Role of interactions in a dissipative many-body localized system

Recent experimental and theoretical efforts have focused on the effect of dissipation on quantum many-body systems in their many-body localized (MBL) phase. While in the presence of dephasing noise such systems reach a unique ergodic state, their dynamics is characterized by slow relaxation manifested in nonexponential decay of self-correlations. Here we shed light on a currently much debated issue, namely, the role of interactions for this relaxation dynamics. We focus on the experimentally relevant situation of the evolution from an initial charge density wave in the presence of strong dephasing noise. We find a crossover from a regime dominated by disorder to a regime dominated by interactions, with an accompanying change of time correlators from stretched exponential to compressed exponential form. The strongly interacting regime can be explained in terms of nucleation and growth dynamics of relaxing regions—reminiscent of the kinetics of crystallization in soft matter systems—and should be observable experimentally. This interaction-driven crossover suggests that the competition between interactions and noise gives rise to a much richer structure of the MBL phase than anticipated so far

Dissipation as a resource for constrained dynamics in open many-body quantum systems

This thesis studies non-equilibrium open quantum systems where the dissipation is crucial to the achievement of novel physical regimes. We focus on atomic systems which allow for the coupling of a ground state to a Rydberg state, relying on the strong interactions between Rydberg atoms to produce the collective behaviour that we aim to investigate. For atoms in an optical lattice undergoing standard dissipation forms, e.g. loss and dephasing, we find these simple settings allow for the production of models contained in the non-equilibrium realm. We start by looking at a system with engineered pair dissipation on a one-dimensional lattice. When the dissipation is strong relative to a tunnelling process it creates a quantum Zeno effect which projects the system onto a Zeno-subspace. This subspace is found to contain complexes which experience a binding due to the dissipation. The properties of these complexes are found to feature spin-orbit coupling and, in certain instances, a flat band. We then study what kinetically constrained models (KCMs) can be reproduced in a lattice system. KCMs are models which typically feature trivial steady states, but a complex relaxation dynamics. These models appear in the fields of glasses and soft matter physics. We find a general framework for the consideration of a quantum Hamiltonian and a classical potential with strong dephasing noise. We then focus on a model mimicking volume excluded KCMs and find characteristic constrained behaviour, such as ergodicity breaking. We apply this framework to the decay of a many-body localised state in an open system with interactions in which we find the decay to be classical in the two interaction limits. For weak interactions, it follows a stretched exponential form due to pair relaxation, while for strong interactions the decay follows a compressed exponential, now being modelled as an Avrami process due to the correlated relaxation. We also find that on-site loss only affects the strong interacting limit. We then move on to the study of universal non-equilibrium behaviour in the directed percolation (DP) class. We consider on-site atomic loss and gain as a substitute for the standard decay channel. We show that this replaces the absorbing state with an enlarged absorbing space, leading to a loss of the DP transition at lower average densities. This class of DP-like systems has received little study, and we present a method of experimentally realising it in current set-ups. We finish with a look at a quantum DP model, where we consider its quantum and classical limits. We find that the transition changes from first to second order as the system becomes more classical, featuring a bi-critical point. We then numerically demonstrate that the same transitions are visible in idealised and Rydberg models

Dissipation as a resource for constrained dynamics in open many-body quantum systems

This thesis studies non-equilibrium open quantum systems where the dissipation is crucial to the achievement of novel physical regimes. We focus on atomic systems which allow for the coupling of a ground state to a Rydberg state, relying on the strong interactions between Rydberg atoms to produce the collective behaviour that we aim to investigate. For atoms in an optical lattice undergoing standard dissipation forms, e.g. loss and dephasing, we find these simple settings allow for the production of models contained in the non-equilibrium realm. We start by looking at a system with engineered pair dissipation on a one-dimensional lattice. When the dissipation is strong relative to a tunnelling process it creates a quantum Zeno effect which projects the system onto a Zeno-subspace. This subspace is found to contain complexes which experience a binding due to the dissipation. The properties of these complexes are found to feature spin-orbit coupling and, in certain instances, a flat band. We then study what kinetically constrained models (KCMs) can be reproduced in a lattice system. KCMs are models which typically feature trivial steady states, but a complex relaxation dynamics. These models appear in the fields of glasses and soft matter physics. We find a general framework for the consideration of a quantum Hamiltonian and a classical potential with strong dephasing noise. We then focus on a model mimicking volume excluded KCMs and find characteristic constrained behaviour, such as ergodicity breaking. We apply this framework to the decay of a many-body localised state in an open system with interactions in which we find the decay to be classical in the two interaction limits. For weak interactions, it follows a stretched exponential form due to pair relaxation, while for strong interactions the decay follows a compressed exponential, now being modelled as an Avrami process due to the correlated relaxation. We also find that on-site loss only affects the strong interacting limit. We then move on to the study of universal non-equilibrium behaviour in the directed percolation (DP) class. We consider on-site atomic loss and gain as a substitute for the standard decay channel. We show that this replaces the absorbing state with an enlarged absorbing space, leading to a loss of the DP transition at lower average densities. This class of DP-like systems has received little study, and we present a method of experimentally realising it in current set-ups. We finish with a look at a quantum DP model, where we consider its quantum and classical limits. We find that the transition changes from first to second order as the system becomes more classical, featuring a bi-critical point. We then numerically demonstrate that the same transitions are visible in idealised and Rydberg models

Nonequilibrium effective field theory for absorbing state phase transitions in driven open quantum spin systems

Phase transitions to absorbing states are among the simplest examples of critical phenomena out of equilibrium. The characteristic feature of these models is the presence of a fluctuationless configuration which the dynamics cannot leave, which has proved a rather stringent requirement in experiments. Recently, a proposal to seek such transitions in highly tuneable systems of cold atomic gases offers to probe this physics and, at the same time, to investigate the robustness of these transitions to quantum coherent effects. Here we specifically focus on the interplay between classical and quantum fluctuations in a simple driven open quantum model which, in the classical limit, reproduces a contact process, which is known to undergo a continuous transition in the "directed percolation" universality class. We derive an effective long-wavelength field theory for the present class of open spin systems and show that, due to quantum fluctuations, the nature of the transition changes from second to first order, passing through a bicritical point which appears to belong instead to the "tricritical directed percolation" class

Coinfection of chickens with H9N2 and H7N9 avian influenza viruses leads to emergence of reassortant H9N9 virus with increased fitness for poultry and a zoonotic potential

An H7N9 low-pathogenicity avian influenza virus (LPAIV) emerged in 2013 through genetic reassortment between H9N2 and other LPAIVs circulating in birds in China. This virus causes inapparent clinical disease in chickens, but zoonotic transmission results in severe and fatal disease in humans. To examine a natural reassortment scenario between H7N9 and G1 lineage H9N2 viruses predominant in the Indian subcontinent, we performed an experimental coinfection of chickens with A/Anhui/1/2013/H7N9 (Anhui/13) virus and A/Chicken/Pakistan/UDL-01/2008/H9N2 (UDL/08) virus. Plaque purification and genotyping of the reassortant viruses shed via the oropharynx of contact chickens showed H9N2 and H9N9 as predominant subtypes. The reassortant viruses shed by contact chickens also showed selective enrichment of polymerase genes from H9N2 virus. The viable “6+2” reassortant H9N9 (having nucleoprotein [NP] and neuraminidase [NA] from H7N9 and the remaining genes from H9N2) was successfully shed from the oropharynx of contact chickens, plus it showed an increased replication rate in human A549 cells and a significantly higher receptor binding to α2,6 and α2,3 sialoglycans compared to H9N2. The reassortant H9N9 virus also had a lower fusion pH, replicated in directly infected ferrets at similar levels compared to H7N9 and transmitted via direct contact. Ferrets exposed to H9N9 via aerosol contact were also found to be seropositive, compared to H7N9 aerosol contact ferrets. To the best of our knowledge, this is the first study demonstrating that cocirculation of H7N9 and G1 lineage H9N2 viruses could represent a threat for the generation of novel reassortant H9N9 viruses with greater virulence in poultry and a zoonotic potential. We evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of the G1 lineage that are enzootic in poultry across the Indian subcontinent and the Middle East. Coinfection of chickens with these viruses resulted in the emergence of novel reassortant H9N9 viruses with genes derived from both H9N2 and H7N9 viruses. The “6+2” reassortant H9N9 (having NP and NA from H7N9) virus was shed from contact chickens in a significantly higher proportion compared to most of the reassortant viruses, showed significantly increased replication fitness in human A549 cells, receptor binding toward human (α2,6) and avian (α2,3) sialic acid receptor analogues, and the potential to transmit via contact among ferrets. This study demonstrated the ability of viruses that already exist in nature to exchange genetic material, highlighting the potential emergence of viruses from these subtypes with zoonotic potential

NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods

Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submit- Avenue, Silver Spring, Maryland 20993; 22Glycoscience Research Laboratory, Genos, Borongajska cesta 83h, 10 000 Zagreb, Croatia; 23Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacˇ ic´ a 1, 10 000 Zagreb, Croatia; 24Department of Chemistry, Georgia State University, 100 Piedmont Avenue, Atlanta, Georgia 30303; 25glyXera GmbH, Brenneckestrasse 20 * ZENIT / 39120 Magdeburg, Germany; 26Health Products and Foods Branch, Health Canada, AL 2201E, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1A 0K9 Canada; 27Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama Higashi-Hiroshima 739–8530 Japan; 28ImmunoGen, 830 Winter Street, Waltham, Massachusetts 02451; 29Department of Medical Physiology, Jagiellonian University Medical College, ul. Michalowskiego 12, 31–126 Krakow, Poland; 30Department of Pathology, Johns Hopkins University, 400 N. Broadway Street Baltimore, Maryland 21287; 31Mass Spec Core Facility, KBI Biopharma, 1101 Hamlin Road Durham, North Carolina 27704; 32Division of Mass Spectrometry, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongwon-gu, Cheongju Chungbuk, 363–883 Korea (South); 33Advanced Therapy Products Research Division, Korea National Institute of Food and Drug Safety, 187 Osongsaengmyeong 2-ro Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 363–700, Korea (South); 34Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; 35Ludger Limited, Culham Science Centre, Abingdon, Oxfordshire, OX14 3EB, United Kingdom; 36Biomolecular Discovery and Design Research Centre and ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, North Ryde, Australia; 37Proteomics, Central European Institute for Technology, Masaryk University, Kamenice 5, A26, 625 00 BRNO, Czech Republic; 38Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany; 39Department of Biomolecular Sciences, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany; 40AstraZeneca, Granta Park, Cambridgeshire, CB21 6GH United Kingdom; 41Merck, 2015 Galloping Hill Rd, Kenilworth, New Jersey 07033; 42Analytical R&D, MilliporeSigma, 2909 Laclede Ave. St. Louis, Missouri 63103; 43MS Bioworks, LLC, 3950 Varsity Drive Ann Arbor, Michigan 48108; 44MSD, Molenstraat 110, 5342 CC Oss, The Netherlands; 45Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5–1 Higashiyama, Myodaiji, Okazaki 444–8787 Japan; 46Graduate School of Pharmaceutical Sciences, Nagoya City University, 3–1 Tanabe-dori, Mizuhoku, Nagoya 467–8603 Japan; 47Medical & Biological Laboratories Co., Ltd, 2-22-8 Chikusa, Chikusa-ku, Nagoya 464–0858 Japan; 48National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG United Kingdom; 49Division of Biological Chemistry & Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158–8501 Japan; 50New England Biolabs, Inc., 240 County Road, Ipswich, Massachusetts 01938; 51New York University, 100 Washington Square East New York City, New York 10003; 52Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, United Kingdom; 53GlycoScience Group, The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland; 54Department of Chemistry, North Carolina State University, 2620 Yarborough Drive Raleigh, North Carolina 27695; 55Pantheon, 201 College Road East Princeton, New Jersey 08540; 56Pfizer Inc., 1 Burtt Road Andover, Massachusetts 01810; 57Proteodynamics, ZI La Varenne 20–22 rue Henri et Gilberte Goudier 63200 RIOM, France; 58ProZyme, Inc., 3832 Bay Center Place Hayward, California 94545; 59Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho Nakagyo-ku, Kyoto, 604 8511 Japan; 60Children’s GMP LLC, St. Jude Children’s Research Hospital, 262 Danny Thomas Place Memphis, Tennessee 38105; 61Sumitomo Bakelite Co., Ltd., 1–5 Muromati 1-Chome, Nishiku, Kobe, 651–2241 Japan; 62Synthon Biopharmaceuticals, Microweg 22 P.O. Box 7071, 6503 GN Nijmegen, The Netherlands; 63Takeda Pharmaceuticals International Co., 40 Landsdowne Street Cambridge, Massachusetts 02139; 64Department of Chemistry and Biochemistry, Texas Tech University, 2500 Broadway, Lubbock, Texas 79409; 65Thermo Fisher Scientific, 1214 Oakmead Parkway Sunnyvale, California 94085; 66United States Pharmacopeia India Pvt. Ltd. IKP Knowledge Park, Genome Valley, Shamirpet, Turkapally Village, Medchal District, Hyderabad 500 101 Telangana, India; 67Alberta Glycomics Centre, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 68Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 69Department of Chemistry, University of California, One Shields Ave, Davis, California 95616; 70Horva´ th Csaba Memorial Laboratory for Bioseparation Sciences, Research Center for Molecular Medicine, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Egyetem ter 1, Hungary; 71Translational Glycomics Research Group, Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Veszprem, Egyetem ut 10, Hungary; 72Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way Newark, Delaware 19711; 73Proteomics Core Facility, University of Gothenburg, Medicinaregatan 1G SE 41390 Gothenburg, Sweden; 74Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Institute of Biomedicine, Sahlgrenska Academy, Medicinaregatan 9A, Box 440, 405 30, Gothenburg, Sweden; 75Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Bruna Straket 16, 41345 Gothenburg, Sweden; 76Department of Chemistry, University of Hamburg, Martin Luther King Pl. 6 20146 Hamburg, Germany; 77Department of Chemistry, University of Manitoba, 144 Dysart Road, Winnipeg, Manitoba, Canada R3T 2N2; 78Laboratory of Mass Spectrometry of Interactions and Systems, University of Strasbourg, UMR Unistra-CNRS 7140, France; 79Natural and Medical Sciences Institute, University of Tu¨ bingen, Markwiesenstrae 55, 72770 Reutlingen, Germany; 80Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; 81Division of Bioanalytical Chemistry, Amsterdam Institute for Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands; 82Department of Chemistry, Waters Corporation, 34 Maple Street Milford, Massachusetts 01757; 83Zoetis, 333 Portage St. Kalamazoo, Michigan 49007 Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license. Received July 24, 2019, and in revised form, August 26, 2019 Published, MCP Papers in Press, October 7, 2019, DOI 10.1074/mcp.RA119.001677 ER: NISTmAb Glycosylation Interlaboratory Study 12 Molecular & Cellular Proteomics 19.1 Downloaded from https://www.mcponline.org by guest on January 20, 2020 ted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide communityderived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods. Molecular & Cellular Proteomics 19: 11–30, 2020. DOI: 10.1074/mcp.RA119.001677.L

Deletion of the Asialyloglycoprotein Receptor-1 Causes Athero-Protective Effects in vitro and in vivo

Introduction: The asialoglycoprotein receptor-1 (ASGR-1) is known to be a hepatic receptor that clears desialylated glycoproteins from the circulation. A loss-of-function mutation in ASGR-1 was reported to associate with a 34% reduction in coronary artery disease (CAD) risk, suggesting a role for ASGR-1 in CAD. Hypothesis: ASGR-1 is an important player in atherosclerosis and deletion of ASGR-1 will reduce atherosclerotic plaque via athero-protective mechanisms in macrophages. Methods and Results: Using immunofluorescence, we detected ASGR-1 in aortic sinus plaques from apolipoprotein (Apo)e-/- mice fed a high cholesterol diet (HCD)-fed apolipoprotein (Apo)e-/- mice. Bone marrow-derived macrophages (BMDMs) from Asgr1-/- mice elicited greater cholesterol efflux (39%, P<0.05) and decreased oxLDL uptake (15%, P<0.05), compared to wildtype BMDMs. Plasma from Asgr-1-/- mice had lower total cholesterol (25%, P<0.05) and LDL cholesterol (36%, P<0.05) concentrations than wildtype control mice. Apoe-/- x Asgr-1-/+ mice fed HCD for 8 weeks developed less plaque in the aortic sinus (32.75%, P<0.001) than Apoe-/- controls, and had fewer circulating neutrophils (38%, P<0.05). In the tandem stenosis model of unstable plaque, Apoe-/- x Asgr-1-/- mice also developed smaller plaques in their carotid arteries (49%, P<0.05), than Apoe-/- controls. Furthermore, ASGR-1 was measured in peripheral blood mononuclear cells (PBMCs) isolated from patient samples (n=10-12/group). ASGR-1 protein levels were higher in PBMCs from patients with coronary plaque (61%, P<0.05), than those without plaque, as determined from coronary angiograms. Conclusions: ASGR-1 plays an important role in atherosclerosis. Deletion of ASGR-1 causes athero-protective effects in macrophages in vitro and reduced plaque burden in vivo. Elevated ASGR-1 levels in PBMCs from clinical blood samples was also associated with the presence of coronary plaque. These studies have significant implications for the potential of ASGR-1 as a therapeutic target for the prevention of atherosclerosis.No Full Tex

Coinfection of Chickens with H9N2 and H7N9 Avian Influenza Viruses Leads to Emergence of Reassortant H9N9 Virus with Increased Fitness for Poultry and a Zoonotic Potential

We evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of the G1 lineage that are enzootic in poultry across the Indian subcontinent and the Middle East. Coinfection of chickens with these viruses resulted in the emergence of novel reassortant H9N9 viruses with genes derived from both H9N2 and H7N9 viruses.</jats:p

Co-infection of chickens with H9N2 and H7N9 avian influenza viruses leads to emergence of reassortant H9N9 virus with increased fitness for poultry and enhanced zoonotic potential

SUMMARYAn H7N9 low pathogenicity avian influenza virus (LPAIV) emerged through genetic reassortment between H9N2 and other LPAIVs circulating in birds in China. This virus causes inapparent clinical disease in chickens, but zoonotic transmission results in severe and fatal disease in humans. We evaluated the consequences of reassortment between the H7N9 and the contemporary H9N2 viruses of G1 lineage that are enzootic in poultry across the Indian sub-continent and the Middle East. Co-infection of chickens with these viruses resulted in emergence of novel reassortant H9N9 viruses carrying genes derived from both H9N2 and H7N9 viruses. These reassortant H9N9 viruses showed significantly increased replication fitness, enhanced pathogenicity in chicken embryos and the potential to transmit via contact among ferrets. Our study highlights that the co-circulation of H7N9 and H9N2 viruses could represent a threat for the generation of novel reassortant viruses with greater virulence in poultry and an increased zoonotic potential. Graphical AbstractIn BriefH9N2 viruses have a high propensity to reassort with other avian influenza viruses. We found that co-infection of chickens with H9N2 and H7N9 led to the emergence of reassortant viruses including the H9N9 subtype. Some reassortant H9N9 viruses exhibited increased replication fitness, increased pathogenicity in the chicken embryo, greater avidity for human and avian cell receptors, lower pH fusion and contact-transmission to ferrets. This study demonstrated the ability of viruses that already exist in nature to exchange genetic material, highlighting the potential emergence of viruses from these subtypes with increased zoonotic potential. There are nine H9 influenza A subtypes carrying different neuraminidase (NA) genes, including H9N9 viruses, while they are not common they do exist in nature as wildtypes (CDC).HighlightsCo-infection of chickens with H7N9 and H9N2 led to emergence of reassortant H9N9 virusesReassortant H9N9 viruses had an increased replication rate in avian and human cellsReassortant H9N9 viruses had a lower pH fusion and significantly higher receptor binding to α 2,3 sialoglycansReassortant H9N9 replicated in ferrets at similar levels compared to H7N9 and transmitted via direct contactFerrets exposed to reassortant H9N9 by aerosol contact were also found to be seropositiveExperimental simulation of events that may occur naturally with circulating viruses has demonstrated the risk of emergence of viruses with increased zoonotic potential.</jats:sec