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| 2. |
- Henderson, Neil C., et al.
(författare)
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Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs
- 2013
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 19:12, s. 1617-1624
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Tidskriftsartikel (refereegranskat)abstract
- Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are believed to be the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not been developed. We report that Cre under control of the promoter of Pdgfrb (Pdgfrb-Cre) inactivates loxP-flanked genes in mouse HSCs with high efficiency. We used this system to delete the gene encoding alpha(v) integrin subunit because various alpha(v)-containing integrins have been suggested as central mediators of fibrosis in multiple organs. Such depletion protected mice from carbon tetrachloride-induced hepatic fibrosis, whereas global loss of beta(3), beta(5) or beta(6) integrins or conditional loss of beta(8) integrins in HSCs did not. We also found that Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of the alpha(v) integrin subunit using this system was protective in other models of organ fibrosis, including pulmonary and renal fibrosis. Pharmacological blockade of alpha(v)-containing integrins by a small molecule (CWHM 12) attenuated both liver and lung fibrosis, including in a therapeutic manner. These data identify a core pathway that regulates fibrosis and suggest that pharmacological targeting of all alpha(v) integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases.
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| 3. |
- Kokkolaras, Michael, et al.
(författare)
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Towards a comprehensive framework for simulation-based vehicle systems design validation
- 2013
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Ingår i: International Journal of Vehicle Design. - 0143-3369 .- 1741-5314. ; 61:.1/2/3/4, s. 233-248
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Tidskriftsartikel (refereegranskat)abstract
- We present an overview of our most recent and ongoing research efforts to develop a comprehensive framework for simulation-based design validation of vehicle systems. Specifically, we present the three major building blocks of our framework: (1) the introduction of an appropriate validation metric for dealing with the multivariate functional data that are the output of dynamic vehicle systems; (2) the robust implementation of a Bayesian interval-based hypothesis testing technique for quantifying the confidence in simulation models used for design under uncertainty; (3) the development of a sequential design optimisation and calibration-based validation methodology that addresses the inadequacy of current validation practices in simulation-based design optimisation. We present a simple yet illustrative example and discuss the techniques being developed currently that will complete the proposed framework
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| 4. |
- Lambert, Sylvie D., et al.
(författare)
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Building the capacity for psycho-Oncology research: a survey of the research barriers and training needs within the International Psycho-Oncology Society
- 2020
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Ingår i: Journal of Psychosocial Oncology Research & Practice. - : Ovid Technologies (Wolters Kluwer Health). - 2637-5974. ; 2:3, s. e023-e023
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Tidskriftsartikel (refereegranskat)abstract
- Background: The International Psycho-Oncology Society (IPOS) is a multidisciplinary professional network that aims to improve psychosocial care for individuals impacted by cancer. IPOS encourages research activity, recognizing that a high-quality evidence base is essential to provide best-practice, data-driven clinical care. This study aimed to determine the barriers to research involvement and the training needs and priorities of IPOS members, with the goal of facilitating the development of training resources tailored to the needs of IPOS members.Methods: A link to an online, cross-sectional survey was disseminated to all registered members of IPOS via email. The online survey platform SimpleSurvey was used, and questions included demographic characteristics and items related to research interests, involvement, and training needs. High priority research training needs were identified as research tasks respondents rated as highly important, yet possessed a low perceived skill level in.Results: Thirty-two percent of IPOS members (n = 142) completed the survey. Participants represented 49 countries and were at a variety of career stages. Overall, participants reported spending an average of 17.3 hours per week on research (range 0-80 hours per week), with 69% of respondents wanting to increase their research involvement. The main barriers to research participation included lack of research funding (80%) and lack of protected time (63%). IPOS members identified 5 high-priority training needs: preparing successful grant applications; preparing research budgets; community-based participatory research; working with decision makers; and finding collaborators or expert consultants. Participants suggested funding access, statistical advisors, and networking and mentorship opportunities as ways to enhance research involvement. Members preferred online training modules (39%) and mentorship programs (19%) as methods by which IPOS could provide research support. IPOS was viewed as being able to contribute to many aspects of research capacity building such as networking, training, and dissemination of research findings.Conclusions: IPOS has an important role in encouraging research capacity building among members. This survey provides an agenda for workshops and training opportunities. Mainly, for respondents it was less about training in research methods and more about training in how to prepare successful grant applications, including budgets, and receiving mentorship on this as well as having opportunities to collaborate with other researchers.
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| 6. |
- Sarin, H., et al.
(författare)
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A comprehensive metric for comparing time histories in validation of simulation models with emphasis on vehicle safety applications
- 2009
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Ingår i: Proceedings of the ASME International Design Engineering Technical Conferences and Computers and Information in Engineering Conference - 2008. - New York : American Society of Mechanical Engineers. - 9780791843253 ; , s. 1275-1286
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Konferensbidrag (refereegranskat)abstract
- Computer modeling and simulation are the cornerstones of product design and development in the automotive industry. Computer-aided engineering tools have improved to the extent that virtual testing may lead to significant reduction in prototype building and testing of vehicle designs. In order to make this a reality, we need to assess our confidence in the predictive capabilities of simulation models. As a first step in this direction, this paper deals with developing a metric to compare time histories that are outputs of simulation models to time histories from experimental tests with emphasis on vehicle safety applications. We focus on quantifying discrepancy between time histories as the latter constitute the predominant form of responses of interest in vehicle safety considerations. First we evaluate popular measures used to quantify discrepancy between time histories in fields such as statistics, computational mechanics, signal processing, and data mining. Then we propose a structured combination of some of these measures and define a comprehensive metric that encapsulates the important aspects of time history comparison. The new metric classifies error components associated with three physically meaningful characteristics (phase, magnitude and topology), and utilizes norms, cross-correlation measures and algorithms such as dynamic time warping to quantify discrepancies. Two case studies demonstrate that the proposed metric seems to be more consistent than existing metrics. It is also shown how the metric can be used in conjunction with ratings from subject matter experts to build regression-based validation models
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| 7. |
- Sarin, H., et al.
(författare)
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Comparing time histories for validation of simulation models : Error measures and metrics
- 2010
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Ingår i: Journal of Dynamic Systems Measurement, and Control. - : ASME International. - 0022-0434 .- 1528-9028. ; 132:6
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Tidskriftsartikel (refereegranskat)abstract
- Computer modeling and simulation are the cornerstones of product design and development in the automotive industry. Computer-aided engineering tools have improved to the extent that virtual testing may lead to significant reduction in prototype building and testing of vehicle designs. In order to make this a reality, we need to assess our confidence in the predictive capabilities of simulation models. As a first step in this direction, this paper deals with developing measures and a metric to compare time histories obtained from simulation model outputs and experimental tests. The focus of the work is on vehicle safety applications. We restrict attention to quantifying discrepancy between time histories as the latter constitute the predominant form of responses of interest in vehicle safety considerations. First, we evaluate popular measures used to quantify discrepancy between time histories in fields such as statistics, computational mechanics, signal processing, and data mining. Three independent error measures are proposed for vehicle safety applications, associated with three physically meaningful characteristics (phase, magnitude, and slope), which utilize norms, cross-correlation measures, and algorithms such as dynamic time warping to quantify discrepancies. A combined use of these three measures can serve as a metric that encapsulates the important aspects of time history comparison. It is also shown how these measures can be used in conjunction with ratings from subject matter experts to build regression-based validation metrics.
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| 8. |
- Ujvari, Beata, et al.
(författare)
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Experimental studies of blowfly (Calliphora stygia) longevity: A little dietary fat is beneficial but too much is detrimental
- 2009
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Ingår i: Comparative Biochemistry and Physiology A. - : Elsevier BV. - 1531-4332. ; 154:3, s. 383-388
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Tidskriftsartikel (refereegranskat)abstract
- This paper is one in a series of experimental studies on the effects of food composition on aging and longevity, using the golden-haired blowfly Calliphora stygia as the animal model Here we examine how diet. fat content affects blowfly life history traits such as longevity, reproduction, feeding rate, body mass, total fat content and membrane fatty acid composition. The highest median and maximum longevity was observed in blowflies fed on low fat diets, while high-fat diets caused more rapid death of the blowflies. A major result was that blowflies feeding on the lowest fat diet had the highest maximal lifespan demonstrating that low levels of diet fat enhanced blowfly lifespan. Diet also influenced gender-specific mortality rates; females lived longer on a high-fat diet, while males lived longer on a low fat diet. Furthermore, we provide data for and explain how blowfly feeding rates, egg production and male harassment affected blowfly longevity. Our results highlight the need for further studies to understand how dietary fats are metabolised and utilised in the golden-haired blowfly. (C) 2009 Elsevier Inc. All rights reserved.
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