| 1. |
- Fadista, Joao, et al.
(författare)
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Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism.
- 2014
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 111:38, s. 13924-13929
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variation can modulate gene expression, and thereby phenotypic variation and susceptibility to complex diseases such as type 2 diabetes (T2D). Here we harnessed the potential of DNA and RNA sequencing in human pancreatic islets from 89 deceased donors to identify genes of potential importance in the pathogenesis of T2D. We present a catalog of genetic variants regulating gene expression (eQTL) and exon use (sQTL), including many long noncoding RNAs, which are enriched in known T2D-associated loci. Of 35 eQTL genes, whose expression differed between normoglycemic and hyperglycemic individuals, siRNA of tetraspanin 33 (TSPAN33), 5'-nucleotidase, ecto (NT5E), transmembrane emp24 protein transport domain containing 6 (TMED6), and p21 protein activated kinase 7 (PAK7) in INS1 cells resulted in reduced glucose-stimulated insulin secretion. In addition, we provide a genome-wide catalog of allelic expression imbalance, which is also enriched in known T2D-associated loci. Notably, allelic imbalance in paternally expressed gene 3 (PEG3) was associated with its promoter methylation and T2D status. Finally, RNA editing events were less common in islets than previously suggested in other tissues. Taken together, this study provides new insights into the complexity of gene regulation in human pancreatic islets and better understanding of how genetic variation can influence glucose metabolism.
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| 2. |
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| 3. |
- Krus, Ulrika, et al.
(författare)
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The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events.
- 2014
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 19:5, s. 883-890
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is triggered by reduced insulin production, caused by genetic and environmental factors such as inflammation originating from the innate immune system. Complement proteins are a component of innate immunity and kill non-self cells by perforating the plasma membrane, a reaction prevented by CD59. Human pancreatic islets express CD59 at very high levels. CD59 is primarily known as a plasma membrane protein in membrane rafts, but most CD59 protein in pancreatic β cells is intracellular. Removing extracellular CD59 disrupts membrane rafts and moderately stimulates insulin secretion, whereas silencing intracellular CD59 markedly suppresses regulated secretion by exocytosis, as demonstrated by TIRF imaging. CD59 interacts with the exocytotic proteins VAMP2 and Syntaxin-1. CD59 expression is reduced by glucose and in rodent diabetes models but upregulated in human diabetic islets, potentially reflecting compensatory reactions. This unconventional action of CD59 broadens the established view of innate immunity in type 2 diabetes.
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| 4. |
- Ottosson-Laakso, Emilia, et al.
(författare)
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Glucose-induced Changes in Gene Expression in Human Pancreatic Islets - Causes or Consequences of Chronic Hyperglycemia
- 2017
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 66:12, s. 3013-3028
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Tidskriftsartikel (refereegranskat)abstract
- Dysregulation of gene expression in islets from type 2 diabetic patients might be causally involved in the development of hyperglycemia or it could develop as a consequence of hyperglycemia, i.e. glucotoxicity. To separate the genes potentially causally involved in pathogenesis from those likely to be secondary to the hyperglycemia we exposed islets from human donors to normal or high glucose concentrations for 24 hours and analyzed gene expression. We compared these findings with gene expression in islets from donors with normal glucose tolerance (NGT) and hyperglycemia (HG, including T2D). The genes whose expression changed in the same direction after short-term glucose exposure as in T2D were considered most likely to be a consequence of hyperglycemia. Genes whose expression changed in HG but not after short-term glucose exposure, in particular genes that also correlated with insulin secretion, were considered the strongest candidates for causal involvement in T2D. E.g. ERO1LB, DOCK10, IGSF11 and PRR14L were down-regulated in HG and correlated positively with insulin secretion suggesting a protective role while TMEM132C was up-regulated in HG and correlated negatively with insulin secretion suggesting a potential pathogenic role.This study provides a catalogue of gene expression changes in human pancreatic islets after exposure to glucose.
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| 5. |
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| 6. |
- Abdalla, Alvaro, et al.
(författare)
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The Effect of Engine Dimensions on Supersonic Aircraft Performance
- 2013
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Ingår i: 4:th CEAS Air & Space Conference.
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Konferensbidrag (refereegranskat)abstract
- In aircraft design a critical part of the design isthe engine selection. This is typically making aselection from exiting engines. Looking at a nextgeneration future fighters, however, where thetime of deployment may be 20-30 years in thefuture this is not a valid approach as there willbe an evolution in the engine designs. E.g. anew European fighter aircraft will most likelybe a collaborative project also involving thedevelopment of an engine for that aircraft. Inthis study conceptual engine-airframe co-designis demonstrated, using models of comparablefidelity for both the engine design and theaircraft design. This co-design leads to a deeperunderstanding of the tradeoffs from both sides,and means that also more radical designs andinnovations can be evaluated in a fair way.
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| 7. |
- Amadori, Kristian, et al.
(författare)
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A Framework for Aerodynamic and Structural Optimization in Conceptual Design
- 2007
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Ingår i: 25th AIAA Applied Aerodynamics Conference, 25-28 June, Miami, FL, USA. - : AIAA. ; , s. 4061-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aircraft design is an inherently multidisciplinary activity that requires different models and tools for various aspects of the design. At Linköping University a novel design framework is being developed to support the initial conceptual design phase of a new aircraft. In this work main attention has been paid to wing design, with respect to aerodynamic efficiency and loads, and to structural analysis. By linking together various modules via a user-friendly interface based on a spreadsheet, the framework allows multidisciplinary analysis and optimizations to be carried out. This paper will present the framework, give an overview of its development status and give an indication on the future work.
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| 8. |
- Amadori, Kristian, 1976-, et al.
(författare)
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Aircraft Conceptual Design Optimization
- 2008
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Ingår i: International Congress of the Aeronautical Sciences ICAS,2008. - Stockholm, Sweden : ICAS.
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Konferensbidrag (refereegranskat)abstract
- Aircraft design is an inherently multidisciplinary activity that requires different models and tools for various aspects of the design. At Linköping University a novel design framework is being developed to support the initial conceptual design phase of new aircraft. By linking together various modules via a userfriendly spreadsheet interface, the framework allows multidisciplinary analysis and optimizations to be carried out. The geometrical model created with a high-end CAD system, contains all the available information on the product and thus it plays a central role in the framework. In this work great attention has been paid to techniques that allow creating robust yet highly flexible CAD models. Two different case studies are presented. The first one is a hypothetic wing-box design that is studied with respect to aerodynamic efficiency and loads, and to structural analysis. In this study two approaches were compared. In one case the wing-box design was optimized with a fixed number of structural elements, where only dimensions and position were allowed to change. Then the same wing-box was analyzed allowing also the number of structural elements to vary. Thus only the parts that are required are left and a more efficient design can be obtained. In the second case study a mission simulation is performed on a UAV-type aircraft. Required data for the simulation are gathered from the CAD model and from aerodynamic analysis carried out with PANAIR, a high order panel code. The obtained data are then used as inputs parameters for flight simulation in order to determined hydraulic systems characteristics.
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| 9. |
- Amadori, Kristian, et al.
(författare)
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Automated Design and Fabrication of Micro Air Vehicles
- 2011
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Ingår i: Journal of Aerospace Engineering. - : SAGE Journals online. - 0893-1321 .- 1943-5525. ; 226:10, s. 1271-1282
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Tidskriftsartikel (refereegranskat)abstract
- A methodology for an automated design and fabrication of micro-air vehicles (MAVs) is presented. A design optimization framework has been developed that interfaces several software systems to generate MAVs to optimally fulfil specific mission requirements. By means of amulti-objective genetic algorithm, families of MAVs are tailored with respect to objectives such as weight and endurance. The framework takes into consideration the airframe and aerodynamic design as well as the selection and positioning of internal components. The selection of propulsion system components is made from a database of off-the-shelf components. In combination with a three-dimensional printer, physical prototypes can be quickly manufactured. A validation of the framework results from flight tests of a real MAV is also presented.
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| 10. |
- Amadori, Kristian, et al.
(författare)
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Evaluation of Automatically Designed Micro Air Vehicles and Flight Testing
- 2010
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Konferensbidrag (refereegranskat)abstract
- The presented work is centered on the evaluation of Micro or Mini Air Vehicles (MAV) that have been automatically designed and manufactured. An in-house developed design framework uses several coupled computer software’s to generate the geometric design in CAD, a well as list of off the shelf components for the propulsion system, and computer code for autonomous flight ready to upload in the intended autopilot. The paper describes the experiences made so far regarding automation of the design process and of manufacturing. Furthermore, it presents results from evaluation and analysis of the optimization algorithm and flight testing, and from continuing work with the framework to achieve deeper understanding of the process and to fine-tune the design automation performance. The flight data is correlated to the predicted performances to validate the models and design process.
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