452 research outputs found

    Studies of stem cell and adhesion proteins in breast cancer

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    Breast cancer is the commonest cancer and second leading cause of cancer death in women. It has been shown that breast cancer tumorigenic/stem cell like cells are CD24-/low CD44+EpCAM+. These cells constitute less than 5% of the cells within a cancer and are probably responsible for recurrence and metastasis. In the first paper of the thesis we show that there is uncoupling of the ERα regulated morphological phenotype from the cancer stem cell phenotype in human breast cancer cells. Experimental silencing of ERα resulted in a reduced epithelial appearance and partial reduction of CD24 mRNA, while levels of CD44 and EpCAM were unaltered. Moreover, knockdown of ERα led to a change in the morphology of the cells similar to the epithelial to mesenchymal transition phenotype and was associated with decreased E-cadherin level. Our findings offer new insights into the regulation of the breast cancer cell phenotype by ERα. In the second and third papers we chose to immunoprecipitate the stem cell and cell adhesion protein EpCAM to identify new EpCAM interacting proteins. We have found a candidate EpCAM associated protein named Endoplasmic Reticulum Aminopeptidase 2 (ERAP2). ERAP2 was co-precipitated and colocalized with EpCAM in breast cancer cells both in the cytoplasm/ER and the plasma membrane. We expressed the two proteins in vitro in presence of dog pancreas rough microsomes (ER vesicles) and confirmed N-linked glycosylation of both proteins and the size of EpCAM. We conclude that the association between ERAP2 and EpCAM is a unique and novel finding, providing new ideas on how antigen presentation may be regulated. In the third paper we continue to search for EpCAM associated proteins using coimmunoprecipitation (IP) and mass spectrometry. We found that Annexin A2 co-precipitated with EpCAM. IP, Western blotting and reverse co-IP confirmed the finding. Furthermore both EpCAM and Annexin A2 colocalized in the cytoplasm and cell membrane in EpCAM+ cells. This association requires more studies to show the role of Annexin A2 in breast cancer. In the fourth paper we have assembled a list of genes potentially associated with the breast cancer stem cells and genes that are involved in epithelial-mesenchymal transition (EMT). We performed a gene expression clustering analysis of breast cancer cell lines using cancer cell lines encyclopedia and GenePattern. We found three clusters, one epithelial (cluster alpha), one mesenchymal (beta) and a third (gamma). Both cluster beta and gamma were characterized by relatively low levels of ESR1 (ERα) as compared to cluster alpha. Clustering analysis performed on clinical samples also generated two distinct groups with low ESR1 levels. Further analysis of these three clusters will show whether there are unique gene expression patterns or overlap between them, especially between cluster beta and gamma. Subsequently we have used the same gene list and analyzed different breast cancer datasets present in the Oncomine ® platform to study relationship between EMT and stem cell phenotypes expressing these genes and their correlation with molecular subtypes, and clinical outcome

    In AUC, a stigma lives on

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    In the American University in Cairo, Egypt\u27s most mentally liberated campus, many students are still reluctant when it comes to addressing the Student Counseling Center when they are facing problems. AUC\u27s Dina Salah ElDin reports

    Indicators of variance in the frequency of terrorist attacks across Egyptian governorates

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    This paper explores different factors associated with the apparent urban concentration of terrorist attacks in Egypt (outside Sinai) since July 2013. The effect of socio-economic variables such as unemployment and poverty on terrorism are assessed in addition to other variables like multitude of targets, logistical considerations, and Islamist support base. Using data collected from local media sources, the results presented in this paper show that support for Islamist parties correlates positively with the number of terrorist attacks. Socio-economic factors like poverty and overall unemployment rate appear to have little explanatory value. The results also suggest that the urban-rural divide in the terrorism literature should not be taken at its face value but rather should be adapted to fit the local context

    Dynamics of Stochastic Systems with Memory (Mathematics and Statistics Colloquium, Wright State University)

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    We describe an approach to the dynamics of stochastic systems with finite memory using multiplicative cocycles in Hilbert space. We introduce the notion of hyperbolicity for stationary solutions of the stochastic differential system. We then establish the existence of smooth stable and unstable manifolds in a neighborhood of a hyperbolic stationary solution. The stable and unstable manifolds are stationary and asymptotically invariant under the stochastic semiflow. The proof uses ideas from infinite-dimensional multiplicative ergodic theory and interpolation arguments

    Improving Building Fabric Energy Efficiency in Hot-Humid Climates using Dynamic Insulation

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    On the Dynamics of Stochastic Differential Equations (Ellis B. Stouffer Colloquium, University of Kansas)

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    We formulate and outline a proof of the Local Stable Manifold Theorem for stochastic differential equations (SDE\u27s) in Euclidean space (joint work with M. Scheutzow). This is a central result in dynamical systems with noise. Starting with the existence of a stochastic flow for an SDE, we introduce the notion of a hyperbolic stationary trajectory. We prove the existence of invariant random stable and unstable manifolds in the neighborhood of a hyperbolic stationary solution. For Stratonovich noise, the stable and unstable manifolds are dynamically characterized using forward and backward solutions of the anticipating SDE
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