Small-Scale X-ray Variability in the Cassiopeia A Supernova Remnant

A comparison of X-ray observations of the Cassiopeia A supernova remnant taken in 2000, 2002, and 2004 with the Chandra ACIS-S3 reveals the presence of several small scale features (<= 10 arcsec) which exhibit significant intensity changes over a 4 year time frame. Here we report on the variability of six features, four of which show count rate increases from ~ 10% to over 90%, and two which show decreases of ~ 30% -- 40%. While extracted 1-4.5 keV X-ray spectra do not reveal gross changes in emission line strengths, spectral fits using non-equilibrium ionization, metal-rich plasma models indicate increased or decreased electron temperatures for features showing increasing or decreasing count rates, respectively. Based on the observed count rate changes and the assumption that the freely expanding ejecta has a velocity of ~ 5000 km/s at the reverse shock front, we estimate the unshocked ejecta to have spatial scale variations of 0.02 - 0.03 pc, which is consistent with the X-ray emitting ejecta belonging to a more diffuse component of the supernova ejecta than that seen in the optically emitting ejecta, which have spatial scales ~ 0.001 pc.Comment: 9 pages, 8 figures, to be published in Astronomical Journa

Treatment with a Substance P Receptor Antagonist Is Neuroprotective in the Intrastriatal 6-Hydroxydopamine Model of Early Parkinson's Disease

Neuroinflammation and blood brain barrier (BBB) dysfunction have been implicated in the pathogenesis of Parkinson's disease (PD). The neuropeptide substance P (SP) is an important mediator of both neuroinflammation and BBB dysfunction through its NK1 receptor in a process known as neurogenic inflammation. Increased SP content has previously been reported following 6-OHDA treatment in vitro, with the levels of SP correlating with cell death. The present study used an in vivo 6-OHDA lesion model to determine if dopaminergic degeneration was associated with increased SP in the substantia nigra and whether this degeneration could be prevented by using a SP, NK1 receptor antagonist. Unilateral, intrastriatal 6-OHDA lesions were induced and SP (10 µg/2 µL) or the NK1 receptor antagonists, N-acetyl-L-tryptophan (2 µL at 50 nM) or L-333,060 (2 µL at 100 nM), administered immediately after the neurotoxin. Nigral SP content was then determined using immunohistochemical and ELISA methods, neuroinflammation and barrier integrity was assessed using Iba-1, ED-1, GFAP and albumin immunohistochemistry, while dopaminergic cell loss was assessed with tyrosine hydroxylase immunohistochemistry. Motor function in all animals was assessed using the rotarod task. Intrastriatal 6-OHDA lesioning produced an early and sustained increase in ipsilateral nigral SP content, along with a breakdown of the BBB and activation of microglia and astrocytes. Further exacerbation of SP levels accelerated disease progression, whereas NK1 receptor antagonist treatment protected dopaminergic neurons, preserved barrier integrity, reduced neuroinflammation and significantly improved motor function. We propose that neurogenic inflammation contributes to dopaminergic degeneration in early experimental PD and demonstrate that an NK1 receptor antagonist may represent a novel neuroprotective therapy

Combination of N-Acetyl-L-Tryptophan and Magnesium Sulphate for the treatment of brain, spinal and nerve injury

This invention relates to a method of therapy of brain, spinal and nerve injury. There is also provided a formulation which is particularly useful in the method. Injury to the brain results in the development of motor and cognitive deficits that contribute to the significant morbidity experienced by survivors of brain injury. Moreover, it is an occurrence that has the highest incidence in younger members of society. Accordingly, injury to the brain is responsible for the greatest loss of productive life as compared to any other disease process. Despite this, there is no effective therapy to improve outcome after brain injury. Use of this therapy significantly improves both motor and cognitive outcome in mild to severe experimental brain injury and has also been found to have beneficial effect also for the treatment of spinal cord and nerve injuries

Modelling the clumping-induced polarimetric variability of hot star winds

Clumping in the winds of massive stars may significantly reduce empirical mass-loss rates, and which in turn may have a large impact on our understanding of massive star evolution. Here, we investigate wind-clumping through the linear polarization induced by light scattering off the clumps. Through the use of an analytic wind clumping model, we predict the time evolution of the linear polarimetry over a large parameter space. We concentrate on the Luminous Blue Variables, which display the greatest amount of polarimetric variability and for which we recently conducted a spectropolarimetric survey. Our model results indicate that the observed level of polarimetric variability can be reproduced for two regimes of parameter space: one of a small number of massive, optically-thick clumps; and one of a very large number of low-mass clumps. Although a systematic time-resolved monitoring campaign is required to distinguish between the two scenarios, we currently favour the latter, given the short timescale of the observed polarization variability. As the polarization is predicted to scale linearly with mass-loss rate, we anticipate that all hot stars with very large mass-loss rates should display polarimetric variability. This is consistent with recent findings that intrinsic polarization is more common in stars with strong H$\alpha$ emission.Comment: 12 pages, 11 figures, accepted to A&

Salvage surgery for a giant melanoma on the back

We report a case of a giant melanoma on the back with a very extreme Breslow thickness. On physical examination a large odorous and ulcerating tumour was seen adjacent to two large crusted lesions, probably in transit metastases. In the right and left axilla enlarged lymph nodes were palpated. The patient underwent salvage surgery consisting of a complete wide excision of the tumors on the back as well as axillary lymph node dissection on both sides. Histopathology showed a malignant melanoma with a Breslow thickness of 48 mm. Four of fifteen nodes in the right axilla and one of nine nodes in the left axilla, were positive for metastatic disease. Also various in transit and subcutaneous metastases were found in the wide excision specimen. The interest of our observation relies in the rarity of a melanoma with such an extreme Breslow thickness and the difficulty in performing adequate palliative therapy that offers quality of life by means of tumor control

The hermitian Wilson-Dirac operator in smooth SU(2) instanton backgrounds

We study the spectral flow of the hermitian Wilson-Dirac operator \ham(m) as a function of $m$ in smooth SU(2) instanton backgrounds on the lattice. For a single instanton background with Dirichlet boundary conditions on \ham(m), we find a level crossing in the spectral flow of \ham(m), and we find the shape of the crossing mode at the crossing point to be in good agreement with the zero mode associated with the single instanton background. With anti-periodic boundary conditions on \ham(m), we find that the instanton background in the singular gauge has the correct spectral flow but the one in regular gauge does not. We also investigate the spectral flows of two instanton and instanton-anti-instanton backgrounds.Comment: 18 pages, Latex file, 12 postscript figure

A Decline in the Nonthermal X-Ray Emission from Cassiopeia A

We present new Chandra ACIS-S3 observations of Cassiopeia A which, when combined with earlier ACIS-S3 observations, show evidence for a steady ~ 1.5-2%/yr decline in the 4.2-6.0 keV X-ray emission between the years 2000 and 2010. The computed flux from exposure corrected images over the entire remnant showed a 17% decline over the entire remnant and a slightly larger (21%) decline from regions along the remnant\u27s western limb. Spectral fits of the 4.2-6.0 keV emission across the entire remnant, forward shock filaments, and interior filaments indicate the remnant\u27s nonthermal spectral powerlaw index has steepened by about 10%, with interior filaments having steeper powerlaw indices. Since TeV electrons, which give rise to the observed X-ray synchrotron emission, are associated with the exponential cutoff portion of the electron distribution function, we have related our results to a change in the cutoff energy and conclude that the observed decline and steepening of the nonthermal X-ray emission is consistent with a deceleration of the remnant\u27s ~5000 km/s forward shock of ~10--40 km/s/y

How to Translate Time: The Temporal Aspects of Rodent and Human Pathobiological Processes in Traumatic Brain Injury.

Traumatic brain injury (TBI) triggers multiple pathobiological responses with differing onsets, magnitudes, and durations. Identifying the therapeutic window of individual pathologies is critical for successful pharmacological treatment. Dozens of experimental pharmacotherapies have been successfully tested in rodent models, yet all of them (to date) have failed in clinical trials. The differing time scales of rodent and human biological and pathological processes may have contributed to these failures. We compared rodent versus human time scales of TBI-induced changes in cerebral glucose metabolism, inflammatory processes, axonal integrity, and water homeostasis based on published data. We found that the trajectories of these pathologies run on different timescales in the two species, and it appears that there is no universal "conversion rate" between rodent and human pathophysiological processes. For example, the inflammatory process appears to have an abbreviated time scale in rodents versus humans relative to cerebral glucose metabolism or axonal pathologies. Limitations toward determining conversion rates for various pathobiological processes include the use of differing outcome measures in experimental and clinical TBI studies and the rarity of longitudinal studies. In order to better translate time and close the translational gap, we suggest 1) using clinically relevant outcome measures, primarily in vivo imaging and blood-based proteomics, in experimental TBI studies and 2) collecting data at multiple post-injury time points with a frequency exceeding the expected information content by two or three times. Combined with a big data approach, we believe these measures will facilitate the translation of promising experimental treatments into clinical use