Selective induction of p53 and chemosensitivity in RB-deficient cells by E1A mutants unable to bind the RB-related proteins

The adenovirus E1A oncoprotein renders primary cells sensitive to the induction of apoptosis by diverse stimuli, including many anticancer agents. E1A-expressing cells accumulate p53 protein, and p53 potentiates drug-induced apoptosis. To determine how E1A promotes chemosensitivity, a series of E1A mutants were introduced into primary human and mouse fibroblasts using high-titer recombinant retroviruses, allowing analysis of E1A in genetically normal cells outside the context of adenovirus infection. Mutations that disrupted apoptosis and chemosensitivity separated into two complementation groups, which correlated precisely with the ability of E1A to associate with either the p300/CBP or retinoblastoma protein families. Furthermore, E1A mutants incapable of binding RB, p107, and p130 conferred chemosensitivity to fibroblasts derived from RB-deficient mice, but not fibroblasts from mice lacking p107 or p130. Hence, inactivation of RB, but not p107 or p130, is required for chemosensitivity induced by E1A. Finally, the same E1A functions that promote drug-induced apoptosis also induce p53. Together, these data demonstrate that p53 accumulation and chemosensitivity are linked to E1A’s oncogenic potential, and identify a strategy to selectively induce apoptosis in RB-deficient tumor cells.

Vitronectin is not essential for normal mammalian development and fertility.

Vitronectin (VN) is an abundant glycoprotein present in plasma and the extracellular matrix of most tissues. Though the precise function of VN in vivo is unknown, it has been implicated as a participant in diverse biological processes, including cell attachment and spreading, complement activation, and regulation of hemostasis. The major site of synthesis appears to be the liver, though VN is also found in the brain at an early stage of mouse organogenesis, suggesting that it may play an important role in mouse development. Genetic deficiency of VN has not been reported in humans or in other higher organisms. To examine the biologic function of VN within the context of the intact animal, we have established a murine model for VN deficiency through targeted disruption of the murine VN gene. Southern blot analysis of DNA obtained from homozygous null mice demonstrates deletion of all VN coding sequences, and immunological analysis confirms the complete absence of VN protein expression in plasma. However, heterozygous mice carrying one normal and one null VN allele and homozygous null mice completely deficient in VN demonstrate normal development, fertility, and survival. Sera obtained from VN-deficient mice are completely deficient in "serum spreading factor" and plasminogen activator inhibitor 1 binding activities. These observations demonstrate that VN is not essential for cell adhesion and migration during normal mouse development and suggest that its role in these processes may partially overlap with other adhesive matrix components.

Water quality : Western Fish Toxicology Station and western Oregon rivers /

Mode of access: Internet.

Contagious bovine pleuropneumonia and Mycoplasma mycoides var. mycoides, 1852-1968 : a bibliography and index ; appendix 1969-April 1970 /

Kept up to date by supplements.

The history and antiquities of the cathedral church of Worcester: illustrated by a series of engravings of views, elevations, plans, and details of that edifice: including an architectural description of the church; and biographical anecdotes of the bishops and of other eminent persons connected with the cathedral.

Includes index.

Vesicular exanthema of swine, 1933-1963 : a bibliography.

Kept up to date by supplements.

Bibliography of foot-and-mouth disease in man, 1695-1965 /

Kept up to date by supplements.

1939 Ice Hockey Team

1941 Ice Hockey Team

Ion exchangers in analytical chemistry

Mode of access: Internet.

A fizikai matematika legújabb eredményei mint a közgazdaság-tudomány lehetséges vizsgálati eszközei (The newest results of physical mathematics as the possible investigation tools of economics)

A közgazdaság-tudomány számos problémája a fizika analóg modelljeinek segítségével nyert megoldást. A közgazdászok körében erőteljesen megoszlanak a vélemények, hogy a közgazdasági modellek mennyire redukálhatók a fizika, vagy más természettudományok eredményeire. Vannak,akik pontosan ezzel magyarázzák,hogy a mai mainstream közgazdasági elmélet átalakult alkalmazott matematikává,ami a gazdasági kérdéseket csak a társadalom-tudományi vonatkozásaitól eltekintve képes vizsgálni. Mások, e tanulmányszerzője is, viszont úgy vélekednek, hogy a közgazdasági problémák egy része, ahol lehetőség van a mérésre, jól modellezhetők a természettudományok technikai arzenáljával. A másik része, amelyekben nem lehet mérni,s tipikusan ilyenek a társadalomtudományi kérdések, ott sokkal komplexebb technikákra lesz szükség. Etanulmány célkitűzése, hogy felvázolja a fizika legújabb, az irreverzibilis dinamika, a relativitáselmélet és a kvantummechanika sztochasztikus matematikai összefüggéseit, amelyekből a közgazdászok választhatnak egy-egy probléma megfogalmazásában és megoldásában. Például az időoperátorok pontos értelmezése jelentős fordulatot hozhat a makroökonómiai elméletekben; vagy az eddigi statikus egyensúlyi referencia pontokat felválthatják a dinamikus,időben változó sztochasztikus egyensúlyi referenciafüggvények, ami forradalmian új megvilágításba helyezhet számos társadalomtudományi, s főleg nemegyensúlyi közgazdasági kérdést.A termodinamika és a biológiai evolúció fogalmait és definícióit Paul A. Samuelson (1947) már adaptálta a közgazdaságtanban, viszont a kvantummechanika legújabb eredményeit, az időoperátorokat stb. nem érintette. E cikk azokat a legújabb fizikai, kémiai és biológiai matematikai összefüggéseket foglalja össze,amelyek hasznosak lehetnek a közgazdasági modellek komplexebb megfogalmazásához. ___________________ The aim of this paper is to out line the newest results of physics,i.e.,the stochastic mathematical relations of relativity theory and quantum mechanics as well as irreversible dynamics which can be applied for some economic problems.For example,the correct interpretation of time operators using for the macroeconomic theories may provide a serious improvement in approach to the reality.The stochastic dynamic equilibrium reference functions will take over the role of recent static equilibrium reference points,which may also reveal some nonequilibrium questions of macroeconomics.The concepts and definitions of thermodynamics and biological evolution have been adopted in economics by Paul A. Samuelson, but he did not concern the newest results of quantum mechanics, e.g., the time operators. Now we do it.In addition, following Samuelson,we show that von Neumann growth model cannot be explained as a peculiar extension of thermodynamic irreversibility.

International stock portfolio selection and performance measures recognizing higher moments of return distributions

Since the seminal works of Markowitz (1952), Sharpe (1964), and Lintner (1965), numerous studies on portfolio selection and performance measure have been based upon the mean-variance framework. However, several researchers (e.g., Arditti (1967, and 1971), Samuelson (1970), and Rubinstein (1973)) argue that the higher moments cannot be neglected unless there is reason to believe that: (i) the asset returns are normally distributed and the investor's utility function is quadratic, or (ii) the empirical evidence demonstrates that higher moments are irrelevant to the investor's decision. Based on the same argument, this dissertation investigates the impact of higher moments of return distributions on three issues concerning the 14 international stock markets.^ First, the portfolio selection with skewness is determined using: the Polynomial Goal Programming in which investor preferences for skewness can be incorporated. The empirical findings suggest that the return distributions of international stock markets are not normally distributed, and that the incorporation of skewness into an investor's portfolio decision causes a major change in the construction of his optimal portfolio. The evidence also indicates that an investor will trade expected return of the portfolio for skewness. Moreover, when short sales are allowed, investors are better off as they attain higher expected return and skewness simultaneously.^ Second, the performance of international stock markets are evaluated using two types of performance measures: (i) the two-moment performance measures of Sharpe (1966), and Treynor (1965), and (ii) the higher-moment performance measures of Prakash and Bear (1986), and Stephens and Proffitt (1991). The empirical evidence indicates that higher moments of return distributions are significant and relevant to the investor's decision. Thus, the higher moment performance measures should be more appropriate to evaluate the performances of international stock markets. The evidence also indicates that various measures provide a vastly different performance ranking of the markets, albeit in the same direction.^ Finally, the inter-temporal stability of the international stock markets is investigated using the Parhizgari and Prakash (1989) algorithm for the Sen and Puri (1968) test which accounts for non-normality of return distributions. The empirical finding indicates that there is strong evidence to support the stability in international stock market movements. However, when the Anderson test which assumes normality of return distributions is employed, the stability in the correlation structure is rejected. This suggests that the non-normality of the return distribution is an important factor that cannot be ignored in the investigation of inter-temporal stability of international stock markets. ^

El Evento ‘Museo’: Aportes sobre el campo teórico de la Museología (1955-2015)

Desde hace mucho tiempo hemos defendido la idea de que Museo no es solo una institución, sino que debe ser entendido también como un proceso, fenómeno, flujo o acontecimiento. En el escenario contemporáneo del conocimiento, es fundamental que se pueda percibir al Museo más allá de su forma institucionalizada: solamente así será posible comprender con alguna precisión y profundidad sus nuevas formas de presentación y las relaciones que se establecen entre este fenómeno y las nuevas representaciones sociales. Este artículo presenta algunas reflexiones sobre el tema a partir del análisis de autores del campo museal, haciendo especial énfasis en los argumentos de base teórico-filosófica, o de base comunicacional, a partir de los cuales la Museología se ha estructurado como campo disciplinario.