The Palma Echo Platform: Rationale and Design of an Echocardiography Core Lab

Background: The metabolic syndrome (MetS) is associated with increased cardiovascular morbidity and mortality. Characterization of cardiac structural and functional abnormalities due to the MetS can help recognize individuals who would benefit the most from preventive interventions. Transthoracic echocardiography (TTE) provides an opportunity to identify those abnormalities in a reproducible and cost-efficient manner. In research settings, implementation of protocols for the acquisition and analysis of TTE images are key to ensure validity and reproducibility, thus facilitating answering relevant questions about the association of the MetS with cardiac alterations. Methods and Results: The Palma Echo Platform (PEP) is a coordinated network that is built up to evaluate the underlying structural and functional cardiac substrate of participants with MetS. Repeated TTE will be used to evaluate 5-year changes in the cardiac structure and function in a group of 565 individuals participating in a randomized trial of a lifestyle intervention for the primary prevention of cardiovascular disease. The echocardiographic studies will be performed at three study sites, and will be centrally evaluated at the PEP core laboratory. Planned analyses will involve evaluating the effect of the lifestyle intervention on cardiac structure and function, and the association of the MetS and its components with changes in cardiac structure and function. Particular emphasis will be placed on evaluating parameters of left atrial structure and function, which have received more limited attention in past investigations. This PEP will be available for future studies addressing comparable questions. Conclusion: In this article we describe the protocol of a central echocardiography laboratory for the study of functional and structural alterations of the MetS.Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Numbers R01HL137338 and K24HL148521, and administrative supplement to promote diversity 3R01HL137338-03S1. This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which was co-funded by the European Regional Development Fund (PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, and PI20/01158); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918); the Recercaixa (number 2013ACUP00194); grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; none of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication

Supernova Model Discrimination with Hyper-Kamiokande

[EN] Core-collapse supernovae are among the most magnificent events in the observable universe. They produce many of the chemical elements necessary for life to exist and their remnants-neutron stars and black holes-are interesting astrophysical objects in their own right. However, despite millennia of observations and almost a century of astrophysical study, the explosion mechanism of core-collapse supernovae is not yet well understood. Hyper-Kamiokande is a next-generation neutrino detector that will be able to observe the neutrino flux from the next galactic core-collapse supernova in unprecedented detail. We focus on the first 500 ms of the neutrino burst, corresponding to the accretion phase, and use a newly-developed, high-precision supernova event generator to simulate Hyper-Kamiokande's response to five different supernova models. We show that Hyper-Kamiokande will be able to distinguish between these models with high accuracy for a supernova at a distance of up to 100 kpc. Once the next galactic supernova happens, this ability will be a powerful tool for guiding simulations toward a precise reproduction of the explosion mechanism observed in nature.We thank MacKenzie Warren, Ken'ichiro Nakazato, Tomonori Totani, Adam Burrows, David Vartanyan, and Irene Tamborra for access to the supernova models used in this work and for answering various related questions. This work was supported by MEXT Grant-in-Aid for Scientific Research on Innovative Areas titled "Exploration of Particle Physics and Cosmology with Neutrinos" under grant No. 18H05535, 18H05536, and 18H5537. In addition, participation of individual researchers has been further supported by funds from JSPS, Japan; the European Union's Horizon 2020 Research and Innovation Programme H2020 grant Nos. RISE-GA822070-JENNIFER2 2020 and RISEGA872549-SK2HK; SSTF-BA1402-06, NRF grant Nos. 20090083526, NRF-2015R1A2A1A05001869, NRF-2016R1D1A 1A02936965, NRF-2016R1D1A3B02010606, NRF-2017R1 A2B4012757, and NRF-2018R1A6A1A06024970 funded by the Korean government (MSIP); JSPS-RFBR Grant #20-5250010/20 and the Ministry of Science and Higher Education under contract #075-15-2020-778, Russia; Brazilian Funding agencies, CNPq and CAPES; STFC ST/R00031X/2, ST/T002891/1, ST/V002872/1, Consolidated Grants, UKRI MR/S032843/1 and MR/S034102/1, UK. Software: BONSAI.(Smy 2007), sntools. (Migenda et al. 2021), WCSim, 124. matplotlib.(Hunter 2007), NumPy.(van der Walt et al. 2011), SciPy.(Virtanen et al. 2020)Abe, K.; Adrich, P.; Aihara, H.; Akutsu, R.; Alekseev, I.; Ali, A.; Ameli, F.... (2021). Supernova Model Discrimination with Hyper-Kamiokande. The Astrophysical Journal. 916(1):1-17. https://doi.org/10.3847/1538-4357/abf7c4117916

Dependence of polytetrafluoroethylene reflectance on thickness at visible and ultraviolet wavelengths in air

[EN] Polytetrafluoroethylene (PTFE) is an excellent diffuse reflector widely used in light collection systems for particle physics experiments. However, the reflectance of PTFE is a function of its thickness. In this work, we investigate this dependence in air for light of wavelengths 260 nm and 450 nm using two complementary methods. We find that PTFE reflectance for thicknesses from 5 mm to 10 mm ranges from 92.5% to 94.5% at 450 nm, and from 90.0% to 92.0% at 260 nm We also see that the reflectance of PIFE of a given thickness can vary by as much as 2.7% within the same piece of material. Finally, we show that placing a specular reflector behind the PTFE can recover the loss of reflectance in the visible without introducing a specular component in the reflectance.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad and the Ministerio de Ciencia, Innovacion y Universidades of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program grants SEV-2014-0398 and CEX2018-000867-S, and the Maria de Maeztu Program MDM-2016-0692; the Generalitat Valenciana under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014 and under projects UID/04559/2020 to fund the activities of LIBPhys-UC; the U.S. Department of Energy under contracts No. DE-AC02-06CH11357 (Argonne National Laboratory), DE-AC0207CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0019223/DE-SC0019054 (University of Texas at Arlington); and the University of Texas at Arlington (USA). DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC2015-18820. JM-A acknowledges support from Fundacion Bancaria "la Caixa" (ID 100010434), grant code LCF/BQ/PI19/11690012. Finally, we thank Brendon Bullard, Paolo Giromini and Neeraj Tata for helpful discussions and assistance with preliminary measurements.Ghosh, S.; Haefner, J.; Martín-Albo, J.; Guenette, R.; Li, X.; Loya Villalpando, A.; Burch, C.... (2020). Dependence of polytetrafluoroethylene reflectance on thickness at visible and ultraviolet wavelengths in air. Journal of Instrumentation. 15(11):1-17. https://doi.org/10.1088/1748-0221/15/11/P11031S1171511Auger, M., Auty, D. J., Barbeau, P. S., Bartoszek, L., Baussan, E., Beauchamp, E., … Cleveland, B. (2012). The EXO-200 detector, part I: detector design and construction. Journal of Instrumentation, 7(05), P05010-P05010. doi:10.1088/1748-0221/7/05/p05010Martín-Albo, J., Muñoz Vidal, J., Ferrario, P., Nebot-Guinot, M., Gómez-Cadenas, J. J., … Cárcel, S. (2016). Sensitivity of NEXT-100 to neutrinoless double beta decay. Journal of High Energy Physics, 2016(5). doi:10.1007/jhep05(2016)159Rogers, L., Clark, R. A., Jones, B. J. P., McDonald, A. D., Nygren, D. R., Psihas, F., … Azevedo, C. D. . (2018). High voltage insulation and gas absorption of polymers in high pressure argon and xenon gases. Journal of Instrumentation, 13(10), P10002-P10002. doi:10.1088/1748-0221/13/10/p10002Silva, C., Pinto da Cunha, J., Pereira, A., Chepel, V., Lopes, M. I., Solovov, V., & Neves, F. (2010). Reflectance of polytetrafluoroethylene for xenon scintillation light. Journal of Applied Physics, 107(6), 064902. doi:10.1063/1.3318681Haefner, J., Neff, A., Arthurs, M., Batista, E., Morton, D., Okunawo, M., … Lorenzon, W. (2017). Reflectance dependence of polytetrafluoroethylene on thickness for xenon scintillation light. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 856, 86-91. doi:10.1016/j.nima.2017.01.057Kravitz, S., Smith, R. J., Hagaman, L., Bernard, E. P., McKinsey, D. N., Rudd, L., … Sakai, M. (2020). Measurements of angle-resolved reflectivity of PTFE in liquid xenon with IBEX. The European Physical Journal C, 80(3). doi:10.1140/epjc/s10052-020-7800-6Geis, C., Grignon, C., Oberlack, U., García, D. R., & Weitzel, Q. (2017). Optical response of highly reflective film used in the water Cherenkov muon veto of the XENON1T dark matter experiment. Journal of Instrumentation, 12(06), P06017-P06017. doi:10.1088/1748-0221/12/06/p06017Allison, J., Amako, K., Apostolakis, J., Arce, P., Asai, M., Aso, T., … Barrand, G. (2016). Recent developments in Geant4. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 835, 186-225. doi:10.1016/j.nima.2016.06.12

Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics

MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery. Herein, the engineering of non-liposomal lipid nanovesicles, named quatsomes (QS), for the delivery of miRNAs and other small RNAs into the cytosol of tumor cells, triggering a tumor-suppressive response is reported. The engineered pH-sensitive nanovesicles have controlled structure (unilamellar), size (24 weeks), and are prepared by a green, GMP compliant, and scalable one-step procedure, which are all unavoidable requirements for the arrival to the clinical practice of NP based miRNA therapeutics. Furthermore, QS protect miRNAs from RNAses and when injected intravenously, deliver them into liver, lung, and neuroblastoma xenografts tumors. These stable nanovesicles with tunable pH sensitiveness constitute an attractive platform for the efficient delivery of miRNAs and other small RNAs with therapeutic activity and their exploitation in the clinics

Low-diffusion Xe-He gas mixtures for rare-event detection: electroluminescence yield

[EN] High pressure xenon Time Projection Chambers (TPC) based on secondary scintillation (electroluminescence) signal amplification are being proposed for rare event detection such as directional dark matter, double electron capture and double beta decay detection. The discrimination of the rare event through the topological signature of primary ionisation trails is a major asset for this type of TPC when compared to single liquid or double-phase TPCs, limited mainly by the high electron diffusion in pure xenon. Helium admixtures with xenon can be an attractive solution to reduce the electron diffu- sion significantly, improving the discrimination efficiency of these optical TPCs. We have measured the electroluminescence (EL) yield of Xe-He mixtures, in the range of 0 to 30% He and demonstrated the small impact on the EL yield of the addition of helium to pure xenon. For a typical reduced electric field of 2.5 kV/cm/bar in the EL region, the EL yield is lowered by similar to 2%, 3%, 6% and 10% for 10%, 15%, 20% and 30% of helium concentration, respectively. This decrease is less than what has been obtained from the most recent simulation framework in the literature. The impact of the addition of helium on EL statistical fluctuations is negligible, within the experimental uncertainties. The present results are an important benchmark for the simulation tools to be applied to future optical TPCs based on Xe-He mixtures.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Marie Sklodowska-Curie Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economa y Competitividad of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program SEV-2014-0398 and the Mara de Maetzu Program MDM-2016-0692; the GVA of Spain under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014, under project UID/FIS/04559/2013 to fund the activities of LIBPhys, and under grants PD/BD/105921/2014, SFRH/BPD/109180/2015; the U.S. Department of Energy under contracts number DEAC02-06CH11357 (Argonne National Laboratory), DE-AC0207CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A& M) and DE-SC0019223/DESC0019054 (University of Texas at Arlington); and the University of Texas at Arlington. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015-18820. We also warmly acknowledge the Laboratori Nazionali del Gran Sasso (LNGS) and the Dark Side collaboration for their help with TPB coating of various parts of the NEXT-White TPC. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Fernandes, A.; Henriques, C.; Mano, R.; González-Díaz, D.; Azevedo, C.; Silva, P.; Gómez-Cadenas, J.... (2020). Low-diffusion Xe-He gas mixtures for rare-event detection: electroluminescence yield. Journal of High Energy Physics (Online). (4):1-18. https://doi.org/10.1007/JHEP04(2020)034S1184D.R. Nygren, Columnar recombination: a tool for nuclear recoil directional sensitivity in a xenon-based direct detection WIMP search, J. Phys. Conf. Ser.460 (2013) 012006 [INSPIRE].G. Mohlabeng et al., Dark matter directionality revisited with a high pressure xenon gas detector, JHEP07 (2015) 092 [arXiv:1503.03937] [INSPIRE].N.S. Phan, R.J. Lauer, E.R. Lee, D. Loomba, J.A.J. Matthews and E.H. Miller, GEM-based TPC with CCD Imaging for Directional Dark Matter Detection, Astropart. Phys.84 (2016) 82 [arXiv:1510.02170] [INSPIRE].J. Martin-Albo et al., Sensitivity of NEXT-100 to neutrinoless double beta decay, JHEP05 (2016) 159 [arXiv:1511.09246] [INSPIRE].K. Nakamura et al., AXEL — a high pressure xenon gas TPC for neutrinoless double beta decay search, Nucl. Instrum. Meth.A 845 (2017) 394 [INSPIRE].D. Yu. Akimov, A.A. Burenkov, V.F. Kuzichev, V.L. Morgunov and V.N. Solovev, Low background experiments with high pressure gas scintillation proportional detector, physics/9704021 [INSPIRE].Yu. M. Gavrilyuk et al., A technique for searching for the 2K capture in124Xe with a copper proportional counter, Phys. Atom. Nucl.78 (2015) 1563 [INSPIRE].Yu. M. Gavrilyuk et al., Results of In-Depth Analysis of Data Obtained in the Experimental Search for 2K (2ν)-Capture in78Kr, Phys. Part. Nucl.49 (2018) 540 [INSPIRE].C.A.N. Conde and A.J.P.L. Policarpo, A Gas Proportional Scintillation Counter, Nucl. Instrum. Meth.53 (1967) 7.A.J.P.L. Policarpo, M.A.F. Alves and C.A.N. Conde, The Argon-Nitrogen Proportional Scintillation Counter, Nucl. Instrum. Meth.55 (1967) 105.J.M.F. dos Santos et al., Development of portable gas proportional scintillation counters for x-ray spectrometry, X-Ray Spectrom.30 (2001) 373.NEXT collaboration, Accurate γ and MeV-electron track reconstruction with an ultra-low diffusion Xenon/TMA TPC at 10 atm, Nucl. Instrum. Meth.A 804 (2015) 8 [arXiv:1504.03678] [INSPIRE].NEXT collaboration, Characterisation of NEXT-DEMO using xenon KαX-rays, 2014 JINST9 P10007 [arXiv:1407.3966] [INSPIRE].NEXT collaboration, Energy calibration of the NEXT-White detector with 1% resolution near Qββof136Xe, JHEP10 (2019) 230 [arXiv:1905.13110] [INSPIRE].R. Lüscher et al., Search for beta beta decay in Xe-136: New results from the Gotthard experiment, Phys. Lett.B 434 (1998) 407 [INSPIRE].NEXT collaboration, First proof of topological signature in the high pressure xenon gas TPC with electroluminescence amplification for the NEXT experiment, JHEP01 (2016) 104 [arXiv:1507.05902] [INSPIRE].NEXT collaboration, Background rejection in NEXT using deep neural networks, 2017 JINST12 T01004 [arXiv:1609.06202] [INSPIRE].NEXT collaboration, The Next White (NEW) Detector, 2018 JINST13 P12010 [arXiv:1804.02409] [INSPIRE].H. Qiao et al., Signal-background discrimination with convolutional neural networks in the PandaX-III experiment using MC simulation, Sci. China Phys. Mech. Astron.61 (2018) 101007 [arXiv:1802.03489] [INSPIRE].NEXT collaboration, Secondary scintillation yield of xenon with sub-percent levels of CO2additive for rare-event detection, Phys. Lett.B 773 (2017) 663 [arXiv:1704.01623] [INSPIRE].C.M.B. Monteiro et al., Secondary Scintillation Yield in Pure Xenon, 2007 JINST2 P05001 [physics/0702142] [INSPIRE].C.M.B. Monteiro, J.A.M. Lopes, J.F. C.A. Veloso and J.M.F. dos Santos, Secondary scintillation yield in pure argon, Phys. Lett.B 668 (2008) 167 [INSPIRE].C.A.B. Oliveira et al., A simulation toolkit for electroluminescence assessment in rare event experiments, Phys. Lett.B 703 (2011) 217 [arXiv:1103.6237] [INSPIRE].E.D.C. Freitas et al., Secondary scintillation yield in high-pressure xenon gas for neutrinoless double beta decay (0νββ) search, Phys. Lett.B 684 (2010) 205 [INSPIRE].C.M.B. Monteiro et al., Secondary scintillation yield from gaseous micropattern electron multipliers in direct dark matter detection, Phys. Lett.B 677 (2009) 133 [INSPIRE].C.M.B. Monteiro, L.M.P. Fernandes, J.F. C.A. Veloso, C.A.B. Oliveira and J.M.F. dos Santos, Secondary scintillation yield from GEM and THGEM gaseous electron multipliers for direct dark matter search, Phys. Lett.B 714 (2012) 18 [INSPIRE].C. Balan et al., MicrOMEGAs operation in high pressure xenon: Charge and scintillation readout, 2011 JINST6 P02006 [arXiv:1009.2960] [INSPIRE].C.M.B. Monteiro, L.M.P. Fernandes, J.F. C.A. Veloso and J.M.F. dos Santos, Secondary scintillation readout from GEM and THGEM with a large area avalanche photodiode, 2012 JINST7 P06012 [INSPIRE].C.D.R. Azevedo et al., An homeopathic cure to pure Xenon large diffusion, 2016 JINST11 C02007 [arXiv:1511.07189] [INSPIRE].C.D.R. Azevedo et al., Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives, Nucl. Intrum. Meth.A 877 (2018) 157 [arXiv:1705.09481] [INSPIRE].NEXT collaboration, Electroluminescence TPCs at the Thermal Diffusion Limit, JHEP01 (2019) 027 [arXiv:1806.05891] [INSPIRE].R.C. Lanza et al., Gas scintillators for imaging of low energy isotopes, IEEE Trans. Nucl. Sci.34 (1987) 406.R. Felkai et al., Helium-Xenon mixtures to improve the topological signature in high pressure gas xenon TPCs, Nucl. Intrum. Meth.A 905 (2018) 82 [arXiv:1710.05600] [INSPIRE].NEXT collaboration, Electron Drift and Longitudinal Diffusion in High Pressure Xenon-Helium Gas Mixtures, 2019 JINST14 P08009 [arXiv:1902.05544] [INSPIRE].J.A.M. Lopes et al., A xenon gas proportional scintillation counter with a UV-sensitive large-area avalanche photodiode, IEEE Trans. Nucl. Sci.48 (2001) 312.C.M.B. Monteiro et al., An argon gas proportional scintillation counter with UV avalanche photodiode scintillation readout, IEEE Trans. Nucl. Sci.48 (2001) 1081.Advanced Photonix, Inc., 1240 Avenida Acaso, Camarillo, CA 93012, U.S.A. .L.M.P. Fernandes et al., Characterization of large area avalanche photodiodes in X-ray and VUV-light detection, 2007 JINST2 P08005 [physics/0702130] [INSPIRE].L.M.P. Fernandes, E.D.C. Freitas, M. Ball, J.J. Gomez-Cadenas, C.M.B. Monteiro, N. Yahlali et al., Primary and secondary scintillation measurements in a xenon Gas Proportional Scintillation Counter, 2010 JINST5 P09006 [Erratum ibid.5 (2010) A12001] [arXiv:1009.2719] [INSPIRE].C.A.B. Oliveira, M. Sorel, J. Martin-Albo, J.J. Gomez-Cadenas, A.L. Ferreira and J.F. C.A. Veloso, Energy Resolution studies for NEXT, 2011 JINST6 P05007 [arXiv:1105.2954] [INSPIRE].D.F. Anderson et al., A large area, gas scintillation proportional counter, Nucl. Instrum. Meth.163 (1979) 125.T.Z. Kowalski et al., Fano factor implications from gas scintillation proportional counter measurements, Nucl. Instrum. Meth.A 279 (1989) 567.T. Doke, Basic properties of high pressure xenon gas as detector medium, in Proceedings of the XeSAT, Tokyo Japan (2005), pg. 92.S.J.C. do Carmo et al., Experimental Study of the ω-Values and Fano Factors of Gaseous Xenon and Ar-Xe Mixtures for X-Rays, IEEE Trans. Nucl. Sci.55 (2008) 2637.A. Buzulutskov, E. Shemyakina, A. Bondar, A. Dolgov, E. Frolov, V. Nosov et al., Revealing neutral bremsstrahlung in two-phase argon electroluminescence, Astropart. Phys.103 (2018) 29 [arXiv:1803.05329] [INSPIRE]

Measurement of the Xe 136 two-neutrino double -decay half-life via direct background subtraction in NEXT

[EN] We report a measurement of the half-life of the 136Xe two-neutrino double-ß decay performed with a novel direct-background-subtraction technique. The analysis relies on the data collected with the NEXT-White detector operated with 136Xe-enriched and 136Xe-depleted xenon, as well as on the topology of double-electron tracks. With a fiducial mass of only 3.5 kg of Xe, a half-life of 2.34+0.80(stat)+0.30(sys)×1021 yr is derived from ¿0.46 ¿0.17 the background-subtracted energy spectrum. The presented technique demonstrates the feasibility of unique background-model-independent neutrinoless double-ß-decay searches.The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under Grant No. 951281-BOLD; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under Grant No. 957202-HIDDEN; the MCIN/AEI/10.13039/501100011033 of Spain and ERDF "A way of making Europe" under Grant No. RTI2018-095979, the Severo Ochoa Program Grant No. CEX2018-000867-S, and the Maria de Maeztu Program Grant No. MDM-2016-0692; the Generalitat Valenciana of Spain under Grants No. PROMETEO/2021/087 and No. CIDEGENT/2019/049; the Portuguese FCT under Project No. UID/FIS/04559/2020 to fund the activities of LIBPhys-UC; the Pazy Foundation (Israel) under Grants No. 877040 and No. 877041; the U.S. Department of Energy under Contracts No. DE-AC02-06CH11357 (Argonne National Laboratory), No. DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), No. DE-FG02-13ER42020 (Texas A&M), No. DE-SC0019054 (Texas Arlington), and No. DE-SC0019223 (Arlington, TX); the U.S. National Science Foundation under Grant No. CHE 2004111; and the Robert A. Welch Foundation under Grant No. Y-203120200401. D.G.D. acknowledges support from the Ramon y Cajal program (Spain) under Contract No. RYC-2015-18820. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Novella, P.; Sorel, M.; Usón, A.; Adams, C.; Almazán, H.; Álvarez-Puerta, V.; Aparicio, B.... (2022). Measurement of the Xe 136 two-neutrino double -decay half-life via direct background subtraction in NEXT. Physical Review C (Online). 105(5):055501-1-055501-8. https://doi.org/10.1103/PhysRevC.105.055501055501-1055501-8105

Radiogenic backgrounds in the NEXT double beta decay experiment

[EN] Natural radioactivity represents one of the main backgrounds in the search for neutrinoless double beta decay. Within the NEXT physics program, the radioactivity- induced backgrounds are measured with the NEXT-White detector. Data from 37.9 days of low-background operations at the Laboratorio Subterraneo de Canfranc with xenon depleted in Xe-136 are analyzed to derive a total background rate of (0.84 +/- 0.02) mHz above 1000 keV. The comparison of data samples with and without the use of the radon abatement system demonstrates that the contribution of airborne-Rn is negligible. A radiogenic background model is built upon the extensive radiopurity screening campaign conducted by the NEXT collaboration. A spectral fit to this model yields the specific contributions of Co-60, K-40, Bi-214 and Tl-208 to the total background rate, as well as their location in the detector volumes. The results are used to evaluate the impact of the radiogenic backgrounds in the double beta decay analyses, after the application of topological cuts that reduce the total rate to (0.25 +/- 0.01) mHz. Based on the best-fit background model, the NEXT-White median sensitivity to the two-neutrino double beta decay is found to be 3.5 sigma after 1 year of data taking. The background measurement in a Q(beta beta)+/- 100 keV energy window validates the best-fit background model also for the neutrinoless double beta decay search with NEXT-100. Only one event is found, while the model expectation is (0.75 +/- 0.12) events.The NEXT collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Marie Sklodowska-Curie Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad and the Ministerio de Ciencia, Innovacion y Universidades of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program SEV-2014-0398 and the Maria de Maetzu Program MDM-2016-0692; the GVA of Spain under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014, under project UID/FIS/04559/2013 to fund the activities of LIBPhys, and under grants PD/BD/105921/2014, SFRH/BPD/109180/2015 and SFRH/BPD/76842/2011; the U.S. Department of Energy under contracts number DE-AC02-06CH11357 (Argonne National Laboratory), DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0019223/DE-SC0019054 (University of Texas at Arlington); and the University of Texas at Arlington. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015-18820. We also warmly acknowledge the Laboratori Nazionali del Gran Sasso (LNGS) and the Dark Side collaboration for their help with TPB coating of various parts of the NEXT-White TPC. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Novella, P.; Palmeiro, B.; Sorel, M.; Usón, A.; Ferrario, P.; Gómez-Cadenas, JJ.; Adams, C.... (2019). Radiogenic backgrounds in the NEXT double beta decay experiment. Journal of High Energy Physics (Online). (10):1-26. https://doi.org/10.1007/JHEP10(2019)051S12610KamLAND-Zen collaboration, Search for Majorana Neutrinos near the Inverted Mass Hierarchy Region with KamLAND-Zen, Phys. Rev. Lett.117 (2016) 082503 [arXiv:1605.02889] [INSPIRE].GERDA collaboration, Improved Limit on Neutrinoless Double-β Decay of76Ge from GERDA Phase II, Phys. Rev. Lett.120 (2018) 132503 [arXiv:1803.11100] [INSPIRE].NEXT collaboration, NEXT-100 Technical Design Report (TDR): Executive Summary, 2012JINST7 T06001 [arXiv:1202.0721] [INSPIRE].M. Redshaw, E. Wingfield, J. McDaniel and E.G. Myers, Mass and double-beta-decay Q value of Xe-136, Phys. Rev. Lett.98 (2007) 053003 [INSPIRE].EXO-200 collaboration, Improved measurement of the 2νββ half-life of136Xe with the EXO-200 detector, Phys. Rev.C 89 (2014) 015502 [arXiv:1306.6106] [INSPIRE].KamLAND-Zen collaboration, Measurement of the double-β decay half-life of136Xe with the KamLAND-Zen experiment, Phys. Rev.C 85 (2012) 045504 [arXiv:1201.4664] [INSPIRE].NEXT collaboration, Initial results on energy resolution of the NEXT-White detector, 2018JINST13 P10020 [arXiv:1808.01804] [INSPIRE].NEXT collaboration, Energy Calibration of the NEXT-White Detector with 1% Resolution Near Qββof136Xe, arXiv:1905.13110 [INSPIRE].NEXT collaboration, Near-Intrinsic Energy Resolution for 30 to 662 keV Gamma Rays in a High Pressure Xenon Electroluminescent TPC, Nucl. Instrum. Meth.A 708 (2013) 101 [arXiv:1211.4474] [INSPIRE].NEXT collaboration, Characterisation of NEXT-DEMO using xenon KαX-rays, 2014JINST9 P10007 [arXiv:1407.3966] [INSPIRE].NEXT collaboration, First proof of topological signature in the high pressure xenon gas TPC with electroluminescence amplification for the NEXT experiment, JHEP01 (2016) 104 [arXiv:1507.05902] [INSPIRE].NEXT collaboration, Demonstration of the event identification capabilities of the NEXT-White detector, arXiv:1905.13141 [INSPIRE].A.D. McDonald et al., Demonstration of Single Barium Ion Sensitivity for Neutrinoless Double Beta Decay using Single Molecule Fluorescence Imaging, Phys. Rev. Lett.120 (2018) 132504 [arXiv:1711.04782] [INSPIRE].P. Thapa et al., Barium Chemosensors with Dry-Phase Fluorescence for Neutrinoless Double Beta Decay, arXiv:1904.05901 [INSPIRE].NEXT collaboration, Ionization and scintillation response of high-pressure xenon gas to alpha particles, 2013 JINST8 P05025 [arXiv:1211.4508] [INSPIRE].NEXT collaboration, Initial results of NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment, 2013 JINST8 P04002 [arXiv:1211.4838] [INSPIRE].NEXT collaboration, Operation and first results of the NEXT-DEMO prototype using a silicon photomultiplier tracking array, 2013 JINST8 P09011 [arXiv:1306.0471] [INSPIRE].NEXT collaboration, Description and commissioning of NEXT-MM prototype: first results from operation in a Xenon-Trimethylamine gas mixture, 2014 JINST9 P03010 [arXiv:1311.3242] [INSPIRE].NEXT collaboration, Ionization and scintillation of nuclear recoils in gaseous xenon, Nucl. Instrum. 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Alvarez et al., Radiopurity control in the NEXT-100 double beta decay experiment: procedures and initial measurements, 2013 JINST8 T01002 [arXiv:1211.3961] [INSPIRE].NEXT collaboration, Radiopurity assessment of the tracking readout for the NEXT double beta decay experiment, 2015 JINST10 P05006 [arXiv:1411.1433] [INSPIRE].NEXT collaboration, Radiopurity assessment of the energy readout for the NEXT double beta decay experiment, 2017 JINST12 T08003 [arXiv:1706.06012] [INSPIRE].NEXT collaboration, Measurement of radon-induced backgrounds in the NEXT double beta decay experiment, JHEP10 (2018) 112 [arXiv:1804.00471] [INSPIRE].NEXT collaboration, Electron drift properties in high pressure gaseous xenon, 2018 JINST13 P07013 [arXiv:1804.01680] [INSPIRE].NEXT collaboration, Calibration of the NEXT-White detector using83m Kr decays, 2018JINST13 P10014 [arXiv:1804.01780] [INSPIRE].NEXT collaboration, Background rejection in NEXT using deep neural networks, 2017JINST12 T01004 [arXiv:1609.06202] [INSPIRE].NEXT collaboration, Application and performance of an ML-EM algorithm in NEXT, 2017JINST12 P08009 [arXiv:1705.10270] [INSPIRE]

Nintedanib targets KIT D816V neoplastic cells derived from induced pluripotent stem cells of systemic mastocytosis

The KIT D816V mutation is found in >80% of patients with systemic mastocytosis (SM) and is key to neoplastic mast cell (MC) expansion and accumulation in affected organs. Therefore, KIT D816V represents a prime therapeutic target for SM. Here, we generated a panel of patient-specific KIT D816V induced pluripotent stem cells (iPSCs) from patients with aggressive SM and mast cell leukemia to develop a patient-specific SM disease model for mechanistic and drug-discovery studies. KIT D816V iPSCs differentiated into neoplastic hematopoietic progenitor cells and MCs with patient-specific phenotypic features, thereby reflecting the heterogeneity of the disease. CRISPR/Cas9n-engineered KIT D816V human embryonic stem cells (ESCs), when differentiated into hematopoietic cells, recapitulated the phenotype observed for KIT D816V iPSC hematopoiesis. KIT D816V causes constitutive activation of the KIT tyrosine kinase receptor, and we exploited our iPSCs and ESCs to investigate new tyrosine kinase inhibitors targeting KIT D816V. Our study identified nintedanib, a US Food and Drug Administration-approved angiokinase inhibitor that targets vascular endothelial growth factor receptor, platelet-derived growth factor receptor, and fibroblast growth factor receptor, as a novel KIT D816V inhibitor. Nintedanib selectively reduced the viability of iPSC-derived KIT D816V hematopoietic progenitor cells and MCs in the nanomolar range. Nintedanib was also active on primary samples of KIT D816V SM patients. Molecular docking studies show that nintedanib binds to the adenosine triphosphate binding pocket of inactive KIT D816V. Our results suggest nintedanib as a new drug candidate for KIT D816V-targeted therapy of advanced SM.Peer reviewe

Demonstration of background rejection using deep convolutional neural networks in the NEXT experiment

[EN] Convolutional neural networks (CNNs) are widely used state-of-the-art computer vision tools that are becoming increasingly popular in high-energy physics. In this paper, we attempt to understand the potential of CNNs for event classification in the NEXT experiment, which will search for neutrinoless double-beta decay in Xe-136. To do so, we demonstrate the usage of CNNs for the identification of electron-positron pair production events, which exhibit a topology similar to that of a neutrinoless double-beta decay event. These events were produced in the NEXT-White high-pressure xenon TPC using 2.6 MeV gamma rays from a Th-228 calibration source. We train a network on Monte Carlo-simulated events and show that, by applying on-the-fly data augmentation, the network can be made robust against differences between simulation and data. The use of CNNs offers significant improvement in signal efficiency and background rejection when compared to previous non-CNN-based analysesThis study used computing resources from Artemisa, co-funded by the European Union through the 2014-2020 FEDER Operative Programme of the Comunitat Valenciana, project DIFEDER/2018/048. This research used resources of the Argonne Leadership Computing Facility, which is a DOE Office of Science User Facility supported under Contract DE-AC02-06CH11357. The NEXT collaboration acknowledges support from the following agencies and institutions: Xunta de Galicia (Centro singularde investigacion de Galicia accreditation 2019-2022), by European Union ERDF, and by the "Maria de Maeztu" Units of Excellence program MDM-2016-0692 and the Spanish Research State Agency"; the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014-2020) under the Grant Agreements No. 674896, 690575 and 740055; the Ministerio de Economia y Competitividad and the Ministerio de Ciencia, Innovacion y Universidades of Spain under grants FIS2014-53371-C04, RTI2018-095979, the Severo Ochoa Program grants SEV-20140398 and CEX2018-000867-S; the GVA of Spain under grants PROMETEO/2016/120 and SEJI/2017/011; the Portuguese FCT under project PTDC/FIS-NUC/2525/2014 and under projects UID/FIS/04559/2020 to fund the activities of LIBPhys-UC; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0019223/DE SC0019054 (University of Texas at Arlington); and the University of Texas at Arlington. DGD acknowledges Ramon y Cajal program (Spain) under contract number RYC-2015 18820. JMA acknowledges support from Fundacion Bancaria "la Caixa" (ID 100010434), grant code LCF/BQ/PI19/11690012. We also warmly acknowledge the Laboratori Nazionali del Gran Sasso (LNGS) and the Dark Side collaboration for their help with TPB coating of various parts of the NEXT-White TPC. Finally, we are grateful to the Laboratorio Subterraneo de Canfranc for hosting and supporting the NEXT experiment.Kekic, M.; Adams, C.; Woodruff, K.; Renner, J.; Church, E.; Del Tutto, M.; Hernando Morata, JA.... (2021). Demonstration of background rejection using deep convolutional neural networks in the NEXT experiment. Journal of High Energy Physics (Online). 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