Development and validation of AMANDA, a new algorithm for selecting highly relevant regions in Molecular Interaction Fields

Descriptors based on Molecular Interaction Fields (MIF) are highly suitable for drug discovery, but their size (thousands of variables) often limits their application in practice. Here we describe a simple and fast computational method that extracts from a MIF a handful of highly informative points (hot spots) which summarize the most relevant information. The method was specifically developed for drug discovery, is fast, and does not require human supervision, being suitable for its application on very large series of compounds. The quality of the results has been tested by running the method on the ligand structure of a large number of ligand-receptor complexes and then comparing the position of the selected hot spots with actual atoms of the receptor. As an additional test, the hot spots obtained with the novel method were used to obtain GRIND-like molecular descriptors which were compared with the original GRIND. In both cases the results show that the novel method is highly suitable for describing ligand-receptor interactions and compares favorably with other state-of-the-art methods.

Suitability of GRIND-based principal properties for the description of molecular similarity and ligand-based virtual screening

The information provided by the alignment-independent GRid Independent Descriptors (GRIND) can be condensed by the application of principal component analysis, obtaining a small number of principal properties (GRIND-PP), which is more suitable for describing molecular similarity. The objective of the present study is to optimize diverse parameters involved in the obtention of the GRIND-PP and validate their suitability for applications, requiring a biologically relevant description of the molecular similarity. With this aim, GRIND-PP computed with a collection of diverse settings were used to carry out ligand-based virtual screening (LBVS) on standard conditions. The quality of the results obtained was remarkable and comparable with other LBVS methods, and their detailed statistical analysis allowed to identify the method settings more determinant for the quality of the results and their optimum. Remarkably, some of these optimum settings differ significantly from those used in previously published applications, revealing their unexplored potential. Their applicability in large compound database was also explored by comparing the equivalence of the results obtained using either computed or projected principal properties. In general, the results of the study confirm the suitability of the GRIND-PP for practical applications and provide useful hints about how they should be computed for obtaining optimum results.

Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands

A series of new benzolactam derivatives was synthesized and the derivatives were evaluated for theiraffinities at the dopamine D1, D2, and D3 receptors. Some of these compounds showed high D2 and/orD3 affinity and selectivity over the D1 receptor. The SAR study of these compounds revealed structuralcharacteristics that decisively influenced their D2 and D3 affinities. Structural models of the complexesbetween some of the most representative compounds of this series and the D2 and D3 receptors wereobtained with the aim of rationalizing the observed experimental results. Moreover, selected compoundsshowed moderate binding affinity on 5-HT2A which could contribute to reducing the occurrence of extrapyramidalside effects as potential antipsychotics.

Multi-receptor binding profile of clozapine and olanzapine: a structural study based on the new beta (2) adrenergic receptor template

Schizophrenia is a devastating mental disorder that has a largeimpact on the quality of life for those who are afflicted and isvery costly for families and society.[1] Although the etiology ofschizophrenia is still unknown and no cure has yet beenfound, it is treatable, and pharmacological therapy often producessatisfactory results. Among the various antipsychoticdrugs in use, clozapine is widely recognized as one ofthemost clinically effective agents, even if it elicits significant sideeffects such as metabolic disorders and agranulocytosis. Clozapineand the closely related compound olanzapine are goodexamples ofdrug s with a complex multi-receptor profile ;[2]they have affinities toward serotonin, dopamine, a adrenergic,muscarinic, and histamine receptors, among others.

Synthesis, binding affinity, and molecular docking analysis of new benzofuranone derivative as pontential antipsychotics

The complex etiology of schizophrenia has prompted researchers to develop clozapine-related multitargetstrategies to combat its symptoms. Here we describe a series of new 6-aminomethylbenzofuranones in aneffort to find new chemical structures with balanced affinities for 5-HT2 and dopamine receptors. Throughbiological and computational studies of 5-HT2A and D2 receptors, we identified the receptor serine residuesS3.36 and S5.46 as the molecular keys to explaining the differences in affinity and selectivity betweenthese new compounds for this group of receptors. Specifically, the ability of these compounds to establishone or two H-bonds with these key residues appears to explain their difference in affinity. In addition, wedescribe compound 2 (QF1004B) as a tool to elucidate the role of 5-HT2C receptors in mediating antipsychoticeffects and metabolic adverse events. The compound 16a (QF1018B) showed moderate to high affinitiesfor D2 and 5-HT2A receptors, and a 5-HT2A/D2 ratio was predictive of an atypical antipsychotic profile.

L'equilibri en la força

Aquesta unitat didàctica desenvolupada durant el Màster de Professorat de Secundària està pensada per ser impartida a l’assignatura Física i Química de 4t d’ESO, més concretament a la part de física, com introducció a la Dinàmica. Es parteix de les idees prèvies de l’alumnat sobre situacions quotidianes on hi actuen forces. Es contrasten aquestes amb una posada en comú i amb l’explicació del professor, que va introduint progressivament conceptes nous com l’equilibri o els vectors, a mesura que es fan necessaris. En les sessions posteriors s’insisteix en el caràcter vectorial de les forces i es centra l’atenció en dos casos particulars: la força de fregament i la força elàstica. Sobre aquestes dues es treballa resolent un cas i fent una experiència pràctica, fomentant la competència comunicativa. La finalitat de la metodologia és acabar construint les Lleis de Newton, les quals hauran d’exposar en una presentació al final de la unitat.

Redefinición del espectador cinematográfico en relación al audiovisual contemporáneo. Un nuevo agente en la producción cultural

El cine se enfrenta, hoy, a múltiples retos en su propia configuración, acompañando un frenético desarrollo tecnológico. Se ha convertido en matriz de la multiplicación audiovisual contemporánea. En este contexto es preciso redefinir al espectador como sujeto que encarna hoy nuevas funciones y ocupa espacios variados en el conjunto de la producción cultural.Se apuesta por una redefinición del espectador cinematográfico en relación a la evolución del audiovisual digital -sus implicaciones tecnológicas y narrativas- y la relación de ambos con las instituciones de la producción cultural contemporánea -sus políticas de acceso y estrategias de adaptación-.Esta aproximación se fundamenta en el reconocimiento de la capacidad productiva de este nuevo agente cultural y las correspondencias que esta evolución implica respecto al panorama audiovisual contemporáneo.

¿Es viable la recogida selectiva en Andratx?

Dados los tiempos que corren, la lluvia incesante de noticias que nos llegan día a día de las acciones destructivas del hombre contra la naturaleza y las imágenes de las consecuencias de ello, parece que para muchos no son suficientes para intentar poner remedio, la cantidad de excusas y argumentos son interminables. Está claro que en la realidad son muchas las teorías y los puntos de vista sobre el alcance real de los daños medioambientales.¿Cómo es posible que en un municipio como Andratx mientras paseas por las calles te tropieces con un torrente lleno de escombros? Nos sorprendió mucho que aún no tuviesen un sistema de reciclaje. Nosotras encontramos interesente saber cuales eran los motivos: ¿no es viable la adaptación de un sistema de recogida selectiva? ¿los ciudadanos no están predispuestos? ¿no es uno de los temas que preocupan a las administraciones?Intentamos buscar respuestas a nuestras preguntas e ideamos el sistema que hemos considerado más oportuno para la población de Andratx y a partir de aquí estudiar su viabilidad.

Paga o cobra : estudi de la morositat en el món empresarial

El tema del nostre treball és la morositat, centrant‐nos en el estudi d’un cas real en la relació entre dues empreses, un client i un proveïdor, en el què el client va presentar signes de morositat, encara que en cap moment va deixar de pagar cap factura al client. En primer lloc, volem analitzar dades sobre la morositat, per saber com és desenvolupa un cas real d’una empresa amb problemes de morositat i quines son les conseqüències de la morositat, centrant‐nos en dues possibles vies: la via judicial, amb una denúncia a l’Administració Concursal, i la que passa per acudir a certes empreses que, en el límit de la llei, fan servir mètodes persuasius, cal dir que Aquest és un dels objectius fonamentals del treball, és a dir, intentar trobar algunes de les possibles solucions a la morositat, així com intentar detectar aquesta i veure si es pot identificar un morós tipus, cosa que trobaríem d’extrema importància.D’altra banda, com es lògic, volem aplicar els coneixements adquirits en aquests últims anys pel que fa al àmbit de la economia, tant en l’anàlisi de les dades com en els altres apartats del treball.

La Promoción de libros impresos a través de Twitter : análisis de los casos Ediciones Deusto, Gestión 2000 y Alienta Editorial

El sector editorial a Espanya s’ha vist obligat a canviar el seu model de negoci a partir de la Revolució Digital del S.XXI. Això inclou la utilització de mitjans socials a través dels quals es busca, entre altres coses, una nova forma de promoció dels seus llibres i un apropament a les noves tendències de la comunicació per a una efectiva relació amb els seus lectors. Recolzat en les teories de la comunicació digital, aquest treball té l’objectiu d’explorar la promoció de llibres imprès a Twitter mitjançant el hashtag. Es du a terme utilitzant una metodologia qualitativa que ha permès fer un ajust entre les dades i la realitat actual de l’ús d’aquesta eina dintre del sector editorial, i per tant ofereix algunes bases i teories per a futures investigacions

Consentimiento informado en endoscopias digestivas: ¿es necesaria una consulta preendoscópica?

Tanto el Convenio Europeo relativo a los Derechos Humanos y la Biomedicina, como la Ley 41/2002 del 14 de noviembre, recogenlas ideas centrales de la teoría del consentimiento informado: el consentimiento como reflejo y ejercicio básico de la autonomía del paciente y la información como requisito indispensable para ese ejercicio. Al consentimiento informado en endoscopia se refiere Benigno Acea, cirujano y miembro del Comité de Ética Asistencial del Complejo Hospitalario Universitario de A Coruña envarios artículos. En ellos defiende la tesis de que el endoscopista está ética y legalmente obligado a informar al paciente y a recabar su consentimiento informado por escrito y que, por tanto, es necesario organizar en los centros sanitarios una consulta previa a la realización de la endoscopia similar a la instaurada para la anestesia. Se trata aquí de analizar esta propuesta al hilo de la clara distinción que la Ley 41/2002 establece entre el derecho de información sanitaria, que regula en el capítulo II, y el derecho al consentimientoinformado, que regula en el capítulo IV bajo el epígrafe del respeto a la autonomía delpaciente, similar a la instaurada para la anestesia. Se trata aquí de analizar esta propuesta al hilo de la clara distinción que la Ley 41/2002 establece entre el derecho de información sanitaria, que regula en el capítulo II, y el derecho al consentimientoinformado, que regula en el capítuloIV bajo el epígrafe del respeto a la autonomía del paciente.

Size dependence of refractive index of Si nanoclusters embedded in SiO2

he complex refractive index of SiO2 layers containing Si nanoclusters (Si-nc) has been measured by spectroscopic ellipsometry in the range from 1.5 to 5.0 eV. It has been correlated with the amount of Si excess accurately measured by x-ray photoelectron spectroscopy and the nanocluster size determined by energy-filtered transmission electron microscopy. The Si-nc embedded in SiO2 have been produced by a fourfold Si+ ion implantation, providing uniform Si excess aimed at a reliable ellipsometric modeling. The complex refractive index of the Si-nc phase has been calculated by the application of the Bruggeman effective-medium approximation to the composite media. The characteristic resonances of the refractive index and extinction coefficient of bulk Si vanish out in Si-nc. In agreement with theoretical simulations, a significant reduction of the refractive index of Si-nc is observed, in comparison with bulk and amorphous silicon. The knowledge of the optical properties of these composite layers is crucial for the realization of Si-based waveguides and light-emitting devices.

Optical-geometrical effects on the photoluminescence spectra of Si nanocrystals embedded in SiO2

We demonstrate that thickness, optical constants, and details of the multilayer stack, together with the detection setting, strongly influence the photoluminescence spectra of Si nanocrystals embedded in SiO2. Due to multiple reflections of the visible light against the opaque silicon substrate, an interference pattern is built inside the oxide layer, which is responsible for the modifications in the measured spectra. This interference effect is complicated by the depth dependence of (i) the intensity of the excitation laser and (ii) the concentration of the emitting nanocrystals. These variations can give rise to apparent features in the recorded spectra, such as peak shifts, satellite shoulders, and even splittings, which can be mistaken as intrinsic material features. Thus, they can give rise to an erroneous attribution of optical bands or estimate of the average particle size, while they are only optical-geometrical artifacts. We have analyzed these effects as a function of material composition (Si excess fraction) and thickness, and also evaluated how the geometry of the detection setup affects the measurements. To correct the experimental photoluminescence spectra and extract the true spectral shape of the emission from Si nanocrystals, we have developed an algorithm based on a modulation function, which depends on both the multilayer sequence and the experimental configuration. This procedure can be easily extended to other heterogeneous systems.

The effect of substrate on high-temperature annealing of GaN epilayers: Si versus sapphire

We have studied the effects of rapid thermal annealing at 1300¿°C on GaN epilayers grown on AlN buffered Si(111) and on sapphire substrates. After annealing, the epilayers grown on Si display visible alterations with craterlike morphology scattered over the surface. The annealed GaN/Si layers were characterized by a range of experimental techniques: scanning electron microscopy, optical confocal imaging, energy dispersive x-ray microanalysis, Raman scattering, and cathodoluminescence. A substantial Si migration to the GaN epilayer was observed in the crater regions, where decomposition of GaN and formation of Si3N4 crystallites as well as metallic Ga droplets and Si nanocrystals have occurred. The average diameter of the Si nanocrystals was estimated from Raman scattering to be around 3¿nm. Such annealing effects, which are not observed in GaN grown on sapphire, are a significant issue for applications of GaN grown on Si(111) substrates when subsequent high-temperature processing is required.

Long-range-interactions induced ordered structures in deposition processes

We present a new model of sequential adsorption in which the adsorbing particles experience dipolar interactions. We show that in the presence of these long-range interactions, highly ordered structures in the adsorbed layer may be induced at low temperatures. The new phenomenology is manifest through significant variations of the pair correlation function and the jamming limit, with respect to the case of noninteracting particles. Our study could be relevant in understanding the adsorption of magnetic colloidal particles in the presence of a magnetic field.