Patients with acute promyelocytic leukemia (APL) usually relapse after all-trans retinoic acid (RA) treatment because this therapy fails to eradicate the malignant clone. Our data showed that KH 1060 and other 20-epi vitamin D3 analogs alone were potent inhibitors of clonal growth of NB4 cells, an APL cell line (ED50, approximately 5 x 10(-11) M). The combination of KH 1060 and 9-cis-RA synergistically and irreversibly enhanced this effect. Neither KH 1060 nor 9-cis-RA (10(-6) M, 3 d) were strong inducers of differentiation of NB4 cells. However, 98% of the cells underwent differentiation to a mature phenotype with features of both granulocytes and monocytes after exposure to a combination of both compounds. Apoptosis only increased after incubation of NB4 cells with 9-cis-RA alone (28%) or with a combination of 9-cis-RA plus KH1060 (32%). Immunohistochemistry showed that the bcl-2 protein decreased from nearly 100% of the wild-type NB4 cells to 2% after incubation with a combination of KH 1060 and 9-cis-RA, and the bax protein increased from 50% of wild-type NB4 cells to 92% after culture with both analogs (5 x 10(-7) M, 3 d). Western blot analysis paralleled these results. Studies of APL cells from one untreated individual paralleled our results with NB4 cells. Taken together, the data demonstrated that nearly all of the NB4 cells can be irreversibly induced to differentiate terminally when exposed to the combination of KH 1060 and 9-cis-RA. 相似文献
Medical practice guidelines are being developed rapidly and advocated as a crucial component in transforming and improving the delivery of health care services. However, little is known about the ability of hospitals to institute guidelines outside of experimental settings. This article approaches guideline implementation from the viewpoint of process innovation assimilation and presents specific recommendations for organizational tactics leading to successful implementation of practice guidelines. 相似文献
Most metal carbides or slicides may be synthesized at room temperature, by ball milling mixtures of elemental powders for some tens of hours with a vibratory mill. Both stable and metastable compounds containing a high density of defects can be obtained. In general, phases stable at low temperatures are synthesized. This observation allows us to confirm recent estimations for the maximum temperature (600 K) attained in these powders during mechanical alloying. Exceptions are found for some MSi2 suicides with M = titanium, iron or molybdenum for which both low- and high-temperature phases are formed. 相似文献
This paper proposes an efficient hybrid approach for solving multi-objective optimization design of a compliant mechanism. The approach is developed by integrating desirability function approach, fuzzy logic system, adaptive neuro-fuzzy inference system, and Lightning attachment procedure optimization. Box–Behnken design is used to form a numerically experimental matrix. First, a refinement of design variables is conducted through analysis of variance and Taguchi approach in terms of considerably eliminating space of design variables and computation efforts. Next, desirability of two objective functions is computed and transferred into the fuzzy logic system. The output of fuzzy logic system is regarded as single combined objective function. Subsequently, a modeling for fuzzy output is developed via adaptive neuro-fuzzy inference system. Then, LAPO algorithm is adopted for solving the optimization problem. By investigating three different numerical examples, performance of the proposed approach is validated. Numerical results revealed that the proposed approach has a computational accuracy better than that of Taguchi-based fuzzy logic reasoning. Finally, case study 1 is chosen as an optimal solution for the mechanism. Furthermore, the effectiveness of proposed approach is greater than that of the Jaya algorithm and TLBO algorithm through Wilcoxon signed rank test and Friedman test. The proposed approach can be used for related engineering fields.
International Journal of Computer Vision - We propose a monocular depth estimation method SC-Depth, which requires only unlabelled videos for training and enables the scale-consistent... 相似文献