Constraining the Nature of Dark Energy using the SKA

We investigate the potential of the Square Kilometer Array Telescope (SKA) to constrain the sound speed of dark energy. The Integrated Sachs Wolfe (ISW) effect results in a significant power spectrum signal when CMB temperature anisotropies are cross-correlated with galaxies detectable with the SKA in HI. We consider using this measurement, the autocorrelation of HI galaxies and the CMB temperature power spectrum to derive constraints on the sound speed. We study the contributions to the cross-correlation signal made by galaxies at different redshifts and use redshift tomography to improve the signal-to-noise. We use a chi-square analysis to estimate the significance of detecting a sound speed different from that expected in quintessence models, finding that there is potential to distinguish very low sound speeds from the quintessence value.Comment: 8 pages, 8 figures; updated references for publication MNRA

Disease-Toxicant Interactions in Manganese Exposed Huntington Disease Mice: Early Changes in Striatal Neuron Morphology and Dopamine Metabolism

YAC128 Huntington's disease (HD) transgenic mice accumulate less manganese (Mn) in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl2-4H2O (50 mg/kg) on days 0, 3 and 6. Striatal medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13 weeks (7 days from initial exposure) and 16 weeks (28 days from initial exposure). No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology

CD4 and CD8 monoclonal antibody therapy in canine renal allografts.

Therapy with CD4 and CD8 monoclonal antibodies was evaluated in dogs which received double-haplotype MHC-mismatched renal allografts. Neither CD4 nor CD8 monoclonal antibodies given alone prolonged allografts survival (creatinine > or = 300 micromol/l) beyond 7 days. However, combined therapy with CD4 and CD8 antibodies given up to day 10 did prolong allograft survival to a median of 14 days. A longer (21 day) course of CD4 and CD8 antibodies did not extend allograft survival further. The effect of prolonged antibody therapy was restricted by the occurrence of both an antiglobulin response and an anaphylactoid reaction to the monoclonal antibody preparation. When the CD4 and CD8 antibodies were combined with a pan-T-cell-depleting Thy-1 antibody, the survival of double-haplotype mismatched allografts was further prolonged (median 16 days). The median survival of single-haplotype mismatched renal allografts on this triple therapy was 21 days, with one surviving to day 36

CD4 and CD8 monoclonal antibody therapy: strategies to prolong renal allograft survival in the dog.

The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this large animal model. Monoclonal antibodies were given for a maximum of 10 days after transplantation. Therapy was stopped prematurely following adverse reactions associated with the recipient developing an antibody response against the foreign (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8 antibodies indicated that saturating doses were achieved. Although neither CD4 nor CD8 alone prolonged allograft survival (rejection by day 7), combination of CD4 and CD8 antibodies resulted in good graft function for a median of 14 days. The effect of removing circulating T lymphocytes was also assessed using a lytic Thy-1 monoclonal antibody. Alone Thy-1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days. Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival