Spectral Properties of the Jacobi Ensembles via the Coulomb Gas approach

Using the Coulomb gas method and standard methods of statistical physics, we compute analytically the joint cumulative probability distribution of the extreme eigenvalues of the Jacobi-MANOVA ensemble of random matrices, in the limit of large matrices. This allows us to derive the rate functions for the large fluctuations to the left and the right of the expected values of the smallest and largest eigenvalues analytically. Our findings are compared with some available known exact results as well as with numerical simulations finding good agreement.Comment: 31 pages, 7 figure

Measurement of the rate of nu_e + d --> p + p + e^- interactions produced by 8B solar neutrinos at the Sudbury Neutrino Observatory

Solar neutrinos from the decay of $^8$B have been detected at the Sudbury Neutrino Observatory (SNO) via the charged current (CC) reaction on deuterium and by the elastic scattering (ES) of electrons. The CC reaction is sensitive exclusively to nu_e's, while the ES reaction also has a small sensitivity to nu_mu's and nu_tau's. The flux of nu_e's from ^8B decay measured by the CC reaction rate is \phi^CC(nu_e) = 1.75 +/- 0.07 (stat)+0.12/-0.11 (sys.) +/- 0.05(theor) x 10^6 /cm^2 s. Assuming no flavor transformation, the flux inferred from the ES reaction rate is \phi^ES(nu_x) = 2.39+/-0.34 (stat.)+0.16}/-0.14 (sys) x 10^6 /cm^2 s. Comparison of \phi^CC(nu_e) to the Super-Kamiokande Collaboration's precision value of \phi^ES(\nu_x) yields a 3.3 sigma difference, providing evidence that there is a non-electron flavor active neutrino component in the solar flux. The total flux of active ^8B neutrinos is thus determined to be 5.44 +/-0.99 x 10^6/cm^2 s, in close agreement with the predictions of solar models.Comment: 6 pages (LaTex), 3 figures, submitted to Phys. Rev. Letter

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Paracrine Hedgehog Signaling Drives Metabolic Changes in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) typically develop in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts (MF). Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role of Hh-dependent MF in hepatocarcinogenesis is unknown. Here we used human HCC samples, a mouse HCC model, and hepatoma cell/MF co-cultures to examine the hypothesis that Hh signaling modulates MF metabolism to generate fuels for neighboring malignant hepatocytes. The results identify a novel paracrine mechanism whereby malignant hepatocytes produce HH-ligands to stimulate glycolysis in neighboring MF, resulting in release of MF-derived lactate that the malignant hepatocytes use as an energy source. This discovery reveals new diagnostic and therapeutic targets that might be exploited to improve the outcomes of cirrhotic patients with HCC

Equality Concerns and the Limits of Self-Governance in Heterogeneous Populations

Mechanisms to overcome social dilemmas provide incentives to maximize efficiency. However, often – such as when agents are heterogeneous – there is a trade-off between efficiency and equality. Agents' concerns for equality in such instances can limit the ability of mechanisms to promote efficiency. We provide evidence for this from a public good experiment using a simple mechanism which allows individuals to communicate periodically with other group members and reward them for their actions. We show that, in homogeneous populations – where there is no tension between efficiency and equality – the mechanism permits group to obtain maximum efficiency. This is not the case in heterogeneous populations where individuals derive different benefits from cooperation. Although almost all heterogeneous groups agree to follow specific contribution rules with positive contributions, most of them either prioritize equality over efficiency or strike a compromise between the two. These findings suggest that equality concerns can impose limits on the ability of heterogeneous populations to reach efficient outcomes through self-governance

Alcohol Activates the Hedgehog Pathway and Induces Related Procarcinogenic Processes in the Alcohol-Preferring Rat Model of Hepatocarcinogenesis

Alcohol consumption promotes hepatocellular carcinoma (HCC). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol is hepatotoxic, habitual alcohol ingestion evokes a recurrent demand for hepatic regeneration. The alcohol-preferring (P) rat model mimics the level of alcohol consumption by humans who habitually abuse alcohol. Previously, we showed that habitual heavy alcohol ingestion amplified age-related hepatocarcinogenesis in P-rats, with over 80% of alcohol-consuming P rats developing HCCs after 18 months of alcohol exposure, compared to only 5% of water-drinking controls

The Chemotactic Defect in Wiskott-Aldrich Syndrome Macrophages Is Due to the Reduced Persistence of Directional Protrusions

Wiskott-Aldrich syndrome protein (WASp) is an actin nucleation promoting factor that is required for macrophages to directionally migrate towards various chemoattractants. The chemotaxis defect of WASp-deficient cells and its activation by Cdc42 in vivo suggest that WASp plays a role in directional sensing, however, its precise role in macrophage chemotaxis is still unclear. Using shRNA-mediated downregulation of WASp in the murine monocyte/macrophage cell line RAW/LR5 (shWASp), we found that WASp was responsible for the initial wave of actin polymerization in response to global stimulation with CSF-1, which in Dictyostelium discoideum amoebae and carcinoma cells has been correlated with the ability to migrate towards chemoattractants. Real-time monitoring of shWASp cells, as well as WASp−/− bone marrow-derived macrophages (BMMs), in response to a CSF-1 gradient revealed that the protrusions from WASp-deficient cells were directional, showing intact directional sensing. However, the protrusions from WASp-deficient cells demonstrated reduced persistence compared to their respective control shRNA and wild-type cells. Further examination showed that tyrosine phosphorylation of WASp was required for both the first wave of actin polymerization following global CSF-1 stimulation and proper directional responses towards CSF-1. Importantly, the PI3K, Rac1 and WAVE2 proteins were incorporated normally in CSF-1 – elicited protrusions in the absence of WASp, suggesting that membrane protrusion driven by the WAVE2 complex signaling is intact. Collectively, these results suggest that WASp and its phosphorylation play critical roles in coordinating the actin cytoskeleton rearrangements necessary for the persistence of protrusions required for directional migration of macrophages towards CSF-1