947 resultados para pro-oxidant activity
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A predictive model of terrorist activity is developed by examining the daily number of terrorist attacks in Indonesia from 1994 through 2007. The dynamic model employs a shot noise process to explain the self-exciting nature of the terrorist activities. This estimates the probability of future attacks as a function of the times since the past attacks. In addition, the excess of nonattack days coupled with the presence of multiple coordinated attacks on the same day compelled the use of hurdle models to jointly model the probability of an attack day and corresponding number of attacks. A power law distribution with a shot noise driven parameter best modeled the number of attacks on an attack day. Interpretation of the model parameters is discussed and predictive performance of the models is evaluated.
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The use of graphical processing unit (GPU) parallel processing is becoming a part of mainstream statistical practice. The reliance of Bayesian statistics on Markov Chain Monte Carlo (MCMC) methods makes the applicability of parallel processing not immediately obvious. It is illustrated that there are substantial gains in improved computational time for MCMC and other methods of evaluation by computing the likelihood using GPU parallel processing. Examples use data from the Global Terrorism Database to model terrorist activity in Colombia from 2000 through 2010 and a likelihood based on the explicit convolution of two negative-binomial processes. Results show decreases in computational time by a factor of over 200. Factors influencing these improvements and guidelines for programming parallel implementations of the likelihood are discussed.
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Because of their limited number of senior positions and fewer alternative career paths, small businesses have a more difficult time attracting and retaining skilled information systems (IS) staff and are thus dependent upon external expertise. Small businesses are particularly dependent on outside expertise when first computerizing. Because small businesses suffer from severe financial constraints. it is often difficult to justify the cost of custom software. Hence. for many small businesses, engaging a consultant to help with identifying suitable packaged software and related hardware, is their first critical step toward computerization. This study explores the importance of proactive client involvement when engaging a consultant to assist with computer system selection in small businesses. Client involvement throughout consultant engagement is found to be integral to project success and frequently lacking due to misconceptions of small businesses regarding their role. Small businesses often overestimate the impact of consultant and vendor support in achieving successful computer system selection and implementation. For consultant engagement to be successful, the process must be viewed as being directed toward the achievement of specific organizational results where the client accepts responsibility for direction of the process.
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Equine laminitis, a disease of the lamellar structure of the horse’s hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Tolllike receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-�), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-inflammatory cytokine production is increased in lamellae and skeletal muscle during equine hyperinsulinaemia. Standardbred horses were treated with either a prolonged, euglycaemic hyperinsulinaemic clamp (p-EHC) or a prolonged, glucose infusion (p-GI), which induced marked and moderate hyperinsulinaemia, respectively. Age-matched control horses were treated simultaneously with a balanced electrolyte solution. Treated horses developed clinical (p-EHC) or subclinical (p-GI) laminitis, whereas controls did not. Skeletal muscle and lamellar protein extracts were analysed by Western blotting for TLR4, IL-6, TNF-� and suppressor of cytokine signalling 3 (SOCS3) expression. Lamellar protein expression of TLR4 and TNF-�, but not IL-6, was increased by the p-EHC, compared to control horses. A significant positive correlation was found between lamellar TLR4 and SOCS3. Skeletal muscle protein expression of TLR4 signalling parameters did not differ between control and p-EHC-treated horses. Similarly, the p-GI did not result in up-regulation of lamellar protein expression of any parameter. The results suggest that insulin-sensitive tissues may not accurately reflect lamellar pathology during hyperinsulinaemia. While TLR4 is present in the lamellae, its activation appears unlikely to contribute significantly to the developmental pathogenesis of hyperinsulinaemic laminitis. However, inflammation may have a role to play in the later stages (e.g., repair or remodelling) of the disease.
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This paper reviews a wide range of literature on environmental management in the field in Queensland, and analyzes this by period and by author. An episodic pattern of activities since European settlement is evident. Periods of exploration (pre-1950) and inventory- compilation (ca. 1950-1970) were followed by two decades of media and non-government organization campaigning (ca. 1970-1990), then an era dominated by government regulatory action (ca. 1990-2010). These eras dominated public perception of what was happening in environmental practice. They were delineated by historic ‘interventions’ (summarily, the end of World War II, the 1971 inflationary crisis, and computerization respectively).
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Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.
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Objectives Given increasing trends of obesity being noted from early in life and that active lifestyles track across time, it is important that children at a very young age be active to combat a foundation of unhealthy behaviours forming. This study investigated, within a theory of planned behaviour (TPB) framework, factors which influence mothers’ decisions about their child’s 1) adequate physical activity (PA) and 2) limited screen time behaviours. Methods Mothers (N = 162) completed a main questionnaire, via on-line or paper-based administration, which comprised standard TPB items in addition to measures of planning and background demographic variables. One week later, consenting mothers completed a follow-up telephone questionnaire which assessed the decisions they had made regarding their child’s PA and screen time behaviours during the previous week. Results Hierarchical multiple regression analyses revealed support for the predictive model, explaining an overall 73% and 78% of the variance in mothers’ intention and 38% and 53% of the variance in mothers’ decisions to ensure their child engages in adequate PA and limited screen time, respectively. Attitude and subjective norms predicted intention in both target behaviours, as did intentions with behaviour. Contrary to predictions, perceived behavioural control (PBC) in PA behaviour and planning in screen time behaviour were not significant predictors of intention, neither was PBC a predictor of either behaviour. Conclusions The findings illustrate the various roles that psycho-social factors play in mothers’ decisions to ensure their child engages in active lifestyle behaviours which can help to inform future intervention programs aimed at combating very young children’s inactivity.
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Background Not getting enough physical activity leads to poorer health. Regular physical activity can reduce the risk of chronic disease and improve one’s health and well-being. The lack of physical activity is a common and growing problem in many countries. We sought to evaluate the effects of community wide, multi-strategic interventions upon the physical activity patterns of populations. Method We undertook a Cochrane Systematic Review which included an extensive search of databases, including studies which met pre-determined criteria, and conducted independent risk of bias assessment and data extraction. Results After the selection process, 25 studies were included in the review. The strategies varied by the number and type of components and their intensity. No studies were identified as low risk of bias. Sixteen studies were identified as having a high risk of bias and thus untrustworthy. Nine studies were of considered to have an unclear risk of bias and some studies held back data they collected. The effects reported were inconsistent across the studies and the measures. Some of the better designed studies showed no improvement in measures of physical activity. Interventions which have an environmental change component seemed to be a promising direction. Those interventions which were primarily a mass media campaign were less likely to be successful. Conclusions Although numerous studies have been undertaken, there is considerable inconsistency in the findings of the available studies and this is confounded by serious methodological issues within the included studies. Simply combining interventions does not necessarily result in increased physical activity as many such studies, including some long term programs, failed to demonstrate efficacy. There is a clear need for well-designed studies and these studies should focus on the quality of measurement of physical activity. The review is currently being updated with newer studies.
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Background Prevention of childhood obesity is a public health priority for Malaysia and many other countries. Physical activity for children is also decreasing at an alarming rate. Both conditions are associated with non-communicable diseases and with significant morbidity and mortality in later life. Systematic reviews of public health interventions provide a useful summary to inform public health practice by combining the results of a range of research studies on a specific intervention into a single report. Systematic reviews are deemed most valuable for health program development and evidence based practice. Unfortunately, many policy makers and practitioners are simply unaware of the evidence: which strategies which are most likely to provide benefit; and which strategies are known to be harmful or useless. This presentation provides a “birds eye” overview based upon recent (since 2007 to present) high quality systematic reviews of public health interventions. Method HealthEvidece.org and the Cochrane Library were searched for systematic reviews which evaluated interventions targeting obesity prevention and increasing physical activity for children. The findings of the included reviews were themed and summarized. Results Seven reviews were identified addressing obesity in the early years, and fifteen reviews addressing obesity more broadly in childhood. Additional reviews were identified aimed at increasing physical activity. The synthesis shows several strategies to be effective, however many popular strategies clearly are not. Several of the reviews were inconclusive due to an absence of robust primary studies. Amongst the findings, interventions undertaken in the school setting appear very promising. Conclusions There is significant evidence from systematic reviews to guide public health practice and policy, and to inform future research.
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The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. Because fMRI records, through the monitoring of blood flow activity, the location of localised brain activity within the brain, the possibility of combining fMRI measurements with EEG, as a joint inversion activity, was discussed and examined in detail. (3) A major goal for the BRI is to improve understanding about ``when'' (at what time) an epileptic seizure actually commenced before it is identified on an eeg recording, ``where'' the source of this initiation is located in the brain, and ``what'' is the initiator. Because of the general agreement in the literature that, in one way or another, epileptic events and seizures represent abnormal synchronisations of localised and/or global brain activity the modelling of synchronisations was examined in some detail. References C. M. Michel, G. Thut, S. Morand, A. Khateb, A. J. Pegna, R. Grave de Peralta, S. Gonzalez, M. Seeck and T. Landis, Electric source imaging of human brain functions, Brain Res. 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The catalytic action of putrescine specific amine oxidases acting in tandem with 4-aminobutyraldehyde dehydrogenase is explored as a degradative pathway in Rhodococcus opacus. By limiting the nitrogen source, increased catalytic activity was induced leading to a coordinated response in the oxidative deamination of putrescine to 4-aminobutyraldehyde and subsequent dehydrogenation to 4-aminobutyrate. Isolating the dehydrogenase by ion exchange chromatography and gel filtration revealed that the enzyme acts principally on linear aliphatic aldehydes possessing an amino moiety. Michaelis-Menten kinetic analysis delivered a Michaelis constant (KM=0.014mM) and maximum rate (Vmax=11.2μmol/min/mg) for the conversion of 4-aminobutyraldehyde to 4-aminobutyrate. The dehydrogenase identified by MALDI-TOF mass spectrometric analysis (E value=0.031, 23% coverage) belongs to a functionally related genomic cluster that includes the amine oxidase, suggesting their association in a directed cell response. Key regulatory, stress and transport encoding genes have been identified, along with candidate dehydrogenases and transaminases for the further conversion of 4-aminobutyrate to succinate. Genomic analysis has revealed highly similar metabolic gene clustering among members of Actinobacteria, providing insight into putrescine degradation notably among Micrococcaceae, Rhodococci and Corynebacterium by a pathway that was previously uncharacterised in bacteria.
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Debates about user-generated content (UGC) often depend on a contrast with its normative opposite, the professionally produced content that is supported and sustained by commercial media businesses or public organisations. UGC is seen to appear within or in opposition to professional media, often as a disruptive, creative, change-making force. Our suggestion is to position UGC not in opposition to professional or "producer media", or in hybridised forms of subjective combination with it (the so-called "pro-sumer" or "pro-am" system), but in relation to different criteria, namely the formal and informal elements in media industries. In this article, we set out a framework for the comparative and historical analysis of UGC systems and their relations with other formal and informal media activity, illustrated with examples ranging from games to talkback radio. We also consider the policy implications that emerge from a historicised reading of UGC as a recurring dynamic within media industries, rather than a manifestation of consumer agency specific to digital cultures.
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Background: Physical activity after breast cancer diagnosis is associated with improved survival. This study examines levels of and changes in physical activity following breast cancer diagnosis, overall and by race. Methods: The Carolina Breast Cancer Study, Phase III, assessed pre- and post-diagnosis physical activity levels in a cohort of 1,735 women, aged 20-74, diagnosed with invasive breast cancer between 2008 and 2011 in 44 counties of North Carolina. Logistic regression and analysis of variance were used to examine whether demographic, behavioral and clinical characteristics were associated with activity levels. Results: Only 35% of breast cancer survivors met current physical activity guidelines post-diagnosis. A decrease in activity following diagnosis was reported by 59% of patients, with the average study participant reducing their activity by 230 minutes (95% CI: 190, 270). Following adjustment for potential confounders, when compared to white women, African-American women were less likely to meet national physical activity guidelines post-diagnosis (odds ratio: 1.38, 95% CI: 1.01, 1.88), reported less weekly post-diagnosis physical activity (182 vs. 215 minutes; p=0.13), and reported higher average reductions in pre- versus post-diagnosis weekly activity (262 vs. 230 minutes; p-value = 0.13). Conclusion: Despite compelling evidence demonstrating the benefits of physical activity post-breast cancer, it is clear that more work needs to be done to promote physical activity in breast cancer patients, especially among African-American women.
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A pro-fibrotic role of matrix metalloproteinase-9 (MMP-9) in tubular cell epithelial-mesenchymal transition (EMT) is well established in renal fibrosis; however studies from our group and others have demonstrated some previously unrecognized complexity of MMP-9 that has been overlooked in renal fibrosis. Therefore, the aim of this study was to determine the expression pattern, origin and the exact mechanism underlying the contribution of MMP-9 to unilateral ureteral obstruction (UUO), a well-established model of renal fibrosis via MMP-9 inhibition. Renal MMP-9 expression in BALB/c mice with UUO was examined on day 1, 3, 5, 7, 9, 11 and 14. To inhibit MMP-9 activity, MMP-2/9 inhibitor or MMP-9-neutralizing antibody was administered daily for 4 consecutive days from day 0-3, 6-9 or 10-13 and tissues harvested at day 14. In UUO, there was a bi-phasic early- and late-stage upregulation of MMP-9 activity. Interestingly, tubular epithelial cells (TECs) were the predominant source of MMP-9 during early stage, whereas TECs, macrophages and myofibroblasts produced MMP-9 during late-stage UUO. Early- and late-stage inhibition of MMP-9 in UUO mice significantly reduced tubular cell EMT and renal fibrosis. Moreover, MMP-9 inhibition caused a significant reduction in MMP-9-cleaved osteopontin and macrophage infiltration in UUO kidney. Our in vitro study showed MMP-9-cleaved osteopontin enhanced macrophage transwell migration and MMP-9 of both primary TEC and macrophage induced tubular cell EMT. In summary, our result suggests that MMP-9 of both TEC and macrophage origin may directly or indirectly contribute to the pathogenesis of renal fibrosis via osteopontin cleavage, which, in turn further recruit macrophage and induce tubular cell EMT. Our study also highlights the time dependency of its expression and the potential of stage-specific inhibition strategy against renal fibrosis.
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Spontaneous play, important for forming the basis of friendships and peer relations, is a complex activity involving the management and production of talk-in-interaction. This paper focuses on the intricacies of social interaction, emphasising the link between alignment and affiliation, and the range and importance of verbal and nonverbal interactive devices available to children. Analysis of the way in which two girls, one of whom has been diagnosed with Asperger’s Syndrome, engage in spontaneous activities demonstrates the potential for interactional difficulty due to the unscripted nature of the interaction. The paper argues for further research into how improvised, unscripted interactions are initiated within moment-by-moment talk, how they unfold, and how they are brought to a close in everyday contexts in order to understand how children create their social worlds.