832 research outputs found
Bioinformatic tools for a genomic scale analysis of protein structure
No full textEl desarrollo de herramientas computacionales para el cálculo y análisis de datos seencuentra actualmente en constante expansión en diferentes campos de la ciencia,particularmente en el campo de las ciencias de la vida, donde la cantidad de datosdisponibles, generados por nuevas técnicas experimentales convierte en fundamental laimplementación de técnicas computacionales para el análisis y manejo de datos y sutransformación en conocimiento. En este sentido, focalizándose en el campo de la bioinformática estructural de proteínas yla quimioinformática, nos hemos concentrado en la generación de herramientas y aplicaciónde las mismas en problemas relacionados con la salud humana. El presente trabajo de tesis tiene como primer objetivo proponer nuevos procedimientospara el descubrimiento de blancos proteicos relevantes en organismos bacterianos, usandocomo caso de estudio Mycobacterium tuberculosis . El segundo objetivo de esta tesis es el de, seleccionado el blanco proteico dentro de ungenoma de interés, estudiar cuáles son las características que debiera cumplir una moléculapara tener buenas probabilidades unirse a dicho blanco y a partir de la misma proponerposibles ligandos derivados de bases de datos de compuestos. El tercer objetivo de esta tesis es poder comprender y predecir cuáles serán los efectosen la función de una proteína determinada (potencialmente cualquiera que sea de interésdel usuario) de mutaciones no sinónimas que se produzcan en su secuencia. Los tres objetivos han sido abordados desde un punto de vista computacional y todos losmétodos desarrollados pueden considerarse herramientas i nsilico. Más allá de suaplicación en organismos o proteínas puntuales como casos de estudio, todos losdesarrollos pueden ser extendidos y reutilizados de manera directa y automática sobre otrosorganismos o proteínas. Los resultados obtenidos han sido validados contra la literatura existente, permitiendoreproducir resultados experimentales y/o manualmente curados de una manera automática,lo que supone una reducción de tiempo y recursos en los procesos en los que estasherramientas están involucradas.The development of computational tool for data calculation and analysis is actually inconstant expansion through the different fields of science, particularly in the field of the lifesciences, where the amount of available data produced by novel experimental techniquesmakes indispensable the implementation of computational techniques to handle and analyzethe data and its transformation into knowledge. In this sense, focusing in the field of the protein's structural bioinformatics and thecheminformatics, we concentrated our efforts in building tools and apply them in problemsrelated to human health. The present thesis work has as first objective to propose novel procedures to discoverrelevant protein targets in bacterial organisms, using as case of study Mycobacteriumtuberculosis . The second objective of this thesis is to, once selected the protein target within a genome,to study which are the properties that a molecule has to fulfill to have good chances ofbinding to this target, and based in it to propose possible ligands derived from a compounddatabase. The third propound objective is to comprehend and predict which will be the effects in theprotein function (potentially any protein of user interest) of nonsynonymousmutations produced in their sequence. All the three objectives has been addressed from a computational point of view and all thedeveloped methods can be considered in-silico tools. Besides of its application in punctualorganisms or protein targets as cases of study, all this developments can be extended andreused in a direct manner over other organisms/proteins. The obtained results has been validated against the existent literature, allowing toreproduce experimental and/or manually curated results in an automatic way, whichsupposes a saving of time and resources in the processes where this tools are involved.Fil: Radusky, Leandro Gabriel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Leandro Castelluccio – Complete Works Archive
No full textThis repository preserves the essential body of work of Leandro Castelluccio—author, psychologist, cognitive neuroscientist, and thinker—whose writings explore the intersections between philosophy, consciousness, ethics, psychology, and neuroscience.
The purpose of this archive is twofold. First, to ensure long-term open access to these works as a cultural and intellectual contribution available to all, beyond technological platforms, institutional constraints, or temporal limitations. Knowledge, at its best, belongs to everyone and transcends the contingencies of the moment.
Second, this archive invites a living intellectual dialogue. Ideas evolve when they are read, re-interpreted, questioned, and expanded upon. The works preserved here are offered not as static monuments, but as open spaces for reflection and co-creation—where new interpretations, studies, and philosophical developments may emerge through time.
This project is organized into curated components that group books, essays, and research publications. All materials reflect final or published versions intended for public and scholarly reference
Bioinformatic tools for a genomic scale analysis of protein structure
No full textEl desarrollo de herramientas computacionales para el cálculo y análisis de datos seencuentra actualmente en constante expansión en diferentes campos de la ciencia,particularmente en el campo de las ciencias de la vida, donde la cantidad de datosdisponibles, generados por nuevas técnicas experimentales convierte en fundamental laimplementación de técnicas computacionales para el análisis y manejo de datos y sutransformación en conocimiento. En este sentido, focalizándose en el campo de la bioinformática estructural de proteínas yla quimioinformática, nos hemos concentrado en la generación de herramientas y aplicaciónde las mismas en problemas relacionados con la salud humana. El presente trabajo de tesis tiene como primer objetivo proponer nuevos procedimientospara el descubrimiento de blancos proteicos relevantes en organismos bacterianos, usandocomo caso de estudio Mycobacterium tuberculosis . El segundo objetivo de esta tesis es el de, seleccionado el blanco proteico dentro de ungenoma de interés, estudiar cuáles son las características que debiera cumplir una moléculapara tener buenas probabilidades unirse a dicho blanco y a partir de la misma proponerposibles ligandos derivados de bases de datos de compuestos. El tercer objetivo de esta tesis es poder comprender y predecir cuáles serán los efectosen la función de una proteína determinada (potencialmente cualquiera que sea de interésdel usuario) de mutaciones no sinónimas que se produzcan en su secuencia. Los tres objetivos han sido abordados desde un punto de vista computacional y todos losmétodos desarrollados pueden considerarse herramientas i nsilico. Más allá de suaplicación en organismos o proteínas puntuales como casos de estudio, todos losdesarrollos pueden ser extendidos y reutilizados de manera directa y automática sobre otrosorganismos o proteínas. Los resultados obtenidos han sido validados contra la literatura existente, permitiendoreproducir resultados experimentales y/o manualmente curados de una manera automática,lo que supone una reducción de tiempo y recursos en los procesos en los que estasherramientas están involucradas.The development of computational tool for data calculation and analysis is actually inconstant expansion through the different fields of science, particularly in the field of the lifesciences, where the amount of available data produced by novel experimental techniquesmakes indispensable the implementation of computational techniques to handle and analyzethe data and its transformation into knowledge. In this sense, focusing in the field of the protein's structural bioinformatics and thecheminformatics, we concentrated our efforts in building tools and apply them in problemsrelated to human health. The present thesis work has as first objective to propose novel procedures to discoverrelevant protein targets in bacterial organisms, using as case of study Mycobacteriumtuberculosis . The second objective of this thesis is to, once selected the protein target within a genome,to study which are the properties that a molecule has to fulfill to have good chances ofbinding to this target, and based in it to propose possible ligands derived from a compounddatabase. The third propound objective is to comprehend and predict which will be the effects in theprotein function (potentially any protein of user interest) of nonsynonymousmutations produced in their sequence. All the three objectives has been addressed from a computational point of view and all thedeveloped methods can be considered in-silico tools. Besides of its application in punctualorganisms or protein targets as cases of study, all this developments can be extended andreused in a direct manner over other organisms/proteins. The obtained results has been validated against the existent literature, allowing toreproduce experimental and/or manually curated results in an automatic way, whichsupposes a saving of time and resources in the processes where this tools are involved.Fil: Radusky, Leandro Gabriel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
VarQ: A Tool for the Structural and Functional Analysis of Human Protein Variants
No full textUnderstanding the functional effect of Single Amino acid Substitutions (SAS), derived from the occurrence of single nucleotide variants (SNVs), and their relation to disease development is a major issue in clinical genomics. Despite the existence of several bioinformatic algorithms and servers that predict if a SAS is pathogenic or not, they give little or no information at all on the reasons for pathogenicity prediction and on the actual predicted effect of the SAS on the protein function. Moreover, few actual methods take into account structural information when available for automated analysis. Moreover, many of these algorithms are able to predict an effect that no necessarily translates directly into pathogenicity. VarQ is a bioinformatic pipeline that incorporates structural information for the detailed analysis and prediction of SAS effect on protein function. It is an online tool which uses UniProt id and automatically analyzes known and user provided SAS for their effect on protein activity, folding, aggregation and protein interactions, among others. We show that structural information, when available, can improve the SAS pathogenicity diagnosis and more important explain its causes. We show that VarQ is able to correctly reproduce previous analysis of RASopathies related mutations, saving extensive and time consuming manual curation. VarQ assessment was performed over a set of previously manually curated RASopathies (diseases that affects the RAS/MAPK signaling pathway) related variants, showing its ability to correctly predict the phenotypic outcome and its underlying cause. This resource is available online at http://varq.qb.fcen.uba.ar/. Supporting Information & Tutorials may be found in the webpage of the tool
Machine learning for potential ligands prediction on new protein tragets
No full textEn el presente trabajo de tesis, abordamos el problema de generación de conjuntos de moléculas pequeñas que puedan comportarse como ligandos acoplándose a una proteína de interés. En la actualidad las bases de datos de moléculas poseen millones de compuestos y poder seleccionar subconjuntos que posean verdaderos ligandos es un problema relevante para la comunidad.Para lograr nuestro objetivo, tomamos como punto de partida una herramienta preexistente denominada LigQ. Esta herramienta permite calcular, dada una proteína como entrada, conjuntos de moléculas candidatas a ser ligandos de la misma, es decir, que puede acoplarse a ella modulando o inhibiendo su actividad. En este trabajo, atacamos específicamente el problema de vincular las propiedades conocidas sobre el sitio de unión en la proteína estudiada con las propiedades de los ligandos candidatos. Las propiedades serán por lo general valores fisicoquímicos, morfológicos y topológicos calculados o conocidos experimentalmente. Para vincular estas propiedades de manera optimal, utilizaremos técnicas de aprendizaje automático y redes neuronales, de manera de enriquecer los conjuntos que la herramienta LigQ presenta, estableciendo una valoración de los compuestos obtenidos en base a los parámetros calculados como óptimos para que una molécula se acople eficientemente a nuestra proteína de interés.In the present thesis work, we approached the problem of generating a set of small molecules that could be behave as ligands coupling to a protein of interest. Current molecules databases are composed of millions of records and to select subsets containing true lingands is a relevant problem for the community.To accomplish our goal, we based our work on a preexistent tool called LigQ. This tool allows to compute, given a target protein as input, sets of molecules that are candidate to be ligands (molecules that can bind the protein, modulating or inhibiting its activity). In this work we attacked the problem of linking the known properties of the studied protein’s binding site with the properties of the candidate ligands. This properties are physicochemical, morphologic and topologic values, computed or experimentally known. To link this properties in an optimal way, we used machine learning and neural networks techniques, with the aim to enrich the output sets given by the LigQ tool, establishing an assessment of the obtained compounds based on the parameters computed as optimum for a molecule to bind our interes protein.Fil: Leto Mera, Francisco. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
A mulher na poesia de cordel de Leandro Gomes de Barros
No full textStudies the presence of the feminine behavior in the twine poetry of Leandro Gomes de Barros, from the brazilian cultural revalorizes in its multiple looks, which if they had reflected, in the diverse scientific, educational and social fields. For in such a way, it establishes the boarding of literary and social analysis from the perception of the feminine universe in the twine. It points out the sprouting of the twine literature, with the focus directed to its characteristics and formal structure. Feminist verifies the epistemological analysis – that she confers practical the feminine behavior as contributing in cultural the popular author twine, the source of the woman participant author and not personage of the twine. From this context, concernment‘s questions to the resistance of the twine literature will be displayed until the contemporary, and the relation of the author twine with the presence of the constituent woman while and/or to be constituted. They will not leave of being boarded: the analysis of the feminine image printed in twines, from the technique and aesthetic xylographical; the presentation of biographical peculiarities of Leandro Gomes de Barros and analysis of the feminine behavior in infancy, adolescence, maturity and oldness. Also relative attributions to the relation will be made man/woman, characterized for the seduction and feminine devoir of the twine literature using itself of concepts of being able constituent, common singularity and.Estuda a presença do comportamento feminino na poesia de cordel de Leandro Gomes de Barros, a partir da revalorização cultural brasileira em seus múltiplos olhares, os quais se refletiram, nos diversos campos científicos, educacionais e sociais. Para tanto, estabelece a abordagem de análise literária e social a partir da percepção do universo feminino no cordel. Situa o surgimento da literatura de cordel, com o foco voltado às suas características e estrutura formal. Verifica a análise epistemológica feminista que confere o comportamento feminino como contribuinte na prática cultural popular cordelista, na vertente de a mulher autora participante e não personagem do cordel. A partir desse contexto, serão expostas questões concernentes à resistência da literatura de cordel até a contemporaneidade, e a relação dos cordelistas com a presença da mulher enquanto ser constituinte e/ou constituída. Não deixarão de ser abordados: a análise de Barros e análise do comportamento feminino na infância, adolescência, maturidade e velhice. Também serão feitas atribuições relativas à relação homem/ da imagem feminina impressa nos cordéis, a partir da técnica e estética xilográfica; a apresentação de peculiaridades biográficas de Leandro Gomes mulher, caracterizada pela sedução e pelo devir feminino da literatura de cordel valendo-se de conceitos de poder constituinte, singularidade e comum.
Palavras-Chave: Poesia de Cordel. Comportamento feminino. Leandro Gomes de Barros
Amending the European Insolvency Regulation to Strengthen Main Proceedings
No full textThe EC Regulation No 1346 on insolvency proceedings allows for the coexistence of different proceedings with respect to the same debtor. This triggers certain problems in terms of efficiency of the insolvency administration within the European Judicial Space, thus menacing the effet utile of the Regulation.
The article focuses on such problems, explaining the shortcomings which affect the Regulation and wondering whether the ECJ case-law managed a solution for them.
As a matter of principle, preventing the opening of secondary proceedings seems in several cases to be a suitable means for protecting the main proceedings’ purposes. However, at the same time, not opening secondary proceedings could hamper the interests of local creditors, which rely on it to safeguard their rights on the grounds of the local lex concursus. The author addresses the main aspects of this tension.
The Regulation is under revision as result of a Proposal of the European Commission, which, inter alia, aims to strike a balance between the aforesaid interests at odds. The author, hence, carries out a critical appraisal of the envisaged amendments having also regard to the recent reactions of the other European Institutions
Protein Frustratometer 2: a tool to localize energetic frustration in protein molecules, now with electrostatics
No full textThe protein frustratometer is an energy landscape theory-inspired algorithm that aims at localizing and quantifying the energetic frustration present in protein molecules. Frustration is a useful concept for analyzing proteins' biological behavior. It compares the energy distributions of the native state with respect to structural decoys. The network of minimally frustrated interactions encompasses the folding core of the molecule. Sites of high local frustration often correlate with functional regions such as binding sites and regions involved in allosteric transitions. We present here an upgraded version of a webserver that measures local frustration. The new implementation that allows the inclusion of electrostatic energy terms, important to the interactions with nucleic acids, is significantly faster than the previous version enabling the analysis of large macromolecular complexes within a user-friendly interface. The webserver is freely available at URL: http://frustratometer.qb.fcen.uba.ar.Fil: Parra, Rodrigo Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Schafer, Nicholas P.. University Aarhus; DinamarcaFil: Radusky, Leandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Tsai, Min-Yeh. Rice University; Estados UnidosFil: Guzovsky, Ana Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Wolynes, Peter G.. Rice University; Estados UnidosFil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin
Towards a New Interface BetweenBrussels I and Arbitration?
No full textArbitral tribunals and state courts are currently called upon to coexist in the European
Judicial Space without being clearly coordinated with each other. The author wonders
whether Regulation (EU) No 1215/2012, irrespective of restating the arbitration exclusion,
brings a novelty in this regard by way of Recital 12—which sets out the arbitration
exclusion’s scope—and Article 73(2)—which safeguards the 1958 New York
Convention. Certain well known issues concerning the interface between Brussels I
and arbitration—such as the risk of conflicting decisions either on the merits or on the
arbitration agreement, the defence against derailing or delaying tactics flouting an arbitration
agreement, the enforcement of anti-suit injunctions or judgments awarding
damages for breach of the obligation to arbitrate—have been reviewed so as to appreciate
whether and to what extent things have really changed
Leandro y Hero : de la Edad Media al Renacimiento europeo
No full textEste trabajo pretende ampliar la investigación de la Fábula de Leandro y Hero de Juan Boscán a partir del estudio de obras de distintas épocas que relatan la misma historia. En el artículo se desvelan posibles fuentes que sirvieron al autor barcelonés para la composición de su fábula con la finalidad de reconstruir su origen. La aparición de unos mismos motivos y episodios en obras tan alejadas en el tiempo permite especular con la posibilidad de la existencia de una fuente común que haya servido de modelo a todas ellas. Por otro lado, en este trabajo también se estudia la influencia que ejerció la fábula de Boscán en la literatura posterior del Siglo de Oro.This work tries to extend the investigation about Fábula de Leandro y Hero by Juan Boscán by the study of some literary works of different times that relate the same history. In this paper are revealed other possible sources that helped the author to write his fable in order to rebuild its origin. The development of the same motifs and chapters in remotes works allows us to gamble on the existence of a common source that would serve as a model for all of them. In addition, in this work is studied the influence that involve Boscan's fable in the subsequent literacy of the Spanish Golden Age
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