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Search Results: 1 - 10 of 17849 matches for " Mark Hepple "
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A Web Service for Biomedical Term Look-Up
Henk Harkema,Ian Roberts,Rob Gaizauskas,Mark Hepple
Comparative and Functional Genomics , 2005, DOI: 10.1002/cfg.459
Abstract: Recent years have seen a huge increase in the amount of biomedical information that is available in electronic format. Consequently, for biomedical researchers wishing to relate their experimental results to relevant data lurking somewhere within this expanding universe of on-line information, the ability to access and navigate biomedical information sources in an efficient manner has become increasingly important. Natural language and text processing techniques can facilitate this task by making the information contained in textual resources such as MEDLINE more readily accessible and amenable to computational processing. Names of biological entities such as genes and proteins provide critical links between different biomedical information sources and researchers' experimental data. Therefore, automatic identification and classification of these terms in text is an essential capability of any natural language processing system aimed at managing the wealth of biomedical information that is available electronically. To support term recognition in the biomedical domain, we have developed Termino, a large-scale terminological resource for text processing applications, which has two main components: first, a database into which very large numbers of terms can be loaded from resources such as UMLS, and stored together with various kinds of relevant information; second, a finite state recognizer, for fast and efficient identification and mark-up of terms within text. Since many biomedical applications require this functionality, we have made Termino available to the community as a web service, which allows for its integration into larger applications as a remotely located component, accessed through a standardized interface over the web.
Compacting the Penn Treebank Grammar
Alexander Krotov,Mark Hepple,Robert Gaizauskas,Yorick Wilks
Computer Science , 1999,
Abstract: Treebanks, such as the Penn Treebank (PTB), offer a simple approach to obtaining a broad coverage grammar: one can simply read the grammar off the parse trees in the treebank. While such a grammar is easy to obtain, a square-root rate of growth of the rule set with corpus size suggests that the derived grammar is far from complete and that much more treebanked text would be required to obtain a complete grammar, if one exists at some limit. However, we offer an alternative explanation in terms of the underspecification of structures within the treebank. This hypothesis is explored by applying an algorithm to compact the derived grammar by eliminating redundant rules -- rules whose right hand sides can be parsed by other rules. The size of the resulting compacted grammar, which is significantly less than that of the full treebank grammar, is shown to approach a limit. However, such a compacted grammar does not yield very good performance figures. A version of the compaction algorithm taking rule probabilities into account is proposed, which is argued to be more linguistically motivated. Combined with simple thresholding, this method can be used to give a 58% reduction in grammar size without significant change in parsing performance, and can produce a 69% reduction with some gain in recall, but a loss in precision.
Mitochondrial Involvement and Impact in Aging Skeletal Muscle
Russell T. Hepple
Frontiers in Aging Neuroscience , 2014, DOI: 10.3389/fnagi.2014.00211
Abstract: Atrophy is a defining feature of aging skeletal muscle that contributes to progressive weakness and an increased risk of mobility impairment, falls, and physical frailty in very advanced age. Amongst the most frequently implicated mechanisms of aging muscle atrophy is mitochondrial dysfunction. Recent studies employing methods that are well-suited to interrogating intrinsic mitochondrial function find that mitochondrial respiration and reactive oxygen species emission changes are inconsistent between aging rat muscles undergoing atrophy and appear normal in human skeletal muscle from septuagenarian physically active subjects. On the other hand, a sensitization to permeability transition seems to be a general property of atrophying muscle with aging and this effect is even seen in atrophying muscle from physically active septuagenarian subjects. In addition to this intrinsic alteration in mitochondrial function, factors extrinsic to the mitochondria may also modulate mitochondrial function in aging muscle. In particular, recent evidence implicates oxidative stress in the aging milieu as a factor that depresses respiratory function in vivo (an effect not present ex vivo). Furthermore, in very advanced age not only does muscle atrophy become more severe and clinically relevant in terms of its impact, but also there is evidence that this is driven by an accumulation of severely atrophied denervated myofibers. As denervation can itself modulate mitochondrial function and recruit mitochondrial-mediated atrophy pathways, future investigations need to address the degree to which skeletal muscle mitochondrial alterations in very advanced age are a consequence of denervation, rather than a primary organelle defect, to refine our understanding of the relevance of mitochondria as a therapeutic target at this more advanced age.
Direct microscopy versus sputum cytology analysis and bleach sedimentation for diagnosis of tuberculosis: a prospective diagnostic study
Pamela Hepple, Pascal Nguele, Jane Greig, Maryline Bonnet, Vinciane Sizaire
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-276
Abstract: We did a prospective diagnostic study in a Médecins Sans Frontières-supported hospital in Mindouli, Republic of Congo. Three sputum samples were obtained from 280 consecutive pulmonary tuberculosis suspects, and were processed according to WHO guidelines for direct smear microscopy. The remainder of each sputum sample was homogenised with 2.6% bleach, sedimented overnight, smeared, and examined blinded to the direct smear result for acid-fast bacilli (AFB). All direct smears were assessed for quality by SCA. If a patient produced fewer than three good-quality sputum samples, further samples were requested. Sediment smear examination was performed independently of SCA result on the corresponding direct smear. Positivity rates were compared using McNemar's test.Excluding SCA, 43.2% of all patients were diagnosed as positive on direct microscopy of up to three samples. 47.9% were diagnosed on sediment microscopy, with 48.2% being diagnosed on direct microscopy, sediment microscopy, or both. The positivity rate increased from 43.2% to 47.9% with a case definition of one positive smear (≥1 AFB/100 high power fields) of three, and from 42.1% to 43.9% with two positive smears. SCA resulted in 87.9% of patients producing at least two good-quality sputum samples, with 75.7% producing three or more. Using a case definition of one positive smear, the incremental yield of bleach sedimentation was 14/121, or 11.6% (95% CI 6.5-18.6, p = 0.001) and in combination with SCA was 15/121, or 12.4% (95% CI 7.1-19.6, p = 0.002). Incremental yields with two positive smears were 5/118, or 4.2% (95% CI 1.4-9.6, p = 0.062) and 7/118, or 5.9% (95% CI 2.4-11.8, p = 0.016), respectively.The combination of bleach sedimentation and SCA resulted in significantly increased microscopy positivity rates with a case definition of either one or two positive smears. Implementation of bleach sedimentation led to a significant increase in the diagnosis of smear-positive patients. Implementation of SCA did
Mitochondrial Function in Permeabilized Cardiomyocytes Is Largely Preserved in the Senescent Rat Myocardium
Martin Picard, Kathryn J. Wright, Darmyn Ritchie, Melissa M. Thomas, Russell T. Hepple
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0043003
Abstract: The aging heart is characterized by a progressive decline in contractile function and diastolic relaxation. Amongst the factors implicated in these changes is a progressive replacement fibrosis secondary to cardiomyoctye death, oxidative damage, and energetic deficit, each of which may be secondary to impaired mitochondrial function. Here, we performed an in-depth examination of mitochondrial function in saponin-permeabilized cardiomyocyte bundles, a preparation where all mitochondria are represented and their structure intact, from young adult (YA) and senescent (SEN) rats (n = 8 per group). When accounting for increased fibrosis (+19%, P<0.01) and proportional decrease in citrate synthase activity in the SEN myocardium (?23%, P<0.05), mitochondrial respiration and reactive oxygen species (H2O2) emission across a range of energized states was similar between age groups. Accordingly, the abundance of electron transport chain proteins was also unchanged. Likewise, except for CuZnSOD (?37%, P<0.05), the activity of antioxidant enzymes was unaltered with aging. Although time to mitochondrial permeability transition pore (mPTP) opening was decreased (?25%, P<0.05) in the SEN heart, suggesting sensitization to apoptotic stimuli, this was not associated with a difference in apoptotic index measured by ELISA. Collectively, our results suggest that the function of existing cardiac ventricular mitochondria is relatively preserved in SEN rat heart when measured in permeabilized cells.
Simultaneous identification of GSTP1 Ile105→Val105 and Ala114→Val114 substitutions using an amplification refractory mutation systempolymerase chain reactionassay: studies in patients with asthma
Anja Hemmingsen, Anthony A Fryer, Michael Hepple, Richard C Strange, Monica A Spiteri
Respiratory Research , 2001, DOI: 10.1186/rr64
Abstract: Because full identification of GSTP1 alleles may identify stronger links with asthma phenotypes, we describe an amplification refractory mutation system (ARMS) assay that allows identification of all genotypes. We explored whether the GSTP1 substitutions influence susceptibility to asthma, atopy and BHR.Among 191 atopic nonasthmatic, atopic asthmatic and nonatopic nonasthmatic individuals, none had the BD, CD, or DD genotypes. GSTP1 BC was significantly associated with reduced risk for atopy (P = 0.031). Compared with AA, trend test analysis identified a significant decrease in the frequency of GSTP1 BC with increasing severity of BHR (P = 0.031). Similarly, the frequency of GSTP1 AA increased with increasing BHR.These data suggest that GSTP1*B and possibly GSTP1*C are protective against asthma and related phenotypes.Polymorphisms in members of the GST supergene family have been associated with individual susceptibility to lung diseases [1]. In the context of asthma GSTP1 — the predominant GST expressed in human lung [2] — is a candidate because this enzyme has a role in cellular protection against oxidative stress [3]. Thus, GSTP1 catalyzes the detoxification of byproducts of lipid and DNA oxidation [1]. Asthma is characterized by airway inflammation [4]. Indeed, BHR reflects the presence of inflammation, and is exhibited by virtually all asthmatic patients. Atopic individuals (as defined by serum IgE levels and skin prick tests) are very likely to have increased airway responsiveness [4]. Thus, studies designed to identify susceptibility genes for asthma must consider the possible interrelationship of BHR and atopy in the expression of the asthma phenotype.We previously showed that the Ile105→Val105 substitution in GSTP1 is strongly associated with severity of BHR [5]. A further polymorphism is present at amino acid 114 (Ala114→Val114), however, indicating that unequivocal identification of GSTP1 alleles requires consideration of both substitutions. These polymorp
Building Intercultural Competence One “Patch” at a Time
Rebecca Spooner-Lane,Donna Tangen,K. Louise Mercer,Erika Hepple
Education Research International , 2013, DOI: 10.1155/2013/394829
Building Intercultural Competence One “Patch” at a Time
Rebecca Spooner-Lane,Donna Tangen,K. Louise Mercer,Erika Hepple,Suzanne Carrington
Education Research International , 2013, DOI: 10.1155/2013/394829
Abstract: This paper describes a program called Patches that was implemented to assist a group of Australian and Malaysian pre-service teachers to enhance their intercultural competence through their involvement in a series of reciprocal learning activities. Each learning experience was considered a “patch” that eventually created a “quilt of intercultural learning.” The purpose of this study was to enhance the intercultural competence of domestic and international students through organized intercultural activities, through a series of reflective writing sessions, and mutual engagement on a common project. The effectiveness of the Patches program was analysed in accordance with Deardorff’s elements of intercultural competence. The qualitative findings indicate that both cohorts of preservice teachers showed elements of intercultural competence through participation in the program, with both groups reporting a deeper appreciation and understanding of how to communicate more effectively in intercultural contexts. 1. Introduction Globalisation of the world’s economic, political, technological, and environmental systems has resulted in the need for academic institutions to prepare graduates with the knowledge, skills, and abilities to work effectively in the global arena. Universities across Australia agree that the development of intercultural competence or the “ability to communicate effectively and appropriately in intercultural situations” [1, page 238], is a key priority in preparing graduates for the global workforce. As a nation with a successful track record in attracting international students to study in both onshore and offshore courses [2], Australian universities are at the forefront of globalization in higher education. Indeed, Australia is the third largest exporter of higher education to South and East Asian countries [3]. It is therefore important for Australian educators to consider how their courses can maximise intercultural learning opportunities for domestic and international students. Both domestic and international students need to obtain at least a “minimal level of intercultural competence in order to operate effectively in an increasingly ethnically and culturally diverse society and globalised economy” [4, page 414]. Eisenchlas and Trevaskes [4] propose that is only through intergroup communication that domestic and international students become competent communicators and develop the skills and attitudes necessary to breakdown cultural barriers. How to assess intercultural competence, however, has not been a strong point for Australian
Mitochondrial Structure and Function Are Disrupted by Standard Isolation Methods
Martin Picard,Tanja Taivassalo,Darmyn Ritchie,Kathryn J. Wright,Melissa M. Thomas,Caroline Romestaing,Russell T. Hepple
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018317
Abstract: Mitochondria regulate critical components of cellular function via ATP production, reactive oxygen species production, Ca2+ handling and apoptotic signaling. Two classical methods exist to study mitochondrial function of skeletal muscles: isolated mitochondria and permeabilized myofibers. Whereas mitochondrial isolation removes a portion of the mitochondria from their cellular environment, myofiber permeabilization preserves mitochondrial morphology and functional interactions with other intracellular components. Despite this, isolated mitochondria remain the most commonly used method to infer in vivo mitochondrial function. In this study, we directly compared measures of several key aspects of mitochondrial function in both isolated mitochondria and permeabilized myofibers of rat gastrocnemius muscle. Here we show that mitochondrial isolation i) induced fragmented organelle morphology; ii) dramatically sensitized the permeability transition pore sensitivity to a Ca2+ challenge; iii) differentially altered mitochondrial respiration depending upon the respiratory conditions; and iv) dramatically increased H2O2 production. These alterations are qualitatively similar to the changes in mitochondrial structure and function observed in vivo after cellular stress-induced mitochondrial fragmentation, but are generally of much greater magnitude. Furthermore, mitochondrial isolation markedly altered electron transport chain protein stoichiometry. Collectively, our results demonstrate that isolated mitochondria possess functional characteristics that differ fundamentally from those of intact mitochondria in permeabilized myofibers. Our work and that of others underscores the importance of studying mitochondrial function in tissue preparations where mitochondrial structure is preserved and all mitochondria are represented.
Denervation Causes Fiber Atrophy and Myosin Heavy Chain Co-Expression in Senescent Skeletal Muscle
Sharon L. Rowan, Karolina Rygiel, Fennigje M. Purves-Smith, Nathan M. Solbak, Douglas M. Turnbull, Russell T. Hepple
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029082
Abstract: Although denervation has long been implicated in aging muscle, the degree to which it is causes the fiber atrophy seen in aging muscle is unknown. To address this question, we quantified motoneuron soma counts in the lumbar spinal cord using choline acetyl transferase immunhistochemistry and quantified the size of denervated versus innervated muscle fibers in the gastrocnemius muscle using the in situ expression of the denervation-specific sodium channel, Nav1.5, in young adult (YA) and senescent (SEN) rats. To gain insights into the mechanisms driving myofiber atrophy, we also examined the myofiber expression of the two primary ubiquitin ligases necessary for muscle atrophy (MAFbx, MuRF1). MN soma number in lumbar spinal cord declined 27% between YA (638±34 MNs×mm?1) and SEN (469±13 MNs×mm?1). Nav1.5 positive fibers (1548±70 μm2) were 35% smaller than Nav1.5 negative fibers (2367±78 μm2; P<0.05) in SEN muscle, whereas Nav1.5 negative fibers in SEN were only 7% smaller than fibers in YA (2553±33 μm2; P<0.05) where no Nav1.5 labeling was seen, suggesting denervation is the primary cause of aging myofiber atrophy. Nav1.5 positive fibers had higher levels of MAFbx and MuRF1 (P<0.05), consistent with involvement of the proteasome proteolytic pathway in the atrophy of denervated muscle fibers in aging muscle. In summary, our study provides the first quantitative assessment of the contribution of denervation to myofiber atrophy in aging muscle, suggesting it explains the majority of the atrophy we observed. This striking result suggests a renewed focus should be placed on denervation in seeking understanding of the causes of and treatments for aging muscle atrophy.
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