| 1. |
- Gomis-Fons, Joaquín, et al.
(författare)
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Model-based design and control of a small-scale integrated continuous end-to-end mAb platform
- 2020
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Ingår i: Biotechnology progress (Print). - : John Wiley and Sons Inc.. - 8756-7938 .- 1520-6033.
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Tidskriftsartikel (refereegranskat)abstract
- A continuous integrated bioprocess available from the earliest stages of process development allows for an easier, more efficient and faster development and characterization of an integrated process as well as production of small-scale drug candidates. The process presented in this article is a proof-of-concept of a continuous end-to-end monoclonal antibody production platform at a very small scale based on a 200 ml alternating tangential flow filtration perfusion bioreactor, integrated with the purification process with a model-based design and control. The downstream process, consisting of a periodic twin-column protein A capture, a virus inactivation, a CEX column and an AEX column, was compactly implemented in a single chromatography system, with a purification time of less than 4 hr. Monoclonal antibodies were produced for 17 days in a high cell density perfusion culture of CHO cells with titers up to 1.0 mg/ml. A digital twin of the downstream process was created by modelling all the chromatography steps. These models were used for real-time decision making by the implementation of control strategies to automatize and optimize the operation of the process. A consistent glycosylation pattern of the purified product was ensured by the steady state operation of the process. Regarding the removal of impurities, at least a 4-log reduction in the HCP levels was achieved. The recovery yield was up to 60%, and a maximum productivity of 0.8 mg/ml/day of purified product was obtained.
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| 2. |
- Ahrens, J., et al.
(författare)
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Measurement of the cosmic ray composition at the knee with the SPASE-2/AMANDA-B10 detectors
- 2004
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Ingår i: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 21:6, s. 565-581
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Tidskriftsartikel (refereegranskat)abstract
- The mass composition of high-energy cosmic rays at energies above 1015 eV can provide crucial information for the understanding of their origin. Air showers were measured simultaneously with the SPASE-2 air shower array and the AMANDA-B10 Cherenkov telescope at the South Pole. This combination has the advantage to sample almost all high-energy shower muons and is thus a new approach to the determination of the cosmic ray composition. The change in the cosmic ray mass composition was measured versus existing data from direct measurements at low energies. Our data show an increase of the mean log atomic mass 〈lnA〉 by about 0.8 between 500 TeV and 5 PeV. This trend of an increasing mass through the "knee" region is robust against a variety of systematic effects. © 2004 Elsevier B.V. All rights reserved.
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| 3. |
- Ahrens, J., et al.
(författare)
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Search for Extraterrestrial Point Sources of Neutrinos with AMANDA-II
- 2004
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 92:7, s. 711021-711025
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Tidskriftsartikel (refereegranskat)abstract
- The results of a search for point sources of high energy neutrinos in the northern hemisphere were presented using AMANDA-II data collected in the year 2000. The results included the flux limits on several active-galactic-nuclei blazars, microquasars, magnetars, and other candidate neutrino sources. A search for excesses above a random background of cosmic ray induced atmospheric neutrinos and misreconstructed downgoing cosmic-rays muons, which revealed no statistically significant neutrino point sources was also presented. It was shown that AMANDA-II had achieved the sensitivity required to probe known TeV γ-ray sources such as the blazar Markarian 501 in its 1997 flaring state at a level where neutrino and γ-ray fluxes were equal.
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| 4. |
- Brechmann, Nils A., et al.
(författare)
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Antibody capture process based on magnetic beads from very high cell density suspension
- 2021
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Ingår i: Biotechnology and Bioengineering. - : John Wiley and Sons Inc. - 0006-3592 .- 1097-0290. ; 118:9, s. 3499-3510
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Tidskriftsartikel (refereegranskat)abstract
- Cell clarification represents a major challenge for the intensification through very high cell density in the production of biopharmaceuticals such as monoclonal antibodies (mAbs). The present report proposes a solution to this challenge in a streamlined process where cell clarification and mAb capture are performed in a single step using magnetic beads coupled with protein A. Capture of mAb from non-clarified CHO cell suspension showed promising results; however, it has not been demonstrated that it can handle the challenge of very high cell density as observed in intensified fed-batch cultures. The performances of magnetic bead-based mAb capture on non-clarified cell suspension from intensified fed-batch culture were studied. Capture from a culture at density larger than 100 × 106 cells/ml provided an adsorption efficiency of 99% and an overall yield of 93% with a logarithmic host cell protein (HCP) clearance of ≈2–3 and a resulting HCP concentration ≤≈5 ppm. These results show that direct capture from very high cell density cell suspension is possible without prior processing. This technology, which brings significant benefits in terms of operational cost reduction and performance improvements such as low HCP, can be a powerful tool alleviating the challenge of process intensification.
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| 5. |
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| 6. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 7. |
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| 8. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 9. |
- Niessen, Peter, et al.
(författare)
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Recent results from the amanda experiment
- 2003
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Ingår i: Proceedings of 38th Rencontres de Moriond on Electroweak Interactions and Unified Theories 15-22 Mar 2003. Les Arcs, France.
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Konferensbidrag (refereegranskat)abstract
- AMANDA (Antarctic Muon And Neutrino Detector Array) is a neutrino telescope built under the southern polar icecap and its scope is to explore the possibility to detect high energy cosmic neutrinos. This should generate insight into the powerful celestial objects where acceleration mechanisms can bring up to 10 20 eV. We describe the achievements and results from the AMANDA-B10 prototype and the preliminary results from the current AMANDA-II detector which show dramatic increase in sensitivity.
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| 10. |
- Pappenreiter, Magdalena, et al.
(författare)
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Product sieving of mAb and its high molecular weight species in different modes of ATF and TFF perfusion cell cultures
- 2023
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Ingår i: Journal of chemical technology and biotechnology (1986). - : Wiley. - 0268-2575 .- 1097-4660. ; 98:7, s. 1658-1672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tangential flow filtration (TFF) systems are widely used cell retention devices in perfusion cultures, but significant challenges occur with their prolonged operation. A well-known and common issue includes membrane fouling, which leads to reduced permeate flow and increased product retention. The fouling behavior in hollow fibers have been studied widely and the application of alternating flow profiles, cell lysis, shear stress, and membrane pore size have been found to be major contributors to this phenomenon. RESULTS: In this work, different process set ups and conditions were tested using magnetic levitation pumps for low shear TFF systems in small-scale perfusion bioreactors (200 mL). A novel concept based on the application of reverse flow across the hollow fiber using two magnetically levitating pumps was validated with a Chinese Hamster Ovary cells (CHO) cell line producing a recombinant monoclonal antibody. Product sieving could be improved by 30% when a dynamic recirculation flow was applied. Furthermore, minimal product retention was achieved by reversing the flow of two alternating pumps with short cycle times. Besides this, a correlation was found between the passage of high molecular weight species to the harvest stream of the perfusion process and the flow direction, as well as the degree of product sieving. CONCLUSION: TFF with a reverse flow is a valuable alternative to an alternating tangential flow (ATF) system for overcoming antibody retention and it can be used at various scales and at a constant bioreactor volume. The comparison of ATF and TFF showed differences in product yield and purity and is, therefore, an important point for process design.
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