| 1. |
- Chami, Nathalie, et al.
(författare)
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Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 8-21
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Tidskriftsartikel (refereegranskat)abstract
- Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
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| 2. |
- Hedbrant, Alexander, Ph.D, 1987-, et al.
(författare)
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Green, Black and Rooibos Tea Inhibit Prostaglandin E2 Formation in Human Monocytes by Inhibiting Expression of Enzymes in the Prostaglandin E2 Pathway
- 2022
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 27:2
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Tidskriftsartikel (refereegranskat)abstract
- The formation of prostaglandin E2 (PGE2) is associated with adverse inflammatory effects. However, long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) comes with risk of severe side effects. Therefore, alternative ways to inhibit PGE2 are warranted. We have investigated the effects of tea extracts and the polyphenols epigallocatechin gallate (EGCG) and quercetin on PGE2 formation, determined by immunoassay, and protein expression, determined by immunoblotting, of cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) in human monocytes. Green and black tea extracts, and with a lower potency, Rooibos tea extract, inhibited lipopolysaccharide (LPS) and calcium ionophore-induced PGE2 formation. In addition, all tea extracts inhibited the LPS-induced expression of mPGES-1, and the green and black tea extracts also inhibited, to a lesser extent, COX-2 expression. The tea extracts only marginally reduced cPLA2 expression and had no effect on COX-1 expression. EGCG, present in green and black tea, and quercetin, present in all three teas, also inhibited PGE2 formation and expression of mPGES-1, COX-2 and cPLA2. Cell-based and cell-free assays were also performed to evaluate direct effects on the enzymatic activity of COX and PGE synthases. Mainly, the cell-free assay demonstrated partial inhibition by the tea extracts and polyphenols. However, the inhibition required higher doses compared to the effects demonstrated on protein expression. In conclusion, green and black tea, and to a lesser extent Rooibos tea, are potent inhibitors of PGE2 formation in human monocytes, and mediate their effects by inhibiting the expression of the enzymes responsible for PGE2 formation, especially mPGES-1.
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| 3. |
- Hedbrant, Alexander, Ph.D, 1987-, et al.
(författare)
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Occupational quartz and particle exposure affect systemic levels of inflammatory markers related to inflammasome activation and cardiovascular disease
- 2023
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The inflammatory responses are central components of diseases associated with particulate matter (PM) exposure, including systemic diseases such as cardiovascular diseases (CVDs). The aim of this study was to determine if exposure to PM, including respirable dust or quartz in the iron foundry environment mediates systemic inflammatory responses, focusing on the NLRP3 inflammasome and novel or established inflammatory markers of CVDs.METHODS: The exposure to PM, including respirable dust, metals and quartz were determined in 40 foundry workers at two separate occasions per worker. In addition, blood samples were collected both pre-shift and post-shift and quantified for inflammatory markers. The respirable dust and quartz exposures were correlated to levels of inflammatory markers in blood using Pearson, Kendall τ and mixed model statistics. Analyzed inflammatory markers included: 1) general markers of inflammation, including interleukins, chemokines, acute phase proteins, and white blood cell counts, 2) novel or established inflammatory markers of CVD, such as growth/differentiation factor-15 (GDF-15), CD40 ligand, soluble suppressor of tumorigenesis 2 (sST2), intercellular/vascular adhesion molecule-1 (ICAM-1, VCAM-1), and myeloperoxidase (MPO), and 3) NLRP3 inflammasome-related markers, including interleukin (IL)-1β, IL-18, IL-1 receptor antagonist (IL-1Ra), and caspase-1 activity.RESULTS: The average respirator adjusted exposure level to respirable dust and quartz for the 40 foundry workers included in the study was 0.65 and 0.020 mg/m3, respectively. Respirable quartz exposure correlated with several NLRP3 inflammasome-related markers, including plasma levels of IL-1β and IL-18, and several caspase-1 activity measures in monocytes, demonstrating a reverse relationship. Respirable dust exposure mainly correlated with non-inflammasome related markers like CXCL8 and sST2. CONCLUSIONS: The finding that NLRP3 inflammasome-related markers correlated with PM and quartz exposure suggest that this potent inflammatory cellular mechanism indeed is affected even at current exposure levels in Swedish iron foundries. The results highlight concerns regarding the safety of current exposure limits to respirable dust and quartz, and encourage continuous efforts to reduce exposure in dust and quartz exposed industries.
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| 4. |
- Prestele, Reinhard, et al.
(författare)
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Hotspots of uncertainty in land-use and land-cover change projections : a global-scale model comparison
- 2016
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Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 22:12, s. 3967-3983
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Tidskriftsartikel (refereegranskat)abstract
- Model-based global projections of future land-use and land-cover (LULC) change are frequently used in environmental assessments to study the impact of LULC change on environmental services and to provide decision support for policy. These projections are characterized by a high uncertainty in terms of quantity and allocation of projected changes, which can severely impact the results of environmental assessments. In this study, we identify hotspots of uncertainty, based on 43 simulations from 11 global-scale LULC change models representing a wide range of assumptions of future biophysical and socioeconomic conditions. We attribute components of uncertainty to input data, model structure, scenario storyline and a residual term, based on a regression analysis and analysis of variance. From this diverse set of models and scenarios, we find that the uncertainty varies, depending on the region and the LULC type under consideration. Hotspots of uncertainty appear mainly at the edges of globally important biomes (e.g., boreal and tropical forests). Our results indicate that an important source of uncertainty in forest and pasture areas originates from different input data applied in the models. Cropland, in contrast, is more consistent among the starting conditions, while variation in the projections gradually increases over time due to diverse scenario assumptions and different modeling approaches. Comparisons at the grid cell level indicate that disagreement is mainly related to LULC type definitions and the individual model allocation schemes. We conclude that improving the quality and consistency of observational data utilized in the modeling process and improving the allocation mechanisms of LULC change models remain important challenges. Current LULC representation in environmental assessments might miss the uncertainty arising from the diversity of LULC change modeling approaches, and many studies ignore the uncertainty in LULC projections in assessments of LULC change impacts on climate, water resources or biodiversity.
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| 5. |
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14th NOLAMP Conference : The 14th Nordic Laser Materials Processing Conference, August 26th – 28th 2013, Gothenburg, Sweden
- 2013
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Samlingsverk (redaktörskap) (övrigt vetenskapligt/konstnärligt)abstract
- Laser is a key element in obtaining a sustainable economy in Europe. Innovative laser processes will play a significant role in future green manufacturing as they provide a precise, well-controlled and highly effective energy deposition to the workpiece. Future challenges are to increase the spectrum of laser manufacturing technologies in all sectors where the laser can offer innovative product solutions, higher product quality, less environmental impact, higher productivity and in turn cost benefits.The NOLAMP conferences address all aspects of laser materials processing from fundamental science to industrial applications. The first NOLAMP conference took place in Oslo in 1987 in a period of intense development of the laser processes and their industrial applications. The NOLAMP has continued on a biannual cycle ever since, strengthening the Nordic laser community by encouraging knowledge transfer and networking. Now, 26 years later, in the forthcoming 14th NOLAMP, the research and development of processes like laser welding, laser hybrid welding, laser cutting and laser surface treatment is still very important, as well as the development of industrial applications and equipment for laser material processing. This time the NOLAMP Conference will be held in Gothenburg, Sweden. In this highly industrialized region of Sweden and with the close distance to Denmark, Norway and Finland, we hope to attract a strong participation from industry and the scientific community. On behalf of the Nordic laser community and Luleå University of Technology, it is our great pleasure to invite you to the 14th NOLAMP conference.
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| 6. |
- Aad, G., et al.
(författare)
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The ATLAS Experiment at the CERN Large Hadron Collider
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08003
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Forskningsöversikt (refereegranskat)abstract
- The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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| 7. |
- Ahlberg, Alexander, et al.
(författare)
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Early self-care rehabilitation of head and neck cancer patients
- 2011
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 131:5, s. 552-61
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Tidskriftsartikel (refereegranskat)abstract
- CONCLUSIONS: No positive effects of early preventive rehabilitation could be identified. The results do not contradict the proposition that rehabilitation based on self-care can be effective but it is important to establish evidence-based training programs and identify proper instruments for selection of patients and evaluation of intervention. OBJECTIVES: Patients with head and neck cancer suffer from functional impairments due to intense treatment. In this study, we investigated the effectiveness of an experimental early preventive rehabilitation using hard, objective end points in a nonselective, longitudinal, prospective cohort study. METHODS: In all, 190 patients were included in the program and received instructions for training before the start of treatment with the aim of reducing swallowing problems and reducing mouth opening and stiffness in the neck. A control group of 184 patients was recruited. RESULTS: There was no difference in weight loss and 2-year survival between the two groups. No positive effects concerning functional impairments were found in patient-reported outcome measures.
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| 8. |
- Ahlberg, Alexander, et al.
(författare)
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Morbidity of supraomohyoidal and modified radical neck dissection combined with radiotherapy for head and neck cancer : a prospective longitudinal study
- 2012
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Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 34:1, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of this study was to show the investigated impact of supraomohyoidal neck dissection and modified radical neck dissection, both combined with radiotherapy, on cervical range of motion (CROM), mouth opening, swallowing, lymphedema, and shoulder function.METHODS: One hundred eight patients who had neck dissections and 98 patients who had non-neck dissections were evaluated in a prospective, nonselective, longitudinal cohort study by a physiotherapist and a speech-language pathologist (SLP) before the start of radiotherapy and up to 12 months after treatment.RESULTS: The incidence of shoulder disability after neck dissection was 18%. Supraomohyoidal neck dissection had no significant effect on the evaluated parameters at any time point. Modified radical neck dissection significantly reduced CROM and mouth opening 2 months after treatment, but after 12 months only cervical rotation was still significantly reduced.CONCLUSION: In patients treated with external beam radiation (EBRT), modified radical neck dissection induced additional morbidity regarding CROM but not regarding mouth opening, swallowing, and lymphedema 1 year after treatment. Both modified radical neck dissection and supraomohyoidal neck dissection induced shoulder disability.
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| 9. |
- Baalsrud Hauge, J. M., et al.
(författare)
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Bridging educational and working environments through pervasive approaches
- 2017
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Ingår i: 3rd International Joint Conference on Serious Games, JCSG 2017. - Cham : Springer Verlag. - 9783319701103 ; , s. 296-307
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Konferensbidrag (refereegranskat)abstract
- In the education of mechanical engineers alternative learning methods like serious games, simulations etc. have been used in past decades to better the learning outcomes. However, a main concern is still the amount of resources used on adapting and modding games as well as the challenges related to the implementation in the class room setting. Typically a positive learning experience does not only rely on the game as such, but how good the facilitator or teacher is to change game mechanics and the narratives so that players with different learning curves, past experience and cognitive abilities all stay in flow and feel immersed. Physical simulation games played in a workshop setting often have this ability, whereas this still seems to be a challenge in digitalized games. The main purpose of this article is to identify mechanics that need to be adapted differently for different user groups in order to keep them in flow, motivated and engaged in order to have a high learning experience and how we can take advantage of technologies like VR to reduce the costs and the resources.
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| 10. |
- Björklund, Michael, et al.
(författare)
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The g-theorem matrices are totally nonnegative
- 2009
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Ingår i: Journal of combinatorial theory. Series A (Print). - : Elsevier BV. - 0097-3165 .- 1096-0899. ; 116, s. 730-732
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Tidskriftsartikel (refereegranskat)abstract
- The g-theorem proved by Billera, Lee, and Stanley states that a sequence is the g-vector of a simplicial polytope if and only if it is an M-sequence. For any d-dimensional simplicial polytope the face vector is gM(d) where M-d is a certain matrix whose entries are sums of binomial coefficients. Bjorner found refined lower and upper bound theorems by showing that the (2 x 2)-minors of M-d are nonnegative. He conjectured that all minors of M-d are nonnegative and that is the result of this note.
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