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State-of-the-art fluoroscopic knee kinematic analysis methods require the patient-specific bone shapes segmented from CT or MRI. Substituting the patient-specific bone shapes with personalizable models, such as statistical shape models (SSM), could eliminate the CT/MRI acquisitions, and thereby decrease costs and radiation dose (when eliminating CT). SSM based kinematics, however, have not yet been evaluated on clinically relevant joint motion parameters.  相似文献   
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The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.  相似文献   
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Aging is characterized by the general decline in tissue and body function and the increased susceptibility to age-related pathologies, such as cancer. To maintain optimal tissue and body function, organisms have developed complex mechanisms for tissue homeostasis. Importantly, it is becoming apparent that these same mechanisms when deregulated also result in the development of age-related disease. The build in failsafe mechanisms of homeostasis, which prevent skewing toward disease, themselves contribute to aspects of aging. Thus, longevity is limited by an intrinsic trade-off between optimal tissue function and disease. Consequently, aging and age-related diseases, such as cancer and diabetes are driven by the same genetic determinants. Illustrative in this respect is the insulin/IGF-1 signaling pathway acting through PI3K/PKB and FOXO. Loss of PKB signaling contributes to diabetes, whereas gain of function of PKB drives cancer. Enhanced FOXO activity, at least in model organism contributes to extended lifespan and acts as a tumor suppressive mechanism. Here, we focus on the linkage between PKB and FOXO as a central switch in contributing to tissue homeostasis and age-related diseases in particular cancer. This article is part of a Special Issue entitled: P13K-AKT-FoxO axis in cancer and aging.  相似文献   
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Question: Dutch fen areas have become embedded in intensively used landscapes, resulting in biodiversity loss. Hence, plant species that colonize open water inducing the formation of species‐rich floating peat mats have disappeared. Despite many restoration efforts, they have not returned. Is natural succession towards floating mats impeded by site conditions, dispersal limitations or changed biotic interactions? Location: Six Dutch fen reserves: De Deelen, De Weerribben, De Wieden, Westbroek, Molenpolder and Terra Nova. Methods: In 62 fen ponds we determined plant species richness and expansion into open water. We related these to habitat quality (chemical composition of soil and surface water, pond morphology), dispersal potential (distance to remnant populations, likelihood of dispersal) and biotic interactions (presence of muskrats [Ondatra zibethicus L.] and the keystone species Stratiotes aloides). Results: Factor analysis showed that plants expanded further into open water and bank vegetation had higher species richness in areas with older ponds and lower muskrat densities. Locally, high turbidity hampered colonization. Whenever the water was clear, colonization was higher in shallow ponds, and in deep ponds only if Stratiotes was present. Species richness was negatively correlated to nutrient availability in soil and positively correlated to hydrological isolation (decreased sulphate concentrations). We also found that species richness was higher in sheltered banks. Conclusions: Multiple habitat characteristics (turbidity, water depth, nutrient and sulphate concentrations) and the influence of muskrats and Stratiotes all play a role in the lack of restoration success in Dutch fen ponds. Dispersal limitations seem to be overruled by habitat limitations, as colonization often fails even when sufficient propagule sources are present, or when connectivity is high.  相似文献   
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