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1.	Kanoni, Stavroula, et al. (författare) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. 2022 Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1 Tidskriftsartikel (refereegranskat)abstract Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
2.	Middeldorp, Christel M., et al. (författare) The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects 2019 Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300 Tidskriftsartikel (refereegranskat)abstract The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
3.	Mathivanan, Suresh, et al. (författare) Human Proteinpedia enables sharing of human protein data. 2008 Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1546-1696 .- 1087-0156. ; 26:2, s. 164-167 Tidskriftsartikel (refereegranskat)
4.	Kun-Rodrigues, Celia, et al. (författare) A comprehensive screening of copy number variability in dementia with Lewy bodies. 2019 Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 75 Tidskriftsartikel (refereegranskat)abstract The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk.
5.	Kun-Rodrigues, Celia, et al. (författare) Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies 2017 Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 49 Tidskriftsartikel (refereegranskat)abstract . C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of . C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of . C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that . C9orf72 repeat expansions are not causally associated with DLB.
6.	Lundgren, Markus, et al. (författare) Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity 2017 Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1 Tidskriftsartikel (refereegranskat)abstract Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
7.	Sim, Thomas G., et al. (författare) Regional variability in peatland burning at mid-to high-latitudes during the Holocene 2023 Ingår i: Quaternary Science Reviews. - : Elsevier. - 0277-3791 .- 1873-457X. ; 305 Tidskriftsartikel (refereegranskat)abstract Northern peatlands store globally-important amounts of carbon in the form of partly decomposed plant detritus. Drying associated with climate and land-use change may lead to increased fire frequency and severity in peatlands and the rapid loss of carbon to the atmosphere. However, our understanding of the patterns and drivers of peatland burning on an appropriate decadal to millennial timescale relies heavily on individual site-based reconstructions. For the first time, we synthesise peatland macrocharcoal re-cords from across North America, Europe, and Patagonia to reveal regional variation in peatland burning during the Holocene. We used an existing database of proximal sedimentary charcoal to represent regional burning trends in the wider landscape for each region. Long-term trends in peatland burning appear to be largely climate driven, with human activities likely having an increasing influence in the late Holocene. Warmer conditions during the Holocene Thermal Maximum (similar to 9e6 cal. ka BP) were associated with greater peatland burning in North America's Atlantic coast, southern Scandinavia and the Baltics, and Patagonia. Since the Little Ice Age, peatland burning has declined across North America and in some areas of Europe. This decline is mirrored by a decrease in wider landscape burning in some, but not all sub-regions, linked to fire-suppression policies, and landscape fragmentation caused by agricultural expansion. Peatlands demonstrate lower susceptibility to burning than the wider landscape in several instances, probably because of autogenic processes that maintain high levels of near-surface wetness even during drought. Nonetheless, widespread drying and degradation of peatlands, particularly in Europe, has likely increased their vulnerability to burning in recent centuries. Consequently, peatland restoration efforts are important to mitigate the risk of peatland fire under a changing climate. Finally, we make recommendations for future research to improve our understanding of the controls on peatland fires.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
8.	Sundaresan, V, et al. (författare) Homozygous deletions at 3-12 in breast and lung cancer 1998 Ingår i: Oncogene. ; 17, s. 1723- Tidskriftsartikel (refereegranskat)
9.	Travnikova, Oksana, et al. (författare) Energy-Dependent Relative Cross Sections in Carbon 1s Photoionization : Separation of Direct Shake and Inelastic Scattering Effects in Single Molecules 2019 Ingår i: Journal of Physical Chemistry A. - : AMER CHEMICAL SOC. - 1089-5639 .- 1520-5215. ; 123:35, s. 7619-7635 Tidskriftsartikel (refereegranskat)abstract We demonstrate that the possibility of monitoring relative photoionization cross sections over a large photon energy range allows us to study and disentangle shake processes and intramolecular inelastic scattering effects. In this gas-phase study, relative intensities of the carbon 1s photoelectron lines from chemically inequivalent carbon atoms in the same molecule have been measured as a function of the incident photon energy in the range of 300-6000 eV. We present relative cross sections for the chemically shifted carbon 1s lines in the photoelectron spectra of ethyl trifluoroacetate (the "ESCA" molecule). The results are compared with those of methyl trifluoroacetate and S-ethyl trifluorothioacetate as well as a series of chloro-substituted ethanes and 2-butyne. In the soft X-ray energy range, the cross sections show an extended X-ray absorption fine structure type of wiggles, as was previously observed for a series of chloroethanes. The oscillations are damped in the hard X-ray energy range, but deviations of cross-section ratios from stoichiometry persist, even at high energies. The current findings are supported by theoretical calculations based on a multiple scattering model. The use of soft and tender X-rays provides a more complete picture of the dominant processes accompanying photoionization. Such processes reduce the main photoelectron line intensities by 20-60%. Using both energy ranges enabled us to discern the process of intramolecular inelastic scattering of the outgoing electron, whose significance is otherwise difficult to assess for isolated molecules. This effect relates to the notion of the inelastic mean free path commonly used in photoemission studies of clusters and condensed matter.
10.	Gallego-Sala, Angela V., et al. (författare) Latitudinal limits to the predicted increase of the peatland carbon sink with warming 2018 Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 8:10, s. 907- Tidskriftsartikel (refereegranskat)abstract The carbon sink potential of peatlands depends on the balance of carbon uptake by plants and microbial decomposition. The rates of both these processes will increase with warming but it remains unclear which will dominate the global peatland response. Here we examine the global relationship between peatland carbon accumulation rates during the last millennium and planetary-scale climate space. A positive relationship is found between carbon accumulation and cumulative photosynthetically active radiation during the growing season for mid- to high-latitude peatlands in both hemispheres. However, this relationship reverses at lower latitudes, suggesting that carbon accumulation is lower under the warmest climate regimes. Projections under Representative Concentration Pathway (RCP)2.6 and RCP8.5 scenarios indicate that the present-day global sink will increase slightly until around AD 2100 but decline thereafter. Peatlands will remain a carbon sink in the future, but their response to warming switches from a negative to a positive climate feedback (decreased carbon sink with warming) at the end of the twenty-first century.
11.	Loisel, Julie, et al. (författare) A database and synthesis of northern peatland soil properties and Holocene carbon and nitrogen accumulation 2014 Ingår i: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 24:9, s. 1028-1042 Tidskriftsartikel (refereegranskat)abstract Here, we present results from the most comprehensive compilation of Holocene peat soil properties with associated carbon and nitrogen accumulation rates for northern peatlands. Our database consists of 268 peat cores from 215 sites located north of 45 degrees N. It encompasses regions within which peat carbon data have only recently become available, such as the West Siberia Lowlands, the Hudson Bay Lowlands, Kamchatka in Far East Russia, and the Tibetan Plateau. For all northern peatlands, carbon content in organic matter was estimated at 42 +/- 3% (standard deviation) for Sphagnum peat, 51 +/- 2% for non-Sphagnum peat, and at 49 +/- 2% overall. Dry bulk density averaged 0.12 +/- 0.07 g/cm(3), organic matter bulk density averaged 0.11 +/- 0.05 g/cm(3), and total carbon content in peat averaged 47 +/- 6%. In general, large differences were found between Sphagnum and non-Sphagnum peat types in terms of peat properties. Time-weighted peat carbon accumulation rates averaged 23 +/- 2 (standard error of mean) g C/m(2)/yr during the Holocene on the basis of 151 peat cores from 127 sites, with the highest rates of carbon accumulation (25-28 g C/m(2)/yr) recorded during the early Holocene when the climate was warmer than the present. Furthermore, we estimate the northern peatland carbon and nitrogen pools at 436 and 10 gigatons, respectively. The database is publicly available at https://peatlands.lehigh.edu.
12.	Amkreutz, J. A. M. P., et al. (författare) Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis 2021 Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:6, s. 921-930 Tidskriftsartikel (refereegranskat)abstract Objective: Autoantibodies, such as anti–citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91–0.93) versus 0.95 g/cm2 (95% CI 0.93–0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08–0.29] versus 0.48 [95% CI 0.33–0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti–carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed. © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
13.	Chawchai, Sakonvan, et al. (författare) Hydroclimatic shifts in northeast Thailand during the last two millennia - the record of Lake Pa Kho 2015 Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 111, s. 62-71 Forskningsöversikt (refereegranskat)abstract The Southeast Asian mainland is located in the central path of the Asian summer monsoon, a region where paleoclimatic data are still sparse. Here we present a multi-proxy (TOC, C/N, delta C-13, biogenic silica, and XRF elemental data) study of a 1.5 m sediment/peat sequence from Lake Pa Kho, northeast Thailand, which is supported by 20 AMS C-14 ages. Hydroclimatic reconstructions for Pa Kho suggest a strengthened summer monsoon between BC 170-AD 370, AD 800-960, and after AD 1450; and a weakening of the summer monsoon between AD 370-800, and AD 1300-1450. Increased run-off and a higher nutrient supply after AD 1700 can be linked to agricultural intensification and land-use changes in the region. This study fills an important gap in data coverage with respect to summer monsoon variability over Southeast Asia during the past 2000 years and enables the mean position of the Intertropical Convergence Zone (ITCZ) to be inferred based on comparisons with other regional studies. Intervals of strengthened/weaker summer monsoon rainfall suggest that the mean position of the ITCZ was located as far north as 35 degrees N between BC 170-AD 370 and AD 800-960, whereas it likely did not reach above 17 degrees N during the drought intervals of AD 370-800 and AD 1300-1450. The spatial pattern of rainfall variation seems to have changed after AD 1450, when the inferred moisture history for Pa Kho indicates a more southerly location of the mean position of the summer ITCZ.
14.	Janzen, Viktor, et al. (författare) Hematopoietic stem cell responsiveness to exogenous signals is limited by Caspase-3 2008 Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 2:6, s. 584-594 Tidskriftsartikel (refereegranskat)abstract Limited responsiveness to inflammatory cytokines is a feature of adult hematopoietic stem cells and contributes to the relative quiescence and durability of the stem cell population in vivo. Here we report that the executioner Caspase, Caspase-3, unexpectedly participates in that process. Mice deficient in Caspase-3 had increased numbers of immunophenotypic long-term repopulating stem cells in association with multiple functional changes, most prominently cell cycling. Though these changes were cell autonomous, they reflected altered activation by exogenous signals. Caspase-3(-/-) cells exhibited cell type-specific changes in phosphorylated members of the Ras-Raf-MEK-ERK pathway in response to specific cytokines, while notably, members of other pathways, such as pSTAT3, pSTAT5, pAKT, pp38 MAPK, pSmad2, and pSmad3, were unaffected. Caspase-3 contributes to stem cell quiescence, dampening specific signaling events and thereby cell responsiveness to microenvironmental stimuli.
15.	Johansson, Minna, et al. (författare) Benefits and harms of screening men for abdominal aortic aneurysm in Sweden: a registry-based cohort study 2018 Ingår i: Lancet. - 0140-6736. ; 391:10138, s. 2441-2447 Tidskriftsartikel (refereegranskat)abstract Background Large reductions in the incidence of abdominal aortic aneurysm (AAA) and AAA-related mortality mean that results from randomised trials of screening for the disorder might be out-dated. The aim of this study was to estimate the effect of AAA screening in Sweden on disease-specific mortality, incidence, and surgery. Methods Individual data on the incidence of AAA, AAA mortality, and surgery for AAA in a cohort of men aged 65 years who were invited to screening between 2006 and 2009, were compared with data from an age-matched contemporaneous cohort of men who were not invited for AAA screening. We also analysed national data for all men aged 40-99 years between Jan 1, 1987, and Dec 31, 2015, to explore background trends. Adjustment for confounding was done by weighting the analyses with a propensity score obtained from a logistic regression model on cohort year, marital status, educational level, income, and whether the patient already had an AAA diagnosis at baseline. Adjustment for differential attrition was also done by weighting the analyses with the inverse probability of still being in the cohort 6 years after screening. Generalised estimating equations were used to adjust the variance for repeated measurement and in response to the weighting. Findings AAA mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65-74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether AAA screening was offered. After 6 years with screening, we found a non-significant reduction in AAA mortality associated with screening (adjusted odds ratio [aOR] 0.76, 95% CI 0.38-1.51), which means that two men (95% CI -3 to 7) avoid death from AAA for every 10 000 men offered screening. Screening was associated with increased odds of AAA diagnosis (aOR 1.52, 95% CI 1.16-1.99; p= 0.002) and an increased risk of elective surgery (aOR 1.59, 95% CI 1.20-2.10; p= 0.001), such that for every 10 000 men offered screening, 49 men (95% CI 25-73) were likely to be overdiagnosed, 19 of whom (95% CI 1-37) had avoidable surgery that increased their risk of mortality and morbidity. Interpretation AAA screening in Sweden did not contribute substantially to the large observed reductions in AAA mortality. The reductions were mostly caused by other factors, probably reduced smoking. The small benefit and substantially less favourable benefit-to-harm balance call the continued justification of the intervention into question. (c) 2018 Elsevier Ltd. All rights reserved.
16.	Kauraniemi, P, et al. (författare) MYB oncogene amplification in hereditary BRCA1 breast cancer 2000 Ingår i: Cancer Research. - 1538-7445. ; 60:19, s. 5323-5328 Tidskriftsartikel (refereegranskat)abstract Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers. Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon.
17.	Kondo, M, et al. (författare) Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells 2001 Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 20:43, s. 6258-6262 Tidskriftsartikel (refereegranskat)
18.	Kristenson, E Maria, et al. (författare) Evaluation of modulators and electron-capture detectors for comprehensive two-dimensional GC of halogenated organic compounds 2003 Ingår i: Journal of Chromatography A. ; 1019:1-2, s. 65-77 Tidskriftsartikel (refereegranskat)abstract AbstractDifferent cryogenic and a heated GC×GC modulator(s) were evaluated and compared for the analysis of high-boiling halogenated compounds. The cryogenic modulators investigated were: (i) the longitudinally modulated cryogenic system; (ii) the liquid-nitrogen-cooled jet modulator (KT2001); (iii) a dual-jet CO2 modulator (made in-house); (iv) a semi-rotating cryogenic modulator (made in-house) and (v) a CO2 loop modulator (KT2003); the heated modulator was the slotted heater system (sweeper). Each modulator was optimised with respect to analyte peak widths at half height in the second-dimension. n-Alkanes, chlorinated alkanes, polychlorinated biphenyls (PCBs) and fluorinated polycyclic aromatic hydrocarbons (F-PAHs) were used as test analytes. The flow rate of the coolant was found to be an important parameter, i.e. the flow rate of the gaseous nitrogen in the KT2001, and of the liquid CO2 in the other cryogenic modulators. For the slotted heater the stroke velocity and pause time were important parameters. This modulator had a limited application range in terms of temperature due to a necessary 100 °C difference between sweeper and oven temperature. All cryogenic modulators were found to be suitable for the GC×GC analysis of high-boiling compounds, but the CO2 modulators are to be preferred to the KT2001 due to a wider application range and slightly narrower peaks. As regards the performance of three commercially available electron-capture detectors (ECDs), the aim was to obtain narrow peak widths in GC×GC, i.e. to avoid band broadening caused by the cell volume. The most important parameters were the flow rate of the make-up gas and the detector temperature which both should be as high as possible. Comparison of analyte peak widths obtained with ECD mode and flame ionisation detection (FID) showed that all ECDs exhibited band broadening compared to the FID. The narrowest peaks were obtained with the Agilent micro-ECD, which has a cell volume of only 150 μl.
19.	Linderholm, Hans W., 1968, et al. (författare) Arctic hydroclimate variability during the last 2000 years – current understanding and research challenges 2018 Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 14, s. 473-514 Forskningsöversikt (refereegranskat)abstract Reanalysis data show an increasing trend in Arctic precipitation over the 20th century, but changes are not homogenous across seasons or space. The observed hydroclimate changes are expected to continue and possibly accelerate in the coming century, not only affecting pan-Arctic natural ecosystems and human activities, but also lower latitudes through the atmospheric and ocean circulations. However, a lack of spatiotemporal observational data makes reliable quantification of Arctic hydroclimate change difficult, especially in a long-term context. To understand Arctic hydroclimate and its variability prior to the instrumental record, climate proxy records are needed. The purpose of this review is to summarise the current understanding of Arctic hydroclimate during the past 2000 years. First, the paper reviews the main natural archives and proxies used to infer past hydroclimate variations in this remote region and outlines the difficulty of disentangling the moisture from the temperature signal in these records. Second, a comparison of two sets of hydroclimate records covering the Common Era from two data-rich regions, North America and Fennoscan-dia, reveals inter- and intra-regional differences. Third, building on earlier work, this paper shows the potential for providing a high-resolution hydroclimate reconstruction for the Arctic and a comparison with last-millennium simulations from fully coupled climate models. In general, hydroclimate proxies and simulations indicate that the Medieval Climate Anomaly tends to have been wetter than the Little Ice Age (LIA), but there are large regional differences. However, the regional coverage of the proxy data is inadequate, with distinct data gaps in most of Eurasia and parts of North America, making robust assessments for the whole Arctic impossible at present. To fully assess pan-Arctic hydroclimate variability for the last 2 millennia, additional proxy records are required.
20.	Löhmann, Ditte J. A., et al. (författare) Associations between pretherapeutic body mass index, outcome, and cytogenetic abnormalities in pediatric acute myeloid leukemia 2019 Ingår i: Cancer Medicine. - : WILEY. - 2045-7634. ; 8:15, s. 6634-6643 Tidskriftsartikel (refereegranskat)abstract Background: Associations between body mass index (BMI), outcome, and leukemia-related factors in children with acute myeloid leukemia (AML) remain unclear. We investigated associations between pretherapeutic BMI, cytogenetic abnormalities, and outcome in a large multinational cohort of children with AML.Methods: We included patients, age 2-17 years, diagnosed with de novo AML from the five Nordic countries (2004-2016), Hong Kong (2007-2016), the Netherlands and Belgium (2010-2016), and Canada and USA (1995-2012). BMI standard deviations score for age and sex was calculated and categorized according to the World Health Organization. Cumulative incidence functions, Kaplan-Meier estimator, Cox regression, and logistic regression were used to investigate associations.Results: In total, 867 patients were included. The median age was 10 years (range 2-17 years). At diagnosis, 32 (4%) were underweight, 632 (73%) were healthy weight, 127 (15%) were overweight, and 76 (9%) were obese. There was no difference in relapse risk, treatment-related mortality or overall mortality across BMI groups. The frequency of t(8;21) and inv(16) increased with increasing BMI. For obese patients, the sex, age, and country adjusted odds ratio of having t(8;21) or inv(16) were 1.9 (95% confidence interval (CI) 1.1-3.4) and 2.8 (95% CI 1.3-5.8), respectively, compared to healthy weight patients.Conclusions: This study did not confirm previous reports of associations between overweight and increased treatment-related or overall mortality in children. Obesity was associated with a higher frequency of t(8;21) and inv(16). AML cytogenetics appear to differ by BMI status.
21.	Martin, Alicia R, et al. (författare) Haplotype Sharing Provides Insights into Fine-Scale Population History and Disease in Finland 2018 Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 102:5, s. 760-775 Tidskriftsartikel (refereegranskat)abstract Finland provides unique opportunities to investigate population and medical genomics because of its adoption of unified national electronic health records, detailed historical and birth records, and serial population bottlenecks. We assembled a comprehensive view of recent population history (≤100 generations), the timespan during which most rare-disease-causing alleles arose, by comparing pairwise haplotype sharing from 43,254 Finns to that of 16,060 Swedes, Estonians, Russians, and Hungarians from geographically and linguistically adjacent countries with different population histories. We find much more extensive sharing in Finns, with at least one ≥ 5 cM tract on average between pairs of unrelated individuals. By coupling haplotype sharing with fine-scale birth records from more than 25,000 individuals, we find that although haplotype sharing broadly decays with geographical distance, there are pockets of excess haplotype sharing; individuals from northeast Finland typically share several-fold more of their genome in identity-by-descent segments than individuals from southwest regions. We estimate recent effective population-size changes through time across regions of Finland, and we find that there was more continuous gene flow as Finns migrated from southwest to northeast between the early- and late-settlement regions than was dichotomously described previously. Lastly, we show that haplotype sharing is locally enriched by an order of magnitude among pairs of individuals sharing rare alleles and especially among pairs sharing rare disease-causing variants. Our work provides a general framework for using haplotype sharing to reconstruct an integrative view of recent population history and gain insight into the evolutionary origins of rare variants contributing to disease.
22.	Oishi, Yumiko, et al. (författare) SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism 2017 Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 25:2, s. 412-427 Tidskriftsartikel (refereegranskat)abstract Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12-24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators. Unexpectedly, rather than requiring LXRs, this late program of anti-inflammatory fatty acid biosynthesis is dependent on SREBP1 and results in the uncoupling of NFκB binding from gene activation. In contrast to previously identified roles of SREBP1 in promoting production of IL1β during the induction phase of inflammation, these studies provide evidence that SREBP1 also contributes to the resolution phase of TLR4-induced gene activation by reprogramming macrophage lipid metabolism.
23.	Palmroth, Minna, et al. (författare) Lower-thermosphere-ionosphere (LTI) quantities : current status of measuring techniques and models 2021 Ingår i: Annales Geophysicae. - : Copernicus Publications. - 0992-7689 .- 1432-0576. ; 39:1, s. 189-237 Tidskriftsartikel (refereegranskat)abstract The lower-thermosphere-ionosphere (LTI) system consists of the upper atmosphere and the lower part of the ionosphere and as such comprises a complex system coupled to both the atmosphere below and space above. The atmospheric part of the LTI is dominated by laws of continuum fluid dynamics and chemistry, while the ionosphere is a plasma system controlled by electromagnetic forces driven by the magnetosphere, the solar wind, as well as the wind dynamo. The LTI is hence a domain controlled by many different physical processes. However, systematic in situ measurements within this region are severely lacking, although the LTI is located only 80 to 200 km above the surface of our planet. This paper reviews the current state of the art in measuring the LTI, either in situ or by several different remote-sensing methods. We begin by outlining the open questions within the LTI requiring high-quality in situ measurements, before reviewing directly observable parameters and their most important derivatives. The motivation for this review has arisen from the recent retention of the Daedalus mission as one among three competing mission candidates within the European Space Agency (ESA) Earth Explorer 10 Programme. However, this paper intends to cover the LTI parameters such that it can be used as a background scientific reference for any mission targeting in situ observations of the LTI.
24.	Piilo, Sanna R., et al. (författare) Consistent centennial-scale change in European sub-Arctic peatland vegetation toward Sphagnum dominance—Implications for carbon sink capacity 2023 Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 29:6, s. 1530-1544 Tidskriftsartikel (refereegranskat)abstract Climate warming is leading to permafrost thaw in northern peatlands, and current predictions suggest that thawing will drive greater surface wetness and an increase in methane emissions. Hydrology largely drives peatland vegetation composition, which is a key element in peatland functioning and thus in carbon dynamics. These processes are expected to change. Peatland carbon accumulation is determined by the balance between plant production and peat decomposition. But both processes are expected to accelerate in northern peatlands due to warming, leading to uncertainty in future peatland carbon budgets. Here, we compile a dataset of vegetation changes and apparent carbon accumulation data reconstructed from 33 peat cores collected from 16 sub-arctic peatlands in Fennoscandia and European Russia. The data cover the past two millennia that has undergone prominent changes in climate and a notable increase in annual temperatures toward present times. We show a pattern where European sub-Arctic peatland microhabitats have undergone a habitat change where currently drier habitats dominated by Sphagnum mosses replaced wetter sedge-dominated vegetation and these new habitats have remained relatively stable over the recent decades. Our results suggest an alternative future pathway where sub-arctic peatlands may at least partly sustain dry vegetation and enhance the carbon sink capacity of northern peatlands.
25.	Ryding, Mauritz J., et al. (författare) X-ray induced fragmentation of size-selected salt cluster-ions stored in an ion trap 2014 Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 4:88, s. 47743-47751 Tidskriftsartikel (refereegranskat)abstract A method for spectroscopic characterization of free ionic clusters and nanoparticles utilizing X-ray synchrotron radiation is presented. We demonstrate that size-selected ammonium bisulphate cluster ions, NH4+(NH4HSO4)(n), captured in a linear ion trap, exhibit well-defined core-level absorption edges in the reconstructed fragment-ion abundance spectra. In addition to the specific photo-fragmentation pathways observed at the N1s-, O1s- and S2p-edges, dissociation also occurs as a consequence of clusters colliding with helium present as buffer gas in the ion trap. Separate off-beam experiments were conducted to establish the activation kinetics of these collision induced dissociation processes. Furthermore, it is demonstrated that the electrons released upon photoionization of background helium are too few in number to produce multiply charged cluster ions, and thereby induce fragmentation of the salt clusters, to any significant degree. The mechanisms for photon absorption and subsequent cluster fragmentation are analysed and discussed. In addition to its inherent element specificity, the method holds promise for cluster structure elucidation resulting from the sensitivity of the near edge absorption structure to the local chemical environment of the excited atom.
26.	Travnikova, Oksana, et al. (författare) The ESCA molecule-Historical remarks and new results 2012 Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 185:8-9, s. 191-197 Tidskriftsartikel (refereegranskat)abstract The C is photoelectron spectrum of ethyl trifluoroacetate (CF3-CO-O-CH2-CH3), also known as the 'ESCA molecule', is the most illustrative showcase of chemical shifts in photoelectron spectroscopy. The binding energies of the four carbon atoms of this molecule spread over more than 8 eV with energy separations ranging from 1.7 to 3.1 eV owing to different chemical environments and hence different charge states of these atoms. The paper discusses history and importance of this spectrum in the field of photoelectron spectroscopy starting from the time of invention of the ESCA technique. The main focus of the paper is a 'revisit' of this spectrum using the most modern experimental and computational tools. Large geometrical changes, different for each ionization site, and the presence of two conformers of ethyl trifluoroacetate influence the spectral lineshapes of all four C 1s lines. These effects are carefully modeled by theory and investigated in the experimental spectrum.
27.	Treat, Claire C., et al. (författare) Widespread global peatland establishment and persistence over the last 130,000 y 2019 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:11, s. 4822-4827 Tidskriftsartikel (refereegranskat)abstract Glacial-interglacial variations in CO2 and methane in polar ice cores have been attributed, in part, to changes in global wetland extent, but the wetland distribution before the Last Glacial Maximum (LGM, 21 ka to 18 ka) remains virtually unknown. We present a study of global peatland extent and carbon (C) stocks through the last glacial cycle (130 ka to present) using a newly compiled database of 1,063 detailed stratigraphic records of peat deposits buried by mineral sediments, as well as a global peatland model. Quantitative agreement between modeling and observations shows extensive peat accumulation before the LGM in northern latitudes (> 40 degrees N), particularly during warmer periods including the last interglacial (130 ka to 116 ka, MIS 5e) and the interstadial (57 ka to 29 ka, MIS 3). During cooling periods of glacial advance and permafrost formation, the burial of northern peatlands by glaciers and mineral sediments decreased active peatland extent, thickness, and modeled C stocks by 70 to 90% from warmer times. Tropical peatland extent and C stocks show little temporal variation throughout the study period. While the increased burial of northern peats was correlated with cooling periods, the burial of tropical peat was predominately driven by changes in sea level and regional hydrology. Peat burial by mineral sediments represents a mechanism for long-term terrestrial C storage in the Earth system. These results show that northern peatlands accumulate significant C stocks during warmer times, indicating their potential for C sequestration during the warming Anthropocene.
28.	Abrahamsson, Jonas, 1954, et al. (författare) Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia 2018 Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:9 Tidskriftsartikel (refereegranskat)abstract BackgroundChildren with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. ProcedureNewly diagnosed patients with AML with bone marrow blast<5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n=279). Neutrophil recovery time was defined as the time from the start of the course to the last day with absolute neutrophil count<0.5x10(9)/l. Linear and Cox regressions were used to investigate associations. ResultsNeutrophil recovery time after the first induction course was positively associated with neutrophil recovery time after the remaining courses, and longer neutrophil recovery time (25 days) was associated with increased risk of grade 3-4 infections (hazard ratio 1.4, 95% confidence interval [CI], 1.1-1.8). Longer neutrophil recovery time after the first induction (>30 days) was associated with the increased risk of relapse (5-year cumulative incidence: 48% vs. 42%, hazard ratio 1.7, 95% CI, 1.1-2.6) for cases not treated with hematopoietic stem cell transplantation in first complete remission. ConclusionLonger neutrophil recovery time after the first induction course was associated with grade 3-4 infections and relapse. If confirmed, this knowledge could be incorporated into risk stratification strategies in pediatric AML.
29.	Abrahamsson, Jonas, 1954, et al. (författare) Use of granulocyte colony-stimulating factor and risk of relapse in pediatric patients treated for acute myeloid leukemia according to NOPHO-AML 2004 and DB AML-01. 2019 Ingår i: Pediatric blood & cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 66:6 Tidskriftsartikel (refereegranskat)abstract Supportive-care use of granulocyte colony-stimulating factor (G-CSF) in pediatric acute myeloid leukemia (AML) remains controversial due to a theoretical increased risk of relapse and limited impact on neutropenic complications. We describe the use of G-CSF in patients treated according to NOPHO-AML 2004 and DB AML-01 and investigated associations with relapse.Patients diagnosed with de novo AML completing the first week of therapy and not treated with hematopoietic stem cell transplantation in the first complete remission were included (n=367). Information on G-CSF treatment after each course (yes/no) was registered prospectively in the study database and detailed information was gathered retrospectively from each center. Descriptive statistics were used to describe G-CSF use and Cox regression to assess the association between G-CSF and risk of relapse.G-CSF as supportive care was given to 128 (35%) patients after 268 (39%) courses, with a large variation between centers (0-93%). The use decreased with time-the country-adjusted odds ratio was 0.8/diagnostic year (95% confidence interval [CI] 0.7-0.9). The median daily dose was 5 μg/kg (range 3-12 μg/kg) and the median cumulative dose was 75 μg/kg (range 7-1460 μg/kg). Filgrastim was used in 82% of G-CSF administrations and infection was the indication in 44% of G-CSF administrations. G-CSF was associated with increased risk of relapse-the adjusted hazard ratio was 1.5 (95% CI 1.1-2.2).G-CSF as supportive care was used in a third of patients, and use decreased with time. Our results indicate that the use of G-CSF may be associated with an increased risk of relapse.
30.	Adolfsson, Karin H., et al. (författare) Importance of Surface Functionalities for Antibacterial Properties of Carbon Spheres 2019 Ingår i: Advanced Sustainable Systems. - : Wiley. - 2366-7486. Tidskriftsartikel (refereegranskat)abstract Carbon spheres (CS) are interesting materials for antibacterial applications. Herein, CS are produced by a green process utilizing microwave-assisted hydrothermal treatment of cellulose. The CS are then postmodified in acidic and basic solutions to evaluate the influence of different functionalities on antibacterial properties. CS contain OH/COOH, C Symbol of the Klingon Empire C, and C Symbol of the Klingon Empire O functionalities, while O-CS produced by acid treatment of CS have additional COOH, and NH/NH2 groups, resulting in carbon spheres with negatively and positively charged groups in dispersion. Treatment with base (Na-CS) removes low molecular weight species with oxygen and results in carbon spheres with the highest C/O ratio. CS, O-CS, and Na-CS have nonporous morphology and are in micro/nanometer sizes, although, smaller sized spheres, hollow spheres, and fragments are also attained in the case of O-CS. O-CS show antibacterial activity toward both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa). The minimum inhibitory concentration is 200 and 400 mu g mL(-1) for S. aureus and P. aeruginosa, respectively, and is achieved only after 3 h of incubation. Neither CS nor Na-CS exhibit antibacterial activity. The antibacterial activity is suggested to originate from electrostatic interactions between O-CS and the bacteria.
31.	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.
32.	Albarqouni, L., et al. (författare) Overdiagnosis and overuse of diagnostic and screening tests in low-income and middle-income countries: a scoping review 2022 Ingår i: Bmj Global Health. - : BMJ. - 2059-7908. ; 7:10 Tidskriftsartikel (refereegranskat)abstract Objective Overdiagnosis and overuse of healthcare services harm individuals, take resources that could be used to address underuse, and threaten the sustainability of health systems. These problems are attracting increasing attention in low-income and middle-income countries (LMICs). Unaware of any review of relevant evidence, we conducted a scoping review of the evidence around overdiagnosis and overuse of diagnostic and screening tests in LMICs. Design Scoping review. Methods We searched PubMed, Embase, PsycINFO, Global Index Medicus for relevant studies published until 24 May 2021, with no restrictions on date or language. We categorised included studies by major focus (overdiagnosis, overuse of tests, or both) and main themes (presence or estimates of extent; drivers; consequences and solutions). Results We identified 2763 unique records and included 162 articles reporting on 154 studies across 55 countries, involving over 2.8 million participants and/or requests for tests. Almost half the studies focused on overdiagnosis (70; 45.5%), one-third on overuse of tests (61; 39.6%) and one-fifth on both (23; 14.9%). Common overdiagnosed conditions included malaria (61; 39.6%) and thyroid cancer (25; 16.2%), estimated to be >70% in China. Overused tests included imaging (n=25 studies) such as CT and MRI; laboratory investigations (n=18) such as serological tests and tumour markers; and procedures (n=14) such as colonoscopy. Drivers included fear of conflict with patients and expanding disease definitions. Common consequences included unnecessary treatments such as antimalarials, and wasted resources, with costs of malaria overdiagnosis estimated at US$86 million in Sudan in 1 year alone. Only 9% of studies discussed solutions, which included addressing inappropriately lowered diagnostic thresholds and reforming test-ordering processes. Conclusions Overdiagnosis and overuse of tests are widespread in LMICs and generate significant harm and waste. Better understanding of the problems and robust evaluation of solutions is needed, informed by a new global alliance of researchers and policy-makers.
33.	Alinezhad, Saeid, et al. (författare) Global expression of AMACR transcripts predicts risk for prostate cancer - a systematic comparison of AMACR protein and mRNA expression in cancerous and noncancerous prostate. 2016 Ingår i: BMC Urology. - : Springer Science and Business Media LLC. - 1471-2490. ; 16:1 Tidskriftsartikel (refereegranskat)abstract The high false negative rates for initial prostate biopsies refer a large number of the men for repeat biopsies each year. Therefore, biomarkers associated with high risk of the presence of malignancy in histologically benign biopsies could provide a tool to discriminate the patients who need repeat biopsy or intensive follow-up from those who do not. Here we examined the diagnostic applicability of alpha-methylacyl CoA racemase (AMACR) and androgen receptor (AR) mRNA expression and AMACR protein levels in benign and cancerous prostatic tissue.
34.	Alinezhad, Saeid, et al. (författare) Validation of novel biomarkers for prostate cancer progression by the combination of bioinformatics, clinical and functional studies 2016 Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5 Tidskriftsartikel (refereegranskat)abstract The identification and validation of biomarkers for clinical applications remains an important issue for improving diagnostics and therapy in many diseases, including prostate cancer. Gene expression profiles are routinely applied to identify diagnostic and predictive biomarkers or novel targets for cancer. However, only few predictive markers identified in silico have also been validated for clinical, functional or mechanistic relevance in disease progression. In this study, we have used a broad, bioinformatics-based approach to identify such biomarkers across a spectrum of progression stages, including normal and tumor-adjacent, premalignant, primary and late stage lesions. Bioinformatics data mining combined with clinical validation of biomarkers by sensitive, quantitative reverse-transcription PCR (qRT-PCR), followed by functional evaluation of candidate genes in disease-relevant processes, such as cancer cell proliferation, motility and invasion. From 300 initial candidates, eight genes were selected for validation by several layers of data mining and filtering. For clinical validation, differential mRNA expression of selected genes was measured by qRT-PCR in 197 clinical prostate tissue samples including normal prostate, compared against histologically benign and cancerous tissues. Based on the qRT-PCR results, significantly different mRNA expression was confirmed in normal prostate versus malignant PCa samples (for all eight genes), but also in cancer-adjacent tissues, even in the absence of detectable cancer cells, thus pointing to the possibility of pronounced field effects in prostate lesions. For the validation of the functional properties of these genes, and to demonstrate their putative relevance for disease-relevant processes, siRNA knock-down studies were performed in both 2D and 3D organotypic cell culture models. Silencing of three genes (DLX1, PLA2G7 and RHOU) in the prostate cancer cell lines PC3 and VCaP by siRNA resulted in marked growth arrest and cytotoxicity, particularly in 3D organotypic cell culture conditions. In addition, silencing of PLA2G7, RHOU, ACSM1, LAMB1 and CACNA1D also resulted in reduced tumor cell invasion in PC3 organoid cultures. For PLA2G7 and RHOU, the effects of siRNA silencing on proliferation and cell-motility could also be confirmed in 2D monolayer cultures. In conclusion, DLX1 and RHOU showed the strongest potential as useful clinical biomarkers for PCa diagnosis, further validated by their functional roles in PCa progression. These candidates may be useful for more reliable identification of relapses or therapy failures prior to the recurrence local or distant metastases.
35.	Aminlashgari, Nina, 1984- (författare) LDI-MS strategies for analysis of polymer degradation products, additives and drugs 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The advancement of mass spectrometry (MS) has been and continues to be a prominent analytical technique for highly accurate determination of analytes. The goal of this thesis was to develop new laser desorption ionization-mass spectrometric (LDI-MS) methods for analysis of polymer degradation products, additives and drugs. Modifications in the sample preparation were evaluated in the presence and absence of surface assisting materials. Various nanoparticles were evaluated as effective absorbents for energy transfer in the LDI procedure of the small molecules.In paper I and II, LDI-MS methods were developed for following the progression of chemical reactions. First, the procedure to optimize microwave assisted hydrothermal degradation products of cellulose were analyzed; second, the synthesis of glucose hexanoate ester plasticizers was monitored as a function of reaction time. The LDI-MS method provided rapid detection for the elucidation of the chemical products and their relative ratios. In contrast, the electrospray ionization-mass spectrometry (ESI-MS) analysis produced a noisy spectrum primarily containing peaks from salt clusters. A surface assisted laser desorption ionization-mass spectrometry (SALDI-MS) method was developed in paper III enabling the identification of poly(e-caprolactone) and its degradation products by using nanoparticles as the substrate. Similar analysis by matrix assisted laser desorption ionization-mass spectrometry (MALDI-MS) was not as successful due to convolution of the analyte peaks with clusters released from the matrix. ESI-MS analysis verified the SALDI-MS method as comparable degradation product patterns were observed. Furthermore, the possibility of using polylactide based nanocomposites as surfaces in the analysis of drugs was evaluated in paper IV. An advantage was the ease of handling compared to the use of free nanoparticles. Paper V introduces the potential of direct examination of oxygen plasma modified parylene C surfaces by a LDI-MS methodology.
36.	BADER, S, et al. (författare) CONSTRUCTION OF A 450KB COSMID CONTIG FROM HUMAN-CHROMOSOME REGION 3P21.3 AND ISOLATION OF CANDIDATE TUMOR-SUPPRESSOR GENES FOR LUNG-CANCER 1995 Ingår i: JOURNAL OF CELLULAR BIOCHEMISTRY. - 0730-2312. ; , s. 47-47 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
37.	Beyerlein, Andreas, et al. (författare) Dietary intake of soluble fiber and risk of islet autoimmunity by 5 y of age: results from the TEDDY study. 2015 Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 102:2, s. 345-352 Tidskriftsartikel (refereegranskat)abstract Deficient soluble fiber intake has been suggested to dysregulate the immune response either directly or through alterations of the microbial composition in the gut.
38.	Bicak, Mesude, et al. (författare) Prostate cancer risk SNP rs10993994 is a trans-eQTL for SNHG11 mediated through MSMB 2020 Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 29:10, s. 1581-1591 Tidskriftsartikel (refereegranskat)abstract How genome-wide association studies-identified single-nucleotide polymorphisms (SNPs) affect remote genes remains unknown. Expression quantitative trait locus (eQTL) association meta-analysis on 496 prostate tumor and 602 normal prostate samples with 117 SNPs revealed novel cis-eQTLs and trans-eQTLs. Mediation testing and colocalization analysis demonstrate that MSMB is a cis-acting mediator for SNHG11 (P < 0.01). Removing rs10993994 in LNCaP cell lines by CRISPR/Cas9 editing shows that the C-allele corresponds with an over 100-fold increase in MSMB expression and 5-fold increase in SNHG11 compared with the T-allele. Colocalization analysis confirmed that the same set of SNPs associated with MSMB expression is associated with SNHG11 expression (posterior probability of shared variants is 66.6% in tumor and 91.4% in benign). These analyses further demonstrate variants driving MSMB expression differ in tumor and normal, suggesting regulatory network rewiring during tumorigenesis.
39.	Blanco-Cano, Xochitl, et al. (författare) Cavitons and spontaneous hot flow anomalies in a hybrid-Vlasov global magnetospheric simulation 2018 Ingår i: Annales Geophysicae. - : COPERNICUS GESELLSCHAFT MBH. - 0992-7689 .- 1432-0576. ; 36:4, s. 1081-1097 Tidskriftsartikel (refereegranskat)abstract In this paper we present the first identification of foreshock cavitons and the formation of spontaneous hot flow anomalies (SHFAs) with the Vlasiator global magnetospheric hybrid-Vlasov simulation code. In agreement with previous studies we show that cavitons evolve into SHFAs. In the presented run, this occurs very near the bow shock. We report on SHFAs surviving the shock crossing into the down-stream region and show that the interaction of SHFAs with the bow shock can lead to the formation of a magnetosheath cavity, previously identified in observations and simulations. We report on the first identification of long-term local weakening and erosion of the bow shock, associated with a region of increased foreshock SHFA and caviton formation, and repeated shock crossings by them. We show that SHFAs are linked to an increase in suprathermal particle pitch-angle spreads. The realistic length scales in our simulation allow us to present a statistical study of global caviton and SHFA size distributions, and their comparable size distributions support the theory that SHFAs are formed from cavitons. Virtual spacecraft observations are shown to be in good agreement with observational studies.
40.	Borgstedt-Bendixen, Sofie E., et al. (författare) Abdominal Complications During Treatment for Pediatric Acute Myeloid Leukemia 2022 Ingår i: Journal of Pediatric Hematology/Oncology. - : Ovid Technologies (Wolters Kluwer Health). - 1077-4114 .- 1536-3678. ; 44:5, s. 220-229 Tidskriftsartikel (refereegranskat)abstract Acute myeloid leukemia (AML) accounts for 15% to 20% of childhood leukemias. Because of high-intensive therapy, up to 5% of patients suffer from treatment-related mortality (TRM). Abdominal complications are frequent, however, literature on this subject is sparse. We aimed to characterize severe abdominal pain (AP) and hyperbilirubinemia experienced by pediatric AML patients treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML 2004 protocol (n=313). Patients were censored at hematopoietic stem cell transplantation and relapse. Toxicity information was collected prospectively. Additional information was requested retrospectively from the treating centers. Sixteen episodes of hyperbilirubinemia and 107 episodes of AP were reported. The treating centers deemed infection (30%) and typhlitis (18%) as the most frequent causes of AP. Six patients developed appendicitis (2%). Patients experiencing concurrent AP and sepsis had a high risk of TRM (36%, n=4). Eighty percent of episodes with hyperbilirubinemia fulfilled the European Society for Bone and Marrow Transplantation criteria for sinusoidal obstruction syndrome. In conclusion, abdominal complications were frequent with infection considered the predominate cause. Most patients with hyperbilirubinemia fulfilled the criteria for sinusoidal obstruction syndrome. AML treatment might be associated with appendicitis. Patients suffering from concurrent AP and sepsis had a high risk of TRM indicating that high awareness of abdominal complications is essential to reduce mortality, especially during sepsis.
41.	Cagnotto, Giovanni, et al. (författare) Abatacept in rheumatoid arthritis: survival on drug, clinical outcomes, and their predictors-data from a large national quality register 2020 Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 22:1 Tidskriftsartikel (refereegranskat)abstract Background There are limited data regarding efficacy of abatacept treatment for rheumatoid arthritis (RA) outside clinical trials. Quality registers have been useful for observational studies on tumor necrosis factor inhibition in clinical practice. The aim of this study was to investigate clinical efficacy and tolerability of abatacept in RA, using a national register. Methods RA patients that started abatacept between 2006 and 2017 and were included in the Swedish Rheumatology Quality register (N = 2716) were investigated. Survival on drug was estimated using Kaplan-Meier analysis. The European League Against Rheumatism (EULAR) good response and Health Assessment Questionnaire (HAQ) response (improvement of >= 0.3) rates (LUNDEX corrected for drug survival) at 6 and at 12 months were assessed. Predictors of discontinuation were investigated by Cox regression analyses, and predictors of clinical response by logistic regression. Significance-based backward stepwise selection of variables was used for the final multivariate models. Results There was a significant difference in drug survival by previous biologic disease-modifying antirheumatic drug (bDMARD) exposure (p < 0.001), with longer survival in bionaive patients. Men (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.74-0.98) and methotrexate users (HR 0.85, 95% CI 0.76-0.95) were less likely to discontinue abatacept, whereas a high pain score predicted discontinuation (HR 1.14 per standard deviation, 95% CI 1.07-1.20). The absence of previous bDMARD exposure, male sex, and a low HAQ score were independently associated with LUNDEX-corrected EULAR good response. The absence of previous bDMARD exposure also predicted LUNDEX-corrected HAQ response. Conclusions In this population-based study of RA, bDMARD naive patients and male patients were more likely to remain on abatacept with a major clinical response.
42.	Castro, J., et al. (författare) Influence of stone column installation on settlement reduction 2014 Ingår i: Computers and Geotechnics. - : Elsevier BV. - 0266-352X .- 1873-7633. ; 59, s. 87-97 Tidskriftsartikel (refereegranskat)abstract The paper presents numerical simulations investigating the settlement reduction caused by stone columns in a natural soft clay. The focus is on the influence of the soft soil alteration caused by column installation. A uniform mesh of end-bearing columns under a distributed load was considered. Therefore, the columns were modelled using the "unit cell" concept, i.e. only one column and the corresponding surrounding soil in axial symmetry. The properties of the soft clay correspond to Bothkennar clay, which is modelled using S-CLAY1 and S-CLAY1S, which are Cam clay type models that account for anisotropy and destructuration. The Modified Cam clay model is also used for comparison. Column installation was modelled independently to avoid mesh distortions, and soft soil alteration was directly considered in the initial input values. The results show that the changes in the stress field, such as the increase of radial stresses and mean stresses and the loss of overconsolidation, are beneficial for high loads and closely spaced columns but, on the contrary, may be negative for low loads, widely spaced columns and overconsolidated soils. Moreover, whilst the rotation of the soil fabric reduces the settlement, in contrast the soil destructuration during column installation reduces the improvement.
43.	Castro, J., et al. (författare) Numerical analyses of stone column installation in Bothkennar clay 2013 Ingår i: Proc. International Conference on Installation Effects in Geotechnical Engineering, Rotterdam, NL, 23-27 March 2013. - : CRC Press. - 9781138000414 ; , s. 212-218 Konferensbidrag (refereegranskat)abstract The paper presents the results of numerical simulations studying the installation effects of stone columns in a natural soft clay. Stone column installation is modelled as an undrained expansion of a cylindrical cavity, using the finite element code PLAXIS that allows for large displacements. The properties of the soft clay correspond to Bothkennar clay, a soft Carse clay from Scotland (UK). The complexity of this material is simulated via two advanced recently developed constitutive formulations able to account for the soil structure, namely S-CLAY1 and S-CLAY1S. Modified Cam Clay model is also used for comparison purposes. The paper shows the new stress field and state parameters after column installation and the subsequent consolidation process. This sets the basis for including installation effects in studying the settlement reduction caused by stone columns.
44.	Castro, J., et al. (författare) Numerical modeling of stone columns with installation effects 2014 Ingår i: Numerical Methods in Geotechnical Engineering - Proceedings of the 8th European Conference on Numerical Methods in Geotechnical Engineering, Delft; Netherlands; 18 June 2014 through 20 June 2014. - 9781138026872 ; 1, s. 523-528 Konferensbidrag (refereegranskat)abstract Stone column installation modifies the state of the surrounding soil, and therefore, influences the ground improvement achieved with the stone column treatment. The paper presents numerical simulations investigating the settlement reduction caused by stone columns in a natural soft clay, accounting for the modification of soil state caused by stone column installation. These installation effects have been previously studied by modelling the installation as an undrained expansion of a cylindrical cavity. A "unit cell", i.e. only one endbearing stone column and its corresponding surrounding soil, is modelled in axial symmetry using the finite element code Plaxis. The properties of the soft clay correspond to Bothkennar clay, a soft (Carse) clay from Scotland (UK). The complexity of this material is simulated via an advanced constitutive formulation able to account for the soil anisotropy, namely S-CLAY1. The results show that the changes in the stress field, such as the increase of radial and mean stresses, and the loss of overconsolidation have a positive influence on the settlement reduction, excepting for low loads. Furthermore, column installation and subsequent loading cause several changes in the soil fabric. Those changes have a positive effect in reducing the settlement because energy is dissipated in the evolution of anisotropy. Parametric studies of the influence of the coefficient of earth pressure at rest after column installation are also presented.
45.	Castro, J., et al. (författare) Numerical simulations of stone column installation 2010 Ingår i: Canadian Geotechnical Journal. ; 47:10, s. 1127-1138 Tidskriftsartikel (refereegranskat)abstract This paper describes the results of numerical simulations investigating the installation effects of stone columns in a natural soft clay. The geometry of the problem is simplified to axial symmetry, considering the installation of one column only. Stone column installation is modelled as an undrained expansion of a cylindrical cavity. The excess pore pressures generated in this process are subsequently assumed to dissipate towards the permeable column. The process is simulated using a finite element code that allows for large displacements. The properties of the soft clay correspond to Bothkennar clay, modelled using S-CLAY1 and S-CLAY1S, which are Cam clay-type models that account for anisotropy and destructuration. Stone column installation alters the surrounding soil. The expansion of the cavity generates excess pore pressures, increases the horizontal stresses of the soil, and most importantly modifies the soil structure. The numerical simulations performed allow quantitative assessment of the post-installation value of the lateral earth pressure coefficient and the changes in soil structure caused by column installation. These effects and their influence on stone column design are discussed.
46.	Chawchai, Sakonvan, et al. (författare) Lake Kumphawapi revisited – a synthesis of Holocene environmental and climatic changes for NE Thailand 2016 Ingår i: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 26:4, s. 614-626 Tidskriftsartikel (refereegranskat)abstract Kumphawapi, which is Thailand’s largest natural freshwater lake, contains a >10,000-year-long climatic and environmental archive. New data sets (stratigraphy, chronology, hydrogen isotopes, plant macrofossil and charcoal records) for two sedimentary sequences are here combined with earlier multi-proxy studies to provide a comprehensive reconstruction of past climatic and environmental changes for Northeast Thailand. Gradually higher moisture availability due to a strengthening of the summer monsoon led to the formation of a large shallow lake in the Kumphawapi basin between >10,700 and c. 7000 cal. BP. The marked increase in moisture availability and lower evaporation between c. 7000 and 6400 cal. BP favoured the growth and expansion of vegetation in and around the shallow lake. The increase in biomass led to gradual overgrowing and infilling, to an apparent lake level lowering and to the development of a wetland. Multiple hiatuses are apparent in all investigated sequences between c. 6500 and 1400 cal. BP and are explained by periodic desiccation events of the wetland and erosion due to the subsequent lake level rise. The rise in lake level, which started c. 2000 cal. BP and reached shallower parts c. 1400 cal. BP, is attributed to an increase in effective moisture availability. The timing of hydroclimatic conditions during the past 2000 years cannot be resolved because of chronological limitations.
47.	Coti, Camille, et al. (författare) Integration of Modern HPC Performance Tools in Vlasiator for Exascale Analysis and Optimization 2024 Ingår i: IEEE International Parallel and Distributed Processing Symposium Workshops (IPDPSW), May 27-31, San Francisco, California, USA.. - 9798350364606 Konferensbidrag (refereegranskat)abstract Key to the success of developing high-performance applications for present and future heterogeneous supercomputers will be the systematic use of measurement and analysis to understand factors that affect delivered performance in the context of parallelization strategy, heterogeneous programming methodology, data partitioning, and scalable algorithm design. The evolving complexity of future exascale platforms makes it unrealistic for application teams to implement their own tools. Similarly, it is naive to expect available robust performance tools to work effectively out-of-the-box, without integration and specialization in respect to application-specific requirements and knowledge. Vlasiator is a powerful massively parallel code for accurate magnetospheric and solar wind plasma simulations. It is being ported to the LUMI HPC system for advanced modeling of the Earth’s magnetosphere and surrounding solar wind. Building on a preexisting Vlasiator performance API called Phiprof, our work significantly advances the performance measurement and analysis capabilities offered to Vlasiator using the TAU, APEX, and IPM tools. The results presented show in-depth characterization of node-level CPU/GPU and MPI communications performance. We highlight the integration of high-level Phiprof events with detailed performance data to expose opportunities for performance tuning. Our results provide important insights to optimize Vlasiator for the upcoming Exascale machines.
48.	Duch, J., et al. (författare) Work function modifications of graphite surface via oxygen plasma treatment 2017 Ingår i: Applied Surface Science. - : Elsevier. - 0169-4332 .- 1873-5584. ; 419, s. 439-446 Tidskriftsartikel (refereegranskat)abstract The surface modification of graphite by oxygen plasma was investigated experimentally (X-ray diffraction, nanoparticle tracking analysis, laser desorption ionization mass spectrometry, thermogravimetry, water contact angle) and by molecular modelling (Density Functional Theory). Generation of surface functional groups (mainly –OHsurf) leads to substantial changes in electrodonor properties and wettability gauged by work function and water contact angle, respectively. The invoked modifications were analyzed in terms of Helmholtz model taking into account the theoretically determined surface dipole moment of graphite—OHsurf system (μ = 2.71 D) and experimentally measured work function increase (from 0.75 to 1.02 eV) to determine the –OH surface coverage (from 0.70 to 1.03 × 1014 groups cm−2). Since the plasma treatment was confined to the surface, the high thermal stability of the graphite material was preserved as revealed by the thermogravimetric analysis. The obtained results provide a suitable quantitative background for tuning the key operating parameters of carbon electrodes: electronic properties, interaction with water and thermal stability.
49.	Engels, Stefan, et al. (författare) Early Weichselian (MIS 5d and 5c) temperatures and environmental changes in northern Fennoscandia as recorded by chironomids and macroremains at Sokli, northeast Finland 2010 Ingår i: Boreas. - : Wiley. - 0300-9483 .- 1502-3885. ; 39:4, s. 689-704 Tidskriftsartikel (refereegranskat)abstract A 25-m-long sediment record spanning the time from the Eemian to the Holocene was recovered from Sokli, northeast Finland. This study focuses on a 6-m-long sediment interval that is dated to the Early Weichselian period (MIS 5d and 5c) and consists of lacustrine and fluvial deposits. Using chironomid remains, botanical and zoological macroremains as well as sediment lithology, we were able to reconstruct past changes in the environment, including climate. The results indicate that the site was situated on a flood-plain during the latter stages of MIS 5d (Herning Stadial) and that summer temperatures might have been similar to 6 degrees C lower than at present. Although this value should be treated with caution, as numerical analysis shows that it has a very poor fit-to-temperature, this low reconstructed value concurs with several other reconstructions that are available from western Europe. During MIS 5c (Brorup interstadial), the depositional environment changed into a lake system, initially with stratification of the water and subsequently with complete mixing and a strong influence of streams. Both chironomid-based and macroremain-based temperature inferences indicate past July air temperatures that were significantly higher than at present. This result is in contrast to other (low-resolution) reconstructions from northern Fennoscandia that indicate past temperatures 6-7 degrees C lower than present using fossil coleopteran assemblages. However, several central European sites indicate that there was a phase during the Brorup interstadial that was characterized by high summer temperatures, and a comparison between the high-resolution reconstructions from western Europe and the results presented in this study suggests that the north south July air temperature gradient between the mid- and high-latitudes was much weaker during the Brorup interstadial than it is at present. High solar insolation values (particularly the obliquity) during the Brorup interstadial might explain the low summer temperature gradient over the European continent. A return to fluvial conditions occurred in the upper parts of the sediment sequence, and, after a brief interval of gyttja deposition under cooling conditions, the site became glaciated during MIS 5b.
50.	Faj, Jennifer, et al. (författare) MPI Performance Analysis in Vlasiator : Unraveling Communication Bottlenecks 2023 Ingår i: SC23 Proccedings. - Denver, Colorado, USA. Konferensbidrag (refereegranskat)abstract Vlasiator is a popular and powerful massively parallel code for accurate magnetospheric and solar wind plasma simulations. This work provides an in-depth analysis of Vlasiator, focusing on MPI performance using the Integrated Performance Monitoring (IPM) tool. We show that MPI non-blocking point-to-point communication accounts for most of the communication time. The communication topology shows a large number of MPI messages exchanging data in a six-dimensional grid. We also show that relatively large messages are used in MPI communication, reaching up to 256MB. As a communication-bound application, we found that using OpenMP in Vlasiator is critical for eliminating intra-node communication. Our results provide important insights for optimizing Vlasiator for the upcoming Exascale machines.

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