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

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

SRC tyrosine kinase is frequently overexpressed and activated in late-stage, poor prognosis ovarian tumours, and preclinical studies have supported the use of targeted SRC inhibitors in the treatment of this disease. The SAPPROC trial investigated the addition of the SRC inhibitor saracatinib (AZD0530) to weekly paclitaxel for the treatment of platinum resistant ovarian cancer; however, this drug combination did not provide any benefit to progression free survival (PFS) of women with platinum resistant disease. In this study we aimed to identify mechanisms of resistance to SRC inhibitors in ovarian cancer cells. Using two complementary strategies; a targeted tumour suppressor gene siRNA screen, and a phospho-receptor tyrosine kinase array, we demonstrate that activation of MAPK signalling, via a reduction in NF1 (neurofibromin) expression or overexpression of HER2 and the insulin receptor, can drive resistance to AZD0530. Knockdown of NF1 in two ovarian cancer cell lines resulted in resistance to AZD0530, and was accompanied with activated MEK and ERK signalling. We also show that silencing of HER2 and the insulin receptor can partially resensitize AZD0530 resistant cells, which was associated with decreased phosphorylation of MEK and ERK. Furthermore, we demonstrate a synergistic effect of combining SRC and MEK inhibitors in both AZD0530 sensitive and resistant cells, and that MEK inhibition is sufficient to completely resensitize AZD0530 resistant cells. This work provides a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials

A measurement of the W+W- production cross-section in pp collisions at center of mass energy =1.96 TeV in the dilepton channel and limits on anomalous WWZ/gamma couplings.

Measurements of the production cross section of W+W7- pairs in pp collisions at 1.96 TeV and limits on trilinear gauge boson coupling (TGC) parameters are presented. The data were recorded with the CDF experiment at Tevatron during the 2001 and 2002 data taking periods in which a total integrated luminosity of 184 pb-1 was collected. The data sample was filtered for events with two leptonic W boson decays where the charged leptons can be either electrons or muons. 17 events are ob served against an expected background of 5.01q 8 events. The resulting cross- section is found to be a(pp -> W+W ) = 14.5l5 (stat)lJ g(syst) 0.9(lum) pb and agrees well with the Standard Model expectation. Limits on the TGC parameters Aac and A are set under both the equal coupling scheme, that assumes the W boson couples identically to the Z and 7, and the HISZ coupling scheme, that requires the couplings to respect SU(2)L x U(l)y gauge symmetry. In both cases this is achieved by using a likelihood fit to the lepton-PT distribution of the 17 candidate events. The resulting limits are found to be: -0.4 < Aac < +0.6 (A = 0) - 0.3 < A < +0.4 (An = 0) for the EQUAL couplings and -0.7 < Ak < +0.9 (A = 0) - 0.4 < A < +0.4 (An = 0) for the HISZ couplings

The impact of leadership and leadership development in higher education: a review of the literature and evidence

Leadership development and its effectiveness has not been explored in depth empirically, especially across university settings. It is therefore timely that the Leadership Foundation has sought to invest in exploring what is known in the area of the impact of leadership development in higher education settings

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

The impact of leadership and leadership development in higher education : a review of the literature and evidence

Leadership development and its effectiveness has not been explored in depth across university settings. Few studies link leadership development programmes to organisational outcomes in Higher Education (HE) or performance assessment exercises, such as the UK Research Excellence Framework (REF). This review explores what is known in the area of the impact of leadership development in HE settings and offers a contribution to further thinking in this field

The political economy of management knowledge : management texts in English healthcare organizations

Have generic management texts and associated knowledges now extensively diffused into public services organizations? If so, why? Our empirical study of English healthcare organizations detects an extensive presence of such texts. We argue that their ready diffusion relates to two macro-level forces: (i) the influence of the underlying political economy of public services reform and (ii) a strongly developed business school/management consulting knowledge nexus. This macro perspective theoretically complements existing explanations from the meso or middle level of analysis which examine diffusion processes within the public services field, and also more micro literature which focuses on agency from individual knowledge leaders

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

SRC tyrosine kinase is frequently overexpressed and activated in late-stage, poor prognosis ovarian tumours, and preclinical studies have supported the use of targeted SRC inhibitors in the treatment of this disease. The SAPPROC trial investigated the addition of the SRC inhibitor saracatinib (AZD0530) to weekly paclitaxel for the treatment of platinum resistant ovarian cancer; however, this drug combination did not provide any benefit to progression free survival (PFS) of women with platinum resistant disease. In this study we aimed to identify mechanisms of resistance to SRC inhibitors in ovarian cancer cells. Using two complementary strategies; a targeted tumour suppressor gene siRNA screen, and a phospho-receptor tyrosine kinase array, we demonstrate that activation of MAPK signalling, via a reduction in NF1 (neurofibromin) expression or overexpression of HER2 and the insulin receptor, can drive resistance to AZD0530. Knockdown of NF1 in two ovarian cancer cell lines resulted in resistance to AZD0530, and was accompanied with activated MEK and ERK signalling. We also show that silencing of HER2 and the insulin receptor can partially resensitize AZD0530 resistant cells, which was associated with decreased phosphorylation of MEK and ERK. Furthermore, we demonstrate a synergistic effect of combining SRC and MEK inhibitors in both AZD0530 sensitive and resistant cells, and that MEK inhibition is sufficient to completely resensitize AZD0530 resistant cells. This work provides a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials

Cross sections for nu(mu) and (nu)over-bar(mu) induced pion production on hydrocarbon in the few-GeV region using MINERvA

Separate samples of charged-current pion production events representing two semi-inclusive channels nu(mu)-CC(pi(+)) and (nu) over bar (mu) -CC(pi(0)) have been obtained using neutrino and antineutrino exposures of the MINERvA detector. Distributions in kinematic variables based upon mu(+/-)-track reconstructions are analyzed and compared for the two samples. The differential cross sections for muon production angle, muon momentum, and four-momentum transfer Q(2) are reported, and cross sections versus neutrino energy are obtained. Comparisons with predictions of current neutrino event generators are used to clarify the role of the Delta(1232) and higher-mass baryon resonances in CC pion production and to show the importance of pion final-state interactions. For the nu(mu)-CC(pi(+)) [(nu) over bar (mu)-(pi(0))] sample, the absolute data rate is observed to lie below (above) the predictions of some of the event generators by amounts that are typically 1-to- 2 sigma. However the generators are able to reproduce the shapes of the differential cross sections for all kinematic variables of either data set