| 1. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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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| 2. |
- Actis, M., et al.
(författare)
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Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
- 2011
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Aldskogius, Håkan, 1943-, et al.
(författare)
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Regulation of boundary cap neural crest stem cell differentiation after transplantation
- 2009
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 27:7, s. 1592-1603
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Tidskriftsartikel (refereegranskat)abstract
- Success of cell replacement therapies for neurological disorders will dependlargely on the optimization of strategies to enhance viability and control thedevelopmental fate of stem cells after transplantation. Once transplanted,stem/progenitor cells display a tendency to maintain an undifferentiatedphenotype or differentiate into inappropriate cell types. Gain and loss offunction experiments have revealed key transcription factors which drivedifferentiation of immature stem/progenitor cells toward more mature stages andeventually to full differentiation. An attractive course of action to promotesurvival and direct the differentiation of transplanted stem cells to a specific cell type would therefore be to force expression of regulatory differentiationmolecules in already transplanted stem cells, using inducible gene expressionsystems which can be controlled from the outside. Here, we explore thishypothesis by employing a tetracycline gene regulating system (Tet-On) to drivethe differentiation of boundary cap neural crest stem cells (bNCSCs) toward asensory neuron fate after transplantation. We induced the expression of the keytranscription factor Runx1 in Sox10-expressing bNCSCs. Forced expression of Runx1strongly increased transplant survival in the enriched neurotrophic environmentof the dorsal root ganglion cavity, and was sufficient to guide differentiationof bNCSCs toward a nonpeptidergic nociceptive sensory neuron phenotype both invitro and in vivo after transplantation. These findings suggest that exogenousactivation of transcription factors expression after transplantation instem/progenitor cell grafts can be a constructive approach to control theirsurvival as well as their differentiation to the desired type of cell and thatthe Tet-system is a useful tool to achieve this.
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| 4. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 5. |
- Breslin, Thomas, et al.
(författare)
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A Novel Anthropomorphic Phantom Composed of Tissue-Equivalent Materials for Use in Experimental Radiotherapy : Design, Dosimetry and Biological Pilot Study
- 2023
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Ingår i: Biomimetics. - 2313-7673. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- The production of anthropomorphic phantoms generated from tissue-equivalent materials is challenging but offers an excellent copy of the typical environment encountered in typical patients. High-quality dosimetry measurements and the correlation of the measured dose with the biological effects elicited by it are a prerequisite in preparation of clinical trials with novel radiotherapy approaches. We designed and produced a partial upper arm phantom from tissue-equivalent materials for use in experimental high-dose-rate radiotherapy. The phantom was compared to original patient data using density values and Hounsfield units obtained from CT scans. Dose simulations were conducted for broad-beam irradiation and microbeam radiotherapy (MRT) and compared to values measured in a synchrotron radiation experiment. Finally, we validated the phantom in a pilot experiment with human primary melanoma cells.
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| 6. |
- Füßling, Matthias, et al.
(författare)
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Status of the array control and data acquisition system for the Cherenkov Telescope Array
- 2016
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Ingår i: Software and Cyberinfrastructure for Astronomy IV. - : SPIE - International Society for Optical Engineering. - 9781510602052
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Konferensbidrag (refereegranskat)abstract
- The Cherenkov Telescope Array (CTA) will be the next-generation ground-based observatory using the atmospheric Cherenkov technique. The CTA instrument will allow researchers to explore the gamma-ray sky in the energy range from 20 GeV to 300 TeV. CTA will comprise two arrays of telescopes, one with about 100 telescopes in the Southern hemisphere and another smaller array of telescopes in the North. CTA poses novel challenges in the field of ground-based Cherenkov astronomy, due to the demands of operating an observatory composed of a large and distributed system with the needed robustness and reliability that characterize an observatory. The array control and data acquisition system of CTA (ACTL) provides the means to control, readout and monitor the telescopes and equipment of the CTA arrays. The ACTL system must be flexible and reliable enough to permit the simultaneous and automatic control of multiple sub-arrays of telescopes with a minimum effort of the personnel on-site. In addition, the system must be able to react to external factors such as changing weather conditions and loss of telescopes and, on short timescales, to incoming scientific alerts from time-critical transient phenomena. The ACTL system provides the means to time-stamp, readout, filter and store the scientific data at aggregated rates of a few GB/s. Monitoring information from tens of thousands of hardware elements need to be channeled to high performance database systems and will be used to identify potential problems in the instrumentation. This contribution provides an overview of the ACTL system and a status report of the ACTL project within CTA.
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| 7. |
- Hindy, George, et al.
(författare)
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Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis
- 2022
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 132:24, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin–9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
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| 8. |
- Kanaykina, Nadya, et al.
(författare)
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In vitro and in vivo effects on neural crest stem celldifferentiation by conditional activation of Runx1 short isoform and its effecton neuropathic pain behavior
- 2010
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 115:1, s. 56-64
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Runx1, a Runt domain transcription factor, controls thedifferentiation of nociceptors that express the neurotrophin receptor Ret,regulates the expression of many ion channels and receptors, and controls thelamina-specific innervation pattern of nociceptive afferents in the spinal cord. Moreover, mice lacking Runx1 exhibit specific defects in thermal and neuropathic pain. We investigated whether conditional activation of Runx1 short isoform(Runx1a), which lacks a transcription activation domain, influencesdifferentiation of neural crest stem cells (NCSCs) in vitro and in vivo duringdevelopment and whether postnatal Runx1a activation affects the sensitivity toneuropathic pain. METHODS: We activated ectopic expression of Runx1a in cultured NCSCs using the Tet-ON gene regulatory system during the formation ofneurospheres and analyzed the proportion of neurons and glial cells originatingfrom NCSCs. In in vivo experiments we applied doxycycline (DOX) to pregnant mice (days 8-11), i.e. when NCSCs actively migrate, and examined the phenotype ofoffsprings. We also examined whether DOX-induced activation of Runx1a in adultmice affects their sensitivity to mechanical stimulation following a constrictioninjury of the sciatic nerve. RESULTS: Ectopic Runx1a expression in cultured NCSCsresulted in predominantly glial differentiation. Offsprings in which Runx1a hadbeen activated showed retarded growth and displayed megacolon, pigment defects,and dystrophic dorsal root ganglia. In the neuropathic pain model, the threshold for mechanical sensitivity was markedly increased following activation of Runx1a.CONCLUSION: These data suggest that Runx1a has a specific role in NCSCdevelopment and that modulation of Runx1a activity may reduce mechanicalhypersensitivity associated with neuropathic pain.
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| 9. |
- Röhrig, Ursula, et al.
(författare)
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Coactosin interferes with the capping of actin filaments
- 1995
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 374:2, s. 284-286
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Tidskriftsartikel (refereegranskat)abstract
- Coactosin, a 16 kDa protein associated with the actin cytoskeleton from Dictyostelium discoideum, was purified by an improved method, in which other components of the cytoskeleton were removed. The highly purified coactosin had no effect on the time course of actin polymerization, but when added to actin in presence of capping proteins, coactosin counteracted the capping activity of these proteins. The capping proteins cap32/34 and severin domain 1 retarded actin polymerization, on addition of coactosin to samples containing one of these capping proteins the time course of actin polymerization became close to controls without capping proteins.
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| 10. |
- Warnke, Clemens, et al.
(författare)
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Cerebrospinal Fluid JC Virus Antibody Index for Diagnosis of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy
- 2014
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 76:6, s. 792-801
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AI(JCV)) in the diagnosis of natalizumab-associated PML.Methods: AI(JCV) was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AI(JCV) was calculated as published.Results:Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AI(JCV) > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AI(JCV) > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AI(JCV) > 1.5.Interpretation: Determination of the AI(JCV) could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML. Ann Neurol 2014;76:792-801
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| 11. |
- Wegner, Carolyn, et al.
(författare)
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Variability in transport of terrigenous material on the shelves and the deep Arctic Ocean during the Holocene
- 2015
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Ingår i: Polar Research. - : Norwegian Polar Institute. - 0800-0395 .- 1751-8369. ; 34
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Tidskriftsartikel (refereegranskat)abstract
- Arctic coastal zones serve as a sensitive filter for terrigenous matter input onto the shelves via river discharge and coastal erosion. This material is further distributed across the Arctic by ocean currents and sea ice. The coastal regions are particularly vulnerable to changes related to recent climate change. We compiled a pan-Arctic review that looks into the changing Holocene sources, transport processes and sinks of terrigenous sediment in the Arctic Ocean. Existing palaeoceanographic studies demonstrate how climate warming and the disappearance of ice sheets during the early Holocene initiated eustatic sea-level rise that greatly modified the physiography of the Arctic Ocean. Sedimentation rates over the shelves and slopes were much greater during periods of rapid sea-level rise in the early and middle Holocene, as a result of the relative distance to the terrestrial sediment sources. However, estimates of suspended sediment delivery through major Arctic rivers do not indicate enhanced delivery during this time, which suggests enhanced rates of coastal erosion. The increased supply of terrigenous material to the outer shelves and deep Arctic Ocean in the early and middle Holocene might serve as analogous to forecast changes in the future Arctic.
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| 12. |
- Werner, Kirstin, et al.
(författare)
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Arctic in Rapid Transition : Priorities for the future of marine and coastal research in the Arctic
- 2016
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Ingår i: Polar Science. - : Elsevier BV. - 1873-9652 .- 1876-4428. ; 10:3, s. 364-373
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Tidskriftsartikel (refereegranskat)abstract
- Understanding and responding to the rapidly occurring environmental changes in the Arctic over the past few decades require new approaches in science. This includes improved collaborations within the scientific community but also enhanced dialogue between scientists and societal stakeholders, especially with Arctic communities. As a contribution to the Third International Conference on Arctic Research Planning (ICARPIII), the Arctic in Rapid Transition (ART) network held an international workshop in France, in October 2014, in order to discuss high-priority requirements for future Arctic marine and coastal research from an early-career scientists (ECS) perspective. The discussion encompassed a variety of research fields, including topics of oceanographic conditions, sea-ice monitoring, marine biodiversity, land-ocean interactions, and geological reconstructions, as well as law and governance issues. Participants of the workshop strongly agreed on the need to enhance interdisciplinarity in order to collect comprehensive knowledge about the modern and past Arctic Ocean's geo-ecological dynamics. Such knowledge enables improved predictions of Arctic developments and provides the basis for elaborate decision-making on future actions under plausible environmental and climate scenarios in the high northern latitudes. Priority research sheets resulting from the workshop's discussions were distributed during the ICARPIII meetings in April 2015 in Japan, and are publicly available online. (C) 2016 Elsevier B.V. and NIPR. All rights reserved.
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