| 11. |
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| 12. |
- 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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| 13. |
- 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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| 14. |
- Bergkvist, Lisa, et al.
(författare)
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Carbon Sequestration Potential f Agroforestry Systems For Phytoremediation In Chinandega, Nicaragua
- 2018
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Ingår i: Linnaeus Eco-Tech 2018. ; , s. 211-211
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Greenhouse gases in the atmosphere have increased to earlier unrecorded levels, causing global climate change that increases GMT and threaten ecosystems and livelihoods. IPCC report suggest that agroforestry offers considerable carbon sequestration (c seq.) potential, especially for developing countries. The purpose of this study is to estimate the c seq. potential in different agroforestry systems suitable in Chinandega, Nicaragua - a deforested region where the ground is polluted by toxaphene and other POP:s. Three scenarios where studied; Shading system using Tectona grandis and Pogostemon cablin; Alley cropping using Erythrina poeppigiana and Ricinus communis and Silvopasture using Cordia alliodora and Brachiaria ruziziensis, the last scenario being divided into two subscenarios; unmanaged (grazed) and managed (harvested) grass. Calculations were performed using the modelling program CO2FIX v. 3.2, with a runtime of 100 years and assuming deforested area with no previous land use. Results show a significantly higher c seq. potential in Shading system (168/217 MgC/ha). Alley cropping yields 71 MgC/ha and Silvopasture results in 80/84 MgC/ha unmanaged and 65/70 MgC/ha managed. The higher number includes products from harvest. All scenarios show fluctuations over time due to thinning and harvesting practices. Phytoremediation potential of POPs has been shown in Ricinus communis and grass species. Soil c seq. is especially important to consider in longterm scenarios as this c seq. can be sustained over longer time. The inclusion of crop residue, the effect of grazing animals or changes in density of trees and crops and environmental fate of the toxic compounds need further assessment before considering large scale applications. Agroforestry practices could contribute to several benefits, including climate change mitigation and phytoremediation.
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| 15. |
- Bredberg, Anders, et al.
(författare)
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Clinical-scale generation of strongly CD83-expressing dendritic cells using extracorporeal photopheresis
- 2007
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Ingår i: Photodermatology, Photoimmunology & Photomedicine. - : Wiley. - 1600-0781 .- 0905-4383. ; 23:4, s. 113-119
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many strategies are currently being pursued in order to generate mature dendritic cells (DC) to be used for immunotherapy. A potent anti-tumour influence by extracorporeal photopheresis has been documented for cutaneous T-cell lymphoma, and a major mechanism of action has been suggested to be generation of DC presenting tumour antigens. Purpose: To determine the potential of a simple clinical photopheresis protocol for large-scale development of mature DC. Methods: A standard monocyte-enriched leukapheresis preparation of 10(9)-10(10) cells was derived during each of five consecutive treatment sessions of a patient with cutaneous T-cell lymphoma. The cells were incubated overnight in autologous plasma with no addition of growth medium. Cell surface lymphocyte, monocyte and DC markers were determined using multi-colour flow cytometry. Results: We find signs of activation of the CD14+ monocytes, as well as the appearance of a minor population of mature DC negative for CD14 but with strong CD83 expression. Conclusions: With a procedure appropriate for routine clinical use, a total number of 10(6)-10(7) DC ready for patient reinfusion can be prepared within 24 h. Our findings indicate the need to further explore the capacity of photopheresis to stimulate cancer patients' anti-tumour defence reaction.
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| 16. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 17. |
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| 18. |
- Bräutigam, Marcus, 1968, et al.
(författare)
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Development of Swedish winter oat with gene technology and molecular breeding
- 2006
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Ingår i: J. Seed Science. - 0039-6990. ; 116:1-2, s. 12-35
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, oat (Avena sativa) is only grown as a spring crop. A Swedish winter oat, on the other hand, would give increased yields and would secure oat in Swedish agriculture. During three consecutive winters we performed field trials with oat aiming at identifying potential winter material. More than 300 varieties, originating from breeding programs all over the world, were tested. Plants were rated according to winter survival, vigour and general performance during the following growth season and more than 20 lines were identified that were cold hardier than present commercial oat varieties. In parallel experiments a cDNA library was constructed from cold induced English winter oat (Gerald) and ca 10000 EST sequences were generated. After data mining a UniGene set of 2800 oat genes was obtained. By detailed analysis of microarray data from cold stressed Arabidopsis and by advanced bioinformatics, gene interactions in the complex cold induced signal transduction pathway were deduced. By comparison to the oat UniGene set, several genes potentially involved in the regulation of cold hardiness in oat were identified. An Agrobacterium mediated transformation protocol was developed for one oat genotype. Key regulatory genes in cold acclimation will be introduced to oat by genetic transformation or modified by TILLING. Such genes will be used as molecular markers in intogression of winter hardiness to commercial oat.
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| 19. |
- Bäckström, Christer, et al.
(författare)
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Automaton Plans
- 2014
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Ingår i: The journal of artificial intelligence research. - : AI ACCESS FOUNDATION. - 1076-9757 .- 1943-5037. ; 51, s. 255-291
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Tidskriftsartikel (refereegranskat)abstract
- Macros have long been used in planning to represent subsequences of operators. Macros can be used in place of individual operators during search, sometimes reducing the effort required to find a plan to the goal. Another use of macros is to compactly represent long plans. In this paper we introduce a novel solution concept called automaton plans in which plans are represented using hierarchies of automata. Automaton plans can be viewed as an extension of macros that enables parameterization and branching. We provide several examples that illustrate how automaton plans can be useful, both as a compact representation of exponentially long plans and as an alternative to sequential solutions in benchmark domains such as LOGISTICS and GRID. We also compare automaton plans to other compact plan representations from the literature, and find that automaton plans are strictly more expressive than macros, but strictly less expressive than HTNs and certain representations allowing efficient sequential access to the operators of the plan.
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| 20. |
- 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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