Targeting Several CAG Expansion Diseases by a Single Antisense Oligonucleotide

To date there are 9 known diseases caused by an expanded polyglutamine repeat, with the most prevalent being Huntington's disease. Huntington's disease is a progressive autosomal dominant neurodegenerative disorder for which currently no therapy is available. It is caused by a CAG repeat expansion in the HTT gene, which results in an expansion of a glutamine stretch at the N-terminal end of the huntingtin protein. This polyglutamine expansion plays a central role in the disease and results in the accumulation of cytoplasmic and nuclear aggregates. Here, we make use of modified 2′-O-methyl phosphorothioate (CUG)n triplet-repeat antisense oligonucleotides to effectively reduce mutant huntingtin transcript and protein levels in patient-derived Huntington's disease fibroblasts and lymphoblasts. The most effective antisense oligonucleotide, (CUG)7, also reduced mutant ataxin-1 and ataxin-3 mRNA levels in spinocerebellar ataxia 1 and 3, respectively, and atrophin-1 in dentatorubral-pallidoluysian atrophy patient derived fibroblasts. This antisense oligonucleotide is not only a promising therapeutic tool to reduce mutant huntingtin levels in Huntington's disease but our results in spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy cells suggest that this could also be applicable to other polyglutamine expansion disorders as well

Exclusive J/ψ detection and physics with ECCE

The file available on this institutional repository is an arXiv preprint which may not have been certified by peer review. The definitive version of record published by Elsevier is available at https://doi.org/10.48550/arXiv.2207.10356.Copyright © The Authors 2023. The EIC Comprehensive Chromodynamics Experiment (ECCE) detector has been recommended as a reference design for the proposed Electron-Ion Collider (EIC) program. This paper presents simulation studies of exclusive J/ψ detection and selected physics impact results in EIC using the projected ECCE detector concept. Exclusive quarkonium photoproduction is one of the most popular processes in EIC, which has a large cross section and a simple final state. Due to the gluonic nature of the exchange Pomeron, this process can be related to the gluon distributions in the nucleus. Preliminary results estimate the excellent statistics benefited from the large cross section of J/ψ photoproduction and superior performance of ECCE detector concept. The precise measurement of exclusive J/ψ photoproduction at EIC will help us to more deeply understand nuclear gluon distributions, near threshold production mechanism and nucleon mass structure.X. Li and W. Zha are supported by the National Natural Science Foundation of China (12005220, 12175223) and MOST (2018YFE0104900). The authors would like to thank the ECCE Consortium for performing a full simulation of their detector design, for providing up-to-date information on EIC run conditions, and for suggestions and comments on the manuscript. X. Li and W. Zha would like to thank Y. Zhou for useful suggestions and discussions related to this analysis. W. Zha is supported by Anhui Provincial Natural Science Foundation No. 2208085J23 and Youth Innovation Promotion Association of Chinese Academy of Sciences. AANL group are supported by the Science Committee of RA , in the frames of the research project 21AG-1C028

Scientific computing plan for the ECCE detector at the Electron Ion Collider

This is the arXiv pre-print which has not been peer reviewed. It is made available under a Creative Commons (CC BY) Attribution Lciense. The corrected version of record is available at: https://doi.org/10.1016/j.nima.2022.167859.Cite as: arXiv:2205.08607 [physics.ins-det] (or arXiv:2205.08607v1 [physics.ins-det] for this version) https://doi.org/10.48550/arXiv.2205.08607 Focus to learn more Journal reference: NIMA 1047, 167859 (2023) Related DOI: https://doi.org/10.1016/j.nima.2022.167859 Focus to learn more Submission history From: Joseph Osborn [view email] [v1] Tue, 17 May 2022 19:53:56 UTC (29,605 KB)Copyright © 2022 The Author(s). The Electron Ion Collider (EIC) is the next generation of precision QCD facility to be built at Brookhaven National Laboratory in conjunction with Thomas Jefferson National Laboratory. There are a significant number of software and computing challenges that need to be overcome at the EIC. During the EIC detector proposal development period, the ECCE consortium began identifying and addressing these challenges in the process of producing a complete detector proposal based upon detailed detector and physics simulations. In this document, the software and computing efforts to produce this proposal are discussed; furthermore, the computing and software model and resources required for the future of ECCE are described.Office of Nuclear Physics in the Office of Science in the Department of Energy, USA; National Science Foundation, USA; Los Alamos National Laboratory Laboratory Directed Research and Development (LDRD), USA 20200022DR

Evaluation of longitudinal double-spin asymmetry measurements in semi-inclusive deep-inelastic scattering from the proton for the ECCE detector design

The evaluation of the measurement of double-spin asymmetries for charge-separated pions and kaons produced in deep-inelastic scattering from the proton using the ECCE detector design concept is presented, for the combinations of lepton and hadron beam energies of 5 × 41 GeV^2 and 18 × 275 GeV^2. The study uses unpolarised simulated data that are processed through a full GEANT simulation of the detector. These data are then reweighted at the parton level with DSSV helicity distributions and DSS fragmentation functions, in order to generate the relevant asymmetries, and subsequently analysed. The performed analysis shows that the ECCE detector concept provides the resolution and acceptance, with a broad coverage in kinematic phase space, needed for a robust extraction of asymmetries. This, in turn, allows for a precise extraction of sea-quark helicity distributions.We acknowledge support from the Office of Nuclear Physics in the Office of Science in the Department of Energy, the National Science Foundation, and the Los Alamos National Laboratory Directed Research and Development (LDRD) 20200022DR. The work of C.V.H. is, in addition, supported by the Atracción de Talento Investigador programme of the Comunidad de Madrid (Spain) No. 2020-T1/TIC-20295. The work of the AANL group is supported by the Science Committee of RA, in the frames of the research project 21AG-1C028

ECCE sensitivity studies for single hadron transverse single spin asymmetry measurements

The file archived on this repository is a pre-print and does not include peer review corrections. Please see the corrected version of record of this paper at: https://doi.org/10.1016/j.nima.2023.168017.Comments: 22 pages, 22 figures, to be submitted to joint ECCE proposal NIM-A volume Subjects: High Energy Physics - Experiment (hep-ex) Report number: ecce-paper-phys-2022-08 Cite as: arXiv:2207.10890 [hep-ex] (or arXiv:2207.10890v1 [hep-ex] for this version) https://doi.org/10.48550/arXiv.2207.10890 Focus to learn more Related DOI: https://doi.org/10.1016/j.nima.2023.168017 Focus to learn more Submission history From: Ralf Seidl [view email] [v1] Fri, 22 Jul 2022 05:52:35 UTC (23,821 KB)Copyright 2022 The Author(s). We performed feasibility studies for various single transverse spin measurements that are related to the Sivers effect, transversity and the tensor charge, and the Collins fragmentation function. The processes studied include semi-inclusive deep inelastic scattering (SIDIS) where single hadrons (pions and kaons) were detected in addition to the scattered DIS lepton. The data were obtained in pythia6 and geant4 simulated e+p collisions at 18 GeV on 275 GeV, 18 on 100, 10 on 100, and 5 on 41 that use the ECCE detector configuration. Typical DIS kinematics were selected, most notably 2 > 1 GeV2, and cover the range from 10−4 to 1. The single spin asymmetries were extracted as a function of and 2, as well as the semi-inclusive variables , which corresponds to the momentum fraction the detected hadron carries relative to the struck parton, and , which corresponds to the transverse momentum of the detected hadron relative to the virtual photon. They are obtained in azimuthal moments in combinations of the azimuthal angles of the hadron transverse momentum and transverse spin of the nucleon relative to the lepton scattering plane. In order to extract asymmetries, the initially unpolarized MonteCarlo was re-weighted in the true kinematic variables, hadron types and parton flavors based on global fits of fixed target SIDIS experiments and +− annihilation data. The expected statistical precision of such measurements is extrapolated to 10 fb−1 and potential systematic uncertainties are approximated given the deviations between true and reconstructed yields. Similar neutron information is obtained by comparing the ECCE e+p pseudo-data with the same from the EIC Yellow Report and scaling the corresponding Yellow Report e+3He pseudo-data uncertainties accordingly. The impact on the knowledge of the Sivers functions, transversity and tensor charges, and the Collins function has then been evaluated in the same phenomenological extractions as in the Yellow Report. The impact is found to be comparable to that obtained with the parametrized Yellow Report detector and shows that the ECCE detector configuration can fulfill the physics goals on these quantitiesWe acknowledge support from the Office of Nuclear Physics in the Office of Science in the Department of Energy, USA, the National Science Foundation, USA, and the Los Alamos National Laboratory Directed Research and Development (LDRD), USA 20200022DR. This work was also partially supported by the National Science Foundation, USA under grant No. PHY-2011763, Grant No. PHY-2012002, the U.S. Department of Energy under contract No.DE-AC05-06OR23177 under which Jefferson Science Associates, LLC, manages and operates Jefferson Lab, and within the framework of the TMD Topical Collaboration

Search for e→τ charged lepton flavor violation at the EIC with the ECCE detector

...The file archived on tis institutional repository is a preprint made available at arXiv, arXiv:2207.10261 [hep-ph], under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). It has not been ceritified by peer review. You are advised to consult the final version published by Elsevier at: https://doi.org/10.1016/j.nima.2023.168276 .The recently approved Electron-Ion Collider (EIC) will provide a unique new opportunity for searches of charged lepton flavor violation (CLFV) and other new physics scenarios. In contrast to the e↔μ CLFV transition for which very stringent limits exist, there is still a relatively large discovery space for the e→τ CLFV transition, potentially to be explored by the EIC. With the latest detector design of ECCE (EIC Comprehensive Chromodynamics Experiment) and projected integral luminosity of the EIC, we find the τ-leptons created in the DIS process ep→τX are expected to be identified with high efficiency. A first ECCE simulation study, restricted to the 3-prong τ-decay mode and with limited statistics for the Standard Model backgrounds, estimates that the EIC will be able to improve the current exclusion limit on e→τ CLFV by an order of magnitude.Office of Nuclear Physics in the Office of Science in the Department of Energy, the National Science Foundation, and the Los Alamos National Laboratory Laboratory Directed Research and Development (LDRD) 20200022DR

Transfer and engineering of immune receptors to improve recognition capacities in crops

Immune receptors are pivotal elements of the plant immune system that act as sentinels for microbial invasion. Knowingly or unknowingly, breeding for resistance has largely relied on the transfer of immune receptor recognition specificities between plant genotypes. For decades such transfers were limited to crossable species. However, advents in transgene technologies have allowed overcoming species barriers. Novel strategies for mining of recognition specificities, combined with our recently increased understanding of immune receptor functioning, allows to increase and alter recognition specificities, which should ultimately increase the spectrum of recognition specificities that are available to control plant diseases in crops