489 resultados para HUMAN ORAL BIOAVAILABILITY


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This paper emerges from my practice-led PhD thesis investigating the ways fiction writers can enter a dialogue with the project of oral history in Australia. In this paper, I survey the current literature in order to identify the status of fiction within the practice of oral history in Australia. I argue that oral historians and fiction writers are, among other things, both concerned with understanding subjectivity. I consider how one of the specific qualities of fiction, that of character, can provide a space to explore subjectivity, and rely on my own writing practice in order to demonstrate how oral history theory can enrich fictive writings. This paper, while positioned in the field of oral history, exists within a wider debate around how the past can legitimately be represented; I argue oral historians and fiction writers can enter a dialogue around shared concerns.

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Premature convergence to local optimal solutions is one of the main difficulties when using evolutionary algorithms in real-world optimization problems. To prevent premature convergence and degeneration phenomenon, this paper proposes a new optimization computation approach, human-simulated immune evolutionary algorithm (HSIEA). Considering that the premature convergence problem is due to the lack of diversity in the population, the HSIEA employs the clonal selection principle of artificial immune system theory to preserve the diversity of solutions for the search process. Mathematical descriptions and procedures of the HSIEA are given, and four new evolutionary operators are formulated which are clone, variation, recombination, and selection. Two benchmark optimization functions are investigated to demonstrate the effectiveness of the proposed HSIEA.

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The importance of the environment to the fulfilment of human rights is widely accepted at international law. What is less well-accepted is the proposition that we, as humans, possess rights to the environment beyond what is necessary to support our basic human needs. The suggestion that a human right to a healthy environment may be emerging at international law raises a number of theoretical and practical challenges for human rights law, with such challenges coming from both within and outside the human rights discourse. It is argued that human rights law can make a positive contribution to environmental protection, but the precise nature of the connection between the environment and human rights warrants more critical analysis. This short paper considers the different ways that the environment is conceptualised in international human rights law and analyses the proposition that a right to a healthy environment is emerging. It identifies some of the challenges which would need to be overcome before such a right could be recognised, including those which draw on the disciplines of deep ecology and earth jurisprudence.

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Nitric oxide is known to be an important inflammatory mediator, and is implicated in the pathophysiology of a range of inflammatory disorders. The aim of this study was to determine the localization and distribution of endothelial NOS (NOS-II) in human gingival tissue, and to ascertain if human gingival fibroblasts express NOS-II when stimulated with interferon gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS). The distribution of NOS-II in inflamed and non-inflamed specimens of human gingivae was studied using a monoclonal antibody against nitric oxide synthase II. Cultures of fibroblasts derived from healthy human gingivae were used for the cell culture experiments. The results from immunohistochemical staining of the tissues indicated an upregulation of NOS-II expression in inflamed compared to non-inflamed gingival tissue. Fibroblasts and inflammatory cells within the inflamed connective tissue were positively stained for NOS-II. In addition, basal keratinocytes also stained strongly for NOS-II, in both healthy and inflamed tissue sections. When cultured human gingival fibroblasts were stimulated by INF-gamma and Porphyromonas gingivalis LPS, NOS-II was more strongly expressed than when the cells were exposed to LPS or IFN-gamma alone. These data suggest that, as for other inflammatory diseases, NO plays a role in the pathophysiology of periodontitis.

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Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.

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Recent findings concerning exhaled aerosol size distributions and the regions in the respiratory tract in which they are generated could have significant implications for human to human spread of lower respiratory tract-specific infections. Even in healthy people, measurable quantities of aerosol are routinely generated from the Lower Respiratory Tract (LRT) during breathing(1-3). We have found that there at least three modes in the exhaled aerosol size distribution of healthy adults(4) (see Figure 1). These modes each have a characteristic size and arise from different parts of the respiratory tract. The respiratory bronchioles produce aerosol during breathing, the larynx during speech and the oral cavity also during speech. The model of the resulting droplet size distribution is therefore called the Bronchial Laryngeal Oral (B.L.O.) tri-modal model of expired aerosol.

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To develop a rapid optimized technique of wide-field imaging of the human corneal subbasal nerve plexus. A dynamic fixation target was developed and, coupled with semiautomated tiling software, a rapid method of capturing and montaging multiple corneal confocal microscopy images was created. To illustrate the utility of this technique, wide-field maps of the subbasal nerve plexus were produced in 2 participants with diabetes, 1 with and 1 without neuropathy. The technique produced montages of the central 3 mm of the subbasal corneal nerve plexus. The maps seem to show a general reduction in the number of nerve fibers and branches in the diabetic participant with neuropathy compared with the individual without neuropathy. This novel technique will allow more routine and widespread use of subbasal nerve plexus mapping in clinical and research situations. The significant reduction in the time to image the corneal subbasal nerve plexus should expedite studies of larger groups of diabetic patients and those with other conditions affecting nerve fibers. The inferior whorl and the surrounding areas may show the greatest loss of nerve fibers in individuals with diabetic neuropathy, but this should be further investigated in a larger cohort.

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There is general agreement in the scientific community that entrepreneurship plays a central role in the growth and development of an economy in rapidly changing environments (Acs & Virgill 2010). In particular, when business activities are regarded as a vehicle for sustainable growth at large, that goes beyond mere economic returns of singular entities, encompassing also social problems and heavily relying on collaborative actions, then we more precisely fall into the domain of ‘social entrepreneurship’(Robinson et al. 2009). In the entrepreneurship literature, prior studies demonstrated the role of intentionality as the best predictor of planned behavior (Ajzen 1991), and assumed that the intention to start a business derives from the perception of desirability and feasibility and from a propensity to act upon an opportunity (Fishbein & Ajzen 1975). Recognizing that starting a business is an intentional act (Krueger et al. 2000) and entrepreneurship is a planned behaviour (Katz & Gartner 1988), models of entrepreneurial intentions have substantial implications for intentionality research in entrepreneurship. The purpose of this paper is to explore the emerging practice of social entrepreneurship by comparing the determinants of entrepreneurial intention in general versus those leading to startups with a social mission. Social entrepreneurial intentions clearly merit to be investigated given that the opportunity identification process is an intentional process not only typical of for profit start-ups, and yet there is a lack of research examining opportunity recognition in social entrepreneurship (Haugh 2005). The key argument is that intentionality in both traditional and social entrepreneurs during the decision-making process of new venture creation is influenced by an individual's perceptions toward opportunities (Fishbein & Ajzen 1975). Besides opportunity recognition, at least two other aspects can substantially influence intentionality: human and social capital (Davidsson, 2003). This paper is set to establish if and to what extent the social intentions of potential entrepreneurs, at the cognitive level, are influenced by opportunities recognition, human capital, and social capital. By applying established theoretical constructs, the paper draws comparisons between ‘for-profit’ and ‘social’ intentionality using two samples of students enrolled in Economy and Business Administration at the University G. d’Annunzio in Pescara, Italy. A questionnaire was submitted to 310 potential entrepreneurs to test the robustness of the model. The collected data were used to measure the theoretical constructs of the paper. Reliability of the multi-item scale for each dimension was measured using Cronbach alpha, and for all the dimensions measures of reliability are above 0.70. We empirically tested the model using structural equation modeling with AMOS. The results allow us to empirically contribute to the argument regarding the influence of human and social cognitive capital on social and non-social entrepreneurial intentions. Moreover, we highlight the importance for further researchers to look deeper into the determinants of traditional and social entrepreneurial intention so that governments can one day define better polices and regulations that promote sustainable businesses with a social imprint, rather than inhibit their formation and growth.

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Ultraendurance exercise training places large energy demands on athletes and causes a high turnover of vitamins through sweat losses, metabolism, and the musculoskeletal repair process. Ultraendurance athletes may not consume sufficient quantities or quality of food in their diet to meet these needs. Consequently, they may use oral vitamin and mineral supplements to maintain their health and performance. We assessed the vitamin and mineral intake of ultraendurance athletes in their regular diet, in addition to oral vitamin and mineral supplements. Thirty-seven ultraendurance triathletes (24 men and 13 women) completed a 7-day nutrition diary including a questionnaire to determine nutrition adequacy and supplement intake. Compared with dietary reference intakes for the general population, both male and female triathletes met or exceeded all except for vitamin D. In addition, female athletes consumed slightly less than the recommended daily intake for folate and potassium; however, the difference was trivial. Over 60% of the athletes reported using vitamin supplements, of which vitamin C (97.5%), vitamin E (78.3%), and multivitamins (52.2%) were the most commonly used supplements. Almost half (47.8%) the athletes who used supplements did so to prevent or reduce cold symptoms. Only 1 athlete used supplements on formal medical advice. Vitamin C and E supplementation was common in ultraendurance triathletes, despite no evidence of dietary deficiency in these 2 vitamins.

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Railway level crossings present an arguably unique interface between two transport systems that differ markedly in their performance characteristics, their degrees of regulation and their safety cultures. Railway level crossings also differ dramatically in the importance they represent as safety issues for the two modes. For rail, they are the location of a large proportion of fatalities within the system and are therefore the focus of much safety concern. For the road system, they comprise only a few percent of all fatalities, although the potential for catastrophic outcomes exist. Rail operators and regulators have traditionally required technologies to be failsafe and to demonstrate high levels of reliability. The resultant level of complexity and cost has both limited their extent of application and led to a need to better understand how motorists comprehend and respond to these systems.

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The numerous interconnections between the environment and human rights are well established internationally. It is understood that environmental issues such as pollution, deforestation or the misuse of resources can impact on individuals’ and communities’enjoyment of fundamental rights, including the right to health, the right to an adequate standard of living, the right to self‐determination and the right to life itself. These are rights which are guaranteed under international human rights law and in relation to which governments bear certain responsibilities. Further, environmental issues can also impact on governments’ capacity to protect and fulfil the rights of their citizens. In this way human rights and environmental protection can be constructed as being mutually supportive. In addition to these links between the environment and human rights, human rights principles arguably offer a framework for identifying and addressing environmental injustice. The justice implications of environmental problems are well documented and there are many examples where pollution, deforestation or other degradation disproportionately impact upon poorer neighbourhoods or areas populated by minority groups. On the international level, environmental injustice exists between developed and developing States, as well as between present and future generations who will inherit the environmental problems we are creating today. This paper investigates the role of human rights principles, laws and mechanisms in addressing these instances of environmental injustice and argues that the framework of human rights norms provides an approach to environmental governance which can help to minimise injustice and promote the interests of those groups which are most adversely affected. Further, it suggests that the human rights enforcement mechanisms which exist at international law could be utilised to lend weight to claims for more equitable environmental policies.

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The automotive industry has been the focus of digital human modeling (DHM) research and application for many years. In the highly competitive marketplace for personal transportation, the desire to improve the customer’s experience has driven extensive research in both the physical and cognitive interaction between the vehicle and its occupants. Human models provide vehicle designers with tools to view and analyze product interactions before the first prototypes are built, potentially improving the design while reducing cost and development time. The focus of DHM research and applications began with prediction and representation of static postures for purposes of driver workstation layout, including assessments of seat adjustment ranges and exterior vision. Now DHMs are used for seat design and assessment of driver reach and ingress/egress. DHMs and related simulation tools are expanding into the cognitive domain, with computational models of perception and motion, and into the dynamic domain with models of physical responses to ride and vibration. Moreover, DHMs are now widely used to analyze the ergonomics of vehicle assembly tasks. In this case, the analysis aims to determine whether workers can be expected to complete the tasks safely and with good quality. This preface provides a review of the literature to provide context for the nine new papers presented in this special issue.

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Immunotherapy is a promising new treatment for patients with advanced prostate and ovarian cancer, but its application is limited by the lack of suitable target antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that is significantly overexpressed in malignant versus healthy prostate and ovarian tissue, making it an attractive target for immunotherapy. We identified a naturally processed, HLA-A*0201-restricted peptide epitope within the signal sequence region of KLK4 that induced CTL responses in vitro in most healthy donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 + cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL responses and identify it as an attractive target for prostate and ovarian cancer immunotherapy.

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Mebendazole (MBZ) was identified as a promising therapeutic on the basis of its ability to induce apoptosis in melanoma cell lines through a B-cell lymphoma 2 (BCL2)-dependent mechanism. We now show that in a human xenograft melanoma model, oral MBZ is as effective as the current standard of care temozolomide in reducing tumor growth. Inhibition of melanoma growth in vivo is accompanied by phosphorylation of BCL2 and decreased levels of X-linked inhibitor of apoptosis (XIAP). Reduced expression of XIAP on treatment with MBZ is partially mediated by its proteasomal degradation. Furthermore, exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating XIAP's inhibition on apoptosis. XIAP expression on exposure to MBZ is indicative of sensitivity to MBZ as MBZ-resistant cells do not show reduced levels of XIAP after treatment. Resistance to MBZ can be reversed partially by siRNA knockdown of cellular levels of XIAP. Our data indicate that MBZ is a promising antimelanoma agent on the basis of its effects on key antiapoptotic proteins.