Presupuestos del análisis cualitativo para el estudio de la toma de decisiones

Se toma como punto de partida el modelo de diseño de investigación cualitativa desarrollado por Joseph Maxwell, cuya concepción sobre el diseño de una investigación es el de una estructura subyacente basada en la interconexión de los componentes del estudio y las implicancias que estos tienen sobre otros, para analizar, si es posible, la corriente neorrealista, considerada como la escuela predominante en el estudio de las relaciones internacionales. El propósito de este trabajo -sustentado en el paradigma interpretativo, que conlleva como supuesto fundacional la necesaria comprensión del sentido de la acción social en el contexto del mundo de la vida y desde la perspectiva de los participantes- es el de relevar el aporte testimonial de quienes han conducido o participado activamente, es decir, los Ministros de Relaciones Exteriores, en la formación de la política exterior del país a partir de la vuelta de la democracia.

Nuevo enlace ferrovial interprovincial Santa Fe-Entre Ríos : Una oportunidad de escala regional

La provincia de Santa Fe, Argentina, se encuentra en una localización estratégica. La potencialidad de la Hidrovía Paraná-Paraguay, los corredores bioceánicos viales y la red existente de trazados ferroviarios le confieren gran dinamismo a su integración económica, social, cultural y política, no sólo hacia el interior del propio territorio, sino también en relación a las demás provincias y más allá de los confines nacionales. La región capital, cuyo núcleo es la ciudad de Santa Fe, se encuentra caracterizada por factores realmente dinámicos: el riesgo hídrico que es intrínseco del área, la intensificación de los flujos económicos pasantes, los procesos de concentración demográfica y la creciente interdependencia entre ciudades, como es el casode Santa Fe y Paraná (capital de la vecina provincia de Entre Ríos), bajo un progresivo proceso de metropolización binuclear. Estos factores, sumados a la escasa cantidad de conexiones físicas sobre el sistema fluvial del río Paraná, han instalado la creciente necesidad de contar con un nuevo enlace interprovincial, adaptado a una hipótesis de reactivación ferroviaria. El proyecto se encuentra en fase preliminar. La cuestión principal gira en torno a la decisión de su localización específica, que deberá considerar el profundo efecto transformador propio de una obra civil de gran calibre, tanto en relación a la plataforma natural como al sistema de asentamientos humanos. También sus alcances territoriales y el impacto potencial en la micro, meso y macroescala. El propósito de la investigación reside en profundizar sobre las dimensiones involucradas por el proyecto (técnica, social, económica, ambiental, de movilidad), en la búsqueda de una toma de posición que permita echar luz sobre los escenarios más beneficiosos y/o menos desfavorables, en relación a las numerosas propuestas de localización que se encuentran actualmente en discusión. El resultado es una matriz analítica basada en variables cuantitativas y cualitativas, que permite una evaluación integral de las propuestas en función de considerar, en síntesis, el grado de impacto sobre la plataforma natural sustentante, sus capacidades para revertir las problemáticas territoriales actuales, y finalmente sus posibilidades para generar nuevos ejes de desarrollo en la región o bien potenciar los existentes. Se concluye que análisis preliminares de tipo pluridimensional son necesarios para someter a discusión, como instancia previa a estudios específicos de factibilidad y viabilidad, puesto que permiten una visualización integral de las variables intervinientes, marcando el camino hacia su adecuada ponderación. Palabras clave: enlace, multimodalidad, región, transformaciones

Operational costs of A 13,000 solar home systems rural electrification programme

This paper presents an assessment and evaluation of the costs of operation and maintenance (O&M) in a real PV rural electrification (PVRE) programme, with the aim of characterizing its costs structure. Based on the extracted data of the 5-years operational costs of a private operator, the programme has been analyzed to take out the most relevant costs involved in the O&M phase as well as the comparative appraisal between the 3 main activities: installation, O&M and management. Through this study we try to answer to the new challenge of decentralized rural electrification based on larger programmes (with tens of thousands of SHSs) and longer maintenance and operation periods (at least 10 years).

Deflexiones transversales de radiación luminosa en estructuras prismáticas de cristal líquido

A novel structure , based on a wedge shaped configuration, is presented . This structure , previously used in one of his forms,for refraction index measurements is analysed in this paper. The results obtained give the possibility of his use in electro snd magneto-optical modulation and deflection.

Aprendizaje colaborativo en enseñanza a distancia: entorno genérico para configurar, realizar y analizar actividades en grupo

En esta tesis se ha profundizado en el estudio y desarrollo de modelos de soporte para el aprendizaje colaborativo a distancia, que ha permitido proponer una arquitectura fundamentada en los principios del paradigma CSCL (Computer Supported Collaborative Learning). La arquitectura propuesta aborda un tipo de problema concreto que requiere el uso de técnicas derivadas del Trabajo Colaborativo, la Inteligencia Artificial, Interfaces de Usuario así como ideas tomadas de la Pedagogía y la Psicología. Se ha diseñado una solución completa, abierta y genérica. La arquitectura aprovecha las nuevas tecnologías para lograr un sistema efectivo de apoyo a la educación a distancia. Está organizada en cuatro niveles: el de Configuración, el de Experiencia, el de Organización y el de Análisis. A partir de ella se ha implementado un sistema llamado DEGREE. En DEGREE, cada uno de los niveles de la arquitectura da lugar a un subsistema independiente pero relacionado con los otros. La aplicación saca partido del uso de espacios de trabajo estructurados. El subsistema Configurador de Experiencias permite definir los elementos de un espacio de trabajo y una experiencia y adaptarlos a cada tipo de usuario. El subsistema Manejador de Experiencias recoge las contribuciones de los usuarios para construir una solución conjunta de un problema. Las intervenciones de los alumnos se estructuran basándose en un grafo conversacional genérico. Además, se registran todas las acciones de los usuarios para representar explícitamente el proceso completo que lleva a la solución. Estos datos también se almacenan en una memoria común que constituye el subsistema llamado Memoria Organizativa de Experiencias. El subsistema Analizador estudia las intervenciones de los usuarios. Este análisis permite inferir conclusiones sobre la forma en que trabajan los grupos y sus actitudes frente a la colaboración, teniendo en cuenta además el conocimiento subjetivo del observador. El proceso de desarrollo en paralelo de la arquitectura y el sistema ha seguido un ciclo de refinamiento en cinco fases con sucesivas etapas de prototipado y evaluación formativa. Cada fase de este proceso se ha realizado con usuarios reales y se han considerado las opiniones de los usuarios para mejorar las funcionalidades de la arquitectura así como la interfaz del sistema. Esta aproximación ha permitido, además, comprobar la utilidad práctica y la validez de las propuestas que sustentan este trabajo.---ABSTRACT---In this thesis, we have studied in depth the development of support models for distance collaborative learning and subsequently devised an architecture based on the Computer Supported Collaborative Learning paradigm principles. The proposed architecture addresses a specific problem: coordinating groups of students to perform collaborative distance learning activities. Our approach uses Cooperative Work, Artificial Intelligence and Human-Computer Interaction techniques as well as some ideas from the fields of Pedagogy and Psychology. We have designed a complete, open and generic solution. Our architecture exploits the new information technologies to achieve an effective system for education purposes. It is organised into four levels: Configuration, Experience, Organisation and Reflection. This model has been implemented into a system called DEGREE. In DEGREE, each level of the architecture gives rise to an independent subsystem related to the other ones. The application benefits from the use of shared structured workspaces. The configuration subsystem allows customising the elements that define an experience and a workspace. The experience subsystem gathers the users' contributions to build joint solutions to a given problem. The students' interventions build up a structure based on a generic conversation graph. Moreover, all user actions are registered in order to represent explicitly the complete process for reaching the group solution. Those data are also stored into a common memory, which constitutes the organisation subsystem. The user interventions are studied by the reflection subsystem. This analysis allows us inferring conclusions about the way in which the group works and its attitudes towards collaboration. The inference process takes into account the observer's subjective knowledge. The process of developing both the architecture and the system in parallel has run through a five-pass cycle involving successive stages of prototyping and formative evaluation. At each stage of that process, we have considered the users' feedback for improving the architecture's functionalities as well as the system interface. This approach has allowed us to prove the usability and validity of our proposal.

Generador de código para BBDD Oracle

RESUMEN Las empresas tienen programas que acceden a sus bases de datos, estos programas pueden quedarse obsoletos o dejar de serles útiles por alguna razón y deben ser actualizados o reemplazados. Sin embargo la base de datos se suele mantener, ya que la estructura de la información no cambia. Llegado el momento de actualizar o migrar ese software que accede a la base de datos, se puede recurrir a una estructura de clases, las cuales están basadas en la metainformación de la base de datos, y así facilitar el desarrollo del nuevo software. La herramienta desarrollada en este proyecto accede a la metainformación de la base de datos, obtiene la estructura de las tablas y a través de plantillas genera las clases necesarias para empezar el nuevo software. Al estar la herramienta basada en plantillas, adaptar éstas a un nuevo lenguaje es sencillo, haciendo la herramienta mucho más polivalente. En conclusión, una herramienta de este tipo puede facilitar el desarrollo de un nuevo software siempre que la estructura de la base de datos se mantenga intacta haciendo que el nuevo proyecto se desarrolle de forma más rápida. ABSTRACT Companies have software that access their databases, this software can become obsolete or fail to be useful for some reason and must be upgraded or replaced. However the database is usually maintained as the information does not change. It is for this reason that when you migrate the software that accesses the database can use a class structure based on information in the database to facilitate the development of new software. The tool developed in this project accesses the metadata of the database to obtain the structure of the tables and through templates generate the necessary classes to start the new software. Being template‐based tool, adapt these to a new language is simple, making a more versatile tool. In conclusion, a tool of this kind can facilitate the development of a new software provided that the structure of the database is intact making the new project develops more quickly.

(4-Aminomethyl)phenylguanidine derivatives as nonpeptidic highly selective inhibitors of human urokinase

Increased expression of the serine protease urokinase-type plasminogen activator (uPA) in tumor tissues is highly correlated with tumor cell migration, invasion, proliferation, progression, and metastasis. Thus inhibition of uPA activity represents a promising target for antimetastatic therapy. So far, only the x-ray crystal structure of uPA inactivated by H-Glu-Gly-Arg-chloromethylketone has been reported, thus limited data are available for a rational structure-based design of uPA inhibitors. Taking into account the trypsin-like arginine specificity of uPA, (4-aminomethyl)phenylguanidine was selected as a potential P1 residue and iterative derivatization of its amino group with various hydrophobic residues, and structure–activity relationship-based optimization of the spacer in terms of hydrogen bond acceptor/donor properties led to N-(1-adamantyl)-N′-(4-guanidinobenzyl)urea as a highly selective nonpeptidic uPA inhibitor. The x-ray crystal structure of the uPA B-chain complexed with this inhibitor revealed a surprising binding mode consisting of the expected insertion of the phenylguanidine moiety into the S1 pocket, but with the adamantyl residue protruding toward the hydrophobic S1′ enzyme subsite, thus exposing the ureido group to hydrogen-bonding interactions. Although in this enzyme-bound state the inhibitor is crossing the active site, interactions with the catalytic residues Ser-195 and His-57 are not observed, but their side chains are spatially displaced for steric reasons. Compared with other trypsin-like serine proteases, the S2 and S3/S4 pockets of uPA are reduced in size because of the 99-insertion loop. Therefore, the peculiar binding mode of the new type of uPA inhibitors offers the possibility of exploiting optimized interactions at the S1′/S2′ subsites to further enhance selectivity and potency. Because crystals of the uPA/benzamidine complex allow inhibitor exchange by soaking procedures, the structure-based design of new generations of uPA inhibitors can rely on the assistance of x-ray analysis.

Estimating the probability for a protein to have a new fold: A statistical computational model

Structural genomics aims to solve a large number of protein structures that represent the protein space. Currently an exhaustive solution for all structures seems prohibitively expensive, so the challenge is to define a relatively small set of proteins with new, currently unknown folds. This paper presents a method that assigns each protein with a probability of having an unsolved fold. The method makes extensive use of protomap, a sequence-based classification, and scop, a structure-based classification. According to protomap, the protein space encodes the relationship among proteins as a graph whose vertices correspond to 13,354 clusters of proteins. A representative fold for a cluster with at least one solved protein is determined after superposition of all scop (release 1.37) folds onto protomap clusters. Distances within the protomap graph are computed from each representative fold to the neighboring folds. The distribution of these distances is used to create a statistical model for distances among those folds that are already known and those that have yet to be discovered. The distribution of distances for solved/unsolved proteins is significantly different. This difference makes it possible to use Bayes' rule to derive a statistical estimate that any protein has a yet undetermined fold. Proteins that score the highest probability to represent a new fold constitute the target list for structural determination. Our predicted probabilities for unsolved proteins correlate very well with the proportion of new folds among recently solved structures (new scop 1.39 records) that are disjoint from our original training set.

The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters

Certain proteins contain subunits that enable their active translocation across the plasma membrane into cells. In the specific case of HIV-1, this subunit is the basic domain Tat49–57 (RKKRRQRRR). To establish the optimal structural requirements for this translocation process, and thereby to develop improved molecular transporters that could deliver agents into cells, a series of analogues of Tat49–57 were prepared and their cellular uptake into Jurkat cells was determined by flow cytometry. All truncated and alanine-substituted analogues exhibited diminished cellular uptake, suggesting that the cationic residues of Tat49–57 play a principal role in its uptake. Charge alone, however, is insufficient for transport as oligomers of several cationic amino acids (histidine, lysine, and ornithine) are less effective than Tat49–57 in cellular uptake. In contrast, a 9-mer of l-arginine (R9) was 20-fold more efficient than Tat49–57 at cellular uptake as determined by Michaelis–Menton kinetic analysis. The d-arginine oligomer (r9) exhibited an even greater uptake rate enhancement (>100-fold). Collectively, these studies suggest that the guanidinium groups of Tat49–57 play a greater role in facilitating cellular uptake than either charge or backbone structure. Based on this analysis, we designed and synthesized a class of polyguanidine peptoid derivatives. Remarkably, the subset of peptoid analogues containing a six-methylene spacer between the guanidine head group and backbone (N-hxg), exhibited significantly enhanced cellular uptake compared to Tat49–57 and even to r9. Overall, a transporter has been developed that is superior to Tat49–57, protease resistent, and more readily and economically prepared.

CKAAPs DB: a conserved key amino acid positions database

The Conserved Key Amino Acid Positions DataBase (CKAAPs DB) provides access to an analysis of structurally similar proteins with dissimilar sequences where key residues within a common fold are identified. The derivation and significance of CKAAPs starting from pairwise structure alignments is described fully in Reddy et al. [Reddy,B.V.B., Li,W.W., Shindyalov,I.N. and Bourne,P.E. (2000) Proteins, in press]. The CKAAPs identified from this theoretical analysis are provided to experimentalists and theoreticians for potential use in protein engineering and modeling. It has been suggested that CKAAPs may be crucial features for protein folding, structural stability and function. Over 170 substructures, as defined by the Combinatorial Extension (CE) database, which are found in approximately 3000 representative polypeptide chains have been analyzed and are available in the CKAAPs DB. CKAAPs DB also provides CKAAPs of the representative set of proteins derived from the CE and FSSP databases. Thus the database contains over 5000 representative poly­peptide chains, covering all known structures in the PDB. A web interface to a relational database permits fast retrieval of structure-sequence alignments, CKAAPs and associated statistics. Users may query by PDB ID, protein name, function and Enzyme Classification number. Users may also submit protein alignments of their own to obtain CKAAPs. An interface to display CKAAPs on each structure from a web browser is also being implemented. CKAAPs DB is maintained by the San Diego Supercomputer Center and accessible at the URL http://ckaaps.sdsc.edu.

Computational method to reduce the search space for directed protein evolution

We introduce a computational method to optimize the in vitro evolution of proteins. Simulating evolution with a simple model that statistically describes the fitness landscape, we find that beneficial mutations tend to occur at amino acid positions that are tolerant to substitutions, in the limit of small libraries and low mutation rates. We transform this observation into a design strategy by applying mean-field theory to a structure-based computational model to calculate each residue's structural tolerance. Thermostabilizing and activity-increasing mutations accumulated during the experimental directed evolution of subtilisin E and T4 lysozyme are strongly directed to sites identified by using this computational approach. This method can be used to predict positions where mutations are likely to lead to improvement of specific protein properties.

A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport

The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of the fibrate drugs and the antidiabetic effects of the glitazone drugs in humans are due to activation of the α (NR1C1) and γ (NR1C3) subtypes, respectively. By contrast, the therapeutic potential of the δ (NR1C2) subtype is unknown, due in part to the lack of selective ligands. We have used combinatorial chemistry and structure-based drug design to develop a potent and subtype-selective PPARδ agonist, GW501516. In macrophages, fibroblasts, and intestinal cells, GW501516 increases expression of the reverse cholesterol transporter ATP-binding cassette A1 and induces apolipoprotein A1-specific cholesterol efflux. When dosed to insulin-resistant middle-aged obese rhesus monkeys, GW501516 causes a dramatic dose-dependent rise in serum high density lipoprotein cholesterol while lowering the levels of small-dense low density lipoprotein, fasting triglycerides, and fasting insulin. Our results suggest that PPARδ agonists may be effective drugs to increase reverse cholesterol transport and decrease cardiovascular disease associated with the metabolic syndrome X.

Minimizing a binding domain from protein A.

We present a systematic approach to minimizing the Z-domain of protein A, a three-helix bundle (59 residues total) that binds tightly (Kd = 10 nM) to the Fc portion of an immunoglobin IgG1. Despite the fact that all the contacts seen in the x-ray structure of the complex with the IgG are derived from residues in the first two helices, when helix 3 is deleted, binding affinity is reduced > 10(5)-fold (Kd > 1 mM). By using structure-based design and phage display methods, we have iteratively improved the stability and binding affinity for a two-helix derivative, 33 residues in length, such that it binds IgG1, with a Kd of 43 nM. This was accomplished by stepwise selection of random mutations from three regions of the truncated Z-peptide: the 4 hydrophobic residues from helix 1 and helix 2 that contacted helix 3 (the exoface), followed by 5 residues between helix 1 and helix 2 (the intraface), and lastly by 19 residues at or near the interface that interacts with Fc (the interface). As selected mutations from each region were compiled (12 in total), they led to progressive increases in affinity for IgG, and concomitant increases in alpha-helical content reflecting increased stabilization of the two-helix scaffold. Thus, by sequential increases in the stability of the structure and improvements in the quality of the intermolecular contacts, one can reduce larger binding domains to smaller ones. Such mini-protein binding domains are more amenable to synthetic chemistry and thus may be useful starting points for the design of smaller organic mimics. Smaller binding motifs also provide simplified and more tractable models for understanding determinants of protein function and stability.

Considerations on the folding topology and evolutionary origin of cadherin domains.

Cell-cell adhesion in zonula adherens and desmosomal junctions is mediated by cadherins, and recent crystal structures of the first domain from murine N-cadherin provide a plausible molecular basis for this adhesive action. A structure-based sequence analysis of this adhesive domain indicates that its fold is common to all extracellular cadherin domains. The cadherin folding topology is also shown to be similar to immunoglobulin-like domains and to other Greek-key beta-sandwich structures, as diverse as domains from plant cytochromes, bacterial cellulases, and eukaryotic transcription factors. Sequence similarities between cadherins and these other molecules are very low, however, and intron patterns are also different. On balance, independent origins for a favorable folding topology seem more likely than evolutionary divergence from an ancestor common to cadherins and immunoglobulins.

Polímeros de coordenação à base de cobalto(II) e N,N'-bis(4-piridil)-1,4,5,8-naftaleno diimida como ligante e suas propriedade estruturais, espectroscópicas e fotoelétricas

Polímeros de coordenação têm atraído a atenção de pesquisadores na última década por conta de sua incrível versatilidade e virtualmente infinito número de possibilidades de combinação de ligantes orgânicos e centros metálicos. Estes compostos normalmente herdam as características magnéticas, eletrônicas e espectroscópicas de seus componentes base. Entretanto, apesar do crescente número de trabalhos na área, ainda são raros os polímeros de coordenação que apresentem condutividade elétrica. Para este fim, utilizou-se a N,N\'-bis(4-piridil)-1,4,5,8-naftaleno diimida, ou NDI-py, que pertence a uma classe de compostos rígidos, planares, quimicamente e termicamente estáveis e que já foram extensamente estudados por suas propriedades fotoeletroquímicas e semicondução do tipo n. O primeiro polímero de coordenação sintetizado, MOF-CoNDI-py-1, indicou ser um polímero linear, de estrutura 1D. O segundo, MOF-CoNDI-py-2, que conta com ácido tereftálico como ligante suporte, é um sólido cristalino com cela unitária monoclínica pertencente ao grupo espacial C2/c, determinado por difração de raios-X de monocristal. A rede apresenta um arranjo trinuclear de íons Co(II) alto spin com coordenados em uma geometria de octaedro distorcido, enquanto os ligantes NDI-py se encontram em um arranjo paralelo na estrutura, em distâncias apropriadas para transferência eletrônica. Com o auxílio de cálculo teóricos a nível de DFT, foi realizado um estudo aprofundado dos espectros eletrônicos e vibracionais, com atribuição das transições observadas, tanto para o MOF-CoNDI-py-2 quanto para o ligante NDI-py livre. A rede de coordenação absorve em toda a região do espectro eletrônico analisada, de 200 nm a 2500 nm, além de apresentar luminescência com característica do ligante. Dispositivos eletrônicos fabricados com um cristal do MOF-CoNDI-py-2 revelaram condutividades da ordem de 7,9 10-3 S cm -1, a maior já observada para um MOF. Além de elevada, a condutividade elétrica dos cristais demonstrou-se altamente anisotrópica, sendo significativamente menos condutor em algumas direções. Os perfis de corrente versus voltagem foram analisados em termos de mecanismos de condutividade, sendo melhores descritos por um mecanismo limitado pelo eletrodo to tipo Space-Charge Limited Current, concordando com a proposta de condutividade através dos planos de NDI-py na rede. A condutividade dos cristais também é fortemente dependente de luz, apresentando fotocondução quando irradiado por um laser vermelho, de 632 nm, enquanto apresenta um comportamento fotorresistivo frente a uma fonte de luz branca. Estes resultados, combinados, trazem um MOF em uma estrutura incomum e com elevada condutividade elétrica, modulada por luz, em medidas diretas de corrente. Não existem exemplos conhecidos de MOFs na literatura com estas características.