2,782 research outputs found
Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution
No full textNon-steroidal anti-inflammatory drugs (NSAIDs) contribute to gastrointestinal ulcer formation by inhibiting epithelial cell migration and mucosal restitution; however, the drug-affected signaling pathways are poorly defined. We investigated whether NSAID inhibition of intestinal epithelial migration is associated with depletion of intracellular polyamines, depolarization of membrane potential (Em) and altered surface expression of K+ channels. Epithelial cell migration in response to the wounding of confluent IEC-6 and IEC-Cdx2 monolayers was reduced by indomethacin (100μM), phenylbutazone (100μM) and NS-398 (100μM) but not by SC-560 (1μM). NSAID-inhibition of intestinal cell migration was not associated with depletion of intracellular polyamines. Treatment of IEC-6 and IEC-Cdx2 cells with indomethacin, phenylbutazone and NS-398 induced significant depolarization of Em, whereas treatment with SC-560 had no effect on Em. The Em of IEC-Cdx2 cells was: −38.5±1.8mV under control conditions; −35.9±1.6mV after treatment with SC-560; −18.8±1.2mV after treatment with indomethacin; and −23.7±1.4mV after treatment with NS-398. Whereas SC-560 had no significant effects on the total cellular expression of Kv1.4 channel protein, indomethacin and NS-398 decreased not only the total cellular expression of Kv1.4, but also the cell surface expression of both Kv1.4 and Kv1.6 channel subunits in IEC-Cdx2. Both Kv1.4 and Kv1.6 channel proteins were immunoprecipitated by Kv1.4 antibody from IEC-Cdx2 lysates, indicating that these subunits co-assemble to form heteromeric Kv channels. These results suggest that NSAID inhibition of epithelial cell migration is independent of polyamine-depletion, and is associated with depolarization of Em and decreased surface expression of heteromeric Kv1 channels.ID: S0006295207001931; M3: Article; Accession Number: S0006295207001931; Author: L.C. Freeman (b); Author: D.F. Narvaez (a); Author: A. McCoy (a); Author: F.B. von Stein (c); Author: S. Young (b); Author: K. Silver (a); Author: S. Ganta (b); Author: D. Koch (b); Author: R. Hunter (b); Author: R.F. Gilmour (c); Author: J.D. Lillich (a, ⁎); Affiliation: Department of Clinical Sciences, Kansas State University, Manhattan, KS 66506, United States; Affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, United States; Affiliation: Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, United States; Keyword: Non-steroidal anti-inflammatory drugs; Keyword: Intestinal epithelial cells; Keyword: Membrane potential; Keyword: Potassium channels; Number of Pages: 12; Language: English;Source type: Electronic(1)http://search.ebscohost.com/login.aspx?direct=true&db=edselp&AN=S0006295207001931&site=eds-live&scope=sit
Developmental psychopathology of children and adolescents with Tourette syndrome - impact of AND
No full textBackground In Tourette syndrome (TS) as a neurodevelopmental disorder not only the tics but also the comorbid conditions change with increasing age. ADHD is highly comorbid with TS and usually impairs psychosocial functioning more than the tics. Its impact on further comorbidity during development is important for clinical practice and still a matter of debate. Method Aspects of developmental psychopathology considering the impact of ADHD were examined by logistic regression (year wisely) in a cross-sectional sample of children and adolescents (n = 5060) from the TIC database. Results In TS+ADHD (compared to TS-ADHD) higher rates of comorbid conditions like OCD, anxiety disorders, CD/ODD and mood disorders were found in children (510 years). In adolescents (1117 years) higher comorbidity rates in TS+ADHD remained only for CD/ODD and mood disorders. Accordingly, for OCD and anxiety disorders there was a steeper year wise increase of these comorbidities in TS-ADHD while it was a similar for CD/ODD and mood disorders in TS-ADHD as well as TS+ADHD. Conclusion Children with TS+ADHD have more comorbidities than the TS-ADHD group, whereas in both adolescent groups this did no longer hold for OCD and anxiety disorders. These findings indicate that in TS comorbid ADHD is associated with high rates of externalizing and internalizing problems, whereas TS without ADHD is associated only with internalizing problems in adolescence
Relationship of Obsessive-Compulsive Disorder to Age-Related Comorbidity in Children and Adolescents With Tourette Syndrome
No full textObjective: Attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) are the 2 most frequent psychiatric disorders co-occurring with Tourette syndrome (TS). Both usually cause greater impairment in psychosocial functioning than the tics themselves. In a previous study, we examined the relationship of attention-deficit/hyperactivity disorder to other comorbid conditions in TS. The relationship of OCD to other comorbidities in TS still remains unclear and is the focus of the present study. Methods: Pearson's chi(2) tests and logistic regressions (year-wise) were used to examine a cross-sectional sample of children and adolescents (n = 5060) diagnosed with TS, taken from the Tourette Syndrome International Database Consortium. We explored the relationship of OCD to other comorbid conditions in TS across different age groups. Results: In children (ages 5-10 y) with TS, higher rates of comorbidities were found in the presence compared with the absence of OCD. Adolescents (ages 11-17 y) with TS + OCD showed higher rates of internalizing (i.e., anxiety and mood) disorders when compared with those with TS - OCD. A year-wise increase of coexisting mood disorders was found for subjects with TS with and without OCD. Conclusions: Overall, children and adolescents with TS + OCD showed higher rates of comorbid disorders compared with those with TS - OCD. This underlines the necessity for a comprehensive assessment of additional comorbidities even if the 2 disorders (TS + OCD) have already been diagnosed.Shire; German Research Society; Schwaab
Overview of Infrastructure Charging, part 4, IMPROVERAIL Project Deliverable 9, “Improved Data Background to Support Current and Future Infrastructure Charging Systems”
No full textImproverail aims are to further support the establishment of railway infrastructure management in accordance with Directive 91/440, as well as the new railway infrastructure directives, by developing the necessary tools for modelling the management of railway infrastructure; by evaluating improved methods for capacity and resources management, which allow the improvement of the Life Cycle Costs (LCC) calculating methods, including elements related to vehicle - infrastructure interaction and external costs; and by improving data background in support of charging for use of railway infrastructure. To achieve these objectives, Improverail is organised along 8 workpackages, with specific objectives, responding to the requirements of the task 2.2.1/10 of the 2nd call made in the 5th RTD Framework Programme in December 1999.This part is the task 7.1 (Review of infrastructure charging systems) to the workpackage 7 (Analysis of the relation between infrastructure cost variation and diversity of infrastructure charging systems).Before explaining the economic characteristics of railway and his basic pricing principles, authors must specify the objectives of railways infrastructure charging.principle of pricing ; rail infrastructure charging ; public service obligation ; rail charging practice ; Europe ; Improverail
Model selection in compositional spaces
No full textThesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2014.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 172-181).We often build complex probabilistic models by composing simpler models-using one model to generate parameters or latent variables for another model. This allows us to express complex distributions over the observed data and to share statistical structure between dierent parts of a model. In this thesis, we present a space of matrix decomposition models defined by the composition of a small number of motifs of probabilistic modeling, including clustering, low rank factorizations, and binary latent factor models. This compositional structure can be represented by a context-free grammar whose production rules correspond to these motifs. By exploiting the structure of this grammar, we can generically and eciently infer latent components and estimate predictive likelihood for nearly 2500 model structures using a small toolbox of reusable algorithms. Using a greedy search over this grammar, we automatically choose the decomposition structure from raw data by evaluating only a small fraction of all models. The proposed method typically finds the correct structure for synthetic data and backs o gracefully to simpler models under heavy noise. It learns sensible structures for datasets as diverse as image patches, motion capture, 20 Questions, and U.S. Senate votes, all using exactly the same code. We then consider several improvements to compositional structure search. We present compositional importance sampling (CIS), a novel procedure for marginal likelihood estimation which requires only posterior inference and marginal likelihood estimation algorithms corresponding to the production rules of the grammar. We analyze the performance of CIS in the case of identifying additional structure within a low-rank decomposition. This analysis yields insights into how one should design a space of models to be recursively searchable. We next consider the problem of marginal likelihood estimation for the production rules. We present a novel method for obtaining ground truth marginal likelihood values on synthetic data, which enables the rigorous quantitative comparison of marginal likelihood estimators. Using this method, we compare a wide variety of marginal likelihood estimators for the production rules of our grammar. Finally, we present a framework for analyzing the sequences of distributions used in annealed importance sampling, a state-of-the-art marginal likelihood estimator, and present a novel sequence of intermediate distributions based on averaging moments of the initial and target distributions.by Roger Baker Grosse.Ph. D
Adjunctive treatment with oral AKL1, a botanical nutraceutical, in chronic obstructive pulmonary disease
No full textClaire Brockwell,1 Sundari Ampikaipakan,1,2 Darren W Sexton,1 David Price,3,4 Daryl Freeman,5 Mike Thomas,6 Muzammil Ali,4 Andrew M Wilson1,21Norwich Medical School, University of East Anglia, Norwich, UK; 2Norfolk and Norwich University Hospital Foundation Trust, Norwich, UK; 3Academic Primary Care, University of Aberdeen, Aberdeen, UK; 4Research in Real Life, Cambridge, UK; 5Mundesley Medical Centre, Mundesley, Norwich, UK; 6Primary Care Research, Aldermoor Health Centre, University of Southampton, Southampton, UKPurpose: The objective of this pilot trial was to evaluate the safety and efficacy of AKL1, a patented botanical formulation containing extracts of Picrorhiza kurroa, Ginkgo biloba, and Zingiber officinale, as add-on therapy for patients with chronic obstructive pulmonary disease (COPD) and chronic cough.Patients and methods: This randomized, double-blind, placebo-controlled trial enrolled male and female patients >18 years old with COPD and Leicester Cough Questionnaire (LCQ) score of <18. The 10-week study period comprised a 2-week single-blind placebo run-in period followed by add-on treatment with AKL1 or placebo twice daily for 8 weeks. The primary study endpoint was the change from week 0 to week 8 in cough-related health status, as assessed by the LCQ.Results: Of 33 patients enrolled, 20 were randomized to AKL1 and 13 to placebo. Patients included 19 (58%) men and 14 (42%) women of mean (standard deviation [SD]) age of 67 (9.4) years; 15 (45%) patients were smokers and 16 (49%) were ex-smokers. The mean (SD) change from baseline in LCQ score at 8 weeks was 2.3 (4.9) in the AKL1 group and 0.6 (3.7) in the placebo group, with mean difference in change of 1.8 (95% confidence interval: –1.5 to 5.1; P=0.28). The St George's Respiratory Questionnaire score improved substantially in the AKL1 treatment group by a mean (SD) of –7.7 (11.7) versus worsening in the placebo group (+1.5 [9.3]), with mean difference in change of –9.2 (95% confidence interval: –19.0 to 0.6; P=0.064). There were no significant differences between treatment groups in change from baseline to week 8 in other patient-reported measures, lung function, or the 6-minute walk distance.Conclusion: Further study is needed with a larger patient population and over a longer duration to better assess the effects of add-on therapy with AKL1 in COPD.Keywords: Leicester Cough Questionnaire, anti-inflammatory, Picrorhiza kurroa, Ginkgo biloba, Zingiber officinal
Twinnia Stone & Jamnback
No full textGenus TWINNIA Stone & Jamnback Twinnia hirticornis Wood Rothfels & Freeman (1966, characterization; cytodendrogram; idiogram; photos of IS partial, CIIS + CIIIS region, and polymorphisms; resolution relative to Prosimulium standard; whole-arm interchange [IIL + IIIL, IIS + IIIS]; as T. nova): Canada Rothfels (1979, cytodendrogram): Canada, USA Rothfels (1980, photo of de novo interchange in polytenes of single cell): [Canada] Adler, Currie & Wood (2004, chromosomal characters in larval key): North America Twinnia hydroides Novák Chubareva (1977 a, 1977 d, description, idiogram): Czech Republic Chubareva (1977 b, description, idiogram, photos of metaphase and polytene complements, polytene chromosome lengths): Czech Republic Chubareva & Petrova (1979, 2003, notes on general polytene features, polytene chromosome lengths): Czech Republic Rothfels (1979, cytodendrogram): Czech Republic Chubareva (1984, photos of metaphase and low-resolution polytene complements): [Czech Republic] Chubareva & Petrova (2008 a, description, photos of metaphase and polytene complements, polytene chromosome lengths): Czech Republic Twinnia magadensis Rubtsov Adler & McCreadie (2002, low-magnification photo of polytene complement): Russia Twinnia nova (Dyar & Shannon) Rothfels & Freeman (1966, characterization; cytodendrogram; idiogram; photos of IS partial, IL, and CIIL + CIIIL region; resolution relative to Prosimulium standard; whole-arm interchange [IIL + IIIL, IIS + IIIS]; as T. biclavata): Canada, USA Rothfels (1979, cytodendrogram): Canada, USA Adler, Currie & Wood (2004, chromosomal characters in larval key): North America Twinnia tibblesi Stone & Jamnback Rothfels & Freeman (1966, characterization, cytodendrogram, idiogram, photos of all arms, resolution relative to Prosimulium standard): Canada, USA Rothfels (1979, cytodendrogram): Canada, USAPublished as part of Adler, Peter H. & Crosskey, Roger W., 2015, Cytotaxonomy of the Simuliidae (Diptera): a systematic and bibliographic conspectus, pp. 1-139 in Zootaxa 3975 (1) on page 23, DOI: 10.11646/zootaxa.3975.1.1, http://zenodo.org/record/19236
RoMEO Studies 6: Rights metadata for open-archiving
No full textThis is the final study in a series of six emanating from the UK JISC-funded RoMEO Project (Rights Metadata for Open-archiving) which investigated the Intellectual Property Rights (IPR) issues relating to academic author self-archiving of research papers. It reports the results of a survey of 542 academic authors showing the level of protection required for their open-access research papers. It then describes the selection of an appropriate means of expressing those rights through metadata and the resulting choice of Creative Commons licences. Finally it outlines proposals for communicating rights metadata via the Open Archives Initiative’s Protocol for Metadata Harvesting (OAI-PMH)
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Developing models for the assessment and the design of the in situ remediation of contaminated sediments
No full textThe sediments in natural environment serve as sinks for contaminants from historical release, particularly hydrophobic organic compounds (HOC) and heavy metals. In-situ remediation, including monitored natural recovery (MNR), in-situ treatment (e.g. sorbing amendment) and in-situ capping, is one of the few alternative economically viable options with a proven record of success for sediment remediation. Modeling is often used to compare in-situ remedial approaches and design a system of meeting long term remedial goals.
The fate and transport of contaminants in a remediation system is commonly modeled using a generalized advection-dispersion-reaction equation with potentially different physical and chemical properties in each layer. An analytical solution was developed with computational efficiency and unconditional stability for the multi-layered transport problem with linear processes and was shown to be more convenient for sensitivity analyses and parameter estimation and implement.
A numerical model, CapSim, has been developed to model the transport and fate under more general conditions. Several important processes in sediment environments, such as nonlinear and kinetically limited sorption, steady and periodic advection, bioturbation, consolidation and deposition, are incorporated in the model. The current model also allows description of multiplied coupled chemical reactions. It builds on a simpler numerical model of Lampert (2009). It allows assessment of the transport and fate of chemicals under the most important dynamic sediment processes.
Performance reference compounds (PRC) are often used to support passive sampling as a means of monitoring sediment processes and in situ remedial processes. An analytical solution was developed for modeling the release of PRC and uptake of target compounds in cylindrical passive sampling system.
In the presence of nonlinear sorbents such as activated carbon, the interpretation and application of PRCs is more difficult. The fate and transport model CapSim was used to simulate the behavior of PRCs and target compounds in a passive sampling system with activated carbon. The impacts from the non-linear sorption of the compounds in activated carbon as well as the competitive sorption between an isotope-labeled PRC and the non-labeled compound are discussed.Chemical Engineerin
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