Oxidative stress and the use of antioxidants in stroke

Transient or permanent interruption of cerebral blood flow by occlusion of a cerebral artery gives rise to an ischaemic stroke leading to irreversible damage or dysfunction to the cells within the affected tissue along with permanent or reversible neurological deficit. Extensive research has identified excitotoxicity, oxidative stress, inflammation and cell death as key contributory pathways underlying lesion progression. The cornerstone of treatment for acute ischaemic stroke remains reperfusion therapy with recombinant tissue plasminogen activator (rt-PA). The downstream sequelae of events resulting from spontaneous or pharmacological reperfusion lead to an imbalance in the production of harmful reactive oxygen species (ROS) over endogenous anti-oxidant protection strategies. As such, anti-oxidant therapy has long been investigated as a means to reduce the extent of injury resulting from ischaemic stroke with varying degrees of success. Here we discuss the production and source of these ROS and the various strategies employed to modulate levels. These strategies broadly attempt to inhibit ROS production or increase scavenging or degradation of ROS. While early clinical studies have failed to translate success from bench to bedside, the combination of anti-oxidants with existing thrombolytics or novel neuroprotectants may represent an avenue worthy of clinical investigation. Clearly, there is a pressing need to identify new therapeutic alternatives for the vast majority of patients who are not eligible to receive rt-PA for this debilitating and devastating disease

Direction-Dependent Polarised Primary Beams in Wide-Field Synthesis Imaging

The process of wide-field synthesis imaging is explored, with the aim of understanding the implications of variable, polarised primary beams for forthcoming Epoch of Reionisation experiments. These experiments seek to detect weak signatures from redshifted 21cm emission in deep residual datasets, after suppression and subtraction of foreground emission. Many subtraction algorithms benefit from low side-lobes and polarisation leakage at the outset, and both of these are intimately linked to how the polarised primary beams are handled. Building on previous contributions from a number of authors, in which direction-dependent corrections are incorporated into visibility gridding kernels, we consider the special characteristics of arrays of fixed dipole antennas operating around 100-200 MHz, looking towards instruments such as the Square Kilometre Array (SKA) and the Hydrogen Epoch of Reionization Arrays (HERA). We show that integrating snapshots in the image domain can help to produce compact gridding kernels, and also reduce the need to make complicated polarised leakage corrections during gridding. We also investigate an alternative form for the gridding kernel that can suppress variations in the direction-dependent weighting of gridded visibilities by 10s of dB, while maintaining compact support.Comment: 15 pages, 4 figures. Accepted for publication in JA

Interferometric Imaging with the 32 Element Murchison Wide-Field Array

The Murchison Wide-Field Array (MWA) is a low-frequency radio telescope, currently under construction, intended to search for the spectral signature of the epoch of reionization (EOR) and to probe the structure of the solar corona. Sited in western Australia, the full MWA will comprise 8192 dipoles grouped into 512 tiles and will be capable of imaging the sky south of 40° declination, from 80 MHz to 300 MHz with an instantaneous field of view that is tens of degrees wide and a resolution of a few arcminutes. A 32 station prototype of the MWA has been recently commissioned and a set of observations has been taken that exercise the whole acquisition and processing pipeline. We present Stokes I, Q, and U images from two ~4 hr integrations of a field 20° wide centered on Pictoris A. These images demonstrate the capacity and stability of a real-time calibration and imaging technique employing the weighted addition of warped snapshots to counter extreme wide-field imaging distortions

Numerical Simulation Based Targeting of the Magushan Skarn Cu-Mo Deposit, Middle-Lower Yangtze Metallogenic Belt, China

The Magushan Cu–Mo deposit is a skarn deposit within the Nanling–Xuancheng mining district of the Middle-Lower Yangtze River Metallogenic Belt (MLYRMB), China. This study presents the results of a new numerical simulation that models the ore-forming processes that generated the Magushan deposit and enables the identification of unexplored areas that have significant exploration potential under areas covered by thick sedimentary sequences that cannot be easily explored using traditional methods. This study outlines the practical value of numerical simulation in determining the processes that operate during mineral deposit formation and how this knowledge can be used to enhance exploration targeting in areas of known mineralization. Our simulation also links multiple subdisciplines such as heat transfer, pressure, fluid flow, chemical reactions, and material migration. Our simulation allows the modeling of the formation and distribution of garnet, a gangue mineral commonly found within skarn deposits (including within the Magushan deposit). The modeled distribution of garnet matches the distribution of known mineralization as well as delineating areas that may well contain high garnet abundances within and around a concealed intrusion, indicating this area should be considered a prospective target during future mineral exploration. Overall, our study indicates that this type of numerical simulation-based approach to prospectivity modeling is both effective and economical and should be considered an additional tool for future mineral exploration to reduce exploration risks when targeting mineralization in areas with thick and unprospective sedimentary cover sequences

Probing the Origins of Voids in the Distribution of Galaxies

If the voids that we see today in the distribution of galaxies existed at recombination, they will leave an imprint on the cosmic microwave background (CMB). On the other hand, if these voids formed much later, their effect on the CMB will be negligible and will not be observed with the current generation of experiments. In this paper, presented at the 2004 Annual Scientific Meeting of the Astronomical Society of Australia, we discuss our ongoing investigations into voids of primordial origin. We show that if voids in the cold dark matter distribution existed at the epoch of decoupling, they could contribute significantly to the apparent rise in CMB power on small scales detected by the Cosmic Background Imager (CBI) Deep Field. Here we present our improved method for predicting the effects of primordial voids on the CMB in which we treat a void as an external source in the cold dark matter (CDM) distribution employing a Boltzmann solver. Our improved predictions include the effects of a cosmological constant (Λ) and acoustic oscillations generated by voids at early times. We find that models with relatively large voids on the last scattering surface predict too much CMB power in an Einstein-de Sitter background cosmology but could be consistent with the current CMB observations in a ΛCDM univers

PSR J1909-3744, a Binary Millisecond Pulsar with a Very Small Duty Cycle

We report the discovery of PSR J1909-3744, a 2.95 millisecond pulsar in a nearly circular 1.53 day orbit. Its narrow pulse width of 43 microseconds allows pulse arrival times to be determined with great accuracy. We have spectroscopically identified the companion as a moderately hot (T = 8500 K) white dwarf with strong absorption lines. Radial velocity measurements of the companion will yield the mass ratio of the system. Our timing data suggest the presence of Shapiro delay; we expect that further timing observations, combined with the mass ratio, will allow the first accurate determination of a millisecond pulsar mass. We have measured the timing parallax and proper motion for this pulsar which indicate a transverse velocity of 140 (+80/-40) km/s. This pulsar's stunningly narrow pulse profile makes it an excellent candidate for precision timing experiments that attempt to detect low frequency gravitational waves from coalescing supermassive black hole binaries.Comment: 12 pages, 4 figures. Accepted for publication in ApJ

Quantum-classical transition in Scale Relativity

The theory of scale relativity provides a new insight into the origin of fundamental laws in physics. Its application to microphysics allows us to recover quantum mechanics as mechanics on a non-differentiable (fractal) spacetime. The Schrodinger and Klein-Gordon equations are demonstrated as geodesic equations in this framework. A development of the intrinsic properties of this theory, using the mathematical tool of Hamilton's bi-quaternions, leads us to a derivation of the Dirac equation within the scale-relativity paradigm. The complex form of the wavefunction in the Schrodinger and Klein-Gordon equations follows from the non-differentiability of the geometry, since it involves a breaking of the invariance under the reflection symmetry on the (proper) time differential element (ds - ds). This mechanism is generalized for obtaining the bi-quaternionic nature of the Dirac spinor by adding a further symmetry breaking due to non-differentiability, namely the differential coordinate reflection symmetry (dx^mu - dx^mu) and by requiring invariance under parity and time inversion. The Pauli equation is recovered as a non-relativistic-motion approximation of the Dirac equation.Comment: 28 pages, no figur

A Study of Giant Pulses from PSR J1824-2452A

We have searched for microsecond bursts of emission from millisecond pulsars in the globular cluster M28 using the Parkes radio telescope. We detected a total of 27 giant pulses from the known emitter PSR J1824-2452A. At wavelengths around 20 cm the giant pulses are scatter-broadened to widths of around 2 microseconds and follow power-law statistics. The pulses occur in two narrow phase-windows which correlate in phase with X-ray emission and trail the peaks of the integrated radio pulse-components. Notably, the integrated radio emission at these phase windows has a steeper spectral index than other emission. The giant pulses exhibit a high degree of polarization, with many being 100% elliptically polarized. Their position angles appear random. Although the integrated emission of PSR J1824-2452A is relatively stable for the frequencies and bandwidths observed, the intensities of individual giant pulses vary considerably across our bands. Two pulses were detected at both 2700 and 3500 MHz. The narrower of the two pulses is 20 ns wide at 3500 MHz. At 2700 MHz this pulse has an inferred brightness temperature at maximum of 5 x 10^37 K. Our observations suggest the giant pulses of PSR J1824-2452A are generated in the same part of the magnetosphere as X-ray emission through a different emission process to that of ordinary pulses.Comment: Accepted by Ap

Self-consistency of relativistic observables with general relativity in the white dwarf-neutron star binary pulsar PSR J1141-6545

Here we report timing measurements of the relativistic binary pulsar PSR J1141-6545 that constrain the component masses and demonstrate that the orbital period derivative \dot Pb = (-4+/-1)x10^-13 is consistent with gravitational wave emission as described by the general theory of relativity. The mass of the neutron star and its companion are 1.30+/-0.02 Mo and 0.986+/-0.020 Mo respectively, suggesting a white dwarf companion, and extending the range of systems for which general relativity provides a correct description. On evolutionary grounds, the progenitor mass of PSR J1141-6545 should be near the minimum for neutron star production. Its mass is two standard deviations below the mean of the other neutron stars, suggesting a relationship between progenitor and remnant masses.Comment: 10 pages, 2 figures, revised version to Ap J Letter

Combined antiapoptotic and antioxidant approach to acute neuroprotection for stroke in hypertensive rats

We hypothesized that targeting key points in the ischemic cascade with combined neuroglobin (Ngb) overexpression and c-jun N-terminal kinase (JNK) inhibition (SP600125) would offer greater neuroprotection than single treatment after in vitro hypoxia/reoxygenation and in a randomized, blinded in vivo experimental stroke study using a clinically relevant rat strain. Male spontaneously hypertensive stroke-prone rats underwent transient middle cerebral artery occlusion (tMCAO) and were divided into the following groups: tMCAO; tMCAO+control GFP-expressing canine adenovirus-2, CAVGFP; tMCAO+Ngb-expressing CAV-2, CAVNgb; tMCAO+SP600125; tMCAO+CAVNgb+SP600125; or sham procedure. Rats were assessed till day 14 for neurologic outcome before infarct determination. In vitro, combined lentivirus-mediated Ngb overexpression+SP600125 significantly reduced oxidative stress and apoptosis compared with single treatment(s) after hypoxia/reoxygenation in B50 cells. In vivo, infarct volume was significantly reduced by CAVNgb, SP600125, and further by CAVNgb+SP600125. The number of Ngb-positive cells in the peri-infarct cortex and striatum was significantly increased 14 days after tMCAO in animals receiving CAVNgb. Neurologic outcome, measured using a 32-point neurologic score, significantly improved with CAVNgb+SP600125 compared with single treatments at 14 days after tMCAO. Combined Ngb overexpression with JNK inhibition reduced hypoxia/reoxygenation-induced oxidative stress and apoptosis in cultured neurons and reduced infarct and improved neurologic outcome more than single therapy after in vivo experimental stroke in hypertensive rats