143 resultados para Acidic transactivating domains
Resumo:
Most information retrieval (IR) models treat the presence of a term within a document as an indication that the document is somehow "about" that term, they do not take into account when a term might be explicitly negated. Medical data, by its nature, contains a high frequency of negated terms - e.g. "review of systems showed no chest pain or shortness of breath". This papers presents a study of the effects of negation on information retrieval. We present a number of experiments to determine whether negation has a significant negative affect on IR performance and whether language models that take negation into account might improve performance. We use a collection of real medical records as our test corpus. Our findings are that negation has some affect on system performance, but this will likely be confined to domains such as medical data where negation is prevalent.
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Software used by architectural and industrial designers – has moved from becoming a tool for drafting, towards use in verification, simulation, project management and project sharing remotely. In more advanced models, parameters for the designed object can be adjusted so a family of variations can be produced rapidly. With advances in computer aided design technology, numerous design options can now be generated and analyzed in real time. However the use of digital tools to support design as an activity is still at an early stage and has largely been limited in functionality with regard to the design process. To date, major CAD vendors have not developed an integrated tool that is able to both leverage specialized design knowledge from various discipline domains (known as expert knowledge systems) and support the creation of design alternatives that satisfy different forms of constraints. We propose that evolutionary computing and machine learning be linked with parametric design techniques to record and respond to a designer’s own way of working and design history. It is expected that this will lead to results that impact on future work on design support systems-(ergonomics and interface) as well as implicit constraint and problem definition for problems that are difficult to quantify.
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Many economic, social and environmental sustainability problems associated with typical urban transportation systems have revealed the importance of three domains of action: vehicle, infrastructure and user. These domains need to be carefully reconsidered in search of a sustainable urban development path. Although intelligent transportation systems have contributed substantially to enhancing efficiency, safety and comfort of travel, questions related to users’ behaviours and preferences, which stimulate considerable environmental effects, still needed to be further examined. In this chapter, options for smart urban transportation infrastructure development and the technological means for achieving broader goals of sustainable communities and urban development are explored.
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Introduction and hypothesis: The aim of this study was to validate a self-administered version of the already validated interviewer-administered Australian pelvic floor questionnaire. Methods: The questionnaire was completed by 163 women attending an urogynecological clinic. Face and convergent validity was assessed. Reliability testing and comparison with the interviewer-administered version was performed in a subset of 105 patients. Responsiveness was evaluated in a subset of 73 women. Results: Missing data did not exceed 4% for any question. Cronbach’s alpha coefficients were acceptable in all domains. Kappa coefficients for the test–retest analyses varied from 0.64–1.0. Prolapse symptoms correlated significantly with the pelvic organ prolapse quantification. Urodynamics confirmed the reported symptom stress incontinence in 70%. The self and interviewer administered questionnaires demonstrated equivalence. Effect sizes ranged from 0.6 to 1.4. Conclusions: This self-administered pelvic floor questionnaire assessed pelvic floor function in a reproducible and valid fashion and due to its responsiveness, can be used for routine clinical assessment and outcome research.
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Banana leaf streak disease, caused by several species of Banana streak virus (BSV), is widespread in East Africa. We surveyed for this disease in Uganda and Kenya, and used rolling-circle amplification (RCA) to detect the presence of BSV in banana. Six distinct badnavirus sequences, three from Uganda and three from Kenya, were amplified for which only partial sequences were previously available. The complete genomes were sequenced and characterised. The size and organisation of all six sequences was characteristic of other badnaviruses, including conserved functional domains present in the putative polyprotein encoded by open reading frame (ORF) 3. Based on nucleotide sequence analysis within the reverse transcriptase/ribonuclease H-coding region of open reading frame 3, we propose that these sequences be recognised as six new species and be designated as Banana streak UA virus, Banana streak UI virus, Banana streak UL virus, Banana streak UM virus, Banana streak CA virus and Banana streak IM virus. Using PCR and species-specific primers to test for the presence of integrated sequences, we demonstrated that sequences with high similarity to BSIMV only were present in several banana cultivars which had tested negative for episomal BSV sequences.
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Sustainability decisions and their impacts may be among the greatest challenges facing the world in the 21st century (Davos 2000). Apart from adaptation on the part of established organizations these challenges are arguably going to require solutions developed by new actors However, young ventures have only recently begun generating research interest within sustainability literature (Shepherd et al. 2009). In particular, little is known about resource behaviours of these ventures and how they adapt to substantial resource constraints. One promising theory that has been identified as a way that some entrepreneurs manage constraints is bricolage: a construct defined as “making do by applying combinations of the resources at hand to new problems and opportunities” (Baker and Nelson 2005: 333). Bricolage may be critical as the means of continued venture success as these ventures are frequently developed in severe resource constraint, owing to higher levels of technical sophistication (Rothaermel and Deeds 2006). Further, they are often developed by entrepreneurs committed to personal and social goals of resourcefulness, including values that focus on conservation rather than consumption of resources (Shepherd et al. 2009). In this paper, using seven novel cases of high potential sustainability firms from CAUSEE we consider how constraints impact resource behaviours and further illustrate and extend bricolage domains previously developed by Baker and Nelson (2005) with recommendations for theory and practice provided.
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Myosin is believed to act as the molecular motor for many actin-based motility processes in eukaryotes. It is becoming apparent that a single species may possess multiple myosin isoforms, and at least seven distinct classes of myosin have been identified from studies of animals, fungi, and protozoans. The complexity of the myosin heavy-chain gene family in higher plants was investigated by isolating and characterizing myosin genomic and cDNA clones from Arabidopsis thaliana. Six myosin-like genes were identified from three polymerase chain reaction (PCR) products (PCR1, PCR11, PCR43) and three cDNA clones (ATM2, MYA2, MYA3). Sequence comparisons of the deduced head domains suggest that these myosins are members of two major classes. Analysis of the overall structure of the ATM2 and MYA2 myosins shows that they are similar to the previously-identified ATM1 and MYA1 myosins, respectively. The MYA3 appears to possess a novel tail domain, with five IQ repeats, a six-member imperfect repeat, and a segment of unique sequence. Northern blot analyses indicate that some of the Arabidopsis myosin genes are preferentially expressed in different plant organs. Combined with previous studies, these results show that the Arabidopsis genome contains at least eight myosin-like genes representing two distinct classes.
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Bronfenbrenner.s Bioecological Model, expressed as the developmental equation, D f PPCT, is the theoretical framework for two studies that bring together diverse strands of psychology to study the work-life interface of working adults. Occupational and organizational psychology is focused on the demands and resources of work and family, without emphasising the individual in detail. Health and personality psychology examine the individual but without emphasis on the individual.s work and family roles. The current research used Bronfenbrenner.s theoretical framework to combine individual differences, work and family to understand how these factors influence the working adult.s psychological functioning. Competent development has been defined as high well-being (measured as life satisfaction and psychological well-being) and high work engagement (as work vigour, work dedication and absorption in work) and as the absence of mental illness (as depression, anxiety and stress) and the absence of burnout (as emotional exhaustion, cynicism and professional efficacy). Study 1 and 2 were linked, with Study 1 as a cross-sectional survey and Study 2, a prospective panel study that followed on from the data used in Study1. Participants were recruited from a university and from a large public hospital to take part in a 3-wave, online study where they completed identical surveys at 3-4 month intervals (N = 470 at Time 1 and N = 198 at Time 3). In Study 1, hierarchical multiple regressions were used to assess the effects of individual differences (Block 1, e.g. dispositional optimism, coping self-efficacy, perceived control of time, humour), work and family variables (Block 2, e.g. affective commitment, skill discretion, work hours, children, marital status, family demands) and the work-life interface (Block 3, e.g. direction and quality of spillover between roles, work-life balance) on the outcomes. There were a mosaic of predictors of the outcomes with a group of seven that were the most frequent significant predictors and which represented the individual (dispositional optimism and coping self-efficacy), the workplace (skill discretion, affective commitment and job autonomy) and the work-life interface (negative work-to-family spillover and negative family-to-work spillover). Interestingly, gender and working hours were not important predictors. The effects of job social support, generally and for work-life issues, perceived control of time and egalitarian gender roles on the outcomes were mediated by negative work-to-family spillover, particularly for emotional exhaustion. Further, the effect of negative spillover on depression, anxiety and work engagement was moderated by the individual.s personal and workplace resources. Study 2 modelled the longitudinal relationships between the group of the seven most frequent predictors and the outcomes. Using a set of non-nested models, the relative influences of concurrent functioning, stability and change over time were assessed. The modelling began with models at Time 1, which formed the basis for confirmatory factor analysis (CFA) to establish the underlying relationships between the variables and calculate the composite variables for the longitudinal models. The CFAs were well fitting with few modifications to ensure good fit. However, using burnout and work engagement together required additional analyses to resolve poor fit, with one factor (representing a continuum from burnout to work engagement) being the only acceptable solution. Five different longitudinal models were investigated as the Well-Being, Mental Distress, Well-Being-Mental Health, Work Engagement and Integrated models using differing combinations of the outcomes. The best fitting model for each was a reciprocal model that was trimmed of trivial paths. The strongest paths were the synchronous correlations and the paths within variables over time. The reciprocal paths were more variable with weak to mild effects. There was evidence of gain and loss spirals between the variables over time, with a slight net gain in resources that may provide the mechanism for the accumulation of psychological advantage over a lifetime. The longitudinal models also showed that there are leverage points at which personal, psychological and managerial interventions can be targeted to bolster the individual and provide supportive workplace conditions that also minimise negative spillover. Bronfenbrenner.s developmental equation has been a useful framework for the current research, showing the importance of the person as central to the individual.s experience of the work-life interface. By taking control of their own life, the individual can craft a life path that is most suited to their own needs. Competent developmental outcomes were most likely where the person was optimistic and had high self-efficacy, worked in a job that they were attached to and which allowed them to use their talents and without too much negative spillover between their work and family domains. In this way, individuals had greater well-being, better mental health and greater work engagement at any one time and across time.
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In an era of hyper-specialization it is unusual to find such a range of concerns as creative economy, media studies, copyright law and 'area' studies, but at the same time it is impossible to do justice to specialist domains without knowing how they fit together.
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Prostate cancer is the second most common cause of cancer-related deaths in Western males. Current diagnostic, prognostic and treatment approaches are not ideal and advanced metastatic prostate cancer is incurable. There is an urgent need for improved adjunctive therapies and markers for this disease. GPCRs are likely to play a significant role in the initiation and progression of prostate cancer. Over the last decade, it has emerged that G protein coupled receptors (GPCRs) are likely to function as homodimers and heterodimers. Heterodimerisation between GPCRs can result in the formation of novel pharmacological receptors with altered functional outcomes, and a number of GPCR heterodimers have been implicated in the pathogenesis of human disease. Importantly, novel GPCR heterodimers represent potential new targets for the development of more specific therapeutic drugs. Ghrelin is a 28 amino acid peptide hormone which has a unique n-octanoic acid post-translational modification. Ghrelin has a number of important physiological roles, including roles in appetite regulation and the stimulation of growth hormone release. The ghrelin receptor is the growth hormone secretagogue receptor type 1a, GHS-R1a, a seven transmembrane domain GPCR, and GHS-R1b is a C-terminally truncated isoform of the ghrelin receptor, consisting of five transmembrane domains. Growing evidence suggests that ghrelin and the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, may have a role in the progression of a number of cancers, including prostate cancer. Previous studies by our research group have shown that the truncated ghrelin receptor isoform, GHS-R1b, is not expressed in normal prostate, however, it is expressed in prostate cancer. The altered expression of this truncated isoform may reflect a difference between a normal and cancerous state. A number of mutant GPCRs have been shown to regulate the function of their corresponding wild-type receptors. Therefore, we investigated the potential role of interactions between GHS-R1a and GHS-R1b, which are co-expressed in prostate cancer and aimed to investigate the function of this potentially new pharmacological receptor. In 2005, obestatin, a 23 amino acid C-terminally amidated peptide derived from preproghrelin was identified and was described as opposing the stimulating effects of ghrelin on appetite and food intake. GPR39, an orphan GPCR which is closely related to the ghrelin receptor, was identified as the endogenous receptor for obestatin. Recently, however, the ability of obestatin to oppose the effects of ghrelin on appetite and food intake has been questioned, and furthermore, it appears that GPR39 may in fact not be the obestatin receptor. The role of GPR39 in the prostate is of interest, however, as it is a zinc receptor. Zinc has a unique role in the biology of the prostate, where it is normally accumulated at high levels, and zinc accumulation is altered in the development of prostate malignancy. Ghrelin and zinc have important roles in prostate cancer and dimerisation of their receptors may have novel roles in malignant prostate cells. The aim of the current study, therefore, was to demonstrate the formation of GHS-R1a/GHS-R1b and GHS-R1a/GPR39 heterodimers and to investigate potential functions of these heterodimers in prostate cancer cell lines. To demonstrate dimerisation we first employed a classical co-immunoprecipitation technique. Using cells co-overexpressing FLAG- and Myc- tagged GHS-R1a, GHS-R1b and GPR39, we were able to co-immunoprecipitate these receptors. Significantly, however, the receptors formed high molecular weight aggregates. A number of questions have been raised over the propensity of GPCRs to aggregate during co-immunoprecipitation as a result of their hydrophobic nature and this may be misinterpreted as receptor dimerisation. As we observed significant receptor aggregation in this study, we used additional methods to confirm the specificity of these putative GPCR interactions. We used two different resonance energy transfer (RET) methods; bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET), to investigate interactions between the ghrelin receptor isoforms and GPR39. RET is the transfer of energy from a donor fluorophore to an acceptor fluorophore when they are in close proximity, and RET methods are, therefore, applicable to the observation of specific protein-protein interactions. Extensive studies using the second generation bioluminescence resonance energy transfer (BRET2) technology were performed, however, a number of technical limitations were observed. The substrate used during BRET2 studies, coelenterazine 400a, has a low quantum yield and rapid signal decay. This study highlighted the requirement for the expression of donor and acceptor tagged receptors at high levels so that a BRET ratio can be determined. After performing a number of BRET2 experimental controls, our BRET2 data did not fit the predicted results for a specific interaction between these receptors. The interactions that we observed may in fact represent ‘bystander BRET’ resulting from high levels of expression, forcing the donor and acceptor into close proximity. Our FRET studies employed two different FRET techniques, acceptor photobleaching FRET and sensitised emission FRET measured by flow cytometry. We were unable to observe any significant FRET, or FRET values that were likely to result from specific receptor dimerisation between GHS-R1a, GHS-R1b and GPR39. While we were unable to conclusively demonstrate direct dimerisation between GHS-R1a, GHS-R1b and GPR39 using several methods, our findings do not exclude the possibility that these receptors interact. We aimed to investigate if co-expression of combinations of these receptors had functional effects in prostate cancers cells. It has previously been demonstrated that ghrelin stimulates cell proliferation in prostate cancer cell lines, through ERK1/2 activation, and GPR39 can stimulate ERK1/2 signalling in response to zinc treatments. Additionally, both GHS-R1a and GPR39 display a high level of constitutive signalling and these constitutively active receptors can attenuate apoptosis when overexpressed individually in some cell types. We, therefore, investigated ERK1/2 and AKT signalling and cell survival in prostate cancer the potential modulation of these functions by dimerisation between GHS-R1a, GHS-R1b and GPR39. Expression of these receptors in the PC-3 prostate cancer cell line, either alone or in combination, did not alter constitutive ERK1/2 or AKT signalling, basal apoptosis or tunicamycin-stimulated apoptosis, compared to controls. In summary, the potential interactions between the ghrelin receptor isoforms, GHS-R1a and GHS-R1b, and the related zinc receptor, GPR39, and the potential for functional outcomes in prostate cancer were investigated using a number of independent methods. We did not definitively demonstrate the formation of these dimers using a number of state of the art methods to directly demonstrate receptor-receptor interactions. We investigated a number of potential functions of GPR39 and GHS-R1a in the prostate and did not observe altered function in response to co-expression of these receptors. The technical questions raised by this study highlight the requirement for the application of extensive controls when using current methods for the demonstration of GPCR dimerisation. Similar findings in this field reflect the current controversy surrounding the investigation of GPCR dimerisation. Although GHS-R1a/GHS-R1b or GHS-R1a/GPR39 heterodimerisation was not clearly demonstrated, this study provides a basis for future investigations of these receptors in prostate cancer. Additionally, the results presented in this study and growing evidence in the literature highlight the requirement for an extensive understanding of the experimental method and the performance of a range of controls to avoid the spurious interpretation of data gained from artificial expression systems. The future development of more robust techniques for investigating GPCR dimerisation is clearly required and will enable us to elucidate whether GHS-R1a, GHS-R1b and GPR39 form physiologically relevant dimers.
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The research is based on studying the early stage of the design process. It aims to identify differences in design approaches across two design domains. The research is based on the analysis of the observational data from the conceptual stage of (i) product and (ii) software design process. The activities captured from the analysis of the design process are utilized to outline similarities and differences across the two domains. This will contribute to a better understanding of the connections between, and integration of, design process variables, and to a better understanding of design expertise transfer to other domain (e.g., science or nursing).
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This paper investigates how software designers use their knowledge during the design process. The research is based on the analysis of the observational and verbal data from three software design teams generated during the conceptual stage of the design process. The knowledge captured from the analysis of the mapped design team data is utilized to generate descriptive models of novice and expert designers. These models contribute to a better understanding of the connections between, and integration of, designer variables, and to a better understanding of software design expertise and its development. The models are transferable to other domains.
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Comorbid depression and anxiety in late life present challenges for geriatric mental health care providers. These challenges include identifying the often complex diagnostic presentations both clinically and in a research context. This potent comorbidity can be conceived as double jeopardy in older adults, further diminishing their quality of life. Geriatric health care providers need to understand psychiatric comorbidity of this type for accurate diagnosis and early referral to specialists, and to coordinate interdisciplinary care. Researchers in the field also need to recognize potential multiple impacts of comorbidities with respect to assessment and treatment domains. This article describes the prevalence of late-life depression and anxiety disorders and reviews studies on this comorbidity in older adults. Risk factors and protective factors for anxiety and depression in later life are reviewed, and information is provided about comparative symptoms, the selection of assessment tools, and challenges to the provision of interdisciplinary, evidence-based care.
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This report analyses the national curriculum and workforce needs of the social work and human services workforce. Australia’s community and health services are among the fastest growing sectors of employment in the nation but the sustainability of an appropriately qualified workforce is threatened. Yet there is little integration of education and workforce planning for the community services sector. This contrasts markedly with the health services sector, where key stakeholders are collaboratively addressing workforce challenges. Our research confirmed rapid growth in the social work and human services workforce and it also identified: • an undersupply of professionally qualified social work and human service practitioners to meet workforce demand; • the rapid ageing of the workforce with many workers approaching retirement; • limited career and salary structures creating disincentives to retention; • a highly diverse qualification base across the workforce. This diversity is inconsistent with the specialist knowledge and skills required of practitioners in many domains of community service provision. Our study revealed a lack of co-ordination across VET and higher education to meet the educational needs of the social work and human services workforce. Our analysis identified: • strong representation of equity groups in social work and related human service programs, although further participation of these groups is still needed; • the absence of clear articulation pathways between VET and higher education programs due the absence of co-ordination and planning between these sectors; • substantial variation in the content of the diverse range of social work and human service programs, with accredited programs conforming to national standards and some others in social and behavioural sciences lacking any external validation; • financial obstacles and disincentives to social work and human service practitioners in achieving postgraduate level qualifications. We recommend that: • DEEWR identify accredited social work and human services courses as a national education priority (similar to education and nursing). This will help ensure the supply of professional workers to this sector; • VET and higher education providers are encouraged to collaboratively develop clear and accessible educational pathways across the educational sectors; • DEEWR undertake a national workforce analysis and planning processes in collaboration with CSDMAC, and all social and community services stakeholders, to ensure workforce sustainability; and • COAG develop a national regulation framework for the social and community services workforce. This would provide sound accountability systems, and rigorous practice and educational standards necessary for quality service provision. It will also ensure much needed public confidence in this workforce.
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This paper seeks to link anthropological and economic treatments of the process of innovation and change, not only within a given ‘complex system’ (e.g. a cosmology; an industry) but also between systems (e.g. cultural and economic systems; but also divine and human systems). The role of the ‘Go-Between’ is considered, both in the anthropological figure of the Trickster (Hyde 1998) and in the Schumpeterian entrepreneur. Both figures parlay appetite (economic wants) into meaning (cultural signs). Both practice a form of creativity based on deception, ‘creative destruction’; renewal by disruption and needs-must adaptation. The disciplinary purpose of the paper is to try to bridge two otherwise disconnected domains – cultural studies and evolutionary economics – by showing that the traditional methods of the humanities (e.g. anthropological, textual and historical analysis) have explanatory force in the context of economic actions and complex-system evolutionary dynamics. The objective is to understand creative innovation as a general cultural attribute rather than one restricted only to accredited experts such as artists; thus to theorise creativity as a form of emergence for dynamic adaptive systems. In this context, change is led by ‘paradigm shifters’ – tricksters and entrepreneurs who create new meanings out of the clash of difference, including the clash of mutually untranslatable communication systems (language, media, culture).