Annual Modulation of Cosmic Relic Neutrinos

The cosmic neutrino background (CvB), produced about one second after the Big Bang, permeates the Universe today. New technological advancements make neutrino capture on beta-decaying nuclei (NCB) a clear path forward towards the detection of the CvB. We show that gravitational focusing by the Sun causes the expected neutrino capture rate to modulate annually. The amplitude and phase of the modulation depend on the phase-space distribution of the local neutrino background, which is perturbed by structure formation. These results also apply to searches for sterile neutrinos at NCB experiments. Gravitational focusing is the only source of modulation for neutrino capture experiments, in contrast to dark-matter direct-detection searches where the Earth's time-dependent velocity relative to the Sun also plays a role.Comment: 6 pages, 2 figure

Model-Independent Jets plus Missing Energy Searches

We present a proposal for performing model-independent jets plus missing energy searches. Currently, these searches are optimized for mSUGRA and are consequently not sensitive to all kinematically-accessible regions of parameter space. We show that the reach of these searches can be broadened by setting limits on the differential cross section as a function of the total visible energy and the missing energy. These measurements only require knowledge of the relevant Standard Model backgrounds and can be subsequently used to limit any theoretical model of new physics. We apply this approach to an example where gluinos are pair-produced and decay to the LSP through a single-step cascade, and show how sensitivity to different gluino masses is altered by the presence of the decay chain. The analysis is closely based upon the current searches done at the Tevatron and our proposal requires only small modifications to the existing techniques. We find that within the MSSM, the gluino can be as light as 125 GeV. The same techniques are applicable to jets and missing energy searches at the Large Hadron Collider.Comment: 22 pages, 6 figures, 3 tables, typos correcte

Decreased expression of caveolin 1 in patients with systemic sclerosis: crucial role in the pathogenesis of tissue fibrosis.

OBJECTIVE: Recent studies have implicated caveolin 1 in the regulation of transforming growth factor beta (TGFbeta) downstream signaling. Given the crucial role of TGFbeta in the pathogenesis of systemic sclerosis (SSc), we sought to determine whether caveolin 1 is also involved in the pathogenesis of tissue fibrosis in SSc. We analyzed the expression of CAV1 in affected SSc tissues, studied the effects of lack of expression of CAV1 in vitro and in vivo, and analyzed the effects of restoration of caveolin 1 function on the fibrotic phenotype of SSc fibroblasts in vitro. METHODS: CAV1 expression in tissues was analyzed by immunofluorescence and confocal microscopy. The extent of tissue fibrosis in Cav1-knockout mice was assessed by histologic/histochemical analyses and quantified by hydroxyproline assays. Cav1-null and SSc fibroblast phenotypes and protein production were analyzed by real-time polymerase chain reaction, immunofluorescence, Western blot, and multiplexed enzyme-linked immunosorbent assay techniques. The effects of restoration of caveolin 1 function in SSc fibroblasts in vitro were also examined using a cell-permeable recombinant CAV1 peptide. RESULTS: CAV1 was markedly decreased in the affected lungs and skin of SSc patients. Cav1-knockout mice developed pulmonary and skin fibrosis. Down-regulation of caveolin 1 was maintained in cultured SSc fibroblasts, and restoration of caveolin 1 function in vitro normalized their phenotype and abrogated TGFbeta stimulation through inhibition of Smad3 activation. CONCLUSION: Caveolin 1 appears to participate in the pathogenesis of tissue fibrosis in SSc. Restoration of caveolin 1 function by treatment with a cell-permeable peptide corresponding to the CAV1 scaffolding domain may be a novel therapeutic approach in SSc

Caveolin-1, TGF-β receptor internalization, and the pathogenesis of systemic sclerosis

PURPOSE OF REVIEW: To review the scientific literature supporting the participation of caveolin-1 in the pathogenesis of tissue fibrosis and the notion that modulation of the caveolin-1 pathway may represent a novel treatment for systemic sclerosis and other fibrotic diseases. RECENT FINDINGS: Caveolin-1 plays an important role in the regulation of transforming growth factor-beta (TGF-beta) signaling owing to its participation in TGF-beta receptor internalization. TGF-beta receptor internalized through caveolin-1 lipid rafts undergoes rapid degradation, effectively decreasing TGF-beta signaling. Studies have shown that caveolin-1 knockdown in vitro markedly increased collagen gene expression in normal human lung fibroblasts. Caveolin-1 was reduced in affected systemic sclerosis lungs and skin and in idiopathic pulmonary fibrosis lung tissues and fibroblasts. Increasing caveolin-1 expression markedly improved bleomycin-induced pulmonary fibrosis. Restoration of caveolin bioavailability employing penetratin, a cell-permeable peptide carrier for a bioactive caveolin-1 fragment, abrogated TGF-beta activation of cultured human dermal fibroblasts. Systemic administration of penetratin-caveolin-1 peptide to mice with bleomycin-induced lung fibrosis reduced fibrosis. SUMMARY: Caveolin-1 plays an important role in the regulation of TGF-beta signaling and participates in the pathogenesis of systemic sclerosis and idiopathic pulmonary fibrosis. Restoration of caveolin function employing active caveolin-1 fragments coupled to cell-permeable carrier peptides may represent a novel approach for their treatment

Hypoxia and hyperglycaemia determine why some endometrial tumours fail to respond to metformin

High expression of Ki67, a proliferation marker, is associated with reduced endometrial cancer-specific survival. Pre-surgical metformin reduces tumour Ki-67 expression in some women with endometrial cancer. Metformin's anti-cancer activity may relate to effects on cellular energy metabolism. Since tumour hypoxia and glucose availability are major cellular redox determinants, we evaluated their role in endometrial cancer response to metformin. Endometrial cancer biopsies from women treated with pre-surgical metformin were tested for the hypoxia markers, HIF-1α and CA-9. Endometrial cancer cell lines were treated with metformin in variable glucose concentrations in normoxia or hypoxia and cell viability, mitochondrial biogenesis, function and energy metabolism were assessed. In women treated with metformin (n = 28), Ki-67 response was lower in hypoxic tumours. Metformin showed minimal cytostatic effects towards Ishikawa and HEC1A cells in conventional medium (25 mM glucose). In low glucose (5.5 mM), a dose-dependent cytostatic effect was observed in normoxia but attenuated in hypoxia. Tumours treated with metformin showed increased mitochondrial mass (n = 25), while in cultured cells metformin decreased mitochondrial function. Metformin targets mitochondrial respiration, however, in hypoxic, high glucose conditions, there was a switch to glycolytic metabolism and decreased metformin response. Understanding the metabolic adaptations of endometrial tumours may identify patients likely to derive clinical benefit from metformin

Laboratory Constraints on the Neutron-Spin Coupling of feV-scale Axions

Ultralight axion-like particles can contribute to the dark matter near the Sun, leading to a distinct, stochastic signature in terrestrial experiments. We search for such particles through their neutron-spin coupling by re-analyzing approximately 40 days of data from a K-$^3$He co-magnetometer with a new frequency-domain likelihood-based formalism that properly accounts for stochastic effects over all axion coherence times relative to the experimental time span. Assuming that axions make up all of the dark matter in the Sun's vicinity, we find a median 95% upper limit on the neutron-spin coupling of $2.4 \times 10^{-10}$ GeV$^{{-1}}$ for axion masses from 0.4 to 4 feV, which is about five orders of magnitude more stringent than previous laboratory bounds in that mass range. Although several peaks in the experiment's magnetic power spectrum suggest the rejection of a white-noise null hypothesis, further analysis of their lineshapes yields no positive evidence for a dark matter axion.Comment: 23 pages, 15 figure

The Dark Matter at the End of the Galaxy

Dark matter density profiles based upon Lambda-CDM cosmology motivate an ansatz velocity distribution function with fewer high velocity particles than the Maxwell-Boltzmann distribution or proposed variants. The high velocity tail of the distribution is determined by the outer slope of the dark matter halo, the large radius behavior of the Galactic dark matter density. N-body simulations of Galactic halos reproduce the high velocity behavior of this ansatz. Predictions for direct detection rates are dramatically affected for models where the threshold scattering velocity is within 30% of the escape velocity.Comment: 10 pages, 5 figure