| 1. |
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| 2. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 6. |
- Vlasceanu, Madalina, et al.
(författare)
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Addressing climate change with behavioral science: A global intervention tournament in 63 countries
- 2024
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors.
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| 7. |
- Aidas, Kestutis, et al.
(författare)
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The Dalton quantum chemistry program system
- 2014
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Ingår i: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Tidskriftsartikel (refereegranskat)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 8. |
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| 9. |
- Sadowski, J., et al.
(författare)
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Structural and magnetic properties of molecular beam epitaxy grown GaMnAs layers
- 2000
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 18:3, s. 1697-1700
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Tidskriftsartikel (refereegranskat)abstract
- GaMnAs layers with Mn contents from 0.05% to 7% were grown by low temperature molecular beam epitaxy. At substrate temperatures lower than 300 degrees C and in this composition range a uniform ternary GaMnAs compound can be grown without MnAs precipitation. Reflection high energy electron diffraction intensity oscillations recorded during GaMnAs growth were used to calibrate the composition of the GaMnAs films with high accuracy (better than 0.1%). Films containing more than 1% Mn exhibit a ferromagnetic phase transition with Curie temperatures from a few up to 70 K depending on the composition and other growth parameters. In contrast to previous reports we have observed this transition also in the case of layers grown at very low substrate temperatures (below 300 degrees C).
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| 10. |
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| 11. |
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| 12. |
- Van Der Wateren, E., et al.
(författare)
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The LOFAR Tied-Array All-Sky Survey: Timing of 35 radio pulsars and an overview of the properties of the LOFAR pulsar discoveries
- 2023
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 669
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Tidskriftsartikel (refereegranskat)abstract
- The LOFAR Tied-Array All-Sky Survey (LOTAAS) is the most sensitive untargeted radio pulsar survey performed at low radio frequencies (119-151 MHz) to date and has discovered 76 new radio pulsars, including the 23.5-s pulsar J0250+5854, which up until recently was the slowest spinning radio pulsar known. In this paper, we report on the timing solutions of 35 pulsars discovered by LOTAAS, which include a nulling pulsar and a mildly recycled pulsar, and thereby complete the full timing analysis of the LOTAAS pulsar discoveries. We give an overview of the findings from the full LOTAAS sample of 76 pulsars, discussing their pulse profiles, radio spectra, and timing parameters. We found that the pulse profiles of some of the pulsars show profile variations in time or frequency, and while some pulsars show signs of scattering, a large majority display no pulse broadening. The LOTAAS discoveries have on average steeper radio spectra and longer spin periods (1.4×), as well as lower spin-down rates (3.1×) compared to the known pulsar population. We discuss the cause of these differences and attribute them to a combination of selection effects of the LOTAAS survey as well as previous pulsar surveys, though we cannot rule out that older pulsars tend to have steeper radio spectra.
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| 13. |
- Lawniczak-Jablonska, K., et al.
(författare)
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Structural and magnetic properties of GaAs:(Mn,Ga)As granular layers
- 2011
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Ingår i: Physica Status Solidi. B: Basic Research. - : Wiley. - 0370-1972. ; 248:7, s. 1609-1614
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Tidskriftsartikel (refereegranskat)abstract
- Granular GaAs:(Mn,Ga)As films were prepared by annealing the Ga0.92Mn0.08As/GaAs layer grown by the MBE method at low temperature. The annealing was performed at 500 or 600 degrees C. It is commonly accepted that this processing should result in formation of cubic zinc blende or hexagonal MnAs inclusions depending on the temperature. We demonstrate that such a priory assumption is not justified. The kind of formed inclusions depends not only on the annealing temperature but also on the number of defects and Mn atoms in the substitutional and interstitial positions in as grown sample. (C) 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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| 14. |
- Lawniczak-Jablonska, K., et al.
(författare)
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Structural and magnetic properties of nanoclusters in GaMnAs granular layers
- 2011
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Ingår i: Journal of Solid State Chemistry. - : Elsevier BV. - 0022-4596. ; 184:6, s. 1530-1539
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Tidskriftsartikel (refereegranskat)abstract
- Structural and magnetic properties of GaAs thin films with embedded nanoclusters were investigated as a function of the annealing temperature and Mn content. Surprisingly, the presence of two kinds of nanoclusters with different structure was detected in most of the samples independently of the thermal processing or Mn content. This proved that the presence of a given type of clusters cannot be assumed a priori as is reported in many papers. The fraction of Mn atoms in each kind of cluster was estimated from the extended X-ray absorption fine structure analysis. This analysis ruled out the possibility of the existence of nanoclusters containing a hypothetic MnAs cubic compound-only (Ga,Mn)As cubic and hexagonal MnAs clusters were detected. Moreover the bimodal distribution of Mn magnetic moments was found, which scales with the estimated fraction of Mn atoms in the cubic and hexagonal clusters. (C) 2011 Elsevier Inc. All rights reserved.
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| 19. |
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| 20. |
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| 21. |
- Bak-Coleman, Joseph B., et al.
(författare)
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Stewardship of global collective behavior
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:27
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Tidskriftsartikel (refereegranskat)abstract
- Collective behavior provides a framework for understanding how the actions and properties of groups emerge from the way individuals generate and share information. In humans, information flows were initially shaped by natural selection yet are increasingly structured by emerging communication technologies. Our larger, more complex social networks now transfer high-fidelity information over vast distances at low cost. The digital age and the rise of social media have accelerated changes to our social systems, with poorly understood functional consequences. This gap in our knowledge represents a principal challenge to scientific progress, democracy, and actions to address global crises. We argue that the study of collective behavior must rise to a crisis discipline just as medicine, conservation, and climate science have, with a focus on providing actionable insight to policymakers and regulators for the stewardship of social systems.
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| 22. |
- Bak-Misiuk, J., et al.
(författare)
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Creation of MnAs nanoclusters during processing of GaMnAs
- 2009
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Ingår i: Radiation Physics And Chemistry. - : Elsevier BV. - 0969-806X. ; 78, s. 116-119
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Konferensbidrag (refereegranskat)abstract
- GaMnAs layers on (0 0 1)-oriented GaAs substrates were grown by the molecular beam epitaxy (MBE) method. Structural properties of samples processed at up to 920 K under hydrostatic Ar pressure up to 1.1 GPa were investigated by X-ray, secondary ion mass spectroscopy and atomic force microscopy methods. The sign of strain (compressive or tensile) of the GaMnAs layers, related to a creation of MnAs nanoclusters, is found to be dependent on processing conditions and on primary structure defects, whereas it was independent of Mn concentration. An influence of the defects structure in as-grown samples on the strain state of processed GaMnAs layers is discussed. (C) 2009 Elsevier Ltd. All rights reserved.
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| 23. |
- Baldanzi, Gabriel, et al.
(författare)
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Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS.
- 2024
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from the Swedish CArdioPulmonary bioImage Study.METHODS: In 8416 participants aged 50-65, time in SED, MPA, and VPA were estimated with hip-worn accelerometer. Gut microbiota was profiled using shotgun metagenomics of faecal samples. We applied multivariable regression models, adjusting for sociodemographic, lifestyle, and technical covariates, and accounted for multiple testing.FINDINGS: Overall, associations between time in SED and microbiota species abundance were in opposite direction to those for MPA or VPA. For example, MPA was associated with lower, while SED with higher abundance of Escherichia coli. MPA and VPA were associated with higher abundance of the butyrate-producers Faecalibacterium prausnitzii and Roseburia spp. We observed discrepancies between specific VPA and MPA associations, such as a positive association between MPA and Prevotella copri, while no association was detected for VPA. Additionally, SED, MPA and VPA were associated with the functional potential of the microbiome. For instance, MPA was associated with higher capacity for acetate synthesis and SED with lower carbohydrate degradation capacity.INTERPRETATION: Our findings suggest that sedentary and physical activity are associated with a similar set of gut microbiota species but in opposite directions. Furthermore, the intensity of physical activity may have specific effects on certain gut microbiota species.FUNDING: European Research Council, Swedish Heart-Lung Foundation, Swedish Research Council, Knut and Alice Wallenberg Foundation.
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| 24. |
- Dynowska, E., et al.
(författare)
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Structural and magnetic properties of GaSb:MnSb granular layers
- 2011
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Ingår i: Radiation Physics and Chemistry. - : Elsevier BV. - 0969-806X. ; 80:10, s. 1051-1057
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Konferensbidrag (refereegranskat)abstract
- The results of structural and magnetic characterization of GaMnSb layers grown on GaSb(0 0 1) and GaAs(1 1 1) substrates are presented. The presence of hexagonal, highly oriented MnSb inclusions embedded in GaSb matrix has been demonstrated. The lattice parameters of these inclusions were the same as those for bulk MnSb for the layers grown on GaSb(1 0 0) substrate while for the layers grown on GaAs(1 1 1) the MnSb inclusions were strained. The influence of a presence of MnSb clusters on the lattice parameter of GaSb matrix has been demonstrated. It was confirmed that in all cases the MnSb clusters exhibit a ferromagnetic: behavior at room temperature. (C) 2011 Elsevier Ltd. All rights reserved.
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| 25. |
- Lokkegaard, Sanne, et al.
(författare)
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MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit
- 2021
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Ingår i: npj Breast Cancer. - : NATURE RESEARCH. - 2374-4677. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser(315,33)), CHK1(Ser(317)), and cdc25b(Ser(323)), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.
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| 26. |
- Okhuijsen-Pfeifer, C, et al.
(författare)
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Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- 2022
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 145-
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Tidskriftsartikel (refereegranskat)abstract
- Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
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| 27. |
- Romanowski, P., et al.
(författare)
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Defect Structure of High-Temperature-Grown GaMnSb/GaSb
- 2010
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Ingår i: Acta Physica Polonica A. - 0587-4246. ; 117:2, s. 341-343
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Konferensbidrag (refereegranskat)abstract
- GaMnSb/GaSb(100) layers with embedded MnSb inclusions have been grown at 720 K using MBE technique. This paper presents the investigation of the defect structure of Ga1-xMnxSb layers with different content of manganese (up to x = 0.07). X-ray diffraction method using conventional and synchrotron radiation was applied. Dimensions and shapes of inclusions were detected by scanning electron microscopy. Depth profiles of elements were measured using secondary ion mass spectroscopy technique.
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| 28. |
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| 29. |
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| 31. |
- Alves, Carla L., et al.
(författare)
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Co-targeting CDK4/6 and AKT with endocrine therapy prevents progression in CDK4/6 inhibitor and endocrine therapy-resistant breast cancer
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy have shown impressive efficacy in estrogen receptor-positive advanced breast cancer. However, most patients will eventually experience disease progression on this combination, underscoring the need for effective subsequent treatments or better initial therapies. Here, we show that triple inhibition with fulvestrant, CDK4/6i and AKT inhibitor (AKTi) durably impairs growth of breast cancer cells, prevents progression and reduces metastasis of tumor xenografts resistant to CDK4/6i-fulvestrant combination or fulvestrant alone. Importantly, switching from combined fulvestrant and CDK4/6i upon resistance to dual combination with AKTi and fulvestrant does not prevent tumor progression. Furthermore, triple combination with AKTi significantly inhibits growth of patient-derived xenografts resistant to combined CDK4/6i and fulvestrant. Finally, high phospho-AKT levels in metastasis of breast cancer patients treated with a combination of CDK4/6i and endocrine therapy correlates with shorter progression-free survival. Our findings support the clinical development of ER, CDK4/6 and AKT co-targeting strategies following progression on CDK4/6i and endocrine therapy combination, and in tumors exhibiting high phospho-AKT levels, which are associated with worse clinical outcome.
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| 32. |
- Arvidsson, Daniel, et al.
(författare)
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Fundament for a methodological standard to process hip accelerometer data to a measure of physical activity intensity in middle-aged individuals.
- 2024
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 34:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a lack of a methodological standard to process accelerometer data to measures of physical activity, which impairs data quality and comparability. This study investigated the effect of different combinations of settings of multiple processing components, on the measure of physical activity and the association with measures of cardiometabolic health in an unselected population of middle-aged individuals.METHODS: Free-living hip accelerometer data, aerobic fitness, body mass index, HDL:total cholesterol ratio, blood glucose, and systolic blood pressure were achieved from 4391 participants 50-64 years old included in The Swedish CArdioPulmonary bioImage Study (SCAPIS) baseline measurement (cross-sectional). Lab data were also included for calibration of accelerometers to provide comparable measure of physical activity intensity and time spent in different intensity categories, as well as to enhance understanding. The accelerometer data processing components were hardware recalibration, frequency filtering, number of accelerometer axes, epoch length, wear time criterium, time composition (min/24 h vs. % of wear time). Partial least regression and ordinary least regression were used for the association analyses.RESULTS: The setting of frequency filter had the strongest effect on the physical activity intensity measure and time distribution in different intensity categories followed by epoch length and number of accelerometer axes. Wear time criterium and recalibration of accelerometer data were less important. The setting of frequency filter and epoch length also showed consistent important effect on the associations with the different measures of cardiometabolic health, while the effect of recalibration, number of accelerometer axes, wear time criterium and expression of time composition was less consistent and less important. There was a large range in explained variance of the measures of cardiometabolic health depending on the combination of processing settings, for example, 12.1%-20.8% for aerobic fitness and 5.8%-14.0% for body mass index.CONCLUSIONS: There was a large variation in the physical activity intensity measure and the association with different measures of cardiometabolic health depending on the combination of settings of accelerometer data processing components. The results provide a fundament for a standard to process hip accelerometer data to assess the physical activity in middle-aged populations.
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| 33. |
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| 34. |
- Bak-Misiuk, J., et al.
(författare)
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Pressure Variation of the Strain State of MnAs Nanoclusters Embedded in GaAs
- 2012
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Ingår i: Acta Physica Polonica. Series A: General Physics, Physics of Condensed Matter, Optics and Quantum Electronics, Atomic and Molecular Physics, Applied Physics. - 0587-4246. ; 121:4, s. 903-905
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Tidskriftsartikel (refereegranskat)abstract
- Granular GaAs:(Mn,Ga)As films were prepared by annealing at 500 degrees C under ambient and enhanced hydrostatic pressure (1.1 GPa), of Ga1-xMnxAs/GaAs layers (x = 0.025, 0.03, 0.04, 0.05 and 0.063) grown at 230 degrees C by molecular beam epitaxy method. Distinct influence of enhanced hydrostatic pressure applied during sample annealing on strain state of inclusions was found. An increase of lattice distortion and of strain of inclusions for the samples treated under hydrostatic pressure is related to different bulk moduli of GaAs and of MnAs
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| 35. |
- Bak-Misiuk, J., et al.
(författare)
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Variation of strain in granular GaAs:MnAs layers
- 2013
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Ingår i: Crystallography Reports. - 1063-7745. ; 58:7, s. 998-1001
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Tidskriftsartikel (refereegranskat)abstract
- Granular GaAs(MnAs) layers with different Mn concentration and various layer thickness were grown by MBE method and subjected to annealing at 500A degrees C under ambient and enhanced hydrostatic pressure. Distinct influence of hydrostatic pressure applied during annealing on strain state of layers as well as on hexagonal MnAs inclusions was found. Pressure induced strain of inclusions is related to different bulk moduli of GaAs and of hexagonal MnAs. Formation of hexagonal inclusions depends on concentration of Mn in interstitial position in as-grown samples.
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| 36. |
- Bak, Nina Friis, et al.
(författare)
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High-dose vitamin D3 supplementation decreases the number of colonic CD103+ dendritic cells in healthy subjects.
- 2018
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Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 57:7, s. 2607-2619
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Tidskriftsartikel (refereegranskat)abstract
- Vitamin D may induce tolerance in the intestinal immune system and has been shown to regulate the phenotype of tolerogenic intestinal dendritic cells (DCs) in vitro. It is unknown whether vitamin D supplementation affects human intestinal DCs in vivo, and we aimed to investigate the tolerability and effect on intestinal CD103+DCs of high-dose vitamin D3 treatment in healthy subjects.Ten healthy subjects received a total of 480,000IU oral vitamin D3 over 15days and colonic biopsies were obtained before and after intervention by endoscopy. Lamina propria mononuclear cells (LPMCs) were isolated from the biopsies, stained with DC surface markers and analysed with flow cytometry. Snap-frozen biopsies were analysed with qPCR for DC and regulatory T cell-related genes.No hypercalcemia or other adverse events occurred in the test subjects. Vitamin D decreased the number of CD103+ DCs among LPMCs (p=0.006). Furthermore, vitamin D induced mRNA expression of TGF-β (p=0.048), TNF-α (p=0.006) and PD-L1 (p=0.02) and tended to induce IL-10 expression (p=0.06). Multivariate factor analysis discriminated between pre- and post-vitamin D supplementation with a combined increased qPCR expression of PD1, PD-L1, TGF-β, IL-10, CD80, CD86, FOXP3, NFATc2 and cathelicidin.High-dose vitamin D supplementation is well tolerated by healthy subjects and has a direct effect on the CD103+ DCs, local cytokine and surface marker mRNA expression in the colonic mucosa, suggestive of a shift towards a more tolerogenic milieu.
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| 37. |
- Baldanzi, Gabriel, et al.
(författare)
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OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study
- 2023
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Ingår i: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
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| 38. |
- Bogetofte, Helle, et al.
(författare)
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PARK2 mutation causes metabolic disturbances and impaired survival of human iPSC-derived neurons
- 2019
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The protein parkin, encoded by the PARK2 gene, is vital for mitochondrial homeostasis, and although it has been implicated in Parkinson’s disease (PD), the disease mechanisms remain unclear. We have applied mass spectrometry-based proteomics to investigate the effects of parkin dysfunction on the mitochondrial proteome in human isogenic induced pluripotent stem cell-derived neurons with and without PARK2 knockout (KO). The proteomic analysis quantified nearly 60% of all mitochondrial proteins, 119 of which were dysregulated in neurons with PARK2 KO. The protein changes indicated disturbances in oxidative stress defense, mitochondrial respiration and morphology, cell cycle control, and cell viability. Structural and functional analyses revealed an increase in mitochondrial area and the presence of elongated mitochondria as well as impaired glycolysis and lactate-supported respiration, leading to an impaired cell survival in PARK2 KO neurons. This adds valuable insight into the effect of parkin dysfunction in human neurons and provides knowledge of disease-related pathways that can potentially be targeted for therapeutic intervention.
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| 39. |
- Dekkers, Koen, et al.
(författare)
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An online atlas of human plasma metabolite signatures of gut microbiome composition.
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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| 40. |
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| 41. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Tidskriftsartikel (refereegranskat)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 42. |
- Ekblom Bak, Elin, 1981-, et al.
(författare)
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Sex- and age-specific associations between cardiorespiratory fitness, CVD morbidity and all-cause mortality in 266.109 adults
- 2019
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Ingår i: Preventive Medicine. - : Elsevier BV. - 0091-7435 .- 1096-0260. ; 127
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate sex- and age-specific associations between cardiorespiratory fitness, all-cause and cause-specific mortality, and cardiovascular disease (CVD) morbidity. 266.109 participants (47% women, 18-74 years) free from CVD, participating in occupational health service screenings in 1995-2015 were included. CRF was assessed as estimated maximal oxygen consumption (estVO(2)max) using a submaximal cycle test. Incident cases of first-time CVD event and death from any cause were ascertained through national registers. There were 4244 CVD events and 2750 cases of all-cause mortality during mean 7.6 years follow-up. Male gender, higher age and lower estVO(2)max were associated with higher all-cause mortality and CVD morbidity incidence rates. Risk reductions with increasing estVO(2)max were present in all age-groups of men and women. No obvious levelling off in risk was identified in the total cohort. However, women and older age-groups showed no further reduction in higher aggregated estVO(2)max levels. CVD specific mortality was more associated with estVO(2)max compared to tumor specific mortality. The risk for all-cause mortality and CVD morbidity decreased by 2.3% and 2.6% per increase in 1 ml.min(-) (1).kg(-1) with no significant sex-differences but more pronounced in the three lower estVO(2)max categories for all-cause mortality (9.1%, 3.8% and 3.3%, respectively). High compared to lower levels of estVO(2)max was not related to a significantly elevated mortality or morbidity. In this large cohort study, CVD morbidity and all-cause mortality were inversely related to estVO(2)max in both men and women of all age-groups. Increasing cardiorespiratory fitness is a clear public health priority.
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| 43. |
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| 44. |
- Gaist, D, et al.
(författare)
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Stroke research in GenomEUtwin
- 2003
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Ingår i: Twin research : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1369-0523. ; 6:5, s. 442-447
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Tidskriftsartikel (refereegranskat)
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| 45. |
- Ghavidel, Amir, et al.
(författare)
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Degradation assessment of archaeological oak (Quercus spp.) buried under oxygen-limited condition
- 2023
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Ingår i: Holzforschung. - : Walter de Gruyter. - 0018-3830 .- 1437-434X. ; 77:3, s. 198-207
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Tidskriftsartikel (refereegranskat)abstract
- The biological deterioration of archaeological wood under oxygen-limited conditions varies due to the limited activities of microorganisms. It is essential to expand the knowledge of the degradation types and the status of archaeological monuments for selecting the proper consolidates. The physical, chemical, and anatomical properties of approximately 600–650 year old archaeological oak collected from an archaeological site in Iasi-Romania were analysed to assess the quality and to identify the degradation types. The results were compared with similar tests on recently-cut oak. X-ray photoelectron spectroscopy (XPS) revealed the presence of more lignin-related peaks in the archaeological oak, which likely reflected the degradation of the wood carbohydrates as evidenced by the decreased oxygen-to-carbon ratio Cox/Cnon-ox. The differences in cellulose crystallinity were not significant suggesting that any cellulose degradation occurred in the amorphous regions. This was also reflected in the dynamic water vapor sorption analysis where the differences in sorption isotherms and hysteresis of archaeological and recently-cut oaks were marginal. Microscopic analysis of the oak cells illustrated bacterial degradation patterns, while the field emission scanning electron microscopy (FESEM) showed the presence of erosion bacteria in the archaeological oak collected from the site with low oxygen conditions.
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| 46. |
- Jensen, PS, et al.
(författare)
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Determination of urea, glucose, and phosphate in dialysate with Fourier transform infrared spectroscopy
- 2004
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Ingår i: Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. - 1386-1425. ; 60:4, s. 899-905
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Tidskriftsartikel (refereegranskat)abstract
- Individual control and quantification of phosphate removal is desirable in dialysis treatment. Currently, no on-line method exists to quantify phosphate removal. We demonstrate that a multivariate calibration model based on infrared transmission spectra is capable of predicting phosphate, urea, and glucose concentrations at clinically relevant levels. The on-line monitoring of these components by infrared spectroscopy is therefore feasible. (C) 2003 Elsevier B.V. All rights reserved.
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| 47. |
- Jensen, PS, et al.
(författare)
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Fourier transform infrared spectroscopy of aqueous solutions using optical subtraction
- 2002
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Ingår i: OPTICAL DIAGNOSTICS AND SENSING OF BIOLOGICAL FLUIDS AND GLUCOSE AND CHOLESTEROL MONITORING II. - : SPIE. - 1996-756X .- 0277-786X. - 0819443638 ; 4624, s. 150-159
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Konferensbidrag (refereegranskat)abstract
- For the analysis of small concentrations of organics in aqueous solutions, a novel add-on accessory for dual-beam / optical subtraction spectroscopy has been built for a commercial Fourier transform infrared spectrometer. A standard FT-IR instrument requires a sample measurement and a separate reference measurement, whereas the optical subtraction instrument directly measures the difference between sample and reference. This has a number of advantages. The time delay between the two measurements is eliminated, and the effective measurement time is improved by a factor of two. Moreover, the optical subtraction provides a large reduction in dynamic range of the measured signal, which prevents detector saturation, and enables effective use of dynamic range of the analog to digital converter in the FT-IR spectrometer. This results in an increased signal to noise ratio, compared to the standard FT-IR instrument. By changing detector and light source the instrument may be used for both near- and mid.-infrared spectroscopy. The increased sensitivity and stability of the optical subtraction instrument compared to the standard instrument is demonstrated by transmission measurements of aqueous urea solutions in the combination band region 4000 to 5000cm(-1) (2000 to 2500nm).
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| 48. |
- Jensen, PS, et al.
(författare)
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Influence of temperature on water and aqueous glucose absorption spectra in the near- and mid-infrared regions at physiologically relevant temperatures
- 2003
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Ingår i: Applied Spectroscopy. - : SAGE Publications. - 1943-3530 .- 0003-7028. ; 57:1, s. 28-36
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Tidskriftsartikel (refereegranskat)abstract
- Near- and mid-infrared absorption spectra of pure water and aqueous 1.0 g/dL glucose solutions in the wavenumber range 8000-950 cm(-1) were measured in the temperature range 30-42 C in steps of 2 degreesC. Measurements were carried out with an FT-IR spectrometer and a variable pathlength transmission cell controlled within 0.02 degreesC. Pathlengths of 50 mum and 0.4 mm were used in the mid- and near-infrared spectral region, respectively. Difference spectra were used to determine the effect of temperature on the water spectra quantitatively. These spectra were obtained by subtracting the 37 degreesC water spectrum from the spectra measured at other temperatures. The difference spectra reveal that the effect of temperature is highest in the vicinity of the strong absorption bands, with a number of isosbestic points with no temperature dependence and relatively flat plateaus in between. On the basis of these spectra, prospects for and limitations on data analysis for infrared diagnostic methods are discussed. As an example, the absorptive properties of glucose were studied in the same temperature range in order to determine the effect of temperature on the spectral shape of glucose. The change in water absorption associated with the addition of glucose has also been studied. An estimate of these effects is given and is related to the expected level of infrared signals from glucose in humans.
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| 49. |
- Jensen, PS, et al.
(författare)
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Online monitoring of urea concentration in dialysate with dual-beam Fourier-transform near-infrared spectroscopy
- 2004
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Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 9:3, s. 553-557
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Tidskriftsartikel (refereegranskat)abstract
- The robustness of a dual-beam, optical null, Fourier-transform near-infrared (FTNIR) spectrometer was investigated by means of online, near-infrared measurements and predictions of urea concentrations in spent dialysate during hemodialysis treatment. Simple multivariate calibration using a few factors based on a small number of prepared samples provided stable and accurate predictions over a period of 1 month. The calibration was robust when faced with adjustment of reference cell intensity and did not require a daily measured reference spectrum. The root-mean-square error of prediction of urea was 0.4 mM based on a two-factor partial least-squares regression model. (C) 2004 Society of Photo-Optical Instrumentation Engineers.
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