchoring protein properties and forms a dynamic cellular protein complex with PKA. The formation of this transient core complex depends on binary interactions with PKA subunits, cAMP levels and cellular GTP-loading accounting for bidirectional consequences on PKA and Rac downstream signaling. We show that GTP-Rac stabilizes the inactive PKA holoenzyme. However, β-adrenergic receptor-mediated activation of GTP-Rac–bound PKA routes signals to the Raf-Mek-Erk cascade, which is critically implicated in cell proliferation. We describe a further mechanism of how cAMP enhances nuclear Erk1/2 signaling: It emanates from transphosphorylation of p21-activated kinases in their evolutionary conserved kinase-activation loop through GTP-Rac compartmentalized PKA activities. Sole transphosphorylation of p21-activated kinases is not sufficient to activate Erk1/2. It requires complex formation of both kinases with GTP-Rac1 to unleash cAMP-PKA–boosted activation of Raf-Mek-Erk. Consequently GTP-Rac functions as a dual kinase-tuning scaffold that favors the PKA holoenzyme and contributes to potentiate Erk1/2 signaling. Our findings offer additional mechanistic insights how β-adrenergic receptor-controlled PKA activities enhance GTP-Rac–mediated activation of nuclear Erk1/2 signaling

Inflammatory Mediators in the Mesenteric Lymph Nodes, Site of a Possible Intermediate Phase in the Immune Response to Feline Coronavirus and the Pathogenesis of Feline Infectious Peritonitis?

Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response. Natural initial enteric FCoV infection may remain subclinical, or result in mild enteric signs or the development of FIP; cats may also carry the virus systemically with no adverse effect. This study screened mesenteric lymph nodes (MLNs), the presumed first site of FCoV spread from the intestine regardless of viraemia, for changes in the transcription of a panel of innate immune response mediators in response to systemic FCoV infection and with FIP, aiming to identify key pathways triggered by FCoV. Cats with and without FIP, the latter with and without FCoV infection in the MLN, were compared. Higher expression levels in FIP were found for toll-like receptors (TLRs) 2, 4 and 8. These are part of the first line of defence and suggest a response to both viral structural proteins and viral nucleic acid. Expression of genes encoding inflammatory cytokines and chemokines, including interleukin (IL)-1β, IL-6, IL-15, tumour necrosis factor (TNF)-α, CXCL10, CCL8, interferon (IFN)-α, IFN-β and IFN-γ, was higher in cats with FIP, consistent with inflammatory pathway activation. Expression of genes encoding transcription factors STAT1 and 2, regulating signalling pathways, particularly of the interferons, was also higher. Among cats without FIP, there were few differences between virus-positive and virus-negative MLNs; however, TLR9 and STAT2 expression were higher with infection, suggesting a direct viral effect. The study provides evidence for TLR involvement in the response to FCoV. This could open up new avenues for therapeutic approaches

Gas driven massive black hole binaries: signatures in the nHz gravitational wave background

Pulsar timing arrays (PTAs) measure nHz frequency gravitational waves (GWs) generated by orbiting massive black hole binaries (MBHBs) with periods between 0.1-10 yr. Previous studies on the nHz GW background assumed that the inspiral is purely driven by GWs. However, torques generated by a gaseous disk can shrink the binary much more efficiently than GW emission, reducing the number of binaries at these separations. We use simple disk models for the circumbinary gas and for the binary-disk interaction to follow the orbital decay of MBHBs through physically distinct regions of the disk, until GWs take over their evolution. We extract MBHB cosmological merger rates from the Millennium simulation, generate Monte Carlo realizations of a population of gas driven binaries, and calculate the corresponding GW amplitudes of the most luminous individual binaries and the stochastic GW background. For steady state alpha-disks with alpha>0.1 we find that the nHz GW background can be significantly modified. The number of resolvable binaries is however not changed by the presence of gas; we predict 1-10 individually resolvable sources to stand above the noise for a 1-50 ns timing precision. Gas driven migration reduces predominantly the number of small total mass or unequal mass ratio binaries, which leads to the attenuation of the mean stochastic GW--background, but increases the detection significance of individually resolvable binaries. The results are sensitive to the model of binary--disk interaction. The GW background is not attenuated significantly for time-dependent models of Ivanov, Papaloizou, & Polnarev (1999).Comment: Accepted by MNRAS, 15 pages, 8 figure