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Evasion of apoptosis allows many cancers to resist chemotherapy. Apoptosis is mediated by the serial activation of caspase family proteins. These proteases are often activated upon the release of cytochrome c from the mitochondria, which is promoted by the proapoptotic Bcl-2 family protein, Bax. This function of Bax is enhanced by the MOAP-1 (modulator of apoptosis protein 1) protein in response to DNA damage. Previously, we reported that MOAP-1 is targeted for ubiquitylation and degradation by the APC/CCdh1ubiquitin ligase. In this study, we identify the HECT (homologous to the E6-AP carboxyl terminus) family E3 ubiquitin ligase, UBR5, as a novel ubiquitin ligase for MOAP-1. We demonstrate that UBR5 interacts physically with MOAP-1, ubiquitylates MOAP-1 in vitro and inhibits MOAP-1 stability in cultured cells. In addition, we show that Dyrk2 kinase, a reported UBR5 interactor, cooperates with UBR5 in mediating MOAP-1 ubiquitylation. Importantly, we found that cisplatin-resistant ovarian cancer cell lines exhibit lower levels of MOAP-1 accumulation than their sensitive counterparts upon cisplatin treatment, consistent with the previously reported role of MOAP-1 in modulating cisplatin-induced apoptosis. Accordingly, UBR5 knockdown increased MOAP-1 expression, enhanced Bax activation and sensitized otherwise resistant cells to cisplatin-induced apoptosis. Furthermore, UBR5 expression was higher in ovarian cancers from cisplatin-resistant patients than from cisplatin-responsive patients. These results show that UBR5 downregulates proapoptotic MOAP-1 and suggest that UBR5 can confer cisplatin resistance in ovarian cancer. Thus UBR5 may be an attractive therapeutic target for ovarian cancer treatment.

AbstractThis study discusses the components' geometry and its effect on the capability of heat transmission and pressure drop because of its evident influence on the performance of micro capillary pumped loop (MCPL). On analyzing the dimensional effect on heat transmission and pressure gradient of MCPL device, some results were yielded and addressed as follows: The vapor line was the most important factor among the components of MCPL in heat transmission and pressure drop. Furthermore, the depth of vapor line was the main parameter because of its drastic effect. In addition, at depth of vapor line, hv, ranging from 20 μm to 150 μm, the amount of heat transferred for system will increase, but decrease the pressure drop. However, for hvlarger than 150 μm, the heat transfer and pressure drop both will reach a limit. A new family of geometrical dimensions of MCPL possessing an excellent heat flux of 178 W/cm2would be obtained. These findings will be useful in designing a better MCPL.

AbstractIn this paper, we introduce a new class of general mixed vector F-implicit complementarity problems and general mixed vector F-implicit variational inequality problems, and study the equivalence between of them under certain assumptions in Banach spaces. We also derive some new existence theorems of solutions for the general mixed vector F-implicit complementarity problems and the general mixed vector F-implicit variational inequality problems by using the FKKM theorem under some suitable assumptions without monotonicity. Moreover, we establish sufficient conditions for the upper semicontinuity and lower semicontinuity of the solution mapping of the general mixed vector F-implicit variational inequality problems.

Oxidative cleavage of cyclic acetals such as (I) or (III) is performed with potassium permanganate under phase‐transfer conditions, yielding ω‐hydroxyalkyl carboxylates such as (II) or (IV).