RCK Domain Model of Calcium Activation in BK Channels

Potassium ion channels are ubiquitously expressed from bacteria to mammals where they are involved in various processes ranging from the regulation of osmotic pressure in a single cell to the electrical response in muscle fibers to the generation of action potentials in neurons. The B K channel family (BK for Big K+ conductance) is an interesting subfamily of K+ channels responsive to both membrane voltage and intracellular calcium ion. The unique, high-affinity Ca2+ sensitivity of B K channels is critical to their physiological function in various cell types. The mechanism by which Ca2+ activates B K channel gating, however, is not well understood. Here we present a structure-based approach to the study of B K channels with the goal of providing a structural and functional model of the Ca2+-activation mechanism. Sequence analysis of BK channel C-terminal domains and domains from prokaryotic homologs reveals the conservation of unique positions defining a novel regulatory domain associated with K conduction, the R C K domain. Crystal structures of R C K domains from prokaryotic sources relate the conservation of sequence to the structure, assembly and function of these domains. W e propose a hypothetical model for the structure and function of the Cterminal domains of B K as a set of R C K domains that conduct the Ca -activation mechanism. The features and constraints predicted by the R C K domain model are tested by the electrophysiological assay of a variety of human B K constructs. The results support a domain structure and assembly consistent with the proposed model for the B K C-terminus. In addition, the results identify residues and regions involved in Ca + activation: the Ca2+-binding event and the transduction of the binding energy through protein conformational changes to the channel domain. The R C K domain model thus provides a framework for the study of Ca2+ activation in B K channels

WikiPathways: building research communities on biological pathways.

Here, we describe the development of WikiPathways (http://www.wikipathways.org), a public wiki for pathway curation, since it was first published in 2008. New features are discussed, as well as developments in the community of contributors. New features include a zoomable pathway viewer, support for pathway ontology annotations, the ability to mark pathways as private for a limited time and the availability of stable hyperlinks to pathways and the elements therein. WikiPathways content is freely available in a variety of formats such as the BioPAX standard, and the content is increasingly adopted by external databases and tools, including Wikipedia. A recent development is the use of WikiPathways as a staging ground for centrally curated databases such as Reactome. WikiPathways is seeing steady growth in the number of users, page views and edits for each pathway. To assess whether the community curation experiment can be considered successful, here we analyze the relation between use and contribution, which gives results in line with other wiki projects. The novel use of pathway pages as supplementary material to publications, as well as the addition of tailored content for research domains, is expected to stimulate growth further

Boundary quantum critical phenomena with entanglement renormalization

We extend the formalism of entanglement renormalization to the study of boundary critical phenomena. The multi-scale entanglement renormalization ansatz (MERA), in its scale invariant version, offers a very compact approximation to quantum critical ground states. Here we show that, by adding a boundary to the scale invariant MERA, an accurate approximation to the critical ground state of an infinite chain with a boundary is obtained, from which one can extract boundary scaling operators and their scaling dimensions. Our construction, valid for arbitrary critical systems, produces an effective chain with explicit separation of energy scales that relates to Wilson's RG formulation of the Kondo problem. We test the approach by studying the quantum critical Ising model with free and fixed boundary conditions.Comment: 8 pages, 12 figures, for a related work see arXiv:0912.289

BridgeDb: standardized access to gene, protein and metabolite identifier mapping services

Many interesting problems in bioinformatics require integration of data from various sources. For example when combining microarray data with a pathway database, or merging co-citation networks with protein-protein interaction networks. Invariably this leads to an identifier mapping problem, where different datasets are annotated with identifiers that are related, but originate from different databases.

Solutions for the identifier mapping problem exist, such as Biomart, Synergizer, Cronos, PICR, HMS and many more. This creates an opportunity for bioinformatics tool developers. Tools can be made to flexibly support multiple mapping services or mapping services could be combined to get broader coverage. This approach requires an interface layer between tools and mapping services. BridgeDb provides such an interface layer, in the form of both a Java and REST API.

Because of the standardized interface layer, BridgeDb is not tied to a specific source of mapping information. You can switch easily between flat files, relational databases and several different web services. Mapping services can be combined to support multi-omics experiments or to integrate custom microarray annotations. BridgeDb isn't just yet another mapping service: it tries to build further on existing work, and integrate multiple partial solutions. The framework is intended for customization and adaptation to any identifier mapping service. 

BridgeDb makes it easy to add an important capability to existing tools. BridgeDb has already been integrated into several popular bioinformatics applications, such as Cytoscape, WikiPathways, PathVisio, Vanted and Taverna. To encourage tool developers to start using BridgeDb, we've created code examples, online documentation, and a mailinglist to ask questions. 

We believe that, to meet the challenges that are encountered in bioinformatics today, the software development process should follow a few essential principles: user friendliness, code reuse, modularity and open source. BridgeDb adheres to these principles, and can serve as a useful model for others to follow. BridgeDb can function to increase user-friendliness of graphical applications. It re-uses work from other projects such as BioMart and MIRIAM. BridgeDb consists of several small modules, integrated through a common interface (API). Components of BridgeDb can be left out or replaced, for maximum flexibility. BridgeDb was open source from the very beginning of the project. The philosophy of open source is closely aligned to academic values, of building on top of the work of giants. 

Many interesting problems in bioinformatics require integration of data from various sources. For example when combining microarray data with a pathway database, or merging co-citation networks with protein-protein interaction networks. Invariably this leads to an identifier mapping problem, where different datasets are annotated with identifiers that are related, but originate from different databases.

Solutions for the identifier mapping problem exist, such as Biomart, Synergizer, Cronos, PICR, HMS and many more. This creates an opportunity for bioinformatics tool developers. Tools can be made to flexibly support multiple mapping services or mapping services could be combined to get broader coverage. This approach requires an interface layer between tools and mapping services. BridgeDb provides such an interface layer, in the form of both a Java and REST API.

Because of the standardized interface layer, BridgeDb is not tied to a specific source of mapping information. You can switch easily between flat files, relational databases and several different web services. Mapping services can be combined to support multi-omics experiments or to integrate custom microarray annotations. BridgeDb isn't just yet another mapping service: it tries to build further on existing work, and integrate multiple partial solutions. The framework is intended for customization and adaptation to any identifier mapping service. 

BridgeDb makes it easy to add an important capability to existing tools. BridgeDb has already been integrated into several popular bioinformatics applications, such as Cytoscape, WikiPathways, PathVisio, Vanted and Taverna. To encourage tool developers to start using BridgeDb, we've created code examples, online documentation, and a mailinglist to ask questions. 

We believe that, to meet the challenges that are encountered in bioinformatics today, the software development process should follow a few essential principles: user friendliness, code reuse, modularity and open source. BridgeDb adheres to these principles, and can serve as a useful model for others to follow. BridgeDb can function to increase user-friendliness of graphical applications. It re-uses work from other projects such as BioMart and MIRIAM. BridgeDb consists of several small modules, integrated through a common interface (API). Components of BridgeDb can be left out or replaced, for maximum flexibility. BridgeDb was open source from the very beginning of the project. The philosophy of open source is closely aligned to academic values, of building on top of the work of giants. 

The BridgeDb library is available at "http://www.bridgedb.org":http://www.bridgedb.org.
A paper about BridgeDb was published in BMC _Bioinformatics_, 2010 Jan 4;11(1):5.

BridgeDb blog: "http://www.helixsoft.nl/blog/?tag=bridgedb":http://www.helixsoft.nl/blog/?tag=bridged

From Scientific Discovery to Cures: Bright Stars within a Galaxy

We propose that data mining and network analysis utilizing public databases can identify and quantify relationships between scientific discoveries and major advances in medicine (cures). Further development of such approaches could help to increase public understanding and governmental support for life science research and could enhance decision making in the quest for cures

«Deseando economizar la sangre cuanto sea posible». De la guerra a muerte al tratado de regularización en el periodo de Independencia de Venezuela, 1813-1824

This work is part of the commemoration of the bicentennial of Independence of the Latin American nations and it was carried out using the qualitative analysis method and the current of peace studies. The purpose is to analyze, from a comparative perspective, the situation experienced in Venezuela since 1813 with the war to death decree and the subsequent stage in the which were in force the humanitarian agreements signed in Trujillo in November 1820 between the Spanish government and the republican government, especially, emphasizing the application of the treaty of regularization of war. This dynamic of war with its different levels of intensity shows the complexity of the conflict in an environment of high social and ethnic polarization. Undoubtedly, those humanitarian standards marked a turning point in saving or alleviating the lives of hundreds of combatants, although it must also be recognized that there were many infractions and interference by some radical sectors.En el marco de la conmemoración del Bicentenario de la Independencia de las naciones hispanoamericanas y, a través del método de análisis cualitativo y de la corriente de los estudios de paz, el propósito de este artículo consiste en analizar, desde una óptica comparativa, la situación vivida en Venezuela a partir de 1813, cuando se promulgó el decreto de guerra a muerte y la posterior etapa en la cual estuvieron en vigencia los acuerdos humanitarios firmados en Trujillo en noviembre de 1820 entre el gobierno español y el gobierno republicano, en especial, haciendo énfasis en la aplicación del tratado de regularización de la guerra. Esta dinámica de la guerra con sus diferentes niveles de intensidad muestra la complejidad del conflicto, en medio de un ambiente de alta polarización social y étnica. Sin duda, aquellas normas humanitarias marcaron un punto de inflexión al salvar o aliviar la vida de cientos de combatientes, aunque debe reconocerse también que hubo muchas infracciones e interferencias por parte de algunos sectores radicales

Conflicto de poderes en torno a las imágenes y alhajas sagradas de los conventos suprimidos en la naciente República de Colombia

El propósito de este artículo consiste en analizar la problemática suscitada en torno a las alhajas de los conventos suprimidos por orden del naciente gobierno de la República de Colombia y su destinación para la financiación de los colegios públicos. Se abrió paso entonces a una serie de conflictos entre el poder legítimo que alegaba el estamento eclesiástico sobre sus elementos sagrados, el afán del gobierno por conseguir recursos para su ambicioso proyecto educativo y, por otro lado, la feligresía que clamaba su justo derecho a mantener su devoción hacia sus imágenes sagradasThe purpose of this article is to analyze the problems that arose around the sacred elements of the convents suppressed by order of the nascent government of the Republic of Colombia and their sale in order to fund public schools. A series of conflicts arose between the legitimate power that the clergy asserted over their sacred elements, the government’s desire to obtain resources for its ambitious educational projects and, on the other hand, the faithful who presented their rightful claim to maintain their devotion to their sacred images

Use of Machine Learning Models of the ”Transformers” Type in the Construction of Services in a Gamified Web app.

The purpose of this document is to describe the use of a natural language processing model in the multiplatform system ”Gamivity” by means of a sentence similarity algorithm to offer a personalized experience module based on the conceptual relationship between questions. For the selection process, certain criteria were chosen that will allow several pre-trained models under the “Transformers” architecture for evaluation, later. These criteria were the language with which the model was altered; Python was the programming language used for the implementation. Regarding the evaluation phase of the selected models, the ”Sentence Transformers” library of the Python programming language was used. In addition, a work environment analogous to the module present in the ”Gamivity” system was built, in which the development platform ”Google Colab” was used to test these models. The criteria for choosing the candidate model were based on its effectiveness in relation to questions as well as the computational cost involved while performing the operations in the said model Based on the applied methodology, the model that yielded the best results was ”paraphrase-multilingual- MiniLM-L12-v2,” modified with a large corpus of text in Spanish and 50 other languages, which showed a degree of precision. When it comes to conceptually relating the questions provided it was found to be optimal, having relatively low computational cost when performing these operations. Keywords: sentence transformers, sentence similarity, relate questions, personalized learning. Resumen El presente documento, tiene como propósito el de describir la utilización de un modelo de procesamiento de lenguaje natural en el sistema multiplataforma “Gamivity”, por medio de un algoritmo de similitud de oraciones para ofrecer un módulo de experiencia personalizada a partir de la relación conceptual entre preguntas. Para el proceso de selección, se establecieron ciertos criterios que permitieron elegir varios modelos pre entrenados bajo la arquitectura “Transformers” para su posterior evaluación. Dichos criterios, fueron el idioma con el que fue entrenado el modelo, así como que el lenguaje de programación utilizado para la implementación fuese Python. En lo que concierne a la fase de evaluación de los modelos seleccionados, se hizo uso de la biblioteca “Sentence Transformers” del lenguaje de programación Python, además se construyó un entorno de trabajo análogo al módulo presente en el sistema “Gamivity”, en la plataforma de desarrollo “Google Colab” para poner a prueba dichos modelos, los criterios para la elección del modelo candidato, se resumen en la eficacia a la hora de relacionar preguntas, así como el coste computacional a la hora de realizar las operaciones involucradas en dicho proceso. A partir de la metodología aplicada, el modelo que mejor resultados generó fue “paraphrase-multilingual-MiniLM L12-v2”, entrenado con un gran corpus de texto en español, así como de otros 50 idiomas, el cual mostró un grado de precisión óptimo a la hora de relacionar conceptualmente las preguntas proporcionadas, así como su relativo bajo coste computacional a la hora de efectuar dichas operaciones. Palabras Clave: sentence transformers, sentence similarity, relacionar preguntas, aprendizaje personalizado

Tools and collaborative environments for bioinformatics research

Advanced research requires intensive interaction among a multitude of actors, often possessing different expertise and usually working at a distance from each other. The field of collaborative research aims to establish suitable models and technologies to properly support these interactions. In this article, we first present the reasons for an interest of Bioinformatics in this context by also suggesting some research domains that could benefit from collaborative research. We then review the principles and some of the most relevant applications of social networking, with a special attention to networks supporting scientific collaboration, by also highlighting some critical issues, such as identification of users and standardization of formats. We then introduce some systems for collaborative document creation, including wiki systems and tools for ontology development, and review some of the most interesting biological wikis. We also review the principles of Collaborative Development Environments for software and show some examples in Bioinformatics. Finally, we present the principles and some examples of Learning Management Systems. In conclusion, we try to devise some of the goals to be achieved in the short term for the exploitation of these technologies