L'analyse des propriétés statistiques de la distribution de la matière dans le cosmos (Grandes Structures, LSS or Large Scale Structure) est l'une des principales sondes cosmologiques qui permettent l'étude du modèle standard cosmologique, en particulier les paramètres caractérisant la matière noire et l'énergie noire. Les Oscillations Acoustiques Baryoniques (BAO's) sont l'une des mesures qui peuvent être extraites de l'étude de la distribution de matière à grande échelle (LSS).L'observation de la distribution cosmique de la matière à partir de l'émission à 21 cm de l'hydrogène atomique neutre (HI) est une nouvelle méthode, complémentaire des relevés optiques pour cartographier la distribution de la matière dans le cosmos. La méthode de cartographie d'intensité (Intensity Mapping) a été proposée depuis moins d'une dizaine d'années comme une méthode efficace pour cartographier en trois dimensions l'émission radio à 21 cm. Elle n'implique en particulier pas la détection des objets individuels (galaxies), et peut donc être effectué avec des instruments plus modestes en taille que ceux comme SKA ou FAST qui sont conçus pour détecter les galaxies à 21 cm à des distances cosmologiques. Des interféromètres radio utilisant un ensemble de réflecteurs cylindriques ou paraboliques fixes, observant le ciel en mode transit sont adaptés à la cartographie d'intensité. Le mode d'observation spécifique de ce type de radio télescope en cartographie d'intensité est étudié dans le cadre de ce travail de thèse. On montre en particulier qu'une méthode spécifique de reconstruction des cartes du ciel à partir des visibilités peut être appliquée aux observations de ces interféromètres fonctionnant en mode transit. Cette méthode correspond à la décomposition en modes m des harmoniques sphériques et est très performante pour la reconstruction de grandes zones du ciel observées en mode transit. Un code de reconstruction fondé sur ce principe a été développé, ainsi que différents critères de comparaison des performances instrumentales, comme le lobe d'antenne synthétisé, le spectre de bruit sur les cartes reconstruites et la réponse globale de l'instrument dans le plan (l,m) des harmoniques sphériques. La méthode a été appliquée à différentes configurations des interféromètres composés de réflecteurs paraboliques ou cylindriques dans le cadre des projets PAON-4 et Tianlai. Outre l'optimisation des configurations des interféromètres Tianlai et PAON-4, le travail présenté inclut une première application de la méthode aux données PAON-4. / The analysis of the statistical properties of the distribution of matter in the cosmos (LSS or Large Scale Structure) is one of the main cosmological probes that allow the study of the cosmological standard model, in particular the parameters characterizing dark matter and dark energy. Baryonic Acoustic Oscillations (BAO's) are one of the measurements that can be extracted from the study of matter distribution in large-scale structure (LSS).The observation of the cosmic distribution of the matter from neutral atomic hydrogen (HI) 21 cm emission is a new method, complementary to the optical observation to map the distribution of matter in the cosmos. In the last decade, the Intensity Mapping method has been proposed as an effective method for mapping the 21cm radio emission in three dimensions. In particular, it does not require the detection of individual objects (galaxies), and can therefore be performed with instruments smaller in size than those such as SKA or FAST, which are designed to detect 21 cm galaxies at cosmological distances. A radio interferometer using a set of fixed cylindrical or parabolic reflectors observing the sky in transit mode are suitable instruments for intensity mapping surveys. The specific observational mode from this type of radio telescope by intensity mapping is studied in the context of this thesis. We show in particular that a specific sky maps reconstruction method from the visibilities can be applied to the observations of these interferometers operating in transit mode. This method corresponds to the m-modes decomposition of the spherical harmonics and is very efficient for the reconstruction of large sky areas observed in transit mode. A reconstruction code based on this principle has been developed, as well as different criteria for the comparison of instrumental performances, such as the synthesized antenna lobe, the noise spectrum of the reconstructed maps and the overall instrument response in the spherical harmonics (l,m) plane. The method has then been applied to different configurations of interferometers composed of parabolic or cylindrical reflectors in the PAON-4 and Tianlai projects. In addition to optimizing the Tianlai and PAON-4 interferometer configurations, the work presented here includes a first application of the method to the PAON-4 data.

The current dissertation provides an examination of health information technology (HIT) by analyzing big datasets. It contains two separate essays focused on: (1) the evolving intellectual structure of the healthcare informatics (HI) and healthcare IT (HIT) scholarly communities, and (2) the impact of social support exchange embedded in social interactions on health promotion outcomes associated with online health community use. Overall, this dissertation extends current theories by applying a unique combination of methods (natural language processing, machine learning, social network analysis, and structural equation modeling etc.) to the analyses of primary datasets. The goal of the first study is to obtain a full understanding of the underlying dynamics of the intellectual structures of HI and its sub-discipline HIT. Using multiple statistical methods including citation and co-citation analysis, social network analysis (SNA), and latent semantic analysis (LSA), this essay shows how HIT research has emerged in IS journals and distinguished itself from the larger HI context. The research themes, intellectual leadership, cohesion of these themes and networks of researchers, and journal presence revealed in our longitudinal intellectual structure analyses foretell how, in particular, these HI and HIT fields have evolved to date and also how they could evolve in the future. Our findings identify which research streams are central (versus peripheral) and which are cohesive (as opposed to disparate). Suggestions for vibrant areas of future research emerge from our analysis. The second part of the dissertation focuses on comprehensively understanding the effect of social support exchange in online health communities on individual members’ health promotion outcomes. This study examines the effectiveness of online consumer-to-consumer social support exchange on health promotion outcomes via analyses of big health data. Based on previous research, we propose a conceptual framework which integrates social capital theory and social support theory in the context of online health communities and test it through a quantitative field study and multiple analyses of a big online health community dataset. Specifically, natural language processing and machine learning techniques are utilized to automate content analysis of digital trace data. This research not only extends current theories of social support exchange in online health communities, but also sheds light on the design and management of such communities.

No description available.

A lesão hipóxico-isquêmica perinatal (HI) é uma das principais causas de mortalidade aguda e morbidade neurológica crônica em lactentes e crianças. Os mecanismos de lesão podem ser classificados em fase primária, latente, secundária e terciária. A inflamação aguda desencadeia a expressão de uma série de genes pró-inflamatórios, que induzem a síntese de fatores de transcrição e de mediadores inflamatórios. Uma posível via de sinalização alterada que pode ter uma importância fundamental na HI depende dos astrócitos e envolve a uma subunidade de uma proteína ligante de cálcio, chamada S100b. Sua inibição parece ter efeito neuroprotetor em modelos de lesão ao sistema nervoso central. Este trabalho teve por objetivo avaliar os efeitos neuroprotetores do ácido arúndico (um inibidor da síntese astrocítica de S100b) administrado pré e pós hipóxia sobre os parâmetros comportamentais, morfológicos e bioquímicos no modelo de hipóxia-isquemia neonatal em ratos Wistar. No 7º dia de vida pós-natal os animais foram submetidos à combinação da oclusão unilateral da artéria carótida direita e exposição a uma atmosfera hipóxica (8% de O2) por 60 minutos. Foram aplicadas injeções intraperitoniais de salina para os grupos Sham e HI+Salina (HIS) e de ácido arúndico nos grupos HI+AA0,1mg/kg pré-hipóxia (HIAA0,1pré), HI+AA 1mg/kg pré-hipóxia (HIAA1 pré), HI+AA10mg/kg pré-hipóxia (HIAA10pré) e HI+AA10 mg/kg pré e pós-hipóxia (HIAA10pré e pós). Os grupos pré receberam ácido arúndico imediatamente antes da hipóxia e o grupo pós, nos intervalos de 1, 24 e 48 horas após a cirurgia. Os resultados demonstraram que o ácido arúndico foi efetivo na dose de 10 mg/kg aplicados pré e pós-hipóxia, sendo capaz de reduzir a lesão tecidual no hipocampo ipsilateral à oclusão da carótida, também promoveu a sobrevivência astrocitária no hipocampo, reduziu a liberação de S100b no líquor, manteve a expressão dos níveis dos transportadores de glutamato (GLT-1 e GLAST) e da glutamina sintetase, contudo não foi capaz de melhorar os déficits cognitivos induzidos pela HI. / Perinatal hypoxic-ischemic injury (HI) is one of the main causes of acute mortality and chronic neurological morbidity in infants and children. Injury mechanisms can be classified as primary, latent, secondary and tertiary. Acute inflammation triggers the expression of a number of proinflammatory genes, which induce the synthesis of transcription factors and inflammatory mediators. One possible signaling pathway altered that may have fundamental importance in HI depends on astrocytes and involves a subunit of a calcium binding protein, called S100b. Its inhibition may have neuroprotective effects on central nervous system injury models. This study aimed to evaluate the neuroprotective effects of arundic acid (an S100b astrocytic synthesis inhibitor) when administered in the pre and post hypoxia periods on behavioral, morphological and biochemical parameters in the neonatal hypoxia-ischemia model in Wistar rats. On the 7th day postnatal life the animals were submitted to a combination of unilateral occlusion of the right carotid artery and exposure to a hypoxic atmosphere (8% O 2) for 60 minutes. Intraperitoneal saline injections were used for the groups Sham and HI + Saline (HIS) and of arundic acid in the groups HI+AA0,1mg/kg pre-hypoxia (HIAA0,1pre), HI+AA 1mg/kg pre-hypoxia (HIAA1pre), HI+AA10mg/kg pre-hypoxia (HIAA10pre) and HI+AA10 mg/kg pre and post-hypoxia (HIAA10pre and post). Pre groups received arundic acid immediately prior to hypoxia and the Post group at intervals of 1, 24 and 48 hours after surgery. The results demonstrated that the arundic acid was effective at a dose of 10 mg/kg applied before and after hypoxia, being able to reduce tissue damage in the ipsilateral hippocampus to carotid occlusion, also promoted astrocytic survival in the hippocampus, reduced extracellular release of S100b in liquor, promoted maintenance of expression of glutamate transporter levels (GLT-1 and GLAST) and glutamine synthetase, but was not able to improve HI-induced cognitive deficits.

Senescent cells interact with the surrounding microenvironment achieving both pro- oncogenic and tumour-suppressive outcomes. In addition to autocrine and paracrine signalling mediated by factors of the senescence-associated secretory phenotype (SASP), we have recently identified that NOTCH1 can drive a unique form of senescence in adjacent cells via juxtacrine signalling. Here, we show that NOTCH1 signalling confers a dramatic impact on chromatin structure during senescence. RAS-induced senescent (RIS) fibroblasts often develop chromatin structures called senescence-associated heterochromatic foci (SAHF). We find that NOTCH1 inhibits SAHF formation at least partially through transcriptional repression of a critical structural component, high-mobility group A (HMGA). Using ATAC-sequencing (assay for transposase accessible chromatin) we demonstrate that nucleosome positioning is substantially altered in RIS and that this re-distribution is also antagonised by NOTCH1, resulting in a distinct chromatin landscape. Importantly, normal or cancer cells that express the NOTCH ligand jagged-1 can drive similar chromatin structural changes in adjacent cells in a cell-cell contact dependent manner. In addition, using a highly optimised chromatin immunoprecipitation (ChIP-seq) protocol and the proximity ligation assay ‘Hi-C’, we demonstrate that HMGA proteins are directly involved in the formation of long-range interactions in RIS cells that may underpin SAHF formation. These ChIP-seq data have also allowed us to identify a unique HMGA1 binding profile, potentially suggesting a novel role for HMGA1 in gene regulation. Together, our data indicate that NOTCH signalling, both cell-autonomously and non-cell-autonomously, can repress HMGA1, a multi-faceted protein that regulates nucleosome positioning (1D structure), SAHF formation (3D structure) and potentially mRNA abundance.

This thesis compares four relevance feedback methods. The Rocchio and Ide dec-hi algorithms for the vector space model and the binary independence model and Okapi BM25 within the probabilistic framework. This is done in a custom-made Information Retrieval system utilizing a collection containing 131 896 LA-Times articles which is part of the TREC ad-hoc collection. The methods are compared on two grounds, using only the relevance information from the 20 highest ranked documents from an initial search and also by using all available relevance information. Although a significant effect of choice of method could be found on the first ground, post-hoc analysis could not determine any statistically significant differences between the methods where Rocchio, Ide dec-hi and Okapi BM25 performed equivalent. All methods except the binary independence model performed significantly better than using no relevance feedback. It was also revealed that although the binary independence model performed far worse on average than the other methods it did outperform them on nearly 20 % of the topics. Further analysis argued that this depends on the lack of query expansion in the binary independence model which is advantageous for some topics although has a negative effect on retrieval efficiency in general. On the second ground Okapi BM25 performed significantly better than the other methods with the binary independence model once again being the worst performer. It was argued that the other methods have problems scaling to large amounts of relevance information where Okapi BM25 has no such issues. / Uppsatsnivå: D

Submitted by Edisangela Bastos (edisangela@ufpa.br) on 2013-03-19T18:17:51Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_ProjetoMonopoloAplicacoes.pdf: 2647457 bytes, checksum: d94a170ab9c2d67aaf91916d9df3e77c (MD5) / Approved for entry into archive by Ana Rosa Silva(arosa@ufpa.br) on 2013-03-27T16:59:01Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_ProjetoMonopoloAplicacoes.pdf: 2647457 bytes, checksum: d94a170ab9c2d67aaf91916d9df3e77c (MD5) / Made available in DSpace on 2013-03-27T16:59:01Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_ProjetoMonopoloAplicacoes.pdf: 2647457 bytes, checksum: d94a170ab9c2d67aaf91916d9df3e77c (MD5) Previous issue date: 2013 / A presente pesquisa trata o projeto e análise de uma antena monopolo planar com geometria modificada visando sua utilização para recepção do sinal de TV digital operante no Brasil na faixa de 470 MHz a 806 MHz. Faixa essa contida no espectro de UHF – Ultra High Frequency (300 MHz a 3 GHz). Para desenvolvimento desse trabalho foi tomado como referência à antena denominada “The Hi Monopole”. Que originalmente foi apresentada para operar em sistemas UWB (Ultra Wide Band) em 3,1 a 10,6 GHz. Para o desenvolvimento do trabalho proposto, diferentes técnicas de adequação da antena podem ser utilizadas para operação em banda larga, tais como: modificação na estrutura da antena, carregamento resistivo, chaveamento, utilização de elementos parasitas e estruturas de casamento. O projeto de antenas banda larga pode ser realizado a partir de três abordagens diferentes: domínio do tempo, domínio da frequência e método de expansão por singularidades. O método no domínio da frequência foi empregado neste trabalho para o projeto da antena proposta, algumas das técnicas supracitadas foram analisadas almejando o aumento da largura de banda, sendo confeccionado um protótipo da antena para validar os conceitos empregados. A antena foi então projetada para a faixa de 470 MHz a 890 MHz. O protótipo construído para essa mesma faixa apresentou bons resultados, o que valida à técnica empregada. Aspectos positivos e negativos do uso desta técnica são discutidos ao longo do trabalho. O programa computacional comercial CST® MICROWAVE STUDIO, baseado na Técnica da Integração Finita (FIT), foi usado para simulações no domínio da frequência. / This research deals with the design and analysis of a planar monopole antenna with modified geometry aiming its use for signal reception of digital TV in Brazil working in the of 470 MHz to 806 MHz. Track this contained in the spectrum of UHF-Ultra High Frequency (300 MHz to 3 GHz). To develop this work was taken as reference the antenna called "The Hi Monopole". What originally was presented to operate in UWB (Ultra Wide Band) at 3.1 to 10.6 GHz. For the development of the proposed work, different techniques of adjustment of the antenna can be used for broadband operation, such as: changes in the structure of antenna, resistive loading, switching, using of parasitic elements and matching structures. The design of broadband antennas can be made from three different approaches: time domain, frequency domain and expansion for singularities method. The frequency domain method was employed in this work to the antenna design proposed, some of the techniques mentioned above were analyzed aiming to increase bandwidth, and made a prototype of the antenna to validate the concepts employed. The antenna was designed for the range of 470 MHz to 890 MHz. the prototype built for this same range presented good results, which validates the technique employed. Positive and negative aspects of use of this technique are discussed throughout the work. The commercial computer program CST® MICROWAVE STUDIO, based on the Finite Integration Technique (FIT) was used for simulations in frequency domain.

Investigating the arrangement of the packed DNA inside the nucleus has revealed the essential role of genome organisation in controlling genome function. Furthermore, genome architecture is highly dynamic and significant chromatin re-organisation occurs in response to environmental changes. However, the mechanisms that drive the 3D organisation of the genome remain largely unknown. To understand the effect of biophysical properties of chromatin on the dynamics and structure of chromosomes, I developed a 3D computational model of the nucleus of the yeast S. cerevisiae during interphase. In the model, each chromosome was a hetero-polymer informed by our bioinformatics analysis for heterogeneous occupancy of chromatin-associated proteins across the genome. Two different conditions were modelled, normal growth (25°C) and heat shock (37°C), where a concerted redistribution of proteins was observed upon transition from one temperature to the other. Movement of chromatin segments was based on Langevin dynamics and each segment had a mobility according to their protein occupancy and the expression level of their corresponding genes. The model provides a significantly improved match with quantitative microscopy measurements of telomere positions, the distributions of 3D distances between pairs of different loci, and the mean squared displacement of a labelled locus. The quantified contacts between chromosomal segments were similar to the observed Hi-C data. At both 25°C and 37°C conditions, the segments that were highly occupied by proteins had high number of interactions with each other, and the highly transcribed genes had lower contacts with other segments. In addition, similar to the experimental observations, heat-shock genes were found to be located closer to the nuclear periphery upon activation in the simulations. It was also shown that the determined distribution of proteins along the genome is crucial to achieve the correct genome organisation. Hence, the heterogeneous binding of proteins, which results in differential mobility of chromatin segments, leads to 3D self-organisation.

The process of generating the vast diversity of immunoglobulin receptors and secreted antibodies begins with the recombination of the joining (JH), diversity (DH) and variable (VH) genes in the immunoglobulin heavy chain locus. The ability to produce antibodies is restricted to the B cell lineage and is tightly regulated, starting with the temporal separation of the recombination process, in which DH-JH precedes VH-DHJH recombination. Successful recombination of both heavy and light chain loci results in the expression of an antigen receptor on the cell surface. Subsequent selection stages remove non‑functional and autoreactivity receptors from the final pool of antigen responding B cells that ultimately give rise to antibody secreting plasma cells. Understanding the complexity of the recombination processes and the diversity of the resulting antibody repertoire has been a major focus of academic and industrial research alike. Therapeutic monoclonal antibodies have seen many successful applications within the clinic and they constitute a billion-dollar industry. However, limitations therein have resulted in the emergence of antibody engineering approaches and the use of natural sources of alternative heavy chain only antibodies (HCAbs/nanobodies). The biotechnology company Crescendo Biologics has taken the highly desired characteristics of HCAbs a step further with the creation of a mouse platform capable of producing fully humanized HCAbs. The Crescendo platform presents a unique opportunity to expand our understanding of how mouse B cell development functions by exploiting the features of heavy chain only antibody production. Furthermore, the platform enables the expansion of our limited knowledge of the epigenetic mechanisms involved in the recombination of the human immunoglobulin heavy chain locus. Using flow cytometry, with dimensionality reduction analysis approaches, I investigated B cell development in the context of HCAbs. These studies revealed a previously uncharacterised developmentally intermediate B cell population. Due to ethical and availability limitations to studies of human bone marrow, the primary pre-selection human B cell repertoire has not been studied in detail. The isolation of several B cell developmental stages and the use of our novel DNA-based high-throughput unbiased repertoire quantification technique, VDJ-seq, allowed me to study recombination of the human IGH locus sequence and observe HCAb repertoire selection within the mouse environment. The adaptation of next generation sequencing techniques to antigen receptor repertoire quantification has provided an unprecedented insight into repertoire diversity and the alterations it undergoes during infection or ageing. Our VDJ-seq assay is unique in its ability to interrogate DNA recombinants. To expand its capabilities, I investigated several limitations of the technique, including mispriming and PCR/sequencing errors, and implemented experimental and bioinformatics solutions to overcome them, which included the creation of a comprehensive analysis workflow. Finally, I have developed and applied a novel network visualisation method for genome-wide promoter interaction data generated by promoter capture Hi-C. The availability of high quality human pluripotent stem cell datasets allowed me to utilise the new techniques to further our understanding of the dynamics of genome organisation during early human embryonic development. This visualisation approach will be directly applicable to understanding B cell development.

Les enveloppes circumstellaires autour des géantes rouges s'établissent pendant de longues périodes qui peuvent durer jusqu'à 10^6 ans. Elles peuvent donc être étendues (~1pc, peut-être plus) et nous avons besoin de différents traceurs complémentaires pour décrire leurs propriétés globales. Je présente dans cette étude un programme conçu pour examiner les propriétés de la matière dans les parties externes des enveloppes circumstellaires autour d'étoiles de la Branche Asymptotique des Géantes (AGB) et leur liaison avec les enveloppes internes. Je présenterai donc des observations HI à 21 cm ainsi que des observations des transitions rotationnelles de la molécule CO pour plusieurs types d'étoiles. Notre interprétation des profils HI observés est que le vent stellaire est freiné par le milieu interstellaire ambiant. Nous avons conçu un modèle sphérique pour tenter de prédire cette émission HI, et je discuterai ses résultats. Dans plusieurs cas, l'émission HI est allongée dans une direction compatible avec le mouvement propre de l'étoile, un phénomène qui est observé de plus en plus couramment et qui pourrait de même s'expliquer dans le cadre d'une interaction avec le milieu local.