The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS) production, whereas the DNA repair enzyme and transcriptional regulator redox factor-1 (ref-1) protects against cell death due to oxidative stimuli. However, the function of ref-1 in regulating intracellular oxidative stress, particularly that induced by rac1, has not been defined. We production), NF-k kB activation, and apoptosis, and also mitigated rac1-regulated H 2 O 2 production and NF-k kB transcriptional activity. We conclude that inhibition of oxidative stress is another mechanism by which ref-1 protects against apoptosis, and that this is achieved through modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel extra-nuclear function of ref-1.

Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6–12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy.Patients and methods: A detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted.Results: Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357).Conclusion: The superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.

An iridoid glucoside, aucubin was isolated from Aucuba japonica leaves and its protective activities against CCl4-induced hepatotoxicity were evaluated by measuring the duration of hypnosis induced by hexobarbital after CCl4 challenge (0.2 ml/kg/day, po) and the levels of serum glutamic-oxalacetic (GOT) and serum glutamic-pyruvic transaminase (GPT). The duration of hypnosis for the saline control group, the CCl4 alone treated group and the aucubin plus CCl4 treated group was 24.8 +/- 8.5, 60.5 +/- 9.5 and 28.0 +/- 3.2 min, respectively. Treatment of mice with aucubin also effectively protected against CCl4-induced increased serum GOT and GPT activities. It was found that aucubin inhibited hepatic RNA and protein syntheses in vivo. Such inhibitory effects of aucubin might be responsible for protective activities against CCl4-induced liver damage.

Residential architecture constitutes one of the largest market segments in the construction sector. However, the attention that it is given in the field of daylight performance simulation is surprisingly low. This poses the question of whether existing daylighting metrics are well suited for residential design. Findings from 79 references are summarized, and a critical review of current climate-based daylighting metrics in the context of residential architecture is provided. It is found that existing workflows often overlook relevant aspects of daylight in residential spaces, such as diurnal and seasonal availability of daylight and access to direct sunlight. Hence, a concept for a new climate-based, annual evaluation framework that overcomes these shortcomings, called the residential daylight score, is introduced.