Recognition by viral and cellular DNA polymerases of nucleosides bearing bases with nonstandard hydrogen bonding patterns.

The ability of DNA polymerases (pols) to catalyze the template-directed synthesis of duplex oligonucleotides containing a nonstandard Watson-Crick base pair between a nucleotide bearing a 5-(2,4-diaminopyrimidine) heterocycle (d kappa) and a nucleotide bearing either deoxyxanthosine (dX) or N1-methyloxoformycin B (pi) has been investigated. The kappa-X and kappa-pi base pairs are jointed by a hydrogen bonding pattern different from and exclusive of those joining the AT and GC base pairs. Reverse transcriptase from human immunodeficiency virus type 1 (HIV-1) incorporates dXTP into an oligonucleotide opposite d kappa in a template with good fidelity. With lower efficiency and fidelity, HIV-1 reverse transcriptase also incorporates d kappa TP opposite dX in the template. With d pi in the template, no incorporation of d kappa TP was observed with HIV reverse transcriptase. The Klenow fragment of DNA pol I from Escherichia coli does not incorporate d kappa TP opposite dX in a template but does incorporate dXTP opposite d kappa. Bovine DNA pols alpha, beta, and epsilon accept neither dXTP opposite d kappa nor d kappa TP opposite d pi. DNA pols alpha and epsilon (but not beta) incorporate d kappa TP opposite dX in a template but discontinue elongation after incorporating a single additional base. These results are discussed in light of the crystal structure for pol beta and general considerations of how polymerases must interact with an incoming base pair to faithfully copy genetic information.

Contactus adherens, a special type of plaque-bearing adhering junction containing M-cadherin, in the granule cell layer of the cerebellar glomerulus.

In the glomeruli of the granule cell layer of mammalian cerebellum, neuronal extensions are interconnected by numerous small, nearly isodiametric (diameters up to 0.1 micron), junctions previously classified as puncta adherentia related to the vinculin-containing, actin microfilament-anchoring junctions of the zonula adherens of epithelial and certain other cells. Using immunofluorescence and immunoelectron microscopy, we have found, however, that these junctions are negative for E- and VE-cadherin, for desmosomal cadherins, and also for vinculin, alpha-actinin, and desmoplakin, but they do contain, in addition to the protein plakoglobin common to all forms of adhering junctions, the plaque proteins alpha- and beta-catenin and the transmembrane glycoprotein M-cadherin previously found as a spread--i.e., not junction bound--plasma membrane protein in certain fetal and regenerating muscle cells and in satellite cells of adult skeletal muscle. We conclude that these M-cadherin-containing junctions of the granule cell layer represent a special type of adhering junction, for which we propose the term contactus adherens (from the Latin contactus, for touch, site of bordering upon, also influence), and we discuss the differences between the various adhering junctions on the basis of their molecular constituents.

Efficient in vivo antitumor effect of an immunotoxin based on ribotoxin α-sarcin in nude mice bearing human colorectal cancer xenografts

Tagging of RNases, such as the ribotoxin α-sarcin, with the variable domains of antibodies directed to surface antigens that are selectively expressed on tumor cells endows cellular specificity to their cytotoxic action. A recombinant single-chain immunotoxin based on the ribotoxin α-sarcin (IMTXA33αS), produced in the generally regarded as safe (GRAS) yeast Pichia pastoris, has been recently described as a promising candidate for the treatment of colorectal cancer cells expressing the glycoprotein A33 (GPA33) antigen, due to its high specific and effective cytotoxic effect on in vitro assays against targeted cells. Here we report the in vivo antitumor effectiveness of this immunotoxin on nude mice bearing GPA33-positive human colon cancer xenografts. Two sets of independent assays were performed, including three experimental groups: control (PBS) and treatment with two different doses of immunotoxin (50 or 100 μg/ injection) (n = 8). Intraperitoneal administration of IMTXA33αS resulted in significant dose-dependent tumor growth inhibition. In addition, the remaining tumors excised from immunotoxin-treated mice showed absence of the GPA33 antigen and a clear inhibition of angiogenesis and proliferative capacity. No signs of immunotoxin-induced pathological changes were observed from specimens tissues.Overall these results show efficient and selective cytotoxic action on tumor xenografts, combined with the lack of severe side effects, suggesting that IMTXA33αS is a potential therapeutic agent against colorectal cancer.

On the development of advanced techniques for mixed-elastohydrodynamic lubrification modelling of journal and sliding bearing systems.

The present thesis is focused on the development of a thorough mathematical modelling and computational solution framework aimed at the numerical simulation of journal and sliding bearing systems operating under a wide range of lubrication regimes (mixed, elastohydrodynamic and full film lubrication regimes) and working conditions (static, quasi-static and transient conditions). The fluid flow effects have been considered in terms of the Isothermal Generalized Equation of the Mechanics of the Viscous Thin Films (Reynolds equation), along with the massconserving p-Ø Elrod-Adams cavitation model that accordingly ensures the so-called JFO complementary boundary conditions for fluid film rupture. The variation of the lubricant rheological properties due to the viscous-pressure (Barus and Roelands equations), viscous-shear-thinning (Eyring and Carreau-Yasuda equations) and density-pressure (Dowson-Higginson equation) relationships have also been taken into account in the overall modelling. Generic models have been derived for the aforementioned bearing components in order to enable their applications in general multibody dynamic systems (MDS), and by including the effects of angular misalignments, superficial geometric defects (form/waviness deviations, EHL deformations, etc.) and axial motion. The bearing exibility (conformal EHL) has been incorporated by means of FEM model reduction (or condensation) techniques. The macroscopic in fluence of the mixedlubrication phenomena have been included into the modelling by the stochastic Patir and Cheng average ow model and the Greenwood-Williamson/Greenwood-Tripp formulations for rough contacts. Furthermore, a deterministic mixed-lubrication model with inter-asperity cavitation has also been proposed for full-scale simulations in the microscopic (roughness) level. According to the extensive mathematical modelling background established, three significant contributions have been accomplished. Firstly, a general numerical solution for the Reynolds lubrication equation with the mass-conserving p - Ø cavitation model has been developed based on the hybridtype Element-Based Finite Volume Method (EbFVM). This new solution scheme allows solving lubrication problems with complex geometries to be discretized by unstructured grids. The numerical method was validated in agreement with several example cases from the literature, and further used in numerical experiments to explore its exibility in coping with irregular meshes for reducing the number of nodes required in the solution of textured sliding bearings. Secondly, novel robust partitioned techniques, namely: Fixed Point Gauss-Seidel Method (PGMF), Point Gauss-Seidel Method with Aitken Acceleration (PGMA) and Interface Quasi-Newton Method with Inverse Jacobian from Least-Squares approximation (IQN-ILS), commonly adopted for solving uid-structure interaction problems have been introduced in the context of tribological simulations, particularly for the coupled calculation of dynamic conformal EHL contacts. The performance of such partitioned methods was evaluated according to simulations of dynamically loaded connecting-rod big-end bearings of both heavy-duty and high-speed engines. Finally, the proposed deterministic mixed-lubrication modelling was applied to investigate the in fluence of the cylinder liner wear after a 100h dynamometer engine test on the hydrodynamic pressure generation and friction of Twin-Land Oil Control Rings.

Impact de l’âge et des variations pluviométriques sur la croissance du pin d’Alep (Pinus halepensis. MILL): Cas du peuplement artificiel de la forêt domaniale de Tlemcen. (Algeria)

La comparaison des résultats de l’analyse dendrochronologique et dendroclimatologique du Pin d’Alep de la forêt domaniale de Tlemcen a été réalisée en conditions stationnelles particulières. L’analyse de la croissance des cernes annuels et des rapports des écarts relatifs des cernes successifs montrent une nette tendance régressive chez les arbres jeunes. La sensibilité moyenne (SM) et les coefficients d’inter datation (SR) respectifs aux jeunes arbres et aux plus âgés confirment la dépendance assez forte des premiers aux facteurs climatiques particulièrement à la pluviométrie. Les résultats de ce travail ont permis d’établir une relation pluviométrie / accroissement radial en fonction de l’âge de leur formation. Ainsi, il est établi qu’à partir de ces résultats particulièrement ceux des valeurs des sensibilités moyennes (SM) que les conséquences probables des variations climatiques influentes sensiblement sur les jeunes sujets. Aussi pour éviter les changements d’ordre physio biologiques liés au vieillissement des arbres, il est préférable de comparer les cernes sur une période de 40 à 50 ans comme c’est le cas des six échantillons choisis dans la zone d’étude.

New theropod remains from the Tiourarén Formation (?Middle Jurassic, Niger) and their bearing on the dental evolution in basal tetanurans

A fragment of a maxilla and isolated theropod teeth from the (?) Middle Jurassic Tiourarén Formation are described. The specimens come from Tadibene, in the rural community of Aderbissinat, Thirozerine Department, Agadez Region, Niger. They were identified through direct comparison with teeth previously described in the literature as well as on the basis of discriminant and morphometric analyses. Our results suggest they belong to Ceratosauridae, Megalosauridae, and the oldest representatives of Spinosauridae. The analyzed sample shows some uncommon characters, such as spinosaurid-like ornamentation in megalosaurid-like teeth, or spinosaurid-like teeth with a low number of denticles, which sheds light on tooth morphology and dental evolution in basal tetanurans and early spinosaurids.

Knowledge-Bearing Elites and Industrial Performance in France and Germany. CES Germany & Europe Working Papers, No. 04.5, December 1993

Most comparative studies of public policies for competitiveness focus on the links among public agencies and industrial sectors. This paper argues that the professions---or knowledge-bearing elites-that animate these organizational links are equally significant. For public policies to promote technological advance, the visions and self-images of knowledge-bearing elites are par­ ticularly important. By examining administrative and technical elites in France and Germany in the 1980s, the paper identifies characteristics that enable these elites to implement policy in some cases, but not in others. France's "state-created" elites were well-positioned to initiate and implement large technology projects, such as digitizing the telecommunications network. Germany's state-recognized elites were, by contrast, better positioned to facilitate framework­ oriented programs that aimed at the diffusion of new technologies throughout industry. The linkages among administrative and technical elites also explain why French policymakers had difficulty adapting policy to changing circumstances over time while German policymakers managed in many cases to learn more from previous policy experiences and to adapt subsequent initiatives accordingly.