| 1. |
- Alsén, Samuel, et al.
(författare)
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Antigen-Presenting B Cells Program the Efferent Lymph T Helper Cell Response
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T-B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined intervals post-immunization. Focusing on gut-draining mesenteric lymph nodes (MLNs), we show that antigen-specific alpha(4)beta(+)(7) gut-homing effector Th cells enter the circulation prior to CXCR5(+)PD-1(+) Tfh-like cells. B cells appear to have no or limited impact on the early generation and egress of gut-homing Th cells but are critical for the subsequent appearance of Tfh-like cells that peak in the lymph before GCs have developed. At this stage, antigen-presenting B cells also reduce the proportion of alpha(4)beta(+)(7) Th cells in the MLN and efferent lymph. Furthermore, cognate B-cell interaction drives a broad transcriptional program in Th cells, including IL-4 that is confined to the Tfh cell lineage. The IL-4-producing Tfh-like cells originate from Bcl6(+) precursors in the LNs and have gut-homing capacity. Hence, B cells program the efferent lymph Th cell response within a limited window of time after antigenic challenge.
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| 2. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 3. |
- Backer, Vibeke, et al.
(författare)
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Clinical characteristics of the BREATHE cohort–a real-life study on patients with asthma and COPD
- 2020
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Ingår i: European clinical respiratory journal. - : Informa UK Limited. - 2001-8525. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The BREATHE study is a cross-sectional study of real-life patients with asthma and/or COPD in Denmark and Sweden aiming to increase the knowledge across severities and combinations of obstructive airway disease. Design: Patients with suspicion of asthma and/or COPD and healthy controls were invited to participate in the study and had a standard evaluation performed consisting of questionnaires, physical examination, FeNO and lung function, mannitol provocation test, allergy test, and collection of sputum and blood samples. A subgroup of patients and healthy controls had a bronchoscopy performed with a collection of airway samples. Results: The study population consisted of 1403 patients with obstructive airway disease (859 with asthma, 271 with COPD, 126 with concurrent asthma and COPD, 147 with other), and 89 healthy controls (smokers and non-smokers). Of patients with asthma, 54% had moderate-to-severe disease and 46% had mild disease. In patients with COPD, 82% had groups A and B, whereas 18% had groups C and D classified disease. Patients with asthma more frequently had childhood asthma, atopic dermatitis, and allergic rhinitis, compared to patients with COPD, asthma + COPD and Other, whereas FeNO levels were higher in patients with asthma and asthma + COPD compared to COPD and Other (18 ppb and 16 ppb vs 12.5 ppb and 14 ppb, p < 0.001). Patients with asthma, asthma + COPD and Other had higher sputum eosinophilia (1.5%, 1.5%, 1.2% vs 0.75%, respectively, p < 0.001) but lower sputum neutrophilia (39.3, 43.5%, 40.8% vs 66.8%, p < 0.001) compared to patients with COPD. Conclusions: The BREATHE study provides a unique database and biobank with clinical information and samples from 1403 real-life patients with asthma, COPD, and overlap representing different severities of the diseases. This research platform is highly relevant for disease phenotype- and biomarker studies aiming to describe a broad spectrum of obstructive airway diseases.
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| 4. |
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| 5. |
- Casillas Trujillo, Luis, et al.
(författare)
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Experimental and theoretical evidence of charge transfer in multi-component alloys : how chemical interactions reduce atomic size mismatch
- 2021
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Ingår i: Materials Chemistry Frontiers. - : Royal Society of Chemistry. - 2052-1537. ; 5:15, s. 5746-5759
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Tidskriftsartikel (refereegranskat)abstract
- Ab initio simulations of a multi-component alloy using density functional theory (DFT) were combined with experiments on thin films of the same material using X-ray photoelectron spectroscopy (XPS) to study the connection between the electronic and atomic structures of multi-component alloys. The DFT simulations were performed on an equimolar HfNbTiVZr multi-component alloy. Structure and charge transfer were evaluated using relaxed, non-relaxed, as well as elemental reference structures. The use of a fixed sphere size model allowed quantification of charge transfer, and separation into different contributions. The charge transfer was generally found to follow electronegativity trends and results in a reduced size mismatch between the elements, and thus causes a considerable reduction of the lattice distortions compared to a traditional assumption based on tabulated atomic radii. A calculation of the average deviation from the average radius (i.e. the so-called δ-parameter) based on the atomic Voronoi volumes gave a reduction of δ from ca. 6% (using the volumes in elemental reference phases) to ca. 2% (using the volumes in the relaxed multi-component alloy phase). The reliability of the theoretical results was confirmed by XPS measurements of a Hf22Nb19Ti18V19Zr21 thin film deposited by sputter deposition. The experimentally observed core level binding energy shifts (CLS), as well as peak broadening due to a range of chemical surroundings, for each element showed good agreement with the calculated DFT values. The single solid solution phase of the sample was confirmed by X-ray diffraction (XRD) and transmission electron microscopy (TEM) including energy dispersive spectroscopy (EDS) with nm-resolution. These observations show that the HfNbTiVZr solid solution phase is non-ideal, and that chemical bonding plays an important part in the structure formation, and presumably also in the properties. Our conclusions should be transferable to other multi-component alloy systems, as well as some other multi-component material systems, and open up interesting possibilities for the design of material properties via the electronic structure and controlled charge transfer between selected metallic elements in the materials.
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| 6. |
- Chou, Chia-Ying, et al.
(författare)
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Precipitation Kinetics During Post-heat Treatment of an Additively Manufactured Ferritic Stainless Steel
- 2022
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Ingår i: Metallurgical and Materials Transactions. A. - : Springer Nature. - 1073-5623 .- 1543-1940. ; 53:8, s. 3073-3082
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Tidskriftsartikel (refereegranskat)abstract
- The microstructure response of laser-powder bed fusion (L-PBF)-processed ferritic stainless steel (AISI 441) during post-heat treatments is studied in detail. Focus is on the precipitation kinetics of the Nb-rich phases: Laves (Fe2Nb) and the cubic carbo-nitride (NbC), as well as the grain structure evolution. The evolution of the precipitates is characterized using scanning and transmission electron microscopy (SEM and TEM) and the experimental results are used to calibrate precipitation kinetics simulations using the precipitation module (TC-PRISMA) within the Thermo-Calc Software package. The calculations reproduce the main trend for both the mean radii for the Laves phase and the NbC, and the amount of Laves phase, as a function of temperature. The calibrated model can be used to optimize the post-heat treatment of additively manufactured ferritic stainless steel components and offer a creator tool for process and structure linkages in an integrated computational materials engineering (ICME) framework for alloy and process development of additively manufactured ferritic steels.
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| 7. |
- Eckerdal, Patricia, 1972-, et al.
(författare)
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Epidural analgesia during Childbirth and Postpartum depressive symptoms : A population-based longitudinal cohort study
- 2020
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Ingår i: Anesthesia and Analgesia. - 0003-2999 .- 1526-7598. ; 130:3, s. 615-624
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Severe pain has been linked to depression, which raises the question of whether epidural analgesia (EDA) during childbirth is associated with a reduced risk of postpartum depression (PPD). This association has been explored previously, but the studies were restricted by small sample sizes and the inability to control for relevant confounders. This study aimed to investigate the association between the administration of EDA and the development of PPD after adjusting for sociodemographic, psychosocial, and obstetric variables.METHODS: Data were retrieved from the Biology, Affect, Stress, Imaging and Cognition (BASIC) project (2009-2017), a population-based longitudinal cohort study of pregnant women conducted at Uppsala University Hospital, Sweden. The outcome was PPD at 6 weeks postpartum, defined as a score of >= 12 points on the Edinburgh Postnatal Depression Scale (EPDS). Information was collected through medical records and self-reported web-based questionnaires during pregnancy and 6 weeks after childbirth. Only primiparous women with spontaneous start of childbirth were included (n = 1503). The association between EDA and PPD was examined in multivariable logistic regression models, adjusting for sociodemographic, psychosocial, and obstetric variables. Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS: Of the 1503 women included in the analysis, 800 (53%) reported use of EDA during childbirth. PPD at 6 weeks postpartum was present in 193 (13%) women. EDA was not associated with higher odds of PPD at 6 weeks postpartum after adjusting for suspected confounders (age, fear of childbirth, antenatal depressive symptoms; adjusted OR [aOR] = 1.22; 95% CI, 0.87-1.72).CONCLUSIONS: EDA was not associated with the risk of PPD at 6 weeks postpartum after adjusting for sociodemographic, psychosocial, and obstetric variables. However, these findings do not preclude a potential association between PPD and childbirth pain or other aspects of EDA that were not assessed in this study.
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| 8. |
- Fischer, M., et al.
(författare)
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Education and health: long-run effects of peers, tracking and years
- 2021
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Ingår i: Economic Policy. - : Oxford University Press (OUP). - 0266-4658 .- 1468-0327. ; 36:105, s. 3-49
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Tidskriftsartikel (refereegranskat)abstract
- We investigate two parallel school reforms in Sweden to assess the long-run health effects of education. One reform only increased years of schooling, while the other increased years of schooling but also removed tracking leading to a more mixed socioeconomic peer group. By differencing the effects of the parallel reforms we separate the effect of de-tracking and peers from that of more schooling. We find that the pure years of schooling reform reduced mortality and improved current health. Differencing the effects of the reforms shows significant differences in the estimated impacts, suggesting that de-tracking and subsequent peer effects resulted in worse health.
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| 9. |
- Glintborg, B., et al.
(författare)
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Uptake and effectiveness of newer biologic and targeted synthetic disease-modifying antirheumatic drugs in psoriatic arthritis: results from five Nordic biologics registries
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 82:6, s. 820-828
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWe aimed to describe the uptake of newer biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in psoriatic arthritis (PsA) in the Nordic countries and to compare their retention and effectiveness. MethodsPatients with PsA starting a b/tsDMARD in 2012-2020 in five Nordic rheumatology registers were included. Uptake and patient characteristics were described, with comorbidities identified from linkages to national patient registries. One-year retention and 6-month effectiveness (proportions achieving low disease activity (LDA) on the Disease Activity Index for PSoriatic Arthritis based on 28-joint evaluation) for the newer b/tsDMARDs (abatacept/apremilast/ixekizumab/secukinumab/tofacitinib/ustekinumab) were compared with adalimumab through adjusted regression models stratified by treatment course (first, second/third, and fourth or more). ResultsIn total, 5659 treatment courses with adalimumab (56% biologic-naive) and 4767 courses with a newer b/tsDMARD (21% biologic-naive) were included. The uptake of newer b/tsDMARDs increased from 2014 and plateaued in 2018. Patient characteristics appeared similar across treatments at treatment start. Adalimumab was more often used as the first course and newer b/tsDMARDs more often in biologic-experienced patients. Used as a second/third b/tsDMARD, the retention rate and the proportion achieving LDA were significantly better for adalimumab (rate 65%, proportion 59%) compared with abatacept (45%, 37%), apremilast (43%, 35%), ixekizumab (LDA only, 40%) and ustekinumab (LDA only, 40%), but not significantly different from other b/tsDMARDs. ConclusionUptake of newer b/tsDMARDs occurred mainly in biologic-experienced patients. Regardless of mode of action, only a minority of patients starting a second or later b/tsDMARD course remained on drug and achieved LDA. Superior outcomes for adalimumab indicate that the positioning of newer b/tsDMARDs in the PsA treatment algorithm remains to be established.
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| 10. |
- Halvorsen, Matthew, et al.
(författare)
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Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1, s. 1842-
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Tidskriftsartikel (refereegranskat)abstract
- Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.
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| 11. |
- Hofving, Tobias, 1989, et al.
(författare)
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The Microenvironment of Small Intestinal Neuroendocrine Tumours Contains Lymphocytes Capable of Recognition and Activation after Expansion
- 2021
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 13:17
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary The body's immune system can recognize tumors because they often contain proteins that are either different from or more abundant than in normal cells. Here, we characterised the immune cells of a rare tumor type called small-intestinal neuroendocrine tumors (SINET). We find that so called tumour-infiltrating lymphocytes (TILs) can be grown in the laboratory and activated by challenging them with digested tumor. This study provides insights into the largely unknown SINET immune landscape and reveals the anti-tumour reactivity of TILs, which might merit adoptive T cell transfer as a feasible treatment option for patients with SINET. Traditionally, immune evasion and immunotherapy have been studied in cancers with a high mutational load such as melanoma or lung cancer. In contrast, small intestinal neuroendocrine tumours (SINETs) present a low frequency of somatic mutations and are described as genetically stable tumours, rendering immunotherapies largely unchartered waters for SINET patients. SINETs frequently metastasise to the regional lymph nodes and liver at the time of diagnosis, and no curative treatments are currently available for patients with disseminated disease. Here, we characterised the immune landscape of SINET and demonstrated that tumour-infiltrating lymphocytes (TILs) can be expanded and activated during autologous tumour challenge. The composition of lymphocyte subsets was determined by immunophenotyping of the SINET microenvironment in one hepatic and six lymph node metastases. TILs from these metastases were successfully grown out, enabling immunophenotyping and assessment of PD-1 expression. Expansion of the TILs and exposure to autologous tumour cells in vitro resulted in increased T lymphocyte degranulation. This study provides insights into the largely unknown SINET immune landscape and reveals the anti-tumour reactivity of TILs, which might merit adoptive T cell transfer as a feasible treatment option for patients with SINET.
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| 12. |
- Högberg, Ulf, 1949-, et al.
(författare)
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Difficult birth is the main contributor to birthrelated fracture and accidents to other neonatal fractures
- 2020
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 109:10, s. 2040-2048
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Specific birthrelated fractures have been studied; underestimates might be a problem. We aimed to assess all fractures diagnosed as birthrelated as well as other neonatal fractures.METHODS: A population-based study on all infants born in Sweden 1997-2014; data was retrieved from the Swedish Health Registers (10th version of International Classification of Diseases. Outcome measures were birthrelated fractures (ICD-10 P-codes) and other neonatal fractures (ICD-10 S-codes).RESULTS: The overall fracture incidence was 2.9 per 1,000 live birth (N=5,336); 92.6% had P-codes and 7.4% (S-codes). Some birthrelated fractures were diagnosed beyond the neonatal period. Other neonatal fractures could have been birthrelated. Clavicle fracture, (88.8%) was associated with adverse maternal- and infant anthropometrics and birth complications. The few neonates with rib fractures all had concomitant clavicle fracture. For skull fractures, a minor part was birthrelated, most were associated with accidents. Half of the long bone fractures were associated with accidents. Birthrelated femur fractures were associated with bone fragility risk factors. Five infants with abuse diagnoses had fractures: skull (4), long bone (2), and rib (1).CONCLUSION: Birthrelated and other neonatal fractures are rarely diagnosed. Difficult birth is the main contributor to birthrelated fracture, and accidents to other neonatal fractures.
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| 13. |
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| 14. |
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| 15. |
- Karlsson, Dennis, 1991-
(författare)
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Additive Manufacturing of Ferritic Materials : A Journey from Stainless Steels to High-Entropy Alloys
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Design of new materials with complex geometries is an important part of new innovative solutions for technical applications. With the use of additive manufacturing (AM), the design possibilities are endless and geometries that are impossible to manufacture by conventional techniques are available. However, the number of alloys commercially available is limited and extensive research is needed to establish new materials with unique properties. An important group of materials is ferritic stainless steels which have a body centered cubic crystal structure. They are often used for their high strength, corrosion resistance or electrical properties at high temperatures. However, they are often less ductile than austenitic stainless steels and issues with cracking may arise during thermal cycling in the L-PBF process. In this thesis, two AM techniques, laser powder bed fusion (L-PBF) and binder jetting were used to produce components of two different ferritic stainless steels and of the AlCoCrFeNi high-entropy alloy (HEA). The main objective was to investigate the microstructural development, phase stabilities and mechanical properties in relation to conventional manufacturing routes. Furthermore, thermodynamic calculations were used to explain the phase stabilities and solidification. L-PBF enables manufacturing of the ferritic stainless steels SS441 and SS446 with excellent mechanical properties. It was shown that solid particles may form in the melt and act as heterogeneous nucleation points, resulting in effective grain refinement for SS441. Other secondary phases can form during the thermal cycling in the L-PBF process, enhancing the mechanical properties. An example is the formation of austenite in SS446. Furthermore, the formation of solid particles and segregated microstructure during solidification was predicted by thermodynamic calculations.The AlCoCrFeNi alloy could be produced with an intriguing hierarchical microstructure and excellent mechanical properties using binder jetting and post-treatments. The microstructure of the final component can also be controlled by pre-annealing of the feedstock powder. Thermodynamic calculations were used to design the phase composition of the alloy. A characteristic single-phase solid solution is only observed at very high temperatures close to the melting point. Hence, the AlCoCrFeNi alloy is not a thermodynamically true HEA, but is stabilized due to kinetic effects during manufacturing.
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| 16. |
- Karlsson, Dennis, et al.
(författare)
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Additive manufacturing of the ferritic stainless steel SS441
- 2020
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Ingår i: Additive Manufacturing. - AMSTERDAM, NETHERLANDS : Elsevier BV. - 2214-8604 .- 2214-7810. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the ferritic stainless steel SS441 was produced with excellent mechanical properties using laser powder bed fusion (L-PBF) compared to samples produced by conventional casting and hot-rolling. In addition, thermodynamic calculations were utilized to study the phase stability at elevated temperatures and to understand the solidification behavior. The hot-rolled sample showed a grain size up to several hundred mu m with additional precipitates of TiN and Nb(C,N). In contrast, the as-built L-PBF samples displayed a grain size in the mu m range. Spherical precipitates with a size of around 50 nm could be observed and were attributed to a corundum phase from the thermodynamic calculations. The printed material shows superior mechanical properties, with more than 30 times higher impact energy compared to the hot-rolled alloy (217 +/- 5 J vs. 7 +/- 0.5 J). Furthermore, the properties are anisotropic for the L-PBF produced alloy, with the highest tensile strength vertical to the build direction. The superior mechanical properties of the L-PBF produced sample can be attributed to a smaller grain size, giving a higher strength according to the Hall-Petch relationship. The anisotropy of the material can be eliminated by heat treatments at 900 degrees C followed by water quenching, but the absolute strength decreases slightly due to formation of intermetallic phases such as Nb(C,N) and the Fe2Nb Laves phase. The results clearly illustrates that L-PBF provides a promising manufacturing mute for enhanced strength of ferritic stainless steels.
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| 17. |
- Karlsson, Dennis, et al.
(författare)
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Structure and phase transformations in gas atomized AlCoCrFeNi high entropy alloy powders
- 2022
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 893
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the crystal structure and phase stability of gas atomized equiatomic AlCoCrFeNi powder was investigated. This alloy is usually described as a high entropy alloy forming a solid solution phase stabilized by a high mixing entropy. However, thermodynamic calculations show that the high entropy phase is stable only at very high temperatures close to the melting point and that a mixture of several phases are the most stable state at lower temperatures. This suggest that kinetic effects may influence the phase composition of atomized powder. The unique features of X-ray diffraction, neutron diffraction as well as transmission electron microscopy were used to study the atomic structure of the atomized powder in detail. The results show that the powder crystallises in an ordered B2 (CsCl-type) structure with a preferred site occupation of Al and Fe on the (1/2 1/2 1/2) position and Co and Ni on the (0 0 0) position. During heat-treatment of the powder, the B2 phase decomposes into fcc and sigma phases and the final phase composition is highly dependent on the heating rate. The effect of heat-treatment on the atomized powder was also investigated and revealed a significant phase transformation with e.g. the formation of sigma phase preferably at the surface of the powder particles. The phase content was also dependent on the size fraction of the powder particles. Sintering of green bodies made with different heat cycles showed that the phase composition of the starting material had a significant impact on the final phase composition and microstructure of the sintered components. The results illustrate the importance of well-defined powder materials for powder consolidation, especially additive manufacturing (binder jetting) of high entropy alloys.
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| 18. |
- Karlsson, Sofia, et al.
(författare)
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Preparedness for peer first response to mining emergencies resulting in injuries: a cross-sectional study
- 2020
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Identify factors of preparedness for peer first response to underground mining emergencies with injured victims.Design: Cross-sectional questionnaire study of Swedish underground mineworkers.Setting: Seven out of nine Swedish underground mines.Participants: A total of 741 mineworkers out of 1022 (73%) participated in this study.Interventions: None.Outcome measures: Level of preparedness for emergencies with injuries in underground mines.Results: Three factors influenced the preparedness of mineworkers for a peer first response: (1) familiarity with rescue procedures during emergencies with injuries; (2) risk perception of emergencies with injuries and (3) experience of using self-protective and first aid equipment. Mineworkers who believed that they knew how to handle emergencies with injuries (OR 1.30, 95% CI 1.22 to 1.38) and those who were trained in the use of self-protective and first aid equipment (OR 1.19, 95% CI 1.07 to 1.32) considered themselves to be better prepared for a peer first response than those who were unfamiliar with the rescue procedures or who had not used self-protective and first aid equipment. However, mineworkers who rated the risk for emergencies with injuries as high considered themselves to be less prepared than those who rated the risk as low (OR 0.95, 95% CI 0.91 to 0.98).Conclusion: This study identified three factors that were important for the peer-support preparedness of underground mineworkers. More research is needed to adapt and contextualise first aid courses to the needs of underground peer responders.
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| 19. |
- Katsogiannos, Petros, et al.
(författare)
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Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery
- 2020
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Ingår i: Endocrine. - : SPRINGER. - 1355-008X .- 1559-0100. ; 67:2, s. 344-353
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).Research design and methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.Results: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components P-LF (power of low frequency) and P-HF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the P-LF/P-HF ratio decreased. None of these changes were seen in the control group.Conclusions: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.
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| 20. |
- Kazadi Mbamba, Christian, et al.
(författare)
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Modelling Industrial Symbiosis of Biogas Production and Industrial Wastewater Treatment Plants – Technical Report
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The present-day treatment of pulp and paper mill effluents can be significantly improved by incorporating biogas production in the context of industrial symbiosis. In this work a new industrial symbiosis concept is presented, the focus being on modelling it in view of process optimization, design improvement and adoption by the pulp and paper industry. The concept consists of a first stage in which pulp and paper mill effluents are treated by high-rate anaerobic digestion in external circulation sludge bed (ECSB) reactors to produce biogas. In the second stage the removal of organic matter contained in the anaerobic effluent stream occurs through aerobic activated sludge treatment, aiming to achieve maximum sludge production with minimum aeration requirements. This sludge should in the case study then be co-digested with residues from fish farming industry to yield methane for energy production, nutrient-rich reject water that can be recycled to the activated sludge treatment for optimum microbial activities and production of a nutrient-rich soil amendment. The overall research aim was in this project to develop a mathematical model that describes the relevant process units and the dynamics of the different processes involving organic matter removal, biogas production and nutrient release. The plant-wide model used integrated activated sludge and anaerobic models with a physico-chemical modelling framework. Through systematic calibration good general agreement was obtained between the full-scale experimental and simulated results at steady state. Acceptable differences between measured and modelled biogas production (flow rate and methane concentration), nutrients release (N and P) and effluent quality (N, P and COD) of 2-3.2 %, 5.3-7.4 % and 1.4-1.9 %, respectively, were observed throughout the full-scale system. Model-based analysis shows that the model can predict and give insight on dynamic behaviours resulting from deliberate changes but also on disturbances in one of the systems and their subsequent impacts within the integrated plant. Additionally, the model allowed the prediction of nutrients release in anaerobic digestion and subsequent consumption upstream in the high-rate anaerobic system or activated sludge system. Simulations show that there is a need for imposing a basic control and operational strategy for efficient reject water recirculation to optimize the concentrations of N and P in the activated sludge system while also achieving nutrient levels required to meet the effluent discharge permits. Overall, the evaluated plant-wide model can jointly describe the relevant physico-chemical and biological processes and is therefore advocated as a tool for future extension of this type of industrial symbiosis concepts between biogas producers and industries producing large amounts of wastewater rich in organic material. The model can be used for design, multi-criteria performance assessment and optimization of different treatment plants.
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| 21. |
- Kierczak, Marcin, 1981-, et al.
(författare)
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Contribution of rare whole-genome sequencing variants to plasma protein levels and the missing heritability
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Despite the success of genome-wide association studies, much of the genetic contribution to complex traits remains unexplained. Here, we analysed high coverage whole genome sequencing data, to evaluate the contribution of rare genetic variants to 414 plasma proteins. The frequency distribution of genetic variants was skewed towards the rare spectrum, and damaging variants were more often rare. We estimated that less than 4.3% of the narrow-sense heritability is expected to be explained by rare variants in our cohort. Using a gene-based approach, we identified Cis-associations for 237 of the proteins, which is slightly more compared to a GWAS (N=213), and we identified 34 loci in Trans. Several associations were driven by rare variants, and rare variants had on average larger phenotypic effects. We conclude therefore that rare variants could be of importance for precision medicine applications, but have a more limited contribution to the missing heritability of complex diseases.
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| 22. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men: the MrOS Sweden cohort
- 2022
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- This study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures. Introduction Anemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures. Method Men from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years. Results Men with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28-3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18-3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06-5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD. Conclusions Anemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture.
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| 23. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High Plasma Erythropoietin Predicts Incident Fractures in Elderly Men with Normal Renal Function : The MrOS Sweden Cohort
- 2020
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Ingår i: Journal of Bone and Mineral Research. - : WILEY. - 0884-0431 .- 1523-4681. ; 35:2, s. 298-305
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical studies on the role of erythropoietin (EPO) in bone metabolism are contradictory. Regeneration models indicate an anabolic effect on bone healing, whereas models on physiologic bone remodeling indicate a catabolic effect on bone mass. No human studies on EPO and fracture risk are available. It is known that fibroblast growth factor 23 (FGF23) affects bone mineralization and that serum concentration of FGF23 is higher in men with decreased estimated glomerular filtration rate (eGFR). Recently, a direct association between EPO and FGF23 has been shown. We have explored the potential association between EPO and bone mineral density (BMD), fracture risk, and FGF23 in humans. Plasma levels of EPO were analyzed in 999 men (aged 69 to 81 years), participating in the Gothenburg part of the population-based Osteoporotic Fractures in Men (MrOS) study, MrOS Sweden. The mean +/- SD EPO was 11.5 +/- 9.0 IU/L. Results were stratified by eGFR 60 mL/min. For men with eGFR >= 60 mL/min (n = 728), EPO was associated with age (r = 0.13, p < 0.001), total hip BMD (r = 0.14, p < 0.001), intact (i)FGF23 (r = 0.11, p = 0.004), and osteocalcin (r = -0.09, p = 0.022). The association between total hip BMD and EPO was independent of age, body mass index (BMI), iFGF23, and hemoglobin (beta = 0.019, p < 0.001). During the 10-year follow-up, 164 men had an X-ray-verified fracture, including 117 major osteoporotic fractures (MOF), 39 hip fractures, and 64 vertebral fractures. High EPO was associated with higher risk for incident fractures (hazard ratio [HR] = 1.43 per tertile EPO, 95% confidence interval [CI] 1.35-1.63), MOF (HR = 1.40 per tertile EPO, 95% CI 1.08-1.82), and vertebral fractures (HR = 1.42 per tertile EPO, 95% CI 1.00-2.01) in a fully adjusted Cox regression model. In men with eGFR<60 mL/min, no association was found between EPO and BMD or fracture risk. We here demonstrate that high levels of EPO are associated with increased fracture risk and increased BMD in elderly men with normal renal function.
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| 24. |
- Kristjansdottir, Hallgerdur Lind, et al.
(författare)
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High platelet count is associated with low bone mineral density: The MrOS Sweden cohort.
- 2021
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Ingår i: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 32:5, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- In elderly ambulatory men, high platelet and high neutrophil counts are related to low bone mineral density (BMD), after adjustment for relevant covariates. Low hemoglobin (hgb) is even associated with low BMD, but this relationship seems to be dependent on estradiol and osteocalcin.Blood and bone cells exist in close proximity to each other in the bone marrow. Accumulating evidence, from both preclinical and clinical studies, indicates that these cell types are interconnected. Our hypothesis was that BMD measurements are associated with blood count variables and bone remodeling markers.We analyzed blood count variables, bone remodeling markers, and BMD, in subjects from the MrOS cohort from Gothenburg, Sweden. Men with at least one blood count variable (hgb, white blood cell count, or platelet count) analyzed were included in the current analysis (n=1005), median age 75.3years (range 69-81years).Our results show that high platelet counts were related to low BMD at all sites (total hip BMD; r=-0.11, P=0.003). No statistically significant association was seen between platelet counts and bone remodeling markers. Neutrophil counts were negatively associated with total body BMD (r=-0.09, P=0.006) and total hip BMD (r=-0.08, P=0.010), and positively related to serum ALP (r=0.15, P<0.001). Hgb was positively related to total hip BMD (r=0.16, P<0.001), and negatively to serum osteocalcin (r=-0.13, P<0.001). The association between platelet and neutrophil counts and total hip BMD was statistically significant after adjustments for other covariates, but the association between hgb and total hip BMD was dependent on estradiol and osteocalcin.Our observations support the hypothesis of an interplay between blood and bone components.
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| 25. |
- Landquist, Birgit, et al.
(författare)
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Uppdaterad och utökad livscykelanalys av svensk grisproduktion
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Förbättrade produktionsresultat inom svensk grisproduktion, användning av biproduk-ter och djurhälsans betydelse har analyserats i en livscykelanalys. Klimatavtrycket för kött från en svensk medelgris är 2,54 kg koldioxidekvivalenter/kg slaktvikt, vilket är bland de lägsta jämfört med tillgängliga internationella studier. Produktionen av foder står för 54 % av klimatavtrycket och hanteringen av stallgödsel för 36 %. Av foderstaten till den svenska integrerade medelslaktgrisen utgjorde biprodukter 10 % och soja 4 %. Baserat på antalet dagars förlängd uppfödningstid för sjuka grisar, visar vi att 3,4 % av klimatavtrycket beror på ökad foderförbrukning orsakad av fyra utvalda sjukdomar i svenska grisbesättningar. Produktionshöjande åtgärder såsom exempelvis friska grisar och hög fodereffektivitet, övergång till förnybara bränslen inom såväl odling av foder som inom grisuppfödning är viktiga åtgärder för att minska klimatavtrycket givet att det inte påverkar andra miljöaspekter, djurhälsa eller djurvälfärd negativt. En central aspekt är fortsatt utveckling mot välbalanserade foderstater med val av foderråvaror med lågt klimatavtryck, användning av biprodukter och inhemska fodergrödor odlade på ett hållbart sätt.
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| 26. |
- Macassa, Gloria, et al.
(författare)
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Perceptions of Health and Wellbeing Among Employees in a Work Integration Social Enterprise in Sweden
- 2023
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Ingår i: Annals of Global Health. - : Ubiquity Press. - 2214-9996. ; 89:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Work Integration Social Enterprises (WISEs) constitute an important vehiclefor providing employment opportunities for disadvantaged groups.Objective: The goal of this qualitative case study is to explore perceptions of health andwellbeing among employees working in a WISE located in the Gävleborg region, in eastcentral Sweden.Methods: Data were gathered using 16 in-depth, semi-structured interviews with thesocial enterprise employees.Results: Findings were categorized into three main categories: the importance of financialindependence and societal benefits; team spirit and a sense of belonging; and improvedquality of life and wellbeing.Conclusion: The participants perceived that working in the WISE gave them a feeling offreedom and increased their self-esteem because of the possibility to earn an income.Also, they were satisfied with their job (e.g., with regard to work quality and flexibility)and believed that their work contributed to society. Moreover, through working in a WISE,the participants felt a sense of belonging and togetherness through interaction with coworkersand managers, and an improved quality of life for themselves and their families.
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| 27. |
- Marattukalam, Jithin J., et al.
(författare)
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Development of process parameters for selective laser melting of a Zr-based bulk metallic glass
- 2020
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Ingår i: Additive Manufacturing. - : Elsevier. - 2214-8604 .- 2214-7810. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Parameters for selective laser melting of Zr59.3Cu28.8Al10.4Nb1.5 (trade name AMZ4), allowing crack-free bulk metallic glass with low porosity, have been developed. The phase formation was found to be strongly influenced by the heating power of the laser. X-ray amorphous samples were obtained with laser power at and below 75 W. The as-processed bulk metallic glass was found to devitrify by a two-stage crystallization process within which the presence of oxygen was concluded to play an essential role. At laser powers above 75 W, the observed crystallites were found to be a cubic phase (Cu2Zr4O). The hardness and Young’s modulus in the as-processed samples was found to increase marginally with increased fraction of the crystalline phase.
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| 28. |
- Marattukalam, Jithin James, et al.
(författare)
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The effect of laser scanning strategies on texture, mechanical properties, and site-specific grain orientation in selective laser melted 316L SS
- 2020
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Ingår i: Materials & design. - : Elsevier BV. - 0264-1275 .- 1873-4197. ; 193
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Tidskriftsartikel (refereegranskat)abstract
- Selective laser melting has been used to demonstrate the striking effect of laser scanning strategies on the crystalline texture in 316L SS. The aligned crystal orientation along the tensile direction (Z-axis) could be varied using the scanning strategy. A strong 〈100〉 single crystalline-like texture is obtained in the direction of the laser scan and a 〈110〉 texture was observed in the build direction when using a bidirectional scan without rotation. Fiber texture was observed along the tensile direction when the bi-directional laser scanning vectors were rotated by 67° (Rot-scan) for each layer. The study highlights a correlation between laser scanning strategies with resulting textures, microstructure, and mechanical properties in as-printed bulk 316L SS. The hardness, Young's modulus, and ultimate tensile strength were significantly influenced by the final microstructure, crystallographic texture, and porosity. Furthermore, the applied laser scanning strategies made it possible to tailor crystallographic textures locally within the component. This was demonstrated by printing characters with a fiber texture, in a matrix with ⟨100⟩ texture parallel to the Z-axis.
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| 29. |
- Nilsson, Fritjof, Docent, 1978-, et al.
(författare)
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Nanocomposites and polyethylene blends: two potentially synergistic strategies for HVDC insulation materials with ultra-low electrical conductivity
- 2021
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Ingår i: Composites Part B: Engineering. - : Elsevier BV. - 1359-8368 .- 1879-1069. ; 204
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Tidskriftsartikel (refereegranskat)abstract
- Among the various requirements that high voltage direct current (HVDC) insulation materials need to satisfy, sufficiently low electrical conductivity is one of the most important. The leading commercial HVDC insulation material is currently an exceptionally clean cross-linked low-density polyethylene (XLPE). Previous studies have reported that the DC-conductivity of low-density polyethylene (LDPE) can be markedly reduced either by including a fraction of high-density polyethylene (HDPE) or by adding a small amount of a well dispersed, semiconducting nanofiller such as Al2O3 coated with a silane. This study demonstrates that by combining these two strategies a synergistic effect can be achieved, resulting in an insulation material with an ultra-low electrical conductivity. The addition of both HDPE and C8–Al2O3 nanoparticles to LDPE resulted in ultra-insulating nanocomposites with a conductivity around 500 times lower than of the neat LDPE at an electric field of 32 kV/mm and 60–90 °C. The new nanocomposite is thus a promising material regarding the electrical conductivity and it can be further optimized since the polyethylene blend and the nanoparticles can be improved independently.
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| 30. |
- Nosratabadi, Ali Reza, et al.
(författare)
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Airway contraction and cytokine release in isolated rat lungs induced by wear particles from the road and tire interface and road vehicle brakes
- 2023
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Ingår i: Inhalation Toxicology. - : Taylor & Francis. - 0895-8378 .- 1091-7691. ; 35:13-14, s. 309-323
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Tidskriftsartikel (refereegranskat)abstract
- The dominant road traffic particle sources are wear particles from the road and tire interface, and from vehicle brake pads. The aim of this work was to investigate the effect of road and brake wear particles on pulmonary function and biomarkers in isolated perfused rat lungs. Particles were sampled from the studded tire wear of three road pavements containing different rock materials in a road simulator; and from the wear of two brake pad materials using a pin-on-disk machine. Isolated rat lungs inhaled the coarse and fine fractions of the sampled particles resulting in an estimated total particle lung dose of 50 μg. The tidal volume (TV) was measured during the particle exposure and the following 50 min. Perfusate and BALF were analyzed for the cytokines TNF, CXCL1 and CCL3. The TV of lungs exposed to rock materials was significantly reduced after 25 min of exposure compared to the controls, for quartzite already after 4 min. The particles of the heavy-duty brake pads had no effect on the TV. Brake particles resulted in a significant elevation of CXCL1 in the perfusate. Brake particles showed significant elevations of all three measured cytokines, and quartzite showed a significant elevation of TNF in BALF. The study shows that the toxic effect on lungs exposed to airborne particles can be investigated using measurements of tidal volume. Furthermore, the study shows that the choice of rock material in road pavements has the potential to affect the toxicity of road wear PM10.
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| 31. |
- Olofsson, Ulf, 1962-, et al.
(författare)
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Nanoparticle emissions from the transport sector: health and policy impacts - the nPETS concept
- 2023
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Ingår i: 2022 Conference Proceedings Transport Research Arena, TRA Lisbon 2022. - : Elsevier BV. ; 72, s. 248-255
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Konferensbidrag (refereegranskat)abstract
- Road, rail, air, and sea transport generate a major fraction of outdoor ultrafine particles. However, there is no common methodology for comparable sub 100 nm particle emissions measurement. This paper presents the nPETS (grant agreement No 954377) concept to understand and mitigate the effects of emerging non-regulated nanoparticle emissions. This paper presents the concept and selected results. For example, nucleation and condensation mechanisms occur more frequently in the urban background site, leading to new particle formation, while mostly fresh emissions are measured in the traffic site.
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| 32. |
- Pacheco, Victor, et al.
(författare)
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Thermal stability and crystallization of a Zr-based metallic glass produced by suction casting and selective laser melting
- 2020
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Ingår i: Journal of Alloys and Compounds. - : ELSEVIER SCIENCE SA. - 0925-8388 .- 1873-4669. ; 825
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Tidskriftsartikel (refereegranskat)abstract
- The thermal stability and crystallization mechanism of the Zr59.3Cu28.8Al10.4Nb1.5 (at%) metallic glass produced through selective laser melting SLM (from industrial grade material) was studied and compared with the same alloy produced by suction casting (from laboratory grade material of high purity). Oxygen- and Al-rich particles of a cubic phase (Fd (3) over barm) with a size of up to 200 nm are detected in the as-built selective laser melted samples by transmission electron microscopy. The crystallization process of the cast and SLM samples is investigated by in-situ X-ray diffraction experiments. In the cast samples, the initial crystallization occurs via the formation of a metastable tetragonal phase (Al2Zr3), together with tetragonal CuZr2 and hexagonal Al3Zr4 type structures, while the SLM samples initially crystallize through the formation of the metastable, oxygen- and Al-rich, cubic phase already present before annealing. The main phases present at the end of the crystallization for both type of samples are the same, mainly CuZr2 and Al3Zr4. The differences in the crystallization paths are attributed to differences in the oxygen levels. In general, the higher oxygen content (similar to 1 at%) of the SLM samples results in a decrease of the thermal stability of the alloy and promotes the formation of an oxygen-rich, metastable cubic phase.
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| 33. |
- Paschalidou, Eirini-Maria, et al.
(författare)
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Corrosion studies on multicomponent CoCrFeMnNi(C) thin films in acidic environments
- 2022
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Ingår i: Electrochimica Acta. - : Elsevier. - 0013-4686 .- 1873-3859. ; 404
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Tidskriftsartikel (refereegranskat)abstract
- The corrosion resistances of near equimolar CoCrFeMnNi magnetron-sputtered thin films with different carbon concentrations were examined in 0.05 M HCl and 0.05 M H2SO4. Polarization curves were recorded with different scan rates with and without reducing the native oxide. The results showed that the carbon concentration and the experimental conditions affected the electrochemical behaviour mainly in the Cr transpassive region. At potentials above 850 mV, the carbon-containing films were more corrosion resistant in 0.05 M HCl than in 0.05 M H2SO4 due to a lower carbon oxidation rate in 0.05 M HCl, facilitating the formation of a Mn-rich oxide layer. (C)& nbsp;2021 The Author(s). Published by Elsevier Ltd.& nbsp;
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| 34. |
- Ronquist, Fredrik, et al.
(författare)
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Completing Linnaeus’s inventory of the Swedish insect fauna: only 5,000 species left?
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Despite more than 250 years of taxonomic research, we still have only a vague idea about the true size and composition of the faunas and floras of the planet. Many biodiversity inventories provide limited insight because they focus on a small taxonomic subsample or a tiny geographic area. Here, we report on the size and composition of the Swedish insect fauna, thought to represent roughly half of the diversity of multicellular life in one of the largest European countries. Our results are based on more than a decade of data from the Swedish Taxonomy Initiative and its massive inventory of the country’s insect fauna, the Swedish Malaise Trap Project The fauna is considered one of the best known in the world, but the initiative has nevertheless revealed a surprising amount of hidden diversity: more than 3,000 new species (301 new to science) have been documented so far. Here, we use three independent methods to analyze the true size and composition of the fauna at the family or subfamily level: (1) assessments by experts who have been working on the most poorly known groups in the fauna; (2) estimates based on the proportion of new species discovered in the Malaise trap inventory; and (3) extrapolations based on species abundance and incidence data from the inventory. For the last method, we develop a new estimator, the combined non-parametric estimator, which we show is less sensitive to poor coverage of the species pool than other popular estimators. The three methods converge on similar estimates of the size and composition of the fauna, suggesting that it comprises around 33,000 species. Of those, 8,600 (26%) were unknown at the start of the inventory and 5,000 (15%) still await discovery. We analyze the taxonomic and ecological composition of the estimated fauna, and show that most of the new species belong to Hymenoptera and Diptera groups that are decomposers or parasitoids. Thus, current knowledge of the Swedish insect fauna is strongly biased taxonomically and ecologically, and we show that similar but even stronger biases have distorted our understanding of the fauna in the past. We analyze latitudinal gradients in the size and composition of known European insect faunas and show that several of the patterns contradict the Swedish data, presumably due to similar knowledge biases. Addressing these biases is critical in understanding insect biomes and the ecosystem services they provide. Our results emphasize the need to broaden the taxonomic scope of current insect monitoring efforts, a task that is all the more urgent as recent studies indicate a possible worldwide decline in insect faunas.
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| 35. |
- Sjögren, Sara E., et al.
(författare)
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Targeting elevated heme levels to treat a mouse model for Diamond-Blackfan Anemia
- 2022
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Ingår i: Experimental Hematology. - : Elsevier BV. - 0301-472X. ; 105, s. 50-61
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Tidskriftsartikel (refereegranskat)abstract
- Diamond-Blackfan anemia (DBA) is a rare genetic disorder in which patients present a scarcity of erythroid precursors in an otherwise normocellular bone marrow. Most, but not all, patients carry mutations in ribosomal proteins such as RPS19, suggesting that compromised mRNA translation and ribosomal stress are pathogenic mechanisms causing depletion of erythroid precursors. To gain further insight to disease mechanisms in DBA, we performed a custom short hairpin RNA (shRNA) based screen against 750 genes hypothesized to affect DBA pathophysiology. Among the hits were two shRNAs against the erythroid specific heme-regulated eIF2α kinase (HRI), which is a negative regulator of mRNA translation. This study shows that shRNA-mediated HRI silencing or loss of one HRI allele improves expansion of Rps19-deficient erythroid precursors, as well as improves the anemic phenotype in Rps19-deficient animals. We found that Rps19-deficient erythroblasts have elevated levels of unbound intracellular heme, which is normalized by HRI heterozygosity. Additionally, targeting elevated heme levels by treating cells with the heme scavenger alpha-1-microglobulin (A1M), increased proliferation of Rps19-deficient erythroid precursors and decreased heme levels in a disease-specific manner. HRI heterozygosity, but not A1M treatment, also decreased the elevated p53 activity observed in Rps19-deficient cells, indicating that p53 activation is caused by ribosomal stress and aberrant mRNA translation and not heme overload in Rps19-deficiency. Together, these findings suggest that targeting elevated heme levels is a promising new treatment strategy for DBA.
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| 36. |
- Strömberg, Ulf, 1964, et al.
(författare)
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Socioeconomic inequality in prostate cancer diagnostics, primary treatment, rehabilitation, and mortality in Sweden
- 2024
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Ingår i: INTERNATIONAL JOURNAL OF CANCER. - : John Wiley & Sons. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- We designed a nationwide study to investigate the association between socioeconomic factors (household income and education) and different aspects of prostate cancer care, considering both individual- and neighbourhood-level variables. Data were obtained from Prostate Cancer data Base Sweden (PCBaSe), a research database with data from several national health care registers including clinical characteristics and treatments for nearly all men diagnosed with prostate cancer in Sweden. Four outcomes were analysed: use of pre-biopsy magnetic resonance imaging (MRI) in 2018-2020 (n = 11,843), primary treatment of high-risk non-metastatic disease in 2016-2020 (n = 6633), rehabilitation (>= 2 dispensed prescriptions for erectile dysfunction within 1 year from surgery in 2016-2020, n = 6505), and prostate cancer death in 7770 men with high-risk non-metastatic disease diagnosed in 2010-2016. Unadjusted and adjusted odds and hazard ratios (OR/HRs) with 95% confidence intervals (CIs) were calculated. Adjusted odds ratio (ORs) comparing low versus high individual education were 0.74 (95% CI 0.66-0.83) for pre-biopsy MRI, 0.66 (0.54-0.81) for primary treatment, and 0.82 (0.69-0.97) for rehabilitation. HR gradients for prostate cancer death were significant on unadjusted analysis only (low vs. high individual education HR 1.41, 95% CI 1.17-1.70); co-variate adjustments markedly attenuated the gradients (low vs. high individual education HR 1.10, 95% CI 0.90-1.35). Generally, neighbourhood-level analyses showed weaker gradients over the socioeconomic strata, except for pre-biopsy MRI. Socioeconomic factors influenced how men were diagnosed with prostate cancer in Sweden but had less influence on subsequent specialist care. Neighbourhood-level socioeconomic data are more useful for evaluating inequality in diagnostics than in later specialist care.
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| 37. |
- Ståhle, Alexander, et al.
(författare)
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Designguide för Smarta gator
- 2022
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Designguiden för smarta gator konkretiserar hur de fyra megatrenderna urbanisering, digitalisering, samhällsförändringar och miljöförändringar leder till nya krav och utformningsprinciper för framtidens gator. Guiden är tänkt att fungera som en inspiration och ett underlag för att förnya svensk gatupolicy på nationell, regional och kommunal nivå.Guiden innehåller utöver en inledning följande kapitel: en historisk tillbakablick (gatans utveckling), gatans användning, gatans delar, gatans design, designprocessen, guidens genomförande.
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| 38. |
- Thellenberg-Karlsson, Camilla, 1972-, et al.
(författare)
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A randomised, double-blind, dose-finding, phase II multicentre study of ODX in the treatment of patients with castration-resistant prostate cancer and skeletal metastases
- 2023
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 181, s. 198-207
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Tidskriftsartikel (refereegranskat)abstract
- Aims: This study aimed to assess the efficacy and safety of ODX, a novel, cytotoxic, bone-targeting drug candidate, in castration-resistant prostate cancer bone metastatic disease.Methods: Patients with progressive disease were randomised to ten cycles of ODX, intravenous infusion Q2W (3, 6, and 9 mg/kg, respectively). The primary objective was to assess the relative change from baseline in bone alkaline phosphatase (B-ALP) and serum-aminoterminal-propeptide of Type I procollagen (S-P1NP) at 12 weeks. The inclusion criteria selected were broad, and a double-blind design was used to ensure objective recruitment of patients for the assessment of efficacy. None of the patients received bone-protecting agents during the ODX treatment period.Results: Fifty-five 21,20 and 14) patients were randomised to ODX (3, 6 and 9 mg/kg), respectively. The lower number of patients in arm 3 was due to too low a recruitment rate towards the end of the study. The median treatment time were 14, 13 and 14 weeks, respectively. The decrease in B-ALP at 12 weeks in study arms 3, 6 and 9 mg/kg was seen in 6/15 (40%), 8/12 (67%) and 5/12 (42%) patients, respectively, whereas the corresponding numbers for P1NP were 8/15 (53%), 8/12 (67%), and 4/12 (33%), respectively. The median decrease in B-ALP and P1NP at 12 weeks for study arms 3, 6 and 9 mg/kg were 37%, 14% and 43%, respectively, and 51%, 40% and 64%, respectively. The decrease in serum C-terminal telopeptide at 12 weeks was seen in the vast majority of patients and in about one-third of patients in bone scan index. ODX was well tolerated, and no drug-related serious adverse events occurred. There were no significant differences between study arms regarding efficacy and safety.Conclusions: ODX was well tolerated and demonstrated inhibitory effects on markers related to the vicious cycle in bone at all three doses. The reduction in metastatic burden, assessed with bone scan index, supports this finding. Studies with continued ODX treatment until disease progression are being planned (ClinicalTrials.gov Identifier: NCT02825628).
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| 39. |
- Vallabani, N. V. Srikanth, et al.
(författare)
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Toxicity and health effects of ultrafine particles : Towards an understanding of the relative impacts of different transport modes
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 231
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Forskningsöversikt (refereegranskat)abstract
- Exposure to particulate matter (PM) has been associated with a wide range of adverse health effects, but it is still unclear how particles from various transport modes differ in terms of toxicity and associations with different human health outcomes. This literature review aims to summarize toxicological and epidemiological studies of the effect of ultrafine particles (UFPs), also called nanoparticles (NPs, <100 nm), from different transport modes with a focus on vehicle exhaust (particularly comparing diesel and biodiesel) and non-exhaust as well as particles from shipping (harbor), aviation (airport) and rail (mainly subway/underground). The review includes both particles collected in laboratory tests and the field (intense traffic environments or collected close to harbor, airport, and in subway). In addition, epidemiological studies on UFPs are reviewed with special attention to studies aimed at distinguishing the effects of different transport modes. Results from toxicological studies indicate that both fossil and biodiesel NPs show toxic effects. Several in vivo studies show that inhalation of NPs collected in traffic environments not only impacts the lung, but also triggers cardiovascular effects as well as negative impacts on the brain, although few studies compared NPs from different sources. Few studies were found on aviation (airport) NPs, but the available results suggest similar toxic effects as traffic-related particles. There is still little data related to the toxic effects linked to several sources (shipping, road and tire wear, subway NPs), but in vitro results highlighted the role of metals in the toxicity of subway and brake wear particles. Finally, the epidemiological studies emphasized the current limited knowledge of the health impacts of source-specific UFPs related to different transport modes. This review discusses the necessity of future research for a better understanding of the relative potencies of NPs from different transport modes and their use in health risk assessment.
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| 40. |
- Venkatakrishnan, Vignesh, 1987, et al.
(författare)
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Novel inhibitory effect of galectin-3 on the respiratory burst induced by Staphylococcus aureus in human neutrophils
- 2023
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Ingår i: Glycobiology. - : OXFORD UNIV PRESS INC. - 1460-2423 .- 0959-6658. ; 33:6, s. 503-511
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Tidskriftsartikel (refereegranskat)abstract
- Among the responders to microbial invasion, neutrophils represent the earliest and perhaps the most important immune cells that contribute to host defense with the primary role to kill invading microbes using a plethora of stored anti-microbial molecules. One such process is the production of reactive oxygen species (ROS) by the neutrophil enzyme complex NADPH-oxidase, which can be assembled and active either extracellularly or intracellularly in phagosomes (during phagocytosis) and/or granules (in the absence of phagocytosis). One soluble factor modulating the interplay between immune cells and microbes is galectin-3 (gal-3), a carbohydrate-binding protein that regulates a wide variety of neutrophil functions. Gal-3 has been shown to potentiate neutrophil interaction with bacteria, including Staphylococcus aureus, and is also a potent activator of the neutrophil respiratory burst, inducing large amounts of granule-localized ROS in primed cells. Herein, the role of gal-3 in regulating S. aureus phagocytosis and S. aureus-induced intracellular ROS was analyzed by imaging flow cytometry and luminol-based chemiluminescence, respectively. Although gal-3 did not interfere with S. aureus phagocytosis per se, it potently inhibited phagocytosis-induced intracellular ROS production. Using the gal-3 inhibitor GB0139 (TD139) and carbohydrate recognition domain of gal-3 (gal-3C), we found that the gal-3-induced inhibitory effect on ROS production was dependent on the carbohydrate recognition domain of the lectin. In summary, this is the first report of an inhibitory role of gal-3 in regulating phagocytosis-induced ROS production.
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| 41. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 42. |
- Widén, Johan, et al.
(författare)
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Mycoplasma pneumonia with severe cold agglutinin hemolysis, thrombocytosis, leukemoid reaction and acute renal failure
- 2023
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Ingår i: IDCases. - : Elsevier BV. - 2214-2509. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Mycoplasma pneumoniae (M. pneumoniae) is a common cause of community acquired pneumonia and although most cases are mild, complications sometimes occur. Cold agglutinin hemolysis is a known complication of M. pneumoniae infection, and usually presents as a mild and transient hemolysis. Here we present a case of infection with M. pneumoniae in a 64-year-old male that caused life threatening hemolysis that required multiple blood transfusions. The patient also presented with acute kidney failure and a marked leukemoid reaction and thrombocytosis. This is a very rare combination of symptoms that could have led the clinicians to suspect a more virulent etiology than M. pneumoniae, thereby delaying adequate antibiotic treatment.
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| 43. |
- Zander, Ulf, et al.
(författare)
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Populärkultur : från världsutställningar till World Wide Web
- 2022. - 1
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Ingår i: Natur & Kulturs globalhistoria 2 : Kultur och makt - Kultur och makt. - 9789127178564 - 9789127178571 ; 2, s. 185-225
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Artikel om populärkulturens kännetecken och dess utbredning i tid och rum.
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