Membrane-elution analysis of content of cyclins A, B1, and E during the unperturbed mammalian cell cycle

<p>Abstract</p> <p>Background</p> <p>Problems with whole-culture synchronization methods for the study of the cell cycle have led to the need for an analysis of protein content during the cell cycle of cells that have not been starved or inhibited. The membrane-elution method is a method that allows the study of the cell cycle by producing a culture of unperturbed, synchronized cells.</p> <p>Results</p> <p>The Helmstetter membrane-elution method for the continuous production of newborn, unperturbed, mammalian cells has been enhanced so that the collection of cells of different cell cycle ages is automated, reproducible, and relatively inexpensive. We have applied the automated membrane-elution method to the analysis of cyclin content during the cell cycle. Cyclin E protein was invariant during the cell cycle. Cyclins B1 and A accumulated continuously during the cell cycle and were degraded at mitosis. Newborn cells had ~0.5% of the cyclin B1 content of dividing cells.</p> <p>Conclusion</p> <p>The expression patterns of cyclins A, B1, and E can be explained by constant mRNA levels during the cell cycle. Previously reported phase specific variations of the cyclins are not strictly necessary for cell-cycle progression. Cells produced by membrane-elution are available to other laboratories for analysis of the cell cycle.</p

Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of a disease spectrum with shared clinical, genetic and pathological features. These include near ubiquitous pathological inclusions of the RNA-binding protein (RBP) TDP-43, and often the presence of a GGGGCC expansion in the C9ORF72 (C9) gene. Previously, we reported that the sequestration of hnRNP H altered the splicing of target transcripts in C9ALS patients. Here, we show that this signature also occurs in half of 50 postmortem sporadic, non-C9 ALS/FTD brains. Furthermore, and equally surprisingly, these ‘like-C9’ brains also contained correspondingly high amounts of insoluble TDP-43, as well as several other disease-related RBPs, and this correlates with widespread global splicing defects. Finally, we show that the like-C9 sporadic patients, like actual C9ALS patients, were much more likely to have developed FTD. We propose that these unexpected links between C9 and sporadic ALS/FTD define a common mechanism in this disease spectrum

Truncated stathmin-2 is a marker of TDP-43 pathology in frontotemporal dementia.

No treatment for frontotemporal dementia (FTD), the second most common type of early-onset dementia, is available, but therapeutics are being investigated to target the 2 main proteins associated with FTD pathological subtypes: TDP-43 (FTLD-TDP) and tau (FTLD-tau). Testing potential therapies in clinical trials is hampered by our inability to distinguish between patients with FTLD-TDP and FTLD-tau. Therefore, we evaluated truncated stathmin-2 (STMN2) as a proxy of TDP-43 pathology, given the reports that TDP-43 dysfunction causes truncated STMN2 accumulation. Truncated STMN2 accumulated in human induced pluripotent stem cell-derived neurons depleted of TDP-43, but not in those with pathogenic TARDBP mutations in the absence of TDP-43 aggregation or loss of nuclear protein. In RNA-Seq analyses of human brain samples from the NYGC ALS cohort, truncated STMN2 RNA was confined to tissues and disease subtypes marked by TDP-43 inclusions. Last, we validated that truncated STMN2 RNA was elevated in the frontal cortex of a cohort of patients with FTLD-TDP but not in controls or patients with progressive supranuclear palsy, a type of FTLD-tau. Further, in patients with FTLD-TDP, we observed significant associations of truncated STMN2 RNA with phosphorylated TDP-43 levels and an earlier age of disease onset. Overall, our data uncovered truncated STMN2 as a marker for TDP-43 dysfunction in FTD

Neutrinos

229 pages229 pages229 pagesThe Proceedings of the 2011 workshop on Fundamental Physics at the Intensity Frontier. Science opportunities at the intensity frontier are identified and described in the areas of heavy quarks, charged leptons, neutrinos, proton decay, new light weakly-coupled particles, and nucleons, nuclei, and atoms

Long-baseline neutrino oscillation physics potential of the DUNE experiment

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all ΑCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all ΑCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22θ13 to current reactor experiments

First results on ProtoDUNE-SP liquid argon time projection chamber performance from a beam test at the CERN Neutrino Platform

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber with an active volume of 7.2× 6.1× 7.0 m3. It is installed at the CERN Neutrino Platform in a specially-constructed beam that delivers charged pions, kaons, protons, muons and electrons with momenta in the range 0.3 GeV/c to 7 GeV/c. Beam line instrumentation provides accurate momentum measurements and particle identification. The ProtoDUNE-SP detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment, and it incorporates full-size components as designed for that module. This paper describes the beam line, the time projection chamber, the photon detectors, the cosmic-ray tagger, the signal processing and particle reconstruction. It presents the first results on ProtoDUNE-SP\u27s performance, including noise and gain measurements, dE/dx calibration for muons, protons, pions and electrons, drift electron lifetime measurements, and photon detector noise, signal sensitivity and time resolution measurements. The measured values meet or exceed the specifications for the DUNE far detector, in several cases by large margins. ProtoDUNE-SP\u27s successful operation starting in 2018 and its production of large samples of high-quality data demonstrate the effectiveness of the single-phase far detector design

Volume III. DUNE far detector technical coordination

open966siAcknowledgments This document was prepared by the DUNE collaboration using the resources of the Fermi National Accelerator Laboratory (Fermilab), a U.S. Department of Energy, Office of Science, HEP User Facility. Fermilab is managed by Fermi Research Alliance, LLC (FRA), acting under Contract No. DE-AC02-07CH11359. The DUNE collaboration also acknowledges the international, national, and regional funding agencies supporting the institutions who have contributed to completing this Technical Design Report.The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay-these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- A nd dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module.openAbi B.; Acciarri R.; Acero M.A.; Adamov G.; Adams D.; Adinolfi M.; Ahmad Z.; Ahmed J.; Alion T.; Monsalve S.A.; Alt C.; Anderson J.; Andreopoulos C.; Andrews M.; Andrianala F.; Andringa S.; Ankowski A.; Antonova M.; Antusch S.; Aranda-Fernandez A.; Ariga A.; Arnold L.O.; Arroyave M.A.; Asaadi J.; Aurisano A.; Aushev V.; Autiero D.; Azfar F.; Back H.; Back J.J.; Backhouse C.; Baesso P.; Bagby L.; Bajou R.; Balasubramanian S.; Baldi P.; Bambah B.; Barao F.; Barenboim G.; Barker G.; Barkhouse W.; Barnes C.; Barr G.; Monarca J.B.; Barros N.; Barrow J.L.; Bashyal A.; Basque V.; Bay F.; Alba J.B.; Beacom J.F.; Bechetoille E.; Behera B.; Bellantoni L.; Bellettini G.; Bellini V.; Beltramello O.; Belver D.; Benekos N.; Neves F.B.; Berger J.; Berkman S.; Bernardini P.; Berner R.M.; Berns H.; Bertolucci S.; Betancourt M.; Bezawada Y.; Bhattacharjee M.; Bhuyan B.; Biagi S.; Bian J.; Biassoni M.; Biery K.; Bilki B.; Bishai M.; Bitadze A.; Blake A.; Siffert B.B.; Blaszczyk F.; Blazey G.; Blucher E.; Boissevain J.; Bolognesi S.; Bolton T.; Bonesini M.; Bongrand M.; Bonini F.; Booth A.; Booth C.; Bordoni S.; Borkum A.; Boschi T.; Bostan N.; Bour P.; Boyd S.; Boyden D.; Bracinik J.; Braga D.; Brailsford D.; Brandt A.; Bremer J.; Brew C.; Brianne E.; Brice S.J.; Brizzolari C.; Bromberg C.; Brooijmans G.; Brooke J.; Bross A.; Brunetti G.; Buchanan N.; Budd H.; Caiulo D.; Calafiura P.; Calcutt J.; Calin M.; Calvez S.; Calvo E.; Camilleri L.; Caminata A.; Campanelli M.; Caratelli D.; Carini G.; Carlus B.; Carniti P.; Terrazas I.C.; Carranza H.; Castillo A.; Castromonte C.; Cattadori C.; Cavalier F.; Cavanna F.; Centro S.; Cerati G.; Cervelli A.; Villanueva A.C.; Chalifour M.; Chang C.; Chardonnet E.; Chatterjee A.; Chattopadhyay S.; Chaves J.; Chen H.; Chen M.; Chen Y.; Cherdack D.; Chi C.; Childress S.; Chiriacescu A.; Cho K.; Choubey S.; Christensen A.; Christian D.; Christodoulou G.; Church E.; Clarke P.; Coan T.E.; Cocco A.G.; Coelho J.; Conley E.; Conrad J.; Convery M.; Corwin L.; Cotte P.; Cremaldi L.; Cremonesi L.; Crespo-Anadon J.I.; Cristaldo E.; Cross R.; Cuesta C.; Cui Y.; Cussans D.; Dabrowski M.; Motta H.D.; Peres L.D.S.; David Q.; Davies G.S.; Davini S.; Dawson J.; De K.; Almeida R.M.D.; Debbins P.; Bonis I.D.; Decowski M.; Gouvea A.D.; Holanda P.C.D.; Astiz I.L.D.I.; Deisting A.; Jong P.D.; Delbart A.; Delepine D.; Delgado M.; Dell'acqua A.; Lurgio P.D.; Neto J.R.D.M.; Demuth D.M.; Dennis S.; Densham C.; Deptuch G.; Roeck A.D.; Romeri V.D.; Vries J.D.; Dharmapalan R.; Dias M.; Diaz F.; Diaz J.; Domizio S.D.; Giulio L.D.; Ding P.; Noto L.D.; Distefano C.; Diurba R.; Diwan M.; Djurcic Z.; Dokania N.; Dolinski M.; Domine L.; Douglas D.; Drielsma F.; Duchesneau D.; Duffy K.; Dunne P.; Durkin T.; Duyang H.; Dvornikov O.; Dwyer D.; Dyshkant A.; Eads M.; Edmunds D.; Eisch J.; Emery S.; Ereditato A.; Escobar C.; Sanchez L.E.; Evans J.J.; Ewart E.; Ezeribe A.C.; Fahey K.; Falcone A.; Farnese C.; Farzan Y.; Felix J.; Fernandez-Martinez E.; Menendez P.F.; Ferraro F.; Fields L.; Filkins A.; Filthaut F.; Fitzpatrick R.S.; Flanagan W.; Fleming B.; Flight R.; Fowler J.; Fox W.; Franc J.; Francis K.; Franco D.; Freeman J.; Freestone J.; Fried J.; Friedland A.; Fuess S.; Furic I.; Furmanski A.P.; Gago A.; Gallagher H.; Gallego-Ros A.; Gallice N.; Galymov V.; Gamberini E.; Gamble T.; Gandhi R.; Gandrajula R.; Gao S.; Garcia-Gamez D.; Garcia-Peris M.A.; Gardiner S.; Gastler D.; Ge G.; Gelli B.; Gendotti A.; Gent S.; Ghorbani-Moghaddam Z.; Gibin D.; Gil-Botella I.; Girerd C.; Giri A.; Gnani D.; Gogota O.; Gold M.; Gollapinni S.; Gollwitzer K.; Gomes R.A.; Bermeo L.G.; Fajardo L.S.G.; Gonnella F.; Gonzalez-Cuevas J.; Goodman M.C.; Goodwin O.; Goswami S.; Gotti C.; Goudzovski E.; Grace C.; Graham M.; Gramellini E.; Gran R.; Granados E.; Grant A.; Grant C.; Gratieri D.; Green P.; Green S.; Greenler L.; Greenwood M.; Greer J.; Griffith C.; Groh M.; Grudzinski J.; Grzelak K.; Gu W.; Guarino V.; Guenette R.; Guglielmi A.; Guo B.; Guthikonda K.; Gutierrez R.; Guzowski P.; Guzzo M.M.; Gwon S.; Habig A.; Hackenburg A.; Hadavand H.; Haenni R.; Hahn A.; Haigh J.; Haiston J.; Hamernik T.; Hamilton P.; Han J.; Harder K.; Harris D.A.; Hartnell J.; Hasegawa T.; Hatcher R.; Hazen E.; Heavey A.; Heeger K.M.; Hennessy K.; Henry S.; Morquecho M.H.; Herner K.; Hertel L.; Hesam A.S.; Hewes J.; Pichardo A.H.; Hill T.; Hillier S.J.; Himmel A.; Hoff J.; Hohl C.; Holin A.; Hoppe E.; Horton-Smith G.A.; Hostert M.; Hourlier A.; Howard B.; Howell R.; Huang J.; Huang J.; Hugon J.; Iles G.; Iliescu A.M.; Illingworth R.; Ioannisian A.; Itay R.; Izmaylov A.; James E.; Jargowsky B.; Jediny F.; Jesus-Valls C.; Ji X.; Jiang L.; Jimenez S.; Jipa A.; Joglekar A.; Johnson C.; Johnson R.; Jones B.; Jones S.; Jung C.; Junk T.; Jwa Y.; Kabirnezhad M.; Kaboth A.; Kadenko I.; Kamiya F.; Karagiorgi G.; Karcher A.; Karolak M.; Karyotakis Y.; Kasai S.; Kasetti S.P.; Kashur L.; Kazaryan N.; Kearns E.; Keener P.; Kelly K.J.; Kemp E.; Ketchum W.; Kettell S.; Khabibullin M.; Khotjantsev A.; Khvedelidze A.; Kim D.; King B.; Kirby B.; Kirby M.; Klein J.; Koehler K.; Koerner L.W.; Kohn S.; Koller P.P.; Kordosky M.; Kosc T.; Kose U.; Kostelecky V.; Kothekar K.; Krennrich F.; Kreslo I.; Kudenko Y.; Kudryavtsev V.; Kulagin S.; Kumar J.; Kumar R.; Kuruppu C.; Kus V.; Kutter T.; Lambert A.; Lande K.; Lane C.E.; Lang K.; Langford T.; Lasorak P.; Last D.; Lastoria C.; Laundrie A.; Lawrence A.; Lazanu I.; Lazur R.; Le T.; Learned J.; Lebrun P.; Miotto G.L.; Lehnert R.; De Oliveira M.L.; Leitner M.; Leyton M.; Li L.; Li S.; Li S.; Li T.; Li Y.; Liao H.; Lin C.; Lin S.; Lister A.; Littlejohn B.R.; Liu J.; Lockwitz S.; Loew T.; Lokajicek M.; Lomidze I.; Long K.; Loo K.; Lorca D.; Lord T.; Losecco J.; Louis W.C.; Luk K.; Luo X.; Lurkin N.; Lux T.; Luzio V.P.; MacFarland D.; MacHado A.; MacHado P.; MacIas C.; MacIer J.; Maddalena A.; Madigan P.; Magill S.; Mahn K.; Maio A.; Maloney J.A.; Mandrioli G.; Maneira J.C.; Manenti L.; Manly S.; Mann A.; Manolopoulos K.; Plata M.M.; Marchionni A.; Marciano W.; Marfatia D.; Mariani C.; Maricic J.; Marinho F.; Marino A.D.; Marshak M.; Marshall C.; Marshall J.; Marteau J.; Martin-Albo J.; Martinez N.; Caicedo D.A.M.; Martynenko S.; Mason K.; Mastbaum A.; Masud M.; Matsuno S.; Matthews J.; Mauger C.; Mauri N.; Mavrokoridis K.; Mazza R.; Mazzacane A.; Mazzucato E.; McCluskey E.; McConkey N.; McFarland K.S.; McGrew C.; McNab A.; Mefodiev A.; Mehta P.; Melas P.; Mellinato M.; Mena O.; Menary S.; Mendez H.; Menegolli A.; Meng G.; Messier M.; Metcalf W.; Mewes M.; Meyer H.; Miao T.; Michna G.; Miedema T.; Migenda J.; Milincic R.; Miller W.; Mills J.; Milne C.; Mineev O.; Miranda O.G.; Miryala S.; Mishra C.; Mishra S.; Mislivec A.; Mladenov D.; Mocioiu I.; Moffat K.; Moggi N.; Mohanta R.; Mohayai T.A.; Mokhov N.; Molina J.A.; Bueno L.M.; Montanari A.; Montanari C.; Montanari D.; Zetina L.M.M.; Moon J.; Mooney M.; Moor A.; Moreno D.; Morgan B.; Morris C.; Mossey C.; Motuk E.; Moura C.A.; Mousseau J.; Mu W.; Mualem L.; Mueller J.; Muether M.; Mufson S.; Muheim F.; Muir A.; Mulhearn M.; Muramatsu H.; Murphy S.; Musser J.; Nachtman J.; Nagu S.; Nalbandyan M.; Nandakumar R.; Naples D.; Narita S.; Navas-Nicolas D.; Nayak N.; Nebot-Guinot M.; Necib L.; Negishi K.; Nelson J.K.; Nesbit J.; Nessi M.; Newbold D.; Newcomer M.; Newhart D.; Nichol R.; Niner E.; Nishimura K.; Norman A.; Northrop R.; Novella P.; Nowak J.A.; Oberling M.; Campo A.O.D.; Olivier A.; Onel Y.; Onishchuk Y.; Ott J.; Pagani L.; Pakvasa S.; Palamara O.; Palestini S.; Paley J.M.; Pallavicini M.; Palomares C.; Pantic E.; Paolone V.; Papadimitriou V.; Papaleo R.; Papanestis A.; Paramesvaran S.; Parke S.; Parsa Z.; Parvu M.; Pascoli S.; Pasqualini L.; Pasternak J.; Pater J.; Patrick C.; Patrizii L.; Patterson R.B.; Patton S.; Patzak T.; Paudel A.; Paulos B.; Paulucci L.; Pavlovic Z.; Pawloski G.; Payne D.; Pec V.; Peeters S.J.; Penichot Y.; Pennacchio E.; Penzo A.; Peres O.L.; Perry J.; Pershey D.; Pessina G.; Petrillo G.; Petta C.; Petti R.; Piastra F.; Pickering L.; Pietropaolo F.; Pillow J.; Plunkett R.; Poling R.; Pons X.; Poonthottathil N.; Pordes S.; Potekhin M.; Potenza R.; Potukuchi B.V.; Pozimski J.; Pozzato M.; Prakash S.; Prakash T.; Prince S.; Prior G.; Pugnere D.; Qi K.; Qian X.; Raaf J.; Raboanary R.; Radeka V.; Rademacker J.; Radics B.; Rafique A.; Raguzin E.; Rai M.; Rajaoalisoa M.; Rakhno I.; Rakotondramanana H.; Rakotondravohitra L.; Ramachers Y.; Rameika R.; Delgado M.R.; Ramson B.; Rappoldi A.; Raselli G.; Ratoff P.; Ravat S.; Razafinime H.; Real J.; Rebel B.; Redondo D.; Reggiani-Guzzo M.; Rehak T.; Reichenbacher J.; Reitzner S.D.; Renshaw A.; Rescia S.; Resnati F.; Reynolds A.; Riccobene G.; Rice L.C.; Rielage K.; Rigaut Y.; Rivera D.; Rochester L.; Roda M.; Rodrigues P.; Alonso M.R.; Rondon J.R.; Roeth A.; Rogers H.; Rosauro-Alcaraz S.; Rossella M.; Rout J.; Roy S.; Rubbia A.; Rubbia C.; Russell B.; Russell J.; Ruterbories D.; Saakyan R.; Sacerdoti S.; Safford T.; Sahu N.; Sala P.; Samios N.; Sanchez M.; Sanders D.A.; Sankey D.; Santana S.; Santos-Maldonado M.; Saoulidou N.; Sapienza P.; Sarasty C.; Sarcevic I.; Savage G.; Savinov V.; Scaramelli A.; Scarff A.; Scarpelli A.; Schaffer T.; Schellman H.; Schlabach P.; Schmitz D.; Scholberg K.; Schukraft A.; Segreto E.; Sensenig J.; Seong I.; Sergi A.; Sergiampietri F.; Sgalaberna D.; Shaevitz M.; Shafaq S.; Shamma M.; Sharma H.R.; Sharma R.; Shaw T.; Shepherd-Themistocleous C.; Shin S.; Shooltz D.; Shrock R.; Simard L.; Simos N.; Sinclair J.; Sinev G.; Singh J.; Singh V.; Sipos R.; Sippach F.; Sirri G.; Sitraka A.; Siyeon K.; Smargianaki D.; Smith A.; Smith A.; Smith E.; Smith P.; Smolik J.; Smy M.; Snopok P.; Nunes M.S.; Sobel H.; Soderberg M.; Salinas C.J.S.; Soldner-Rembold S.; Solomey N.; Solovov V.; Sondheim W.E.; Sorel M.; Soto-Oton J.; Sousa A.; Soustruznik K.; Spagliardi F.; Spanu M.; Spitz J.; Spooner N.J.; Spurgeon K.; Staley R.; Stancari M.; Stanco L.; Steiner H.; Stewart J.; Stillwell B.; Stock J.; Stocker F.; Stokes T.; Strait M.; Strauss T.; Striganov S.; Stuart A.; Summers D.; Surdo A.; Susic V.; Suter L.; Sutera C.; Svoboda R.; Szczerbinska B.; Szelc A.; Talaga R.; Tanaka H.; Oregui B.T.; Tapper A.; Tariq S.; Tatar E.; Tayloe R.; Teklu A.; Tenti M.; Terao K.; Ternes C.A.; Terranova F.; Testera G.; Thea A.; Thompson J.L.; Thorn C.; Timm S.; Tonazzo A.; Torti M.; Tortola M.; Tortorici F.; Totani D.; Toups M.; Touramanis C.; Trevor J.; Trzaska W.H.; Tsai Y.T.; Tsamalaidze Z.; Tsang K.; Tsverava N.; Tufanli S.; Tull C.; Tyley E.; Tzanov M.; Uchida M.A.; Urheim J.; Usher T.; Vagins M.; Vahle P.; Valdiviesso G.; Valencia E.; Vallari Z.; Valle J.W.; Vallecorsa S.; Berg R.V.; De Water R.G.V.; Forero D.V.; Varanini F.; Vargas D.; Varner G.; Vasel J.; Vasseur G.; Vaziri K.; Ventura S.; Verdugo A.; Vergani S.; Vermeulen M.A.; Verzocchi M.; De Souza H.V.; Vignoli C.; Vilela C.; Viren B.; Vrba T.; Wachala T.; Waldron A.V.; Wallbank M.; Wang H.; Wang J.; Wang Y.; Wang Y.; Warburton K.; Warner D.; Wascko M.; Waters D.; Watson A.; Weatherly P.; Weber A.; Weber M.; Wei H.; Weinstein A.; Wenman D.; Wetstein M.; While M.R.; White A.; Whitehead L.H.; Whittington D.; Wilking M.J.; Wilkinson C.; Williams Z.; Wilson F.; Wilson R.J.; Wolcott J.; Wongjirad T.; Wood K.; Wood L.; Worcester E.; Worcester M.; Wret C.; Wu W.; Wu W.; Xiao Y.; Yang G.; Yang T.; Yershov N.; Yonehara K.; Young T.; Yu B.; Yu J.; Zalesak J.; Zambelli L.; Zamorano B.; Zani A.; Zazueta L.; Zeller G.; Zennamo J.; Zeug K.; Zhang C.; Zhao M.; Zhivun E.; Zhu G.; Zimmerman E.D.; Zito M.; Zucchelli S.; Zuklin J.; Zutshi V.; Zwaska R.Abi B.; Acciarri R.; Acero M.A.; Adamov G.; Adams D.; Adinolfi M.; Ahmad Z.; Ahmed J.; Alion T.; Monsalve S.A.; Alt C.; Anderson J.; Andreopoulos C.; Andrews M.; Andrianala F.; Andringa S.; Ankowski A.; Antonova M.; Antusch S.; Aranda-Fernandez A.; Ariga A.; Arnold L.O.; Arroyave M.A.; Asaadi J.; Aurisano A.; Aushev V.; Autiero D.; Azfar F.; Back H.; Back J.J.; Backhouse C.; Baesso P.; Bagby L.; Bajou R.; Balasubramanian S.; Baldi P.; Bambah B.; Barao F.; Barenboim G.; Barker G.; Barkhouse W.; Barnes C.; Barr G.; Monarca J.B.; Barros N.; Barrow J.L.; Bashyal A.; Basque V.; Bay F.; Alba J.B.; Beacom J.F.; Bechetoille E.; Behera B.; Bellantoni L.; Bellettini G.; Bellini V.; Beltramello O.; Belver D.; Benekos N.; Neves F.B.; Berger J.; Berkman S.; Bernardini P.; Berner R.M.; Berns H.; Bertolucci S.; Betancourt M.; Bezawada Y.; Bhattacharjee M.; Bhuyan B.; Biagi S.; Bian J.; Biassoni M.; Biery K.; Bilki B.; Bishai M.; Bitadze A.; Blake A.; Siffert B.B.; Blaszczyk F.; Blazey G.; Blucher E.; Boissevain J.; Bolognesi S.; Bolton T.; Bonesini M.; Bongrand M.; Bonini F.; Booth A.; Booth C.; Bordoni S.; Borkum A.; Boschi T.; Bostan N.; Bour P.; Boyd S.; Boyden D.; Bracinik J.; Braga D.; Brailsford D.; Brandt A.; Bremer J.; Brew C.; Brianne E.; Brice S.J.; Brizzolari C.; Bromberg C.; Brooijmans G.; Brooke J.; Bross A.; Brunetti G.; Buchanan N.; Budd H.; Caiulo D.; Calafiura P.; Calcutt J.; Calin M.; Calvez S.; Calvo E.; Camilleri L.; Caminata A.; Campanelli M.; Caratelli D.; Carini G.; Carlus B.; Carniti P.; Terrazas I.C.; Carranza H.; Castillo A.; Castromonte C.; Cattadori C.; Cavalier F.; Cavanna F.; Centro S.; Cerati G.; Cervelli A.; Villanueva A.C.; Chalifour M.; Chang C.; Chardonnet E.; Chatterjee A.; Chattopadhyay S.; Chaves J.; Chen H.; Chen M.; Chen Y.; Cherdack D.; Chi C.; Childress S.; Chiriacescu A.; Cho K.; Choubey S.; Christensen A.; Christian D.; Christodoulou G.; Church E.; Clarke P.; Coan T.E.; Cocco A.G.; Coelho J.; Conley E.; Conrad J.; Convery M.; Corwin L.; Cotte P.; Cremaldi L.; Cremonesi L.; Crespo-Anadon J.I.; Cristaldo E.; Cross R.; Cuesta C.; Cui Y.; Cussans D.; Dabrowski M.; Motta H.D.; Peres L.D.S.; David Q.; Davies G.S.; Davini S.; Dawson J.; De K.; Almeida R.M.D.; Debbins P.; Bonis I.D.; Decowski M.; Gouvea A.D.; Holanda P.C.D.; Astiz I.L.D.I.; Deisting A.; Jong P.D.; Delbart A.; Delepine D.; Delgado M.; Dell'acqua A.; Lurgio P.D.; Neto J.R.D.M.; Demuth D.M.; Dennis S.; Densham C.; Deptuch G.; Roeck A.D.; Romeri V.D.; Vries J.D.; Dharmapalan R.; Dias M.; Diaz F.; Diaz J.; Domizio S.D.; Giulio L.D.; Ding P.; Noto L.D.; Distefano C.; Diurba R.; Diwan M.; Djurcic Z.; Dokania N.; Dolinski M.; Domine L.; Douglas D.; Drielsma F.; Duchesneau D.; Duffy K.; Dunne P.; Durkin T.; Duyang H.; Dvornikov O.; Dwyer D.; Dyshkant A.; Eads M.; Edmunds D.; Eisch J.; Emery S.; Ereditato A.; Escobar C.; Sanchez L.E.; Evans J.J.; Ewart E.; Ezeribe A.C.; Fahey K.; Falcone A.; Farnese C.; Farzan Y.; Felix J.; Fernandez-Martinez E.; Menendez P.F.; Ferraro F.; Fields L.; Filkins A.; Filthaut F.; Fitzpatrick R.S.; Flanagan W.; Fleming B.; Flight R.; Fowler J.; Fox W.; Franc J.; Francis K.; Franco D.; Freeman J.; Freestone J.; Fried J.; Friedland A.; Fuess S.; Furic I.; Furmanski A.P.; Gago A.; Gallagher H.; Gallego-Ros A.; Gallice N.; Galymov V.; Gamberini E.; Gamble T.; Gandhi R.; Gandrajula R.; Gao S.; Garcia-Gamez D.; Garcia-Peris M.A.; Gardiner S.; Gastler D.; Ge G.; Gelli B.; Gendotti A.; Gent S.; Ghorbani-Moghaddam Z.; Gibin D.; Gil-Botella I.; Girerd C.; Giri A.; Gnani D.; Gogota O.; Gold M.; Gollapinni S.; Gollwitzer K.; Gomes R.A.; Bermeo L.G.; Fajardo L.S.G.; Gonnella F.; Gonzalez-Cuevas J.; Goodman M.C.; Goodwin O.; Goswami S.; Gotti C.; Goudzovski E.; Grace C.; Graham M.; Gramellini E.; Gran R.; Granados E.; Grant A.; Grant C.; Gratieri D.; Green P.; Green S.; Greenler L.; Greenwood M.; Greer J.; Griffith C.; Groh M.; Grudzinski J.; Grzelak K.; Gu W.; Guarino V.; Guenette R.; Guglielmi A.; Guo B.; Guthikonda K.; Gutierrez R.; Guzowski P.; Guzzo M.M.; Gwon S.; Habig A.; Hackenburg A.; Hadavand H.; Haenni R.; Hahn A.; Haigh J.; Haiston J.; Hamernik T.; Hamilton P.; Han J.; Harder K.; Harris D.A.; Hartnell J.; Hasegawa T.; Hatcher R.; Hazen E.; Heavey A.; Heeger K.M.; Hennessy K.; Henry S.; Morquecho M.H.; Herner K.; Hertel L.; Hesam A.S.; Hewes J.; Pichardo A.H.; Hill T.; Hillier S.J.; Himmel A.; Hoff J.; Hohl C.; Holin A.; Hoppe E.; Horton-Smith G.A.; Hostert M.; Hourlier A.; Howard B.; Howell R.; Huang J.; Huang J.; Hugon J.; Iles G.; Iliescu A.M.; Illingworth R.; Ioannisian A.; Itay R.; Izmaylov A.; James E.; Jargowsky B.; Jediny F.; Jesus-Valls C.; Ji X.; Jiang L.; Jimenez S.; Jipa A.; Joglekar A.; Johnson C.; Johnson R.; Jones B.; Jones S.; Jung C.; Junk T.; Jwa Y.; Kabirnezhad M.; Kaboth A.; Kadenko I.; Kamiya F.; Karagiorgi G.; Karcher A.; Karolak M.; Karyotakis Y.; Kasai S.; Kasetti S.P.; Kashur L.; Kazaryan N.; Kearns E.; Keener P.; Kelly K.J.; Kemp E.; Ketchum W.; Kettell S.; Khabibullin M.; Khotjantsev A.; Khvedelidze A.; Kim D.; King B.; Kirby B.; Kirby M.; Klein J.; Koehler K.; Koerner L.W.; Kohn S.; Koller P.P.; Kordosky M.; Kosc T.; Kose U.; Kostelecky V.; Kothekar K.; Krennrich F.; Kreslo I.; Kudenko Y.; Kudryavtsev V.; Kulagin S.; Kumar J.; Kumar R.; Kuruppu C.; Kus V.; Kutter T.; Lambert A.; Lande K.; Lane C.E.; Lang K.; Langford T.; Lasorak P.; Last D.; Lastoria C.; Laundrie A.; Lawrence A.; Lazanu I.; Lazur R.; Le T.; Learned J.; Lebrun P.; Miotto G.L.; Lehnert R.; De Oliveira M.L.; Leitner M.; Leyton M.; Li L.; Li S.; Li S.; Li T.; Li Y.; Liao H.; Lin C.; Lin S.; Lister A.; Littlejohn B.R.; Liu J.; Lockwitz S.; Loew T.; Lokajicek M.; Lomidze I.; Long K.; Loo K.; Lorca D.; Lord T.; Losecco J.; Louis W.C.; Luk K.; Luo X.; Lurkin N.; Lux T.; Luzio V.P.; MacFarland D.; MacHado A.; MacHado P.; MacIas C.; MacIer J.; Maddalena A.; Madigan P.; Magill S.; Mahn K.; Maio A.; Maloney J.A.; Mandrioli G.; Maneira J.C.; Manenti L.; Manly S.; Mann A.; Manolopoulos K.; Plata M.M.; Marchionni A.; Marciano W.; Marfatia D.; Mariani C.; Maricic J.; Marinho F.; Marino A.D.; Marshak M.; Marshall C.; Marshall J.; Marteau J.; Martin-Albo J.; Martinez N.; Caicedo D.A.M.; Martynenko S.; Mason K.; Mastbaum A.; Masud M.; Matsuno S.; Matthews J.; Mauger C.; Mauri N.; Mavrokoridis K.; Mazza R.; Mazzacane A.; Mazzucato E.; McCluskey E.; McConkey N.; McFarland K.S.; McGrew C.; McNab A.; Mefodiev A.; Mehta P.; Melas P.; Mellinato M.; Mena O.; Menary S.; Mendez H.; Menegolli A.; Meng G.; Messier M.; Metcalf W.; Mewes M.; Meyer H.; Miao T.; Michna G.; Miedema T.; Migenda J.; Milincic R.; Miller W.; Mills J.; Milne C.; Mineev O.; Miranda O.G.; Miryala S.; Mishra C.; Mishra S.; Mislivec A.; Mladenov D.; Mocioiu I.; Moffat K.; Moggi N.; Mohanta R.; Mohayai T.A.; Mokhov N.; Molina J.A.; Bueno L.M.; Montanari A.; Montanari C.; Montanari D.; Zetina L.M.M.; Moon J.; Mooney M.; Moor A.; Moreno D.; Morgan B.; Morris C.; Mossey C.; Motuk E.; Moura C.A.; Mousseau J.; Mu W.; Mualem L.; Mueller J.; Muether M.; Mufson S.; Muheim F.; Muir A.; Mulhearn M.; Muramatsu H.; Murphy S.; Musser J.; Nachtman J.; Nagu S.; Nalbandyan M.; Nandakumar R.; Naples D.; Narita S.; Navas-Nicolas D.; Nayak N.; Nebot-Guinot M.; Necib L.; Negishi K.; Nelson J.K.; Nesbit J.; Nessi M.; Newbold D.; Newcomer M.; Newhart D.; Nichol R.; Niner E.; Nishimura K.; Norman A.; Northrop R.; Novella P.; Nowak J.A.; Oberling M.; Campo A.O.D.; Olivier A.; Onel Y.; Onishchuk Y.; Ott J.; Pagani L.; Pakvasa S.; Palamara O.; Palestini S.; Paley J.M.; Pallavicini M.; Palomares C.; Pantic E.; Paolone V.; Papadimitriou V.; Papaleo R.; Papanestis A.; Paramesvaran S.; Parke S.; Parsa Z.; Parvu M.; Pascoli S.; Pasqualini L.; Pasternak J.; Pater J.; Patrick C.; Patrizii L.; Patterson R.B.; Patton S.; Patzak T.; Paudel A.; Paulos B.; Paulucci L.; Pavlovic Z.; Pawloski G.; Payne D.; Pec V.; Peeters S.J.; Penichot Y.; Pennacchio E.; Penzo A.; Peres O.L.; Perry J.; Pershey D.; Pessina G.; Petrillo G.; Petta C.; Petti R.; Piastra F.; Pickering

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Volume I. Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE\u27s physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Prospects for beyond the Standard Model physics searches at the Deep Underground Neutrino Experiment

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE’s sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach