875 resultados para Human voice
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There are currently 23,500 level crossings in Australia, broadly divided active level crossings with flashing lights; and passive level crossings controlled by stop and give way signs. The current strategy is to annually upgrade passive level crossings with active controls within a given budget, but the 5,900 public passive crossings are too numerous to be upgraded all. The rail industry is considering alternative options to treat more crossings. One of them is to use lower cost equipment with reduced safety integrity level, but with a design that would fail to a safe state: in case of the impossibility for the system to know whether a train is approaching, the crossing changes to a passive crossing. This is implemented by having a STOP sign coming in front of the flashing lights. While such design is considered safe in terms of engineering design, questions remain on human factors. In order to evaluate whether such approach is safe, we conducted a driving simulator study where participants were familiarized with the new active crossing, before changing the signage to a passive crossing. Our results show that drivers treated the new crossing as an active crossing after the novelty effect had passed. While most participants did not experience difficulties with the crossing being turned back to a passive crossing, a number of participants experienced difficulties stopping in time at the first encounter of such passive crossing. Worse, a number of drivers never realized the signage had changed, highlighting the link between the decision to brake and stop at an active crossing to the lights flashing. Such results show the potential human factor issues of changing an active crossing to a passive crossing in case of failure of the detection of the train.
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When working with the world’s most vulnerable populations there are questions surrounding the salience of physical activity promotion programs given the multitude of basic needs that must first be met. Indeed, physical activity may be a low priority for individuals seeking safety, reunification with loved ones, and food for their families, as a subsistence lifestyle makes excess weight gain, diabetes, and cardiovascular disease irrelevant. Yet, when working with people from a refugee background for whom these challenges all too frequently apply, opportunities for sport and activity have repeatedly surfaced as desirable and needed, yet are utterly deficient. If we conceptualize physical activity purely as a chronic disease prevention tool, its significance within under-resourced communities is most assuredly lost; however, if we harness the power of physical activity to serve as an agent of positive social change, then it instantly becomes more meaningful and necessary.
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The Intergovernmental Panel on Climate Change (IPCC) has published its latest report upon the impacts of global warming, highlighting the pernicious impact of climate change upon public health, well-being, and even the survival of the human race.
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The human genome project was a grand scientific enterprise which attracted both hyperbole and ridicule alike. The project was lauded as “the moon shot of the life sciences”, the “holy grail of man”, “the code of codes”, and “the book of life”. Such rhetoric has also received scorn. President George Bush senior managed to deflate the pretensions of the project with the accidental slip that it was the “human gnome initiative”. In The Sequence, Kevin Davies seeks to go beyond such metaphors, and provide a candid and honest account of the race of the human genome project. The author is indebted to the authoritative book The Gene Wars, which considered the early struggles over the human genome project. Robert Cook-Deegan observes that there was initially much debate over whether there should be a Human Genome Project at all: The debate became one of “big” science versus “small” science. The reliance on systematic technology development and goal-directed gene-mapping efforts presaged a new style for biology, one that elicited excitement from those attracted to whiz-bang technologies but drew gasps of revulsion from those who aspired to cultivate biology on a more modest scale and with decentralized organisation. The battle was, among other things, over whose vision would control the budget and which scientific aesthetic would prevail.
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The Anti-Counterfeiting Trade Agreement (ACTA) 2011 - Twitter hashtag #ACTA - is a controversial trade agreement designed to provide for stronger enforcement of intellectual property rights.
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The Prime Minister of Australia, Tony Abbott, has said that ‘Australia is Open for Business’. His trade and investment minister, Andrew Robb, has vigorously pursued bilateral trade agreements with neighbours, South Korea, Japan, China, and India — as well as the regional trade agreement, the Trans-Pacific Partnership. Such trade activity raises questions about the relationship between trade policy and human rights. If we are open for business, should we be open for business for countries engaged in human rights abuses? Should enter into trade agreements, which could have an adverse upon human rights? The Trans-Pacific Partnership highlights a range of problems with Australia’s treaty-making process. One important issue is the question of the relationship between trade and human rights.
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This paper analyzes the application of rights-based approaches to disaster displacement in the Asia-Pacific region in order to assess whether the current framework is sufficient to protect the rights of internally displaced persons. It identifies that disaster-induced displacement is increasingly prevalent in the region and that economic and social conditions in many countries mean that the impact of displacement is often prolonged and more severe. The paper identifies the relevant human rights principles which apply in the context of disaster-induced displacement and examines their implementation in a number of soft-law instruments. While it identifies shortcomings in impementation and enforcement, the paper concludes that a rights-based approach could be enhanced by greater engagement with existing human rights treaties and greater implementation of soft-law principles, and that no new instrument is required.
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Bombyx mori silk fibroin membranes provide a potential delivery vehicle for both cells and extracellular matrix (ECM) components into diseased or injured tissues. We have previously demonstrated the feasibility of growing retinal pigment epithelial cells (RPE) on fibroin membranes with the view to repairing the retina of patients afflicted with age-related macular degeneration (AMD). The goal of the present study was to investigate the feasibility of incorporating the ECM component elastin, in the form of human recombinant tropoelastin, into these same membranes. Two basic strategies were explored: (1) membranes prepared from blended solutions of fibroin and tropoelastin; and (2) layered constructs prepared from sequentially cast solutions of fibroin, tropoelastin, and fibroin. Optimal conditions for RPE attachment were achieved using a tropoelastin-fibroin blend ratio of 10 to 90 parts by weight. Retention of tropoelastin within the blend and layered constructs was confirmed by immunolabelling and Fourier-transform infrared spectroscopy (FTIR). In the layered constructs, the bulk of tropoelastin was apparently absorbed into the initially cast fibroin layer. Blend membranes displayed higher elastic modulus, percentage elongation, and tensile strength (p < 0.01) when compared to the layered constructs. RPE cell response to fibroin membranes was not affected by the presence of tropoelastin. These findings support the potential use of fibroin membranes for the co-delivery of RPE cells and tropoelastin.
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Human factors such as distraction, fatigue, alcohol and drug use are generally ignored in car-following (CF) models. Such ignorance overestimates driver capability and leads to most CF models’ inability in realistically explaining human driving behaviors. This paper proposes a novel car-following modeling framework by introducing the difficulty of driving task measured as the dynamic interaction between driving task demand and driver capability. Task difficulty is formulated based on the famous Task Capability Interface (TCI) model, which explains the motivations behind driver’s decision making. The proposed method is applied to enhance two popular CF models: Gipps’ model and IDM, and named as TDGipps and TDIDM respectively. The behavioral soundness of TDGipps and TDIDM are discussed and their stabilities are analyzed. Moreover, the enhanced models are calibrated with the vehicle trajectory data, and validated to explain both regular and human factor influenced CF behavior (which is distraction caused by hand-held mobile phone conversation in this paper). Both the models show better performance than their predecessors, especially in presence of human factors.
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Background The genetic mutation resulting in osteogenesis imperfecta (OI) type V was recently characterised as a single point mutation (c.-14C > T) in the 5' untranslated region (UTR) of IFITM5, a gene encoding a transmembrane protein with expression restricted to skeletal tissue. This mutation creates an alternative start codon and has been shown in a eukaryotic cell line to result in a longer variant of IFITM5, but its expression has not previously been demonstrated in bone from a patient with OI type V. Methods Sanger sequencing of the IFITM5 5' UTR was performed in our cohort of subjects with a clinical diagnosis of OI type V. Clinical data was collated from referring clinicians. RNA was extracted from a bone sample from one patient and Sanger sequenced to determine expression of wild-type and mutant IFITM5. Results: All nine subjects with OI type V were heterozygous for the c.-14C > T IFITM5 mutation. Clinically, there was heterogeneity in phenotype, particularly in the manifestation of bone fragility amongst subjects. Both wild-type and mutant IFITM5 mRNA transcripts were present in bone. Conclusions The c.-14C > T IFITM5 mutation does not result in an RNA-null allele but is expressed in bone. Individuals with identical mutations in IFITM5 have highly variable phenotypic expression, even within the same family.
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Humans and microbes have developed a symbiotic relationship over time, and alterations in this symbiotic relationship have been linked to several immune mediated diseases such as inflammatory bowel disease, type 1 diabetes and spondyloarthropathies. Improvements in sequencing technologies, coupled with a renaissance in 16S rRNA gene based community profiling, have enabled the characterization of microbiomes throughout the body including the gut. Improved characterization and understanding of the human gut microbiome means the gut flora is progressively being explored as a target for novel therapies including probiotics and faecal microbiota transplants. These innovative therapies are increasingly used for patients with debilitating conditions where conventional treatments have failed. This review discusses the current understanding of the interplay between host genetics and the gut microbiome in the pathogenesis of spondyloarthropathies, and how this may relate to potential therapies for these conditions.
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Asthma prevalence in children has remained relatively constant in many Western countries, but hospital admissions for younger age groups have increased over time.1 Although the role of outdoor aeroallergens as triggers for asthma exacerbations requiring hospitalization in children and adolescents is complex, there is evidence that increasing concentrations of grass pollen are associated with an increased risk of asthma exacerbations in children.2 Human rhinovirus (HRV) infections are implicated in most of the serious asthma exacerbations in school-age children.3 In previous research, HRV infections and aeroallergen exposure have usually been studied independently. To our knowledge, only 1 study has examined interactions between these 2 factors,4 but lack of power prevented any meaningful interpretation...
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Our understanding of the origin and fate of the IgE-switched B cell has been markedly improved by studies in mouse models. The immediate precursor of the IgE-switched B cell is either a relatively naive nonswitched B cell or a mature IgG-switched B cell. These 2 routes are referred to as the direct and indirect pathways, respectively. IgE responses derived from each pathway differ significantly, largely reflecting the difference in time spent in a germinal center and thus time for clonal expansion, somatic hypermutation, affinity maturation, and acquisition of a memory phenotype. The clinical and therapeutic implications for IgE responses in human subjects are still a matter of debate, largely because the immunization procedures used in the animal models are significantly different from classical atopic sensitization to allergens from pollen and mites. On the basis of the limited information available, it seems likely that these atopic IgE responses are characterized by a relatively low IgG/IgE ratio, low B-cell memory, and modest affinity maturation, which fits well with the direct switching pathway. It is still unresolved how the IgE response evolves to cover a wide epitope repertoire involving many epitopes per allergen, as well as many different allergens from a single allergen source. © 2013 American Academy of Allergy, Asthma & Immunology.
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The aim of this study was to investigate the molecular basis of human IgE-allergen interaction by screening a phage-displayed peptide library with an allergen-specific human IgE-mimicking monoclonal antibody (mAb). A mAb that reacted with major grass pollen allergens was successfully identified and shown to inhibit human IgE-allergen interaction. Biopanning of a phage-displayed random peptide library with this mAb yielded a 12 amino acid long mimotope. A synthetic peptide based on this 12-mer mimotope inhibited mAb and human IgE binding to grass pollen extracts. Our results indicate that such synthetic peptide mimotopes of allergens have potential as novel therapeutic agents. © 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
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Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (106–107 CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.