Expression and Regulation of Human Cytochrome P450 4F Isoforms in Tissue Samples and Under TNF-Alpha Challenges

CYP4F (Cytochrome P4504F) enzymes metabolize endogenous molecules including leukotrienes, prostaglandins and arachidonic acid. The involvement of these endogenous compounds in inflammation has led to the hypothesis that changes in the inflamed tissue environment may affect the expression of CYP4Fs during the pro-inflammatory state, which in turn may modulate inflammatory conditions during the anti-inflammatory state. We demonstrated that inflamed tissues have different levels of CYP4F isoform expression profiles in a number of human samples when compared to the average population. The CYP4F isoform expression levels change with the degree of inflammation present in tissue. Further investigation in cell culture studies revealed that inflammatory cytokines, in particular TNF-α, play a role in regulating the expression of the CYP4F family. One of the isoforms, CYP4F11, had different characteristics than that of the other five CYP4F family members. CYP4F11 metabolizes xenobiotics while the other isoforms metabolize endogenous compounds with higher affinity. CYP4F11 also was expressed at high quantities in the brain, and was up-regulated by TNF-α, while the other isoforms were not expressed at high quantities in the brain and were down-regulated by TNF-α. We identified the AP-1 protein of the JNK pathway as the signaling protein that causes significant increase in CYP4F11 expression. Since TNF-α stimulation causes a simultaneous activation of both JNK pathway and NF-κB signaling, we investigated further the role that NF-κB plays on expression of the CYP4F11 gene. We concluded that although there is a significant increase in CYP4F11 expression in the presence of TNF-α, the activation of NF-κB signaling inhibits CYP4F11 expression in a time dependent manner. The expression of CYP4F11 is only significantly increased after 24 hours of treatment with TNF-α; at shorter time points NF-κB signaling overpowers the JNK pathway activation. We believe that these findings may in the future lead to improved drug design for modulating inflammation.

Reduced synchronization persistence in neural networks derived from atm-deficient mice

Many neurodegenerative diseases are characterized by malfunction of the DNA damage response. Therefore, it is important to understand the connection between system level neural network behavior and DNA. Neural networks drawn from genetically engineered animals, interfaced with micro-electrode arrays allowed us to unveil connections between networks’ system level activity properties and such genome instability. We discovered that Atm protein deficiency, which in humans leads to progressive motor impairment, leads to a reduced synchronization persistence compared to wild type synchronization, after chemically imposed DNA damage. Not only do these results suggest a role for DNA stability in neural network activity, they also establish an experimental paradigm for empirically determining the role a gene plays on the behavior of a neural network.

Marco computacional para la definición de un modelo bio-inspirado en la señalización celular

Las Redes de Procesadores Evolutivos-NEP propuestas en [Mitrana et al., 2001], son un modelo computacional bio-inspirado a partir de la evolución de poblaciones de células, definiendo a nivel sintáctico algunas propiedades biológicas. En este modelo, las células están representadas por medio de palabras que describen secuencias de ADN. Informalmente, en algún instante de tiempo, el sistema evolutivo está representado por una colección de palabras cada una de las cuales representa una célula. El espacio genotipo de las especies, es un conjunto que recoge aquellas palabras que son aceptadas como sobrevivientes (es decir, como \correctas"). Desde el punto de vista de la evolución, las células pertenecen a especies y su comunidad evoluciona de acuerdo a procesos biológicos como la mutación y la división celular. éstos procesos representan el proceso natural de evolución y ponen de manifiesto una característica intrínseca de la naturaleza: el paralelismo. En este modelo, estos procesos son vistos como operaciones sobre palabras. Formalmente, el modelo de las NEP constituyen una arquitectura paralela y distribuida de procesamiento simbólico inspirada en la Máquina de conexión [Hillis, 1981], en el Paradigma de Flujo Lógico [Errico and Jesshope, 1994] y en las Redes de Procesadores Paralelos de Lenguajes (RPPL) [Csuhaj-Varju and Salomaa, 1997]. Al modelo NEP se han ido agregando nuevas y novedosas extensiones hasta el punto que actualmente podemos hablar de una familia de Redes de Procesadores Bio-inspirados (NBP) [Mitrana et al., 2012b]. Un considerable número de trabajos a lo largo de los últimos años han demostrado la potencia computacional de la familia NBP. En general, éstos modelos son computacionalmente completos, universales y eficientes [Manea et al., 2007], [Manea et al., 2010b], [Mitrana and Martín-Vide, 2005]. De acuerdo a lo anterior, se puede afirmar que el modelo NEP ha adquirido hasta el momento un nivel de madurez considerable. Sin embargo, aunque el modelo es de inspiración biológica, sus metas siguen estando motivadas en la Teoría de Lenguajes Formales y las Ciencias de la Computación. En este sentido, los aspectos biológicos han sido abordados desde una perspectiva cualitativa y el acercamiento a la realidad biológica es de forma meramente sintáctica. Para considerar estos aspectos y lograr dicho acercamiento es necesario que el modelo NEP tenga una perspectiva más amplia que incorpore la interacción de aspectos tanto cualitativos como cuantitativos. La contribución de esta Tesis puede considerarse como un paso hacia adelante en una nueva etapa de los NEPs, donde el carácter cuantitativo del modelo es de primordial interés y donde existen posibilidades de un cambio visible en el enfoque de interés del dominio de los problemas a considerar: de las ciencias de la computación hacia la simulación/modelado biológico y viceversa, entre otros. El marco computacional que proponemos en esta Tesis extiende el modelo de las Redes de Procesadores Evolutivos (NEP) y define arquitectura inspirada en la definición de bloques funcionales del proceso de señalización celular para la solución de problemas computacionales complejos y el modelado de fenómenos celulares desde una perspectiva discreta. En particular, se proponen dos extensiones: (1) los Transductores basados en Redes de Procesadores Evolutivos (NEPT), y (2) las Redes Parametrizadas de Procesadores Evolutivos Polarizados (PNPEP). La conservación de las propiedades y el poder computacional tanto de NEPT como de PNPEP se demuestra formalmente. Varias simulaciones de procesos relacionados con la señalización celular son abordadas sintáctica y computacionalmente, con el _n de mostrar la aplicabilidad e idoneidad de estas dos extensiones. ABSTRACT Network of Evolutionary Processors -NEP was proposed in [Mitrana et al., 2001], as a computational model inspired by the evolution of cell populations, which might model some properties of evolving cell communities at the syntactical level. In this model, cells are represented by words which encode their DNA sequences. Informally, at any moment of time, the evolutionary system is described by a collection of words, where each word represents one cell. Cells belong to species and their community evolves according to mutations and division which are defined by operations on words. Only those cells accepted as survivors (correct) are represented by a word in a given set of words, called the genotype space of the species. This feature is analogous with the natural process of evolution. Formally, NEP is based on an architecture for parallel and distributed processing inspired from the Connection Machine [Hillis, 1981], the Flow Logic Paradigm [Errico and Jesshope, 1994] and the Networks of Parallel Language Processors (RPPL) [Csuhaj-Varju and Salomaa, 1997]. Since the date when NEP was proposed, several extensions and variants have appeared engendering a new set of models named Networks of Bio-inspired Processors (NBP) [Mitrana et al., 2012b]. During this time, several works have proved the computational power of NBP. Specifically, their efficiency, universality, and computational completeness have been thoroughly investigated [Manea et al., 2007, Manea et al., 2010b, Mitrana and Martín-Vide, 2005]. Therefore, we can say that the NEP model has reached its maturity. Nevertheless, although the NEP model is biologically inspired, this model is mainly motivated by mathematical and computer science goals. In this context, the biological aspects are only considered from a qualitative and syntactical perspective. In view of this lack, it is important to try to keep the NEP theory as close as possible to the biological reality, extending their perspective incorporating the interplay of qualitative and quantitative aspects. The contribution of this Thesis, can be considered as a starting point in a new era of the NEP model. Then, the quantitative character of the NEP model is mandatory and it can address completely new different types of problems with respect to the classical computational domain (e.g. from the computer science to system biology). Therefore, the computational framework that we propose extends the NEP model and defines an architecture inspired by the functional blocks from cellular signaling in order to solve complex computational problems and cellular phenomena modeled from a discrete perspective. Particularly, we propose two extensions, namely: (1) Transducers based on Network of Evolutionary Processors (NEPT), and (2) Parametrized Network of Polarized Evolutionary Processors (PNPEP). Additionally, we have formally proved that the properties and computational power of NEP is kept in both extensions. Several simulations about processes related with cellular signaling both syntactical and computationally have been considered to show the model suitability.

LR property of non-well-formed scales

This article studies generated scales having exactly three different step sizes within the language of algebraic combinatorics on words. These scales and their corresponding step-patterns are called non well formed. We prove that they can be naturally inserted in the Christoffel tree of well-formed words. Our primary focus in this study is on the left- and right-Lyndon factorization of these words. We will characterize the non-well-formed words for which both factorizations coincide. We say that these words satisfy the LR property and show that the LR property is satisfied exactly for half of the non-well-formed words. These are symmetrically distributed in the extended Christoffel tree. Moreover, we find a surprising connection between the LR property and the Christoffel duality. Finally, we prove that there are infinitely many Christoffel–Lyndon words among the set of non-well-formed words and thus there are infinitely many generated scales having as step-pattern a Christoffel–Lyndon word.

A PUBLICIDADE E AS MINISSÉRIES DA REDE GLOBO: ADAPTAÇÃO E PERSUASÃO

Esta pesquisa tem por finalidade compreender como a Rede Globo de Televisão, através dos anúncios publicitários das minisséries adaptadas da literatura brasileira, é capaz de valorizar o produto e a sua imagem institucional, ao enfatizar a origem literária da produção. Ao informar e destacar os atributos de um produto através de um jogo de palavras, o anúncio publicitário é capaz de persuadir e seduzir o consumidor a construir uma imagem que o leve à compra e à satisfação de um desejo ou necessidade. O corpus do estudo são as peças veiculadas no jornal O Estado de São Paulo, entre 1982 e 2008. Como procedimentos metodológicos, optou-se pela Análise de Conteúdo, e as principais conclusões confirmam a hipótese da pesquisa e ainda trazem uma discussão sobre quais são os principais efeitos que essa valorização traz para a emissora

Designing a model for a corpus-driven dictionary of academic English

University students encounter difficulties with academic English because of its vocabulary, phraseology, and variability, and also because academic English differs in many respects from general English, the language which they have experienced before starting their university studies. Although students have been provided with many dictionaries that contain some helpful information on words used in academic English, these dictionaries remain focused on the uses of words in general English. There is therefore a gap in the dictionary market for a dictionary for university students, and this thesis provides a proposal for such a dictionary (called the Dictionary of Academic English; DOAE) in the form of a model which depicts how the dictionary should be designed, compiled, and offered to students. The model draws on state-of-the-art techniques in lexicography, dictionary-use research, and corpus linguistics. The model demanded the creation of a completely new corpus of academic language (Corpus of Academic Journal Articles; CAJA). The main advantages of the corpus are its large size (83.5 million words) and balance. Having access to a large corpus of academic language was essential for a corpus-driven approach to data analysis. A good corpus balance in terms of domains enabled a detailed domain-labelling of senses, patterns, collocates, etc. in the dictionary database, which was then used to tailor the output according to the needs of different types of student. The model proposes an online dictionary that is designed as an online dictionary from the outset. The proposed dictionary is revolutionary in the way it addresses the needs of different types of student. It presents students with a dynamic dictionary whose contents can be customised according to the user's native language, subject of study, variant spelling preferences, and/or visual preferences (e.g. black and white).

Quiralidade, superfície de energia potencial e dinâmica de complexos envolvendo H2O2 + gases nobres

Tese (doutorado)—Universidade de Brasília, Instituto de Física, 2015.

Figure(s) de sang : amours secrètes, troubles fratries et « miscégénation » dans The Searchers, The Unforgiven et The Missing

International audience

Fringe Types and KOS Systematics: Examining the Limits of the Population Perspective of Knowledge Organization Systems

We find ourselves, after the close of the twentieth century, looking back at a mass of responses to the knowledge organization problem. Many institutions, such as the Dewey Decimal Classification (Furner, 2007), have grown up to address it. Increasingly, many diverse discourses are appropriating the problem and crafting a wide variety of responses. This includes many artistic interpretations of the act and products of knowledge organization. These surface as responses to the expressive power or limits of the Library and Information Studies institutions (e.g., DDC) and their often primarily utilitarian gaze.One way to make sense of this diversity is to approach the study from a descriptive stance, inventorying the population of types of KOS. This population perspective approaches the phenomenon of types and boundaries of Knowledge Organization Systems (KOS) as one that develops out of particular discourses, for particular purposes. For example, both DDC and Martianus Capella, a 5th Century encyclopedist, are KOS in this worldview. Both are part of the population of KOS. Approaching the study of KOS from the population perspective allows the researcher a systematic look at the diversity emergent at the constellation of different factors of design and implementation. However, it is not enough to render a model of core types, but we have to also consider the borders of KOS. Fringe types of KOS inform research, specifically to the basic principles of design and implementation used by others outside of the scholarly and professional discourse of Library and Information Studies.Four examples of fringe types of KOS are presented in this paper. Applying a rubric developed in previous papers, our aim here is to show how the conceptual anatomy of these fringe types relates to more established KOS, thereby laying bare the definitions of domain, purpose, structure, and practice. Fringe types, like Beghtol’s examples (2003), are drawn from areas outside of Library and Information Studies proper, and reflect the reinvention of structures to fit particular purposes in particular domains. The four fringe types discussed in this paper are (1) Roland Barthes’ text S/Z which “indexes” a text of an essay with particular “codes” that are meant to expose the literary rhythm of the work; (2) Mary Daly’s Wickedary, a reference work crafted for radical liberation theology – and specifically designed to remove patriarchy from the language used by what the author calls “wild women”; (3) Luigi Serafini’s Codex Seraphinianus a work of book art that plays on the trope of universal encyclopedia and back-of- the book index; and (4) Martinaus Capella – and his Marriage of Mercury and Philology, a fifth century encyclopedia. We compared these using previous analytic taxonomies (Wright, 2008; Tennis, 2006; Tudhope, 2006, Soergel, 2001, Hodge, 2000).

How the whiteness embedded in health services impacts on the health and well-being of Aboriginal peoples

Aboriginal women are treated differently by non-indigenous health care providers based on perceptions of Aboriginality and skin colour and white race privilege within health care environments. The experiences shared below are from some of the Aboriginal woman respondents in a research project undertaken within Rockhampton, a regional area in Central Queensland (Fredericks, 2003). The experiences give an insight into how the Aboriginal women interviewed felt and their observations of how other Aboriginal women were treated within health care settings based on skin colour and perceptions of Aboriginality. A number of the women demonstrated a personal in-depth analysis of the issues surrounding place, skin colour and Aboriginality. For example, one of the women, who I named Kay, identified one particular health service organisation and stated that, ‘it is a totally white designed space. There is nothing that identifies me to that place. I just won’t go there as a client because I don’t feel they cater for me as a black woman’. Kay’s words give us an understanding of the reality experienced by Aboriginal women as they move in and out of places within health environments and broader society. Some of these experiences are examples of direct racism, whilst other examples are subtle and demonstrate how whiteness manifests and plays out within places. I offer acknowledgement and honour to the Aboriginal women who shared their stories and gave me a glimpse of their realities in the research project from which the findings presented in this chapter are taken. It is to this research project that is the subject of this chapter.

Building TRACE (translations censored) theatre corpus: some methodological questions on text selection

Editores:Micaela Muñoz-Calvo; Carmen Buesa-Gómez

Expression of VEGFR-2 on HaCaT cells is regulated by VEGF and plays an active role in mediating VEGF induced effects

Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 play important roles in mitogenesis and chemotaxis of endothelial cells. In normal human skin, VEGF is expressed and secreted by epidermal keratinocytes. Emerging data suggest that keratin

The spacing effect depends on an encoding deficit, retrieval, and time in working memory: evidence from once-presented words.

The spacing effect in list learning occurs because identical massed items suffer encoding deficits and because spaced items benefit from retrieval and increased time in working memory. Requiring the retrieval of identical items produced a spacing effect for recall and recognition, both for intentional and incidental learning. Not requiring retrieval produced spacing only for intentional learning because intentional learning encourages retrieval. Once-presented words provided baselines for these effects. Next, massed and spaced word pairs were judged for matches on their first three letters, forcing retrieval. The words were not identical, so there was no encoding deficit. Retrieval could and did cause spacing only for the first word of each pair; time in working memory, only for the second.

The body language: The spontaneous influence of congruent bodily arousal on the awareness of emotional words

Nowadays, the idea of a reciprocal influence of physiological and psychological processes seems to be widely accepted. For instance, current theories of embodied emotion suggest that knowledge about an emotion concept involves simulations of bodily experienced emotional states relevant to the concept. In line with this framework, the present study investigated whether actual levels of physiological arousal interact with the processing of emotional words. Participants performed 2 blocks of an attentional blink task, once after a cycling session (increased arousal) and once after a relaxation session (reduced arousal). Concretely, participants were instructed to detect and report 2 target words (T1 and T2) presented among a series of nonword distractors. T1 and T2 were either neutral, high arousal, or low arousal words. Results revealed that increased physiological arousal led to improved reports of high arousal T2 words, whereas reduced physiological arousal led to improved reports of low arousal T2 words. Neutral T2 remained unaffected by the arousing conditions. These findings emphasize that actual levels of physiological arousal modulate the cognitive access to arousal (in-)congruent emotional concepts and suggest a direct grounding of emotion knowledge in our bodily systems of arousal.