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Sökning: WFRF:(Jani M)

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1.
  • Tran, K. B., et al. (författare)
  • The global burden of cancer attributable to risk factors, 2010-19: a systematic analysis for the Global Burden of Disease Study 2019
  • 2022
  • Ingår i: Lancet. - 0140-6736. ; 400:10352, s. 563-591
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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  • 2017
  • Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
  • Tidskriftsartikel (refereegranskat)
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  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Horikoshi, Momoko, et al. (författare)
  • New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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9.
  • Beaumont, Robin N, et al. (författare)
  • Genome-wide association study of offspring birth weight in 86,577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.
  • 2018
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 1460-2083 .- 0964-6906. ; 27:4, s. 742-756
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P<5x10-8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.
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10.
  • Smolen, JS, et al. (författare)
  • EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
  • 2017
  • Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 960-977
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
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  • Tyrrell, Jessica, et al. (författare)
  • Genetic Evidence for Causal Relationships Between Maternal Obesity-Related Traits and Birth Weight.
  • 2016
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 315:11, s. 1129-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Neonates born to overweight or obese women are larger and at higher risk of birth complications. Many maternal obesity-related traits are observationally associated with birth weight, but the causal nature of these associations is uncertain.To test for genetic evidence of causal associations of maternal body mass index (BMI) and related traits with birth weight.Mendelian randomization to test whether maternal BMI and obesity-related traits are potentially causally related to offspring birth weight. Data from 30,487 women in 18 studies were analyzed. Participants were of European ancestry from population- or community-based studies in Europe, North America, or Australia and were part of the Early Growth Genetics Consortium. Live, term, singleton offspring born between 1929 and 2013 were included.Genetic scores for BMI, fasting glucose level, type 2 diabetes, systolic blood pressure (SBP), triglyceride level, high-density lipoprotein cholesterol (HDL-C) level, vitamin D status, and adiponectin level.Offspring birth weight from 18 studies.Among the 30,487 newborns the mean birth weight in the various cohorts ranged from 3325 g to 3679 g. The maternal genetic score for BMI was associated with a 2-g (95% CI, 0 to 3 g) higher offspring birth weight per maternal BMI-raising allele (P=.008). The maternal genetic scores for fasting glucose and SBP were also associated with birth weight with effect sizes of 8 g (95% CI, 6 to 10 g) per glucose-raising allele (P=7×10(-14)) and -4 g (95% CI, -6 to -2 g) per SBP-raising allele (P=1×10(-5)), respectively. A 1-SD (≈4 points) genetically higher maternal BMI was associated with a 55-g higher offspring birth weight (95% CI, 17 to 93 g). A 1-SD (≈7.2 mg/dL) genetically higher maternal fasting glucose concentration was associated with 114-g higher offspring birth weight (95% CI, 80 to 147 g). However, a 1-SD (≈10 mm Hg) genetically higher maternal SBP was associated with a 208-g lower offspring birth weight (95% CI, -394 to -21 g). For BMI and fasting glucose, genetic associations were consistent with the observational associations, but for systolic blood pressure, the genetic and observational associations were in opposite directions.In this mendelian randomization study, genetically elevated maternal BMI and blood glucose levels were potentially causally associated with higher offspring birth weight, whereas genetically elevated maternal SBP was potentially causally related to lower birth weight. If replicated, these findings may have implications for counseling and managing pregnancies to avoid adverse weight-related birth outcomes.
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  • Graco-Roza, Caio, et al. (författare)
  • Distance decay 2.0 – A global synthesis of taxonomic and functional turnover in ecological communities
  • 2022
  • Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 31:7, s. 1399-1421
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Understanding the variation in community composition and species abundances (i.e., beta-diversity) is at the heart of community ecology. A common approach to examine beta-diversity is to evaluate directional variation in community composition by measuring the decay in the similarity among pairs of communities along spatial or environmental distance. We provide the first global synthesis of taxonomic and functional distance decay along spatial and environmental distance by analysing 148 datasets comprising different types of organisms and environments.Location: Global.Time period: 1990 to present.Major taxa studied: From diatoms to mammals.Method: We measured the strength of the decay using ranked Mantel tests (Mantel r) and the rate of distance decay as the slope of an exponential fit using generalized linear models. We used null models to test whether functional similarity decays faster or slower than expected given the taxonomic decay along the spatial and environmental distance. We also unveiled the factors driving the rate of decay across the datasets, including latitude, spatial extent, realm and organismal features.Results: Taxonomic distance decay was stronger than functional distance decay along both spatial and environmental distance. Functional distance decay was random given the taxonomic distance decay. The rate of taxonomic and functional spatial distance decay was fastest in the datasets from mid-latitudes. Overall, datasets covering larger spatial extents showed a lower rate of decay along spatial distance but a higher rate of decay along environmental distance. Marine ecosystems had the slowest rate of decay along environmental distances.Main conclusions: In general, taxonomic distance decay is a useful tool for biogeographical research because it reflects dispersal-related factors in addition to species responses to climatic and environmental variables. Moreover, functional distance decay might be a cost-effective option for investigating community changes in heterogeneous environments.
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  • Ismail, M, et al. (författare)
  • Levels and Potential Health Hazards of Chlorinated Pesticidesin Surface Water Samples of Charsadda Area of Pakistan Using SPME-GC-ECD Technique
  • 2021
  • Ingår i: Water S.A.. - : MDPI. - 0378-4738 .- 1816-7950. ; 13, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, we determined the levels of chlorinated pesticide residues in surfacewater samples collected from the Charsadda district (KPK, Pakistan). SPME-GC-ECD with COMBIPAL CTC autosampler was used for extraction and analysis of 20 organochlorine pesticides in thecollected water samples. For maximum efficiency of the SPME procedure, several parameters werestudied, including the extraction and desorption time of the fiber, solution pH, agitation of samples,and stirring speed, etc. This method showed good liner response, with R2 values in the range of0.9887 to 0.9999 for all pesticides. This method also provided good percent recoveries at 1 µg L−1(87.5to 106.0%) and at 2 µg L−1(88.5 to 109.2%). Lower limits of detection for all 20 chlorinated pesticideswere found to be lower than their maximum permissible contamination levels. Approximately 50%of the surface water samples collected from the Charsadda district were found to be contaminatedwith the pesticides γ-BHC, heptachlor, aldrin and dieldrin, with maximum concentrations of 0.023,0.108, 0.014 and 0.013 µg L−1, respectively. For adults and children, the cancer risk from water dueto contamination by various pesticides ranged from 0 to 33.29 × 10−6. The non-carcinogenic riskfrom each pollutant in the water samples of the Charsadda district was found to be in the order ofheptachlor > aldrin > dieldrin > γ-BHC. However, the pesticides α-BHC, β-BHC, heptachlor epoxide,chlordane, endrin, 4,40-DDD, endrin ketone, 4,40-DDT, endosulfan sulfate and methoxychlor werenot detected in any of the surface water samples of investigated in the present study.
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14.
  • Rodriguez, Sébastien, et al. (författare)
  • Science goals and new mission concepts for future exploration of Titan's atmosphere, geology and habitability : titan POlar scout/orbitEr and in situ lake lander and DrONe explorer (POSEIDON)
  • 2022
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 54:2-3, s. 911-973
  • Tidskriftsartikel (refereegranskat)abstract
    • In response to ESA’s “Voyage 2050” announcement of opportunity, we propose an ambitious L-class mission to explore one of the most exciting bodies in the Solar System, Saturn’s largest moon Titan. Titan, a “world with two oceans”, is an organic-rich body with interior-surface-atmosphere interactions that are comparable in complexity to the Earth. Titan is also one of the few places in the Solar System with habitability potential. Titan’s remarkable nature was only partly revealed by the Cassini-Huygens mission and still holds mysteries requiring a complete exploration using a variety of vehicles and instruments. The proposed mission concept POSEIDON (Titan POlar Scout/orbitEr and In situ lake lander DrONe explorer) would perform joint orbital and in situ investigations of Titan. It is designed to build on and exceed the scope and scientific/technological accomplishments of Cassini-Huygens, exploring Titan in ways that were not previously possible, in particular through full close-up and in situ coverage over long periods of time. In the proposed mission architecture, POSEIDON consists of two major elements: a spacecraft with a large set of instruments that would orbit Titan, preferably in a low-eccentricity polar orbit, and a suite of in situ investigation components, i.e. a lake lander, a “heavy” drone (possibly amphibious) and/or a fleet of mini-drones, dedicated to the exploration of the polar regions. The ideal arrival time at Titan would be slightly before the next northern Spring equinox (2039), as equinoxes are the most active periods to monitor still largely unknown atmospheric and surface seasonal changes. The exploration of Titan’s northern latitudes with an orbiter and in situ element(s) would be highly complementary in terms of timing (with possible mission timing overlap), locations, and science goals with the upcoming NASA New Frontiers Dragonfly mission that will provide in situ exploration of Titan’s equatorial regions, in the mid-2030s. 
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  • Lehtipalo, Katrianne, et al. (författare)
  • The effect of acid-base clustering and ions on the growth of atmospheric nano-particles
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere.
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  • Mattila, Mirjami M., et al. (författare)
  • Androgen and fibroblast growth factor 8 (FGF8) downregulation of thrombospondin 1 (TSP1) in mouse breast cancer cells
  • 2006
  • Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 253:1-2, s. 36-43
  • Tidskriftsartikel (refereegranskat)abstract
    • In the search for androgen target genes responsible for malignant growth in S115 mouse mammary tumor cells we found that thrombospondin 1 (TSP1) expression was strongly downregulated by testosterone (Te). Experiments with cycloheximide suggested that Te repression of TSP1 was dependent on de novo protein synthesis. TSPI repression by Te was preceded by the induction of fibroblast growth factor 8 (FGF8) expression. FGF8 has previously been shown to mediate androgen effects on proliferation of S 115 cells by autocrine/paracrine mechanisms. It has also been shown to increase breast cancer cell growth as tumors in nude mice and to stimulate tumor angiogenesis. We studied here the possibility that FGF8 belonged to the Te-induced de novo synthesized proteins that mediate the effect of Te on TSP1 expression in these cells. We found that addition of FGF8b to in vitro cultures or ectopic expression of FGF8b in S115 cells repressed TSP1 expression at mRNA and protein levels even in the absence of Te. FGF2, another angiogenic member of FGF family, also downregulated TSPI mRNA level in the in vitro cultures of S115 cells. The antisense oligonucleotides for FGF8 did not, however, prevent Te-repression of TSP1 mRNA expression and a neutralizing anti-FGF8b antibody only partially opposed Te induced downregulation of TSP1. These results suggest that both androgen and FGF8 inhibit TSP1 expression independently. They also suggest that opposite to many other androgen-induced responses in S115 cells, the effect of Te on the expression TSP1 is not mediated by FGF8.
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17.
  • Sarmiento Pico, Luis, et al. (författare)
  • Elucidating the nature of the proton radioactivity and branching ratio on the first proton emitter discovered 53mCo
  • 2023
  • Ingår i: Nature Communications. - 2041-1723. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • The observation of a weak proton-emission branch in the decay of the 3174keV 53mCo isomeric state marked the discovery of proton radioactivity in atomic nuclei in 1970. Here we show, based on the partial half-lives and the decay energies of the possible proton-emission branches, that the exceptionally high angular momentum barriers, lp = 9 and lp = 7, play a key role in hindering the proton radioactivity from 53mCo, making them very challenging to observe and calculate. Indeed, experiments had to wait decades for significant advances in accelerator facilities and multi-faceted state-of-the-art decay stations to gain full access to all observables. Combining data taken with the TASISpec decay station at the Accelerator Laboratory of the University of Jyväskylä, Finland, and the ACTAR TPC device on LISE3 at GANIL, France, we measured their branching ratios as bp1 = 1.3(1)% and bp2 = 0.025(4)%. These results were compared to cutting-edge shell-model and barrier penetration calculations. This description reproduces the order of magnitude of the branching ratios and partial half-lives, despite their very small spectroscopic factors.
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  • Elo, Teresa D., et al. (författare)
  • Stromal Activation Associated with Development of Prostate Cancer in Prostate-Targeted Fibroblast Growth Factor 8b Transgenic Mice
  • 2010
  • Ingår i: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 12:11, s. 94-915
  • Tidskriftsartikel (refereegranskat)abstract
    • Expression of fibroblast growth factor 8 (FGF-8) is commonly increased in prostate cancer. Experimental studies have provided evidence that it plays a role in prostate tumorigenesis and tumor progression. To study how increased FGF-8 affects the prostate, we generated and analyzed transgenic (TG) mice expressing FGF-8b under the probasin promoter that targets expression to prostate epithelium. Prostates of the TG mice showed an increased size and changes in stromal and epithelial morphology progressing from atypia and prostatic intraepithelial neoplasia (mouse PIN, mPIN) lesions to tumors with highly variable phenotype bearing features of adenocarcinoma, carcinosarcoma, and sarcoma. The development of mPIN lesions was preceded by formation of activated stroma containing increased proportion of fibroblastic cells, rich vasculature, and inflammation. The association between advancing stromal and epithelial alterations was statistically significant. Microarray analysis and validation with quantitative polymerase chain reaction revealed that expression of osteopontin and connective tissue growth factor was markedly upregulated in TG mouse prostates compared with wild type prostates. Androgen receptor staining was decreased in transformed epithelium and in hypercellular stroma but strongly increased in the sarcoma-like lesions. In conclusion, our data demonstrate that disruption of FGF signaling pathways by increased epithelial production of FGF-8b leads to strongly activated and atypical stroma, which precedes development of mPIN lesions and prostate cancer with mixed features of adenocarcinoma and sarcoma in the prostates of TG mice. The results suggest that increased FGF-8 in human prostate may also contribute to prostate tumorigenesis by stromal activation.
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23.
  • Harrison, C, et al. (författare)
  • Comorbidity versus multimorbidity: Why it matters
  • 2021
  • Ingår i: Journal of multimorbidity and comorbidity. - : SAGE Publications. - 2633-5565. ; 11, s. 2633556521993993-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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24.
  • Kirkby, Jasper, et al. (författare)
  • Ion-induced nucleation of pure biogenic particles
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533:7604, s. 521-526
  • Tidskriftsartikel (refereegranskat)abstract
    • Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood(1). Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours(2). It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere(3,4), and that ions have a relatively minor role(5). Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded(6,7). Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of a-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.
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25.
  • Laskar, A. H., et al. (författare)
  • Stable Isotopic Characterization of Nor'westers of Southern Assam, NE India
  • 2015
  • Ingår i: Journal of Climate Change. - : IOS Press. - 2395-7611 .- 2395-7697. ; 1:1-2, s. 75-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Stable oxygen and hydrogen isotopic compositions (delta O-18 and delta D) of rainwater collected between 2009 and 2011 CE from Hailakandi, southern Assam, north-eastern India have been measured to characterize the extreme rainfall phenomena, delineate moisture sources, determine amount effect and assess the prospect of local proxies for paleoclimate studies. The delta O-18 values range from +0.7 to -13.8 parts per thousand while delta D varies between +12 and -98 parts per thousand. During the pre-monsoon months (March to May), heavy rains and thunderstorms, called nor'westers (Kal Baisakhi in local parlance), occur in some years giving rainfall as much as the monsoons. Strong evaporation and localised convection due to elevated air and sea surface temperature in the region and over the adjacent Bay of Bengal seem to cause nor'wester activity. No amount effect is observed in rain. The d-excess values for nor'wester rains is very different from those of monsoon rain; very low d-excess values (up to -26 parts per thousand) were observed in 2010 CE and attributed to vapour originated from re-evaporation of freshwater, contributed by the lowland water bodies and rivers. The meteoric water line for the nor'wester rains, unlike that for the monsoon season, is significantly different from the Global Meteoric Water Line (GMWL). During the monsoon, the rain becomes progressively more depleted in the heavier isotopes (D and O-18), with the lowest 6 values occurring in Sep-Oct. Oxygen isotope-based paleoclimatic study in this region appears to be confounded by a strong dependence of the rainwater isotopic composition on the source of moisture, uneven distribution of rains during the monsoon and the pre-monsoon seasons and the absence of amount effect.
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26.
  • Lehtipalo, Katrianne, et al. (författare)
  • Multicomponent new particle formation from sulfuric acid, ammonia, and biogenic vapors
  • 2018
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:12
  • Tidskriftsartikel (refereegranskat)abstract
    • A major fraction of atmospheric aerosol particles, which affect both air quality and climate, form from gaseous precursors in the atmosphere. Highly oxygenated organic molecules (HOMs), formed by oxidation of biogenic volatile organic compounds, are known to participate in particle formation and growth. However, it is not well understood how they interact with atmospheric pollutants, such as nitrogen oxides (NOx) and sulfur oxides (SOx) from fossil fuel combustion, as well as ammonia (NH3) from livestock and fertilizers. Here, we show how NOx suppresses particle formation, while HOMs, sulfuric acid, and NH3 have a synergistic enhancing effect on particle formation. We postulate a novel mechanism, involving HOMs, sulfuric acid, and ammonia, which is able to closely reproduce observations of particle formation and growth in daytime boreal forest and similar environments. The findings elucidate the complex interactions between biogenic and anthropogenic vapors in the atmospheric aerosol system.
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27.
  • Msafiri, F, et al. (författare)
  • Frequent Anti-V1V2 Responses Induced by HIV-DNA Followed by HIV-MVA with or without CN54rgp140/GLA-AF in Healthy African Volunteers
  • 2020
  • Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 8:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial were assessed in healthy African volunteers who had been primed three times with HIV-DNA (subtype A, B, C) and then randomized into two groups; group 1 was boosted twice with HIV-MVA (CRF01_AE) and group 2 with the same HIV-MVA coadministered with subtype C envelope (Env) protein (CN54rgp140/GLA-AF). The fine specificity of plasma Env-specific antibody responses was mapped after the final vaccination using linear peptide microarray technology. Binding IgG antibodies to the V1V2 loop in CRF01_AE and subtype C Env and Env-specific IgA antibodies were determined using enzyme-linked immunosorbent assay. Functional antibody-dependent cellular cytotoxicity (ADCC)-mediating antibody responses were measured using luciferase assay. Mapping of linear epitopes within HIV-1 Env demonstrated strong targeting of the V1V2, V3, and the immunodominant region in gp41 in both groups, with additional recognition of two epitopes located in the C2 and C4 regions in group 2. A high frequency of V1V2-specific binding IgG antibody responses was detected to CRF01_AE (77%) and subtype C antigens (65%). In conclusion, coadministration of CN54rgp140/GLA-AF with HIV-MVA did not increase the frequency, breadth, or magnitude of anti-V1V2 responses or ADCC-mediating antibodies induced by boosting with HIV-MVA alone.
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28.
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29.
  • Wagner, Robert, et al. (författare)
  • The role of ions in new particle formation in the CLOUD chamber
  • 2017
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 17:24, s. 15181-15197
  • Tidskriftsartikel (refereegranskat)abstract
    • The formation of secondary particles in the atmosphere accounts for more than half of global cloud condensation nuclei. Experiments at the CERN CLOUD (Cosmics Leaving OUtdoor Droplets) chamber have underlined the importance of ions for new particle formation, but quantifying their effect in the atmosphere remains challenging. By using a novel instrument setup consisting of two nanoparticle counters, one of them equipped with an ion filter, we were able to further investigate the ion-related mechanisms of new particle formation. In autumn 2015, we carried out experiments at CLOUD on four systems of different chemical compositions involving monoterpenes, sulfuric acid, nitrogen oxides, and ammonia. We measured the influence of ions on the nucleation rates under precisely controlled and atmospherically relevant conditions. Our results indicate that ions enhance the nucleation process when the charge is necessary to stabilize newly formed clusters, i.e., in conditions in which neutral clusters are unstable. For charged clusters that were formed by ion-induced nucleation, we were able to measure, for the first time, their progressive neutralization due to recombination with oppositely charged ions. A large fraction of the clusters carried a charge at 1.5 nm diameter. However, depending on particle growth rates and ion concentrations, charged clusters were largely neutralized by ion-ion recombination before they grew to 2.5 nm. At this size, more than 90% of particles were neutral. In other words, particles may originate from ion-induced nucleation, although they are neutral upon detection at diameters larger than 2.5 nm. Observations at Hyytiala, Finland, showed lower ion concentrations and a lower contribution of ion-induced nucleation than measured at CLOUD under similar conditions. Although this can be partly explained by the observation that ion-induced fractions decrease towards lower ion concentrations, further investigations are needed to resolve the origin of the discrepancy.
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30.
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31.
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32.
  • Ahola, Virpi, et al. (författare)
  • The Glanville fritillary genome retains an ancient karyotype and reveals selective chromosomal fusions in Lepidoptera
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 4737-
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have reported that chromosome synteny in Lepidoptera has been well conserved, yet the number of haploid chromosomes varies widely from 5 to 223. Here we report the genome (393 Mb) of the Glanville fritillary butterfly (Melitaea cinxia; Nymphalidae), a widely recognized model species in metapopulation biology and eco-evolutionary research, which has the putative ancestral karyotype of n = 31. Using a phylogenetic analyses of Nymphalidae and of other Lepidoptera, combined with orthologue-level comparisons of chromosomes, we conclude that the ancestral lepidopteran karyotype has been n = 31 for at least 140 My. We show that fusion chromosomes have retained the ancestral chromosome segments and very few rearrangements have occurred across the fusion sites. The same, shortest ancestral chromosomes have independently participated in fusion events in species with smaller karyotypes. The short chromosomes have higher rearrangement rate than long ones. These characteristics highlight distinctive features of the evolutionary dynamics of butterflies and moths.
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33.
  • Akimoto, Chizuru, et al. (författare)
  • A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories
  • 2014
  • Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 51:6, s. 419-424
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9-100%), and the mean specificity was 98.0% (87.5-100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.
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34.
  • Almeida, Joao, et al. (författare)
  • Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere
  • 2013
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 502:7471, s. 359-
  • Tidskriftsartikel (refereegranskat)abstract
    • Nucleation of aerosol particles from trace atmospheric vapours is thought to provide up to half of global cloud condensation nuclei(1). Aerosols can cause a net cooling of climate by scattering sunlight and by leading to smaller but more numerous cloud droplets, which makes clouds brighter and extends their lifetimes(2). Atmospheric aerosols derived from human activities are thought to have compensated for a large fraction of the warming caused by greenhouse gases(2). However, despite its importance for climate, atmospheric nucleation is poorly understood. Recently, it has been shown that sulphuric acid and ammonia cannot explain particle formation rates observed in the lower atmosphere(3). It is thought that amines may enhance nucleation(4-16), but until now there has been no direct evidence for amine ternary nucleation under atmospheric conditions. Here we use the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that dimethylamine above three parts per trillion by volume can enhance particle formation rates more than 1,000-fold compared with ammonia, sufficient to account for the particle formation rates observed in the atmosphere. Molecular analysis of the clusters reveals that the faster nucleation is explained by a base-stabilization mechanism involving acid-amine pairs, which strongly decrease evaporation. The ion-induced contribution is generally small, reflecting the high stability of sulphuric acid-dimethylamine clusters and indicating that galactic cosmic rays exert only a small influence on their formation, except at low overall formation rates. Our experimental measurements are well reproduced by a dynamical model based on quantum chemical calculations of binding energies of molecular clusters, without any fitted parameters. These results show that, in regions of the atmosphere near amine sources, both amines and sulphur dioxide should be considered when assessing the impact of anthropogenic activities on particle formation.
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35.
  • Arca Sedda, Manuel, et al. (författare)
  • The missing link in gravitational-wave astronomy A summary of discoveries waiting in the decihertz range
  • 2021
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51, s. 1427-1440
  • Tidskriftsartikel (refereegranskat)abstract
    • Since 2015 the gravitational-wave observations of LIGO and Virgo have transformed our understanding of compact-object binaries. In the years to come, ground-based gravitational-wave observatories such as LIGO, Virgo, and their successors will increase in sensitivity, discovering thousands of stellar-mass binaries. In the 2030s, the space-based LISA will provide gravitational-wave observations of massive black holes binaries. Between the similar to 10-10(3) Hz band of ground-based observatories and the similar to 10(-4)-10(- 1) Hz band of LISA lies the uncharted decihertz gravitational-wave band. We propose a Decihertz Observatory to study this frequency range, and to complement observations made by other detectors. Decihertz observatories are well suited to observation of intermediate-mass (similar to 10(2)-10(4)M(circle dot)) black holes; they will be able to detect stellar-mass binaries days to years before they merge, providing early warning of nearby binary neutron star mergers and measurements of the eccentricity of binary black holes, and they will enable new tests of general relativity and the Standard Model of particle physics. Here we summarise how a Decihertz Observatory could provide unique insights into how black holes form and evolve across cosmic time, improve prospects for both multimessenger astronomy and multiband gravitational-wave astronomy, and enable new probes of gravity, particle physics and cosmology.
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36.
  • Basir, A., et al. (författare)
  • Proficiency in Informatics and Communication Technology Application to Improve Agricultural Counseling Performance in Luwu Regency, Indonesia
  • 2023
  • Ingår i: E3S Web Conf.. - : EDP Sciences.
  • Konferensbidrag (refereegranskat)abstract
    • Informatics and Communication Technology (ICT) provides relevant agricultural information, which is essential in agricultural development attempts, in timely fashion. Aiming to find out if it is able to improve the efficiency of agricultural counseling agents, this study examined agricultural counseling agents in Luwu Regency, South Sulawesi, Indonesia. As explanatory quantitative research, simple random sampling was applied to respondents of google form questionnaire and the data were analyzed as per Structural Equation Model (SEM) and supported by smart PLS application. The result came out with R2 value of 0.868, representing the agricultural counseling agent's proficiency and ICT application signified agricultural counseling agent's efficiency at 86.8 %. It is therefore conclusive that agricultural counseling agent's efficiency in extension activities relies on both their proficiency and ICT application.
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37.
  • Beck, Lisa J., et al. (författare)
  • Differing Mechanisms of New Particle Formation at Two Arctic Sites
  • 2021
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 48:4
  • Tidskriftsartikel (refereegranskat)abstract
    • New particle formation in the Arctic atmosphere is an important source of aerosol particles. Understanding the processes of Arctic secondary aerosol formation is crucial due to their significant impact on cloud properties and therefore Arctic amplification. We observed the molecular formation of new particles from low-volatility vapors at two Arctic sites with differing surroundings. In Svalbard, sulfuric acid (SA) and methane sulfonic acid (MSA) contribute to the formation of secondary aerosol and to some extent to cloud condensation nuclei (CCN). This occurs via ion-induced nucleation of SA and NH3 and subsequent growth by mainly SA and MSA condensation during springtime and highly oxygenated organic molecules during summertime. By contrast, in an ice-covered region around Villum, we observed new particle formation driven by iodic acid but its concentration was insufficient to grow nucleated particles to CCN sizes. Our results provide new insight about sources and precursors of Arctic secondary aerosol particles.
  •  
38.
  • Bolla, Jani Reddy, et al. (författare)
  • A Mass-Spectrometry-Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
  • 2020
  • Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:9, s. 3523-3528
  • Tidskriftsartikel (refereegranskat)abstract
    • Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non-specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid-binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent-resistant lipids bound at the dimer interface in the leucine transporter show decreased k(off) rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid-II results in the formation of a 1:1 protein-lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non-annular lipids based on their exchange rates in solution.
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39.
  • Bulanova, Daria, et al. (författare)
  • Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
  • 2017
  • Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 9:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.
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40.
  • Burlakovs, J., et al. (författare)
  • Application of anaerobic digestion for biogas and methane production from fresh beach-cast biomass
  • 2022
  • Ingår i: 3rd EAGE Global Energy Transition, GET 2022. - : European Association of Geoscientists and Engineers, EAGE. - 9781713863618 ; , s. 61-65, s. 1-5
  • Konferensbidrag (refereegranskat)abstract
    • In this research, biogas production potential from beach wrack collected in Riga Gulf (Ragaciems, Jaunķemeri, Bigauņciems) and in coastline of Sweden (Kalmar) was studied using an anaerobic digestion method. Selected beach wrack masses laying ashore and containing macroalgal biomass of common macroalgae types specific to the Baltic Sea were mixed for consolidated samples. Anoxic fermentation of untreated beach wrack was carried out in 16 bioreactors applying a single filling mode at 38 °C. The study revealed that by utilizing beach wrack accumulated ashore as a feedstock for anaerobic digestion methane can be utilized if pretreatment and conditioning of the samples are performed. The study was continued for selected brown algae containing biomass tested with three dewatering pretreatment methods: a) keeping in tap water for 24 hours; b) washing with running fresh water for one hour, and c) drying to relatively constant weight. The resulting methane outcome was compared with the data corresponding to raw brown algae. The study confirmed that washing of macroalgal biomass applied as pretreatment prior to anaerobic fermentation avoids inhibition of salts and promotes biomethane production.
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41.
  • Burlakovs, Juris, 1977-, et al. (författare)
  • Implementation of new concepts in waste management in tourist metropolitan areas
  • 2020
  • Ingår i: 2019 9TH INTERNATIONAL CONFERENCE ON ENVIRONMENT SCIENCE AND ENGINEERING (ICESE 2019). - : IOP Publishing. ; , s. 1-10
  • Konferensbidrag (refereegranskat)abstract
    • The urban waste in tourist cities needs comprehensive global research efforts and proceeded action as for metropolitan areas huge impact and load on waste management is generated. Waste management and resource conservation strategies are prepared in state-of-the-art level however implementation and future improvement of the current situation is crucial. Some examples in waste prevention and management for better tourism, waste and resource management are provided in the paper as outcomes from Horizon2020 project "Urban Strategies for Waste Management in Tourist Cities". The policy and tools based on information gathered by scientists, municipal and NGOs experience (e.g. separation of bio-waste in catering industries, "sin-wastes" as from the bars, nightclubs and smoker places, reuse of unnecessary items that can serve for others and many more) are described. In addition, regulatory instruments (e.g. ban of plastic bags, reduction of allowed bio-waste in landfilling), economic instruments (taxes) and voluntary agreements (e.g. deposit systems; cleaning actions by volunteers) might be used to implement and elaborate the situation within environmental management and prevention practices in tourist metropolitan cities. Food waste prevention, beach and littoral management, special practices for festival waste and large amount specific waste generating facilities (e.g., entertainment industry, cruises etc.) are of high importance. The future outlook may be concentrated on digitalizing of waste flows and using the "big data" concept for better and smarter waste management.
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42.
  • Burlakovs, Juris, 1977-, et al. (författare)
  • Magnetometry and electromagnetic screening of dumps - fast solution for geoenvironmental information aquisition
  • 2021
  • Ingår i: 82nd EAGE Conference and Exhibition 2021. - : European Association of Geoscientists and Engineers, EAGE. - 9781713841449 ; , s. 3032-3036
  • Konferensbidrag (refereegranskat)abstract
    • Dumps and landfills are the end place of unwanted material and disposed products. Burried resources may be landfill mined and environmental pollution diminished. The problem is lack of information on unknown dump sites of former times – there remote sensing and traditional geodesy, proximal sensing techniques could be used. Near surface geophysical methods are valuable for screening of areas where drilling is limited due to technological limitations and anthropogenic unhomogenousity of material. The aim of this study was to determine whether screening of magnetometry and geoelectrical methods may be useful for old burried dumps recognition. Protonmagnetometer was used in Eastern Latvia to detect burried dump in forest, already covered by soil and vegetation. Induced polarisation and electric resistivity research was done in Southern Sweden for the macro-content analysis of dump hills composed of glass industry residuals and construction waste mixture. Surveying helped to determine macroproperties such as geomorphology and physical type of material underneath the surface. Results allowed spatially characterize dumpsite masses (location and dimensions) and identify the internal structure of a these sites. This is valuable information in order to estimate the material recovery potential of landfills.
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43.
  • Christianty, F. M., et al. (författare)
  • The effects of Carica papaya L. juice on plasma aspartate transaminase/ alanine transaminase level and liver histopathology in paracetamol-induced mice
  • 2020
  • Ingår i: Annals of Tropical Medicine and Public Health. - : Wolters Kluwer. - 1755-6783 .- 0974-6005. ; 23:8, s. 1248-1252
  • Tidskriftsartikel (refereegranskat)abstract
    • Liver is one of the primary and largest metabolic organs in the body. The function of the liver can be disturbed and damaged by paracetamol and liver damage can be prevented with papaya (Carica papaya L.). The purpose of this study was to know the effects of C. papaya juice on plasma AST/ALT level and liver histopathology in paracetamol-induced mice. Amount 25 Balb-C mice (Mus musculus) were divided into five treatment groups, there were normal, negative control, papaya juice dose (200, 400, 600) mg kg-1 bw-1 groups. The treatment was carried out for 7 d and then all mice (without normal groups) was induced by paracetamol. On the 8th d, blood was collected and all mice were sacrificed. The materials used in this study include C. papaya juice, CMC Na, paracetamol, AST and ALT reagents, Hematoxylin-Eosin and used Experimental Laboratory methods. One Way ANOVA and Kruskal Wallis with a confidence level of 95 % and followed by a post hoc test (LSD) to determine differences between groups. Showed that pretreatment with papaya juice could prevent liver damage and inhibit the increase of plasma AST/ALT level and papaya juice dose 600 mg kg-1 bw-1 had significant effects on plasma AST/ALT level and liver histopathology in paracetamol-induced mice. Carica papaya L. juice can be used as a hepatoprotective agent. 
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44.
  • De Lima, Carlos, et al. (författare)
  • Convergent Communication, Sensing and Localization in 6G Systems: An Overview of Technologies, Opportunities and Challenges
  • 2021
  • Ingår i: IEEE Access. - 2169-3536 .- 2169-3536. ; 9, s. 26902-26925
  • Forskningsöversikt (refereegranskat)abstract
    • Herein, we focus on convergent 6G communication, localization and sensing systems by identifying key technology enablers, discussing their underlying challenges, implementation issues, and recommending potential solutions. Moreover, we discuss exciting new opportunities for integrated localization and sensing applications, which will disrupt traditional design principles and revolutionize the way we live, interact with our environment, and do business. Regarding potential enabling technologies, 6G will continue to develop towards even higher frequency ranges, wider bandwidths, and massive antenna arrays. In turn, this will enable sensing solutions with very fine range, Doppler, and angular resolutions, as well as localization to cm-level degree of accuracy. Besides, new materials, device types, and reconfigurable surfaces will allow network operators to reshape and control the electromagnetic response of the environment. At the same time, machine learning and artificial intelligence will leverage the unprecedented availability of data and computing resources to tackle the biggest and hardest problems in wireless communication systems. As a result, 6G will be truly intelligent wireless systems that will provide not only ubiquitous communication but also empower high accuracy localization and high-resolution sensing services. They will become the catalyst for this revolution by bringing about a unique new set of features and service capabilities, where localization and sensing will coexist with communication, continuously sharing the available resources in time, frequency, and space. This work concludes by highlighting foundational research challenges, as well as implications and opportunities related to privacy, security, and trust.
  •  
45.
  • Einarsdottir, Elisabet, et al. (författare)
  • Identification of NCAN as a candidate gene for developmental dyslexia.
  • 2017
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A whole-genome linkage analysis in a Finnish pedigree of eight cases with developmental dyslexia (DD) revealed several regions shared by the affected individuals. Analysis of coding variants from two affected individuals identified rs146011974G > A (Ala1039Thr), a rare variant within the NCAN gene co-segregating with DD in the pedigree. This variant prompted us to consider this gene as a putative candidate for DD. The RNA expression pattern of the NCAN gene in human tissues was highly correlated (R > 0.8) with that of the previously suggested DD susceptibility genes KIAA0319, CTNND2, CNTNAP2 and GRIN2B. We investigated the association of common variation in NCAN to brain structures in two data sets: young adults (Brainchild study, Sweden) and infants (FinnBrain study, Finland). In young adults, we found associations between a common genetic variant in NCAN, rs1064395, and white matter volume in the left and right temporoparietal as well as the left inferior frontal brain regions. In infants, this same variant was found to be associated with cingulate and prefrontal grey matter volumes. Our results suggest NCAN as a new candidate gene for DD and indicate that NCAN variants affect brain structure.
  •  
46.
  • Hansson, Karin, et al. (författare)
  • Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma
  • 2020
  • Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:562
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroblastoma is a childhood malignancy with often dismal prognosis; relapse is common despite intense treatment. Here, we used human tumor organoids representing multiple MYCN-amplified high-risk neuroblastomas to perform a high-throughput drug screen with approved or emerging oncology drugs. Tumor-selective effects were calculated using drug sensitivity scores. Several drugs with previously unreported anti-neuroblastoma effects were identified by stringent selection criteria. ARRY-520, an inhibitor of kinesin spindle protein (KSP), was among those causing reduced viability. High expression of the KSP-encoding gene KIF11 was associated with poor outcome in neuroblastoma. Genome-scale loss-of-function screens in hundreds of human cancer cell lines across 22 tumor types revealed that KIF11 is particularly important for neuroblastoma cell viability. KSP inhibition in neuroblastoma patient-derived xenograft (PDX) cells resulted in the formation of abnormal monoastral spindles, mitotic arrest, up-regulation of mitosis-associated genes, and apoptosis. In vivo, KSP inhibition caused regression of MYCN-amplified neuroblastoma PDX tumors. Furthermore, treatment of mice harboring orthotopic neuroblastoma PDX tumors resulted in increased survival. Our results suggested that KSP inhibition could be a promising treatment strategy in children with high-risk neuroblastoma.
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47.
  • Huuhtanen, Jani, et al. (författare)
  • IFN-alfa with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
  • 2022
  • Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 132:17
  • Tidskriftsartikel (refereegranskat)abstract
    • In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-alpha is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-alpha in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCR beta sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8(+) recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-alpha reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-alpha had costimulatory effects on TCR signaling. Our work supports the combination of IFN-alpha with TKI therapy, as IFN-alpha broadens the immune repertoire and restores immunological function.
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