A search for direct muon production in the forward direction

We propose to search for direct muon production in the forward direction from 300 GeV protons incident on a heavy nuclear target. By using the first stage of the Ml beam as a source of a diffracted proton beam and the second and third stages of Ml as a spectrometer, one can make a measurement of the direct muon to pion ratio at values of x between 0.3 and 0.75. If this ratio is on the order of 10{sup -4}, the event rates are on the order of 800 direct muons/hr. at an x of .5. The modifications to the Ml beam are minor

Solar models and solar neutrino oscillations

We provide a summary of the current knowledge, theoretical and experimental, of solar neutrino fluxes and of the masses and mixing angles that characterize solar neutrino oscillations. We also summarize the principal reasons for doing new solar neutrino experiments and what we think may be learned from the future measurements.Comment: Submitted to the Neutrino Focus Issue of New Journal of Physics at http://www.njp.or

Testing the inverse-square law of gravity on a 465-m tower

We have performed a test of Newton’s universal theory of gravitation by comparing gravity measured on a tower to an upward continuation of the surface gravity field. We measured gravity at 12 heights on a 465-m tower at the Nevada Test Site and, in addition, made measurements at 281 locations on the ground. The surface points fell within 91 optimally chosen sectors that extended out to 2.6 km from the tower. These data were combined with 60000 additional surface gravity measurements within 300 km of the tower. We used a surface integral derived from Laplace’s equation to upward continue the surface gravity field and our observations are consistent with the Newtonian predictions to within (-60±95)×10^-8 m sec^-2 at the top of the tower

Damping of supernova neutrino transitions in stochastic shock-wave density profiles

Supernova neutrino flavor transitions during the shock wave propagation are known to encode relevant information not only about the matter density profile but also about unknown neutrino properties, such as the mass hierarchy (normal or inverted) and the mixing angle theta_13. While previous studies have focussed on "deterministic" density profiles, we investigate the effect of possible stochastic matter density fluctuations in the wake of supernova shock waves. In particular, we study the impact of small-scale fluctuations on the electron (anti)neutrino survival probability, and on the observable spectra of inverse-beta-decay events in future water-Cherenkov detectors. We find that such fluctuations, even with relatively small amplitudes, can have significant damping effects on the flavor transition pattern, and can partly erase the shock-wave imprint on the observable time spectra, especially for sin^2(theta_13) > O(10^-3).Comment: v2 (23 pages, including 6 eps figures). Typos removed, references updated, matches the published versio

Profiling CpG island field methylation in both morphologically normal and neoplastic human colonic mucosa

Aberrant CpG island (CGI) methylation occurs early in colorectal neoplasia. Quantitative methylation-specific PCR profiling applied to biopsies was used to quantify low levels of CGI methylation of 18 genes in the morphologically normal colonic mucosa of neoplasia-free subjects, adenomatous polyp patients, cancer patients and their tumours. Multivariate statistical analyses distinguished tumour from mucosa with a sensitivity of 78.9% and a specificity of 100% (P=3 × 10−7). In morphologically normal mucosa, age-dependent CGI methylation was observed for APC, AXIN2, DKK1, HPP1, N33, p16, SFRP1, SFRP2 and SFRP4 genes, and significant differences in CGI methylation levels were detected between groups. Multinomial logistic regression models based on the CGI methylation profiles from normal mucosa correctly identified 78.9% of cancer patients and 87.9% of non-cancer (neoplasia-free+polyp) patients (P=4.93 × 10−7) using APC, HPP1, p16, SFRP4, WIF1 and ESR1 methylation as the most informative variables. Similarly, CGI methylation of SFRP4, SFRP5 and WIF1 correctly identified 61.5% of polyp patients and 78.9% of neoplasia-free subjects (P=0.0167). The apparently normal mucosal field of patients presenting with neoplasia has evidently undergone significant epigenetic modification. Methylation of the genes selected by the models may play a role in the earliest stages of the development of colorectal neoplasia

ROCK1 and LIMK2 Interact in Spread but Not Blebbing Cancer Cells

Cancer cells migrating within a 3D microenvironment are able to adopt either a mesenchymal or amoeboid mode of migration. Amoeboid migration is characterised by membrane blebbing that is dependent on the Rho effectors, ROCK1/2. We identify LIMK2 as the preferred substrate for ROCK1 but find that LIMK2 did not induce membrane blebbing, suggesting that a LIMK2 pathway is not involved in amoeboid-mode migration. In support of this hypothesis, novel FRET data demonstrate a direct interaction between ROCK1 and LIMK2 in polarised but not blebbing cells. Our results point to a specific role for the ROCK1:LIMK2 pathway in mesenchymal-mode migration

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions