Snake Venom Components: Tools and Cures to Target Cardiovascular Diseases

Cardiovascular diseases (CVDs) are considered as a major cause of death worldwide. Therefore, identifying and developing therapeutic strategies to treat and reduce the prevalence of CVDs is a major medical challenge. Several drugs used for the treatment of CVDs, such as captopril, emerged from natural products, namely snake venoms. These venoms are complex mixtures of bioactive molecules, which, among other physiological networks, target the cardiovascular system, leading to them being considered in the development and design of new drugs. In this review, we describe some snake venom molecules targeting the cardiovascular system such as phospholipase A2 (PLA2), natriuretic peptides (NPs), bradykinin-potentiating peptides (BPPs), cysteine-rich secretory proteins (CRISPs), disintegrins, fibrinolytic enzymes, and three-finger toxins (3FTXs). In addition, their molecular targets, and mechanisms of action—vasorelaxation, inhibition of platelet aggregation, cardioprotective activities—are discussed. The dissection of their biological effects at the molecular scale give insights for the development of future snake venom-derived drugs.     

Spin State Tunes Oxygen Atom Transfer towards FeIVO Formation in FeII Complexes

Oxoiron(IV) complexes bearing tetradentate ligands have been extensively studied as models for the active oxidants in non-heme iron-dependent enzymes. These species are commonly generated by oxidation of their ferrous precursors. The mechanisms of these reactions have seldom been investigated. In this work, the reaction kinetics of complexes [Fe^II(CH₃CN)₂L](SbF₆)₂ ( [1](SbF₆)₂ and [2](SbF₆)₂ ) and [Fe^II(CF₃SO₃)₂L] ( [1](OTf)₂ and [2](OTf)₂ ( 1 , L=^Me,HPytacn; 2 , L=^nP,HPytacn; ^R,R′Pytacn=1-[(6-R′-2-pyridyl)methyl]-4,7- di-R-1,4,7-triazacyclononane) with Bu₄NIO₄ to form the corresponding [Fe^IV(O)(CH₃CN)L]²⁺ ( 3 , L=^Me,HPytacn; 4 , L=^nP,HPytacn) species was studied in acetonitrile/acetone at low temperatures. The reactions occur in a single kinetic step with activation parameters independent of the nature of the anion and similar to those obtained for the substitution reaction with Cl⁻ as entering ligand, which indicates that formation of [Fe^IV(O)(CH₃CN)L]²⁺ is kinetically controlled by substitution in the starting complex to form [Fe^II(IO₄)(CH₃CN)L]⁺ intermediates that are converted rapidly to oxo complexes 3 and 4 . The kinetics of the reaction is strongly dependent on the spin state of the starting complex. A detailed analysis of the magnetic susceptibility and kinetic data for the triflate complexes reveals that the experimental values of the activation parameters for both complexes are the result of partial compensation of the contributions from the thermodynamic parameters for the spin-crossover equilibrium and the activation parameters for substitution. The observation of these opposite and compensating effects by modifying the steric hindrance at the ligand illustrates so far unconsidered factors governing the mechanism of oxygen atom transfer leading to high-valent iron oxo species.     

Model-independent constraints on spin observables

We discuss model-independent constraints on spin observables in exclusive and inclusive reactions, with special attention to the case of photoproduction.     

On the probability that n and [n c] are coprime

We prove that for any positive real number which is not an integer, the density of the integers which are coprime to , a result conjectured by Moser, Lambek and Erd Hs. This revised version was published online in June 2006 with corrections to the Cover Date.     

Clustering for routing in densely populated areas

This paper introduces a new approach for generating school bus routes in a dense urban area. First, a districting algorithm is used to determine clusters including appropriate numbers of students. Then, for each cluster, a route and the stops along this route are determined. Numerical results are reported and compared with those obtained previously. Although the algorithm has been developped and tested in a specific context, it could easily be extended to more general vehicle routing problems.     

Spectral distributions for long range perturbations

We study distributions which generalize the concept of spectral shift function, for pseudo-differential operators on . We call such distributions spectral distributions. Relations between relative scattering determinants and spectral distributions are established; they lead to the definition of regularized scattering phase. These relations are analogous to the usual one for the standard spectral shift function. We give several asymptotic properties in the high energy and semiclassical limits where both nontrapping and trapping cases are considered. In particular, we prove Breit-Wigner formulae for the regularized scattering phases, for semiclassical Schrödinger operators with long-range potentials.     

Roughness analysis of the cracked surfaces of a face centered cubic alloy

Intergranular and transgranular fracture surfaces obtained in a face centered cubic alloy are studied using 3D maps reconstructed by scanning electron microscopy stereo imaging. The roughness exponents measured in the intergranular and transgranular surfaces, respectively, zeta = 0.83 +/- 0.05 and zeta = 0.75 +/- 0.05, are in agreement with the universal roughness value of 3D fractures. However, the slightly smaller value related to the transgranular surface could be a consequence of crystallographic transgranular zones disseminated on the surface whose roughness exponent zeta = 0.65 +/- 0.07 is close to the one usually measured on 2D fractures.     

Influence of the slow wave on the relation between the angular resonances and the leaky guided modes properties for a poroelastic plate embedded in water

A numerical study of the guided modes in a water-saturated poroelastic plate that obeys the Biot theory is presented. In the first part, we study the leaky guided modes and the angular resonances when the slow wave does not propagate. Two types of guided modes exist. The first ones occur from coupling of the fast longitudinal wave with the shear wave; most of them propagate whatever the frequency is, provided that it is not close to their cut-off frequencies. The leaky guided modes of the second type occur from coupling of the two longitudinal waves and the shear wave. These modes do not propagate (they are highly damped) as long as the slow wave remains diffusive. We show that the characteristics of the angular resonances can be linked to the leaky guided waves of the first type in the same way as for an elastic plate. The guided modes of the second type may not be associated to angular resonances. In the second part, we consider a thinner plate in a higher frequency range so that the slow wave can propagate. Once again its influence is studied both on the leaky guided modes and on the angular resonances.