| 1. |
- Brechmann, Nils A., et al.
(författare)
-
Antibody capture process based on magnetic beads from very high cell density suspension
- 2021
-
Ingår i: Biotechnology and Bioengineering. - : John Wiley and Sons Inc. - 0006-3592 .- 1097-0290. ; 118:9, s. 3499-3510
-
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.
|
|
| 2. |
- Brechmann, Nils Arnold, et al.
(författare)
-
Pilot-scale process for magnetic bead purification of antibodies directly from non-clarified CHO cell culture
- 2019
-
Ingår i: Biotechnology progress (Print). - : AIChE. - 8756-7938 .- 1520-6033.
-
Tidskriftsartikel (refereegranskat)abstract
- High capacity magnetic protein A agarose beads, LOABeads PrtA, were used in the developmentof a new process for affinity purification of monoclonal antibodies (mAbs) from non-clarifiedCHO cell broth using a pilot-scale magnetic separator. The LOABeads had a maximum bindingcapacity of 65 mg/mL and an adsorption capacity of 25–42 mg IgG/mL bead in suspension for anIgG concentration of 1 to 8 g/L. Pilot-scale separation was initially tested in a mAb capture stepfrom 26 L clarified harvest. Small-scale experiments showed that similar mAb adsorptions wereobtained in cell broth containing 40 Å~ 106 cells/mL as in clarified supernatant. Two pilot-scalepurification runs were then performed on non-clarified cell broth from fed-batch runs of 16 L,where a rapid mAb adsorption ≥96.6% was observed after 1 h. This process using 1 L of magnetic beads had an overall mAb yield of 86% and 16 times concentration factor. After this single proteinA capture step, the mAb purity was similar to the one obtained by column chromatography, whilethe host cell protein content was very low, <10 ppm. Our results showed that this magnetic beadmAb purification process, using a dedicated pilot-scale separation device, was a highly efficientsingle step, which directly connected the culture to the downstream process without cell clarification.Purification of mAb directly from non-clarified cell broth without cell separation can providesignificant savings in terms of resources, operation time, and equipment, compared to legacy procedure of cell separation followed by column chromatography step.
|
|
| 3. |
- Eriksson, Anna U., et al.
(författare)
-
Near infrared optical projection tomography for assessments of beta-cell mass distribution in diabetes research
- 2013
-
Ingår i: Journal of Visualized Experiments. - : MyJove Corporation. - 1940-087X. ; 71
-
Tidskriftsartikel (refereegranskat)abstract
- By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR)2; 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction2 and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations3. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans.
|
|
| 4. |
- Eriksson, Daniel, et al.
(författare)
-
Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
- 2018
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
|
|
| 5. |
- Eriksson, D, et al.
(författare)
-
Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
|
|
| 6. |
- Eriksson Linsmeier, Cecilia, et al.
(författare)
-
Can histology solve the riddle of non-functioning electrodes; factors influencing the biocompatibillity of brain machine interfaces.
- 2011
-
Ingår i: Progress in Brain Research. - 0079-6123. ; 194, s. 181-189
-
Bokkapitel (refereegranskat)abstract
- Neural interfaces hold great promise to become invaluable clinical and diagnostic tools in the near future. However, the biocompatibility and the long-term stability of the implanted interfaces are far from optimized. There are several factors that need to be addressed and standardized when improving the long-term success of an implanted electrode. We have chosen to focus on three key factors when evaluating the evoked tissue responses after electrode implantation into the brain: implant size, fixation mode, and evaluation period. Further, we show results from an ultrathin multichannel wire electrode that has been implanted in the rat cerebral cortex for 1 year. To improve biocompatibility of implanted electrodes, we would like to suggest that free-floating, very small, flexible, and, in time, wireless electrodes would elicit a diminished cell encapsulation. We would also like to suggest standardized methods for the electrode design, the electrode implantation method, and the analyses of cell reactions after implantation into the CNS in order to improve the long-term success of implanted neural interfaces.
|
|
| 7. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 8. |
- Näsman, Mattias, 1989-, et al.
(författare)
-
A promised land? : First summary of the research program
- 2023
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This document lays out the background for the research program “A promised land? Drivers, challenges and opportunities related to the (green) industrialization of Northern Sweden,” (nr. M22-0029) awarded by the Swedish Riksbankens Jubileumsfond’s in 2022. The document summarizes work in progress and may therefore be updated and republished in different versions according to the requirements of the program. This interdisciplinary program aims to understand the economic, social, and political challenges and opportunities of the ongoing industrial transformation in northern Sweden. A key element of the program is to identify drivers, obstacles, and preconditions in a historical, present, and forward-looking process-perspective.
|
|
| 9. |
- Tillberg, Anders, 1954-
(författare)
-
A multidisciplinary risk assessment of dental restorative materials.
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amalgam has been used as a dental restorative material for centuries, but its potential health effects and biopersistance has lead to a decreased use especially in the Nordic countries. New materials have been introduced, partly to replace the mercury containing amalgam and partly because of esthetical reasons. The possible health effects of amalgam have been studied extensively and the material has been replaced with other less well-examined materials during the last few decades. The prevalence of side effects of dental materials is considered to be low in relation to the vast number of dental treatments undertaken. With the introduction of new and more complex materials, side effects related to dental treatment may increase. Epidemiological data suggest that the side effects of dental resins that have almost completely replaced amalgam fillings in Scandinavia, possess a risk for adverse reactions; however, the causal relation has not been fully established. Therefore, the type and extent of side effects caused by resin-based materials are of great interest. The aims of the study were: - to describe the change in health over time for patients with problems related to their dental materials. The hypothesis was that the patients could be divided into subgroups based on their symptoms and that the ability to recover differs between these groups [Paper I]. Furthermore, to determine whether factors such as the replacement of dental restorative materials and follow-up time had any impact on the perceived health. - to assess the long-term development of symptoms and their social consequences among patients referred for diagnosis and treatment of symptoms related to dental materials [Paper II] - to investigate the possible risks with dental restorative materials other than amalgam [Paper III]. - to describe side effects assessed to be caused by resin-based materials that occurred in a group of patients as well as treatment and long-term consequences of the reactions [Paper IV]. A questionnaire was sent to 614 patients [Paper I and II] that had been referred to the School of Dentistry, Umeå, Sweden, with symptoms allegedly caused by dental materials. The questionnaire contained questions on, among others; civil status, present health, medical and dental treatment and other measures and precautions taken because of psychosocial problems related to current employment situation, feelings, self-image and coping behavior. Moreover, information was collected [Paper III] from the Swedish Dental Materials Register 2003 (DentMr), a compilation of MSDS for 487 materials, and information from the user guide of the materials. The Material Safety Data Sheets (MSDS) included in the DentMR were examined regarding the given composition of the products, the occurrence of CAS-numbers and the risk- and safety phrases of the substances. Information was collected [Paper IV] on 36 patients with reactions to resin-based restorative materials from the Swedish National Register of Side-Effects of Dental Materials. Patients with complex symptoms had a more unfavorable long-term prognosis concerning persistent complaints than those with local symptoms only. Furthermore, the results indicate that the patients might experience health improvements after removal of their dental restorative materials. However, the reason for this improvement was unclear. Replacement of dental restorative materials had no significant impact on the ability to recover completely. Our results also indicate a relationship between patients’ self-related health and social consequences in daily life. Those with remaining complex symptoms had more often stopped working or had decreased their work hours because of their symptoms The information about hazards with dental materials seems insufficiently described in MSDS and there might be materials with side effects unknown to both patients and dental professionals. A literature search indicated that some of the listed substances had possible hazards, e.g. substances with embryotoxic and neurotoxic potential. The patients were very heterogeneous; a few with only local symptom free reactions while other had more complex symptoms. The latter group would gain from a multidisciplinary approach, i.e. dental, medical, as well as social and psychological factors have to be considered when developing care management programs for this group of patients. Furthermore, there is a need for stronger regulations of dental materials, such as those applied to pharmaceutical drugs. Finally, it was found that the majority of symptoms suspected to be caused by resin-based materials were local or a combination of local and extra-oral symptoms that appeared within the first 24 hours after treatment. The most frequent adverse effect reported was skin problems/dermatitis. It appears as though immediate reactions to resin based materials are not uncommon and more prevalent than allergic reactions. Still, we have had, difficulties in verifying associations between the dental restorative materials and adverse reactions and also to identify the offending component.
|
|
| 10. |
- Aad, G., et al.
(författare)
-
The ATLAS Experiment at the CERN Large Hadron Collider
- 2008
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08003
-
Forskningsöversikt (refereegranskat)abstract
- The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
|
|
