Insulin and insulin-like growth factor-I signal transduction requires p21ras

We have investigated the role of cellular p21ras protein in insulin and insulin-like growth factor-I (IGF-I) signaling pathways. Insulin stimulation increased Ras-GTP formation in Rat-1 fibroblasts overexpressing normal human insulin receptors (HIRc-B), far greater than in parental Rat-1 fibroblasts, indicating that competent insulin receptors mediate this response. Cellular microinjection of a dominant-negative mutant p21ras protein (N17 ras) or anti-p21ras monoclonal antibody (Y13-259) into HIRc-B cells reduced insulin- and IGF-I-stimulated DNA synthesis by 75-90%. Insulin-induced c-fos protein expression was also inhibited by 74%. Microinjection of oncogenic p21ras (T-24 ras) into HIRc-B cells activated the mitogenic pathway, and coinjection of N17 ras and T-24 ras showed that oncogenic p21ras rescued the cells from the N17 ras blockade. This later finding indicates that T-24 ras acts downstream of N17 ras. In conclusion, 1) microinjection of a dominant interferring ras mutant into quiescent cells abrogated subsequent insulin and IGF-I mitogenic signaling; 2) oncogenic ras protein rescued cells from the N17 ras blockade, indicating that T24 ras action is downstream of the site of N17 inhibition; and 3) p21ras is an intermediate signaling molecule in the insulin/IGF-I signal transduction pathway and is required for gene expression and DNA synthesis.     

Thermodynamic analysis of the refining of technical boron nitride

The efficiency of the process of refining technical boron nitride was assessed based on calculations of the chemical equilibrium in the B-N-O-C-Cl-H system. Three refining mixtures, CCl₄ + H₂, CCl₄ + NH₃ and CHCl₃ + NH₃, were considered. The analysis indicates that the use of ammonia-containing mixtures is more convenient, a lower residual oxygen content, lower contamination of the product by carbon and a better overall boron balance emerging. The calculations of the equilibrium composition of the solid phase enabled suitable technological conditions of the refining process (temperature and starting composition of the gaseous phase) to be established. The calculated results are compared with experimental data, and some observed differences are discussed.     

Effect of insulin on farnesyltransferase. Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor

We have previously demonstrated that insulin activates farnesyltransferase (FTase) and augments the amounts of farnesylated p21 (Goalstone, M. L., and Draznin, B. (1996) J. Biol. Chem. 271, 27585-27589). We postulated that this aspect of insulin action might explain the "priming effect" of insulin on the cellular response to other growth factors. In the present study, we show the specificity of the effect of insulin on FTase. Insulin, but not insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), or platelet-derived growth factor (PDGF), stimulated the phosphorylation of the alpha-subunit of FTase and the amounts of farnesylated p21. Even though all four growth factors utilized the Ras pathway to stimulate DNA synthesis, only insulin used this pathway to influence FTase. Insulin failed to stimulate FTase in cells expressing the chimeric insulin/IGF-1 receptor and in cells derived from the insulin receptor knock-out animals. Insulin potentiated the effects of IGF-1, EGF, and PDGF on DNA synthesis in cells expressing the wild type insulin receptor, but this potentiation was inhibited in the presence of the FTase inhibitor, alpha-hydroxyfarnesylphosphonic acid. We conclude that the effect of insulin on FTase is specific, requires the presence of an intact insulin receptor, and serves as a conduit for the "priming" influence of insulin on the nuclear effects of other growth factors.     

Thickness determination of a water film on dye-doped ice by fluorescence spectroscopy

A new method for measuring the thickness of a micrometer-thin water film on ice is presented. The method is based on confocal detection of fluorescence light, emitted by a special coumarin dye dissolved in ice as well as in water. The spectral position of the fluorescence maximum depends strongly on the matrix surrounding the dye molecules. Thus the analysis of the spectra obtained while the focal position perpendicular to the liquid-ice interface is scanned provides the possibility of measuring the thickness of the water film with the vertical resolution of the confocal system. We demonstrate this principle by a model system.     

Beyond loop bounds: comparing annotation languages for worst-case execution time analysis

Worst-case execution time (WCET) analysis is concerned with computing a precise-as-possible bound for the maximum time the execution of a program can take. This information is indispensable for developing safety-critical real-time systems, e. g., in the avionics and automotive fields. Starting with the initial works of Chen, Mok, Puschner, Shaw, and others in the mid and late 1980s, WCET analysis turned into a well-established and vibrant field of research and development in academia and industry. The increasing number and diversity of hardware and software platforms and the ongoing rapid technological advancement became drivers for the development of a wide array of distinct methods and tools for WCET analysis. The precision, generality, and efficiency of these methods and tools depend much on the expressiveness and usability of the annotation languages that are used to describe feasible and infeasible program paths. In this article we survey the annotation languages which we consider formative for the field. By investigating and comparing their individual strengths and limitations with respect to a set of pivotal criteria, we provide a coherent overview of the state of the art. Identifying open issues, we encourage further research. This way, our approach is orthogonal and complementary to a recent approach of Wilhelm et al. who provide a thorough survey of WCET analysis methods and tools that have been developed and used in academia and industry.     

Programs That Test Themselves

The AutoTest framework automates the software testing process by relying on programs that contain the instruments of their own verification, in the form of contract-oriented specifications of classes and their individual routines.     

An introduction to the shift realization for finite dimensional continuous time systems

A new approach is presented for the realization of continuous-time finite dimensional linear systems. Using standard results on Laplace transforms our results are also used to present a new derivation of Fuhrmann's shift realization for rational matrix functions.