Comparison of μ2‐scaled Hückel theory and Hartree–Fock theory of boranes and carboranes

The μ2‐scaled Hückel method is used to calculate the electronic energy surfaces of the four boranes BnH2−n (n=8–11) and the carborane C2B8H2−10. These electronic energy surfaces and their minimum energy geometries are directly compared to both the single crystal x‐ray determined structures and to Hartree–Fock optimized geometries. Bond distances differ on the average by 0.04 Å between alternate methods. It is shown that μ2‐scaled Hückel results may be directly interpreted by analysis of the highest occupied and lowest unoccupied molecular orbitals. Also studied by the μ2‐scaled Hückel and Hartree–Fock methods are the isomerization pathways of B8H2−8, B11H2−11, and C2B8H2−10. Reaction barriers and transition state geometries found by the two different calculational methods are in fair agreement with each other and known literature values. Using the μ2‐scaled Hückel method one can readily deduce that the B8H2−8 and B11H2−11 isomerizations are Woodward–Hoffmann allowed reactions. In the case of B8H2−8 this allowed mechanism is contrasted to an alternate Woodward–Hoffmann forbidden pathway. Hartree–Fock calculations on the C2B8H2−10 confirm earlier μ2‐scaled Hückel based findings, that a second less stable isomer of C2B8H2−10 exists which, in contradiction to Wade’s rules of electron deficient clusters, has a pair of open square faces in the cluster. © 1994 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70455/2/JCPSA6-101-12-10753-1.pd

Antiviral properties of two trimeric recombinant gp41 proteins

BACKGROUND: As it is the very first step of the HIV replication cycle, HIV entry represents an attractive target for the development of new antiviral drugs. In this context, fusion inhibitors are the third class of anti-HIV drugs to be used for treatment, in combination with nucleoside analogues and antiproteases. But the precise mechanism of HIV fusion mechanism is still unclear. Gp41 ectodomain-derived synthetic peptides represent ideal tools for clarifying this mechanism, in order to design more potent anti-HIV drugs. RESULTS: Two soluble trimeric recombinant gp41 proteins, termed Rgp41B and Rgp41A were designed. Both comprise the N- and C-terminal heptad repeat regions of the ectodomain of HIV-1 gp41, connected by a 7-residue hydrophilic linker, in order to mimic the trimeric fusogenic state of the transmembrane glycoprotein. Both recombinant proteins were found to inhibit HIV-1 entry into target cells in a dose-dependent manner. Rgp41A, the most potent inhibitor, was able to inhibit both X4 and R5 isolates into HeLa cells and primary T lymphocytes. X4 viruses were found to be more susceptible than R5 isolates to inhibition by Rgp41A. In order to elucidate how the trimeric recombinant gp41 protein can interfere with HIV-1 entry into target cells, we further investigated its mode of action. Rgp41A was able to bind gp120 but did not induce gp120-gp41 dissociation. Furthermore, this inhibitor could also interfere with a late step of the fusion process, following the mixing of lipids. CONCLUSION: Taken together, our results suggest that Rgp41A can bind to gp120 and also interfere with a late event of the fusion process. Interestingly, Rgp41A can block membrane fusion without preventing lipid mixing. Although further work will be required to fully understand its mode of action, our results already suggest that Rgp41A can interfere with multiple steps of the HIV entry process

Numerical Simulations of the Inviscid Primitive Equations in a Limited Domain

National audienceThis work is dedicated to the numerical computations of the primitive equations (PEs) of the ocean without viscosity with nonlocal (mode by mode) boundary conditions. We consider the 2D nonlinear PEs, and firstly compute the solutions in a "large" rectangular domain D with periodic boundary conditions in the horizontal direction. Then we consider a subdomain D', in which we compute a second numerical solution with transparent boundary conditions. Two objectives are achieved. On the one hand the absence of blow-up in these computations indicates that the PEs without viscosity are well-posed when supplemented with the boundary conditions. On the other hand they show a very good coincidence on the subdomain D' of the two solutions, thus showing also the computational relevance of these new boundary conditions. We end this study with some numerical simulations of the linearized primitive equations, which correspond to the theoretical results established by the authors, and evidence the transparent properties of the boundary conditions

Sheet nacre growth mechanism: a Voronoi model.

Xavier Bourrat is in ISTO's lab since January 2005International audienceShell nacre (mother of pearl) of Pinctada margaritifera was analyzed by scanning electron microscopy. The originality of this work concerns the sampling performed to observe incipient nacre on the mantle side. The whole animal is embedded in methyl methacrylate followed by separation of the shell from the hardened mantle. It is revealed this way how each future nacre layer pre-exists as a film or compartment. Experimental observations also show for the first time, the progressive lateral crystallization inside this film, finishing under the form of a non-periodic pattern of polygonal tablets of bio-aragonite. It is evidenced that nuclei appear in the film in the vicinity of the zone where aragonite tablets of the underlying layer get in contact to each other. A possible explanation is given to show how nucleation is probably launched in time and space by a signal coming from the underlying layer. Finally, it is evidenced that tablets form a Voronoi tiling of the space: this suggests that their growth is controlled by an "aggregation-like" process of "crystallites" and not directly by the aragonite lattice growth

Multiscale structure of sheet nacre.

This work was conducted on Pinctada maxima nacre (mother of pearl) in order to understand its multiscale ordering and the role of the organic matrix in its structure. Intermittent-contact atomic force microscopy with phase detection imaging reveals a nanostructure within the tablet. A continuous organic framework divides each tablet into nanograins. Their shape is supposed to be flat with a mean extension of 45 nm. TEM performed in the darkfield mode evidences that at least part of the intracrystalline matrix is crystallized and responds like a ‘single crystal'. The tablet is a ‘hybrid composite'. The organic matrix is continuous. The mineral phase is thus finely divided still behaving as a single crystal. It is proposed that each tablet results from the coherent aggregation of nanograins keeping strictly the same crystallographic orientation thanks to a hetero-epitaxy mechanism. Finally, high-resolution TEM performed on bridges from one tablet to the next, in the overlying row, did not permit to evidence a mineral lattice but crystallized organic bridges. The same organic bridges were evidenced by SEM in the interlaminar sequence

Metformin reduces left ventricular eccentric remodeling in experimental volume overload in the rat

Left ventricular hypertrophy (LVH) is often associated with a change in myocardial energy substrate preference from fatty acids to glucose. A possible anti hypertrophic treatment strategy could aim at stimulating or restoring normal myocardial energy metabolism. Metformin, an adenosine monophosphate-activated protein kinase (AMPK) activator used in the management of glucose metabolism in diabetes, is also a fatty acid oxidation stimulator. The effect of metformin on the development of eccentric LVH and ventricular function in chronic left ventricular (LV) volume overload (VO) is unknown. This study was designed to study this question in a VO rat model caused by severe aortic valve regurgitation (AR). Male Wistar rats were divided in four groups (13-15 animals / group): Shams (S) treated or not (C) with metformin (M; 100 mg/kg/d PO) and severe ARreceiving or not metformin. Treatment was started one week before surgery and the animals were sacrificed 9 weeks later. As expected AR rats developed severe eccentric LVH during the course of the protocol. Metformin treatment did not influence the total heart weight. However, LV remodeling associated with the severe VO was severe in ARM than in ARC. Fractional shortening, a marker of systolic function, was significantly higher in ARM compared to ARC group. Metformin also increased the activity of enzymes associated with fatty acid oxidation while inhibiting phosphofructokinase, a glycolytic enzyme. A 2 month treatment with metformin reduced LV eccentric remodeling associated with severe VO and helped maintain a better systolic function

Low autocrine interferon beta production as a gene therapy approach for AIDS: Infusion of interferon beta-engineered lymphocytes in macaques chronically infected with SIVmac251

BACKGROUND: The aim of this study was to evaluate gene therapy for AIDS based on the transduction of circulating lymphocytes with a retroviral vector giving low levels of constitutive macaque interferon β production in macaques chronically infected with a pathogenic isolate of SIVmac251. RESULTS: Two groups of three animals infected for more than one year with a pathogenic primary isolate of SIVmac251 were included in this study. The macaques received three infusions of their own lymphocytes transduced ex vivo with the construct encoding macaque IFN-β (MaIFN-β or with a vector carrying a version of the MaIFN-β gene with a deletion preventing translation of the mRNA. Cellular or plasma viremia increased transiently following injection in most cases, regardless of the retroviral construct used. Transduced cells were detected only transiently after each infusion, among the peripheral blood mononuclear cells of all the animals, with copy numbers of 10 to 1000 per 10(6 )peripheral mononuclear cells. CONCLUSION: Long-term follow-up indicated that the transitory presence of such a small number of cells producing such small amounts of MaIFN-β did not prevent animals from the progressive decrease in CD4(+ )cell count typical of infection with simian immunodeficiency virus. These results reveal potential pitfalls for future developments of gene therapy strategies of HIV infection