De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods

Background: In the post-genomic era where sequences are being determined at a rapid rate, we are highly reliant on computational methods for their tentative biochemical characterization. The Pfam database currently contains 3,786 families corresponding to ``Domains of Unknown Function'' (DUF) or ``Uncharacterized Protein Family'' (UPF), of which 3,087 families have no reported three-dimensional structure, constituting almost one-fourth of the known protein families in search for both structure and function. Results: We applied a `computational structural genomics' approach using five state-of-the-art remote similarity detection methods to detect the relationship between uncharacterized DUFs and domain families of known structures. The association with a structural domain family could serve as a start point in elucidating the function of a DUF. Amongst these five methods, searches in SCOP-NrichD database have been applied for the first time. Predictions were classified into high, medium and low-confidence based on the consensus of results from various approaches and also annotated with enzyme and Gene ontology terms. 614 uncharacterized DUFs could be associated with a known structural domain, of which high confidence predictions, involving at least four methods, were made for 54 families. These structure-function relationships for the 614 DUF families can be accessed on-line at http://proline.biochem.iisc.ernet.in/RHD_DUFS/. For potential enzymes in this set, we assessed their compatibility with the associated fold and performed detailed structural and functional annotation by examining alignments and extent of conservation of functional residues. Detailed discussion is provided for interesting assignments for DUF3050, DUF1636, DUF1572, DUF2092 and DUF659. Conclusions: This study provides insights into the structure and potential function for nearly 20 % of the DUFs. Use of different computational approaches enables us to reliably recognize distant relationships, especially when they converge to a common assignment because the methods are often complementary. We observe that while pointers to the structural domain can offer the right clues to the function of a protein, recognition of its precise functional role is still `non-trivial' with many DUF domains conserving only some of the critical residues. It is not clear whether these are functional vestiges or instances involving alternate substrates and interacting partners. Reviewers: This article was reviewed by Drs Eugene Koonin, Frank Eisenhaber and Srikrishna Subramanian.

Segregating Discourse Segments from Engineering Documents for Knowledge Acquisition

The broader goal of the research being described here is to automatically acquire diagnostic knowledge from documents in the domain of manual and mechanical assembly of aircraft structures. These documents are treated as a discourse used by experts to communicate with others. It therefore becomes possible to use discourse analysis to enable machine understanding of the text. The research challenge addressed in the paper is to identify documents or sections of documents that are potential sources of knowledge. In a subsequent step, domain knowledge will be extracted from these segments. The segmentation task requires partitioning the document into relevant segments and understanding the context of each segment. In discourse analysis, the division of a discourse into various segments is achieved through certain indicative clauses called cue phrases that indicate changes in the discourse context. However, in formal documents such language may not be used. Hence the use of a domain specific ontology and an assembly process model is proposed to segregate chunks of the text based on a local context. Elements of the ontology/model, and their related terms serve as indicators of current context for a segment and changes in context between segments. Local contexts are aggregated for increasingly larger segments to identify if the document (or portions of it) pertains to the topic of interest, namely, assembly. Knowledge acquired through such processes enables acquisition and reuse of knowledge during any part of the lifecycle of a product.

Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model

Chromatin acetylation is attributed with distinct functional relevance with respect to gene expression in normal and diseased conditions thereby leading to a topical interest in the concept of epigenetic modulators and therapy. We report here the identification and characterization of the acetylation inhibitory potential of an important dietary flavonoid, luteolin. Luteolin was found to inhibit p300 acetyltransferase with competitive binding to the acetyl CoA binding site. Luteolin treatment in a xenografted tumor model of head and neck squamous cell carcinoma (HNSCC), led to a dramatic reduction in tumor growth within 4 weeks corresponding to a decrease in histone acetylation. Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and miRNA profile including up-regulation of p53 induced miR-195/215, let7C; potentially translating into a tumor suppressor function. It also led to down regulation of oncomiRNAs such as miR-135a, thereby reflecting global changes in the microRNA network. Furthermore, a direct correlation between the inhibition of histone acetylation and gene expression was established using chromatin immunoprecipitation on promoters of differentially expressed genes. A network of dysregulated genes and miRNAs was mapped along with the gene ontology categories, and the effects of luteolin were observed to be potentially at multiple levels: at the level of gene expression, miRNA expression and miRNA processing.

El concepto de “texto medieval” en el trabajo ecdótico : un ejemplo surgido de los avatares en la tradición manuscrita de la “Crónica de Sancho IV”

Resumen: La realidad manuscrita del texto medieval implica asumir la problemática en torno al concepto de texto con el que habrá de trabajar el editor al pretender establecer el texto crítico de una obra determinada. Las diferentes concepciones en torno a dicha ontología textual influyen en el tipo particular de trabajo ecdótico que se pretenda realizar. El artículo pretende, a partir del caso de la edición de la Crónica de Sancho IV, proponer un modelo de edición que contemple las variantes que la obra fue manifestando a lo largo de su tradición con el objetivo de dar cuenta de la naturaleza mutable del texto medieval en función de su intencionalidad política.

La percepción de los valores morales

Resumen: El autor aborda un tema que a veces pasa inadvertido aun para muchos adherentes al iusnaturalismo: el conocimiento de la ley natural. Mientras abundan estudios que centran sus argumentos en la existencia de esta normativa supra positiva o que ahondan su ontología y extensión, sin embargo a veces no se repara en una cuestión liminar que resulta necesario dilucidar: ¿cómo se conocen los principios y las conclusiones de la ley natural?, ¿es naturalmente conocida?, ¿qué se entiende por “naturalmente”? Sobre el contenido de la ley natural el documento afirma que “no es un conjunto cerrado y completo de normas morales, sino la fuente de inspiración constante, presente y operativa de las diversas etapas de la economía de la salvación”. El término “percepción” hace referencia a una “experiencia” y que por tanto es exterior. Se concluye entonces que consiste en un conocimiento objetivo (no innato) de los preceptos morales, más allá de la presencia natural de un hábito que permite su captación (sindéresis).

La nupcialidad entre la estética teológica y la ontología trinitaria

Resumen: Este artículo se propone situar la categoría de nupcialidad en la circularidad hermenéutica entre lo antropológico y lo trinitario, a fin de recuperar su poder especulativo y reconfigurador tanto para la teología como para la filosofía y la mística contemporáneas. Para ello se apela a la fuerza de las existencias teologales de Juan de la Cruz, Edith Stein y Christophe Lebreton. A partir de sus testimonios el artículo postula una relación fecunda entre Estética teológica y Ontología trinitaria que redunda en una caracterización actualizada de la nupcialidad compuesta por ocho notas distintivas que el texto desarrolla.

“Ser” como interpretación de la realidad

Resumen: En un contexto de descrédito de la Metafísica, José Gómez Caffarena plantea una reflexión especulativa que, afianzada en lo humano, ‘diga’ de modo veraz y relevante lo esencial de la estructura última de lo real. Para ello desarrolla una ontología que, afianzada en unos presupuestos metodológicos genuinamente trascendentales, respete tanto el límite de lo fenoménico como la pretensión de verdad desde la que se hace. Este escrito discute la viabilidad última de dicha propuesta precisamente porque su posibilidad supondría ir más allá de lo que el método permite.

Geometria et Geometriae : e mathematica ad philosopiam

Resumen: Luego de exponer las posibilidades filosóficas que las geometrías abren a las orientaciones de nuevos espacios, el artículo considera los procedimientos euclidianos y la conexión con las geometrías no-euclidianas. Hay muchas posiciones acerca de las bases filosóficas de las distintas geometrías. Hay además formulaciones muy importantes, desde la gnoseología a la ontología, respecto de las extensiones métricas de la alta geometría.

El problema de la causalidad en las ciencias económicas

[ES] En el presente artículo se aborda el problema de la causalidad en las Ciencias Económicas. Partiendo de la diferenciación entre ciencias duras y blandas, y de la supuesta clasificicación de la economía en este segundo grupo, se realiza un análisis de los diferentes paradigmas ontológicos que soportan la investigación científica, para a continuación trasladar la causalidad desde el ámbito ontológico al gnoseológico. Posteriormente se profundiza en la conjunción de la metodología hipotético-deductiva con el método correlacional, generando una causalidad probabilística. Dicha causalidad, contextualizada de forma científica, permite la realización y contrastación de inferencias predictivas, a través de las cuales las Ciencias Ecnómicas pueden encontrar su ubicación en los niveles mas extrictos de la investigación científica.

Ontologies for representation of folk song metadata

The digital management of collections in museums, archives, libraries and galleries is an increasingly important part of cultural heritage studies. This paper describes a representation for folk song metadata, based on the Web Ontology Language (OWL) implementation of the CIDOC Conceptual Reference Model. The OWL representation facilitates encoding and reasoning over a genre ontology, while the CIDOC model enables a representation of complex spatial containment and proximity relations among geographic regions. It is shown how complex queries of folk song metadata, relying on inference and not only retrieval, can be expressed in OWL and solved using a description logic reasoner.

SNOMED CT sare semantikoa euskaratzeko aplikazioa

[EU]Master bukaerako proiektu honetan, SNOMED CT sare semantikoa euskaratzeko aplikazioaren lehenengo urratsak azaltzen ditugu. Horretarako, SNOMED CTren sakoneko analisia egin dugu, eta bio-zientzien domeinuko euskarazko baliabideak aztertu ditugu. Aplikazioaren diseinu osoa egin dugu, euskarazko ordainak lortzeko algoritmo bat definituz. Algoritmo horren lehenengo urratsa izan da inplementatu duguna, hiztegi espezializatuen parekatzeari dagokiona, alegia. Aplikazioaren hastapen hauetan emaitza itxaropentsuak lortu ditugu.

Hacia una economía holográfica. Una revisión de la ciencia económica a partir de la ontoepistemología oriental

363 p.

Técnicas Conceptuales en la Gestión de Proyectos Software

205 p.

Arte e história do ser: a conferência a origem da obra de arte e a gênese do conceito de história do ser na obra de Martin Heidegger nos anos 1930

O estudo desenvolvido nesta tese teve por intenção investigar a relação entre a questão da arte e a história do ser, tal como esta irá progressivamente se construir na obra de Martin Heidegger, sobretudo a partir de meados da década de 1930. Com isso, pretendeu-se identificar e destacar o papel fundamental que a abordagem desta questão deteve para a chamada viragem (Kehre) e os rumos posteriores da obra deste filósofo, conduzindo seu pensamento para além dos limites da analítica existencial empreendida em Ser e Tempo (1927) e em direção à construção da chamada "história do ser" e à questão do acabamento da metafísica como niilismo, na última fase de seu pensamento e em obras como o Beiträge zur Philosofie (1938). Para tal, partimos da investigação do ensaio A origem da obra de arte, publicado em meados da década de 1930, devido ao caráter central (não apenas em sentido cronológico) que esse texto ocupa para a abordagem do problema, posto nele Heidegger empreender a revisão de conceitos como Zuhandenheit e Vorhandenheit, de modo a assim abrir lugar, em sua ontologia, para este ente que a obra de arte é, com isso permitindo que o acontecimento do ser pudesse vir a ser pensando em novas bases e em perspectiva histórico-hermenêutica.

Formal methods in the foundations of science

The intent of this study is to provide formal apparatus which facilitates the investigation of problems in the methodology of science. The introduction contains several examples of such problems and motivates the subsequent formalism.

A general definition of a formal language is presented, and this definition is used to characterize an individual’s view of the world around him. A notion of empirical observation is developed which is independent of language. The interplay of formal language and observation is taken as the central theme. The process of science is conceived as the finding of that formal language that best expresses the available experimental evidence.

To characterize the manner in which a formal language imposes structure on its universe of discourse, the fundamental concepts of elements and states of a formal language are introduced. Using these, the notion of a basis for a formal language is developed as a collection of minimal states distinguishable within the language. The relation of these concepts to those of model theory is discussed.

An a priori probability defined on sets of observations is postulated as a reflection of an individual’s ontology. This probability, in conjunction with a formal language and a basis for that language, induces a subjective probability describing an individual’s conceptual view of admissible configurations of the universe. As a function of this subjective probability, and consequently of language, a measure of the informativeness of empirical observations is introduced and is shown to be intuitively plausible – particularly in the case of scientific experimentation.

The developed formalism is then systematically applied to the general problems presented in the introduction. The relationship of scientific theories to empirical observations is discussed and the need for certain tacit, unstatable knowledge is shown to be necessary to fully comprehend the meaning of realistic theories. The idea that many common concepts can be specified only by drawing on knowledge obtained from an infinite number of observations is presented, and the problems of reductionism are examined in this context.

A definition of when one formal language can be considered to be more expressive than another is presented, and the change in the informativeness of an observation as language changes is investigated. In this regard it is shown that the information inherent in an observation may decrease for a more expressive language.

The general problem of induction and its relation to the scientific method are discussed. Two hypotheses concerning an individual’s selection of an optimal language for a particular domain of discourse are presented and specific examples from the introduction are examined.