58 research outputs found
Gauge fields and infinite chains of dualities
We show that the particle states of Maxwell's theory, in dimensions, can
be represented in an infinite number of ways by using different gauge fields.
Using this result we formulate the dynamics in terms of an infinite set of
duality relations which are first order in space-time derivatives. We derive a
similar result for the three form in eleven dimensions where such a possibility
was first observed in the context of E11. We also give an action formulation
for some of the gauge fields. In this paper we give a pedagogical account of
the Lorentz and gauge covariant formulation of the irreducible representations
of the Poincar\'e group, used previously in higher spin theories, as this plays
a key role in our constructions. It is clear that our results can be
generalised to any particle.Comment: 37 page
Collapse of superconductivity in a hybrid tin-graphene Josephson junction array
When a Josephson junction array is built with hybrid
superconductor/metal/superconductor junctions, a quantum phase transition from
a superconducting to a two-dimensional (2D) metallic ground state is predicted
to happen upon increasing the junction normal state resistance. Owing to its
surface-exposed 2D electron gas and its gate-tunable charge carrier density,
graphene coupled to superconductors is the ideal platform to study the
above-mentioned transition between ground states. Here we show that decorating
graphene with a sparse and regular array of superconducting nanodisks enables
to continuously gate-tune the quantum superconductor-to-metal transition of the
Josephson junction array into a zero-temperature metallic state. The
suppression of proximity-induced superconductivity is a direct consequence of
the emergence of quantum fluctuations of the superconducting phase of the
disks. Under perpendicular magnetic field, the competition between quantum
fluctuations and disorder is responsible for the resilience at the lowest
temperatures of a superconducting glassy state that persists above the upper
critical field. Our results provide the entire phase diagram of the disorder
and magnetic field-tuned transition and unveil the fundamental impact of
quantum phase fluctuations in 2D superconducting systems.Comment: 25 pages, 6 figure
Hard Superconductivity of a Soft Metal in the Quantum Regime
Superconductivity is inevitably suppressed in reduced dimensionality.
Questions of how thin superconducting wires or films can be before they lose
their superconducting properties have important technological ramifications and
go to the heart of understanding coherence and robustness of the
superconducting state in quantum-confined geometries. Here, we exploit quantum
confinement of itinerant electrons in a soft metal to stabilize superconductors
with lateral dimensions of the order of a few millimeters and vertical
dimensions of only a few atomic layers. These extremely thin superconductors
show no indication of defect- or fluctuation-driven suppression of
superconductivity and sustain supercurrents of up to 10% of the depairing
current density. The extreme hardness of the critical state is attributed to
quantum trapping of vortices. This study paints a conceptually appealing,
elegant picture of a model nanoscale superconductor with calculable critical
state properties. It indicates the intriguing possibility of exploiting robust
superconductivity at the nanoscale.Comment: 15 pages, 4 figures, submitted to Nature Physic
Telomerase promoter mutations in cancer: an emerging molecular biomarker?
JoĂŁo Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to
the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the âalternative mechanism of telomere lengtheningâ (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target
The impact of viral mutations on recognition by SARS-CoV-2 specific TÂ cells.
We identify amino acid variants within dominant SARS-CoV-2 TÂ cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific TÂ cells assessed by IFN-Îł and cytotoxic killing assays. Complete loss of TÂ cell responsiveness was seen due to Q213K in the Aâ01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the Bâ27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the Aâ03:01/Aâ11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ TÂ cell lines unable to recognize variant epitopes have diverse TÂ cell receptor repertoires. These data demonstrate the potential for TÂ cell evasion and highlight the need for ongoing surveillance for variants capable of escaping TÂ cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC â IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC
Spatial growth rate of emerging SARS-CoV-2 lineages in England, September 2020-December 2021
This paper uses a robust method of spatial epidemiological analysis to assess the spatial growth rate of multiple lineages of SARS-CoV-2 in the local authority areas of England, September 2020âDecember 2021. Using the genomic surveillance records of the COVID-19 Genomics UK (COG-UK) Consortium, the analysis identifies a substantial (7.6-fold) difference in the average rate of spatial growth of 37 sample lineages, from the slowest (Delta AY.4.3) to the fastest (Omicron BA.1). Spatial growth of the Omicron (B.1.1.529 and BA) variant was found to be 2.81Ă faster than the Delta (B.1.617.2 and AY) variant and 3.76Ă faster than the Alpha (B.1.1.7 and Q) variant. In addition to AY.4.2 (a designated variant under investigation, VUI-21OCT-01), three Delta sublineages (AY.43, AY.98 and AY.120) were found to display a statistically faster rate of spatial growth than the parent lineage and would seem to merit further investigation. We suggest that the monitoring of spatial growth rates is a potentially valuable adjunct to outbreak response procedures for emerging SARS-CoV-2 variants in a defined population
Tracking SARS-CoV-2 mutations and variants through the COG-UK-Mutation Explorer
COG-UK Mutation Explorer (COG-UK-ME, https://sars2.cvr.gla.ac.uk/cog-uk/âlast accessed date 16 March 2022) is a web resource that displays knowledge and analyses on SARS-CoV-2 virus genome mutations and variants circulating in the UK, with a focus on the observed amino acid replacements that have an antigenic role in the context of the human humoral and cellular immune response. This analysis is based on more than 2 million genome sequences (as of March 2022) for UK SARS-CoV-2 data held in the CLIMB-COVID centralised data environment. COG-UK-ME curates these data and displays analyses that are cross-referenced to experimental data collated from the primary literature. The aim is to track mutations of immunological importance that are accumulating in current variants of concern and variants of interest that could alter the neutralising activity of monoclonal antibodies (mAbs), convalescent sera, and vaccines. Changes in epitopes recognised by T cells, including those where reduced T cell binding has been demonstrated, are reported. Mutations that have been shown to confer SARS-CoV-2 resistance to antiviral drugs are also included. Using visualisation tools, COG-UK-ME also allows users to identify the emergence of variants carrying mutations that could decrease the neutralising activity of both mAbs present in therapeutic cocktails, e.g. Ronapreve. COG-UK-ME tracks changes in the frequency of combinations of mutations and brings together the curated literature on the impact of those mutations on various functional aspects of the virus and therapeutics. Given the unpredictable nature of SARS-CoV-2 as exemplified by yet another variant of concern, Omicron, continued surveillance of SARS-CoV-2 remains imperative to monitor virus evolution linked to the efficacy of therapeutics
Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes
Summary Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine
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