[Abstract unavailable

All-polymer solar cells have shown great potential as flexible and portable power generators. These devices should offer good mechanical endurance with high power-conversion efficiency for viability in commercial applications. In this work, we develop highly efficient and mechanically robust all-polymer solar cells that are based on the PBDTTTPD polymer donor and the P(NDI2HD-T) polymer acceptor. These systems exhibit high power-conversion efficiency of 6.64%. Also, the proposed all-polymer solar cells have even better performance than the control polymer-fullerene devices with phenyl-C61-butyric acid methyl ester (PCBM) as the electron acceptor (6.12%). More importantly, our all-polymer solar cells exhibit dramatically enhanced strength and flexibility compared with polymer/PCBM devices, with 60- and 470-fold improvements in elongation at break and toughness, respectively. The superior mechanical properties of all-polymer solar cells afford greater tolerance to severe deformations than conventional polymer-fullerene solar cells, making them much better candidates for applications in flexible and portable devices.

Knockout of caspase-8, a cysteine protease that participates in the signaling for cell death by receptors of the TNF/nerve growth factor family, is lethal to mice in utero. To explore tissue-specific roles of this enzyme, we established its conditional knockout using the Cre/loxP recombination system. Consistent with its role in cell death induction, deletion of caspase-8 in hepatocytes protected them from Fas-induced caspase activation and death. However, application of the conditional knockout approach to investigate the cause of death of caspase-8 knockout embryos revealed that this enzyme also serves cellular functions that are nonapoptotic. Its deletion in endothelial cells resulted in degeneration of the yolk sac vasculature and embryonal death due to circulatory failure. Caspase-8 deletion in bone-marrow cells resulted in arrest of hemopoietic progenitor functioning, and in cells of the myelomonocytic lineage, its deletion led to arrest of differentiation into macrophages and to cell death. Thus, besides participating in cell death induction by receptors of the TNF/nerve growth factor family, caspase-8, apparently independently of these receptors, also mediates nonapoptotic and perhaps even antiapoptotic activities.

O-linked-N-acetylglucosamine (O-GlcNAc) has emerged as a critical regulator of diverse cellular processes, but its role in embryonic stem cells (ESCs) and pluripotency has not been investigated. Here we show that O-GlcNAcylation directly regulates core components of the pluripotency network. Blocking O-GlcNAcylation disrupts ESC self-renewal and reprogramming of somatic cells to induced pluripotent stem cells. The core reprogramming factors Oct4 and Sox2 are O-GlcNAcylated in ESCs, but the O-GlcNAc modification is rapidly removed upon differentiation. O-GlcNAc modification of threonine 228 in Oct4 regulates Oct4 transcriptional activity and is important for inducing many pluripotency-related genes, including Klf2, Klf5, Nr5a2, Tbx3, and Tcl1. A T228A point mutation that eliminates this O-GlcNAc modification reduces the capacity of Oct4 to maintain ESC self-renewal and reprogram somatic cells. Overall, our study makes a direct connection between O-GlcNAcylation of key regulatory transcription factors and the activity of the pluripotency network.

Cisplatin is one of the most commonly used anticancer drugs. It kills cancer cells by damaging their DNA, and hence cellular DNA repair capacity is an important determinant of its efficacy. Here, we investigated the repair of cisplatin-induced DNA damage in mouse liver and testis tissue extracts prepared at regular intervals over the course of a day. We find that the XPA protein, which plays an essential role in repair of cisplatin damage by nucleotide excision repair, exhibits circadian oscillation in the liver but not in testis. Consequently, removal of cisplatin adducts in liver extracts, but not in testis extracts, exhibits a circadian pattern with zenith at ∼5 pm and nadir at ∼5 am. Furthermore, we find that the circadian oscillation of XPA is achieved both by regulation of transcription by the core circadian clock proteins including cryptochrome and by regulation at the posttranslational level by the HERC2 ubiquitin ligase. These findings may be used as a guide for timing of cisplatin chemotherapy.C hronochemotherapy is the administration of chemotherapeutic drugs at specific times of the day so as to optimize efficacy and minimize side effects of the drug (1, 2). Cisplatin is one of the three most commonly used chemotherapeutic drugs (3) for which chronotherapy is thought to have some beneficial effects. Factors that modulate the efficacy of cisplatin therapy include drug uptake and efflux, DNA adduct formation, DNA repair, and cellular proliferation (4, 5). Cisplatin produces DNA intra-and interstrand diadducts and DNA-protein crosslinks (4), and it is well established that the intrastrand diadducts Pt-(GpG), Pt-(ApG), and Pt-(GpXpG), that constitute up to 90% of the total DNA lesions, are the main cause of its cytotoxicity and hence its therapeutic effects. These lesions are removed exclusively by nucleotide excision repair (excision repair) in mammalian cells and hence the status of excision repair is an important factor in the success of chemotheraphy with cisplatin (4, 6).In humans and mice, excision repair is carried out by the coordinated action of six core repair factors, RPA, XPA, XPC, TFIIH, XPG, and XPF-ERCC1, which remove the damage in the form of 24-32 nt-long oligomers; the resulting gap is filled by DNA polymerases and ligated (7-9).Recently, we found that the rate of excision repair of a UV photoproduct in the mouse brain exhibits a daily rhythm (10). Furthermore, it appears that this rhythmic pattern is due to the circadian (circa ¼ about, dies ¼ day) oscillation of the XPA (xeroderma pigmentosum A) protein that is one of the ratelimiting factors in excision repair. Even though in that study the damaged-DNA substrate was a UV photoproduct, we suggested that the findings were relevant to the repair of cisplatin because nucleotide excision repair is the only repair system capable of removing bulky DNA lesions produced by UV or by UVmimetic agents such as cisplatin (11). Although cisplatin is used for treating certain brain cancers, the blood-brain barrier is a serious impediment for its gen...

We demonstrate the realization of the high-brightness and high-efficiency light emitting diodes (LEDs) using dislocation-free indium gallium nitride (InGaN)/gallium nitride (GaN) multiquantum-well (MQW) nanorod (NR) arrays by metal organic-hydride vapor phase epitaxy (MO−HVPE). MQW NR arrays (NRAs) on sapphire substrate are buried in spin-on glass (SOG) to isolating individual NRs and to bring p-type NRs in contact with p-type electrodes. The MQW NRA LEDs have similar electrical characteristics to conventional broad area (BA) LEDs. However, due to the lack of dislocations and the large surface areas provided by the sidewalls of NRs, both internal and extraction efficiencies are significantly enhanced. At 20 mA dc current, the MQW NRA LEDs emit about 4.3 times more light than the conventional BA LEDs, even though overall active volume of the MQW NRA LEDs is much smaller than conventional LEDs. Moreover, the fabrication processes involved in producing MQW NRA LEDs are almost the same for conventional BA LEDs. It is, thus, not surprising that the total yield of these MQW NRA LEDs is essentially the same as that of conventional BA LEDs. The present method of utilizing dislocation-free MQW NRA LEDs is applicable to super-bright white LEDs as well as other semiconductor LEDs for improving total external efficiency and brightness of LEDs.

Summary Mice deficient in caspase-8, FADD, or cFLIP, present defects in yolk sac vascularization and embryonic lethality at E10.5. Ablation of RIPK3, a kinase that promotes a form of necrotic cell death, has recently been shown to rescue embryonic lethality in caspase-8 deficient animals. Here we show that while FADD, RIPK3 double knockouts develop normally, the lethal effects of cFLIP deletion are not rescued by RIPK3 deficiency. Remarkably, embryos lacking FADD, cFLIP, and RIPK3 develop normally. Distinct regions of apoptosis were observed in E9.5 FLIP, RIPK3 double knockout embryos, but not in caspase-8−/− or FADD−/− embryos. In vitro studies using death receptor stimulation show that the FADD-caspase-8-cFLIPL complex blocks RIPK3-dependent necrosis, while cFLIPL blocks RIPK3-independent apoptosis promoted by the FADD-caspase-8 complex. Together, these results suggest the cross-regulation of two distinct processes in development and death-receptor signaling: RIPK3-dependent signaling (including necrosis) controlled by the enzymatic activity of the FADD-caspase-8-cFLIPL complex, and cFLIPL control of RIPK3-independent apoptosis by FADD-caspase-8.

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