| 1. |
- Andersson, Carl-Henrik, et al.
(author)
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A Genetic Variant of the Sortilin 1 Gene isAssociated with Reduced Risk ofAlzheimer's Disease
- 2016
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 53:4, s. 1353-1363
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder represented by the accumulation of intracellular tau protein and extracellular deposits of amyloid-β (Aβ) in the brain. The gene sortilin 1 (SORT1) has previously been associated with cardiovascular disease in gene association studies. It has also been proposed to be involved in AD pathogenesis through facilitating Aβ clearance by binding apoE/Aβ complexes prior to cellular uptake. However, the neuropathological role of SORT1 in AD is not fully understood. To evaluate the associations between gene variants of SORT1 and risk of AD, we performed genetic analyses in a Swedish case-control cohort. Ten single nucleotide polymorphisms (SNPs), covering the whole SORT1 gene, were selected and genotyped in 620 AD patients and 1107 controls. The SNP rs17646665, located in a non-coding region of the SORT1 gene, remained significantly associated with decreased risk of AD after multiple testing (pc=0.0061). In addition, other SNPs were found to be nominally associated with risk of AD, as well as altered cognitive function and the CSF biomarker Aβ42, but these associations did not survive correction for multiple testing. The fact that SORT1 has been strongly associated with risk of cardiovascular disease is intriguing as cardiovascular disease is also regarded as a risk factor for AD. Finally, increased knowledge about SORT1 function has a potential to increase our understanding of APOE, the strongest risk factor for AD.
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| 2. |
- Angserud, Jenny, et al.
(author)
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On a wear test for rock drill inserts
- 2013
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In: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 301:1-2, s. 109-115
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Journal article (peer-reviewed)abstract
- In this work wear of cemented carbide rock drill inserts is evaluated by using a rotating rock cylinder as counter surface. The influence on wear rate and degradation mechanisms from varying dry and wet conditions, cemented carbide grade, abrasive particle type and size as well as load is studied. The used abrasive media are alumina and silica.Test results show high repeatability and the three tested cemented carbide grades can be differentiated, even though their relative difference in sample hardness is modest. The loads used, 100–200 N, are sufficiently high to cause fracture and wear of the granite rock. The degraded microstructure of inserts tested under wet and dry conditions as well as with added silica particles is similar to field worn inserts. Hence, the same wear mechanisms occur and the test successfully mimics rock drill wear. Typical insert wear includes cracking and fragmentation of WC grains, depletion of Co binder phase and adhered material originating from the rock.Tests under dry conditions always cause less measured wear than tests under wet conditions.Addition of alumina particles, which are harder than the used cemented carbide samples, causes a significant wear rate increase but does not provide wear similar to rock drilling.
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| 3. |
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| 4. |
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| 5. |
- Ekborn, Andreas, et al.
(author)
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High-dose cisplatin with amifostine : ototoxicity and pharmacokinetics
- 2004
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In: The Laryngoscope. - : Wiley. - 0023-852X .- 1531-4995. ; 114:9, s. 1660-1667
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Journal article (peer-reviewed)abstract
- OBJECTIVES/HYPOTHESIS: Ototoxicity is a common side effect of high-dose cisplatin treatment. Thiol-containing chemoprotectors ameliorate cisplatin ototoxicity under experimental conditions. The trial was initiated to test the efficacy of amifostine protection in high-dose cisplatin treatment (125-150 mg/m) for metastatic malignant melanoma, to correlate the ototoxic outcome with cisplatin pharmacokinetics, and to evaluate the importance of using a selective analytical method for the quantification of cisplatin. STUDY DESIGN: Prospective study of 15 patients with stage IV malignant melanoma. METHODS: Clinical follow-up of therapeutic response, pure-tone audiometry, and analysis of cisplatin and its monohydrated complex in blood ultrafiltrate by liquid chromatography with postcolumn derivatization were performed. Ultrafiltered blood platinum was analyzed by inductively coupled plasma mass spectrometry. RESULTS: Ototoxicity and gastrointestinal toxicity were the most prominent side effects. Three patients ultimately required hearing aids. All patients had audiometric changes at one or more frequencies after the second treatment course, and all but one patient reported auditory symptoms. No correlation was found between hearing loss and blood cisplatin pharmacokinetics. Platinum levels determined by inductively coupled plasma mass spectrometry were higher than total platinum levels calculated from cisplatin and monohydrated complex concentrations obtained by liquid chromatography analysis. CONCLUSION: Ototoxicity was unacceptable despite amifostine treatment. Cisplatin pharmacokinetics during the first treatment course were not predictive of hearing loss. Amifostine caused a lowering of dose-normalized area under the concentration-time curve for cisplatin and monohydrated complex. Use of the unselective inductively coupled plasma mass spectrometry analysis leads to an overestimation of active drug. Selective analysis of cisplatin is especially important when evaluating cisplatin pharmacokinetics during chemoprotector treatment.
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| 6. |
- Hellberg, Victoria, et al.
(author)
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Cisplatin and oxaliplatin toxicity : importance of cochlear kinetics as a determinant for ototoxicity
- 2009
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In: Journal of the National Cancer Institute. - Cary : Oxford University Press. - 0027-8874 .- 1460-2105. ; 101:1, s. 37-47
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Journal article (peer-reviewed)abstract
- BACKGROUND: Cisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained.METHODS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration-time curve (AUC). Statistical tests were two-sided.RESULTS: In HCT-116 cells, cisplatin (20 microM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 microM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 microg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 microM x minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics.CONCLUSION: Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.
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| 7. |
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| 8. |
- Holmberg, Kenneth, et al.
(author)
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Residual stresses in TiN, DLC and MoS2 coated surfaces with regard to their tribological fracture behaviour
- 2009
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In: Wear. - : Elsevier BV. - 0043-1648 .- 1873-2577. ; 267:12, s. 2142-2156
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Journal article (peer-reviewed)abstract
- Thin hard coatings on components and tools are used increasingly due to the rapid development in deposition techniques, tribological performance and application skills. The residual stresses in a coated surface are crucial for its tribological performance. Compressive residual stresses in PVD deposited TiN and DLC coatings were measured to be in the range of 0.03-4 GPa on steel substrate and 0.1-1.3 GPa on silicon. MoS2 coatings had tensional stresses in the range of 0.8-1.3 on steel and 0.16 GPa compressive stresses on silicon. The fracture pattern of coatings deposited on steel substrate were analysed both in bend testing and scratch testing. A micro-scale finite element method (FEM) modelling and stress simulation of a 2 m TiN-coated steel surface was carried out and showed a reduction of the generated tensile buckling stresses in front of the sliding tip when compressive residual stresses of 1 GPa were included in the model. However, this reduction is not similarly observed in the scratch groove behind the tip, possibly due to sliding contact-induced stress relaxation. Scratch and bending tests allowed calculation of the fracture toughness of the three coated surfaces, based on both empirical crack pattern observations and FEM stress calculation, which resulted in highest values for TiN coating followed by MoS2 and DLC coatings, being KC = 4-11, about 2, and 1-2 MPa m1/2, respectively. Higher compressive residual stresses in the coating and higher elastic modulus of the coating correlated to increased fracture toughness of the coated surface.
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| 9. |
- Jalde, Francesca Campoccia, et al.
(author)
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Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist : A Randomized Crossover Pilot Study
- 2018
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In: Anesthesiology. - 0003-3022 .- 1528-1175. ; 129:4, s. 769-777
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Journal article (peer-reviewed)abstract
- Background: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. Methods: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. Results: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. Conclusions: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.
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| 10. |
- Kjellman, M., et al.
(author)
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A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors
- 2021
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In: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:9, s. 840-849
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Journal article (peer-reviewed)abstract
- Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.
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| 11. |
- Landgren, Sara, 1980, et al.
(author)
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A novel ARC gene polymorphism is associated with reduced risk of Alzheimer's disease
- 2012
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In: Journal of Neural Transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 119:7, s. 833-842
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) is the most common neurodegenerative disease, and is clinically characterized by cognitive disturbances and the accumulation of the amyloid beta (A beta) peptides in plaques in the brain. Recent studies have shown the links between AD and the immediate-early gene Arc (activity-regulated cytoskeleton-associated protein), involved in synaptic plasticity and memory consolidation. For example, AD mouse models show a decreased expression of Arc mRNA in the brain. In additional, acute A beta application to brain slices leads to a widespread ARC protein diffusion, unlike the normal defined localization to synapses. In this study, we investigated genetic variation in human ARC and the risk of developing AD. To this end, we genotyped 713 subjects diagnosed with AD and 841 controls without dementia. ARC was sequenced in a group of healthy individuals, and seven previously known SNPs and three novel SNPs were identified. Two of the newly found SNPs were intronic and one, +2852(G/A), was located in the 3'UTR. Three tag SNPs were selected, including the novel SNP +2852(G/A), to relate to risk of AD, Mini Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarker levels of total tau (T-tau), hyperphosphorylated tau181 (P-tau(181)) and A beta(1-42). The AA genotype of the newly found 3'-UTR SNP +2852(A/G), was associated with a decreased risk of AD (p (c) = 0.005; OR = 0.74; 95 % CI: 0.61-0.89). No associations of single SNPs or haplotypes with MMSE score or CSF biomarkers were found. Here we report a novel ARC SNP associated with a reduced risk of developing AD. To our knowledge, this is the first study associating a gene variant of ARC with any disease. The location of the SNP within the 3'UTR indicates that dendritic targeting of ARC mRNA could be involved in the molecular mechanisms underlying this protective function. However, further investigation of the importance of this SNP for ARC function, ARC processing and the pathology of AD is needed.
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| 12. |
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| 13. |
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| 14. |
- Pivodic, Aldina, 1978, et al.
(author)
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Development and validation of a new clinical decision support tool to optimize screening for retinopathy of prematurity
- 2022
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In: British Journal of Ophthalmology. - : BMJ Publishing Group Ltd. - 0007-1161 .- 1468-2079. ; 106:11, s. 1573-1580
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Journal article (peer-reviewed)abstract
- BACKGROUND/AIMS: Prematurely born infants undergo costly, stressful eye examinations to uncover the small fraction with retinopathy of prematurity (ROP) that needs treatment to prevent blindness. The aim was to develop a prediction tool (DIGIROP-Screen) with 100% sensitivity and high specificity to safely reduce screening of those infants not needing treatment. DIGIROP-Screen was compared with four other ROP models based on longitudinal weights.METHODS: Data, including infants born at 24-30 weeks of gestational age (GA), for DIGIROP-Screen development (DevGroup, N=6991) originate from the Swedish National Registry for ROP. Three international cohorts comprised the external validation groups (ValGroups, N=1241). Multivariable logistic regressions, over postnatal ages (PNAs) 6-14 weeks, were validated. Predictors were birth characteristics, status and age at first diagnosed ROP and essential interactions.RESULTS: ROP treatment was required in 287 (4.1%)/6991 infants in DevGroup and 49 (3.9%)/1241 in ValGroups. To allow 100% sensitivity in DevGroup, specificity at birth was 53.1% and cumulatively 60.5% at PNA 8 weeks. Applying the same cut-offs in ValGroups, specificities were similar (46.3% and 53.5%). One infant with severe malformations in ValGroups was incorrectly classified as not needing screening. For all other infants, at PNA 6-14 weeks, sensitivity was 100%. In other published models, sensitivity ranged from 88.5% to 100% and specificity ranged from 9.6% to 45.2%.CONCLUSIONS: DIGIROP-Screen, a clinical decision support tool using readily available birth and ROP screening data for infants born GA 24-30 weeks, in the European and North American populations tested can safely identify infants not needing ROP screening. DIGIROP-Screen had equal or higher sensitivity and specificity compared with other models. DIGIROP-Screen should be tested in any new cohort for validation and if not validated it can be modified using the same statistical approaches applied to a specific clinical setting.
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| 15. |
- Pivodic, Aldina, et al.
(author)
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Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity
- 2023
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In: JAMA ophthalmology. - : American Medical Association (AMA). - 2168-6165 .- 2168-6173. ; 141:8, s. 716-716
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Journal article (peer-reviewed)abstract
- Importance The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants.Objective To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models.Design, Setting, and Participants This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023.Main Outcomes and Measures Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed.Results Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, −0.9 weeks; 95% CI, −1.5 to −0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6% (95% CI, 45.6-47.5) for the prescreen model and 76.9% (95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38% (95% CI, 32-46) for DIGIROP prescreen, 53% (95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46% (95% CI, 39-53) for WINROP.Conclusion and Relevance Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.
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| 16. |
- Pivodic, Aldina, 1978, et al.
(author)
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Prognostic Value of Parenteral Nutrition Duration on Risk of Retinopathy of Prematurity Development and Validation of the Revised DIGIROP Clinical Decision Support Tool
- 2023
-
In: JAMA ophthalmology. - : AMER MEDICAL ASSOC. - 2168-6165 .- 2168-6173. ; 141:8, s. 716-724
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Journal article (peer-reviewed)abstract
- IMPORTANCE The prognostic impact of parenteral nutrition duration (PND) on retinopathy of prematurity (ROP) is not well studied. Safe prediction models can help optimize ROP screening by effectively discriminating high-risk from low-risk infants. OBJECTIVE To evaluate the prognostic value of PND on ROP; to update and validate the Digital ROP (DIGIROP) 2.0 birth into prescreen and screen prediction models to include all ROP-screened infants regardless of gestational age (GA) and incorporate PND; and to compare the DIGIROP model with the Weight, IGF-1, Neonatal, and ROP (WINROP) and Postnatal Growth and ROP (G-ROP) models. DESIGN, SETTING, AND PARTICIPANTS This retrospective study included 11 139 prematurely born infants from 2007 to 2020 from the Swedish National Registry for ROP. Extended Poisson and logistic models were applied. Data were analyzed from August 2022 to February 2023. MAIN OUTCOMES AND MEASURES Any ROP and ROP requiring treatment were studied in relation to PND. ROP treatment was the outcome in DIGIROP models. Sensitivity, specificity, area under the receiver operating characteristic curve, and adjusted OR (aOR) with 95% CI were the main measures. Internal and external validations were performed. RESULTS Of 11 139 screened infants, 5071 (45.5%) were girls, and the mean (SD) gestational age was 28.5 (2.4) weeks. ROP developed in 3179 infants (29%), treatment was given in 599 (5%), 7228 (65%) had PND less than 14 days, 2308 (21%) had PND for 14 days or more, and 1603 (14%) had unknown PND. PND was significantly correlated with ROP severity (Spearman r = 0.45; P < .001). Infants with 14 days or more of PND vs less than 14 days had faster progression from any ROP to ROP treatment (adjusted mean difference, -0.9 weeks; 95% CI, -1.5 to -0.3; P = .004). Infants with PND for 14 days or more vs less than 14 days had higher odds of any ROP (aOR, 1.84; 95% CI, 1.62-2.10; P < .001) and of severe ROP requiring treatment (aOR, 2.20; 95% CI, 1.73-2.80; P < .001). Among all 11 139 infants, the DIGIROP 2.0 models had 100% sensitivity (95% CI, 99.4-100). The specificity was 46.6%(95% CI, 45.6-47.5) for the prescreen model and 76.9%(95% CI, 76.1-77.7) for the screen model. G-ROP as well as the DIGIROP 2.0 prescreen and screen models showed 100% sensitivity on a validation subset (G-ROP: sensitivity, 100%; 95% CI, 93-100; DIGIROP prescreen: sensitivity, 100%; 95% CI, 93-100; DIGIROP screen: sensitivity, 100%; 95% CI, 93-100), whereas WINROP showed 89% sensitivity (95% CI, 77-96). Specificity for each prediction model was 29% (95% CI, 22-36) for G-ROP, 38%(95% CI, 32-46) for DIGIROP prescreen, 53%(95% CI, 46-60) for DIGIROP screen at 10 weeks, and 46%(95% CI, 39-53) for WINROP. CONCLUSION AND RELEVANCE Based on more than 11 000 ROP-screened infants born in Sweden, PND of 14 days or more corresponded to a significantly higher risk of having any ROP and receiving ROP treatment. These findings provide evidence to support consideration of using the updated DIGIROP 2.0 models instead of the WINROP or G-ROP models in the management of ROP.
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| 17. |
- Rodhe, Staffan, 1946-
(author)
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Matematikens utveckling i Sverige fram till 1731
- 2002
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Doctoral thesis (other academic/artistic)abstract
- This thesis contains two parts:In the first papers I consider the development of mathematics up till around 1720. I have done a special study of the period between 1710 and 1720, when you could find three Swedes writing about contemporary mathematics, Christopher Polhem, Emanuel Swedenborg and Anders Gabriel Duhre. Especially Duhre has been of interest in his writings about series.The second part of the thesis deals with the first Swedish internationally well-known mathematician Samuel Klingenstierna. The study of his life and mathematics finishes with his arrival back to Sweden after his long travel to the centers of science in Europe. There are lots of new facts added to his biography during that period. Klingenstierna was involved in the actual mathematical discussions between Johann and Nicholaus Bernoulli, Fontenelle, Clairaut, Cramer and Stirling. I present the contents of some of Klingenstierna's manuscripts, which he wrote in Basel, Paris and London, for instance a problem of calculus of variation, a formula of the circumference of an ellipse and a formula to get a good approximation for the number π.
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| 18. |
- Sharma, Anoop Kumar, et al.
(author)
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Genotoxicity, inflammation and physico-chemical properties of fine particle samples from an incineration energy plant and urban air
- 2007
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In: Mutation Research/Genetic Toxicology and Environmental Mutagenesis. - : Elsevier BV. - 1383-5718. ; 633:2, s. 95-111
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Journal article (peer-reviewed)abstract
- Airborne particulate matter (PM) was sampled by use of an electrostatic sampler in an oven hall and a receiving hall in a waste-incineration energy plant, and from urban air in a heavy-traffic street and from background air in Copenhagen. PM was sampled for 1–2 weeks, four samples at each site. The samples were extracted and examined for mutagenicity in Salmonella typhimurium strains TA98, YG1041 and YG5161, for content of inorganic elements and for the presence of eight polycyclic aromatic hydrocarbons. The induction of IL-6 and IL-8 mRNA expression and the presence of DNA damage – tested by the comet assay – were determined after 24-h incubations with human A549 lung epithelial cells.The PM2.5 concentration was about twofold greater in the oven hall than in the receiving hall. The particle size distribution in the receiving hall was similar to that in street air (maximum mode at about 25 nm), but the distribution was completely different in the oven hall (maximum mode at about 150 nm). Also chemically, the samples from the oven hall were highly different from the other samples.PM extracts from the receiving hall, street and background air were more mutagenic than the PM extracts from the oven hall. PM from all four sites caused similar levels of DNA damage in A549 cells; only the oven hall samples gave results that were statistically significantly different from those obtained with street-air samples.The receiving hall and the urban air samples were similarly inflammatory (relative IL-8 mRNA expression), whereas the oven hall did not cause a statistically significant increase in IL-8 mRNA expression. A principal component analysis separated the oven hall and the receiving hall by the first principal component. These two sites were separated from street and background air with the second principal component. Several clusters of constituents were identified. One cluster consisted of all the polycyclic aromatic hydrocarbons (PAH), several groups of metals and one group of the biological endpoints (DNA damage, IL-6 and IL-8 mRNA expression). The PAH and the inorganic content of the air in the receiving hall may be due to vehicle emissions and suspended waste particles. The inorganic content in the street and background air may have been influenced by break wear, road emissions and long-range transport. The results from a partial least-square regression analysis predicted that both PAHs and a group of metals including Fe and Mn contributed to IL-6 and IL-8 induction. Only Mn and Sr were predicted to influence DNA damage statistically significantly. Among the PAHs only chrysene had influence on DNA damage.The PM from the oven hall was markedly different from the PM at other locations in particle size distribution, chemical composition and the resulting biological effects when A549 cells were incubated with the PM. These characteristics and observations in the oven hall indicated that the PM source was oven exhaust, which was well combusted.
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| 19. |
- von Otter, Malin, 1978, et al.
(author)
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Kinesin Light Chain 1 Gene Haplotypes in Three Conformational Diseases
- 2010
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In: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 229-236
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Journal article (peer-reviewed)abstract
- A functional intracellular transport system is essential to maintain cell shape and function especially in elongated cells, e.g. neurons and lens fibre cells. Impaired intracellular transport has been suggested as a common pathological mechanism for age-related diseases characterised by protein aggregation. Here, we hypothesise that common genetic variation in the transport protein kinesin may influence the risk of Parkinson's disease (PD), Alzheimer's disease (AD) and age-related cataract. This case-control study involves a PD material (165 cases and 190 controls), an AD material (653 cases and 845 controls) and a cataract material (495 cases and 183 controls). Genetic variation in the kinesin light chain 1-encoding gene (KLC1) was tagged by six tag single nucleotide polymorphisms (SNPs). Single SNPs and haplotypes were analysed for associations with disease risk, age parameters, mini-mental state examination scores and cerebrospinal fluid biomarkers for AD using logistic or linear regression. Genetic variation in KLC1 did not influence risk of PD. Weak associations with risk of AD were seen for rs8007903 and rs3212079 (P (c) = 0.04 and P (c) = 0.02, respectively). Two SNPs (rs8007903 and rs8702) influenced risk of cataract (P (c) = 0.0007 and P (c) = 0.04, respectively). However, the allele of rs8007903 that caused increased risk of AD caused reduced risk of cataract, speaking against a common functional effect of this particular SNP in the two diseases. Haplotype analyses did not add significantly to the associations found in the single SNP analyses. Altogether, these results do not convincingly support KLC1 as a major susceptibility gene in any of the studied diseases, although there is a small effect of KLC1 in relation to cataract.
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| 20. |
- von Otter, Malin, 1978, et al.
(author)
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Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract
- 2010
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In: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 131:2, s. 105-110
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Journal article (peer-reviewed)abstract
- Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 21. |
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| 22. |
- Wallin, Pontus, et al.
(author)
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Individanpassad vuxenutbildning : Med fokus på digitala verktyg
- 2019. - 1
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Reports (peer-reviewed)abstract
- Skolforskningsinstitutet arbetar kontinuerligt med att ringa in undervisningsnära ämnesområden där behovet av vetenskapligt grundad kunskap bedöms vara stort. Det sker i dialog med verksamma i skolan, med representanter för myndigheter och organisationer inom skolväsendet samt med forskare inom det utbildningsvetenskapliga fältet.Ett viktigt område som har identifierats under det arbetet gäller individanpassad undervisning inom vuxenutbildning. I behovsinventeringen framkom också att det finns behov av att sammanställa forskning om hur digitala verktyg används inom bland annat distansundervisning inom vuxenutbildning. Genom denna systematiska översikt vill vi sammanställa sådan forskning och göra den tillgänglig för lärare och andra verksamma inom komvux i Sverige.Översikten utgår ifrån följande övergripande frågeställningar:Vad kännetecknar individanpassad undervisning som möter vuxna elevers olikheter?Hur kan lärare använda digitala verktyg för att individanpassa undervisningen?Individanpassad undervisning inom vuxenutbildningMed individanpassad undervisning inom vuxenutbildning menar vi lärares metoder och arbetssätt som möter vuxna elevers olikheter i form av förutsättningar för lärande och behov i undervisningen. Vi har identifierat tre övergripande strategier för individanpassad undervisning:• gruppering• differentierad undervisning• individuell handledning.Gruppering innebär att elever delas in i grupper eller kurser utifrån deras förutsättningar och behov. Differentierad undervisning innebär att lärare tar hänsyn till elevers olikheter inom ramen för en kurs eller undervisningsgrupp. Individuell handledning innebär att elever ges individuellt stöd av läraren. I de studier som ingår i översikten relaterar forskarna oftast till någon eller några av dessa strategier för individanpassad undervisning.ResultatDet vetenskapliga underlaget består av 15 studier. Fyra av studierna har genomförts vid komvux i Sverige. Två studier har genomförts vid vuxenutbildning i övriga Skandinavien, vilken i hög utsträckning liknar komvux i Sverige. Ytterligare nio studier har genomförts i sammanhang som liknar komvux i Sverige men som också kan skilja sig något i fråga om hur utbildningen organiseras eller vilka elever som deltar.De ingående studierna skiljer sig i fråga om vilken forskningsmetod som använts. Även om studierna är av olika karaktär ger alla en förståelse för eller förklaringar till vad som kännetecknar individanpassad undervisning som möter vuxna elevers olikheter. En del av studierna kan dessutom beskriva eller förklara hur lärare kan använda digitala verktyg för att individanpassa undervisningen.Undervisning som möter vuxna elevers olikheterLärare har en nyckelroll i hur undervisningen utformas och genomförs. Men läraren är inte den enda som påverkar elevers lärande i en undervisningssituation. För den enskilda eleven kan andra elever också spela en viktig roll. Speciellt elever som har liten erfarenhet av studier kan vara beroende av att ta efter mer erfarna elever. Att imitera andra elever kan möjliggöra för elever med liten erfarenhet av utbildning att lära sig studieteknik och det sammanhang som undervisningsmiljön innebär. Lärare som vill individanpassa sin undervisning behöver överväga hur undervisningsmiljön möjliggör för elever att imitera andra elever för att på så sätt nå ett framgångsrikt lärande.Vuxna elever kan ha en mångfald av erfarenheter som lärare kan knyta an till i undervisningen. Genom att visa kunskap om och intresse för elevers tidigare erfarenheter kan läraren bedriva en undervisning som är anpassad för den enskilda eleven. Genom en sådan undervisning kan en typ av resonans uppnås mellan elevens erfarenheter och ämnesinnehållet i undervisningen. Eleven kan på så vis finna igenkänning i kunskapsinnehållet och engagemang för undervisningen.En undervisningsmiljö är också en plats för att skapa en gemensam kultur och en social arena som stimulerar till lärande. Betydelsen av interaktion och dialog mellan elever samt mellan elever och lärare ska inte underskattas vid skapandet av en miljö som gynnar elevers lärande. Det kan finnas elever som först behöver etablera relationer och interaktionsmönster i en undervisningsmiljö för att ett lärande ska bli möjligt.Att individanpassa undervisningen med hjälp av digitala verktygAtt introducera digitala verktyg i undervisningen kan påverka möjligheterna till individanpassning på olika sätt. Till digitala verktyg räknar vi teknisk utrustning, programvara och it-tjänster. Om digitala verktyg används för att genomföra exempelvis distansundervisning påverkas förutsättningarna för att individanpassa undervisningen på ett sätt som både innebär möjligheter och utmaningar. Ett exempel på möjlighet är att lärare på ett enkelt sätt kan förmedla ett omfattande kursmaterial till eleverna. Till utmaningarna hör bland annat att lärare kan få sämre överblick över vad eleverna gör och hur de lär sig.Vuxna elever har olika förutsättningar att tillgodogöra sig undervisning som sker med stöd av digitala verktyg. En lärare som är medveten om detta kan vara uppmärksam på om en elev har behov av extra hjälp och stöd. Lärare kan erbjuda elever olika sätt att studera för att kunna hitta ett upplägg som passar dem. För vissa elever kan exempelvis distansutbildning vara det bästa alternativet medan samma typ av distansutbildning bland annat kan innebära en förhöjd risk för avhopp för andra elever.Digitala verktyg kan fungera som ett komplement i och till klassrumsundervisningen. Digitala verktyg erbjuder lärare möjligheter att bland annat tillhandahålla inspelade lektioner som elever vid behov kan ta del av vid upprepade tillfällen. Att påkalla lärarens uppmärksamhet i en klassrumssituation för att be om repetition kan upplevas som svårt av vissa elever. Med tillgång till inspelade lektioner kan elever med behov av repetition få ett extra stöd. En förutsättning är att eleverna har tillgång till och förmåga att använda digitala verktyg på avsett sätt.En god introduktion till digitala verktyg är viktigt. Samtliga elever kan behöva stöd för att kunna använda digitala verktyg för lärande. Med tydlighet kring verktygen för lärande kan eleverna ta ansvar för sin användning av verktygen, göra det som förväntas av dem och be om hjälp vid behov.Användning av resultatenUndervisningen inom skolväsendet i Sverige ska vila på vetenskaplig grund och be-prövad erfarenhet. Vidare ska vuxenutbildningen anpassas utifrån individens behov och förutsättningar. Därmed är lärare inom komvux ålagda att utforma och genomföra en individanpassad undervisning som vilar på vetenskaplig grund och beprövad erfarenhet. Resultaten i den här systematiska översikten utgör en vetenskaplig grund för lärare att utgå ifrån. Men översikten visar också att det finns mycket mark kvar att bryta. Forskare har ett viktigt arbete framför sig med att förstärka den vetenskapliga grunden på området.Det finns aspekter av undervisningen som lärare inte kan råda över. Omfattningen av grupperingen av elever och resurser till individuell handledning kan vara på förhand givna. Men oavsett sådana förutsättningar kan lärare ta inspiration av forskningen som ingår i den här översikten. Resultaten från de vetenskapliga studierna ger lärare möjlighet att reflektera kring och utveckla sin undervisning. Forskningen ger inga tydliga svar på frågan om vad som är den bästa generella metoden för att bedriva en lyckad individanpassad undervisning som möter vuxna elevers olikheter. Existerande forskning på området kan bara ge exempel på vad som händer i en undervisningssituation i olika sammanhang med givna förutsättningar. Genom att inta ett vetenskapligt förhållningssätt bör lärare också vara kritiska till resultaten och själva avgöra hur exempel som lyfts i studierna relaterar till den egna undervisningssituationen.Urvalet av forskningVi har gått igenom 16 845 sökträffar, varav 251 studier har granskats i fulltext. Av dessa bedömdes totalt 15 studier kunna bidra till att besvara den systematiska översiktens frågeställningar.Studierna som utgör underlag för översikten fokuserar på olika aspekter av undervisningen samt användningen av digitala verktyg inom ramen för undervisningen. Några studier undersöker vad elever inom vuxenutbildning har för förutsättningar för lärande. Sådana studier kan hjälpa till att beskriva och förklara grundförutsättningarna för lärares undervisning inom vuxenutbildning. I andra studier som ingår i översikten är syftet snarare att undersöka vad vuxna elever har för behov i sitt lärande. Dessa studier kan hjälpa lärare att identifiera vad de kan göra för att utforma individanpassad under-visning i specifika undervisningssituationer. Slutligen finns det artiklar i underlaget som utforskar och prövar olika metoder och arbetssätt som lärare använder för att individanpassa undervisningen för att möta elevers olikheter. Dessa studier kan ge lärare vägledning för hur undervisningen kan utformas och genomföras. Endast ett fåtal studier undersöker vad undervisningen ger för effekter på elevers kunskapsresultat.
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| 23. |
- Wallin, Staffan, et al.
(author)
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Electronic Interactions and Energy Transfer in Oligothiophene-Linked bis-Porphyrins
- 2006
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In: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-905X .- 1474-9092. ; 5:9, s. 828-834
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Journal article (peer-reviewed)abstract
- The photophysical and spectroscopic properties of a series of bis-porphyrin compounds meso-meso-linked via oligothiophene bridges are reported. In particular the effects of the different bridges on the porphyrin properties as well as their ability to enhance energy transfer is investigated. The main findings are: a splitting of the degeneracy of the porphyrin Soret band transition with a lower energy transition aligned along the bridge, a dramatic decrease in triplet lifetime and the occurrence of "superexchange" as the main mechanism for mediating singlet-singlet energy transfer in the case where the bridge is a quaterthiophene. Our results show significant perturbations of the intrinsic porphyrin properties induced by the bridge, which are important for the function of porphyrin assemblies.
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| 25. |
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| 26. |
- Wallin, Staffan, et al.
(author)
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Femtosecond Transient Absorption Anisotropy Study on [Ru(bpy)3]2+ and [Ru(bpy)(py)4]2+. Ultrafast Interligand Randomization of the MLCT State
- 2005
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In: J. Phys. Chem. A. - : American Chemical Society (ACS). ; :109, s. 4697-4704
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Journal article (peer-reviewed)abstract
- It is known that the relaxed excited state of [Ru(bpy)3]2+ is best described as a metal to ligand charge transfer (MLCT) state having one formally reduced bipyridine and two neutral. Previous reports have suggested [Malone, R. et al. J.Chem. Phys 1991, 95, 8970] that the electron "hops" from ligand to ligand in the MLCT state with a time constant of about 50 ps in acetonitrile. However, we have done transient absorption anisotropy measurements indicating that already after one picosecond the molecule has no memory of which bipyridine was initially photoselected, which suggest an ultrafast interligand randomization of the MLCT state.
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| 27. |
- Wallin, Staffan, et al.
(author)
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State-Selective Electron Transfer in an Unsymmetric Acceptor-Zn(II)porphyrin-Acceptor Triad : Toward a Controlled Directionality of Electron Transfer from the Porphyrin S-2 and S-1 States as a Basis for a Molecular Switch
- 2010
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In: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 114:4, s. 1709-1721
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Journal article (peer-reviewed)abstract
- A series of Zn(II) porphyrin (ZnP) compounds covalently linked to different electron acceptor units, naphthaleneimide (NI) and naphthalenedimide (NDI), are reported. The aim was to demonstrate a state-selective direction of electron transfer, where excitation to the lowest excited S-1 state of the porphyrin (Q-band excitation) would give electron transfer to the NDI unit, while excitation to the higher S-2 state (Soret-hand excitation) would give electron transfer to the NI unit. This would constitute a basis for an opto-electronic Switch in which the direction of electron transfer and the resulting dipole moment can be controlled by using light input of different color. Indeed, electron transfer from the S-1 state to NDI Occurred in solvents of both high and low polarity, whereas no electron transfer to NDI was observed from the S-2 state. With NI as acceptor instead, very rapid (tau = 200-400 fs) electron transfer from the S-2 state occurred in all solvents. This was followed by an ultrafast (tau approximate to 100 fs) recombination to Populate the porphyrin S-1 state in nearly quantitative yield. The charge-separated state ZnP+NI- was spectroscopically observed, and evidence was obtained that recombination Occurred from a vibrationally excited ("hot") ZnP+NI- state in the more polar solvents. In these solvents, the thermally relaxed ZnP+NI- state lies at lower energy than the S-1 state so that further charge separation occurred from S-1 to form ZnP+NI-. This resulted in a highly unusual "ping-pong" sequence where the reaction went back and forth between locally excited ZnP states and charge-separated states: S-2 double right arrow ZnP+NI"hot"- double right arrow S-1 double right arrow ZnP+NI- double right arrow S-0. The electron transfer dynamics and its solvent dependence are discussed, as well as the function of the present Molecules as molecular switches.
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| 28. |
- Wallin, Staffan, 1972-
(author)
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The Fate of Electronically Excited States : Ultrafast Electron and Energy Transfer in Solvated Donor-Acceptor Systems
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Processes where a molecule absorbs visible light and then disposes of the excess energy via electron/energy transfer reactions have an important role both in nature (e.g. in photosynthesis) and in many technical applications (e.g. in photography and photovoltaics). This thesis uses different spectroscopical techniques, mainly ultrafast transient absorption, to study such processes. The thesis can roughly be divided into three parts.In the first part, donor-acceptor systems linked by different conjugated bridges are studied. The objective was to see to what extent the conjugated link could enhance excited state energy or electron transfer, via so-called superexchange processes. The studied links do enhance the electron/energy transfer but in the electron transfer study the resulting charge separated state was very short lived.The second part explores the possibility of constructing acceptor-donor-acceptor triads where the direction of electron transfer is determined by the electronic state of the donor. Direct evidence of electron transfer in the form of radical absorption was found from both the first and the second excited states of the donor.In the last part, two common chromophores were investigated by transient absorption anisotropy. In the case of Ru(bpy)32+, it was found that the complex lost all memory of the polarization of the exciting light much faster than what was previously thought. This means that electron transfer between ligands is normally not the rate limiting step in electron transfer reactions involving this complex. In the case of zinc porphyrin, it was seen that the measured anisotropy differed depending on which electronic state was excited suggesting differences in the degree of coherence.
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