| 1. |
- Glimelius, Ingrid, 1975-, et al.
(författare)
-
Predictors of histology, tissue eosinophilia and mast cell infiltration in Hodgkin's Lymphoma : a population-based study
- 2011
-
Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 87:3, s. 208-216
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Classical Hodgkin’s lymphoma (HL) lesions comprise few tumour cells, surrounded by numerous inflammatory cells. Like in other malignancies, the microenvironment is presumed to be clinically important in HL; however, microenvironment predictors remain poorly characterised. The aim of this study was to investigate how selected patient characteristics and genetic factors affect HL phenotype, in particular tissue eosinophilia, mast cell counts and HL histological subtype.Methods: In a population-based study, patients with HL were interviewed about potential HL risk factors. Available tumours, n = 448, were classified histologically; the number of eosinophils and mast cells were estimated, and eosinophil cationic protein (ECP) and eosinophil protein-x (EPX) gene polymorphisms were determined. Associations were assessed in regression models.Results: Self-reported history of asthma was predictive of having tumour eosinophilia [≥200 eosinophils/10 high power fields, univariate odds ratio (OR) = 2.22, 95% CI 1.06–4.64, P = 0.03]. High numbers of eosinophils were predominantly seen in patients carrying the genotype ECP434GG [multivariate relative levels (RLs) = 1.84, 95% CI 1.02–3.30, P = 0.04]. Lower number of eosinophils was seen in Epstein–Barr virus (EBV)-positive tumours (univariate RL = 0.52, 95% CI 0.3–0.9, P = 0.02) and in older patients (univariate RL = 0.85, 95% CI 0.73–0.99, P = 0.03). Well-known factors such as young age, female sex and EBV-negative status predicted nodular sclerosis histology.Conclusion: The number of eosinophils in HL tumours is influenced by patient traits such as asthma, ECP genotype and EBV status. EBV status was predictive of histology.
|
|
| 2. |
- Glimelius, Ingrid, et al.
(författare)
-
Tissue microarray and digital image analysis : a methodological study with special reference to the microenvironment in Hodgkin lymphoma
- 2012
-
Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 61:1, s. 26-32
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: Cancer research has moved from solely investigating the tumour cells to also including analysis of the tumour microenvironment; however, the methods utilized have not been evaluated for this change. The aim of this study was to compare tissue microarrays (TMA) to whole tissue sections (WS) with regard to cells in the tumour microenvironment. Manual evaluation and digital image analyses (DIA) were utilized and also compared.Methods and results: TMA slides from 117 Hodgkin lymphoma patients were immunostained for forkhead box protein 3 (FoxP3) [identifying regulatory T cells (T(reg) )], and 39 corresponding WS were also analysed. Manual evaluation and DIA were utilized for all patients on both the TMA and the WS. A correlation coefficient of 0.83 was obtained for the proportion of T(reg) in TMA versus WS using manual evaluation and a correlation coefficient of 0.77 with DIA. T(reg) counts using manual evaluation correlated in turn with DIA, with a coefficient of 0.79 for the 117 TMA sections and 0.65 for the 39 WS.Conclusion: Because a high correlation was observed between TMA and WS, TMA can be utilized when evaluating cells in the tumour microenvironment. DIA appears to provide a reliable measurement method, provided that manual control of the tumour slides is conducted.
|
|
| 3. |
- Gudmundsson, Magnus, et al.
(författare)
-
Two-site double-core-hole states formed when fast protons capture electrons from aligned N2
- 2011
-
Ingår i: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 44:17, s. 175201-
-
Tidskriftsartikel (refereegranskat)abstract
- We report on an experimental investigation of 1.04 MeV H++N2 electron transfer collisions. The fast protons were stored in the electron-cooler ion-storage ring, CRYRING and the molecular nitrogen target was provided with a supersonic gas jet. We report momentum distributions of atomic nitrogen dissociation products Nq+ with charge states q+ (q=1, 2, 3) which are detected in coincidence with neutralized projectiles. Further, we investigate the influence of the angle between the direction of the incoming projectile beam and the target molecular axis. The orientation of the latter is determined a posteriorly from the momentum vector of one emitted atomic nitrogen fragment ion. We find signicantly higher total yields, dominated by N+, of charged atomic dissociation products when the N2 molecular axis is perpendicular to the incoming H+-beam. The relative contributions from N2+- and N3+- fragments, however, are strongest when the N2 axis is aligned -or close to aligned- with the ion beam. This, we suggest, is due to increased probabilities for formation of two-site double-core-hole states.
|
|
| 4. |
- Johansson, Sten, et al.
(författare)
-
Investigation of localized damage in single crystals subjected to thermalmechanical fatigue (TMF)
- 2010
-
Ingår i: Procedia Engineering. - : ELSEVIER SCIENCE BV. - 1877-7058. ; 2:1, s. 657-666
-
Tidskriftsartikel (refereegranskat)abstract
- The deformation and damage mechanisms arising during thermalmechanical fatigue (TMF) of a CMSX-4 and high-Cr single crystal super alloy, SCA425 have been investigated and a completely new failure mechanism involving recrystallization and oxidation has been discovered. The primary deformation mechanism is slip along the {111} planes. The deformation is highly localised to a number of bands, where recrystallization eventually occur during the thermalmechanical fatigue process. When the final failure occurs along these recrystallized bands it is accompanied by the formation of voids due to the presence of grain boundaries. The damage process is further enhanced by oxidation, since recrystallization occurs more easily in the gamma depleted zone under the oxide scale. The macroscopic as well as the microscopic damage and fracture mechanisms are varying with alloy and heat treatment. The aim of this work is to further investigate, discuss the local damage mechanisms responsible for TMF damage. Of special interest is the localisation of damage into twins and extremely localized rafted deformation bands.
|
|
| 5. |
- Leidermark, Daniel, et al.
(författare)
-
A combined critical plane and critical distance approach for predicting fatigue crack initiation in notched single-crystal superalloy components
- 2011
-
Ingår i: International Journal of Fatigue. - : Elsevier. - 0142-1123 .- 1879-3452. ; 33:10, s. 1351-1359
-
Tidskriftsartikel (refereegranskat)abstract
- The fatigue crack initiation in notched single-crystal components of material MD2 is investigated and analysed. A critical plane approach in combination with a critical distance method has been adopted, in which the total shear strain ranges on the discrete crystallographic slip planes are evaluated. To determine the critical distance two approaches were evaluated, a mean value approach and a cycle dependent approach. Furthermore, a Coffin-Manson type of expression (derived from the results of a set of 12 smooth specimens) is used to predict the number of cycles to fatigue crack initiation. The numerical procedure is applied to a series of experiments, in which notched single-crystal components were exposed to uniaxial cyclic loading in the nominal [001] crystal direction at 500 degrees C with R(epsilon) = 0. A good correlation between the experimental results and the simulated results was found.
|
|
| 6. |
- Leidermark, Daniel, 1980-
(författare)
-
Crystal plasticity and crack initiation in a single-crystal nickel-base superalloy : Modelling, evaluation and applications
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this dissertation the work done in the projects KME-410/502 will be presented.The overall objective in these projects is to evaluate and develop tools for designingagainst fatigue in single-crystal nickel-base superalloys in gas turbines. Experimentshave been done on single-crystal nickel-base superalloy specimens in order toinvestigate the mechanical and fatigue behaviour of the material. The constitutivebehaviour has been modelled and veried by FE-simulations of the experiments.Furthermore, the microstructural degradation during long-time ageing has been investigatedwith respect to the material's yield limit. The eect has been includedin the constitutive model by lowering the resulting yield limit. Moreover, the fatiguecrack initiation of a component has been analysed and modelled by using acritical plane approach in combination with a critical distance method. Finally, asan application, the derived single-crystal model was applied to all the individualgrains in a coarse grained specimen to predict the dispersion in fatigue crack initiationlife depending on random grain distributions.This thesis is divided into three parts. In the rst part the theoretical framework,based upon continuum mechanics, crystal plasticity, the critical plane approachand the critical distance method, is derived. This framework is then used in thesecond part, which consists of six included papers. Finally, in the third part, detailsof the used numerical procedures are presented.
|
|
| 7. |
- Leidermark, Daniel, et al.
(författare)
-
Evaluation of Fatigue Crack Initiation in a Notched Single-crystal Superalloy Component
- 2011
-
Ingår i: Procedia Engineering. - : Elsevier. - 1877-7058. ; 10, s. 619-624
-
Tidskriftsartikel (refereegranskat)abstract
- The fatigue crack initiation in a notched single-crystal nickel-base superalloy component at 500 °C was investigated and analysed. A critical plane approach in combination with a critical distance method has been adopted, in which the total shear strain ranges on the discrete slip planes are evaluated. Furthermore, a Coffin-Manson type of expression is used to predict the number of cycles to fatigue crack initiation. The experimental test specimens were studied by microscopy to determine on which crystallographic plane the fatigue initiation occurred. A good correlation between the experimental results and the simulated results were found.
|
|
| 8. |
- Leidermark, Daniel, et al.
(författare)
-
Fatigue crack initiation in a notched single-crystal superalloy component
- 2010
-
Ingår i: Procedia Engineering. - : Elsevier. - 1877-7058. ; 2:1, s. 1067-1075
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, the fatigue crack initiation in notched single-crystal test specimens of material MD2 is investigated and analysed. A critical plane approach is adopted, in which the total strain ranges on the discrete slip planes are evaluated. Furthermore, a Coffin-Manson type of expression is used to describe the number of cycles to fatigue crack initiation. This relation is determined from a set of smooth test specimens loaded uniaxially in the [001], [011] and directions at 500 °C with Rε=−1. The numerical procedure is then applied to a series of experiments, in which notched single-crystal test specimens were exposed to uniaxial cyclic loading in the [001] direction at 500 °C with Rε=0.
|
|
| 9. |
- Leidermark, Daniel, 1980-
(författare)
-
Modelling of constitutive and fatigue behaviour of a single-crystal nickel-base superalloy
- 2010
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this licentiate thesis the work done in the project KME410 will be presented. The overall objective of this project is to evaluate and develop tools for designing against fatigue in single-crystal nickel-base superalloys in gas turbines. Experiments have been done on single-crystal nickel-base superalloy specimens in order to investigate the mechanical behaviour of the material. The constitutive behaviour has been modelled and verified by simulations of the experiments. Furthermore, the microstructural degradation during long-time ageing has been investigated with respect to the component’s yield limit. The effect has been included in the constitutive model by lowering the resulting yield limit. Finally, the fatigue crack initiation of a component has been analysed and modelled by using a critical plane approach.This thesis is divided into three parts. In the first part the theoretical framework, based upon continuum mechanics, crystal plasticity and the critical plane approach, is derived. This framework is then used in the second part, which consists of three included papers. Finally, in the third part, details are presented of the used numerical procedures.
|
|
| 10. |
- Leidermark, Daniel, et al.
(författare)
-
Modelling of TMF Crack Initiation in Smooth Single-Crystal Superalloy Specimens
- 2014
-
Konferensbidrag (refereegranskat)abstract
- In this paper the TMF crack initiation behaviour of the single-crystal nickel-base superalloyMD2 is investigated and modelled. TMF tests were performed in both IP and OP for varying mechanicalstrain ranges in the [001] crystallographic direction until TMF crack initiation was obtained. Acrystal plasticity-creep model was used in conjunction with a critical-plane approach, to evaluate thenumber of cycles to TMF crack initiation. The critical-plane model was evaluated and calibrated ata stable TMF cycle, where the effect of the stress relaxation had attenuated. This calibrated criticalplanemodel is able to describe the TMF crack initiation, taking tension/compression asymmetry aswell as stress relaxation anisotropy into account, with good correlation to the real fatigue behaviour.
|
|
| 11. |
- Leidermark, Daniel, et al.
(författare)
-
Tension/Compression asymmetry of a single-crystal superalloy in virgin and degraded condition
- 2010
-
Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 58:15, s. 4986-4997
-
Tidskriftsartikel (refereegranskat)abstract
- The mechanical behaviour at room temperature of a single-crystal superalloy exposed to long term ageing at elevated temperature has been investigated, a topic important for the material’s resistance to thermal-mechanical fatigue. Specimens with several different crystallographic orientations were plastically deformed in either tension or compression before and after the long term furnace exposure. While the thermally activated degradation of the microstructure causes a reduction in yield limit of up to 25% for specimens initially deformed in the |001 and |011| directions, none or only moderate reduction was seen for specimens initially deformed along the |111| direction. This can be explained by the strong correlation between yield limit reduction and the amount of γ coarsening. By introducing an isotropic degradation function in a newly developed crystal plasticity model, the constitutive behaviour of both virgin and degraded materials has been described with good agreement with the experimental results.
|
|
| 12. |
- Leidermark, Daniel, 1980-, et al.
(författare)
-
The effect of random grain distributions on fatigue crack initiation in a notched coarse grained superalloy specimen
- 2012
-
Ingår i: Computational materials science. - : Elsevier. - 0927-0256 .- 1879-0801. ; 51:1, s. 273-280
-
Tidskriftsartikel (refereegranskat)abstract
- Coarse grained superalloys are of large interest in high temperature applications, and can be found in e.g.gas turbine components, where great care must be given with respect to high temperature fatigue. Due tothe large grain size, the material behaviour at e.g. sharp notches cannot be considered homogeneous. As aconsequence, the fatigue behaviour is likely to expose a large variation. In order to numerically investigatethis variation, a Monte Carlo analysis has been carried out by 100 FE-simulations of notched specimens,where placements and orientations of the grains were randomised. Furthermore, each grain wasmodelled as a unique single-crystal, displaying both anisotropic elastic and plastic behaviour and tension/compression asymmetry. The effect of randomness was investigated by the obtained dispersion infatigue crack initiation life. It was concluded that the fatigue life behaviour of coarse grained nickel-basesuperalloys may show a considerable variation, which cannot be captured by one single deterministicanalysis based on data for a homogenised material. Furthermore, the dispersion is of such a magnitudethat it needs to be taken into account in industrial applications where highly stressed coarse grainedmaterials are used.
|
|
| 13. |
- Rekić, Dinko, 1984, et al.
(författare)
-
Model based design and analysis of phase II HIV-1 trials
- 2013
-
Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 40:4, s. 487-496
-
Tidskriftsartikel (refereegranskat)abstract
- This work explores the advantages of a model based drug development (MBDD) approach for the design and analysis of antiretroviral phase II trials. Two different study settings were investigated: (1) a 5-arm placebo-controlled parallel group dose-finding/proof of concept (POC) study and (2) a comparison of investigational drug and competitor. Studies were simulated using a HIV-1 dynamics model in NONMEM. The Monte-Carlo Mapped Power method determined the sample size required for detecting a dose-response relationship and a significant difference in effect compared to the competitor using a MBDD approach. Stochastic simulation and re-estimation were used for evaluation of model parameter precision and bias given different sample sizes. Results were compared to those from an unpaired, two-sided t test and ANOVA (p a parts per thousand currency sign 0.05). In all scenarios, the MBDD approach resulted in smaller study sizes and more precisely estimated treatment effect than conventional statistical analysis. Using a MBDD approach, a sample size of 15 patients could be used to show POC and estimate ED50 with a good precision (relative standard error, 25.7 %). A sample size of 10 patients per arm was needed using the MBDD approach for detecting a difference in treatment effect of a parts per thousand yen20 % at 80 % power, a 3.4-fold reduction in sample size compared to a t test. The MBDD approach can be used to achieve more precise dose-response characterization facilitating decision making and dose selection. If necessitated, the sample size needed to reach a desired power can potentially be reduced compared to traditional statistical analyses. This may allow for comparison against competitors already in early clinical studies.
|
|
| 14. |
- Röshammar, Daniel, 1979, et al.
(författare)
-
Non-linear mixed effects modeling of antiretroviral drug response after administration of lopinavir, atazanavir and efavirenz containing regimens to treatment-naive HIV-1 infected patients
- 2011
-
Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1567-567X .- 1573-8744. ; 38:6, s. 727-742
-
Tidskriftsartikel (refereegranskat)abstract
- The objective of this analysis was to compare three methods of handling HIV-RNA data below the limit of quantification (LOQ) when describing the time-course of antiretroviral drug response using a drug-disease model. Treatment naive Scandinavian HIV-positive patients (n = 242) were randomized to one of three study arms. Two nucleoside reverse transcriptase inhibitors were administrated in combination with 400/100 mg lopinavir/ritonavir twice daily, 300/100 mg atazanavir/ritonavir once a day or 600 mg efavirenz once a day. The viral response was monitored at screening, baseline and at 1, 2, 3, 4, 12, 24, 48, 96, 120, and 144 weeks after study initiation. Data up to 400 days was fitted using a viral dynamics non-linear mixed effects drug-disease model in NONMEM. HIV-RNA data below LOQ of 50 copies/ml plasma (39%) was omitted, replaced by LOQ/2 or included in the analysis using a likelihood-based method (M3 method). Including data below LOQ using the M3 method substantially improved the model fit. The drug response parameter expressing the fractional inhibition of viral replication was on average (95% CI) estimated to 0.787 (0.721-0.864) for lopinavir and atazanavir treatment arms and 0.868 (0.796-0.923) for the efavirenz containing regimen. At 400 days after treatment initiation 90% (76-100) of the lopinavir and atazanavir treated patients were predicted to have undetectable viral levels and 96% (89-100%) for the efavirenz containing treatment. Including viral data below the LOQ rather than omitting or replacing data provides advantages such as better model predictions and less biased parameter estimates which are of importance when quantifying antiretroviral drug response.
|
|
| 15. |
- Segersäll, Mikael, et al.
(författare)
-
Creep and Stress Relaxation Anisotropy of a Single-Crystal Superalloy
- 2014
-
Ingår i: Metallurgical and Materials Transactions. A. - : Springer. - 1073-5623 .- 1543-1940. ; 45:5, s. 2532-2544
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, the TMF stress relaxation and creep behavior at 1023 K and 1223 K (750 °C and 950 °C) have been investigated for a Ni-based single-crystal superalloy. Specimens with three different crystal orientations along their axes were tested; 〈001〉, 〈011〉, and 〈111〉, respectively. A highly anisotropic behavior during TMF stress relaxation was found where the 〈111〉 direction significantly shows the worst properties of all directions. The TMF stress relaxation tests were performed in both tension and compression and the results indicate a clear tension/compression asymmetry for all directions where the greatest asymmetry was observed for the 〈001〉 direction at 1023 K (750 °C); here the creep rate was ten times higher in compression than tension. This study also shows that TMF cycling seems to influence the creep rate during stress relaxation temporarily, but after some time it decreases again and adapts to the pre-unloading creep rate. Creep rates from the TMF stress relaxation tests are also compared to conventional constant load creep rates and a good agreement is found.
|
|
| 16. |
|
|
| 17. |
- Segersäll, Mikael, et al.
(författare)
-
Low-Cycle Fatigue Behaviour of a Ni-Based Single-Crystal Superalloy
- 2014
-
Ingår i: Advanced Materials Research. - : Trans Tech Publications Inc.. - 1022-6680 .- 1662-8985. ; 891-892, s. 416-421
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, low-cycle fatigue (LCF) tests at 500 degrees C in the < 001 >, < 011 > and < 111 > directions have been performed for the Ni-based single-crystal superalloy MD2. All tests were carried out in strain control with R-is an element of = -1. The < 001 > direction has the lowest stiffness of the three directions and also shows the best fatigue properties in this study followed by the < 011 > and < 111 > directions, respectively. It is well recognised that Ni-based single-crystal superalloys show a tension/compression asymmetry in yield strength and this study shows that a tension/compression asymmetry is also present during LCF conditions. At mid-life, the < 001 > direction generally has a higher stress in tension than in compression, while the opposite is true for the < 011 > direction. For the < 111 > direction the asymmetry is found to be strain range dependent. The < 011 > and < 111 > directions show a cyclic hardening behaviour when comparing cyclic stress-strain curves with monotonic stress-strain curves. In addition, the < 011 > and < 111 > directions show a serrated yielding behaviour for a number of cycles while the yielding of the < 001 > direction is more stable.
|
|
| 18. |
- Segersäll, Mikael
(författare)
-
Nickel-Based Single-Crystal Superalloys : the crystal orientation influence on high temperature properties
- 2013
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Superalloys are a group of materials that are used in high temperature applications, for example gas turbines and aero engines. Gas turbines are most commonly used for power generation, and it is only the very critical components which are exposed to the most severe conditions within the turbine, which are made from superalloy material.Today, energy consumption in many parts of the world is very high and is tending to increase. This implies that all power generating sources, including gas turbines, must aim for higher efficiency. For the gas turbine industry, it is a continuous challenge to develop more energy-efficient turbines. One way to do this is to increase the temperature within the hot stage of the turbine. However, increased temperature in the hot stage also challenges the materials that are used there. Today’s materials are already pushed to the limit, i.e. they cannot be exposed to the temperatures which are required to further increase the turbine efficiency. To solve this problem, research which later can lead to better superalloys that can withstand even higher temperatures, has to be conducted within the area of superalloys.The aim of this licentiate thesis is to increase our knowledge about deformation and damage mechanisms that occur in the microstructure in superalloys when they are subjected to high temperatures and loads. This knowledge can later be used when developing new superalloys. In addition, increased knowledge of what is happening within the material when it is exposed to those severe conditions, will facilitate the development of material models. Material models are used for FEM simulations, when trying to predict life times in gas turbine components during the design process.This licentiate thesis is based on results from thermomechanical fatigue (TMF) testing of Ni-based single-crystal superalloys. Results show that the deformation within the microstructure during TMF is localized to several deformation bands. In addition, the deformation mechanisms are mainly twinning and shearing of the microstructure. Results also indicate that TMF cycling seems to influence the creep rate of single-crystal superalloys.
|
|
