94 research outputs found
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Demonstration of the event identification capabilities of the NEXT-White detector
In experiments searching for neutrinoless double-beta decay, the possibility of identifying the two emitted electrons is a powerful tool in rejecting background events and therefore improving the overall sensitivity of the experiment. In this paper we present the first measurement of the efficiency of a cut based on the different event signatures of double and single electron tracks, using the data of the NEXT-White detector, the first detector of the NEXT experiment operating underground. Using a 228Th calibration source to produce signal-like and background-like events with energies near 1.6 MeV, a signal efficiency of 71.6 ± 1.5 stat± 0.3 sys% for a background acceptance of 20.6 ± 0.4 stat± 0.3 sys% is found, in good agreement with Monte Carlo simulations. An extrapolation to the energy region of the neutrinoless double beta decay by means of Monte Carlo simulations is also carried out, and the results obtained show an improvement in background rejection over those obtained at lower energies. [Figure not available: see fulltext.
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Radiogenic backgrounds in the NEXT double beta decay experiment
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 Subterráneo de Canfranc with xenon depleted in 136Xe 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 60Co, 40K, 214Bi and 208Tl 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 3.5σ after 1 year of data taking. The background measurement in a Qββ±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. [Figure not available: see fulltext.]
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Energy calibration of the NEXT-White detector with 1% resolution near Q ββ of 136Xe
Excellent energy resolution is one of the primary advantages of electroluminescent high-pressure xenon TPCs. These detectors are promising tools in searching for rare physics events, such as neutrinoless double-beta decay (ββ0ν), which require precise energy measurements. Using the NEXT-White detector, developed by the NEXT (Neutrino Experiment with a Xenon TPC) collaboration, we show for the first time that an energy resolution of 1% FWHM can be achieved at 2.6 MeV, establishing the present technology as the one with the best energy resolution of all xenon detectors for ββ0ν searches. [Figure not available: see fulltext.
HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico
Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA
Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7473G>A (p.=) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of 3 mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that 4 of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease.info:eu-repo/semantics/publishedVersio
Unraveling the effect of silent, intronic and missense mutations on VWF splicing: contribution of next generation sequencing in the study of mRNA
Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. clinicaltrials.gov identifier:02869074
Electroluminescence TPCs at the thermal diffusion limit
[EN] The NEXT experiment aims at searching for the hypothetical neutrinoless double-beta decay from the 136Xe isotope using a high-purity xenon TPC. Efficient discrimination of the events through pattern recognition of the topology of primary ionisation tracks is a major requirement for the experiment. However, it is limited by the diffusion of electrons. It is known that the addition of a small fraction of a molecular gas to xenon reduces electron diffusion. On the other hand, the electroluminescence (EL) yield drops and the achievable energy resolution may be compromised. We have studied the effect of adding several molecular gases to xenon (CO2, CH4 and CF4) on the EL yield and energy resolution obtained in a small prototype of driftless gas proportional scintillation counter. We have compared our results on the scintillation characteristics (EL yield and energy resolution) with a microscopic simulation, obtaining the diffusion coefficients in those conditions as well. Accordingly, electron diffusion may be reduced from about 10 mm/ sqrt(¿) for pure xenon down to 2.5 mm/sqrt(m) using additive concentrations of about 0.05%, 0.2% and 0.02% for CO2, CH4 and CF4, respectively. Our results show that CF4 admixtures present the highest EL yield in those conditions, but very poor energy resolution as a result of huge fluctuations observed in the EL formation. CH4 presents the best energy resolution despite the EL yield being the lowest. The results obtained with xenon admixtures are extrapolated to the operational conditions of the NEXT-100 TPC. CO2 and CH4 show potential as molecular additives in a large xenon TPC. While CO2 has some operational constraints, making it difficult to be used in a large TPC, CH4 shows the best performance and stability as molecular additive to be used in the NEXT-100 TPC, with an extrapolated energy resolution of 0.4% at 2.45 MeV for concentrations below 0.4%, which is only slightly worse than the one obtained for pure xenon. We demonstrate the possibility to have an electroluminescence TPC operating very close to the thermal diffusion limit without jeopardizing the TPC performance, if CO2 or CH4 are chosen as additives.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 of Spain under grants FIS2014-53371-C04, 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-AC02-07CH11359 (Fermi National Accelerator Laboratory), DE-AC02-06CH11357 (Argonne National Laboratory), DE-FG02-13ER42020 (Texas A&M) and DE-SC0017721 (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.Henriques, CAO.; Monteiro, CMB.; Gonzalez-Diaz, D.; Azevedo, CDR.; Freitas, EDC.; Mano, RDP.; Jorge, MR.... (2019). Electroluminescence TPCs at the thermal diffusion limit. Journal of High Energy Physics (Online). 1:1-20. https://doi.org/10.1007/JHEP01(2019)027S1201NEXT collaboration, J. Martín-Albo et al., Sensitivity of NEXT-100 to neutrinoless double beta decay, JHEP 05 (2016) 159 [ arXiv:1511.09246 ] [ INSPIRE ].T. Brunner et al., An RF-only ion-funnel for extraction from high-pressure gases, Intern. J. Mass Spectrom. 379 (2015) 110 [ INSPIRE ].PANDAX-III collaboration, J. Galan, Microbulk MicrOMEGAs for the search of 0νββ of 136 Xe in the PandaX-III experiment, 2016 JINST 11 P04024 [ arXiv:1512.09034 ] [ 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 in 124 Xe with a copper proportional counter, Phys. Atom. Nucl. 78 (2015) 1563 [ INSPIRE ].D.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 ].XENON collaboration, E. Aprile et al., First Dark Matter Search Results from the XENON1T Experiment, Phys. Rev. Lett. 119 (2017) 181301 [ arXiv:1705.06655 ] [ INSPIRE ].XENON100 collaboration, E. Aprile et al., Dark Matter Results from 225 Live Days of XENON100 Data, Phys. Rev. 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Aprile et al., Search for two-neutrino double electron capture of 124 Xe with XENON100, Phys. Rev. C 95 (2017) 024605 [ arXiv:1609.03354 ] [ INSPIRE ].R. Lüscher et al., Search for ββ decay in 136 Xe: new results from the Gotthard experiment, Phys. Lett. B 434 (1998) 407 [ INSPIRE ].NEXT collaboration, P. Ferrario et al., First proof of topological signature in the high pressure xenon gas TPC with electroluminescence amplification for the NEXT experiment, JHEP 01 (2016) 104 [ arXiv:1507.05902 ] [ INSPIRE ].NEXT collaboration, D. Lorca et al., Characterisation of NEXT-DEMO using xenon K α X-rays, 2014 JINST 9 P10007 [ arXiv:1407.3966 ] [ INSPIRE ].NEXT collaboration, D. González-Díaz et al., 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 ].C.M.B. Monteiro et al., Secondary Scintillation Yield in Pure Xenon, 2007 JINST 2 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 ].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 JINST 6 P02006 [ arXiv:1009.2960 ] [ INSPIRE ].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, J. Renner et al., Background rejection in NEXT using deep neural networks, 2017 JINST 12 T01004 [ arXiv:1609.06202 ] [ INSPIRE ].T. Himi et al., Emission spectra from Ar-Xe, Ar-Kr, Ar-N2, Ar-CH4, Ar-CO2 and Xe-N2 gas proportional scintillation counters, Nucl. Instrum. Meth. 205 (1983) 591.C.D.R. Azevedo et al., An homeopathic cure to pure Xenon large diffusion, 2016 JINST 11 C02007 [ arXiv:1511.07189 ] [ INSPIRE ].NEXT collaboration, C.A.O. Henriques et al., Secondary scintillation yield of xenon with sub-percent levels of CO 2 additive for rare-event detection, Phys. Lett. B 773 (2017) 663 [ arXiv:1704.01623 ] [ INSPIRE ].P.C.P.S. Simões, J.M.F. dos Santos and C.A.N. Conde, Driftless gas proportional scintillation counter pulse analysis using digital processing techniques, X Ray Spectrom. 30 (2001) 342.P.C.P.S. Simões et al., A new method for pulse analysis of driftless-gas proportional scintillation counters, Nucl. Instrum. Meth. A 505 (2003) 247.C.D.R. Azevedo et al., Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives, Nucl. Instrum. Meth. A 877 (2018) 157 [ arXiv:1705.09481 ] [ INSPIRE ].L.M.P. Fernandes et al., Primary and secondary scintillation measurements in a xenon Gas Proportional Scintillation Counter, 2010 JINST 5 P09006 [Erratum ibid. 5 (2010) A12001] [ arXiv:1009.2719 ] [ INSPIRE ].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.J.A.M. Lopes et al., A xenon gas proportional scintillation counter with a UV-sensitive large-area avalanche photodiode, IEEE Trans. Nucl. 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Álvarez et al., The NEXT-100 experiment for neutrinoless double beta decay searches (Conceptual Design Report), arXiv:1106.3630 [ INSPIRE ].NEXT collaboration, V. Álvarez et al., Operation and first results of the NEXT-DEMO prototype using a silicon photomultiplier tracking array, 2013 JINST 8 P09011 [ arXiv:1306.0471 ] [ INSPIRE ]
Molecular Characterization of the Region 7q22.1 in Splenic Marginal Zone Lymphomas
Splenic marginal zone lymphomas (SMZL) are an uncommon type of B-cell non-Hodgkin's lymphoma (NHL-B) in which no specific chromosomal translocations have been described. In contrast, the most frequent cytogenetic abnormality is the loss of the long arm of chromosome 7 (7q). Previous reports have located this loss in the 7q32 region. In order to better characterize the genomic imbalances in SMZL, molecular studies were carried out in 73 patients with SMZL. To gain insight into the mapping at 7q a tiling array was also used. The results confirmed the loss of 7q as the most frequent change. In addition, several abnormalities, including 4q22.1, 1q21.3–q22, 6q25.3, 20q13.33, 3q28, 2q23.3–q24.1 and 17p13, were also present. A loss of 7q22.1 at 99925039–101348479 bp was observed in half of the cases. The region of 7q22.1 has not previously been characterised in SMZL. Our results confirmed the presence of a new region of loss on chromosome 7 in these NHL
Barriers to Non-Viral Vector-Mediated Gene Delivery in the Nervous System
Efficient methods for cell line transfection are well described, but, for primary neurons, a high-yield method different from those relying on viral vectors is lacking. Viral transfection has several drawbacks, such as the complexity of vector preparation, safety concerns, and the generation of immune and inflammatory responses when used in vivo. However, one of the main problems for the use of non-viral gene vectors for neuronal transfection is their low efficiency when compared with viral vectors. Transgene expression, or siRNA delivery mediated by non-viral vectors, is the result of multiple processes related to cellular membrane crossing, intracellular traffic, and/or nuclear delivery of the genetic material cargo. This review will deal with the barriers that different nanoparticles (cationic lipids, polyethyleneimine, dendrimers and carbon nanotubes) must overcome to efficiently deliver their cargo to central nervous system cells, including internalization into the neurons, interaction with intracellular organelles such as lysosomes, and transport across the nuclear membrane of the neuron in the case of DNA transfection. Furthermore, when used in vivo, the nanoparticles should efficiently cross the blood-brain barrier to reach the target cells in the brain
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