Solving Maximum Clique Problem for Protein Structure Similarity

Computing the similarity between two protein structures is a crucial task in molecular biology, and has been extensively investigated. Many protein structure comparison methods can be modeled as maximum weighted clique problems in specific k-partite graphs, referred here as alignment graphs. In this paper we present both a new integer programming formulation for solving such clique problems and a dedicated branch and bound algorithm for solving the maximum cardinality clique problem. Both approaches have been integrated in VAST, a software for aligning protein 3D structures largely used in the National Center for Biotechnology Information, an original clique solver which uses the well known Bron and Kerbosch algorithm (BK). Our computational results on real protein alignment instances show that our branch and bound algorithm is up to 116 times faster than BK.

Időskori gondoskodás eltérő várható élettartam esetén

Nyugdíjba vonuláskor a befizetett járulék egy meghatározott képlet szerint nyugdíjkifizetést eredményez. A nyugdíjképletek jellemzően a várhatóan hosszabb ideig élőknek kedveznek a későbbi nyugdíjba vonulás kelleténél nagyobb honorálása miatt. Ebben a munkában egy olyan időskori öngondoskodási rendszert mutatok be, ahol a nyugdíjas rugalmasan alakíthatja jövedelmét az (élet)járadékszolgáltatás és az egyéni bankszámla között. Állami beavatkozással az antiszelekcióból eredő jóléti veszteség csökkenthető, de nem szüntethető meg.

Los mecanismos de nivelación en el sistema de financiación de 2009: Una propuesta de indicadores para el análisis de su eficiencia

Este trabajo analiza el funcionamiento del sistema de financiación de las Comunidades Autónomas de régimen común en España aprobado en la Ley 22/2009, desde la perspectiva específica del análisis de sus mecanismos de nivelación. Con esa finalidad,se propone una batería de indicadores de reordenación, indicadores de intensidad de la nivelación e indicadores de distorsiones de la nivelación que se aplica para la evaluación del desempeño del sistema vigente, en comparación con el aprobado en 2001, y que puede asimismo utilizarse para la evaluación de sistemas comparados. Los resultados ponen de manifiesto que el sistema aprobado en 2009 mejora el funcionamiento del sistema anterior, en la medida en que aumenta la intensidad de la nivelación y se reduce la prevalencia y la intensidad de las principales distorsiones que se detectaban en sus resultados de nivelación (reordenaciones. sobrenivelaciones y desnivelaciones).

Contribution à l'étude de la physiopathologie des effets secondaires associés aux iECA : approche expérimentale et clinique des mécanismes régulant l'activité pharmacologique des kinines

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes.

The goal of this study was to determine whether beta(1)-adrenergic receptor (AR) and beta(2)-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One potential mechanism is that cardiac beta(2)-AR can activate both G(s) and G(i) proteins, whereas cardiac beta(1)-AR couples only to G(s). To avoid complicated crosstalk between beta-AR subtypes, we expressed beta(1)-AR or beta(2)-AR individually in adult beta(1)/beta(2)-AR double knockout mouse cardiac myocytes by using adenoviral gene transfer. Stimulation of beta(1)-AR, but not beta(2)-AR, markedly induced myocyte apoptosis, as indicated by increased terminal deoxynucleotidyltransferase-mediated UTP end labeling or Hoechst staining positive cells and DNA fragmentation. In contrast, beta(2)-AR (but not beta(1)-AR) stimulation elevated the activity of Akt, a powerful survival signal; this effect was fully abolished by inhibiting G(i), G(beta gamma), or phosphoinositide 3 kinase (PI3K) with pertussis toxin, beta ARK-ct (a peptide inhibitor of G(beta gamma)), or LY294002, respectively. This indicates that beta(2)-AR activates Akt via a G(i)-G(beta gamma)-PI3K pathway. More importantly, inhibition of the G(i)-G(beta gamma)-PI3K-Akt pathway converts beta(2)-AR signaling from survival to apoptotic. Thus, stimulation of a single class of receptors, beta(2)-ARs, elicits concurrent apoptotic and survival signals in cardiac myocytes. The survival effect appears to predominate and is mediated by the G(i)-G(beta gamma)-PI3K-Akt signaling pathway.

The effects of aging on the BTBR mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.

Contribution à l'étude de la physiopathologie des effets secondaires associés aux iECA : approche expérimentale et clinique des mécanismes régulant l'activité pharmacologique des kinines

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Brominated flame retardants and biomagnification factors in marine species in the North-East Atlantic

BACKGROUND: Concentrations of brominated flame retardants (BFRs) are reported to increase in marine ecosystems. OBJECTIVES: Characterize exposure to BFRs in animals from different trophic levels in North-East Atlantic coastal marine ecosystems along a latitudinal gradient from southern Norway to Spitsbergen, Svalbard, in the Arctic. Calanoid species were collected from the Oslofjord (59°N), Froan (64°N), and Spitsbergen (> 78°N); Atlantic cod (Gadus morhua) from the Oslofjord and Froan; polar cod (Boreogadus saida) from Bear Island (74°N) and Spitsbergen; harbor seal (Phoca vitulina) from the Oslofjord, Froan, and Spitsbergen; and ringed seal (Phoca vitulina) from Spitsbergen. Eggs of common tern (Sterna hirundo) were collected from the Oslofjord, and eggs of arctic terns (Sterna paradisaea) from Froan and Spitsbergen. RESULTS: Levels of polybrominated diphenylethers (PBDEs) and hexabromocyclododecane (HBCD) generally decreased as a function of increasing latitude, reflecting distance from release sources. The clear latitudinal decrease in levels of BFRs was not pronounced in the two tern species, most likely because they are exposed during migration. The decabrominated compound BDE-209 was detected in animals from all three ecosystems, and the highest levels were found in arctic tern eggs from Spitsbergen. HBCD was found in animals from all trophic levels, except for in calanoids at Froan and Spitsbergen. CONCLUSIONS: Even though the levels of PBDEs and HBCD are generally low in North-East Atlantic coastal marine ecosystems, there are concerns about the relatively high presence of BDE-209 and HBCD.

Sherman Alexie’s "The Toughest Indian in the World": Amalgamating the Oral and the Written Traditions

This article argues that The Toughest Indian in the World (2000) by Native-American author Sherman Alexie combines elements of his tribal (oral) tradition with others coming from the Western (literary) short-story form. Like other Native writers — such as Momaday, Silko or Vizenor — , Alexie is seen to bring into his short fiction characteristics of his people’s oral storytelling that make it much more dialogical and participatory. Among the author’s narrative techniques reminiscent of the oral tradition, aggregative repetitions of patterned thoughts and strategically-placed indeterminacies play a major role in encouraging his readers to engage in intellectual and emotional exchanges with the stories. Assisted by the ideas of theorists such as Ong (1988), Evers and Toelken (2001), and Teuton (2008), this article shows how Alexie’s short fiction is enriched and revitalized by the incorporation of oral elements. The essay also claims that new methods of analysis and assessment may be needed for this type of bicultural artistic forms. Despite the differences between the two modes of communication, Alexie succeeds in blending features and techniques from both traditions, thus creating a new hybrid short-story form that suitably conveys the trying experiences faced by his characters.

'That Puissant City': John Milton's Roman Sojourns 1638-1639

John Milton’s sojourns in Rome (1638-9) are attested by his comments in Defensio Secunda, by the minutes of the English College, by Latin encomia which he received from Roman academicians, and, not least, by his Latin letter to Lucas Holstenius (19/29 March 1639), and several Latin poems which he composed in the course of his residency in the capital city: Ad Salsillum, and three Latin epigrams extolling the praises of the virtuosa soprano, Leonora Baroni. Read together, these texts serve to reveal much about Milton’s participation in, and reaction to, the ‘Puissant City’, (History of Britain, Bk 2).

The present monograph presents fresh evidence of Milton's integration into the academic and cultural life of seventeenth-century Rome. It argues that his links with two Roman academies: the Accademia dei Fantastici and Accademia degli Umoristi constitute a sustained participation in an academic community paralleling that of his independently attested performance in Florentine academies (on which I have published extensively). It also investigates his links with Alessandro Cherubini, David Codner, Giovanni Batista Doni, and the Baroni circle hymned in three published anthologies.

Chapter 1: Milton and the Accademia dei Fantastici investigates the cultural climate surrounding Milton's Ad Salsillum by examining two of that academy's publications: the Poesie dei Signori Accademici Fantastici di Roma (Rome, 1637) and the Academia Tenuta da Fantastici a. 12 di Maggio 1655 (Rome, 1655), the latter celebrating the creation of Fabio Chigi as Pope Alexander VII on 5 April 1655. Read in a new light, Milton’s self-fashioning, it is argued, takes its place not only alongside Salzilli’s encomium in Milton's honour, and his Italian sonnets in the 1637 Poesie, but also in relation to other poems in that collection, and the academy's essentially Catholic eulogistic trend. The chapter also provides fresh evidence of Salzilli’s survival of the illness described in Milton’s poem by his epistolary correspondence with Tomaso Stigliani.

Chapter 2: Milton and the Vatican argues for links between Milton’s Latin letter to Holstenius and a range of Holstenius’ published works: his edition of the axioms of the later Pythagoreans gifted by him to Milton, and his published neo-Platonic works. This is achieved by mutual appropriation of Similitudes in a series of Miltonic similes, the anabasis/katabasis motifs in a reworking of the Platonic theory of the transmigration of souls, and allusion to etymological details highlighted in Holstenius’ published editions. The chapter also reveals Milton’s alertness to typographical procedures and, by association, to Holstenius’ recent role (1638) as Director of the press of the Biblioteca Vaticana.

Chapter 3: Milton and the Accademia degli Umoristi argues for Milton’s likely participation in this Roman academy, as suggested by his links with its members. His three Latin epigrams in praise of Leonora Baroni, the only female member of the Umoristi, have hitherto been studied in relation to the 1639 Applausi in her honour. In a new reading, Milton, it is suggested, invokes and interrogates Catholic doctrine before a Catholic audience only to view the whole through the lens of a neo-Platonic Hermeticism (by echoing the phraseology of the sixteenth-century Franciscan Hannibal Rosselli) that refreshingly transcends religious difference. Crucially, the hitherto neglected L’Idea della Veglia (Rome, 1640) includes further encomiastic verse, sonnets to, and by Leonora, and details of the conversazioni hosted by her family at the precise time of Milton’s Roman sojourns. Milton may well have been a participant. The chapter concludes in an assessment of his links with the youthful prodigy Alessandro Cherubini, and of his audience with Francesco Barberini.

Chapter 4: Milton at a Roman Opera analyses the potential impact of ‘Chi Soffre, Speri’, which he attended on 18/28 February 1639, mounted by Francesco Barberini to inaugurate the recently completed theatre of the Palazzo Barberini. A detailed analysis of the opera's libretto, music, and theatricality casts a backward glance to Milton's Comus, and a forward glance to Paradise Lost. It also assesses Milton’s musical interests at this time, as attested by his links with Doni, and his purchase of works by Monteverdi and others.

Chapter 5: Milton’s English Connections in Rome develops the work of Miller and Chaney by investigating Milton’s co-diners at the English College in Rome on 30 October 1638, and by analysing his links between David Codner (alias Matteo Selvaggio), and the family of Jane Savage, Marchioness of Winchester, lamented by Milton in 1631. It also assesses his potential relations with the Englishman Thomas Gawen, who ‘accidentally sometimes fell into the company of John Milton’ (Antony Wood).

Ex Vivo Smooth Muscle Pharmacological Effects of a Novel Bradykinin-Related Peptide, and Its Analogue, from Chinese Large Odorous Frog, Odorrana livida Skin Secretions

Bradykinin-related peptides (BRPs) are one of the most extensively studied frog secretions-derived peptide families identified from many amphibian species. The diverse primary structures of BRPs have been proven essential for providing valuable information in understanding basic mechanisms associated with drug modification. Here, we isolated, identified and characterized a dodeca-BRP (RAP-L1, T6-BK), with primary structure RAPLPPGFTPFR, from the skin secretions of Chinese large odorous frogs, Odorrana livida. This novel peptide exhibited a dose-dependent contractile property on rat bladder and rat ileum, and increased the contraction frequency on rat uterus ex vivo smooth muscle preparations; it also showed vasorelaxant activity on rat tail artery smooth muscle. In addition, the analogue RAP-L1, T6, L8-BK completely abolished these effects on selected rat smooth muscle tissues, whilst it showed inhibition effect on bradykinin-induced rat tail artery relaxation. By using canonical antagonist for bradykinin B1 or B2 type receptors, we found that RAP-L1, T6-BK -induced relaxation of the arterial smooth muscle was very likely to be modulated by B2 receptors. The analogue RAP-L1, T6, L8-BK further enhanced the bradykinin inhibitory activity only under the condition of co-administration with HOE140 on rat tail artery, suggesting a synergistic inhibition mechanism by which targeting B2 type receptors.

Consumos e estilos de vida no ensino superior: o caso dos estudantes da ULisboa-2012

A entrada no ensino superior é um momento de viragem marcante na biografia de qualquer estudante. Para além da oportunidade em obter uma aprendizagem formal altamente qualificada numa determinada área de conhecimento, o acesso ao ensino superior confronta os jovens com papeis e expectativas mais exigente enquanto estudantes, novos métodos pedagógicos, sistemas de avaliação e conteúdos programáticos, todo um conjunto de alterações que exige dos estudantes capacidade em modificar rotinas e adquirir novos hábitos de estudo. É nesta medida que a investigação sobre estudantes do ensino superior no âmbito das ciências sociais tem explorado, sobretudo, questões relacionadas às condições socioculturais subjacentes às escolhas vocacionais, aos desempenhos escolares, e aos efeitos das qualificações formais nas inserções profissionais. A viragem que os estudantes vivenciam com a transição para o ensino superior, no entanto, não acontece apenas ao nível do percurso propriamente escolar e laboral, mas ganha extensão em outras dimensões da vida, menos conhecidas de um ponto de vista científico. As instituições de ensino superior são, efectivamente, um contexto onde os estudantes entram em contacto com novas realidades culturais e sociais, susceptíveis de reconfigurar os seus círculos sociais, quadros simbólicos de referência e hábitos quotidianos. A reconfiguração que ocorre neste momento de passagem é acrescida do facto de a entrada no ensino superior ser, frequentemente, concomitante a outros processos de autonomização juvenil que possibilitam ao jovem uma margem mais alargada de acção e decisão sobre si próprio, bem como uma maior capacidade de gestão e negociação do seu tempo, práticas quotidianas, corpo e saúde, recursos materiais e redes sociais. Tais condições de autonomização acrescem quando a entrada no ensino superior exige ao estudante a deslocação permanente face à sua residência habitual, emancipando-o relativamente ao controlo mais próximo da sua família de origem. Novas práticas e hábitos de consumo podem assim tomar lugar ou sair reforçados no estilo de vida do estudante com a sua entrada no ensino superior, por via da integração em novos círculos sociais, da adopção de novos valores de referência, na procura de processos adaptativos de compensação dos níveis de tensão experienciada e/ou da ampliação da liberdade de acção.

The generating function of the generalized Fibonacci sequence

Using tools of the theory of orthogonal polynomials we obtain the generating function of the generalized Fibonacci sequence established by Petronilho for a sequence of real or complex numbers {Qn} defined by Q0 = 0, Q1 = 1, Qm = ajQm−1 + bjQm−2, m ≡ j (mod k), where k ≥ 3 is a fixed integer, and a0, a1, . . . , ak−1, b0, b1, . . . , bk−1 are 2k given real or complex numbers, with bj #0 for 0 ≤ j ≤ k−1. For this sequence some convergence proprieties are obtained.

Niveles de actividad física de niños y adolescentes durante las clases de educación física en tres colegios oficiales de Bogotá

La clase de educación física es un espacio en el cual los niños y adolescentes pueden incrementar los niveles de actividad física y alcanzar las recomendaciones emitidas por la Organización Mundial de la Salud (OMS), sin embargo, existe poca evidencia científica a nivel nacional sobre las actividades físicas que realizan los estudiantes dentro del ámbito escolar, específicamente dentro de las clases de educación física y sus relaciones con el contexto; es por esto que el objetivo de este estudio fue evaluar los niveles de actividad física de niños y adolescentes durante las clases de educación física en tres colegios oficiales de Bogotá, Colombia, por medio de la herramienta SOFIT. Estudio de diseño descriptivo y transversal realizado entre octubre de 2014 y mayo de 2015. Las observaciones se llevaron a cabo en tres colegios oficiales de la ciudad de Bogotá ubicados en las localidades de Tunjuelito y Ciudad Bolívar que aceptaron su participación en la investigación. Se obtuvo la aprobación para participar de 1361 estudiantes (682 niñas y 679 niños) de 5 a 17 años de los cuales 180 estudiantes (93 niños y 87 niñas) fueron seleccionados de manera aleatoria sistemática, siguiendo el protocolo SOFIT para observar su nivel de actividad física durante las clases de educación física. El 45,23% del tiempo de la clase de educación física los estudiantes mantuvieron un comportamiento sedentario; mientras que el 30.91% y el 23.86% del tiempo de la clase presentaron un nivel de actividad física moderada (AFM) y vigorosa (AFV) respectivamente. El nivel de actividad física moderada a vigorosa (AFMV), fue de 54,78% es decir, 35,27 minutos de la clase. Los docentes no promovieron la actividad física en un 56,47% del tiempo de la clase y se encontró que ningún docente promovió la actividad física fuera de la clase, es decir, alentando a sus estudiantes a que practicaran cualquier forma de actividad física en horas extraescolares. El contexto de la clase que más se desarrolló fue la condición física con un 35,66% del tiempo de la clase, seguido por los contextos de generalidades 24,83% y habilidades 23,84%. El contexto de la clase generalidades está asociada significativamente y de manera negativa (β=-0,32, p=0,006) con menor porcentaje de tiempo en AFM y AFV, las variables activas de SOFIT, lo que sugiere que las clases deben invertir menos tiempo en este contexto e incrementar el porcentaje de tiempo en los otros contextos como condición física y habilidades para aumentar la cantidad de minutos de AFMV en los estudiantes.

Evaluación del desempeño de pruebas diagnósticas de tuberculosis en pacientes VIH positivo en dos hospitales públicos de Bogotá

La tuberculosis TB es una de las principales causas de muerte en el mundo en individuos con infección por VIH. En Colombia esta coinfección soporta una carga importante en la población general convirtiéndose en un problema de salud pública. En estos pacientes las pruebas diagnósticas tienen sensibilidad inferior y la enfermedad evoluciona con mayor frecuencia hacia formas diseminadas y rápidamente progresivas y su diagnóstico oportuno representa un reto en Salud. El objetivo de este proyecto es evaluar el desempeño de las pruebas diagnósticas convencionales y moleculares, para la detección de TB latente y activa pacientes con VIH, en dos hospitales públicos de Bogotá. Para TB latente se evaluó la concordancia entre las pruebas QuantiFERON-TB (QTF) y Tuberculina (PPD), sugiriendo superioridad del QTF sobre la PPD. Se evaluaron tres pruebas diagnósticas por su sensibilidad y especificidad, baciloscopia (BK), GenoType®MTBDR plus (Genotype) y PCR IS6110 teniendo como estándar de oro el cultivo. Los resultados de sensibilidad (S) y especificidad (E) de cada prueba con una prevalencia del 19,4 % de TB pulmonar y extrapulmonar en los pacientes que participaron del estudio fue: BK S: 64% E: 99,1%; Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 73% E: 95,5%, de la misma forma se determinaron los valores predictivos positivos y negativos (VPP y VPN) BK: 88,9% y 94,8%, Genotype S: 77,8% E: 94,5%; PCRIS6110 S: 90% y 95,7%. Se concluyó bajo análisis de curva ROC que las pruebas muestran un rendimiento diagnóstico similar por separado en el diagnóstico de TB en pacientes con VIH, aumentando su rendimiento diagnostico cuando se combinan