Revisiting the implications of Liouville's theorem to the anisotropy of cosmic rays

We present a solution to Liouville's equation for an ensemble of charged particles propagating in magnetic fields. The solution is presented using an expansion in spherical harmonics of the phase space density, allowing a direct interpretation of the distribution of arrival directions of cosmic rays. The results are found for chosen conditions of variability and source distributions. We show there are two conditions for an initially isotropic flux of particles to remain isotropic while traveling through a magnetic field: isotropy and homogeneity of the sources. The formalism is used to analyze the data measured by the Pierre Auger Observatory, contributing to the understanding of the dependence of the dipole amplitude with energy and predicting the energy in which the quadrupole signal should be measured

Observation of a large-scale anisotropy in the arrival directions of cosmic rays above 8 × 10 18 eV

Cosmic rays are atomic nuclei arriving from outer space that reach the highest energies observed in nature. Clues to their origin come from studying the distribution of their arrival directions. Using 3 × 10 4 cosmic rays with energies above 8 × 10 18 electron volts, recorded with the Pierre Auger Observatory from a total exposure of 76,800 km2 sr year, we determined the existence of anisotropy in arrival directions. The anisotropy, detected at more than a 5.2σ level of significance, can be described by a dipole with an amplitude of 6.5 +1.3 -0.9 percent toward right ascension αd = 100 ± 10 degrees and declination δd = -24 +12 -13 degrees. That direction indicates an extragalactic origin for these ultrahighenergy particles.La nómina completa de autores puede verse en el archivo asociado a este ítem.Facultad de Ciencias Exacta

Observation of a large-scale anisotropy in the arrival directions of cosmic rays above 8 × 10 18 eV

Cosmic rays are atomic nuclei arriving from outer space that reach the highest energies observed in nature. Clues to their origin come from studying the distribution of their arrival directions. Using 3 × 10 4 cosmic rays with energies above 8 × 10 18 electron volts, recorded with the Pierre Auger Observatory from a total exposure of 76,800 km2 sr year, we determined the existence of anisotropy in arrival directions. The anisotropy, detected at more than a 5.2σ level of significance, can be described by a dipole with an amplitude of 6.5 +1.3 -0.9 percent toward right ascension αd = 100 ± 10 degrees and declination δd = -24 +12 -13 degrees. That direction indicates an extragalactic origin for these ultrahighenergy particles.La nómina completa de autores puede verse en el archivo asociado a este ítem.Facultad de Ciencias Exacta

EUSO-SPB1 mission and science

The Extreme Universe Space Observatory on a Super Pressure Balloon 1 (EUSO-SPB1) was launched in 2017 April from Wanaka, New Zealand. The plan of this mission of opportunity on a NASA super pressure balloon test flight was to circle the southern hemisphere. The primary scientific goal was to make the first observations of ultra-high-energy cosmic-ray extensive air showers (EASs) by looking down on the atmosphere with an ultraviolet (UV) fluorescence telescope from suborbital altitude (33 km). After 12 days and 4 h aloft, the flight was terminated prematurely in the Pacific Ocean. Before the flight, the instrument was tested extensively in the West Desert of Utah, USA, with UV point sources and lasers. The test results indicated that the instrument had sensitivity to EASs of ⪆ 3 EeV. Simulations of the telescope system, telescope on time, and realized flight trajectory predicted an observation of about 1 event assuming clear sky conditions. The effects of high clouds were estimated to reduce this value by approximately a factor of 2. A manual search and a machine-learning-based search did not find any EAS signals in these data. Here we review the EUSO-SPB1 instrument and flight and the EAS search

Observation of a large-scale anisotropy in the arrival directions of cosmic rays above 8 × 10 18 eV

Cosmic rays are atomic nuclei arriving from outer space that reach the highest energies observed in nature. Clues to their origin come from studying the distribution of their arrival directions. Using 3 × 10 4 cosmic rays with energies above 8 × 10 18 electron volts, recorded with the Pierre Auger Observatory from a total exposure of 76,800 km2 sr year, we determined the existence of anisotropy in arrival directions. The anisotropy, detected at more than a 5.2σ level of significance, can be described by a dipole with an amplitude of 6.5 +1.3 -0.9 percent toward right ascension αd = 100 ± 10 degrees and declination δd = -24 +12 -13 degrees. That direction indicates an extragalactic origin for these ultrahighenergy particles.La nómina completa de autores puede verse en el archivo asociado a este ítem.Facultad de Ciencias Exacta

PEPTIDE-CONJUGATED MORPHOLINO OLIGOMERS FOR TREATMENT OF SPINAL MUSCULAR ATROPHY

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease and the first known genetic cause of infant mortality. It is caused by the homozygous mutations in the Survival Motor Neuron 1 (SMN1) gene, resulting in deficiency of functional SMN protein. The pathologic aspect of SMA is the progressive loss of Motor Neurons (MNs) in the ventral horn of the spinal cord, which causes the loss of muscle function, paralysis and premature death. A first drug for SMA, Nusinersen an antisense oligonucleotide (ASO) has been recently been approved. In fact, one of the most promising strategies in order to increase the SMN protein levels is the use of ASOs to redirect the splicing of the paralogous gene SMN2 to increase the production of the functional SMN protein. ASOs with different chemical structure are currently used in clinical trials, included the ASO with Morpholino (MO) chemistry studied in this work. MO oligomers are particularly suitable for in vivo applications thanks to their optimal safety and efficacy profile. One of the issues related to the administration of ASOs is that they are not able to cross the blood-brain barrier and they must be administered by relatively invasive intrathecal injection to reach the central nervous system (CNS). Therefore, we aimed to improve the efficacy of MO and to develop a non-invasive systemic delivery in an in vivo SMA murine model. First, to increase the efficacy of MO oligomers, we tested, both in vitro and in vivo, four new MO sequences targeting the region involved in the alternative splicing of SMN2 mRNA, called intronic splicing silencer N1 (ISS-N1). Simultaneously, to improve the delivery of MO to affected tissues, we conjugated it to cell-penetrating peptides (CPPs), an approach already used to enhance the cellular and tissue uptake and the pharmacological profile of ASOs, but never explored in SMA. We tested three different CPPs: Tat, R6, and (RXRRBR)2XB, which were linked to our already validated MO sequence [HSMN2Ex7D(-10,-34)]. We administered the conjugates in pre-symptomatic and symptomatic SMA mice to determine their therapeutic efficacy versus unconjugated-MO. We showed that optimization of the target sequence can enhance the splice-correction action of MO oligomers and that the effect of the co-administration of different MO sequences is superior to the delivery of a single sequence. Furthermore, we showed that CPP-MO compounds can up-regulate the SMN protein into the CNS of SMA\uf0447 transgenic murine models as well as their average lifespan and motor performance after local and systemic injection. Our data proved that the CPP-MO conjugates can be a suitable strategy to increase the cellular uptake after an intrathecal administration and to deliver MO oligomers to the CNS after a systemic injection. The presented results provided the basis for the selection of the most efficient CPPs and will set the stage for future clinical trials

EuCAPT White Paper: Opportunities and Challenges for Theoretical Astroparticle Physics in the Next Decade

Astroparticle physics is undergoing a profound transformation, due to a series of extraordinary new results, such as the discovery of high-energy cosmic neutrinos with IceCube, the direct detection of gravitational waves with LIGO and Virgo, and many others. This white paper is the result of a collaborative effort that involved hundreds of theoretical astroparticle physicists and cosmologists, under the coordination of the European Consortium for Astroparticle Theory (EuCAPT). Addressed to the whole astroparticle physics community, it explores upcoming theoretical opportunities and challenges for our field of research, with particular emphasis on the possible synergies among different subfields, and the prospects for solving the most fundamental open questions with multi-messenger observations.Comment: White paper of the European Consortium for Astroparticle Theory (EuCAPT). 135 authors, 400 endorsers, 133 pages, 1382 reference

Statuspassagen und Risikolagen im Lebensverlauf: Institutionelle Steuerung und individuelle Handlungsstrategien: Finanzierungsantrag für die vierte Forschungsphase 1997-1999

"Der Finanzierungsantrag des Sfb 186 für die vierte Forschungsphase 1997-1999 gibt Einblicke in die Forschungsbasis und Forschungsziele des Sonderforschungsbereichs. Das Forschungsprogramm betritt Neuland: Es wird versucht, einem Verständnis von interdisziplinärer Forschung gerecht zu werden, das die analytisch-methodische Arbeitsteilung zwischen der Strukturanalyse gesellschaftlicher Verhältnisse und der Interpretation sozialer Erfahrungsmuster überwinden will. Dazu werden Ansätze der Jugend- und Berufsbildungsforschung, Familiensoziologie, Arbeits(markt-)soziologie, Medizinsoziologie und Sozialpolitikforschung so aufeinander bezogen, dass Institutionen und Akteure, Normalitätsunterstellungen und Lebensverläufe und ihre Veränderungen auf der Untersuchungsebene von Statuspassagen betrachtet werden. Als Leitmotive für den Sonderforschungsbereich ergeben sich folgende Fragenkomplexe: Wie bearbeiten die Institutionen des Arbeitsmarktes, der Berufsbildung, der familialen Reproduktion und der sozialstaatlichen Sicherung die sozialen Risiken: inwieweit haben sich ihre Normalitäts-Konzeptionen, Zuständigkeiten und Praktiken seit Mitte der 70er Jahre verändert? Wird es zu Risikoumverteilungen oder zu einer Kumulation von Risiken bei bestimmten Sozialgruppen kommen und mit welchen gesellschaftspolitischen Konsequenzen? Welche Möglichkeiten und Grenzen für eine Umgestaltung der männlichen und weiblichen Normalbiographie ergeben sich längerfristig aus neuen Lebensentwürfen, Risikolagen und deren institutioneller Bearbeitung? Wie arrangieren sich die Individuen mit den Diskontinuitäten im Lebenslauf und den Friktionen zwischen institutionalisierten Lebenslaufmustern und individuellen Lebensentwürfen, und wie werden diskontinuierliche Statuspassagen von verschiedenen sozialen Gruppen bewältigt? In der vierten Förderungsphase (1997-1999) richtet sich die Leitfrage auf die Struktur konzeptioneller Vorstellungen von Lebenslaufpolitik in den Arbeitsbereichen des Sonderforschungsbereichs 186, also auf lebenslaufpolitische Grundsatzfragen und Konzepte hinsichtlich Familie, Bildung, Arbeit und Beruf, Gesundheit und Sozialpolitik/ soziale Sicherung und auf die institutionellen Rahmensetzungen von Lebenslaufpolitik in diesen Feldern. Beides unterliegt gegenwärtig einem starken Veränderungsdruck durch die Internationalisierung von Kapital, Arbeit und Recht. Der Sfb 186 bezieht in allen Projektbereichen die drei Ebenen des sozialen Wandels in seine Analysen ein: Sozialstrukturen, Institutionen und Individuen. Die Projekte arbeiten mit mehreren unterschiedlichen Datensätzen. Ein ständiges Problem aller bisherigen Förderungsphasen war deshalb, das Vorantreiben der Integration der Datenerhebungen und Datenanalysen bei Mehrebenenerhebungen und Methodenmix. Die Lösung erfordert besondere Anstrengungen, da der Sonderforschungsbereich mit Längsschnittdaten unterschiedlichen Typs arbeitet und nicht mit Querschnittserhebungen.

A 3-Year Sample of Almost 1,600 Elves Recorded Above South America by the Pierre Auger Cosmic-Ray Observatory

Elves are a class of transient luminous events, with a radial extent typically greater than 250 km, that occur in the lower ionosphere above strong electrical storms.We report the observation of 1,598 elves, from 2014 to 2016, recorded with unprecedented time resolution (100 ns) using the fluorescence detector (FD) of the Pierre Auger Cosmic-Ray Observatory. The Auger Observatory is located in the Mendoza province of Argentina with a viewing footprint for elve observations of 3 · 106 km2, reaching areas above the Pacific and Atlantic Oceans, as well as the Córdoba region, which is known for severe convective thunderstorms. Primarily designed for ultrahigh energy cosmic-ray observations, the Auger FD turns out to be very sensitive to the ultraviolet emission in elves. The detector features modified Schmidt optics with large apertures resulting in a field of view that spans the horizon, and year-round operation on dark nights with low moonlight background, when the local weather is favorable. The measured light profiles of 18% of the elve events have more than one peak, compatible with intracloud activity. Within the 3-year sample, 72% of the elves correlate with the far-field radiation measurements of the World Wide Lightning Location Network. The Auger Observatory plans to continue operations until at least 2025, including elve observations and analysis. To the best of our knowledge, this observatory is the only facility on Earth that measures elves with year-round operation and full horizon coverage. Co-authors: A. Aab, P. Abreu,M. Aglietta, I. F.M. Albuquerque, J.M. Albury, I. Allekotte, A. Almela, J. Alvarez Castillo, J. Alvarez-Muniz, G. A. Anastasi,L. Anchordoqui, B. Andrada, S. Andringa, C. Aramo, H. Asorey, P. Assis, G. Avila, A.M. Badescu, A. Bakalova, A. Balaceanu,F. Barbato, R. J. Barreira Luz, S. Baur, K. H. Becker, J.A. Bellido, C. Berat,M. E. Bertaina, X. Bertou, P. L. Biermann, J. Biteau, S. G. Blaess, A. Blanco, J. Blazek, C. Bleve,M. Bohaˇcova, D. Boncioli, C. Bonifazi, N. Borodai, A. M. Botti, J. Brack,T. Bretz, A. Bridgeman, F. L. Briechle, P. Buchholz, A. Bueno, S. Buitink,M. Buscemi, K. S. Caballero-Mora, L. Caccianiga, L. Calcagni, A. Cancio, F. Canfora, J.M. Carceller, R. Caruso, A. Castellina, F. Catalani, G. Cataldi, L. Cazon,M. Cerda, J. A. Chinellato,J. Chudoba, L. Chytka, R.W. Clay, A. C. Cobos Cerutti, R. Colalillo, A. Coleman,M. R. Coluccia, R. Conceicao, A. Condorelli, G. Consolati,F. Contreras,M. J. Cooper, S. Coutu, C. E. Covault, B. Daniel, S. Dasso, K. Daumiller, B. R. Dawson, J. A. Day, R.M. de Almeida,S. J. de Jong, G. Mauro, J. R. T. de Mello Neto, I. Mitri, J. de Oliveira, F. O. de Oliveira Salles, V. de Souza, J. Debatin,M. del Rio, O. Deligny,N. Dhital,M. L. Diaz Castro, F. Diogo, C. Dobrigkeit, J. C. D\u27Olivo, Q. Dorosti, R. C. dos Anjos, M. T. Dova, A. Dundovic, J. Ebr, R. Engel,M. Erdmann, C. O. Escobar, A. Etchegoyen, H. Falcke, J. Farmer, G. Farrar, A. C. Fauth, N. Fazzini, F. Feldbusch,F. Fenu, L. P. Ferreyro, J.M. Figueira, A. Filipˇciˇc, M. M. Freire, T. Fujii, A. Fuster, B. Garcia, H. Gemmeke, A. Gherghel-Lascu,P. L. Ghia, U. Giaccari,M. Giammarchi,M. Giller, D. Głas, J. Glombitza, F. Gobbi, G. Golup,M. Gomez Berisso, P. F. Gomez Vitale,J. P. Gongora, N. Gonzalez, I. Goos, D. Gora, A. Gorgi,M. Gottowik, T. D. Grubb, F. Guarino, G. P. Guedes, E. Guido,R. Halliday, M. R. Hampel, P. Hansen, D. Harari, T. A. Harrison, V. M. Harvey, A. Haungs, T. Hebbeker, D. Heck, P. Heimann,G. C. Hill, C. Hojvat, E. M. Holt, P. Homola, J. R. Horandel, P. Horvath,M. Hrabovsky, T. Huege, J. Hulsman, A. Insolia,P. G. Isar, I. Jandt, J. A. Johnsen,M. Josebachuili, J. Jurysek, A. Kaapa, K. H. Kampert, B. Keilhauer, N. Kemmerich, J. Kemp,H. O. Klages, M. Kleifges, J. Kleinfeller, R. Krause, D. Kuempel, G. Kukec Mezek, A. Kuotb Awad, B. L. Lago, D. LaHurd, R. G. Lang,R. Legumina,M. A. Leigui de Oliveira, V. Lenok, A. Letessier-Selvon, I. Lhenry-Yvon, O. C. Lippmann, D. Lo Presti, L. Lopes, R. Lopez, A. Lopez Casado,R. Lorek, Q. Luce, A. Lucero,M. Malacari, G. Mancarella, D. Mandat, B. C. Manning, P. Mantsch, A. G. Mariazzi, I. C. Mari，s, G. Marsella, D. Martello, H. Martinez, O. Martinez Bravo,M. Mastrodicasa, H. J. Mathes, S. Mathys, J. Matthews, G. Matthiae, E. Mayotte,P. O. Mazur, G. Medina-Tanco, D. Melo, A. Menshikov, K.-D. Merenda, S. Michal,M. I. Micheletti, L. Middendorf, L. Miramonti, B. Mitrica,D. Mockler, S. Mollerach, F. Montanet, C. Morello, G. Morlino,M. Mostafa, A. L. Muller,M. A. Muller, S. Muller, R. Mussa,L. Nellen, P. H. Nguyen,M. Niculescu-Oglinzanu,M. Niechciol, D. Nitz, D. Nosek, V. Novotny, L. Noža, A Nucita, L.A. Nunez,A. Olinto,M. Palatka, J. Pallotta,M. P. Panetta, P. Papenbreer, G. Parente, A. Parra, M. Pech, F. Pedreira, J. Pe，kala,R. Pelayo, J. Pena-Rodriguez, L. A. S. Pereira,M. Perlin, L. Perrone, C. Peters, S. Petrera, J. Phuntsok, T. Pierog,M. Pimenta,V. Pirronello,M. Platino, J. Poh, B. Pont, C. Porowski, R. R. Prado, P. Privitera,M. Prouza, A. Puyleart, S. Querchfeld,S. Quinn, R. Ramos-Pollan, J. Rautenberg, D. Ravignani, M. Reininghaus, J. Ridky, F. Riehn,M. Risse, P. Ristori, V. Rizi, W. Rodrigues de Carvalho, J. Rodriguez Rojo,M. J. Roncoroni, M. Roth, E. Roulet, A. C. Rovero, P. Ruehl, S. J. Saffi, A. Saftoiu, F. Salamida,H. Salazar, G. Salina,J. D. Sanabria Gomez, F. Sanchez, E.M. Santos, E. Santos, F. Sarazin, R. Sarmento, C. Sarmiento-Cano, R. Sato,P. Savina,M. Schauer, V. Scherini, H. Schieler, M. Schimassek,M. Schimp, F. Schluter, D. Schmidt, O. Scholten, P. Schovanek, F. G. Schroder, S. Schroder, J. Schumacher, S. J. Sciutto,M. Scornavacche, R. C. Shellard, G. Sigl, G. Silli, O. Sima, R. Šmida,G.R. Snow, P. Sommers, J. F. Soriano, J. Souchard, R. Squartini, D. Stanca, S. Staniˇc, J. Stasielak, P. Stassi, M. Stolpovskiy,A. Streich, F. Suarez,M. Suarez-Duran, T. Sudholz, T. Suomijarvi, A.D. Supanitsky, J. Šupik, Z. Szadkowski, A. Taboada, O. A. Taborda, A. Tapia, C. Timmermans, C. J. Todero Peixoto, B. Tome, G. Torralba Elipe, A. Travaini, P. Travnicek,M. Trini, M. Tueros, R. Ulrich,M. Unger,M. Urban, J. F. Valdes Galicia, I. Valino, L. Valore, P. van Bodegom, A.M. van den Berg, A. van Vliet, E. Varela, B. Vargas Cardenas,D. Veberiˇc, C. Ventura, I. D. Vergara Quispe, V. Verzi, J. Vicha, L. Villasenor, J. Vink, S. Vorobiov, H. Wahlberg, A. A. Watson, M. Weber, A. Weindl,M.Wieden´ ski, L. Wiencke, H. Wilczyn´ ski, T.Winchen, M. Wirtz, D. Wittkowski, B. Wundheiler, L. Yang, A. Yushkov, E. Zas, D. Zavrtanik, M. Zavrtanik, L. Zehrer, A. Zepeda, B. Zimmermann,M. Ziolkowski, Z. Zongand F. Zuccarello Data set attached as supplementary file