228 resultados para Human immune systems
Resumo:
A fear of imminent information overload predates the World Wide Web by decades. Yet, that fear has never abated. Worse, as the World Wide Web today takes the lion’s share of the information we deal with, both in amount and in time spent gathering it, the situation has only become more precarious. This chapter analyses new issues in information overload that have emerged with the advent of the Web, which emphasizes written communication, defined in this context as the exchange of ideas expressed informally, often casually, as in verbal language. The chapter focuses on three ways to mitigate these issues. First, it helps us, the users, to be more specific in what we ask for. Second, it helps us amend our request when we don't get what we think we asked for. And third, since only we, the human users, can judge whether the information received is what we want, it makes retrieval techniques more effective by basing them on how humans structure information. This chapter reports on extensive experiments we conducted in all three areas. First, to let users be more specific in describing an information need, they were allowed to express themselves in an unrestricted conversational style. This way, they could convey their information need as if they were talking to a fellow human instead of using the two or three words typically supplied to a search engine. Second, users were provided with effective ways to zoom in on the desired information once potentially relevant information became available. Third, a variety of experiments focused on the search engine itself as the mediator between request and delivery of information. All examples that are explained in detail have actually been implemented. The results of our experiments demonstrate how a human-centered approach can reduce information overload in an area that grows in importance with each day that passes. By actually having built these applications, I present an operational, not just aspirational approach.
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We advocate for the use of predictive techniques in interactive computer music systems. We suggest that the inclusion of prediction can assist in the design of proactive rather than reactive computational performance partners. We summarize the significant role prediction plays in human musical decisions, and the only modest use of prediction in interactive music systems to date. After describing how we are working toward employing predictive processes in our own metacreation software we reflect on future extensions to these approaches.
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Digital Human Models (DHM) have been used for over 25 years. They have evolved from simple drawing templates, which are nowadays still used in architecture, to complex and Computer Aided Engineering (CAE) integrated design and analysis tools for various ergonomic tasks. DHM are most frequently used for applications in product design and production planning, with many successful implementations documented. DHM from other domains, as for example computer user interfaces, artificial intelligence, training and education, or the entertainment industry show that there is also an ongoing development towards a comprehensive understanding and holistic modeling of human behavior. While the development of DHM for the game sector has seen significant progress in recent years, advances of DHM in the area of ergonomics have been comparatively modest. As a consequence, we need to question if current DHM systems are fit for the design of future mobile work systems. So far it appears that DHM in Ergonomics are rather limited to some traditional applications. According to Dul et al. (2012), future characteristics of Human Factors and Ergonomics (HFE) can be assigned to six main trends: (1) global change of work systems, (2) cultural diversity, (3) ageing, (4) information and communication technology (ICT), (5) enhanced competiveness and the need for innovation, and; (6) sustainability and corporate social responsibility. Based on a literature review, we systematically investigate the capabilities of current ergonomic DHM systems versus the ‘Future of Ergonomics’ requirements. It is found that DHMs already provide broad functionality in support of trends (1) and (2), and more limited options in regards to trend (3). Today’s DHM provide access to a broad range of national and international databases for correct differentiation and characterization of anthropometry for global populations. Some DHM explicitly address social and cultural modeling of groups of people. In comparison, the trends of growing importance of ICT (4), the need for innovation (5) and sustainability (6) are addressed primarily from a hardware-oriented and engineering perspective and not reflected in DHM. This reflects a persistent separation between hardware design (engineering) and software design (information technology) in the view of DHM – a disconnection which needs to be urgently overcome in the era of software defined user interfaces and mobile devices. The design of a mobile ICT-device is discussed to exemplify the need for a comprehensive future DHM solution. Designing such mobile devices requires an approach that includes organizational aspects as well as technical and cognitive ergonomics. Multiple interrelationships between the different aspects result in a challenging setting for future DHM. In conclusion, the ‘Future of Ergonomics’ pose particular challenges for DHM in regards to the design of mobile work systems, and moreover mobile information access.
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Background The incidence of malignant mesothelioma is increasing. There is the perception that survival is worse in the UK than in other countries. However, it is important to compare survival in different series based on accurate prognostic data. The European Organisation for Research and Treatment of Cancer (EORTC) and the Cancer and Leukaemia Group B (CALGB) have recently published prognostic scoring systems. We have assessed the prognostic variables, validated the EORTC and CALGB prognostic groups, and evaluated survival in a series of 142 patients. Methods Case notes of 142 consecutive patients presenting in Leicester since 1988 were reviewed. Univariate analysis of prognostic variables was performed using a Cox proportional hazards regression model. Statistically significant variables were analysed further in a forward, stepwise multivariate model. EORTC and CALGB prognostic groups were derived, Kaplan-Meier survival curves plotted, and survival rates were calculated from life tables. Results Significant poor prognostic factors in univariate analysis included male sex, older age, weight loss, chest pain, poor performance status, low haemoglobin, leukocytosis, thrombocytosis, and non-epithelial cell type (p<0.05). The prognostic significance of cell type, haemoglobin, white cell count, performance status, and sex were retained in the multivariate model. Overall median survival was 5.9 (range 0-34.3) months. One and two year survival rates were 21.3% (95% CI 13.9 to 28.7) and 3.5% (0 to 8.5), respectively. Median, one, and two year survival data within prognostic groups in Leicester were equivalent to the EORTC and CALGB series. Survival curves were successfully stratified by the prognostic groups. Conclusions This study validates the EORTC and CALGB prognostic scoring systems which should be used both in the assessment of survival data of series in different countries and in the stratification of patients into randomised clinical studies.
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The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as histone acetyltransferases or HATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The proinflammatory environment is increasingly being recognised as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential & current development of histone deacetylases for the treatment of diseases for which a proinflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the proinflammatory environment. © 2009 Bentham Science Publishers Ltd.
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Re-programming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time-course dependent changes in the muscular transcriptome following an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h post-exercise from eight healthy, endurance-trained, male individuals. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three h post-exercise, 102 gene sets were up-regulated [family wise error rate (FWER), P < 0.05]; including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1-signaling. Forty-eight h post-exercise, among 19 enriched gene sets (FWER, P < 0.05), two gene sets related to actin cytoskeleton remodeling were up-regulated. Ninety-six h post-exercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of which were up-regulated; including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h post-exercise transcriptome indicates substantial transcriptional activity, potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.
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Purpose: To identify a 15-KDa novel hypoxia-induced secreted protein in head and neck squamous cell carcinomas (HNSCC) and to determine its role in malignant progression. Methods: We used surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and tandem MS to identify a novel hypoxia-induced secreted protein in FaDu cells. We used immunoblots, real-time polymerase chain reaction (PCR), and enzyme-linked immunoabsorbent assay to confirm the hypoxic induction of this secreted protein as galectin-1 in cell lines and xenografts. We stained tumor tissues from 101 HNSCC patients for galectin-1, CA IX (carbonic anhydrase IX, a hypoxia marker) and CDS (a T-cell marker). Expression of these markers was correlated to each other and to treatment outcomes. Results: SELDI-TOF studies yielded a hypoxia-induced peak at 15 kDa that proved to be galectin-1 by MS analysis. Immunoblots and PCR studies confirmed increased galectin-1 expression by hypoxia in several cancer cell lines. Plasma levels of galectin-1 were higher in tumor-bearing severe combined immunodeficiency (SCID) mice breathing 10% O 2 compared with mice breathing room air. In HNSCC patients, there was a significant correlation between galectin-1 and CA IX staining (P = .01) and a strong inverse correlation between galectin-1 and CDS staining (P = .01). Expression of galectin-1 and CDS were significant predictors for overall survival on multivariate analysis. Conclusion: Galectin-1 is a novel hypoxia-regulated protein and a prognostic marker in HNSCC. This study presents a new mechanism on how hypoxia can affect the malignant progression and therapeutic response of solid tumors by regulating the secretion of proteins that modulate immune privilege. © 2005 by American Society of Clinical Oncology.
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Several chronic infections known to be associated with malignancy have established oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. © 2001 Cancer Research Campaign http://www.bjcancer.com.
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Recent studies have demonstrated that angiogenesis and suppressed cell- mediated immunity (CMI) play a central role in the pathogenesis of malignant disease facilitating tumour growth, invasion and metastasis. In the majority of tumours, the malignant process is preceded by a pathological condition or exposure to an irritant which itself is associated with the induction of angiogenesis and/or suppressed CMI. These include: cigarette smoking, chronic bronchitis and lung cancer; chronic oesophagitis and oesophageal cancer; chronic viral infections such as human papilloma virus and ano-genital cancers, chronic hepatitis B and C and hepatocellular carcinoma, and Epstein- Barr virus (EBV) and lymphomas; chronic inflammatory conditions such as Crohn's disease and ulcerative colitis and colorectal cancer; asbestos exposure and mesothelioma and excessive sunlight exposure/sunburn and malignant melanoma. Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. The increased blood supply would facilitate the development and proliferation of an abnormal clone or clones of cells arising as the result of: (a) an inherited genetic abnormality; and/or (b) acquired somatic mutations, the latter due to local production and/or enhanced delivery of carcinogens and mutagenic growth factors. With progressive detrimental mutations and growth-induced tumour hypoxia, the transformed cell, to a lesser or greater extent, may amplify the angiogenic process and CMI suppression, thereby facilitating further tumour growth and metastasis. There is accumulating evidence that long-term treatment with cyclo-oxygenase inhibitors (aspirin and indomethacin), cytokines such as interferon-α, anti-oestrogens (tamoxifen and raloxifene) and captopril significantly reduces the incidence of solid tumours such as breast and colorectal cancer. These agents are anti-angiogenic and, in the case of aspirin, indomethacin and interferon-α have proven immunomodulatory effects. Collectively these observations indicate that angiogenesis and suppressed CMI play a central role in the development and progression of malignant disease. (C) 2000 Elsevier Science Ltd.
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This thesis documented pathogenic species of nontuberculous mycobacteria in the Brisbane water distribution system. When water and shower aerosol strains were compared with human strains of mycobacteria, the study found that the likelihood of acquiring infection from municipal water was specific for four main species. The method for isolation of mycobacteria from water was refined, followed by sampling from 220 sites across Brisbane. A variety of species (incl 15 pathogens) were identified and genotypically compared to human strains. For M. abscessus and M. lentiflavum, water strains clustered with human strains. Pathogenic strains of M. kansasii were found, though non-pathogenic strains dominated. Waterborne strains of M. fortuitum differed to human strains. Extensive home sampling of 20 patients with NTM disease, supported the theory that the risk of acquiring NTM from water or shower aerosols appears species specific for M. avium, M. kansasii, M. lentiflavum and M. abscessus.
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Total Artificial Hearts are mechanical pumps which can be used to replace the failing natural heart. This novel study developed a means of controlling a new design of pump to reproduce physiological flow bringing closer the realisation of a practical artificial heart. Using a mathematical model of the device, an optimisation algorithm was used to determine the best configuration for the magnetic levitation system of the pump. The prototype device was constructed and tested in a mock circulation loop. A physiological controller was designed to replicate the Frank-Starling like balancing behaviour of the natural heart. The device and controller provided sufficient support for a human patient while also demonstrating good response to various physiological conditions and events. This novel work brings the design of a practical artificial heart closer to realisation.
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This thesis presents social requirements and design considerations from a study evaluating interactive approaches to social navigation and user-generated information sharing in urban environments using mobile devices. It investigates innovative ways to leverage mobile information and communication technology in order to provide a social navigation platform for residents and visitors in and for public urban places. Through a design case study this work presents CityFlocks, a mobile information system that offers an easy way for information-seeking new residents or visitors to access tacit knowledge from local people about their new community. It is intended to enable visitors and new residents in a city to tap into the knowledge and experiences of local residents in order to gather information about their new environment. Its design specifically aims to lower existing barriers of access and facilitate social navigation in urban places. In various user tests it evaluates two general user interaction alternatives – direct and indirect social navigation – and analyses which interaction method works better for people using a mobile device to socially navigate urban environments. The outcomes are relevant for the user interaction design of future mobile information systems that leverage the social navigation approach.
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Emerging infectious diseases present a complex challenge to public health officials and governments; these challenges have been compounded by rapidly shifting patterns of human behaviour and globalisation. The increase in emerging infectious diseases has led to calls for new technologies and approaches for detection, tracking, reporting, and response. Internet-based surveillance systems offer a novel and developing means of monitoring conditions of public health concern, including emerging infectious diseases. We review studies that have exploited internet use and search trends to monitor two such diseases: influenza and dengue. Internet-based surveillance systems have good congruence with traditional surveillance approaches. Additionally, internet-based approaches are logistically and economically appealing. However, they do not have the capacity to replace traditional surveillance systems; they should not be viewed as an alternative, but rather an extension. Future research should focus on using data generated through internet-based surveillance and response systems to bolster the capacity of traditional surveillance systems for emerging infectious diseases.
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The introduction of safety technologies into complex socio-technical systems requires an integrated and holistic approach to HF and engineering, considering the effects of failures not only within system boundaries, but also at the interfaces with other systems and humans. Level crossing warning devices are examples of such systems where technically safe states within the system boundary can influence road user performance, giving rise to other hazards that degrade safety of the system. Chris will discuss the challenges that have been encountered to date in developing a safety argument in support of low-cost level crossing warning devices. The design and failure modes of level crossing warning devices are known to have a significant influence on road user performance; however, quantifying this effect is one of the ongoing challenges in determining appropriate reliability and availability targets for low-cost level crossing warning devices.
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Enterovirus 71 (EV71) is one of the main etiological agents for Hand, Foot and Mouth Disease (HFMD) and has been shown to be associated with severe clinical manifestation. Currently, there is no antiviral therapeutic for the treatment of HFMD patients owing to a lack of understanding of EV71 pathogenesis. This study seeks to elucidate the transcriptomic changes that result from EV71 infection. Human whole genome microarray was employed to monitor changes in genomic profiles between infected and uninfected cells. The results reveal altered expression of human genes involved in critical pathways including the immune response and the stress response. Together, data from this study provide valuable insights into the host–pathogen interaction between human colorectal cells and EV71.