985 resultados para Gregory, Kenneth J
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Ageing results in a progressive, intrinsic and generalised imbalance of the control of regulatory systems. A key manifestation of this complex biological process includes the attenuation of the universal stress response. Here we provide the first global assessment of the ageing process as it affects the heat shock response, utilising human peripheral lymphocytes and cDNA microarray analysis. The genomic approach employed in our preliminary study was supplemented with a proteomic approach. In addition, the current study correlates the in vivo total antioxidant status with the age-related differential gene expression as well as the translational kinetics of heat shock proteins (hsps). Most of the genes encoding stress response proteins on the 4224 element microarray used in this study were significantly elevated after heat shock treatment of lymphocytes obtained from both young and old individuals albeit to a greater extent in the young. Cell signaling and signal transduction genes as well as some oxidoreductases showed varied response. Results from translational kinetics of induction of major hsps, from 0 to 24 It recovery period were broadly consistent with the differential expression of HSC 70 and HSP 40 genes. Total antioxidant levels in plasma from old individuals were found to be significantly lower by comparison with young, in agreement with the widely acknowledged role of oxidant homeostasis in the ageing process. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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Trans-membrane proteins of the p24 family are abundant, oligomeric proteins predominantly found in cis-Golgi membranes. They are not easily studied in vivo and their functions are controversial. We found that p25 can be targeted to the plasma membrane after inactivation of its canonical KKXX motif (KK to SS, p25SS), and that p25SS causes the co-transport of other p24 proteins beyond the Golgi complex, indicating that wild-type p25 plays a crucial role in retaining p24 proteins in cis-Golgi membranes. We then made use of these observations to study the intrinsic properties of these proteins, when present in a different membrane context. At the cell surface, the p25SS mutant segregates away from both the transferrin receptor and markers of lipid rafts, which are enriched in cholesterol and glycosphingolipids. This suggests that p25SS localizes to, or contributes to form, specialized membrane domains, presumably corresponding to oligomers of p25SS and other p24 proteins. Once at the cell surface, p25SS is endocytosed, together with other p24 proteins, and eventually accumulates in late endosomes, where it remains confined to well-defined membrane regions visible by electron microscopy. We find that this p25SS accumulation causes a concomitant accumulation of cholesterol in late endosomes, and an inhibition of their motility - two processes that are functionally linked. Yet, the p25SS-rich regions themselves seem to-exclude not only Lamp1 but also accumulated cholesterol. One may envision that p25SS accumulation, by excluding cholesterol from oligomers, eventually overloads neighboring late endosomal membranes with cholesterol beyond their capacity (see Discussion). In any case, our data show that p25 and presumably other p24 proteins are endowed with the intrinsic capacity to form highly specialized domains that control membrane composition and dynamics. We propose that p25 and other p24 proteins control the fidelity of membrane transport by maintaining cholesterol-poor membranes in the Golgi complex.
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Two experiments using a temporal occlusion paradigm (the first with expert and novice participants and the second with participants of intermediate skill) were conducted to examine the capability of tennis players to predict the direction of an opponent's service in situ. In both experiments two different response conditions, reflecting differing degrees of perception-action coupling, were employed. In a coupled condition players were required to make a movement-based response identical to that which they would use to hit a return of service in a game situation, whereas in an uncoupled condition a verbal prediction of service direction was required. Experiment 1 provided clear evidence of superior prediction accuracy under the coupled response condition when ball flight was available, plus some limited evidence to suggest that superior prediction accuracy under uncoupled response conditions might hold true if only advance (pre-contact) information was available. Experiment 2 showed the former finding to be a robust one, but was unable to reveal any support for the latter. Experiment 1 also revealed that expert superiority is more apparent for predictions made under natural (coupled) than uncoupled response-mode conditions. Collectively, these findings suggest that different perceptual processes may be in operation in anticipatory tasks which depend on skill level, the type of information presented, and degree of perception-action coupling inherent in the task requirements.
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Purpose: For treatment of various knee disorders, muscles are trained in open or closed kinetic chain tasks. Coordination between the heads of the quadriceps muscle is important for stability and optimal joint loading for both the tibiofemoral and the patellofemoral joint. The aim of this study was to examine whether the quadriceps femoris muscles are activated differently in open versus closed kinetic chain tasks. Methods: Ten healthy men and women (mean age 28.5 +/- 0.7) extended the knees isometrically in open and closed kinetic chain tasks in a reaction time paradigm using moderate force. Surface electromyography (EMG) recordings were made from four different parts of the quadriceps muscle. The onset and amplitude of EMG and force data were measured. Results: In closed chain knee extension, the onset of EMG activity of the four different muscle portions of the quadriceps was more simultaneous than in the open chain. In open chain, rectus femoris (RF) had the earliest EMG onset while vastus medialis obliquus was activated last (7 +/- 13 ms after RF EMG onset) and with smaller amplitude (40 +/- 30% of maximal voluntary contraction (MVC)) than in closed chain (46 +/- 43% MVC). Conclusions: Exercise in closed kinetic chain promotes more balanced initial quadriceps activation than does exercise in open kinetic chain. This may be of importance in designing training programs aimed toward control of the patellofemoral joint.
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Objectives: To describe what is known of quality of life for colorectal cancer patients, to review what has been done in the Australian setting and to identify emerging directions for future research to address current gaps in knowledge. Method: A literature search (using Medline, PsychInfo, CINAHL and Sociological Abstracts) was conducted and 41 articles identified for review. Results: Three key areas relating to quality of life in colorectal cancer patients emerged from the literature review: the definition and measurement of quality of life; predictors of quality of life; and the relationship of quality of life to survival. Results of existing studies are inconsistent in relation to quality of life over time and its relationship to survival. Small sample sizes and methodological limitations make interpretation difficult. Conclusions: There is a need for large-scale, longitudinal, population-based studies describing the quality of life experienced by colorectal cancer patients and its determinants. Measurement and simultaneous adjustment for potential confounding factors would productively advance knowledge in this area, as would an analysis of the economic cost of morbidity to the community and an assessment of the cost effectiveness of proposed interventions. Implications: As the Australian population ages, the prevalence of colorectal cancer within the community will increase. This burden of disease presents as a priority area for public health research. An improved understanding of quality of life and its predictors will inform the development and design of supportive interventions for those affected by the disease.
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Objective: To examine the association between gain in motor and cognitive functional status with patient satisfaction 3-6 mo after rehabilitation discharge. Design: Patient satisfaction and changes in functional status were examined in 18,375 patients with stroke who received inpatient medical rehabilitation. Information was obtained from 144 hospitals and rehabilitation facilities contributing records to the Uniform Data System for Medical Rehabilitation and the National Follow-up Services. Results: Data analysis revealed significant (P < 0.05) differences in satisfaction responses based on whether information was collected from patient self-report or from a family member proxy, and the two subsets were analyzed separately. Logistic regression revealed the following significant predictors of satisfaction for data collected from stroke patients: cognitive and motor gain, rehospitalization, who the patient was living with at follow-up, age, and follow-up therapy. In the patient-reported data subset, compared with patients who showed improved cognitive or motor functional status, those with no change, respectively, had a 31% and 33% reduced risk of dissatisfaction. In addition, rehospitalized patients had a higher risk of dissatisfaction. For the proxy reported data subset, significant influences on satisfaction were health maintenance, rehospitalization, stroke type, ethnicity, cognitive FIM(TM) gain, length of stay, and follow-up therapy. Conclusions: Ratings of satisfaction with rehabilitation services were affected by change in functional status and whether the information was collected from patient rating or proxy response.
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Objectives: To examine the changes in torque output resulting from fatigue, as well as changes in electromyographic measures of trunk muscles during isometric axial rotation and to compare these changes between directions of axial rotation. Design: Subjects performed fatiguing right and left isometric axial rotation of the trunk at 80% of maximum voluntary contraction while standing upright. Setting: A rehabilitation center. Participants: Twenty-three men with no history of back pain. Interventions: Not applicable. Main Outcome Measures: Surface electromyographic Signals were recorded from 6 trunk muscles bilaterally. The primary torque in the transverse plane and the coupling torques in sagittal and coronal planes were also measured. Results: During the fatiguing axial rotation contraction, coupling torques of both sagittal and coronal planes were slightly decreased and no difference was found between directions of axial rotation. Decreasing median frequency and an increase in electromyographic amplitude were also found in trunk muscles with different degrees of changes in individual muscles. There were significant differences (P
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Background Wide testing of the aldosterone: renin ratio among hypertensive individuals has revealed primary aldosteronism to be common, with most patients normokalaemic. Some investigators, however, have reported aldosterone-producing adenoma to be rare among patients so detected. Objective To test the hypothesis that differences among reported studies in the rate of detection of aldosterone-producing adenoma (as opposed to bilateral adrenal hyperplasia) reflect differences in the procedures used for diagnosis of primary aldosteronism, and the methods used to identify aldosterone-producing adenomas. Methods In the newly established Princess Alexandra Hospital Hypertension Unit (PAHHU), we used procedures developed by Greenslopes Hospital Hypertension Unit (which reports that more than 30% of patients with primary aldosteronism have aldosterone-producing adenomas) to diagnose primary aldosteronism and determine the subtype. All patients with an increased aldosterone: renin ratio (measured after correction for hypokalaemia and while the patient was not receiving interfering medications) underwent fludrocortisone suppression testing to confirm or exclude primary aldosteronism; if they were positive, they underwent genetic testing to exclude glucocorticoid-remediable aldosteronism before adrenal venous sampling was used to differentiate lateralizing from bilateral primary aldosteronism. Results This approach allowed PAHHU to diagnose, within 2 years, 54 patients [only seven (13%) hypokalaemic] with primary aldosteronism. All tested negative for glucocorticoid-remediable aldosteronism. Aldosterone production was lateralized to one adrenal in 15 patients (31%; only six hypokalaemic) and was bilateral in 34 (69%; all normokalaemic) of 49 patients who underwent adrenal venous sampling. Among patients with lateralizing adrenal hyperplasia, computed tomography revealed an ipsilateral mass in only six and a contralateral lesion in one. Fourteen patients underwent unilateral adrenalectomy, which cured the hypertension in seven and improved it in the remainder. In patients with bilateral primary aldlosteronism, hypertension responded to spironolactone (112.5-50 mg/ day) or amiloride (2.5-10 mg/day). Conclusion When performed with careful regard to confounding factors, measurement of the aldosterone: renin ratio in all hypertensive individuals, followed by fludrocortisone suppression testing to confirm or exclude primary aldosteronism and adrenal venous sampling to determine the subtype, can result in the detection of significant numbers of patients with specifically treatable or potentially curable hypertension. (C) 2003 Lippincott Williams Wilkins.
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Nesta dissertação discutimos os movimentos em torno da temática da apropriação evidenciando o deslocamento do objeto de uso comum para o campo da arte em três movimentos paradigmáticos: o Dadaísmo, o Surrealismo e o Novo Realismo, e seus desdobramentos na arte contemporânea no sentido de legado cultural. Permitimo-nos transitar pelas demais vertentes dos processos de apropriação na arte nova-iorquina e europeia seguindo as propostas da arte com objetos. Investigamos os processos envolvidos nas controvérsias do ready-made, executado por Marcel Duchamp desde 1913, para dar partida ao percurso histórico das manifestações onde ocorre o objet trouvé, a colagem e a assemblagem. Nosso objetivo é responder à pergunta com a qual o filósofo Arthur C. Danto inicia suas investigações filosóficas acerca das apropriações e condições que fazem de um objeto comum uma obra de arte. Para tanto buscamos as teorias de Abrahan Moles e Jean Baudrillard acerca do objeto industrializado e Roland Barthes com as questões metalingüísticas de sua função-signo. Para discutir tais relações da arte com os objetos, recorremos aos textos de Peter Bürger, André Breton, Pierre Restany, Gregory Battcock, Walter Benjamin, Hal Foster e outros. Destacamos alguns trabalhos artísticos, evidenciando o objeto caixa, tratado como um utilitário com forma e finalidade definidas, reafirmando-se como objeto de consumo, no discurso sobre a poética do espaço de Gaston Bachelard. A pesquisa propõe analisar as transformações radicais das estruturas conservadoras da arte e especular sobre o gesto de apropriação dos objetos, com algumas reflexões direcionadas sobre o objeto e a transgressividade da apropriação como experiência de tensão e poder.
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Distante quatro décadas de seu aparecimento, o modelo de precificação de ativos de capital proposto pelo Nobel William Sharpe e por John Lintner, conhecido como CAPM, é ainda o modelo mais amplamente utilizado na estimativa do custo de capital de empresas e na avaliação de carteiras. O fato se deve às poderosas previsões permitidas pelo modelo sobre a medida do risco e a relação entre risco e retorno. O objetivo deste artigo é mostrar que o CAPM apresenta algumas falhas empíricas associadas a simplifi cações teóricas e difi culdades de implementação de testes que sejam válidos para o modelo. A conclusão do artigo é que as limitações do CAPM representam desafi os a serem explicados por modelos alternativos.
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Muito se tem dito e escrito sobre as peculiaridades da administração estratégica nas micro e pequenas empresas (MPE). Pouco, entretanto, tem sido feito em termos de trabalho empírico, de cunho quantitativo, quando comparado com o volume de pesquisa que trata de grandes empresas. Nesse sentido, o presente artigo buscou explorar o processo de formação de estratégias nessas empresas, descrevendo seus principais aspectos e, principalmente, verificando se há características desse processo que podem ser associadas a níveis de desempenho acima (e/ou abaixo) da média. Para tanto, utilizou-se a análise de regressão linear múltipla para entender as relações existentes entre as variáveis do processo de formação da estratégia consideradas no estudo e o desempenho; e, ainda, a análise discriminante para determinar os indicadores que diferenciam os grupos de empresas com desempenho acima e abaixo da média. Os resultados apontaram uma tendência à utilização de processos de formação de estratégia deliberados e formais. Por outro lado, reconhecemos também, uma tendência de inovação e mudança. O desempenho acima da média das micro e pequenas empresas, ao que parece, é resultado de uma receita balanceada desses dois ingredientes.
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Este artículo presenta una matriz de factores a tomar en cuenta para priorizar las cadenas de valor agrícolas seleccionadas como foco de las iniciativas público-privadas para impulsar su desarrollo. Dichos factores dan especial importancia a temas de responsabilidad social empresarial. Se ilustra su uso con datos y una revisión de la literatura sobre Perú.