443 research outputs found
Brain MRI and biological diagnosis in five Tunisians MLD patients
Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is characterized by an accumulation of sulfatides in the central and peripheral nervous system. It is due to the enzyme deficiency of the sulfatide sulfatase i.e. arylsulfatase A (ASA). we studied 5/200 cases of MLD and clearly distinguished three clinical forms. One of them presented the juvenile form; two presented the late infantile form; and two other presented the adult form. The Magnetic Resonance Imaging (MRI) of these patients showed a diffuse, bilateral and symmetrical demyelination. The biochemical diagnosis of MLD patients evidencing the low activity of ASA and sulfatide accumulation
Population Carrier Rates of Pathogenic ARSA Gene Mutations: Is Metachromatic Leukodystrophy Underdiagnosed?
BACKGROUND: Metachromatic leukodystrophy (MLD) is a severe neurometabolic disease caused mainly by deficiency of arylsulfatase A encoded by the ARSA gene. Based on epidemiological surveys the incidence of MLD per 100,000 live births varied from 0.6 to 2.5. Our purpose was to estimate the birth prevalence of MLD in Poland by determining population frequency of the common pathogenic ARSA gene mutations and to compare this estimate with epidemiological data. METHODOLOGY: We studied two independently ascertained cohorts from the Polish background population (N∼3000 each) and determined carrier rates of common ARSA gene mutations: c.459+1G>A, p.P426L, p.I179S (cohort 1) and c.459+1G>A, p.I179S (cohort 2). PRINCIPAL FINDINGS: Taking into account ARSA gene mutation distribution among 60 Polish patients, the expected MLD birth prevalence in the general population (assuming no selection against homozygous fetuses) was estimated as 4.0/100,000 and 4.1/100,000, respectively for the 1(st) and the 2(nd) cohort with a pooled estimate of 4.1/100,000 (CI: 1.8-9.4) which was higher than the estimate of 0.38 per 100,000 live births based on diagnosed cases. The p.I179S mutation was relatively more prevalent among controls than patients (OR = 3.6, P = 0.0082, for a comparison of p.I179S frequency relative to c.459+1G>A between controls vs. patients). CONCLUSIONS/SIGNIFICANCE: The observed discrepancy between the measured incidence of metachromatic leukodystrophy and the predicted carriage rates suggests that MLD is substantially underdiagnosed in the Polish population. The underdiagnosis rate may be particularly high among patients with p.I179S mutation whose disease is characterized mainly by psychotic symptoms
ER stress protein AGR2 precedes and is involved in the regulation of pancreatic cancer initiation
The work was supported by a grant A12008 from CR-UK (L. Dumartin, N.R. Lemoine and T. Crnogorac-Jurcevic)
Imaging and imagination: understanding the endo-lysosomal system
Lysosomes are specialized compartments for the degradation of endocytosed and intracellular material and essential regulators of cellular homeostasis. The importance of lysosomes is illustrated by the rapidly growing number of human disorders related to a defect in lysosomal functioning. Here, we review current insights in the mechanisms of lysosome biogenesis and protein sorting within the endo-lysosomal system. We present increasing evidence for the existence of parallel pathways for the delivery of newly synthesized lysosomal proteins directly from the trans-Golgi network (TGN) to the endo-lysosomal system. These pathways are either dependent or independent of mannose 6-phosphate receptors and likely involve multiple exits for lysosomal proteins from the TGN. In addition, we discuss the different endosomal intermediates and subdomains that are involved in sorting of endocytosed cargo. Throughout our review, we highlight some examples in the literature showing how imaging, especially electron microscopy, has made major contributions to our understanding of the endo-lysosomal system today
All-sky search in early O3 LIGO data for continuous gravitational-wave signals from unknown neutron stars in binary systems
Rapidly spinning neutron stars are promising sources of continuous gravitational waves. Detecting such a signal would allow probing of the physical properties of matter under extreme conditions. A significant fraction of the known pulsar population belongs to binary systems. Searching for unknown neutron stars in binary systems requires specialized algorithms to address unknown orbital frequency modulations. We present a search for continuous gravitational waves emitted by neutron stars in binary systems in early data from the third observing run of the Advanced LIGO and Advanced Virgo detectors using the semicoherent, GPU-accelerated, binaryskyhough pipeline. The search analyzes the most sensitive frequency band of the LIGO detectors, 50-300 Hz. Binary orbital parameters are split into four regions, comprising orbital periods of three to 45 days and projected semimajor axes of two to 40 light seconds. No detections are reported. We estimate the sensitivity of the search using simulated continuous wave signals, achieving the most sensitive results to date across the analyzed parameter space
Search of the early O3 LIGO data for continuous gravitational waves from the Cassiopeia A and Vela Jr. supernova remnants
partially_open1412sìWe present directed searches for continuous gravitational waves from the neutron stars in the Cassiopeia A (Cas A) and Vela Jr. supernova remnants. We carry out the searches in the LIGO detector data from the first six months of the third Advanced LIGO and Virgo observing run using the weave semicoherent method, which sums matched-filter detection-statistic values over many time segments spanning the observation period. No gravitational wave signal is detected in the search band of 20–976 Hz for assumed source ages greater than 300 years for Cas A and greater than 700 years for Vela Jr. Estimates from simulated continuous wave signals indicate we achieve the most sensitive results to date across the explored parameter space volume, probing to strain magnitudes as low as
∼6.3×10^−26 for Cas A and ∼5.6×10^−26 for Vela Jr. at frequencies near 166 Hz at 95% efficiency.openAbbott, R.; Abbott, T. D.; Acernese, F.; Ackley, K.; Adams, C.; Adhikari, N.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agarwal, D.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Aiello, L.; Ain, A.; Ajith, P.; Albanesi, S.; Allocca, A.; Altin, P. A.; Amato, A.; Anand, C.; Anand, S.; Ananyeva, A.; Anderson, S. B.; Anderson, W. G.; Andrade, T.; Andres, N.; Andrić, T.; Angelova, S. V.; Ansoldi, S.; Antelis, J. M.; Antier, S.; Appert, S.; Arai, K.; Araya, M. C.; Areeda, J. S.; Arène, M.; Arnaud, N.; Aronson, S. M.; Arun, K. G.; Asali, Y.; Ashton, G.; Assiduo, M.; Aston, S. M.; Astone, P.; Aubin, F.; Austin, C.; Babak, S.; Badaracco, F.; Bader, M. K. M.; Badger, C.; Bae, S.; Baer, A. M.; Bagnasco, S.; Bai, Y.; Baird, J.; Ball, M.; Ballardin, G.; Ballmer, S. W.; Balsamo, A.; Baltus, G.; Banagiri, S.; Bankar, D.; Barayoga, J. C.; Barbieri, C.; Barish, B. C.; Barker, D.; Barneo, P.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Bawaj, M.; Bayley, J. C.; Baylor, A. C.; Bazzan, M.; Bécsy, B.; Bedakihale, V. M.; Bejger, M.; Belahcene, I.; Benedetto, V.; Beniwal, D.; Bennett, T. F.; Bentley, J. D.; BenYaala, M.; Bergamin, F.; Berger, B. K.; Bernuzzi, S.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Beveridge, D.; Bhandare, R.; Bhardwaj, U.; Bhattacharjee, D.; Bhaumik, S.; Bilenko, I. A.; Billingsley, G.; Bini, S.; Birney, R.; Birnholtz, O.; Biscans, S.; Bischi, M.; Biscoveanu, S.; Bisht, A.; Biswas, B.; Bitossi, M.; Bizouard, M.-A.; Blackburn, J. K.; Blair, C. D.; Blair, D. G.; Blair, R. M.; Bobba, F.; Bode, N.; Boer, M.; Bogaert, G.; Boldrini, M.; Bonavena, L. D.; Bondu, F.; Bonilla, E.; Bonnand, R.; Booker, P.; Boom, B. A.; Bork, R.; Boschi, V.; Bose, N.; Bose, S.; Bossilkov, V.; Boudart, V.; Bouffanais, Y.; Bozzi, A.; Bradaschia, C.; Brady, P. 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A.; Dietrich, T.; Di Fiore, L.; Di Fronzo, C.; Di Giorgio, C.; Di Giovanni, F.; Di Giovanni, M.; Di Girolamo, T.; Di Lieto, A.; Ding, B.; Di Pace, S.; Di Palma, I.; Di Renzo, F.; Divakarla, A. K.; Dmitriev, A.; Doctor, Z.; D’Onofrio, L.; Donovan, F.; Dooley, K. L.; Doravari, S.; Dorrington, I.; Drago, M.; Driggers, J. C.; Drori, Y.; Ducoin, J.-G.; Dupej, P.; Durante, O.; D’Urso, D.; Duverne, P.-A.; Dwyer, S. E.; Eassa, C.; Easter, P. J.; Ebersold, M.; Eckhardt, T.; Eddolls, G.; Edelman, B.; Edo, T. B.; Edy, O.; Effler, A.; Eichholz, J.; Eikenberry, S. S.; Eisenmann, M.; Eisenstein, R. A.; Ejlli, A.; Engelby, E.; Errico, L.; Essick, R. C.; Estellés, H.; Estevez, D.; Etienne, Z.; Etzel, T.; Evans, M.; Evans, T. M.; Ewing, B. E.; Fafone, V.; Fair, H.; Fairhurst, S.; Farah, A. M.; Farinon, S.; Farr, B.; Farr, W. M.; Farrow, N. W.; Fauchon-Jones, E. J.; Favaro, G.; Favata, M.; Fays, M.; Fazio, M.; Feicht, J.; Fejer, M. M.; Fenyvesi, E.; Ferguson, D. L.; Fernandez-Galiana, A.; Ferrante, I.; Ferreira, T. A.; Fidecaro, F.; Figura, P.; Fiori, I.; Fishbach, M.; Fisher, R. P.; Fittipaldi, R.; Fiumara, V.; Flaminio, R.; Floden, E.; Fong, H.; Font, J. A.; Fornal, B.; Forsyth, P. W. F.; Franke, A.; Frasca, S.; Frasconi, F.; Frederick, C.; Freed, J. P.; Frei, Z.; Freise, A.; Frey, R.; Fritschel, P.; Frolov, V. V.; Fronzé, G. G.; Fulda, P.; Fyffe, M.; Gabbard, H. A.; Gadre, B. U.; Gair, J. R.; Gais, J.; Galaudage, S.; Gamba, R.; Ganapathy, D.; Ganguly, A.; Gaonkar, S. G.; Garaventa, B.; García-Núñez, C.; García-Quirós, C.; Garufi, F.; Gateley, B.; Gaudio, S.; Gayathri, V.; Gemme, G.; Gennai, A.; George, J.; Gerberding, O.; Gergely, L.; Gewecke, P.; Ghonge, S.; Ghosh, Abhirup; Ghosh, Archisman; Ghosh, Shaon; Ghosh, Shrobana; Giacomazzo, B.; Giacoppo, L.; Giaime, J. A.; Giardina, K. D.; Gibson, D. R.; Gier, C.; Giesler, M.; Giri, P.; Gissi, F.; Glanzer, J.; Gleckl, A. E.; Godwin, P.; Goetz, E.; Goetz, R.; Gohlke, N.; Goncharov, B.; González, G.; Gopakumar, A.; Gosselin, M.; Gouaty, R.; Gould, D. W.; Grace, B.; Grado, A.; Granata, M.; Granata, V.; Grant, A.; Gras, S.; Grassia, P.; Gray, C.; Gray, R.; Greco, G.; Green, A. C.; Green, R.; Gretarsson, A. M.; Gretarsson, E. M.; Griffith, D.; Griffiths, W.; Griggs, H. L.; Grignani, G.; Grimaldi, A.; Grimm, S. J.; Grote, H.; Grunewald, S.; Gruning, P.; Guerra, D.; Guidi, Gianluca; Guimaraes, A. R.; Guixé, G.; Gulati, H. K.; Guo, H.-K.; Guo, Y.; Gupta, Anchal; Gupta, Anuradha; Gupta, P.; Gustafson, E. K.; Gustafson, R.; Guzman, F.; Haegel, L.; Halim, O.; Hall, E. D.; Hamilton, E. Z.; Hammond, G.; Haney, M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hannuksela, O.; Hansen, H.; Hansen, T. J.; Hanson, J.; Harder, T.; Hardwick, T.; Haris, K.; Harms, J.; Harry, G. M.; Harry, I. W.; Hartwig, D.; Haskell, B.; Hasskew, R. K.; Haster, C.-J.; Haughian, K.; Hayes, F. J.; Healy, J.; Heidmann, A.; Heidt, A.; Heintze, M. C.; Heinze, J.; Heinzel, J.; Heitmann, H.; Hellman, F.; Hello, P.; Helmling-Cornell, A. F.; Hemming, G.; Hendry, M.; Heng, I. S.; Hennes, E.; Hennig, J.; Hennig, M. H.; Hernandez, A. G.; Vivanco, F. Hernandez; Heurs, M.; Hild, S.; Hill, P.; Hines, A. S.; Hochheim, S.; Hofman, D.; Hohmann, J. N.; Holcomb, D. G.; Holland, N. A.; Hollows, I. J.; Holmes, Z. J.; Holt, K.; Holz, D. E.; Hopkins, P.; Hough, J.; Hourihane, S.; Howell, E. J.; Hoy, C. G.; Hoyland, D.; Hreibi, A.; Hsu, Y.; Huang, Y.; Hübner, M. T.; Huddart, A. D.; Hughey, B.; Hui, V.; Husa, S.; Huttner, S. H.; Huxford, R.; Huynh-Dinh, T.; Idzkowski, B.; Iess, A.; Ingram, C.; Isi, M.; Isleif, K.; Iyer, B. R.; JaberianHamedan, V.; Jacqmin, T.; Jadhav, S. J.; Jadhav, S. P.; James, A. L.; Jan, A. Z.; Jani, K.; Janquart, J.; Janssens, K.; Janthalur, N. N.; Jaranowski, P.; Jariwala, D.; Jaume, R.; Jenkins, A. C.; Jenner, K.; Jeunon, M.; Jia, W.; Johns, G. R.; Jones, A. W.; Jones, D. I.; Jones, J. D.; Jones, P.; Jones, R.; Jonker, R. J. G.; Ju, L.; Junker, J.; Juste, V.; Kalaghatgi, C. V.; Kalogera, V.; Kamai, B.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kao, Y.; Kapadia, S. J.; Kapasi, D. P.; Karat, S.; Karathanasis, C.; Karki, S.; Kashyap, R.; Kasprzack, M.; Kastaun, W.; Katsanevas, S.; Katsavounidis, E.; Katzman, W.; Kaur, T.; Kawabe, K.; Kéfélian, F.; Keitel, D.; Key, J. S.; Khadka, S.; Khalili, F. Y.; Khan, S.; Khazanov, E. A.; Khetan, N.; Khursheed, M.; Kijbunchoo, N.; Kim, C.; Kim, J. C.; Kim, K.; Kim, W. S.; Kim, Y.-M.; Kimball, C.; Kinley-Hanlon, M.; Kirchhoff, R.; Kissel, J. S.; Kleybolte, L.; Klimenko, S.; Knee, A. M.; Knowles, T. D.; Knyazev, E.; Koch, P.; Koekoek, G.; Koley, S.; Kolitsidou, P.; Kolstein, M.; Komori, K.; Kondrashov, V.; Kontos, A.; Koper, N.; Korobko, M.; Kovalam, M.; Kozak, D. B.; Kringel, V.; Krishnendu, N. V.; Królak, A.; Kuehn, G.; Kuei, F.; Kuijer, P.; Kumar, A.; Kumar, P.; Kumar, Rahul; Kumar, Rakesh; Kuns, K.; Kuwahara, S.; Lagabbe, P.; Laghi, D.; Lalande, E.; Lam, T. L.; Lamberts, A.; Landry, M.; Lane, B. B.; Lang, R. N.; Lange, J.; Lantz, B.; La Rosa, I.; Lartaux-Vollard, A.; Lasky, P. D.; Laxen, M.; Lazzarini, A.; Lazzaro, C.; Leaci, P.; Leavey, S.; Lecoeuche, Y. K.; Lee, H. M.; Lee, H. W.; Lee, J.; Lee, K.; Lehmann, J.; Lemaître, A.; Leroy, N.; Letendre, N.; Levesque, C.; Levin, Y.; Leviton, J. N.; Leyde, K.; Li, A. K. Y.; Li, B.; Li, J.; Li, T. G. F.; Li, X.; Linde, F.; Linker, S. D.; Linley, J. N.; Littenberg, T. B.; Liu, J.; Liu, K.; Liu, X.; Llamas, F.; Llorens-Monteagudo, M.; Lo, R. K. L.; Lockwood, A.; London, L. T.; Longo, A.; Lopez, D.; Portilla, M. Lopez; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lott, T. P.; Lough, J. D.; Lousto, C. O.; Lovelace, G.; Lucaccioni, J. F.; Lück, H.; Lumaca, D.; Lundgren, A. P.; Lynam, J. E.; Macas, R.; MacInnis, M.; Macleod, D. M.; MacMillan, I. A. O.; Macquet, A.; Hernandez, I. Magaña; Magazzù, C.; Magee, R. M.; Maggiore, R.; Magnozzi, M.; Mahesh, S.; Majorana, E.; Makarem, C.; Maksimovic, I.; Maliakal, S.; Malik, A.; Man, N.; Mandic, V.; Mangano, V.; Mango, J. L.; Mansell, G. L.; Manske, M.; Mantovani, M.; Mapelli, M.; Marchesoni, F.; Marion, F.; Mark, Z.; Márka, S.; Márka, Z.; Markakis, C.; Markosyan, A. S.; Markowitz, A.; Maros, E.; Marquina, A.; Marsat, S.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinez, M.; Martinez, V. A.; Martinez, V.; Martinovic, K.; Martynov, D. V.; Marx, E. J.; Masalehdan, H.; Mason, K.; Massera, E.; Masserot, A.; Massinger, T. J.; Masso-Reid, M.; Mastrogiovanni, S.; Matas, A.; Mateu-Lucena, M.; Matichard, F.; Matiushechkina, M.; Mavalvala, N.; McCann, J. J.; McCarthy, R.; McClelland, D. E.; McClincy, P. K.; McCormick, S.; McCuller, L.; McGhee, G. I.; McGuire, S. C.; McIsaac, C.; McIver, J.; McRae, T.; McWilliams, S. T.; Meacher, D.; Mehmet, M.; Mehta, A. K.; Meijer, Q.; Melatos, A.; Melchor, D. A.; Mendell, G.; Menendez-Vazquez, A.; Menoni, C. S.; Mercer, R. A.; Mereni, L.; Merfeld, K.; Merilh, E. L.; Merritt, J. D.; Merzougui, M.; Meshkov, S.; Messenger, C.; Messick, C.; Meyers, P. M.; Meylahn, F.; Mhaske, A.; Miani, A.; Miao, H.; Michaloliakos, I.; Michel, C.; Middleton, H.; Milano, L.; Miller, A.; Miller, A. L.; Miller, B.; Millhouse, M.; Mills, J. C.; Milotti, E.; Minazzoli, O.; Minenkov, Y.; Mir, Ll. M.; Miravet-Tenés, M.; Mishra, C.; Mishra, T.; Mistry, T.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Mo, Geoffrey; Moguel, E.; Mogushi, K.; Mohapatra, S. R. P.; Mohite, S. R.; Molina, I.; Molina-Ruiz, M.; Mondin, M.; Montani, M.; Moore, C. J.; Moraru, D.; Morawski, F.; More, A.; Moreno, C.; Moreno, G.; Morisaki, S.; Mours, B.; Mow-Lowry, C. M.; Mozzon, S.; Muciaccia, F.; Mukherjee, Arunava; Mukherjee, D.; Mukherjee, Soma; Mukherjee, Subroto; Mukherjee, Suvodip; Mukund, N.; Mullavey, A.; Munch, J.; Muñiz, E. A.; Murray, P. G.; Musenich, R.; Muusse, S.; Nadji, S. 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Search for subsolar-mass black hole binaries in the second part of Advanced LIGO’s and Advanced Virgo’s third observing run
We describe a search for gravitational waves from compact binaries with at least one component with mass 0.2–1.0 M and mass
ratio q ≥ 0.1 in Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO) and Advanced Virgo data collected
between 2019 November 1, 15:00 UTC and 2020 March 27, 17:00 UTC. No signals were detected. The most significant candidate
has a false alarm rate of 0.2 yr−1. We estimate the sensitivity of our search over the entirety of Advanced LIGO’s and Advanced
Virgo’s third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one
subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black
holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the
merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the
PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs fPBH 0.6 (at 90 per cent confidence)
in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions, we are unable to rule out fPBH = 1.
For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes,
we find an upper bound fDBH < 10−5 on the fraction of atomic dark matter collapsed into black holes
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