210 resultados para L1-norm
Resumo:
This paper will present program developers and institutional administrators with a program delivery model suitable for cross cultural international delivery developing students from industry through to master’s level tertiary qualifications. The model was designed to meet the needs of property professionals from an industry where technical qualifications are the norm and tertiary qualifications are emerging. A further need was to develop and deliver a program that enhanced the University’s current program profile in both the domestic and international arenas. Early identification of international educational partners, industry need and the ability to service the program were vital to the successful development of Master of Property program. The educational foundations of the program rest in educational partners, local tutorial support, international course management, cultural awareness of and in content, online communication fora, with a delivery focus on problem-based learning, self-directed study, teamwork and the development of a global understanding and awareness of the international property markets. In enrolling students from a diverse cultural background with technical qualifications and/or extensive work experience there are a number of educational barriers to be overcome for all students to successfully progress and complete the program. These barriers disappear when the following mechanisms are employed: individual student pathways, tutorial support by qualified peers, enculturation into tertiary practice, assessment tasks that recognise cultural norms and values, and finally that value is placed on the experiential knowledge, cultural practices and belief systems of the students.
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We constructed a novel autonomously replicating gene expression shuttle vector, with the aim of developing a system for transiently expressing proteins at levels useful for commercial production of vaccines and other proteins in plants. The vector, pRIC, is based on the mild strain of the geminivirus Bean yellow dwarf virus (BeYDV-m) and is replicationally released into plant cells from a recombinant Agrobacterium tumefaciens Ti plasmid. pRIC differs from most other geminivirus-based vectors in that the BeYDV replication-associated elements were included in cis rather than from a co-transfected plasmid, while the BeYDV capsid protein (CP) and movement protein (MP) genes were replaced by an antigen encoding transgene expression cassette derived from the non-replicating A. tumefaciens vector, pTRAc. We tested vector efficacy in Nicotiana benthamiana by comparing transient cytoplasmic expression between pRIC and pTRAc constructs encoding either enhanced green fluorescent protein (EGFP) or the subunit vaccine antigens, human papillomavirus subtype 16 (HPV-16) major CP L1 and human immunodeficiency virus subtype C p24 antigen. The pRIC constructs were amplified in planta by up to two orders of magnitude by replication, while 50% more HPV-16 L1 and three- to seven-fold more EGFP and HIV-1 p24 were expressed from pRIC than from pTRAc. Vector replication was shown to be correlated with increased protein expression. We anticipate that this new high-yielding plant expression vector will contribute towards the development of a viable plant production platform for vaccine candidates and other pharmaceuticals. © 2009 Blackwell Publishing Ltd.
Resumo:
Human papillomaviruses (HPV) are responsible for the most common human sexually transmitted viral infections, and high-risk types are responsible for causing cervical and other cancers. The minor capsid protein L2 of HPV plays important roles in virus entry into cells, localisation of viral components to the nucleus, in DNA binding, capsid formation and stability. It also elicits antibodies that are more cross-reactive between HPV types than does the major capsid protein L1, making it an attractive potential target for new-generation, more broadly protective subunit vaccines against HPV infections. However, its low abundance in natural capsids-12-72 molecules per 360 copies of L1-limits its immunogenicity. This review will explore the biological roles of the protein, and prospects for its use in new vaccines. © 2009 Springer-Verlag.
Resumo:
Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.
Resumo:
As cervical cancer is causally associated with 14 high-risk types of human papillomavirus (HPV), a successful HPV vaccine will have a major impact on this disease. Although some persistent HPV infections progress to cervical cancer, host immunity is generally able to clear most HPV infections. Both cell-mediated and antibody responses have been implicated in influencing the susceptibility, persistence or clearance of genital HPV infection. There have been two clinical trials that show that vaccines based on virus-like particles (VLPs) made from the major capsid protein, L1, are able to type specifically protect against cervical intra-epithelial neoplasia and infection. However, there is no evidence that even a mixed VLP vaccine will protect against types not included in the vaccine, and a major challenge that remains is how to engineer protection across a broader spectrum of viruses. Strategies for production of HPV vaccines using different vaccine vectors and different production systems are also reviewed. © 2005 Elsevier Ltd. All rights reserved.
Resumo:
Recombinant human papillomavirus (HPV) virus-like particles (VLPs) made from the major capsid protein L1 are promising vaccine candidates for use as vaccines against genital and other HPV infections, and particularly against HPV-16. However, HPV-16 genotype variants have different binding affinities for neutralising mouse Mabs raised against HPV-16 L1 VLPs. This paper analyses, using a panel of well-characterised Mabs, the effects on the antigenicity of various C- and N-terminal deletants of HPV-16 L1 made in insect cells via recombinant baculovirus, of an A → T mutation at residue 266 (A266T), and of a C → G mutation at conserved position 428 (C428G). The effects of these changes on assembly of the variant L1s were studied by electron microscopy. Binding of Mab H16:E70 to A266T was reduced by almost half in comparison to wild type L1. Retention of the C-terminal region 428-483 was critical for the binding of conformation-specific Mabs (H16:V5, H16:E70, H16:U4 and H16:9A) whereas deletion of the nuclear localisation signal (NLS) or the C428G mutation or an N-terminal deletion (residues 2-9) did not affect the antigenicity. The N-terminal deletion resulted in a mixed population of 30 and 55 nm VLPs, which differs from the same construct expressed in Escherichia coli, whereas pentamer aggregates resulted from deletion of the 428-465 region or the C428G mutation. The results have implications both for considering use of single-genotype HPV vaccines, and for design of novel second-generation vaccines. © 2006 Elsevier B.V. All rights reserved.
Resumo:
Human papillomaviruses are the etiological agents of cervical cancer, one of the two most prevalent cancers in women in developing countries. Currently available prophylactic vaccines are based on the L1 major capsid protein, which forms virus-like particles when expressed in yeast and insect cell lines. Despite their recognized efficacy, there are significant shortcomings: the vaccines are expensive, include only two oncogenic virus types, are delivered via intramuscular injection and require a cold chain. Plant expression systems may provide ways of overcoming some of these problems, in particular the expense. In this article, we report recent promising advances in the production of prophylactic and therapeutic vaccines against human papillomavirus by expression of the relevant antigens in plants, and discuss future prospects for the use of such vaccines. © 2010 Expert Reviews Ltd.
Resumo:
There is overwhelming evidence that persistent infection with high-risk human papillomaviruses (HR-HPV) is the main risk factor for invasive cancer of the cervix. Due to this global public health burden, two prophylactic HPV L1 virus-like particles (VLP) vaccines have been developed. While these vaccines have demonstrated excellent type-specific prevention of infection by the homologous vaccine types (high and low risk HPV types), no data have been reported on the therapeutic effects in people already infected with the low-risk HPV type. In this study we explored whether regression of CRPV-induced papillomas could be achieved following immunisation of out-bred New Zealand White rabbits with CRPV VLPs. Rabbits immunised with CRPV VLPs had papillomas that were significantly smaller compared to the negative control rabbit group (P ≤ 0.05). This data demonstrates the therapeutic potential of PV VLPs in a well-understood animal model with potential important implications for human therapeutic vaccination for low-risk HPVs. © 2008 Govan et al; licensee BioMed Central Ltd.
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Australia is experiencing an unprecedented expansion in mining due to intense demand from Asian economies thirsty for Australia’s non-renewable resources, with over $260 billion worth of capital investment currently in the pipeline (BREE 10). The scale of the present boom coupled with the longer term intensification of competitiveness in the global resources sector is changing the very nature of mining operations in Australia. Of particular note is the increasingly heavy reliance on a non-resident workforce, currently sourced from within Australia but with some recent proposals for projects to draw on overseas guest workers. This is no longer confined, as it once was, to remote, short term projects or to exploration and construction phases of operations, but is emerging as the preferred industry norm. Depending upon project location, workers may either fly-in, fly-out (FIFO) or drive-in, drive-out (DIDO), the critical point being that these operations are frequently undertaken in or near established communities. Drawing primarily on original fieldwork in one of Australia’s mining regions at the forefront of the boom, this paper explores some of the local impacts of new mining regimes, in particular their tendency to undermine collective solidarities, promote social division and fan cultural conflict.
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There’s nothing like travel to broaden the mind. As a young man living in Britain during the 1980s I thought I knew about human obesity, but it took a visit to the US to show me what an epidemic looks like. Nowadays I live in Australia, where human obesity is rife. We have plenty of fat horses too (Sillence et al., 2006), but they are noticeable. In fact, it was only recently during a return visit to Britain, that I was finally sold on the concept of an equine obesity epidemic. It seems that in the UK, the fat horse or pony is now so commonplace that it has come to represent the norm in the eyes of many owners. I met clinicians who claim to have forgotten what a fit horse looks like, and heard anecdotes of a responsible owner who kept their animals in a healthy body condition, only to be reported to the RSPCA for ‘cruelty’. Round and shiny have become the order of the day and, as we have learned from the tsunami of human obesity, once a problem reaches a certain scale it can seem unstoppable, despite the attendant risks, costs and consequences.
Resumo:
A randomized controlled trial evaluated the effectiveness of a 4-wk extended theory of planned behavior (TPB) intervention to promote regular physical activity and healthy eating among older adults diagnosed with Type 2 diabetes or cardiovascular disease (N = 183). Participants completed TPB measures of attitude, subjective norm, perceived behavioral control, and intention, as well as planning and behavior, at preintervention and 1 wk and 6 wk postintervention for each behavior. No significant time-by-condition effects emerged for healthy eating. For physical activity, significant time-by-condition effects were found for behavior, intention, planning, perceived behavioral control, and subjective norm. In particular, compared with control participants, the intervention group showed short-term improvements in physical activity and planning, with further analyses indicating that the effect of the intervention on behavior was mediated by planning. The results indicate that TPB-based interventions including planning strategies may encourage physical activity among older people with diabetes and cardiovascular disease.
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The three-component reaction-diffusion system introduced in [C. P. Schenk et al., Phys. Rev. Lett., 78 (1997), pp. 3781–3784] has become a paradigm model in pattern formation. It exhibits a rich variety of dynamics of fronts, pulses, and spots. The front and pulse interactions range in type from weak, in which the localized structures interact only through their exponentially small tails, to strong interactions, in which they annihilate or collide and in which all components are far from equilibrium in the domains between the localized structures. Intermediate to these two extremes sits the semistrong interaction regime, in which the activator component of the front is near equilibrium in the intervals between adjacent fronts but both inhibitor components are far from equilibrium there, and hence their concentration profiles drive the front evolution. In this paper, we focus on dynamically evolving N-front solutions in the semistrong regime. The primary result is use of a renormalization group method to rigorously derive the system of N coupled ODEs that governs the positions of the fronts. The operators associated with the linearization about the N-front solutions have N small eigenvalues, and the N-front solutions may be decomposed into a component in the space spanned by the associated eigenfunctions and a component projected onto the complement of this space. This decomposition is carried out iteratively at a sequence of times. The former projections yield the ODEs for the front positions, while the latter projections are associated with remainders that we show stay small in a suitable norm during each iteration of the renormalization group method. Our results also help extend the application of the renormalization group method from the weak interaction regime for which it was initially developed to the semistrong interaction regime. The second set of results that we present is a detailed analysis of this system of ODEs, providing a classification of the possible front interactions in the cases of $N=1,2,3,4$, as well as how front solutions interact with the stationary pulse solutions studied earlier in [A. Doelman, P. van Heijster, and T. J. Kaper, J. Dynam. Differential Equations, 21 (2009), pp. 73–115; P. van Heijster, A. Doelman, and T. J. Kaper, Phys. D, 237 (2008), pp. 3335–3368]. Moreover, we present some results on the general case of N-front interactions.
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Abstract Background The quantum increases in home Internet access and available online health information with limited control over information quality highlight the necessity of exploring decision making processes in accessing and using online information, specifically in relation to children who do not make their health decisions. Objectives To understand the processes explaining parents’ decisions to use online health information for child health care. Methods Parents (N = 391) completed an initial questionnaire assessing the theory of planned behaviour constructs of attitude, subjective norm, and perceived behavioural control, as well as perceived risk, group norm, and additional demographic factors. Two months later, 187 parents completed a follow-up questionnaire assessing their decisions to use online information for their child’s health care, specifically to 1) diagnose and/or treat their child’s suspected medical condition/illness and 2) increase understanding about a diagnosis or treatment recommended by a health professional. Results Hierarchical multiple regression showed that, for both behaviours, attitude, subjective norm, perceived behavioural control, (less) perceived risk, group norm, and (non) medical background were the significant predictors of intention. For parents’ use of online child health information, for both behaviours, intention was the sole significant predictor of behaviour. The findings explain 77% of the variance in parents’ intention to treat/diagnose a child health problem and 74% of the variance in their intentions to increase their understanding about child health concerns. Conclusions Understanding parents’ socio-cognitive processes that guide their use of online information for child health care is important given the increase in Internet usage and the sometimes-questionable quality of health information provided online. Findings highlight parents’ thirst for information; there is an urgent need for health professionals to provide parents with evidence-based child health websites in addition to general population education on how to evaluate the quality of online health information.
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We test the broken windows theory using a field experiment in a shared area of an academic workplace(the department common room). More specifically, we explore academics’ and postgraduate students’ behavior under an order condition (a clean environment) and a disorder condition (a messy environment). We find strong evidence that signs of disorderly behavior trigger littering: In 59% of the cases, subjects litter in the disorder treatment as compared to 18% in the order condition. These results remain robust in a multivariate analysis even when controlling for a large set of factors not directly examined by previous studies. Overall, when academic staff and postgraduate students observe that others have violated the social norm of keeping the common room clean, all else being equal, the probability of littering increases by around 40%.
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In the spirit of previous work in the compliance literature (e.g., tax, littering), we investigate whether environmental social norms affect volunteering in environmental organizations. Using two ‘environmental morale’ variables as indirect measures, we analyze the impact of social norms on the incidence of unpaid work in environmental organizations. In addition, we test whether violation of a specific environmental norm initiates a conditional cooperation response. We explore a large individual data set covering 32 countries from both Western and Eastern Europe, and extend the number of countries investigated to test the robustness of the relationship at the macro level. Our results indicate a strong positive relationship between the proxies for environmental social norms and volunteering in environmental organizations. The relationship persists despite our various robustness checks.