The three-dimensional structure of bothropasin, the main hemorrhagic factor from Bothrops jararaca venom: Insights for a new classification of snake venom metalloprotease subgroups

Bothropasin is a 48 kDa hemorrhagic PIII snake venom metalloprotease (SVMP) isolated from Bothrops jararaca, containing disintegrin/cysteine-rich adhesive domains. Here we present the crystal structure of bothropasin complexed with the inhibitor POL647. The catalytic domain consists of a scaffold of two subdomains organized similarly to those described for other SVMPs, including the zinc and calcium-binding sites. The free cysteine residue Cys(189) is located within a hydrophobic core and it is not available for disulfide bonding or other interactions. There is no identifiable secondary structure for the disintegrin domain, but instead it is composed mostly of loops stabilized by seven disulfide bonds and by two calcium ions. The ECD region is in a loop and is structurally related to the RGD region of RGD disintegrins, which are derived from I`ll SVMPs. The ECD motif is stabilized by the Cys(117)_Cys(310) disulfide bond (between the disintegrin and cysteine-rich domains) and by one calcium ion. The side chain of Glu(276) of the ECD motif is exposed to solvent and free to make interactions. In bothropasin, the HVR (hyper-variable region) described for other Pill SVMPs in the cysteine-rich domain, presents a well-conserved sequence with respect to several other Pill members from different species. We propose that this subset be referred to as PIII-HCR (highly conserved region) SVMPs. The differences in the disintegrin-like, cysteine-rich or disintegrin-like cysteine-rich domains may be involved in selecting target binding, which in turn could generate substrate diversity or specificity for the catalytic domain. (C) 2008 Elsevier Ltd. All rights reserved.

U-curve: A branch-and-bound optimization algorithm for U-shaped cost functions on Boolean lattices applied to the feature selection problem

This paper presents the formulation of a combinatorial optimization problem with the following characteristics: (i) the search space is the power set of a finite set structured as a Boolean lattice; (ii) the cost function forms a U-shaped curve when applied to any lattice chain. This formulation applies for feature selection in the context of pattern recognition. The known approaches for this problem are branch-and-bound algorithms and heuristics that explore partially the search space. Branch-and-bound algorithms are equivalent to the full search, while heuristics are not. This paper presents a branch-and-bound algorithm that differs from the others known by exploring the lattice structure and the U-shaped chain curves of the search space. The main contribution of this paper is the architecture of this algorithm that is based on the representation and exploration of the search space by new lattice properties proven here. Several experiments, with well known public data, indicate the superiority of the proposed method to the sequential floating forward selection (SFFS), which is a popular heuristic that gives good results in very short computational time. In all experiments, the proposed method got better or equal results in similar or even smaller computational time. (C) 2009 Elsevier Ltd. All rights reserved.

Weak hypergraph regularity and linear hypergraphs

We consider conditions which allow the embedding of linear hypergraphs of fixed size. In particular, we prove that any k-uniform hypergraph H of positive uniform density contains all linear k-uniform hypergraphs of a given size. More precisely, we show that for all integers l >= k >= 2 and every d > 0 there exists Q > 0 for which the following holds: if His a sufficiently large k-uniform hypergraph with the property that the density of H induced on every vertex subset of size on is at least d, then H contains every linear k-uniform hypergraph F with l vertices. The main ingredient in the proof of this result is a counting lemma for linear hypergraphs, which establishes that the straightforward extension of graph epsilon-regularity to hypergraphs suffices for counting linear hypergraphs. We also consider some related problems. (C) 2009 Elsevier Inc. All rights reserved.

Molecular characterization of Mycobacterium massiliense and Mycobacterium bolletii in isolates collected from outbreaks of infections after laparoscopic surgeries and cosmetic procedures

An outbreak of infections affecting 311 patients who had undergone different invasive procedures occurred in 2004 and 2005 in the city of Belem, in the northern region of Brazil. Sixty-seven isolates were studied; 58 were from patients who had undergone laparoscopic surgeries, 1 was from a patient with a postinjection abscess, and 8 were from patients who had undergone mesotherapy. All isolates were rapidly growing nonpigmented mycobacteria and presented a pattern by PCR-restriction enzyme analysis of the hsp65 gene with BstEII of bands of 235 and 210 bp and with HaeIII of bands of 200, 70, 60, and 50 bp, which is common to Mycobacterium abscessus type 2, Mycobacterium bolletii, and Mycobacterium massiliense. hsp65 and. rpoB gene sequencing of a subset of 20 isolates was used to discriminate between these three species. hsp65 and rpoB sequences chosen at random from 11 of the 58 isolates from surgical patients and the postinjection abscess isolate presented the highest degrees of similarity with the corresponding sequences of M. massiliense. In the same way, the eight mesotherapy isolates were identified as M. bolletii. Molecular typing by pulsed-field gel electrophoresis (PFGE) grouped all 58 surgical isolates, while the mesotherapy isolates presented three different PFGE patterns and the postinjection abscess isolate showed a unique PFGE pattern. In conclusion, molecular techniques for identification and typing were essential for the discrimination of two concomitant outbreaks and one case, the postinjection abscess, not related to either outbreak all of which were originally attributed to a single strain of M. abscessus.

Size and power properties of some tests in the Birnbaum-Saunders regression model

The Birnbaum-Saunders distribution has been used quite effectively to model times to failure for materials subject to fatigue and for modeling lifetime data. In this paper we obtain asymptotic expansions, up to order n(-1/2) and under a sequence of Pitman alternatives, for the non-null distribution functions of the likelihood ratio, Wald, score and gradient test statistics in the Birnbaum-Saunders regression model. The asymptotic distributions of all four statistics are obtained for testing a subset of regression parameters and for testing the shape parameter. Monte Carlo simulation is presented in order to compare the finite-sample performance of these tests. We also present two empirical applications. (C) 2010 Elsevier B.V. All rights reserved.

Comparing diagnostic tests with missing data

When missing data occur in studies designed to compare the accuracy of diagnostic tests, a common, though naive, practice is to base the comparison of sensitivity, specificity, as well as of positive and negative predictive values on some subset of the data that fits into methods implemented in standard statistical packages. Such methods are usually valid only under the strong missing completely at random (MCAR) assumption and may generate biased and less precise estimates. We review some models that use the dependence structure of the completely observed cases to incorporate the information of the partially categorized observations into the analysis and show how they may be fitted via a two-stage hybrid process involving maximum likelihood in the first stage and weighted least squares in the second. We indicate how computational subroutines written in R may be used to fit the proposed models and illustrate the different analysis strategies with observational data collected to compare the accuracy of three distinct non-invasive diagnostic methods for endometriosis. The results indicate that even when the MCAR assumption is plausible, the naive partial analyses should be avoided.

HOMEOMORPHISMS OF THE ANNULUS WITH A TRANSITIVE LIFT II

Let f be a homeomorphism of the closed annulus A that preserves the orientation, the boundary components and that has a lift (f) over tilde to the in finite strip (A) over tilde which is transitive. We show that, if the rotation number of (f) over tilde restricted to both boundary components of A is strictly positive, then there exists a closed nonempty connected set Gamma subset of (A) over tilde such that Gamma subset of] - infinity,0] x [0,1], Gamma is unbounded, the projection of to Gamma A is dense, Gamma - (1, 0) subset of Gamma and (f) over tilde(Gamma) subset of Gamma. Also, if p(1) is the projection on the first coordinate of (A) over tilde, then there exists d > 0 such that, for any (z) over tilde is an element of Gamma, lim sup (n ->infinity) p(1)((f) over tilde (n) ((Z) over tilde)) - p(1) ((Z) over tilde)/n < -d.

Homeomorphisms of the annulus with a transitive lift

Let f be a homeomorphism of the closed annulus A that preserves the orientation, the boundary components and that has a lift (f) over tilde to the infinite strip (A) over tilde which is transitive. We show that, if the rotation numbers of both boundary components of A are strictly positive, then there exists a closed nonempty unbounded set B(-) subset of (A) over tilde such that B(-) is bounded to the right, the projection of B to A is dense, B - (1, 0) subset of B and (f) over tilde (B) subset of B. Moreover, if p(1) is the projection on the first coordinate of (A) over tilde, then there exists d > 0 such that, for any (z) over tilde is an element of B(-), lim sup (n ->infinity) p1((f) over tilde (n)((z) over tilde)) - p(1) ((z) over tilde)/n < - d. In particular, using a result of Franks, we show that the rotation set of any homeomorphism of the annulus that preserves orientation, boundary components, which has a transitive lift without fixed points in the boundary is an interval with 0 in its interior.

On maximizing measures of homeomorphisms on compact manifolds

We prove that given a compact n-dimensional connected Riemannian manifold X and a continuous function g : X -> R, there exists a dense subset of the space of homeomorphisms of X such that for all T in this subset, the integral integral(X) g d mu, considered as a function on the space of all T-invariant Borel probability measures mu, attains its maximum on a measure supported on a periodic orbit.

HFD groups in the Solovay model

Hajnal and Juhasz proved that under CH there is a hereditarily separable, hereditarily normal topological group without non-trivial convergent sequences that is countably compact and not Lindelof. The example constructed is a topological subgroup H subset of 2(omega 1) that is an HFD with the following property (P) the projection of H onto every partial product 2(I) for I is an element of vertical bar omega(1)vertical bar(omega) is onto. Any such group has the necessary properties. We prove that if kappa is a cardinal of uncountable cofinality, then in the model obtained by forcing over a model of CH with the measure algebra on 2(kappa), there is an HFD topological group in 2(omega 1) which has property (P). Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.

Genericity of Nondegenerate Critical Points and Morse Geodesic Functionals

We consider a family of variational problems on a Hilbert manifold parameterized by an open subset of a Banach manifold, and we discuss the genericity of the nondegeneracy condition for the critical points. Using classical techniques, we prove an abstract genericity result that employs the infinite dimensional Sard-Smale theorem, along the lines of an analogous result of B. White [29]. Applications are given by proving the genericity of metrics without degenerate geodesics between fixed endpoints in general (non compact) semi-Riemannian manifolds, in orthogonally split semi-Riemannian manifolds and in globally hyperbolic Lorentzian manifolds. We discuss the genericity property also in stationary Lorentzian manifolds.

Examples of Self-Iterating Lie Algebras, 2

We study properties of self-iterating Lie algebras in positive characteristic. Let R = K[t(i)vertical bar i is an element of N]/(t(i)(p)vertical bar i is an element of N) be the truncated polynomial ring. Let partial derivative(i) = partial derivative/partial derivative t(i), i is an element of N, denote the respective derivations. Consider the operators v(1) = partial derivative(1) + t(0)(partial derivative(2) + t(1)(partial derivative(3) + t(2)(partial derivative(4) + t(3)(partial derivative(5) + t(4)(partial derivative(6) + ...))))); v(2) = partial derivative(2) + t(1)(partial derivative(3) + t(2)(partial derivative(4) + t(3)(partial derivative(5) + t(4)(partial derivative(6) + ...)))). Let L = Lie(p)(v(1), v(2)) subset of Der R be the restricted Lie algebra generated by these derivations. We establish the following properties of this algebra in case p = 2, 3. a) L has a polynomial growth with Gelfand-Kirillov dimension lnp/ln((1+root 5)/2). b) the associative envelope A = Alg(v(1), v(2)) of L has Gelfand-Kirillov dimension 2 lnp/ln((1+root 5)/2). c) L has a nil-p-mapping. d) L, A and the augmentation ideal of the restricted enveloping algebra u = u(0)(L) are direct sums of two locally nilpotent subalgebras. The question whether u is a nil-algebra remains open. e) the restricted enveloping algebra u(L) is of intermediate growth. These properties resemble those of Grigorchuk and Gupta-Sidki groups.

Dually discrete spaces

A neighbourhood assignment in a space X is a family O = {O-x: x is an element of X} of open subsets of X such that X is an element of O-x for any x is an element of X. A set Y subset of X is a kernel of O if O(Y) = U{O-x: x is an element of Y} = X. We obtain some new results concerning dually discrete spaces, being those spaces for which every neighbourhood assignment has a discrete kernel. This is a strictly larger class than the class of D-spaces of [E.K. van Douwen, W.F. Pfeffer, Some properties of the Sorgenfrey line and related spaces, Pacific J. Math. 81 (2) (1979) 371-377]. (c) 2008 Elsevier B.V. All rights reserved.

Hyperbolicity of semigroup algebras

Let A be a finite-dimensional Q-algebra and Gamma subset of A a Z-order. We classify those A with the property that Z(2) negated right arrow U(Gamma) and refer to this as the hyperbolic property. We apply this in case A = K S is a semigroup algebra, with K = Q or K = Q(root-d). A complete classification is given when KS is semi-simple and also when S is a non-semi-simple semigroup. (c) 2008 Elsevier Inc. All rights reserved.

ENERGY OF GLOBAL FRAMES

The energy of a unit vector field X on a closed Riemannian manifold M is defined as the energy of the section into T(1) M determined by X. For odd-dimensional spheres, the energy functional has an infimum for each dimension 2k + 1 which is not attained by any non-singular vector field for k > 1. For k = 1, Hopf vector fields are the unique minima. In this paper we show that for any closed Riemannian manifold, the energy of a frame defined on the manifold, possibly except on a finite subset, admits a lower bound in terms of the total scalar curvature of the manifold. In particular, for odd-dimensional spheres this lower bound is attained by a family of frames defined on the sphere minus one point and consisting of vector fields parallel along geodesics.