903 resultados para cross-domain distinguishing features
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Background: Factors that individually influence blood sugar control, health-related quality of life, and diabetes self-care behaviors have been widely investigated; however, most previous diabetes studies have not tested an integrated association between a series of factors and multiple health outcomes. ---------- Objectives: The purposes of this study are to identify risk factors and protective factors and to examine the impact of risk factors and protective factors on adaptive outcomes in people with type 2 diabetes.---------- Design: A descriptive correlational design was used to examine a theoretical model of risk factors, protective factors, and adaptive outcomes.---------- Settings: This study was conducted at the endocrine outpatient departments of three hospitals in Taiwan. Participants A convenience sample of 334 adults with type 2 diabetes aged 40 and over.---------- Methods: Data were collected by a self-reported questionnaire and physiological examination. Using the structural equation modeling technique, measurement and structural regression models were tested.---------- Results: Age and life events reflected the construct of risk factors. The construct of protective factors was explained by diabetes symptoms, coping strategy, and social support. The construct of adaptive outcomes comprised HbA1c, health-related quality of life, and self-care behaviors. Protective factors had a significant direct effect on adaptive outcomes (β = 0.68, p < 0.001); however, risk factors did not predict adaptive outcomes (β = − 0.48, p = 0.118).---------- Conclusions: Identifying and managing risk factors and protective factors are an integral part of diabetes care. This theoretical model provides a better understanding of how risk factors and protective factors work together to influence multiple adaptive outcomes in people living with type 2 diabetes.
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To date, biodegradable networks and particularly their kinetic chain lengths have been characterized by analysis of their degradation products in solution. We characterize the network itself by NMR analysis in the solvent-swollen state under magic angle spinning conditions. The networks were prepared by photoinitiated cross-linking of poly(dl-lactide)−dimethacrylate macromers (5 kg/mol) in the presence of an unreactive diluent. Using diffusion filtering and 2D correlation spectroscopy techniques, all network components are identified. By quantification of network-bound photoinitiator fragments, an average kinetic chain length of 9 ± 2 methacrylate units is determined. The PDLLA macromer solution was also used with a dye to prepare computer-designed structures by stereolithography. For these networks structures, the average kinetic chain length is 24 ± 4 methacrylate units. In all cases the calculated molecular weights of the polymethacrylate chains after degradation are maximally 8.8 kg/mol, which is far below the threshold for renal clearance. Upon incubation in phosphate buffered saline at 37 °C, the networks show a similar mass loss profile in time as linear high-molecular-weight PDLLA (HMW PDLLA). The mechanical properties are preserved longer for the PDLLA networks than for HMW PDLLA. The initial tensile strength of 47 ± 2 MPa does not decrease significantly for the first 15 weeks, while HMW PDLLA lost 85 ± 5% of its strength within 5 weeks. The physical properties, kinetic chain length, and degradation profile of these photo-cross-linked PDLLA networks make them most suited materials for orthopedic applications and use in (bone) tissue engineering.
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Visual impairment is an important contributing factor in falls among older adults, which is one of the leading causes of injury and injury-related death in this population. Visual impairment is also associated with greater disability among older adults, including poorer health-related quality of life, increased frailty and reduced postural stability. The majority of this evidence, however, is based on measures of central visual function, rather than peripheral visual function. As such, there is comparatively limited research on the associations between peripheral visual function, disability and falls, and even fewer studies involving older adults with specific diseases which affect peripheral visual function, the most common of which is glaucoma. Glaucoma is one of the leading causes of irreversible vision loss among older adults, affecting around 3 per cent of adults aged over 60 years. The condition is characterised by retinal nerve fibre loss, primarily affecting peripheral visual function. Importantly, the number of older adults with glaucomatous visual impairment is projected to increase as the ageing population grows. The first component of the thesis examined the cross-sectional association between glaucomatous visual impairment and health-related quality of life (Study 1a), functional status (Study 1b) and postural stability (Study 1c) among older adults. A cohort of 74 community-dwelling adults with glaucoma (mean age 74.2 ± 5.9 years) was recruited and completed a baseline assessment. A number of visual function measures was assessed, including central visual function (visual acuity and contrast sensitivity), motion sensitivity, retinal nerve fibre analysis and monocular and binocular visual field measures (monocular 24-2 and binocular integrated visual fields (IVF): IVF-60 and IVF-120). The analyses focused on the associations between the outcomes measures and severity and location of visual field loss, as this is the primary visual function affected by glaucoma. In Study 1a, we examined the association between visual field loss and health-related quality of life, measured by the Short Form 36-item Health Survey (SF-36). Greater binocular visual field loss, on both IVF measures, was associated with lower SF-36 physical component scores, adjusted for age and gender (Pearson's r =|0.32| to |0.36|, p<0.001). Furthermore, inferior visual field loss was more strongly associated with the SF-36 physical component than superior field loss. No association was found between visual field loss and SF-36 mental component scores. The association between visual field loss and functional status was examined in Study 1b. Functional status outcomes measures included a physical activity questionnaire (Physical Activity Scale for the Elderly, PASE), performance tests (six-minute walk test, timed up and go test and lower leg strength) and an overall functional status score. Significant, but weak, correlations were found between binocular visual field loss and PASE and overall functional status scores, adjusted for age and gender (Pearson's r =|0.24| to |0.33|, p<0.05). Greater inferior visual field loss, independent of superior visual field loss, was significantly associated with poorer physical performance results and lower overall functional status scores. In Study 1c, we examined the association between visual field loss and postural stability, using a swaymeter device which recorded body movement during four conditions: eyes open and closed, on a firm and foam surface. Greater binocular visual field loss was associated with increased postural sway, both on firm and foam surfaces, independent of age and gender (Pearson’s r =|0.44| to |0.46|, p <0.001). Furthermore, inferior visual field was a stronger contributor to postural stability, more so than the superior visual field, particularly on the foam condition with the eyes open. Greater visual field loss was associated with a reduction in the visual contribution to postural sway, which underlies the observed association with postural sway. The second component of the thesis examined the association between severity and location of visual field loss and falls during a 12-month longitudinal follow-up. The number of falls was assessed prospectively using monthly fall calendars. Of the 71 participants who successfully completed the follow up (mean age 73.9 ± 5.7 years), 44% reported one or more falls, and around 20% reported two or more falls. After adjusting for age and gender, every 10 points missed on the IVF-120 increased the rate of falls by 25% (rate ratio 1.25, 95% confidence interval 1.08 - 1.44) or every 5dB reduction in IVF-60 increased the rate of falls by 47% (rate ratio 1.47, 95% confidence interval 1.16 - 1.87). Inferior visual field loss was a significant predictor of falls, more so than superior field loss, highlighting the importance of the inferior visual field area in safe and efficient navigation. Further analyses indicated that postural stability, more so than functional status, may be a potential mediating factor in the relationship between visual field loss and falls. Future research is required to confirm this causal pathway. In addition, the use of topical beta-blocker medications was not associated with an increased rate of falls in this cohort, compared with the use of other topical anti-glaucoma medications. In summary, greater binocular visual field loss among older adults with glaucoma was associated with poorer health-related quality of life in the physical domain, reduced functional status, greater postural instability and higher rates of falling. When the location of visual field loss was examined, inferior visual field loss was consistently more strongly associated with these outcomes than superior visual field loss. Insights gained from this research improve our understanding of the association between glaucomatous visual field loss and disability, and its link with falls among older adults. The clinical implications of this research include the need to include visual field screening in falls risk assessments among older adults and to raise awareness of these findings to eye care practitioners and adults with glaucoma. The findings also assist in developing further research to examine strategies to reduce disability and prevent falls among older adults with glaucoma to promote healthy ageing and independence for these individuals.
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Osteoarthritis (OA) is the most common musculoskeletal disorder and represents a major health burden to society. In the course of the pathological development of OA, articular cartilage chondrocytes (ACCs) undergo atypical phenotype changes characterized by the expression of hypertrophic differentiation markers. Also, the adjacent subchondral bone shows signs of abnormal mineral density and enhanced production of bone turnover markers, indicative of osteoblast dysfunction. Collectively these findings indicate that the pathological changes typical of OA, involve alterations of the phenotypic properties of cells in both the subchondral bone and articular cartilage. However, the mechanism(s) by which these changes occur during OA development are not completely understood. The purpose of this project was to address the question of how subchondral bone osteoblasts (SBOs) and ACCs interact with each other with respect to regulation of respective cells’ phenotypic properties and in particular the involvement of mitogen activated protein kinase (MAPK) signalling pathways under normal and OA joint condition. We also endeavoured to test the influence of cross-talk between SBOs and ACCs isolated from normal and OA joint on matrix metalloproteinase (MMP) expression. For this purpose tissues from the knees of OA patients and normal controls were collected to isolate SBOs and ACCs. The cellular cross-talk of SBOs and ACCs were studied by means of both direct and indirect co-culture systems, which made it possible to identify the role of both membrane bound and soluble factors. Histology, immunohistochemistry, qRT-PCR, zymography, ELISA and western blotting were some of the techniques applied to distinguish the changes in the co-cultured vs. non co-cultured cells. The MAPK signalling pathways were probed by using targeted MAPK inhibitors, and their activity monitored by western blot analysis using phospho MAPK specific antibodies. Our co-culture studies demonstrated that OA ACCs enhanced the SBOs differentiation compared to normal ACCs. We demonstrated that OA ACCs induced these phenotypic changes in the SBOs via activating an ERK1/2 signalling pathway. The findings from this study thus provided clear evidence that OA ACCs play an integral role in altering the SBO phenotype. In the second study, we tested the influence of normal SBOs and OA SBOs on ACCs phenotype changes. The results showed that OA SBOs increased the hypertrophic gene expression in co-cultured ACCs compared to normal SBOs, a phenotype which is considered as pathological to the health and integrity of articular cartilage. It was demonstrated that these phenotype changes occurred via de-activation of p38 and activation of ERK1/2 signaling pathways. These findings suggest that the pathological interaction of OA SBOs with ACCs is mediated by cross-talking between ERK1/2 and p38 pathways, resulting in ACCs undergoing hypertrophic differentiation. Subsequent experiments to determine the effect on MMP regulation, of SBOs and ACCs cross-talk, revealed that co-culturing OA SBOs with ACCs significantly enhanced the proteolytic activity and expression of MMP-2 and MMP-9. In turn, co-culture of OA ACCs with SBOs led to abundant MMP-2 expression in SBOs. Furthermore, we showed that the addition of ERK1/2 and JNK inhibitors reversed the elevated MMP-2 and MMP-9 production which otherwise resulted from the interactions of OA SBOs-ACCs. Thus, this study has demonstrated that the altered interactions between OA SBOs-ACCs are capable of triggering the pathological pathways leading to degenerative changes seen in the osteoarthritic joint. In conclusion, the body of work presented in this dissertation has given clear in vitro evidence that the altered bi-directional communication of SBOs and ACCs may play a role in OA development and that this process was mediated by MAPK signalling pathways. Targeting these altered interactions by the use of MAPK inhibitors may provide the scientific rationale for the development of novel therapeutic strategies in the treatment and management of OA.
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This book (256 pages, written in Korean) is a critical essay that reviews, questions, and criticises Korean and Eastern immigrants’ thinking and behaviour styles in Australia from their cultural perspectives, and discuss and proposes a creative cultural dimension for their better life in a multicultural context. Multiculturalism is not supportive of Eastern cultures because of individualistic collection of cultures, while transculturalism facilitates nurture of their culture in a community-oriented way within multicultural circumstances. Korean and Eastern immigrants, sharing oriental cultural systems and values, should approach to the Australian multicultural context with transculturalism which allows creating new cultural values in collaboration with and by participation into local communities. ------------------------------------------------------------ Many Eastern immigrants live in their own ethnic communities without or less interacting with Australian (communities). The author defines this phenomenon as “reverse immigration”. Reverse immigration refers to re-immigrating to their ethnic community in Australia or to their birth country despite they did not anticipate that this would happen to them before immigration to Australia. The author argues that Easterners’ collectivistic culture often devalues individuality and vice versa. Cultural clash between West and East often forces the immigrants to choose reverse immigration because of their lack of understanding of Western culture and their cultural characteristics such as low individuality, high power distance, and high uncertainty avoidance. For example, a vague boundary between individualist and collectivist in a collectivistic context (within their ethnic group) often leads to maladjustment to local communities and enhancement of cultural conservatism. The author proposes that the cultural clash can be overcome by cross-cultural activities named “transculturalism”. To Eastern immigrants, transculturalism can be achieved by acculturation of their two predominant cultures, the third-person perspective and generalised others. In a multicultural context, the former refers to the ability to share another person's feelings and emotions as if they were your own, and the latter does the ability to manage community and public expectations. When both cultural values are used for quality interactions between East and West, they allow Eastern immigrants to be more creative and critical and Australian to be more socially inclusive and culturally tolerant. With these discussions, the author discusses cultural differences throughout the book with four topics (chapters) and proposes transculturalism as a solution to the reverse immigration. ------------------------------------------------------------ Chapter 1 criticises Koreans’ attitudes and methods towards learning English that is less pragmatic and practical, but more likely to be a scholarly study. The author explains that Koreans’ non-pragmatic towards learning English has been firmly built based on their traditional systems and values that Koreans view English as a discipline and an aim of academic achievements rather than a means of communication. Within their cultural context, English can be perceived as more than a language, but something like vastly superior to their language and culture. Their collectivistic culture regards English as an unreachable and heterogeneous one that may threaten their cultural identity, so that “scholarly studying” is only the way to achieve (not learn) it. This discourages the immigrants to engage and involve in daily dialogues by “using” English as a second language. The author further advises the readers to be aware of Eastern collectivistic culture in communication and interaction that sometimes completely reverses private and public topics in a Western context. This leads them to feel that they have no content to talk to natives. ------------------------------------------------------------ Chapter 2 compares between Korea and Australia in terms of their educational systems and values, and proposes how Eastern overseas students can achieve critical and creative thinking within a Western educational setting. Interestingly, this chapter includes an explanation of why Eastern overseas students easily fail assessments including essay writing, oral presentations and discussions. One of the reasons the author explains is that Eastern students are not familiar to criticise others and think creatively, especially when they recognise that their words and ideas may harm the collectivistic harmony. Western educational systems focuses on enhancement of individuality such as self-confidence, self-esteem, and self-expression, while Eastern educational systems foster group-oriented values such as interpersonal relationship, and strong moral and spiritual values. Yet, the author argues that the collectivistic approach to criticism and creativity is often more critical and creative than Western individuals when they know what they are supposed to do for a group (or a community). Therefore, Eastern students need to think their cultural merits and demerits by using an individual perspective rather than generalised others’ perspective. The latter often discourages individual participation in a community, and the generalised others in a Western culture is weaker than Eastern. Furthermore, Western educational systems do not educate students to transform (loose) their individuality to fit into a group or a community. Rather they cultivate individuality for community prosperity. ------------------------------------------------------------ Chapter 3 introduces various cases of reverse immigration in workplaces that many immigrants return to their country or their ethnic community after many trials for acculturation. Reverse immigration is unexpected and not planned before immigration, so that its emotional embarrassment increases such severe social loneliness. Most Eastern immigrant workers have tried to adjust themselves in this new cultural environment at the early stages of immigration. However, their cultural features of collectivism, high power distance, high uncertainty avoidance, and long-term oriented cultures suppress individual initiative and eliminate the space for experiments in ways of acculturation. The author argues that returning to their ethnic community (physically and psychologically) leads to two significant problems: their distorted parenting and becoming more conservatives. The former leads the first generation of immigrants to pressure their children to pursue extrinsic or materialist values, such as financial success, fame and physical appearance, rather than on intrinsic values, while the latter refers to their isolated conservative characters because of their remoteness from the changes of their own country. The author also warns that their ethnic and religious groups actively strengthens immigrants’ social loneliness and systematically discourages immigrants’ interests and desire to be involving into local communities. The ethnic communities and leaders have not been interacting with Australian local communities and, as a result, are eager to conserve outdated cultural systems values. Even they have a tendency to weed out those people who wish to settle down within Australian local communities. They believe that those people can threaten their community’s survival and continuity. ------------------------------------------------------------ Chapter 4 titled multiculturalism argues that Korean and Eastern immigrants should more precisely understand Australia as a multicultural society in a way of collaboratively creating new cultural values. The author introduces multiculturalism with its definitions and history in Australia and argues the limitations of multiculturalism from an Easterner’s perspective. With well known tragedies of the second generations of U.S. immigrants, Cho Seung-Hui, a university student, massacred 32 people on the Virginia Tech before committing suicide and Hidal Hassan, an Army psychiatrist, killed 13 people at Fort Hood and the responses of ethnic community, the author explains that their mental illness may be derived from their parents’ (or ethnic group) culturally isolated attitude and socially static viewpoint of U.S. (Western system and values). The author insists that multiculturalism may restrict Eastern immigrants’ engagement and involvement in local communities. Multiculturalism has been systematically and historically developed based on Western systems and cultural values. In other words, multiculturalism requires high self-confidence and self-esteem that Eastern immigrants less prioritise them. It has been generally known that Easterners put more weight on human relationship than Westerners, but the author claims that this is not true. Within an individualistic culture, Westerners are more interested in building person-to-person connections and relationships. While Easterners are more interested in how individuals can achieve a sense of belonging within a group and a community. Therefore, multiculturalism is an ideology which forces Eastern immigrants to discard their strong desire to be part of a group and does not give a sense of belonging. In a consequence, the author advises that Eastern immigrants should aim towards “transculturalism” which allows them to actively participate in and contribute to their multicultural community. Transculturalism does not ask Easterners to discard their cultural values, but enables them to be a collectivistic individualist (a community leader) who is capable of developing new cultural values in a more creative and productive way. Furthermore, transculturalism encourages Western Australians in a multicultural context to collaborate with ethnic minorities to build a better community.
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A Flat Bed Rail Wagon (FBRW) has been proposed as an alternative solution for replacing bridges on low traffic volume roads. The subject matter for this paper is to investigate the impediment to load transfer from cross girders to main girder, through visually identifiable structural flaws. Namely, the effect of having large openings at close proximity to the connection of the main girder to the cross girder of a FBRW was examined. It was clear that openings locally reduce the section modulus of the secondary members; however it was unclear how these reductions would affect the load transfer to the main girder. The results are presented through modeling grillage action for which the loads applied onto the FBRW were distributed through cross girders to the main girder.
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The use of appropriate features to characterize an output class or object is critical for all classification problems. This paper evaluates the capability of several spectral and texture features for object-based vegetation classification at the species level using airborne high resolution multispectral imagery. Image-objects as the basic classification unit were generated through image segmentation. Statistical moments extracted from original spectral bands and vegetation index image are used as feature descriptors for image objects (i.e. tree crowns). Several state-of-art texture descriptors such as Gray-Level Co-Occurrence Matrix (GLCM), Local Binary Patterns (LBP) and its extensions are also extracted for comparison purpose. Support Vector Machine (SVM) is employed for classification in the object-feature space. The experimental results showed that incorporating spectral vegetation indices can improve the classification accuracy and obtained better results than in original spectral bands, and using moments of Ratio Vegetation Index obtained the highest average classification accuracy in our experiment. The experiments also indicate that the spectral moment features also outperform or can at least compare with the state-of-art texture descriptors in terms of classification accuracy.
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This research shows that gross pollutant traps (GPTs) continue to play an important role in preventing visible street waste—gross pollutants—from contaminating the environment. The demand for these GPTs calls for stringent quality control and this research provides a foundation to rigorously examine the devices. A novel and comprehensive testing approach to examine a dry sump GPT was developed. The GPT is designed with internal screens to capture gross pollutants—organic matter and anthropogenic litter. This device has not been previously investigated. Apart from the review of GPTs and gross pollutant data, the testing approach includes four additional aspects to this research, which are: field work and an historical overview of street waste/stormwater pollution, calibration of equipment, hydrodynamic studies and gross pollutant capture/retention investigations. This work is the first comprehensive investigation of its kind and provides valuable practical information for the current research and any future work pertaining to the operations of GPTs and management of street waste in the urban environment. Gross pollutant traps—including patented and registered designs developed by industry—have specific internal configurations and hydrodynamic separation characteristics which demand individual testing and performance assessments. Stormwater devices are usually evaluated by environmental protection agencies (EPAs), professional bodies and water research centres. In the USA, the American Society of Civil Engineers (ASCE) and the Environmental Water Resource Institute (EWRI) are examples of professional and research organisations actively involved in these evaluation/verification programs. These programs largely rely on field evaluations alone that are limited in scope, mainly for cost and logistical reasons. In Australia, evaluation/verification programs of new devices in the stormwater industry are not well established. The current limitations in the evaluation methodologies of GPTs have been addressed in this research by establishing a new testing approach. This approach uses a combination of physical and theoretical models to examine in detail the hydrodynamic and capture/retention characteristics of the GPT. The physical model consisted of a 50% scale model GPT rig with screen blockages varying from 0 to 100%. This rig was placed in a 20 m flume and various inlet and outflow operating conditions were modelled on observations made during the field monitoring of GPTs. Due to infrequent cleaning, the retaining screens inside the GPTs were often observed to be blocked with organic matter. Blocked screens can radically change the hydrodynamic and gross pollutant capture/retention characteristics of a GPT as shown from this research. This research involved the use of equipment, such as acoustic Doppler velocimeters (ADVs) and dye concentration (Komori) probes, which were deployed for the first time in a dry sump GPT. Hence, it was necessary to rigorously evaluate the capability and performance of these devices, particularly in the case of the custom made Komori probes, about which little was known. The evaluation revealed that the Komori probes have a frequency response of up to 100 Hz —which is dependent upon fluid velocities—and this was adequate to measure the relevant fluctuations of dye introduced into the GPT flow domain. The outcome of this evaluation resulted in establishing methodologies for the hydrodynamic measurements and gross pollutant capture/retention experiments. The hydrodynamic measurements consisted of point-based acoustic Doppler velocimeter (ADV) measurements, flow field particle image velocimetry (PIV) capture, head loss experiments and computational fluid dynamics (CFD) simulation. The gross pollutant capture/retention experiments included the use of anthropogenic litter components, tracer dye and custom modified artificial gross pollutants. Anthropogenic litter was limited to tin cans, bottle caps and plastic bags, while the artificial pollutants consisted of 40 mm spheres with a range of four buoyancies. The hydrodynamic results led to the definition of global and local flow features. The gross pollutant capture/retention results showed that when the internal retaining screens are fully blocked, the capture/retention performance of the GPT rapidly deteriorates. The overall results showed that the GPT will operate efficiently until at least 70% of the screens are blocked, particularly at high flow rates. This important finding indicates that cleaning operations could be more effectively planned when the GPT capture/retention performance deteriorates. At lower flow rates, the capture/retention performance trends were reversed. There is little difference in the poor capture/retention performance between a fully blocked GPT and a partially filled or empty GPT with 100% screen blockages. The results also revealed that the GPT is designed with an efficient high flow bypass system to avoid upstream blockages. The capture/retention performance of the GPT at medium to high inlet flow rates is close to maximum efficiency (100%). With regard to the design appraisal of the GPT, a raised inlet offers a better capture/retention performance, particularly at lower flow rates. Further design appraisals of the GPT are recommended.
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Introduction. There are two binding sites on the β1-adrenoceptor (AR), β1H and β1L corresponding to high and low affinity binding sites respectively, which can be activated to cause cardiostimulation. Some β-blockers that block β1AR and β2ARs can activate β1LARs at higher concentrations than those required to cause blockade. The β2AR does not form a corresponding low affinity binding site and therefore we postulated that heterologous amino acids are responsible for the formation of β1LAR. Aim. To investigate whether heterologous amino acids of transmembrane domain V (TMDV) of β1AR and β2ARs contribute to β1LAR. Methods. β1ARs, β2ARs and mutant β1ARs containing all (β1(β2TMDV)AR) or single amino acids of TMDV of the β2AR were prepared and stably expressed in Chinese Hamster Ovary cells. Concentration-effect curves for cyclicAMP accumulation were carried out for (-)-CGP12177 in the absence or presence of (-)-bupranolol. Results. The potencies (pEC50) of (-)-CGP12177 were β2AR (9.24 ± 0.14, n = 5), β1(V230I)AR (9.07 ± 0.07, n = 10), β1(β2TMDV)AR (8.86 ± 0.10, n = 15), β1(R222Q)AR (8.09 ± 0.29, n = 6), β1AR (8.00 ± 0.11, n = 11). The affinities (pKB) of (-)-bupranolol were β2AR (9.82 ± 0.52, n = 5), β1(V230I)AR (7.64 ± 0.12, n = 8), β1(β2TMV)AR (8.06 ± 0.17, n = 8), β1(R222Q)AR (7.33 ± 0.23, n = 5), β1AR (7.23 ± 0.23, n = 5). Discussion. The potency of (-)-CGP12177 was higher at β2AR than at β1AR consistent with activation through a low affinity site at the β1AR (β1LAR). The presence of V230 in β1AR accounted for the lower potency of (-)-CGP 12177. The affinity of (-)-bupranolol was lower at β1AR compared to β2AR. The presence of V230 in β1AR accounted in part for the lower affinity. In conclusion TMDV of the β1AR contributes in part to the low affinity binding site of β1AR.
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There are two binding sites on the β1-adrenoceptor (AR), β1H and β1L corresponding to high and low affinity binding sites respectively, which can be activated to cause cardiostimulation (reviewed Kaumann and Molenaar, 2008). Some β-blockers that block β1AR and β2ARs can activate β1LARs at higher concentrations than those required to cause blockade. The β2AR does not form a corresponding low affinity binding site (Baker et al 2002) and therefore we postulated that heterologous amino acids are responsible for the formation of β1LAR. Our aim was to investigate whether heterologous amino acids of transmembrane domain V (TMDV) of β1AR and β2ARs contribute to β1LAR. β1ARs, β2ARs and mutant β1ARs containing all (β1(β2TMDV)AR) or single amino acids of TMDV of the β2AR were prepared and stably expressed in Chinese Hamster Ovary cells. Concentration-effect curves for cyclicAMP accumulation were carried out for (-)-CGP12177 or (-)-isoprenaline in the absence or presence of (-)-bupranolol. _______________________________________________________________________ (-)-CGP 12177 (-)-Bupranolol affinity (pKB) pEC50 vs (-)-CGP 12177 vs (-)-isoprenaline _______________________________________________________________________ β1AR 8.00 ± 0.11 (11) 7.23 ± 0.23 (5) 9.52 ± 0.28 (5) β2AR (high density) 9.24 ± 0.14 (5) 9.82 ± 0.52 (8) xPaulxxxxxxx β2AR (low density) no effect β1(β2TMV)AR 8.86 ± 0.10 (15) 8.06 ± 0.17 (8) 9.08 ± 0.22 (6) β1(V230I)AR 9.07 ± 0.07 (10) 7.64 ± 0.12 (8) 9.36 ± 0.28 (9) β1(R222Q)AR 8.09 ± 0.29 (6) 7.33 ± 0.23 (5) 9.36 ± 0.08 (6) β1(V230A)AR 7.59 ± 0.09 (6) 7.32 ± 0.24 (4) 8.62 ± 0.18 (5) _______________________________________________________________________ The potency of (-)-CGP12177 was higher at β2AR than at β1AR consistent with activation through a low affinity site at the β1AR (β1LAR) but not β2AR. The presence of V230 in β1AR accounted for the lower potency of (-)-CGP 12177. The affinity of (-)-bupranolol at β1AR and mutants was higher when determined with (-)-isoprenaline than with (-)-CGP 12177. The affinity of (-)-bupranolol determined against (-)-CGP 12177 was lower at β1AR compared to β2AR. The presence of V230 in β1AR accounted in part for the lower affinity. In conclusion V230 of the β1AR contributes in part to the low affinity binding site of β1AR. Baker JG, Hall IP, Hill SJ (2002). Pharmacological characterization of CGP12177 at the human β2-adrenoceptor. Br J Pharmacol 137, 400−408 Kaumann AJ, Molenaar P (2008) The low-affinity site of the β1-adrenoceptor and its relevance to cardiovascular pharmacology. Pharmacol Ther 118, 303-336
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With regard to the long-standing problem of the semantic gap between low-level image features and high-level human knowledge, the image retrieval community has recently shifted its emphasis from low-level features analysis to high-level image semantics extrac- tion. User studies reveal that users tend to seek information using high-level semantics. Therefore, image semantics extraction is of great importance to content-based image retrieval because it allows the users to freely express what images they want. Semantic content annotation is the basis for semantic content retrieval. The aim of image anno- tation is to automatically obtain keywords that can be used to represent the content of images. The major research challenges in image semantic annotation are: what is the basic unit of semantic representation? how can the semantic unit be linked to high-level image knowledge? how can the contextual information be stored and utilized for image annotation? In this thesis, the Semantic Web technology (i.e. ontology) is introduced to the image semantic annotation problem. Semantic Web, the next generation web, aims at mak- ing the content of whatever type of media not only understandable to humans but also to machines. Due to the large amounts of multimedia data prevalent on the Web, re- searchers and industries are beginning to pay more attention to the Multimedia Semantic Web. The Semantic Web technology provides a new opportunity for multimedia-based applications, but the research in this area is still in its infancy. Whether ontology can be used to improve image annotation and how to best use ontology in semantic repre- sentation and extraction is still a worth-while investigation. This thesis deals with the problem of image semantic annotation using ontology and machine learning techniques in four phases as below. 1) Salient object extraction. A salient object servers as the basic unit in image semantic extraction as it captures the common visual property of the objects. Image segmen- tation is often used as the �rst step for detecting salient objects, but most segmenta- tion algorithms often fail to generate meaningful regions due to over-segmentation and under-segmentation. We develop a new salient object detection algorithm by combining multiple homogeneity criteria in a region merging framework. 2) Ontology construction. Since real-world objects tend to exist in a context within their environment, contextual information has been increasingly used for improving object recognition. In the ontology construction phase, visual-contextual ontologies are built from a large set of fully segmented and annotated images. The ontologies are composed of several types of concepts (i.e. mid-level and high-level concepts), and domain contextual knowledge. The visual-contextual ontologies stand as a user-friendly interface between low-level features and high-level concepts. 3) Image objects annotation. In this phase, each object is labelled with a mid-level concept in ontologies. First, a set of candidate labels are obtained by training Support Vectors Machines with features extracted from salient objects. After that, contextual knowledge contained in ontologies is used to obtain the �nal labels by removing the ambiguity concepts. 4) Scene semantic annotation. The scene semantic extraction phase is to get the scene type by using both mid-level concepts and domain contextual knowledge in ontologies. Domain contextual knowledge is used to create scene con�guration that describes which objects co-exist with which scene type more frequently. The scene con�guration is represented in a probabilistic graph model, and probabilistic inference is employed to calculate the scene type given an annotated image. To evaluate the proposed methods, a series of experiments have been conducted in a large set of fully annotated outdoor scene images. These include a subset of the Corel database, a subset of the LabelMe dataset, the evaluation dataset of localized semantics in images, the spatial context evaluation dataset, and the segmented and annotated IAPR TC-12 benchmark.
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This paper introduces a model to facilitate delegation, including ad-hoc delegation, in cross security domain activities. Specifically, this paper proposes a novel delegation constraint management model to manage and track delegation constraints across security domains. An algorithm to trace the authority of delegation constraints is introduced as well as an algorithm to form a delegation constraint set and detect/prevent potential conflicts. The algorithms and the management model are built upon a set of formal definitions of delegation constraints.
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For several reasons, the Fourier phase domain is less favored than the magnitude domain in signal processing and modeling of speech. To correctly analyze the phase, several factors must be considered and compensated, including the effect of the step size, windowing function and other processing parameters. Building on a review of these factors, this paper investigates a spectral representation based on the Instantaneous Frequency Deviation, but in which the step size between processing frames is used in calculating phase changes, rather than the traditional single sample interval. Reflecting these longer intervals, the term delta-phase spectrum is used to distinguish this from instantaneous derivatives. Experiments show that mel-frequency cepstral coefficients features derived from the delta-phase spectrum (termed Mel-Frequency delta-phase features) can produce broadly similar performance to equivalent magnitude domain features for both voice activity detection and speaker recognition tasks. Further, it is shown that the fusion of the magnitude and phase representations yields performance benefits over either in isolation.
Resumo:
This paper presents a method of voice activity detection (VAD) suitable for high noise scenarios, based on the fusion of two complementary systems. The first system uses a proposed non-Gaussianity score (NGS) feature based on normal probability testing. The second system employs a histogram distance score (HDS) feature that detects changes in the signal through conducting a template-based similarity measure between adjacent frames. The decision outputs by the two systems are then merged using an open-by-reconstruction fusion stage. Accuracy of the proposed method was compared to several baseline VAD methods on a database created using real recordings of a variety of high-noise environments.
Resumo:
In many product categories of durable goods such as TV, PC, and DVD player, the largest component of sales is generated by consumers replacing existing units. Aggregate sales models proposed by diffusion of innovation researchers for the replacement component of sales have incorporated several different replacement distributions such as Rayleigh, Weibull, Truncated Normal and Gamma. Although these alternative replacement distributions have been tested using both time series sales data and individual-level actuarial “life-tables” of replacement ages, there is no census on which distributions are more appropriate to model replacement behaviour. In the current study we are motivated to develop a new “modified gamma” distribution by two reasons. First we recognise that replacements have two fundamentally different drivers – those forced by failure and early, discretionary replacements. The replacement distribution for each of these drivers is expected to be quite different. Second, we observed a poor fit of other distributions to out empirical data. We conducted a survey of 8,077 households to empirically examine models of replacement sales for six electronic consumer durables – TVs, VCRs, DVD players, digital cameras, personal and notebook computers. This data allows us to construct individual-level “life-tables” for replacement ages. We demonstrate the new modified gamma model fits the empirical data better than existing models for all six products using both a primary and a hold-out sample.