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1.
  • 2017
  • swepub:Mat__t
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3.
  • Ramilowski, JA, et al. (author)
  • Functional annotation of human long noncoding RNAs via molecular phenotyping
  • 2020
  • In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
  • Journal article (peer-reviewed)abstract
    • Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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4.
  • Tamagawa, T., et al. (author)
  • Correlation between musculoskeletal structure of the hand and primate locomotion: Morphometric and mechanical analysis in prehension using the cross- and triple-ratios
  • 2020
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
  • Journal article (peer-reviewed)abstract
    • Biometric ratios of the relative length of the rays in the hand have been analyzed between primate species in the light of their hand function or phylogeny. However, how relative lengths among phalanges are mechanically linked to the grasping function of primates with different locomotor behaviors remains unclear. To clarify this, we calculated cross and triple-ratios, which are related to the torque distribution, and the torque generation mode at different joint angles using the lengths of the phalanges and metacarpal bones in 52 primates belonging to 25 species. The torque exerted on the finger joint and traction force of the flexor tendons necessary for a cylindrical grip and a suspensory hand posture were calculated using the moment arm of flexor tendons measured on magnetic resonance images, and were compared among Hylobates spp., Ateles sp., and Papio hamadryas. Finally, the torques calculated from the model were validated by a mechanical study detecting the force exerted on the phalanx by pulling the digital flexor muscles during suspension in these three species. Canonical discriminant analysis of cross and triple-ratios classified primates almost in accordance with their current classification based on locomotor behavior. The traction force was markedly reduced with flexion of the MCP joint parallel to the torque in brachiating primates; this was notably lower in the terrestrial quadrupedal primates than in the arboreal primates at mild flexion. Our mechanical study supported these features in the torque and traction force generation efficiencies. Our results suggest that suspensory or terrestrial quadrupedal primates have hand structures that can exert more torque at a suspensory posture, or palmigrade and digitigrade locomotion, respectively. Furthermore, our study suggests availability of the cross and triple-ratios as one of the indicators to estimate the hand function from the skeletal structure.
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5.
  • Tasmin, S., et al. (author)
  • Short-term exposure to ambient particulate matter and emergency ambulance dispatch for acute illness in Japan
  • 2016
  • In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 566-567, s. 528-535
  • Journal article (peer-reviewed)abstract
    • Short-term exposure to air pollution may be linked to negative health outcomes that require an emergency medical response. However, few studies have been undertaken on this phenomenon to date. The aim of this study therefore was to examine the association between short-term exposure to ambient suspended particulate matter (SPM) and emergency ambulance dispatches (EADs) for acute illness in Japan. Daily EAD data, daily mean SPM and meteorological data were obtained for four prefectures in the Kanto region of Japan for the period from 2007 to 2011. The area-specific association between daily EAD for acute illness and SPM was explored using generalized linear models while controlling for ambient temperature, relative humidity, seasonality, long-term trends, day of the week and public holidays. Stratified analyses were conducted to evaluate the modifying effects of age, sex and medical conditions. Area-specific estimates were combined using meta-analyses. For the total study period the mean level of SPM was 23.7 μg/m3. In general, higher SPM was associated with a significant increase in EAD for acute illness [estimated pooled relative risk (RR): 1.008, 95% CI: 1.007 to 1.010 per 10 μg/m3 increase in SPM at lag 0-1]. The effects of SPM on EAD for acute illness were significantly greater for moderate/mild medical conditions (e.g. cases that resulted in <3 weeks hospitalization or no hospitalization) when compared to severe medical conditions (e.g. critical cases, and cases that led to >3 weeks hospitalization or which resulted in death). Using EAD data, this study has shown the adverse health effects of ambient air pollution. This highlights the importance of reducing the level of air pollution in order to maintain population health and well-being.
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  • Ad, Niv, et al. (author)
  • Surgical Ablation for Atrial Fibrillation in Cardiac Surgery. A Consensus Statement of the international Society of Minimally Invasive Cardiothoracic Surgery (ISMICS)
  • 2010
  • In: Innovations. - 1556-9845. ; 5:2, s. 74-83
  • Journal article (peer-reviewed)abstract
    • Objective: This purpose of this consensus conference was to determine whether surgical atrial fibrillation (AF) ablation during cardiac surgery improves clinical and resource outcomes compared with cardiac surgery alone in adults undergoing cardiac surgery for valve or coronary artery bypass grafting. Methods: Before the consensus conference, the consensus panel reviewed the best available evidence, whereby systematic reviews, randomized trials, and nonrandomized trials were considered in descending order of validity and importance. Evidence-based statements were created, and consensus processes were used to determine the ensuing recommendations. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of recommendation. Results: The consensus panel agreed on the following statements in patients with AF undergoing cardiac surgery concomitant surgical ablation: 1. Improves the achievement of sinus rhythm at discharge and 1 year (level A); this effect is sustained up to 5 years (level B). Does not reduce the use of antiarrhythmic drugs at 12 months after surgery (level A; 36.0% vs. 45.4%), although trials were not designed to answer this question. 2. Does not increase the requirement for permanent pacemaker implantation (4.4% vs. 4.8%; level A). 3. Does not increase the risk of perioperative mortality (level A), stroke (level A), myocardial infarction (level B), cardiac tamponade (level A), reoperative bleeding (level A), esophageal injury (level B), low cardiac output (level A), intraaortic balloon (level B), congestive heart failure (level B), ejection fraction (EF; level B), pleural effusion (level A), pneumonia (level A), renal dysfunction (level B), and mediastinitis (level A). The incidence of esophageal injury remains to be low (level B). 4. Does not reduce mortality at 1 year (level A). There is a possible reduction in mortality beyond 1 year (level B), but no difference in stroke (level A), myocardial infarction (level A), and heart failure (level B). EF is increased (+4.1% more than control; level A). 5. Has been shown to improve exercise tolerance at 1 year (level A), but no impact on quality of life at 3 months and 1 year (level A); however, the methodology used and the number of trials studying these outcomes are insufficient. 6. Increases cardiopulmonary bypass and cross-clamp times (level A), with no difference in intensive care unit and hospital length of stay (level A). Overall costs were not reported. Conclusions: Given these evidence-based statements, the consensus panel stated that, in patients with persistent and permanent AF undergoing cardiac surgery, concomitant surgical ablation is recommended to increase incidence of sinus rhythm at short- and long-term follow-up (class 1, level A); to reduce the risk of stroke and thromboembolic events (class 2a, level B); to improve EF (class 2a, level A); and to exercise tolerance (class 2a, level A) and long-term survival (class 2a, level B).
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8.
  • Cheung, Mark C. M., et al. (author)
  • Probing the Physics of the Solar Atmosphere with the Multi-slit Solar Explorer (MUSE). II. Flares and Eruptions
  • 2022
  • In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
  • Journal article (peer-reviewed)abstract
    • Current state-of-the-art spectrographs cannot resolve the fundamental spatial (subarcseconds) and temporal (less than a few tens of seconds) scales of the coronal dynamics of solar flares and eruptive phenomena. The highest-resolution coronal data to date are based on imaging, which is blind to many of the processes that drive coronal energetics and dynamics. As shown by the Interface Region Imaging Spectrograph for the low solar atmosphere, we need high-resolution spectroscopic measurements with simultaneous imaging to understand the dominant processes. In this paper: (1) we introduce the Multi-slit Solar Explorer (MUSE), a spaceborne observatory to fill this observational gap by providing high-cadence (<20 s), subarcsecond-resolution spectroscopic rasters over an active region size of the solar transition region and corona; (2) using advanced numerical models, we demonstrate the unique diagnostic capabilities of MUSE for exploring solar coronal dynamics and for constraining and discriminating models of solar flares and eruptions; (3) we discuss the key contributions MUSE would make in addressing the science objectives of the Next Generation Solar Physics Mission (NGSPM), and how MUSE, the high-throughput Extreme Ultraviolet Solar Telescope, and the Daniel K Inouye Solar Telescope (and other ground-based observatories) can operate as a distributed implementation of the NGSPM. This is a companion paper to De Pontieu et al., which focuses on investigating coronal heating with MUSE.
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  • Kahn, Suzana A., et al. (author)
  • Notch1 regulates the initiation of metastasis and self-renewal of Group 3 medulloblastoma
  • 2018
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
  • Journal article (peer-reviewed)abstract
    • Medulloblastoma is the most common malignant brain tumor of childhood. Group 3 medulloblastoma, the most aggressive molecular subtype, frequently disseminates through the leptomeningeal cerebral spinal fluid (CSF) spaces in the brain and spinal cord. The mechanism of dissemination through the CSF remains poorly understood, and the molecular pathways involved in medulloblastoma metastasis and self-renewal are largely unknown. Here we show that NOTCH1 signaling pathway regulates both the initiation of metastasis and the self-renewal of medulloblastoma. We identify a mechanism in which NOTCH1 activates BMI1 through the activation of TWIST1. NOTCH1 expression and activity are directly related to medulloblastoma metastasis and decreased survival rate of tumor-bearing mice. Finally, medulloblastoma-bearing mice intrathecally treated with anti-NRR1, a NOTCH1 blocking antibody, present lower frequency of spinal metastasis and higher survival rate. These findings identify NOTCH1 as a pivotal driver of Group 3 medulloblastoma metastasis and self-renewal, supporting the development of therapies targeting this pathway.
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11.
  • Mall, Moritz, et al. (author)
  • Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates
  • 2017
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 544:7649, s. 245-249
  • Journal article (peer-reviewed)abstract
    • Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs. In reprogramming, the same factors are often used to reprogram many different donor cell types. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors, it remains unclear how identical combinations of transcription factors can silence so many different donor programs. Distinct lineage repressors would have to be induced in different donor cell types. Here, by studying the reprogramming of mouse fibroblasts to neurons, we found that the pan neuron-specific transcription factor Myt1-like (Myt1l) exerts its pro-neuronal function by direct repression of many different somatic lineage programs except the neuronal program. The repressive function of Myt1l is mediated via recruitment of a complex containing Sin3b by binding to a previously uncharacterized N-terminal domain. In agreement with its repressive function, the genomic binding sites of Myt1l are similar in neurons and fibroblasts and are preferentially in an open chromatin configuration. The Notch signalling pathway is repressed by Myt1l through silencing of several members, including Hes1. Acute knockdown of Myt1l in the developing mouse brain mimicked a Notch gain-of-function phenotype, suggesting that Myt1l allows newborn neurons to escape Notch activation during normal development. Depletion of Myt1l in primary postmitotic neurons de-repressed non-neuronal programs and impaired neuronal gene expression and function, indicating that many somatic lineage programs are actively and persistently repressed by Myt1l to maintain neuronal identity. It is now tempting to speculate that similar 'many-but-one' lineage repressors exist for other cell fates; such repressors, in combination with lineage-specific activators, would be prime candidates for use in reprogramming additional cell types.
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12.
  • Monemar, Bo, et al. (author)
  • Optical characterization of InGaN/GaN MQW structures without in phase separation
  • 2001
  • In: Physica status solidi. B, Basic research. - 0370-1972 .- 1521-3951. ; 228:1, s. 157-160
  • Journal article (peer-reviewed)abstract
    • Photoluminescence and cathodoluminescence spectroscopies are used to investigate the properties of the band edge emission of InGaN/(In)GaN multiple quantum well (MQW) structures which do not show evidence of phase separation in high resolution electron microscopy. The data still show a clear low energy peak in the spectra. about 0.1 eV below the main exciton peak. Possible interpretations of this second peak are discussed.
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13.
  • Pozina, Galia, et al. (author)
  • InGaN/GaN multiple quantum wells grown by metalorganic vapor phase epitaxy with mass transport
  • 2000
  • In: Applied Physics Letters. - 0003-6951 .- 1077-3118. ; 77:11, s. 1638-1640
  • Journal article (peer-reviewed)abstract
    • We report on studies of In0.12Ga0.88N/GaN heterostructures with three 35-Angstrom-thick quantum wells (QWs) grown on sapphire substrates by metalorganic vapor phase epitaxy with employment of mass transport. The structure is demonstrated to show good structural and optical properties. The threading dislocation density is less than 10(7) cm(-2) for the mass-transport regions. The photoluminescence (PL) spectrum is dominated by the rather narrow near-band gap emission at 2.97 eV with a linewidth of 40 meV. This emission has a typical PL decay time about 5 ns at 2 K within the PL contour. With increasing excitation intensity, an additional transition with longer decay time (about 200 ns) is enhanced at energy about 2.85 eV. The position of this line depends strongly on the excitation power. We explain the data in terms of a model, where the PL is a result of contribution from at least two nonequivalent QWs, which could be realized due to a potential gradient across the layers. (C) 2000 American Institute of Physics. [S0003- 6951(00)04337-0].
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14.
  • Pozina, Galia, et al. (author)
  • Luminescence of InGaN/GaN multiple quantum wells grown by mass-transport
  • 2001
  • In: Materials Science Forum, Vols. 353-356. ; , s. 791-794
  • Conference paper (peer-reviewed)abstract
    • We present an optical study of an In0.12Ga0.88N/GaN structure containing three quantum wells (QW) grown by metalorganic vapor phase epitaxy using mass transport. The mass-transport regions demonstrate a high structural quality with a threading dislocation density less than 10(7) cm(-2). The photoluminescence (PL) spectrum is dominated by a 40 meV - narrow line centered at 2.97 eV at 2 K. This emission has a typical PL decay time about 5 ns at 2 K within the PL contour. An additional line with longer decay time (about 200 ns) is observed at an energy of similar to2.85 eV. The position of this line shifts towards higher energies with increasing excitation power. The data are explained in terms of a model, where the PL originates from two nonequivalent quantum wells, which could be realized due to a potential gradient across the layers.
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15.
  • Pozina, Galia, et al. (author)
  • Photoluminescence of InGaN/GaN multiple quantum wells grown by mass transport
  • 2001
  • In: Journal of Crystal Growth. - 0022-0248 .- 1873-5002. ; 230:3-4, s. 473-476
  • Journal article (peer-reviewed)abstract
    • We report on studies of an In0.12Ga0.88N/GaN structure with three 35 Å thick quantum wells (QWs) grown by metalorganic vapor phase epitaxy with employment of mass transport. The mass-transport regions demonstrate a threading dislocation density less than 107 cm-2. The photoluminescence (PL) spectrum is dominated by a 40 meV-narrow line centered at 2.97 eV at 2 K. This emission has a typical PL decay time of about 5 ns at 2 K within the PL contour. An additional line with longer decay time (about 200 ns) is observed at an energy about 2.85 eV. The position of this line shifts towards higher energies with increasing excitation power. The data are consistent with a model, where the PL originates from at least two nonequivalent QWs, which could be realized due to a potential gradient across the layers. © 2001 Elsevier Science B.V. All rights reserved.
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