| 1. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 2. |
- Gaugaz, Fabienne Z, et al.
(författare)
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The impact of cyclopropane configuration on the biological activity of cyclopropyl-epothilones
- 2014
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Ingår i: ChemMedChem. - : Wiley. - 1860-7179 .- 1860-7187. ; 9:10, s. 2227-2232
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Tidskriftsartikel (refereegranskat)abstract
- Two cis-12,13-cyclopropyl-epothilone B variants have been synthesized, differing only in the configuration of the stereocenters at C12 and C13. The syntheses were based on a common allylic alcohol intermediate that was converted into the corresponding diastereomeric hydroxymethyl-cyclopropanes by means of stereoselective Charette cyclopropanations. Macrocyclizations were accomplished through ring-closing metathesis (RCM). Substantial differences between the two compounds were found with regard to microtubule binding affinity, antiproliferative activity and their effects on the cellular microtubule network. While the analogue with the cyclopropane moiety oriented in a corresponding way to the epoxide configuration in natural epothilones was almost equipotent with epothilone A, the other was significantly less active. Based on these findings, natural epothilone-like activity of cis-fused 12,13-cyclopropyl-epothilone analogues is tightly linked to the natural orientation of the cyclopropane moiety.
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| 3. |
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| 4. |
- Kaufmann, Markus, 1980-
(författare)
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Cost Optimization of Aircraft Structures
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Composite structures can lower the weight of an airliner significantly. Due to the higher process complexity and the high material cost, however, the low weight often comes with a significant increase in production cost. The application of cost-effective design strategies is one mean to meet this challenge. In this thesis, a simplified form of direct operating cost is suggested as a comparative value that in combination with multidisciplinary optimization enables the evaluation of a design solution in terms of cost and weight. The proposed cost optimization framework takes into account the manufacturing cost, the non-destructive testing cost and the lifetime fuel consumption based on the weight of the aircraft, thus using a simplified version of the direct operating cost as the objective function. The manufacturing cost can be estimated by means of different techniques. For the proposed optimization framework, feature-based parametric cost models prove to be most suitable. Paper A contains a parametric study in which a skin/stringer panel is optimized for a series of cost/weight ratios (weight penalties) and material configurations. The weight penalty (defined as the specific lifetime fuel burn) is dependent on the fuel consumption of the aircraft, the fuel price and the viewpoint of the optimizer. It is concluded that the ideal choice of the design solution is neither low-cost nor low-weight but rather a combination thereof. Paper B proposes the inclusion of non-destructive testing cost in the design process of composite components, and the adjustment of the design strength of each laminate according to inspection parameters. Hence, the scan pitch of the ultrasonic testing is regarded as a variable, representing an index for the guaranteed material quality. It is shown that the cost for non-destructive testing can be lowered if the quality level of the laminate is assigned and adjusted in an early design stage. In Paper C and Paper D the parameters of the manufacturing processes are upgraded during the cost optimization of the component. In Paper C, the framework is extended by the cost-efficient adaptation of parameters in order to reflect the situation when machining an aluminum component. For different weight penalties, the spar thickness and stringer geometry of the provided case study vary. In addition, another cutter is chosen with regard to the modified shape of the stringer. In Paper D, the methodology is extended to the draping of composite fabrics, thus optimizing not only the stacking layup, but also the draping strategy itself. As in the previous cases, the design alters for different settings of the weight penalty. In particular, one can see a distinct change in fiber layup between the minimum weight and the minimum cost solution. Paper E summarizes the work proposed in Papers A-D and provides a case study on a C-spar component. Five material systems are used for this case study and compared in terms of cost and weight. The case study shows the impact of the weight penalty, the material cost and the labor rate on the choice of the material system. For low weight penalties, for example, the aluminum spar is the most cost-effective solution. For high weight penalties, the RTM system is favorable. The paper also discusses shortcomings with the presented methodology and thereby opens up for future method developments.
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| 5. |
- Kaufmann, Markus, 1980-, et al.
(författare)
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Cost optimization of composite aircraft structures including variable laminate qualities
- 2008
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Ingår i: Composites Science And Technology. - : Elsevier. - 0266-3538 .- 1879-1050. ; 68:13, s. 2748-2754
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Tidskriftsartikel (refereegranskat)abstract
- Composite structures can lower the weight of an airliner significantly. The increased production cost, however, requires the application of cost-effective design strategies in which cost, weight and the desired laminate quality are taken into account. This paper proposes an optimization framework for composite aircraft structures that minimizes the direct operating cost on a part level. In addition to previous models, a non-destructive testing model is implemented that calculates design allowables of a laminate based on ultrasonic scan parameters. In a case study, the effect of the laminate quality on the direct operating cost is discussed. It is investigated how the permissible flaw size and therefore the scan pitch of a composite laminate can influence the optimal solution in terms of cost and weight; thus, the manufacturing cost, the non-destructive testing cost and the weight of a component can be balanced by optimizing the laminate quality in an early design phase.
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| 6. |
- Kaufmann, Markus, 1980-
(författare)
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Cost/Weight Optimization of Aircraft Structures
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Composite structures can lower the weight of an airliner significantly. The increased production cost, however, requires the application of cost-effective design strategies. Hence, a comparative value is required which is used for the evaluation of a design solution in terms of cost and weight. The direct operating cost (DOC) can be used as this comparative value; it captures all costs that arise when the aircraft is flown. In this work, a cost/weight optimization framework for composite structures is proposed. It takes into account manufacturing cost, non-destructive testing cost and the lifetime fuel consumption based on the weight of the aircraft, thus using a simplified version of the DOC as the objective function. First, the different phases in the design of an aircraft are explained. It is then focused on the advantages and drawbacks of composite structures, the design constraints and allowables, and non-destructive inspection. Further, the topics of multiobjective optimization and the combined optimization of cost and weight are addressed. Manufacturing cost can be estimated by means of different techniques; here, feature-based cost estimations and parametric cost estimations proved to be most suitable for the proposed framework. Finally, a short summary of the appended papers is given. The first paper contains a parametric study in which a skin/stringer panel is optimized for a series of cost/weight ratios (weight penalties) and material configurations. The weight penalty, defined as the specific lifetime fuel burn, is dependent on the fuel consumption of the aircraft, the fuel price and the viewpoint of the optimizer. It is concluded that the ideal choice of the design solution is neither low-cost nor low-weight but rather a combination thereof. The second paper proposes the inclusion of non-destructive testing cost in the design process of the component, and the adjustment of the design strength of each laminate according to the inspection parameters. Hence, the scan pitch of the ultrasonic testing is regarded as a variable, representing an index for the (guaranteed) laminate quality. It is shown that the direct operating cost can be lowered when the quality level of the laminate is assigned and adjusted in an early design stage.
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| 7. |
- Kaufmann, Markus, 1980-, et al.
(författare)
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Cost/weight optimization of composite prepreg structures for best draping strategy
- 2010
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Ingår i: Composites. Part A, Applied science and manufacturing. - : Elsevier. - 1359-835X .- 1878-5840. ; 41:4, s. 464-472
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Tidskriftsartikel (refereegranskat)abstract
- The application of hand-laid carbon fiber prepreg is very expensive from a labor perspective. Therefore the manufacturing cost should be included in the design process. In this work, we propose a novel optimization framework which contains a draping simulation in combination with a detailed cost estimation package and the calculation of the structural performance based on FE. We suggest applying the methodology in two steps. First, a draping knowledge database is generated in which combinations of seed points and reference angles are evaluated in terms of fiber angle deviation, scrap, ultrasonic cuts and material shear. Second, a cost/weight optimization framework picks the best sets of plies during the subsequent optimization. The methodology is tested by means of a curved C-spar which is designed using plain weave and unidirectional prepreg. Different objectives in the generation of the draping database lead to different design solutions.
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| 8. |
- Kaufmann, Markus, 1980-, et al.
(författare)
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Integrated cost/weight optimization of aircraft structures
- 2010
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Ingår i: Structural and multidisciplinary optimization (Print). - Berlin Heidelberg : Springer. - 1615-147X .- 1615-1488. ; 41:2, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- A methodology for a combined cost/weight optimization of aircraft components is proposed. The objective function is formed by a simplified form of direct operating cost, i.e. by a weighted sum of the manufacturing costs and the component weight. Hence, the structural engineer can perform the evaluation of a design solution based on economical values rather than pure cost or weight targets.The parameter that governs the balance between manufacturing cost and weight is called weight penalty and incorporates the effect of fuel burn, environmental impact or contractual penalties due to overweight. Unlike previous work, the analytical cost model and structural models are replaced by commercially available software packages that allow a more realistic model of the manufacturing costs; further, arbitrary constraints for the structural analysis can be implemented. By means of parametric studies it is shown that the design solution strongly depends on the magnitude of the weight penalty.
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| 9. |
- Kaufmann, Markus, et al.
(författare)
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Integrated cost/weight optimization of composite skin/stringer elements
- 2007
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Ingår i: Proceedings of the 16th International Conference on Composite Materials. - : Springer. - 9784931136052 ; , s. 325-334
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Konferensbidrag (refereegranskat)abstract
- In this paper, a methodology for a combined cost/weight optimization of composite elements is proposed. The methodology is similar to the work of Curran et al. [1], where the objective function is formed by manufacturing costs and a so-called weight penalty. This weight penalty could include the effect of fuel burn, environmental impact or con-tractual penalties due to overweight, and depends on the view of the "optimizer". In our approach, the analytical cost model is replaced by a commercial software package that allows a more realistic model of the manufacturing costs. In the spotlight is a parameter study, in which the weight penalty is varied from zero to infinity, literally varying from pure cost to pure weight opti-mization. This is done for three material configura-tions: a metal/metal, a composite/metal and a com-posite/composite skin/stringer panel. It is shown that the design solution depends on the magnitude of the weight penalty and that - depending on this magni-tude - another material configuration has to be re-garded as the optimum.
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| 10. |
- Kaufmann, Markus, 1980-, et al.
(författare)
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Manufacturing process adaptation for integrated cost/weight optimisation of aircraft structures
- 2009
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Ingår i: Plastics, rubber and composites. - : Maney Publishing. - 1465-8011 .- 1743-2898. ; 38:2, s. 162-166(5)
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Tidskriftsartikel (refereegranskat)abstract
- A methodology is developed that enables cost-efficient design of composite aircraft structures. In earlier work, a cost/weight optimisation framework was presented. This framework is here enhanced by a module that minimises the manufacturing cost in each iteration by adaptation of manufacturing parameters. The proposed framework is modular and applicable to a variety of parts and geometries. Commercially available software is used in all steps of theoptimisation. The framework extension is added to an existing cost/weight optimisation implementation and tested on an airliner centre wing box rear spar. Three optimisation runs are performed, and a low cost, an intermediate and a low weight design solution are found. The difference between the two extreme solutions is 4.4% in manufacturing cost and 9.7% in weight. Based on these optimisation trials, the effect of the introduced parameter adaptation module is analysed.
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