Dissertations / Theses: 'Active responses' – Grafiati (2024)

Abstract:

Adaptive Immunantworten gegen Mycobacterium tuberculosis (M. tuberculosis) sind von entscheidender Bedeutung für die effektive Eindämmung des Erregers sowie den Schutz vor einer erneuten, sekundären Tuberkulose (TB). Obwohl Schlüsselfaktoren wie die Th1 Zytokine IFN-gamma und TNF-alpha bekannt sind, blieben Bemühungen zur Identifizierung eindeutiger immunologischer Parameter, welche ausschlaggebend für den Krankheitsverlauf sind, bislang erfolglos. Ein besseres Verständnis der zugrunde liegenden Immunprozesse sowie die Identifikation projektiver Biomarker für TB sind zentrale Ziele dieser Arbeit. Zur Bearbeitung dieser Fragestellungen wurden adaptive Immunantworten gegen M. tuberculosis in gesunden Probanden mit LTBI und Patienten mit aktiver TB analysiert. Hierfür wurde die Erkennung unterschiedlicher Proteine des Erregers durch die Messung IFN-gamma exprimierender CD4+ CD45RO+ Gedächtnis T Zellen untersucht. Eine Besonderheit war die Einbeziehung sogenannter Latenz-assoziierter Proteine, welche in Zusammenhang mit Dormanz und Reaktivierung des Bakteriums stehen. 7 Tage in vitro Inkubation in Verbindung mit einer zweimaligen Restimulation belegten eine spezifische Erkennung durch CD4+ CD45RO+ T Zellen für die Mehrheit der getesteten Proteine bei Spendern mit LTBI. Der darauf folgende Vergleich zwischen Patienten mit aktiver TB und Personen mit LTBI zeigte signifikant höhere T Zell Antworten für 7 der 35 M. tuberculosis Proteine während LTBI. Bemerkenswerterweise konnten spezifische T Zellen für eines der Protein, nämlich Rv3407, ausschließlich während LTBI gemessen werden und nicht bei Patienten mit aktiver TB. Diskriminanz Analysen zeigten, dass eine Unterscheidung zwischen LTBI und TB Patienten basierend auf T Zell Antwort gegen ausgewählte Latenz-assoziierte Antigene mit einer Genauigkeit von 82% möglich ist. Erneut erwies sich Rv3407 als der mit Abstand bedeutendste Faktor innerhalb der ausgewählten M. tuberculosis Proteine.
Adaptive immune responses to Mycobacterium tuberculosis (M. tuberculosis) are crucial for an efficient containment of the pathogen and protection against secondary tuberculosis (TB). Although key mediators like the Th1 cytokines IFN-gamma and TNF-alpha released by M. tuberculosis-specific T cells are known, the immunological correlates determining the outcome of infection remain elusive. A better understanding of the underlying immune processes and the identification of protective biomarkers for TB are central aims of this thesis. To address these topics adaptive immune responses to M. tuberculosis were analyzed in healthy LTBI and patients with active pulmonary TB. The recognition of M. tuberculosis derived antigens was studied by measuring the expression of IFN-gamma in CD4+ CD45RO+ memory T cells. A special hallmark was the inclusion of latency proteins associated with dormancy, reactivation and resuscitation of the pathogen. Seven days in vitro incubation of PBMC and two rounds of restimulation followed by FACS analysis revealed T cell mediated recognition of the majority of tested latency-associated proteins in donors with LTBI. Comparison between active TB and LTBI documented significantly higher T-cell responses against 7 of 35 tested M. tuberculosis latency-associated antigens in LTBI. Notably, T cells specific for one M. tuberculosis antigen, namely Rv3407, were exclusively detected in the subgroup of LTBI. Discrimination analysis revealed that the T-cell response against selected antigens with our novel assay is capable of distinguishing TB patients and LTBI with 82% accuracy using cross-validation. Again Rv3407 was by far the most influential component present in this cluster. Peptide pool stimulation in a similar fashion identified single distinct candidate epitopes within Rv3407 in four LTBI.

Abstract:

Active shooter events in K-12 schools have increased since 1990, and developing response policies to such events is a responsibility of school personnel. A paucity of data regarding options-based response practices existed with no focus on policy processes. The purpose of this qualitative multi-case study was to describe the decision-making processes used in school districts when approving the inclusion of options-based responses to active shooter events in Emergency Operations Plans (EOPs). The research questions addressed processes that shaped the development of options-based responses to active shooter policies in 3 K-12 school districts within the Midwest. The conceptual framework was informed by the theory of policy paradox and the concepts of situational awareness and resilience. Structured interviews were conducted with 12 school personnel and safety professionals involved in 3 high schools; EOPs and state and federal regulations and guidelines were reviewed. An analysis of the interview responses and document reviews using four levels of descriptive coding required a cross-case analytic technique to discover patterns, connections, and themes. Law enforcement and school personnel worked together to create policy and to implement trainings related to options-based response. Results included enhancing situational awareness and empowering teachers and students to become responsible for their safety. These findings can be used to inform and guide school leaders in their efforts to make policy and implementation decisions regarding active shooter policies in EOPs. The potential for social change exists in more school personnel understanding and implementing options-based response policies and making the lives of K-12 students safer.

Abstract:

Based upon the premise that both exercising (E) and non-exercising (NE) muscle play major roles during exercise, oxygen consumption and blood flow (BF) have been extensively monitored at the tissue level. Near infrared spectroscopy is a non-invasive technique that measures haemodynamic changes within muscle, indicating very specific oxygenation patterns and blood distribution. This series of studies investigated, initially, the contribution of E and NE arm muscle during small muscle mass, upper body activity (one-arm cranking) and, subsequently, greater muscle mass exercise (traditional leg cycling with (G) or without (NG) grip). The initial pilot study determined considerable differences between oxygenation status in both E and NE triceps brachii (TB) and biceps brachii as exercise intensity increased and concluded further investigation was warranted in TB. Study 2 confirmed that NE tissue suffered reduced oxygen supply at workloads above 70% peak power (PP), the E TB deoxygenating at intensities between 40% and 60% PP. The wearing of a restraint made little difference to stabilization at the highest intensities and increased activity was found within the NE ann. Study 3 concluded that a probable initial metabolite increase had an effect on NE tissue, although only at the highest workload (70% PP), a reflection of lactate (La) consumption. However, in contrast, E muscle was influenced between the two lower intensities (40% and 60% PP). BY increased in both E and NE tissue. Study 4 isolated the forearm and noted significant haemodynamic changes in NG at the highest work intensities, but also that body position effected leg oxygenation. It is proposed that a balance between vasoconstriction and vasodilation, instigated by La production, exists to redistribute BF. The withdrawal of the vasoconstictory signal post-exercise adjusts BF to E and NE arm tissue similarly. The NE tissue, therefore, plays a diverse, yet vitally important role during exercise and recovery.

Abstract:

Thesis (MSc MedSc)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: BackgroundThe QuantiFERON In-Tube (QFT IT) assay is an Interferon-gamma release assay(IGRA) which is currently used to detect Mycobacterium tuberculosis (M. tb) infection. Ithowever cannot differentiate between latent infection and active tuberculosis (TB)disease. In an attempt to improve this tool to accurately diagnose active TB, the releaseof a variety of markers should be assessed in combination with Interferon gamma (IFN-γ). Luminex analysis was previously done on QFT plasma and promising candidateswere identified which could be of great value in treatment response studies. IFN-γELISpot, are not only used to detect M.tb infection, but is also implicated in vaccine trailsto assess immunogenicity. The IFN-γ ELISpot and flow cytometry are the most commonassays to assess these phenomena during clinical trials. Our aim therefore was todevelop a multi platform immune analysis assay using the QFT IT system.Study design and methodThe first approach of this study was to optimize the QFT IT assay for flowcytometry applications. The following questions formed part of the optimization study:How does the QFT whole blood assay (QFT-WBA) compare to the currently used WBA?Is antigen re-stimulation required after the initial incubation time and for how long shouldcells be re-stimulated in the presence of Brefeldin A? The second approach was to usethe optimized QFT-WBA for community controls (CTRL), household contacts (HHC) andTB cases, which were recruited from the high TB incidence areas Ravensmead, Uitsigand Elsies River. The infection status of each participant was determined by IFN-γ ELISA and Luminex analysis was performed to measured wide range of cytokineexpression. In addition immune cell markers like CD14, CD4, CD8, CD19, and T cellreceptor gamma delta (TCRγδ) were characterized; polyfunctional characteristics (IFN-γ,Tumor necrosis factor-alpha (TNF-α) and Interleukin-2 (IL-2)) and proliferation (Ki-67+)of T cells determined by flow cytometry.ResultsAfter stimulating the whole blood of the study participants for 22 hours with the M.tb specific antigens, early secreted antigenic target 6 kDa (ESAT-6), culture filtrateprotein-10 kDa (CFP-10) and TB7.7 the levels of TNF-α producing CD4 T cells wereelevated in TB cases compared to HHCs. After stimulating the whole blood for 6 daysTNF-α producing T cells declined in TB cases and HHC showed a higher expression.CD40L+CD4+ (p=0.0225) was increased in HHC while IL-9+CD8+ (0.3230) wasdecreased in HHC compared to TB cases. Other markers such as IL-5(AG-NIL), IL-13(Ag-NIL), FGF basicAg, GM-CSFNIL, VEGFNIL/(Ag-NIL), MIP-1βAg and MCP-1Ag/(Ag-NIL) showedsignificant differences between HHC and TB cases.ConclusionsThe responses in the QFT-based assay were generally comparable to the WBAthat is routinely used. The differences of TNF-α expression seen in QFT-WBA and QFTLPAcould be explained by the fact that effector T cell responses were measured in theshort term assay and the central memory T cell responses in the long term assay. Ourstudy therefore shows that the QFT-based tests can be used to simultaneously assess awide range of immunological markers and not only IFN-γ expression.
AFRIKAANSE OPSOMMING: AgtergrondDie QuantiFERON In Tube (QFT IT) toets is ‘n Interferon-gamma vrystellingstoets(IGRA) wat huidiglik dien as ‘n maatstaf van Mycobacterium tuberculosis (M. tb) infeksie.Hierdie toets kan egter nie onderskei tussen latente infeksie en aktiewe tuberkulose(TB) nie. ‘n Noemenswaardige verbetering in die vermoë van hierdie toets om aktieweTB te diagnoseer, berus op die studie van ‘n verskeidenheid vrygestelde merkers,insluitend Interferon gamma (IFN-γ). In vorige Luminex studies op QFT plasma, isbelowende kandidate geïdentifiseer wat van groot waarde kan wees vir studies watfokus op die reaksie tot behandeling. Die IFN-γ ELISpot dien nie net as ‘n maatstaf vanM.tb infeksie nie, maar word ook in vaksienproewe betrek om die aard van immuniteit teondersoek. Die IFN-γ ELISpot toets sowel as vloeisitometriese toetse, is van die meesalgemene toetse om hierdie verskynsels te meet, tydens kliniese proewe. Die doel vanhierdie studie was dus om die QFT IT sisteem te ontwikkel as ‘n basis vir ‘n multiplatformimmunologiese analiseringstoets.Studie ontwerp en metodeDie inleidende benadering van hierdie studie was die optimisering van die QFT ITtoets, vir vloeisitometrie doeleindes. Die volgende vrae het deel uitgemaak van dieoptimiseringstudie: Hoe vergelyk die QFT heelbloedtoets (QFT-WBA) met huidige WBAswat in gebruik is? Word meermalige antigeenstimulasies benodig na die oorspronklikeinkubasieperiode en hoe lank moet die tydperk wees vir sellulêre opvolgstimulasie, indie teenwoordigheid van Brefeldin A? As ‘n tweede benadering, was om die geoptimiseerde QFT-WBA te gebruik vir gemeenskapskontroles (CTRL), huishoudelikekontakte (HHC) en TB gevalle. Al drie hierdie groepe was opgeneem uit Ravensmead,Uitsig en Elsies Rivier, areas met betreklik hoë vlakke van TB infeksie. Elke persoon indie studie se vlak van infeksie is vasgestel met behulp van die IFN-γ ELISA en Luminexanaliese was uitgevoer, om ‘n wye verskeidenheid uitdrukkingsvlakke van sitokiene temeet. Dies meer, was immuunselmerkers soos CD14, CD4, CD8, CD19 en T selreseptor gamma delta (TCRγδ) gekarakteriseer. Meervuldige funskionele karakteristieke(IFN-γ, Tumor nekrose faktor-alpha (TNF-α) en Interleukin-2 (IL-2)) envermenigvuldiging van T-selle, was vasgestel deur middel van vloeisitometrie.ResultateNadat die heelbloed van studiedeelnemers gestimuleers was met M. tb spesifiekeantigene, vroeë afskeidings antigeniese teiken 6kDa (ESAT-6), kultuurfiltraatproteïn10kDa (CFP-10) en TB7.7, vir 22 uur, was gevind dat vlakke van TNF-α produserendeCD4 T selle hoër was in TB pasïente, in vergelyking met HHCs. Nadat die heelbloed vir6 dae gestimuleer was, het die vlak van TNF-α produserende T-selle afgeneem in TBpasïente, terwyl dit hoër was in HCC. CD40L+CD4+ (p=0.0225) het hoër vlakke bereikin HHC, terwyl IL-9+CD8+ (0.3230) vlakke afgeneem het, in vergelyking met TBpasïente. Ander merkers soos,onder andere, IL-5(AG-NIL), IL-13(Ag-NIL), FGF basicAg, GMCSFNIL,VEGFNIL/(Ag-NIL), MIP-1βAg and MCP-1Ag/(Ag-NIL), het noemenswaardige verskillegeopenbaar tussen HHC en TB pasïente.

Abstract:

It is now well established that exercise of a strenuous and/or prolonged nature can lead to transient perturbations in immune function. The clinical significance of participating in such acute bouts of exercise in combination with other life stressors (e.g. inadequate nutrition) may be an increased incidence of upper respiratory illness (URI) (e.g. sore throat, runny nose). Many proposed nutritional countermeasures to exercise-induced immune dysfunction have been shown to be ineffective. The aims of this thesis were to determine the effects of bovine colostrum (COL) on in vitro and in vivo measures of immunity taken at rest and/or following prolonged (≥ 2 h) exercise and the incidence of URI during regular training in active males. Study 1 (Chapter 3) demonstrated that acute COL supplementation improved the recovery of bacterial stimulated neutrophil degranulation and enhanced salivary lysozyme concentration following 2.5 h of cycling. There was also greater fMLP-stimulated oxidative burst throughout the COL trial compared to PLA. These effects are suggested to be partly due to components and/or metabolites of COL that become bioavailable following digestion of the supplement which may explain why Study 2 (Chapter 4) demonstrated a greater effect on fMLP-stimulated oxidative burst with 4 weeks of COL supplementation. Study 3 (Chapter 5) found a lower proportion of URI days and lower number of URI episodes with 12 weeks of COL supplementation. Although there was no effect on selected measures of in vitro immune function taken at rest (fMLP oxidative burst, salivary secretory IgA and antimicrobial peptides), COL did blunt increases in salivary bacterial load over the winter period, which may provide a novel marker of in vivo immunity. Despite no effect of prior infection with Epstein-Barr virus (EBV) on URI incidence in Study 4 (Chapter 6), those who were seropositive and undergoing COL supplementation had a lower number of URI days vii than seronegative counterparts. Study 5 (Chapter 7) observed a lack of effect of COL supplementation on the overall magnitude of an in vivo measure of T-cell-mediated immunity to a novel antigen following prolonged exercise but there was evidence that COL may increase the sensitivity of responses to such antigenic challenge.

Abstract:

Thesis (Ph. D.)--University of Missouri-Columbia, 2005.
"December 2005" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.

Abstract:

Thesis (Ph. D.)--West Virginia University, 2006.
Title from document title page. Document formatted into pages; contains xiv, 197 p. : ill. Vita. Includes abstract. Includes bibliographical references.

Abstract:

Propelled by the significant socio-economic issues presented by obesity and an ageing population, research has identified links between physical activity, metabolism and disease, and quality of life. Our overall aim was to implement an empirically informed, palatable acute endurance exercise intervention that elicits beneficial hormonal responses with the potential for improved health/quality of life across the lifespan. Two groups of similar male participants (Study 1: n = 6; age, 28 ± 5 yrs.; BMI, 25 ± 4 kg/m2 - Study 2: n = 7; age, 26 ± 7 yrs.; BMI, 25 ± 4 kg/m2) performed equal work (varying duration) moderate (80 % GET) (M) and heavy (30 % D) (H) (Study 1), and H and very heavy (60 % D) (VH) (Study 2) acute constant work-load cycle ergometer exercise trials, respectively (Chapter 3). Analysis of bioptic material indicated increased mRNA (GAPDH normalised) in skeletal muscle for IL-6: baseline (B) vs. M (P = 0.006), H (P < 0.001) and VH (P < 0.001), and M vs. VH (P = 0.02); TNFα: B vs. VH (P = 0.04) and SOCS3 B vs. M (P = 0.02) and VH (P = 0.04). Exercise was without effect in subcutaneous adipose tissue (Chapter 4). The systemic concentrations of IL-6 increased and remained elevated for 24 hrs. in response to exercise. The increase was greatest following M (P = 0.001). IGF-I and cortisol concentrations declined by 60 min post-exercise (P = 0.001 and P = 0.04, respectively) (M, H and VH). GH increased to peak at the end of exercise (P < 0.001) (M, H and VH) (Chapter 5). To investigate the effect of age, groups of male participants (Study 3: 20 - 30 yrs., n = 8; 30 - 40 yrs., n = 10; 40 - 50 yrs., n = 8; 50 - 60 yrs., n = 8) performed a similar 30 min bout of heavy (30 % D) domain exercise (Chapter 6). The systemic concentrations of IL-6 displayed a bi-phasic profile in all groups. IL-6 increased during exercise at 10 min and then 60 min post-exercise (P < 0.001). Insulin and leptin declined during exercise in all groups (P < 0.001 and P = 0.002, respectively). Adiponectin was unchanged. GH increased similarly in all groups to peak again at the end of exercise (P < 0.001). IGF-I was unchanged. Concentrations were consistently higher in the 20 - 30 group however (P = 0.001). Cortisol declined similarly post-exercise in all groups (P < 0.001). We suggest that the oxygen uptake dynamics approach used here should be used when investigating physiological phenomenon potentially sensitive to skeletal muscle metabolic threshold events. We conclude that the exercise-induced hormone and cytokine responses studied in recreationally active health males between 20 and 60 yrs. age most likely reflects the requirements of metabolism. Further work should assess the effectiveness of this modified approach against resistance exercise in a training study format.

Abstract:

Advances in computer technology have hastened the development and dissemination of a wide range of electronic media into the workplace and educational settings. Electronic media offer many advantages, including quicker access to information and easier information sharing among professions. However, electronic reading media have still not been well integrated into these settings, especially for non-routine cognitive tasks like active reading. Conflicting results from different measures (e.g., performance, preference) have been reported regarding their efficacy. Despite the fact that there are no significant performance differences between reading from paper and reading from electronic media, people still show a preference for reading from paper and resist changes in the workplace, which often results in the abandonment of electronic reading media. Therefore, in order to maximize the potential benefits from electronic reading media, researchers and designers need more valid ways to assess the effectiveness of electronic reading media than relying on existing methods using outcome-based measures of reading.
Although the act of reading is primarily a cognitive process, there are relatively few comprehensive empirical reports on how the use of different reading media impacts cognitive processes like reading strategies. Moreover, researchers have rarely considered generational differences, even though generation-specific reading practices could significantly affect readers\' current reading practices using different media.
Therefore, the overall objective of this research was to develop and evaluate a new method to test the effectiveness of reading medium in terms of supporting design and evaluation. Specifically, this research examined how reading strategies can be used as a process measure. The research consisted of three parts: (1) investigating readers\' use of reading strategies using different types of media, (2) identifying the relationship between readers\' use of reading strategies and their performance and subjective response, and (3) identifying the relationship between readers\' use of reading strategies and cognitive load. Resultant findings are expected to improve how we measure the effectiveness of electronic reading media.
First, readers\' use of reading strategies for different types of media was examined and associated generational differences were investigated. A laboratory experiment was conducted in which three generations of participants (Baby Boomers, Generation X, and Generation Y) were asked to perform an active reading task (a simulated work-related reading task) with three types of media (paper, computer, and iPad). Readers\' uses of reading strategies were identified from task observation and Retrospective Think Aloud (RTA) sessions. Quantitative analyses revealed significant differences in readers\' use of reading strategies, and which depended on both the type of media and individual attributes (generation). Detailed qualitative analyses were conducted to help explain the underlying reasons for these differences in the use of reading strategies.
Second, based on the identified reading strategies, the relationships between readers\' use of reading strategies and their performance and subjective responses were examined. Such outcome measures have traditionally been used to assess the efficacy of different reading media. However, previous studies have generated conflicting results and did not clearly demonstrate the underlying aspects that influence readers\' performance and subjective responses. The results of this study showed a clear association between readers\' use of reading strategies and their performance and subjective responses. Accordingly, it was revealed that participants who used the reading strategies they developed in their formative period exhibited higher subjective responses.
Third, again based on the identified reading strategies, the association between readers\' use of reading strategies and cognitive load was examined. Reading from electronic media has been regarded as requiring more cognitive resources than reading from paper. However, it has not been well understood precisely which aspects of reading from different media actually influence cognitive load in terms of cognitive and metacognitive perspectives. The results reported herein showed an association between reading strategies and cognitive load. Therefore, this study revealed that the use of reading strategies was critical to their cognitive load.
Overall, this research demonstrated how reading strategies could be used as process measures to assess the effectiveness of specific media for active reading activities. The way in which people interact with a text (readers\' use of reading strategies) was affected by the medium, as well as by generation-specific reading practices. The extent to which reading strategies can explain reading differences was confirmed, by investigating the associations between readers\' use of reading strategies and other measures. These findings can contribute to the design of reading media and help to determine the most suitable reading media for active reading activities (e.g., work-related reading activities). In addition, the findings also support the importance of culturally situated experience for non-routine cognitive activities and the use of an integrated approach that takes into account both cognitive and cultural aspects in designing human-computer interaction for non-routine cognitive activities.
Ph. D.

Abstract:

Nesta dissertação, o objetivo é investigar um conjunto de redações do Exame Nacional do Ensino Médio (Enem)/2012, analisando as relações dialógicas estabelecidas pelos escreventes a partir da interação ativa com as vozes reportadas para a defesa de um ponto de vista sobre o tema: O movimento imigratório para o Brasil no século XXI. Desde 2009, o Enem seleciona candidatos para o ingresso no ensino superior e a redação é o instrumento que solicita a elaboração de um texto dissertativo-argumentativo. A partir do total de 2720 redações cedidas pelo Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira (Inep), o corpus foi constituído por 121 redações, segundo dois critérios: (a) a faixa de desempenho de 200 a 1000 pontos, respeitando a diversidade de notas, e (b) as cinco regiões brasileiras, marcando a representatividade regional. A fundamentação teórica deste trabalho centra-se na perspectiva dialógica da linguagem de Bakhtin e o Círculo, principalmente, nos conceitos de enunciado concreto e discurso citado, e na perspectiva ideológica dos estudos de letramento. Assumindo o trabalho com a escrita como um processo de compreensão responsiva, esta pesquisa buscou compreender cada texto como uma réplica ativa à proposta de redação e aos discursos oficiais que dela ecoam. No conjunto das redações, foram identificados quatro tipos de réplicas, que serviram como eixos norteadores para a análise dos modos heterogêneos de como os escreventes responderam às instruções objetivas da proposta e ao tema da imigração: (i) réplicas à exigência dissertativa; (ii) réplicas aos textos da coletânea, (iii) réplicas à imagem da identidade nacional e (iv) réplicas à história oficial do Brasil. Dentro de cada uma dessas réplicas, os resultados mostraram que os escreventes utilizaram procedimentos linguístico-discursivos para a construção do texto argumentativo, tais como: citações nos diferentes estágios composicionais da dissertação, paráfrases associadas à síntese, cópia e imitação dos textos da coletânea, construções referenciais para a caracterização do Brasil, como o uso de slogans, a mobilização de alusões históricas e narrativas da colonização. Tais procedimentos foram usados para assumir posicionamentos polêmicos e não polêmicos, alguns empregados com tendência à reprodução da palavra alheia e outros com vistas a sua reelaboração. Sob um olhar dialógico-axiológico, a análise da apreensão dos discursos de dentro e de fora da coletânea constatou não só o engendramento ativo dos sujeitos na produção de sentidos, mas os seus direcionamentos para os interlocutores presumidos e para as vozes institucionais dentro da rede de relações que envolve o projeto de escrita na avaliação do Enem. As réplicas puderam mostrar percursos discursivos construídos no diálogo com diferentes repertórios sociais, culturais e linguísticos, sinalizando que o trabalho com a escrita não está desvinculado dos contextos sócio-históricos das práticas letradas dos escreventes, refletindo e refratando os modelos normativos.
In this dissertation, the goal is to investigate a collection of essays from the National Secondary Brazilian Examination (Enem)/2012, analyzing the dialogic relations established by the writers from the active interaction with the reported voices to defend a point of view on the topic \"the immigration movement to Brazil in the 21st century\". Since 2009, Enem selects candidates for admission to higher education and the writing is the instrument that calls for the development of a dissertative-argumentative text. From the total of 2720 essays provided by the National Institute for Educational Studies Anísio Teixeira (INEP), the corpus was consisted of 121 essays, according to two criteria of selection: a) the performance range of 200-1000 points, respecting the diversity of scores, and b) the five Brazilian regions, marking the regional representation. The theoretical foundation of this work focuses on the dialogic language perspective of Bakhtin and the Circle, mainly, the concepts of \"utterance\" and \"quoted speech,\" and the ideological perspective of the literacy studies. Assuming the job with writing as a process of responsive understanding, this research sought to understand each text as an active response to the writing proposal and to the official discourses. In all the texts, four types of responses were identified, which served as a guide for the analysis of the heterogeneous modes of how the participants answered to the instructions of the proposal and to the issue of immigration: (i) responses to the dissertation requirement; (ii) responses to the texts of the collection, (iii) responses to the image of national identity and (iv) responses to the official history of Brazil. Within each of these responses, the results showed that the subjects used linguistic-discursive procedures for the construction of the argumentative text, such as: quotes in different compositional stages of the dissertation, paraphrases associated with synthesis, copy and imitation of the texts from the collection, characterization of Brazil as the use of slogans, the mobilization of historical allusions and narrative of colonization. These procedures were used to take controversial positions and not controversial ones, some employed with the tendency to reproduce the alien word and others with the tendency to remake them. Under a dialogical axiological perspective, the analysis of the comprehension of the inside and outside discourses of the collection found not only the active gendering of the subjects in the production of meanings, but their directions for the presumed actors and to the institutional voices within the network relationships of the writing project on the assessment of Enem. The responses could show discursive routes constructed in dialogue with different social, cultural and linguistic repertoires, signaling that the work with writing is not disconnected from the socio historical contexts of the student´s literate practices, reflecting and refracting the normative models.

Abstract:

This thesis explored whether haemodynamic responses to psychological stress test predict future blood pressure (BP) levels: the Reactivity Hypothesis. The research included a systematic review and two prospective cohort studies in the UK and Thai samples. In addition, the Blunted Reactivity Hypothesis, which posits that cardiovascular reactivity is inversely related to symptoms of anxiety and depression, was examined in cross-sectional analyses. A systematic review with meta-analysis and meta-regression with 41 prospective cohort studies (from 1950 to 2012) examined whether cardiovascular responses to psychological stress tests predict future BP levels, hypertension status, preclinical coronary heart disease (CHD) and cardiac events. Three possible moderators were included in analyses: type of task (active versus passive coping), age group (children versus adults), and duration of follow-up (short versus long-term follow-up). The review found that systolic BP reactions to psychological stress tests predict future systolic BP levels and that there was better prediction in child samples with shorter follow-up periods. Similarly, diastolic BP reactions to psychological stress predicted future diastolic BP levels. Cardiovascular reactions to psychological stress tests did not predict hypertension, preclinical CHD, or cardiac events. Cross-sectional analysis of two studies conducted in the UK and Thailand provided some evidence that anxiety and depressive symptoms were negatively associated with cardiovascular reactivity: these findings supported the Blunted Cardiovascular Hypothesis. However, these relationships were observed in the UK sample, but not in the Thai sample. Further, Thai participants responded to psychological stress task with large cardiovascular reactions, of a similar magnitude to the UK participants and observed in previous studies of Europeans and North Americans. Finally, prospective analyses revealed that systolic BP responses to mental arithmetic predict future systolic BP levels after one year of follow-up in both UK and Thai individuals, after controlling for baseline cardiovascular activity and traditional risk factors. In contrast, haemodynamic responses did not predict future BP. These results provide support for the “Reactivity Hypothesis” although the effect sizes were relatively small. However, responses to only one of the three stressors, mental arithmetic, predicted future BP implicating beta-adrenergically mediated cardiovascular responses. However, there was no physiologic evidence (i.e., cardiac output responses) that suggested beta-adrenergic mechanisms. Accordingly, future studies should examine alternate mechanisms (e.g., platelet aggregation and endothelial function) and cardiovascular responses in larger samples with a longer follow-up to further clarify the predictive value of reactivity in the development of hypertension, along with potential mechanisms.

Abstract:

Thesis (MMed) -- Stellenbosch University, 2010.
Bibliography
Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence to treatment predict the expected response to HAART and differences if any, in the pattern of response as measured by CD4 count, weight gain and haemoglobin levels in two cohorts of patients in Roma, The Kingdom of Lesotho.Method: Data were collected randomly from a computerised database of the Antiretroviral Centre of the hospital and two cohorts of 151 subjects in each of the two arms of the study were identified from hospital records from January 2008. Each of these subjects was followed up over a period of 12 months with data obtained for at least 2 visits within the 12 month span. Data were obtained at baseline, 3 months and also at 6 and 12 months marks. Data on characteristics were compared between the two arms. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints as well as for each endpoint separately.Results: In all 302 patients had their records analysed and comparison of clinical and immunological response patterns in patients taking AZT and TDF-containing ART regimens and the possible prediction of which the regimen would be better and within which population. Despite the perceived mismatch between two NRTIs it can be concluded from the results of this study that, overall, the inclusion of AZT in treatment regimen showed a modest protective effect over the TDF counterpart as measured by the endpoints of the discriminative powers of the Receiver Operating Curves of the explanatory variables being 66% , 77% and 66% for CD4, Haemoglobin and Weight respectively, and 63%, 70% and 65% for the same variables in the AZT and TDF arms of the study respectively.Conclusion: In a population of HIV patients on treatment in resource-limited settings AZT-containing regimens appear to show a slight improvement over the TDF-containing ones.

Abstract:

This thesis investigates the possibility of controlling the response of a general multi-degree of freedom structure to a relatively distant blast load using passive and semi-active devices. A relatively distant blast is one that applies significant momentum to the structure, but does not destroy the face of the structure. Three multi-storey structures, and one single-storey structure, are modelled using non-linear finite elements with structural columns discretised into multiple elements to accurately capture the effects of higher order modes that are typically excited in such blast load responses. The single-storey model structure is subjected to blast loads of varying duration, magnitude and shape, and the critical aspects of the response are investigated over a range of structural periods in the form of blast load response spectra. The optimal device arrangements are found to be those that reduce the first peak of the structural displacement and thus also reduce the subsequent free vibration of the structure. For a given blast load, various passive and semi-active devices, as well as device architectures, are investigated. The optimal device architecture was found to be one that spanned approximately two-thirds the height of the structure. Depending on what damage parameters are considered critical for a given structure, different devices and arrangements are appropriate. The main factors in choosing a semi-active device and its control architecture, or arrangement, are the tradeoffs between permanent deflection, free vibration, base shear and device capacity limitations. Overall, the results present a first analysis on the effectiveness of semi-active devices and the unique force-displacement properties they offer for mitigating non-catastrophic blast loads.

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Environmental or structural testing work often involves measurements on a test specimen which is attached to a larger structure of finite mechanical input impedance. It would be useful to select from a range of load impedances associated with the larger structure without altering it mechanically. This thesis describes the application of active control techniques to such a problem, and presents theoretical and experimental work which attempts to determine the range of load impedances which can be simulated in practice. Two approaches are presented. The first considers modification of the frequency response of a simple test structure using feedback control. Experimental work using a digital control system demonstrates modification of the modal parameters of the fundamental mode of vibration of a cantilever. The relative merits of state estimation/feedback and a more pragmatic proportional plus integral plus derivative (PID) controller are discussed, and the PID-type controller is used for experimental work which demonstrates independent control of the first two modes of a cantilever. The second approach considers simulation of the desired impedance function by electronic means. The input impedance of an electrodynamic shaker can be modified by using a filter which operates on a signal proportional to the acceleration produced by the shaker and which is fed back to the shaker input. A `black-box' model of a simple shaker allows the design of a feedback controller which when implemented leads to the desired closed-loop response. Experimental results show the simulation of fourth and sixth order systems using a second order test system, for which an eighth order controller is required. Extension of the analysis to a two-channel system allows the electronic simulation of a mechanically coupled system using shakers which are not mechanically coupled. Although experimental results are presented, the complexity of the controller matrix is seen as a limiting factor for this approach.

Abstract:

The GB power system will see huge growth in transmission connected wind farms over the next decade, driven by European clean energy targets. The majority of the UK’s wind development is likely to be offshore and many of these wind farms will be interfaced to the grid through power converters. This will lead to a loss of intrinsic inertia and an increasing challenge for the system operator to keep grid frequency stable. Given this challenge, there is increasing interest in understanding the capabilities of converter control systems to provide a synthesised response to grid transients. It is interesting to consider whether this response should be demanded of wind turbines, with a consequential reduction in their output, or if advanced energy storage can provide a viable solution. In order to investigate how large offshore wind farms could contribute to securing the power system, wind turbine and wind farm models have been developed. These have been used to design a patented method of protecting permanent magnet generator’s converters under grid faults. Furthermore, these models have enabled investigation of methods by which a wind turbine can provide inertial and frequency response. Conventionally inertial response relies on the derivative of a filtered measurement of system frequency; this introduces either noise, delay or both. This research proposes alternative methods, without these shortcomings, which are shown to have fast response. Overall, wind farms are shown to be technically capable of providing both high and low frequency response; however, holding reserves for low frequency response inevitably requires spilling wind. Wind’s intermittency and full output operation are in tension with the need of the power system for reliable frequency response reserves. This means that whilst wind farms can meet the technical requirements to hold reserves, they bid uncompetitive prices in the market. This research shows that frequency response market prices are likely to rise in future suggesting that the Vanadium Redox Flow Battery is one technology which could enter this market and also complement wind power. Novel control incorporating fuzzy logic to manage the battery is developed to allow a hybrid wind and storage system to aggregate the benefits of frequency response and daily price arbitrage. However, the research finds that the costs of smoothing wind power output are a burden on the store’s revenue, leading to a method of optimising the combined response from an energy store and generator that is the subject of a patent application. Furthermore, whilst positive present value may be derived from this application, the long payback periods do not represent attractive investments without a small storage subsidy.

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Most systems in Nature manifest complex transport phenomena arising from the interplay of multiple time and length scales, be them intrinsic in the system’s dynamics or externally enforced. It is the case, for instance, of a colony of migrating cells whose competing mechanisms of self-propulsion and interaction allow for the reorganization into different tissues. Or, by ‘zooming in’ and looking at the same system on a different scale, it is the case of the ionic channels located in the membranes of the aforesaid cells. These channels typically exhibit extraordinary ion selectivity and water permeability due to the interplay between geometric confinement, surface properties and external drivings. Whether to investigate the collective structures of the former system, or the nanofluidic properties of the latter one rests on the interests of the reader. In any case, she will find some food for thought in this thesis. Here we aim at the study of the transport properties of two very different classes of systems: active matter and electrolytes under confinement. In the examples above drawn from biology, cell tissues belongs to the class of active matter and protein channels are the archetype nanometric ionic systems. We tackle the problem from a purely statistical physics viewpoint by constructing minimal models to study the system’s response to outside influences and, by doing so, learn something about its internal properties.In the case of active matter, the challenge resides in the intrinsically out-of-equilibrium nature of its constituents, having the ability to self-propel by consuming fuel stored in the environment. In Part I of the manuscript, we study how the interplay between self-propulsion and steric interactions affects the linear response of active systems. First, we construct a very general theoretical framework which allows to derive general constraints that arbitrarily out-of-equilibrium systems must fulfilled. Then, we apply it to two different minimal models of active systems to derive generalized fluctuation-dissipation relations and Green-Kubo expressions. In Part II of the manuscript we investigate the surface-dominated transport of electrolytes in (i) a nanofluidic diode and (ii) a scanning ionic conductance microscopy configuration. In both cases, we develop a theory of ionic conductivity that rationalizes previous experimental results. By doing so, we shed light on the importance of the surface versus bulk competition in controlling ionic transport and we propose a new approach to exploit it for the imaging of surface charge with nanometric resolution.
La mayoría de los sistemas en la Naturaleza manifiestan fenómenos de transporte complejos que surgen de la interacción de múltiples escalas de tiempo y longitud, ya sean intrínsecas en la dinámica del sistema o forzadas externamente. Es el caso, por ejemplo, de una colonia de células migratorias cuyos mecanismos competitivos de autopropulsión e interacción permiten la reorganización en diferentes tejidos; o, al "acercar" y mirar el mismo sistema en una escala diferente, es el caso de los canales iónicos ubicados en las membranas de las células mencionadas. Estos canales exhiben típicamente una selectividad de iones extraordinaria y permeabilidad al agua debido a la interacción entre el confinamiento geométrico, las propiedades de la superficie y los conductos externos. Ya sea para investigar las estructuras colectivas del primer sistema, o las propiedades nanofluídicas del último, se basa en los intereses del lector. En cualquier caso, encontrará algo de reflexión en esta tesis.

Abstract:

Flocking, the collective motion of systems consisting of many agents, is a ubiquitous phenomenon in nature, observed both in biological and artificial systems. The understanding of such systems is important from both a theoretical point of view, as it extends the field of statistical physics to non-equilibrium systems, and from a practical point of view, due to the emergence of applications that are based on the modelling. In the present thesis I numerically investigated several aspects of flocking dynamics, simulating systems consisting of up to millions of particles. One first problem I worked on regarded the flocks response to external perturbations, something that had received little attention so far. The result was a scaling relation, connecting the asymptotic response of a flock to the strength of the external fleld affecting it. Additionally, my preliminary results point towards a generalised fluctuation-dissipation relation for the short-time response, with two different effective temperatures depending on the direction at which the perturbing field is applied. Another aspect I studied was the stability and dynamical properties of non-confined active systems (finite flocks in open space). The results showed that these flocks are stable only when an attracting 'social force' keeps the agents from drifting away from each other. The velocity fluctuations correlations were found to be different than the asymptotic limit predictions of hydrodynamic theories for infinite flocks. Finally, I studied the clustering dynamics of flocking systems. The conclusion was that the non-equilibrium clustering in the ordered phase is regulated by an anisotropic percolation transition, while it does not drive the order-disorder transition, contrary to earlier conjectures. I believe the results of this work answer some important questions in the field of ordered active matter, while at the same time opening new and intriguing ones, that will hopefully be tackled in the near future.

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The purpose of this study was to examine whether physical activity status of healthy adult males (N = 59) while in a coping strategy condition (association, disassociation, or control) influences psychophysiological responses to an acute painful stimulus. Measures of pain tolerance, state anxiety, body awareness, and salivary cortisol were investigated. Results indicated no significant differences between physical activity groups for pain tolerance, stress responses (i.e., self-reported state anxiety and cortisol levels), or body awareness. Though, those who indicated using a disassociation coping technique during the exit interview tolerated the acute, surface pain longer. More research is required to further understand the effects of physical activity and coping strategies on pain perception and psychophysiological responses.

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The knowledge of blood vessel biomechanics is used for understanding and developing treatments for cardiovascular disease. The objective of this project was to develop an experimental protocol, for education and research, that separates active diameter response from the passive, as a function of the intraluminal pressure in a pressure myograph. The design process was performed in three steps. First the protocol was designed for an artificial vessel and then expanded to include passive properties of blood vessels, finally further developments needed to analyze active blood vessels were suggested. The system was built as a pressure myograph containing a vessel chamber where the vessel was mounted on two cannulas, two pressure sensors for calculating the intraluminal pressure, and one microscope equipped with a camera for diameter observations. Reference data for the artificial vessel material was acquired from a uniaxial tensile test. The results was in the form of stress-stretch relations. Both the results from the artificial vessel and the passive blood vessel was in a acceptable reference range. The results indicate that the experimental protocol can be used for testing passive properties of both artificial vessels and small blood vessels. No results were obtained for active blood vessels, thus the experimental protocol can not be used for separating the active response to diameter change of blood vessels. However, further developments of the experimental protocol are discussed.
Kunskap om blodkärlens biomekanik används för att förstå och utveckla behandlingsmetoder mot hjärt- och kärlsjukdomar. Syftet med det här projektet var att utveckla ett experiment som mäter små blodkärls diameter och vätsketryck in vitro. Experimentet skulle sedan separera det aktiva muskelbidraget till diameterförändring från det passiva bidraget. Genom att göra detta kan kunskapen om biomekaniken hos blodkärl utvecklas inom såväl forskning som utbildning. Experimentet utvecklades i tre steg. Först utvecklades det för artificiella blodkärl och anpassades sedan för passiva blodkärl. slu*tligen diskuteras vidareutvecklingar av experimentet gällande de aktiva egenskaperna för blodkärl. Experimentet utformades genom att ett kärl placerades i en kammare. Blodkärlet fästes i vardera ände på varsin kanyl som var kopplade till trycksensorer. För att registrera diametern placerades kammaren under ett kameramikroskop. Resultatet består av spänning-sträcknings diagram. Både resultatet för det artificiella blodkärlet och det passiva blodkärlet var inom ett godkänt referensintervall. Dessa resultat stödjer antagandet att experimentet kan användas för att studera passiva egenskaper av artificiella och verkliga blodkärl med storlek mellan 1.9-4.4 mm i ytterdiameter. Ingen mätdata från aktiva blodkärl kunde samlas in, utan utvecklingskrav på systemet för hantering av aktiva blodkärl har föreslagits.

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La contractilité cellulaire, un phénomène orchestrée par le système d'actomyosine, est un régulateur critique d'une large gamme de processus cellulaires, y compris l'établissem*nt de la polarité cellulaire, la migration cellulaire, l'intégrité des tissus au cours de la morphogenèse ou du développement. Une simple perturbation de la génération de la force et des propriétés mécaniques des cellules peut affecter leurs fonctions physiologiques et par conséquent peut conduire à des défauts pathologiques y compris le cancer.Cependant, les mécanismes qui contrôlent la production de la force par le système acto-myosine et leurs modes de régulation dans les cellules ne sont pas pleinement compris. Au cours de ma thèse, j'ai utilisé un système biomimétique fait d'un ensemble minimal de protéines purifiées pour étudier les propriétés contractiles du système actomyosin.L'objectif était de comprendre comment l'architecture des filaments d'actine peut modifier la réponse contractile. A cet effet, j'étais d'abord intéressée par la construction d'une variété d'organisation de l'actine qui servira après comme substrat pour les moteurs moléculaires (la myosine) lors de la contraction.Afin de comprendre les principes généraux qui dictent l'assemblage de l'actine, nous avons développé un modèle numérique qui nous a permis d'identifier les paramètres clés, y compris l'interaction entre les filaments d'actine, les propriétés mécaniques de ces filaments et l'activation par contact entre une région de nucléation et les filaments d'actine qui poussent à partir d'un motif adjacent. Ce modèle a été utilisé en premier lieu pour implémenter les propriétés reliées à l'actine et en second lieu pour évaluer la réponse contractile des structures d'actine induite par la myosine.Durant ma thèse, j'ai pu démontrer que le niveau de connectivité module la déformation du réseau d'actine induite par la myosine, selon leur architecture. J'ai montré aussi que les protéines de pontages des filaments d'actine sont nécessaires pour effectuer une déformation et générer des forces au niveau des réseaux d'actine dynamiques en présence de la myosine. De plus, nous avons développé les simulations numériques dans le but de relier la déformation macroscopique des structures d'actines due à la myosine avec le mécanisme microscopique sous-jacent.Ce travail a révélé comment la variété des réseaux d'actine contracte d'une façon différente même en respectant les mêmes conditions biochimiques et a démontré l'importance de l'effet du réarrangement dynamique des structures d'actine sur la modulation de sa contractilité
Cellular contractility – the internal generation of force by a cell orchestrated by theactomyosin machinery – is a critical regulator of a wide range of cellular processes includingthe establishment of cell polarity, cell migration, tissue integrity or morphogenesis duringdevelopment. Disruptions of the force generation and of mechanical properties of living cellsaffect their physiological functions and consequently can lead to pathological defectsincluding cancer. However, the parameters or mechanisms that drive force production by theactin-myosin system and their mode of regulation in cells are not fully understood. During myPhD, I used biomimetic system made of a minimum set of proteins to study the properties ofactomyosin contractile systems. The goal was to understand how/if the actin architecture canmediate the contractile response. For this purpose, I was first interested in building a varietyof actin organization that will serve next as substrate for myosin during contraction. Tounderstand the general principles that dictate geometrically-controlled actin assembly, wedeveloped a model that allowed us to identify key parameters including filaments/filamentsinteraction, filament mechanical property and contact activation between actin filamentsgrowing from the adjacent pattern and the nucleation area. These actin templates were usedthen to evaluate the response of oriented actin structures to myosin-induced contractility. Idemonstrated that crosslinking level modulates the myosin-induced deformation of actinnetworks according to their architecture. I showed also that crosslinkers are necessary tosustain myosin-driven deformation and force production of dynamic actin networks. Inaddition, we developed numerical simulation in order to relate the observed myosin-drivenactin deformation with the underlying microscopic mechanism. This work revealed howdiverse cellular actin networks contract differently to a define set of biochemical conditionsand hence how dynamic rearrangements can modulate network contractility

Abstract:

SyfteAtt undersöka hur stor bedövningseffekt som kan uppnås efter injektion med aktiv (lidokain) eller in-aktiv substans (koksaltlösning) samt att undersöka om deltagarna korrekt kan identifiera vilken injektion de fått, när de vet att det är en 50/50 chans att de har fått lidokain eller koksalt.Material och metod20 friska frivilliga deltagare randomiserades in i två grupper. En grupp fick injektion med aktiv substans och en med in-aktiv substans. Deltagarna informerades om att chansen att få aktiv eller in-aktiv substans var lika, 50 %. Deltagarna utsattes för ett specifikt smärtsamt stimulus före och efter injektionen. De graderade sedan sin smärtintensitet på en 0-10 NRS-skala. Följande dag tillfrågades deltagarna vilken substans de trodde de hade fått.Students T-test användes för att beräkna skillnaden i smärtintensitet före och efter injektion i båda grupperna. Fischer’s exakta test användes för att beräkna kvalitativa data. P <0,05 ansågs vara statistiskt signifikant.ResultatDet var en statistiskt signifikant skillnad mellan den aktiva (NRS 2,9) och den in-aktiva (NRS 0,0) gruppen gällande förändringen i smärtintensitet före injektion och efter injektion. Alla deltagare kunde korrekt identifiera vilken injektion de fått.slu*tsatsIngen bedövningseffekt kunde mätas efter injektion med inaktiv substans hos friska individer när deltagarna visste att det var en 50/50 möjlighet att de skulle få den aktiva substansen. Alla individer kunde korrekt avgöra om de fått injektion med aktivt bedövningsmedel eller in-aktivt koksalt.
AimTo investigate the amount of anesthetic effect that can be achieved following injection with active (lidocaine) or non-active (saline) agent and to examine if the participants correctly can identify which injection they received when there is a 50/50 chance that they have received lidocaine or saline.Materials and Method20 healthy volunteers were randomized in two groups. One group got injection with active agent and one with non-active agent. The participants were instructed that chances of receiving active versus non-active agent were equal, 50 %. The participants were exposed to a specific painful stimulus before and after the injection and they had to rate their pain score on an 0-10 NRS-scale. The following day, the participants were asked what agent they thought they had received.Students T-test was used to calculate the difference in pain intensity between pre- and post-injection in both groups. Fisher's exact test was used to calculate qualitative variables. P<0.05 was considered statistically significant.ResultsThere was a statistically significant difference between the active (NRS 2.9) and the non-active (NRS 0.0) group regarding the change in pain intensity rating from pre-injection to post-injection. All participants could correctly identify which injection they received.ConclusionNo anesthetic effect could be measured after injection with non-active substance in healthy individuals when there was a 50/50 level of uncertainty that the individual would receive the active agent. All individuals could correctly determine whether they received active anesthesia or non-active saline.

Abstract:

Many environmental stresses result in increased generation of active oxygen species (AOS) in plant cells, leading to the induction of protective mechanisms. In this study, signalling components linking AOS perception to downstream responses were examined, with particular emphasis on H₂O₂ signalling. All AOS investigated had an early [Ca²⁺]_cyt peak in common, but differed in other aspects of their Ca²⁺ signatures, indicating that the plant is able to discriminate between different types of AOS. An early event in AOS signal transduction may involve changes in the cellular redox balance as reduction of glutathione levels prior to stress application increased the height of the first [Ca²⁺]_cyt peak. Inhibiting or enhancing the height of the H₂O₂-triggered Ca²⁺ signature lead to inhibition or enhancement of GST1 and APX1 induction, respectively, demonstrating that the Ca²⁺ signature is required for induction of genes encoding antioxidant enzymes. OX1, encoding a putative ser/thr kinase, was shown to be involved in signal transduction in response to H₂O₂-generating stresses. Transcript levels of OX1 were increased upon treatment with H₂O₂ and a range of abiotic and biotic stresses as well as ABA, all of which have been shown to result in H₂O₂ accumulation. Inhibition of stress-induced [Ca²⁺]_cyt elevations inhibited OX1 induction, placing the OX1 kinase downstream of Ca²⁺ in the signalling chain. OX1 is required for full activation of AtMPKS and AtMPK6 in response to ozone fumigation, indicating that OX1 functions upstream of these MAP kinases. An ox1 null-mutant displayed enhanced susceptibility to infection with a virulent Peronospora parasitica isolate as well as reduced induction of several defence genes. In addition, the ox1 mutant exhibited shorter root hairs and an early flowering phenotype. AOS treatment induced several genes encoding AtERF transcription factors, but did not have an effect on other members of this family. Induction occurred in an ethylene-independent but Ca²⁺-dependent manner.

Abstract:

The main purpose of this research is to investigate the effectiveness and feasibility of semi-active control systems for structural protection during severe earthquake loading. However, the research reported herein also involves analytical studies on the effect of adding viscous damping to the second and fourth quadrants of the force-displacement curve, and laboratory and field testing of a fibre-optic gyroscope (FOG) for measuring rotations in civil engineering structures.The concept of the 2-4 viscous damping is introduced to reduce the response of single-degree-of-freedom (SDOF) systems subjected to harmonic and earthquake excitations. This concept involves the addition of structural viscous damping to the second and fourth quadrants of the force-displacement graph. Time-history analyses and response spectra for various SDOF systems are carried out to assess the effect of adding 2-4 viscous damping. The analytical results indicate that the addition of 2-4 viscous damping is beneficial for reducing the harmonic and seismic response of a wide range of SDOF systems.A newly developed semi-active resettable device is proposed to reduce the seismic response of a one-fifth scale structure. The device is investigated as part of a resettable tendon system installed in the structure. Nonlinear dynamic analyses are performed to determine the optimal configuration of the resettable tendon in the structure. Several shake table tests are performed on the structure equipped with two resettable devices. The dynamic characteristics of the structure and the devices are described. Various earthquake records at different levels of intensity are used during the seismic testing. Different control laws are employed to manipulate the hysteretic behaviour of the devices. The results of the shake table tests validate the effectiveness of the resettable devices to reduce the seismic response of structures.Analytical studies are performed to determine the optimal utilization of the resettable devices in a twelve-storey reinforced concrete building. The seismic performance of the structure is discussed in relation to the number and distribution of the devices. Inelastic time-history analyses are carried out to assess the effectiveness of the devices to reduce the seismic response of the building. The impact of various tendon arrangements and different control laws on the earthquake response is investigated. Relevant issues for the implementation of the resettable devices in actual building systems are identified.Finally, a new measurement concept based on the use of the fibre-optic gyroscope is proposed to measure rotation rates, rotations, displacements and inter-storey drifts of civil engineering structures. FOGs are compact, easy to install and, unlike conventional linear potentiometers, do not require a fixed reference frame to operate. Measurements recorded during the seismic testing of the one-fifth scale structure and displacement measurements at the Sky Tower in Auckland validate the suitability of the FOGs for applications in civil engineering.

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Active flow control by a jet over a 12.5% thick elliptic profile is investigated numerically.Unsteady flowfields are calculated with a Navier Stokes solver. The numerical method is firstvalidated without the jet and with the presence of steady-blowing and pulsating jets. Three jettypes, namely steady, pulsating and synthetic jets, are next compared with each other and it isshown that the most drag reduction is achieved by a synthetic jet and the most lift enhancementis achieved by a steady jet. The influences of the jet location, the jet velocity, the jet frequency,the jet slot length and the jet angle on the flowfield is parametrically studied. It is shown thatthe jet location and the jet velocity are the most effective parameters. The jet parameters areoptimized to minimize the drag coefficient while keeping the jet power constant. The drag isreduced by 32.5% for the angle of attack 0 and by 24% for the angle of attack 4.

Abstract:

Thesis (E.A.A. and S.M.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 2000.
Includes bibliographical references (p. 143-149).
by Miguel Ortega-Morales.
E.A.A.and S.M.

Abstract:

The active magnetic bearing (AMB) is a relatively new technology which hasmany advantages compared with conventional bearing design. In an AMB system,the rolling-element back-up bearings are indispensable to protect the magneticbearing rotor and stator, and other stationary seals along the rotor shaft. In thispaper, a theoretical formulation is proposed and solved numerically to examine thetransient response of the flexible rotor, from the time just previous to the AMBshuts down and including the rotor drop onto the back-up bearing. The backwardwhirl of the rotor, which may lead to the destructive damage of the machinery, hasbeen analytically predicted at very light support damping and very high supportdamping. Also, the vibration due to the non-linearity of the contact point geometryhas been included in the analysis. The influence of the support damping on thedisplacement of the disk and also the contact force between the journal and theinner-race of the back-up bearing have been computed for various rotor systemparameters. By comparing these results with the optimum support damping forthe simple flexible rotor model, it is shown that this support damping optimizationcan be applicable for specifying the required optimum range of support dampingfor the back-up bearings of AMB systems.
Master of Science

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Interleukin-1-beta (IL-1β) is a potent proinflammatory cytokine. A primary outcome of IL-1β signaling is the activation of NFκB, a transcription factor that induces a large number of immune molecules, apoptotic factors, anti-apoptotic factors, and other transcription factors. Recent work has demonstrated that the activation of NFκB involves a multistep redox-signaling cascade that requires endocytosis of the interleukin receptor (IL-1R1)/ligand pair and superoxide production by NADPH oxidase 2 (Nox2) within the resulting newly formed early endosome. Hydrogen peroxide produced by the rapid dismutation of superoxide is necessary for the subsequent downstream recruitment of IL-1R1 effectors (TRAF6, IKK kinases) and ultimately the activation of NFκB. In this thesis, I have further dissected the spatial and temporal events that coordinate signaling processes of the IL-1β pathway. Using a combination of biophotonic imaging, immunofluorescence imaging, and lipid raft density gradient isolation, I demonstrate that both Nox2 and IL-1R1 are constitutively present in lipid raft microdomains on the plasma membrane. Stimulation by IL-1β induces endocytosis of Nox2 and IL-1R1 from the plasma membrane into caveolin-1, lipid raft positive early endosomes. Further, inhibition of lipid raft mediated endocytosis or deletion of caveolin-1 inhibits activation of NFκB, by IL-1β. We have also identified Vav1 as the Rac1 guanine exchange factor that is recruited to caveolin-1 positive lipid rafts following IL-1β stimulation, and demonstrated that dominant negative Vav1 inhibits NFκB activation by IL-1β. Following this work, I utilized assays for redox sensitivity and mass spectrometry to demonstrate that C70, C73, and C105 are hydrogen peroxide sensitive cysteines within the RING domain of TRAF6. I further demonstrate that hydrogen peroxide does not alter the E3 ubiquitin ligase activity associated with the TRAF6 RING domain. My findings suggest that the redox sensitivity of the RING domain mediates TRAF6 recruitment to the receptor complex. This is supported by the observation that hydrogen peroxide treatment of TRAF6, but not early signaling effectors (IL-1R1, IRAK1, IRAK4, MyD88) mediates TRAF6 recruitment to the IL-1 receptor complex. Further, mutation of the identified redox sensitive cysteines inhibits IL-1β signaling and NFκB activation. This research has helped to refine the understanding of the IL-1β signaling pathway, and may ultimately lead to new therapeutic targets for controlling inflammation.

Abstract:

Since the early 80s, the computer industry has undergone great expansion. Processors are becoming faster and more powerful. Power management issues in computing systems are becoming more and more complex and challenging. An evolution began when the high-performance Pentium processor was driven by a non-standard, less-than-5V power supply, instead of drawing its power from the 5V plane on the system board. A so-called Voltage Regulator Module (VRM) is put close to the processor in order to provide the power as quickly as possible. Nowadays, for desktop and workstation applications, VRM input voltage has moved to the 12V output of the silver box. In the meantime, microprocessors will run at very low voltage (below 1V), will consume up to 100A of current, and will have dynamics of about 400A/us. In the near future, VRM will be replaced with VRD because of the parasitic components effect. The specifications requirements for VRD are even more challenging than VRM. With this kind of tight tolerance, high current and fast current slew rate, transient response requirements for VRD design are very challenging, especially for step-down transient. During step-down transient, there is some additional energy stored in inductor. Traditional switching regulator like multi-phase buck can do nothing for this even by saturating the duty cycle to 0. All of the additional energy in inductor will be dumped into output cap and cause a large voltage spike at the output voltage. Even for step-up transient, traditional linear control like voltage loop control canâ t provide enough bandwidth because of the slow compensation and slow slew rate of the error amplifier. So the voltage drop is still quite large. Comparing with traditional linear controlled switching regulator such as voltage control and current control buck converter, active clamp has a lot of the advantages for the transient response. With proper design, active clamp can generate a very high bandwidth since there is no compensator needed in the control loop. Since active clamp bypasses inductor and is connected directly to the output cap, it can quickly source and sink current from the output cap even during the step-down transient and prevent overshooting of the output voltage. This is the biggest advantage for active clamp comparing with traditional linear control. In this thesis, a new active clamp structure is proposed. Several new concepts are proposed like non-linear Gm, built-in offset Gm, error signal feedback and AVP design. A one-channel buck converter with new active clamp and voltage loop control is implemented and verified using real transistors based on 0.5um CMOS process.
Master of Science

Abstract:

Fuel supply issues are a major concern in remote island communities and this is an engineering field that needs to be analyzed in detail for transition to sustainable energy systems. Power generation in remote communities such as the islands of the Maldives relies on power generation systems primarily dependent on diesel generators. As a consequence, power generation is easily disrupted by factors such as the delay in transportation of diesel or rises in fuel price, which limits shipment quantity. People living in remote communities experience power outages often, but find them just as disruptive as people who are connected to national power grids. The use of renewable energy sources could help to improve this situation, however, such systems require huge initial investments. Remote power systems often operate with the help of financial support from profit-making private agencies and government funding. Therefore, investing in such hybrid systems is uncommon. Current electrical power generation systems operating in remote communities adopt an open loop control system, where the power supplier generates power according to customer demand. In the event of generation constraints, the supplier has no choice but to limit the power supplied and this often results in power cuts. Most smart grids that are being established in developed grids adopt a closed loop feedback control system. The smart grids integrated with demand side management tools enable the power supplier to keep customers informed about their daily energy consumption. Electric utility companies use different demand response techniques to achieve peak energy demand reduction by eliciting behavior change. Their feedback information is commonly based on factors such as cost of energy, environmental concerns (carbon dioxide intensity) and the risk of black-outs due to peak loads. However, there is no information available on the significant link between the constraints in resources and the feedback to the customers. In resource-constrained power grids such as those in remote areas, there is a critical relationship between customer demand and the availability of power generation resources. This thesis develops a feedback control strategy that can be adopted by the electrical power suppliers to manage a resource-constrained remote electric power grid such that the most essential load requirements of the customers are always met. The control design introduces a new concept of demand response called participatory demand response (PDR). PDR technique involves cooperative behavior of the entire community to achieve quality of life objectives. It proposes the idea that if customers understand the level of constraint faced by the supplier, they will voluntarily participate in managing their loads, rather than just responding to a rise in the cost of energy. Implementation of the PDR design in a mini-grid consists of four main steps. First, the end-use loads have to be characterized using energy audits, and then they have to be classified further into three different levels of essentiality. Second, the utility records have to be obtained and the hourly variation factors for the appliances have to be calculated. Third, the reference demand curves have to be generated. Finally, the operator control system has to be designed and applied to train the utility operators.A PDR case study was conducted in the Maldives, on the island of Fenfushi. The results show that a significant reduction in energy use was achieved by implementing the PDR design on the island. The overall results from five different constraint scenarios practiced on the island showed that during medium constrained situations, load reductions varied between 4.5kW (5.8%) and 7.7kW (11.3%). A reduction of as much as 10.7kW (15%) was achieved from the community during a severely constrained situation.

Abstract:

This master thesis studies the potential benefit of iterative selection of the concentrations evaluated when building mathematical dose-response curves (and response surfaces when there are two drugs) using experimental measurements. The reference alternative is to use a standard two-fold dilution series or ten-fold dilution series measured in replicates. The standard 4-parameter Hill dose-response model is used as a reference and for simulations. Models to screen for synergy between two different substances are also developed in this thesis.

Abstract:

Major depressive disorder (MDD) is a growing health problem. Current treatment options are not always effective and take several weeks of regular administration before an improvement can be seen in symptoms. Sub-anaesthetic doses of ketamine have been found to have antidepressant effects in previously treatment-resistant MDD after just one dose. However, ketamine also produces short term psychosis-like side effects which are undesirable for MDD patients. Ketamine is known to be an NMDA receptor antagonist, binding within the channel pore to block ion flow, however the molecular mechanism(s) underlying its antidepressant and psychosis-like effects are still unclear. In this thesis several genetically modified mouse lines were used to probe the molecular events involved in ketamine's actions. Firstly, a mouse line in which the c-terminal domain (CTD) of the NMDAR subtype GluN2B had been replaced with that of GluN2A, and a second line in which the opposite replacement had taken place, were used to investigate the role of the CTD in the NMDAR response to ketamine. It was found that the GluN2B CTD is required for the short-term psychosis-like response to a sub-anaesthetic dose of ketamine. This is interesting as the channel pore region, containing the binding site for ketamine, is unaltered in these mutants. Therefore, this finding implicates GluN2B CTD specific intracellular signalling molecules in this action of ketamine and raises the question of whether the CTD itself is able to respond to ketamine binding within the pore to induce signalling changes, perhaps via a conformational change. Secondly, a mouse line, in which the activity-regulated synaptic protein Arc has been tagged with a fluorescent marker, was used to investigate the response of synapses to both anaesthetic and sub-anaesthetic doses of ketamine. In this experiment tagged Arc protein was visible as punctate accumulations at synapses. A novel method termed 'synaptome mapping' was used to image these accumulations across entire coronal sections and to quantify their number, size and intensity. Using this method alterations to the Arc synaptome map were detected 1h, 6h and 24h following ketamine administration. The two doses used produced different changes to this map, with the sub-anaesthetic antidepressant dose inducing increases in Arc puncta number across many brain regions, whereas the anaesthetic dose induced short term (1h) increases followed by longer term decreases in Arc puncta number. This finding links long-term increases in Arc at the synapse with an antidepressant response to ketamine.

Abstract:

When proteins are unable to fold properly in the endoplasmic reticulum (ER), theresultant formation of misfolded proteins causes stress of the ER. Cells with ER stressoften have a higher abundance of reactive oxygen species (ROS). Previous studiessuggest that ROS could aggravate ER stress by further disrupting the ER proteinfolding process. More recent studies suggest that the unfolded protein responsesignaling pathways activated by ER stress could lead to the production of ROS. Suchstudies lead to the hypothesis that ER stress could be promoted by ROS, and viceversa. The aim of the present study is to test the above hypothesis by studying howROS could be generated in ER-stressed cells. This is followed by investigating if ROScould increase or decrease the level of ER stress in cells. Finally, the extent of ERstress induced cell death in the presence and absence of ROS is assessed.The treatment of HeLa cells with tunicamycin (Tm), a common ER-stressinducing agent, resulted in the elevation of intracellular ROS that could be detectedwith the ROS-reactive probe dichlorodihydrofluorescein (DCF), but notdihydroethidium which is relatively specific towards superoxide anion. TheTm-induced elevation of ROS could be prevented by co-incubation of cells with thiolreductants such as dithiothreitol and N-acetylcysteine but not with the free radicalscavenger ascorbate. The tunicamycin-induced elevation of ROS level could also beprevented by the over-expression of catalase in HeLa. These data is consistent withthe idea that hydrogen peroxide is a major form of ROS produced in Tm-treated cells.In addition to elevation of ROS level, HeLa cells treated with tunicamycin alsoresulted in the phosphorylation of PERK and eIF2α, and the splicing of XBP-1. In thepresence of cycloheximide to inhibit protein synthesis so as to deplete proteinsubstrates for folding in the ER, tunicamycin-induced ER stress was greatlyminimized as was evident by the absence of both the phosphorylation of PERK andsplicing of XBP-1. However, the phosphorylation of eIF2α and elevation ofDCF-detectable ROS remained unaffected. The cycloheximde-resistantphosphorylation of eIF2α could be prevented when cells were co-treated with thiolreductants, or upon the over-expression of catalase. These data suggest that theproduction of ROS in Tm-treated cells does not require the presence of ER stress as aprerequisite. Furthermore, the ROS so produced could induce phosphorylation ofeIF2α without the need to cause ER stress in the first place.The quenching of ROS through the use of thiol reductants, or the over-expressionof catalase, had no effect on inhibition of protein synthesis in cells treated withtunicamycin. However, the extent of cell death was significantly increased. The dataobtained in this study is not consistent with the idea that ROS is a downstreamproduct of ER stress, capable of inducing more ER-stress by a feedback mechanism.Therefore, a mutually enhancing effect between ER stress and ROS may not exist.The ROS found in stressed cells may serve to extend cellular survival under thecondition of continuous stress.
published_or_final_version
Biochemistry
Doctoral
Doctor of Philosophy