| 1. |
- Andersson, Sandra, 1978-
(författare)
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Validation of antibodies for tissue based immunoassays
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In situ protein detection in human tissues using antibodies reveals the cellular protein localization, and affinity-based proteomic studies can help to discover proteins involved in the development of diseases. However, antibodies often suffer from cross-reactivity, and the lack of positive and negative tissue controls for uncharacterized proteins complicates the mapping of the proteome. The aim of this thesis is thus to improve the methodology for validating antibodies used for immunostaining on formalin-fixed paraffin-embedded tissues.Two of the papers include comparisons between mRNA-expression and immunostaining of corresponding protein. In paper I, ISH and IHC staining patterns were compared on consecutive TMA-slides. The study of well-characterized genes showed that ISH could be used for validation of antibodies. ISH was further used for antibody evaluation, and could validate four out of nine antibodies showing potentially interesting staining patterns. In paper III, transcriptomic data generated by RNA-sequencing were used to identify tissue specific expression in lymphohematopoietic tissues. An increased expression in one or more of these tissues compared to other tissue types was seen for 693 genes, and these were further compared to the staining patterns of corresponding proteins in tissues.Antibody labeling is necessary for many immunoassays. In paper II, two techniques for antibody-biotinylation were compared, aiming to find a stringent labeling method for antibodies used for immunostaining on TMAs. The ZBPA-method, binding specifically to Fc-part of antibodies, was found to be superior to the Lightning Link-biotinylation kit targeting amine groups, since labeling of amine groups on stabilizing proteins in the antibody buffer causes unspecific staining.The localization of the estrogen receptor beta (ERβ) in human normal and cancer tissues was studied in paper IV. Thorough evaluation of 13 antibodies using positive and negative control cell lines showed that only one antibody, PPZ0506, is specific for ERβ in all three immunoassays used. Contradictory to previously published data, tissue profiling using PPZ0506 showed that ERβ is expressed in a limited number of normal and cancer tissues.In conclusion, the present investigations present tools for validation of antibodies used for large-scale studies of protein expression in tissues.
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| 2. |
- Carlsson, Jörgen, et al.
(författare)
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EGFR-expression in primary urinary bladder cancer and corresponding metastases and the relation to HER2-expression. On the possibility to target these receptors with radionuclides
- 2015
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Ingår i: Radiology and Oncology. - : Walter de Gruyter GmbH. - 1318-2099 .- 1581-3207. ; 49:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- Background. There is limited effect of tyrosine kinase inhibitors or "naked" antibodies binding EGFR or HER2 for therapy of metastasized urinary bladder canter and these methods are therefore not routinely used. Targeting radionuclides to the extracellular domain of the receptors is potentially a better possibility. Methods. EGFR- and HER2-expression was analyzed for primary tumors and corresponding metastases from 72 patients using immunohistochemistry and the internationally recommended HercepTest. Intracellular mutations were not analyzed since only the receptors were considered as targets and intracellular abnormalities should have minor effect on radiation dose. Results. EGFR was positive in 71% of the primary tumors and 69% of corresponding metastases. Local and distant metastases were EGFR-positive in 75% and 66% of the cases, respectively. The expression frequency of HER2 in related lesions was slightly higher (data from previous study). The EGFR-positive tumors expressed EGFR in metastases in 86% of the cases. The co-expression of EGFR and HER2 was 57% for tumors and 53% for metastases. Only 3% and 10% of the lesions were negative for both receptors in tumors and metastases, respectively. Thus, targeting these receptors with radionuclides might be applied for most patients. Conclusions. At least one of the EGFR- or HER2-receptors was present in most cases and co-expressed in more than half the cases. It is therefore interesting to deliver radionuclides for whole-body receptor-analysis, dosimetry and therapy. This can hopefully compensate for resistance to other therapies and more patients can hopefully be treated with curative instead of palliative intention.
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| 3. |
- Johnson, Tomas, 1979, et al.
(författare)
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A Multi-Scale Simulation Method for the Prediction of Edge Wicking in Multi-Ply Paperboard
- 2015
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Ingår i: Nordic Pulp and Paper Research Journal. - 2000-0669 .- 0283-2631. ; 30:4, s. 640-650
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Tidskriftsartikel (refereegranskat)abstract
- When liquid packaging board is made aseptic in the filling machine the unsealed edges of the board are exposed to a mixture of water and hydrogen peroxide. A high level of liquid penetration may lead to aesthetic as well as functional defects. To be able to make a priori predictions of the edge wicking properties of a certain paperboard material is therefore of great interest to the paper industry as well as to packaging manufacturers. In this paper an extended multi-scale model of edge wicking in multi-ply paperboard is presented. The geometric and physical properties of the paperboard are modeled on the micro-scale, and include fillers and fines. The absolute air permeabilities and pore size distributions are validated with experimental and tomographic values. On the macro-scale random porosity and sizing distributions, time and sizing dependent contact angles, and inter-ply dependence are modeled. Arbitrary shapes of the paperboard are handled through an unstructured 3D surface mesh. Stationary and transient edge wicking simulations are validated against experiments with excellent agreement. The simulations show that the diffusive menisci between the liquid and air phases together with the two-ply model is necessary to achieve good agreement with the transient edge wicking experiments.
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| 4. |
- Kettil, Gustav, 1990, et al.
(författare)
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A Multiscale Method for Discrete Fiber Network Models
- 2018
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Ingår i: 6th European Conference on Computational Mechanics (Solids, Structures and Coupled Problems). 7th European Conference on Computational Fluid Dynamics, 11-15 June 2018, Glasgow, UK.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The mechanics of paper depends on the properties of its fibers and bonds. Modeling paper as a network [1] will include effects of single fibers and bonds, capturing heterogeneous properties. In the ISOP (Innovative Simulation of Paper) project at Fraunhofer-Chalmers Centre, the forming process is simulated [2, 3]. To investigate the mechanical properties of the resulting simulated paper sheets a network approach is utilized. Numerical investigation of fiber networks is demanding due to the large number of fibers and bonds, fluctuation of their properties, and the non-regular network structure. Multiscale methods are useful tools to circumvent such problems. In this work a multi-scale approach for fiber networks is developed, based on a FEM-method for continua [4]. Consider a fiber network governed by a model resulting in an equation Kx = F, where K describes the network properties, x are node displacements, and F are applied forces. The idea of the multi-scale method is to consider a subset of all nodes, denoted coarse nodes, which in turn represents a coarse grid. At each coarse node a basis function is defined similarly as in the finite element method. By solving a system including the coarse nodes an approximation would be attained, however this approximation would leave out the fine scale effects of the heterogeneous network. Instead the coarse basis functions are modified by solving a local system at each coarse node, including surrounding fine nodes. These modified basis functions are thereafter used when solving the global system, resulting in an approximation of the network displacements now including effects from the fine scale.
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| 5. |
- Kettil, Gustav, 1990, et al.
(författare)
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Detailed Simulations of Early Paper Forming
- 2015
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Ingår i: COST FP1005 Fibre Suspension Flow Modelling Final Conference Trondheim 2015 June 9-11.
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Konferensbidrag (refereegranskat)abstract
- Computer simulations are important to increase the knowledge of the processes involved in paper making. Because of the complexity of the paper processes the development of simulation tools requires models and numerical methods which capture as much as possible of the real physical phenomena. In this paper a framework for simulation of fiber suspension flow is presented. The framework is founded on a fluid solver for the Navier-Stokes equations and a fiber model based on finite strain beam theory including shearing. Moreover, the coupling between fibers and fluid is resolved with the immersed boundary method and the interaction between the fibers is calculated using a model based on DLVO-theory.
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| 6. |
- Kettil, Gustav, 1990, et al.
(författare)
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Novel Contact Forces for Immersed Boundary Paper Forming Simulations
- 2015
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Ingår i: Online proceedings: http://tappi.sclivelearningcenter.com/; PF2 - The Past, Present and Future of CFD Papermaking; PaperCon 2015 Atlanta April 19-22.
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Konferensbidrag (refereegranskat)abstract
- To be able to simulate the different processes involved in paper machines, models, numerical methods and algorithms have to be developed which capture as much as possible of the real physical phenomena. In this paper a model for calculation of the chemical and physical interaction between objects included in a fiber suspension is presented. The contact force model is based on DLVO theory [1, 2] and uses so-called contact points distributed along the fiber suspension objects. The contact model has been used in an existing framework to simulate the build-up of low density paper webs. In the framework fibers are modeled as elliptical cylinders whose movements are described by finite-strain beam theory which includes shearing. The fluid flow is computed using a Navier-Stokes solver and immersed boundary methods are utilized to resolve the flow around each fiber. For validation, the air permeability and thickness of the paper webs have been measured and compared with simulated data. The result demonstrates that the software can be used to simulate paper forming.
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