Evolution in the Cluster Early-type Galaxy Size-Surface Brightness Relation at z =~ 1

We investigate the evolution in the distribution of surface brightness, as a function of size, for elliptical and S0 galaxies in the two clusters RDCS J1252.9-2927, z=1.237 and RX J0152.7-1357, z=0.837. We use multi-color imaging with the Advanced Camera for Surveys on the Hubble Space Telescope to determine these sizes and surface brightnesses. Using three different estimates of the surface brightnesses, we find that we reliably estimate the surface brightness for the galaxies in our sample with a scatter of < 0.2 mag and with systematic shifts of \lesssim 0.05 mag. We construct samples of galaxies with early-type morphologies in both clusters. For each cluster, we use a magnitude limit in a band which closely corresponds to the rest-frame B, to magnitude limit of M_B = -18.8 at z=0, and select only those galaxies within the color-magnitude sequence of the cluster or by using our spectroscopic redshifts. We measure evolution in the rest-frame B surface brightness, and find -1.41 \+/- 0.14 mag from the Coma cluster of galaxies for RDCS J1252.9-2927 and -0.90 \+/- 0.12 mag of evolution for RX J0152.7-1357, or an average evolution of (-1.13 \+/- 0.15) z mag. Our statistical errors are dominated by the observed scatter in the size-surface brightness relation, sigma = 0.42 \+/- 0.05 mag for RX J0152.7-1357 and sigma = 0.76 \+/- 0.10 mag for RDCS J1252.9-2927. We find no statistically significant evolution in this scatter, though an increase in the scatter could be expected. Overall, the pace of luminosity evolution we measure agrees with that of the Fundamental Plane of early-type galaxies, implying that the majority of massive early-type galaxies observed at z =~ 1 formed at high redshifts.Comment: Accepted in ApJ, 16 pages in emulateapj format with 15 eps figures, 6 in colo

Spread Supersymmetry

In the multiverse the scale of SUSY breaking, \tilde{m} = F_X/M_*, may scan and environmental constraints on the dark matter density may exclude a large range of \tilde{m} from the reheating temperature after inflation down to values that yield a LSP mass of order a TeV. After selection effects, the distribution for \tilde{m} may prefer larger values. A single environmental constraint from dark matter can then lead to multi-component dark matter, including both axions and the LSP, giving a TeV-scale LSP lighter than the corresponding value for single-component LSP dark matter. If SUSY breaking is mediated to the SM sector at order X^* X, only squarks, sleptons and one Higgs doublet acquire masses of order \tilde{m}. The gravitino mass is lighter by a factor of M_*/M_Pl and the gaugino masses are suppressed by a further loop factor. This Spread SUSY spectrum has two versions; the Higgsino masses are generated in one from supergravity giving a wino LSP and in the other radiatively giving a Higgsino LSP. The environmental restriction on dark matter fixes the LSP mass to the TeV domain, so that the squark and slepton masses are order 10^3 TeV and 10^6 TeV in these two schemes. We study the spectrum, dark matter and collider signals of these two versions of Spread SUSY. The Higgs is SM-like and lighter than 145 GeV; monochromatic photons in cosmic rays arise from dark matter annihilations in the halo; exotic short charged tracks occur at the LHC, at least for the wino LSP; and there are the eventual possibilities of direct detection of dark matter and detailed exploration of the TeV-scale states at a future linear collider. Gauge coupling unification is as in minimal SUSY theories. If SUSY breaking is mediated at order X, a much less hierarchical spectrum results---similar to that of the MSSM, but with the superpartner masses 1--2 orders of magnitude larger than in natural theories.Comment: 20 pages, 5 figure

CAF01 Potentiates Immune Responses and Efficacy of an Inactivated Influenza Vaccine in Ferrets

Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6′-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines

The Cosmological Constant

This is a review of the physics and cosmology of the cosmological constant. Focusing on recent developments, I present a pedagogical overview of cosmology in the presence of a cosmological constant, observational constraints on its magnitude, and the physics of a small (and potentially nonzero) vacuum energy.Comment: 50 pages. Submitted to Living Reviews in Relativity (http://www.livingreviews.org/), December 199

Parallel Odor Processing by Two Anatomically Distinct Olfactory Bulb Target Structures

The olfactory cortex encompasses several anatomically distinct regions each hypothesized to provide differential representation and processing of specific odors. Studies exploring whether or not the diversity of olfactory bulb input to olfactory cortices has functional meaning, however, are lacking. Here we tested whether two anatomically major olfactory cortical structures, the olfactory tubercle (OT) and piriform cortex (PCX), differ in their neural representation and processing dynamics of a small set of diverse odors by performing in vivo extracellular recordings from the OT and PCX of anesthetized mice. We found a wealth of similarities between structures, including odor-evoked response magnitudes, breadth of odor tuning, and odor-evoked firing latencies. In contrast, only few differences between structures were found, including spontaneous activity rates and odor signal-to-noise ratios. These results suggest that despite major anatomical differences in innervation by olfactory bulb mitral/tufted cells, the basic features of odor representation and processing, at least within this limited odor set, are similar within the OT and PCX. We predict that the olfactory code follows a distributed processing stream in transmitting behaviorally and perceptually-relevant information from low-level stations

Selective Regulation of NR2B by Protein Phosphatase-1 for the Control of the NMDA Receptor in Neuroprotection

An imbalance between pro-survival and pro-death pathways in brain cells can lead to neuronal cell death and neurodegeneration. While such imbalance is known to be associated with alterations in glutamatergic and Ca2+ signaling, the underlying mechanisms remain undefined. We identified the protein Ser/Thr phosphatase protein phosphatase-1 (PP1), an enzyme associated with glutamate receptors, as a key trigger of survival pathways that can prevent neuronal death and neurodegeneration in the adult hippocampus. We show that PP1α overexpression in hippocampal neurons limits NMDA receptor overactivation and Ca2+ overload during an excitotoxic event, while PP1 inhibition favors Ca2+ overload and cell death. The protective effect of PP1 is associated with a selective dephosphorylation on a residue phosphorylated by CaMKIIα on the NMDA receptor subunit NR2B, which promotes pro-survival pathways and associated transcriptional programs. These results reveal a novel contributor to the mechanisms of neuroprotection and underscore the importance of PP1-dependent dephosphorylation in these mechanisms. They provide a new target for the development of potential therapeutic treatment of neurodegeneration

Organizing Effects of Sex Steroids on Brain Aromatase Activity in Quail

Preoptic/hypothalamic aromatase activity (AA) is sexually differentiated in birds and mammals but the mechanisms controlling this sex difference remain unclear. We determined here (1) brain sites where AA is sexually differentiated and (2) whether this sex difference results from organizing effects of estrogens during ontogeny or activating effects of testosterone in adulthood. In the first experiment we measured AA in brain regions micropunched in adult male and female Japanese quail utilizing the novel strategy of basing the microdissections on the distribution of aromatase-immunoreactive cells. The largest sex difference was found in the medial bed nucleus of the stria terminalis (mBST) followed by the medial preoptic nucleus (POM) and the tuberal hypothalamic region. A second experiment tested the effect of embryonic treatments known to sex-reverse male copulatory behavior (i.e., estradiol benzoate [EB] or the aromatase inhibitor, Vorozole) on brain AA in gonadectomized adult males and females chronically treated as adults with testosterone. Embryonic EB demasculinized male copulatory behavior, while vorozole blocked demasculinization of behavior in females as previously demonstrated in birds. Interestingly, these treatments did not affect a measure of appetitive sexual behavior. In parallel, embryonic vorozole increased, while EB decreased AA in pooled POM and mBST, but the same effect was observed in both sexes. Together, these data indicate that the early action of estrogens demasculinizes AA. However, this organizational action of estrogens on AA does not explain the behavioral sex difference in copulatory behavior since AA is similar in testosterone-treated males and females that were or were not exposed to embryonic treatments with estrogens

Proteoglycan-4 Regulates Fibroblast to Myofibroblast Transition and Expression of Fibrotic Genes in the Synovium

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo. Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or isotype control antibodies and cellular uptake of rhPRG4 was determined following a 30-min incubation and α-SMA expression following a 24-h incubation. HEK-TGF-β cells were treated with TGF-β ± rhPRG4 and Smad3 phosphorylation was determined using immunofluorescence and TGF-β/Smad pathway activation was determined colorimetrically. We probed for stress fibers and focal adhesions (FAs) in TGF-β-treated murine fibroblasts and fibroblast migration was quantified ± rhPRG4. Synovial expression of fibrotic markers: α-SMA, collagen type-I, and PLOD2 in Prg4 gene-trap (Prg4GT) and recombined Prg4GTR animals were studied at 2 and 9 months of age. Synovial expression of α-SMA and PLOD2 was determined in 2-month-old Prg4GT/GT&Cd44−/− and Prg4GTR/GTR&Cd44−/− animals. Results: PRG4 reduced α-SMA content in OA synoviocytes (p \u3c 0.001). rhPRG4 was internalized by OA synoviocytes via CD44 and CD44 neutralization attenuated rhPRG4’s antifibrotic effect (p \u3c 0.05). rhPRG4 reduced pSmad3 signal in HEKTGF- β cells (p \u3c 0.001) and TGF-β/Smad pathway activation (p \u3c 0.001). rhPRG4 reduced the number of stress fiberpositive myofibroblasts, FAs mean size, and cell migration in TGF-β-treated NIH3T3 fibroblasts (p \u3c 0.05). rhPRG4 inhibited fibroblast migration in a macrophage and fibroblast co-culture model without altering active or total TGF-β levels. Synovial tissues of 9-month-old Prg4GT/GT animals had higher α-SMA, collagen type-I, and PLOD2 (p \u3c 0.001) content and Prg4 re-expression reduced these markers (p \u3c 0.01). Prg4 re-expression also reduced α-SMA and PLOD2 staining in CD44-deficient mice. Conclusion: PRG4 is an endogenous antifibrotic modulator in the joint and its effect on myofibroblast formation is partially mediated by CD44, but CD44 is not required to demonstrate an antifibrotic effect in vivo