The oncoprotein H-RasV12 increases mitochondrial metabolism

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Features and Outcomes of 899 Patients With Drug-Induced Liver Injury: The DILIN Prospective Study

The drug-induced liver injury network (DILIN) is conducting a prospective study of patients with DILI in the United States. We present characteristics and subgroup analyses from the first 1257 patients enrolled in the study

NEXT GENERATION FUNCTIONAL COMPONENTS FOR SPACE TELEMETRY DATA PROCESSING

International Telemetering Conference Proceedings / November 04-07, 1991 / Riviera Hotel and Convention Center, Las Vegas, NevadaSpace telemetry data processing elements for flight and ground systems are currently developed using discrete components on a project-by-project basis. The adoption of various standards, such as those recommended by the Consultative Committee for Space Data Systems (CCSDS), brings commonality of requirements across future NASA communications elements and affords the opportunity to create standard components to meet these requirements. Over the past five years, NASA’s Goddard Space Flight Center (GSFC) has developed a series of high performance Very Large Scale Integration (VLSI) components for space data systems. These standard components have enabled the development of high performance data systems that are an order of magnitude more compact and cost effective than systems of the previous generation. Recent advances in design automation tools and integrated circuit densities have yielded the means to achieve yet another leap in the integration levels, performance and cost reduction of space data systems. Design automation tools can generate complex integrated circuit designs from high level technology independent functional descriptions. A single reusable functional description can be targeted to a variety of circuit technologies including CMOS, ECL and GaAs. With available densities of over 1 million integrated transistors in both CMOS and GaAs technologies, standard components integrating multiple processing elements are realizable for both flight and ground projects. This paper describes the ongoing efforts of the Microelectronics Systems Branch at GSFC to create highly integrated components to meet functions outlined by the CCSDS using design automation techniques.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

Frame Synchronization At 300 Mbps And Beyond ...

International Telemetering Conference Proceedings / October 29-November 02, 1990 / Riviera Hotel and Convention Center, Las Vegas, NevadaWhile most current ground based space telemetry acquisition systems are designed for and support data rates up to a few megabits per second (Mbps), NASA’s Tracking and Data Relay Satellite System (TDRSS) can support downlink rates up to 300 Mbps. In addition, the Advanced TDRSS (ATDRSS) is expected to support rates up to 650 Mbps. These high data rates will be required to support NASA’s future large scale operational programs such as the Space Station Freedom and the Earth Observation System. At the Goddard Space Flight Center, a prototype Frame Synchronizer card is under development which will operate at a minimum of 300 Mbps while providing a full suite of programmable functions such as 32 bit correlation, search-check-lock strategy, bit slip tolerance, fly wheeling, etc. In addition, cumulative quality data generation, on-board self diagnostics, and status/control processing are all integrated in this single card design. This level of functionality and very high data rate is made possible by the design of NASA application specific Gallium Arsenide (GaAs) Very Large Scale Integrated (VLSI) circuits to support space telemetry data system standards specified by the Consultative Committee for Space Data Systems. This paper will describe functions performed by this card and its supporting VLSI components.International Foundation for TelemeteringProceedings from the International Telemetering Conference are made available by the International Foundation for Telemetering and the University of Arizona Libraries. Visit http://www.telemetry.org/index.php/contact-us if you have questions about items in this collection

Cytochrome c oxidase is activated by the oncoprotein Ras and is required for A549 lung adenocarcinoma growth

Abstract Background Constitutive activation of Ras in immortalized bronchial epithelial cells increases electron transport chain activity, oxygen consumption and tricarboxylic acid cycling through unknown mechanisms. We hypothesized that members of the Ras family may stimulate respiration by enhancing the expression of the Vb regulatory subunit of cytochrome c oxidase (COX). Results We found that the introduction of activated H-RasV12 into immortalized human bronchial epithelial cells increased eIF4E-dependent COX Vb protein expression simultaneously with an increase in COX activity and oxygen consumption. In support of the regulation of COX Vb expression by the Ras family, we also found that selective siRNA-mediated inhibition of K-Ras expression in A549 lung adenocarcinoma cells reduced COX Vb protein expression, COX activity, oxygen consumption and the steady-state concentration of ATP. We postulated that COX Vb-mediated activation of COX activity may be required for the anchorage-independent growth of A549 cells as soft agar colonies or as lung xenografts. We transfected the A549 cells with COX Vb small interfering or shRNA and observed a significant reduction of their COX activity, oxygen consumption, ATP and ability to grow in soft agar and as poorly differentiated tumors in athymic mice. Conclusion Taken together, our findings indicate that the activation of Ras increases COX activity and mitochondrial respiration in part via up-regulation of COX Vb and that this regulatory subunit of COX may have utility as a Ras effector target for the development of anti-neoplastic agents.</p

Selective inhibition of choline kinase simultaneously attenuates MAPK and PI3K/AKT signaling

Choline is an essential anabolic substrate for the synthesis of phospholipids. Choline kinase phosphorylates choline to phosphocholine that serves as a precursor for the production of phosphatidylcholine, the major phospholipid constituent of membranes and substrate for the synthesis of lipid signaling molecules. Nuclear magnetic resonance (NMR)-based metabolomic studies of human tumors have identified a marked increase in the intracellular concentration of phosphocholine relative to normal tissues. We postulated that the observed intracellular pooling of phosphocholine may be required to sustain the production of the pleiotropic lipid second messenger, phosphatidic acid. Phosphatidic acid is generated from the cleavage of phosphatidylcholine by phospholipase D2 and is a key activator of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT survival signaling pathways. In this study we show that the steady-state concentration of phosphocholine is increased by the ectopic expression of oncogenic H-Ras(V12) in immortalized human bronchial epithelial cells. We then find that small interfering RNA (siRNA) silencing of choline kinase expression in transformed HeLa cells completely abrogates the high concentration of phosphocholine, which in turn decreases phosphatidylcholine, phosphatidic acid and signaling through the MAPK and PI3K/AKT pathways. This simultaneous reduction in survival signaling markedly decreases the anchorage-independent survival of HeLa cells in soft agar and in athymic mice. Last, we confirm the relative importance of phosphatidic acid for this pro-survival effect as phosphatidic acid supplementation fully restores MAPK signaling and partially rescues HeLa cells from choline kinase inhibition. Taken together, these data indicate that the pooling of phosphocholine in cancer cells may be required to provide a ready supply of phosphatidic acid necessary for the feed-forward amplification of cancer survival signaling pathways.James Graham Brown Cancer CenterUnited States Department of Health & Human Services National Institutes of Health (NIH) - USA (1 R01 CA11642801)Kentucky Lung Cancer Research Progra