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1.
  • Kulmala, M., et al. (författare)
  • General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
  • 2011
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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  • Wilking, N., et al. (författare)
  • Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
  • 2007
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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3.
  • Villa, Luisa L., et al. (författare)
  • Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions
  • 2007
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 356:19, s. 1915-1927
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.
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  • Paavonen, J, et al. (författare)
  • Baseline demographic characteristics of subjects enrolled in international quadrivalent HPV (types 6/11/16/18) vaccine clinical trials
  • 2008
  • Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 24:6, s. 1623-1634
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In Phase II/III trials, administration of quadrivalent human papillomavirus (HPV) (types 6/11/16/18) L1 virus-like-particle vaccine was highly effective in preventing HPV6/11/16/18-related cervical intraepithelial neoplasia and non-invasive cervical cancer in women aged 16-26 years who were naïve to these HPV types at enrollment. However, the makeup and extent of catch-up vaccination programs among young women is unclear, because a proportion of this population will likely already have been exposed to one or more vaccine-HPV-types. OBJECTIVE: Herein we analyze baseline data from the quadrivalent HPV vaccine clinical trial program to investigate variables which may help shape catch-up vaccine implementation policies. METHODS: Female adolescents and young adults aged 16-26 years were randomized into five clinical trials. Baseline data regarding demographics, sexual history, pregnancy history, and other characteristics were collected at enrollment. At the baseline gynecological examination during enrollment, specimens were obtained for Pap testing. Swabs of external genital, lateral vaginal, and cervical sites for HPV polymerase chain reaction (PCR) testing were taken, and serum samples were obtained for HPV serology testing. Regional analyses of data were conducted. RESULTS: Overall, 72% of subjects enrolled worldwide were naïve by both serology and PCR to all four vaccine HPV types. Few subjects were seropositive and/or PCR positive for more than two vaccine-related HPV types. Of all subjects with HSIL at enrollment, 78% were positive to at least one vaccine-related HPV type at enrollment. Regional differences in HPV and STD prevalence were evident. Study limitations included under-representation of women with >/=4 sexual partners and possible underestimation of prior HPV exposure. CONCLUSIONS: Our findings demonstrate that sexually active 16-26 year-old women with
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6.
  • Pietila, EA, et al. (författare)
  • Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 3904-
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to its dynamic nature, the evolution of cancer cell-extracellular matrix (ECM) crosstalk, critically affecting metastasis and treatment resistance, remains elusive. Our results show that platinum-chemotherapy itself enhances resistance by progressively changing the cancer cell-intrinsic adhesion signaling and cell-surrounding ECM. Examining ovarian high-grade serous carcinoma (HGSC) transcriptome and histology, we describe the fibrotic ECM heterogeneity at primary tumors and distinct metastatic sites, prior and after chemotherapy. Using cell models from systematic ECM screen to collagen-based 2D and 3D cultures, we demonstrate that both specific ECM substrates and stiffness increase resistance to platinum-mediated, apoptosis-inducing DNA damage via FAK and β1 integrin-pMLC-YAP signaling. Among such substrates around metastatic HGSCs, COL6 was upregulated by chemotherapy and enhanced the resistance of relapse, but not treatment-naïve, HGSC organoids. These results identify matrix adhesion as an adaptive response, driving HGSC aggressiveness via co-evolving ECM composition and sensing, suggesting stromal and tumor strategies for ECM pathway targeting.
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  • Villa, L., et al. (författare)
  • Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials
  • 2007
  • Ingår i: The Lancet. - 1474-547X. ; 369:9576, s. 1861-1868
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cervical cancer and its obligate precursors, cervical intraepithelial neoplasia grades 2 and 3 (CIN2/3), and adenocarcinona in situ (AIS), are caused by oncogenic human papillomavirus (HPV). In this combined analysis of four clinical trials we assessed the effect of prophylactic HPV vaccination on these diseases. Methods 20 583 women aged 16-26 years were randomised to receive quadrivalent HPV6/11/16/18 vaccine (n=9087), its HPV16 vaccine component (n=1204), or placebo (n=10292). They underwent periodic Papanicolaou testing, with colposcopy or biopsy for detected abnormalities. The primary composite endpoint was the combined incidence of HPV16/18-related CIN2/3, AIS, or cervical cancer. These trials are registered at ClinicalTrials.gov, numbers NCT00365378, NCT00365716, NCT00092521, and NCT00092534. Findings Mean follow-up was 3.0 years (SD 0.66) after first dose. In women negative for HPV16 or HPV18 infection during the vaccination regimen (n=17129, per protocol), vaccine efficacy was 99% for the primary endpoint (95% Cl 93-100), meeting the statistical criterion for success. In an intention-to-treat analysis of all randomised women (including those who were HPV16/18 naive or HPV16/18-infected at day 1), efficacy was 44% (95% Cl 31-55); all but one case in vaccine recipients occurred in women infected with HPV16 or HPV18 before vaccination. In a second intention-to-treat analysis we noted an 18% reduction (95% CI 7-29) in the overall rate of CIN2/3 or AIS due to any HPV type. Interpretation Administration of HPV vaccine to HPV-naive women, and women who are already sexually active, could substantially reduce the incidence of HPV16/18-related cervical precancers and cervical cancer.
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9.
  • Hakola, L., et al. (författare)
  • Maternal fatty acid intake during pregnancy and the development of childhood overweight : a birth cohort study
  • 2017
  • Ingår i: Pediatric Obesity. - : WILEY. - 2047-6302 .- 2047-6310. ; 12, s. 26-37
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMaternal diet during pregnancy may contribute to the risk of offspring adiposity. ObjectivesThe objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7years. MethodsIn a prospective Finnish birth cohort with 3807 mother-child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. ResultsIn girls, maternal intake ratio of n-6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27-3.20] and the highest 1.7 [1.03-2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p=0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid+eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60-1.57] and the highest 0.5 [0.26-0.88] vs. the two middle quartiles, p=0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. ConclusionsMaternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys.
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  • Ramonet, M., et al. (författare)
  • The fingerprint of the summer 2018 drought in Europe on ground-based atmospheric CO 2 measurements : Atmospheric CO 2 anomaly
  • 2020
  • Ingår i: Philosophical Transactions of the Royal Society B: Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
  • Tidskriftsartikel (refereegranskat)abstract
    • During the summer of 2018, a widespread drought developed over Northern and Central Europe. The increase in temperature and the reduction of soil moisture have influenced carbon dioxide (CO 2) exchange between the atmosphere and terrestrial ecosystems in various ways, such as a reduction of photosynthesis, changes in ecosystem respiration, or allowing more frequent fires. In this study, we characterize the resulting perturbation of the atmospheric CO 2 seasonal cycles. 2018 has a good coverage of European regions affected by drought, allowing the investigation of how ecosystem flux anomalies impacted spatial CO 2 gradients between stations. This density of stations is unprecedented compared to previous drought events in 2003 and 2015, particularly thanks to the deployment of the Integrated Carbon Observation System (ICOS) network of atmospheric greenhouse gas monitoring stations in recent years. Seasonal CO 2 cycles from 48 European stations were available for 2017 and 2018. Earlier data were retrieved for comparison from international databases or national networks. Here, we show that the usual summer minimum in CO 2 due to the surface carbon uptake was reduced by 1.4 ppm in 2018 for the 10 stations located in the area most affected by the temperature anomaly, mostly in Northern Europe. Notwithstanding, the CO 2 transition phases before and after July were slower in 2018 compared to 2017, suggesting an extension of the growing season, with either continued CO 2 uptake by photosynthesis and/or a reduction in respiration driven by the depletion of substrate for respiration inherited from the previous months due to the drought. For stations with sufficiently long time series, the CO 2 anomaly observed in 2018 was compared to previous European droughts in 2003 and 2015. Considering the areas most affected by the temperature anomalies, we found a higher CO 2 anomaly in 2003 (+3 ppm averaged over 4 sites), and a smaller anomaly in 2015 (+1 ppm averaged over 11 sites) compared to 2018. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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15.
  • Andersen, JH, et al. (författare)
  • Getting the measure of eutrophication in the Baltic Sea: towards improved assessment principles and methods
  • 2011
  • Ingår i: Biogeochemistry. - 0168-2563. ; 106:2, s. 137-156
  • Tidskriftsartikel (refereegranskat)abstract
    • The eutrophication status of the entire Baltic Sea is classified using a multi-metric indicator-based assessment tool. A total of 189 areas are assessed using indicators where information on reference conditions (RefCon), and acceptable deviation (AcDev) from reference condition could be combined with national monitoring data from the period 2001–2006. Most areas (176) are classified as ‘affected by eutrophication’ and only two open water areas and 11 coastal areas are classified as ‘unaffected by eutrophication’. The classification is made by application of the recently developed HELCOM Eutrophication Assessment Tool (HEAT), which is described in this paper. The use of harmonized assessment principles and the HEAT tool allows for direct comparisons between different parts of the Baltic Sea despite variations in monitoring activities. The impaired status of 176 areas is directly related to nutrient enrichment and elevated loads from upstream catchments. Baltic Sea States have implemented nutrient management strategies since years which have reduced nutrient inputs. However, eutrophication is still a major problem for large parts of the Baltic Sea. The 2007 Baltic Sea Action Plan is projected to further reduce nutrient inputs aiming for a Baltic Sea unaffected by eutrophication by 2021.
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  • Foo, Kylie S, et al. (författare)
  • Human ISL1+ ventricular progenitors self-assemble into an in vivo functional heart patch and preserve cardiac function post infarction
  • 2018
  • Ingår i: Molecular Therapy. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 1525-0016. ; 26:7, s. 1644-1659
  • Tidskriftsartikel (refereegranskat)abstract
    • The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the generation of an enriched pool of hPSC-derived ventricular progenitors (HVPs), which can expand, differentiate, self-assemble, and mature into a functional ventricular patch in vivo without the aid of any gel or matrix. We documented a specific temporal window, in which the HVPs will engraft in vivo. On day 6 of differentiation, HVPs were enriched by depleting cells positive for pluripotency marker TRA-1-60 with magnetic-activated cell sorting (MACS), and 3 million sorted cells were sub-capsularly transplanted onto kidneys of NSG mice where, after 2 months, they formed a 7 mm x 3 mm x 4 mm myocardial patch resembling the ventricular wall. The graft acquired several features of maturation: expression of ventricular marker (MLC2v), desmosomes, appearance of T-tubule-like structures, and electrophysiological action potential signature consistent with maturation, all this in a non-cardiac environment. We further demonstrated that HVPs transplanted into un-injured hearts of NSG mice remain viable for up to 8 months. Moreover, transplantation of 2 million HVPs largely preserved myocardial contractile function following myocardial infarction. Taken together, our study reaffirms the promising idea of using progenitor cells for regenerative therapy. Correction in Mol Ther. 2021 Jan 6;29(1):409, DOI: 10.1016/j.ymthe.2020.11.015
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  • Jukonen, J, et al. (författare)
  • Aggressive and recurrent ovarian cancers upregulate ephrinA5, a non-canonical effector of EphA2 signaling duality
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 8856-
  • Tidskriftsartikel (refereegranskat)abstract
    • Erythropoietin producing hepatocellular (Eph) receptors and their membrane-bound ligands ephrins are variably expressed in epithelial cancers, with context-dependent implications to both tumor-promoting and -suppressive processes in ways that remain incompletely understood. Using ovarian cancer tissue microarrays and longitudinally collected patient cells, we show here that ephrinA5/EFNA5 is specifically overexpressed in the most aggressive high-grade serous carcinoma (HGSC) subtype, and increased in the HGSC cells upon disease progression. Among all the eight ephrin genes, high EFNA5 expression was most strongly associated with poor overall survival in HGSC patients from multiple independent datasets. In contrast, high EFNA3 predicted improved overall and progression-free survival in The Cancer Genome Atlas HGSC dataset, as expected for a canonical inducer of tumor-suppressive Eph receptor tyrosine kinase signaling. While depletion of either EFNA5 or the more extensively studied, canonically acting EFNA1 in HGSC cells increased the oncogenic EphA2-S897 phosphorylation, EFNA5 depletion left unaltered, or even increased the ligand-dependent EphA2-Y588 phosphorylation. Moreover, treatment with recombinant ephrinA5 led to limited EphA2 tyrosine phosphorylation, internalization and degradation compared to ephrinA1. Altogether, our results suggest a unique function for ephrinA5 in Eph-ephrin signaling and highlight the clinical potential of ephrinA5 as a cell surface biomarker in the most aggressive HGSCs.
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  • Kellokumpu-Lehtinen, PLI, et al. (författare)
  • Triweekly docetaxel versus biweekly docetaxel as a treatment for advanced castration resistant prostate cancer: Quality of life analysis
  • 2014
  • Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:4
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • 23 Background: Bi-weekly docetaxel (T) with prednisone improved progression free survival and overall survival when compared with the standard tri-weekly T as first-line treatment for advanced castration resistant prostate cancer (CRPC) (Lancet Oncol. 2013;14:117-124). We report here the quality of life (QoL) results of this prospective randomized trial. Methods: Three hundred and forty-six patients were randomly allocated centrally to receive intravenous therapy T of either 75 mg/m² d1 q3 wks (the triweekly arm) or 50 mg/m² d1 and d 14, q4 wks (the biweekly arm) (identifier NCT00255606). Prednisone (10 mg/d) was administered orally in both groups. The baseline patients characteristics were well balanced between the groups with respect to the performance status, mean age (69, range 45 to 87 vs. 68, range 46 to 85), and median serum prostate-specific antigen (PSA) content (109 µg/L, range 11 to 1,230 vs. 116 µg/L, range 12 to 1,870). Quality of life (QoL), the frequency and severity of symptoms including pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) version 4.0 questionnaire. Results: The baseline (QoL) of both treatment groups was compared to QoL after six months of the treatment within each treatment group and between groups. Changes in fatigue, symptoms of pain and nausea, and the overall performance status did not differ between the groups. There were statistically significant differences in overall quality of life values (p=0.010) and discomforting pain values (p=0.028) favoring the bi-weekly treatment arm. Conclusions: Bi-weekly T is better tolerated than the tri-weekly standard T. Following the results from the clinical outcome and the QoL outcome in the PROSTY trial we would recommend the use of bi-weekly docetaxel as first line treatment of CRPC Clinical trial information: NCT00255606.
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  • Keskitalo, S, et al. (författare)
  • Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease
  • 2019
  • Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 4, s. 14-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.
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22.
  • Kim, J., et al. (författare)
  • Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
  • 2016
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:1, s. 293-304
  • Tidskriftsartikel (refereegranskat)abstract
    • Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study,we focus on a challenging size range, i.e., particles that have grown to diameters of 10 and 15 nm following nucleation, and measure their water uptake. Water uptake is useful information for indirectly obtaining chemical composition of aerosol particles. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at sub-saturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) campaign performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from alpha-pinene oxidation. The hygroscopicity parameter kappa decreased with increasing particle size, indicating decreasing acidity of particles. No clear effect of the sulfuric acid concentration on the hygroscopicity of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15 nm particles sharply decreased with decreasing sulfuric acid concentrations. In particular, when the concentration of sulfuric acid was 5.1 x 10(6) molecules cm(-3) in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured kappa of 15 nm particles was 0.31 +/- 0.01: close to the value reported for dimethylaminium sulfate (DMAS) (kappa(DMAS) similar to 0.28). Furthermore, the difference in kappa between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The kappa values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from alpha-pinene ozonolysis play a significant role in particle growth even at 10 nm sizes.
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  • Laaksonen, A., et al. (författare)
  • The role of VOC oxidation products in continental new particle formation
  • 2008
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 8:10, s. 2657-2665
  • Tidskriftsartikel (refereegranskat)abstract
    • Aerosol physical and chemical properties and trace gas concentrations were measured during the QUEST field campaign in March-April 2003, in Hyytiala, Finland. Our aim was to understand the role of oxidation products of VOC's such as mono- and sesquiterpenes in atmospheric nucleation events. Particle chemical compositions were measured using the Aerodyne Aerosol Mass Spectrometer, and chemical compositions of aerosol samples collected with low-pressure impactors and a high volume sampler were analysed using a number of techniques. The results indicate that during and after new particle formation, all particles larger than 50 nm in diameter contained similar organic substances that are likely to be mono- and sesquiterpene oxidation products. The oxidation products identified in the high volume samples were shown to be mostly aldehydes. In order to study the composition of particles in the 10-50 nm range, we made use of Tandem Differential Mobility Analyzer results. We found that during nucleation events, both 10 and 50 nm particle growth factors due to uptake of ethanol vapour correlate strongly with gas-phase monoterpene oxidation product (MTOP) concentrations, indicating that the organic constituents of particles smaller than 50 nm in diameter are at least partly similar to those of larger particles. We furthermore showed that particle growth rates during the nucleation events are correlated with the gas-phase MTOP concentrations. This indicates that VOC oxidation products may have a key role in determining the spatial and temporal features of the nucleation events. This conclusion was supported by our aircraft measurements of new 3-10 nm particle concentrations, which showed that the nucleation event on 28 March 2003, started at the ground layer, i.e. near the VOC source, and evolved together with the mixed layer. Furthermore, no new particle formation was detected upwind away from the forest, above the frozen Gulf of Bothnia.
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  • Lehtinen, J. J., et al. (författare)
  • Topological changes in the magnetic field of LQ Hya during an activity minimum
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 660
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. Previous studies have related surface temperature maps, obtained with the Doppler imaging (DI) technique, of LQ Hya with long-term photometry. Here, we compare surface magnetic field maps, obtained with the Zeeman Doppler imaging (ZDI) technique, with contemporaneous photometry, with the aim of quantifying the star's magnetic cycle characteristics. Methods. We inverted Stokes IV spectropolarimetry, obtained with the HARPSpol and ESPaDOnS instruments, into magnetic field and surface brightness maps using a tomographic inversion code that models high signal-to-noise ratio mean line profiles produced by the least squares deconvolution (LSD) technique. The maps were compared against long-term ground-based photometry acquired with the T3 0.40 m Automatic Photoelectric Telescope (APT) at Fairborn Observatory, which offers a proxy for the spot cycle of the star, as well as with chromospheric Ca II H&K activity derived from the observed spectra. Results. The magnetic field and surface brightness maps reveal similar patterns relative to previous DI and ZDI studies: nonaxisymmetric polar magnetic field structure, void of fields at mid-latitudes, and a complex structure in the equatorial regions. There is a weak but clear tendency of the polar structures to be linked with a strong radial field and the equatorial ones with the azimuthal field. We find a polarity reversal in the radial field between 2016 and 2017 that is coincident with a spot minimum seen in the long-term photometry, although the precise relation of chromospheric activity to the spot activity remains complex and unclear. The inverted field strengths cannot be easily related with the observed spottedness, but we find that they are partially connected to the retrieved field complexity. Conclusions. This field topology and the dominance of the poloidal field component, when compared to global magnetoconvection models for rapidly rotating young suns, could be explained by a turbulent dynamo, where differential rotation does not play a major role (so-called alpha(2)Omega(2) or alpha(2) dynamos) and axi- and non-axisymmetric modes are excited simultaneously. The complex equatorial magnetic field structure could arise from the twisted (helical) wreaths often seen in these simulations, while the polar feature would be connected to the mostly poloidal non-axisymmetric component that has a smooth spatial structure.
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  • Merino Martinez, R, et al. (författare)
  • Human exposome assessment platform
  • 2021
  • Ingår i: Environmental epidemiology (Philadelphia, Pa.). - 2474-7882. ; 5:6, s. e182-
  • Tidskriftsartikel (refereegranskat)
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  • Sopanen, S, et al. (författare)
  • Prymnesium parvum exotoxins affect the grazing and viability of the calanoid copepod Eurytemora affinis
  • 2008
  • Ingår i: Marine Ecology Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 361, s. 191-202
  • Tidskriftsartikel (refereegranskat)abstract
    • The calanoid copepod Eurytemora affinis from the northern Baltic Sea was exposed to cell-free filtrates of the toxic haptophyte Prymnesium parvum as well as to cell mixtures of P. parvum and Rhodomonas salina. To test the effects of P. parvum exudates and allelopathy on selective grazers, copepods were incubated (1) in increasing concentrations of cell-free filtrates of P. parvum in the presence of good food (R, salina), (2) in 1:1 cell mixtures at 2 cell concentrations of P. parvum and R. salina and (3) in R. salina cell suspension, which was used as a control for good-quality food. P. parvum cultures were grown in nutrient-balanced (+NP) or limited (-N or -P) media to obtain different levels of toxicity. Survival, ingestion, faecal pellet production rates and egg production were measured over 3 d, together with measurements of P. parvum toxicity (hemolytic activity) (HA). Most of the copepods incubated in high-filtrate concentrations died or became severely impaired, although (HA) in filtrates was under the detection limit. Further, the ingestion and faecal pellet production rates were suppressed in the highest filtrate concentrations in nutrient-limited treatments. Higher cell density in cell mixtures resulted in significantly lower faecal pellet production, although survival remained high. Our results show that HA is not a good overall indicator of the total harmful effects of P. parvum on grazers. Besides monospecific P. parvum diets, filtrates and cell mixtures have negative effects on grazers, and these effects are stronger under nutrient-depleted conditions; however, the presence of good-quality food lowers harmful effects for copepods. The negative effects caused either by direct intoxication or by food limitation following from strong allelopathic effects of P. parvum on other components of nano- and microplankton suggest that P. parvum blooms have a realistic potential to be deleterious for copepod secondary production, irrespective of the presence of alternative food sources.
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  • Willamo, T., et al. (författare)
  • Zeeman-Doppler imaging of five young solar-type stars
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The magnetic activity of the Sun changes with the solar cycle. Similar cycles are found in other stars as well, but their details are not known to a similar degree. Characterising stellar magnetic cycles is important for the understanding of the stellar and solar dynamos that are driving the magnetic activity.Aims. We present spectropolarimetric observations of five young, solar-type stars and compare them to previous observations, with the aim to identify and characterise stellar equivalents of the solar cycle.Methods. We use Zeeman-Doppler imaging (ZDI) to map the surface magnetic field and brightness of our targets. The magnetic field is decomposed into spherical harmonic expansions, from which we report the strengths of the axisymmetric versus non-axisymmetric and poloidal versus toroidal components, and we compare them to the Rossby numbers of the stars.Results. We present five new ZDI maps of young, solar-type stars from December 2017. Of special interest is the case of V1358 Ori, which had gone through a polarity reversal between our observations and earlier ones. A less evident polarity reversal might also have occurred in HD 35296. There is a preference for a more axisymmetric field, and possibly a more toroidal field, for the more active stars with lower Rossby number, but a larger sample should be studied to draw any strong conclusions from this. For most of the individual stars, the amounts of toroidal and poloidal field have stayed on levels similar to those in earlier observations.Conclusions. We find evidence for a magnetic polarity reversal having occurred in V1358 Ori. An interesting target for future observations is I1 Ori, which may have a short magnetic cycle of a few years. The correlation between the brightness maps and the magnetic field is mostly poor, which could indicate the presence of small-scale magnetic features of different polarities that cancel one another out and are thus not resolved in our maps.
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38.
  • Allander, T, et al. (författare)
  • Human bocavirus and acute wheezing in children
  • 2007
  • Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 44:7, s. 904-910
  • Tidskriftsartikel (refereegranskat)
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42.
  • Barreiro, A, et al. (författare)
  • Relative importance of the different negative effects of the toxic haptophyte Prymnesium parvum on Rhodomonas salina and Brachionus plicatilis
  • 2005
  • Ingår i: Aquatic Microbial Ecology. - : Inter-Research Science Center. - 0948-3055 .- 1616-1564. ; 38:3, s. 259-267
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to determine the relative importance of the different processes/mechanisms by which the toxic haptophyte Prymnesium parvum, cultured under different nutrient conditions, affects non-toxic phytoplankton competitors and microzooplankton grazers. P. parvum was cultured under steady-state growth in different nutrient conditions: nitrogen depleted (-N), phosphorus depleted (-P) and balanced nitrogen and phosphorus (+NP). Cells from each nutrient condition and culture cell-free filtrates, alone and combined with non-toxic prey (Rhodomonas salina), were used as food for the rotifer Brachionus plicatilis. An additional experiment was carried out to test the effect of P. parvum cells and culture cell-free filtrate on R. salina. The highest haemolytic activity values were achieved by -P F parvum cultures, followed by -N. However, the negative effect of R parvum on R. salina and rotifers did not correlate with haemolytic activity but with the number of P. parvum cells. -N-cultured P. parvum were the most toxic for both R. salina and rotifers, followed by +NP. Therefore, haemolytic activity is not a good indicator of the total potential toxicity of R parvum. The growth rate of R. salina was negatively affected by cell-free filtrates but the effect of P, parvum predation was greater. Rotifers fed on both toxic and non-toxic algae, indicating that they did not select against the toxic alga. The P. parvum cell-free filtrate had an effect on B. plicatilis, although this was weak, B, plicatilis was also indirectly affected by P. parvum due to the negative effects of the toxic alga on their prey (R. salina). However, the greatest negative effect of P. parvum on the rotifers was due to ingestion of the toxic cells. Therefore, the phytoplankton competitor R. salina is more affected by P. parvum predation and the grazer B. plicatilis is more affected by ingestion of the toxic cells, the effects of excreted compounds being secondary.
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  • Bychkov, D, et al. (författare)
  • Deep learning identifies morphological features in breast cancer predictive of cancer ERBB2 status and trastuzumab treatment efficacy
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 4037-
  • Tidskriftsartikel (refereegranskat)abstract
    • The treatment of patients with ERBB2 (HER2)-positive breast cancer with anti-ERBB2 therapy is based on the detection of ERBB2 gene amplification or protein overexpression. Machine learning (ML) algorithms can predict the amplification of ERBB2 based on tumor morphological features, but it is not known whether ML-derived features can predict survival and efficacy of anti-ERBB2 treatment. In this study, we trained a deep learning model with digital images of hematoxylin–eosin (H&E)-stained formalin-fixed primary breast tumor tissue sections, weakly supervised by ERBB2 gene amplification status. The gene amplification was determined by chromogenic in situ hybridization (CISH). The training data comprised digitized tissue microarray (TMA) samples from 1,047 patients. The correlation between the deep learning–predicted ERBB2 status, which we call H&E-ERBB2 score, and distant disease-free survival (DDFS) was investigated on a fully independent test set, which included whole-slide tumor images from 712 patients with trastuzumab treatment status available. The area under the receiver operating characteristic curve (AUC) in predicting gene amplification in the test sets was 0.70 (95% CI, 0.63–0.77) on 354 TMA samples and 0.67 (95% CI, 0.62–0.71) on 712 whole-slide images. Among patients with ERBB2-positive cancer treated with trastuzumab, those with a higher than the median morphology–based H&E-ERBB2 score derived from machine learning had more favorable DDFS than those with a lower score (hazard ratio [HR] 0.37; 95% CI, 0.15–0.93; P = 0.034). A high H&E-ERBB2 score was associated with unfavorable survival in patients with ERBB2-negative cancer as determined by CISH. ERBB2-associated morphology correlated with the efficacy of adjuvant anti-ERBB2 treatment and can contribute to treatment-predictive information in breast cancer.
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