Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Identification of candidate Parkinson disease genes by integrating genome-wide association study, expression, and epigenetic data sets

Importance Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD. Objective To investigate what genes and genomic processes underlie the risk of sporadic PD. Design and Setting This genetic association study used the bioinformatic tools Coloc and transcriptome-wide association study (TWAS) to integrate PD case-control GWAS data published in 2017 with expression data (from Braineac, the Genotype-Tissue Expression [GTEx], and CommonMind) and methylation data (derived from UK Parkinson brain samples) to uncover putative gene expression and splicing mechanisms associated with PD GWAS signals. Candidate genes were further characterized using cell-type specificity, weighted gene coexpression networks, and weighted protein-protein interaction networks. Main Outcomes and Measures It was hypothesized a priori that some genes underlying PD loci would alter PD risk through changes to expression, splicing, or methylation. Candidate genes are presented whose change in expression, splicing, or methylation are associated with risk of PD as well as the functional pathways and cell types in which these genes have an important role. Results Gene-level analysis of expression revealed 5 genes (WDR6 [OMIM 606031], CD38 [OMIM 107270], GPNMB [OMIM 604368], RAB29 [OMIM 603949], and TMEM163 [OMIM 618978]) that replicated using both Coloc and TWAS analyses in both the GTEx and Braineac expression data sets. A further 6 genes (ZRANB3 [OMIM 615655], PCGF3 [OMIM 617543], NEK1 [OMIM 604588], NUPL2 [NCBI 11097], GALC [OMIM 606890], and CTSB [OMIM 116810]) showed evidence of disease-associated splicing effects. Cell-type specificity analysis revealed that gene expression was overall more prevalent in glial cell types compared with neurons. The weighted gene coexpression performed on the GTEx data set showed that NUPL2 is a key gene in 3 modules implicated in catabolic processes associated with protein ubiquitination and in the ubiquitin-dependent protein catabolic process in the nucleus accumbens, caudate, and putamen. TMEM163 and ZRANB3 were both important in modules in the frontal cortex and caudate, respectively, indicating regulation of signaling and cell communication. Protein interactor analysis and simulations using random networks demonstrated that the candidate genes interact significantly more with known mendelian PD and parkinsonism proteins than would be expected by chance. Conclusions and Relevance Together, these results suggest that several candidate genes and pathways are associated with the findings observed in PD GWAS studies

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

PRISM (Polarized Radiation Imaging and Spectroscopy Mission): an extended white paper

Contains fulltext : 126057.pdf (preprint version ) (Open Access

QUBIC Experiment Toward the First Light

The Q & U Bolometric Interferometer for Cosmology (QUBIC) is a cosmology experiment that aims to measure the B-mode polarization of the cosmic microwave background (CMB). Measurements of the primordial B-mode pattern of the CMB polarization are in fact among the most exciting goals in cosmology as it would allow testing of the inflationary paradigm. Many experiments are attempting to measure the B-modes, from the ground and the stratosphere, using imaging Stokes polarimeters. The QUBIC collaboration developed an innovative concept to measure CMB polarization using bolometric interferometry. This approach mixes the high sensitivity of bolometric detectors with the accurate control of systematics due to the interferometric layout of the instrument. We present the calibration results for the Technological Demonstrator, before its commissioning in the Argentinian observing site and preparation for first light.Fil: D'Alessandro, G.. Università degli studi di Roma "La Sapienza"; ItaliaFil: Battistelli, E. S.. Università degli studi di Roma "La Sapienza"; ItaliaFil: de Bernardis, P.. Università degli studi di Roma "La Sapienza"; ItaliaFil: De Petris, M.. Università degli studi di Roma "La Sapienza"; ItaliaFil: Gamboa Lerena, Martín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Observatorio Astronómico de La Plata - Sede Central; ArgentinaFil: Grandsire, L.. Apc. Astroparticule Et Cosmologie; FranciaFil: Hamilton, Jean-christophe. Apc. Astroparticule Et Cosmologie; FranciaFil: Marnieros, S.. Université Paris-saclay; FranciaFil: Masi, S.. Università degli studi di Roma "La Sapienza"; ItaliaFil: Mennella, A.. Università degli Studi di Milano; ItaliaFil: Mousset, L.. Apc. Astroparticule Et Cosmologie; FranciaFil: O'Sullivan, C.. Maynooth University; Estados UnidosFil: Piat, M.. Apc. Astroparticule Et Cosmologie; FranciaFil: Tartari, A.. Istituto Nazionale Di Fisica Nucleare, Sezione Di Pisa; ItaliaFil: Torchinsky, S. A.. Apc. Astroparticule Et Cosmologie; FranciaFil: Voisin, F.. Apc. Astroparticule Et Cosmologie; FranciaFil: Ade, P.. Cardiff University; Reino UnidoFil: Alberro, José Gabriel. Universidad Nacional de La Plata; ArgentinaFil: Almela, Daniel Alejandro. Comisión Nacional de Energía Atómica; ArgentinaFil: Amico, Georgina. Università degli studi di Roma "La Sapienza"; ItaliaFil: Arnaldi, Luis Horacio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Auguste, D.. Université Paris-saclay; FranciaFil: Aumont, J.. Institut National Des Sciences de L'univers; FranciaFil: Azzoni, S.. University of Oxford; Reino UnidoFil: Banfi, S.. Università Degli Studi Di Milano-bicocca; ItaliaFil: Baù, A.. Università Degli Studi Di Milano-bicocca; ItaliaFil: Bélier, B.. Centre de Nanosciences Et de Nanotechnologies; FranciaFil: Bennett, D.. Maynooth University; Estados UnidosFil: Bergé, L.. Université Paris-saclay; FranciaFil: Bernard, J.-Ph.. Institut National Des Sciences de L'univers; FranciaFil: Cobos Cerutti, Agustin Cleto. Comisión Nacional de Energía Atómica; ArgentinaFil: Duca, C.. Comisión Nacional de Energía Atómica; ArgentinaFil: Etchegoyen, Alberto. Comisión Nacional de Energía Atómica; ArgentinaFil: Fasciszewski, A.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Ferreyro, L. P.. Comisión Nacional de Energía Atómica; ArgentinaFil: Fracchia, D.. Comisión Nacional de Energía Atómica; ArgentinaFil: Garcia, Beatriz Elena. Comisión Nacional de Energía Atómica; ArgentinaFil: García Redondo, Manuel Elías. Comisión Nacional de Energía Atómica; ArgentinaFil: Gómez Berisso, M.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: González, M.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Hampel, Matias Rolf. Comisión Nacional de Energía Atómica; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Kristukat, Ralf Christian. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Melo, D.. Comisión Nacional de Energía Atómica; ArgentinaFil: Mundo, Luis Mariano. Universidad Nacional de La Plata; ArgentinaFil: Pastoriza, Hernan. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Platino, Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Rasztocky, Emiliano. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Ringegni, Pablo Lorenzo. Universidad Nacional de La Plata; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Salum, Juan Manuel. Comisión Nacional de Energía Atómica; ArgentinaFil: Scoccola, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Observatorio Astronómico de La Plata - Sede Central; ArgentinaFil: Supanitsky, Alberto Daniel. Comisión Nacional de Energía Atómica; Argentin

The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population‐Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight

The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. To perform the largest PD genome-wide association study restricted to a single country. We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. © 2019 International Parkinson and Movement Disorder Society

The Genetic Architecture of Parkinson Disease in Spain: Characterizing Population-Specific Risk, Differential Haplotype Structures, and Providing Etiologic Insight.

The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. To perform the largest PD genome-wide association study restricted to a single country. We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. © 2019 International Parkinson and Movement Disorder Society

Moving beyond neurons:the role of cell type-specific gene regulation in Parkinson’s disease heritability

Abstract Parkinson’s disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability attributable to common variation does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set highly expressed in astrocytic, microglial, and oligodendrocyte subtypes, and in LoF-intolerant genes, which were found highly expressed in almost all tested cellular subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes detectable across several cell types

QUBIC VII: The feedhorn-switch system of the technological demonstrator

We present the design, manufacturing and performance of the horn-switch system developed for the technological demonstrator of QUBIC (the Q&U Bolometric Interferometer for Cosmology). This system consists of 64 back-to-back dual-band (150 GHz and 220 GHz) corrugated feed-horns interposed with mechanical switches used to select desired baselines during the instrument self-calibration. We manufactured the horns in aluminum platelets milled by photo-chemical etching and mechanically tightened with screws. The switches are based on steel blades that open and close the waveguide between the back-to-back horns and are operated by miniaturized electromagnets. The measured electromagnetic performance of the feedhorns agrees with simulations. In particular we obtained a return loss around -20 dB up to 230 GHz and beam patterns in agreement with single-mode simulations down to -30 dB. The switches for this prototype were designed and built for the 150 GHz band. In this frequency range we find return and insertion losses consistent with expectations (< -25 dB and ∼-0.1 dB, respectively) and an isolation larger than 70 dB. In this paper we also show the current development status of the feedhorn-switch system for the QUBIC full instrument, based on an array of 400 horn-switch assemblies.Fil: Cavaliere, F.. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Mennella, A.. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Zannoni, M.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Battaglia, P.. Istituto Nazionale di Astrofisica; ItaliaFil: Battistelli, E. S.. Università di Roma; ItaliaFil: De Bernardis, P.. Università di Roma; ItaliaFil: Burke, D.. National University of Ireland Galway; IrlandaFil: D'Alessandro, G.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: De Petris, M.. Università di Roma; ItaliaFil: Franceschet, C.. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Grandsire, L.. Universite de Paris; FranciaFil: Hamilton, J. C.. Universite de Paris; FranciaFil: Maffei, Brenda Luciana. Centre National de la Recherche Scientifique; FranciaFil: Manzan, E.. Università degli Studi di Milano; ItaliaFil: Marnieros, S.. Centre National de la Recherche Scientifique; FranciaFil: Masi, S.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: O'sullivan, Cinthia Virginia. National University of Ireland Galway; IrlandaFil: Passerini, A.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Pezzotta, F. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Piat, M.. Universite de Paris; FranciaFil: Tartari, A.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Torchinsky, S. A.. Universite de Paris; Francia. Centre National de la Recherche Scientifique. Observatoire de Paris; FranciaFil: Viganò, D.. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Voisin, F.. Universite de Paris; FranciaFil: Ade, P.. Cardiff University; Reino UnidoFil: Alberro, José Gabriel. Universidad Nacional de La Plata. Facultad de Ingeniería. Uidet Grupo de Ensayos Mecánicos Aplicados; ArgentinaFil: Almela, A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Amico, G.. Università di Roma; ItaliaFil: Arnaldi, Luis Horacio. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: Auguste, D.. Centre National de la Recherche Scientifique; FranciaFil: Aumont, J.. Centre National de la Recherche Scientifique; FranciaFil: Azzoni, S.. University of Oxford; Reino UnidoFil: Banfi, S.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Baù, A.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Bélier, B.. Centre de Nanosciences et de Nanotechnologies; FranciaFil: Bennett, D.. National University of Ireland Galway; IrlandaFil: Bergé, L.. Centre National de la Recherche Scientifique; FranciaFil: Bernard, J. P.. Centre National de la Recherche Scientifique; FranciaFil: Bersanelli, M.. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Bigot Sazy, M. A.. Universite de Paris; FranciaFil: Bonaparte, J.. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Bonis, J.. Centre National de la Recherche Scientifique; FranciaFil: Bunn, E.. University of Richmond; Estados UnidosFil: Buzi, D.. Università di Roma; ItaliaFil: Chanial, P.. Universite de Paris; FranciaFil: Chapron, C.. Universite de Paris; FranciaFil: Charlassier, R.. Universite de Paris; FranciaFil: Cobos Cerutti, Agustin Cleto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Columbro, F.. Università di Roma; ItaliaFil: Coppolecchia, A.. Università di Roma; ItaliaFil: De Gasperis, G.. Universita Tor Vergata; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: De Leo, M.. Università di Roma; Italia. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Dheilly, S.. Universite de Paris; FranciaFil: Duca, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Dumoulin, L.. Centre National de la Recherche Scientifique; FranciaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Fasciszewski Zeballos, Alejandro Miguel. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Ferreyro, Luciano Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Fracchia, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Gamboa Lerena, Martín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Ganga, K. M.. Universite de Paris; FranciaFil: Garcia, Beatriz Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: García Redondo, Manuel Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Gaspard, M.. Centre National de la Recherche Scientifique; FranciaFil: Gayer, D.. National University of Ireland Galway; IrlandaFil: Gervasi, M.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Giard, M.. Centre National de la Recherche Scientifique; FranciaFil: Gilles, V.. Università di Roma; ItaliaFil: Giraud Heraud, Y.. Universite de Paris; FranciaFil: Gomez Berisso, Mariano. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: González, M.. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: Gradziel, M.. National University of Ireland Galway; IrlandaFil: Hampel, Matias Rolf. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: Henrot Versillé, S.. Centre National de la Recherche Scientifique; FranciaFil: Incardona, F.. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Jules, E.. Centre National de la Recherche Scientifique; FranciaFil: Kaplan, J.. Universite de Paris; FranciaFil: Kristukat, Ralf Christian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lamagna, L.. Università di Roma; ItaliaFil: Loucatos, S.. Universite de Paris; Francia. University of Manchester; Reino UnidoFil: Louis, T.. Centre National de la Recherche Scientifique; FranciaFil: Marty, W.. Centre National de la Recherche Scientifique; FranciaFil: Mattei, A.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: May, A.. Universidad Nacional de San Martín; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: McCulloch, M.. Universidad Nacional de San Martín; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Mele, L.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Melo, Diego Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Montier, L.. Centre National de la Recherche Scientifique; FranciaFil: Mousset, L.. Universite de Paris; FranciaFil: Mundo, Luis Mariano. Universidad Nacional de La Plata. Facultad de Ingeniería. Uidet Grupo de Ensayos Mecánicos Aplicados; ArgentinaFil: Murphy, J. A.. National University of Ireland Galway; IrlandaFil: Murphy, J. D.. National University of Ireland Galway; IrlandaFil: Nati, F.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Olivieri, Enrique Daniel. Centre National de la Recherche Scientifique; FranciaFil: Oriol, C.. Centre National de la Recherche Scientifique; FranciaFil: Paiella, A.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Pajot, F.. Centre National de la Recherche Scientifique; FranciaFil: Pastoriza, Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; ArgentinaFil: Pelosi, A.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Perbost, C.. Universite de Paris; FranciaFil: Perciballi, M.. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Piacentini, F.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Piccirillo, Luis Alberto. Universidad Nacional de San Martín; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Pisano, G.. Cardiff University; Reino UnidoFil: Platino, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Polenta, Gustavo Alberto. Centre D'etudes de Saclay; FranciaFil: Prêle, D.. Universite de Paris; FranciaFil: Puddu, R.. Italian Space Agency; ItaliaFil: Rambaud, D.. Centre National de la Recherche Scientifique; FranciaFil: Rasztocky, Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica de Chile; ChileFil: Ringegni, P.. Universidad Nacional de La Plata. Facultad de Ingeniería. Uidet Grupo de Ensayos Mecánicos Aplicados; ArgentinaFil: Romero, Gustavo Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Pontificia Universidad Católica de Chile; ChileFil: Salum, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Schillaci, A.. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Scoccola, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; ArgentinaFil: Scully, S.. National University of Ireland Galway; IrlandaFil: Spinelli, S. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Stankowiak, G.. Universite de Paris; FranciaFil: Stolpovskiy, M.. Universite de Paris; FranciaFil: Supanitsky, Alberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Thermeau, J. P.. Universite de Paris; FranciaFil: Timbie, P.. University of Wisconsin; Estados UnidosFil: Tomasi, M. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Tucker, C.. Cardiff University; Reino UnidoFil: Tucker, G.. Brown University; Estados UnidosFil: Vittorio, N.. Universita Tor Vergata; ItaliaFil: Wicek, F.. Centre National de la Recherche Scientifique; FranciaFil: Wright, María. Universidad Nacional de San Martín; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Constituyentes; ArgentinaFil: Zullo, Antonia. Istituto Nazionale di Fisica Nucleare; Itali