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- Ackermann, M., et al.
(author)
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THE SPECTRUM AND MORPHOLOGY OF THE FERMI BUBBLES
- 2014
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 793:1, s. 64-
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Journal article (peer-reviewed)abstract
- The Fermi bubbles are two large structures in the gamma-ray sky extending to 55 degrees above and below the Galactic center. We analyze 50 months of Fermi Large Area Telescope data between 100MeV and 500 GeV above 10 degrees in Galactic latitude to derive the spectrum and morphology of the Fermi bubbles. We thoroughly explore the systematic uncertainties that arise when modeling the Galactic diffuse emission through two separate approaches. The gamma-ray spectrum is well described by either a log parabola or a power law with an exponential cutoff. We exclude a simple power law with more than 7 sigma significance. The power law with an exponential cutoff has an index of 1.9 +/- 0.2 and a cutoff energy of 110 +/- 50 GeV. We find that the gamma-ray luminosity of the bubbles is 4.4(-0.9)(+2.4) x 10(37) erg s(-1). We confirm a significant enhancement of gamma-ray emission in the southeastern part of the bubbles, but we do not find significant evidence for a jet. No significant variation of the spectrum across the bubbles is detected. The width of the boundary of the bubbles is estimated to be 3.4(-2.6)(+3.7) deg. Both inverse Compton (IC) models and hadronic models including IC emission from secondary leptons fit the gamma-ray data well. In the IC scenario, synchrotron emission from the same population of electrons can also explain the WMAP and Planck microwave haze with a magnetic field between 5 and 20 mu G.
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- Reiner, A. T., et al.
(author)
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Concise Review: Developing Best-Practice Models for the Therapeutic Use of Extracellular Vesicles
- 2017
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In: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 6:8
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Research review (peer-reviewed)abstract
- Growing interest in extracellular vesicles (EVs, including exosomes and microvesicles) as therapeutic entities, particularly in stem cell-related approaches, has underlined the need for standardization and coordination of development efforts. Members of the International Society for Extracellular Vesicles and the Society for Clinical Research and Translation of Extracellular Vesicles Singapore convened a Workshop on this topic to discuss the opportunities and challenges associated with development of EV-based therapeutics at the preclinical and clinical levels. This review outlines topic-specific action items that, if addressed, will enhance the development of best-practice models for EV therapies.
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- Kim, Dae-Kyum, et al.
(author)
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EVpedia: A Community Web Portal for Extracellular Vesicles Research
- 2015
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In: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 31:6, s. 933-939
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Journal article (peer-reviewed)abstract
- Motivation: Extracellular vesicles (EVs) are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for EV-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for EVs research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools and a personalized function. EVpedia includes 6879 publications, 172 080 vesicular components from 263 high-throughput datasets, and has been accessed more than 65 000 times from more than 750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of EV research.
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| 9. |
- Hesselson, Stephanie E, et al.
(author)
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Genetic variation in the proximal promoter of ABC and SLC superfamilies : liver and kidney specific expression and promoter activity predict variation
- 2009
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:9, s. e6942-
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Journal article (peer-reviewed)abstract
- Membrane transporters play crucial roles in the cellular uptake and efflux of an array of small molecules including nutrients, environmental toxins, and many clinically used drugs. We hypothesized that common genetic variation in the proximal promoter regions of transporter genes contribute to observed variation in drug response. A total of 579 polymorphisms were identified in the proximal promoters (-250 to +50 bp) and flanking 5' sequence of 107 transporters in the ATP Binding Cassette (ABC) and Solute Carrier (SLC) superfamilies in 272 DNA samples from ethnically diverse populations. Many transporter promoters contained multiple common polymorphisms. Using a sliding window analysis, we observed that, on average, nucleotide diversity (pi) was lowest at approximately 300 bp upstream of the transcription start site, suggesting that this region may harbor important functional elements. The proximal promoters of transporters that were highly expressed in the liver had greater nucleotide diversity than those that were highly expressed in the kidney consistent with greater negative selective pressure on the promoters of kidney transporters. Twenty-one promoters were evaluated for activity using reporter assays. Greater nucleotide diversity was observed in promoters with strong activity compared to promoters with weak activity, suggesting that weak promoters are under more negative selective pressure than promoters with high activity. Collectively, these results suggest that the proximal promoter region of membrane transporters is rich in variation and that variants in these regions may play a role in interindividual variation in drug disposition and response.
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| 11. |
- Clayton, Aled, et al.
(author)
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Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
- 2018
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In: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
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Journal article (other academic/artistic)abstract
- © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.
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- Johannsson, Gudmundur, 1960, et al.
(author)
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Once-weekly Somapacitan is Effective and Well Tolerated in Adults with GH Deficiency: A Randomized Phase 3 Trial.
- 2020
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:4
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Journal article (peer-reviewed)abstract
- Growth hormone (GH) replacement requires daily GH injections, which is burdensome for some adult patients with GH deficiency (AGHD).To demonstrate efficacy and safety of somapacitan, a once-weekly reversible albumin-binding GH derivative, versus placebo in AGHD.Randomized, parallel-group, placebo-controlled (double-blind) and active-controlled (open-label) phase 3 trial, REAL 1 (NCT02229851).Clinics in 17 countries.Treatment-naïve patients with AGHD (n = 301 main study period, 272 extension period); 257 patients completed the trial.Patients were randomized 2:2:1 to once-weekly somapacitan, daily GH, or once-weekly placebo for 34 weeks (main period). During the 52-week extension period, patients continued treatment with somapacitan or daily GH.Body composition measured using dual-energy x-ray absorptiometry (DXA). The primary endpoint was change in truncal fat percentage to week 34. Insulin-like growth factor 1 (IGF-I) standard deviation score (SDS) values were used to dose titrate.At 34 weeks, somapacitan significantly reduced truncal fat percentage (estimated difference: -1.53% [-2.68; -0.38]; P = 0.0090), demonstrating superiority compared with placebo, and it improved other body composition parameters (including visceral fat and lean body mass) and IGF-I SDS. At 86 weeks, improvements were maintained with both somapacitan and daily GH. Somapacitan was well tolerated, with similar adverse events (including injection-site reactions) compared with daily GH.In AGHD patients, somapacitan administered once weekly demonstrated superiority over placebo, and the overall treatment effects and safety of somapacitan were in accordance with known effects and safety of GH replacement for up to 86 weeks of treatment. Somapacitan may provide an effective alternative to daily GH in AGHD. A short visual summary of our work is available (1).
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| 14. |
- Johannsson, Gudmundur, 1960, et al.
(author)
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Safety and convenience of once-weekly somapacitan in adult GH deficiency: A 26-week randomized, controlled trial
- 2018
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In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 178:5, s. 491-499
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Journal article (peer-reviewed)abstract
- Objective: Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed. Design: 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (NCT02382939). Methods: Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n=61) or once-daily Norditropin (n=31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results: Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P=0.0171). Conclusions: In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin. © 2018 European Society of Endocrinology Printed in Great Britain.
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| 15. |
- Tran, C. -T, et al.
(author)
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A study on transient heat transfer of the EU-ABWR external core catcher using the Phase-change Effective Convectivity Model
- 2015
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In: International Topical Meeting on Nuclear Reactor Thermal Hydraulics 2015, NURETH 2015. - : American Nuclear Society. - 9781510811843 ; , s. 6821-6834
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Conference paper (peer-reviewed)abstract
- In advanced designs of Nuclear Power Plants (NPPs), for mitigation of severe accident consequences, on the one hand, the In-Vessel Retention (IVR) concept has been implemented. On the other hand in other new NPP designs (Generation HI and III+) with large power reactors, the External Core Catcher (ECC) has been widely adopted. Assessment of ECC design robustness is largely based on analysis of heat transfer of a melt pool formed in the ECC. Transient heat transfer analysis of an ECC is challenging due to (i) uncertainty in the in-vessel accident progression and subsequent vessel failure modes; (ii) long transient, (iii) high Rayleigh number and complex flows involving phase change of the melt pool formed in an ECC. The present paper is concerned with analysis of transient melt pool heat transfer in the ECC of new Advanced Boiling Water Reactor (ABWR) designed by Toshiba Corporation (Japan). According to the ABWR severe accident management strategy, the ECC is initially dry. In order to prevent steam explosion flooding is initiated after termination of melt relocation from the vessel. The ECC full of melt is cooled from the top directly by water and from the bottom through the ECC walls. In order to assess sustainability of the ECC, heat transfer simulation of a stratified melt pool formed in the ECC is carried out. The problem addressed in this work is heat flux distribution at ECC boundaries when cooling is applied (i) from the bottom, (ii) from the top and from the bottom. To perform melt pool heat transfer simulation, we employ Phase-change Effective Convectivity Model (PECM) which was originally developed as a computationally efficient, sufficiently accurate, 2D/3D accident analysis tools for simulation of transient melt pool heat transfer in the reactor lower plenum. Thermal loads from the melt pool to ECC boundaries are determined for selected ex-vessel accident scenarios. Performance of the ECC, efficiency of severe accident management (SAM) measures and procedures are evaluated based on results of PECM simulation and severe accident analysis.
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