829 resultados para Critical to Satisfaction


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Thesis (Ph.D.)--University of Washington, 2016-08

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Thesis (Ph.D.)--University of Washington, 2016-07

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Research in ubiquitous and pervasive technologies have made it possible to recognise activities of daily living through non-intrusive sensors. The data captured from these sensors are required to be classified using various machine learning or knowledge driven techniques to infer and recognise activities. The process of discovering the activities and activity-object patterns from the sensors tagged to objects as they are used is critical to recognising the activities. In this paper, we propose a topic model process of discovering activities and activity-object patterns from the interactions of low level state-change sensors. We also develop a recognition and segmentation algorithm to recognise activities and recognise activity boundaries. Experimental results we present validates our framework and shows it is comparable to existing approaches.

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The tumour microenvironment (TME) is an important factor in determining the growth and metastasis of colorectal cancer, and can aid tumours by both establishing an immunosuppressive milieu, allowing the tumour avoid immune clearance, and by hampering the efficacy of various therapeutic regimens. The tumour microenvironment is composed of many cell types including tumour, stromal, endothelial and immune cell populations. It is widely accepted that cells present in the TME acquire distinct functional phenotypes that promote tumorigenesis. One such cell type is the mesenchymal stromal cell (MSC). Evidence suggests that MSCs exert effects in the colorectal tumour microenvironment including the promotion of angiogenesis, invasion and metastasis. MSCs immunomodulatory capacity may represent another largely unexplored central feature of MSCs tumour promoting capacity. There is considerable evidence to suggest that MSCs and their secreted factors can influence the innate and adaptive immune responses. MSC-immune cell interactions can skew the proliferation and functional activity of T-cells, dendritic cells, natural killer cells and macrophages, which could favour tumour growth and enable tumours to evade immune cell clearance. A better understanding of the interactions between the malignant cancer cell and stromal components of the TME is key to the development of more specific and efficacious therapies for colorectal cancer. Here, we review and explore MSC- mediated mechanisms of suppressing anti-tumour immune responses in the colon tumour microenvironment. Elucidation of the precise mechanism of immunomodulation exerted by tumour-educated MSCs is critical to inhibiting immunosuppression and immune evasion established by the TME, thus providing an opportunity for targeted and efficacious immunotherapy for colorectal cancer growth and metastasis.

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Retinitis pigmentosa (RP) is a degenerative retinal disease leading to photoreceptor cell loss. In 2011, our group identified the synthetic progesterone ‘Norgestrel’ as a potential treatment for RP. Subsequent research showed Norgestrel to work through progesterone receptor membrane component 1 (PGRMC1) activation and upregulation of neuroprotective basic fibroblast growth factor (bFGF). Using trophic factor deprivation of 661W photoreceptor-like cells, we aimed to further elucidate the mechanism leading to Norgestrel-induced neuroprotection. In the present manuscript, we show by flow cytometry and live-cell immunofluorescence that Norgestrel induces an increase in cytosolic calcium in both healthy and stressed 661Ws over 24h. Specific PGRMC1 inhibition by AG205 (1 μM) showed this rise to be PGRMC1-dependent, primarily utilising calcium from extracellular sources, for blockade of L-type calcium channels by verapamil (50 μM) prevented a Norgestrel-induced calcium influx in stressed cells. Calcium influx was also shown to be bFGF-dependent, for siRNA knock down of bFGF prevented Norgestrel-PGRMC1 induced changes in cytosolic calcium. Notably, we demonstrate PGRMC1-activation is necessary for Norgestrel-induced bFGF upregulation. We propose that Norgestrel protects through the following pathway: binding to and activating PGRMC1 expressed on the surface of photoreceptor cells, PGRMC1 activation drives bFGF upregulation and subsequent calcium influx. Importantly, raised intracellular calcium is critical to Norgestrel's protective efficacy, for extracellular calcium chelation by EGTA abrogates the protective effects of Norgestrel on stressed 661W cells in vitro.

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O caráter competitivo dos mercados na área do turismo tem-se acentuado nas últimas décadas e, por conseguinte, cada vez mais os destinos têm de conseguir demonstrar a sua diferenciação. Ao desempenhar um papel fundamental no comportamento dos consumidores e, em particular, na tomada de decisão sobre os destinos a visitar, a imagem do destino na mente dos consumidores finais e dos intermediários que os comercializam é fundamental para o sucesso dos destinos. Desta forma, a imagem dos destinos turísticos tem sido alvo de extensa investigação, uma vez que a compreensão da imagem percebida dos destinos e também da imagem projetada através dos diversos canais de promoção poderá permitir a identificação de aspetos a melhorar nas suas estratégias de marketing, uma maior eficiência dos recursos financeiros investidos no estímulo da procura turística e uma maior eficácia na atração dos turistas que, consecutivamente, avaliam potenciais novos destinos a visitar. A presente dissertação tem como objeto de estudo o destino turístico Portugal e debruça-se sobre a análise da imagem percebida, na perspetiva dos intermediários turísticos dos cinco países que mais enviam turistas para Portugal, e da imagem projetada no portal oficial de promoção deste destino. Os seus objetivos centrais prendem-se com a comparação destas duas vertentes da imagem, no sentido de apurar as suas diferenças e semelhanças e, assim, apurar contributos relevantes para as estratégias de promoção do destino Portugal, e ainda a identificação dos fatores determinantes da imagem percebida de Portugal pelos intermediários turísticos analisados e das suas consequências ao nível da lealdade atitudinal. De uma forma global, conclui-se que a imagem percebida e a imagem projetada de Portugal como destino turístico apresentam semelhanças em alguns aspetos e diferenças noutros. Além disso, verifica-se que um conjunto de fatores determinantes exerce influência sobre a imagem percebida de Portugal como destino turístico e que esta tem efeito sobre a lealdade atitudinal dos intermediários turísticos, traduzida nas intenções de recomendação do destino.

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Asian elephants (Elephas maximus) are critically endangered and live in fragmented populations spread across 13 countries. Yet in comparison to the African savannah elephant (Loxodonta africana), relatively little is known about the social structure of wild Asian elephants because the species is mostly found in low visibility habitat. A better understanding of Asian elephant social structure is critical to mitigate human-elephant conflicts that arise due to increasing human encroachments into elephant habitats. In this dissertation, I examined the social structure of Asian elephants at three sites: Yala, Udawalawe, and Minneriya National Parks in Sri Lanka, where the presence of large open areas and high elephant densities are conducive to behavioral observations. First, I found that the size of groups observed at georeferenced locations was affected by forage availability and distance to water, and the effects of these environmental factors on group size depended on site. Second, I discovered that while populations at different sites differed in the prevalence of weak associations among individuals, a core social structure of individuals sharing strong bonds and organized into highly independent clusters was present across sites. Finally, I showed that the core social structure preserved across sites was typically composed of adult females associating with each other and with other age-sex classes. In addition, I showed that females are social at all life stages, whereas males gradually transition from living in a group to a more solitary lifestyle. Taking into consideration these elements of Asian elephant social structure will help conservation biologists develop effective management strategies that account for both human needs and the socio-ecology of the elephants.

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Coffee berries are known to release several volatile organic compounds, among which is the spiroacetal, conophthorin, an attractant for the coffee berry borer Hypothenemus hampei. Elucidating the effects of other spiroacetals released by coffee berries is critical to understanding their chemo-ecological roles in the host discrimination and colonization process of the coffee berry borer, and also for their potential use in the management of this pest. Here, we show that the coffee berry spiroacetals frontalin and 1,6-dioxaspiro [4.5] decane (referred thereafter as brocain), are also used as semiochemicals by the coffee berry borer for host colonization. Bioassays and chemical analyses showed that crowding coffee berry borers from 2 to 6 females per berry, reduced borer fecundity, which appeared to correlate with a decrease in the emission rates of conophthorin and frontalin over time. In contrast, the level of brocain did not vary significantly between borer-uninfested and infested berries. Brocain was attractive at lower doses, but repellent at higher doses while frontalin alone or in a blend was critical for avoidance. Field assays with a commercial attractant comprising a mixture of ethanol and methanol (1:1), combined with frontalin, confirmed the repellent effect of this compound by disrupting capture rates of H. hampei females by 77% in a coffee plantation. Overall, our results suggest that the levels of frontalin and conophthorin released by coffee berries determine the host colonization behaviour of H. hampei, possibly through a 'push-pull' system, whereby frontalin acts as the 'push' (repellent) and conophthorin acting as the 'pull' (attractant). Furthermore, our results reveal the potential use of frontalin as a repellent for management of this coffee pest.

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This research aimed to identify the link between the layout of workspaces in offices and the design strategies for environmental comfort. Strategies surveyed were focused on the thermal, visual and luminic comfort. In this research, visual comfort is related to issues of visual integration within and between the interior and exterior of the building. This is a case study conducted at the administrative headquarters of Centro Regional Nordeste do Instituto de Pesquisas Espaciais (INPE-CRN), located in Natal/RN. The methodological strategy used was the Post-Occupancy Evaluation, which combined the survey data on the building (layout of workspaces, bioclimatic strategies adopted in the design, use of these strategies) with some techniques aimed at acquiring qualitative information related to users. The workspace layout is primordial to satisfaction and productivity of workers. Issues such as concentration, communication, privacy, personal identity, density and space efficiency, barriers (access, visual and even ventilation and lighting), among others, are associated with the layout. The environmental comfort is one of the essential elements to maintaining life quality in workplace. Moreover, it is an important factor in user`s perception of the space in which he or she are inserted. Both layout and environmental comfort issues should be collected and analyzed in the establishment phase of the programming step. That way, it is possible to get adequate answers to these questions in subsequent project phases. It was found that changes in the program that occurred over time, especially concerning persons (number and characteristics), resulted in changes in layout, generating high density and inflexible environments. It turns difficult to adjust the furniture to the occupants` requirement, including comfort needs. However, the presence of strategies for environmental quality provides comfort to spaces, ensuring that, even in situations not considered optimal, users perceive the environment in a positive way. It was found that the relationship between environmental comfort and layout takes the following forms: in changing the perception of comfort, depending on the layout of the arrangements; adjustments in layout, due to needs for comfort; and the elevation of user satisfaction and environmental quality due to the presence of strategies comfort even in situations of inadequate layout

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Policymakers make many demands of our schools to produce academic success. At the same time, community organizations, government agencies, faith-based institutions, and other groups often are providing support to students and their families, especially those from high-poverty backgrounds, that are meant to impact education but are often insufficient, uncoordinated, or redundant. In many cases, these institutions lack access to schools and school leaders. What’s missing from the dominant education reform discourse is a coordinated education-focused approach that mobilizes community assets to effectively improve academic and developmental outcomes for students. This study explores how education-focused comprehensive community change initiatives (CCIs) that utilize a partnership approach are organized and sustained. In this study, I examine three research questions: 1. Why and how do school system-level community change initiative (CCI) partnerships form? 2. What are the organizational, financial, and political structures that support sustainable CCIs? What, in particular, are their connections to the school systems they seek to impact? 3. What are the leadership functions and structures found within CCIs? How are leadership functions distributed across schools and agencies within communities? To answer these questions, I used a cross-case study approach that employed a secondary data analysis of data that were collected as part of a larger research study sponsored by a national organization. The original study design included site visits and extended interviews with educators, community leaders and practitioners about community school initiatives, one type of CCI. This study demonstrates that characteristics of sustained education-focused CCIs include leaders that are critical to starting the CCIs and are willing to collaborate across institutions, a focus on community problems, building on previous efforts, strategies to improve service delivery, a focus on education and schools in particular, organizational arrangements that create shared leadership and ownership for the CCI, an intermediary to support the initial vision and collaborative leadership groups, diversified funding approaches, and political support. These findings add to the literature about the growing number of education-focused CCIs. The study’s primary recommendation—that institutions need to work across boundaries in order to sustain CCIs organizationally, financially, and politically—can help policymakers as they develop new collaborative approaches to achieving educational goals.

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Introdução: A notificação de eventos tornou-se um importante instrumento para a melhoria da qualidade no sistema de saúde. Partilhar a ocorrência de eventos na área dos cuidados de saúde é fundamental para a implementação de mecanismos de prevenção que aumentem a segurança do doente. Objetivo: Conhecer a adesão dos enfermeiros à notificação de eventos nos serviços de internamento e unidades de cuidados intensivos de um hospital central. Metodologia: Estudo exploratório descritivo, com abordagem quantitativa. Resultados: Relativamente aos eventos em que o dano é trágico, a grande maioria das vezes são notificados. Em relação à queda, todos os profissionais com quem ocorreu este evento, notificaram. Os enfermeiros apontam como principais barreiras à notificação de eventos: o esquecimento decorrente do excesso de trabalho; a evolução do evento tornar desnecessária a notificação e a aplicação informática para notificação ser complicada, não ser intuitiva. Conclusões: Após a recolha de dados verificamos, que quando ocorrem eventos, os enfermeiros notificam-nos poucas vezes. Os resultados obtidos apontam algumas orientações para a melhoria da cultura de segurança na instituição, ressalvando-se a necessidade de formação na área da segurança e da notificação antes de o evento acontecer.

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Abstract The two-component based chemotaxis signal transduction system allows flagellated bacteria to sense their surrounding chemical environment and move towards more favorable conditions. The attractant signals can be sensed by transmembrane chemoreceptors, and then transmitted to the histidine kinase CheA. Once activated, CheA interacts with the response regulator CheY through phosphorelay, which causes a change in the rotation of the flagella. The direction of flagella rotation determines whether a cell swims straight or just tumbles. Cells also need adaptation to respond to a change in chemical concentrations, and return to their prestimulated level. Adaptation in the B. subtilis chemotaxis system is achieved by three coordinated systems: the methylation system, the CheC/CheD/CheY-p system and the CheV system. CheD, the previously identified receptor deamidase, was shown to be critical to the ability of B. subtilis to perform chemotaxis and is the main focus of this study. This study started from characterization of the enzymatic mechanism of CheD. Results showed that CheD deamidase uses a cysteine hydrolase mechanism. The catalytic triad consisting of Cys33-His50-Thr27, and Ser27 is essential for receptor recognition and binding. In addition, in this study CheC was found to inhibit CheD’s deamidase activity. Through mutant screening, Phe102 on CheD was found to be the essential site to interact with CheC. Furthermore, the CheD/CheC interaction is necessary for the robust chemotaxis in vivo as demonstrated by the cheD (F102E) mutant, which lacks the ability to swim on swarm plates. Despite its deamidase activity, we hypothesized that CheD’s main role is its involvement in the CheD-CheC-CheY-p negative feedback pathway during adaptation. In particular, CheD is likely to help stabilize the transient kinase-activating state through binding to receptors. When CheY-p level is increased, CheC-CheY-p complex may attract CheD away from receptors. In this study, CheC-CheD binding kinetics with CheY or CheYp presence was successfully obtained by a series of SPR experiments. The increased affinity of CheD for CheC in presence of CheYp but not CheY makes likely the hypothesis that CheC-CheD-CheY interact as part of a negative feedback pathway during adaptation. Last, the interaction between CheD and chemoreceptor McpC was studied in order to better understand the role of CheD in adaptation. Results showed that Q304 and Q305 on McpC are essential to recruit CheD. Additionally, the reduced levels of CheD in mcpC (Q304A) or (Q305A) mutants suggested that the dynamic interaction between CheD and receptors is vital to maintain the normal CheD level. These findings suggest more complicated roles of CheD than its previously identified function as a receptor deamidase, and will lead to a clearer picture of the coordination of the three adaptational systems in the B. subtilis chemotactic sensory transduction system.

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The pig slaughter process involve different steps that can influence the microbiological quality of carcasses. At this, the understanding of the slaughter process on the microbiological aspects is necessary for the implementation and evaluation of critical control points. The microbiological control of the slaughter process should involve the evaluation of pathogens prevalence and levels of quality and hygiene indicator microorganisms. This study aimed at investigating the influence of steps slaughter process on the microbiological levels of pig carcasses, and evaluate if there is correlation between pathogens (Salmonella spp. and Listeria monocytogenes) and indicators (aerobic mesophilic counts, total coliforms, Escherichia coli and Enterobacteriaceae) microorganisms. A high Salmonella soroprevalence in pigs were founded before the slaughter (57.49 %). While the Salmonella prevalence in carcasses at the initial stage of the slaughter was 26.67 % and in the final stage 1.11 %, L. monocytogenes was detected only in the final washing and cooling steps, with a prevalence of 21.11 and 8.89 %, respectively. The aerobic mesophilic counts, Enterobacteriaceae, total coliforms and E. coli levels in initial steps of slaughter process were 4.25 ± 0.37; 1.25 ± 0.38; 1.10 ± 0.35 and 0.86 ± 0.36, respectively. At the end of slaughter process the results were lower (ranging from 0.16 at 2.70 log CFU/cm2). The step that most reduced microbiological levels was the scalding. The dehairing was a critical step that led to a significant increase of microorganisms levels in the process (p < 0.05). The evisceration not proved to be a critical step on the increase of microbial levels, differently of the final washing, which showed significant increases (p < 0.05) over the levels of aerobic counts, total coliforms, E. coli and enterobacterias (0.30; 0.36; 0.27 and 0.42 log respectively) and Salmonella spp. and L. monocytogenes. The chilling contributes significantly to the reduction of microbiological levels of carcasses, bringing them to levels below the all process stages, with the exception of scalding. No correlation between the hygiene indicator microorganisms used and presence of Salmonella spp. and L. monocytogenes were obtained (p < 0.05). The results show that steps in the process are critical to the sanitary profile, which implies the need to implement actions in the process to reducing the microbiological levels.