| 1. |
- Hofving, Tobias, 1989, et al.
(författare)
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SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors
- 2021
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear. Methods: Utilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/− mouse model was used to detect entero-endocrine cell hyperplasia with IHC. Results: Analyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/− mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease. Conclusions: Hemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs.
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| 2. |
- Alin, Niklas, 1963, et al.
(författare)
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3D Unsteady Computations for Submarine-Like Bodies
- 2005
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Ingår i: 43rd AIAA Aerospace Sciences Meeting and Exhibit, Reno, Nevada, Jan. 10-13, 2005. ; , s. 353-369
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Konferensbidrag (refereegranskat)abstract
- Results from a computational study using Unsteady Reynolds Averaged Navier Stokes (URANS) models and Large Eddy Simulation (LES) of flows past submarine-like bodies are here presented. The aims are to evaluate URANS and LES for high-Re number hydrodynamic flows, to investigate the influence of the turbulence and subgrid turbulence modeling, and to discuss some features of submarine hydrodynamics. For this purpose we have chosen to examine the flow past a prolate spheroid at 10° and 20° angle of attack at a body length Re number of 4-106, and the flow past the DARPA-2 Suboff bare hull and fully appended hull configurations at a body length Re number of 12-106. For both cases experimental data is available for comparison. One finite element and one finite volume flow solver has been used - both with the capability of employing a range of turbulence models and with the capacity of using unstructured and hybrid grids. Better agreement between predictions and experimental data is obtained with LES than with the URANS models, but at a considerably higher price, due to the finer grids and finer temporal resolution in LES.
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| 3. |
- Alizadehheidari, Mohammadreza, 1987, et al.
(författare)
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Nanoconfined Circular and Linear DNA: Equilibrium Conformations and Unfolding Kinetics
- 2015
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Ingår i: Macromolecules. - : American Chemical Society (ACS). - 0024-9297 .- 1520-5835. ; 48:3, s. 871-878
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Tidskriftsartikel (refereegranskat)abstract
- Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of confined DNA from the circular to linear configuration as a light-induced double-strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to what extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA. Finally, we determine the rate of unfolding and show that this rate is larger for more confined DNA, possibly reflecting the corresponding larger difference in entropy between the circular and linear configurations.
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| 4. |
- Alizadehheidari, Mohammadreza, 1987, et al.
(författare)
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Unfolding of nanoconfined circular DNA
- 2015
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Ingår i: BIOPHYSICAL JOURNAL. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 108:2 Supplement 1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
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| 7. |
- Bensow, Rickard, 1972, et al.
(författare)
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Large Eddy Simulations for Marine Flows
- 2007
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Ingår i: STG-Lectureday "CFD in Ship Design", Hamburg, Germany.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 8. |
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| 9. |
- Berntsson, Thore, 1947, et al.
(författare)
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Towards Sustainabel Oil Refinery - Pre-study for larger co-operation project
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- In this report, the Chalmers EnergiCentrum (CEC) presents the results of a pre-study commissioned by Preem relating to the effective production of future vehicle fuels.This pre-study was made up of three studies focusing on energy streamlining, the utilisation of waste heat and carbon-dioxide separation and biorefinement relating to the gasification and hydration of vegetable oils. One of the common starting points for these studies was the current situation at the Preem refineries in Göteborg and Lysekil from where the measurement data were obtained and analysed. The report summarises the knowledge situation based on current research in the individual technical fields. The results present some interesting future opportunities for developing the sustainable production of future vehicle fuels. The sections vary, as the areas that have been examined differ and the sections have been written by different people. The reports ends with some joint conclusions and a number of questions which could be included and answered in a more extensive future main study, as part of a developed research partnership between Preem and the Chalmers University of Technology. The preliminary results of this work were analysed with the client at workshops on 1 October and 29 November 2007. The report is written in English combined with an extensive summary in Swedish including a proposal on a future main study. The study was conducted by the Chalmers EnergiCentrum (CEC), in collaboration with a number of researchers in the CEC’s network. They included Thore Berntsson, Jessica Algehed, Erik Hektor and Lennart Persson Elmeroth, all from Heat and Power Technology, Börje Gevert, Chemical and Biological Engineering, Tobias Richards, Forest Products and Chemical Engineering, Filip Johnsson and Anders Lyngfelt, Energy Technology, and Per-Åke Franck and Anders Åsblad, CIT Industriell Energianalys AB. The client, Preem, was represented by Bengt Ahlén, Sören Eriksson, Johan Jervehed, Bertil Karlsson, Gunnar Olsson, Ulf Kuylenstierna, Stefan Nyström, Martin Sjöberg and Thomas Ögren. Tobias Richards was responsible for compiling the report and Bertil Pettersson was the project manager.
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| 10. |
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| 11. |
- De Roos, André M, et al.
(författare)
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Simplifying a physiologically structured population model to a stage-structured biomass model.
- 2008
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Ingår i: Theoretical Population Biology. - : Elsevier Inc.. - 0040-5809 .- 1096-0325. ; 73:1, s. 47-62
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Tidskriftsartikel (refereegranskat)abstract
- We formulate and analyze an archetypal consumer-resource model in terms of ordinary differential equations that consistently translates individual life history processes, in particular food-dependent growth in body size and stage-specific differences between juveniles and adults in resource use and mortality, to the population level. This stage-structured model is derived as an approximation to a physiologically structured population model, which accounts for a complete size-distribution of the consumer population and which is based on assumptions about the energy budget and size-dependent life history of individual consumers. The approximation ensures that under equilibrium conditions predictions of both models are completely identical. In addition we find that under non-equilibrium conditions the stage-structured model gives rise to dynamics that closely approximate the dynamics exhibited by the size-structured model, as long as adult consumers are superior foragers than juveniles with a higher mass-specific ingestion rate. When the mass-specific intake rate of juvenile consumers is higher, the size-structured model exhibits single-generation cycles, in which a single cohort of consumers dominates population dynamics throughout its life time and the population composition varies over time between a dominance by juveniles and adults, respectively. The stage-structured model does not capture these dynamics because it incorporates a distributed time delay between the birth and maturation of an individual organism in contrast to the size-structured model, in which maturation is a discrete event in individual life history. We investigate model dynamics with both semi-chemostat and logistic resource growth.
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| 12. |
- de Roos, André M., et al.
(författare)
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Stage-specific predator species help each other to persist while competing for a single prey
- 2008
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Ingår i: Proceedings from the National Academy of Science of the United States of America. - Washington, USA : The National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 105:37, s. 13930-13935
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Tidskriftsartikel (refereegranskat)abstract
- Prey in natural communities are usually shared by many predator species. How predators coexist while competing for the same prey is one of the fundamental questions in ecology. Here we show that competing predator species may not only coexist on a single prey but even help each other to persist, if they specialize on different life history stages of the prey. By changing the prey size distribution a predator species may in fact increase the amount of prey available for its competitor. Surprisingly, a predator may even not be able to persist at all unless its competitor is also present. The competitor thus increases significantly the range of conditions for which a particular predator can persist. This “emergent facilitation” is a long-term, population-level effect that results from asymmetric increases in the rate of prey maturation and reproduction when predation relaxes competition among prey. Emergent facilitation explains observations of correlated increases of predators on small and large conspecific prey as well as concordance in their distribution patterns. Our results suggest that emergent facilitation may promote the occurrence of complex, stable community food webs and that persistence of these communities could critically depend on diversity within predator guilds.
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| 13. |
- Fureby, Christer, 1964, et al.
(författare)
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Scale Similarity Revisited in LES
- 2005
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Ingår i: Proceedings for 4th Symposium on Turbulence and Shear Flow Phenomena.
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Hofving, Tobias, 1989, et al.
(författare)
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The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines
- 2018
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Ingår i: Endocrine-Related Cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 25:3, s. 367-380
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Tidskriftsartikel (refereegranskat)abstract
- Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.
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| 15. |
- Hofving, Tobias, et al.
(författare)
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The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines
- 2018
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Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 25:3, s. 367-380
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Tidskriftsartikel (refereegranskat)abstract
- Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number rofiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.
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| 23. |
- Persson, Tobias, 1978
(författare)
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Numerical Simulation of High Reynolds Number Wall Bounded Flow
- 2005
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, four different numerical methods are used for predictions of high Reynoldsnumber (Re), wall bounded flows; Large Eddy Simulation (LES) with two different subgrid(turbulence) models, the One Equation Eddy Viscosity model (OEEVM) and the MixedModel (MM), Monotone Integrated LES (MILES), Detached Eddy Simulation (DES) andReynolds Averaged Navier Stokes (RANS). The LES calculations are combined with a wallmodel based on the law-of-the-wall and in DES a hybrid RANS/LES method is used forhandling the near wall region. These methods are validated against several well known,generic flow cases; a jet flow at Re=95,000, fully developed turbulent channel flow atRet=395, 595 and 1800, flow past a circular cylinder at Re=3900 and 140,000, flow past aprolate spheroid at 10° and 20° angle of attack at Re=1.6·10^6, flow around an axisymmetrichill at Re=1.3·10^5 and flow past the DARPA Suboff configuration AFF-1 and AFF-8 atRe=12·10^6.The focus of this thesis is on LES and subgrid modeling in LES, and LES-MM and LESOEEVMis used in all validation cases, while DES is used in the axisymmetric hill and thecircular cylinder cases. The MILES model is only used in the cylinder case and RANS only inthe axisymmetric hill case. A careful theoretical investigation is performed of LES-MM,where a reformulation of the LES equations is proposed. LES-MM also performs the bestprediction of the flow field compared with the other numerical methods, especially for themore complex cases.Keywords: LES, DES, subgrid model, validation, near-wall, numerical simulation, highReynolds number, turbulence
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