Docking, virtual high throughput screening and in silico fragment-based drug design.

ABSTRACT The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high throughput screening and fragment-based ligand design.

Eines interactives per l'aprenentatge de la dinàmica i el control dels convertidors de potència

El projecte s'ha centrat en el disseny i desenvolupament de laboratoris virtuals per a la docència del dispositius i mètodes de gestió d’energia. Això s’ha realitzat a dos nivells clarament diferenciats, el primer grup de laboratoris correspon als convertidors electrònics de potencia i el segon grup de laboratoris correspon a un conjunt de casos d’aplicacions concretes. En el primer grup es descriu el detall del funcionament dels diferents elements mentre que en el segon els descriuen les idees i conceptes bàsics de funcionament. Els laboratoris virtuals de convertidors electrònics de potència inclouen el convertidor elevador (boost), el convertidor reductor (buck), i convertidors acobladors magnèticament. Aquestes permeten estudiar el comportament dinàmica des d’un punt de vista commutat o bé promitjat, les aplicacions incorporen també la possibilitat de sintonitzar els controladors. Aquestes aplicacions han estat desenvolupades per ser un complement per les sessions de pràctiques presencials. Els laboratoris virtuals d’aplicacions, inclouen els sistema de transport metropolità, el vehicle híbrid i els sistemes de gestió de talls transitoris en el subministrament d’energia principalment. Aquestes laboratoris permeten introduir els estudiants de forma qualitativa en els diferents conceptes i tècniques emprades en els sistemes de generació, transport i transformació d’energia. Totes les aplicacions han estat desenvolupades emprant Easy JAVA Simulations, aquesta eina permet desenvolupar laboratoris multiplataforma fàcilment distribuïbles a través d’internet.

Disseny i optimització metològica de sistemes telemàtics interactius per a la millora de la docència universitària : l'entorn BSCW i nous recursos docents

Aquest projecte de dos anys de durada, ha tingut com a objectius: el disseny i la creació de recursos multimèdia, així com, l’optimització de metodologies d'aplicació de sistemes telemàtics interactius per a la millora de la docència universitària. Com a entorn telemàtic s’ha utilitzat la plataforma de treball cooperatiu BSCW (Basic Support for Cooperative Work). S'ha dissenyat i produït un recurs multimèdia enfocat a l'alumnat de l'assignatura troncal Ciències naturals i la seva didàctica de la diplomatura de Mestre d'Educació Primària, que porta per títol 'Alimentació i nutrició humanes i la seva didàctica’ i es pot consultar a: http://www.ub.edu/didactica_ciencies/mqd06/. Aquest material està format per dues unitats: a) Alimentació i nutrició; b) L'ensenyament-aprenentatge de la digestió humana des d'una perspectiva constructivista. Les unitats s'han orientat a la millora de la formació inicial dels futurs mestres i tenen un enfocament de clar caire constructivista, amb exercicis interactius de detecció de concepcions alternatives, així com organitzadors previs, posteriors nodes expositius i d'obtenció d'informació, exercicis interactius destinats al canvi conceptual i una interactivitat d'avaluació final amb un cert caràcter sumatiu. Cada unitat es tanca amb un mapa conceptual dels continguts tractats. La metodologia emprada en la seva elaboració és una evolució de la que l'equip de la Universitat Pompeu Fabra va encetar en la web ‘Aracné. Ciència en xarxa’: http://www.edu365.com/aulanet/aracne/ (usuari i contrasenya: guest100), i va perfeccionar a 'Idees i vincles en el segle XX. La ciència': http://www.xtec.es/aulanet/seglexx/ (cal permetre que s'obrin finestres emergents), en ambdós casos hi ha col·laborat professorat del nostre grup d'innovació docent de la UB.

Same wording, distinct concepts? Testing differences between expectancies and motives in a mediation model of alcohol outcomes.

Per definition, alcohol expectancies (after alcohol I expect X), and drinking motives (I drink to achieve X) are conceptually distinct constructs. Theorists have argued that motives mediate the association between expectancies and drinking outcomes. Yet, given the use of different instruments, do these constructs remain distinct when assessment items are matched? The present study tested to what extent motives mediated the link between expectancies and alcohol outcomes when identical items were used, first as expectancies and then as motives. A linear structural equation model was estimated based on a national representative sample of 5,779 alcohol-using students in Switzerland (mean age = 15.2 years). The results showed that expectancies explained up to 38% of the variance in motives. Together with motives, they explained up to 48% of the variance in alcohol outcomes (volume, 5+ drinking, and problems). In 10 of 12 outcomes, there was a significant mediated effect that was often higher than the direct expectancy effect. For coping, the expectancy effect was close to zero, indicating the strongest form of mediation. In only one case (conformity and 5+ drinking), there was a direct expectancy effect but no mediation. To conclude, the study demonstrates that motives are distinct from expectancies even when identical items are used. Motives are more proximally related to different alcohol outcomes, often mediating the effects of expectancies. Consequently, the effectiveness of interventions, particularly those aimed at coping drinkers, should be improved through a shift in focus from expectancies to drinking motives.

Application of detection probabilities to the design of amphibian monitoring programs in temporary ponds

Failure to detect a species in an area where it is present is a major source of error in biological surveys. We assessed whether it is possible to optimize single-visit biological monitoring surveys of highly dynamic freshwater ecosystems by framing them a priori within a particular period of time. Alternatively, we also searched for the optimal number of visits and when they should be conducted. We developed single-species occupancy models to estimate the monthly probability of detection of pond-breeding amphibians during a four-year monitoring program. Our results revealed that detection probability was species-specific and changed among sampling visits within a breeding season and also among breeding seasons. Thereby, the optimization of biological surveys with minimal survey effort (a single visit) is not feasible as it proves impossible to select a priori an adequate sampling period that remains robust across years. Alternatively, a two-survey combination at the beginning of the sampling season yielded optimal results and constituted an acceptable compromise between sampling efficacy and survey effort. Our study provides evidence of the variability and uncertainty that likely affects the efficacy of monitoring surveys, highlighting the need of repeated sampling in both ecological studies and conservation management.

Nest-box design for the study of diurnal raptors and owls is still an overlooked point in ecological, evolutionary and conservation studies: a review

The use of artificial nest-boxes has led to significant progress in bird conservation and in our understanding of the functional and evolutionary ecology of free-ranging birds that exploit cavities for roosting and reproduction. Nest-boxes and their improved accessibility have made it easier to perform comparative and experimental field investigations. However, concerns about the generality and applicability of scientific studies involving birds breeding in nest-boxes have been raised because the occupants of boxes may differ from conspecifics occupying other nest sites. Here we review the existing evidence demonstrating the importance of nest-box design to individual life-history traits in three falcon (Falconiformes) and seven owl (Strigiformes) species, as well as the extent to which publications on these birds describe the characteristics of exploited artificial nest-boxes in their 'methods' sections. More than 60% of recent publications did not provide any details on nest-box design (e.g. size, shape, material), despite several calls >15 years ago to increase the reporting of such information. We exemplify and discuss how variation in nest-box characteristics can affect or confound conclusions from nest-box studies and conclude that it is of overall importance to present details of nest-box characteristics in scientific publications.

Biogeography of Triatominae (Hemiptera: Reduviidae) in Ecuador: implications for the design of control strategies

Chagas disease control strategies strongly depend on the triatomine vector species involved in Trypanosoma cruzi transmission within each area. Here we report the results of the identification of specimens belonging to various species of Triatominae captured in Ecuador (15 species from 17 provinces) and deposited in the entomological collections of the Catholic University of Ecuador (Quito), Instituto Oswaldo Cruz (Brazil), the Natural History Museum London (UK), the London School of Hygiene and Tropical Medicine (UK), the National Institute of Hygiene (Quito), and the Vozandes Hospital (Quito). A critical review of published information and new field records are presented. We analysed these data in relation to the life zones where triatomines occur (11 life zones, excluding those over 2,200 m altitude), and provide biogeographical maps for each species. These records are discussed in terms of epidemiological significance and design of control strategies. Findings relevant to the control of the main vector species are emphasised. Different lines of evidence suggest that Triatoma dimidiata is not native to Ecuador-Peru, and that synanthropic populations of Rhodnius ecuadoriensis in southern Ecuador-northern Peru might be isolated from their sylvatic conspecifics. Local eradication of T. dimidiata and these R. ecuadoriensis populations might therefore be attainable. However, the presence of a wide variety of native species indicates the necessity for a strong longitudinal surveillance system.

Design of a Control Slide for Cyanoacrylate Polymerization : Application to the CA-Bluestar Sequence

Casework expercience has shown that, in some cases, long exposures of surfaces subjected to cyanoacrylate (CA) fuming had detrimental effects on the subsequent application of Bluestar. This study aimed to develop a control mechanism to monitor the amount of CA deposited prior to the subsequent treatment. A control slide bearing spots of sodium hydroxide (NaOH) of known concentrations and volume was designed and validated against both scanning electron microscopy (SEM) observations and latent print examiners' assessments of the quality of the developed marks. The control slide allows one to define three levels of development that were used to monitor the Bluestar reaction on depleting footwear marks left in diluted blood. The appropriate conditions for a successful application of both CA and Bluestar were determined.

Echolocation calls of the bats of Trinidad, West Indies: is guild membership reflected in echolocation signal design?

Time-expanded echolocation calls were recorded from 29 species of Neotropical bats in lowland moist tropical forest in Trinidad, West Indies with three aims (I) to describe the echolocation calls of the members of a diverse Neotropical bat community, especially members of the family Phyllostomidae, whose calls are not well documented (2) to investigate whether multivariate analysis of calls allows species and foraging guilds to be identified and (3) to evaluate the use of bat detectors in surveying the phyllostomids of Neotropical forests. The calls of 12 species of the family Phyllostomidae are described here for the first time and a total of 29 species, belonging to five families (Emballonuridae, Mormoopidae, Phyllostomidae, Molossidae and Vespertilionidae) were recorded Quadratic discriminant function analysis (DFA) was used to obtain classification rates for each one of 11 individual species and for six guilds (based on diet, foraging mode and habitat) comprising 26 species Overall classification rates were low compared to similar studies conducted in the Palaeotropics We suggest that this may be due to a combination of ecological plasticity for certain species and a loose relationship between echolocation call shape, fine-grained resource partitioning and resource acquisition in phyllostomids

Polymorphism of the Human Immunodeficiency Virus Type 1 in Brazil: Genetic Characterization of the nef Gene and Implications for Vaccine Design

Most of the Brazilian HIV-1 samples have been characterized based on the structural genes (env, gag and pol) and no data concerning the variability of the accessory genes such as nef have been available so far. Considering the role of the nef on virus biology and the inclusion of this region in some HIV/AIDS vaccine products under testing, the purpose of this study was to document the genetic diversity of the nef gene in third-four HIV-1 Brazilian samples previously subtyped based on the env C2-V3 region. Although only few non-subtype B samples have already been analyzed so far, the cytotoxic Tlymphocyte epitopes encoded in this region were relatively conserved among the subtypes, with some amino acid signatures mainly in the subtype C samples. Considering the increasing of the non-B HIV-1 subtypes worldwide, in special the subtype C, more data should be generated concerning the genetic and antigenic variability of these subtypes, as well as the study of the impact of such polymorphism in HIV/AIDS vaccine design and testing.

Design of Novel Frequency Generation Circuit with Application to Ultra-Wideband Distributed Oscillators

Given the urgence of a new paradigm in wireless digital trasmission which should allow for higher bit rate, lower latency and tigher delay constaints, it has been proposed to investigate the fundamental building blocks that at the circuital/device level, will boost the change towards a more efficient network architecture, with high capacity, higher bandwidth and a more satisfactory end user experience. At the core of each transciever, there are inherently analog devices capable of providing the carrier signal, the oscillators. It is strongly believed that many limitations in today's communication protocols, could be relieved by permitting high carrier frequency radio transmission, and having some degree of reconfigurability. This led us to studying distributed oscillator architectures which work in the microwave range and possess wideband tuning capability. As microvave oscillators are essentially nonlinear devices, a full nonlinear analyis, synthesis, and optimization had to be considered for their implementation. Consequently, all the most used nonlinear numerical techniques in commercial EDA software had been reviewed. An application of all the aforementioned techniques has been shown, considering a systems of three coupled oscillator ("triple push" oscillator) in which the stability of the various oscillating modes has been studied. Provided that a certain phase distribution is maintained among the oscillating elements, this topology permits a rise in the output power of the third harmonic; nevertheless due to circuit simmetry, "unwanted" oscillating modes coexist with the intenteded one. Starting with the necessary background on distributed amplification and distributed oscillator theory, the design of a four stage reverse mode distributed voltage controlled oscillator (DVCO) using lumped elments has been presented. All the design steps have been reported and for the first time a method for an optimized design with reduced variations in the output power has been presented. Ongoing work is devoted to model a wideband DVCO and to implement a frequency divider.