| 1. |
- Govaere, O., et al.
(författare)
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Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
- 2022
-
Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:5, s. 1001-1012
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1-/- and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNF-ɑ. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. © 2021 The Authors
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| 2. |
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| 3. |
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| 4. |
- Wein, Marc N., et al.
(författare)
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SIKs control osteocyte responses to parathyroid hormone
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.
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| 5. |
- Göransson, J., et al.
(författare)
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Performance of a System for Rapid Phenotypic Antimicrobial Susceptibility Testing of Gram-Negative Bacteria Directly from Positive Blood Culture Bottles
- 2023
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Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- The rapid administration of optimal antimicrobial treatment is paramount for the treatment of bloodstream infections (BSIs), and rapid antimicrobial susceptibility testing (AST) results are essential. Q-linea has developed the ASTar system, a rapid phenotypic AST device. Here, we report the performance of the ASTar BC G- (Gram-negative) kit when assessed according to the ISO 20776-2:2007 standard for performance evaluation of in vitro diagnostic AST devices. The evaluated ASTar BC G- kit uses a broad panel of 23 antimicrobials for the treatment of BSIs caused by Gram-negative fastidious and nonfastidious bacteria across a range of 6 to 14 2-fold dilutions, including cefoxitin as a screening agent for AmpC-producing Enterobacterales. The ASTar system processes blood culture samples to generate data on MICs and susceptible, intermediate, or resistant (SIR) category. The automated protocol includes concentration determination and concentration adjustment to enable a controlled inoculum, followed by broth microdilution (BMD) and microscopy performed continuously to generate MIC values within approximately 6 h once the test is run on the ASTar system. The performance of the ASTar system was assessed against the ISO 20776-2:2007 standard BMD reference method. Testing was performed across three sites, with results from 412 contrived blood cultures and 74 fresh clinical blood cultures. The ASTar system was also tested for reproducibility, with triplicate testing of 11 strains. The accuracy study comprised 8,650 data points of bacterium-antimicrobial tests. The ASTar system demonstrated an overall essential agreement (EA) of 95.8% (8,283/8,650) and a categorical agreement (CA) of 97.6% (8,433/8,639) compared to the reference BMD method. The overall rate of major discrepancies (MDs) was 0.9% (62/6,845), and that of very major discrepancies (VMDs) was 2.4% (30/1,239). This study shows that the ASTar system delivers reproducible results with overall EA and CA of >95%.
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| 6. |
- Koehbach, Johannes, et al.
(författare)
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Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:52, s. 21183-21188
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families. Their unique structural topology, high stability, and tolerance to sequence variation make them promising templates for the development of peptide-based pharmaceuticals. However, the mechanisms underlying their biological activities remain largely unknown; specifically, a receptor for a native cyclotide has not been reported hitherto. Using bioactivity-guided fractionation of an herbal peptide extract known to indigenous healers as "kalata-kalata," the cyclotide kalata B7 was found to induce strong contractility on human uterine smooth muscle cells. Radioligand displacement and second messenger-based reporter assays confirmed the oxytocin and vasopressin V-1a receptors, members of the G protein-coupled receptor family, as molecular targets for this cyclotide. Furthermore, we show that cyclotides can serve as templates for the design of selective G protein-coupled receptor ligands by generating an oxytocin-like peptide with nanomolar affinity. This nonapeptide elicited dose-dependent contractions on human myometrium. These observations provide a proof of concept for the development of cyclotide-based peptide ligands.
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| 7. |
- Aboye, Teshome Leta, et al.
(författare)
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Interlocking disulfides in circular proteins : toward efficient oxidative folding of cyclotides.
- 2011
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 14:1, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are ultrastable plant proteins characterized by the presence of a cyclic amide backbone and three disulfide bonds that form a cystine knot. Because of their extreme stability, there has been significant interest in developing these molecules as a drug design scaffold. For this potential to be realized, efficient methods for the synthesis and oxidative folding of cyclotides need to be developed, yet we currently have only a basic understanding of the folding mechanism and the factors influencing this process. In this study, we determine the major factors influencing oxidative folding of the different subfamilies of cyclotides. The folding of all the cyclotides examined was heavily influenced by the concentration of redox reagents, with the folding rate and final yield of the native isomer greatly enhanced by high concentrations of oxidized glutathione. Addition of hydrophobic solvents to the buffer also enhanced the folding rates and appeared to alter the folding pathway. Significant deamidation and isoaspartate formation were seen when oxidation conditions were conducive to slow folding. The identification of factors that influence the folding and degradation pathways of cyclotides will facilitate the development of folding screens and optimized conditions for producing cyclotides and grafted analogs as stable peptide-based therapeutics.
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| 8. |
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| 9. |
- Abrahamsson, L., et al.
(författare)
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Behöver arbetslinjen inte forskning?
- 2007
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Ingår i: Svenska Dagbladet Brännpunkt (debattinlägg). ; :2007-11-28
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Bouchouireb, Hamza, 1991-
(författare)
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Advancing the life cycle energy optimisation methodology
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle, while complying with a set of functional constraints. This effectively balances trade-offs, and therewith avoids sub-optimal shifting between the energy demand for the cradle-to-production of materials, operation of the vehicle, and end-of-life phases. This work further develops the LCEO methodology and expands its scope through three main methodological contributions which, for illustrative purposes, were applied to a vehicle sub-system design case study.An End-Of-Life (EOL) model, based on the substitution with a correction factor method, is included to estimate the energy credits and burdens that originate from EOL vehicle processing. Multiple recycling scenarios with different levels of assumed induced recyclate material property degradation were built, and their impact on the LCEO methodology's outcomes was compared to that of scenarios based on landfilling and incineration with energy recovery. The results show that the inclusion of EOL modelling in the LCEO methodology can alter material use patterns and significantly effect the life cycle energy of the optimal designs.Furthermore, the previous model is expanded to enable holistic vehicle product system design with the LCEO methodology. The constrained optimisation of a vehicle sub-system, and the design of a subset of the processes which are applied to it during its life cycle, are simultaneously optimised for a minimal product system life cycle energy. In particular, a subset of the EOL processes' parameters are considered as continuous design variables with associated barrier functions that control their feasibility. The results show that the LCEO methodology can be used to find an optimal design along with its associated ideal synthetic EOL scenario. Moreover, the ability of the method to identify the underlying mechanisms enabling the optimal solution's trade-offs is further demonstrated.Finally, the functional scope of the methodology is expanded through the inclusion of shape-related variables and aerodynamic drag estimations. Here, vehicle curvature is taken into account in the LCEO methodology through its impact on the aerodynamic drag and therewith its related operational energy demand. In turn, aerodynamic drag is considered through the estimation of the drag coefficient of a vehicle body shape using computational fluid dynamics simulations. The aforementioned coefficient is further used to estimate the energy required by the vehicle to overcome aerodynamic drag. The results demonstrate the ability of the LCEO methodology to capitalise on the underlying functional alignment of the structural and aerodynamic requirements, as well as the need for an allocation strategy for the aerodynamic drag energy within the context of vehicle sub-system redesign.Overall, these methodological developments contributed to the exploration of the ability of the LCEO methodology to handle life cycle and functional trade-offs to achieve life cycle energy optimal vehicle designs.
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| 11. |
- Bouchouireb, Hamza, 1991-
(författare)
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Life Cycle Energy Optimisation: A multidisciplinary engineering design optimisation framework for sustainable vehicle development
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis explores how the systemic-level environmental footprint of light-duty vehicles could be reduced through integrative design using the Life Cycle Energy Optimisation (LCEO) methodology. This methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle; while complying with a set of functional constraints, thereby avoiding any sub-optimal energy demand shifts between the vehicle's different life cycle phases. This thesis further develops the LCEO methodology and expands its scope through four main methodological contributions. This work also contributes in establishing the methodology as a standalone design approach and provides guidelines for its most effective use.Initially, an End-of-Life (EOL) model, based on the substitution with a correction factor method, is included to estimate the energy credits and burdens that originate from EOL vehicle processing. Multiple recycling scenarios with varying levels of induced recyclate material property degradation were built, and their associated resulting optimal vehicle subsystem designs were compared to those associated with landfilling and incineration with energy recovery scenarios. The results show how the structural material use patterns, as well as the very mechanisms enabling the embodiment of the Life Cycle Energy (LCE) optimal designs, are impacted by taking into consideration the effect of a vehicle's EOL phase. In particular, the material intensity-space allocation trade-off was identified as a key factor in the realisation of the LCE optimal designs.This coupling existing between optimal use of material and space allocation was further explored by functionally expanding the LCEO methodology's scope to handle aerodynamic functional requirements. This involved the definition of a novel allocation strategy for the energy necessary to overcome aerodynamic drag, as well as the development of a parametrised vehicle body model that ensures that the LCE knock-on effects of aerodynamically motivated design decisions are fully accounted for at the targeted subsystem level.The expanded methodology was subsequently applied to perform the aero-structural life cycle-driven design optimisation of a vehicle subsystem, with the impact of the constitutive material's circularity potential being included through the previously developed EOL model and scenarios. The results demonstrate the significant extent of the coupling existing between a vehicle's fundamental aerodynamic shape, and a vehicle's structural material composition, including its EOL characteristics, within the LCEO context.Beyond the vehicle level implications, the LCEO methodology's position within the broader vehicle-design methodology context was further characterised by comparing its outcomes to those of the purely lightweight and purely aerodynamic approaches. It was found that the LCE optimal designs were distinctly clustered from their mono-disciplinary counterparts. They offered up to 20% energy savings over the lightweight alternatives by being, on average, larger, heavier and more aerodynamics designs; while also being shorter and lighter than the optimal aerodynamic configurations.Subsequently, a mixed integer nonlinear programming formulation of this expanded LCEO methodology was developed to include the effects of battery energy storage systems on the LCE optimal vehicle designs. In particular, the vehicle's battery size and number of such batteries needed over its life cycle were introduced as variables subject to a range and a cycle life constraint. The former is derived from the battery-capacity-to-structural-mass ratio of recent production vehicles, while the second ensures that the batteries' cycle lives are sufficient for the entirety of the vehicle's use phase. Additionally, three battery chemistries with varying characteristics were included: lithium nickel manganese cobalt oxide (NMC), lithium iron phosphate (LFP) and lithium cobalt oxide (LCO); along with an EOL recycling scenario. The results of the coupled aero-structural-battery energy storage LCE-driven design optimisations demonstrate that battery chemistry and recycling potential have a significant impact on the system's design in terms of overall LCE footprint, battery size and number, as well as aerodynamic shape. More specifically, a change in battery composition was found to lead to up to 12.5% variation in drag coefficient, while battery recycling can on average reduce a vehicle's associated LCE by 32%.Finally, elements of robust design and uncertainty quantification were included into the LCEO methodology, in order to evaluate the impact of uncertainty on the resulting LCE optimal designs. Specifically, uncertainty was introduced through the assumption that the material properties of a subset of the optimisation's candidate materials are described by statistical distributions, as opposed to a priori fixed values, thereby changing the nature of the optimisation problem from deterministic to stochastic. This change is handled through a multilevel representation hierarchy for the targeted subsystem's model, and using the Multilevel Monte Carlo (MLMC) approach in the optimisation process to evaluate the expected compliance of a given design with the transport-related functional requirements. the results demonstrate how the robust design configurations both constitute a significant departure from their deterministic counterparts and depend on the EOL scenario considered, while only incurring a marginal LCE premium. Moreover, this work also further illustrated the performance increase associated with the use of the MLMC estimator in lieu of the classical Monte Carlo one within an optimisation under uncertainty framework.Overall, the work presented in this doctoral thesis has contributed to the development of the state-of-the-art of the LCEO methodology to enable the early-stage conceptual design of more sustainable vehicle configurations, and demonstrated how the methodology is at its most effective when leveraging its cross-scalar and cross-disciplinary nature to enable integrative functional vehicle design.
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| 12. |
- Bouchouireb, Hamza, 1991-, et al.
(författare)
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The inclusion of End-Of-Life modelling in the Life Cycle Energy Optimisation methodology
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this work, an End-Of-Life (EOL) model is included in the Life Cycle Energy Optimisation (LCEO) methodology to account for the energy burdens and credits stemming from a vehicle’s EOL processing phase and balance them against the vehicle’s functional requirements and production and use phase energies. The substitution with a correction factor allocation method is used to model the contribution of recycling to the EOL phase’s energy. The methodology is illustrated through the optimisation of the design of a simplified vehicle sub-system. For the latter, multiple recycling scenarios with varying levels of assumed recycling induced material property degradation were built, and their impact on the vehicle sub-system’s optimal solutions was compared to that of scenarios based on landfilling and incineration with energy recovery. The results show that the inclusion of EOL modelling in the LCEO methodology can significantly alter material use patterns thereby effecting the life cycle energy of the optimal designs. Indeed, the vehicle sub-system’s optimal designs associated with the recycling scenarios are on average substantially heavier, and less life cycle energy demanding, than their landfilling or incineration with energy recovery-related counterparts.
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| 13. |
- Bouchouireb, Hamza, et al.
(författare)
-
The inclusion of end-of-life modelling in the life cycle energy optimisation methodology
- 2021
-
Ingår i: Journal of Mechanical Design. - : ASME International. - 1050-0472 .- 1528-9001. ; 143:5
-
Tidskriftsartikel (refereegranskat)abstract
- In this work, an End-Of-Life (EOL) model is included in the Life Cycle Energy Optimisation (LCEO) methodology to account for the energy burdens and credits stemming from a vehicle's EOL processing phase and balance them against the vehicle's functional requirements and production and use phase energies. The substitution with a correction factor allocation method is used to model the contribution of recycling to the EOL phase's energy. The methodology is illustrated through the optimisation of the design of a simplified vehicle sub-system. For the latter, multiple recycling scenarios with varying levels of assumed recycling induced material property degradation were built, and their impact on the vehicle sub-system's optimal solutions was compared to that of scenarios based on landfilling and incineration with energy recovery. The results show that the vehicle sub-system's optimal designs are significantly dependent on the EOL scenario considered. In particular, the optimal designs associated with the recycling scenarios are on average substantially heavier, and less life cycle energy demanding, than their landfilling or incineration with energy recovery-related counterparts; thus, demonstrating how the inclusion of EOL modelling in the LCEO methodology can significantly alter material use patterns, thereby effecting the very mechanisms enabling the embodiment of the resulting life cycle energy optimal designs.
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| 14. |
- Bouchouireb, Hamza, et al.
(författare)
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The inclusion of vehicle shape and aerodynamic drag estimations within the life cycle energy optimisation methodology
- 2019
-
Ingår i: Procedia CIRP. - : Elsevier. - 2212-8271 .- 2212-8271. ; 84, s. 902-907
-
Tidskriftsartikel (refereegranskat)abstract
- The present work describes a widening of the scope of the Life Cycle Energy Optimisation (LCEO) methodology with the addition of shape-related design variables. They describe the curvature of a vehicle which impacts its aerodynamic drag and therewith its operational energy demand. Aerodynamic drag is taken into account through the estimation of the drag coefficient of the vehicle body shape using computational fluid dynamics simulations. Subsequently, the aforementioned coefficient is used to calculate the operational energy demand associated with the vehicle. The methodology is applied to the design of the roof of a simplified 2D vehicle model which is both mechanically and geometrically constrained. The roof is modelled as a sandwich structure with its design variables consisting of the material compositions of the different layers, their thicknesses as well as the shape variables. The efficacy of the LCEO methodology is displayed through its ability to deal with the arising functional conflicts while simultaneously leveraging the design benefits of the underlying functional alignments. On average, the optimisation process resulted in 2.5 times lighter and 4.5 times less life cycle energy-intensive free shape designs. This redesign process has also underlined the necessity of defining an allocation strategy for the energy necessary to overcome drag within the context of vehicle sub-system redesign.
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| 15. |
- Bouchouireb, Hamza, 1991-, et al.
(författare)
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Towards holistic energy-efficient vehicle product system design: The case for a penalized continuous end-of-life model in the life cycle energy optimisation methodology
- 2019
-
Ingår i: Proceedings of the International Conference on Engineering Design. - : Cambridge University Press. - 2220-4334 .- 2220-4342. ; 1, s. 2901-2910
-
Tidskriftsartikel (refereegranskat)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle, while complying with a set of functional constraints. This effectively balances trade-offs, and therewith avoids sub-optimal shifting between the energy demand for the cradle-to-production of materials, operation of the vehicle, and end-of-life phases. The present work describes the extension of the LCEO methodology to perform holistic product system optimisation. The constrained design of an automotive component and the design of a subset of the processes which are applied to it during its life cycle are simultaneously optimised to achieve a minimal product system life cycle energy. A subset of the processes of the end-of-life phase of a vehicle’s roof are modelled through a continuous formulation. The roof is modelled as a sandwich structure with its design variables being the material compositions and the thicknesses of the different layers. The results show the applicability of the LCEO methodology to product system design and the use of penalisation to ensure solution feasibility.
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| 16. |
- Bouchouireb, Hamza, 1991-, et al.
(författare)
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Vehicle aerodynamic shape significantly impacted by vehicle material composition and material circularity potential in life cycle energy optimal vehicle design
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This paper explores how the systemic-level energy consumption of light-duty vehicles could be reduced through integrative design. To this end, the Life Cycle Energy Optimisation (LCEO) methodology is used to achieve the coupled optimal use of materials (including their circularity potential) and vehicle aerodynamic shape to reduce the overall Life Cycle Energy (LCE) footprint of light-duty vehicles, with the results being compared to the lightweight and aerodynamic alternatives. Initially, the methodology is functionally expanded to handle aerodynamic functional requirements through the definition of a novel allocation strategy for the aerodynamic energy, and a parametrised simple vehicle body model that ensures that the LCE knock-on effects of aerodynamically-motivated design decisions are fully accounted for. Subsequently, the methodology is used to perform the first, to the knowledge of the authors, aero-structural LCE-driven design optimisation of a vehicle subsystem, with the impact of the materials’ circularity potential being taken into account through various end-of-life (EOL) processing scenarios, including recycling. The results show that the environmental footprint of light-duty vehicles could significantly be reduced through integrative early-stage design. Specifically, it shows that a life cycle energy optimal vehicle's aerodynamic shape is significantly impacted by the vehicle's material composition and the latter's EOL characteristics — particularly recycling potential. Furthermore, LCE optimal vehicles have been found to be on average longer, heavier and more aerodynamic than their lightweight counterparts, as well as offering up to 20% energy savings per vehicle; while also being shorter and lighter than optimal aerodynamic configurations.
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| 17. |
- Burman, Robert, 1979-, et al.
(författare)
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Evaluation of toxicity and anti-tumour activity of cycloviolacin O2 in mice.
- 2010
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Ingår i: Biopolymers. - : Wiley. - 0006-3525 .- 1097-0282. ; 94:5, s. 626-634
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Tidskriftsartikel (refereegranskat)abstract
- Cycloviolacin O2 is a small cyclic cysteine-rich protein belonging to the group of plant proteins called cyclotides. This cyclotide has been previously shown to exert cytotoxic activity against a variety of human tumor cell lines as well as primary cultures of human tumor cells in vitro. This study is the first evaluation of its tolerability and antitumor activity in vivo. Maximal-tolerated doses were estimated to 1.5 mg/kg for single intravenous (i.v.) dosing and 0.5 mg/kg for daily repeated dosing, respectively. Two different in vivo methods were used: the hollow fiber method with single dosing (i.v. 1.0 mg/kg) and traditional xenografts with repeated dosing over 2 weeks (i.v. 0.5 mg/kg daily, 5 days a week). The human tumor cell lines used displayed dose-dependent in vitro sensitivity (including growth in hollow fibers to confirm passage of cycloviolacin O2 through the polyvinylidene fluoride fibers), with IC50 values in the micromolar range. Despite this sensitivity in vitro, no significant antitumor effects were detected in vivo, neither with single dosing in the hollow fiber method nor with repeated dosing in xenografts. In summary, the results indicate that antitumor effects are minor or absent at tolerable (sublethal) doses, and cycloviolacin O2 has a very abrupt in vivo toxicity profile, with lethality after single injection at 2 mg/kg, but no signs of discomfort to the animals at 1.5 mg/kg. Repeated dosing of 1 mg/kg gave a local-inflammatory reaction at the site of injection after 2–3 days; lower doses were without complications.
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| 18. |
- Craik, David J., et al.
(författare)
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Nomenclature of homodetic cyclic peptides produced from ribosomal precursors : An IUPAC task group interim report
- 2016
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Ingår i: Biopolymers. - : Wiley. - 0006-3525 .- 1097-0282. ; 106:6, s. 917-924
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Tidskriftsartikel (refereegranskat)abstract
- In 2015, an International Union of Pure and Applied Chemistry (IUPAC) Task Group was formed to develop nomenclature recommendations for homodetic cyclic peptides produced from ribosomal precursors. Delegates of the 2015 International Conference on Circular Proteins (ICCP) were presented with the strengths and weaknesses of four published approaches to homodetic cyclic peptide nomenclature, and a summary of the ensuing discussion is presented here. This interim report presents a potentially novel suggestion-the use of Cahn-Ingold-Prelog rules to specify amino acid priority in homodetic peptides for consistent numbering. Indeed, this might be the first extension of the Cahn-Ingold-Prelog rules in five decades. The authors invite interested parties to contact the corresponding author with suggestions for the improvement of the proposed nomenclature; these ideas will be discussed and considered for inclusion in the final report.
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| 19. |
- Dalelkhan, B., et al.
(författare)
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Ambipolar transport in narrow bandgap semiconductor InSb nanowires
- 2020
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 12:15, s. 8159-8165
-
Tidskriftsartikel (refereegranskat)abstract
- We report on a transport measurement study of top-gated field effect transistors made out of InSb nanowires grown by chemical vapor deposition. The transistors exhibit ambipolar transport characteristics revealed by three distinguished gate-voltage regions: In the middle region where the Fermi level resides within the bandgap, the electrical resistance shows an exponential dependence on temperature and gate voltage. With either more positive or negative gate voltages, the devices enter the electron and hole transport regimes, revealed by the resistance decreasing linearly with decreasing temperature. From the transport measurement data of a 1 μm-long device made from a nanowire of 50 nm in diameter, we extracted a bandgap energy of 190-220 meV. The off-state current of this device is found to be suppressed within the measurement noise at a temperature of T = 4 K. A shorter, 260 nm-long device is found to exhibit a finite off-state current and a circumference-normalized on-state hole current of 11 μA μm-1 at VD = 50 mV which is the highest for such a device to our knowledge. The ambipolar transport characteristics make the InSb nanowires attractive for CMOS electronics, hybrid electron-hole quantum systems and hole based spin qubits.
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| 20. |
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| 21. |
- Jank, Merle-Hendrikje, et al.
(författare)
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Advancing energy efficient early-stage vehicle design through inclusion of end-of-life phase in the life cycle energy optimisation methodology
- 2017
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Ingår i: 12th International Conference on Ecological Vehicles and Renewable Energies Conference, EVER.
-
Konferensbidrag (refereegranskat)abstract
- Environmentally-friendly energy-efficient vehicles are an important contributor to meet future global transportation needs. To minimise the environmental impact of a vehicle throughout its entire life cycle, the life cycle energy optimisation (LCEO) methodology has been proposed. Using the proxy of life cycle energy, this methodology balances the energy consumption of vehicle production, operation and end-of-life scenarios. The overall aim is to design a vehicle where life cycle energy is at a minimum. While previous work only included vehicle production and operation, this paper aims at advancing the LCEO methodology by including an end-of-life phase. A simplified design study was conducted to illustrate how vehicle design changes when end-of-life treatment is included. Landfilling, incineration and recycling have been compared as end-of-life treatments, although the focus was put on recycling. The results reveal that the optimal design not only changes with the inclusion of an end-of-life phase but it changes with specific end-of-life treatment.
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| 22. |
- Leta Aboye, Teshome, et al.
(författare)
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Ultra-stable peptide scaffolds for protein engineering-synthesis and folding of the circular cystine knotted cyclotide cycloviolacin O2
- 2008
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 9:1, s. 103-113
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Tidskriftsartikel (refereegranskat)abstract
- The cyclic cystine knot motif, as defined by the cyclotide peptide family, is an attractive scaffold for protein engineering. To date, however, the utilisation of this scaffold has been limited by the inability to synthesise members of the most diverse and biologically active subfamily, the bracelet cyclotides. This study describes the synthesis and first direct oxidative folding of a bracelet cyclotide-cycloviolacin O2-and thus provides an efficient method for exploring the most potent cyclic cystine knot peptides. The linear chain of cycloviolacin O2 was assembled by solid-phase Fmoc peptide synthesis and cyclised by thioester-mediated native chemical ligation, and the inherent difficulties of folding bracelet cyclotides were successfully overcome in a single-step reaction. The folding pathway was characterised and was found to include predominating fully oxidised intermediates that slowly converted to the native peptide structure.
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| 23. |
- Nordmark, Gunnel, et al.
(författare)
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Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's syndrome
- 2011
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Ingår i: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 12:2, s. 100-109
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10−5, OR 1.68, the family with sequence similarity 167 member A–B-lymphoid tyrosine kinase (FAM167A–BLK) locus, P=4.7 × 10−4, OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10−4, OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
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| 24. |
- O'Reilly, Ciarán J., et al.
(författare)
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Life cycle energy optimisation : A proposed methodology for integrating environmental considerations early in the vehicle engineering design process
- 2016
-
Ingår i: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 135, s. 750-759
-
Tidskriftsartikel (refereegranskat)abstract
- To enable the consideration of life cycle environmental impacts in the early stages of vehicle design, a methodology using the proxy of life cycle energy is proposed in this paper. The trade-offs in energy between vehicle production, operational performance and end-of-life are formulated as a mathematical problem, and simultaneously balanced with other transport-related functionalities, and may be optimised. The methodology is illustrated through an example design study, which is deliberately kept simple in order to emphasise the conceptual idea. The obtained optimisation results demonstrate that there is a unique driving-scenario-specific design solution, which meets functional requirements with a minimum life cycle energy cost. The results also suggest that a use-phase focussed design may result in a solution, which is sub-optimal from a life cycle point-of-view. © 2016 The Authors
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| 25. |
- O'Reilly, Ciarán J., et al.
(författare)
-
Life-cycle energy optimisation for sustainable vehicle design
- 2014
-
Ingår i: FISITA 2014 World Automotive Congress - Proceedings. - : FISITA.
-
Konferensbidrag (refereegranskat)abstract
- A methodology is presented in this paper, in which the trade-offs in energy between vehicle production, operational performance and end-of-life are formulated as a mathematical problem that may be optimised. This methodology enables the consideration of the life-cycle environmental impact, through the proxy of life-cycle energy, in the very first stages of transport vehicle design where it can be concurrently balanced with other functionalities. The methodology is illustrated through a sandwich panel design case study. The optimisation results for this case demonstrate that a design solution does exist, which meets functional requirements with a minimum life-cycle energy cost. They also highlight that a pure lightweight design may result in a solution, which is sub-optimal from a life cycle point-of-view. © 2014, FISITA. All rights reserved.
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| 26. |
- Plan, Manuel Rey R, et al.
(författare)
-
The cyclotide fingerprint in Oldenlandia affinis : elucidation of chemically modified, linear and novel macrocyclic peptides
- 2007
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 8:9, s. 1001-1011
-
Tidskriftsartikel (refereegranskat)abstract
- The complete suite of cyclotides present in Oldenlandia affinis (Rubiaceae), the plant that was originally found to contain this unique family of circular proteins, has been characterised. This study expands the number of known cyclotides in this plant to 17, of which nine new sequences (kalata B9-B17) were characterised in this work. In addition, five derivatives that contain oxidation products of the conserved tryptophan were identified, and it was shown that the formation of these derivatives is catalysed by exposure to sunlight. Furthermore, we describe two linear cyclotide analogues. These acyclic peptides have three intact disulfide bonds, and their N and C termini coincide with the hypothesised cleavage sites from the precursor protein. This work increases our knowledge about the sequence variation that is accommodated by the cyclic cystine knot scaffold, confirms its applicability as a template for drug design, and also shows the first natural degradation pathways for cyclotides. These pathways have important implications for the persistence and environmental fate of the cyclotides if used as crop-protection agents.
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| 27. |
- Rice, H. J., et al.
(författare)
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Design of a Kelvin cell acoustic metamaterial
- 2020
-
Ingår i: Journal of Sound and Vibration. - : ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. - 0022-460X .- 1095-8568. ; 472
-
Tidskriftsartikel (refereegranskat)abstract
- Advancements in 3D print technology now allow the printing of structured acoustic absorptive materials at appropriate microscopic scales and sample sizes. Optimisation of parameter sets associated with a Kelvin Cell structure have the potential to develop various metabehaviours in the associated acoustic responses. The repeatability of the fundamental cell unit also provide a route for the development of viable macro models to simulate built up structures based on detailed models of the individual cell units. This paper describes a process to model, print and test such a sample. Manufacturing restraints will initially guide the optimised design and introduce response uncertainties associated with surface finishes and critical geometric dimensions. A "micro to macro" model is developed using a full visco thermal acoustic model of a single cell to develop a frequency dependent cell transfer matrix. The transfer matrices for the repeated cells may then be combined until sufficient material depth is achieved and efficiently generate an absorptivity for the material layer. Two prints using different processes (digital light processing (DLP) and selective laser melting (SLM)) of nominally the same kelvin cell structure. For the metal print the model predicts the absorptivity well once an allowance is made for the surface roughness. The DLP has a smoother finish with a lower geometric fidelity; however the DLP sample is still well modelled by the process.
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| 28. |
- Schöggl, Josef-Peter, et al.
(författare)
-
Barriers to sustainable and circular product design : A theoretical and empirical prioritisation in the European automotive industry
- 2024
-
Ingår i: Journal of Cleaner Production. - 0959-6526 .- 1879-1786. ; 434
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the increasing availability of tools and methods for sustainable and circular product design (DfS), their uptake in practice is slow. This is also true in the automotive industry, where DfS is an important measure for addressing the industry's negative environmental and social impacts. To facilitate DfS implementation, this paper uses an analytic hierarchy process (AHP) and offers, for the first time, a classification and prioritisation of the barriers that need to be overcome when implementing DfS into vehicle development processes. Based on a systematic literature review and on an expert workshop, the top 15 DfS barrier factors were derived and divided equally into five groups, following a multi-level structure. These factors and groups formed the input for a survey-based analytic hierarchy process with 38 European industry experts. The results show that strategic issues are the most important barriers, followed by the group of operational, personal, external, and tool-related barriers. Among the 15 barrier factors identified, the top five were (1) an unclear link to profitability, (2) lack of top management support, (3) difficulties in handling trade-offs, (4) high operational costs, and (5) a lack of integration of DfS into corporate strategy. The results indicate that while external constraints already exert pressure on automotive companies, they still face particular challenges when attempting to integrate sustainability into corporate strategies and in transferring such strategies to DfS activities at the operational level. The study results may be used to inform managerial policy and further research.
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| 29. |
- Strandberg, G., et al.
(författare)
-
Bespoke climate indicators for the Swedish energy sector − a stakeholder focused approach
- 2024
-
Ingår i: Climate Services. - Göteborg : IVL Svenska Miljöinstitutet. - 2405-8807. ; 34, s. 100486-100486
-
Tidskriftsartikel (refereegranskat)abstract
- Climate change concerns the energy sector to a high degree because the sector is sensitive both to changing conditions for power and heat production, and to changing demand for electricity, heating and cooling. In this study potential consequences of climate change on different parts of the Swedish energy sector were assessed in a series of workshops, where climate and energy scientists, energy systems experts and analysts met with representativesof the energy sector to assess the vulnerability of the sector and consider what climate indicators could be used to assess impacts of relevance. The impact of climate change depends on the energy type. Hydropower, for which production is naturally linked to weather and climate, is significantly impacted by climate change. For other forms of production, such as nuclear power, other factors such as e.g. policy and technology development are more important. The series of workshops held in this study, where different aspects of climate change and consequences were discussed, proved very successful and has increased our understanding of climate impacts on the energy system.
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| 30. |
- Ahwazi, Danial, et al.
(författare)
-
Investigation of the specificity and mechanism of action of the ULK1/AMPK inhibitor SBI-0206965
- 2021
-
Ingår i: Biochemical Journal. - 0264-6021. ; 478:15, s. 2977-2997
-
Tidskriftsartikel (refereegranskat)abstract
- SBI-0206965, originally identified as an inhibitor of the autophagy initiator kinase ULK1, has recently been reported as a more potent and selective AMP-activated protein kinase (AMPK) inhibitor relative to the widely used, but promiscuous inhibitor Compound C/ Dorsomorphin. Here, we studied the effects of SBI-0206965 on AMPK signalling and metabolic readouts in multiple cell types, including hepatocytes, skeletal muscle cells and adipocytes. We observed SBI-0206965 dose dependently attenuated AMPK activator (991)-stimulated ACC phosphorylation and inhibition of lipogenesis in hepatocytes. SBI-0206965 (≥25 μM) modestly inhibited AMPK signalling in C2C12 myotubes, but also inhibited insulin signalling, insulin-mediated/AMPK-independent glucose uptake, and AICA-riboside uptake. We performed an extended screen of SBI-0206965 against a panel of 140 human protein kinases in vitro, which showed SBI-0206965 inhibits several kinases, including members of AMPK-related kinases (NUAK1, MARK3/4), equally or more potently than AMPK or ULK1. This screen, together with molecular modelling, revealed that most SBI-0206965-sensitive kinases contain a large gatekeeper residue with a preference for methionine at this position. We observed that mutation of the gatekeeper methionine to a smaller side chain amino acid (threonine) rendered AMPK and ULK1 resistant to SBI-0206965 inhibition. These results demonstrate that although SBI-0206965 has utility for delineating AMPK or ULK1 signalling and cellular functions, the compound potently inhibits several other kinases and critical cellular functions such as glucose and nucleoside uptake. Our study demonstrates a role for the gatekeeper residue as a determinant of the inhibitor sensitivity and inhibitor-resistant mutant forms could be exploited as potential controls to probe specific cellular effects of SBI-0206965.
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| 31. |
- Alkmim, M. H., et al.
(författare)
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Model-based acoustic characterisation of muffler components and extrapolation to inhomogeneous thermal conditions
- 2018
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Ingår i: Proceedings of ISMA 2018 - International Conference on Noise and Vibration Engineering and USD 2018 - International Conference on Uncertainty in Structural Dynamics. - : KU Leuven - Departement Werktuigkunde. - 9789073802995 ; , s. 3009-3020
-
Konferensbidrag (refereegranskat)abstract
- A methodology for evaluating the acoustic behaviour of two-port inhomogeneous media in experimentally unavailable thermal conditions is proposed. The method consists of an inverse estimation of the geometrical and material properties of the object at room temperature followed by a forced thermal input. The properties of interest for the inverse estimation are the spatially-varying cross-section and/or bulk properties. The underlying model relies on a transfer matrix approach, allowing for a representation of spatially inhomogeneous objects as piece-wise equivalent homogeneous fluids, while ensuring continuity conditions between successive elements. A model of non-stationary thermal conduction is used as a first approximation, where an integral formulation accounts for the cumulative effect of multiple homogeneous elements. In order to evaluate the validity of the extrapolation, a validation against a fully numerical simulation is presented in two cases, namely a simple expansion chamber and a complex muffler.
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Berg, Lena M, et al.
(författare)
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Factors influencing clinicians' perceptions of interruptions as disturbing or non-disturbing : a qualitative study
- 2016
-
Ingår i: International Emergency Nursing. - : Elsevier. - 1755-599X .- 1878-013X. ; 27, s. 11-16
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Emergency departments consist of multiple systems requiring interaction with one another while still being able to operate independently, creating frequent interruptions in the clinical workflow. Most research on interruptions in health care settings has focused on the relationship between interruptions and negative outcomes. However, there are indications that not all interruptions are negatively perceived by those being interrupted. Therefore, this study aimed to explore factors that influence when a clinician perceives interruptions as non-disturbing or disturbing in an emergency department context.METHOD: Explorative design based on interviews with 10 physicians and 10 registered nurses at two Swedish emergency departments. Data were analyzed using qualitative content analysis.RESULT: Factors influencing whether emergency department clinicians perceived interruptions as non-disturbing or disturbing were identified: clinician's constitution, external factors of influence and the nature of the interrupted task. The clinicians' perceptions were related to a complex of attributes inherent in these three factors at the time of the interruption. Thus, the same type of interruption could be perceived as either non-disturbing or disturbing contingent on the surrounding circumstances in which the event occurred.CONCLUSION: Emergency department clinicians' perceptions of interruptions as non-disturbing or disturbing were related to the character of identified influencing factors.
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| 36. |
- Berg, Lena M, et al.
(författare)
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Interruptions in emergency department work : an observational and interview study
- 2013
-
Ingår i: BMJ Quality and Safety. - : BMJ. - 2044-5415 .- 2044-5423. ; 22:8, s. 656-663
-
Tidskriftsartikel (refereegranskat)abstract
- Objectiv.e Frequent interruptions are assumed to have a negative effect on healthcare clinicians’ working memory that could result in risk for errors and hence threatening patient safety. The aim of this study was to explore interruptions occurring during common activities of clinicians working in emergency departments.Method. Totally 18 clinicians, licensed practical nurses, registered nurses and medical doctors, at two Swedish emergency departments were observed during clinical work for 2 h each. A semistructured interview was conducted directly after the observation to explore their perceptions of interruptions. Data were analysed using non-parametric statistics, and by quantitative and qualitative content analysis.Results. The interruption rate was 5.1 interruptions per hour. Most often the clinicians were exposed to interruptions during activities involving information exchange. Calculated as percentages of categorised performed activities, preparation of medication was the most interrupted activity (28.6%). Face-to-face interaction with a colleague was the most common way to be interrupted (51%). Most common places for interruptions to occur were the nurses’ and doctors’ stations (68%). Medical doctors were the profession interrupted most often and were more often recipients of interruptions induced by others than causing self-interruptions. Most (87%) of the interrupted activities were resumed. Clinicians often did not regard interruptions negatively. Negative perceptions were more likely when the interruptions were considered unnecessary or when they disturbed the work processes.Conclusions. Clinicians were exposed to interruptions most often during information exchange. Relative to its occurrence, preparation of medication was the most common activity to be interrupted, which might increase risk for errors. Interruptions seemed to be perceived as something negative when related to disturbed work processes.
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| 37. |
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| 38. |
- Bouchouireb, Hamza, et al.
(författare)
-
A preliminary investigation of robust design and uncertainty quantification within the life cycle energy optimisation methodology
- 2021
-
Ingår i: Resource Efficient Vehicles Conference, rev2021.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology aims at finding a design solution that uses a minimum amount of cumulative energy demand over the different phases of the vehicle's life cycle, while complying with a set of functional constraints. This effectively balances trade-offs, and therewith avoids sub-optimal shifting between the energy demand for the cradle- to-production of materials, operation of the vehicle, and end-of-life phases. The present work describes the inclusion of robust design aspects and uncertainty quantification into the LCEO framework. In particular, uncertainty is introduced through the assumption that the material and energy properties of a subset of the optimisation’s candidate materials are described by statistical distributions as opposed to a priori fixed values. Subsequently, the nature of the LCEO-associated optimisation problem is changed from deterministic to stochastic. This change is handled by defining a multilevel representation hierarchy, and using the Multilevel Monte Carlo (MLMC) approach in the optimisation process to evaluate the expected compliance of a given design with the transport-related functional requirements. The extended framework is applied to the robust design optimisation of a subsystem of a vehicle model which is both mechanically and geometrically constrained. The ability of the LCEO methodology to include robust design aspects early during the vehicle design process, while simultaneously handling functional conflicts, to result in a robust life cycle energy optimal design is demonstrated. Furthermore, the performance increase obtained by the use of the MLMC approach instead of the classical Monte Carlo approach within an optimisation under uncertainty framework is illustrated.
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| 39. |
- Bouchouireb, Hamza, 1991-, et al.
(författare)
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Exploring the aero-structural-battery energy storage coupling within the early-stage development of life cycle energy optimal electric vehicles
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The Life Cycle Energy Optimisation (LCEO) methodology is used to explore the coupling existing between an electric vehicle's aerodynamic shape, structural material composition and design, and the properties of its onboard battery's chemistry in order to enable the development of more sustainable vehicle configurations. To this end, a mixed integer nonlinear programming formulation of the LCEO methodology was developed to include the effects of battery energy storage systems on the Life Cycle Energy (LCE) optimal vehicle designs. In particular, the vehicle's battery size and number of such batteries needed over its life cycle were introduced as variables subject to a range and a battery cycle life constraint. The former is derived from the battery-capacity-to-structural-mass ratio of recent production vehicles, while the latter ensures that the batteries' cycle lives are sufficient for the entirety of the vehicle's use phase. Additionally, three lithium-based battery chemistries with varying properties were included: lithium nickel manganese cobalt oxide (NMC), lithium iron phosphate (LFP) and lithium cobalt oxide (LCO); along with a closed-loop end-of-life recycling scenario for the battery materials. The results of the coupled aero-structural-battery energy storage LCE-driven design optimisations demonstrate that battery chemistry and recycling potential have a significant impact on the system's design in terms of overall LCE footprint, battery size and number, as well as aerodynamic shape. More specifically, a change in battery composition was found to lead to up to 12.5% variation in drag coefficient, while battery recycling can on average reduce a vehicle's associated LCE by 32%. Furthermore, battery material recycling was found to decrease the role played by the specific energy and cycle lives of the batteries, and increase that played by their embodied energy. Consequently, the LFP battery chemistry was found to be the best performer from an LCE perspective in the presence of battery material recycling; while the NMC chemistry was found to perform marginally better in the absence of the latter.
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| 40. |
- Burman, Robert, et al.
(författare)
-
Cyclotide proteins and precursors from the genus Gloeospermum : filling a blank spot in the cyclotide map of Violaceae
- 2010
-
Ingår i: Phytochemistry. - : Elsevier BV. - 0031-9422 .- 1873-3700. ; 71:1, s. 13-20
-
Tidskriftsartikel (refereegranskat)abstract
- Cyclotides are disulfide-rich plant proteins that are exceptional in their cyclic structure; their N and C termini are joined by a peptide bond, forming a continuous circular backbone, which is reinforced by three interlocked disulfide bonds. Cyclotides have been found mainly in the coffee (Rubiaceae) and violet (Violaceae) plant families. Within the Violaceae, cyclotides seem to be widely distributed, but the cyclotide complements of the vast majority of Violaceae species have not yet been explored. This study provides insight into cyclotide occurrence, diversity and biosynthesis in the Violaceae, by identifying mature cyclotide proteins, their precursors and enzymes putatively involved in their biosynthesis in the tribe Rinoreeae and the genus Gloeospermum. Twelve cyclotides from two Panamanian species, Gloeospermum pauciflorum Hekking and Gloeospermum blakeanum (Standl.) Hekking (designated Glopa A-E and Globa A-G, respectively) were characterised through cDNA screening and protein isolation. Screening of cDNA for the oxidative folding enzymes protein-disulfide isomerase (PDI) and thioredoxin (TRX) resulted in positive hits in both species. These enzymes have demonstrated roles in oxidative folding of cyclotides in Rubiaceae, and results presented here indicate that Violaceae plants have evolved similar mechanisms of cyclotide biosynthesis. We also describe PDI and TRX sequences from a third cyclotide-expressing Violaceae species, Viola biflora L., which further support this hypothesis.
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| 41. |
- Burman, Robert, et al.
(författare)
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Distribution of circular proteins in plants : large-scale mapping of cyclotides in the Violaceae
- 2015
-
Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- During the last decade there has been increasing interest in small circular proteins found in plants of the violet family (Violaceae). These so-called cyclotides consist of a circular chain of approximately 30 amino acids, including six cysteines forming three disulfide bonds, arranged in a cyclic cystine knot (CCK) motif. In this study we map the occurrence and distribution of cyclotides throughout the Violaceae. Plant material was obtained from herbarium sheets containing samples up to 200 years of age. Even the oldest specimens contained cyclotides in the preserved leaves, with no degradation products observable, confirming their place as one of the most stable proteins in nature. Over 200 samples covering 17 of the 23-31 genera in Violaceae were analyzed, and cyclotides were positively identified in 150 species. Each species contained a unique set of between one and 25 cyclotides, with many exclusive to individual plant species. We estimate the number of different cyclotides in the Violaceae to be 5000-25,000, and propose that cyclotides are ubiquitous among all Violaceae species. Twelve new cyclotides from six phylogenetically dispersed genera were sequenced. Furthermore, the first glycosylated derivatives of cyclotides were identified and characterized, further increasing the diversity and complexity of this unique protein family.
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| 42. |
- Cameron, Christopher J., et al.
(författare)
-
On the balancing of structural and acoustic performance of a sandwich panel based on topology, property, and size optimization
- 2014
-
Ingår i: Journal of Sound and Vibration. - : Elsevier BV. - 0022-460X .- 1095-8568. ; 333:13, s. 2677-2698
-
Tidskriftsartikel (refereegranskat)abstract
- Balancing structural and acoustic performance of a multi-layered sandwich panel is a formidable undertaking. Frequently the gains achieved in terms of reduced weight, still meeting the structural design requirements, are lost by the changes necessary to regain acceptable acoustic performance. To alleviate this, a design method for a multifunctional load bearing vehicle body panel is proposed which attempts to achieve a balance between structural and acoustic performance. The approach is based on numerical modelling of the structural and acoustic behaviour in a combined topology, size, and property optimization in order to achieve a three dimensional optimal distribution of structural and acoustic foam materials within the bounding surfaces of a sandwich panel. In particular the effects of the coupling between one of the bounding surface face sheets and acoustic foam are examined for its impact on both the structural and acoustic overall performance of the panel. The results suggest a potential in introducing an air gap between the acoustic foam parts and one of the face sheets, provided that the structural design constraints are met without prejudicing the layout of the different foam types.
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| 43. |
- Carstens, Bodil B., et al.
(författare)
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Isolation, characterization, and synthesis of the Barrettides : disulfide-containing peptides from the marine sponge Geodia barretti
- 2015
-
Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 78:8, s. 1886-1893
-
Tidskriftsartikel (refereegranskat)abstract
- Two disulfide-containing peptides, barrettides A (1) and B (2), from the cold-water marine sponge Geodia barretti are described. Those 31 amino acid residue long peptides were sequenced using mass spectrometry methods and structurally characterized using NMR spectroscopy. The structure of 1 was confirmed by total synthesis using the solid-phase peptide synthesis approach that was developed. The two peptides were found to differ only at a single position in their sequence. The three-dimensional structure of 1 revealed that these peptides possess a unique fold consisting of a long β-hairpin structure that is cross-braced by two disulfide bonds in a ladder-like arrangement. The peptides are amphipathic in nature with the hydrophobic and charged residues clustered on separate faces of the molecule. The barrettides were found not to inhibit the growth of either Escherichia coli or Staphylococcus aureus but displayed antifouling activity against barnacle larvae (Balanus improvisus) without lethal effects in the concentrations tested. (Figure Presented).
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| 44. |
- Cielniak, Grzegorz, 1975-, et al.
(författare)
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Appearance-based tracking of persons with an omnidirectional vision sensor
- 2003
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Ingår i: IEEE Computer Society Conference on Computer Vision and Pattern Recognition Workshops. - : IEEE. - 0769519008
-
Konferensbidrag (refereegranskat)abstract
- This paper addresses the problem of tracking a moving person with a single, omnidirectional camera. An appearance-based tracking system is described which uses a self-acquired appearance model and a Kalman filter to estimate the position of the person. Features corresponding to ``depth cues'' are first extracted from the panoramic images, then an artificial neural network is trained to estimate the distance of the person from the camera. The estimates are combined using a discrete Kalman filter to track the position of the person over time. The ground truth information required for training the neural network and the experimental analysis was obtained from another vision system, which uses multiple webcams and triangulation to calculate the true position of the person. Experimental results show that the tracking system is accurate and reliable, and that its performance can be further improved by learning multiple, person-specific appearance models
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| 45. |
- Cuenca, J., et al.
(författare)
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Deterministic and statistical methods for the characterisation of poroelastic media from multi-observation sound absorption measurements
- 2022
-
Ingår i: Mechanical systems and signal processing. - : Elsevier BV. - 0888-3270 .- 1096-1216. ; 163
-
Tidskriftsartikel (refereegranskat)abstract
- This paper proposes a framework for the estimation of the transport and elastic properties of open-cell poroelastic media based on sound absorption measurements. The sought properties are the Biot-Johnson-Champoux-Allard model parameters, namely five transport parameters, two elastic properties and the mass density, as well as the sample thickness. The methodology relies on a multi-observation approach, consisting in combining multiple independent measurements into a single dataset, with the aim of over-determining the problem. In the present work, a poroelastic sample is placed in an impedance tube and tested in two loading conditions, namely in a rigid-backing configuration and coupled to a resonant expansion chamber. Given the nonmonotonic nature of the experimental data, an incremental parameter estimation procedure is used in order to guide the model parameters towards the global solution without terminating at local minima. A statistical inversion approach is also discussed, providing refined point estimates, uncertainty ranges and parameter correlations. The methodology is applied to the characterisation of a sample of melamine foam and provides estimates of all nine parameters with compact uncertainty ranges. It is shown that the model parameters are retrieved with a lower uncertainty in the multi-observation case, as compared with a single-observation case. The method proposed here does not require prior knowledge of the thickness or any of the properties of the sample, and can be carried out with a standard two-microphone impedance tube.
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| 46. |
- Cuenca, J., et al.
(författare)
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Material parameter identification of coupled resonant systems using impedance tubes
- 2019
-
Ingår i: Proceedings of the 26th International Congress on Sound and Vibration, ICSV 2019. - : Canadian Acoustical Association. - 9781999181000
-
Konferensbidrag (refereegranskat)abstract
- This work studies the estimation of material properties in complex systems subjected to dynamic coupling and exhibiting a resonant behaviour. The model parameter search can be conveniently formulated as an inverse estimation procedure consisting in minimising a distance between predicted and measured responses. However, classical optimisation algorithms face the existence of local minima, which are due to resonances and geometrical symmetries in the system of interest. An incremental approach is here presented, consisting of an estimation of the model parameters using a sequence of sub-problems. The starting sub-problem is chosen as a limiting case where the system exhibits an asymptotic, non-resonant behaviour, sensitive to a subset of the unknown model parameters. Subsequent sub-problems gradually incorporate the full complexity of the problem and its sensitivity to the complete set of model parameters. As a result, the inverse estimation procedure is guided to the true solution of the problem, while avoiding local minima. The approach is applied to the estimation of geometrical and material properties of systems including expansion chambers and porous media, using impedance tube measurements as the experimental target. In order to examine the methodology and its inherent features, two inversion approaches are applied, namely a deterministic framework using a gradient-based optimiser and a Bayesian framework using a Markov chain Monte Carlo method. In particular, the sensitivity of the solution to variations in the model parameters is explored at the various stages of the step-wise procedure
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| 47. |
- Dazel, Olivier, et al.
(författare)
-
A normal modes technique to reduce the order of poroelastic models : application to 2D and coupled 3D models
- 2013
-
Ingår i: International Journal for Numerical Methods in Engineering. - : Wiley-Blackwell. - 0029-5981 .- 1097-0207. ; 96:2, s. 110-128
-
Tidskriftsartikel (refereegranskat)abstract
- A reduced-order model for structures involving poroelastic materials is proposed in this paper. The approach is based on a separation of the solid and fluid phases of the porous material into separate substructures. For each individual substructure, a decoupled normal mode basis is considered, from which a set of vectors for the decomposition is selected. The preserved modes are completed by an additional family to correct for the influence of the static response of the non-preserved. It is shown that the only neglected phenomenons in the model are the inertia of the non-preserved modes and part of their intercoupling. The following three features render the proposed scheme computationally attractive: (i) real valued matrices are involved in the transformations; (ii) the assembly of complex, frequency dependent matrices is only performed at the stage of solving for a particular frequency; and (iii) the number of normal modes required are selected using a novel method.The computational efficacy is demonstrated, on a simple but realistic 3D case, through numerical results obtained using a reduced number of DOFs, showing a significant reduction of computational cost compared with traditional methods.
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| 48. |
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| 49. |
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| 50. |
- Ericsson, Andreas, et al.
(författare)
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A combined electromagnetic and acoustic analysis of a triaxial carbon fiber weave for reflector antenna applications
- 2016
-
Ingår i: Aerospace Science and Technology. - : Elsevier. - 1270-9638 .- 1626-3219. ; 58, s. 401-417
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Tidskriftsartikel (refereegranskat)abstract
- Fiber composites are widely used for space applications such as antennas, solar panels and spacecraft support structures. This paper presents a combined electromagnetic and acoustic analysis of a triaxial carbon fiber weave structure, designed for ultra lightweight reflector antennas in satellite communication systems. The electromagnetic and acoustic performance of the structure are analyzed over a wide range of parametric studies, both at a microscopic and mesoscopic length scale. The electromagnetic study indicates that the main parameter governing the electromagnetic reflection performance of the weave is the electric conductivity of the carbon fibers, given that the weave structure is significantly smaller than the wavelength of the incident signals. The acoustic study identifies a critical threshold in the mesoscale geometry in order to avoid a critically high resistive behavior of the weave structure, driven by viscous effects. Design guidelines are drawn from these analyses in order to achieve a trade-off between the electromagnetic reflection properties and the resistance to acoustic loading of such composite materials. These combined analyses allow to deepen the understanding from both an electromagnetic and acoustic perspective in order to open for some new design possibilities.
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