Representation of foreseeable choice outcomes in orbitofrontal cortex triplet-wise interactions.

Shared neuronal variability has been shown to modulate cognitive processing. However, the relationship between shared variability and behavioral performance is heterogeneous and complex in frontal areas such as the orbitofrontal cortex (OFC). Mounting evidence shows that single-units in OFC encode a detailed cognitive map of task-space events, but the existence of a robust neuronal ensemble coding for the predictability of choice outcome is less established. Here, we hypothesize that the coding of foreseeable outcomes is potentially unclear from the analysis of units activity and their pairwise correlations. However, this code might be established more conclusively when higher-order neuronal interactions are mapped to the choice outcome. As a case study, we investigated the trial-to-trial shared variability of neuronal ensemble activity during a two-choice interval-discrimination task in rodent OFC, specifically designed such that a lose-switch strategy is optimal by repeating the rewarded stimulus in the upcoming trial. Results show that correlations among triplets are higher during correct choices with respect to incorrect ones, and that this is sustained during the entire trial. This effect is not observed for pairwise nor for higher than third-order correlations. This scenario is compatible with constellations of up to three interacting units assembled during trials in which the task is performed correctly. More interestingly, a state-space spanned by such constellations shows that only correct outcome states that can be successfully predicted are robust over 100 trials of the task, and thus they can be accurately decoded. However, both incorrect and unpredictable outcome representations were unstable and thus non-decodeable, due to spurious negative correlations. Our results suggest that predictability of successful outcomes, and hence the optimal behavioral strategy, can be mapped out in OFC ensemble states reliable over trials of the task, and revealed by sufficiency complex neuronal interactions

155-day Periodicity in Solar Cycles 3 and 4

The near 155 days solar periodicity, so called Rieger periodicity, was first detected in solar flares data and later confirmed with other important solar indices. Unfortunately, a comprehensive analysis on the occurrence of this periodicity during previous centuries can be further complicated due to the poor quality of the sunspot number time-series. We try to detect the Rieger periodicity during the solar cycles 3 and 4 using information on aurorae observed at mid and low latitudes. We use two recently discovered aurora datasets, observed in the last quarter of the 18th century from UK and Spain. Besides simple histograms of time between consecutive events we analyse monthly series of number of aurorae observed using different spectral analysis (MTM and Wavelets). The histograms show the probable presence of Rieger periodicity during cycles 3 and 4. However different spectral analysis applied has only confirmed undoubtedly this hypothesis for solar cycle 3.Comment: 13 pages, 6 figures, to appear in New Astronom

Pharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Disease

14 páginas; 9 figuras.Lafora disease (LD, OMIM 254780) is a rare fatal neurodegenerative disorder that usually occurs during childhood with generalized tonic-clonic seizures, myoclonus, absences, drop attacks or visual seizures. Unfortunately, at present, available treatments are only palliatives and no curative drugs are available yet. The hallmark of the disease is the accumulation of insoluble polyglucosan inclusions, called Lafora bodies (LBs), within the neurons but also in heart, muscle and liver cells. Mouse models lacking functional EPM2A or EPM2B genes (the two major loci related to the disease) recapitulate the Lafora disease phenotype: they accumulate polyglucosan inclusions, show signs of neurodegeneration and have a dysregulation of protein clearance and endoplasmic reticulum stress response. In this study, we have subjected a mouse model of LD (Epm2b-/-) to different pharmacological interventions aimed to alleviate protein clearance and endoplasmic reticulum stress. We have used two chemical chaperones, trehalose and 4-phenylbutyric acid. In addition, we have used metformin, an activator of AMP-activated protein kinase (AMPK), as it has a recognized neuroprotective role in other neurodegenerative diseases. Here, we show that treatment with 4-phenylbutyric acid or metformin decreases the accumulation of Lafora bodies and polyubiquitin protein aggregates in the brain of treated animals. 4-Phenylbutyric acid and metformin also diminish neurodegeneration (measured in terms of neuronal loss and reactive gliosis) and ameliorate neuropsychological tests of Epm2b-/- mice. As these compounds have good safety records and are already approved for clinical uses on different neurological pathologies, we think that the translation of our results to the clinical practice could be straightforward.This work was supported by grants from the Spanish Ministry of Education and Science SAF2011-27442, Fundació La Marato de TV3 (ref. 100130) and an ACCI2012 action from CIBERER. A.B. holds a postdoctoral fellowship from the Program “Junta para la Ampliación de Estudios” (JAE-Doc) co-funded by the European Social Fund (ESF).Peer reviewe

New insight into the SSC8 genetic determination of fatty acid composition in pigs

[EN] Background:Fat content and fatty acid composition in swine are becoming increasingly studied because of their effect on sensory and nutritional quality of meat. A QTL (quantitative trait locus) for fatty acid composition in backfat was previously detected on porcine chromosome 8 (SSC8) in an Iberian x Landrace F-2 intercross. More recently, a genome-wide association study detected the same genomic region for muscle fatty acid composition in an Iberian x Landrace backcross population. ELOVL6, a strong positional candidate gene for this QTL, contains a polymorphism in its promoter region (ELOVL6:c.-533C < T), which is associated with percentage of palmitic and palmitoleic acids in muscle and adipose tissues. Here, a combination of single-marker association and the haplotype-based approach was used to analyze backfat fatty acid composition in 470 animals of an Iberian x Landrace F2 intercross genotyped with 144 SNPs (single nucleotide polymorphisms) distributed along SSC8. Results:Two trait-associated SNP regions were identified at 93 Mb and 119 Mb on SSC8. The strongest statistical signals of both regions were observed for palmitoleic acid (C16:1(n-7)) content and C18:0/C16:0 and C18:1(n-7)/C16:1 (n-7) elongation ratios. MAML3 and SETD7 are positional candidate genes in the 93 Mb region and two novel microsatellites in MAML3 and nine SNPs in SETD7 were identified. No significant association for the MAML3 microsatellite genotypes was detected. The SETD7:c. 700G > T SNP, although statistically significant, was not the strongest signal in this region. In addition, the expression of MAML3 and SETD7 in liver and adipose tissue varied among animals, but no association was detected with the polymorphisms in these genes. In the 119 Mb region, the ELOVL6:c.-533C > T polymorphism showed a strong association with percentage of palmitic and palmitoleic fatty acids and elongation ratios in backfat. Conclusions:Our results suggest that the polymorphisms studied in MAML3 and SETD7 are not the causal mutations for the QTL in the 93 Mb region. However, the results for ELOVL6 support the hypothesis that the ELOVL6:c.-533C > T polymorphism has a pleiotropic effect on backfat and intramuscular fatty acid composition and that it has a role in the determination of the QTL in the 119 Mb region.This work was funded by MICINN AGL2008-04818-C03/GAN and MINECO AGL2011-29821-C02 and the Innovation Programme Consolider-Ingenio 2010 (CSD2007-00036). M. Revilla is a Master's student of Animal Breeding and Biotechnology of Reproduction (Polytechnical University of Valencia and Autonomous University of Barcelona). Y. Ramayo-Caldas was funded by a FPU grant (AP2008-01450), J. Corominas by a FPI scholarship from the Ministry of Education (BES-2009-018223) and A. Puig-Oliveras by a PIF scholarship (458-01-1/2011). This manuscript has been proofread by Chuck Simons, a native English speaking university instructor in English.Revilla, M.; Ramayo-Caldas, Y.; Castelló, A.; Corominas, J.; Puig-Oliveras, A.; Ibañez Escriche, N.; Muñoz, M.... (2014). New insight into the SSC8 genetic determination of fatty acid composition in pigs. Genetics Selection Evolution. 46. https://doi.org/10.1186/1297-9686-46-28S46Clarke, R., Frost, C., Collins, R., Appleby, P., & Peto, R. (1997). Dietary lipids and blood cholesterol: quantitative meta-analysis of metabolic ward studies. BMJ, 314(7074), 112-112. doi:10.1136/bmj.314.7074.112Mensink, R. P., & Katan, M. B. (1992). Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology, 12(8), 911-919. doi:10.1161/01.atv.12.8.911Hunter, J. E., Zhang, J., & Kris-Etherton, P. M. (2009). Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. The American Journal of Clinical Nutrition, 91(1), 46-63. doi:10.3945/ajcn.2009.27661Astrup, A., Dyerberg, J., Elwood, P., Hermansen, K., Hu, F. B., Jakobsen, M. U., … Willett, W. C. (2011). The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010? The American Journal of Clinical Nutrition, 93(4), 684-688. doi:10.3945/ajcn.110.004622Harris, W. S., Poston, W. C., & Haddock, C. K. (2007). Tissue n−3 and n−6 fatty acids and risk for coronary heart disease events. Atherosclerosis, 193(1), 1-10. doi:10.1016/j.atherosclerosis.2007.03.018Lopez-Huertas, E. (2010). Health effects of oleic acid and long chain omega-3 fatty acids (EPA and DHA) enriched milks. A review of intervention studies. Pharmacological Research, 61(3), 200-207. doi:10.1016/j.phrs.2009.10.007Guo, T., Ren, J., Yang, K., Ma, J., Zhang, Z., & Huang, L. (2009). Quantitative trait loci for fatty acid composition in longissimus dorsi and abdominal fat: results from a White Duroc × Erhualian intercross F2population. Animal Genetics, 40(2), 185-191. doi:10.1111/j.1365-2052.2008.01819.xUemoto, Y., Soma, Y., Sato, S., Ishida, M., Shibata, T., Kadowaki, H., … Suzuki, K. (2011). Genome-wide mapping for fatty acid composition and melting point of fat in a purebred Duroc pig population. Animal Genetics, 43(1), 27-34. doi:10.1111/j.1365-2052.2011.02218.xClop, A., Ovilo, C., Perez-Enciso, M., Cercos, A., Tomas, A., Fernandez, A., … Noguera, J. L. (2003). Detection of QTL affecting fatty acid composition in the pig. Mammalian Genome, 14(9), 650-656. doi:10.1007/s00335-002-2210-7Ramayo-Caldas, Y., Mercadé, A., Castelló, A., Yang, B., Rodríguez, C., Alves, E., … Folch, J. M. (2012). Genome-wide association study for intramuscular fatty acid composition in an Iberian × Landrace cross1. Journal of Animal Science, 90(9), 2883-2893. doi:10.2527/jas.2011-4900Muñoz, M., Rodríguez, M. C., Alves, E., Folch, J. M., Ibañez-Escriche, N., Silió, L., & Fernández, A. I. (2013). Genome-wide analysis of porcine backfat and intramuscular fat fatty acid composition using high-density genotyping and expression data. BMC Genomics, 14(1), 845. doi:10.1186/1471-2164-14-845Ramos, A. M., Crooijmans, R. P. M. A., Affara, N. A., Amaral, A. J., Archibald, A. L., Beever, J. E., … Groenen, M. A. M. (2009). Design of a High Density SNP Genotyping Assay in the Pig Using SNPs Identified and Characterized by Next Generation Sequencing Technology. PLoS ONE, 4(8), e6524. doi:10.1371/journal.pone.0006524Estellé, J., Mercadé, A., Pérez-Enciso, M., Pena, R. N., Silió, L., Sánchez, A., & Folch, J. M. (2009). Evaluation ofFABP2as candidate gene for a fatty acid composition QTL in porcine chromosome 8. Journal of Animal Breeding and Genetics, 126(1), 52-58. doi:10.1111/j.1439-0388.2008.00754.xEstellé, J., Fernández, A. I., Pérez-Enciso, M., Fernández, A., Rodríguez, C., Sánchez, A., … Folch, J. M. (2009). A non-synonymous mutation in a conserved site of theMTTPgene is strongly associated with protein activity and fatty acid profile in pigs. Animal Genetics, 40(6), 813-820. doi:10.1111/j.1365-2052.2009.01922.xPurcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., … Sham, P. C. (2007). PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses. The American Journal of Human Genetics, 81(3), 559-575. doi:10.1086/519795Pérez-Enciso, M., & Misztal, I. (2011). Qxpak.5: Old mixed model solutions for new genomics problems. BMC Bioinformatics, 12(1). doi:10.1186/1471-2105-12-202Storey, J. D., & Tibshirani, R. (2003). Statistical significance for genomewide studies. Proceedings of the National Academy of Sciences, 100(16), 9440-9445. doi:10.1073/pnas.1530509100Druet, T., & Georges, M. (2009). A Hidden Markov Model Combining Linkage and Linkage Disequilibrium Information for Haplotype Reconstruction and Quantitative Trait Locus Fine Mapping. Genetics, 184(3), 789-798. doi:10.1534/genetics.109.108431Werle, E., Schneider, C., Renner, M., Völker, M., & Fiehn, W. (1994). Convenient single-step, one tube purification of PCR products for direct sequencing. Nucleic Acids Research, 22(20), 4354-4355. doi:10.1093/nar/22.20.4354Ballester, M., Cordón, R., & Folch, J. M. (2013). DAG Expression: High-Throughput Gene Expression Analysis of Real-Time PCR Data Using Standard Curves for Relative Quantification. PLoS ONE, 8(11), e80385. doi:10.1371/journal.pone.0080385Karim, L., Takeda, H., Lin, L., Druet, T., Arias, J. A. C., Baurain, D., … Coppieters, W. (2011). Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature. Nature Genetics, 43(5), 405-413. doi:10.1038/ng.814Oyama, T., Harigaya, K., Sasaki, N., Okamura, Y., Kokubo, H., Saga, Y., … Kitagawa, M. (2011). Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo. Development, 138(23), 5235-5246. doi:10.1242/dev.062802Pajvani, U. B., Qiang, L., Kangsamaksin, T., Kitajewski, J., Ginsberg, H. N., & Accili, D. (2013). Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability. Nature Medicine, 19(8), 1054-1060. doi:10.1038/nm.3259Syreeni, A., El-Osta, A., Forsblom, C., Sandholm, N., Parkkonen, M., … Tarnow, L. (2011). Genetic Examination of SETD7 and SUV39H1/H2 Methyltransferases and the Risk of Diabetes Complications in Patients With Type 1 Diabetes. Diabetes, 60(11), 3073-3080. doi:10.2337/db11-0073Chakrabarti, S. K., Francis, J., Ziesmann, S. M., Garmey, J. C., & Mirmira, R. G. (2003). Covalent Histone Modifications Underlie the Developmental Regulation of Insulin Gene Transcription in Pancreatic β Cells. Journal of Biological Chemistry, 278(26), 23617-23623. doi:10.1074/jbc.m303423200Ramayo-Caldas, Y., Mach, N., Esteve-Codina, A., Corominas, J., Castelló, A., Ballester, M., … Folch, J. M. (2012). Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition. BMC Genomics, 13(1), 547. doi:10.1186/1471-2164-13-547Corominas, J., Ramayo-Caldas, Y., Puig-Oliveras, A., Pérez-Montarelo, D., Noguera, J. L., Folch, J. M., & Ballester, M. (2013). Polymorphism in the ELOVL6 Gene Is Associated with a Major QTL Effect on Fatty Acid Composition in Pigs. PLoS ONE, 8(1), e53687. doi:10.1371/journal.pone.005368

Proposal of a Viscous Model for Nonviscously Damped Beams Based on Fractional Derivatives

[EN] Viscoelastic materials are widely used in structural dynamics for the control of the vibrations and energy dissipation. They are characterized by damping forces that depend on the history of the velocity response via hereditary functions involved in convolution integrals, leading to a frequency-dependent damping matrix. In this paper, one-dimensional beam structures with viscoelastic materials based on fractional derivatives are considered. In this work, the construction of a new equivalent viscous system with fictitious parameters but capable of reproducing the response of the viscoelastic original one with acceptable accuracy is proposed. This allows us to take advantage of the well-known available numerical tools for viscous systems and use them to find response of viscoelastic structures. The process requires the numerical computation of complex frequencies. The new fictitious viscous parameters are found to be matching the information provided by the frequency response functions. New mass, damping, and stiffness matrices are found, which in addition have the property of proportionality, so they become diagonal in the modal space. The theoretical results are contrasted with two different numerical examples.Lázaro, M.; Molines Cano, J.; Ferrer Ballester, I.; Albero Gabarda, V. (2018). Proposal of a Viscous Model for Nonviscously Damped Beams Based on Fractional Derivatives. Shock and Vibration. 2018:1-14. https://doi.org/10.1155/2018/5957831S114201

Automatic quantification of cardiomyocyte dimensions and connexin 43 lateralization in fluorescence images

Cardiomyocytes’ geometry and connexin 43 (CX43) amount and distribution are structural features that play a pivotal role in electrical conduction. Their quantitative assessment is of high interest in the study of arrhythmias, but it is usually hampered by the lack of automatic tools. In this work, we propose a software algorithm (Myocyte Automatic Retrieval and Tissue Analyzer, MARTA) to automatically detect myocytes from fluorescent microscopy images of cardiac tissue, measure their morphological features and evaluate the expression of CX43 and its degree of lateralization. The proposed software is based on the generation of cell masks, contouring of individual cells, enclosing of cells in minimum area rectangles and splitting of these rectangles into end-to-end and middle compartments to estimate CX43 lateral-to-total ratio. Application to human ventricular tissue images shows that mean differences between automatic and manual methods in terms of cardiomyocyte length and width are below 4 µm. The percentage of lateral CX43 also agrees between automatic and manual evaluation, with the interquartile range approximately covering from 3% to 30% in both cases. MARTA is not limited by fiber orientation and has an optimized speed by using contour filtering, which makes it run hundreds of times faster than a trained expert. Developed for CX43 studies in the left ventricle, MARTA is a flexible tool applicable to morphometric and lateralization studies of other markers in any heart chamber or even skeletal muscle. This open-access software is available online

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

Monte Carlo characterization of PETALO, a full-body liquid xenon-based PET detector

[EN] New detector approaches in Positron Emission Tomography imaging will play an important role in reducing costs, lowering administered radiation doses, and improving overall performance. PETALO employs liquid xenon as the active scintillating medium and UV-sensitive silicon photomultipliers for scintillation readout. The scintillation time in liquid xenon is fast enough to register time-of-flight information for each detected coincidence, and sufficient scintillation is produced with low enough fluctuations to obtain good energy resolution. The present simulation study examines a full-body-sized PETALO detector and evaluates its potential performance in PET image reconstruction.This work was supported by the European Research Council under grant ID 757829 and by Ministerio de Economia y Competitividad for grant FPA2016-78595-C3-1-R.Renner, J.; Romo-Luque, C.; Aliaga, RJ.; Álvarez-Puerta, V.; Ballester Merelo, FJ.; Benlloch-Rodríguez, J.; Carrión, J.... (2022). Monte Carlo characterization of PETALO, a full-body liquid xenon-based PET detector. Journal of Instrumentation. 17(5):1-14. https://doi.org/10.1088/1748-0221/17/05/P0504411417