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1.
  • Kanai, M, et al. (author)
  • 2023
  • swepub:Mat__t
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  • Niemi, MEK, et al. (author)
  • 2021
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  • 2017
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  • Acharya, B. S., et al. (author)
  • Introducing the CTA concept
  • 2013
  • In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
  • Journal article (other academic/artistic)abstract
    • The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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  • Ruilope, LM, et al. (author)
  • Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
  • 2019
  • In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
  • Journal article (peer-reviewed)abstract
    • <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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  • Namkoong, H, et al. (author)
  • DOCK2 is involved in the host genetics and biology of severe COVID-19
  • 2022
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
  • Journal article (peer-reviewed)abstract
    • Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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  • Wang, QBS, et al. (author)
  • The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
  • 2022
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
  • Journal article (peer-reviewed)abstract
    • Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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  • Actis, M., et al. (author)
  • Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
  • 2011
  • In: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
  • Journal article (peer-reviewed)abstract
    • Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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11.
  • Bouyoucef, S E, et al. (author)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Journal article (peer-reviewed)
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12.
  • Cossarizza, A., et al. (author)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Journal article (peer-reviewed)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Abe, K., et al. (author)
  • J-PARC Neutrino Beamline Upgrade Technical Design Report
  • 2019
  • Reports (peer-reviewed)abstract
    • In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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  • Abe, K., et al. (author)
  • Neutron tagging following atmospheric neutrino events in a water Cherenkov detector
  • 2022
  • In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 17:10
  • Journal article (peer-reviewed)abstract
    • We present the development of neutron-tagging techniques in Super-Kamiokande IV using a neural network analysis. The detection efficiency of neutron capture on hydrogen is estimated to be 26%, with a mis-tag rate of 0.016 per neutrino event. The uncertainty of the tagging efficiency is estimated to be 9.0%. Measurement of the tagging efficiency with data from an Americium-Beryllium calibration agrees with this value within 10%. The tagging procedure was performed on 3,244.4 days of SK-IV atmospheric neutrino data, identifying 18,091 neutrons in 26,473 neutrino events. The fitted neutron capture lifetime was measured as 218 +/- 9 mu s.
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  • 2019
  • Journal article (peer-reviewed)
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  • Dotto, T. S., et al. (author)
  • Ocean variability beneath Thwaites Eastern Ice Shelf driven by the Pine Island Bay Gyre strength
  • 2022
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • West Antarctic ice-shelf thinning is primarily caused by ocean-driven basal melting. Here we assess ocean variability below Thwaites Eastern Ice Shelf (TEIS) and reveal the importance of local ocean circulation and sea-ice. Measurements obtained from two sub-ice-shelf moorings, spanning January 2020 to March 2021, show warming of the ice-shelf cavity and an increase in meltwater fraction of the upper sub-ice layer. Combined with ocean modelling results, our observations suggest that meltwater from Pine Island Ice Shelf feeds into the TEIS cavity, adding to horizontal heat transport there. We propose that a weakening of the Pine Island Bay gyre caused by prolonged sea-ice cover from April 2020 to March 2021 allowed meltwater-enriched waters to enter the TEIS cavity, which increased the temperature of the upper layer. Our study highlights the sensitivity of ocean circulation beneath ice shelves to local atmosphere-sea-ice-ocean forcing in neighbouring open oceans.
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  • Silvano, Alessandro, et al. (author)
  • Observing Antarctic Bottom Water in the Southern Ocean
  • 2023
  • In: Frontiers in Marine Science. - 2296-7745. ; 10
  • Research review (peer-reviewed)abstract
    • Dense, cold waters formed on Antarctic continental shelves descend along the Antarctic continental margin, where they mix with other Southern Ocean waters to form Antarctic Bottom Water (AABW). AABW then spreads into the deepest parts of all major ocean basins, isolating heat and carbon from the atmosphere for centuries. Despite AABW's key role in regulating Earth's climate on long time scales and in recording Southern Ocean conditions, AABW remains poorly observed. This lack of observational data is mostly due to two factors. First, AABW originates on the Antarctic continental shelf and slope where in situ measurements are limited and ocean observations by satellites are hampered by persistent sea ice cover and long periods of darkness in winter. Second, north of the Antarctic continental slope, AABW is found below approximately 2 km depth, where in situ observations are also scarce and satellites cannot provide direct measurements. Here, we review progress made during the past decades in observing AABW. We describe 1) long-term monitoring obtained by moorings, by ship-based surveys, and beneath ice shelves through bore holes; 2) the recent development of autonomous observing tools in coastal Antarctic and deep ocean systems; and 3) alternative approaches including data assimilation models and satellite-derived proxies. The variety of approaches is beginning to transform our understanding of AABW, including its formation processes, temporal variability, and contribution to the lower limb of the global ocean meridional overturning circulation. In particular, these observations highlight the key role played by winds, sea ice, and the Antarctic Ice Sheet in AABW-related processes. We conclude by discussing future avenues for observing and understanding AABW, impressing the need for a sustained and coordinated observing system.
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  • Andrei, N., et al. (author)
  • Boundary and defect CFT : open problems and applications
  • 2020
  • In: Journal of Physics A: Mathematical and Theoretical. - : IOP PUBLISHING LTD. - 1751-8113 .- 1751-8121. ; 53:45
  • Research review (peer-reviewed)abstract
    • A review of Boundary and defect conformal field theory: open problems and applications, following a workshop held at Chicheley Hall, Buckinghamshire, UK, 7-8 Sept. 2017. We attempt to provide a broad, bird's-eye view of the latest progress in boundary and defect conformal field theory in various sub-fields of theoretical physics, including the renormalization group, integrability, conformal bootstrap, topological field theory, supersymmetry, holographic duality, and more. We also discuss open questions and promising research directions in each of these sub-fields, and combinations thereof.
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  • Andrews, RA, et al. (author)
  • Sharing international experiences in disasters : summary and action plan
  • 2001
  • In: Prehospital and Disaster Medicine. - : Cambridge University Press. - 1049-023X .- 1945-1938. ; 16:1, s. 42-45
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: The discussions in this theme provided an opportunity to share specific experiences with disasters that occurred outside of the Asia-Pacific Rim. METHODS: Details of the methods used are provided in the preceding paper. The chairs moderated all presentations and produced a summary that was presented to an assembly of all of the delegates. Since the findings from the Theme 7 and Theme 3 groups were similar, the chairs of both groups presided over one workshop that resulted in the generation of a set of action plans that then were reported to the collective group of all delegates. RESULTS: The main points developed during the presentations and discussion included: (1) disaster response planning, (2) predetermined command and organizational structure, (3) rapid response capability, (4) mitigation, and (5) communications and alternatives. DISCUSSION: The action plans presented are in common with those presented by Theme 3, and include: (1) plan disaster responses including the different types, identification of hazards, training based on experiences, and provision of public education; (2) improving coordination and control; (3) maintaining communications assuming infrastructure breakdown; (4) maximizing mitigation through standardized evaluations, creation of a legal framework, and recognition of advocacy and public participation; and (5) providing resources and knowledge through access to existing therapies, using the media, and increasing decentralization of hospital inventories. CONCLUSIONS: Most of the problems that occurred outside the Asia-Pacific rim relative to disaster management are similar to those experienced within it. They should be addressed in common with the rest of the world.
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  • Hanna, Stephanie J., et al. (author)
  • Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans
  • 2023
  • In: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 14
  • Journal article (peer-reviewed)abstract
    • Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded T-cells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified gold-specific clones were CD8+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans.
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  • Palasingh, Chonnipa, 1992, et al. (author)
  • Modification of xylan via an oxidation–reduction reaction
  • 2022
  • In: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 292
  • Journal article (peer-reviewed)abstract
    • Xylan is a biopolymer readily available from forest resources. Various modification methods, including oxidation with sodium periodate, have been shown to facilitate the engineering applications of xylan. However, modification procedures are often optimized for semicrystalline high molecular weight polysaccharide cellulose rather than for lower molecular weight and amorphous polysaccharide xylan. This paper elucidates the procedure for the periodate oxidation of xylan into dialdehyde xylan and its further reduction into a dialcohol form and is focused on the modification work up. The oxidation–reduction reaction decreased the molecular weight of xylan while increased the dispersity more than 50%. Unlike the unmodified xylan, all the modified grades could be solubilized in water, which we see essential for facilitating the future engineering applications of xylan. The selection of quenching and purification procedures and pH-adjustment of the reduction step had no significant effect on the degree of oxidation, molecular weight and only a minor effect on the hydrodynamic radius in water. Hence, it is possible to choose the simplest oxidation-reduction route without time consuming purification steps within the sequence.
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  • Pawlaczyk, K, et al. (author)
  • Vascular endothelial growth factor in dialysate in relation to intensity of peritoneal inflammation
  • 2008
  • In: The International journal of artificial organs. - : SAGE Publications. - 0391-3988 .- 1724-6040. ; 31:6, s. 535-544
  • Journal article (peer-reviewed)abstract
    • Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution. Methods Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (μg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected. Results LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/μL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-α, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2±5.9; LPS 0.01, 38.9±11.6; LPS 0.1, 43.0±5.9; LPS 1.0, 46.6±11.3; Control, 14.5±9.8; p<0.0005 for all LPS vs. Control). Conclusions The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-α, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.
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