| 1. |
- Forssén, Patrik, 1966-, et al.
(författare)
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Reliable Strategy for Analysis of Complex Biosensor Data
- 2018
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 90:8, s. 5366-5374
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Tidskriftsartikel (refereegranskat)abstract
- When using biosensors, analyte biomolecules of several different concentrations are percolated over a chip with immobilized ligand molecules that form complexes with analytes. However, in many cases of biological interest, e.g., in antibody interactions, complex formation steady-state is not reached. The data measured are so-called sensorgram, one for each analyte concentration, with total complex concentration vs time. Here we present a new four-step strategy for more reliable processing of this complex kinetic binding data and compare it with the standard global fitting procedure. In our strategy, we first calculate a dissociation graph to reveal if there are any heterogeneous interactions. Thereafter, a new numerical algorithm, AIDA, is used to get the number of different complex formation reactions for each analyte concentration level. This information is then used to estimate the corresponding complex formation rate constants by fitting to the measured sensorgram one by one. Finally, all estimated rate constants are plotted and clustered, where each cluster represents a complex formation. Synthetic and experimental data obtained from three different QCM biosensor experimental systems having fast (close to steady-state), moderate, and slow kinetics (far from steady-state) were evaluated using the four-step strategy and standard global fitting. The new strategy allowed us to more reliably estimate the number of different complex formations, especially for cases of complex and slow dissociation kinetics. Moreover, the new strategy proved to be more robust as it enables one to handle system drift, i.e., data from biosensor chips that deteriorate over time.
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| 2. |
- Lupu, Diana, et al.
(författare)
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The ENDpoiNTs Project : Novel Testing Strategies for Endocrine Disruptors Linked to Developmental Neurotoxicity
- 2020
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 21:11
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Tidskriftsartikel (refereegranskat)abstract
- Ubiquitous exposure to endocrine-disrupting chemicals (EDCs) has caused serious concerns about the ability of these chemicals to affect neurodevelopment, among others. Since endocrine disruption (ED)-induced developmental neurotoxicity (DNT) is hardly covered by the chemical testing tools that are currently in regulatory use, the Horizon 2020 research and innovation action ENDpoiNTs has been launched to fill the scientific and methodological gaps related to the assessment of this type of chemical toxicity. The ENDpoiNTs project will generate new knowledge about ED-induced DNT and aims to develop and improve in vitro, in vivo, and in silico models pertaining to ED-linked DNT outcomes for chemical testing. This will be achieved by establishing correlative and causal links between known and novel neurodevelopmental endpoints and endocrine pathways through integration of molecular, cellular, and organismal data from in vitro and in vivo models. Based on this knowledge, the project aims to provide adverse outcome pathways (AOPs) for ED-induced DNT and to develop and integrate new testing tools with high relevance for human health into European and international regulatory frameworks.
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| 3. |
- Multia, Evgen, et al.
(författare)
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Thermodynamic and kinetic approaches for evaluation of monoclonal antibody - Lipoprotein interactions
- 2017
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 518, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins. Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy Distribution (AED) calculations provided information on the heterogeneity of the interactions without any a priori model assumptions. The AED calculations evidenced a homogenous binding site distribution for the interactions. Quartz Crystal Microbalance (QCM) studies were used to evaluate thermodynamics and kinetics of the Low-Density Lipoprotein (LDL) and anti-apoB-100 Mab interactions. High affinity and selectivity were observed, and the emerging data sets were analysed with so called Interaction Maps. In thermodynamic studies, the interaction between LDL and anti-apoB-100 Mab was found to be predominantly enthalpy driven. Both techniques were also used to study antibody interactions with Intermediate-Density (IDL) and Very Low Density (VLDL) Lipoproteins. By screening affinity constants for IDL-VLDL sample in a single injection we were able to distinguish affinity constants for both subpopulations using the numerical Interaction Map tool.
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| 4. |
- Nyberg, Lars, et al.
(författare)
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Skogsmarkens kemi i Värmland : En jämförelse av ståndortskarteringen och Värmlandsundersökningen
- 1998
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten redovisar en jämförelse av två markkemiska undersökningar i Värmland, Värmlandsundersökningen på 180 platser 1994, och den nationella ståndortskarte-ringen på upp till 89 platser 1983-87. I jämförelsen har data för mark-pH, utbytbart förråd av katjoner och mineraljordens totalinnehåll av element tagits med. Jämförelsen påverkades av ett antal faktorer som skiljde sig åt i de båda undersökningarna, t ex att antalet provpunkter var olika, att provtagningen i ståndortskarteringen omfattade olika typer av jordmåner medan Värmlandsundersökningen endast omfattade podsolerade jordar och att de kemiska analyserna utfördes med delvis olika metoder.För mark-pH och de olika katjonerna i det utbytbara förrådet var såväl medelnivåerna som de regionala variationsmönstren olika för ståndortskarteringen och Värmlands-undersökningen. Skill-naden i nivå kan förklaras av att rikare jordar ingick i ståndorts-karteringen. Dessutom kan surt ned-fall under de ca tio år som skiljde undersökning-arna i tiden ha sänkt mark-pH och minskat det utbytbara förrådet av baskatjoner, även om det sura nedfallet minskat under perioden. Jämförelser av huvudelementen i mine-raljorden visade på relativt god överensstämmelse mellan ståndortskarteringen och Värmlandsundersökningen, såväl vad gäller medelnivå i länet och vad gäller den geo-grafiska variationen. För spårelementen i mineraljorden skilde medelnivåerna stort mellan ståndortskarteringen och Värmlandsundersökningen, troligen beroende på att provtagningsdjupen var olika
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| 5. |
- Rydell, Alexis, 1982-
(författare)
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Partsrelationer vid nedläggningar av produktionsenheter
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nedläggningar är en återkommande företeelse på den svenska arbetsmarknaden. I föreliggande avhandling av Alexis Rydell ligger fokus på relationerna mellan ledning och arbetstagarorganisationer under nedläggningsprocesser. Ett nedläggningsbeslut skapar spänning mellan parterna, inte minst eftersom nedläggningsbeslutet ofta innebär negativa konsekvenser för de anställda. Avhandlingen visar hur olika förhållningssätt mellan parterna kan skapa olika förutsättningar för att reducera spänningen och mildra de negativa konsekvenserna. Utifrån fallstudier identifieras nyckelfaktorer för partssamverkan och hur konstruktiva lösningar kan möjliggöras under processen. Dessutom analyseras vilka kontextuella faktorer som påverkar processen och dess potentiella inverkan på utfallen. Avslutningsvis presenteras ett förslag till modell för partsrelationer i nedläggningar.
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| 6. |
- Sapounidou, Maria, et al.
(författare)
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From Cohort to Cohort : A Similar Mixture Approach (SMACH) to Evaluate Exposures to a Mixture Leading to Thyroid-Mediated Neurodevelopmental Effects Using NHANES Data
- 2023
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Ingår i: Toxics. - : MDPI. - 2305-6304. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal exposure to a mixture (MIX N) of eight endocrine-disrupting chemicals has been associated with language delay in children in a Swedish pregnancy cohort. A novel approach was proposed linking this epidemiological association with experimental evidence, where the effect of MIX N on thyroid hormone signaling was assessed using the Xenopus eleuthero-embryonic thyroid assay (XETA OECD TG248). From this experimental data, a point of departure (PoD) was derived based on OECD guidance. Our aim in the current study was to use updated toxicokinetic models to compare exposures of women of reproductive age in the US population to MIX N using a Similar Mixture Approach (SMACH). Based on our findings, 66% of women of reproductive age in the US (roughly 38 million women) had exposures sufficiently similar to MIX N. For this subset, a Similar Mixture Risk Index (SMRIHI) was calculated comparing their exposures to the PoD. Women with SMRIHI > 1 represent 1.1 million women of reproductive age. Older women, Mexican American and other/multi race women were less likely to have high SMRIHI values compared to Non-Hispanic White women. These findings indicate that a reference mixture of chemicals identified in a Swedish cohort—and tested in an experimental model for establishment of (PoDs)—is also of health relevance in a US population.
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