Recongurable computing technology has progressed to a stage where it is now possible to achieve orders of magnitude performance and power eciency gains over conventional computer architectures for a subset of high performance computing applications. In this thesis, we investigate the potential of recongurable computers to accelerate genomic sequence alignment specically for genome sequencing applications. We present a highly optimized implementation of a parallel sequence alignment algorithm for the Berkeley Emulation Engine (BEE2) recongurable computer, allowing a single BEE2 to align simultaneously hundreds of sequences. For each recongurable processor (FPGA), we demonstrate a 61X speedup versus a state-of-the-art implementation on a modern conventional CPU core, and a 56X improvement in performance-per-Watt. We also show that our implementation is highly scalable and we provide performance results from a cluster implementation using 32 FPGAs. We conclude that reconfigurable computers provide an excellent platform on which to run sequence alignment, and that clusters of recongurable computers will be able to cope far more easily with the vast quantities of data produced by new ultra-high-throughput sequencers.

There exist several challenges in supporting mobile applications. For example, creating a separate target application for each device type, leaving developers with a huge maintenance chore. Most desktop applications run on largely homogenous hardware so instead of writing the same code over and over again, developers only need to write modules to implement a particular need. This is because even though there are differences in PC hardware configurations, the same desktop application will work fine on any hardware as the operating system provides an abstract layer. This is the way mobile applications are expected to work. However, this has been divided into dozens of ill-assorted versions. Java mobile applications developers spend more time rewriting code to run on different versions of mobile devices more than they do actually creating application in the first place. This is an intolerable burden for small mobile developers, and it stifles mobile software innovation overall. Mobile devices differ in a variety of attributes, such as screen size, colour depth and the optional hardware devices they support such as cameras, GPS etc. The differences often require special code or project settings for successful deployment for each device a developer is targeting but this creates a huge logistical overhead. One potential solution that is shipped with NetBeans IDE is to add a new configuration for each device, modify the project properties, add some pre-processing code, then build and deploy the application. In most cases, one configuration for each distribution of the Java Archive (JAR) one plans to build for the project is created. For example, if a developer is planning to support three different screen sizes using two sets of vendor specific APIs, one needs to create six configurations. This reduces the performance of the application drastically and increases the size at the same time. This is not acceptable for mobile devices where memory size and processor performance are limited. The goal of this research work is to support mobile application development through a Java IDE (the NetBeans IDE in this case). Therefore, our approach will be to modify the NetBeans IDE to better address the difficulty that was mentioned above – namely targeting applications for different platforms. Our solution is to integrate another type of a preprocessor into the NetBeans IDE that will help alleviate the problems of the existing tool. Our approach is to directly implement this inside the NetBeans IDE to further support mobile application development with the NetBeans IDE.

APOBEC3 proteins, in particular APOBEC3G/F, are important innate host factors that contribute to protection from HIV-1 infection by inducing high levels of guanine to adenine nucleotide substitutions (termed hypermutation) during HIV-1 viral replication. These nucleotide substitutions occur at different rates and locations across the HIV-1 genome and are thought to be particularly more frequent in the pol region. The virus has evolved ways to counteract these host factors by inducing degradation of APOBEC3G/F proteins through protein interactions with HIV-1 Vif. The aim of this thesis is to characterize and investigate the role of APOBEC3G/F-mediated hypermutation in the HIV-1 genome. We identified a subset of women from the Pumwani Commercial Sex Worker (CSW) cohort with significantly higher rates of hypermutated proviruses in pol. This degree of hypermutation correlated to less severe HIV disease progression as measured by CD4+ T cell count. This was in agreement with previous studies that evidence of APOBEC-mediated hypermutation correlate with reduced disease progression, confirming APOBEC3G/F proteins role in HIV-1 disease. Furthermore, we investigated the in vitro and ex vivo interaction between HIV-1 Vif and APOBEC3G from subjects infected with hypermutated and non-hypermutated proviruses. In vitro studies indicated that HIV-1 Vif protein expression in subjects with hypermutated proviruses were quite divergent and levels of APOBEC3G also differed between subjects. Ex vivo studies in subjects with hypermutated proviruses indicated that endogenous APOBEC3G expression was greater than in subjects with hypermutated proviruses. Both studies suggest that host and viral factors such as APOBEC3G and HIV-1 Vif are playing an influential role in HIV-1 pathogenesis. Further investigations into these interactions may lead to novel strategies into the development of therapeutic drugs for the fight against HIV-1.

HIV-1 integrase (IN) enzyme employs several viral and cellular proteins for nuclear translocation and crucial integration of viral cDNA. Successful identification of new viral/cellular interactions may shed light for better understanding of HIV-1 replication. 293T cells were transiently transfected with pYEF-1-TAP-IN and cell lysate were subjected to Tandem Affinity Purification system to pull down putative IN-interacting cellular partners. A number of distinct bands from the Coomassie-stained gel were excised followed by in-gel digestion and mass spectrometry. Putative cellular partners of HIV-1 IN were heat shock protein 60 (HSP60), β-tubulin, γ-actin, ATP synthase alpha subunit and histone H1.2 were identified by mass spectrometry. Additionally, SF3A3 (splicing factor 3A3), another previously reported factor, was successfully co-immunoprecipitated with IN. The C-terminal portion of IN was found to be the region of interaction with SF3A3. Overall, this study has provided better understanding of IN dynamics enriching existing knowledge of HIV-1 IN biology.

Objective: Serpins are serine protease inhibitors that are involved in a wide variety of biological functions in nature. They are known to regulate inflammation processes as well as provide host defense against microorganisms. Recent evidence has associated many types of mucosal serpins with a protective phenotype against HIV infection in women. Our hypothesis is that serpins with known antiviral activity against HIV-1 are correlated with protection in a group of HIV exposed seronegative individuals (HIV-resistant) from the Pumwani sex worker cohort. Study design: Cervico-vaginal lavage (CVL) fluid was collected from 66 HIV-positive, 82 HIV-negative and 84 HIV-resistant sex workers from the cohort. Clinical and epidemiological information was recorded at the time of sample collection. CVL protein levels were determined by BCA assay and serpin (A1 and A3) concentrations by a commercially available ELISA kit. Mucosal serpin concentrations were compared against clinical and epidemiological factors as well as sexual practices. Results: Serpin A1 was significantly higher in the HIV-resistant group compared to the HIV-negative controls (Anova: p=0.0470*). Total concentration of serpin A3 did not reach statistical significance between groups. Serpins did not correlate with age, sexual practices, contraceptive use or number of pregnancies. Serpins were differentially abundant during different stages of the menstrual cycle whereas serpin A1 was elevated during the proliferation phase but not in secretory phase (p=0.0275*). Conclusion: Serpin A1 was correlated with HIV-protection in this group of HESN women. This work will contribute to a more complete understanding of mechanisms of resistance and susceptibility to HIV infection.

Conté Annex de 171 pàgines amb la traducció només consultable a la tesi en paper. / The PhD entitled "Luisa Sigea de Velasco: philosophical reflections of a sixteenth-century Spanish docta puella" focuses on verifying and justifying if Luisa Sigea (1522-1560) was a genuine philosopher. To carry out this research, we analyze her philosophical dialogue: Duarum virginum colloquium de vita aulica et privata (1552). We also translated this dialogue into Catalan ["Diàleg de dues donzelles sobre la vida àulica i la vida retirada"]. Our research focused on doing a philosophical analysis of the dialogue. Luisa Sigea aims at finding out whether the best life to come next to God and experience happiness is the court lifestyle or the secluded one. To answer this question, Sigea goes through a set of political, anthropological and epistemological reflections that are subordinated to the ethical aim of reaching God and achieving happiness / La tesi doctoral titulada "Luisa Sigea de Velasco: reflexions filosòfiques d’una docta puella espanyola del segle XVI" està dirigida a comprovar i justificar si Luisa Sigea (1522-1560) fou una autèntica filòsofa. Per poder portar a terme aquesta recerca ens hem basat en el diàleg que aquesta pensadora escrigué titulat "Duarum virginum colloquium de vita aulica et privata" (1552), el qual hem traduït al català ["Diàleg de dues donzelles sobre la vida àulica i la vida retirada"]. El nostre treball d’investigació ha consistit a fer una anàlisi filosòfica d’aquest diàleg. L’objectiu d’aquesta obra de Luisa Sigea és descobrir quin és el millor estil de vida per poder arribar al costat de Déu i gaudir de la vida feliç: l’estil de vida àulic o l’estil de vida retirada. Per poder respondre a aquesta qüestió, Sigea desenvolupa una sèrie de reflexions polítiques, antropològiques i epistemològiques que subordina a l’objectiu ètic d’arribar a Déu i a la felicitat

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La vejez es la etapa de la vida en la que es mayor la proporción de personas con discapacidad. Cabe destacar no obstante, que conservar el sentimiento de calidad de vida depende de los recursos personales y el entorno. Actualmente se reconoce que las personas mayores prefieren continuar viviendo en su casa; incluso en soledad y con discapacidades. Esta investigación pretende avanzar en el conocimiento de la influencia del género, el nivel de estudios, la red social y la autonomía en la soledad residencial de las personas mayores de 75 años; más específicamente, explicar la medida en que el género y el nivel de instrucción de las familias influyen en la percepción sobre su comportamiento. La investigación se enmarca bajo el paradigma crítico social y está guiada por la teoría del estructuralismo constructivista y la sociología de la acción, desde los planteamientos teóricos de Pierre Bourdieu. Los hallazgos destacan el reto que supone el envejecimiento de la población y los cambios en la estructura familiar. Ponen de manifiesto la escasa orientación profesional en los cuidados familiares y cuestionan los motivos por los que la soledad residencial es preferida. Por ello destacan la necesidad de conocer los valores y creencias de las personas mayores para promover estrategias de incremento de la autonomía personal. La investigación sugiere que la excesiva fragmentación existente en los recursos sociosanitarios dirigidos a las personas mayores disminuye su eficacia. Y pone de manifiesto el desconocimiento existente sobre la percepción de ser útiles que los mayores y familia tienen de los mismos. Este trabajo evidencia la necesidad de que la atención sociosanitaria se libere de la influencia en exclusiva del paradigma biológico, así como la de desterrarlos cuidados geriátricos entendidos y practicados como caridad. Propone diferenciar, a la vez, tanto en el hogar como en las instituciones, las actividades de cuidar, dar apoyo y acompañar. Sugiere que los servicios sociales tienen que ser más personalizados y que deben mejorar su accesibilidad. / Old age is the stage in life with the highest ratio of disabled people. Nonetheless, it is important to add that a conserved perception of a good quality of life will depend on each person’s financial means and background. It is now acknowledged that most elderly people prefer to continue living in their own homes, even if they are alone and suffer from a disability. This research study aims to gain a deeper insight into the influence of gender, the level of education, social network and autonomy on whether an elderly person of over 75 years of age lives in an old people’s home or not. More specifically, it aims to explain the extent to which gender and the family’s level of education influence perceptions of their behaviour. The study is set within the field of social criticism, using the theory of structuralist constructivism and active sociology as a guide, based on Pierre Bourdieu’s theoretical approach. The findings demonstrate the challenge that the ageing population represents and changes in the structure of families. It highlights the low professional focus on family care and questions why living in an old people’s home is preferred, emphasizing the need to gain a better understanding of elderly peoples’ values and beliefs in order to promote strategies aimed at increasing personal autonomy. The study suggests that the current over-fragmentation of social and health care resources for the elderly has a negative effect on their efficiency. It also highlights the current lack of awareness that the elderly and families have of their own usefulness. Likewise, it demonstrates a need for the social and health services to free themselves from the sole influence of the biological paradigm (or medical model), no longer regarding or practising geriatric care as if it were a form of charity. In turn, it suggests that a differentiation should be made among the activities of caring for, offering support for and accompanying the elderly, both in homes and in institutions, proposing more customized social services and better access to them. In short, the study recommends the strengthening of community services, allowing the elderly to stay in their own homes if they wish, while freeing families from the obligation of having to care for them.

HIV-1 integrase (IN) enzyme employs several viral and cellular proteins for nuclear translocation and crucial integration of viral cDNA. Successful identification of new viral/cellular interactions may shed light for better understanding of HIV-1 replication. 293T cells were transiently transfected with pYEF-1-TAP-IN and cell lysate were subjected to Tandem Affinity Purification system to pull down putative IN-interacting cellular partners. A number of distinct bands from the Coomassie-stained gel were excised followed by in-gel digestion and mass spectrometry. Putative cellular partners of HIV-1 IN were heat shock protein 60 (HSP60), β-tubulin, γ-actin, ATP synthase alpha subunit and histone H1.2 were identified by mass spectrometry. Additionally, SF3A3 (splicing factor 3A3), another previously reported factor, was successfully co-immunoprecipitated with IN. The C-terminal portion of IN was found to be the region of interaction with SF3A3. Overall, this study has provided better understanding of IN dynamics enriching existing knowledge of HIV-1 IN biology.