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- Andersson, Henrik, et al.
(författare)
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Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells
- 2010
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Ingår i: JOURNAL OF BIOTECHNOLOGY. - : Elsevier Science B.V., Amsterdam.. - 0168-1656 .- 1873-4863. ; 150:1, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.
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| 4. |
- Asp, Julia, 1973, et al.
(författare)
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Cardiomyocyte clusters derived from human embryonic stem cells share similarities with human heart tissue.
- 2010
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Ingår i: Journal of molecular cell biology. - : Oxford University Press (OUP). - 1759-4685 .- 1674-2788. ; 2:5, s. 276-83
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Tidskriftsartikel (refereegranskat)abstract
- Cardiotoxicity testing is a key activity in the pharmaceutical industry in order to detect detrimental effects of new drugs. A reliable human in vitro model would both be beneficial in selection of lead compounds and be important for reducing animal experimentation. However, the human heart is a complex organ composed of many distinct types of cardiomyocytes, but cardiomyocyte clusters (CMCs) derived from human embryonic stem cells could be an option for a cellular model. Data on functional properties of CMCs demonstrate similarities to their in vivo analogues in human. However, development of an in vitro model requires a more thorough comparison of CMCs to human heart tissue. Therefore, we directly compared individually isolated CMCs to human fetal, neonatal, adult atrial and ventricular heart tissues. Real-time qPCR analysis of mRNA levels and protein staining of ion channels and cardiac markers showed in general a similar expression pattern in CMCs and human heart. Moreover, a significant decrease in beat frequency was noted after addition of Zatebradine, a blocker to I(f) involved in regulation of spontaneous contraction in CMCs. The results underscore the similarities of CMCs to human cardiac tissue, and further support establishment of novel cardiotoxicity assays based on the CMCs in drug discovery.
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- Bäckström, Christer, et al.
(författare)
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From Macro Plans to Automata Plans
- 2012
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Ingår i: ECAI 2012. 20th European Conference on Artificial Intelligence, 27-31 2012, August, Montpellier, France. - 9781614990970 - 9781614990987 ; , s. 91-96
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Konferensbidrag (refereegranskat)abstract
- Macros have a long-standing role in planning as a tool for representing repeating subsequences of operators. Macros are useful both for guiding search towards a solution and for representing plans compactly. In this paper we introduce automata plans which consist of hierarchies of finite state automata. Automata plans can be viewed as an extension of macros that enables parametrization and branching. We provide several examples of the utility of automata plans, and prove that automata plans are strictly more expressive than macro plans. We also prove that automata plans admit polynomialtime sequential access of the operators in the underlying “flat” plan, and identify a subset of automata plans that admit polynomial-time random access. Finally, we compare automata plans with other representations allowing polynomial-time sequential access.
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| 6. |
- Bäckström, Christer, et al.
(författare)
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Macros, Reactive Plans and Compact Representations
- 2012
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Ingår i: ECAI 2012. 20th European Conference on Artificial Intelligence 27-31 August 2+12, Montpellier, France. - 9781614990970 - 9781614990987 ; , s. 85-90
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Konferensbidrag (refereegranskat)abstract
- The use and study of compact representations of objects is widespread in computer science. AI planning can be viewed as the problem of finding a path in a graph that is implicitly described by a compact representation in a planning language. However, compact representations of the path itself (the plan) have not received much attention in the literature. Although both macro plans and reactive plans can be considered as such compact representations, little emphasis has been placed on this aspect in earlier work. There are also compact plan representations that are defined by their access properties, for instance, that they have efficient random access or efficient sequential access. We formally compare two such concepts with macro plans and reactive plans, viewed as compact representations, and provide a complete map of the relationships between them.
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- Chawade, Aakash, 1980, et al.
(författare)
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Development of a model system to identify differences in spring and winter oat
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Our long-term goal is to develop a Swedish winter oat (Avena sativa). To identify molecular differences that correlate with winter hardiness, a winter oat model comprising of both non-hardy spring lines and winter hardy lines is needed. To achieve this, we selected 294 oat breeding lines, originating from various Russian, German, and American winter oat breeding programs and tested them in the field in south- and western Sweden. By assaying for winter survival and agricultural properties during four consecutive seasons, we identified 14 breeding lines of different origins that not only survived the winter but also were agronomically better than the rest. Laboratory tests including electrolytic leakage, controlled crown freezing assay, expression analysis of the AsVrn1 gene and monitoring of flowering time suggested that the American lines had the highest freezing tolerance, although the German lines performed better in the field. Finally, six lines constituting the two most freezing tolerant lines, two intermediate lines and two spring cultivars were chosen to build a winter oat model system. Metabolic profiling of non-acclimated and cold acclimated leaf tissue samples isolated from the six selected lines revealed differential expression patterns of 245 metabolites including several sugars, amino acids, organic acids and 181 hitherto unknown metabolites. The expression patterns of 107 metabolites showed significant interactions with either a cultivar or a time-point. Further identification, characterisation and validation of these metabolites will lead to an increased understanding of the cold acclimation process in oats. Furthermore, by using the winter oat model system, differential sequencing of crown mRNA populations would lead to identification of various biomarkers to facilitate winter oat breeding. © 2012 Chawade et al.
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| 8. |
- Finstad, Anders G., et al.
(författare)
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Competitive exclusion along climate gradients : energy efficiency influences the distribution of two salmonid fishes
- 2011
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 17:4, s. 1703-1711
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Tidskriftsartikel (refereegranskat)abstract
- We tested the importance of thermal adaptations and energy efficiency in relation to the geographical distribution of two competing freshwater salmonid fish species. Presence–absence data for Arctic char and brown trout were obtained from 1502 Norwegian lakes embracing both temperature and productivity gradients. The distributions were contrasted with laboratory-derived temperature scaling models for food consumption, growth and energy efficiency. Thermal performances of the two species were almost identical. However, Arctic char exhibited double the growth efficiency (per unit of food) and appear to have out-competed brown trout from cold, low-productivity lakes, perhaps by scramble competition. Brown trout, for which previous reports have shown to be aggressive and dominant, have likely excluded the more energy-efficient Arctic char from relatively warm, productive lakes, perhaps by contest competition. Competitive interaction changing in outcome with lake productivity, rather than thermal performance, is likely a major determinant of the range distribution of the two species. Our study highlights the need for more focus on choice of relevant ecophysiological traits in ecological climate impact studies and species distribution modelling.
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- Gustavsson, Anders, et al.
(författare)
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Corrigendum to “Cost of disorders of the brain in Europe 2010” [Eur. Neuropsychopharmacol. 21 (2011) 718–779]
- 2012
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 22:3, s. 237-238
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Tidskriftsartikel (refereegranskat)abstract
- The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.
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| 10. |
- Herlitz, Johan, et al.
(författare)
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Suspicion and treatment of severe sepsis : An overview of the prehospital chain of care
- 2012
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Ingår i: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central. - 1757-7241. ; 20:42
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundSepsis is a life-threatening condition where the risk of death has been reported to be even higher than that associated with the major complications of atherosclerosis, i.e. myocardial infarction and stroke. In all three conditions, early treatment could limit organ dysfunction and thereby improve the prognosis.AimTo describe what has been published in the literature a/ with regard to the association between delay until start of treatment and outcome in sepsis with the emphasis on the pre-hospital phase and b/ to present published data and the opportunity to improve various links in the pre-hospital chain of care in sepsis.MethodsA literature search was performed on the PubMed, Embase (Ovid SP) and Cochrane Library databases.ResultsIn overall terms, we found a small number of articles (n=12 of 1,162 unique hits) which addressed the prehospital phase. For each hour of delay until the start of antibiotics, the prognosis appeared to become worse. However, there was no evidence that prehospital treatment improved the prognosis.Studies indicated that about half of the patients with severe sepsis used the emergency medical service (EMS) for transport to hospital. Patients who used the EMS experienced a shorter delay to treatment with antibiotics and the start of early goal-directed therapy (EGDT). Among EMS-transported patients, those in whom the EMS staff already suspected sepsis at the scene had a shorter delay to treatment with antibiotics and the start of EGDT.There are insufficient data on other links in the prehospital chain of care, i.e. patients, bystanders and dispatchers.ConclusionSevere sepsis is a life-threatening condition. Previous studies suggest that, with every hour of delay until the start of antibiotics, the prognosis deteriorates. About half of the patients use the EMS. We need to know more about the present situation with regard to the different links in the prehospital chain of care in sepsis.
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