302 resultados para Random Access
Resumo:
Product reviews are the foremost source of information for customers and manufacturers to help them make appropriate purchasing and production decisions. Natural language data is typically very sparse; the most common words are those that do not carry a lot of semantic content, and occurrences of any particular content-bearing word are rare, while co-occurrences of these words are rarer. Mining product aspects, along with corresponding opinions, is essential for Aspect-Based Opinion Mining (ABOM) as a result of the e-commerce revolution. Therefore, the need for automatic mining of reviews has reached a peak. In this work, we deal with ABOM as sequence labelling problem and propose a supervised extraction method to identify product aspects and corresponding opinions. We use Conditional Random Fields (CRFs) to solve the extraction problem and propose a feature function to enhance accuracy. The proposed method is evaluated using two different datasets. We also evaluate the effectiveness of feature function and the optimisation through multiple experiments.
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This portrait of the global debate over patent law and access to essential medicines focuses on public health concerns about HIV/AIDS, malaria, tuberculosis, the SARS virus, influenza, and diseases of poverty. The essays explore the diplomatic negotiations and disputes in key international fora, such as the World Trade Organization, the World Health Organization and the World Intellectual Property Organization. Drawing upon international trade law, innovation policy, intellectual property law, health law, human rights and philosophy, the authors seek to canvass policy solutions which encourage and reward worthwhile pharmaceutical innovation while ensuring affordable access to advanced medicines. A number of creative policy options are critically assessed, including the development of a Health Impact Fund, prizes for medical innovation, the use of patent pools, open-source drug development and forms of 'creative capitalism'.
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Historically, there have been intense conflicts over the ownership and exploitation of pharmaceutical drugs and diagnostic tests dealing with infectious diseases. Throughout the 1980’s, there was much scientific, legal, and ethical debate about which scientific group should be credited with the discovery of the human immunodeficiency virus, and the invention of the blood test devised to detect antibodies to the virus. In May 1983, Luc Montagnier, Françoise Barré-Sinoussi, and other French scientists from the Pasteur Institute in Paris, published a paper in Science, detailing the discovery of a virus called lymphadenopathy (LAV). A scientific rival, Robert Gallo of the National Cancer Institute, identified the AIDS virus and published his findings in the May 1984 issue of Science. In May 1985, the United States Patent and Trademark Office awarded the American patent for the AIDS blood test to Gallo and the Department of Health and Human Services. In December 1985, the Institut Pasteur sued the Department of Health and Human Services, contending that the French were the first to identify the AIDS virus and to invent the antibody test, and that the American test was dependent upon the French research. In March 1987, an agreement was brokered by President Ronald Reagan and French Prime Minister Jacques Chirac, which resulted in the Department of Health and Human Services and the Institut Pasteur sharing the patent rights to the blood test for AIDS. In 1992, the Federal Office of Research Integrity found that Gallo had committed scientific misconduct, by falsely reporting facts in his 1984 scientific paper. A subsequent investigation by the National Institutes of Health, the United States Congress, and the US attorney-general cleared Gallo of any wrongdoing. In 1994, the United States government and French government renegotiated their agreement regarding the AIDS blood test patent, in order to make the distribution of royalties more equitable... The dispute between Luc Montagnier and Robert Gallo was not an isolated case of scientific rivalry and patent races. It foreshadowed further patent conflicts over research in respect of HIV/AIDS. Michael Kirby, former Justice of the High Court of Australia diagnosed a clash between two distinct schools of philosophy - ‘scientists of the old school... working by serendipity with free sharing of knowledge and research’, and ‘those of the new school who saw the hope of progress as lying in huge investments in scientific experimentation.’ Indeed, the patent race between Robert Gallo and Luc Montagnier has been a precursor to broader trade disputes over access to essential medicines in the 1990s and 2000s. The dispute between Robert Gallo and Luc Montagnier captures in microcosm a number of themes of this book: the fierce competition for intellectual property rights; the clash between sovereign states over access to medicines; the pressing need to defend human rights, particularly the right to health; and the need for new incentives for research and development to combat infectious diseases as both an international and domestic issue.
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This article considers the race to sequence the Severe Acute Respiratory Syndrome virus ('the SARS virus') in light of the debate over patent law and access to essential medicines. Part II evaluates the claims of public research institutions in Canada, the United States, and Hong Kong, and commercial companies, to patent rights in respect of the SARS virus. It highlights the dilemma of ’defensive patenting' - the tension between securing private patent rights and facilitating public disclosure of information and research. Part III considers the race to patent the SARS virus in light of wider policy debates over gene patents. It examines the application of such patent criteria as novelty, inventive step, utility, and secret use. It contends that there is a need to reform the patent system to accommodate the global nature of scientific inquiry, the unique nature of genetics, and the pace of technological change. Part IV examines the role played by the World Trade Organization and the World Health Organization in dealing with patent law and access to essential medicines. The article contends that there is a need to ensure that the patent system is sufficiently flexible and adaptable to accommodate international research efforts on infectious diseases.
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The chemokine receptor CCR5 contains seven transmembrane-spanning domains. It binds chemokines and acts as co-receptor for macrophage (m)-tropic (or R5) strains of HIV-1. Monoclonal antibodies (mAb) to CCR5, 3A9 and 5C7, were used for biopanning a nonapeptide cysteine (C)-constrained phage-displayed random peptide library to ascertain contact residues and define tertiary structures of possible epitopes on CCR5. Reactivity of antibodies with phagotopes was established by enzyme-linked immunosorbent assay (ELISA). mAb 3A9 identified a phagotope C-HASIYDFGS-C (3A9/1), and 5C7 most frequently identified C-PHWLRDLRV-C (5C7/1). Corresponding peptides were synthesized. Phagotopes and synthetic peptides reacted in ELISA with corresponding antibodies and synthetic peptides inhibited antibody binding to the phagotopes. Reactivity by immunofluorescence of 3A9 with CCR5 was strongly inhibited by the corresponding peptide. Both mAb 3A9 and 5C7 reacted similarly with phagotopes and the corresponding peptide selected by the alternative mAb. The sequences of peptide inserts of phagotopes could be aligned as mimotopes of the sequence of CCR5. For phage 3A9/1, the motif SIYD aligned to residues at the N terminus and FG to residues on the first extracellular loop; for 5C7/1, residues at the N terminus, first extracellular loop, and possibly the third extracellular loop could be aligned and so would contribute to the mimotope. The synthetic peptides corresponding to the isolated phagotopes showed a CD4-dependent reactivity with gp120 of a primary, m-tropic HIV-1 isolate. Thus reactivity of antibodies raised to CCR5 against phage-displayed peptides defined mimotopes that reflect binding sites for these antibodies and reveal a part of the gp120 binding sites on CCR5.
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Ross River virus (RRV) is the predominant cause of epidemic polyarthritis in Australia, yet the antigenic determinants are not well defined. We aimed to characterize epitope(s) on RRV-E2 for a panel of monoclonal antibodies (MAbs) that recognize overlapping conformational epitopes on the E2 envelope protein of RRV and that neutralize virus infection of cells in vitro. Phage-displayed random peptide libraries were probed with the MAbs T1E7, NB3C4, and T10C9 using solution-phase and solid-phase biopanning methods. The peptides VSIFPPA and KTAISPT were selected 15 and 6 times, respectively, by all three of the MAbs using solution-phase biopanning. The peptide LRLPPAP was selected 8 times by NB3C4 using solid-phase biopanning; this peptide shares a trio of amino acids with the peptide VSIFPPA. Phage that expressed the peptides VSIFPPA and LRLPPAP were reactive with T1E7 and/or NB3C4, and phage that expressed the peptides VSIFPPA, LRLPPAP, and KTAISPT partially inhibited the reactivity of T1E7 with RRV. The selected peptides resemble regions of RRV-E2 adjacent to sites mutated in neutralization escape variants of RRV derived by culture in the presence of these MAbs (E2 210-219 and 238-245) and an additional region of E2 172-182. Together these sites represent a conformational epitope of E2 that is informative of cellular contact sites on RRV.
Resumo:
Biopanning of phage-displayed random peptide libraries is a powerful technique for identifying peptides that mimic epitopes (mimotopes) for monoclonal antibodies (mAbs). However, peptides derived using polyclonal antisera may represent epitopes for a diverse range of antibodies. Hence following screening of phage libraries with polyclonal antisera, including autoimmune disease sera, a procedure is required to distinguish relevant from irrelevant phagotopes. We therefore applied the multiple sequence alignment algorithm PILEUP together with a matrix for scoring amino acid substitutions based on physicochemical properties to generate guide trees depicting relatedness of selected peptides. A random heptapeptide library was biopanned nine times using no selecting antibodies, immunoglobulin G (IgG) from sera of subjects with autoimmune diseases (primary biliary cirrhosis (PBC) and type 1 diabetes) and three murine ascites fluids that contained mAbs to overlapping epitope(s) on the Ross River Virus envelope protein 2. Peptides randomly sampled from the library were distributed throughout the guide tree of the total set of peptides whilst many of the peptides derived in the absence of selecting antibody aligned to a single cluster. Moreover peptides selected by different sources of IgG aligned to separate clusters, each with a different amino acid motif. These alignments were validated by testing all of the 53 phagotopes derived using IgG from PBC sera for reactivity by capture ELISA with antibodies affinity purified on the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the major autoantigen in PBC: only those phagotopes that aligned to PBC-associated clusters were reactive. Hence the multiple sequence alignment procedure discriminates relevant from irrelevant phagotopes and thus a major difficulty with biopanning phage-displayed random peptide libraries with polyclonal antibodies is surmounted.
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Antibody screening of phage-displayed random peptide libraries to identify mimotopes of conformational epitopes is promising. However, because interpretations can be difficult, an exemplary system has been used in the present study to investigate whether variation in the peptide sequences of selected phagotopes corresponded with variation in immunoreactivity. The phagotopes, derived using a well-characterized monoclonal antibody, CII-C1, to a known conformational epitope on type II collagen, C1, were tested by direct and inhibition ELISA for reactivity with CII-C1. A multiple sequence alignment algorithm, PILEUP, was used to sort the peptides expressed by the phagotopes into clusters. A model was prepared of the C1 epitope on type II collagen. The 12 selected phagotopes reacted with CII-C1 by both direct ELISA (titres from < 100-11 200) and inhibition ELISA (20-100% inhibition); the reactivity varied according to the peptide sequence and assay format. The differences in reactivity between the phagotopes were mostly in accord with the alignment, by PILEUP, of the peptide sequences. The finding that the phagotopes functionally mimicked the C1 epitope on collagen was validated in that amino acids RRL at the amino terminal of many of the peptides were topographically demonstrable on the model of the C1 epitope. Notably, one phagotope that expressed the widely divergent peptide C-IAPKRHNSA-C also mimicked the C1 epitope, as judged by reactivity in each of the assays used: these included cross-inhibition of CII-C1 reactivity with each of the other phagotopes and inhibition by a synthetic peptide corresponding to that expressed by the most frequently selected phagotope, RRLPFGSQM. Thus, it has been demonstrated that multiple phage-displayed peptides can mimic the same epitope and that observed immunoreactivity of selected phagotopes with the selecting mAb can depend on the primary sequence of the expressed peptide and also on the assay format used.
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The world has experienced a large increase in the amount of available data. Therefore, it requires better and more specialized tools for data storage and retrieval and information privacy. Recently Electronic Health Record (EHR) Systems have emerged to fulfill this need in health systems. They play an important role in medicine by granting access to information that can be used in medical diagnosis. Traditional systems have a focus on the storage and retrieval of this information, usually leaving issues related to privacy in the background. Doctors and patients may have different objectives when using an EHR system: patients try to restrict sensible information in their medical records to avoid misuse information while doctors want to see as much information as possible to ensure a correct diagnosis. One solution to this dilemma is the Accountable e-Health model, an access protocol model based in the Information Accountability Protocol. In this model patients are warned when doctors access their restricted data. They also enable a non-restrictive access for authenticated doctors. In this work we use FluxMED, an EHR system, and augment it with aspects of the Information Accountability Protocol to address these issues. The Implementation of the Information Accountability Framework (IAF) in FluxMED provides ways for both patients and physicians to have their privacy and access needs achieved. Issues related to storage and data security are secured by FluxMED, which contains mechanisms to ensure security and data integrity. The effort required to develop a platform for the management of medical information is mitigated by the FluxMED's workflow-based architecture: the system is flexible enough to allow the type and amount of information being altered without the need to change in your source code.
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Since we still know very little about stem cells in their natural environment, it is useful to explore their dynamics through modelling and simulation, as well as experimentally. Most models of stem cell systems are based on deterministic differential equations that ignore the natural heterogeneity of stem cell populations. This is not appropriate at the level of individual cells and niches, when randomness is more likely to affect dynamics. In this paper, we introduce a fast stochastic method for simulating a metapopulation of stem cell niche lineages, that is, many sub-populations that together form a heterogeneous metapopulation, over time. By selecting the common limiting timestep, our method ensures that the entire metapopulation is simulated synchronously. This is important, as it allows us to introduce interactions between separate niche lineages, which would otherwise be impossible. We expand our method to enable the coupling of many lineages into niche groups, where differentiated cells are pooled within each niche group. Using this method, we explore the dynamics of the haematopoietic system from a demand control system perspective. We find that coupling together niche lineages allows the organism to regulate blood cell numbers as closely as possible to the homeostatic optimum. Furthermore, coupled lineages respond better than uncoupled ones to random perturbations, here the loss of some myeloid cells. This could imply that it is advantageous for an organism to connect together its niche lineages into groups. Our results suggest that a potential fruitful empirical direction will be to understand how stem cell descendants communicate with the niche and how cancer may arise as a result of a failure of such communication.
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OBJECTIVE A comprehensive life course perspective of women's experiences in obtaining and using contraception in Australia is lacking. This paper explores free-text comments about contraception provided by women born between 1973 and 1978 who participated in the Australian Longitudinal Study on Women's Health (ALSWH). METHODS The ALSWH is a national population-based cohort study involving over 40,000 women from three age groups, who are surveyed every three years. An initial search identified 1600 comments from 690 women across five surveys from 1996 (when they were aged 18-23 years) to 2009 (31-36 years). The analysis included 305 comments from 289 participants. Factors relating to experiences of barriers to access and optimal contraceptive use were identified and explored using thematic analysis. RESULTS Five themes recurred across the five surveys as women aged: (i) side effects affecting physical and mental health; (ii) lack of information about contraception; (iii) negative experiences with health services; (iv) contraceptive failure; and (v) difficulty with accessing contraception. CONCLUSION Side effects of hormonal contraception and concerns about contraceptive failure influence women's mental and physical health. Many barriers to effective contraception persist throughout women's reproductive lives. Further research is needed into reducing barriers and minimising negative experiences, to ensure optimal contraceptive access for Australian women.
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Introduction The epidemic of nutrition related non-communicable diseases such as type 2 diabetes mellitus and obesity has reached to epidemic portion in the Sri Lanka. However, to date, detailed data on food consumption in the Sri Lankan population is limited. The aim of this study is to identify energy and major nutrient intake among Sri Lankan adults. Methods A nationally-representative sample of adults was selected using a multi-stage random cluster sampling technique. Results Data from 463 participants (166 Males, 297 Females) were analyzed. Total energy intake was significantly higher in males (1913 ± 567 kcal/d) than females (1514 ± 458 kcal/d). However, there was no significant gender differences in the percentage of energy from carbohydrate (Male: 72.8 ± 6.4%, Female: 73.9 ± 6.7%), fat (Male: 19.9 ± 6.1%, Female: 18.5 ± 5.7%) and proteins (Male: 10.6 ± 2.1%, Female: 10.9 ± 5.6%). Conclusion The present study provides the first national estimates of energy and nutrient intake of the Sri Lankan adult population.
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Background The number of citations received by an article is considered as an objective marker judging the importance and the quality of the research work. The present study aims to study the determinants of citations for research articles published by Sri Lankan authors. Methods Papers were selectively retrieved from the SciVerse Scopus® (Elsevier Properties S.A, USA) database for 10 years from 1st January 1997 to 31st December 2006, of which 50% were selected for inclusion by simple random sampling. The primary outcome measure was citation rate (defined as the number of citations during the 2 subsequent years after publication). Citation data was collected using the SciVerse Scopus® Citation Analyzer and self citations were excluded. A linear regression analysis was performed with ‘number of citations’ as the continuous dependent variable and other independent variables. Result The number of publications has steadily increased during the period of study. Over three quarter of papers were published in international journals. More than half of publications were research studies (55.3%), and most of the research studies were descriptive cross-sectional studies (27.1%). The mean number of citations within 2 years of publication was 1.7 and 52.1% of papers were not cited within the first two years of publication. The mean number of citations for collaborative studies (2.74) was significantly higher than that of non-collaborative studies (0.66). The mean number of citations did not significantly change depending on whether the publication had a positive result (2.08) or not (2.92) and was also not influenced by the presence (2.30) or absence (1.99) of the main study conclusion in the title of the article. In the linear regression model, the journal rank, number of authors, conducting the study abroad, being a research study or systematic review/meta-analysis and having regional and/or international collaboration all significantly increased the number of citations. Conclusion The journal rank, number of authors, conducting the study abroad, being a research study or systematic review/meta-analysis and having regional and/or international collaboration all significantly increased the number of citations. However, the presence of a positive result in the study did not influence the citation rate.
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This paper explores the nature of interfaces to support people in accessing their files at tabletop displays embedded in the environment. To do this, we designed a study comparing people's interaction with two very different classes of file system access interface: Focus, explicitly designed for tabletops, and the familiar hierarchical Windows Explorer. In our within-subjects double-crossover study, participants collaborated on 4 planning tasks. Based on video, logs, questionnaires and interviews, we conclude that both classes of interface have a place. Notably, Focus contributed to improved collaboration and more efficient use of the workspace than with Explorer. Our results inform a set of recommendations for future interfaces enabling this important class of interaction -- supporting access to files for collaboration at tabletop devices embedded in an ubicomp environment.