GC-selective DNA-binding antibiotic, Mithramycin A, reveals multiple points of control in the regulation of Hdm2 protein synthesis

The primary role of the Hdm2/Mdm2 oncoprotein is to regulate the levels and activity of the transcription factor p53. Hdm2 synthesis is itself tightly controlled and, as demonstrated by a recently described SNP (SNP309) in the hdm2-P2 promoter, minor variations in Hdm2 expression have phenotypic consequences on radiation sensitivity and cancer predisposition. To further define mechanisms regulating Hdm2 expression, we have investigated the effects of the GC-selective DNA-binding drug, Mithramycin A (MA) on hdm2 mRNA transcription, trafficking, and translation. Firstly we show that the constitutive hdm2-P1 promoter is inhibited by MA. We define, for the first time, the minimal sequence elements that are required for P1-promoter activity and identify those which confer MA sensitivity. Secondly, MA induces p53-dependent transcription from the hdm2-P2 promoter. Thirdly, and critically, MA also inhibits Hdm2 synthesis at the post-transcriptional level, with negative effects on hdm2 mRNA nuclear export and translation. This study highlights the complex interplay between the pathways that regulate Hdm2 protein synthesis in cancer cells, and furthermore emphasizes the export of hdm2 mRNA from the nucleus to the cytoplasm as a key point of control in this process.<br/><br/

Evaluation of battery models for prediction of electric vehicle range

Three analytical models for predicting electric vehicle battery output and the corresponding electric vehicle range for various driving cycles were evaluated. The models were used to predict output and range, and then compared with experimentally determined values determined by laboratory tests on batteries using discharge cycles identical to those encountered by an actual electric vehicle while on SAE cycles. Results indicate that the modified Hoxie model gave the best predictions with an accuracy of about 97 to 98% in the best cases and 86% in the worst case. A computer program was written to perform the lengthy iterative calculations required. The program and hardware used to automatically discharge the battery are described

Computer program for crossed-beam studies of clear air turbulence, Program description /MLTCOR/ Final report, 14 May 1968 - 13 Aug. 1969

Computer program for studies of aerodynamic and clear atmospheric turbulenc

Skylab extravehicular mobility unit thermal simulator

The analytical methods, thermal model, and user's instructions for the Skylab Extravehicular Mobility Unit (SEMU) routine are presented. This digital computer program was developed for detailed thermal performance predictions of the SEMU on the NASA-JSC Univac 1108 computer system. It accounts for conductive, convective, and radiant heat transfer as well as fluid flow and special component characterization. The program provides thermal performance predictions for a 967 node thermal model in one thirty-sixth (1/36) of mission time when operated at a calculating interval of three minutes (mission time). The program has the operational flexibility to: (1) accept card or magnetic tape data input for the thermal model describing the SEMU structure, fluid systems, crewman and component performance, (2) accept card and/or magnetic tape input of internally generated heat and heat influx from the space environment, and (3) output tabular or plotted histories of temperature, flow rates, and other parameters describing system operating modes

The Legal Environment and the Choice of Default Resolution Alternatives: An Empirical Analysis

In addition to standard foreclosure, three other methods of resolution for mortgage defaults are available: bankruptcy protection, surrender of deed to the lender, and pre-foreclosure sale. This paper develops a model that specifies the choice of resolution method as a function of the state-specific legal environment and local area economic conditions. A large national data set is used to estimate a multinomial logit choice model for the 1987 to 1991 period. The results indicate that the choice of default resolution alternative is sensitive to the legal environment. The results imply that selected legal reforms will tend to improve the efficiency of the default resolution process.

Two-dimensional global manifolds of vector fields

We describe an efficient algorithm for computing two-dimensional stable and unstable manifolds of three-dimensional vector fields. Larger and larger pieces of a manifold are grown until a sufficiently long piece is obtained. This allows one to study manifolds geometrically and obtain important features of dynamical behavior. For illustration, we compute the stable manifold of the origin spiralling into the Lorenz attractor, and an unstable manifold in zeta(3)-model converging to an attracting limit cycle

Poverty and Inequality in the UK: 2008

In this Commentary, we assess the changes to average incomes, inequality and poverty that have occurred under the first 10 years of the Labour government, with a particular focus on the changes that have occurred in the latest year of data. This analysis is based upon the latest figures from the DWP's Households Below Average Income (HBAI) series, published on 10 June 2008 (Department for Work and Pensions, 2008c). The HBAI series takes household income as its measure of living standards and is derived from the Family Resources Survey, a survey of around 28,000 households in the United Kingdom that asks detailed questions about income from a range of sources

Blue frontiers: managing the environmental costs of aquaculture

The report begins with an overview of the current status of world aquaculture. It then goes on to describe an approach for estimating the current combined biophysical resource demands of aquaculture for producer countries and regions. Following a comparison of these results with those available for other animal food production sectors the report then examines the consequences of likely future trends in production on the environmental impacts of aquaculture. Finally, the policy implications of the report’s findings are discussed along with the research agenda that should be pursued to meet the challenge of sustainable food production