Search for long lived charged massive particles in pp collisions at s-hat = 1.8TeV

We report a search for the production of long-lived charged massive particles in a data sample of 90   pb-1 of √s=1.8   TeV pp̅ collisions recorded by the Collider Detector at Fermilab. The search uses the muonlike penetration and anomalously high ionization energy loss signature expected for such a particle to discriminate it from backgrounds. The data are found to agree with background expectations, and cross section limits of O(1) pb are derived using two reference models, a stable quark and a stable scalar lepton

Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer

The development of hepatocellular carcinoma (HCC) in persons who are persistently infected with hepatitis C virus (HCV) is a growing problem worldwide. Current antiviral therapies are not effective in many patients with chronic hepatitis C, and a greater understanding of the factors leading to progression to HCC will be necessary to design novel approaches to prevention of HCV-associated HCC. The lack of a small animal model of chronic HCV infection has hampered understanding of these factors. Since HCV is an RNA virus with little potential for integration of its genetic material into the host genome, the mechanisms underlying HCV promotion of cancer are likely to differ from other models of viral carcinogenesis. In patients persistently infected with HCV, chronic inflammation resulting from immune responses against infected hepatocytes is associated with progressive fibrosis and cirrhosis. Cirrhosis is an important risk factor for HCC independent of HCV infection, and a majority of HCV-associated HCC arises in the setting of cirrhosis. However, a significant minority arises in the absence of cirrhosis, indicating that cirrhosis is not a prerequisite for cancer. Other lines of evidence suggest that direct, virus-specific mechanisms may be involved. Transgenic mice expressing HCV proteins develop cancer in the absence of inflammation or immune recognition of the transgene. In vitro studies have revealed multiple interactions of HCV-encoded proteins with cell cycle regulators and tumor suppressor proteins, raising the possibility that HCV can disrupt control of cellular proliferation, or impair the cell's response to DNA damage. A combination of virus-specific, host genetic, environmental, and immune-related factors are likely to determine the progression to HCC in patients who are chronically infected with HCV. Here, we summarize current knowledge of the virus-specific mechanisms that may contribute to HCV-associated HCC

Competing and noncompeting activities of miR-122 and the 5' exonuclease Xrn1 in regulation of hepatitis C virus replication

Hepatitis C virus (HCV) replication is dependent on microRNA 122 (miR-122), a liver-specific microRNA that recruits Argonaute 2 to the 5′ end of the viral genome, stabilizing it and slowing its decay both in cell-free reactions and in infected cells. Here we describe the RNA degradation pathways against which miR-122 provides protection. Transfected HCV RNA is degraded by both the 5′ exonuclease Xrn1 and 3′ exonuclease exosome complex, whereas replicating RNA within infected cells is degraded primarily by Xrn1 with no contribution from the exosome. Consistent with this, sequencing of the 5′ and 3′ ends of RNA degradation intermediates in infected cells confirmed that 5′ decay is the primary pathway for HCV RNA degradation. Xrn1 knockdown enhances HCV replication, indicating that Xrn1 decay and the viral replicase compete to set RNA abundance within infected cells. Xrn1 knockdown and miR-122 supplementation have equal, redundant, and nonadditive effects on the rate of viral RNA decay, indicating that miR-122 protects HCV RNA from 5′ decay. Nevertheless, Xrn1 knockdown does not rescue replication of a viral mutant defective in miR-122 binding, indicating that miR-122 has additional yet uncharacterized function(s) in the viral life cycle

Identification, Motivation and Facilitation of Domestic Tourism in a Small Island

This paper presents a case concerning domestic tourism in the Isle of Man, British Isles; a small maritime nation with Norse heritage. Qualitative interviews find the existence of considerable domestic tourism activity conducted by island residents, including daytrips and overnight stays, and explore the motivational and facilitating factors which underpin this. Such behaviour is identified by residents as touristic and distinct from other leisure pursuits. Yet recognition of domestic tourism in small geographic spaces is currently almost entirely absent. This article attempts to highlight the issue and draw attention to attendant benefits of domestic tourism which include economic and social inputs. These may be relevant to a small island community, and in the case of the Isle of Man help to support an otherwise ailing tourism industry

Hepatitis C Virus Infection Causes Cell Cycle Arrest at the Level of Initiation of Mitosis

Chronic infection with the hepatitis C virus (HCV) is associated with increased risk for hepatocellular carcinoma (HCC). Chronic immune-mediated inflammation is likely to be an important factor in the development of HCV-associated HCC, but direct effects of HCV infection on the host cell cycle may also play a role. Although overexpression studies have revealed multiple interactions between HCV-encoded proteins and host cell cycle regulators and tumor suppressor proteins, the relevance of these observations to HCV-associated liver disease is not clear. We determined the net effect of these interactions on regulation of the cell cycle in the context of virus infection. Flow cytometry of HCV-infected carboxyfluorescein succinimidyl ester-labeled hepatoma cells indicated a slowdown in proliferation that correlated with abundance of viral antigen. A decrease in the proportions of infected cells in G1 and S phases with an accumulation of cells in G2/M phase was observed, compared to mock-infected controls. Dramatic decreases in markers of mitosis, such as phospho-histone H3, in infected cells suggested a block to mitotic entry. In common with findings described in the published literature, we observed caspase 3 activation, suggesting that cell cycle arrest is associated with apoptosis. Differences were observed in patterns of cell cycle disturbance and levels of apoptosis with different strains of HCV. However, the data suggest that cell cycle arrest at the interface of G2 and mitosis is a common feature of HCV infection

Search for quark-lepton compositeness and a heavy W boson using the ev channel in pp(overbar) collisions at (square root)s = 1.8 TeV

We present searches for quark-lepton compositeness and a heavy W′ boson at high electron-neutrino transverse mass. We use ∼110pb-1 of data collected in pp̅ collisions at √s = 1.8TeV by the CDF Collaboration during 1992–1995. The data are consistent with standard model expectations. Limits are set on the quark-lepton compositeness scale Λ, the ratio of partial cross sections σ(W′→eν)/σ(W→eν), and the mass of a W′ boson with standard model couplings. We exclude Λ<2.81TeV and a W′ boson with mass below 754GeV/c2 at the 95% confidence level. Combining with our previously published limit obtained using the muon channel, we exclude a W′ boson with mass below 786GeV/c2 at the 95% confidence level

Search for the supersymmetric partner of the top quark in dileption events from pp colisions at ûs = 1.8TeV

We have searched for pair production of the supersymmetric partner of the top quark (stop) in 107   pb-1 of pp̅ collisions at √s=1.8   TeV collected by the Collider Detector at Fermilab (CDF). Each stop is assumed to decay into a lepton, bottom quark, and supersymmetric neutrino. Such a scenario would give rise to events with two leptons, two hadronic jets, and a substantial imbalance of transverse energy. No evidence of such a stop signal has been found. We exclude stop masses in the region (80≤mt˜≤135   GeV/c2) in the mass plane of stop versus sneutrino