Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen

Central nervous system (CNS) disease is a major feature of simian immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS lesions in SIV-infected macaques and the potential associations with viral strain and disease course, we performed a retrospective analysis of necropsies on 124 macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all animals. The incidence of SIVE correlated significantly with shortened survival (P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors (animals that died within 200 days) compared to only 18% (16/89) of normal progressors (animals that lived longer than 200 days) (P=0.011). Animals with SIVE had higher viral loads in peripheral blood than those that did not, but this difference did not reach statistical significance. Similarly, while animals infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51) than animals infected with molecularly cloned SIVmac239 and its T-cell tropic derivatives (18.5%; 10/54) this difference was not statistically significant. In this study rapid disease progression and SIVE were highly correlated making separation of viral determinants of virulence from those of neurovirulence difficult.     

Enforcing Efficient Equilibria in Network Design Games via Subsidies

The efficient design of networks has been an important engineering task that involves challenging combinatorial optimization problems. Typically, a network designer has to select among several alternatives which links to establish so that the resulting network satisfies a given set of connectivity requirements and the cost of establishing the network links is as low as possible. The Minimum Spanning Tree problem, which is well-understood, is a nice example.In this paper, we consider the natural scenario in which the connectivity requirements are posed by selfish users who have agreed to share the cost of the network to be established according to a well-defined rule. The design proposed by the network designer should now be consistent not only with the connectivity requirements but also with the selfishness of the users. Essentially, the users are players in a so-called network design game and the network designer has to propose a design that is an equilibrium for this game. As it is usually the case when selfishness comes into play, such equilibria may be suboptimal. In this paper, we consider the following question: can the network designer enforce particular designs as equilibria or guarantee that efficient designs are consistent with users’ selfishness by appropriately subsidizing some of the network links? In an attempt to understand this question, we formulate corresponding optimization problems and present positive and negative results.     

Computer simulations of signal transduction mechanism in {alpha}1B-adrenergic and m3-muscarinic receptors

Molecular dynamices simulations of the hamster _1Badrenergicand the rat m3-muscarinic seven-helix bundle receptor modelshave been carried out. The free, agonist-bound and antagonist-boundforms have been considered. Moreover, three mutant forms ofthe m3-muscarinic recep-tor (N507A, N507D and N507S) have alsobeen simulated; among these, the N507S mutant shows a constitutiveactivity. A comparative structural/dynamics analysis has beenperformed to elucidate (i) the perturbations induced by thefunctionally different ligands upon binding to their targetreceptor, (ii) the features of the three single-point mutantswith respect to the receptor wild type and (iii) the propertiesshared by the agonist-boundforms of the _1B-adrenergic receptorand the m3-muscarinic receptor and by the constitutively activemutant N507S. The consistency obtained between the structuralrearrangement of the transmembrane seven-helix bundle modelsconsidered, and the experimental pharmacological efficaciesof the ligands and of the mutants, constitute an important validationof the 3-D models obtained and allow the inference of the mechanismof ligand- or mutation-induced receptor activation at the molecularlevel.     

Tandem mass spectrometry and nuclear magnetic resonance spectroscopy studies of Candida bombicola sophorolipids and product formed on hydrolysis by cutinase

Natural mixtures of sophorolipids produced by the yeast Candida bombicola have been analyzed by fast atom bombardment (FAB)-MS and collision-induced dissociation (CID)-MS. Some pure components have been analysed by two-dimensional NMR spectroscopy. The presence of acidic, lactonic, and O-acetylated forms and the position of double bonds in the fatty acid part of these glycolipids can be easily inferred from positive and negative ion FAB-mass spectra. Details about position of O-acetylation can be obtained from CID mass spectra of [M+H]+ and [M-H]- ions and from the NMR spectra. Differences in CID fragmentation between protonated and sodiated molecular ions are discussed in detail. Enzymatic hydrolysis of 6',6"-di-O-acetyl sophorolipid lactone by cutinase from Fusarium solani results specifically in the removal of the 6'-O-acetyl group, whereas the 6"-O-acetyl and lactone group are resistant. This specificity is explained from a three-dimensional model of the sophorolipid generated on the basis of the short 1H,1H distances as inferred from the NMR (ROESY) spectra.     

Plasma-derived proteins in airway defence, disease and repair of epithelial injury

One significant characteristic of the airway mucosa in vivo, that cannot easily be mimicked in vitro, is its microcirculation, which generates a highly dynamic, biologically active milieu of plasma-derived molecules that may pass to the airway lumen in vivo. New data on the mechanisms of airway mucosal exudation indicate that the protein systems of circulating plasma may contribute significantly to the biology and immunology of the lamina propria, its surface epithelium and the luminal surface, not only in injured airways, but also in airways that are activated but display no sign of oedema, epithelial disruption, or increased absorption capacity. We suggest that present knowledge of the mechanisms of plasma exudation, together with rapidly emerging information (not detailed herein) on receptors, target cells and cellular responses to the plasma-derived molecules, must be considered in any realistic model that investigates "immuno-inflammatory" mechanisms of the airway mucosa.     

Exploring and comparing the best “direct methods” forthe efficient training of MLP-networks

It is well known that the main difficulties of the algorithms based on backpropagation are the susceptibility to local minima and the slow adaptivity to the patterns during the training. In this paper, we present a class of algorithms, which overcome the above difficulties by utilizing some "direct" numerical methods for the computation of the matrices of weights. In particular, we investigate the performances of the FBFBK-LSB (least-squares backpropagation) algorithms and iterative conjugate gradient singular-value decomposition (ICGSVD), respectively, introduced by Barmann and Biegler-Konig (1993) and by the authors. Numerical results on several benchmark problems show a major reliability and/or efficiency of our algorithm ICGSVD.     

Salient structural elements based texture synthesis

Salient structural elements are ubiquitous in natural textures, and their distribution exhibits some stochastic distribution features. Current texture synthesis algorithms can neither preserve the integrity of the elements nor capture this distributive information. We present an algorithm to treat this high-level visual information. Here, we address the issue by taking specific care of the structural elements. Our texture synthesis process grows the target texture one structural element at a time. A Markov ...     

Performance of One-Round Walks in Linear Congestion Games

We investigate the approximation ratio of the solutions achieved after a one-round walk in linear congestion games. We consider the social functions Sum, defined as the sum of the players’ costs, and Max, defined as the maximum cost per player, as a measure of the quality of a given solution. For the social function Sum and one-round walks starting from the empty strategy profile, we close the gap between the upper bound of \(2+\sqrt{5}\approx 4.24\) given in Christodoulou et al. (Proceedings of the 23rd International Symposium on Theoretical Aspects of Computer Science (STACS), LNCS, vol. 3884, pp. 349–360, Springer, Berlin, 2006) and the lower bound of 4 derived in Caragiannis et al. (Proceedings of the 33rd International Colloquium on Automata, Languages and Programming (ICALP), LNCS, vol. 4051, pp. 311–322, Springer, Berlin, 2006) by providing a matching lower bound whose construction and analysis require non-trivial arguments. For the social function Max, for which, to the best of our knowledge, no results were known prior to this work, we show an approximation ratio of \(\Theta(\sqrt[4]{n^{3}})\) (resp. \(\Theta(n\sqrt{n})\)), where n is the number of players, for one-round walks starting from the empty (resp. an arbitrary) strategy profile.     

On the Convergence of Multicast Games in Directed Networks

We investigate the convergence of the price of anarchy after a limited number of moves in the classical multicast communication game when the underlying communication network is directed. Namely, a subset of nodes of the network are interested in receiving the transmission from a given source node and can share the cost of the used links according to fixed cost sharing methods. At each step, a single receiver is allowed to modify its communication strategy, that is to select a communication path from the source, and assuming a selfish or rational behavior, it will make a best response move, that is it will select a solution yielding the minimum possible payment or shared cost. We determine lower and upper bounds on the price of anarchy, that is the highest possible ratio among the overall cost of the links used by the receivers and the minimum possible cost realizing the required communications, after a limited number of moves under the fundamental Shapley cost sharing method. In particular, assuming that the initial set of connecting paths can be arbitrary, we show an $O(r\sqrt{r})We investigate the convergence of the price of anarchy after a limited number of moves in the classical multicast communication game when the underlying communication network is directed. Namely, a subset of nodes of the network are interested in receiving the transmission from a given source node and can share the cost of the used links according to fixed cost sharing methods. At each step, a single receiver is allowed to modify its communication strategy, that is to select a communication path from the source, and assuming a selfish or rational behavior, it will make a best response move, that is it will select a solution yielding the minimum possible payment or shared cost. We determine lower and upper bounds on the price of anarchy, that is the highest possible ratio among the overall cost of the links used by the receivers and the minimum possible cost realizing the required communications, after a limited number of moves under the fundamental Shapley cost sharing method. In particular, assuming that the initial set of connecting paths can be arbitrary, we show an O(r?r)O(r\sqrt{r}) upper bound on the price of anarchy after 2 rounds, during each of which all the receivers move exactly once, and a matching lower bound, that we also extend to W(r^k?{r})\Omega(r\sqrt[k]{r}) for any number k≥2 rounds, where r is the number of receivers. Similarly, exactly matching upper and lower bounds equal to r are determined for any number of rounds when starting from the empty state in which no path has been selected. Analogous results are obtained also with respect to other three natural cost sharing methods considered in the literature, that is the egalitarian, path-proportional and egalitarian-path proportional ones. Most results are also extended to the undirected case in which the communication links are bidirectional.