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EphB2, a receptor tyrosine kinase regulated by the β-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus a...
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EphB2, a receptor tyrosine kinase regulated by the β-catenin/Tcf4 complex, is expressed in the proliferative compartment of mouse intestine and regulates bidirectional migration of intestinal precursor cells in the crypt-villus axis through repulsive interaction with Ephrin-B ligands. Recently, it has been shown that reduction of EphB activity accelerates colon tumour progression in the ApcMin/+ mice. In this study, we examined the expression of EphB2 in normal colon, adenomas, primary colorectal cancers (CRCs), lymph node metastases and liver metastases using immunohistochemistry on tissue microarrays. In addition, EphB2 was overexpressed in SW480 colon cancer cells to study its effect in vitro. We found that EphB2 was expressed in 100% of normal colon crypt base cells, 78% of adenomas, 55.4% of primary CRCs, 37.8% of lymph node metastases and 32.9% of liver metastases (all differences were statistically significant at P < 0.001 compared with primary CRCs). Patients with CRCs that lose EphB2 expression had more advanced tumour stage (P = 0.005), poor differentiation (P < 0.001), poor overall survival (P = 0.005) and disease-free survival (P = 0.001), with the latter being independent of tumour stage. In vitro studies showed that overexpression of EphB2 inhibited colon cancer cell growth in colony formation assay and activation of EphB2 receptor inhibited colon cancer cell adhesion and migration. Our data demonstrated a progressive loss of EphB2 expression in each critical step of colon carcinogenesis, including the onset of invasion, dedifferentiation and metastasis which are paralleled by adverse patient outcome. EphB2 may achieve its tumour suppressor function through regulation of cell survival, adhesion and migration.
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This paper examines the operating characteristics of a class of tandem Banyan switching fabrics (TBSF's) built using bi-delta networks. We use the functional equivalence between bi-delta networks to induce an equivalence between T...
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This paper examines the operating characteristics of a class of tandem Banyan switching fabrics (TBSF's) built using bi-delta networks. We use the functional equivalence between bi-delta networks to induce an equivalence between TBSF's. A weaker form of equivalence guaranteeing identical performance under conditions of symmetric traffic is studied, and a sufficient condition for weak equivalence between functionally distinct TBSF's is established. These results hold for a variety of conflict resolution policies (CRP's) in addition to the one studied by Tobagi et al. (see IEEE J. Select. Areas Commun., vol.9, p.1173, 1991). Simulations indicate that a TBSF constructed by cascading omega networks, (or in fact any other TBSF in its weak equivalence class), performs better than the two TBSF's studied by Tobagi et al., and converges rapidly to a theoretical lower bound on the loss rate, in the region of interest. It is also shown that this loss rate is almost independent of the size of such a TBSF in the region of interest.
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Human colonic epithelial cell renewal, proliferation, and differentiation are stringently controlled by numerous regulatory pathways. To identify genetic programs of human colonic epithelial cell differentiation in vivo as well as...
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Human colonic epithelial cell renewal, proliferation, and differentiation are stringently controlled by numerous regulatory pathways. To identify genetic programs of human colonic epithelial cell differentiation in vivo as well as candidate marker genes that define colonic epithelial stem/progenitor cells and the stem cell niche, we applied gene expression analysis of normal human colon tops and basal crypts by using expression microarrays with 30,000 genes. Nine hundred and sixty-nine cDNA clones were found to be differentially expressed between human colon crypts and tops. Pathway analysis revealed the differential expression of genes involved in cell cycle maintenance and apoptosis, as well as genes in bone morphogenetic protein (BMP), Notch, Wnt, EPH, and MYC signaling pathways. BMP antagonists gremlin 1, gremlin 2, and chordin-like 1 were found to be expressed by colon crypts. In situ hybridization and RT-PCR confirmed that these BMP antagonists are expressed by intestinal cryptal myofibroblasts and smooth muscle cells at the colon crypt. In vitro analysis demonstrated that gremlin 1 partially inhibits Caco-2 cell differentiation upon confluence and activates Wnt signaling in normal rat intestinal epithelial cells. Collectively, the expression data set provides a comprehensive picture of human colonic epithelial cell differentiation. Our study also suggests that BMP antagonists are candidate signaling components that make up the intestinal epithelial stem cell niche.
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In this work, an exact solution for the steady state Navier-Stokes equations in cylindrical coordinates is presented by similarity transformation technique. The solution involves the flow between two stretchable infinite disks wit...
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In this work, an exact solution for the steady state Navier-Stokes equations in cylindrical coordinates is presented by similarity transformation technique. The solution involves the flow between two stretchable infinite disks with accelerated stretching velocity. The similarity equation was solved numerically and the effects of disk stretching parameter and stretching Reynolds number were studied. With the increase of the stretching Reynolds numbers, the fluid begins with a creeping type flow at R=0 to a typical boundary layer type flow for large Reynolds numbers. The pressure parameter β changes from a positive number to a negative value with the increase of non-zero stretching parameter. The upper wall stretching parameter also greatly affects the velocity distribution between the two disks with a downward net flow for γ≠ 1. The results are also useful as a benchmark problem for the validation of three-dimensional numerical computation code.
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Activated on the surface of nanometre-sized TiO_2, NO gas can easily react with aliphatic cyclic amines and aryl free radicals at RT under atmospheric pressure to offer NONOates and cupferron sodiums, respectively.
An increasing ...
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Activated on the surface of nanometre-sized TiO_2, NO gas can easily react with aliphatic cyclic amines and aryl free radicals at RT under atmospheric pressure to offer NONOates and cupferron sodiums, respectively.
An increasing knowledge of the role of nitric oxide (NO) in a number of physiological and pathological processes has stimulated efforts to target the NO pathway pharmacologically. Since NO is a pleiotropic molecule, the selective delivery of NO to the specific tissues has recently been attracting much attention, particularly in the field of anticancer therapy. Among the various NO donors that directly or indirectly release NO being used in biomedical research, nitrogen-bound diazen-1-ium-1,2-diolate (formally known as NONOate) is the most important, owing to its ability to deliver NO to some specific tissues.
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