| 1. |
- Fadista, Joao, et al.
(author)
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Global genomic and transcriptomic analysis of human pancreatic islets reveals novel genes influencing glucose metabolism.
- 2014
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In: 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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Journal article (peer-reviewed)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.
(author)
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The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events.
- 2014
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In: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 19:5, s. 883-890
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Journal article (peer-reviewed)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. |
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| 5. |
- Abdalla, Alvaro, et al.
(author)
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The Effect of Engine Dimensions on Supersonic Aircraft Performance
- 2013
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In: 4:th CEAS Air & Space Conference.
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Conference paper (peer-reviewed)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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| 6. |
- Amadori, Kristian, et al.
(author)
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Automated Design and Fabrication of Micro Air Vehicles
- 2011
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In: Journal of Aerospace Engineering. - : SAGE Journals online. - 0893-1321 .- 1943-5525. ; 226:10, s. 1271-1282
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Journal article (peer-reviewed)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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| 7. |
- Amadori, Kristian, et al.
(author)
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Evaluation of Automatically Designed Micro Air Vehicles and Flight Testing
- 2010
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Conference paper (peer-reviewed)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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| 8. |
- Amadori, Kristian, et al.
(author)
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Flexible and Robust CAD Models for Design Automation
- 2012
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In: Advanced Engineering Informatics. - : Elsevier BV. - 1474-0346 .- 1873-5320. ; 26:2, s. 180-195
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Journal article (peer-reviewed)abstract
- This paper explores novel methodologies for enabling Multidisciplinary Design Optimization (MDO) of complex engineering products. To realize MDO, Knowledge Based Engineering (KBE) is adopted with the aim of achieving design reuse and automation. The aim of the on-going research at Linköping University is to shift from manual modelling of disposable geometries to Computer Aided Design (CAD) automation by introducing generic high-level geometry templates. Instead of repeatedly modelling similar instances of objects, engineers should be able to create more general models that can represent entire classes of objects. The proposed methodology enables utilization of commercial design tools, hence taking industrial feasibility into consideration. High Level CAD templates (HLCt) will be proposed and discussed as the building blocks of flexible and robust CAD models, which in turn enables high-fidelity geometry in the MDO loop. Quantification of the terms flexibility and robustness is also presented, providing a means to measure the quality of the geometry models. Finally, application examples are presented in which the outlined framework is evaluated. The applications have been chosen from three ongoing research projects aimed at automating the design of transport aircraft, industrial robots, and micro air vehicles.
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| 9. |
- Amadori, Kristian
(author)
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Geometry Based Design Automation : Applied to Aircraft Modelling and Optimization
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Product development processes are continuously challenged by demands for increased efficiency. As engineering products become more and more complex, efficient tools and methods for integrated and automated design are needed throughout the development process. Multidisciplinary Design Optimization (MDO) is one promising technique that has the potential to drastically improve concurrent design. MDO frameworks combine several disciplinary models with the aim of gaining a holistic perspective of a system, while capturing the synergies between different subsystems. Among all disciplines, the geometric model is recognized as playing a key role, because it collects most of the data required to any other disciplinary analysis. In the present thesis, methodologies to enable multidisciplinary optimization in early aircraft design phases are studied. In particular, the research aims at putting the CAD geometric model in the loop. This requires the ability to automatically generate or update the geometric model, here referred to as geometry-based design automation.The thesis proposes the use of Knowledge Based Engineering (KBE) techniques to achieve design reuse and automation. In particular, so called High Level CAD templates (HLCts) are suggested to automate geometry generation and updates. HLCts can be compared to parametric LEGO® blocks containing a set of design and analysis parameters. These are produced and stored in libraries, giving engineers or a computer agent the possibility to first topologically select the templates and then modify the shape of each template parametrically.Since parameterization is central to modelling by means of HLCts, a thorough analysis of the subject is also performed. In most of the literature on MDO and KBE two recurring requirements concerning the geometrical model are expressed: the model should be flexible and robust. However, these requirements have never been properly formulated or defined. Hence, in the thesis a mathematical formulation for geometry model robustness and flexibility are proposed. These formulations ultimately allow the performance of geometric models to be precisely measured and compared.Finally, a prototyping and validation process is presented. The aim is to quickly and cost-effectively validate analytical results from an MDO process. The proposed process adopts different manufacturing techniques depending on the size and purpose of the intended prototype. In the last part of the thesis, three application examples are presented. The examples are chosen from research projects that have been carried out at Linköping University and show how the proposed theoretical results have been successfully employed in practice.
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| 10. |
- Amadori, Kristian, et al.
(author)
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Multidisciplinary Optimization of Wing Structure Using Parametric Models
- 2013
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Conference paper (other academic/artistic)abstract
- Aircraft design is an inherently multidisciplinary activity that requires integrating different models and tools to reach a well-balanced and optimized product. At Linköping University a design framework is being developed to support the initial design space exploration and the conceptual design phase. Main characteristics of the framework are its flexible database in XML format, together with close integration of automated CAD and other tools, which allows the developed geometry to be directly used in the subsequent preliminary design phase. In particular, the aim of the proposed work is to test the framework by designing, optimizing and studying a transport aircraft wing with respect to aerodynamic, geometry, structural and accessability constraints. The project will provide an initial assessment of the capability of the framework, both in terms of processing speed and accuracy of the results.
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