| 1. |
- Dahl, Martin, et al.
(author)
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Effects of shading and simulated grazing on carbon sequestration in a tropical seagrass meadow
- 2016
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In: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 104:3, s. 654-664
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Journal article (peer-reviewed)abstract
- 1. There is an ongoing world-wide decline of seagrass ecosystems, one of the world's most efficient carbon sink habitats. In spite of this, there is a clear lack of studies experimentally testing the effects of anthropogenic disturbances on carbon sequestration of seagrass systems. 2. We assessed the effects of two disturbances of global concern on the carbon sink function in a five-month in situ experiment within a tropical seagrass (Thalassia hemprichii) meadow by testing the impacts of shading and simulated grazing at two levels of intensity using shading cloths and clipping of shoot tissue. We measured the effects of these disturbances on the carbon sequestration process by assessing the net community production (NCP), carbon and nitrogen content in tissue biomass, and organic matter and THAA (total hydrolysable amino acids) in the sediment down to 40 cm depth. 3. Treatments of high-intensity shading and high-intensity clipping were similarly impacted and showed a significantly lower NCP and carbon content in the below-ground biomass compared to the seagrass control. No significant effects were seen in organic carbon, total nitrogen, C:N ratio and THAA in the sediment for the seagrass treatments. However, both clipping treatments showed different depth profiles of carbon and THAA compared to the seagrass control, with lower organic carbon and THAA content in the surface sediment. This can be explained by the clipping of shoot tissue causing a less efficient trapping of allochthonous carbon and reduced input of shredded seagrass leaves to the detritus sediment layer. In the clipping plots, erosion of the surface sediment occurred, which was also most likely caused by the removal of above-ground plant biomass. 4. Synthesis. Our findings show that during the course of this experiment, there were no impacts on the sedimentary carbon while the high-intensity disturbances caused a clear depletion of carbon biomass and reduced the seagrass meadow's capacity to sequester carbon. From a long-term perspective, the observed effect on the carbon biomass pool in the high-intensity treatments and the sediment erosion in the clipping plots may lead to loss in sedimentary carbon.
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| 2. |
- Estenberg, Martin, 1970-
(author)
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"Ett snäpp högre" : En studie av historielärares hanterande av tankeredskap.
- 2016
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Licentiate thesis (other academic/artistic)abstract
- Abstract The aim with this study is to examine how practicing history teachers in upper secondary school deal with historical thinking concepts. The three main questions are: which concepts do teachers use in their courses and when do they use them? How can teachers’ use of different historical thinking concepts be described in terms of reconstruction and construction? What factors influence teachers when they work with historical thinking concepts? To answer these questions, the material, for example tests, lesson plans and notes of seven teachers has been analyzed. These analysis were followed by interviews with the teachers. The empirical data have been handled in two steps. The first step is a survey of what historical thinking concepts teachers use and when they use them. The survey was done as a detailed reading of the teachers’ material. In this survey two historical thinking concepts, evidence and cause and consequence, have been selected for further analysis, which is the second step. The results show that when teachers deal with the historical thinking concept of evidence they show their students models and ways to handle evidence. This is not the case when teachers handle the historical thinking concept of cause and consequence. Models are shown here as well but not to the same extent. The result also shows that the teachers’ handling of evidence in a greater extent leads to construction compared with their handling of cause and consequence. The explanations provided in the study also point to the different character between the two concepts and what form of test the teachers’ use and what words are used to communicate for example cause and consequence. Furthermore, the explanations also indicate that the teachers’ view of what historical knowledge contains of, together with what kind of students and what other subject they teach play some part in their dealing with historical thinking concepts.
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| 3. |
- Gullström, Martin, et al.
(author)
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Blue Carbon Storage in Tropical Seagrass Meadows Relates to Carbonate Stock Dynamics, Plant–Sediment Processes, and Landscape Context : Insights from the Western Indian Ocean
- 2018
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In: Ecosystems (New York. Print). - : Springer Science and Business Media LLC. - 1432-9840 .- 1435-0629. ; 21:3, s. 551-566
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Journal article (peer-reviewed)abstract
- Globally, seagrass ecosystems are considered major blue carbon sinks and thus indirect contributors to climate change mitigation. Quantitative estimates and multi-scale appraisals of sources that underlie long-term storage of sedimentary carbon are vital for understanding coastal carbon dynamics. Across a tropical–subtropical coastal continuum in the Western Indian Ocean, we estimated organic (Corg) and inorganic (Ccarb) carbon stocks in seagrass sediment. Quantified levels and variability of the two carbon stocks were evaluated with regard to the relative importance of environmental attributes in terms of plant–sediment properties and landscape configuration. The explored seagrass habitats encompassed low to moderate levels of sedimentary Corg (ranging from 0.20 to 1.44% on average depending on species- and site-specific variability) but higher than unvegetated areas (ranging from 0.09 to 0.33% depending on site-specific variability), suggesting that some of the seagrass areas (at tropical Zanzibar in particular) are potentially important as carbon sinks. The amount of sedimentary inorganic carbon as carbonate (Ccarb) clearly corresponded to Corg levels, and as carbonates may represent a carbon source, this could diminish the strength of seagrass sediments as carbon sinks in the region. Partial least squares modelling indicated that variations in sedimentary Corg and Ccarb stocks in seagrass habitats were primarily predicted by sediment density (indicating a negative relationship with the content of carbon stocks) and landscape configuration (indicating a positive effect of seagrass meadow area, relative to the area of other major coastal habitats, on carbon stocks), while seagrass structural complexity also contributed, though to a lesser extent, to model performance. The findings suggest that accurate carbon sink assessments require an understanding of plant–sediment processes as well as better knowledge of how sedimentary carbon dynamics are driven by cross-habitat links and sink–source relationships in a scale-dependent landscape context, which should be a priority for carbon sink conservation.
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| 4. |
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| 5. |
- Hillberg, Emil, et al.
(author)
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Active Network Management for All : ANM4L a collaborative research project
- 2020
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Reports (other academic/artistic)abstract
- Developments of the power system are driven by the need to decrease the environmental footprint, to meet international climate goals, pushing for fossil‐free energy system. The transition towards clean energy will require power systems to adapt on a global scale with significant investments needed in fossil‐free electricity generation and transport. Renewable Energy Sources (RES) play an increasingly important role in the power system and may become the dominant sources of electricity. Significant RES are integrated in distribution grids globally, resulting in an increased need for distribution grids to perform new and complex tasks necessary for continued grid stability. The rapidity of small‐scale investments calls for agile, alternative grid development solutions. This agility is furthermore necessary to meet challenges arising from demand scenarios encompassing intermittent renewables along with electrification of transport and heat sectors. New technologies and markets are emerging to provide flexibility in consumption, generation, and power transfer capacity. Active Network Management (ANM) solutions provides alternative methods for planning and operation of the power system, through monitoring and control of multiple grid assets. This paper presents an overview of the ongoing project ANM4L, where a toolbox will be developed to support operation and planning of distribution grids.The project ANM4L (Active network management for all - anm4l.eu), will develop and demonstrate innovative ANM solutions for increasing integration of distributed generation in electricity distribution systems. ANM solutions will consider management of active and reactive power to avoid overload situations and maintain voltage limits. The goal is to decrease the need of curtailment of renewable energy, theoretically enabling further integration of distributed generation potentially even above the current design limitations of the electricity network. Core research and development activities of the ANM4L project include development of: ANM methods for local energy systems. Economic considerations to provide decision support. A toolbox to support the planning and operation. The toolbox, methods and business models for ANM will be demonstrated in real life distribution grids in both Sweden and Hungary. Furthermore, the project will consider the replicability and scalability necessary for these ANM solutions to be applied across the EU.
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| 6. |
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| 7. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Ansell - Schultz, Anna, et al.
(author)
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Reduced retromer function results in the accumulation of amyloid-beta oligomers
- 2018
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In: Molecular and Cellular Neuroscience. - : Academic Press. - 1044-7431 .- 1095-9327. ; 93, s. 18-26
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Journal article (peer-reviewed)abstract
- Alzheimers disease (AD) is a neurodegenerative disorder characterized by a progressive loss of multiple cognitive functions. Accumulation of amyloid beta oligomers (oA beta) play a major role in the neurotoxicity associated with the disease process. One of the early affected brain regions is the hippocampus, wherein a reduction of the vacuolar protein sorting-associated protein 35 (VPS35), the core protein comprising the retromer complex involved in cellular cargo sorting, has been identified. To investigate the role of the retromer function on the accumulation and clearance of oA beta, we reduced retromer function by selectively inhibiting VPS35 gene expression using siRNA in differentiated neuronal SH-SY5Y cells. As cell-to-cell transfer of oA beta to new brain regions is believed to be important for disease progression we investigated the effect of VPS35 reduction both in cells with direct uptake of oA beta and in cells receiving oA beta from donor cells. We demonstrate that reduced retromer function increases oA beta accumulation in both cell systems, both the number of cells containing intracellular oA beta and the amount within them. This effect was shown at different time points and regardless if the AD originated from the extracellular milieu or via a direct neuronal cell-to-cell transfer. Interestingly, not only did reduced VPS35 cause oA beta accumulation, but oA beta treatment alone also lead to a reduction of VPS35 protein content. The accumulated oA beta seems to co-localize with VPS35 and early endosome markers. Together, these findings provide evidence that reduced retromer function decreases the ability for neurons to transport and clear neurotoxic oA beta received through different routes resulting in the accumulation of oA beta. Thus, enhancing retromer function may be a potential therapeutic strategy to slow down the pathophysiology associated with the progression of AD.
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| 13. |
- Asplund Samuelsson, Johannes, et al.
(author)
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Diversity and expression of bacterial metacaspases in an aquatic ecosystem
- 2016
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In: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 7, s. 1-18
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Journal article (peer-reviewed)abstract
- Metacaspases are distant homologs of metazoan caspase proteases, implicated in stress response, and programmed cell death (PCD) in bacteria and phytoplankton. While the few previous studies on metacaspases have relied on cultured organisms and sequenced genomes, no studies have focused on metacaspases in a natural setting. We here present data from the first microbial community-wide metacaspase survey; performed by querying metagenomic and metatranscriptomic datasets from the brackish Baltic Sea, a water body characterized by pronounced environmental gradients and periods of massive cyanobacterial blooms. Metacaspase genes were restricted to ~4% of the bacteria, taxonomically affiliated mainly to Bacteroidetes, Alpha- and Betaproteobacteria and Cyanobacteria. The gene abundance was significantly higher in larger or particle-associated bacteria (<0.8 μm), and filamentous Cyanobacteria dominated metacaspase gene expression throughout the bloom season. Distinct seasonal expression patterns were detected for the three metacaspase genes in Nodularia spumigena, one of the main bloom-formers. Clustering of normalized gene expression in combination with analyses of genomic and assembly data suggest functional diversification of these genes, and possible roles of the metacaspase genes related to stress responses, i.e., sulfur metabolism in connection to oxidative stress, and nutrient stress induced cellular differentiation. Co-expression of genes encoding metacaspases and nodularin toxin synthesis enzymes was also observed in Nodularia spumigena. The study shows that metacaspases represent an adaptation of potentially high importance for several key organisms in the Baltic Sea, most prominently Cyanobacteria, and open up for further exploration of their physiological roles in microbes and assessment of their ecological impact in aquatic habitats.
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| 14. |
- Bagge, Joakim, et al.
(author)
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Impact of stationary-phase pore size on chromatographic performance using oligonucleotide separation as a model
- 2020
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In: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1634, s. 1-10
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Journal article (peer-reviewed)abstract
- A combined experimental and theoretical study was performed to understand how the pore size of packing materials with pores 60-300 angstrom in size affects the separation of 5-50-mer oligonucleotides. For this purpose, we developed a model in which the solutes were described as thin rods to estimate the accessible surface area of the solute as a function of the pore size and solute size. First, an analytical investigation was conducted in which we found that the selectivity increased by a factor of 2.5 when separating 5- and 15-mer oligonucleotides using packing with 300 angstrom rather than 100 angstrom pores. We complemented the analytical investigation by theoretically demonstrating how the selectivity is dependent on the column's accessible surface area as a function of solute size. In the preparative investigation, we determined adsorption isotherms for oligonucleotides using the inverse method for separations of a 9- and a 10-mer. We found that preparative columns with a 60 angstrom-pore-size packing material provided a 10% increase in productivity as compared with a 300 A packing material, although the surface area of the 60 angstrom packing is as much as five time larger.
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| 15. |
- Bay-Richter, Cecilie, et al.
(author)
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A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality
- 2015
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In: Brain, behavior, and immunity. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0889-1591 .- 1090-2139. ; 43, s. 110-117
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Journal article (peer-reviewed)abstract
- Background: Patients with depression and suicidality suffer from low-grade neuroinflammation. Proinflammatory cytokines activate indoleamine 2,3-dioxygenase, an initial enzyme of the kynurenine pathway. This pathway produces neuroactive metabolites, including quinolinic- and kynurenic acid, binding to the glutamate N-methyl-D-aspartate-receptor, which is hypothesized to be part of the neural mechanisms underlying symptoms of depression. We therefore hypothesized that symptoms of depression and suicidality would fluctuate over time in patients prone to suicidal behavior, depending on the degree of inflammation and kynurenine metabolite levels in the cerebrospinal fluid (CSF). Methods: We measured cytokines and kynurenine metabolites in CSF, collected from suicide attempters at repeated occasions over 2 years (total patient samples n = 143, individuals n = 30) and healthy controls (n = 36). The association between the markers and psychiatric symptoms was assessed using the Montgomery Asberg Depression Rating Scale and the Suicide Assessment Scale. Results: Quinolinic acid was increased and kynurenic acid decreased over time in suicidal patients versus healthy controls. Furthermore, we found a significant association between low kynurenic acid and severe depressive symptoms, as well as between high interleukin-6 levels and more severe suicidal symptoms. Conclusions: We demonstrate a long-term dysregulation of the kynurenine pathway in the central nervous system of suicide attempters. An increased load of inflammatory cytokines was coupled to more severe symptoms. We therefore suggest that patients with a dysregulated kynurenine pathway are vulnerable to develop depressive symptoms upon inflammatory conditions, as a result the excess production of the NMDA-receptor agonist quinolinic acid. This study provides a neurobiological framework supporting the use of NMDA-receptor antagonists in the treatment of suicidality and depression. (C) 2014 Elsevier Inc. All rights reserved.
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| 16. |
- Berg, Carlo, et al.
(author)
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Dissection of Microbial Community Functions during a Cyanobacterial Bloom in the Baltic Sea via Metatranscriptomics
- 2018
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745.
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Journal article (peer-reviewed)abstract
- Marine and brackish surface waters are highly dynamic habitats that undergo repeated seasonal variations in microbial community composition and function throughout time. While succession of the various microbial groups has been well investigated, little is known about the underlying gene-expression of the microbial community. We investigated microbial interactions via metatranscriptomics over a spring to fall seasonal cycle in the brackish Baltic Sea surface waters, a temperate brackish water ecosystem periodically promoting massive cyanobacterial blooms, which have implications for primary production, nutrient cycling, and expansion of hypoxic zones. Network analysis of the gene expression of all microbes from 0.22 to 200 mu m in size and of the major taxonomic groups dissected the seasonal cycle into four components that comprised genes peaking during different periods of the bloom. Photoautotrophic nitrogen-fixing Cyanobacteria displayed the highest connectivity among the microbes, in contrast to chemoautotrophic ammonia-oxidizing Thaumarchaeota, while heterotrophs dominated connectivity among pre- and post-bloom peaking genes. The network was also composed of distinct functional connectivities, with an early season balance between carbon metabolism and ATP synthesis shifting to a dominance of ATP synthesis during the bloom, while carbon degradation, specifically through the glyoxylate shunt, characterized the post-bloom period, driven by Alphaproteobacteria as well as by Gammaproteobacteria of the SAR86 and SAR92 clusters. Our study stresses the exceptionally strong biotic driving force executed by cyanobacterial blooms on associated microbial communities in the Baltic Sea and highlights the impact cyanobacterial blooms have on functional microbial community composition.
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| 17. |
- Bergsten, Göran, et al.
(author)
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PapG-dependent adherence breaks mucosal inertia and triggers the innate host response
- 2004
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 189:9, s. 1734-1742
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Journal article (peer-reviewed)abstract
- Mucosal pathogens differ from normal flora constituents in that they provoke a host response that upsets mucosal integrity. We investigated whether the elaboration of discrete adherence factors is sufficient to break the inertia of the mucosal barrier. PapG-mediated adherence was selected as an example, because P fimbrial expression characterizes uropathogenic Escherichia coli and because adherence starts the attack on the mucosal barrier. Patients were inoculated intravesically with transformed nonvirulent E. coli strains expressing functional P fimbriae (E. coli pap(+)) or mutant fimbriae lacking the adhesin (E. coli DeltapapG). E. coli pap(+) was shown to activate the innate host response, and adherent gfp(+) bacteria were observed on excreted uroepithelial cells. E. coli DeltapapG failed to trigger a response and was nonadhesive. We conclude that PapG-mediated adherence breaks mucosal inertia in the human urinary tract by triggering innate immunity and propose that this activation step differentiates asymptomatic carriage from infection.
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| 18. |
- Bernardo, Ricardo, et al.
(author)
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Combined solar and membrane drying technologies for sustainable fruit preservation in low-income countries – prototype development, modelling, and testing
- 2021
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In: Solar Energy Advances. - : Elsevier BV. - 2667-1131. ; 1
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Journal article (peer-reviewed)abstract
- This investigation consisted of developing and evaluating solar dryers together with semi-permeable membrane pouches for drying juicy fruits in low-income tropical countries. Two design iterations were carried out including prototype modelling and testing. The latest developed solar dryers were a passive and an active solar dryer. Modelling was initially carried out mathematically using an equation solver software followed by computational fluid dynamics. Preliminary measurements were carried out on a small-scale solar dryer. Thereafter, full-scale models were developed and tested, both in laboratory and in real conditions in Mozambique. Results from modelling were validated against measurements in laboratory in Sweden and field trials in Mozambique. Prototype building and testing in Mozambique was undertaken in collaboration with local farmers and a university. Measurement results show that the dryers help to prevent microbial growth through increased temperatures. The drying flux was increased by 50% for the passive, and by 100% for the active solar dryers compared to the ambient controls that did not use a solar dryer. The total drying time was below four days for all pouches in the dryers. The active solar dryer was shown to have the shortest drying time and the highest capacity (more pouches) but also the highest costs. Mould growth and juice fermentation were observed on control pouches drying in open air. These problems were solved with the use of solar dryer technology. However, some challenges with the membrane pouches require further development including degradation of the membrane when exposed to direct sunlight.
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| 19. |
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| 20. |
- Bjursell, Cecilia, 1970-, et al.
(author)
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Continued growth later in life – older adults learning
- 2021
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Conference paper (peer-reviewed)abstract
- The demographic changes have resulted in an increased proportion of older people in the population in several countries. To have a large proportion of older people in the population is a situation that is historically unique and basically something positive. Despite this, the aging population is discussed as a problem as it puts pressure on pension systems and health care systems. As education and learning have contributed to positive development in several ways, the interest for older adults learning has increased. Education that occurs later in life can be considered as a means of supporting participation in an extended working life, as a democratic citizen, and as a way of promoting well-being.Research on older adults learning is considered the fastest growing branch of adult education in post-industrial countries and one of the most crucial challenges facing current adult European education (Formosa, 2000). Older adults learning focuses on the diverse provision of late-life learning, the motivations and interests of older learners, participation in and emancipatory policies for older adult learning, and the benefits of learning at different levels (Schmidt-Hertha, Formosa & Fragoso, 2019). Research in a Swedish context has provided insights into different aspects of older adults learning, such as intergenerational relationships, motivations and benefits, inclusion and participation, online and offline learning, working-life and guidance. The presentation will engage in a dialogue about these topics.
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| 21. |
- Brandberg, Martin, 1972, et al.
(author)
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A comparative study on simple and interference reaction times in women and men.
- 2018
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In: Conference program, The 13th Nordic Meeting in Neuropsychology, Stockholm, 2018.
-
Conference paper (other academic/artistic)abstract
- Introduction: studies on reaction time (RT) indicate faster reactions for men than women. However, when comparing samples across decades, this difference seems to decrease. The aim of this study was to explore reaction times in a large contemporary sample of adult males and females (age range = 15-82). Methods: Simple reaction time and interference reaction time (a go/no go reaction task) were measured with the Vienna Reaction Apparatus (Wiener Reaktionstest, Schuhfried), RT, version S1 and S2 for simple reaction time and version S3 and S4 for interference reaction time. Results: men responded faster on the interference reaction task, S3 (M=441,57, SD=80,86) than women (M=461,53, SD=91,53). This difference was significant, t(3,7) = p<0,001 and represent a small sized effect, d = .21. There were no significant differences regarding simple reaction time (S1 and S2) or on the other interference task (S4). In regards to intraindividual variability there was a significant difference, t(3.1), p =.002, d =.21, with less variability in males (M =65.99) as compared to females (M=70,45) on S3. Conclusions: when comparing groups, men performed slightly faster on one of the interference tasks. However, there were no significant differences on the other measures. This result is consistent with previous studies indicating a decrease in differences on reaction times, comparing men and women.
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| 22. |
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| 24. |
- Broeren, Jurgen, et al.
(author)
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Neglect assessment as an application of virtual reality.
- 2007
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In: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 116:3, s. 157-63
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Journal article (peer-reviewed)abstract
- OBJECTIVE: In this study a cancellation task in a virtual environment was applied to describe the pattern of search and the kinematics of hand movements in eight patients with right hemisphere stroke. METHODS: Four of these patients had visual neglect and four had recovered clinically from initial symptoms of neglect. The performance of the patients was compared with that of a control group consisting of eight subjects with no history of neurological deficits. RESULTS: Patients with neglect as well as patients clinically recovered from neglect showed aberrant search performance in the virtual reality (VR) task, such as mixed search pattern, repeated target pressures and deviating hand movements. The results indicate that in patients with a right hemispheric stroke, this VR application can provide an additional tool for assessment that can identify small variations otherwise not detectable with standard paper-and-pencil tests. CONCLUSION: VR technology seems to be well suited for the assessment of visually guided manual exploration in space.
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| 25. |
- Broeren, Jurgen, et al.
(author)
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Virtual rehabilitation after stroke.
- 2008
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In: Studies in health technology and informatics. - 0926-9630 .- 1879-8365. ; 136, s. 77-82
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Journal article (peer-reviewed)abstract
- The purpose of this project was to investigate the effects of Virtual Reality technology and haptics for stroke rehabilitation. Twenty-nine stroke subjects, 17 women, and 12 men aged 44-85 years, participated in three different studies. All participants responded favorable to the use of the VR activity station. A change of attitude took place after the subjects were exposed to playing computer games. The general experience with the VR application approach suggests that this treatment concept is promising in stroke rehabilitation, with a wide range of applicability.
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| 26. |
- Brundin, L., et al.
(author)
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An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
- 2016
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Journal article (peer-reviewed)abstract
- Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
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| 27. |
- Byström, Martin, et al.
(author)
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Five-Year Results of a Randomized, Controlled Trial of Collagenase Treatment Compared With Needle Fasciotomy for Dupuytren Contracture
- 2022
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In: Journal of Hand Surgery. - : Elsevier BV. - 0363-5023. ; 47:3, s. 211-217
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Journal article (peer-reviewed)abstract
- Purpose: Over the past decade, collagenase treatment and needle fasciotomy (NF) have gained widespread popularity in the treatment of Dupuytren contracture. This prospective study was designed to compare the results of these treatments in terms of clinical and patient-reported outcomes. Methods: A prospective, randomized, controlled trial included patients with a contracture of 20° or more in a single metacarpophalangeal joint. Patients were allocated to treatment with either NF or collagenase Clostridium histolyticum. The primary outcome was a reduction in the metacarpophalangeal joint contracture to less than 5°. Secondary outcomes included recurrence, the presence of Dupuytren cords, and changes in patient-reported outcomes. The participants were examined 5 years after the intervention. Results: The study cohort comprised 156 patients divided into 2 equally sized groups. After 5 years, data were collected from 143 (92 %) of the initially enrolled participants. The mean time for the clinical follow-up was 5.1 years. In the remaining cohort without a second procedure, 51% (23 patients) in the collagenase Clostridium histolyticum group and 47% (27 patients) in the NF group still had extension deficits of less than 5°. Among the participants with a successful initial procedure, the recurrence rate was 56% (36 patients) in the collagenase Clostridium histolyticum group and 45% (30 patients) in the NF group. There were no differences between the 2 treatments in regard to passive joint extension, reduction of contracture, range of motion, or patient-reported outcomes. Conclusions: The 5-year outcomes for NF are similar to those for collagenase in terms of sustained correction, recurrence, presence of Dupuytren cords, and patient-reported outcomes for the treatment of metacarpophalangeal joint contractures. Type of study/level of evidence: Therapeutic I. © 2021 American Society for Surgery of the Hand
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| 28. |
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| 29. |
- Dupont, Chris L., et al.
(author)
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Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549-
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Journal article (peer-reviewed)abstract
- Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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| 30. |
- Emanuel, Robyn M, et al.
(author)
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Myeloproliferative Neoplasm (MPN) Symptom Assessment Form Total Symptom Score : Prospective International Assessment of an Abbreviated Symptom Burden Scoring System Among Patients With MPNs
- 2012
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In: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:33, s. 4098-4103
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Journal article (peer-reviewed)abstract
- PURPOSE Myeloproliferative neoplasm (MPN) symptoms are troublesome to patients, and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies. We aimed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy.PATIENTS AND METHODSThe Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) was calculated as the mean score for 10 items from two previously validated scoring systems. Questions focus on fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers.RESULTS MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 (standard deviation [SD], 16.3). MPN-SAF TSS results significantly differed among MPN disease subtypes (P < .001), with a mean of 18.7 (SD, 15.3), 21.8 (SD, 16.3), and 25.3 (SD, 17.2) for patients with essential thrombocythemia, polycythemia vera, and myelofibrosis, respectively. The MPN-SAF TSS strongly correlated with overall quality of life (QOL; r = 0.59; P < .001) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) functional scales (all P < .001 and absolute r ≥ 0.50 except social functioning r = 0.48). No significant trends were present when comparing therapy subgroups. The MPN-SAF TSS had excellent internal consistency (Cronbach's α = .83). Factor analysis identified a single underlying construct, indicating that the MPN-SAF TSS is an appropriate, unified scoring method.CONCLUSIONThe MPN-SAF TSS is a concise, valid, and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospective MPN symptom study to date. This new prospective scoring method may be used to assess MPN symptom burden in both clinical practice and trial settings.
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| 31. |
- Enmark, Martin, 1984-, et al.
(author)
-
A closer study of peak distortions in supercritical fluid chromatography as generated by the injection
- 2015
-
In: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1400, s. 131-139
-
Journal article (peer-reviewed)abstract
- Abstract In SFC the sample cannot be dissolved in the mobile phase, so it is often dissolved in pure modifier, or another liquid, sometimes resulting in serious distortions of the eluted peak profiles already at moderately high injection volumes. It is suspected the reasons for these effects are solvent strength mismatch and/or viscosity mismatch. This study presents a systematic and fundamental investigation of the origin of these peak deformations due to the injection solvent effects in SFC, using both systematic experiments and numerical modeling. The first set of experiments proved that the injection volume and the elution strength of the sample solution had a major impact of the shapes of the eluted peaks. Secondly, the sample band elution profile was numerically modeled on a theoretical basis assuming both un-retained and retained co-solvent injection plugs, respectively. These calculations quantitatively confirmed our first set of experiments but also pointed out that there is also an additional significant effect. Third, viscous fingering experiments were performed using viscosity contrast conditions imitating those encountered in SFC. These experiments clearly proved that viscous fingering effects play a significant role. A new method for determination of adsorption isotherms of solvents was also developed, called the “Retention Time Peak Method” (RTPM). The RTPM was used for fast estimation of the adsorption isotherms of the modifier and required using only two experiments.
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| 32. |
- Enmark, Martin, et al.
(author)
-
A Deeper Investigation of Strange Preparative Band Shapes of a Simple Racemic Solute on tris-(3, 5- dimethylphenyl)carbamoyl Cellulose as Chiral Stationary Phase
- 2011
-
Conference paper (peer-reviewed)abstract
- The adsorption equilibria of racemic methyl mandelate on a tris-(3, 5-dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) has a peculiar behavior. The preparative band shape of the more retained enantiomer was very unusual with an inflection point at low concentrations whereas the less retained enantiomer shows normal type I adsorption behavior. For a deeper understanding of this separation adsorption isotherms were determined and further analyzed with Scatchard plots combined with adsorption energy distribution calculations. The less retained enantiomer was best described by Tóth adsorption isotherm while the second enantiomer was best described with a bi-Moreau adsorption isotherm. The Moreau model is an extension of the Langmuir model including non-ideal adsorbate-adsorbate interactions; here the unusual model provided an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated by synthetically generated raw adsorption slope data. It was demonstrated that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-ideal adsorbate-adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature
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| 33. |
- Enmark, Martin, et al.
(author)
-
A Deeper Understanding of a Complex Adsorption Behavior in a Common Chiral, Separation System
- 2011
-
Conference paper (peer-reviewed)abstract
- The adsorption equilibria of racemic methyl mandelate on a tris-(3,5-dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) was investigated. This separation has previously been performed and analyzed on a methylcellulose tribenzoate coated CSP. In that case, both enantiomers could be described with a bi-Langmuir adsorption isotherm, convex upwards (type I). In our case, two fundamentally different properties were observed. First, the elution order was reversed. Furthermore, only the less retained enantiomer shows type I adsorption behavior, while the adsorption isotherm of the more retained compound contained an inflection point at low concentration. To analyze these differences, adsorption isotherms were determined and further analyzed using Scatchard plots and adsorption energy distribution calculations. The less retained enantiomer was best described by Tóth adsorption isotherm while the second enantiomer was best described with a bi-Moreau adsorption isotherm. The Moreau model is an extension of the Langmuir model including non-ideal adsorbate-adsorbate interactions; here the unusual model provided an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated by synthetically generated raw adsorption slope data. It was demonstrated that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-idealadsorbate-adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature.
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| 34. |
- Enmark, Martin, 1984-, et al.
(author)
-
A Retention-Matching Strategy for Method Transfer in Supercritical Fluid Chromatography : Introducing the Isomolar Plot Approach
- 2021
-
In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 93:16, s. 6385-6393
-
Journal article (peer-reviewed)abstract
- A strategy to match any retention shifts due to increased or decreased pressure drop during supercritical fluid chromatography (SFC) method transfer is presented. The strategy relies on adjusting the co-solvent molarity without the need to adjust the back-pressure regulator. Exact matching can be obtained with minimal changes in separation selectivity. To accomplish this, we introduce the isomolar plot approach, which shows the variation in molar co-solvent concentration depending on the mass fraction of co-solvent, pressure, and temperature, here exemplified by CO2-methanol. This plot allowed us to unify the effects of the co-solvent mass fraction and density on retention in SFC. The approach, which was verified on 12 known empirical retention models for each enantiomer of six basic pharmaceuticals, allowed us to numerically calculate the apparent retention factor for any column pressure drop. The strategy can be implemented either using a mechanistic approach if retention models are known or empirically by iteratively adjusting the co-solvent mass fraction. As a rule of thumb for the empirical approach, we found that the relative mass fraction adjustment needed is proportional to the relative change in the retention factor caused by a change in the pressure drop. Different proportionality constants were required to match retention in the case of increasing or decreasing pressure drops.
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| 35. |
- Enmark, Martin, et al.
(author)
-
A systematic investigation of algorithm impact in preparative chromatography with experimental verifications
- 2011
-
In: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673 .- 1873-3778. ; 1218:5, s. 662-672
-
Journal article (peer-reviewed)abstract
- Computer-assisted optimization of chromatographic separations requires finding the numerical solution of the Equilibrium-Dispersive (ED) mass balance equation. Furthermore, the competitive adsorption isotherms needed for optimization are often estimated numerically using the inverse method that also solves the ED equations. This means that the accuracy of the estimated adsorption isotherm parameters explicitly depends on the numerical accuracy of the algorithm that is used to solve the ED equations. The fast and commonly used algorithm for this purpose, the Rouchon Finite Difference (RFD) algorithm, has often been reported not to be able to accurately solve the ED equations for all practical preparative experimental conditions, but its limitations has never been completely and systematically investigated. In this study, we thoroughly investigate three different algorithms used to solve the ED equations: the RFD algorithm, the Orthogonal Collocation on Finite Elements (OCFE) method and a Central Difference Method (CDM) algorithm, both for increased theoretical understanding and for real cases of industrial interest. We identified discrepancies between the conventional RFD algorithm and the more accurate OCFE and CDM algorithms for several conditions, such as low efficiency, increasing number of simulated components and components present at different concentrations. Given high enough efficiency, we experimentally demonstrate good prediction of experimental data of a quaternary separation problem using either algorithm, but better prediction using OCFE/CDM for a binary low efficiency separation problem or separations when the compounds have different efficiency. Our conclusion is to use the RFD algorithm with caution when such conditions are present and that the rule of thumb that the number of theoretical plates should be greater than 1000 for application of the RFD algorithm is underestimated in many cases
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| 36. |
- Enmark, Martin, et al.
(author)
-
A systematic investigation on the accuracy of computer simulations for optical isomers in industrial settings
- 2010
-
Conference paper (peer-reviewed)abstract
- Predicting the band profiles of typical chromatographic separations using the approach of the inverse method (IM) [2] requires finding the numerical solution of the Equilibrium-Dispersive (ED) mass balance equation [1]. The accuracy of the determination of the competitive adsorption isotherms is therefore explicitly dependent on the choice of algorithm to solve the ED model. Earlier studies have shown that the well known RFD algorithm [3] has limitations in its accuracy for certain simulated conditions such as column efficiency and adsorption isotherm type [5]. In this study, we thoroughly investigate three different algorithms, the rapid and well known Rouchon Finite Difference (RFD) algorithm [3], the Orthogonal Collocation on Finite Elements (OCFE) method [4] and the Central Difference Method (CDM) algorithm developed by us. Firstly, a systematic investigation is made, comparing the different algorithms under a broad range of different synthetic conditions. Secondly, we apply all three algorithms using the IM on real experimental systems; (I) one high efficiency quaternary separation and (II) one pharmaceutical industry application with a chiral intermediate separation. We have found discrepancies between the conventional (RFD) and the more accurate (OCFE and CDM) algorithms for several synthetic conditions such as low efficiency, increasing number of simulated components and components present at different concentrations. Given high enough efficiency, we experimentally demonstrate good prediction of experimental data of a quaternary separation problem using either algorithm but better prediction of OCFE/CDM for a binary low efficiency separation problem. Our conclusion is to use the RFD algorithm with caution when any of the particular conditions we have investigated is valid. When the highest accuracy is sought, there is no doubt that OCFE or CDM should be the algorithms of choice. However, given the computational speed of RFD, we also recommend it for preliminary parameter fitting. For conditions where we have shown the algorithms to produce practically identical solutions, RFD can be applied with greater certainty. It remains to be thoroughly investigated the effect on the particular shape of the adsorption isotherm on the obtained solution, for example type III having inflection points.
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| 37. |
- Enmark, Martin, et al.
(author)
-
A thermodynamic and kinetic study of an unusual adsorption behavior-Methyl Mandelate on commercially available Tris-(3,5- dimethylphenyl)carbamoyl Cellulose Chiral Stationary Phase
- 2012
-
Conference paper (other academic/artistic)abstract
- The adsorption equilibria of racemic methyl mandelate on a tris-(3,5- dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) was investigated. The following were observed, the less retained enantiomer shows “Langmuirian†(type I) adsorption behavior, while the adsorption isotherm of the more retained compound contained an inflection point at low concentration. To analyze these differences, adsorption isotherms were determined and further analyzed using Scatchard plots and adsorption energy distribution (AED) calculations. The less retained enantiomer was best described by heterogeneous unimodal adsorption model (Tóth) while the second enantiomer was best described with a heterogeneous adsorption model with adsorbate-adsorbate interactions (bi-Moreau). The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-idealadsorbate-adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature. This is an industrial – academic cooperation in the Fundamental Separation Science Group www.separationscience.se
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| 38. |
- Enmark, Martin, et al.
(author)
-
Adsorption Isotherm Determination for Reliable Phase System Characterization in SFC : Challenges and Pitfalls
- 2012
-
Conference paper (peer-reviewed)abstract
- Recently the pharmaceutical industry has started to replace HPLC with SFC because of incentives to lower the environmental impact and as well as increasing performance. Reliable characterization of the adsorption processes in SFC, is therefore of utmost importance. The key thermodynamic phase system information is obtained by rigorous determination of adsorption isotherms over a broad concentration range. If properly processed, this data gives not only correct information about the degree of heterogeneity but also the values of the energy of interactions and monolayer capacities of each individual type of adsorption site in the phase system; ultimately, this can result in identification of the types of interactions (dipole-dipole, van der Waals interactions etc.). In this study, we will present the transfer of LC adsorption characterization methods to SFC conditions using several model compounds with several different methods for adsorption isotherm determination traditionally applied with success in LC, and now modified for SFC. We have limited our investigation to methanol as modifier and used the operational conditions, temperature and backpressure most typically observed in industrial settings; in addition, we have used commercial standard SFC-equipment. The results clearly shows that adsorption isotherm determinations in SFC are considerably more complicated than in LC; we will go through the most important pitfalls and give guidelines for more rigorous determinations of adsorption data in SFC. This is an industrial – academic cooperation in the Fundamental Separation Science Group www.separationscience.se
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| 39. |
- Enmark, Martin, 1984-, et al.
(author)
-
Analytical and preparative separation of phosphorothioated oligonucleotides : Columns and ion-pair reagents
- 2020
-
In: Analytical and Bioanalytical Chemistry. - : Springer. - 1618-2642 .- 1618-2650. ; 412:2, s. 299-309
-
Journal article (peer-reviewed)abstract
- Oligonucleotide drugs represent an emerging area in the pharmaceutical industry. Solid-phase synthesis generates many structurally closely related impurities, making efficient separation systems for purification and analysis a key challenge during pharmaceutical drug development. To increase the fundamental understanding of the important preparative separation step, mass-overloaded injections of a fully phosphorothioated 16mer, i.e., deoxythymidine oligonucleotide, were performed on a C18 and a phenyl column. The narrowest elution profiles were obtained using the phenyl column, and the 16mer could be collected with high purity and yield on both columns. The most likely contribution to the successful purification was the quantifiable displacement of the early-eluting shortmers on both columns. In addition, the phenyl column displayed better separation of later-eluting impurities, such as the 17mer impurity. The mass-overloaded injections resulted in classical Langmuirian elution profiles on all columns, provided the concentration of the ion-pairing reagent in the eluent was sufficiently high. Two additional column chemistries, C4 and C8, were also investigated in terms of their selectivity and elution profile characteristics for the separation of 520mers fully phosphorothioated deoxythymidine oligonucleotides. When using triethylamine as ion-pairing reagent to separate phosphorothioated oligonucleotides, we observed peak broadening caused by the partial separation of diastereomers, predominantly seen on the C4 and C18 columns. When using the ion-pair reagent tributylamine, to suppress diastereomer separation, the greatest selectivity was found using the phenyl column followed by C18. The present results will be useful when designing and optimizing efficient preparative separations of synthetic oligonucleotides.
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| 40. |
- Enmark, Martin, 1984-, et al.
(author)
-
Building machine-learning-based models for retention time and resolution predictions in ion pair chromatography of oligonucleotides
- 2022
-
In: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1671
-
Journal article (peer-reviewed)abstract
- Support vector regression models are created and used to predict the retention times of oligonucleotides separated using gradient ion-pair chromatography with high accuracy. The experimental dataset consisted of fully phosphorothioated oligonucleotides. Two models were trained and validated using two pseudo orthogonal gradient modes and three gradient slopes. The results show that the spread in retention time differs between the two gradient modes, which indicated varying degree of sequence dependent separation. Peak widths from the experimental dataset were calculated and correlated with the guanine cytosine content and retention time of the sequence for each gradient slope. This data was used to predict the resolution of the n - 1 impurity among 250 0 0 0 random 12-and 16-mer sequences; showing one of the investigated gradient modes has a much higher probability of exceeding a resolution of 1.5, particularly for the 16-mer sequences. Sequences having a high guanine-cytosine content and a terminal C are more likely to not reach critical resolution. The trained SVR models can both be used to identify characteristics of different separation methods and to assist in the choice of method conditions, i.e. to optimize resolution for arbitrary sequences. The methodology presented in this study can be expected to be applicable to predict retention times of other oligonucleotide synthesis and degradation impurities if provided enough training data.
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| 41. |
- Enmark, Martin, et al.
(author)
-
Characterization of an unusual adsorption behavior of racemic methyl-mandelate on a tris-(3,5-dimethylphenyl) carbamoyl cellulose chiral stationary phase
- 2011
-
In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1218:38, s. 6688-6696
-
Journal article (peer-reviewed)abstract
- An interesting adsorption behavior of racemic methyl mandelate on a tris-(3,5-dimethylphenyl)carbamoyl cellulose chiral stationary phase was theoretically and experimentally investigated. The overloaded band of the more retained enantiomer had a peculiar shape indicating a type V adsorption isotherm whereas the overloaded band of the less retained enantiomer had a normal shape indicating a type I adsorption behavior. For a closer characterization of this separation, adsorption isotherms were determined and analyzed using an approach were Scatchard plots and adsorption energy distribution (AED) calculations are combined for a deeper analysis. It was found that the less retained enantiomer was best described by a Tóth adsorption isotherm while the second one was best described with a bi-Moreau adsorption isotherm. The latter model comprises non-ideal adsorbate–adsorbate interactions, providing an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated using synthetically generated raw adsorption slope data. It was found that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and found to be exothermic; i.e. the adsorbate–adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process revealed that the average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature.
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| 42. |
- Enmark, Martin, et al.
(author)
-
Characterization of the Adsorption of Racemic Methyl Mandelate on Tris-(3,5-dimethylphenyl)carbamoyl Cellulose Chiral Stationary Phase
- 2011
-
Conference paper (peer-reviewed)abstract
- The adsorption equilibria of racemic methyl mandelate on a tris-(3,5-dimethylphenyl)carbamoyl cellulose chiral stationary phase (CSP) was investigated. This separation has previously been performed and analyzed on a methylcellulose tribenzoate coated CSP. In that case, both enantiomers could be described with a bi-Langmuir adsorption isotherm, convex upwards (type I). In our case, two fundamentally different properties were observed. First, the elution order was reversed. Furthermore, only the less retained enantiomer shows type I adsorption behavior, while the adsorption isotherm of the more retained compound contained an inflection point at low concentration. To analyze these differences, adsorption isotherms were determined and further analyzed using Scatchard plots and adsorption energy distribution calculations. The less retained enantiomer was best described by Tóth adsorption isotherm while the second enantiomer was best described with a bi-Moreau adsorption isotherm. The Moreau model is an extension of the Langmuir model including non-ideal adsorbate-adsorbate interactions; here the unusual model provided an explanation to the non-ideal adsorption of the more retained enantiomer. Furthermore, the possibility of using the Moreau model as a local model for adsorption in AED calculations was evaluated by synthetically generated raw adsorption slope data. It was demonstrated that the AED accurately could predict the number of adsorption sites for the generated data. The adsorption behavior of both enantiomers was also studied at several different temperatures and it was found to be exothermic; in addition, the non-idealadsorbate-adsorbate interaction strength decreases with increasing temperature. Stochastic analysis of the adsorption process could identify a single kinetic site for each enantiomer. The average amount of adsorption/desorption events increases and the sojourn time decreases with increasing temperature.
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| 43. |
- Enmark, Martin, et al.
(author)
-
Computer Assisted Optimization of Pharmaceutical Purification - The Impact of Algorithms and Experimental Approach
- 2010
-
Conference paper (peer-reviewed)abstract
- Computer assisted process optimization of chromatographic separations requires the selection of computer algorithms and measurement of relevant parameters. In this study, we will investigate how the choice of algorithms and the number of performed initial experiments affect the estimated optimal separations conditions. We will focus on conditions typically encountered for slurry packing coated 20 µm CSP in large-scale columns used for pharmaceutical intermediate purification.Probably the most essential for parameters in this context are the adsorption isotherm parameters for the components. The rapid "inverse method" is commonly used and this method requires that one numerically solve the mass balance equations describing the chromatographic process. Here we thoroughly investigate how different algorithms that solve the Equilibrium-Dispersive (ED) mass balance equations will affect the estimated adsorption isotherm parameters.Furthermore, we will investigate and compare how different strategies affect the prediction of the optimal separation conditions. First, we will use a more rapid approach that requires a minimum of experiments and uses standard algorithms to estimate optimal conditions. Secondly, we will use a more exact approach that requires more experiments and uses more advanced simulation- and optimization algorithms
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| 44. |
- Enmark, Martin, 1984-, et al.
(author)
-
Determination of adsorption isotherms in supercritical fluid chromatography
- 2013
-
In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1312, s. 124-133
-
Journal article (peer-reviewed)abstract
- Abstract In this study we will demonstrate the potential of modern integrated commercial analytical SFC-systems for rapid and reliable acquisition of thermodynamic data. This will be done by transferring the following adsorption isotherm determination methods from liquid chromatography (LC) to supercritical fluid chromatography (SFC): Elution by Characteristic Points (ECP), the Retention Time Method (RTM), the Inverse Method (IM) and the Perturbation Peak (PP) method. In order to transfer these methods to SFC in a reliable, reproducible way we will demonstrate that careful system verification using external sensors of mass flow, temperature and pressure are needed first. The adsorption isotherm data generated by the different methods were analyzed and compared and the adsorption isotherms ability to predict new experimental elution profiles was verified by comparing experiments with simulations. It was found that adsorption isotherm data determined based on elution profiles, i.e., ECP, IM and RTM, were able to accurately predict overloaded experimental elution profiles while the more tedious and time-consuming PP method, based on small injections on concentration plateaus, failed in doing so.
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| 45. |
- Enmark, Martin, 1984-, et al.
(author)
-
Development of a unified gradient theory for ion-pair chromatography using oligonucleotide separations as a model case
- 2023
-
In: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1691
-
Journal article (peer-reviewed)abstract
- Ion-pair chromatography is the de facto standard for separating oligonucleotides and related impurities, particularly for analysis but also often for small-scale purification. Currently, there is limited understanding of the quantitative modeling of both analytical and overloaded elution profiles obtained during gradient elution in ion-pair chromatography. Here we will investigate a recently introduced gradient mode, the so-called ion-pairing reagent gradient mode, for both analytical and overloaded separations of oligonucleotides. The first part of the study demonstrates how the electrostatic theory of ion-pair chromatography can be applied for modeling gradient elution of oligonucleotides. When the ion-pair gradient mode is used in a region where the electrostatic surface potential can be linearized, a closed-form expression of retention time can be derived. A unified retention model was then derived, applicable for both ion-pair reagent gradient mode as well as co-solvent gradient mode. The model was verified for two different experimental systems and homo- and heteromeric oligonucleotides of different lengths. Quantitative modeling of overloaded chromatography using the ion-pairing reagent gradient mode was also investigated. Firstly, a unified adsorption isotherm model was developed for both gradient modes. Then, adsorption isotherms parameter of a model oligonucleotide and two major synthetic impurities were estimated using the inverse method. Secondly, the parameters of the adsorption isotherm were then used to investigate how the productivity of oligonucleotide varies with injection volume, gradient slope, and initial retention factor. Here, the productivity increased when using a shallow gradient slope combined with a low initial retention factor. Finally, experiments were conducted to confirming some of the model predictions. Comparison with the conventional co-solvent gradient mode showed that the ion-pairing reagent gradient leads to both higher yield and productivity while consuming less co-solvent.
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| 46. |
- Enmark, Martin, et al.
(author)
-
Enantioseparation of omeprazole effect of different packing particle size on productivity
- 2012
-
In: Journal of Chromatography A. - Amsterdam : Elsevier. - 0021-9673. ; 1240:1, s. 123-131
-
Journal article (peer-reviewed)abstract
- Enantiomeric separation of omeprazole has been extensively studied regarding both product analysis and preparation using several different chiral stationary phases. In this study, the preparative chiral separation of omeprazole is optimized for productivity using three different columns packed with amylose tris (3,5-dimethyl phenyl carbamate) coated macroporous silica (5, 10 and 25 Όm) with a maximum allowed pressure drop ranging from 50 to 400 bar. This pressure range both covers low pressure process systems (50–100 bar) and investigates the potential for allowing higher pressure limits in preparative applications in a future. The process optimization clearly show that the larger 25 Όm packing material show higher productivity at low pressure drops whereas with increasing pressure drops the smaller packing materials have substantially higher productivity. Interestingly, at all pressure drops, the smaller packing material result in lower solvent consumption (L solvent/kg product); the higher the accepted pressure drop, the larger the gain in reduced solvent consumption. The experimental adsorption isotherms were not identical for the different packing material sizes; therefore all calculations were recalculated and reevaluated assuming identical adsorption isotherms (with the 10 Όm isotherm as reference) which confirmed the trends regarding productivity and solvent consumption.
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| 47. |
- Enmark, Martin, et al.
(author)
-
Evaluation of scale-up from analytical to preparative supercritical fluid chromatography
- 2015
-
In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1425, s. 280-286
-
Journal article (peer-reviewed)abstract
- An approach for reliable transfer from analytical to preparative scale supercritical fluid chromatography was evaluated. Here, we accounted for the conditions inside the columns as well as to the fact that most analytical instruments are volume-controlled while most preparative scale units are mass-controlled. The latter is a particular problem when performing pilot scale experiments and optimizations prior to scaling up to production scale. This was solved by measuring the mass flow, the pressure and the temperature on the analytical unit using external sensors. Thereafter, it was revealed with a design of experiments approach that the methanol fraction and the pressure are the two most important parameters to control for preserved retention throughout the scale-up; for preserved selectivity the temperature was most important in this particular system. Using this approach, the resulting chromatograms from the preparative unit agreed well with those from the analytical unit while keeping the same column length and particles size. A brief investigation on how the solute elution volume varies with the volumetric flow rate revealed a complex dependency on pressure, density and apparent methanol content. Since the methanol content is a parameter of great importance to control during the scale up, we must be careful when changing operational and column design conditions which generates deviations in pressure, density and methanol content between different columns. (C) 2015 Elsevier B.V. All rights reserved.
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| 48. |
- Enmark, Martin, 1984-, et al.
(author)
-
Investigation of factors influencing the separation of diastereomers of phosphorothioated oligonucleotides
- 2019
-
In: Analytical and Bioanalytical Chemistry. - : Springer. - 1618-2642 .- 1618-2650. ; 411:15, s. 3383-3394
-
Journal article (peer-reviewed)abstract
- This study presents a systematic investigation of factors influencing the chromatographic separation of diastereomers of phosphorothioated pentameric oligonucleotides as model solutes. Separation was carried out under ion-pairing conditions using an XBridge C18 column. For oligonucleotides with a single sulfur substitution, the diastereomer selectivity was found to increase with decreasing carbon chain length of the tertiary alkylamine used as an ion-pair reagent. Using an ion-pair reagent with high selectivity for diastereomers, triethylammonium, it was found the selectivity increased with decreased ion-pair concentration and shallower gradient slope. Selectivity was also demonstrated to be dependent on the position of the modified linkage. Substitutions at the center of the pentamer resulted in higher diastereomer selectivity compared to substitutions at either end. For mono-substituted oligonucleotides, the retention order and stereo configuration were consistently found to be correlated, with Rp followed by Sp, regardless of which linkage was modified. The type of nucleobase greatly affects the observed selectivity. A pentamer of cytosine has about twice the diastereomer selectivity of that of thymine. When investigating the retention of various oligonucleotides eluted using tributylammonium as the ion-pairing reagent, no diastereomer selectivity could be observed. However, retention was found to be dependent on both the degree and position of sulfur substitution as well as on the nucleobase. When analyzing fractions collected in the front and tail of overloaded injections, a significant difference was found in the ratio between Rp and Sp diastereomers, indicating that the peak broadening observed when using tributylammonium could be explained by partial diastereomer separation.
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| 49. |
- Enmark, Martin, 1984-, et al.
(author)
-
Investigation of plateau methods for adsorption isotherm determination in supercritical fluid chromatography
- 2014
-
In: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1354, s. 129-138
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Journal article (peer-reviewed)abstract
- The Perturbation Peak (PP) method and Frontal analysis (FA) are considered as the most accurate methods for adsorption isotherms determination in liquid chromatography. In this study we investigate and explain why this is not the case in Supercritical Fluid Chromatography (SFC), where the PP method does not work at all, using a modern analytical system. The main reason was found to be that the solute to be studied must be dissolved in the MeOH reservoir before it is mixed with CO2. Since the solute occupies a certain partial volume in the reservoir, the larger the solute content the larger this fractional volume will be, and the final MeOH fraction in the mobile phase will then be smaller compared to the bulk mobile phase without solute in the modifier. If the retention of small injections on the concentration plateaus, i.e., “analytical-size” perturbation peaks, is sensitive to small variations of MeOH in the eluent, this will seriously decrease the accuracy of the PP method. This effect was verified and compensated for and we also demonstrated that the same problem will occur in frontal analysis, another concentration plateau method.
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- Enmark, Martin, 1984-, et al.
(author)
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Investigation of robustness for supercritical fluid chromatography separation of peptides : Isocratic vs gradient mode
- 2018
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In: Journal of Chromatography A. - : Elsevier. - 0021-9673 .- 1873-3778. ; 1568, s. 177-187
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Journal article (peer-reviewed)abstract
- We investigated and compared the robustness of supercritical fluid chromatography (SFC) separations of the peptide gramicidin, using either isocratic or gradient elution. This was done using design of experiments in a design space of co-solvent fraction, water mass fraction in co-solvent, pressure, and temperature. The density of the eluent (CO2-MeOH-H2O) was experimentally determined using a Coriolis mass flow meter to calculate the volumetric flow rate required by the design. For both retention models, the most important factor was the total co-solvent fraction and water mass fraction in co-solvent. Comparing the elution modes, we found that gradient elution was more than three times more robust than isocratic elution. We also observed a relationship between the sensitivity to changes and the gradient steepness and used this to draw general conclusions beyond the studied experimental system. To test the robustness in a practical context, both the isocratic and gradient separations were transferred to another laboratory. The gradient elution was highly reproducible between laboratories, whereas the isocratic system was not. Using measurements of the actual operational conditions (not the set system conditions), the isocratic deviation was quantitatively explained using the retention model. The findings indicate the benefits of using gradient elution in SFC as well as the importance of measuring the actual operational conditions to be able to explain observed differences between laboratories when conducting method transfer.
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