| 1. |
- Jonsson, Pär, et al.
(författare)
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Constrained randomization and multivariate effect projections improve information extraction and biomarker pattern discovery in metabolomics studies involving dependent samples
- 2015
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 11:6, s. 1667-1678
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Tidskriftsartikel (refereegranskat)abstract
- Analytical drift is a major source of bias in mass spectrometry based metabolomics confounding interpretation and biomarker detection. So far, standard protocols for sample and data analysis have not been able to fully resolve this. We present a combined approach for minimizing the influence of analytical drift on multivariate comparisons of matched or dependent samples in mass spectrometry based metabolomics studies. The approach is building on a randomization procedure for sample run order, constrained to independent randomizations between and within dependent sample pairs (e.g. pre/post intervention). This is followed by a novel multivariate statistical analysis strategy allowing paired or dependent analyses of individual effects named OPLS-effect projections (OPLS-EP). We show, using simulated data that OPLS-EP gives improved interpretation over existing methods and that constrained randomization of sample run order in combination with an appropriate dependent statistical test increase the accuracy and sensitivity and decrease the false omission rate in biomarker detection. We verify these findings and prove the strength of the suggested approach in a clinical data set consisting of LC/MS data of blood plasma samples from patients before and after radical prostatectomy. Here OPLS-EP compared to traditional (independent) OPLS-discriminant analysis (OPLS-DA) on constrained randomized data gives a less complex model (3 versus 5 components) as well a higher predictive ability (Q2 = 0.80 versus Q2 = 0.55). We explain this by showing that paired statistical analysis detects 37 unique significant metabolites that were masked for the independent test due to bias, including analytical drift and inter-individual variation.
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| 2. |
- Meyer, H., et al.
(författare)
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Overview of progress in European medium sized tokamaks towards an integrated plasma-edge/wall solution
- 2017
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Ingår i: Nuclear Fusion. - : Institute of Physics Publishing (IOPP). - 0029-5515 .- 1741-4326. ; 57:10
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Tidskriftsartikel (refereegranskat)abstract
- Integrating the plasma core performance with an edge and scrape-off layer (SOL) that leads to tolerable heat and particle loads on the wall is a major challenge. The new European medium size tokamak task force (EU-MST) coordinates research on ASDEX Upgrade (AUG), MAST and TCV. This multi-machine approach within EU-MST, covering a wide parameter range, is instrumental to progress in the field, as ITER and DEMO core/pedestal and SOL parameters are not achievable simultaneously in present day devices. A two prong approach is adopted. On the one hand, scenarios with tolerable transient heat and particle loads, including active edge localised mode (ELM) control are developed. On the other hand, divertor solutions including advanced magnetic configurations are studied. Considerable progress has been made on both approaches, in particular in the fields of: ELM control with resonant magnetic perturbations (RMP), small ELM regimes, detachment onset and control, as well as filamentary scrape-off-layer transport. For example full ELM suppression has now been achieved on AUG at low collisionality with n = 2 RMP maintaining good confinement H-H(98,H-y2) approximate to 0.95. Advances have been made with respect to detachment onset and control. Studies in advanced divertor configurations (Snowflake, Super-X and X-point target divertor) shed new light on SOL physics. Cross field filamentary transport has been characterised in a wide parameter regime on AUG, MAST and TCV progressing the theoretical and experimental understanding crucial for predicting first wall loads in ITER and DEMO. Conditions in the SOL also play a crucial role for ELM stability and access to small ELM regimes.
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| 3. |
- Akbarnejad, Shahin, et al.
(författare)
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Analysis on Experimental Investigation and Mathematical Modeling of Incompressible Flow Through Ceramic Foam Filters
- 2016
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Ingår i: Metallurgical and materials transactions. B, process metallurgy and materials processing science. - : Springer. - 1073-5615 .- 1543-1916. ; 47:4, s. 2229-2243
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents experimental results of pressure drop measurements on 30, 50, and 80 pores per inch (PPI) commercial alumina ceramic foam filters (CFF) and compares the obtained pressure drop profiles to numerically modeled values. In addition, it is aimed at investigating the adequacy of the mathematical correlations used in the analytical and the computational fluid dynamics (CFD) simulations. It is shown that the widely used correlations for predicting pressure drop in porous media continuously under-predict the experimentally obtained pressure drop profiles. For analytical predictions, the negative deviations from the experimentally obtained pressure drop using the unmodified Ergun and Dietrich equations could be as high as 95 and 74 pct, respectively. For the CFD predictions, the deviation to experimental results is in the range of 84.3 to 88.5 pct depending on filter PPI. Better results can be achieved by applying the Forchheimer second-order drag term instead of the Brinkman-Forchheimer drag term. Thus, the final deviation of the CFD model estimates lie in the range of 0.3 to 5.5 pct compared to the measured values.
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| 4. |
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| 5. |
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| 6. |
- Björkblom, Benny, et al.
(författare)
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Metabolomic screening of pre-diagnostic serum samples identifies association between alpha- and gamma-tocopherols and glioblastoma risk
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:24, s. 37043-37053
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma is associated with poor prognosis with a median survival of one year. High doses of ionizing radiation is the only established exogenous risk factor. To explore new potential biological risk factors for glioblastoma, we investigated alterations in metabolite concentrations in pre-diagnosed serum samples from glioblastoma patients diagnosed up to 22 years after sample collection, and undiseased controls. The study points out a latent biomarker for future glioblastoma consisting of nine metabolites (gamma-tocopherol, alpha-tocopherol, erythritol, erythronic acid, myo-inositol, cystine, 2-keto-L-gluconic acid, hypoxanthine and xanthine) involved in antioxidant metabolism. We detected significantly higher serum concentrations of alpha-tocopherol (p=0.0018) and gamma-tocopherol (p=0.0009) in future glioblastoma cases. Compared to their matched controls, the cases showed a significant average fold increase of alpha- and gamma-tocopherol levels: 1.2 for alpha-T (p=0.018) and 1.6 for gamma-T (p=0.003). These tocopherol levels were associated with a glioblastoma odds ratio of 1.7 (alpha-T, 95% CI: 1.0-3.0) and 2.1 (gamma-T, 95% CI: 1.2-3.8). Our exploratory metabolomics study detected elevated serum levels of a panel of molecules with antioxidant properties as well as oxidative stress generated compounds. Additional studies are necessary to confirm the association between the observed serum metabolite pattern and future glioblastoma development.
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| 7. |
- Björkblom, Benny, et al.
(författare)
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Pre-diagnostic plasma metabolites linked to future brain tumor development
- 2018
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 20, s. 288-289
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: The Northern Sweden Health and Disease Study is a unique population-based biobank linked to the clinical data registries. The samples originate from over 133 000 individuals living in the northern part of Sweden, and primarily collected during health checkups from the age of 40 years. Our project aims to investigate alterations in metabolite signatures in blood plasma of healthy blood donors that later in life developed a tumor. Brain tumors, especially glioblastoma is associated with poor prognosis. To explore early events of metabolic reprograming linked to future diagnosis, we investigated alterations in metabolite concentrations in plasma collected several years before diagnosis with matched healthy controls.MATERIALS AND METHODS: In total 392 analytical samples (256 repeated timepoint and 136 single timepoint, case-control samples) were analyzed using GCTOFMS. Constrained randomization of run order was utilized to maximize information output and minimize the false discovery rate. By use of reference databases, we could with high confidence quantify and identify 150 plasma metabolites. We detected metabolites with significant alterations in concertation between pre-clinical glioma cases and healthy controls by the effect projection approach based on orthogonal partial least squares (OPLSEP).RESULTS AND CONCLUSIONS: For the repeated blood samples, we designed and applied a novel multivariate strategy for high resolution biomarker pattern discovery. We utilize the fact that we have available samples from two repeated time points prior to diagnosis for each future glioma case and their matched controls to construct a small design of experiment (DoE) of four samples for each match pair. The data for each individual DoE was evaluated by OPLS-EP to determine the effect of each individual metabolite in relation to control-case, time and their interaction. Finally, latent significance calculations by means of OPLS were used to extract and evaluate the correct latent biomarker and highlight true significance of individual metabolites. Our study presents an approach to minimize confounding effects due to systematic noise from sampling, the analytical method, as well as take into account personalized metabolic levels over time, enabling biomarker detection within a smaller sample group. We will present and discuss the latest results and biomarkers from this exploratory metabolomics study at the meeting
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| 8. |
- Borssén, Magnus, et al.
(författare)
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DNA methylation holds prognostic information in relapsed precursor B-cell acute lymphoblastic leukemia
- 2018
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Ingår i: Clinical Epigenetics. - : BIOMED CENTRAL LTD. - 1868-7083 .- 1868-7075. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few biological markers are associated with survival after relapse of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In pediatric T-cell ALL, we have identified promoter-associated methylation alterations that correlate with prognosis. Here, the prognostic relevance of CpG island methylation phenotype (CIMP) classification was investigated in pediatric BCP-ALL patients.Methods: Six hundred and one BCP-ALL samples from Nordic pediatric patients (age 1-18) were CIMP classified at initial diagnosis and analyzed in relation to clinical data.Results: Among the 137 patients that later relapsed, patients with a CIMP-profile (n = 42) at initial diagnosis had an inferior overall survival (pOS(5years) 33%) compared to CIMP+ patients (n = 95, pOS(5years) 65%) (p = 0.001), which remained significant in a Cox proportional hazards model including previously defined risk factors.Conclusion: CIMP classification is a strong candidate for improved risk stratification of relapsed BCP-ALL.
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| 9. |
- Byström, Pär, et al.
(författare)
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Declining coastal piscivore populations in the Baltic Sea : where and when do sticklebacks matter?
- 2015
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 44:Suppl 3, s. S462-S471
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Tidskriftsartikel (refereegranskat)abstract
- Intraguild predation interactions make fish communities prone to exhibit alternative stable states with either piscivore or prey fish dominance. In the Baltic Sea, local declines of coastal piscivores like perch (Perca fluviatilis) have been observed to coincide with high densities of sticklebacks (Gasterosteus aculeatus). Mechanisms behind this shift between piscivore and stickleback dominance were studied both experimentally and in field. Results showed that predation by sticklebacks has a strong negative effect on perch larvae survival, but this effect rapidly decreases with increasing perch size, likely due to gape limitations and digestion constraints in sticklebacks. Large spatial and temporal variations in patterns of stickleback migration into perch spawning sites were observed. Whether or not high density of sticklebacks will cause declines in coastal piscivore populations is suggested to depend on the availability of spawning sites in which sticklebacks do not migrate into or arrive late in the reproduction season of coastal piscivores.
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| 10. |
- Chen, Chao, et al.
(författare)
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A Mathematical Modeling Study of the Influence of Small Amounts of KCl Solution Tracers on Mixing in Water and its Residence Time Distribution in a Continuous Flow Reactor-Metallurgical Tundish
- 2015
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Ingår i: Chemical Engineering Science. - : Pergamon Press. - 0009-2509 .- 1873-4405. ; 137, s. 914-937
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In an earlier research (Chen et al., 2015a) a mathematical model was established to simulate tracer mixing (a KCl solution). The predicted Residence Time Distribution (RTD) curves showed good agreements with experimental RID curves for larger amounts of tracer additions. However, for smaller additions (50 mL) of a KCl solution into water, the predicted RID curves tended to deviate from the experimental RTD curves for a tundish (a continuous flow reactor). The current paper focuses on the possibilities that the predictability for smaller additions could be resolved by using a suitable turbulence model. The performance of five different turbulence models representing different modeling techniques and levels of complexity were tested in combination with using a density-coupled mixed composition fluid model to simulate the mixing, i.e. the following models: LVEL, Chen-Kim k-epsilon, MMK k-epsilon, Explicit Algebraic Reynolds Stress Model (EARSM), and Large Eddy Simulation (LES): Wall-Adapting Local Eddy-viscosity (WALE). The results indicate that models that tend to resolve turbulence structures renders better predictions of the mixing process of smaller tracer amounts. In addition, the influence of different tracer amounts on the flow in tundish was assessed. The simulation results for 75 mL, 100 mL, 150 mL, and 250 mL KCl tracer additions were compared. The results showed that in an upward flow the tracer will, sooner or later (dependent on the tracer amount), sink to the bottom. This is due to the higher density of the tracer compared to the density of water. From a physical modeling perspective, this issue is like the "butterfly effect". It is showed that for a slight increase of the amount of tracer, the flow field might be disturbed. This, in turn, will result in a shifted RTD curve.
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