| 1. |
- Malm, Magdalena, 1983-, et al.
(författare)
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Evolution from adherent to suspension: systems biology of HEK293 cell line development
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production attributes and is currently used for manufacturing of several therapeutic proteins and viral vectors. Despite the increased popularity of this strain we still have limited knowledge on the genetic composition of its derivatives. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.
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| 2. |
- Meijer, S. L., et al.
(författare)
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Gene deletion of cytosolic ATP: citrate lyase leads to altered organic acid production in Aspergillus niger
- 2009
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Ingår i: Journal of Industrial Microbiology and Biotechnology. - : Oxford University Press (OUP). - 1367-5435 .- 1476-5535. ; 36:10, s. 1275-1280
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Tidskriftsartikel (refereegranskat)abstract
- With the availability of the genome sequence of the filamentous fungus Aspergillus niger, the use of targeted genetic modifications has become feasible. This, together with the fact that A. niger is well established industrially, makes this fungus an attractive micro-organism for creating a cell factory platform for production of chemicals. Using molecular biology techniques, this study focused on metabolic engineering of A. niger to manipulate its organic acid production in the direction of succinic acid. The gene target for complete gene deletion was cytosolic ATP: citrate lyase (acl), which had previously been identified by using genome-scale stoichiometric metabolic model simulations. The acl gene was deleted using the bipartite gene-targeting method, and the mutant was characterized in batch cultivation. It was found that the succinic acid yield was increased threefold by deleting the acl gene. Additionally, the total amount of organic acids produced in the deletion strain was significantly increased. Genome-scale stoichiometric metabolic predictions can be used for identifying gene targets. Deletion of the acl led to increased succinic acid production by A. niger.
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| 3. |
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| 4. |
- Nielsen, Jens B, 1962, et al.
(författare)
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Improving the economics of NASH/NAFLD treatment through the use of systems biology
- 2017
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Ingår i: Drug Discovery Today. - : Elsevier BV. - 1359-6446 .- 1878-5832. ; 22:10, s. 1532-1538
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Tidskriftsartikel (refereegranskat)abstract
- Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD). We surveyed NASH therapies currently in development, and found a significant variety of targets and approaches. Evaluation and clinical testing of these targets is an expensive and time-consuming process. Systems biology approaches could enable the quantitative evaluation of the likely efficacy and safety of different targets. This motivated our review of recent systems biology studies that focus on the identification of targets and development of effective treatments for NASH. We discuss the potential broader use of genome-scale metabolic models and integrated networks in the validation of drug targets, which could facilitate more productive and efficient drug development decisions for the treatment of NASH.
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| 5. |
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| 6. |
- Saghaleyni, Rasool, 1987, et al.
(författare)
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Enhanced metabolism and negative regulation of ER stress support higher erythropoietin production in HEK293 cells
- 2022
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 39:11
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant protein production can cause severe stress on cellular metabolism, resulting in limited titer and product quality. To investigate cellular and metabolic characteristics associated with these limitations, we compare HEK293 clones producing either erythropoietin (EPO) (secretory) or GFP (non-secretory) protein at different rates. Transcriptomic and functional analyses indicate significantly higher metabolism and oxidative phosphorylation in EPO producers compared with parental and GFP cells. In addition, ribosomal genes exhibit specific expression patterns depending on the recombinant protein and the production rate. In a clone displaying a dramatically increased EPO secretion, we detect higher gene expression related to negative regulation of endoplasmic reticulum (ER) stress, including upregulation of ATF6B, which aids EPO production in a subset of clones by overexpression or small interfering RNA (siRNA) knockdown. Our results offer potential target pathways and genes for further development of the secretory power in mammalian cell factories.
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| 7. |
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Advances in Dynamics of Vehicles on Roads and Tracks : Proceedings of the 26th Symposium of the International Association of Vehicle System Dynamics, IAVSD 2019, August 12-16, 2019, Gothenburg, Sweden
- 2020
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Proceedings (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- This volume contains the official proceedings of the 26th IAVSD Symposium on Dynamics of Vehicles on Roads and Tracks, which took place on 12–16 August 2019, at the Lindholmen Conference Centre in Gothenburg, Sweden. The main objective of the International Association for Vehicle System Dynamics (IAVSD, see www.iavsd.org) is to promote the development of, and applications in, the field of ground vehicle system dynamics. The IAVSD Symposium on Dynamics of Vehicles on Roads and Tracks is a leading international symposium bringing together researchers, scientists and engineers from academia and industry to present and exchange their latest ideas and results. These biennial symposia, held at various locations around the world, have contributed greatly to a better understanding of ground vehicle system dynamics-related problems. The organisers of the 26th Symposium were the Department of Mechanics and Maritime Sciences, Chalmers Railway Mechanics (CHARMEC), which is the Centre of Excellence in Railway Mechanics at Chalmers University of Technology, and the Vehicle and Traffic Safety Centre at Chalmers (SAFER). Both centres are part of the Transport Area of Advance hosted at Chalmers University of Technology. The symposium was attended by 380 delegates from 28 countries and five continents (Africa, Asia, Australia, Europe and North America). Most participants arrived from China (88), Sweden (73), UK (36), Germany (32), Japan (25), Austria (18), Italy (12) and Korea (11). Each day of the symposium started with a plenary session and an invited state-of-the-art presentation (60 minutes). These state-of-the-art papers have been published in the journal Vehicle System Dynamics (Taylor & Francis), volume 57, issue number 7 (July 2019). After the morning coffee break, the presentations were divided into five parallel sessions with various themes on road and railway vehicle dynamics. The number of extended abstracts submitted to the symposium was 338 with 131 related to road vehicle dynamics and 207 to railway vehicle dynamics. After peer review by the International Scientific Committee, 63 road abstracts and 83 railway abstracts were selected for 30-minute oral presentations, while 38 road and 47 railway abstracts were selected for poster presentations (3-minute oral introduction followed by individual discussions in front of each poster). Out of those, 218 presentations were selected for publication as full papers in this book, which represents the official conference proceedings. Part of the chapters gathered in this book covers different topics in railway vehicle system dynamics such as adhesion and friction, vehicle modelling, condition monitoring, wheel and rail profiles, active suspension, switches and crossings, and wheel out-of-roundness. Further topics include vibration and control, track modelling, traction and braking, vehicle design and components, safety and derailment analysis, wheel‒rail contact, wheel and rail damage, pantograph‒catenary dynamics, and wheel and rail wear. The remaining chapters cover themes in road vehicle system dynamics such as advanced driver-assistance systems (ADAS), handling dynamics, driving automation, integrated chassis control and powertrain/driveline control. Further topics include state estimation, standards, assessment and validation, tyre modelling, suspension and ride, and specialised vehicles. We expect that this volume of the Lecture Notes in Mechanical Engineering, published by Springer Nature, will serve as a timely reference guide and a source of inspiration for scientists and engineers in the field of ground vehicle system dynamics.
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| 8. |
- Aggestam, Emil, 1992, et al.
(författare)
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Dynamic interaction between vehicle and slab track – Influence of track design parameters
- 2018
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Ingår i: The Dynamics of Vehicles on Roads and Tracks. - 9781138035713 ; 2, s. 699-704
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Konferensbidrag (refereegranskat)abstract
- The vertical dynamic interaction between a high-speed railway vehicle and slab track is simulated in the time domain using a two-dimensional track model. The transient interaction problem is solved using an extended state-space vector approach in combination with a complex-valued modal superposition technique for the track model. The presented slab track model includes two layers of concrete beams, where the panels of the upper layer are described by possibly coupled beams of finite length, while the roadbed in the lower layer is a continuous beam. Both rail and concrete layers are modelled using Rayleigh-Timoshenko beam theory. The presented model is applied to calculate the influences of foundation stiffness gradient and track design parameters on various track responses. In particular, the influences of the thickness of the roadbed on the load distribution on the foundation, and of the stiffness of the rail pad on the bending moment in the concrete panels, are investigated in two demonstration examples.
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| 9. |
- Aggestam, Emil, 1992, et al.
(författare)
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Innovative requirements and evaluation methods for slab track design
- 2024
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Ingår i: Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit. - 0954-4097 .- 2041-3017. ; 238:6, s. 651-661
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Tidskriftsartikel (refereegranskat)abstract
- With increasing train speeds and reduced time windows for maintenance work, the interest in the application of slab track technology to increase the capacity of high-speed railways has grown. Slab track may still be considered a relatively young technology, but with several different designs available on the market. Current research on slab tracks commonly focuses on improved methods. In contrast, the formulation of requirements, and evaluation towards these, are seldom investigated. In this paper, state-of-the-art simulation models are employed to illustrate and address the needs for innovative requirements in terms of structural integrity and robustness, life cycle cost (LCC) and environmental footprint of new and existing slab track designs. Based on demonstration examples, it is argued that current standards may lead to overly conservative designs inducing higher LCC and environmental footprint than necessary. Extensions of the standards in terms of LCC and environmental footprint are suggested. The conflict of interest between structural integrity and robustness, LCC and environmental footprint is discussed, and suggestions for how to optimise slab track structures are proposed.
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| 10. |
- Aggestam, Emil, 1992, et al.
(författare)
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Multi-objective design optimisation of transition zones between different railway track forms
- 2018
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Ingår i: Proceedings of the 11th International Conference on Contact Mechanics and Wear of Rail/wheel Systems, CM 2018. - : TU Delft. - 2590-0609. - 9789461869630 ; , s. 1-6
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Konferensbidrag (refereegranskat)abstract
- The vertical dynamic interaction between vehicle and railway track is simulated in the time domain using an extended state space vector approach. The track model includes a transition zone between slab track on a bridge and ballasted track on an embankment. By considering a multi-objective optimisation problem, solved using a genetic algorithm, selected vehicle and track responses are simultaneously minimised by optimising the distributions of rail pad stiffness and sleeper spacing in the transition zone. It is shown that the magnitudes of the maximum dynamic loads in the optimised transition zone can be reduced to be similar as the magnitudes far away from the transition zone.
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