Pharmacokinetics of angiotensin converting enzyme inhibitors.

1. The pharmacokinetics of most ACE inhibitors have been evaluated indirectly by the measurements of plasma ACE activity and circulating levels of angiotensin I and II. 2. Although plasma ACE activity is very useful to study the degree and the time-course of ACE inhibition, one has to be aware that very different results can be obtained depending on the substrate employed in the assay. It is therefore impossible to compare the results of different inhibitors unless an identical methodology is used. 3. A clear dissociation between plasma angiotensin II levels and the antihypertensive effects of ACE inhibitors has been reported. This observation is in part linked to problems with the measurement of angiotensin II. New methods of determination of plasma angiotensin II have now allowed demonstration of the complete disappearance of plasma angiotensin II following acute ACE inhibition. During chronic treatment, however, angiotensin II generation is effectively blocked only during part of the day, but blood pressure remains controlled permanently. 4. Among the different pharmacokinetic characteristics of ACE inhibitors presently available, the route of excretion and to a lesser degree the half-life appear to be the most clinically relevant. However, the importance of the ability of ACE inhibitors to inhibit tissue renin-angiotensin systems remains to be defined.

Optimization of a mouse immunization protocol with Paracoccidioides brasiliensis antigens

The objectives of the present study were to optimize the protocol of mouse immunization with Paracoccidioides brasiliensis antigens (Rifkind's protocol) and to test the modulation effect of cyclophosphamide (Cy) on the delayed hypersensitivity response (DHR) of immunized animals. Experiments were carried out using one to four immunizing doses of either crude particulate P. brasiliensis antigen or yeast-cell antigen, followed by DHR test four or seven days after the last immunizing dose. The data demonstrated that an immunizing dose already elicited response; higher DHR indices were obtained with two or three immunizing doses; there were no differences between DHR indices of animals challenged four or seven days after the last dose. Overall the inoculation of two or three doses of the yeast-cell antigen, which is easier to prepare, and DHR test at day 4 simplify the original Rifkind's immunization protocol and shorten the duration of the experiments. The modulation effect of Cy on DHR was assayed with administration of 2.5, 20 and 100 mg/kg weight at seven day intervals starting from day 4 prior to the first immunizing dose. Only the treatment with 2.5 mg Cy increased the DHR indices. Treatment with 100 mg Cy inhibited the DHR, whereas 20 mg Cy did not affect the DHR indices. Results suggest an immunostimulating effect of low dose of Cy on the DHR of mice immunized with P. brasiliensis antigens.

Multilocus enzyme electrophoresis study of Bacillus sphaericus

Multilocus enzyme electrophoresis (MLEE) has been used in the study of some Bacillus species. In this work we applied MLEE and numerical analysis in the study of the Bacillus sphaericus group. B. sphaericus can be distinguished from other entomopathogenic Bacillus by a unique allele (NP-4). Within the species, all insect pathogens were recovered in the same phenetic cluster and all of these strains have the same band position (electrophoresis migration) on the agarose gel (ADH-2). The entomopathogenic group of B. sphaericus seems to be a clonal population, having two widespread frequent genotypes (zymovar 59 and zymovar 119).

Analysis and optimization of the satellite-to-plane link of an aeronautical global system

En aquest projecte s’ha analitzat i optimitzat l’enllaç satèl·lit amb avió per a un sistema aeronàutic global. Aquest nou sistema anomenat ANTARES està dissenyat per a comunicar avions amb estacions base mitjançant un satèl·lit. Aquesta és una iniciativa on hi participen institucions oficials en l’aviació com ara l’ECAC i que és desenvolupat en una col·laboració europea d’universitats i empreses. El treball dut a terme en el projecte compren bàsicament tres aspectes. El disseny i anàlisi de la gestió de recursos. La idoneïtat d’utilitzar correcció d’errors en la capa d’enllaç i en cas que sigui necessària dissenyar una opció de codificació preliminar. Finalment, estudiar i analitzar l’efecte de la interferència co-canal en sistemes multifeix. Tots aquests temes són considerats només per al “forward link”. L’estructura que segueix el projecte és primer presentar les característiques globals del sistema, després centrar-se i analitzar els temes mencionats per a poder donar resultats i extreure conclusions.

Line search multilevel optimization as computational methods for dense optical flow

We evaluate the performance of different optimization techniques developed in the context of optical flowcomputation with different variational models. In particular, based on truncated Newton methods (TN) that have been an effective approach for large-scale unconstrained optimization, we develop the use of efficient multilevel schemes for computing the optical flow. More precisely, we evaluate the performance of a standard unidirectional multilevel algorithm - called multiresolution optimization (MR/OPT), to a bidrectional multilevel algorithm - called full multigrid optimization (FMG/OPT). The FMG/OPT algorithm treats the coarse grid correction as an optimization search direction and eventually scales it using a line search. Experimental results on different image sequences using four models of optical flow computation show that the FMG/OPT algorithm outperforms both the TN and MR/OPT algorithms in terms of the computational work and the quality of the optical flow estimation.

Restriction site-associated DNA sequencing, genotyping error estimation and de novo assembly optimization for population genetic inference.

Restriction site-associated DNA sequencing (RADseq) provides researchers with the ability to record genetic polymorphism across thousands of loci for nonmodel organisms, potentially revolutionizing the field of molecular ecology. However, as with other genotyping methods, RADseq is prone to a number of sources of error that may have consequential effects for population genetic inferences, and these have received only limited attention in terms of the estimation and reporting of genotyping error rates. Here we use individual sample replicates, under the expectation of identical genotypes, to quantify genotyping error in the absence of a reference genome. We then use sample replicates to (i) optimize de novo assembly parameters within the program Stacks, by minimizing error and maximizing the retrieval of informative loci; and (ii) quantify error rates for loci, alleles and single-nucleotide polymorphisms. As an empirical example, we use a double-digest RAD data set of a nonmodel plant species, Berberis alpina, collected from high-altitude mountains in Mexico.

An algorithm for semi-infinite polynomial optimization

"Vegeu el resum a l'inici del document del fitxer adjunt."

A linear optimization technique for graph pebbling

Graph pebbling is a network model for studying whether or not a given supply of discrete pebbles can satisfy a given demand via pebbling moves. A pebbling move across an edge of a graph takes two pebbles from one endpoint and places one pebble at the other endpoint; the other pebble is lost in transit as a toll. It has been shown that deciding whether a supply can meet a demand on a graph is NP-complete. The pebbling number of a graph is the smallest t such that every supply of t pebbles can satisfy every demand of one pebble. Deciding if the pebbling number is at most k is NP 2 -complete. In this paper we develop a tool, called theWeight Function Lemma, for computing upper bounds and sometimes exact values for pebbling numbers with the assistance of linear optimization. With this tool we are able to calculate the pebbling numbers of much larger graphs than in previous algorithms, and much more quickly as well. We also obtain results for many families of graphs, in many cases by hand, with much simpler and remarkably shorter proofs than given in previously existing arguments (certificates typically of size at most the number of vertices times the maximum degree), especially for highly symmetric graphs. Here we apply theWeight Function Lemma to several specific graphs, including the Petersen, Lemke, 4th weak Bruhat, Lemke squared, and two random graphs, as well as to a number of infinite families of graphs, such as trees, cycles, graph powers of cycles, cubes, and some generalized Petersen and Coxeter graphs. This partly answers a question of Pachter, et al., by computing the pebbling exponent of cycles to within an asymptotically small range. It is conceivable that this method yields an approximation algorithm for graph pebbling.

A parameter-free approach for solving combinatorial optimization problems through biased randomization of efficient heuristics

This paper discusses the use of probabilistic or randomized algorithms for solving combinatorial optimization problems. Our approach employs non-uniform probability distributions to add a biased random behavior to classical heuristics so a large set of alternative good solutions can be quickly obtained in a natural way and without complex conguration processes. This procedure is especially useful in problems where properties such as non-smoothness or non-convexity lead to a highly irregular solution space, for which the traditional optimization methods, both of exact and approximate nature, may fail to reach their full potential. The results obtained are promising enough to suggest that randomizing classical heuristics is a powerful method that can be successfully applied in a variety of cases.

On the stability of the optimal value and the optimal set in optimization problems

The paper develops a stability theory for the optimal value and the optimal set mapping of optimization problems posed in a Banach space. The problems considered in this paper have an arbitrary number of inequality constraints involving lower semicontinuous (not necessarily convex) functions and one closed abstract constraint set. The considered perturbations lead to problems of the same type as the nominal one (with the same space of variables and the same number of constraints), where the abstract constraint set can also be perturbed. The spaces of functions involved in the problems (objective and constraints) are equipped with the metric of the uniform convergence on the bounded sets, meanwhile in the space of closed sets we consider, coherently, the Attouch-Wets topology. The paper examines, in a unified way, the lower and upper semicontinuity of the optimal value function, and the closedness, lower and upper semicontinuity (in the sense of Berge) of the optimal set mapping. This paper can be seen as a second part of the stability theory presented in [17], where we studied the stability of the feasible set mapping (completed here with the analysis of the Lipschitz-like property).

Artificial Snow Optimization in Winter Sport Destinations Using a Multi-agent Simulation

This paper presents the Juste-Neige system for predicting the snow height on the ski runs of a resort using a multi-agent simulation software. Its aim is to facilitate snow cover management in order to i) reduce the production cost of artificial snow and to improve the profit margin for the companies managing the ski resorts; and ii) to reduce the water and energy consumption, and thus to reduce the environmental impact, by producing only the snow needed for a good skiing experience. The software provides maps with the predicted snow heights for up to 13 days. On these maps, the areas most exposed to snow erosion are highlighted. The software proceeds in three steps: i) interpolation of snow height measurements with a neural network; ii) local meteorological forecasts for every ski resort; iii) simulation of the impact caused by skiers using a multi-agent system. The software has been evaluated in the Swiss ski resort of Verbier and provides useful predictions.

A single mutation in enzyme I of the sugar phosphotransferase system confers penicillin tolerance to Streptococcus gordonii.

Tolerance is a poorly understood phenomenon that allows bacteria exposed to a bactericidal antibiotic to stop their growth and withstand drug-induced killing. This survival ability has been implicated in antibiotic treatment failures. Here, we describe a single nucleotide mutation (tol1) in a tolerant Streptococcus gordonii strain (Tol1) that is sufficient to provide tolerance in vitro and in vivo. It induces a proline-to-arginine substitution (P483R) in the homodimerization interface of enzyme I of the sugar phosphotransferase system, resulting in diminished sugar uptake. In vitro, the susceptible wild-type (WT) and Tol1 cultures lost 4.5 and 0.6 log(10) CFU/ml, respectively, after 24 h of penicillin exposure. The introduction of tol1 into the WT (WT P483R) conferred tolerance (a loss of 0.7 log(10) CFU/ml/24 h), whereas restitution of the parent sequence in Tol1 (Tol1 R483P) restored antibiotic susceptibility. Moreover, penicillin treatment of rats in an experimental model of endocarditis showed a complete inversion in the outcome, with a failure of therapy in rats infected with WT P483R and the complete disappearance of bacteria in animals infected with Tol1 R483P.