Apoptosis-inducing factor (AIF) exhibits reactive oxygen species (ROS)-generating NADH oxidase activity of unknown significance, which is dispensable for apoptosis. We knocked out the aif gene in two human colon carcinoma cell lines that displayed lower mitochondrial complex I oxidoreductase activity and produced less ROS, but showed increased sensitivity to peroxide-or drug-induced apoptosis. AIF knockout cells failed to form tumors in athymic mice or grow in soft agar. Only AIF with intact NADH oxidase activity restored complex I activity and anchorage-independent growth of aif knockout cells, and induced aif-transfected mouse NIH3T3 cells to form foci. AIF knockdown in different carcinoma cell types resulted in lower superoxide levels, enhanced apoptosis sensitivity and loss of tumorigenicity. Antioxidants sensitized AIF-expressing cells to apoptosis, but had no effect on tumorigenicity. In summary, AIF-mediated resistance to chemical stress involves ROS and probably also mitochondrial complex I. AIF maintains the transformed state of colon cancer cells through its NADH oxidase activity, by mechanisms that involve complex I function. On both counts, AIF represents a novel type of cancer drug target.

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Based on the boost full bridge isolated converter (BFBIC) topology and considering the sudden changes in the external environment, a global maximum power point tracking (GMPPT) control strategy based on an improved gray wolf optimizer (IGWO) algorithm is proposed in this paper. In the strategy, a nonlinear tangent trigonometric function as a convergence factor is integrated into the gray wolf optimizer (GWO) algorithm. In addition, the active-clamp circuit and phase-shift are used to implement the soft switch technology for BFBIC converter in photovoltage (PV) system. Finally, the maximum power point tracking (MPPT) performance on PV system with the proposed IGWO algorithm under static and dynamic partial shading conditions (PSCs) was investigated and compared with other common perturb and observe(P&O), particle swarm optimization (PSO), artificial bee colony (ABC), adapt inertia weight salp swarm algorithm (WSSA), salp swarm algorithm with grey wolf optimizer (SSA-GWO), SSA with PSO (SSA-PSO), enhanced GWO (EGWO) MPPT algorithms. The effectiveness and stability of the proposed control strategy are validated, especially tracking speed under PSCs. Simulation results show that the BFBIC topology with the proposed IGWO algorithm outperforms other algorithms on most cases, especially only takes the tracking time of 0.24s and reaches the efficiency of 98.54% under the most severe PSCs. INDEX TERMS Boost full bridge isolated converter (BFBIC), improved grey wolf optimizer (IGWO), global maximum power point tracking (GMPPT), partial shading conditions (PSCs)

The involution of the corpus luteum (CL) at parturition is an example of physiological apoptosis, a complex process involving massive vascular regression while luteal cells undergo apoptosis. In the present study, changes in gene expression associated with physiological apoptosis were examined. Three genes isolated in our laboratory because of their association with apoptotic processes in the ovary, mammary gland, and prostate served as the focus of our investigation: Y81, Gas-1, and the gene IAP encoding integrin-associated protein. Y81 is a novel gene for which three transcripts are apparent. A Y81 cDNA clone representing the longest transcript has been isolated; it shows an open reading frame exhibiting a region of very high homology with members of the frizzled family, the prototypes of which are cell autonomous polarity genes encoding seven-pass transmembrane receptor proteins, for example the receptor for Wingless. Gas-1 is known as a growth-arrest gene that inhibits DNA synthesis when microinjected into cells. Integrin-associated protein is a beta 3-integrin-binding protein for which, recently, a thrombo-spondin-binding activity has been recognized. These three genes, all sharply up-regulated in the course of physiological involution processes in the ovarian CL, in mammary gland, and in prostate, seem promising candidates-by virtue of their specific expression in distinct tissues undergoing programmed cell death-as mediators of stimuli leading to apoptosis and subsequent phagocytosis. In this study, sulfated glycoprotein-2, previously observed in many instances of physiological apoptosis, was further employed as an indicator for incipient apoptosis, and stromelysin was followed as a marker for the tissue remodeling activity that is intimately associated with apoptosis during involution.

The differential display method has been used in our laboratory as a coincidence analysis to isolate genes expressed in common in each of three different rat tissues undergoing physiological apoptosis: mammary gland, ovarian corpus luteum and ventral prostate. The most interesting of these isolates, DDC-4, shows a clear association with apoptosis, its expression being confined to these three organs, and only during their involution. Using DDC-4 as probe, we screened a rat ovarian cDNA library to obtain full-length isolates. One isolate, Y81