Searching for novel gene functions in yeast : identification of thousands of novel molecular interactions by protein-fragment complementation assay followed by automated gene function prediction and high-throughput lipidomics

La compréhension de processus biologiques complexes requiert des approches expérimentales et informatiques sophistiquées. Les récents progrès dans le domaine des stratégies génomiques fonctionnelles mettent dorénavant à notre disposition de puissants outils de collecte de données sur l’interconnectivité des gènes, des protéines et des petites molécules, dans le but d’étudier les principes organisationnels de leurs réseaux cellulaires. L’intégration de ces connaissances au sein d’un cadre de référence en biologie systémique permettrait la prédiction de nouvelles fonctions de gènes qui demeurent non caractérisées à ce jour. Afin de réaliser de telles prédictions à l’échelle génomique chez la levure Saccharomyces cerevisiae, nous avons développé une stratégie innovatrice qui combine le criblage interactomique à haut débit des interactions protéines-protéines, la prédiction de la fonction des gènes in silico ainsi que la validation de ces prédictions avec la lipidomique à haut débit. D’abord, nous avons exécuté un dépistage à grande échelle des interactions protéines-protéines à l’aide de la complémentation de fragments protéiques. Cette méthode a permis de déceler des interactions in vivo entre les protéines exprimées par leurs promoteurs naturels. De plus, aucun biais lié aux interactions des membranes n’a pu être mis en évidence avec cette méthode, comparativement aux autres techniques existantes qui décèlent les interactions protéines-protéines. Conséquemment, nous avons découvert plusieurs nouvelles interactions et nous avons augmenté la couverture d’un interactome d’homéostasie lipidique dont la compréhension demeure encore incomplète à ce jour. Par la suite, nous avons appliqué un algorithme d’apprentissage afin d’identifier huit gènes non caractérisés ayant un rôle potentiel dans le métabolisme des lipides. Finalement, nous avons étudié si ces gènes et un groupe de régulateurs transcriptionnels distincts, non préalablement impliqués avec les lipides, avaient un rôle dans l’homéostasie des lipides. Dans ce but, nous avons analysé les lipidomes des délétions mutantes de gènes sélectionnés. Afin d’examiner une grande quantité de souches, nous avons développé une plateforme à haut débit pour le criblage lipidomique à contenu élevé des bibliothèques de levures mutantes. Cette plateforme consiste en la spectrométrie de masse à haute resolution Orbitrap et en un cadre de traitement des données dédié et supportant le phénotypage des lipides de centaines de mutations de Saccharomyces cerevisiae. Les méthodes expérimentales en lipidomiques ont confirmé les prédictions fonctionnelles en démontrant certaines différences au sein des phénotypes métaboliques lipidiques des délétions mutantes ayant une absence des gènes YBR141C et YJR015W, connus pour leur implication dans le métabolisme des lipides. Une altération du phénotype lipidique a également été observé pour une délétion mutante du facteur de transcription KAR4 qui n’avait pas été auparavant lié au métabolisme lipidique. Tous ces résultats démontrent qu’un processus qui intègre l’acquisition de nouvelles interactions moléculaires, la prédiction informatique des fonctions des gènes et une plateforme lipidomique innovatrice à haut débit , constitue un ajout important aux méthodologies existantes en biologie systémique. Les développements en méthodologies génomiques fonctionnelles et en technologies lipidomiques fournissent donc de nouveaux moyens pour étudier les réseaux biologiques des eucaryotes supérieurs, incluant les mammifères. Par conséquent, le stratégie présenté ici détient un potentiel d’application au sein d’organismes plus complexes.

A study of the large-scale structure of the wind of WR 134

Diverses méthodes ont été utilisées pour étudier les étoiles Wolf-Rayet (WR) dans le but de comprendre les phénomènes physiques variés qui prennent place dans leur vent dense. Pour étudier la variabilité qui n'est pas strictement périodique et ayant des caractéristiques différentes d'une époque à l'autre, il faut observer pendant des périodes de temps suffisamment longues en adopter un échantillonnage temporel élevé pour être en mesure d'identifier les phénomènes physiques sous-jacents. À l'été 2013, des astronomes professionnels et amateurs du monde entier ont contribué à une campagne d'observation de 4 mois, principalement en spectroscopie, mais aussi en photométrie, polarimétrie et en interférométrie, pour observer les 3 premières étoiles Wolf-Rayet découvertes: WR 134 (WN6b), WR 135 (WC8) et WR 137 (WC7pd + O9). Chacune de ces étoiles est intéressante à sa manière, chacune présentant une variété différente de structures dans son vent. Les données spectroscopiques de cette campagne ont été réduites et analysées pour l'étoile présumée simple WR 134 pour mieux comprendre le comportement de sa variabilité périodique à long terme dans le cadre d'une étude des régions d'interactions en corotation (CIRs) qui se retrouvent dans son vent. Les résultats de cette étude sont présentés dans ce mémoire.

Sexual and relationship intimacy among women with provoked vestibulodynia and their partners : associations with sexual satisfaction, sexual function, and pain self-efficacy

Introduction Provoked vestibulodynia (PVD) is the most frequent subtype of vulvodynia. Women report negative consequences of PVD on their sexual and romantic relationships. Researchers have recently highlighted the importance of examining interpersonal factors such as intimacy, and of including both women and their partners in study designs. Aim The aim of this study was to investigate sexual and relationship intimacy as defined by the Interpersonal Process Model of Intimacy and their associations with sexual satisfaction, sexual function, pain self-efficacy, and pain intensity among women with PVD and their partners. Methods Ninety-one heterosexual women (M age = 27.38, SD = 6.04) diagnosed with PVD and their partners (M age = 29.37, SD = 7.79) completed measures of sexual and relationship intimacy, sexual satisfaction, sexual function, pain self-efficacy, and pain intensity. Main Outcome Measures Dependent measures were the (i) Global Measure of Sexual Satisfaction Scale; (ii) Female Sexual Function Index; (iii) Painful Intercourse Self-Efficacy Scale; and (iv) visual analog scale of pain intensity during intercourse. Results After controlling for women's age, women's greater sexual intimacy (β = 0.49, P < 0.001) was associated with women's greater sexual satisfaction and higher pain self-efficacy (β = 0.39, P = 0.001), beyond the effects of partners’ sexual intimacy. Also, women's greater sexual intimacy (β = 0.24, P = 0.05) and women's greater relationship intimacy (β = 0.54, P = 0.003) were associated with greater women's sexual function, beyond the effects of partners’ sexual and relationship intimacy. Conclusions Women's self-reported sexual and relationship intimacy in the couple relationship may promote higher sexual satisfaction, sexual function, and pain self-efficacy, as well as possibly foster greater sexual well-being among women with PVD. The authors discuss implications for the inclusion of emotional and interpersonal aspects of the couple's dynamic in clinical interventions and future research in PVD.

Women with provoked vestibulodynia experience clinically significant reductions in pain regardless of treatment : results from a 2-year follow up study.

Introduction Provoked vestibulodynia (PVD) is a prevalent genital pain syndrome that has been assumed to be chronic, with little spontaneous remission. Despite this assumption, there is a dearth of empirical evidence regarding the progression of PVD in a natural setting. Although many treatments are available, there is no single treatment that has demonstrated efficacy above others. Aims The aims of this secondary analysis of a prospective study were to (i) assess changes over a 2-year period in pain, depressive symptoms, and sexual outcomes in women with PVD; and (ii) examine changes based on treatment(s) type. Methods Participants completed questionnaire packages at Time 1 and a follow-up package 2 years later. Main Outcome Measures Visual analog scale of genital pain, Global Measure of Sexual Satisfaction, Female Sexual Function Index, Beck Depression Inventory, Dyadic Adjustment Scale, and sexual intercourse attempts over the past month. Results Two hundred thirty-nine women with PVD completed both time one and two questionnaires. For the sample as a whole, there was significant improvement over 2 years on pain ratings, sexual satisfaction, sexual function, and depressive symptoms. The most commonly received treatments were physical therapy, sex/psychotherapy, and medical treatment, although 41.0% did not undergo any treatment. Women receiving no treatment also improved significantly on pain ratings. No single treatment type predicted better outcome for any variable except depressive symptoms, in which women who underwent surgery were more likely to improve. Discussion These results suggest that PVD may significantly reduce in severity over time. Participants demonstrated clinically significant pain improvement, even when they did not receive treatment. Furthermore, the only single treatment type predicting better outcomes was surgery, and only for depressive symptoms, accounting for only 2.3% of the variance. These data do not demonstrate the superiority of any one treatment and underscore the need to have control groups in PVD treatment trials, otherwise improvements may simply be the result of natural progression.

Spatial and Temporal Variability of some Meteorological Parameters over Tropical Indian Ocean

The objective of the present study is to understand the spatial and temporal variability of sea surface temperature(SST), precipitable water, zonal and meridional components of wind stress over the tropical Indian Ocean to understand the different scales of variability of these features of Indian Ocean. Empirical Orthogonal Function (EOF) and wavelet analysis techniques are utilized to understand the standing oscillations and multi scale oscillations respectively. The study has been carried out over Indian Ocean and South Indian Ocean. For the present study, NCEP/NCAR(National Center for Environmental Prediction National Center for Atmospheric Research) reanalyzed daily fields of sea surface temperature, zonal and meridional surface wind components and precipitable water amount during 1960-1998 are used. The principle of EOF analysis and the methodology used for the analysis of spatial and temporal variance modes.

ARMA modeling of time series based on rational approximation of spectral density function

This study is concerned with Autoregressive Moving Average (ARMA) models of time series. ARMA models form a subclass of the class of general linear models which represents stationary time series, a phenomenon encountered most often in practice by engineers, scientists and economists. It is always desirable to employ models which use parameters parsimoniously. Parsimony will be achieved by ARMA models because it has only finite number of parameters. Even though the discussion is primarily concerned with stationary time series, later we will take up the case of homogeneous non stationary time series which can be transformed to stationary time series. Time series models, obtained with the help of the present and past data is used for forecasting future values. Physical science as well as social science take benefits of forecasting models. The role of forecasting cuts across all fields of management-—finance, marketing, production, business economics, as also in signal process, communication engineering, chemical processes, electronics etc. This high applicability of time series is the motivation to this study.

Analysis discrete function theory

There is a recent trend to describe physical phenomena without the use of infinitesimals or infinites. This has been accomplished replacing differential calculus by the finite difference theory. Discrete function theory was first introduced in l94l. This theory is concerned with a study of functions defined on a discrete set of points in the complex plane. The theory was extensively developed for functions defined on a Gaussian lattice. In 1972 a very suitable lattice H: {Ci qmxO,I qnyo), X0) 0, X3) 0, O < q < l, m, n 5 Z} was found and discrete analytic function theory was developed. Very recently some work has been done in discrete monodiffric function theory for functions defined on H. The theory of pseudoanalytic functions is a generalisation of the theory of analytic functions. When the generator becomes the identity, ie., (l, i) the theory of pseudoanalytic functions reduces to the theory of analytic functions. Theugh the theory of pseudoanalytic functions plays an important role in analysis, no discrete theory is available in literature. This thesis is an attempt in that direction. A discrete pseudoanalytic theory is derived for functions defined on H.

Speech sample estimation from composite zerocrossings and encoding via adaptive switching of transforms

This thesis investigates the potential use of zerocrossing information for speech sample estimation. It provides 21 new method tn) estimate speech samples using composite zerocrossings. A simple linear interpolation technique is developed for this purpose. By using this method the A/D converter can be avoided in a speech coder. The newly proposed zerocrossing sampling theory is supported with results of computer simulations using real speech data. The thesis also presents two methods for voiced/ unvoiced classification. One of these methods is based on a distance measure which is a function of short time zerocrossing rate and short time energy of the signal. The other one is based on the attractor dimension and entropy of the signal. Among these two methods the first one is simple and reguires only very few computations compared to the other. This method is used imtea later chapter to design an enhanced Adaptive Transform Coder. The later part of the thesis addresses a few problems in Adaptive Transform Coding and presents an improved ATC. Transform coefficient with maximum amplitude is considered as ‘side information’. This. enables more accurate tfiiz assignment enui step—size computation. A new bit reassignment scheme is also introduced in this work. Finally, sum ATC which applies switching between luiscrete Cosine Transform and Discrete Walsh-Hadamard Transform for voiced and unvoiced speech segments respectively is presented. Simulation results are provided to show the improved performance of the coder

A study of industrial co-operatives in kerala with special reference to modern small scale sector

The report of the Steering Committee of the Kerala State Planning Board for the preparation of the VIII five Year Plan on Industry and Hiningzslisted several factors inhibiting and promoting growth of small industrial units. Kerala's educated manpower, the native intelligence of the Keralites best suited for taking up logic—based professions and availability of a Hell—developed and broad~based physical infrastructure particularly in the transport and communications sectors, are a few of the positive factors identified. On the negative side, may be mentioned high wage rates, preference on the part of the educated for white collar Jobs, lack of entrepreneurship, paucity of essential resources for industrial use, high density of population and the distance factor which places Kerala away from the major domestic markets. In this context, it would appear that the industrial co-operative movement could possibly play a vital role in accelerating-the momentum of small industrial development of Kerala which has a Health of highly educated and skilled manpower. However, in spite of the encouragement extended by the Government, the movement does not seem to have.been picking up in the modern small scale sector. The present study is an attempt to analyse the factors that have affected the performance of the industrial co—operatives in the small scale industrial sector of Kerala.

Squeezed thermal phonons precurse nonthermal melting of silicon as a function of fluence

A femtosecond-laser pulse can induce ultrafast nonthermal melting of various materials along pathways that are inaccessible under thermodynamic conditions, but it is not known whether there is any structural modification at fluences just below the melting threshold. Here, we show for silicon that in this regime the room-temperature phonons become thermally squeezed, which is a process that has not been reported before in this material. We find that the origin of this effect is the sudden femtosecond-laser-induced softening of interatomic bonds, which can also be described in terms of a modification of the potential energy surface. We further find in ab initio molecular-dynamics simulations on laser-excited potential energy surfaces that the atoms move in the same directions during the first stages of nonthermal melting and thermal phonon squeezing. Our results demonstrate how femtosecond-laser-induced coherent fluctuations precurse complete atomic disordering as a function of fluence. The common underlying bond-softening mechanism indicates that this relation between thermal squeezing and nonthermal melting is not material specific.

A Log-linear model of grain size influence on the geochemistry of sediments

Sediment composition is mainly controlled by the nature of the source rock(s), and chemical (weathering) and physical processes (mechanical crushing, abrasion, hydrodynamic sorting) during alteration and transport. Although the factors controlling these processes are conceptually well understood, detailed quantification of compositional changes induced by a single process are rare, as are examples where the effects of several processes can be distinguished. The present study was designed to characterize the role of mechanical crushing and sorting in the absence of chemical weathering. Twenty sediment samples were taken from Alpine glaciers that erode almost pure granitoid lithologies. For each sample, 11 grain-size fractions from granules to clay (ø grades <-1 to >9) were separated, and each fraction was analysed for its chemical composition. The presence of clear steps in the box-plots of all parts (in adequate ilr and clr scales) against ø is assumed to be explained by typical crystal size ranges for the relevant mineral phases. These scatter plots and the biplot suggest a splitting of the full grain size range into three groups: coarser than ø=4 (comparatively rich in SiO2, Na2O, K2O, Al2O3, and dominated by “felsic” minerals like quartz and feldspar), finer than ø=8 (comparatively rich in TiO2, MnO, MgO, Fe2O3, mostly related to “mafic” sheet silicates like biotite and chlorite), and intermediate grains sizes (4≤ø <8; comparatively rich in P2O5 and CaO, related to apatite, some feldspar). To further test the absence of chemical weathering, the observed compositions were regressed against three explanatory variables: a trend on grain size in ø scale, a step function for ø≥4, and another for ø≥8. The original hypothesis was that the trend could be identified with weathering effects, whereas each step function would highlight those minerals with biggest characteristic size at its lower end. Results suggest that this assumption is reasonable for the step function, but that besides weathering some other factors (different mechanical behavior of minerals) have also an important contribution to the trend. Key words: sediment, geochemistry, grain size, regression, step function

Review of key physical processes in shallow waters

A presentation for 2 Units in SOES 6018 and SOES 6060, on physical processes in shallow water. This module aims to ensure that MSc Oceanography, MSc Marine Science, Policy & Law and MSc Marine Resource Management students are equipped with the skills they need to function as professional marine scientists, in addition to / in conjuction with the skills training in other MSc modules. The module covers training in fieldwork techniques, communication & research skills, IT & data analysis and professional development.

Asociación entre relaciones románticas y la calidad de sueño percibida por jóvenes universitarios

Introducción: Uno de los aspectos con mayor variación durante la adolescencia es el sueño, el cual se ve afectado por factores biológicos así como por los estados afectivos y emocionales. En esta etapa, los individuos establecen sus primeras relaciones sentimentales románticas, vínculos esenciales para la maduración de las relaciones sociales y psicosexuales. Este trabajo busca determinar la asociación existente entre las relaciones sentimentales románticas y sus características, con la calidad sueño percibida por los jóvenes. Metodología: Estudio realizado en una población de 1794 estudiantes de ciencias de la salud entre los 18 y 25 años de edad en Bogotá, Colombia, entre 2012 y 2013. Se obtuvo una muestra probabilística con asignación proporcional de 443 sujetos, estratificada por programa académico y sexo. Utilizando dos cuestionarios de auto reporte se exploraron las características de las relaciones sentimentales y la calidad de sueño percibida. Resultados: El 64% (IC 95%: 59,4-68,9%) de la población estudiada se encontró en una relación sentimental romántica. Estos sujetos tuvieron latencias de sueño prolongadas con menor frecuencia que quienes no tenían en una relación (p <0,05). La calidad de sueño percibida se asoció al nivel de satisfacción que tuvieron los sujetos en su relación, así como la atracción por su pareja. Rasgos obsesivos, ansiosos, temerosos y evitativos en la relación disminuyeron la calidad de sueño percibida. Conclusión: Las relaciones sentimentales románticas y sus características se asocian con la calidad de sueño percibida por los individuos. Se requieren estudios que determinen causalidad en esta asociación y definan potenciales estrategias de intervención al respecto.

Tempus Post Mortem?* Adaptação portuguesa da transcendental-future time perspective scale (TFTPS)

Integrado no conceito mais geral da perspetiva temporal, o futuro transcendental tem sido conceptualizado como uma dimensão que abrange as crenças sobre o futuro a partir da morte imaginada do corpo físico até ao infinito. A transcendental-future time perspective scale (TFTPS) é uma escala unidimensional composta por 10 itens que avalia as cognições relacionadas com este espaço temporal. O objetivo deste estudo é apresentar a adaptação à língua e cultura portuguesa desta escala, assim como a sua estrutura fatorial e características psicométricas numa amostra de 346 participantes com idades compreendidas entre os 17 e os 54 anos (M = 19.87, DP = 4.27). Os resultados encontrados através da análise fatorial exploratória validaram a unidimensionalidade da escala (65.94 % de variância total explicada, α = 0.87).