863 resultados para inhibition zones


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As global warming entails new conditions for the built environment, the thermal and energy performance of existing buildings, which are designed based on current weather data, may become unclear and remain a great concern. Through building computer simulation and qualitative analysis of the weighted factor for the outdoor temperature impact on building energy and thermal performance, this paper investigates the sensitivity of different office building zoning to the potential global warming. A standard office building type is examined for all eight capital cities in Australia. Results show that comparing the middle and top floors, except for cool climate (i.e. Hobart), the ground floor appears to be the most sensitive to the effect of global warming and has the highest tendency for a overheating problem. From the analysis of the responses of different zone orientations to the outdoor air temperature increase, it is also found that there are widely varied responses between zone orientations, with South zone (in the southern hemisphere) being the most sensitive. With an increased external air temperature, the variation between different floors or zone orientations will become more significant, up to 53 percent increase of overheating hours in Darwin and 47 percent increase of cooling load in Hobart.

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Queensland's new State Planning Policy for Coastal Protection, released in March and approved in April 2011 as part of the Queensland Coastal Plan, stipulates that local governments prepare and implement adaptation strategies for built up areas projected to be subject to coastal hazards between present day and 2100. Urban localities within the delineated coastal high hazard zone (as determined by models incorporating a 0.8 meter rise in sea level and a 10% increase in the maximum cyclone activity) will be required to re-evaluate their plans to accommodate growth, revising land use plans to minimise impacts of anticipated erosion and flooding on developed areas and infrastructure. While implementation of such strategies would aid in avoidance or minimisation of risk exposure, communities are likely to face significant challenges in such implementation, especially as development in Queensland is so intensely focussed upon its coasts with these new policies directing development away from highly desirable waterfront land. This paper examines models of planning theory to understand how we plan when faced with technically complex problems towards formulation of a framework for evaluating and improving practice.

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Subchondral bone sclerosis is a well-recognised manifestation of osteoarthritis (OA). The osteocyte cell network is now considered to be central to the regulation of bone homeo-stasis; however, it is not known whether the integrity of the osteocyte cell network is altered in OA patients. The aim of this study was to investigate OA osteocyte phenotypic changes and its potential role in OA subchondral bone pathogenesis. The morphological and phenotypic changes of osteocytes in OA samples were investigated by micro-CT, SEM, histology, im-munohistochemistry, TRAP staining, apoptosis assay and real-time PCR studies. We demonstrated that in OA subchondral bone, the osteocyte morphology was altered showing rough and rounded cell body with fewer and disorganized dendrites compared with the os-teocytes in control samples. OA osteocyte also showed dysregulated expression of osteocyte markers, apoptosis, and degradative enzymes, indicating that the phenotypical changes in OA osteocytes were accompanied with OA subchondral bone remodelling (increased osteoblast and osteoclast activity) and increased bone volume with altered mineral content. Significant alteration of osteocytes identified in OA samples indicates a potential regulatory role of osteocytes in subchondral bone remodelling and mineral metabolism during OA pathogene-sis.

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As global warming entails new conditions for the built environment, the thermal behavior of existing buildings, which were designed based on current weather data, may become unclear and remain a great concern. Through building computer simulation, this paper investigates the sensitivity of different office building zoning to the potential global warming. From the sample office building examined, it is found that compared with the middle and top floors, the ground floor for most cities appears to be most sensitive to the effect of global warming and has the highest tendency to having the overheating problem. From the analysis of the responses of different zone orientations to the outdoor air temperature increase, it is also found that there are widely different responses between different zone orientations, with South or Core zone being most sensitive. With an increased external air temperature, the difference between different floors or different zone orientations will become more significant.

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The creative cities literature gives an emphasis to developing cultural amenity and creative clusters in inner city areas, in order to attract both international visitors and what Richard Florida termed the “creative class”. But many creative workers live in outer urban zones (suburbs). How do creative industries policies meet their needs? This paper reports on a three-year study supported by the Australian Research Council into creative workforce in Australian suburbs in the cities of Melbourne and Brisbane.

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Background Excessive speed contributes to the incidence and severity of road crashes. The Theory of Planned Behaviour (TPB) has successfully explained variance in speeding intentions and behaviour. However, studies have shown that more than 40% of the variance in outcome measures of speeding remains unexplained, thus, suggesting additional constructs may help to enhance the TPB’s predictive power. Therefore, this study examined mindfulness; a promising construct which has not yet been tested as an additional TPB predictor. Aims The aims of this study were to explore drivers’ beliefs about speeding in school zones using the extended TPB as a framework and to examine the effect that mindfulness had on driver speeding behaviour in school zones. Methods Australian drivers (N = 17) participated in one of four focus group discussions. The overall sample was comprised of five males and twelve females who were aged between 17 to56 years. All participants were recruited via purposive sampling among 1st year psychology students at a large South East Queensland University. The group discussions took approximately one hour and were guided by a structured interview schedule which sought to elicit drivers’ beliefs, thoughts and opinions on speeding in school zones and the factors which motivate such behaviour. Results Overall, thematic analysis revealed some similar issues emerged across the groups. . In particular and perhaps somewhat unsurprisingly, given public concerns regarding the want to ensure the safety of school children, there was much agreement that speeding in school zones was dangerous and unacceptable. Somewhat paradoxically however, some participants also agreed that they had unintentionally or mindlessly sped in school zones. There were several factors that drivers believed influenced their speeding in school zones including their current mood (e.g., if in a bad mood, anxious, or excited they may be more likely to drive without awareness of, and being attentive to, their driving environment) and the extent to which they were familiar with the environment (i.e., more familiar contexts, more likely to drive mindlessly). Thus, although drivers expressed a belief that speeding in school zones was dangerous and acceptable, the extent to which a driver is mindful does influence whether or not a driver may actually engage in speeding in this context. Discussion and conclusions This study highlights the potential role of mindfulness in helping to explain speeding behaviour in school zones. Mindless drivers may speed unintentionally and while unintentional still be endangering the safety and lives of school children. The findings of this research suggest that unintentional speeding, especially in school zones, may be reduced by countermeasures which heighten the extent to which drivers are mindful of approaching and/or driving through a school zone, such as street markings and engineering measures (e.g.,flashing lights and speed bumps).

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The effect of plasma taken from normotensive humans, while on a low and high sodium diet, on [Na + K]-ATPase and 3H-ouabain binding was measured in tubules from guinea-pig kidneys. Plasma from the high sodium, compared to the low sodium, diet period: (a) inhibited [Na + K]-ATPase activity; (b) decreased 3H-ouabain affinity for binding sites; (c) increased the number of available 3H-ouabain binding sites; (d) decreased [Na + K]-ATPase turnover (activity/3H-ouabain binding sites). The inhibition of [Na + K]-ATPase suggests an increase in a (possible) natriuretic factor. The decreased affinity of 3H-ouabain binding suggests an endogenous ouabainoid, which may be the natriuretic factor.

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Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX and BAK are critical regulators of mitochondrial apoptosis. New strategies for targeting NSCLC in a mitochondria-independent manner should bypass this common mechanism of apoptosis block. BRCA1 mutation frequency in lung cancer is low; however, decreased BRCA1 mRNA and protein expression levels have been reported in a significant proportion of lung adenocarcinomas. BRCA1 mutation/deficiency confers a defect in homologous recombination DNA repair that has been exploited by synthetic lethality through inhibition of PARP (PARPi) in breast and ovarian cells; however, it is not known whether this same synthetic lethal mechanism exists in NSCLC cells. Additionally, it is unknown whether the mitochondrial apoptotic pathway is required for BRCA1/PARPi-mediated synthetic lethality. Here we demonstrate that silencing of BRCA1 expression by RNA interference sensitizes NSCLC cells to PARP inhibition. Importantly, this sensitivity was not attenuated in cells harbouring mitochondrial apoptosis block induced by co-depletion of BAX and BAK. Furthermore, we demonstrate that BRCA1 inhibition cannot override platinum resistance, which is often mediated by loss of mitochondrial apoptosis signalling, but can still sensitize to PARP inhibition. Finally we demonstrate the existence of a BRCA1-deficient subgroup (11–19%) of NSCLC patients by analysing BRCA1 protein levels using immunohistochemistry in two independent primary NSCLC cohorts. Taken together, the existence of BRCA1-immunodeficient NSCLC suggests that this molecular subgroup could be effectively targeted by PARP inhibitors in the clinic and that PARP inhibitors could be used for the treatment of BRCA1-immunodeficient, platinum-resistant tumours.

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Osteoarthritis is characterized by degenerative alterations of articular cartilage including both the degradation of extracellular matrix and the death of chondrocytes. The PI3K/Akt pathway has been demonstrated to involve in both processes. Inhibition of its downstream target NF-kB reduces the degradation of extracellular matrix via decreased production of matrix metalloproteinases while inhibition of mTOR increased autophagy to reduce chondrocyte death. However, mTOR feedback inhibits the activity of the PI3K/Akt pathway and inhibition of mTOR could result in increased activity of the PI3K/Akt/NF-kB pathway. We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome.

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OBJECTIVE: The fibroblast growth factor (FGF) family of signaling molecules has been associated with chemoresistance and poor prognosis in a number of cancer types, including lung, breast, ovarian, prostate, and head and neck carcinomas. Given the identification of activating mutations in the FGF receptor 2 (FGFR2) receptor tyrosine kinase in a subset of endometrial tumors, agents with activity against FGFRs are currently being tested in clinical trials for recurrent and progressive endometrial cancer. Here, we evaluated the effect of FGFR inhibition on the in vitro efficacy of chemotherapy in endometrial cancer cell lines. METHODS: Human endometrial cancer cell lines with wild-type or activating FGFR2 mutations were used to determine any synergism with concurrent use of the pan-FGFR inhibitor, PD173074, and the chemotherapeutics, doxorubicin and paclitaxel, on cell proliferation and apoptosis. RESULTS: FGFR2 mutation status did not alter sensitivity to either chemotherapeutic agent alone. The combination of PD173074 with paclitaxel or doxorubicin showed synergistic activity in the 3 FGFR2 mutant cell lines evaluated. In addition, although nonmutant cell lines were resistant to FGFR inhibition alone, the addition of PD173074 potentiated the cytostatic effect of paclitaxel and doxorubicin in a subset of FGFR2 wild-type endometrial cancer cell lines. CONCLUSIONS: Together these data suggest a potential therapeutic benefit to combining an FGFR inhibitor with standard chemotherapeutic agents in endometrial cancer therapy particularly in patients with FGFR2 mutation positive tumors.

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Noncompliance with speed limits is one of the major safety concerns in roadwork zones. Although numerous studies have attempted to evaluate the effectiveness of safety measures on speed limit compliance, many report inconsistent findings. This paper aims to review the effectiveness of four categories of roadwork zone speed control measures: Informational, Physical, Enforcement, and Educational measures. While informational measures (static signage, variable message signage) evidently have small to moderate effects on speed reduction, physical measures (rumble strips, optical speed bars) are found ineffective for transient and moving work zones. Enforcement measures (speed camera, police presence) have the greatest effects, while educational measures also have significant potential to improve public awareness of roadworker safety and to encourage slower speeds in work zones. Inadequate public understanding of roadwork risks and hazards, failure to notice signs, and poor appreciation of safety measures are the major causes of noncompliance with speed limits.

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This elicitation study was designed to explore salient behavioural, normative, and control beliefs in accordance with the Theory Planned Behaviour (TPB) and in relation to drivers’ speeding behaviour in school zones. The study also explored mindfulness and habit as additional constructs in the TPB framework. The aim of this study was to identify those beliefs which influenced drivers’ speeding behaviour in school zones and thus gain greater insight into the motivating factors underpinning the behaviour which may inform interventions to reduce this behaviour. Seventeen Australian drivers participated in one of a series of focus group discussions. Overall, conceptual content analysis revealed some similar issues across the groups. In particular, highlighting the influence of behavioural and normative beliefs, there was much agreement that there were no real advantages to speeding in school zones with the behaviour considered dangerous and unacceptable and likely to also be regarded as such by important others. In addition, given the public concern about safety of school children, acknowledgment of such concern represented an important factor discouraging one’s likelihood of engaging in speeding in school zones (i.e., complying with the school zone speed limit). However, despite normative support not to speed, and the need to ensure children’s safety as an important factor discouraging speeding, the study also found that there was a tendency for drivers to report unintentionally speeding in a school zone. Instances of unintentional speeding were reported as occurring due to several reasons including a driver’s current affective state (e.g., more likely to speed in a school zone if they were in a bad mood), the extent to which they were familiar with the environment (i.e., more likely to drive mindlessly – on ‘autopilot’ - in more familiar contexts) and when feeling fatigued. The theoretical implications of including mindfulness and habit with TPB constructs and the practical implications in terms of suggested interventions are discussed.