| 1. |
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| 2. |
- Aliu, E., et al.
(författare)
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Constraints on Very High Energy Emission from GRB 130427A
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 795:1
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Tidskriftsartikel (refereegranskat)abstract
- Prompt emission from the very fluent and nearby (z = 0.34) gamma-ray burst GRB 130427A was detected by several orbiting telescopes and by ground-based, wide-field-of-view optical transient monitors. Apart from the intensity and proximity of this GRB, it is exceptional due to the extremely long-lived high-energy (100 MeV to 100 GeV) gamma-ray emission, which was detected by the Large Area Telescope on the Fermi Gamma-Ray Space Telescope for ~70 ks after the initial burst. The persistent, hard-spectrum, high-energy emission suggests that the highest-energy gamma rays may have been produced via synchrotron self-Compton processes though there is also evidence that the high-energy emission may instead be an extension of the synchrotron spectrum. VERITAS, a ground-based imaging atmospheric Cherenkov telescope array, began follow-up observations of GRB 130427A ~71 ks (~20 hr) after the onset of the burst. The GRB was not detected with VERITAS; however, the high elevation of the observations, coupled with the low redshift of the GRB, make VERITAS a very sensitive probe of the emission from GRB 130427A for E > 100 GeV. The non-detection and consequent upper limit derived place constraints on the synchrotron self-Compton model of high-energy gamma-ray emission from this burst.
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| 3. |
- D’Ammando, F., et al.
(författare)
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The most powerful flaring activity from the NLSy1 PMN J0948+0022
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 446:3, s. 2456-2467
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Tidskriftsartikel (refereegranskat)abstract
- We report on multifrequency observations performed during 2012 December–2013 August of the first narrow-line Seyfert 1 galaxy detected in γ-rays, PMN J0948+0022 (z = 0.5846). A γ-ray flare was observed by the Large Area Telescope on board Fermi during 2012 December–2013 January, reaching a daily peak flux in the 0.1–100 GeV energy range of (155 ± 31) × 10−8 ph cm−2 s−1 on 2013 January 1, corresponding to an apparent isotropic luminosity of ∼1.5 × 1048 erg s−1. The γ-ray flaring period triggered Swift and Very Energetic Radiation Imaging Telescope Array System (VERITAS) observations in addition to radio and optical monitoring by Owens Valley Radio Observatory, Monitoring Of Jets in Active galactic nuclei with VLBA Experiments, and Catalina Real-time Transient Survey. A strong flare was observed in optical, UV, and X-rays on 2012 December 30, quasi-simultaneously to the γ-ray flare, reaching a record flux for this source from optical to γ-rays. VERITAS observations at very high energy (E > 100 GeV) during 2013 January 6–17 resulted in an upper limit of F>0.2 TeV < 4.0 × 10−12 ph cm−2 s−1. We compared the spectral energy distribution (SED) of the flaring state in 2013 January with that of an intermediate state observed in 2011. The two SEDs, modelled as synchrotron emission and an external Compton scattering of seed photons from a dust torus, can be modelled by changing both the electron distribution parameters and the magnetic field.
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| 4. |
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| 5. |
- Hartley, Philippa, et al.
(författare)
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SKA Science Data Challenge 2: analysis and results
- 2023
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 1967-1993
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Tidskriftsartikel (refereegranskat)abstract
- The Square Kilometre Array Observatory (SKAO) will explore the radio sky to new depths in order to conduct transformational science. SKAO data products made available to astronomers will be correspondingly large and complex, requiring the application of advanced analysis techniques to extract key science findings. To this end, SKAO is conducting a series of Science Data Challenges, each designed to familiarize the scientific community with SKAO data and to drive the development of new analysis techniques. We present the results from Science Data Challenge 2 (SDC2), which invited participants to find and characterize 233 245 neutral hydrogen (H i) sources in a simulated data product representing a 2000 h SKA-Mid spectral line observation from redshifts 0.25-0.5. Through the generous support of eight international supercomputing facilities, participants were able to undertake the Challenge using dedicated computational resources. Alongside the main challenge, 'reproducibility awards' were made in recognition of those pipelines which demonstrated Open Science best practice. The Challenge saw over 100 participants develop a range of new and existing techniques, with results that highlight the strengths of multidisciplinary and collaborative effort. The winning strategy - which combined predictions from two independent machine learning techniques to yield a 20 per cent improvement in overall performance - underscores one of the main Challenge outcomes: that of method complementarity. It is likely that the combination of methods in a so-called ensemble approach will be key to exploiting very large astronomical data sets.
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| 6. |
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| 7. |
- Langerak, A. W., et al.
(författare)
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EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations
- 2012
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:10, s. 2159-2171
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Forskningsöversikt (refereegranskat)abstract
- PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
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| 8. |
- Roepstorff, P., et al.
(författare)
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Application of Plasma Desorption Mass Spectrometry to Molecular Weight Determination of Structural Protein from Insect Cuticle
- 1986
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Ingår i: Journal of Mass Spectrometry. - : Wiley. - 1076-5174 .- 1096-9888. ; 13:12, s. 689-691
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Tidskriftsartikel (refereegranskat)abstract
- During sequence determination of a structural protein from the cuticle of the migratory locust, Locusta migratoria, a discrepancy was found between the molecular weight calculated from the sequence data (15 323) and that estimated by SDS-gel electrophoresis (21 600). The protein contains several repeated sequences, and the discrepancy might indicate that part of the sequence was missing or that the protein contained a large prosthetic group. The molecular weight of the protein was determined by 127I-plasma desorption mass spectrometry to be 15 329±50 which confirms the sequence data and shows the molecular weight determination based on SDS-electrophoresis to be too high.
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| 9. |
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| 10. |
- Baenas, Isabel, et al.
(författare)
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Impact of COVID-19 Lockdown in Eating Disorders : A Multicentre Collaborative International Study
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background. The COVID-19 lockdown has had a significant impact on mental health. Patients with eating disorders (ED) have been particularly vulnerable. Aims. (1) To explore changes in eating-related symptoms and general psychopathology during lockdown in patients with an ED from various European and Asian countries; and (2) to assess differences related to diagnostic ED subtypes, age, and geography. Methods. The sample comprised 829 participants, diagnosed with an ED according to DSM-5 criteria from specialized ED units in Europe and Asia. Participants were assessed using the COVID-19 Isolation Scale (CIES). Results. Patients with binge eating disorder (BED) experienced the highest impact on weight and ED symptoms in comparison with other ED subtypes during lockdown, whereas individuals with other specified feeding and eating disorders (OFSED) had greater deterioration in general psychological functioning than subjects with other ED subtypes. Finally, Asian and younger individuals appeared to be more resilient. Conclusions. The psychopathological changes in ED patients during the COVID-19 lockdown varied by cultural context and individual variation in age and ED diagnosis. Clinical services may need to target preventive measures and adapt therapeutic approaches for the most vulnerable patients.
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| 11. |
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| 12. |
- Buijs, J, et al.
(författare)
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Inter- and intra-molecular migration of peptide amide hydrogens during electrospray ionization
- 2001
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Ingår i: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY. - : ELSEVIER SCIENCE INC. - 1044-0305. ; 12:4, s. 410-419
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Tidskriftsartikel (refereegranskat)abstract
- The isotopic exchange of amide hydrogens in proteins in solution strongly depends on the surrounding protein structure, thereby allowing structural studies of proteins by mass spectrometry. However, during electrospray ionization (ESI), gas phase processe
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| 13. |
- Di Renzo, G C, et al.
(författare)
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Intrapartum GBS screening and antibiotic prophylaxis : a European consensus conference
- 2015
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Ingår i: The Journal of Maternal-Fetal & Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 7-8, s. 766-782
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Group B streptococcus (GBS) remains worldwide a leading cause of severe neonatal disease. Since the end of the 1990s, various strategies for prevention of the early onset neonatal disease have been implemented and have evolved. When a universal antenatal GBS screening-based strategy is used to identify women who are given an intrapartum antimicrobial prophylaxis, a substantial reduction of incidence up to 80% has been reported in the USA as in other countries including European countries. However recommendations are still a matter of debate due to challenges and controversies on how best to identify candidates for prophylaxis and to drawbacks of intrapartum administration of antibiotics. In Europe, some countries recommend either antenatal GBS screening or risk-based strategies, or any combination, and others do not have national or any other kind of guidelines for prevention of GBS perinatal disease. Furthermore, accurate population-based data of incidence of GBS neonatal disease are not available in some countries and hamper good effectiveness evaluation of prevention strategies. To facilitate a consensus towards European guidelines for the management of pregnant women in labor and during pregnancy for the prevention of GBS perinatal disease, a conference was organized in 2013 with a group of experts in neonatology, gynecology-obstetrics and clinical microbiology coming from European representative countries. The group reviewed available data, identified areas where results were suboptimal, where revised procedures and new technologies could improve current practices for prevention of perinatal GBS disease. The key decision issued after the conference is to recommend intrapartum antimicrobial prophylaxis based on a universal intrapartum GBS screening strategy using a rapid real time testing.
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| 14. |
- Dixon-Suen, Suzanne C, et al.
(författare)
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Physical activity, sedentary time and breast cancer risk : a Mendelian randomisation study
- 2022
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Ingår i: British Journal of Sports Medicine. - : BMJ Publishing Group Ltd. - 0306-3674 .- 1473-0480. ; 56:20, s. 1157-1170
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.METHODS: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (nsnps=5) or sedentary time (nsnps=6), or accelerometer-measured (nsnps=1) or self-reported (nsnps=5) vigorous physical activity.RESULTS: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).CONCLUSION: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
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| 15. |
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| 16. |
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| 17. |
- Fernández-Aranda, Fernando, et al.
(författare)
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COVID Isolation Eating Scale (CIES) : Analysis of the impact of confinement in eating disorders and obesity—A collaborative international study
- 2020
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Ingår i: European Eating Disorders Review. - : Wiley. - 1072-4133 .- 1099-0968. ; 28:6, s. 871-883
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Tidskriftsartikel (refereegranskat)abstract
- Confinement during the COVID-19 pandemic is expected to have a serious and complex impact on the mental health of patients with an eating disorder (ED) and of patients with obesity. The present manuscript has the following aims: (1) to analyse the psychometric properties of the COVID Isolation Eating Scale (CIES), (2) to explore changes that occurred due to confinement in eating symptomatology; and (3) to explore the general acceptation of the use of telemedicine during confinement. The sample comprised 121 participants (87 ED patients and 34 patients with obesity) recruited from six different centres. Confirmatory Factor Analyses (CFA) tested the rational-theoretical structure of the CIES. Adequate goodness-of-fit was obtained for the confirmatory factor analysis, and Cronbach alpha values ranged from good to excellent. Regarding the effects of confinement, positive and negative impacts of the confinement depends of the eating disorder subtype. Patients with anorexia nervosa (AN) and with obesity endorsed a positive response to treatment during confinement, no significant changes were found in bulimia nervosa (BN) patients, whereas Other Specified Feeding or Eating Disorder (OSFED) patients endorsed an increase in eating symptomatology and in psychopathology. Furthermore, AN patients expressed the greatest dissatisfaction and accommodation difficulty with remote therapy when compared with the previously provided face-to-face therapy. The present study provides empirical evidence on the psychometric robustness of the CIES tool and shows that a negative confinement impact was associated with ED subtype, whereas OSFED patients showed the highest impairment in eating symptomatology and in psychopathology.
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| 18. |
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| 19. |
- Genkinger, J. M., et al.
(författare)
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Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer : risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer
- 2020
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Ingår i: Annals of Oncology. - : OXFORD UNIV PRESS. - 0923-7534 .- 1569-8041. ; 31:1, s. 103-114
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Tidskriftsartikel (refereegranskat)abstract
- Background: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk.Patients and methods: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models.Results: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI >= 35.0 kg/m(2) with 21-22.9 kg/m(2). When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m(2) in early adulthood and BMI >= 30.0 kg/m(2) at baseline compared with BMI <25.0 kg/m(2) in early adulthood and BMI <30.0 kg/m(2) at baseline. Baseline waist circumference, comparing >= 110 cm with <90 cm, and waist-to-hip ratio, comparing >= 1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing >= 1.90 m with <1.65 m.Conclusion: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.
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| 20. |
- Holmbäck, Jan, et al.
(författare)
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Preclinical development of sodium fusidate antibiotic cutaneous spray based on water-free lipid formulation system
- 2022
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- Topical antibiotics are a key component in the management of mild to moderate skin and soft tissue infections. There are, however, concerns about the emerging bacterial resistance against topical antibacterial agents such as fusidic acid, due to the prolonged treatment period of its marketed dosage forms. Improving the efficacy of topical formulations could potentially shorten the treatment period and avoid the resistance growth. To provide a more effective drug delivery, a water-free lipid-based formulation system (AKVANO (R)) which can be applied by spraying, has been developed. In the current paper, different formulations containing sodium fusidate were evaluated for their in vitro skin permeability using artificial skin mimicking membranes and antibacterial properties using ex vivo and in vivo skin wound infection models. The novel formulations containing sodium fusidate showed a much higher skin permeation (up to 60% of nominal amount) than the commercially available Fucidin (R) cream (3%). These formulations also gave a significantly stronger antibacterial effect than Fucidin cream showing a clear dose-response relationship for the sodium fusidate content. A spray product based on the described formulation technology would therefore require a shorter treatment time and thereby lower the risk for the development of bacterial resistance. Spray administration of these formulations provides an even layer on the skin surface from which the solvent quickly evaporates and thereby facilitates a non-touch application where no rubbing is required.
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| 21. |
- Håkansson, H., et al.
(författare)
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In vivo and in vitro toxicity of fractionated fish lipids, with particular regard to their content of chlorinated organic compounds
- 1991
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Ingår i: Pharmacology and Toxicology. - : Wiley. - 0901-9928 .- 1600-0773. ; 69:6, s. 459-471
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Tidskriftsartikel (refereegranskat)abstract
- Six different lipid matrices (the intact lipid (IL), four lipid fractions with different polarity, and the free fatty acids (FFAs) obtained by hydrolysis of the triacylglycerol (TAG) containing fraction) were obtained from salmon (Salmo salar) and eel (Anguilla anguilla), each collected at a contaminated and a comparatively uncontaminated catch site along the coast of Scandinavia. The lipid matrices were studied in toxicological test systems representing various biological functions of different organ systems from several species and trophic levels. The results were evaluated with particular respect to the concentrations of extractable organically bound chlorine (EOCl) in the matrices tested. In some test systems, the specimens with a higher EOCl concentration appeared to be more toxic. For example, the TAG containing fraction (F2) from Idefjord eel, having a higher EOCl content than F2 from Oslofjord eel, reduced the number and hatchability of eggs laid by zebrafish. Both IL and F2 of Idefjord eel increased mortality and reduced the oxygen/nitrogen-ratio in blue mussels. Non-polar compounds (F1) from Bothnian Sea salmon induced 7-ethoxyresurofin O-deethylase (EROD) activity in rainbow trout hepatocytes, whereas F1 from Senja salmon did not. F1 from Bothnian Sea salmon also reduced the number of T-cells in foetal mouse thymus anlagen in vitro compared with the cell number in anlagen exposed to F1 from Senja salmon. A positive correlation between EOCl concentration and test response was found for EROD activity in rainbow trout hepatocytes and for ATP-leakage in Erlich ascites tumour cells when testing the phospolipid containing fraction (F4). However, in most test systems the fish oils, irrespective of EOCl content, were of low toxicity, and the observed effects need to be verified in future studies.
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| 22. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 23. |
- Kämpfer, Peter, et al.
(författare)
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Proposal of Coetzeea brasiliensis gen. nov. sp. nov. isolated from larvae of Anopheles darlingi
- 2016
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Ingår i: International Journal of Systematic and Evolutionary Microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 66, s. 5211-5217
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Tidskriftsartikel (refereegranskat)abstract
- A Gram-stain-negative, rod-shaped strain, Braz8T, isolated from larvae ofAnopheles darlingiwas investigatedusing a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that strainBraz8Twas related most closely to species of the genusThorsellia, with 95.6, 96.5 and 96.6% similarity to thetype strains ofThorsellia anophelis,Thorsellia kandunguensisandThorsellia kenyensis, respectively, andformed a separate branch in the phylogenetic tree next to the monophyletic cluster of the genusThorsellia.Chemotaxonomic data supported the allocation of the strain to the familyThorselliaceae. The major fatty acidswere C18:1!7c, C16:0and C14:0. The quinone system was composed of ubiquinones Q-8 and Q-7 (1:0.3),the predominant polar lipids were diphosphatidylglycerol and phosphatidylglycerol, and the polyamine patternshowed the major compound putrescine. However, qualitative and quantitative differences in the majorpolyamine, polar lipid profile and fatty acid patterns distinguished strain Braz8Tfrom species of the genusThorsellia. Phylogenetic analysis based on 16S rRNA gene sequences, average nucleotide identity, DNA–DNAhybridization, multilocus sequence analysis as well as physiological and biochemical tests distinguished strainBraz8Tboth genotypically and phenotypically from the threeThorselliaspecies but also showed its placementin the familyThorselliaceae. Thus, strain Braz8Tis considered to represent a novel species of a new genus mostclosely related to the genusThorsellia, for which the nameCoetzeea brasiliensisgen. nov., sp. nov. is proposed.The type strain ofCoetzeea brasiliensisis Braz8T(=LMG 29552T=CIP 111088T)
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| 24. |
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| 25. |
- Permyakov, Sergei E, et al.
(författare)
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A novel method for preparation of HAMLET-like protein complexes
- 2011
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Ingår i: Biochimie. - : Elsevier BV. - 1638-6183 .- 0300-9084. ; 93:9, s. 501-1495
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Tidskriftsartikel (refereegranskat)abstract
- Some natural proteins induce tumor-selective apoptosis. α-Lactalbumin (α-LA), a milk calcium-binding protein, is converted into an antitumor form, called HAMLET/BAMLET, via partial unfolding and association with oleic acid (OA). Besides triggering multiple cell death mechanisms in tumor cells, HAMLET exhibits bactericidal activity against Streptococcus pneumoniae. The existing methods for preparation of active complexes of α-LA with OA employ neutral pH solutions, which greatly limit water solubility of OA. Therefore these methods suffer from low scalability and/or heterogeneity of the resulting α-LA - OA samples. In this study we present a novel method for preparation of α-LA - OA complexes using alkaline conditions that favor aqueous solubility of OA. The unbound OA is removed by precipitation under acidic conditions. The resulting sample, bLA-OA-45, bears 11 OA molecules and exhibits physico-chemical properties similar to those of BAMLET. Cytotoxic activities of bLA-OA-45 against human epidermoid larynx carcinoma and S. pneumoniae D39 cells are close to those of HAMLET. Treatment of S. pneumoniae with bLA-OA-45 or HAMLET induces depolarization and rupture of the membrane. The cells are markedly rescued from death upon pretreatment with an inhibitor of Ca(2+) transport. Hence, the activation mechanisms of S. pneumoniae death are analogous for these two complexes. The developed express method for preparation of active α-LA - OA complex is high-throughput and suited for development of other protein complexes with low-molecular-weight amphiphilic substances possessing valuable cytotoxic properties.
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| 26. |
- Permyakov, Sergei E, et al.
(författare)
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Oleic acid is a key cytotoxic component of HAMLET-like complexes
- 2012
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Ingår i: Biological Chemistry. - 1437-4315. ; 393:1-2, s. 85-92
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Tidskriftsartikel (refereegranskat)abstract
- HAMLET is a complex of α-lactalbumin (α-LA) with oleic acid (OA) that selectively kills tumor cells and Streptococcus pneumoniae. To assess the contribution of the proteinaceous component to cytotoxicity of HAMLET, OA complexes with proteins structurally and functionally distinct from α-LA were prepared. Similar to HAMLET, the OA complexes with bovine β-lactoglobulin (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45, respectively) induced S. pneumoniae D39 cell death. The activation mechanisms of S. pneumoniae death for these complexes were analogous to those for HAMLET, and the cytotoxicity of the complexes increased with OA content in the preparations. The half-maximal inhibitory concentration for HEp-2 cells linearly decreased with rise in OA content in the preparations, and OA concentration in the preparations causing HEp-2 cell death was close to the cytotoxicity of OA alone. Hence, the cytotoxic action of these complexes against HEp-2 cells is induced mostly by OA. Thermal stabilization of bLG upon association with OA implies that cytotoxicity of bLG-OA-45 complex cannot be ascribed to molten globule-like conformation of the protein component. Overall, the proteinaceous component of HAMLET-like complexes studied is not a prerequisite for their activity; the cytotoxicity of these complexes is mostly due to the action of OA.
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| 27. |
- Rath, Emma M, et al.
(författare)
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BAMLET kills chemotherapy-resistant mesothelioma cells, holding oleic acid in an activated cytotoxic state
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
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Tidskriftsartikel (refereegranskat)abstract
- Malignant pleural mesothelioma is an aggressive cancer with poor prognosis. Here we have investigated in vitro efficacy of BAMLET and BLAGLET complexes (anti-cancer complexes consisting of oleic acid and bovine α-lactalbumin or β-lactoglobulin respectively) in killing mesothelioma cells, determined BAMLET and BLAGLET structures, and investigated possible biological mechanisms. We performed cell viability assays on 16 mesothelioma cell lines. BAMLET and BLAGLET having increasing oleic acid content inhibited human and rat mesothelioma cell line proliferation at decreasing doses. Most of the non-cancer primary human fibroblasts were more resistant to BAMLET than were human mesothelioma cells. BAMLET showed similar cytotoxicity to cisplatin-resistant, pemetrexed-resistant, vinorelbine-resistant, and parental rat mesothelioma cells, indicating the BAMLET anti-cancer mechanism may be different to drugs currently used to treat mesothelioma. Cisplatin, pemetrexed, gemcitabine, vinorelbine, and BAMLET, did not demonstrate a therapeutic window for mesothelioma compared with immortalised non-cancer mesothelial cells. We demonstrated by quantitative PCR that ATP synthase is downregulated in mesothelioma cells in response to regular dosing with BAMLET. We sought structural insight for BAMLET and BLAGLET activity by performing small angle X-ray scattering, circular dichroism, and scanning electron microscopy. Our results indicate the structural mechanism by which BAMLET and BLAGLET achieve increased cytotoxicity by holding increasing amounts of oleic acid in an active cytotoxic state encapsulated in increasingly unfolded protein. Our structural studies revealed similarity in the molecular structure of the protein components of these two complexes and in their encapsulation of the fatty acid, and differences in the microscopic structure and structural stability. BAMLET forms rounded aggregates and BLAGLET forms long fibre-like aggregates whose aggregation is more stable than that of BAMLET due to intermolecular disulphide bonds. The results reported here indicate that BAMLET and BLAGLET may be effective second-line treatment options for mesothelioma.
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| 28. |
- Rath, Emma M, et al.
(författare)
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Small-angle X-ray scattering of BAMLET at pH 12 : a complex of α-lactalbumin and oleic acid
- 2014
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Ingår i: Proteins. - : Wiley. - 0887-3585. ; 82:7, s. 8-1400
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Tidskriftsartikel (refereegranskat)abstract
- BAMLET (Bovine Alpha-lactalbumin Made LEthal to Tumors) is a member of the family of the HAMLET-like complexes, a novel class of protein-based anti-cancer complexes that incorporate oleic acid and deliver it to cancer cells. Small angle X-ray scattering (SAXS) was performed on the complex at pH 12, examining the high pH structure as a function of oleic acid added. The SAXS data for BAMLET species prepared with a range of oleic acid concentrations indicate extended, irregular, partially unfolded protein conformations that vary with the oleic acid concentration. Increases in oleic acid concentration correlate with increasing radius of gyration without an increase in maximum particle dimension, indicating decreasing protein density. The models for the highest oleic acid content BAMLET indicate an unusual coiled elongated structure that contrasts with apo-α-lactalbumin at pH 12, which is an elongated globular molecule, suggesting that oleic acid inhibits the folding or collapse of the protein component of BAMLET to the globular form. Circular dichroism of BAMLET and apo-α-lactalbumin was performed and the results suggest that α-lactalbumin and BAMLET unfold in a continuum of increasing degree of unfolded states. Taken together, these results support a model in which BAMLET retains oleic acid by non-specific association in the core of partially unfolded protein, and represent a new type of lipoprotein structure.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Adler, Anneli, et al.
(författare)
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Lignin-first biorefining of Nordic poplar to produce cellulose fibers could displace cotton production on agricultural lands
- 2022
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Ingår i: Joule. - : Elsevier BV. - 2542-4351. ; 6:8, s. 1845-1858
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Tidskriftsartikel (refereegranskat)abstract
- Here, we show that lignin-first biorefining of poplar can enable the production of dissolving cellulose pulp that can produce regenerated cellulose, which could substitute cotton. These results in turn indicate that agricultural land dedicated to cotton could be reclaimed for food production by extending poplar plantations to produce textile fibers. Based on climate-adapted poplar clones capable of growth on marginal lands in the Nordic region, we estimate an environmentally sustainable annual biomass production of ∼11 tonnes/ha. At scale, lignin-first biorefining of this poplar could annually generate 2.4 tonnes/ha of dissolving pulp for textiles and 1.1 m3 biofuels. Life cycle assessment indicates that, relative to cotton production, this approach could substantially reduce water consumption and identifies certain areas for further improvement. Overall, this work highlights a new value chain to reduce the environmental footprint of textiles, chemicals, and biofuels while enabling land reclamation and water savings from cotton back to food production.
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| 33. |
- Aevarsson, Arnthór, et al.
(författare)
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Going to extremes - a metagenomic journey into the dark matter of life
- 2021
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Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12
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Forskningsöversikt (refereegranskat)abstract
- The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
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| 34. |
- Alissa, S., et al.
(författare)
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Distribution of the adapted-NRTK correction data via VDES for the shipping navigation safety
- 2021
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Ingår i: Proceedings of the 34th International Technical Meeting of the Satellite Division of the Institute of Navigation, ION GNSS+ 2021. - : Institute of Navigation. - 9780936406299 ; , s. 521-534
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Konferensbidrag (refereegranskat)abstract
- In this study the maritime communication system VDES (VHF Data Exchange System) is proposed to distribute Network-RTK (NRTK) correction data to shipborne GNSS receivers in fairways, port areas, or inland water ways. The transport layer used for transmission of VDES messages (related to the standard IEC61162-450) is the UDP multicast protocol. This makes it possible to transmit the RTCM packages from the VDES transponder to the shipborne GNSS receivers as a UDP payload without any additional formatting. In order to minimize the impact on the overall VDES data capacity in a local service area, NRTK correction data shall at most occupy a single VDES slot with a net capacity of 650 bytes denoted Link ID 19. This is the fastest link in VDES. Update rates may vary but are preferably at 1Hz. However, depending on the number of visible satellites NRTK correction data size changes instantly and the data rate can therefore sometimes be in excess of 1000 byte/s per reference station to be distributed. In order to comply with the VDES requirements, the Lantmäteriet Adjustment Solution (LAS) for GNSS correction data adjustment was developed and is presented in this paper. The responsibility of this solution is to produce a correction data stream that complies with the bandwidth limitation of 650 bytes/s. To provide corrections for a potentially large number of users, dissemination is done by broadcasting corrections for a grid of VRSs. The proposed solution has therefore also the capability to combine several correction data streams from several Virtual Reference Stations (VRSs) into one single correction data stream. To reduce the required data rate, the LAS has the ability to filter streamed GNSS correction data in the RTCM3 MSM format constellation-wise, satellite-wise, and signal-wise. The objective is to achieve optimal performance in terms of accuracy for the ship's differential positioning solution, while at the same time adhering to constraints that might locally apply for individual transmitters. For this paper LAS was configured to interface with the SWEPOS to provide reference data to static and kinematic testing scenarios. The results presented here were obtained using RTK post-processing with RTKLib for a combination of GPS and Galileo multi-frequency observations. Results indicated that LAS solution can achieve robust positioning performance with decimeter-level accuracy which meet the requirements expected for the navigation safety at Sea. Adapted-NRTK correction data (LAS data) via VDES has the potential to be part of a world-wide standard VDES application for all vessels sailing under SOLAS and for ships that voluntarily uses VDES in the near future (inland, yachts, navies, leisure).
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| 35. |
- Alissa, S., et al.
(författare)
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Low bandwidth network-rtk correction dissemination for high accuracy maritime navigation
- 2021
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Ingår i: TransNav, International Journal on Marine Navigation and Safety of Sea Transportation. - : Faculty of Navigation, Gdynia Maritime University. - 2083-6473 .- 2083-6481. ; 15:1, s. 171-179
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Tidskriftsartikel (refereegranskat)abstract
- More than half of the incidents reported to EMSA relate to nautical events such as collision, groundings and contacts. Knowledge of accurate and high-integrity positioning is therefore not only a need for future automated shipping but a base for today’s safe navigation. Examples on accidents include Ever Given in the Suez Canal and HNoMS Helge Ingstad in Norway. A Network-RTK (NRTK) service can be used as an augmentation technique to improve performance of shipborne GNSS receivers for future positioning of manned and unmanned vessels in restricted areas, such as port areas, fairways, and inland water ways. NRTK service providers generate RTK corrections based on the observations of networks of GNSS reference stations which enables the users to determine their position with centimeter accuracy in real-time using a shipborne GNSS receiver. Selection of appropriate communication channels for dissemination of NRTK corrections data is the key to a secure positioning (localization) service. In PrePare-Ships project, the modern maritime communication system VDES (VHF Data Exchange System) is proposed to distribute SWEPOS (NRTK in Sweden) correction data to shipborne positioning modules. VDES is a very reliable technique and it is compatible with most onboard functionalities. In order to minimize the impact on the overall VDES data capacity in a local area, NRTK correction data shall only occupy a single VDES slot with a net capacity of 650 bytes. Update rates may vary but are preferably at 1Hz. However, NRTK correction data size changes instantly, depending on the number of visible GNSS satellites, and the data rate can therefore sometimes reach in excess of 1000 byte/s. In this study, a smart technique is proposed to reduce size of NRTK correction data to instantly adapt with the VDES requirements by choosing a combination of specific signals, satellites or even constellations such that the data rate is not more than 650 byte/s, and at the same time it achieves optimal positioning performance with the accuracy required by the PrePare-Ships project application.
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| 36. |
- Almehed, Sverker, et al.
(författare)
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A Silicon-Tungsten Electromagnetic Calorimeter for LEP
- 1991
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 305:2, s. 320-330
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Tidskriftsartikel (refereegranskat)abstract
- This report describes a silicon-tungsten electromagnetic calorimeter used to determine some beam properties and luminosity in the DELPHI experiment at LEP. The polar angular range covered by this detector is 5–8 mrad, which allows the detection of a Bhabha rate about 10 times the rate of produced Z particles at the peak cross section.
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| 37. |
- Alqahtani, Fulwah Y, et al.
(författare)
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Capsule Independent Antimicrobial Activity Induced by Nanochitosan against Streptococcus pneumoniae
- 2021
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Ingår i: Polymers. - : MDPI AG. - 2073-4360. ; 13:17, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Streptococcus pneumoniae remains a major cause of community-acquired pneumonia, meningitis, and other diseases, contributing significantly to high morbidity and mortality worldwide. Although it responds to antibiotics, their use is becoming limited due to the rise in antibiotic resistance, which necessitates the development of new therapeutics. Nanotechnology is used to counteract antimicrobial resistance. In this regard, polymeric nanoparticles (NPs) made of natural, biodegradable, biocompatible, and cationic polymers such as Chitosan (CNPs) exhibit wide-spectrum antimicrobial activity. Therefore, this study aimed to prepare CNPs, characterize their physiochemical characteristics: particle size (PZ), polydispersity index (PDI), and zeta potential (ZP), and investigate their antimicrobial activity against Streptococcus pneumoniae TIGR4 (virulent serotype 4) and its capsular mutant (∆cps).METHODS: CNPs were prepared at 1, 2.5, and 5 mg/mL concentrations using the ion gelation method. Then, PZ, PDI, and ZP were characterized using a Zetasizer. Transmission electron microscopy (TEM) was used to visualize the CNP's morphology. Broth and agar dilution methods were used to assess their antimicrobial activity. Cytotoxicity of prepared NPs on A549 cells and their effect on pneumococcal hemolysis were also investigated.RESULTS: Spherical CNPs were produced with PZ ranging from 133.3 nm ± 0.57 to 423 nm ± 12.93 PDI < 0.35, and ZP from 19 ± 0.115 to 27 ± 0.819. The prepared CNPs exhibited antibacterial activity against TIGR4 and its capsule mutant with a minimum inhibitory concentration (MIC90) of 0.5 to 2.5 mg/mL in a non-acidic environment. The hemolysis assay results revealed that CNPs reduced bacterial hemolysis in a concentration-dependent manner. Their mammalian cytotoxicity results indicated that CNPs formed from low concentrations of Chitosan (Cs) were cytocompatible.CONCLUSION: Nanochitosan particles showed anti-pneumococcal activity regardless of the presence of capsules. They resulted in a concentration-dependent reduction in bacterial hemolysis and were cytocompatible at a lower concentration of Cs. These findings highlight the potential of CNPs in the treatment of pneumococcal diseases.
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| 38. |
- Ardestani, Shahrzad, et al.
(författare)
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B2SHARE : An open eScience data sharing platform
- 2015
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Ingår i: Proceedings - 11th IEEE International Conference on eScience. - : IEEE. ; , s. 448-453
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Konferensbidrag (refereegranskat)abstract
- Scientific data sharing is becoming an essential service for data driven science and can significantly improve the scientific process by making reliable, and trustworthy data available. Thereby reducing redundant work, and providing insights on related research and recent advancements. For data sharing services to be useful in the scientific process, they need to fulfill a number of requirements that cover not only discovery, and access to data. But to ensure the integrity, and reliability of published data as well. B2SHARE, developed by the EUDAT project, provides such a data sharing service to scientific communities. For communities that wish to download, install and maintain their own service, it is also available as software. B2SHARE is developed with a focus on user-friendliness, reliability, and trustworthiness, and can be customized for different organizations and use-cases. In this paper we discuss the design, architecture, and implementation of B2SHARE. We show its usefulness in the scientific process with some case studies in the biodiversity field.
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| 39. |
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| 40. |
- Asproth, Viveca, et al.
(författare)
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Visualization of Critical Factors in a Decision Support System for Management of Flooding
- 2006
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Ingår i: MicroCAD '06.
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Konferensbidrag (refereegranskat)abstract
- Flooding is a natural occurrence and no drainage systems or flood protection measures can give an absolute protection from all flooding events. The impact of flooding on a community and the health and safety risks are significant. Globally flooding is one of the natural catastrophes that every year causes most victims and the greatest economical effects. In Sweden and other European countries death caused by flooding is relatively unusual, but the damages in tangible assets and the cost for the society are considerable. In case of flooding many authorities and organizations become involved and there is a problem to take in the whole situation and have a common picture when many incidents happen at the same time. There is also a lack of efficient tools showing critical buildings and constructions such as roads, railroads, water-purifying plant, etc, in combination with actual and forecasted water-levels. In this paper we discuss how the critical factors can be visualized in the CRISSI system. The complexity challenges according to the laws of complexity are also considered.
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| 41. |
- Berg, J, et al.
(författare)
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Crater formation in Langmuir-Blodgett films induced by electronic sputtering with fast heavy ions
- 1987
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Ingår i: Applied Physics Letters. - 0003-6951 .- 1077-3118. ; 51:17, s. 1379-
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Tidskriftsartikel (refereegranskat)abstract
- Secondary ion formation by fast heavy ion impact (electronic sputtering) on Langmuir–Blodgett films of fatty acids has been studied. The results show unambiguously that molecular ions originate from molecules in layers other than the surface layer. Furthermore, the results indicate that craters may be formed in electronic sputtering of such films. The depth of the craters depends on the stopping power of the incident ion and lower limits of the order of 100–200 Å are obtained from the ion data.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Carlson, Jan, et al.
(författare)
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SaveCCM : An Analysable Component Model for Real-Time Systems
- 2006
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Ingår i: Electronic Notes in Theoretical Computer Science. - : Elsevier BV. - 1571-0661. ; 160:1, s. 127-140
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Tidskriftsartikel (refereegranskat)abstract
- Component based development is a promising approach for embedded systems. Typical for embedded software is the presence of resource constraints in multiple dimensions. An essential dimension is time, since many embedded systems have real-time requirements. We define a formal semantics of a component language for embedded systems, SaveCCM, a language designed with vehicle applications and safety concerns in focus. The semantics is defined by a transformation into timed automata with tasks, a formalism that explicitly models timing and real-time task scheduling. A simple SaveCCM system with a PI controller is used as a case study. Temporal properties of the PI controller have been successfully verified using the timed automata model checker Uppaal.
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| 46. |
- Challis, Pontus, et al.
(författare)
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Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016)
- 2024
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Ingår i: Archives of Disease in Childhood-Fetal and Neonatal Edition. - : BMJ Publishing Group Ltd. - 1359-2998 .- 1468-2052. ; 109, s. 87-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants.Design Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage >= II) were validated against hospital records.Patients All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden.Main outcome measures NEC incidence.Results The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047).Conclusions The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.
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| 47. |
- Chao, Yashuan, et al.
(författare)
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In vitro and in vivo biofilm formation by pathogenic streptococci
- 2017
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Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1064-3745. ; 1535, s. 285-299
-
Bokkapitel (refereegranskat)abstract
- This manuscript presents novel approaches to grow and evaluate Streptococcal biofilm formation using the human respiratory pathogen Streptococcus pneumoniae (the pneumococcus) as the main model organism on biological surfaces in vitro and in vivo. Most biofilm models are based on growth on abiotic surfaces, which is relevant for many pathogens whose growth on surfaces or medical devices is a major cause of disease transmission and infections, especially in hospital environments. However, most infections with commensal organisms require biofilm formation on biological surfaces in the host at the site of colonization or infection. In vitro model systems incorporating biological components from the host and taking into account the host environment of the infectious site are not well described. In a series of publications, we have shown that S. pneumoniae form complex biofilms in the nasopharynx of mice and have devised methodology to evaluate the biofilm structure and function in this environment. We have also been able to recapitulate this biofilm phenotype in vitro by incorporating crucial factors associated with the host environment. Although the protocols presented in this manuscript are focused on S. pneumoniae, the same methodology can and has been used for other Streptococcal species that form biofilms on mucosal surfaces.
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| 48. |
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| 49. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 50. |
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