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1. Soluble Triggering Receptors Expressed on Myeloid Cells (sTREM) in Acute Ischemic Stroke: A Potential Pathway of sTREM-1 and sTREM-2 Associated with Disease Severity

Author

Greta Salafia, Angelica Carandina, Roberto Maria Sacco, Evelyn Ferri, Nicola Montano, Beatrice Arosio, and Eleonora Tobaldini

Subjects
ischemic stroke, neuroinflammation, soluble TREM-1, soluble TREM-2, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

In 2022, stroke emerged as the most significant cerebrovascular disorder globally, causing 6.55 million deaths. Microglia, crucial for CNS preservation, can exacerbate brain damage in ischemic stroke by triggering neuroinflammation. This process is mediated by receptors on microglia, triggering receptors expressed on myeloid cells (TREM-1 and TREM-2), which have contrasting roles in neuroinflammation. In this study, we recruited 38 patients within 4.5 h from the onset of ischemic stroke. The degree of severity was evaluated by means of the National Institutes of Health Stroke Scale (NIHSS) at admission (T0) and after one week of ischemic events (TW) and the Modified Rankin Scale (mRS) at three months. The plasma concentration of TREMs (sTREM) was analyzed by next-generation ELISA at T0 and TW. The sTREM-1 concentrations at T0 were associated with mRS, while the sTREM-2 concentrations at T0 were associated with both the NIHSS at T0 and the mRS. A strong correlation between sTREM-1 and sTREM-2 was observed, suggesting a dependent modulation of the levels. This study provides insights into the potential pathway of TREM-1 and TREM-2 as a future biomarker for stratifying high-risk patients with ischemic stroke.

Published
2024
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2. Altered Extracellular Vesicle miRNA Profile in Prodromal Alzheimer’s Disease

Author

Caterina Visconte, Chiara Fenoglio, Maria Serpente, Paola Muti, Andrea Sacconi, Marta Rigoni, Andrea Arighi, Vittoria Borracci, Marina Arcaro, Beatrice Arosio, Evelyn Ferri, Maria Teresa Golia, Elio Scarpini, and Daniela Galimberti

Subjects
extracellular vesicles, Alzheimer’s disease (AD), miRNA, biomarker, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Extracellular vesicles (EVs) are nanosized vesicles released by almost all body tissues, representing important mediators of cellular communication, and are thus promising candidate biomarkers for neurodegenerative diseases like Alzheimer’s disease (AD). The aim of the present study was to isolate total EVs from plasma and characterize their microRNA (miRNA) contents in AD patients. We isolated total EVs from the plasma of all recruited subjects using ExoQuickULTRA exosome precipitation solution (SBI). Subsequently, circulating total EVs were characterized using Nanosight nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. A panel of 754 miRNAs was determined with RT-qPCR using TaqMan OpenArray technology in a QuantStudio 12K System (Thermo Fisher Scientific). The results demonstrated that plasma EVs showed widespread deregulation of specific miRNAs (miR-106a-5p, miR-16-5p, miR-17-5p, miR-195-5p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-296-5p, miR-30b-5p, miR-532-3p, miR-92a-3p, and miR-451a), some of which were already known to be associated with neurological pathologies. A further validation analysis also confirmed a significant upregulation of miR-16-5p, miR-25-3p, miR-92a-3p, and miR-451a in prodromal AD patients, suggesting these dysregulated miRNAs are involved in the early progression of AD.

Published
2023
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3. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernández, Laura Montrreal, Carmen Antúnez, Anna Antonell, Rick M. Tankard, Joshua C. Bis, Rebecca Sims, Céline Bellenguez, Inés Quintela, Antonio González-Perez, Miguel Calero, Emilio Franco-Macías, Juan Macías, Rafael Blesa, Laura Cervera-Carles, Manuel Menéndez-González, Ana Frank-García, Jose Luís Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Mónica Diez-Fairen, Carmen Lage, Sebastián García-Madrona, Pablo García-González, Emilio Alarcón-Martín, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Pérez-Cordón, Alberto Benussi, Alberto Rábano, Alessandro Padovani, Alessio Squassina, Alexandre de Mendonça, Alfonso Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belén Pastor, Ana Espinosa, Anaïs Corma-Gómez, Angel Martín Montes, Ángela Sanabria, Anita L. DeStefano, Anja Schneider, Annakaisa Haapasalo, Anne Kinhult Ståhlbom, Anne Tybjærg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbatón-Anchuelo, Arvid Rongve, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Børge G. Nordestgaard, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martínez Rodríguez, Carmen Muñoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina B. Ferreira, Caterina Chillotti, Chandra A. Reynolds, Chiara Fenoglio, Christine Van Broeckhoven, Christopher Clark, Claudia Pisanu, Claudia L. Satizabal, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland, Dan Rujescu, Daniel Alcolea, Daniela Galimberti, David Wallon, Davide Seripa, Edna Grünblatt, Efthimios Dardiotis, Emrah Düzel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Küçükali, Florence Pasquier, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gaël Nicolas, Geir Selbæk, Gemma Ortega, Geneviève Chêne, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg, Hilkka Soininen, Ida K. Karlsson, Ignacio Alvarez, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen, Jean-Sebastien Vidal, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber, Jonathan L. Haines, Jonathan Vogelgsang, Juan A. Pineda, Juan Fortea, Julius Popp, Jürgen Deckert, Katharina Buerger, Kevin Morgan, Klaus Fließbach, Kristel Sleegers, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay A. Farrer, Li-San Wang, Luca Kleineidam, Lucia Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram, M. Candida Deniz-Naranjo, Magda Tsolaki, Maitée Rosende-Roca, Malin Löwenmark, Marc Hulsman, Marco Spallazzi, Margaret A. Pericak-Vance, Margaret Esiri, María Bernal Sánchez-Arjona, Maria Carolina Dalmasso, María Teresa Martínez-Larrad, Marina Arcaro, Markus M. Nöthen, Marta Fernández-Fuertes, Martin Dichgans, Martin Ingelsson, Martin J. Herrmann, Martin Scherer, Martin Vyhnalek, Mary H. Kosmidis, Mary Yannakoulia, Matthias Schmid, Michael Ewers, Michael T. Heneka, Michael Wagner, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja M. van Schoor, Nazib M. Seidu, Nerisa Banaj, Nicola J. Armstrong, Nikolaos Scarmeas, Norbert Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez, Ondrej Lerch, Paola Bossù, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Per Hoffmann, Peter A. Holmans, Peter Fischer, Peter Riederer, Qiong Yang, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Hägg, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi, Valentina Escott-Price, Vilmantas Giedraitis, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian, Yolande A. L. Pijnenburg, EADB contributors, DEGESCO consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ consortia, Patrick Gavin Kehoe, Guillermo Garcia-Ribas, Pascual Sánchez-Juan, Pau Pastor, Jordi Pérez-Tur, Gerard Piñol-Ripoll, Adolfo Lopez de Munain, Jose María García-Alberca, María J. Bullido, Victoria Álvarez, Alberto Lleó, Luis M. Real, Pablo Mir, Miguel Medina, Philip Scheltens, Henne Holstege, Marta Marquié, María Eugenia Sáez, Ángel Carracedo, Philippe Amouyel, Gerard D. Schellenberg, Julie Williams, Sudha Seshadri, Cornelia M. van Duijn, Karen A. Mather, Raquel Sánchez-Valle, Manuel Serrano-Ríos, Adelina Orellana, Lluís Tárraga, Kaj Blennow, Martijn Huisman, Ole A. Andreassen, Danielle Posthuma, Jordi Clarimón, Mercè Boada, Wiesje M. van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. van der Lee, and Agustín Ruiz

Subjects
Science
Abstract

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Published
2021
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4. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Author

Itziar de Rojas, Sonia Moreno-Grau, Niccolo Tesi, Benjamin Grenier-Boley, Victor Andrade, Iris E. Jansen, Nancy L. Pedersen, Najada Stringa, Anna Zettergren, Isabel Hernández, Laura Montrreal, Carmen Antúnez, Anna Antonell, Rick M. Tankard, Joshua C. Bis, Rebecca Sims, Céline Bellenguez, Inés Quintela, Antonio González-Perez, Miguel Calero, Emilio Franco-Macías, Juan Macías, Rafael Blesa, Laura Cervera-Carles, Manuel Menéndez-González, Ana Frank-García, Jose Luís Royo, Fermin Moreno, Raquel Huerto Vilas, Miquel Baquero, Mónica Diez-Fairen, Carmen Lage, Sebastián García-Madrona, Pablo García-González, Emilio Alarcón-Martín, Sergi Valero, Oscar Sotolongo-Grau, Abbe Ullgren, Adam C. Naj, Afina W. Lemstra, Alba Benaque, Alba Pérez-Cordón, Alberto Benussi, Alberto Rábano, Alessandro Padovani, Alessio Squassina, Alexandre de Mendonça, Alfonso Arias Pastor, Almar A. L. Kok, Alun Meggy, Ana Belén Pastor, Ana Espinosa, Anaïs Corma-Gómez, Angel Martín Montes, Ángela Sanabria, Anita L. DeStefano, Anja Schneider, Annakaisa Haapasalo, Anne Kinhult Ståhlbom, Anne Tybjærg-Hansen, Annette M. Hartmann, Annika Spottke, Arturo Corbatón-Anchuelo, Arvid Rongve, Barbara Borroni, Beatrice Arosio, Benedetta Nacmias, Børge G. Nordestgaard, Brian W. Kunkle, Camille Charbonnier, Carla Abdelnour, Carlo Masullo, Carmen Martínez Rodríguez, Carmen Muñoz-Fernandez, Carole Dufouil, Caroline Graff, Catarina B. Ferreira, Caterina Chillotti, Chandra A. Reynolds, Chiara Fenoglio, Christine Van Broeckhoven, Christopher Clark, Claudia Pisanu, Claudia L. Satizabal, Clive Holmes, Dolores Buiza-Rueda, Dag Aarsland, Dan Rujescu, Daniel Alcolea, Daniela Galimberti, David Wallon, Davide Seripa, Edna Grünblatt, Efthimios Dardiotis, Emrah Düzel, Elio Scarpini, Elisa Conti, Elisa Rubino, Ellen Gelpi, Eloy Rodriguez-Rodriguez, Emmanuelle Duron, Eric Boerwinkle, Evelyn Ferri, Fabrizio Tagliavini, Fahri Küçükali, Florence Pasquier, Florentino Sanchez-Garcia, Francesca Mangialasche, Frank Jessen, Gaël Nicolas, Geir Selbæk, Gemma Ortega, Geneviève Chêne, Georgios Hadjigeorgiou, Giacomina Rossi, Gianfranco Spalletta, Giorgio Giaccone, Giulia Grande, Giuliano Binetti, Goran Papenberg, Harald Hampel, Henri Bailly, Henrik Zetterberg, Hilkka Soininen, Ida K. Karlsson, Ignacio Alvarez, Ildebrando Appollonio, Ina Giegling, Ingmar Skoog, Ingvild Saltvedt, Innocenzo Rainero, Irene Rosas Allende, Jakub Hort, Janine Diehl-Schmid, Jasper Van Dongen, Jean-Sebastien Vidal, Jenni Lehtisalo, Jens Wiltfang, Jesper Qvist Thomassen, Johannes Kornhuber, Jonathan L. Haines, Jonathan Vogelgsang, Juan A. Pineda, Juan Fortea, Julius Popp, Jürgen Deckert, Katharina Buerger, Kevin Morgan, Klaus Fließbach, Kristel Sleegers, Laura Molina-Porcel, Lena Kilander, Leonie Weinhold, Lindsay A. Farrer, Li-San Wang, Luca Kleineidam, Lucia Farotti, Lucilla Parnetti, Lucio Tremolizzo, Lucrezia Hausner, Luisa Benussi, Lutz Froelich, M. Arfan Ikram, M. Candida Deniz-Naranjo, Magda Tsolaki, Maitée Rosende-Roca, Malin Löwenmark, Marc Hulsman, Marco Spallazzi, Margaret A. Pericak-Vance, Margaret Esiri, María Bernal Sánchez-Arjona, Maria Carolina Dalmasso, María Teresa Martínez-Larrad, Marina Arcaro, Markus M. Nöthen, Marta Fernández-Fuertes, Martin Dichgans, Martin Ingelsson, Martin J. Herrmann, Martin Scherer, Martin Vyhnalek, Mary H. Kosmidis, Mary Yannakoulia, Matthias Schmid, Michael Ewers, Michael T. Heneka, Michael Wagner, Michela Scamosci, Miia Kivipelto, Mikko Hiltunen, Miren Zulaica, Montserrat Alegret, Myriam Fornage, Natalia Roberto, Natasja M. van Schoor, Nazib M. Seidu, Nerisa Banaj, Nicola J. Armstrong, Nikolaos Scarmeas, Norbert Scherbaum, Oliver Goldhardt, Oliver Hanon, Oliver Peters, Olivia Anna Skrobot, Olivier Quenez, Ondrej Lerch, Paola Bossù, Paolo Caffarra, Paolo Dionigi Rossi, Paraskevi Sakka, Patrizia Mecocci, Per Hoffmann, Peter A. Holmans, Peter Fischer, Peter Riederer, Qiong Yang, Rachel Marshall, Rajesh N. Kalaria, Richard Mayeux, Rik Vandenberghe, Roberta Cecchetti, Roberta Ghidoni, Ruth Frikke-Schmidt, Sandro Sorbi, Sara Hägg, Sebastiaan Engelborghs, Seppo Helisalmi, Sigrid Botne Sando, Silke Kern, Silvana Archetti, Silvia Boschi, Silvia Fostinelli, Silvia Gil, Silvia Mendoza, Simon Mead, Simona Ciccone, Srdjan Djurovic, Stefanie Heilmann-Heimbach, Steffi Riedel-Heller, Teemu Kuulasmaa, Teodoro del Ser, Thibaud Lebouvier, Thomas Polak, Tiia Ngandu, Timo Grimmer, Valentina Bessi, Valentina Escott-Price, Vilmantas Giedraitis, Vincent Deramecourt, Wolfgang Maier, Xueqiu Jian, Yolande A. L. Pijnenburg, EADB contributors, DEGESCO consortium, IGAP (ADGC, CHARGE, EADI, GERAD), PGC-ALZ consortia, Patrick Gavin Kehoe, Guillermo Garcia-Ribas, Pascual Sánchez-Juan, Pau Pastor, Jordi Pérez-Tur, Gerard Piñol-Ripoll, Adolfo Lopez de Munain, Jose María García-Alberca, María J. Bullido, Victoria Álvarez, Alberto Lleó, Luis M. Real, Pablo Mir, Miguel Medina, Philip Scheltens, Henne Holstege, Marta Marquié, María Eugenia Sáez, Ángel Carracedo, Philippe Amouyel, Gerard D. Schellenberg, Julie Williams, Sudha Seshadri, Cornelia M. van Duijn, Karen A. Mather, Raquel Sánchez-Valle, Manuel Serrano-Ríos, Adelina Orellana, Lluís Tárraga, Kaj Blennow, Martijn Huisman, Ole A. Andreassen, Danielle Posthuma, Jordi Clarimón, Mercè Boada, Wiesje M. van der Flier, Alfredo Ramirez, Jean-Charles Lambert, Sven J. van der Lee, and Agustín Ruiz

Subjects
Science
Published
2023
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5. Sarcopenia and Cognitive Decline in Older Adults: Targeting the Muscle–Brain Axis

Author

Beatrice Arosio, Riccardo Calvani, Evelyn Ferri, Hélio José Coelho-Junior, Angelica Carandina, Federica Campanelli, Veronica Ghiglieri, Emanuele Marzetti, and Anna Picca

Subjects
brain-derived neurotrophic factor (BDNF), cytokine, cognition, inflammation, mitochondria, myokines, Nutrition. Foods and food supply, TX341-641
Abstract

Declines in physical performance and cognition are commonly observed in older adults. The geroscience paradigm posits that a set of processes and pathways shared among age-associated conditions may also serve as a molecular explanation for the complex pathophysiology of physical frailty, sarcopenia, and cognitive decline. Mitochondrial dysfunction, inflammation, metabolic alterations, declines in cellular stemness, and altered intracellular signaling have been observed in muscle aging. Neurological factors have also been included among the determinants of sarcopenia. Neuromuscular junctions (NMJs) are synapses bridging nervous and skeletal muscle systems with a relevant role in age-related musculoskeletal derangement. Patterns of circulating metabolic and neurotrophic factors have been associated with physical frailty and sarcopenia. These factors are mostly related to disarrangements in protein-to-energy conversion as well as reduced calorie and protein intake to sustain muscle mass. A link between sarcopenia and cognitive decline in older adults has also been described with a possible role for muscle-derived mediators (i.e., myokines) in mediating muscle–brain crosstalk. Herein, we discuss the main molecular mechanisms and factors involved in the muscle–brain axis and their possible implication in cognitive decline in older adults. An overview of current behavioral strategies that allegedly act on the muscle–brain axis is also provided.

Published
2023
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6. VAMP2 Expression and Genotype Are Possible Discriminators in Different Forms of Dementia

Author

Andrea Saul Costa, Evelyn Ferri, Franca Rosa Guerini, Paolo Dionigi Rossi, Beatrice Arosio, and Mario Clerici

Subjects
dementia, mixed dementia, SNARE complex, VAMP2, gene expression, biomarker, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Vascular alterations often overlap with neurodegeneration, resulting in mixed forms of dementia (MD) that are hard to differentiate from Alzheimer’s Disease (AD). The 26 bp intergenic polymorphism of VAMP2, a key component of SNARE complex, as well as its mRNA and protein levels are associated with neurological diseases. We evaluated ApoE4 and VAMP2 26 bp Ins/Del genotype distribution in 177 AD, 132 MD, 115 Mild Cognitive Impairment (MCI) and 250 individuals without cognitive decline (CT), as well as VAMP2 gene expression in a subset of 73 AD, 122 MD, 103 MCI and 140 CT. Forty-two MCI evolved to AD (22 MCI-AD) or MD (20 MCI-MD) over time. VAMP2 mRNA was higher in MD compared to AD (p = 0.0013) and CT (p = 0.0017), and in MCI-MD compared to MCI-AD (p < 0.001) after correcting for age, gender, MMSE and ApoE4 +/− covariates (pc = 0.004). A higher VAMP2 expression was observed in subjects carrying the minor allele Del compared to those carrying the Ins/Ins genotype (p = 0.012). Finally, Del/Del genotype was more frequently carried by MD/MCI-MD compared to CT (pc = 0.036). These results suggest that VAMP2 mRNA expression can discriminate mixed form of dementia from AD, possibly being a biomarker of AD evolution in MCI patients.

Published
2022
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7. Liver Enzymes in a Cohort of Community-Dwelling Older Persons: Focus on Sex Contribution

Author

Evelyn Ferri, Paolo D. Rossi, Martina Scichilone, Tiziano A. Lucchi, and Beatrice Arosio

Subjects
liver, sex, aging, dementia, alanine aminotransferase, aspartate aminotransferase, Nutrition. Foods and food supply, TX341-641
Abstract

Dysfunctions in liver metabolic activities may increase the risk of cognitive impairment and dementia. In a cohort of community-dwelling older persons investigated for a suspected cognitive decline, we studied the association between liver status and dementia, considering sex and frailty contribution. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and the AST/ALT ratio were used to assess liver function in 419 older adults (248 persons with dementia and 171 age- and sex-matched subjects without cognitive decline). Although the serum concentrations of the liver enzymes were in the physiologic range, patients with dementia showed lower ALT concentrations (p = 0.005) and higher AST/ALT ratios (p = 0.003) compared to controls. The same differences were found when comparing men with and without dementia (ALT, p = 0.009; AST/ALT ratio, p = 0.003) but disappeared in women. Curiously, comparing women and men with the same diagnosis, the ALT concentrations were lower (p = 0.008), and the AST/ALT ratio was higher (p = 0.001) in control women than men, whereas no significant difference was found between persons with dementia. In conclusion, in our cohort of older people living in the community, the association between serum aminotransferases and dementia was remarked. Moreover, our results support attention to sex difference in liver function, suggesting a role in the pathogenesis of dementia.

Published
2022
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8. Age-Associated Glia Remodeling and Mitochondrial Dysfunction in Neurodegeneration: Antioxidant Supplementation as a Possible Intervention

Author

Anna Picca, Evelyn Ferri, Riccardo Calvani, Hélio J. Coelho-Júnior, Emanuele Marzetti, and Beatrice Arosio

Subjects
astrocytes, extracellular vesicles, inflammation, microglia, mitochondrial quality, mitophagy, Nutrition. Foods and food supply, TX341-641
Abstract

Aging induces substantial remodeling of glia, including density, morphology, cytokine expression, and phagocytic capacity. Alterations of glial cells, such as hypertrophy of lysosomes, endosomes and peroxisomes, and the progressive accumulation of lipofuscin, lipid droplets, and other debris have also been reported. These abnormalities have been associated with significant declines of microglial processes and reduced ability to survey the surrounding tissue, maintain synapses, and recover from injury. Similarly, aged astrocytes show reduced capacity to support metabolite transportation to neurons. In the setting of reduced glial activity, stressors and/or injury signals can trigger a coordinated action of microglia and astrocytes that may amplify neuroinflammation and contribute to the release of neurotoxic factors. Oxidative stress and proteotoxic aggregates may burst astrocyte-mediated secretion of pro-inflammatory cytokines, thus activating microglia, favoring microgliosis, and ultimately making the brain more susceptible to injury and/or neurodegeneration. Here, we discuss the contribution of microglia and astrocyte oxidative stress to neuroinflammation and neurodegeneration, highlight the pathways that may help gain insights into their molecular mechanisms, and describe the benefits of antioxidant supplementation-based strategies.

Published
2022
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9. Sarcopenia and Menopause: The Role of Estradiol

Author

Annalisa Geraci, Riccardo Calvani, Evelyn Ferri, Emanuele Marzetti, Beatrice Arosio, and Matteo Cesari

Subjects
aging, endocrinology, hormones, menopause, muscle, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

During aging and menopausal transition in women, a progressive muscle degeneration (i.e. decrease in quality and muscle function) occurs. This muscle dysfunction, caused by decreased proliferation of muscle satellite cells, increased levels of inflammatory markers, and altered levels of sex hormones, exposes women to a raised incidence of sarcopenia. In this regard, hormonal balance and, in particular, estradiol, seems to be essential in skeletal muscle function. The role of the estradiol on satellite cells and the release of inflammatory cytokines in menopausal women are reviewed. In particular, estradiol has a beneficial effect on the skeletal muscle by stimulating satellite cell proliferation. Skeletal muscle can respond to estrogenic hormonal control due to the presence of specific receptors for estradiol at the level of muscle fibers. Additionally, estradiol can limit inflammatory stress damage on skeletal muscle. In this review, we primarily focused on the role of estradiol in sarcopenia and on the possibility of using Estradiol Replacement Therapy, which combined with nutritional and physical activity programs, can counteract this condition representing a valid tool to treat sarcopenia in women.

Published
2021
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10. Whole-genome sequencing analysis of semi-supercentenarians

Author

Paolo Garagnani, Julien Marquis, Massimo Delledonne, Chiara Pirazzini, Elena Marasco, Katarzyna Malgorzata Kwiatkowska, Vincenzo Iannuzzi, Maria Giulia Bacalini, Armand Valsesia, Jerome Carayol, Frederic Raymond, Alberto Ferrarini, Luciano Xumerle, Sebastiano Collino, Daniela Mari, Beatrice Arosio, Martina Casati, Evelyn Ferri, Daniela Monti, Benedetta Nacmias, Sandro Sorbi, Donata Luiselli, Davide Pettener, Gastone Castellani, Claudia Sala, Giuseppe Passarino, Francesco De Rango, Patrizia D'Aquila, Luca Bertamini, Nicola Martinelli, Domenico Girelli, Oliviero Olivieri, Cristina Giuliani, Patrick Descombes, and Claudio Franceschi

Subjects
longevity, ageing, clonal hematopoiesis, sequencing, geroscience, semi-supercentenarians, Medicine, Science, Biology (General), QH301-705.5
Abstract

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.

Published
2021
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11. The sTREM2 Concentrations in the Blood: A Marker of Neurodegeneration?

Author

Evelyn Ferri, Paolo Dionigi Rossi, Annalisa Geraci, Simona Ciccone, Matteo Cesari, and Beatrice Arosio

Subjects
TREM2, Alzheimer's disease, idiopathic normal pressure hydrocephalus, neurodegeneration, biomarker, Biology (General), QH301-705.5
Abstract

Microglia performs a variety of functions during brain development designed to maintain brain homeostasis. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in microglial cells modulating phagocytosis, cytokine production, cell proliferation, and cell survival. Interestingly, the levels of soluble TREM2 (the secreted ectodomain of TREM2, sTREM2) were higher in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients than subjects without cognitive decline. It is noteworthy that, while CSF sTREM2 levels have been extensively studied, few studies have investigated sTREM2 in blood producing conflicting results. We aimed to investigate the levels of sTREM2 in CSF and blood from a cohort of well-characterized AD comparing the results to those obtained in patients suffering from idiopathic normal pressure hydrocephalus (iNPH), a potentially reversible cognitive impairment. Our findings underlined a significantly lower plasma sTREM2 concentration in AD patients compared to iNPH subjects [39.1 ng/mL (standard deviation (SD), 15.0) and 47.2 ng/mL (SD, 19.5), respectively; p = 0.01], whereas no difference was revealed between the two groups in the CSF sTREM2 levels. The adjusted regression analyses evidenced in AD patients an association between plasma and CSF sTREM2 levels [B = 0.411; 95% confidence interval (CI), 0.137–0.685, p = 0.004], as well as β-amyloid concentrations (B = 0.035; 95% CI, 0.007–0.063, p = 0.01) and an association between CSF sTREM2 and phospho-Tau concentrations (B = 0.248; 95% CI, 0.053–0.443; p = 0.01). No significant relation was found in iNPH patients. In conclusion, these differences in sTREM2 profiles between AD and iNPH reinforce the notion that this receptor has a role in neurodegeneration.

Published
2021
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12. Characterization of Vitamin D Status in Older Persons with Cognitive Impairment

Author

Beatrice Arosio, Paolo Dionigi Rossi, Evelyn Ferri, Matteo Cesari, and Giovanni Vitale

Subjects
aging, vitamin D, cognitive impairment, frailty, dementia, Nutrition. Foods and food supply, TX341-641
Abstract

Vitamin D exerts a role in the maintenance of cognitive abilities and in frailty. Although several studies evaluated the interactions between vitamin D and cognitive impairment, results were conflicting. In a cohort of community-dwelling older persons, we described the association between vitamin D levels and cognitive decline and all-cause dementia evaluating frailty’s contribution. Our cohort included 509 adults, aged 64–92 years: 176 patients with mild cognitive impairment (MCI), 59 with Alzheimer’s Disease (AD), 26 with idiopathic Normal Pressure Hydrocephalus (iNPH), 133 with mixed dementia (MD) and 115 without cognitive decline. Frailty was measured by frailty index, and serum 25-hydroxyvitamin D concentrations through electrochemiluminescence immunoassays. We found a significant association between vitamin D levels and Mini Mental State Examination independently of cognitive impairment, age, sex and frailty. The patients with dementia (AD and MD) showed the lowest vitamin D levels, while MCI patients showed higher levels than the other groups. The most severe deficiency was observed in MD patients, the most aged as well as cognitively and functionally impaired. In conclusion, in our community-dwelling older persons investigated for a suspected cognitive impairment, we observed an association between vitamin D levels and cognitive decline, regardless of the frailty status.

Published
2022
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13. Novel Insight into the Serum Sphingolipid Fingerprint Characterizing Longevity

Author

Pietro Barbacini, Enrica Torretta, Beatrice Arosio, Evelyn Ferri, Daniele Capitanio, Manuela Moriggi, and Cecilia Gelfi

Subjects
sphingolipids, mass spectrometry, nitric oxide, ROS, longevity, aging, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Sphingolipids (SLs) are structural components of the lipid bilayer regulating cell functions. In biological fluids, their distribution is sex-specific and is at variance in aging and many disorders. The aim of this study is to identify SL species associated with the decelerated aging of centenarians. SLs, extracted from serum of adults (Ad, 35–37 years old), aged (Ag, 75–77 years old) and centenarian (C, 105–107 years old) women were analyzed by LC-MS/MS in combination with mRNA levels in peripheral blood mononuclear cells (PBMCs) of SL biosynthetic enzymes. Results indicated in Ag and C vs. Ad a comparable ceramides (Cers) increase, whereas dihydroceramide (dhCer) decreased in C vs. Ad. Hexosylceramides (HexCer) species, specifically HexCer 16:0, 22:0 and 24:1 acyl chains, increased in C vs. Ag representing a specific trait of C. Sphingosine (Sph), dihydrosphingosine (dhSph), sphingosine-1-phosphate (S1P) and dihydrosphingosine-1-phosphate (dhS1P), increased both in Ag and C vs. Ad, with higher levels in Ag, indicating a SL fine-tuning associated with a reduced physiological decline in C. mRNA levels of enzymes involved in ceramide de novo biosynthesis increased in Ag whereas enzymes involved in sphingomyelin (SM) degradation increased in C. Collectively, results suggest that Ag produce Cers by de novo synthesis whereas C activate a protective mechanism degrading SMs to Cers converting it into glycosphingolipids.

Published
2022
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14. The Biological Foundations of Sarcopenia: Established and Promising Markers

Author

Martina Casati, Andrea Saul Costa, Daniele Capitanio, Luisa Ponzoni, Evelyn Ferri, Simone Agostini, and Elisa Lori

Subjects
aging, sarcopenia, biomarkers, neuromuscular junction, SNAP25, Medicine (General), R5-920
Abstract

Sarcopenia, the progressive loss of muscle mass and strength, is one of the major health issues in older adults, given its high prevalence accompanied by huge clinical and socioeconomic implications. Age-related changes in skeletal muscle can be attributed to mechanisms both directly and indirectly related to muscle homeostasis. Indeed, a wide spectrum of age-related modifications in the organism was shown to play a key role in the pathogenesis of sarcopenia. Not surprisingly, sarcopenia has sometimes been indicated as a syndrome stemming from the aging process, and not as univocal standalone disease. Due to the multidimensionality of sarcopenia, a single biomarker approach is not enough to explain the biology of this condition. The aim of this review is to suggest innovative and promising sarcopenia markers investigating the link between skeletal muscle and brain. Indeed, as a neurological origin of sarcopenia has been hypothesized, a new perspective on sarcopenia biomarkers may focus on the dysfunction of the neuromuscular junctions (NMJs). The core SNARE synaptosomal-associated protein of 25 kDa (SNAP25) accumulates in the plasma membrane of nerve terminals at NMJs and regulates exocytosis at peripheral and central synapses. Interestingly, mice studies have shown that SNAP25 affects the neuromuscular function. SNARE complex and, in particular, SNAP25 may represent a promising pathway to explore the molecular and cellular mechanisms regulating muscular homeostasis and concur at profiling the sarcopenia biological background.

Published
2019
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15. Vitamin D Receptor Polymorphisms in Sex-Frailty Paradox

Author

Beatrice Arosio, Franca Rosa Guerini, Andrea Saul Costa, Alessandra Dicitore, Evelyn Ferri, Daniela Mari, Erminio Torresani, Mario Clerici, Matteo Cesari, and Giovanni Vitale

Subjects
aging, vitamin D, frailty, vitamin D receptor, Nutrition. Foods and food supply, TX341-641
Abstract

The “male-female health-survival paradox” evidences that the survival advantage observed in women is linked to higher rates of disability and poor health status compared to men, a phenomenon also called the “sex-frailty paradox”. The depletion of vitamin D seems to play a role in the fragilization of old persons, and genetic polymorphisms of the vitamin D receptor (VDR) gene seem to be involved in regulating the vitamin D pathway. This study correlated the VDR gene polymorphisms (FokI, ApaI, BsmiI, and TaqI) with frailty, computed by frailty index (FI), in 202 persons (127 women and 75 men, aged from 60 to 116 years), aiming to capture the involvement of vitamin D in the sex-frailty paradox. The results showed slightly higher FI (p = 0.05), lower levels of 25(OH)D (p = 0.04), and higher levels of parathyroid hormone PTH (p = 0.002) and phosphorus (p < 0.001) in women than in men. Interestingly, the ApaI minor allele (Aa + aa) showed a significant positive association with FI (p = 0.03) and a negative association with inorganic phosphorus values (p = 0.04) compared to AA genotype only in women, regardless of age. The exact mechanism and the causal role that, in old women, links ApaI polymorphism with frailty are still unclear. However, we could speculate that a specific genetic profiling, other than 25(OH)D levels, play a role in the sex-frailty paradox.

Published
2020
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16. Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

Author

Evelyn Ferri, Emanuele Marzetti, Riccardo Calvani, Anna Picca, Matteo Cesari, and Beatrice Arosio

Subjects
skeletal muscle, muscle aging, sarcopenia, mitochondria, mitochondrial dysfunction, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

Published
2020
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17. Protein signature in cerebrospinal fluid and serum of Alzheimer's disease patients: The case of apolipoprotein A-1 proteoforms.

Author

Chiara Fania, Beatrice Arosio, Daniele Capitanio, Enrica Torretta, Cristina Gussago, Evelyn Ferri, Daniela Mari, and Cecilia Gelfi

Subjects
Medicine, Science
Abstract

In the diagnosis of Alzheimer's disease (AD) total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181), and the 42 amino acid isoform of alpha β-amyloid (Aβ) are well established surrogate CSF markers. However, there is a constant need for new diagnostic markers to identify the disease at a very early stage. The identification of new molecules for AD diagnosis and monitoring in CSF is hampered by several "confounding" factors including intra- and inter-individual, pre-analytical and analytical variabilities. In an attempt to partially overcome patient's variability and to determine new molecules significantly dysregulated in CSF, we assessed the proteome profile of low molecular weight protein species in CSF and serum of the same patients. CSFs and sera from 36 ADs, 32 iNPHs (idiopathic normal pressure hydrocephalus) and 12 controls were compared by MALDI profiling (non-parametric statistics, CV0.750). After protein identification by mass spectrometry, the proteoform composition was assessed by 2-D DIGE/MS. Results indicated that CSF of iNPH can be used as control. Serum and CSF of AD patients shows a specific protein profile compared to iNPH samples. A variation (p

Published
2017
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18. Centenarians

Author

Evelyn Ferri, Marco Proietti, Matteo Cesari, and Beatrice Arosio

Published
2022

19. Biological Frailty Index in centenarians

Author

Daniela Mari, Beatrice Arosio, Annalisa Geraci, Evelyn Ferri, and Matteo Cesari

Subjects
Aged, 80 and over, Male, Aging, Frailty, business.industry, Geriatrics gerontology, Frail Elderly, Frailty Index, Northern italy, Cohort Studies, Italy, Interquartile range, Centenarians, Cohort, Humans, Medicine, Female, Geriatrics and Gerontology, business, Geriatric Assessment, Aged, Demography, Subclinical infection
Abstract

This study measured the subclinical frailty of centenarians by looking at the accumulation of their biological abnormalities. For this aim, a biological Frailty Index (FI) was computed in centenarians living in Northern Italy. The median value of the biological FI was 0.33 (interquartile range, IQR 0.28–0.41). The biological FI did not significantly differ between women (0.34, IQR 0.31–0.39) and men (0.32, IQR 0.26–0.43). The biological FI seems to have a narrower distribution compared to clinical FI we previously computed in the same cohort. In conclusion, our study suggests that centenarians benefit from exceptional biological reserves that might be underestimated by clinical appearances.

Published
2021

20. CUORE opens the door to tonne-scale cryogenics experiments

Author

L. Canonica, L. Marini, Kevin Hickerson, J. Schmidt, Massimiliano Clemenza, Carlo Cosmelli, S. Copello, L. Gladstone, M. Guerzoni, L. Ma, J. Johnston, A. Leder, M. Iannone, Irene Nutini, Paolo Carniti, Vladimir Datskov, R. J. Creswick, M. M. Deninno, G. Fantini, F. Bellini, I. C. Bandac, Yu-Gang Ma, D. Santone, V. Sharma, C. Brofferio, P. J. Mosteiro, A. Caminata, Ezio Previtali, B. Welliver, Evelyn Ferri, H. Z. Huang, G. Keppel, K. E. Lim, X. G. Cao, F. Bragazzi, Ettore Fiorini, V. Novati, C. Rusconi, N. Chott, T. Wise, C. Crescentini, R. Gaigher, L. Zanotti, Andrea Giachero, C. Maiano, N. Moggi, C. Martinez Amaya, S. S. Nagorny, A. Pelosi, G. Piperno, D. Q. Adams, L. Risegari, K. Alfonso, F. Terranova, Davide Chiesa, C. Rosenfeld, Deqing Fang, S. Pagan, S. Dell'Oro, M. L. Di Vacri, D. Mayer, Samuele Sangiorgio, Stefano Nisi, P. T. Surukuchi, S. Morganti, S. Zucchelli, J. Camilleri, A. Nucciotti, M. Sisti, P. Gorla, E. V. Hansen, F. Ferroni, C. Tomei, Elena Sala, L. Ioannucci, D. Speller, F. Alessandria, M. I. Martínez, Eugene E. Haller, C. Alduino, F. Rimondi, G. Ceruti, K. Wilson, L. Taffarello, Marisa Pedretti, R. Hennings-Yeomans, S. Pirro, Carlo Ligi, M. Faverzani, M. Beretta, Y. Mei, M. Tessaro, Jeffrey W. Beeman, M. Capodiferro, A. Bersani, N. D. Scielzo, M. Barucci, L. Cappelli, D. Biare, C. J. Davis, A. Camacho, Jonathan Ouellet, D. Conventi, J. Wallig, K. M. Heeger, L. Pagnanini, A. Giuliani, G. Bari, M. Cariello, Lindley Winslow, A. Campani, S. L. Wagaarachchi, M. Maino, Guoqiang Zhang, M. Carrettoni, R. Mazza, A. Branca, A. Bryant, J. Nikkel, C. Pira, H.W. Wang, M. Perego, T. I. Banks, S. Zimmermann, Ke Han, Reina H. Maruyama, S. Ghislandi, T. O'Donnell, S. Di Domizio, Simone Capelli, R. W. Kadel, Stuart J. Freedman, G. Ventura, A. Drobizhev, C. Bulfon, C. Zarra, Laura Cardani, V. Dompè, M. Balata, L. Di Paolo, A. D'Addabbo, L. Pattavina, B. K. Fujikawa, Stefano Pozzi, Alan R. Smith, D. Orlandi, Larissa M. Ejzak, M. Vignati, B. X. Zhu, V. Pettinacci, L. Kogler, E. Celi, L. Tatananni, S.H. Fu, E. Andreotti, M. A. Franceschi, R. Cereseto, I. Dafinei, M. Sakai, D. D'Aguanno, F. Stivanello, R. G. Huang, D. Schaeffer, C. Guandalini, F. Orio, Vasundhara Singh, B. Schmidt, B. S. Wang, O. Azzolini, Kai Vetter, M. Olcese, Jeremy S. Cushman, V. Palmieri, Eric B. Norman, M. Guetti, T. Napolitano, M. Biassoni, F. Del Corso, R. Faccini, Giovanni Benato, A. Buccheri, C. Salvioni, Yu. G. Kolomensky, R. Pedrotta, Lorenzo Cassina, C. Nones, A. Puiu, Marco Pallavicini, S. Quitadamo, G. Pessina, James R. Wilson, R. Liu, Massimiliano Nastasi, M. Pavan, E. Olivieri, L. Gironi, F. T. Avignone, Claudio Gotti, N. Casali, F. Reindl, Oliviero Cremonesi, J. Goett, M. Tenconi, C. Pagliarone, C. Rossi, A. Chiarini, C. Bucci, T. D. Gutierrez, Adams, D, Alduino, C, Alessandria, F, Alfonso, K, Andreotti, E, Avignone, F, Azzolini, O, Balata, M, Bandac, I, Banks, T, Bari, G, Barucci, M, Beeman, J, Bellini, F, Benato, G, Beretta, M, Bersani, A, Biare, D, Biassoni, M, Bragazzi, F, Branca, A, Brofferio, C, Bryant, A, Buccheri, A, Bucci, C, Bulfon, C, Camacho, A, Camilleri, J, Caminata, A, Campani, A, Canonica, L, Cao, X, Capelli, S, Capodiferro, M, Cappelli, L, Cardani, L, Cariello, M, Carniti, P, Carrettoni, M, Casali, N, Cassina, L, Celi, E, Cereseto, R, Ceruti, G, Chiarini, A, Chiesa, D, Chott, N, Clemenza, M, Conventi, D, Copello, S, Cosmelli, C, Cremonesi, O, Crescentini, C, Creswick, R, Cushman, J, D'Addabbo, A, D'Aguanno, D, Dafinei, I, Datskov, V, Davis, C, Corso, F, Dell'Oro, S, Deninno, M, Di Domizio, S, Dompe, V, Di Vacri, M, Di Paolo, L, Drobizhev, A, Ejzak, L, Faccini, R, Fang, D, Fantini, G, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fu, S, Fujikawa, B, Gaigher, R, Ghislandi, S, Giachero, A, Gironi, L, Giuliani, A, Gladstone, L, Goett, J, Gorla, P, Gotti, C, Guandalini, C, Guerzoni, M, Guetti, M, Gutierrez, T, Haller, E, Han, K, Hansen, E, Heeger, K, Hennings-Yeomans, R, Hickerson, K, Huang, R, Huang, H, Iannone, M, Ioannucci, L, Johnston, J, Kadel, R, Keppel, G, Kogler, L, Kolomensky, Y, Leder, A, Ligi, C, Lim, K, Liu, R, Ma, L, Ma, Y, Maiano, C, Maino, M, Marini, L, Martinez, M, Amaya, C, Maruyama, R, Mayer, D, Mazza, R, Mei, Y, Moggi, N, Morganti, S, Mosteiro, P, Nagorny, S, Napolitano, T, Nastasi, M, Nikkel, J, Nisi, S, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O'Donnell, T, Olcese, M, Olivieri, E, Orio, F, Orlandi, D, Ouellet, J, Pagan, S, Pagliarone, C, Pagnanini, L, Pallavicini, M, Palmieri, V, Pattavina, L, Pavan, M, Pedretti, M, Pedrotta, R, Pelosi, A, Perego, M, Pessina, G, Pettinacci, V, Piperno, G, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Puiu, A, Quitadamo, S, Reindl, F, Rimondi, F, Risegari, L, Rosenfeld, C, Rossi, C, Rusconi, C, Sakai, M, Sala, E, Salvioni, C, Sangiorgio, S, Santone, D, Schaeffer, D, Schmidt, B, Schmidt, J, Scielzo, N, Sharma, V, Singh, V, Sisti, M, Smith, A, Speller, D, Stivanello, F, Surukuchi, P, Taffarello, L, Tatananni, L, Tenconi, M, Terranova, F, Tessaro, M, Tomei, C, Ventura, G, Vetter, K, Vignati, M, Wagaarachchi, S, Wallig, J, Wang, B, Wang, H, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Wise, T, Zanotti, L, Zarra, C, Zhang, G, Zhu, B, Zimmermann, S, Zucchelli, S, Adams D.Q., Alduino C., Alessandria F., Alfonso K., Andreotti E., Avignone F.T., Azzolini O., Balata M., Bandac I., Banks T.I., Bari G., Barucci M., Beeman J.W., Bellini F., Benato G., Beretta M., Bersani A., Biare D., Biassoni M., Bragazzi F., Branca A., Brofferio C., Bryant A., Buccheri A., Bucci C., Bulfon C., Camacho A., Camilleri J., Caminata A., Campani A., Canonica L., Cao X.G., Capelli S., Capodiferro M., Cappelli L., Cardani L., Cariello M., Carniti P., Carrettoni M., Casali N., Cassina L., Celi E., Cereseto R., Ceruti G., Chiarini A., Chiesa D., Chott N., Clemenza M., Conventi D., Copello S., Cosmelli C., Cremonesi O., Crescentini C., Creswick R.J., Cushman J.S., D'Addabbo A., D'Aguanno D., Dafinei I., Datskov V., Davis C.J., Del Corso F., Dell'Oro S., Deninno M.M., Di Domizio S., Dompe V., Di Vacri M.L., Di Paolo L., Drobizhev A., Ejzak L., Faccini R., Fang D.Q., Fantini G., Faverzani M., Ferri E., Ferroni F., Fiorini E., Franceschi M.A., Freedman S.J., Fu S.H., Fujikawa B.K., Gaigher R., Ghislandi S., Giachero A., Gironi L., Giuliani A., Gladstone L., Goett J., Gorla P., Gotti C., Guandalini C., Guerzoni M., Guetti M., Gutierrez T.D., Haller E.E., Han K., Hansen E.V., Heeger K.M., Hennings-Yeomans R., Hickerson K.P., Huang R.G., Huang H.Z., Iannone M., Ioannucci L., Johnston J., Kadel R., Keppel G., Kogler L., Kolomensky Y.G., Leder A., Ligi C., Lim K.E., Liu R., Ma L., Ma Y.G., Maiano C., Maino M., Marini L., Martinez M., Amaya C.M., Maruyama R.H., Mayer D., Mazza R., Mei Y., Moggi N., Morganti S., Mosteiro P.J., Nagorny S.S., Napolitano T., Nastasi M., Nikkel J., Nisi S., Nones C., Norman E.B., Novati V., Nucciotti A., Nutini I., O'Donnell T., Olcese M., Olivieri E., Orio F., Orlandi D., Ouellet J.L., Pagan S., Pagliarone C.E., Pagnanini L., Pallavicini M., Palmieri V., Pattavina L., Pavan M., Pedretti M., Pedrotta R., Pelosi A., Perego M., Pessina G., Pettinacci V., Piperno G., Pira C., Pirro S., Pozzi S., Previtali E., Puiu A., Quitadamo S., Reindl F., Rimondi F., Risegari L., Rosenfeld C., Rossi C., Rusconi C., Sakai M., Sala E., Salvioni C., Sangiorgio S., Santone D., Schaeffer D., Schmidt B., Schmidt J., Scielzo N.D., Sharma V., Singh V., Sisti M., Smith A.R., Speller D., Stivanello F., Surukuchi P.T., Taffarello L., Tatananni L., Tenconi M., Terranova F., Tessaro M., Tomei C., Ventura G., Vetter K.J., Vignati M., Wagaarachchi S.L., Wallig J., Wang B.S., Wang H.W., Welliver B., Wilson J., Wilson K., Winslow L.A., Wise T., Zanotti L., Zarra C., Zhang G.Q., Zhu B.X., Zimmermann S., Zucchelli S., Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and CUORE

Subjects
Cryostat, Nuclear and High Energy Physics, Physics - Instrumentation and Detectors, Physics::Instrumentation and Detectors, FOS: Physical sciences, Cryogenic temperatures, Dilution refrigerator, Low temperature calorimeter, Neutrinoless double beta decay, Rare event searches, Ton-scale detector, Cryogenic temperatures, Neutrinoless double beta decay, Dilution refrigerator, Ton-scale detector, Low temperature calorimeter, Rare event searches, cryogenics, CUORE performance, Cryogenics, Rare event searche, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 7. Clean energy, 01 natural sciences, CUORE, double-beta decay: (0neutrino), Double beta decay, 0103 physical sciences, Cryogenic particle detectors, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Nuclear Experiment (nucl-ex), Aerospace engineering, 010306 general physics, Nuclear Experiment, activity report, Physics, 010308 nuclear & particles physics, business.industry, Astrophysics::Instrumentation and Methods for Astrophysics, Cryogenic temperature, Instrumentation and Detectors (physics.ins-det), CUORE performance, Semiconductor detector, cryogenics: design, cryogenics, Neutrino, business, performance
Abstract

The past few decades have seen major developments in the design and operation of cryogenic particle detectors. This technology offers an extremely good energy resolution - comparable to semiconductor detectors - and a wide choice of target materials, making low temperature calorimetric detectors ideal for a variety of particle physics applications. Rare event searches have continued to require ever greater exposures, which has driven them to ever larger cryogenic detectors, with the CUORE experiment being the first to reach a tonne-scale, mK-cooled, experimental mass. CUORE, designed to search for neutrinoless double beta decay, has been operational since 2017 at a temperature of about 10 mK. This result has been attained by the use of an unprecedentedly large cryogenic infrastructure called the CUORE cryostat: conceived, designed and commissioned for this purpose. In this article the main characteristics and features of the cryogenic facility developed for the CUORE experiment are highlighted. A brief introduction of the evolution of the field and of the past cryogenic facilities are given. The motivation behind the design and development of the CUORE cryogenic facility is detailed as are the steps taken toward realization, commissioning, and operation of the CUORE cryostat. The major challenges overcome by the collaboration and the solutions implemented throughout the building of the cryogenic facility will be discussed along with the potential improvements for future facilities. The success of CUORE has opened the door to a new generation of large-scale cryogenic facilities in numerous fields of science. Broader implications of the incredible feat achieved by the CUORE collaboration on the future cryogenic facilities in various fields ranging from neutrino and dark matter experiments to quantum computing will be examined., Comment: 45 pages, 14 figures

Published
2022

21. A Thermal Model for Low Temperature TeO 2 Calorimeters

Author

S. Quitadamo, C. Brofferio, M. Faverzani, M. Biassoni, G. Pessina, Evelyn Ferri, Irene Nutini, Paolo Carniti, C. Gotti, A. Giachero, S. Ghislandi, Biassoni, M, Brofferio, C, Carniti, P, Faverzani, M, Ferri, E, Ghislandi, S, Giachero, A, Gotti, C, Nutini, I, Pessina, G, and Quitadamo, S

Subjects
Bolometer response function, NTD, Materials science, Low-temperature calorimeter, Thermodynamics, General Materials Science, Thermal model, Neutrinoless double beta decay, Condensed Matter Physics, Atomic and Molecular Physics, and Optics
Abstract

In this paper, we present the application of a simplified thermal model in order to extract some of the fundamental parameters needed to understand the response function of low-temperature calorimeters consisting of TeO 2 crystals read-out by neutron transmutation doped (NTD) thermistors operated at temperatures T∼ 10 mK. To this aim, four detectors were hosted in two different holders, one made of copper and the other made of Stratasys VeroClear TM, a 3D-printed plastic material very similar to acrylic. The static characterization of the detectors through the analysis of their load curves at different temperatures, guided by the thermal model, enabled the identification of the main thermal link to the heat sink of the two systems: the glue between the crystal and the copper frame (scaling as T3) for the detectors in the copper holder, and the NTD gold read-out wires (scaling as T2.5) for the detectors in the plastic holder. As a subdominant contribution, we could also extract the electron–phonon decoupling characteristic of our NTDs, described by a thermal conductance scaling as T4.

Published
2022

22. Development of Microwave Kinetic Inductance Detectors for IR Single-Photon Counting

Author

Evelyn Ferri, Andrea Vinante, A. Nucciotti, M. Faverzani, Benno Margesin, Andrea Giachero, A. Puiu, Renato Mezzena, Mezzena, R, Faverzani, M, Ferri, E, Giachero, A, Margesin, B, Nucciotti, A, Puiu, A, and Vinante, A

Subjects
Materials science, Microwave kinetic inductance detector, chemistry.chemical_element, 01 natural sciences, Kinetic inductance, 010305 fluids & plasmas, law.invention, Resonator, law, 0103 physical sciences, General Materials Science, Ti/TiN multilayer films, 010306 general physics, Laser diode, business.industry, Microwave kinetic inductance detectors, Detector, Condensed Matter Physics, Atomic and Molecular Physics, and Optics, Photon counting, Single-photon detector, Capacitor, chemistry, Optoelectronics, business, Tin, Microwave
Abstract

We have developed microwave kinetic inductance detectors suitable for near-IR single-photon counting. Our films are made of titanium and titanium nitride, deposited in a multilayer structure Ti/TiN/Ti/TiN with a total thickness of 44nm. The film has a transition temperature of 1.2K and a surface kinetic inductance of 34pH/sq. The resonator was designed with lumped elements and consists of two blocks of interdigitated capacitors connected by a meandered stripe inductor. The resonator resonance frequency is 6.8GHz, and the internal quality factor is 125,000. The detector is read out with the usual homodyne scheme and calibrated with light pulses produced by a laser diode with wavelength 1550nm. For the 0- and 1-photon peaks, we measure a FWHM energy resolution of 0.44eV and 0.56eV, respectively. This resolution is sufficient to resolve events with up to 4 photons.

Published
2019

23. Author response: Whole-genome sequencing analysis of semi-supercentenarians

Author

Sebastiano Collino, Massimo Delledonne, Patrick Descombes, Armand Valsesia, Benedetta Nacmias, Sandro Sorbi, Evelyn Ferri, Frederic Raymond, Davide Pettener, Domenico Girelli, Patrizia D'Aquila, Francesco De Rango, Daniela Mari, Martina Casati, Luciano Xumerle, Giuseppe Passarino, Cristina Giuliani, Maria Giulia Bacalini, Katarzyna Malgorzata Kwiatkowska, Claudio Franceschi, Alberto Ferrarini, Daniela Monti, Donata Luiselli, Chiara Pirazzini, Beatrice Arosio, Jérôme Carayol, Oliviero Olivieri, Gastone Castellani, Luca Bertamini, Vincenzo Iannuzzi, Claudia Sala, Paolo Garagnani, Julien Marquis, Nicola Martinelli, and Elena Marasco

Subjects
Whole genome sequencing, Computational biology, Biology
Published
2021

24. Search for Double-Beta Decay of $\mathrm{^{130}Te}$ to the $0^+$ States of $\mathrm{^{130}Xe}$ with CUORE

Author

Davide Chiesa, S. Di Domizio, Laura Cardani, B. K. Fujikawa, Stefano Pozzi, M. Vignati, Massimiliano Clemenza, Carlo Cosmelli, A. Giuliani, Monica Sisti, C. Pagliarone, V. Sharma, S. Zimmermann, A. Branca, Deqing Fang, S. Dell'Oro, B. Schmidt, L. Pattavina, L. Pagnanini, B. S. Wang, C. Brofferio, Marco Pallavicini, Lindley Winslow, F. Terranova, S. Morganti, O. Azzolini, S. Copello, S. Pagan, Kai Vetter, G. Pessina, Paolo Carniti, C. Rusconi, Carlo Ligi, L. Taffarello, L. Ma, Virendra Singh, Yudi Ma, H. Z. Huang, C. Rosenfeld, S. Pirro, A. Campani, C. Pira, Ettore Fiorini, S. L. Wagaarachchi, Andrea Giachero, P. Gorla, F. Ferroni, J. Camilleri, Xiangyu Cao, C. Tomei, Ke Han, Reina H. Maruyama, Stuart J. Freedman, L. Canonica, L. Marini, D. Q. Adams, Simone Capelli, K. Alfonso, G. Keppel, D. Speller, D. Mayer, C. J. Davis, Y. Mei, C. Nones, A. Puiu, I. Dafinei, Irene Nutini, J. Johnston, V. Pettinacci, A. Caminata, V. Dompè, A. D'Addabbo, J. Nikkel, G. Fantini, K. M. Heeger, Ezio Previtali, P. T. Surukuchi, T. O'Donnell, Yu. G. Kolomensky, N. D. Scielzo, R. G. Huang, B. Welliver, K. Wilson, Jonathan Ouellet, G. Bari, E. Celi, M. A. Franceschi, S. Zucchelli, M. Faverzani, Evelyn Ferri, N. Moggi, Eric B. Norman, L. Cappelli, M. Sakai, T. Napolitano, Samuele Sangiorgio, Oliviero Cremonesi, A. Nucciotti, M. Biassoni, C. Alduino, Claudio Gotti, N. Casali, Giovanni Benato, C. Bucci, T. D. Gutierrez, L. Gironi, F. T. Avignone, F. Bellini, R. J. Creswick, M. Pavan, Massimiliano Nastasi, James R. Wilson, S. H. Fu, Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CUORE, and Département de Physique des Particules (ex SPP) (DPhP)

Subjects
Particle physics, experimental methods, Physics and Astronomy (miscellaneous), FOS: Physical sciences, Dirac Neutrino, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], Neutrinoless Double Beta Decay, 7. Clean energy, 01 natural sciences, Bayesian, decay modes, crystal, CUORE, background: low, bolometer, Double beta decay, Neutrino, 0103 physical sciences, excited state, double-beta decay: (2neutrino), Beta (velocity), Sensitivity (control systems), bayesian analysis, Nuclear Experiment (nucl-ex), Particle Physics, 010306 general physics, Engineering (miscellaneous), Nuclear Experiment, lepton number: violation, excited states, Physics, 010308 nuclear & particles physics, Majorana Neutrino, Gamma ray, sensitivity, Lepton number, gamma ray: emission, Excited state, Double beta decay, excited states, bayesian analysis, CUORE, Neutrinoless Double Beta Decay, Particle Physics, Neutrino, Majorana Neutrino, Dirac Neutrino
Abstract

The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay ($0\nu\beta\beta$) in the isotope $\mathrm{^{130}Te}$. In this work we present the latest results on two searches for the double beta decay (DBD) of $\mathrm{^{130}Te}$ to the first $0^{+}_2$ excited state of $\mathrm{^{130}Xe}$: the $0\nu\beta\beta$ decay and the Standard Model-allowed two-neutrinos double beta decay ($2\nu\beta\beta$). Both searches are based on a 372.5 kg$\times$yr TeO$_2$ exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90\% Credible Interval (C.I.) of the given searches were estimated as $\mathrm{S^{0\nu}_{1/2} = 5.6 \times 10^{24} \: \mathrm{yr}}$ for the ${0\nu\beta\beta}$ decay and $\mathrm{S^{2\nu}_{1/2} = 2.1 \times 10^{24} \: \mathrm{yr}}$ for the ${2\nu\beta\beta}$ decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at $90\%$ C.I. on the decay half lives is obtained as: $\mathrm{(T_{1/2})^{0\nu}_{0^+_2} > 5.9 \times 10^{24} \: \mathrm{yr}}$ for the $0\nu\beta\beta$ mode and $\mathrm{(T_{1/2})^{2\nu}_{0^+_2} > 1.3 \times 10^{24} \: \mathrm{yr}}$ for the $2\nu\beta\beta$ mode. These represent the most stringent limits on the DBD of $^{130}$Te to excited states and improve by a factor $\sim5$ the previous results on this process., Comment: 13 pages, 6 figures

Published
2021

26. Novel technique for the study of pileup events in cryogenic bolometers

Author

Valentyn Novosad, Andrea Giachero, R. Nipoti, Jie Zhang, H. Z. Huang, V. G. Yefremenko, G. Keppel, D. Mayer, C. Nones, A. Puiu, S. Nisi, A. Armatol, K. Wilson, I. Colantoni, A. Barresi, P. Loaiza, C. Oriol, G. Pessina, V. Sanglard, L. Imbert, M. Faverzani, M. Beretta, S. Copello, C. Pagliarone, F.A. Danevich, A. Branca, Jonathan Ouellet, T. O'Donnell, Paolo Carniti, Massimiliano Clemenza, G. Bari, S. Di Domizio, Kai Vetter, C. Rosenfeld, D. L. Helis, Monica Sisti, Federico Ferri, H. Khalife, V. Boldrini, P. Gorla, P. Pari, F. Ferroni, Tomas Polakovic, B. Schmidt, Stefano Dell'Oro, A. Charrier, J. Billard, C. Tomei, S. H. Fu, N. Casali, Laura Cardani, G. Wang, Jie Yang, B. K. Fujikawa, R. J. Creswick, Davide Chiesa, P. Gras, M. Chapellier, C. Pira, Joseph A. Formaggio, L. Pagnanini, P. T. Surukuchi, C. Brofferio, L. Wang, Massimiliano Nastasi, Stefano Pozzi, E. Figueroa-Feliciano, Haiping Peng, V. Shlegel, V. Sharma, E. V. Hansen, A. S. Barabash, B. Paul, M. Gros, Evelyn Ferri, Oliviero Cremonesi, S. Zucchelli, James Nikkel, Ezio Previtali, J. Gascon, R. Mariam, C. C. Chang, L. Ma, Yu. G. Kolomensky, Luigi Cappelli, L. Taffarello, B. Welliver, A. Giuliani, M. Madhukuttan, Matias Velázquez, C. Augier, S. Marnieros, V. Yumatov, Goran Karapetrov, G. Fantini, A. Cazes, Danielle Speller, James R. Wilson, A. Cruciani, X. F. Navick, S. Pirro, V. V. Kobychev, J. Camilleri, A. Franceschi, Changbo Fu, C. Rusconi, J. A. Scarpaci, A. Juillard, L. Bergé, R. Rizzoli, M. M. Zarytskyy, V. Dompè, G. D'Imperio, Irene Nutini, A. D'Addabbo, P. de Marcillac, M. De Jesus, O. G. Polischuk, F. Bellini, A. Ressa, D. Baudin, M. Xue, M. Pavan, Lindley Winslow, A. Drobizhev, I. Dafinei, S. L. Wagaarachchi, F. Collamati, V. Pettinacci, Simone Capelli, E. Olivieri, S. I. Konovalov, Eric B. Norman, L. Pattavina, M. I. Martínez, T. Napolitano, L. Marini, V.I. Tretyak, D. Misiak, D. V. Poda, J. Johnston, M. Biassoni, E. Armengaud, Vasundhara Singh, S. Milana, O. Azzolini, L. Gironi, F. T. Avignone, Whitney Armstrong, Y. Liu, C. Bucci, T. D. Gutierrez, R. G. Huang, F. Mancarella, L. Yan, S. Pagan, B. Mauri, M. de Combarieu, E. Celi, C. Gotti, A. S. Zolotarova, Ke Han, Reina H. Maruyama, A. Tsymbaliuk, Y. Mei, K. M. Heeger, O. Tellier, L. Dumoulin, Giovanni Benato, Armatol A., Armengaud E., Armstrong W., Augier C., Avignone F.T., Azzolini O., Barabash A., Bari G., Barresi A., Baudin D., Bellini F., Benato G., Beretta M., Berge L., Biassoni M., Billard J., Boldrini V., Branca A., Brofferio C., Bucci C., Camilleri J., Capelli S., Cappelli L., Cardani L., Carniti P., Casali N., Cazes A., Celi E., Chang C., Chapellier M., Charrier A., Chiesa D., Clemenza M., Colantoni I., Collamati F., Copello S., Cremonesi O., Creswick R.J., Cruciani A., D'Addabbo A., D'Imperio G., Dafinei I., Danevich F.A., De Combarieu M., De Jesus M., De Marcillac P., Dell'Oro S., Di Domizio S., Dompe V., Drobizhev A., Dumoulin L., Fantini G., Faverzani M., Ferri E., Ferri F., Ferroni F., Figueroa-Feliciano E., Formaggio J., Franceschi A., Fu C., Fu S., Fujikawa B.K., Gascon J., Giachero A., Gironi L., Giuliani A., Gorla P., Gotti C., Gras P., Gros M., Gutierrez T.D., Han K., Hansen E.V., Heeger K.M., Helis D.L., Huang H.Z., Huang R.G., Imbert L., Johnston J., Juillard A., Karapetrov G., Keppel G., Khalife H., Kobychev V.V., Kolomensky Y.G., Konovalov S., Liu Y., Loaiza P., Ma L., Madhukuttan M., Mancarella F., Mariam R., Marini L., Marnieros S., Martinez M., Maruyama R.H., Mauri B., Mayer D., Mei Y., Milana S., Misiak D., Napolitano T., Nastasi M., Navick X.F., Nikkel J., Nipoti R., Nisi S., Nones C., Norman E.B., Novosad V., Nutini I., O'Donnell T., Olivieri E., Oriol C., Ouellet J.L., Pagan S., Pagliarone C., Pagnanini L., Pari P., Pattavina L., Paul B., Pavan M., Peng H., Pessina G., Pettinacci V., Pira C., Pirro S., Poda D.V., Polakovic T., Polischuk O.G., Pozzi S., Previtali E., Puiu A., Ressa A., Rizzoli R., Rosenfeld C., Rusconi C., Sanglard V., Scarpaci J., Schmidt B., Sharma V., Shlegel V., Singh V., Sisti M., Speller D., Surukuchi P.T., Taffarello L., Tellier O., Tomei C., Tretyak V.I., Tsymbaliuk A., Velazquez M., Vetter K.J., Wagaarachchi S.L., Wang G., Wang L., Welliver B., Wilson J., Wilson K., Winslow L.A., Xue M., Yan L., Yang J., Yefremenko V., Yumatov V., Zarytskyy M.M., Zhang J., Zolotarova A., Zucchelli S., Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Rayonnement Matière de Saclay (IRAMIS), Science et Ingénierie des Matériaux et Procédés (SIMaP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), CUPID, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Armatol, A, Armengaud, E, Armstrong, W, Augier, C, Avignone, F, Azzolini, O, Barabash, A, Bari, G, Barresi, A, Baudin, D, Bellini, F, Benato, G, Beretta, M, Berge, L, Biassoni, M, Billard, J, Boldrini, V, Branca, A, Brofferio, C, Bucci, C, Camilleri, J, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Cazes, A, Celi, E, Chang, C, Chapellier, M, Charrier, A, Chiesa, D, Clemenza, M, Colantoni, I, Collamati, F, Copello, S, Cremonesi, O, Creswick, R, Cruciani, A, D'Addabbo, A, D'Imperio, G, Dafinei, I, Danevich, F, De Combarieu, M, De Jesus, M, De Marcillac, P, Dell'Oro, S, Di Domizio, S, Dompe, V, Drobizhev, A, Dumoulin, L, Fantini, G, Faverzani, M, Ferri, E, Ferri, F, Ferroni, F, Figueroa-Feliciano, E, Formaggio, J, Franceschi, A, Fu, C, Fu, S, Fujikawa, B, Gascon, J, Giachero, A, Gironi, L, Giuliani, A, Gorla, P, Gotti, C, Gras, P, Gros, M, Gutierrez, T, Han, K, Hansen, E, Heeger, K, Helis, D, Huang, H, Huang, R, Imbert, L, Johnston, J, Juillard, A, Karapetrov, G, Keppel, G, Khalife, H, Kobychev, V, Kolomensky, Y, Konovalov, S, Liu, Y, Loaiza, P, Ma, L, Madhukuttan, M, Mancarella, F, Mariam, R, Marini, L, Marnieros, S, Martinez, M, Maruyama, R, Mauri, B, Mayer, D, Mei, Y, Milana, S, Misiak, D, Napolitano, T, Nastasi, M, Navick, X, Nikkel, J, Nipoti, R, Nisi, S, Nones, C, Norman, E, Novosad, V, Nutini, I, O'Donnell, T, Olivieri, E, Oriol, C, Ouellet, J, Pagan, S, Pagliarone, C, Pagnanini, L, Pari, P, Pattavina, L, Paul, B, Pavan, M, Peng, H, Pessina, G, Pettinacci, V, Pira, C, Pirro, S, Poda, D, Polakovic, T, Polischuk, O, Pozzi, S, Previtali, E, Puiu, A, Ressa, A, Rizzoli, R, Rosenfeld, C, Rusconi, C, Sanglard, V, Scarpaci, J, Schmidt, B, Sharma, V, Shlegel, V, Singh, V, Sisti, M, Speller, D, Surukuchi, P, Taffarello, L, Tellier, O, Tomei, C, Tretyak, V, Tsymbaliuk, A, Velazquez, M, Vetter, K, Wagaarachchi, S, Wang, G, Wang, L, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Xue, M, Yan, L, Yang, J, Yefremenko, V, Yumatov, V, Zarytskyy, M, Zhang, J, Zolotarova, A, and Zucchelli, S

Subjects
data analysis method, double beta decay, nuclear tests of fundamental interactions, Particle decays, Physics - Instrumentation and Detectors, double beta decay, FOS: Physical sciences, Cryogenics, MESH: numerical calculation, 01 natural sciences, law.invention, benchmark, bolometer, double-beta decay: (0neutrino), law, Double beta decay, 0103 physical sciences, Electronic engineering, MESH: benchmark, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], numerical calculations, 010306 general physics, time resolution, nuclear tests of fundamental interactions, Physics, Signal generator, 010308 nuclear & particles physics, Bolometer, Detector, Time resolution, MESH: data analysis method, Instrumentation and Detectors (physics.ins-det), MESH: bolometer, Gran Sasso, Neutrinoless Double Beta decay, Neutrino Physics, MESH: cryogenics, efficiency, cryogenics, pile-up, Rise time, MESH: Gran Sasso, Benchmark (computing), MESH: double-beta decay: (0neutrino), Neutrinoless double-beta decay, MESH: efficiency, Particle decays, MESH: time resolution, MESH: pile-up
Abstract

International audience; Precise characterization of detector time resolution is of crucial importance for next-generation cryogenic-bolometer experiments searching for neutrinoless double-beta decay, such as CUPID, in order to reject background due to pile-up of two-neutrino double-beta decay events. In this paper, we describe a technique developed to study the pile-up rejection capability of cryogenic bolometers. Our approach, which consists of producing controlled pile-up events with a programmable waveform generator, has the benefit that we can reliably and reproducibly control the time separation and relative energy of the individual components of the generated pile-up events. The resulting data allow us to optimize and benchmark analysis strategies to discriminate between individual and pile-up pulses. We describe a test of this technique performed with a small array of detectors at the Laboratori Nazionali del Gran Sasso, in Italy; we obtain a 90% rejection efficiency against pulser-generated pile-up events with rise time of ~15 ms down to time separation between the individual events of 2 ms.

Published
2021

27. A CUPID Li$_2$ $^{100} $MoO$_4$ scintillating bolometer tested in the CROSS underground facility

Author

A. S. Barabash, V. Yumatov, G. D'Imperio, M. De Deo, Ezio Previtali, J. M. Calvo-Mozota, Evelyn Ferri, B. Welliver, L. Gironi, L. Marini, E. Guerard, D. Misiak, D. V. Poda, J. Johnston, V. Dompè, F. T. Avignone, Whitney Armstrong, A. Charrier, O. Tellier, I. Colantoni, A. D'Addabbo, S. Di Domizio, P. Pari, Tomas Polakovic, Massimiliano Clemenza, V. Shlegel, R. Mariam, Yu. G. Kolomensky, Luigi Cappelli, Monica Sisti, M. Pavan, S. Zucchelli, Laura Cardani, P. de Marcillac, C. Augier, Goran Karapetrov, X.-F. Navick, B. K. Fujikawa, Stefano Pozzi, L. Pagnanini, P. T. Surukuchi, O. Azzolini, G. Fantini, Federico Ferri, B. Schmidt, C. Oriol, C. Pagliarone, E. Celi, T. O'Donnell, S. H. Fu, S. Dell'Oro, Giovanni Benato, M. Xue, Yuting Liu, Ch. Bourgeois, C. C. Chang, Stefano Nisi, James R. Wilson, S. Milana, G. Olivier, A. Cruciani, A. Franceschi, Changbo Fu, I. Dafinei, M. Chapellier, C. Gotti, S. Copello, C. Brofferio, S. Pirro, Jie Yang, V. Sharma, D. L. Helis, A. Barresi, J. Camilleri, R. Rizzoli, L. Ma, L. Dumoulin, Davide Chiesa, A. S. Zolotarova, Paolo Carniti, V. Pettinacci, A. Juillard, A. Candela, M. Gros, M. Madhukuttan, I. C. Bandac, M. De Jesus, E. V. Hansen, O. G. Polischuk, A. Drobizhev, Ke Han, F. Bellini, A. Ressa, Reina H. Maruyama, V.I. Tretyak, F.A. Danevich, J. A. Scarpaci, C. Bucci, T. D. Gutierrez, M. Faverzani, Matias Velázquez, P. Loaiza, Kai Vetter, Massimiliano Nastasi, S. I. Konovalov, L. Taffarello, D. Reynet, V. V. Kobychev, L. Bergé, J. Gascon, V. Sanglard, L. Yan, L. Imbert, Virendra Singh, M. M. Zarytskyy, Valentyn Novosad, C. Rosenfeld, Danielle Speller, Andrea Giachero, N. Casali, A. Branca, L. Pattavina, A. Ianni, E. Olivieri, R. J. Creswick, Eric B. Norman, V. Boldrini, P. Gras, K. Wilson, S. Pagan, J. Billard, S. Marnieros, Li Wang, T. Napolitano, R. Nipoti, A. Cazes, P. Gorla, F. Ferroni, E. Figueroa-Feliciano, C. Tomei, C. Pira, Haiping Peng, Oliviero Cremonesi, M. Biassoni, D. Mayer, Jonathan Ouellet, G. Bari, Lindley Winslow, M. de Combarieu, Joseph A. Formaggio, A. Tsymbaliuk, Y. Mei, A. Armatol, K. M. Heeger, R. G. Huang, F. Mancarella, B. Paul, M. I. Martínez, G. Pessina, Jie Zhang, C. Nones, A. Puiu, A. Giuliani, B. Mauri, James Nikkel, Irene Nutini, G. Wang, H. Z. Huang, V. G. Yefremenko, G. Keppel, H. Khalife, E. Armengaud, D. Baudin, M. Beretta, S. L. Wagaarachchi, F. Collamati, Simone Capelli, Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des 2 Infinis Irène Joliot-Curie (IJCLab), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Rayonnement Matière de Saclay (IRAMIS), Science et Ingénierie des Matériaux et Procédés (SIMaP), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), CUPID, CROSS, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Armatol A., Armengaud E., Armstrong W., Augier C., Iii F.T.A., Azzolini O., Bandac I.C., Barabash A.S., Bari G., Barresi A., Baudin D., Bellini F., Benato G., Beretta M., Berge L., Bourgeois C., Biassoni M., Billard J., Boldrini V., Branca A., Brofferio C., Bucci C., Calvo-Mozota J.M., Camilleri J., Candela A., Capelli S., Cappelli L., Cardani L., Carniti P., Casali N., Cazes A., Celi E., Chang C., Chapellier M., Charrier A., Chiesa D., Clemenza M., Colantoni I., Collamati F., Copello S., Cremonesi O., Creswick R.J., Cruciani A., D'Addabbo A., D'Imperio G., Dafinei I., Danevich F.A., De Combarieu M., Deo M.D., Jesus M.D., De Marcillac P., Dell'Oro S., Domizio S.D., Dompe V., Drobizhev A., Dumoulin L., Fantini G., Faverzani M., Ferri E., Ferri F., Ferroni F., Figueroa-Feliciano E., Formaggio J., Franceschi A., Fu C., Fu S., Fujikawa B.K., Gascon J., Giachero A., Gironi L., Giuliani A., Gorla P., Gotti C., Gras P., Gros M., Guerard E., Gutierrez T.D., Han K., Hansen E.V., Heeger K.M., Helis D.L., Huang H.Z., Huang R.G., Ianni A., Imbert L., Johnston J., Juillard A., Karapetrov G., Keppel G., Khalife H., Kobychev V.V., Kolomensky Y.G., Konovalov S.I., Liu Y., Loaiza P., Ma L., Madhukuttan M., Mancarella F., Mariam R., Marini L., Marnieros S., Martinez M., Maruyama R.H., Mauri B., Mayer D., Mei Y., Milana S., Misiak D., Napolitano T., Nastasi M., Navick X.-F., Nikkel J., Nipoti R., Nisi S., Nones C., Norman E.B., Novosad V., Nutini I., O'Donnell T., Olivier G., Olivieri E., Oriol C., Ouellet J.L., Pagan S., Pagliarone C., Pagnanini L., Pari P., Pattavina L., Paul B., Pavan M., Peng H., Pessina G., Pettinacci V., Pira C., Pirro S., Poda D.V., Polakovic T., Polischuk O.G., Pozzi S., Previtali E., Puiu A., Ressa A., Reynet D., Rizzoli R., Rosenfeld C., Sanglard V., Scarpaci J.A., Schmidt B., Sharma V., Shlegel V.N., Singh V., Sisti M., Speller D., Surukuchi P.T., Taffarello L., Tellier O., Tomei C., Tretyak V.I., Tsymbaliuk A., Velazquez M., Vetter K.J., Wagaarachchi S.L., Wang G., Wang L., Welliver B., Wilson J., Wilson K., Winslow L.A., Xue M., Yan L., Yang J., Yefremenko V., Yumatov V.I., Zarytskyy M.M., Zhang J., Zolotarova A.S., Zucchelli S., Armatol, A, Armengaud, E, Armstrong, W, Augier, C, Avignone F. T., I, Azzolini, O, Bandac, I, Barabash, A, Bari, G, Barresi, A, Baudin, D, Bellini, F, Benato, G, Beretta, M, Berge, L, Bourgeois, C, Biassoni, M, Billard, J, Boldrini, V, Branca, A, Brofferio, C, Bucci, C, Calvo-Mozota, J, Camilleri, J, Candela, A, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Cazes, A, Celi, E, Chang, C, Chapellier, M, Charrier, A, Chiesa, D, Clemenza, M, Colantoni, I, Collamati, F, Copello, S, Cremonesi, O, Creswick, R, Cruciani, A, D'Addabbo, A, D'Imperio, G, Dafinei, I, Danevich, F, De Combarieu, M, Deo, M, Jesus, M, De Marcillac, P, Dell'Oro, S, Domizio, S, Dompe, V, Drobizhev, A, Dumoulin, L, Fantini, G, Faverzani, M, Ferri, E, Ferri, F, Ferroni, F, Figueroa-Feliciano, E, Formaggio, J, Franceschi, A, Fu, C, Fu, S, Fujikawa, B, Gascon, J, Giachero, A, Gironi, L, Giuliani, A, Gorla, P, Gotti, C, Gras, P, Gros, M, Guerard, E, Gutierrez, T, Han, K, Hansen, E, Heeger, K, Helis, D, Huang, H, Huang, R, Ianni, A, Imbert, L, Johnston, J, Juillard, A, Karapetrov, G, Keppel, G, Khalife, H, Kobychev, V, Kolomensky, Y, Konovalov, S, Liu, Y, Loaiza, P, Ma, L, Madhukuttan, M, Mancarella, F, Mariam, R, Marini, L, Marnieros, S, Martinez, M, Maruyama, R, Mauri, B, Mayer, D, Mei, Y, Milana, S, Misiak, D, Napolitano, T, Nastasi, M, Navick, X, Nikkel, J, Nipoti, R, Nisi, S, Nones, C, Norman, E, Novosad, V, Nutini, I, O'Donnell, T, Olivier, G, Olivieri, E, Oriol, C, Ouellet, J, Pagan, S, Pagliarone, C, Pagnanini, L, Pari, P, Pattavina, L, Paul, B, Pavan, M, Peng, H, Pessina, G, Pettinacci, V, Pira, C, Pirro, S, Poda, D, Polakovic, T, Polischuk, O, Pozzi, S, Previtali, E, Puiu, A, Ressa, A, Reynet, D, Rizzoli, R, Rosenfeld, C, Sanglard, V, Scarpaci, J, Schmidt, B, Sharma, V, Shlegel, V, Singh, V, Sisti, M, Speller, D, Surukuchi, P, Taffarello, L, Tellier, O, Tomei, C, Tretyak, V, Tsymbaliuk, A, Velazquez, M, Vetter, K, Wagaarachchi, S, Wang, G, Wang, L, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Xue, M, Yan, L, Yang, J, Yefremenko, V, Yumatov, V, Zarytskyy, M, Zhang, J, Zolotarova, A, and Zucchelli, S

Subjects
gas and liquid scintillators), Physics - Instrumentation and Detectors, Accurate estimation, Physics::Instrumentation and Detectors, Bolometer, Analytical chemistry, Double-beta decay, FOS: Physical sciences, Cryogenic detector, Radiopurity, 01 natural sciences, 030218 nuclear medicine & medical imaging, law.invention, Particle identification, Particle identification methods, 03 medical and health sciences, Particle identification method, 0302 clinical medicine, CUORE, law, 0103 physical sciences, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Detector array, Instrumentation, Mathematical Physics, Event triggered, Physics, Lithium molybdate, 010308 nuclear & particles physics, Astrophysics::Instrumentation and Methods for Astrophysics, Instrumentation and Detectors (physics.ins-det), Scintillators, scintillation and light emission processes (solid, gas and liquid scintillators), Double-beta decay detectors, scintillation and light emission processes (solid, Double-beta decay detector, Cryogenic detectors, Scintillators, Crystal scintillator, Energy (signal processing)
Abstract

A scintillating bolometer based on a large cubic Li$_{2}$$^{100}$MoO$_4$ crystal (45 mm side) and a Ge wafer (scintillation detector) has been operated in the CROSS cryogenic facility at the Canfranc underground laboratory in Spain. The dual-readout detector is a prototype of the technology that will be used in the next-generation $0\nu2\beta$ experiment CUPID. The measurements were performed at 18 and 12 mK temperature in a pulse tube dilution refrigerator. This setup utilizes the same technology as the CUORE cryostat that will host CUPID and so represents an accurate estimation of the expected performance. The Li$_{2}$$^{100}$MoO$_4$ bolometer shows a high energy resolution of 6 keV FWHM at the 2615 keV $\gamma$ line. The detection of scintillation light for each event triggered by the Li$_{2}$$^{100}$MoO$_4$ bolometer allowed for a full separation ($\sim$8$\sigma$) between $\gamma$($\beta$) and $\alpha$ events above 2 MeV. The Li$_{2}$$^{100}$MoO$_4$ crystal also shows a high internal radiopurity with $^{228}$Th and $^{226}$Ra activities of less than 3 and 8 $\mu$Bq/kg, respectively. Taking also into account the advantage of a more compact and massive detector array, which can be made of cubic-shaped crystals (compared to the cylindrical ones), this test demonstrates the great potential of cubic Li$_{2}$$^{100}$MoO$_4$ scintillating bolometers for high-sensitivity searches for the $^{100}$Mo $0\nu2\beta$ decay in CROSS and CUPID projects., Comment: 19 pages, 7 figures, 1 table

Published
2021

28. Whole-genome sequencing analysis of semi-supercentenarians

Author

Evelyn Ferri, Luciano Xumerle, Julien Marquis, Oliviero Olivieri, Gastone Castellani, Cristina Giuliani, Patrizia D'Aquila, Sandro Sorbi, Daniela Mari, Claudia Sala, Maria Giulia Bacalini, Paolo Garagnani, Patrick Descombes, Nicola Martinelli, Beatrice Arosio, Sebastiano Collino, Jérôme Carayol, Frederic Raymond, Benedetta Nacmias, Luca Bertamini, Davide Pettener, Domenico Girelli, Giuseppe Passarino, Vincenzo Iannuzzi, Katarzyna Malgorzata Kwiatkowska, Martina Casati, Donata Luiselli, Claudio Franceschi, Daniela Monti, Massimo Delledonne, Francesco De Rango, Elena Marasco, Armand Valsesia, Chiara Pirazzini, Alberto Ferrarini, Garagnani P., Marquis J., Delledonne M., Pirazzini C., Marasco E., Kwiatkowska K.M., Iannuzzi V., Bacalini M.G., Valsesia A., Carayol J., Raymond F., Ferrarini A., Xumerle L., Collino S., Mari D., Arosio B., Casati M., Ferri E., Monti D., Nacmias B., Sorbi S., Luiselli D., Pettener D., Castellani G., Sala C., Passarino G., De Rango F., D'aquila P., Bertamini L., Martinelli N., Girelli D., Olivieri O., Giuliani C., Descombes P., and Franceschi C.

Subjects
0301 basic medicine, Male, DNA Repair, semi-supercentenarians, medicine.disease_cause, Genome, Germline, genomic, Cohort Studies, 0302 clinical medicine, 80 and over, genetics, Biology (General), media_common, Genetics, Aged, 80 and over, Mutation, geroscience, General Neuroscience, Longevity, General Medicine, sequencing, Middle Aged, 3. Good health, Italy, ageing, clonal hematopoiesis, genomics, human, longevity, Cohort, Medicine, Female, Genetic Background, Research Article, QH301-705.5, DNA repair, Science, media_common.quotation_subject, semi-supercentenarian, Genomics, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Humans, Aged, Whole genome sequencing, General Immunology and Microbiology, Whole Genome Sequencing, Genetics and Genomics, 030104 developmental biology, Clonal Hematopoiesi, genetic, Cohort Studie, 030217 neurology & neurosurgery
Abstract

Extreme longevity is the paradigm of healthy aging as individuals who reached the extreme decades of human life avoided or largely postponed all major age-related diseases. In this study, we sequenced at high coverage (90X) the whole genome of 81 semi-supercentenarians and supercentenarians [105+/110+] (mean age: 106.6 ± 1.6) and of 36 healthy unrelated geographically matched controls (mean age 68.0 ± 5.9) recruited in Italy. The results showed that 105+/110+ are characterized by a peculiar genetic background associated with efficient DNA repair mechanisms, as evidenced by both germline data (common and rare variants) and somatic mutations patterns (lower mutation load if compared to younger healthy controls). Results were replicated in a second independent cohort of 333 Italian centenarians and 358 geographically matched controls. The genetics of 105+/110+ identified DNA repair and clonal haematopoiesis as crucial players for healthy aging and for the protection from cardiovascular events.

Published
2021

29. Vitamin E and Alzheimer’s disease: the mediating role of cellular aging

Author

Simona Ciccone, Marta Mansi, Beatrice Arosio, Paolo Rossi, Martina Casati, Patrizia Bastiani, Virginia Boccardi, Michela Scamosci, Laura Bertagnoli, Patrizia Mecocci, and Evelyn Ferri

Subjects
Male, Aging, medicine.medical_specialty, Antioxidant, medicine.medical_treatment, Nitrosative stress, Disease, Oxidative phosphorylation, medicine.disease_cause, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Humans, Vitamin E, 030212 general & internal medicine, Cellular Senescence, Telomere length, business.industry, Healthy subjects, Telomere Homeostasis, Endocrinology, chemistry, Cellular Aging, Oxidative stress, Case-Control Studies, Disease Progression, Female, Tocotrienol, Geriatrics and Gerontology, Alzheimer’s disease, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

Vitamin E represents a potent antioxidant and anti-inflammatory system, playing a role in Alzheimer’s disease (AD). Different plasma concentrations of the forms of vitamin E are observed in AD compared to cognitively healthy subjects. Since these modifications may modulate the markers of oxidative stress and cellular aging, we aim to explore the relationship between vitamin E forms and leukocyte telomere length (LTL) in AD. 53 AD subjects and 40 cognitively healthy controls (CTs) were enrolled. The vitamin E forms (α-, β-, γ- and δ-tocopherol, α-, β-, γ- and δ-tocotrienol), the ratio of α-tocopherylquinone/α-tocopherol and 5-nitro-γ-tocopherol/γ-tocopherol (markers of oxidative/nitrosative damage) and LTL were measured. Regression model was used to explore the associations of vitamin E forms and LTL with AD. The interaction of LTL in the association between vitamin E forms and AD was tested. AD subjects showed significantly lower concentrations of α-, β-, γ- and δ-tocopherol, α- and δ-tocotrienol, total tocopherols, total tocotrienols and total vitamin E compared to CTs. AD subjects showed higher values of nitrosative/oxidative damage. The adjusted analyses confirmed a significant relationship of AD with plasma concentrations of α- and β-tocopherols, δ-tocotrienol, total tocopherols, total tocotrienol, total vitamin E and oxidative/nitrosative damage. However, nitrosative damage was significantly associated with AD only in subjects with higher LTL and not in those expressing marked cellular aging. Our study confirms the role of vitamin E in AD pathology and indicates that nitrosative damage influences the association with AD only in subjects characterized by longer LTL.

Published
2020

30. Perspectives of lowering CUORE thresholds with Optimum Trigger

Author

Monica Sisti, A. Bersani, C. Brofferio, G. Fantini, A. Caminata, Marco Pallavicini, B. Welliver, C. Pagliarone, R. G. Huang, M. Faverzani, Y. u. G. Kolomensky, H. Z. Huang, G. Keppel, Massimiliano Nastasi, Yudi Ma, S. Pozzi, S. L. Wagaarachchi, C. Cosmelli, A. Giuliani, C. Pira, C. Rusconi, Ke Han, A. Branca, N. D. Scielzo, Reina H. Maruyama, N. Casali, Stefano Dell'Oro, Lucia Canonica, F. Bellini, I. Dafinei, V. Novati, T. Wise, V. Pettinacci, Davide Chiesa, Stefano Zucchelli, Laura Cardani, L. Gironi, M. Pavan, B. K. Fujikawa, Y. Mei, V. Singh, D. D'Aguanno, F. T. Avignone, L. Taffarello, R. J. Creswick, C. Rosenfeld, P. Gorla, Danielle Speller, F. Ferroni, C. Tomei, M. Vignati, E. Previtali, Simone Capelli, D. Q. Adams, L. Marini, C. J. Davis, K. Alfonso, T. O'Donnell, B. Schmidt, N. Chott, C. Nones, A. Puiu, Lindley Winslow, S. Zimmermann, Oliviero Cremonesi, J. Johnston, L. Pattavina, Irene Nutini, S. Copello, C. Bucci, Miriam Lucio Martinez, Paolo Carniti, Sergio Di Domizio, S. Pirro, Xi-Guang Cao, E. Fiorini, S. J. Freedman, K. M. Heeger, Luigi Cappelli, T. D. Gutierrez, F. Terranova, K. Wilson, G. Pessina, B. S. Wang, Jonathan Ouellet, G. Bari, O. Azzolini, Evelyn Ferri, N. Moggi, Samuele Sangiorgio, A. Nucciotti, C. Alduino, Jeremy S. Cushman, S. Morganti, L. Zanotti, Carlo Ligi, A. Campani, V. Dompè, A. D'Addabbo, A. Leder, J. S. Wilson, Franceschi, Eric B. Norman, M. Sakai, T. Napolitano, M. Biassoni, Giovanni Benato, A. Drobizhev, C. Gotti, A. Giachero, D. Q. Fang, Massimiliano Clemenza, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Physics, History, CUORE, 010308 nuclear & particles physics, Physics::Instrumentation and Detectors, WIMP nucleus: scattering, trigger: programming, 01 natural sciences, Large target, tellurium: oxygen, Computer Science Applications, Education, Combinatorics, energy: threshold, Low energy, double-beta decay: (0neutrino), 0103 physical sciences, High Energy Physics::Experiment, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 010306 general physics, activity report, energy: low
Abstract

Author(s): Dompe, V; Adams, DQ; Alduino, C; Alfonso, K; Avignone, FT; Azzolini, O; Bari, G; Bellini, F; Benato, G; Bersani, A; Biassoni, M; Branca, A; Brofferio, C; Bucci, C; Caminata, A; Campani, A; Canonica, L; Cao, XG; Capelli, S; Cappelli, L; Cardani, L; Carniti, P; Casali, N; Chiesa, D; Chott, N; Clemenza, M; Copello, S; Cosmelli, C; Cremonesi, O; Creswick, RJ; Cushman, JS; D'Addabbo, A; D'Aguanno, D; Dafinei, I; Davis, CJ; Dell'Oro, S; Domizio, SD; Drobizhev, A; Fang, DQ; Fantini, G; Faverzani, M; Ferri, E; Ferroni, F; Fiorini, E; Franceschi, MA; Freedman, SJ; Fujikawa, BK; Giachero, A; Gironi, L; Giuliani, A; Gorla, P; Gotti, C; Gutierrez, TD; Han, K; Heeger, KM; Huang, RG; Huang, HZ; Johnston, J; Keppel, G; Kolomensky, YG; Leder, A; Ligi, C; Ma, YG; Marini, L; Martinez, M; Maruyama, RH; Mei, Y; Moggi, N; Morganti, S; Napolitano, T; Nastasi, M; Nones, C; Norman, EB; Novati, V; Nucciotti, A; Nutini, I; O'Donnell, T; Ouellet, JL; Pagliarone, CE; Pallavicini, M; Pattavina, L; Pavan, M; Pessina, G; Pettinacci, V; Pira, C | Abstract: CUORE is a cryogenic experiment that focuses on the search of neutrinoless double beta decay in 130Te and it is located at the Gran Sasso National Laboratories. Its detector consists of 988 TeO2 crystals operating at a base temperature of ∼10 mK. It is the first ton-scale bolometric experiment ever realized for this purpose. Thanks to its large target mass and ultra-low background, the CUORE detector is also suitable for the search of other rare phenomena. In particular the low energy part of the spectra is interesting for the detection of WIMP-nuclei scattering reactions. One of the most important requirements to perform these studies is represented by the achievement of a stable energy threshold lower than 10 keV. Here, the CUORE capability to accomplish this purpose using a low energy software trigger will be presented and described.

Published
2020

31. TES Microcalorimeters for PTOLEMY

Author

Flavio Gatti, Evelyn Ferri, Andrea Giachero, A. Nucciotti, M. Faverzani, R. Filippo, Michele Biasotti, M. Rajteri, A. Puiu, E. Monticone, Rajteri, M, Biasotti, M, Faverzani, M, Ferri, E, Filippo, R, Gatti, F, Giachero, A, Monticone, E, Nucciotti, A, and Puiu, A

Subjects
Physics, Photon, business.industry, Transition-edge sensor, Electron, Condensed Matter Physics, 01 natural sciences, Atomic and Molecular Physics, and Optics, 010305 fluids & plasmas, Cosmic neutrino background, Key point, Optics, 0103 physical sciences, General Materials Science, Thin film, 010306 general physics, business, High electron, Penetration depth, Visible spectrum
Abstract

The PTOLEMY project is devoted to directly detect the cosmic neutrino background. A key point for the project success is the development of a device which is capable of detecting electrons with an energy resolution lower than 0.05eV. Microcalorimeters based on transition-edge sensors are among the best candidates since they already reach 0.11eV of energy resolution for telecomm photons. To further improve the energy resolution, while maintaining a suitable saturation energy, it is necessary to reduce the transition temperature. This could be achieved by proximity effect of a normal-superconducting bilayer. To this aim, TiAu very thin films are under development to demonstrate the feasibility of reaching 0.05eV energy resolution for light pulses of few eV. Thanks to the high electron stopping power of metals, the penetration depth of low energy incident electrons is limited to few nanometers and, with respect to visible light, we expect a high detection efficiency, while keeping similar dark counts and energy resolution.

Published
2020

32. Lowering the Energy Threshold of the CUORE Experiment: Benefits in the Surface Alpha Events Reconstruction: Comparison Between Optimum Trigger and Derivative Trigger Performance in the Search for 0 νββ

Author

L. Pattavina, Marco Pallavicini, L. Canonica, L. Marini, S. Di Domizio, C. Bucci, T. D. Gutierrez, G. Pessina, K. Wilson, Stefano Dell'Oro, Jonathan Ouellet, J. Johnston, G. Bari, Laura Cardani, L. Zanotti, J. Nikkel, L. Gironi, F. T. Avignone, H. Z. Huang, B. K. Fujikawa, G. Keppel, Stefano Pozzi, Y. G. Ma, Massimiliano Clemenza, Carlo Cosmelli, Davide Chiesa, C. Nones, A. Puiu, V. Pettinacci, S. Zucchelli, N. D. Scielzo, L. Pagnanini, C. Brofferio, T. O'Donnell, D. Q. Fang, Claudio Gotti, Ke Han, Reina H. Maruyama, M. Vignati, C. Rusconi, Stuart J. Freedman, D. D'Aguanno, Ettore Fiorini, V. Novati, James R. Wilson, Andrea Giachero, C. Rosenfeld, P. Gorla, F. Ferroni, C. Tomei, M. A. Franceschi, C. Pagliarone, D. Q. Adams, R. G. Huang, N. Casali, F. Terranova, Vasundhara Singh, K. Alfonso, C. J. Davis, Monica Sisti, B. Schmidt, Eric B. Norman, B. S. Wang, L. Ma, O. Azzolini, Y. Mei, Lindley Winslow, V. Sharma, T. Napolitano, S. Copello, I. Dafinei, M. Sakai, Paolo Carniti, Silvia Capelli, Xi-Guang Cao, Massimiliano Nastasi, K. M. Heeger, F. Bellini, S. Pirro, L. Cappelli, Oliviero Cremonesi, M. Biassoni, R. J. Creswick, G. Fantini, M. Pavan, V. Dompè, Giovanni Benato, A. D'Addabbo, C. Pira, A. Caminata, Ezio Previtali, S. Morganti, B. Welliver, Carlo Ligi, Evelyn Ferri, N. Moggi, Samuele Sangiorgio, A. Campani, A. Nucciotti, C. Alduino, M. Faverzani, Yu. G. Kolomensky, A. Branca, L. Taffarello, A. Giuliani, Danielle Speller, S. L. Wagaarachchi, N. Chott, Irene Nutini, S. Zimmermann, Campani, A, Adams, D, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Caminata, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, D'Addabbo, A, D'Aguanno, D, Dafinei, I, Davis, C, Dell'Oro, S, Di Domizio, S, Dompe, V, Fang, D, Fantini, G, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gorla, P, Gotti, C, Gutierrez, T, Han, K, Heeger, K, Huang, R, Huang, H, Johnston, J, Keppel, G, Kolomensky, Y, Ligi, C, Ma, Y, Ma, L, Marini, L, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Napolitano, T, Nastasi, M, Nikkel, J, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O'Donnell, T, Ouellet, J, Pagliarone, C, Pagnanini, L, Pallavicini, M, Pattavina, L, Pavan, M, Pessina, G, Pettinacci, V, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Puiu, A, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Schmidt, B, Scielzo, N, Sharma, V, Singh, V, Sisti, M, Speller, D, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Zanotti, L, Zimmermann, S, Zucchelli, S, Campani A., Adams D.Q., Alduino C., Alfonso K., Avignone F.T., Azzolini O., Bari G., Bellini F., Benato G., Biassoni M., Branca A., Brofferio C., Bucci C., Caminata A., Canonica L., Cao X.G., Capelli S., Cappelli L., Cardani L., Carniti P., Casali N., Chiesa D., Chott N., Clemenza M., Copello S., Cosmelli C., Cremonesi O., Creswick R.J., D'Addabbo A., D'Aguanno D., Dafinei I., Davis C.J., Dell'Oro S., Di Domizio S., Dompe V., Fang D.Q., Fantini G., Faverzani M., Ferri E., Ferroni F., Fiorini E., Franceschi M.A., Freedman S.J., Fujikawa B.K., Giachero A., Gironi L., Giuliani A., Gorla P., Gotti C., Gutierrez T.D., Han K., Heeger K.M., Huang R.G., Huang H.Z., Johnston J., Keppel G., Kolomensky Y.G., Ligi C., Ma Y.G., Ma L., Marini L., Maruyama R.H., Mei Y., Moggi N., Morganti S., Napolitano T., Nastasi M., Nikkel J., Nones C., Norman E.B., Novati V., Nucciotti A., Nutini I., O'Donnell T., Ouellet J.L., Pagliarone C.E., Pagnanini L., Pallavicini M., Pattavina L., Pavan M., Pessina G., Pettinacci V., Pira C., Pirro S., Pozzi S., Previtali E., Puiu A., Rosenfeld C., Rusconi C., Sakai M., Sangiorgio S., Schmidt B., Scielzo N.D., Sharma V., Singh V., Sisti M., Speller D., Taffarello L., Terranova F., Tomei C., Vignati M., Wagaarachchi S.L., Wang B.S., Welliver B., Wilson J., Wilson K., Winslow L.A., Zanotti L., Zimmermann S., and Zucchelli S.

Subjects
Particle physics, Bolometers for dark matter research, Physics::Instrumentation and Detectors, trigger algorithm, 01 natural sciences, Coincidence, law.invention, CUORE, WIMP, law, Double beta decay, 0103 physical sciences, General Materials Science, Neutrinoless double beta decay, 010306 general physics, Axion, Physics, 010308 nuclear & particles physics, Scattering, Bolometer, Astrophysics::Instrumentation and Methods for Astrophysics, Trigger algorithms, Condensed Matter Physics, Digital signal processing, Atomic and Molecular Physics, and Optics, Energy (signal processing)
Abstract

CUORE is a tonne-scale cryogenic experiment located at the Laboratori Nazionali del Gran Sasso that exploits bolometric technique to search for neutrinoless double beta decay of 130Te. Thanks to its very low background and large mass, CUORE is also a powerful tool to study a broad class of phenomena, such as solar axions and WIMP scattering. The ability to conduct such sensitive searches crucially depends on the energy threshold, which has to be kept as low as possible. In this contribution, we show how the trigger algorithm affects the sensitivity to low-energy phenomena and the interpretation of the energy spectrum. In particular, we focus on the impact that the trigger algorithm has on the identification of the coincidence events among different crystals and, consequently, on the reconstruction of the background.

Published
2020

33. Status and results from the CUORE experiment

Author

C. Bucci, T. D. Gutierrez, Silvia Capelli, Massimiliano Nastasi, C. Pira, L. Gironi, F. T. Avignone, X. G. Cao, S. Di Domizio, V. Dompè, L. Taffarello, Danielle Speller, L. Cappelli, Laura Cardani, H. Z. Huang, M. Pavan, M. A. Franceschi, B. K. Fujikawa, Stefano Pozzi, Carlo Ligi, C. Pagliarone, Y. Mei, Massimiliano Clemenza, Carlo Cosmelli, Stefano Dell'Oro, A. D’Addabbo, M. Vignati, Lindley Winslow, A. Campani, S. Zucchelli, G. Keppel, K. Wilson, Davide Chiesa, Claudio Gotti, R. G. Huang, M. Faverzani, Jonathan Ouellet, G. Bari, A. Branca, C. Brofferio, L. Ma, Deqing Fang, S. Pirro, C. Rusconi, N. Casali, A. Caminata, Ezio Previtali, S. Zimmermann, S. L. Wagaarachchi, S. Morganti, T. O'Donnell, B. Welliver, K. M. Heeger, G. Fantini, C. Nones, A. Puiu, V. Pettinacci, V. Sharma, D. D'Aguanno, J. Nikkel, N. Chott, Oliviero Cremonesi, Marco Pallavicini, G. Pessina, A. Giuliani, Yu. G. Kolomensky, Ke Han, Reina H. Maruyama, C. Rosenfeld, Stuart J. Freedman, P. Gorla, F. Ferroni, C. Tomei, C. J. Davis, L. Zanotti, Irene Nutini, Evelyn Ferri, Yu-Gang Ma, F. Terranova, N. Moggi, Samuele Sangiorgio, P. T. Surukuchi, A. Nucciotti, L. Pagnanini, C. Alduino, S. Copello, Paolo Carniti, Ettore Fiorini, V. Novati, Andrea Giachero, D. Q. Adams, K. Alfonso, L. Pattavina, N. D. Scielzo, L. Canonica, L. Marini, Vasundhara Singh, J. Johnston, B. Schmidt, B. S. Wang, O. Azzolini, I. Dafinei, M. Sakai, James R. Wilson, F. Bellini, Monica Sisti, R. J. Creswick, Giovanni Benato, Eric B. Norman, T. Napolitano, M. Biassoni, Campani, A, Adams, D, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Caminata, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, D'Addabbo, A, D'Aguanno, D, Dafinei, I, Davis, C, Dell'Oro, S, Di Domizio, S, Dompe, V, Fang, D, Fantini, G, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gorla, P, Gotti, C, Gutierrez, T, Han, K, Heeger, K, Huang, R, Huang, H, Johnston, J, Keppel, G, Kolomensky, Y, Ligi, C, Ma, Y, Ma, L, Marini, L, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Napolitano, T, Nastasi, M, Nikkel, J, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O'Donnell, T, Ouellet, J, Pagliarone, C, Pagnanini, L, Pallavicini, M, Pattavina, L, Pavan, M, Pessina, G, Pettinacci, V, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Puiu, A, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Schmidt, B, Scielzo, N, Sharma, V, Singh, V, Sisti, M, Speller, D, Surukuchi, P, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Zanotti, L, Zimmermann, S, Zucchelli, S, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPhP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CUORE, and Département de Physique des Particules (ex SPP) (DPP)

Subjects
Nuclear and High Energy Physics, data analysis method, background: model, [PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex], 01 natural sciences, Combinatorics, CUORE, double-beta decay: (0neutrino), bolometer, 0103 physical sciences, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], Neutrinoless double beta decay, 010306 general physics, activity report, Physics, 010308 nuclear & particles physics, 29.90.+r, Astronomy and Astrophysics, Background model, Atomic and Molecular Physics, and Optics, tellurium: nuclide, data management, Two-neutrino double beta decay, background model, two-neutrino double beta decay, experimental results
Abstract

Author(s): Campani, A; Adams, DQ; Alduino, C; Alfonso, K; Avignone, FT; Azzolini, O; Bari, G; Bellini, F; Benato, G; Biassoni, M; Branca, A; Brofferio, C; Bucci, C; Caminata, A; Canonica, L; Cao, XG; Capelli, S; Cappelli, L; Cardani, L; Carniti, P; Casali, N; Chiesa, D; Chott, N; Clemenza, M; Copello, S; Cosmelli, C; Cremonesi, O; Creswick, RJ; D'Addabbo, A; D'Aguanno, D; Dafinei, I; Davis, CJ; Dell'oro, S; Di Domizio, S; Dompe, V; Fang, DQ; Fantini, G; Faverzani, M; Ferri, E; Ferroni, F; Fiorini, E; Franceschi, MA; Freedman, SJ; Fujikawa, BK; Giachero, A; Gironi, L; Giuliani, A; Gorla, P; Gotti, C; Gutierrez, TD; Han, K; Heeger, KM; Huang, RG; Huang, HZ; Johnston, J; Keppel, G; Kolomensky, YG; Ligi, C; Ma, YG; Ma, L; Marini, L; Maruyama, RH; Mei, Y; Moggi, N; Morganti, S; Napolitano, T; Nastasi, M; Nikkel, J; Nones, C; Norman, EB; Novati, V; Nucciotti, A; Nutini, I; O'Donnell, T; Ouellet, JL; Pagliarone, CE; Pagnanini, L; Pallavicini, M; Pattavina, L; Pavan, M; Pessina, G; Pettinacci, V; Pira, C; Pirro, S; Pozzi, S | Abstract: The Cryogenic Underground Observatory for Rare Events (CUORE) is a tonne-scale cryogenic experiment located at the Laboratori Nazionali del Gran Sasso that exploits bolometric technique to search for neutrinoless double beta decay (0νββ) of 130Te. The detector consists of a segmented array of 988 natural TeO2 cubic crystals arranged in a cylindrical compact structure of 19 towers. The detector construction was completed in August 2016 and data taking started in Spring 2017. In this work, we present a brief description of the bolometric technique for rare events search and the CUORE detector, then we concentrate on the data analysis results. In this respect, we focus on the procedure for data processing and on the first 0νββ results we obtained from a total TeO2 exposure of 86.3kg yr. Next, we illustrate the main background sources and the CUORE background model, from which we obtain the most precise measurement of 130Te 2νββ half-life to date. Finally, we discuss the improvements achieved with 2018 and 2019 detector optimization campaigns and the current perspectives of our experiment.

Published
2020

34. Characterization of the low temperature behavior of thin Titanium/Titanium Nitride multilayer films

Author

Renato Mezzena, Benno Margesin, C Giordano, Andrea Giachero, A. Puiu, M. Faverzani, Evelyn Ferri, A. Nucciotti, Faverzani, M, Ferri, E, Giachero, A, Giordano, C, Margesin, B, Mezzena, R, Nucciotti, A, and Puiu, A

Subjects
010302 applied physics, Materials science, Silicon, Transition temperature, Metals and Alloys, chemistry.chemical_element, Nitride, Condensed Matter Physics, 01 natural sciences, Titanium nitride, titanium nitride, multilayers Ti/TiNfilms, resistivity, superconducting transition temperature, proximity effect, chemistry.chemical_compound, chemistry, Electrical resistance and conductance, Electrical resistivity and conductivity, 0103 physical sciences, Materials Chemistry, Ceramics and Composites, Electrical and Electronic Engineering, Composite material, 010306 general physics, Tin, Titanium
Abstract

Titanium and titanium nitride layers were alternately sputtered on a high resistivity silicon wafer to obtain a multilayer film structure, for a total thickness ranging between 34 and 180 nm. The electrical resistance of the Ti/TiN film was characterized from room temperature down to the superconducting transition. Both the resistivity just above the transition and the critical temperature were investigated as a function of the total film thickness and the single TiN layer thickness, respectively. The obtained resistivity range is 67–312 μΩ cm. Exploiting the proximity effect, we were able to tune the critical temperature in the 0.29–4.5 K range. A comparison between experimental data and theoretical models is proposed in order to facilitate the a priori design of superconducting detectors.

Published
2020

35. Corrigendum to 'Peripheral Blood Mononuclear Cells as a Laboratory to Study Dementia in the Elderly'

Author

Cristina Gussago, Beatrice Arosio, Evelyn Ferri, Enzo Tedone, Martina Casati, Mauro Maccarrone, Claudio D'Addario, Paolo Rossi, Paola Nicolini, and Daniela Mari

Subjects
0301 basic medicine, medicine.medical_specialty, Tau pathology, General Immunology and Microbiology, business.industry, Published Erratum, General Medicine, Environmental exposure, Creative commons, medicine.disease, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Inflammatory molecules, Medicine, Dementia, In patient, business, Psychiatry, Corrigendum
Abstract

The article titled “Peripheral Blood Mononuclear Cells as a Laboratory to Study Dementia in the Elderly” [1] was found to contain a substantial amount of material from previously published articles including the following sources: (i)Manraj S. Bhamra and Nicholas J. Ashton, “Finding a pathological diagnosis for Alzheimer’s disease: Are inflammatory molecules the answer?: Proteomics and 2DE”, Electrophoresis, 2012. 10.1002/elps.201200161. [2] (not cited)(ii)Kelly M. Bakulski, Laura S. Rozek, Dana C. Dolinoy, Henry L. Paulson and Howard Hu, “Alzheimer’s Disease and Environmental Exposure to Lead: The Epidemiologic Evidence and Potential Role of Epigenetics”, Current Alzheimer Research (2012) 9: 563. 10.2174/156720512800617991. [3] (cited as reference [75])(iii)Cristina Gussago, “Il Recettore Adenosinico A2a Come Possibile Biomarcatore Nella Diagnosi Differenziale Delle Demenze Nell’anziano”, Universita Degli Studi Di Milano. 10.13130%2Fgussago-cristina_phd2014-03-10. [4] (not cited)(iv)B. Arosio, A. Bulbarelli, S. Bastias Candia, E. Lonati, L. Mastronardi, P. Romualdi, S. Candeletti, C. Gussago, D. Galimberti, E. Scarpini, B. Dell Osso, C. Altamura, M. Maccarrone, L. Bergamaschini, C. D Addario, D. Mari. “Pin1 Contribution to Alzheimer s Disease: Transcriptional and Epigenetic Mechanisms in Patients with Late-Onset Alzheimer s Disease”, Neurodegenerative Diseases, 2012.10.1159/000333799. [5] (cited as reference [66])(v)K. Ando, P. Dourlen, A. V. Sambo et al., “Tau pathology modulates Pin1 post-translational modifications and may be relevant as biomarker,” Neurobiology of Aging, vol. 34, no. 3, pp. 757–769, 2013. 10.1016/j.neurobiolaging.2012.08.004. [6] (cited as reference [69]) The authors apologise in particular for not acknowledging the work of Bhamra and Ashton (2012). Copyright © 2020 Beatrice Arosio et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Published
2020

36. The Biological Foundations of Sarcopenia: Established and Promising Markers

Author

Andrea Saul Costa, Martina Casati, Daniele Capitanio, Luisa Ponzoni, Evelyn Ferri, Simone Agostini, and E. M. Lori

Subjects
0301 basic medicine, Mini Review, Disease, Neuromuscular junction, sarcopenia, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, medicine, lcsh:R5-920, neuromuscular junction, business.industry, aging, biomarkers, SNAP25, Skeletal muscle, General Medicine, musculoskeletal system, medicine.disease, body regions, 030104 developmental biology, medicine.anatomical_structure, Sarcopenia, Medicine, Biomarker (medicine), lcsh:Medicine (General), business, human activities, Neuroscience, 030217 neurology & neurosurgery, Homeostasis
Abstract

Sarcopenia, the progressive loss of muscle mass and strength, is one of the major health issues in older adults, given its high prevalence accompanied by huge clinical and socioeconomic implications. Age-related changes in skeletal muscle can be attributed to mechanisms both directly and indirectly related to muscle homeostasis. Indeed, a wide spectrum of age-related modifications in the organism was shown to play a key role in the pathogenesis of sarcopenia. Not surprisingly, sarcopenia has sometimes been indicated as a syndrome stemming from the aging process, and not as univocal standalone disease. Due to the multidimensionality of sarcopenia, a single biomarker approach is not enough to explain the biology of this condition. The aim of this review is to suggest innovative and promising sarcopenia markers investigating the link between skeletal muscle and brain. Indeed, as a neurological origin of sarcopenia has been hypothesized, a new perspective on sarcopenia biomarkers may focus on the dysfunction of the neuromuscular junctions (NMJs). The core SNARE synaptosomal-associated protein of 25 kDa (SNAP25) accumulates in the plasma membrane of nerve terminals at NMJs and regulates exocytosis at peripheral and central synapses. Interestingly, mice studies have shown that SNAP25 affects the neuromuscular function. SNARE complex and, in particular, SNAP25 may represent a promising pathway to explore the molecular and cellular mechanisms regulating muscular homeostasis and concur at profiling the sarcopenia biological background.

Published
2019

37. The CUORE Detector and Results

Author

James R. Wilson, C. Rosenfeld, S. Morganti, N. D. Scielzo, Carlo Ligi, V. Dompè, A. D'Addabbo, A. Campani, P. Gorla, F. Ferroni, C. Tomei, Monica Sisti, S. Copello, S. L. Wagaarachchi, J. Nikkel, L. Zanotti, Paolo Carniti, C. Pira, M. Faverzani, N. Casali, N. Chott, Simone Capelli, C. J. Davis, Giovanni Benato, H. Z. Huang, G. Keppel, L. Gironi, Ettore Fiorini, F. Terranova, G. Fantini, C. Nones, A. Puiu, S. Zucchelli, V. Novati, Andrea Giachero, Massimiliano Clemenza, Carlo Cosmelli, F. T. Avignone, Irene Nutini, Yu. G. Kolomensky, Massimiliano Nastasi, L. Canonica, L. Marini, V. Pettinacci, K. Wilson, Eric B. Norman, T. O'Donnell, D. Q. Adams, Vasundhara Singh, Jonathan Ouellet, K. Alfonso, S. Di Domizio, J. Johnston, Claudio Gotti, G. Bari, Y. Mei, D. D'Aguanno, T. Napolitano, Evelyn Ferri, Laura Cardani, L. Taffarello, Stefano Dell'Oro, B. K. Fujikawa, Stefano Pozzi, F. Bellini, B. Schmidt, Y. G. Ma, Oliviero Cremonesi, M. Biassoni, Danielle Speller, B. S. Wang, Xi-Guang Cao, C. Brofferio, M. Vignati, M. Pavan, L. Pagnanini, K. M. Heeger, Davide Chiesa, O. Azzolini, N. Moggi, Marco Pallavicini, C. Rusconi, C. Bucci, T. D. Gutierrez, R. J. Creswick, Samuele Sangiorgio, Lindley Winslow, A. Giuliani, Ke Han, Reina H. Maruyama, I. Dafinei, M. Sakai, G. Pessina, Stuart J. Freedman, L. Pattavina, A. Nucciotti, C. Alduino, S. Zimmermann, S. Pirro, L. Ma, D. Q. Fang, A. Branca, M. A. Franceschi, R. G. Huang, L. Cappelli, C. Pagliarone, A. Caminata, Ezio Previtali, B. Welliver, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Nutini, I, Adams, D, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Caminata, A, Campani, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, D’Addabbo, A, D’Aguanno, D, Dafinei, I, Davis, C, Dell’Oro, S, Domizio, S, Dompè, V, Fang, D, Fantini, G, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gorla, P, Gotti, C, Gutierrez, T, Han, K, Heeger, K, Huang, R, Huang, H, Johnston, J, Keppel, G, Kolomensky, Y, Ligi, C, Ma, Y, Ma, L, Marini, L, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Napolitano, T, Nastasi, M, Nikkel, J, Nones, C, Norman, E, Novati, V, Nucciotti, A, O’Donnell, T, Ouellet, J, Pagliarone, C, Pagnanini, L, Pallavicini, M, Pattavina, L, Pavan, M, Pessina, G, Pettinacci, V, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Puiu, A, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Schmidt, B, Scielzo, N, Singh, V, Sisti, M, Speller, D, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Zanotti, L, Zimmermann, S, Zucchelli, S, Nutini I., Adams D.Q., Alduino C., Alfonso K., Avignone F.T., Azzolini O., Bari G., Bellini F., Benato G., Biassoni M., Branca A., Brofferio C., Bucci C., Caminata A., Campani A., Canonica L., Cao X.G., Capelli S., Cappelli L., Cardani L., Carniti P., Casali N., Chiesa D., Chott N., Clemenza M., Copello S., Cosmelli C., Cremonesi O., Creswick R.J., D'Addabbo A., D'Aguanno D., Dafinei I., Davis C.J., Dell'Oro S., Domizio S.D., Dompe V., Fang D.Q., Fantini G., Faverzani M., Ferri E., Ferroni F., Fiorini E., Franceschi M.A., Freedman S.J., Fujikawa B.K., Giachero A., Gironi L., Giuliani A., Gorla P., Gotti C., Gutierrez T.D., Han K., Heeger K.M., Huang R.G., Huang H.Z., Johnston J., Keppel G., Kolomensky Y.G., Ligi C., Ma Y.G., Ma L., Marini L., Maruyama R.H., Mei Y., Moggi N., Morganti S., Napolitano T., Nastasi M., Nikkel J., Nones C., Norman E.B., Novati V., Nucciotti A., O'Donnell T., Ouellet J.L., Pagliarone C.E., Pagnanini L., Pallavicini M., Pattavina L., Pavan M., Pessina G., Pettinacci V., Pira C., Pirro S., Pozzi S., Previtali E., Puiu A., Rosenfeld C., Rusconi C., Sakai M., Sangiorgio S., Schmidt B., Scielzo N.D., Singh V., Sisti M., Speller D., Taffarello L., Terranova F., Tomei C., Vignati M., Wagaarachchi S.L., Wang B.S., Welliver B., Wilson J., Wilson K., Winslow L.A., Zanotti L., Zimmermann S., Zucchelli S., and Département de Physique des Particules (ex SPP) (DPhP)

Subjects
Particle physics, 0 νββ, Cryogenics, CUORE, Macro-calorimeters, Neutrinos, Physics::Instrumentation and Detectors, Cryogenic, 01 natural sciences, tellurium: oxygen, 010305 fluids & plasmas, crystal, double-beta decay: (0neutrino), Double beta decay, 0103 physical sciences, Neutrino, [PHYS.HEXP]Physics [physics]/High Energy Physics - Experiment [hep-ex], General Materials Science, Beta (velocity), [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 010306 general physics, activity report, detector: design, Physics, 0νββ, 0 nu beta beta, Detector, Astrophysics::Instrumentation and Methods for Astrophysics, Condensed Matter Physics, Atomic and Molecular Physics, and Optics, High Energy Physics::Experiment, tellurium: nuclide, Macro-calorimeter, experimental results
Abstract

The cryogenic underground observatory for rare events (CUORE) is a cryogenic experiment searching for neutrinoless double beta decay ($$0\nu \beta \beta$$0νββ) of $${^{130}\hbox {Te}}$$130Te. The detector consists of an array of $$988\,{\hbox {TeO}_{2}}$$988TeO2 crystals arranged in a compact cylindrical structure of 19 towers. We report the CUORE initial operations and optimization campaigns. We then present the CUORE results on $$0\nu \beta \beta$$0νββ and $$2\nu \beta \beta$$2νββ decay of $${^{130}\hbox {Te}}$$130Te obtained from the analysis of the physics data acquired in 2017.

Published
2019

38. Status of the HOLMES Experiment

Author

Joseph W. Fowler, M. Faverzani, M. Ribeiro-Gomez, Dorothea Schumann, Carl D. Reintsema, Daniel Schmidt, G. Gallucci, Evelyn Ferri, Ulli Köster, S. Ragazzi, F. Siccardi, A. Bevilaqua, Joel N. Ullom, M. Borghesi, L. Parodi, Stefano Nisi, M. Balata, A. Nucciotti, A. Puiu, John A. B. Mates, G. Ceruti, Emilio Andrea Maugeri, D. Bennet, D. Backer, Michele Biasotti, Bradley K. Alpert, M. De Gerone, Gene C. Hilton, Leila R. Vale, G. Pessina, Daniel S. Swetz, S. Heinitz, M. Lusignoli, Flavio Gatti, Andrea Giachero, Johnathon D. Gard, Rugard Dressler, Institut Laue-Langevin (ILL), ILL, Faverzani, M, Alpert, B, Balata, M, Backer, D, Bennet, D, Bevilaqua, A, Biasotti, M, Borghesi, M, Ceruti, G, De Gerone, M, Dressler, R, Ferri, E, Fowler, J, Gallucci, G, Gard, J, Gatti, F, Giachero, A, Heinitz, S, Hilton, G, Köster, U, Lusignoli, M, Mates, J, Maugeri, E, Nisi, S, Nucciotti, A, Parodi, L, Pessina, G, Puiu, A, Ragazzi, S, Reintsema, C, Ribeiro-Gomez, M, Schmidt, D, Schumann, D, Siccardi, F, Swetz, D, Ullom, J, and Vale, L

Subjects
Photon, experimental methods, Electron capture, Physics::Instrumentation and Detectors, electron: capture, Electron, 01 natural sciences, 7. Clean energy, HOLMES, 010305 fluids & plasmas, Nuclear physics, Neutrino mass, 0103 physical sciences, Atom, calorimeter, General Materials Science, Sensitivity (control systems), holmium: nuclide, neutrino: mass, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 010306 general physics, Transition edge sensors, detector: design, activity report, Physics, Isotope, Condensed Matter Physics, sensitivity, Atomic and Molecular Physics, and Optics, pile-up, Excited state, High Energy Physics::Experiment, Neutrino, Neutrino ma, Transition edge sensor
Abstract

International audience; The absolute neutrino mass is still an unknown parameter in the modern landscape of particle physics. The HOLMES experiment aims at exploiting the calorimetric approach to directly measure the neutrino mass through the kinematic measurement of the decay products of the weak process decay of $^{163}$Ho. This low energy decaying isotope, in fact, undergoes electron capture emitting a neutrino and leaving the daughter atom, $^{163}$Dy$^*$, in an atomic excited state. This, in turn, relaxes by emitting electrons and, to a considerably lesser extent, photons. The high-energy portion of the calorimetric spectrum of this decay is affected by the non-vanishing neutrino mass value. Given the small fraction of events falling within the region of interest, to achieve a high experimental sensitivity on the neutrino mass, it is important to have a high activity combined with a very small undetected pileup contribution. To achieve these targets, the final configuration of HOLMES foresees the deployment of a large number of $^{163}$Ho ion-implanted TESs characterized by an ambitiously high activity of 300 Hz each. In this paper, we outline the status of the major tasks that will bring HOLMES to achieve a statistical sensitivity on the neutrino mass as low as 2 eV/c$^2$.

Published
2019

39. The Frailty Index in centenarians and their offspring

Author

Giovanni Vitale, Matteo Cesari, Daniela Mari, Beatrice Arosio, Evelyn Ferri, and Martina Casati

Subjects
Male, Aging, Cross-sectional study, Offspring, Frail Elderly, Frailty Index, Correlation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, Geriatric Assessment, Aged, Aged, 80 and over, Frailty, business.industry, Case-control study, Middle Aged, Control subjects, Cross-Sectional Studies, Case-Control Studies, Cohort, Adult Children, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Demography, Cohort study
Abstract

Frailty has been indicated as a way for capturing biological aging of the individual and Frailty Index (FI) may serve for this purpose. This study designed the FI in a cohort of centenarians, their offspring and control subjects sex- and age-matched with offspring. The FI mean value was 0.47 (SD 0.13) in centenarians, 0.15 (SD 0.12) in their offspring, and 0.22 (SD 0.14) in controls (p

Published
2019

40. The Triggering Receptor Expressed on Myeloid Cells-2 (TREM-2) as Expression of the Relationship between Microglia and Alzheimer's Disease: A Novel Marker for a Promising Pathway to Explore

Author

Martina Casati, Evelyn Ferri, Cristina Gussago, and Beatrice Arosio

Subjects
0301 basic medicine, Risk, medicine.medical_specialty, Myeloid, Disease, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Internal medicine, Medicine, Humans, Receptors, Immunologic, Receptor, Membrane Glycoproteins, Microglia, business.industry, TREM2, General Medicine, Rheumatology, 030104 developmental biology, medicine.anatomical_structure, Myeloid cells, Cancer research, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

Alzheimer’s disease (AD) is a common neurodegenerative disorder, strongly related with age. It has been reported that genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2), a cell-surface receptor expressed in microglial cells, greatly increase the risk of AD, thus suggesting an involvement of the microglia in the AD pathogenesis. The aim of this report is to provide an overview of the TREM2 and of its possible implication in the pathogenesis of AD.

Published
2019

41. Gut microbiota and physical frailty through the mediation of sarcopenia

Author

Matteo Cesari, Domenico Azzolino, Beatrice Arosio, Evelyn Ferri, and Martina Casati

Subjects
0301 basic medicine, Aging, Mediation (statistics), Sarcopenia, Anabolism, Gut flora, Bioinformatics, digestive system, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Genetics, medicine, Animals, Humans, Muscle, Skeletal, Molecular Biology, Aged, biology, Frailty, Cell Biology, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, stomatognathic diseases, 030104 developmental biology, Mitochondrial abnormalities, Dysbiosis, 030217 neurology & neurosurgery, Homeostasis
Abstract

The changing physiology and lifestyle of older people affect the gut microbiota composition. In particular, the age-related diet modifications can alter the gut microbiota biodiversity and determine the relative abundance of specific microbial taxa, resulting in microbiota dysbiosis with negative consequences for the host physiology. Unhealthy microbiota may then induce an acceleration of the age-related physiological changes, consequently concurring at determining the characteristic complexity of frail older persons. One of the major clinical manifestations of frailty is represented by the individual's physical decline. Besides of a well-established clinical phenotype of frailty, the qualitative and quantitative skeletal muscle impairment (i.e., sarcopenia) is today of particular interest for potentially serving as target for (pharmacological and non-pharmacological) interventions to prevent incident disability. Evidence suggests that gut microbiota is able to influence the skeletal muscle homeostasis via microbiota-dependent metabolites, thus representing the possible biological substratum for the sarcopenia onset. In fact, the rearrangements of gut microbiota as well as the alteration of its functions contribute at increasing the anabolic resistance, releasing pro-inflammatory mediators, determining mitochondrial abnormalities with consequent oxidation, and causing insulin resistance. In this article, the link between gut microbiota and physical frailty is discussed. It is especially explained the role that sarcopenia may play in this likely bidirectional relationship.

Published
2019

42. High-resolution high-speed microwave-multiplexed low temperature microcalorimeters for the HOLMES experiment

Author

Dan Becker, G. Gallucci, Michele Biasotti, Daniel S. Swetz, D. Bennet, Joel N. Ullom, M. Borghesi, Leila R. Vale, Joseph W. Fowler, G. Pessina, John A. B. Mates, Gene C. Hilton, Johnathon D. Gard, M. De Gerone, J. Hays–Wehle, Andrea Giachero, A. Puiu, Carl D. Reintsema, Daniel Schmidt, Angiola Orlando, Evelyn Ferri, Bradley K. Alpert, A. Nucciotti, M. Faverzani, Alpert, B, Becker, D, Bennet, D, Biasotti, M, Borghesi, M, Gallucci, G, De Gerone, M, Faverzani, M, Ferri, E, Fowler, J, Gard, J, Giachero, A, Hays–wehle, J, Hilton, G, Mates, J, Nucciotti, A, Orlando, A, Pessina, G, Puiu, A, Reintsema, C, Schmidt, D, Swetz, D, Ullom, J, and Vale, L

Subjects
Physics, Physics and Astronomy (miscellaneous), 010308 nuclear & particles physics, Electron capture, Detector, X-ray detector, Response time, lcsh:Astrophysics, 01 natural sciences, Exponential function, Computational physics, Rise time, lcsh:QB460-466, 0103 physical sciences, lcsh:QC770-798, lcsh:Nuclear and particle physics. Atomic energy. Radioactivity, X-ray detectors, neutrino physics, neutrino mass, 010306 general physics, Engineering (miscellaneous), Electron neutrino, Microwave
Abstract

We present the first performance results obtained with microwave multiplexed Transition Edge Sensors prototypes specifically designed for the HOLMES experiment, a project aimed at directly measuring the electron neutrino mass through the calorimetric measurement of the $$^{163}$$ Ho electron capture spectrum. The detectors required for such an experiment feature a high energy resolution at the Q–value of the transition, around $$\sim $$ 2.8 keV, and a fast response time combined with the compatibility to be multiplexed in large arrays in order to collect a large statistics while keeping the pile-up contribution as small as possible. In addition, the design has to be suitable for future ion-implantation of $$^{163}$$ Ho. The results obtained in these tests allowed us to identify the optimal detector design among several prototypes. The chosen detector achieved an energy resolution of (4.5 ± 0.3) eV on the chlorine K $$_\alpha $$ line, at $$\sim $$ 2.6 keV, obtained with an exponential rise time of 14 $$\upmu $$ s. The achievements described in this paper pose a milestone for the HOLMES detectors, setting a baseline for the subsequent developments, aiming to the actual ion-implantation of the $$^{163}$$ Ho nuclei. In the first section the HOLMES experiment is outlined along with its physics goal, while in the second section the HOLMES detectors are described; the experimental set-up and the calibration source used for the measurements described in this paper are reported in Sects. 3 and 4, respectively; finally, the details of the data analysis and the results obtained are reported in Sect. 6.

Published
2019

43. CUORE: The first bolometric experiment at the ton scale for the search for neutrino-less double beta decay

Author

James R. Wilson, N. Moggi, Monica Sisti, Carlo Cosmelli, Samuele Sangiorgio, Lindley Winslow, Jeremy S. Cushman, C. Rosenfeld, A. Nucciotti, Claudio Gotti, C. Alduino, C. Bucci, T. D. Gutierrez, S. Copello, V. Pettinacci, P. Gorla, F. Ferroni, C. Tomei, C. Brofferio, M. Faverzani, Stefano Pirro, D. D'Aguanno, S. Morganti, Paolo Carniti, A. Giuliani, Davide Chiesa, C. Rusconi, C. J. Davis, I. Dafinei, M. Sakai, M. Pavan, S. Zucchelli, K. Wilson, Y. Mei, N. Chott, S. Di Domizio, L. Cappelli, Eric B. Norman, T. Napolitano, V. Dompè, Oliviero Cremonesi, Jonathan Ouellet, G. Bari, A. D'Addabbo, Stefano Dell'Oro, M. Clemenza, Laura Cardani, T. Wise, D. Q. Fang, B. K. Fujikawa, Vasundhara Singh, Stefano Pozzi, Xi-Guang Cao, H. Z. Huang, K. M. Heeger, G. Keppel, M. Biassoni, L. Taffarello, C. Pagliarone, S. Zimmermann, Marco Pallavicini, T. O'Donnell, A. Caminata, Carlo Ligi, Yu. G. Kolomensky, Ezio Previtali, G. Pessina, B. Schmidt, Danielle Speller, B. S. Wang, B. Welliver, M. Vignati, O. Azzolini, Irene Nutini, Ettore Fiorini, V. Novati, Andrea Giachero, A. Campani, C. Pira, L. Pattavina, A. Drobizhev, Silvia Capelli, C. Nones, A. Puiu, F. Terranova, Yu-Gang Ma, Massimiliano Nastasi, D. Q. Adams, K. Alfonso, N. Casali, Giovanni Benato, M. A. Franceschi, G. Fantini, A. Branca, R. G. Huang, Ke Han, Reina H. Maruyama, Stuart J. Freedman, S. L. Wagaarachchi, L. Gironi, F. T. Avignone, A. Bersani, R. J. Creswick, F. Bellini, A. Leder, N. D. Scielzo, L. Zanotti, L. Canonica, L. Marini, J. Johnston, Evelyn Ferri, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Adams D.Q., Alduino C., Alfonso K., Avignone F.T., Azzolini O., Bari G., Bellini F., Benato G., Bersani A., Biassoni M., Branca A., Brofferio C., Bucci C., Caminata A., Campani A., Canonica L., Cao X.G., Capelli S., Cappelli L., Cardani L., Carniti P., Casali N., Chiesa D., Chott N., Clemenza M., Copello S., Cosmelli C., Cremonesi O., Creswick R.J., Cushman J.S., D'Addabbo A., D'Aguanno D., Dafinei I., Davis C.J., Dell'Oro S., Di Domizio S., Dompe V., Drobizhev A., Fang D.Q., Fantini G., Faverzani M., Ferri E., Ferroni F., Fiorini E., Franceschi M.A., Freedman S.J., Fujikawa B.K., Giachero A., Gironi L., Giuliani A., Gorla P., Gotti C., Gutierrez T.D., Han K., Heeger K.M., Huang R.G., Huang H.Z., Johnston J., Keppel G., Kolomensky Y.G., Leder A., Ligi C., Ma Y.G., Marini L., Maruyama R.H., Mei Y., Moggi N., Morganti S., Napolitano T., Nastasi M., Nones C., Norman E.B., Novati V., Nucciotti A., Nutini I., O'Donnell T., Ouellet J.L., Pagliarone C.E., Pallavicini M., Pattavina L., Pavan M., Pessina G., Pettinacci V., Pira C., Pirro S., Pozzi S., Previtali E., Puiu A., Rosenfeld C., Rusconi C., Sakai M., Sangiorgio S., Schmidt B., Scielzo N.D., Singh V., Sisti M., Speller D., Taffarello L., Terranova F., Tomei C., Vignati M., Wagaarachchi S.L., Wang B.S., Welliver B., Wilson J., Wilson K., Winslow L.A., Wise T., Zanotti L., Zimmermann S., Zucchelli S., Département de Physique des Particules (ex SPP) (DPhP), Adams, D, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Bersani, A, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Caminata, A, Campani, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, Cushman, J, D'Addabbo, A, D'Aguanno, D, Dafinei, I, Davis, C, Dell'Oro, S, Di Domizio, S, Dompe, V, Drobizhev, A, Fang, D, Fantini, G, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gorla, P, Gotti, C, Gutierrez, T, Han, K, Heeger, K, Huang, R, Huang, H, Johnston, J, Keppel, G, Kolomensky, Y, Leder, A, Ligi, C, Ma, Y, Marini, L, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Napolitano, T, Nastasi, M, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O'Donnell, T, Ouellet, J, Pagliarone, C, Pallavicini, M, Pattavina, L, Pavan, M, Pessina, G, Pettinacci, V, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Puiu, A, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Schmidt, B, Scielzo, N, Singh, V, Sisti, M, Speller, D, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Wise, T, Zanotti, L, Zimmermann, S, and Zucchelli, S

Subjects
Cryostat, Nuclear and High Energy Physics, Physics::Instrumentation and Detectors, Dark matter, energy resolution, 01 natural sciences, tellurium: oxygen, law.invention, Nuclear physics, energy: threshold, CUORE, Bolometers, Neutrinoless double beta decay, Ton-scale detector, double-beta decay: (0neutrino), bolometer, law, Observatory, Double beta decay, 0103 physical sciences, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 010306 general physics, Instrumentation, activity report, background: suppression, detector: design, Neutrinoless double beta decay, Ton-scale detector, Bolometers, Physics, 010308 nuclear & particles physics, Bolometer, Detector, sensitivity, cryogenics, High Energy Physics::Experiment, Neutrino, performance
Abstract

The Cryogenic Underground Observatory for Rare Events (CUORE) is the most massive bolometric experiment searching for neutrino-less double beta (0 ν β β ) decay. The detector consists of an array of 988 TeO 2 crystals (742 kg) arranged in a compact cylindrical structure of 19 towers. This paper will describe the CUORE experiment, including the cryostat, and present the detector performance during the first year of running. Additional detail will describe the effort made in improving the energy resolution in the 130Te 0 ν β β decay region of interest (ROI) and the suppression of backgrounds. A description of work to lower the energy threshold in order to give CUORE the sensitivity to search for other rare events, such as dark matter, will also be provided.

Published
2019

44. Thermal kinetic inductance detectors for soft X-ray spectroscopy

Author

Peter K. Day, P. Fresch, A. Puiu, Andrea Giachero, B. Margesin, S. Di Domizio, M. Vignati, Angelo Cruciani, L. Minutolo, A. D'Addabbo, Renato Mezzena, M. Faverzani, Evelyn Ferri, A. Nucciotti, Faverzani, M, Cruciani, A, D’Addabbo, A, Day, P, Di Domizio, S, Ferri, E, Fresch, P, Giachero, A, Margesin, B, Mezzena, R, Minutolo, L, Nucciotti, A, Puiu, A, and Vignati, M

Subjects
Nuclear and High Energy Physics, Silicon, X-ray detector, chemistry.chemical_element, 02 engineering and technology, 01 natural sciences, Multiplexing, Kinetic inductance, Resonator, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, Microwave kinetic inductance detectors, Superconducting detectors, X-ray detectors, 010306 general physics, Spectroscopy, Instrumentation, Physics, business.industry, Detector, 020207 software engineering, X–ray detectors, Microwave kinetic inductance detectors, Superconducting detectors, chemistry, Optoelectronics, business, Microwave
Abstract

Superconducting microwave microresonators are low temperature detectors (LTDs) suitable for large-scale frequency domain multiplexing readout. A promising approach consists in operating the resonators in quasi-thermal equilibrium mode: the resonator acts as a thermometer sensing the temperature rise of an absorbing material caused by an energy release. Our aim is to develop such detectors to perform spectroscopy in the keV range, with a possible future application to a next generation experiment aimed at directly measuring the neutrino mass . Still, the best configuration in terms of detector design and material must be found. Resonators made of several Ti/TiN multilayer films, which is a high kinetic inductance superconducting material previously developed by our group, were recently produced. The resonators are deposited onto a silicon slab and the sensitive area, thermally coupled to a gold absorber, is kept suspended by means of a SiN x membrane. In this way we plan to exploit the excellent energy resolution of LTDs combined with the simple multiplexing scheme of the resonators. In this contribution we present the devices along with our project, with its status and perspectives.

Published
2019

45. CUORE: The first bolometric experiment at the ton scale for rare decay searches

Author

A. Bersani, L. Pattavina, Oliviero Cremonesi, Massimiliano Clemenza, Carlo Cosmelli, C. Pagliarone, C. Rosenfeld, P. Gorla, H. Z. Huang, G. Keppel, F. Ferroni, C. Tomei, K. Wilson, V. Palmieri, C. Nones, Eric B. Norman, A. Puiu, Jonathan Ouellet, G. Bari, Claudio Gotti, T. Napolitano, C. Brofferio, L. Gironi, F. T. Avignone, C. J. Davis, A. Caminata, Ezio Previtali, B. Welliver, S. Copello, Guoqiang Zhang, Lorenzo Cassina, Evelyn Ferri, Paolo Carniti, L. Canonica, A. Giuliani, S. Di Domizio, M. M. Deninno, Davide Chiesa, L. Marini, C. Rusconi, Ettore Fiorini, M. Biassoni, N. Moggi, V. Novati, Andrea Giachero, F. Bellini, S. Zimmermann, Laura Cardani, J. Johnston, Ke Han, A. Branca, B. K. Fujikawa, Stefano Pozzi, L. Gladstone, D. Q. Adams, K. Alfonso, M. L. Di Vacri, Reina H. Maruyama, Samuele Sangiorgio, Stuart J. Freedman, C. Bucci, S. L. Wagaarachchi, T. D. Gutierrez, Miriam Lucio Martinez, Stefano Dell'Oro, R. Hennings-Yeomans, A. Nucciotti, R. J. Creswick, Stefano Pirro, N. Chott, D. D'Aguanno, C. Alduino, M. Vignati, M. Faverzani, S. Zucchelli, L. Cappelli, Giovanni Benato, N. Casali, Marco Pallavicini, Irene Nutini, Yu. G. Kolomensky, G. Pessina, S. Morganti, F. Terranova, Yu-Gang Ma, F. Reindl, H. W. Wang, T. O'Donnell, S. S. Nagorny, Y. Mei, Lindley Winslow, V. Dompè, M. Sakai, Xi-Guang Cao, A. D'Addabbo, K. M. Heeger, Carlo Ligi, N. D. Scielzo, A. Campani, T. Wise, L. Taffarello, Danielle Speller, L. Zanotti, I. Dafinei, C. Pira, A. Leder, D. Santone, Vasundhara Singh, B. Schmidt, B. S. Wang, D. Q. Fang, O. Azzolini, A. Drobizhev, Jeremy S. Cushman, M. A. Franceschi, R. G. Huang, Silvia Capelli, Massimiliano Nastasi, M. Pavan, James R. Wilson, Monica Sisti, Adams D.Q., Alduino C., Alfonso K., Avignone F.T., Azzolini O., Bari G., Bellini F., Benato G., Bersani A., Biassoni M., Branca A., Brofferio C., Bucci C., Caminata A., Campani A., Canonica L., Cao X.G., Capelli S., Cappelli L., Cardani L., Carniti P., Casali N., Cassina L., Chiesa D., Chott N., Clemenza M., Copello S., Cosmelli C., Cremonesi O., Creswick R.J., Cushman J.S., D'Addabbo A., D'Aguanno D., Dafinei I., Davis C.J., Dell'Oro S., Deninno M.M., Domizio S.D., Vacri M.L.D., Dompe V., Drobizhev A., Fang D.Q., Faverzani M., Ferri E., Ferroni F., Fiorini E., Franceschi M.A., Freedman S.J., Fujikawa B.K., Giachero A., Gironi L., Giuliani A., Gladstone L., Gorla P., Gotti C., Gutierrez T.D., Han K., Heeger K.M., Hennings-Yeomans R., Huang R.G., Huang H.Z., Johnston J., Keppel G., Kolomensky Y.G., Leder A., Ligi C., Ma Y.G., Marini L., Martinez M., Maruyama R.H., Mei Y., Moggi N., Morganti S., Nagorny S.S., Napolitano T., Nastasi M., Nones C., Norman E.B., Novati V., Nucciotti A., Nutini I., O'Donnell T., Ouellet J.L., Pagliarone C.E., Pallavicini M., Palmieri V., Pattavina L., Pavan M., Pessina G., Pira C., Pirro S., Pozzi S., Previtali E., Puiu A., Reindl F., Rosenfeld C., Rusconi C., Sakai M., Sangiorgio S., Santone D., Schmidt B., Scielzo N.D., Singh V., Sisti M., Speller D., Taffarello L., Terranova F., Tomei C., Vignati M., Wagaarachchi S.L., Wang B.S., Wang H.W., Welliver B., Wilson J., Wilson K., Winslow L.A., Wise T., Zanotti L., Zhang G.Q., Zimmermann S., Zucchelli S., Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département de Physique des Particules (ex SPP) (DPP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Département de Physique des Particules (ex SPP) (DPhP), Adams, D, Alduino, C, Alfonso, K, Avignone, F, Azzolini, O, Bari, G, Bellini, F, Benato, G, Bersani, A, Biassoni, M, Branca, A, Brofferio, C, Bucci, C, Caminata, A, Campani, A, Canonica, L, Cao, X, Capelli, S, Cappelli, L, Cardani, L, Carniti, P, Casali, N, Cassina, L, Chiesa, D, Chott, N, Clemenza, M, Copello, S, Cosmelli, C, Cremonesi, O, Creswick, R, Cushman, J, D’Addabbo, A, D’Aguanno, D, Dafinei, I, Davis, C, Dell’Oro, S, Deninno, M, Domizio, S, Vacri, M, Dompè, V, Drobizhev, A, Fang, D, Faverzani, M, Ferri, E, Ferroni, F, Fiorini, E, Franceschi, M, Freedman, S, Fujikawa, B, Giachero, A, Gironi, L, Giuliani, A, Gladstone, L, Gorla, P, Gotti, C, Gutierrez, T, Han, K, Heeger, K, Hennings-Yeomans, R, Huang, R, Huang, H, Johnston, J, Keppel, G, Kolomensky, Y, Leder, A, Ligi, C, Ma, Y, Marini, L, Martinez, M, Maruyama, R, Mei, Y, Moggi, N, Morganti, S, Nagorny, S, Napolitano, T, Nastasi, M, Nones, C, Norman, E, Novati, V, Nucciotti, A, Nutini, I, O’Donnell, T, Ouellet, J, Pagliarone, C, Pallavicini, M, Palmieri, V, Pattavina, L, Pavan, M, Pessina, G, Pira, C, Pirro, S, Pozzi, S, Previtali, E, Puiu, A, Reindl, F, Rosenfeld, C, Rusconi, C, Sakai, M, Sangiorgio, S, Santone, D, Schmidt, B, Scielzo, N, Singh, V, Sisti, M, Speller, D, Taffarello, L, Terranova, F, Tomei, C, Vignati, M, Wagaarachchi, S, Wang, B, Wang, H, Welliver, B, Wilson, J, Wilson, K, Winslow, L, Wise, T, Zanotti, L, Zhang, G, Zimmermann, S, and Zucchelli, S

Subjects
Nuclear and High Energy Physics, Cryogenic, Superconductive Devices, Physics::Instrumentation and Detectors, Cryogenic, 01 natural sciences, tellurium: oxygen, Combinatorics, CUORE, bolometer, double-beta decay: (0neutrino), Superconductive Devices, 0103 physical sciences, [PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det], 010306 general physics, Instrumentation, detector: design, activity report, Physics, 010308 nuclear & particles physics, Astrophysics::Instrumentation and Methods for Astrophysics, Superconductive Device, cryogenics, Physics::Accelerator Physics, High Energy Physics::Experiment, performance
Abstract

Author(s): Adams, DQ; Alduino, C; Alfonso, K; Avignone, FT; Azzolini, O; Bari, G; Bellini, F; Benato, G; Bersani, A; Biassoni, M; Branca, A; Brofferio, C; Bucci, C; Caminata, A; Campani, A; Canonica, L; Cao, XG; Capelli, S; Cappelli, L; Cardani, L; Carniti, P; Casali, N; Cassina, L; Chiesa, D; Chott, N; Clemenza, M; Copello, S; Cosmelli, C; Cremonesi, O; Creswick, RJ; Cushman, JS; D'Addabbo, A; D'Aguanno, D; Dafinei, I; Davis, CJ; Dell'Oro, S; Deninno, MM; Domizio, SD; Vacri, MLD; Dompe, V; Drobizhev, A; Fang, DQ; Faverzani, M; Ferri, E; Ferroni, F; Fiorini, E; Franceschi, MA; Freedman, SJ; Fujikawa, BK; Giachero, A; Gironi, L; Giuliani, A; Gladstone, L; Gorla, P; Gotti, C; Gutierrez, TD; Han, K; Heeger, KM; Hennings-Yeomans, R; Huang, RG; Huang, HZ; Johnston, J; Keppel, G; Kolomensky, YG; Leder, A; Ligi, C; Ma, YG; Marini, L; Martinez, M; Maruyama, RH; Mei, Y; Moggi, N; Morganti, S; Nagorny, SS; Napolitano, T; Nastasi, M; Nones, C; Norman, EB; Novati, V; Nucciotti, A; Nutini, I; O'Donnell, T; Ouellet, JL; Pagliarone, CE; Pallavicini, M | Abstract: The Cryogenic Underground Observatory for Rare Events (CUORE) is the first bolometric experiment searching for neutrinoless double beta decay that has been able to reach the 1-ton scale. The detector consists of an array of 988 TeO2 crystals arranged in a cylindrical compact structure of 19 towers. The construction of the experiment and, in particular, the installation of all towers in the cryostat was completed in August 2016 and data taking started in spring 2017. In this contribution the achievement of the commissioning phase and the performance of the detector and the cryostat during the first physics run will be presented.

Published
2019

47. Down-regulation of adenosine A1 and A2A receptors in peripheral cells from idiopathic normal-pressure hydrocephalus patients

Author

Beatrice Arosio, Paolo Rossi, Valeria Scortichini, C. Nani, Evelyn Ferri, Cristina Gussago, Martina Casati, Daniela Mari, Lara Assolari, and L. Magni

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Receptor, Adenosine A2A, Central nervous system, Down-Regulation, Adenosine A2A receptor, Inflammation, 03 medical and health sciences, Adenosine A1 receptor, 0302 clinical medicine, Internal medicine, medicine, Humans, Neuroinflammation, Aged, Aged, 80 and over, Receptor, Adenosine A1, business.industry, medicine.disease, Adenosine, Hydrocephalus, Normal Pressure, Pathophysiology, Hydrocephalus, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Neurology, Leukocytes, Mononuclear, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Idiopathic normal-pressure hydrocephalus (iNPH) is a neurological disease that usually develops in the elderly. Natural history of iNPH is still unknown. It has been hypothesized that cerebrovascular diseases could have a role in etiology of chronic hydrocephalus and studies show an increased prevalence of cardiovascular diseases in iNPH patients. Moreover, evidences show a possible alteration of immune system in iNPH patients. Adenosine (Ado) is a metabolite produced in response to metabolic stress and injury. Adenosine and its receptors play an important role in vascular protection and in the modulation of inflammatory reactions and neuroinflammation. Our aim is to evaluate gene and protein expression of A1R and A2AR in the peripheral blood mononuclear cells (PBMCs) from iNPH patients compared to control subjects. We investigate if Ado system, that plays an important role in central nervous system, in vascular system, and also in inflammation, is involved in pathophysiology of iNPH disease. Our analysis showed that A1R mRNA levels and A1R density in PBMCs from iNPH patients were significantly lower than CT subjects (0.84 ± 0.12 and 2.42 ± 0.42, p

Published
2016

48. Vitamin D Receptor Polymorphisms in Sex-Frailty Paradox

Author

Evelyn Ferri, Beatrice Arosio, Andrea Saul Costa, Alessandra Dicitore, Mario Clerici, Giovanni Vitale, Matteo Cesari, Franca Rosa Guerini, Daniela Mari, and Erminio Torresani

Subjects
Male, Frailty Index, Parathyroid hormone, vitamin D, Calcitriol receptor, chemistry.chemical_compound, 0302 clinical medicine, Genotype, Health Status Indicators, aging, frailty, vitamin D receptor, Aged, 80 and over, Nutrition and Dietetics, biology, Phosphorus, Middle Aged, FokI, Italy, Parathyroid Hormone, Female, lcsh:Nutrition. Foods and food supply, medicine.medical_specialty, TaqI, Frail Elderly, lcsh:TX341-641, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Sex Factors, Internal medicine, medicine, Vitamin D and neurology, Humans, Genetic Predisposition to Disease, Alleles, Aged, Polymorphism, Genetic, business.industry, Minor allele frequency, Endocrinology, chemistry, biology.protein, Receptors, Calcitriol, Calcium, business, 030217 neurology & neurosurgery, Food Science
Abstract

The “male-female health-survival paradox” evidences that the survival advantage observed in women is linked to higher rates of disability and poor health status compared to men, a phenomenon also called the “sex-frailty paradox”. The depletion of vitamin D seems to play a role in the fragilization of old persons, and genetic polymorphisms of the vitamin D receptor (VDR) gene seem to be involved in regulating the vitamin D pathway. This study correlated the VDR gene polymorphisms (FokI, ApaI, BsmiI, and TaqI) with frailty, computed by frailty index (FI), in 202 persons (127 women and 75 men, aged from 60 to 116 years), aiming to capture the involvement of vitamin D in the sex-frailty paradox. The results showed slightly higher FI (p = 0.05), lower levels of 25(OH)D (p = 0.04), and higher levels of parathyroid hormone PTH (p = 0.002) and phosphorus (p < 0.001) in women than in men. Interestingly, the ApaI minor allele (Aa + aa) showed a significant positive association with FI (p = 0.03) and a negative association with inorganic phosphorus values (p = 0.04) compared to AA genotype only in women, regardless of age. The exact mechanism and the causal role that, in old women, links ApaI polymorphism with frailty are still unclear. However, we could speculate that a specific genetic profiling, other than 25(OH)D levels, play a role in the sex-frailty paradox.

Published
2020

49. Thyroid hormones and frailty in persons experiencing extreme longevity

Author

Rita Ostan, Francesco De Rango, Daniela Mari, Evelyn Ferri, Giovanni Vitale, Matteo Cesari, Giuseppe Passarino, Daniela Monti, Claudio Franceschi, and Beatrice Arosio

Subjects
0301 basic medicine, Gerontology, Thyroid Hormones, Aging, Offspring, media_common.quotation_subject, Longevity, Population, Thyroid Gland, Thyrotropin, Context (language use), Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Genetics, medicine, Humans, education, Molecular Biology, media_common, Aged, 80 and over, education.field_of_study, Frailty, business.industry, Thyroid, Stressor, Cell Biology, Thyroxine, 030104 developmental biology, medicine.anatomical_structure, Italy, Triiodothyronine, Centenarian, business, 030217 neurology & neurosurgery, Hormone
Abstract

The aging phenotype is quite heterogeneous, being the result of the capability of each individual to successfully or unsuccessfully response to stressors. The reduction of homeostatic reserve characterizing aging is accompanied by a remodeling of the endocrine system. Frailty has been indicated as a promising way for capturing the physiological decline as well as the biological aging of the individuals. In particular, the Frailty Index (FI), based on the assumption that health deficits tend to accumulate with aging, represents a quantitative measure of extreme interest.The study aims to correlate the thyroid hormone levels with FI in a population of centenarians and their offspring to capture the effects of thyroid remodeling in extreme longevity.The study described 593 well-characterized Italian subjects, including 180 centenarians, as well as 276 centenarian's offspring and 137 age-matched controls.FT3 levels and FT3/FT4 ratio were significantly lower (p 0.001) and TSH levels higher (p 0.001) in centenarians compared to the other groups, analysing both overall subjects and excluding subjects with hormone levels out of the normal ranges. In overall centenarians, we observed a negative correlation between FI and FT3 (ρ: -0.281, p 0.001), FT3/FT4 (ρ: -0.344, p 0.001) and TSH (ρ: -0.223, p 0.003) and a positive association between FI and FT4 (ρ: 0.189, p = 0.001). In centenarians with hormone levels within the normal ranges, similar negative correlations were observed between FI and FT3 (ρ: -0.201, p = 0.02) and FT3/FT4 (ρ: -0.264, p = 0.002). In this sub-analysis, FI positively correlated with FT4 and age (ρ: 0.167, p = 0.05; ρ: 0.219, p = 0.005, respectively). Conversely, no significant correlations were observed between hormone levels and FI in offspring and controls.We found an association between thyroid hormone levels and frailty in centenarians, underlying the significant role of thyroid in the aging process and longevity.

Published
2020

50. Apolipoprotein E gene in physiological and pathological aging

Author

Evelyn Ferri, Paolo Dionigi Rossi, Cristina Gussago, Matteo Cesari, Simona Ciccone, Martina Casati, Beatrice Arosio, and Daniela Mari

Subjects
0301 basic medicine, Apolipoprotein E, Male, Aging, Genotype, Apolipoprotein E2, media_common.quotation_subject, Apolipoprotein E4, Longevity, Apolipoprotein E3, Physiology, Disease, Biology, Cohort Studies, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Alzheimer Disease, Humans, Registries, Cognitive decline, Allele, Pathological, Alleles, media_common, Aged, Aged, 80 and over, Polymorphism, Genetic, 030104 developmental biology, Logistic Models, Cohort, Female, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Introduction The genetic background plays a role on longevity. The distribution of the apolipoprotein E gene (APOE) variants (e2, e3, e4) may differ across age groups, especially in the oldest old and despite geographical and ethnic specificities. Since the e4 variant is associated with Alzheimer’s disease (AD), it might represent an opportunity for exploring the relationship of APOE with physiological and pathological aging. Aim To explore the role played by APOE genotype/alleles on physiological and pathological brain aging. Materials and Methods The study was conducted in a cohort of centenarians (n = 106), and two cohorts of octogenarians (without cognitive decline, n = 351 controls; and with AD, n = 294). Results No significant differences in genotype/allele distributions were observed comparing controls to centenarians. The prevalence of e2/e3, e3/e3, e3/e4 and e4/e4 genotypes were significantly different in centenarians compared to AD. The prevalence of e2 and e3 alleles were significantly higher in centenarians, whereas the e4 was less frequent. The e4 allele was positively associated with AD, whereas a negative association was found for e2 and e3 alleles. Conclusions Our study indicates that e4 allele is strongly associated with AD. APOE significantly affects AD risk, but apparently not longevity.

Published
2018

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