| 421. |
- Kågedal, Matts, et al.
(author)
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Non-linear mixed effects modelling of positron emission tomography data for simultaneous estimation of radioligand kinetics and occupancy in healthy volunteers
- 2012
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In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 61:4, s. 849-856
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Journal article (peer-reviewed)abstract
- The aim of this work was to develop a model simultaneously estimating (11)C-AZD9272 radioligand kinetics and the relationship between plasma concentration of AZD9272 and receptor occupancy in the human brain.AZD9272 is a new chemical entity pharmacologically characterised as a noncompetitive antagonist at the metabotropic glutamate receptor subtype 5 (mGluR5). Positron emission tomography (PET) was used to measure the time course of ((11)C-AZD9272) in the brain. The study included PET measurements in six healthy volunteers where the radioligand was given as a tracer dose alone as well as post oral treatment with different doses of unlabelled AZD9272. Estimation of radioligand kinetics, including saturation of receptor binding was performed by use of non-linear mixed effects modelling. Data from the regions with the highest (ventral striatum) and lowest (cerebellum) radioligand concentrations were included in the analysis. It was assumed that the extent of non-displaceable brain uptake was the same in both regions while the rate of CNS uptake and the receptor density differed.The results of the analysis showed that AZD9272 binding at the receptor is saturable with an estimated plasma concentration corresponding to 50% occupancy of approximately 200nM. The density of the receptor binding sites was estimated to 800nM and 200nM in ventral striatum and cerebellum respectively. By simultaneously analysing data from several PET measurements and different brain regions in a non-linear mixed effects framework it was possible to estimate parameters of interest that would otherwise be difficult to quantify.
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| 422. |
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| 423. |
- Larsnäs, Mats, et al.
(author)
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Mattetipspromenad och Europas kyrkor i mobilen
- 2009
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In: Datorn i utbildningen. - 1100-3650. ; :2, s. 6-9
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Journal article (pop. science, debate, etc.)abstract
- De flesta elever har en mobiltelefon, så varför inte integrera den i skolarbetet? På Smedingeskolan i Kungsbacka har både elever och lärare testat att använda mobilen för olika uppgifter i matte och SO. Tillsammans med lärarutbildningen på Malmö högskola utvecklar man nu idéerna vidare.
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| 424. |
- LarsOlle, Anders, et al.
(author)
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A multi-criteria decision support model for optimal stump harvesting
- 2012
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Conference paper (other academic/artistic)abstract
- A multi-criteria decision support model for optimal stump harvesting Sweden was developed. The model quantifies the effect of harvesting each individual stump over a harvesting object in four criteria's: - Biodiversity (Biodiversity value index) - Economy (SEK) - Greenhouse gas emissions (CO2) - Soil and water (Soil and water preservation index) The four criteria's are sometimes in conflict to each other, and uses values that are not directly comparable. The intended use for this model is to contribute with the objective evaluation of all four criteria's in the decision in what stumps to harvest and what stumps to leave in the harvesting object. The model uses individual stump data (e.g. position, tree species and stump biomass) and harvesting object GIS data (roads, elevation map, soil map, terrain map). Primary data on individual stumps comes from the logging system in the stem harvesters: GPS and operator classification. Such data are routinely collected in harvesters. Official map data for the harvesting object are available from the Swedish mapping, cadastral and land registration authority (Lantmäteriet). This includes the topographic map and elevation maps data in 2 m resolution. Also, GIS data are collected in the inspections before harvesting the stems. The biodiversity sub-model considers different types of wood-dependent organisms (lichens, mosses, insects and fungi) in terms of their habitat requirements, vulnerability, sun exposure preferences, locality, etc. A panel of external experts has drawn up a grading scale of stump values for the different taxonomic groups. The proximity to key habitats and exposure to sunlight are derived from a spatial model. In the economic sub-model the potential net return from each stump is calculated based on estimated revenue from harvested stump biomass and the costs of stump harvesting and transport (based on cost functions and GIS calculations of transport distances). An energy and climate sub-model incorporates greenhouse gas (GHG) emissions from forest operations and the effect of advancing GHG emissions when stump biomass is incinerated instead of being left to decompose. Soil and water issues are handled within a sub-model estimating the consequences for long-term soil fertility (nutrient cycling and soil compaction) and water (leaching of plant nutrients and mercury, and particle transport due to soil damage by heavy machinery). Each criteria is evaluated in totally four sub-models. To be able to compare the resulting value from each of the criteria, a harvesting index from 0 to 1 is calculated for each stump. The value 0 represents ‘Not at all suitable for harvest’ and 1 ‘Highly suitable for harvest’. Through this, a stump of high biodiversity value is assigned a low harvesting index in the biodiversity sub-model and a large, easily accessible stump is assigned a high harvesting index in the economic sub-model. When calculating the total net index, the harvesting index from each criteria has to be weighed together using one coefficient for each criteria. The weighing coefficient for each criteria is chosen according to the preferences of the decision maker. The tool offers the end-user possibilities to prioritise and plan for cost-effective stump harvesting, while minimising negative environmental impacts.
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| 425. |
- Larsson, Anna H, et al.
(author)
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Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer
- 2012
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 12, s. 282-
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Journal article (peer-reviewed)abstract
- Background: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional independent patient cohorts and to examine the correlation between PODXL mRNA and protein levels in a subset of tumours. Method: PODXL protein expression was analyzed by immunohistochemistry in tissue microarrays with tumour samples from a consecutive, retrospective cohort of 270 CRC patients (cohort 1) and a prospective cohort of 337 CRC patients (cohort 2). The expression of PODXL mRNA was measured by real-time quantitative PCR in a subgroup of 62 patients from cohort 2. Spearman's Rho and Chi-Square tests were used for analysis of correlations between PODXL expression and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modelling were applied to assess the relationship between PODXL expression and time to recurrence (TTR), disease free survival (DFS) and overall survival (OS). Results: High PODXL protein expression was significantly associated with unfavourable clinicopathological characteristics in both cohorts. In cohort 1, high PODXL expression was associated with a significantly shorter 5-year OS in both univariable (HR = 2.28; 95% CI 1.43-3.63, p = 0.001) and multivariable analysis (HR = 2.07; 95% CI 1.25-3.43, p = 0.005). In cohort 2, high PODXL expression was associated with a shorter TTR (HR = 2.93; 95% CI 1.26-6.82, p = 0.013) and DFS (HR = 2.44; 95% CI 1.32-4.54, p = 0.005), remaining significant in multivariable analysis, HR = 2.50; 95% CI 1.05-5.96, p = 0.038 for TTR and HR = 2.11; 95% CI 1.13-3.94, p = 0.019 for DFS. No significant correlation could be found between mRNA levels and protein expression of PODXL and there was no association between mRNA levels and clinicopathological parameters or survival. Conclusions: Here, we have validated the previously demonstrated association between immunohistochemical expression of PODXL and poor prognosis in CRC in two additional independent patient cohorts. The results further underline the potential utility of PODXL as a biomarker for more precise prognostication and treatment stratification of CRC patients.
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| 426. |
- Larsson, Niklas, et al.
(author)
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Equilibrium sampling through membranes (ESTM) of acidic organic pollutants using hollow fibre modules in continuous steady-state mode.
- 2009
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In: Chemosphere. - : Elsevier BV. - 1879-1298 .- 0045-6535. ; 76:9, s. 1213-1220
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Journal article (peer-reviewed)abstract
- Hollow fibre (HF) membrane modules were applied in continuous mode for equilibrium sampling through membranes (ESTM) of polar organic pollutants. Phenolic compounds (chlorophenols, cresols and phenol) served as model substances and ESTM was tuned towards the measurement of freely dissolved concentrations (C(free)). HF membrane modules were constructed using thin-walled membrane, 1-m module length and low packing density in order to optimise the uptake kinetics of the analytes into the acceptor solution. Such custom made devices were tested and compared to commercially available modules. The former modules performed best for continuous ESTM. The custom made modules provided steady-state equilibrium within 20-40min and enrichment that was in general agreement with calculated distribution ratios between acceptor and sample. In experiments during which sample concentration was changed, acceptor response time to decreased sample concentration was around 30min for custom built modules. In the presence of commercial humic acids, analytes showed lower steady-state enrichment, which is due to a decrease in C(free). Continuous ESTM may be automated and is suggested for use in online determination of C(free) of pollutants and studies on sorption of pollutants. Future studies should include optimisation of the membrane liquid and factors regarding the residence time of the acceptor solution in the fibre lumen. Qualitative aspects of DOM should also be included, as natural DOM can be fractionated. C(free) could be correlated to DOM properties that have previously been shown to influence sorption, such as aromaticity, carboxylic acid content and molecular size.
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| 427. |
- Larsson, Robin, et al.
(author)
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Fuel efficient relative orbit control strategies for formation flying and rendezvous within PRISMA
- 2006
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Conference paper (peer-reviewed)abstract
- This article will outline the relative orbit control, including guidance and control tasks developed for the PRISMA technology in-orbit formation flying testbed mission. The focus is on real-time implementable solutions, working in arbitrary orbits (0 ≤ e < 1). The algorithms presented are based on linear Model Predictive Control(MPC). The computational heavy part of a MPC approach is usually to setup the matrices, associated with the linear program, if zero order hold discretization methods are used. This article introduces a different approach which uses the state transition matrices developed in [1], that accommodate steps of arbitrary length. This approach allows much larger time steps than the time varying dynamics would allow when zero order hold discretizing the dynamics. The computational complexity will instead depend on the number of state constraints and the number of allowed control inputs. These two factors can be designed to meet real-time execution requirements. The initial tests show that the expected ΔV consumption compares well to previous works in this area with only a small fraction of the computational load. To date, a version of the control algorithm for the Proximity Operations has been implemented and successfully demonstrated in real-time on flight representative hardware as a part of SSC's demonstration at the 6th International ESA Conference on Guidance, Navigation and Control Systems. The maximum processor load increase over one second was about 3%, on a Leon2 processor running at 32 MHz, with code not optimized for computational efficiency.
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| 428. |
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| 429. |
- Lauss, Martin, et al.
(author)
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Genome-Wide DNA Methylation Analysis in Melanoma Reveals the Importance of CpG Methylation in MITF Regulation.
- 2015
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In: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 135:7, s. 1820-1828
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Journal article (peer-reviewed)abstract
- The microphthalmia-associated transcription factor (MITF) is a key regulator of melanocyte development and a lineage-specific oncogene in melanoma; a highly lethal cancer known for its unpredictable clinical course. MITF is regulated by multiple intracellular signaling pathways although the exact mechanisms that determine MITF expression and activity remain incompletely understood. In this study, we obtained genome-wide DNA methylation profiles from 50 stage IV melanomas, normal melanocytes, keratinocytes and dermal fibroblasts, and utilized The Cancer Genome Atlas (TCGA) data for experimental validation. By integrating DNA methylation and gene expression data we found that hypermethylation of MITF and its co-regulated differentiation pathway genes, corresponded to decreased gene expression levels. In cell lines with a hypermethylated MITF-pathway, over-expression of MITF did not alter the expression level or methylation status of the MITF pathway genes. In contrast however, demethylation treatment of these cell lines induced MITF-pathway activity, confirming that gene-regulation was controlled via methylation. The discovery that the activity of the master regulator of pigmentation, MITF, and its downstream targets may be regulated by hypermethylation has significant implications for understanding the development and evolvement of melanoma.Journal of Investigative Dermatology accepted article preview online, 23 February 2015. doi:10.1038/jid.2015.61.
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| 430. |
- Lauvås, Per, et al.
(author)
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Ren formativ bedömning : en ny bedömningspraktik
- 2019
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Book (other academic/artistic)abstract
- Kunskapsbedömning kan – kanske mer än något annat man gör som lärare – påverka elevernas kunskapsutveckling och motivation i skolan. Men denna påverkan är inte nödvändigtvis positiv. Bedömningen kan ge kraftigt negativa effekter för elevernas kunskapsutveckling och motivation, såväl som kraftigt positiva. Vilka effekterna blir, beror i stor utsträckning på hur man arbetar med bedömning, inte minst vad gäller relationen mellan formativ och summativ bedömning. Det som börjar bli alltmer tydligt, ju mer vi lär oss om formativ och summativ bedömning, är nämligen att de inte fungerar så väl ihop. En bedömningspraktik där man blandar formativ och summativ bedömning, tycks vara den som ger flest negativa effekter – samtidigt som det troligen är just en sådan bedömningspraktik, som är vanligast i både skola och högre utbildning idag. I den här boken ges därför ett delvis nytt perspektiv på bedömning, vars viktigaste princip är att summativ och formativ bedömning hålls åtskilda i så hög grad som möjligt, så att den formativa bedömningen är ”ren formativ bedömning”.
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