Infinite Symmetry in the Quantum Hall Effect

Free planar electrons in a uniform magnetic field are shown to possess the symmetry of area-preserving diffeomorphisms ($W$-infinity algebra). Intuitively, this is a consequence of gauge invariance, which forces dynamics to depend only on the flux. The infinity of generators of this symmetry act within each Landau level, which is infinite-dimensional in the thermodynamical limit. The incompressible ground states corresponding to completely filled Landau levels (integer quantum Hall effect) are shown to be infinitely symmetric, since they are annihilated by an infinite subset of generators. This geometrical characterization of incompressibility also holds for fractional fillings of the lowest level (simplest fractional Hall effect) in the presence of Haldane's effective two-body interactions. Although these modify the symmetry algebra, the corresponding incompressible ground states proposed by Laughlin are again symmetric with respect to the modified infinite algebra.Comment: 28 page

Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer

Background: In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies. Methods: We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls. Results: We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines. Conclusions: Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient’s progression and therapeutic response.The study was financially supported by FIS (ISCIII) and ERDF/FSE funds (PI15/00186, PI18/0050, and ERDF/FSE, A way to make Europe). The authors gratefully acknowledge the Colombian Ministry for Science, Technology and Innovation (MINCIENCIAS), Code 568-2012, for providing J.S. with partial funding for this study

Transcriptome and proteome mapping in the sheep atria reveal molecular featurets of atrial fibrillation progression.

Atrial fibrillation (AF) is a progressive cardiac arrhythmia that increases the risk of hospitalization and adverse cardiovascular events. There is a clear demand for more inclusive and large-scale approaches to understand the molecular drivers responsible for AF, as well as the fundamental mechanisms governing the transition from paroxysmal to persistent and permanent forms. In this study, we aimed to create a molecular map of AF and find the distinct molecular programmes underlying cell type-specific atrial remodelling and AF progression. We used a sheep model of long-standing, tachypacing-induced AF, sampled right and left atrial tissue, and isolated cardiomyocytes (CMs) from control, intermediate (transition), and late time points during AF progression, and performed transcriptomic and proteome profiling. We have merged all these layers of information into a meaningful three-component space in which we explored the genes and proteins detected and their common patterns of expression. Our data-driven analysis points at extracellular matrix remodelling, inflammation, ion channel, myofibril structure, mitochondrial complexes, chromatin remodelling, and genes related to neural function, as well as critical regulators of cell proliferation as hallmarks of AF progression. Most important, we prove that these changes occur at early transitional stages of the disease, but not at later stages, and that the left atrium undergoes significantly more profound changes than the right atrium in its expression programme. The pattern of dynamic changes in gene and protein expression replicate the electrical and structural remodelling demonstrated previously in the sheep and in humans, and uncover novel mechanisms potentially relevant for disease treatment. Transcriptomic and proteomic analysis of AF progression in a large animal model shows that significant changes occur at early stages, and that among others involve previously undescribed increase in mitochondria, changes to the chromatin of atrial CMs, and genes related to neural function and cell proliferation.This work was supported by the Spanish government (BFU2017-84914-P to M.M.; FPI Fellowship to A.A.-F.; FPU Fellowship to R.R.), and in part by grants to J.J. from the National Heart, Lung and Blood Institute (R01 grant HL122352 NIH/NHLBI), the Leducq Foundation (Transatlantic Network of Excellence Program on Structural Alterations in the Myocardium and the Substrate for Cardiac Fibrillation), and the University of Michigan Health System–Peking University Health Science Center Joint Institute for Translational and Clinical Research (UMHS-PUHSC; project: Molecular Mechanisms of Fibrosis and the Progression from Paroxysmal to Persistent Atrial Fibrillation). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Acoustic signal detection through the cross-correlation method in experiments with different signal to noise ratio and reverberation conditions

[EN] The study and application of signal detection techniques based on cross-correlation method for acoustic transient signals in noisy and reverberant environments are presented. These techniques are shown to provide high signal to noise ratio, good signal discernment from very close echoes and accurate detection of signal arrival time. The proposed methodology has been tested on different signal to noise ratio and reverberation conditions using real data collected in several experiences related to acoustic systems in astroparticle detectors. This work focuses on the acoustic detection applied to tasks of positioning in underwater structures and calibration such those as ANTARES and KM3NeT deep-sea neutrino telescopes, as well as, in particle detection through acoustic events for the COUPP/PICO detectors. Moreover, a method for obtaining the real amplitude of the signal in time (voltage) by using cross correlation has been developed and tested and is described in this work.This work has been supported by the Ministerio de Economía y Competitividad (Spanish Government), project ref. FPA2012-37528-C02-02 and Multidark (CSD2009-00064). It has also being funded by Generalitat Valenciana, Prometeo/2009/26, and ACOMP/2014/153. Thanks to the ANTARES Collaboration for the help in the measurements made in the ANTARES deep-sea neutrino telescope.Adrián Martínez, S.; Bou Cabo, M.; Felis, I.; Llorens Alvarez, CD.; Martínez Mora, JA.; Saldaña, M.; Ardid Ramírez, M. (2015). Acoustic signal detection through the cross-correlation method in experiments with different signal to noise ratio and reverberation conditions. Lecture Notes in Computer Science. 8629:66-79. https://doi.org/10.1007/978-3-662-46338-3_7S66798629Ageron, M., et al. (ANTARES Collaboration): ANTARES: the first undersea neutrino telescope. Nucl. Instr. Meth. A 656, 11–38 (2011)The KM3NeT Collaboration: KM3NeT technical design report (2010). ISBN 978-90-6488-033-9. www.km3net.orgBehnke, E., et al. (COUPP Collaboration): First dark matter search results from a 4-kg CF3I bubble chamber operated in a deep underground site. Phys. Rev. D 86, 052001 (2012)Ardid, M.: Positioning system of the ANTARES neutrino telescope. Nucl. Instr. Meth. A 602, 174–176 (2009)Larosa, G., Ardid, M.: KM3NeT acoustic position calibration of the KM3NeT neutrino telescope. Nucl. Instr. Meth. A 718, 502–503 (2013)Ardid, M.: ANTARES: an underwater network of sensors for neutrino astronomy and deep-sea research. Ad Hoc Sensor Wirel. Netw. 8, 21–34 (2009)Bou-Cabo, M., Ardid, M., Felis, I.: Acoustic studies for alpha background rejection in dark matter bubble chamber detectors. In: Proceedings of the IV International Workshop in Low Radioactivity Techniques. AIP Conference Proceedings, vol. 1549, pp. 142–147 (2013)Proakis, J.G., Manolakis, D.G.: Digital Signal Processing, 3rd edn. Prentice Hall, Upper Saddle River (1996)Saldaña, M.: Acoustic system development for the underwater neutrino telescope positioning KM3NeT, Bienal de Física (2013)Ardid, M., et al.: Acoustic transmitters for underwater neutrino telescopes. Sensors 12, 4113–4132 (2012)Felis, I., Bou-Cabo, M., Ardid, M.: Sistemas acústicos para la detección de Materia Oscura, Bienal de Física (2013)Llorens, C.D., et al.: The sound emission board of the KM3NeT acoustic positioning system. J. Instrum. 7, C01001 (2012)Graf, K.: Experimental studies within ANTARES towards acoustic detection of ultra high energy neutrinos in the deep sea. Ph.D. thesis, U. Erlangen, FAU-PI1-DISS-08-001 (2008

Expansion cone for the 3-inch PMTs of the KM3NeT optical modules

[EN] Detection of high-energy neutrinos from distant astrophysical sources will open a new window on the Universe. The detection principle exploits the measurement of Cherenkov light emitted by charged particles resulting from neutrino interactions in the matter containing the telescope. A novel multi-PMT digital optical module (DOM) was developed to contain 31 3-inch photomultiplier tubes (PMTs). In order to maximize the detector sensitivity, each PMT will be surrounded by an expansion cone which collects photons that would otherwise miss the photocathode. Results for various angles of incidence with respect to the PMT surface indicate an increase in collection efficiency by 30% on average for angles up to 45 degrees with respect to the perpendicular. Ray-tracing calculations could reproduce the measurements, allowing to estimate an increase in the overall photocathode sensitivity, integrated over all angles of incidence, by 27% (for a single PMT). Prototype DOMs, being built by the KM3NeT consortium, will be equipped with these expansion cones.This work is supported through the EU, FP6 Contract no. 011937, FP7 grant agreement no. 212252, and the Dutch Ministry of Education, Culture and Science.Adrián Martínez, S.; Ageron, M.; Aguilar, JA.; Aharonian, F.; Aiello, S.; Albert, A.; Alexandri, M.... (2013). Expansion cone for the 3-inch PMTs of the KM3NeT optical modules. Journal of Instrumentation. 8(3):1-19. https://doi.org/10.1088/1748-0221/8/03/T03006S1198

Implementation and first results of the KM3NeT real-time core-collapse supernova neutrino search

[EN] The KM3NeT research infrastructure is uncon- struction in the Mediterranean Sea. KM3NeT will study atmospheric and astrophysical neutrinos with two multi- purpose neutrino detectors, ARCA and ORCA, primar-ily aimed at GeV¿PeV neutrinos. Thanks to the multi-photomultiplier tube design of the digital optical modules, KM3NeT is capable of detecting the neutrino burst from a Galactic or near-Galactic core-collapse supernova. This potential is already exploitable with the first detection units deployed in the sea. This paper describes the real-time imple- mentation of the supernova neutrino search, operating on the two KM3NeT detectors since the first months of 2019. A quasi-online astronomy analysis is introduced to study the time profile of the detected neutrinos for especially signifi- cant events. The mechanism of generation and distribution of alerts, as well as the integration into the SNEWS and SNEWS 2.0 global alert systems, are described. The approach for the follow-up of external alerts with a search for a neutrino excess in the archival data is defined. Finally, an overview of the cur-rent detector capabilities and a report after the first two years of operation are given.The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Generalitat Valenciana: Prometeo (PROMETEO/2020/019), Grisolia (ref. GRISOLIA/2018/119) and GenT (refs. CIDEGENT/2018/034, /2019/043, /2020/049) programs, Junta de Andalucia (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 101025085), Spain.Aiello, S.; Albert, A.; Alshamsi, M.; Alves Garre, S.; Aly, Z.; Ambrosone, A.; Ameli, F.... (2022). Implementation and first results of the KM3NeT real-time core-collapse supernova neutrino search. The European Physical Journal C. 82(4):1-16. https://doi.org/10.1140/epjc/s10052-022-10137-y11682

Nanobeacon: A time calibration device for the KM3NeT neutrino telescope

[EN] The KM3NeT Collaboration is currently constructing a multi-site high-energy neutrino telescope in the Mediterranean Sea consisting of matrices of pressure-resistant glass spheres, each holding a set of 31 small-area photomultipliers. The main goals of the telescope are the observation of neutrino sources in the Universe and the measurement of the neutrino oscillation parameters with atmospheric neutrinos. A relative time synchronisation between photomultipliers of the nanosecond arder needed to guarantee the required angular resolution of the detector. Due to the large detector volumes to be instrumented by KM3NeT, a cost reduction of the different systems is a priority. To this end, the inexpensive Nanobeacon has been designed and developed by the KM3NeT Collaboration to be used for detector time-calibration studies. At present, more than 600 Nanobeacons have been already produced. The characterisation of the optical pulse and the wavelength emission profile of the devices is critica! for the time calibration. The optical pulse rise time has been quantified as less than 3 ns, while the Full Width Half Maximum is less than 6 ns. The wavelength drift, due to a variation of the supply voltage, has also been qualified as lower than 10 nm for the full range of the Nanobeacon. In this paper, more details about the main features of the Nanobeacon design, production and operation, together with the main properties of the light pulse generated are described.The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris Ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion.. Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Generalitat Valenciana: Prometeo (PROMETEO/2020/019), Grisolia (ref. GRISOLIA/2018/119) and GenT (refs. CIDEGENT/2018/034,/2019/043,/2020/049) programs, Junta de Andalucia (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 101025085), Spain.Aiello, S.; Albert, A.; Alshamsi, M.; Alves Garre, S.; Aly, Z.; Ambrosone, A.; Ameli, F.... (2022). Nanobeacon: A time calibration device for the KM3NeT neutrino telescope. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 1040:1-13. https://doi.org/10.1016/j.nima.2022.167132113104