| 1. |
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| 2. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 3. |
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| 4. |
- Wang, QBS, et al.
(author)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 5. |
- Schael, S, et al.
(author)
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Precision electroweak measurements on the Z resonance
- 2006
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Research review (peer-reviewed)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 6. |
- Schael, S., et al.
(author)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
-
Research review (peer-reviewed)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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| 13. |
- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 14. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 15. |
- Meech, K. J., et al.
(author)
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EPOXI: Comet 103P/Hartley 2 Observations from a Worldwide Campaign
- 2011
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In: Astrophysical Journal Letters. - London : IOP. - 2041-8213 .- 2041-8205. ; 734:L1, s. 1-9
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Journal article (peer-reviewed)abstract
- Earth- and space-based observations provide synergistic information for space mission encounters by providing data over longer timescales, at different wavelengths and using techniques that are impossible with an in situ flyby. We report here such observations in support of the EPOXI spacecraft flyby of comet 103P/Hartley 2. The nucleus is small and dark, and exhibited a very rapidly changing rotation period. Prior to the onset of activity, the period was ~16.4?hr. Starting in 2010 August the period changed from 16.6?hr to near 19?hr in December. With respect to dust composition, most volatiles and carbon and nitrogen isotope ratios, the comet is similar to other Jupiter-family comets. What is unusual is the dominance of CO 2 -driven activity near perihelion, which likely persists out to aphelion. Near perihelion the comet nucleus was surrounded by a large halo of water-ice grains that contributed significantly to the total water production.
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| 16. |
- Nango, E., et al.
(author)
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A three-dimensional movie of structural changes in bacteriorhodopsin
- 2016
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 354:6319, s. 1552-1557
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Journal article (peer-reviewed)abstract
- Bacteriorhodopsin (bR) is a light-driven proton pump and a model membrane transport protein. We used time-resolved serial femtosecond crystallography at an x-ray free electron laser to visualize conformational changes in bR from nanoseconds to milliseconds following photoactivation. An initially twisted retinal chromophore displaces a conserved tryptophan residue of transmembrane helix F on the cytoplasmic side of the protein while dislodging a key water molecule on the extracellular side. The resulting cascade of structural changes throughout the protein shows how motions are choreographed as bR transports protons uphill against a transmembrane concentration gradient.
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| 17. |
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| 20. |
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| 21. |
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| 22. |
- Andersson, V., et al.
(author)
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Large-Area Balloon-Borne Polarized Gamma Ray Observer (PoGO)
- 2005
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In: Proceedings of the 22nd Texas Symposium on Relativistic Astrophysics at Stanford. ; , s. 736-743
-
Conference paper (peer-reviewed)abstract
- We are developing a new balloon-borne instrument (PoGO), to measure polarization of soft gamma rays (30-200 keV) using asymmetry in azimuth angle distribution of Compton scattering. PoGO is designed to detect 10 % polarization in 100mCrab sources in a 6-8 hour observation and bring a new dimension to studies on gamma ray emission/transportation mechanism in pulsars, AGNs, black hole binaries, and neutron star surface. The concept is an adaptation to polarization measurements of well-type phoswich counter consisting of a fast plastic scintillator (the detection part), a slow plastic scintillator (the active collimator) and a BGO scintillator (the bottom anti-counter). PoGO consists of close-packed array of 217 hexagonal well-type phoswich counters and has a narrow field-of-view (~ 5 deg2) to reduce possible source confusion. A prototype instrument has been tested in the polarized soft gamma-ray beams at Advanced Photon Source (ANL) and at Photon Factory (KEK). On the results, the polarization dependence of EGS4 has been validated and that of Geant4 has been corrected.
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| 23. |
- Schiller, D, et al.
(author)
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The Human Affectome
- 2024
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In: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Journal article (peer-reviewed)
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| 24. |
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| 25. |
- Aprile, E., et al.
(author)
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Search for New Physics in Electronic Recoil Data from XENONnT
- 2022
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In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 129:16
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Journal article (peer-reviewed)abstract
- We report on a blinded analysis of low-energy electronic recoil data from the first science run of the XENONnT dark matter experiment. Novel subsystems and the increased 5.9 ton liquid xenon target reduced the background in the (1, 30) keV search region to (15.8±1.3) events/(ton×year×keV), the lowest ever achieved in a dark matter detector and ∼5 times lower than in XENON1T. With an exposure of 1.16 ton-years, we observe no excess above background and set stringent new limits on solar axions, an enhanced neutrino magnetic moment, and bosonic dark matter.
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| 26. |
- Knowles, N J, et al.
(author)
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Family - Picornaviridae
- 2012
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In: Virus Taxonomy. - San Diego - London : Elsevier. - 9780123846846 ; , s. 855-881
-
Book chapter (peer-reviewed)abstract
- This chapter focuses on Picornaviridae family whose member genuses includeEnterovirus, Cardiovirus, Aphthovirus, Hepatovirus, and Parechovirus. The virions of this family consist of a capsid with no envelope and surrounds a core of ssRNA. Hydrated native particles are 30 nm in diameter, but vary from 22 to 30 nm in electron micrographs due to drying and flattening during preparation. The virions contain one molecule of positive sense, ssRNA, and possess a single long ORF. The UTRs at both termini contain regions of secondary structure, which are essential to genome function. In addition to the major CPs, 1A, 1B, 1C and 1D, and 3B (VPg), small amounts of 1AB (VP0) are commonly seen in lieu of one or more copies of 1A and 1B. Protein 1A is small in hepatoviruses, and 1AB is uncleaved in avihepatoviruses, kobuviruses, parechoviruses, and a number of unclassified picornaviruses. Some picornaviruses carry a sphingosine-like molecule in a cavity located inside 1D, and protein 1A generally has a molecule of myristic acid covalently attached to the amino terminal glycine. The virion RNA is infectious and serves as both the genome and the viral mRNA. Infection is generally cytolytic, but persistent infections are common with some species and reported with others. Poliovirus infected cells undergo extensive vacuolation as membranes are reorganized into viral replication complexes.
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| 27. |
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| 28. |
- Aprile, E., et al.
(author)
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An approximate likelihood for nuclear recoil searches with XENON1T data
- 2022
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:11
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Journal article (peer-reviewed)abstract
- The XENON collaboration has published stringent limits on specific dark matter – nucleon recoil spectra from dark matter recoiling on the liquid xenon detector target. In this paper, we present an approximate likelihood for the XENON1T 1 t-year nuclear recoil search applicable to any nuclear recoil spectrum. Alongside this paper, we publish data and code to compute upper limits using the method we present. The approximate likelihood is constructed in bins of reconstructed energy, profiled along the signal expectation in each bin. This approach can be used to compute an approximate likelihood and therefore most statistical results for any nuclear recoil spectrum. Computing approximate results with this method is approximately three orders of magnitude faster than the likelihood used in the original publications of XENON1T, where limits were set for specific families of recoil spectra. Using this same method, we include toy Monte Carlo simulation-derived binwise likelihoods for the upcoming XENONnT experiment that can similarly be used to assess the sensitivity to arbitrary nuclear recoil signatures in its eventual 20 t-year exposure.
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| 29. |
- Aprile, E., et al.
(author)
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Application and modeling of an online distillation method to reduce krypton and argon in XENON1T
- 2022
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In: Progress of Theoretical and Experimental Physics. - : Oxford University Press (OUP). - 2050-3911. ; 2022:5
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Journal article (peer-reviewed)abstract
- A novel online distillation technique was developed for the XENON1T dark matter experiment to reduce intrinsic background components more volatile than xenon, such as krypton or argon, while the detector was operating. The method is based on a continuous purification of the gaseous volume of the detector system using the XENON1T cryogenic distillation column. A krypton-in-xenon concentration of (360 +/- 60) ppq was achieved. It is the lowest concentration measured in the fiducial volume of an operating dark matter detector to date. A model was developed and fitted to the data to describe the krypton evolution in the liquid and gas volumes of the detector system for several operation modes over the time span of 550 days, including the commissioning and science runs of XENON1T. The online distillation was also successfully applied to remove Ar-37 after its injection for a low-energy calibration in XENON1T. This makes the usage of Ar-37 as a regular calibration source possible in the future. The online distillation can be applied to next-generation liquid xenon time projection chamber experiments to remove krypton prior to, or during, any science run. The model developed here allows further optimization of the distillation strategy for future large-scale detectors.
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| 30. |
- Aprile, E., et al.
(author)
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Double-weak decays of 124Xe and 136Xe in the XENON1T and XENONnT experiments
- 2022
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In: Physical Review C. - 2469-9985 .- 2469-9993. ; 106:2
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Journal article (peer-reviewed)abstract
- We present results on the search for two-neutrino double-electron capture (2νECEC) of 124Xe and neutrinoless double-β decay (0νββ) of 136Xe in XENON1T. We consider captures from the K shell up to the N shell in the 2νECEC signal model and measure a total half-life of T2νECEC1/2=(1.1±0.2stat±0.1sys)×1022yr with a 0.87 kg yr isotope exposure. The statistical significance of the signal is 7.0σ. We use XENON1T data with 36.16 kg yr of 136Xe exposure to search for 0νββ. We find no evidence of a signal and set a lower limit on the half-life of T0νββ1/2>1.2×1024 yr at 90%CL. This is the best result from a dark matter detector without an enriched target to date. We also report projections on the sensitivity of XENONnT to 0νββ. Assuming a 275 kg yr 136Xe exposure, the expected sensitivity is T0νββ1/2>2.1×1025 yr at 90%CL, corresponding to an effective Majorana mass range of ⟨mββ⟩<(0.19–0.59)eV/c2.
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| 31. |
- Aprile, E., et al.
(author)
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Effective Field Theory and Inelastic Dark Matter Results from XENON1T
-
Other publication (other academic/artistic)abstract
- In this work we expand on the XENON1T nuclear recoil searches and study the individual signals of Dark Matter interactions from operators up to dimension-eight in a Chiral Effective Field Theory (ChEFT) as well as a model of inelastic Dark Matter using data from the two science runs of the detector totalling 1 tonne*year exposure. For these analyses we extended the region of interest from [4.9, 40.9]keVnr to [4.9, 54.4]keVnr to enhance our sensitivity for signals that peak at nonzero energies. We show that the data is consistent with a background only hypothesis, with small excesses in the models which peak between 20 and 50keVnr, obtaining a maximum local discovery significance of 1.7 for the VVs ChEFT model for a WIMP mass of 70GeV/c2, and 1.8 for an iDM particle of 50GeV/c2 with a mass splitting of 100keV/c2. For each model we report 90% confidence level upper limits. We also report limits on three benchmark models of WIMP interaction using ChEFT for which we investigate the effect of isospin breaking interactions, reporting up to 6 orders of magnitude weaker limits with respect to the isospin conserving case driven by cancellations in the expected rate.
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| 32. |
- Aprile, E., et al.
(author)
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Emission of single and few electrons in XENON1T and limits on light dark matter
- 2022
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 106:2
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Journal article (peer-reviewed)abstract
- Delayed single- and few-electron emissions plague dual-phase time projection chambers, limiting their potential to search for light-mass dark matter. This paper examines the origins of these events in the XENON1T experiment. Characterization of the intensity of delayed electron backgrounds shows that the resulting emissions are correlated, in time and position, with high-energy events and can effectively be vetoed. In this work we extend previous S2-only analyses down to a single electron. From this analysis, after removing the correlated backgrounds, we observe rates <30 events/(electron×kg×day) in the region of interest spanning 1 to 5 electrons. We derive 90% confidence upper limits for dark matter-electron scattering, first direct limits on the electric dipole, magnetic dipole, and anapole interactions, and bosonic dark matter models, where we exclude new parameter space for dark photons and solar dark photons.
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| 33. |
- Aprile, E., et al.
(author)
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Energy resolution and linearity of XENON1T in the MeV energy range
- 2020
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:8
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Journal article (peer-reviewed)abstract
- Xenon dual-phase time projection chambers designed to search for weakly interacting massive particles have so far shown a relative energy resolutionwhich degrades with energy above similar to 200 keV due to the saturation effects. This has limited their sensitivity in the search for rare events like the neutrinoless double-beta decay of Xe-136 at its Q value, Q(beta beta) similar or equal to 2.46 MeV. For the XENON1T dual-phase time projection chamber, we demonstrate that the relative energy resolution at 1 sigma/mu is as low as (0.80 +/- 0.02)% in its one-ton fiducial mass, and for single-site interactions at Q(beta beta). We also present a new signal correction method to rectify the saturation effects of the signal readout system, resulting in more accurate position reconstruction and indirectly improving the energy resolution. The very good result achieved in XENON1T opens up new windows for the xenon dual-phase dark matter detectors to simultaneously search for other rare events.
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| 34. |
- Aprile, E., et al.
(author)
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Excess electronic recoil events in XENON1T
- 2020
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In: Physical Review D. - 1550-7998 .- 1550-2368. ; 102:7
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Journal article (peer-reviewed)abstract
- We report results from searches for new physics with low-energy electronic recoil data recorded with the XENONIT detector. With an exposure of 0.65 tonne-years and an unprecedentedly low background rate of 76 +/- 2(stat) events/(tonne x year x keV) between 1 and 30 keV, the data enable one of the most sensitive searches for solar axions, an enhanced neutrino magnetic moment using solar neutrinos, and bosonic dark matter. An excess over known backgrounds is observed at low energies and most prominent between 2 and 3 keV. The solar axion model has a 3.4 sigma significance, and a three-dimensional 90% confidence surface is reported for axion couplings to electrons, photons, and nucleons. This surface is inscribed in the cuboid defined by g(ae) < 3.8 x 10(-12), g(ae)g(an)(eff) < 4.8 x 10(-18), and g(ae)g(a gamma) < 7.7 x 10(-22) GeV-1, and excludes either g(ae) = 0 or g(ae)g(a gamma) = g(ae)ge(an)(eff), = 0. The neutrino magnetic moment signal is similarly favored over background at 3.2 sigma, and a confidence interval of mu(nu) is an element of (1.4, 2.9) x 10(-11) mu(B) (90% C.L.) is reported. Both results are in strong tension with stellar constraints. The excess can also be explained by beta decays of tritium at 3.2 sigma significance with a corresponding tritium concentration in xenon of (6.2 +/- 2.0) x 10(-25) mol/mol. Such a trace amount can neither be confirmed nor excluded with current knowledge of its production and reduction mechanisms. The significances of the solar axion and neutrino magnetic moment hypotheses arc decreased to 2.0 sigma and 0.9 sigma, respectively, if an unconstrained tritium component is included in the fitting. With respect to bosonic dark matter, the excess favors a monoenergetic peak at (2.3 +/- 0.2) keV (68% C.L.) with a 3.0 sigma global (4.0 sigma local) significance over background. This analysis sets the most restrictive direct constraints to date on pseudoscalar and vector bosonic dark matter for most masses between 1 and 210 keV/c(2). We also consider the possibility that Ar-37 may be present in the detector, yielding a 2.82 keV peak from electron capture. Contrary to tritium, the Ar-37 concentration can be tightly constrained and is found to be negligible.
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| 35. |
- Aprile, E., et al.
(author)
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Material radiopurity control in the XENONnT experiment
- 2022
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 82:7
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Journal article (peer-reviewed)abstract
- The selection of low-radioactive construction materials is of the utmost importance for rare-event searches and thus critical to the XENONnT experiment. Results of an extensive radioassay program are reported, in which material samples have been screened with gamma-ray spectroscopy, mass spectrometry, and 222Rn emanation measurements. Furthermore, the cleanliness procedures applied to remove or mitigate surface contamination of detector materials are described. Screening results, used as inputs for a XENONnT Monte Carlo simulation, predict a reduction of materials background (∼∼17%) with respect to its predecessor XENON1T. Through radon emanation measurements, the expected 222Rn activity concentration in XENONnT is determined to be 4.2 (+0.5−0.7) μBq/kg, a factor three lower with respect to XENON1T. This radon concentration will be further suppressed by means of the novel radon distillation system.
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| 36. |
- Aprile, E., et al.
(author)
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Projected WIMP sensitivity of the XENONnT dark matter experiment
- 2020
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :11
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Journal article (peer-reviewed)abstract
- XENONnT is a dark matter direct detection experiment, utilizing 5.9 t of instrumented liquid xenon, located at the INFN Laboratori Nazionali del Gran Sasso. In this work, we predict the experimental background and project the sensitivity of XENONnT to the detection of weakly interacting massive particles (WIMPs). The expected average differential background rate in the energy region of interest, corresponding to (1, 13) keV and (4, 50) keV for electronic and nuclear recoils, amounts to 12.3 +/- 0.6 (keV t y)(-1) and (2.2 +/- 0.5) x 10(-3 )(keV t y)(-1), respectively, in a 4t fiducial mass. We compute unified confidence intervals using the profile construction method, in order to ensure proper coverage. With the exposure goal of 20 t y, the expected sensitivity to spin-independent WIMP-nucleon interactions reaches a cross-section of 1.4 x 10(-48) cm(2) for a 50 GeV/c(2) mass WIMP at 90% confidence level, more than one order of magnitude beyond the current best limit, set by XENON1T. In addition, we show that for a 50 GeV/c(2) WIMP with cross-sections above 2.6 x 10(-48) cm(2) (5.0 x 10(-48) cm(2)) the median XENONnT discovery significance exceeds 3 sigma (5 sigma). The expected sensitivity to the spin-dependent WIMP coupling to neutrons (protons) reaches 2.2 x 10(-43) cm(2) (6.0 x 10(-42) cm(2)).
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| 37. |
- Aprile, E., et al.
(author)
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Search for Coherent Elastic Scattering of Solar B-8 Neutrinos in the XENON1T Dark Matter Experiment
- 2021
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 126:9
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Journal article (peer-reviewed)abstract
- We report on a search for nuclear recoil signals from solar B-8 neutrinos elastically scattering off xenon nuclei in XENON1T data, lowering the energy threshold from 2.6 to 1.6 keV. We develop a variety of novel techniques to limit the resulting increase in backgrounds near the threshold. No significant B-8 neutrinolike excess is found in an exposure of 0.6 t x y. For the first time, we use the nondetection of solar neutrinos to constrain the light yield from 1-2 keV nuclear recoils in liquid xenon, as well as nonstandard neutrino-quark interactions. Finally, we improve upon world-leading constraints on dark matter-nucleus interactions for dark matter masses between 3 and 11 GeV c(-2) by as much as an order of magnitude.
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| 38. |
- Aprile, E., et al.
(author)
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Search for inelastic scattering of WIMP dark matter in XENON1T
- 2021
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 103:6
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Journal article (peer-reviewed)abstract
- We report the results of a search for the inelastic scattering of weakly interacting massive particles (WIMPs) in the XENON1T dark matter experiment. Scattering off Xe-129 is the most sensitive probe of inelastic WIMP interactions, with a signature of a 39.6 keV deexcitation photon detected simultaneously with the nuclear recoil. Using an exposure of 0.83 tonne-years, we find no evidence of inelastic WIMP scattering with a significance of more than 2 sigma. A profile-likelihood ratio analysis is used to set upper limits on the cross section of WIMP-nucleus interactions. We exclude new parameter space for WIMPs heavier than 100 GeV/c(2), with the strongest upper limit of 3.3 x 10(-39) cm(2) for 130 GeV/c(2) WIMPs at 90% confidence level.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Zell, R., et al.
(author)
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ICTV Virus Taxonomy Profile : Picornaviridae
- 2017
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In: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 98:10, s. 2421-2422
-
Journal article (peer-reviewed)abstract
- The family Picornaviridae comprises small non-enveloped viruses with RNA genomes of 6.7 to 10.1 kb, and contains > 30 genera and > 75 species. Most of the known picornaviruses infect mammals and birds, but some have also been detected in reptiles, amphibians and fish. Many picornaviruses are important human and veterinary pathogens and may cause diseases of the central nervous system, heart, liver, skin, gastrointestinal tract or upper respiratory tract. Most picornaviruses are transmitted by the faecal-oral or respiratory routes. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Picornaviridae, which is available at www. ictv. global/report/picornaviridae.
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| 46. |
- Austin, John, et al.
(author)
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Chemistry-climate model simulations of spring Antarctic ozone
- 2010
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In: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 115, s. D00M11-
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Journal article (peer-reviewed)abstract
- Coupled chemistry-climate model simulations covering the recent past and continuing throughout the 21st century have been completed with a range of different models. Common forcings are used for the halogen amounts and greenhouse gas concentrations, as expected under the Montreal Protocol (with amendments) and Intergovernmental Panel on Climate Change A1b Scenario. The simulations of the Antarctic ozone hole are compared using commonly used diagnostics: the minimum ozone, the maximum area of ozone below 220 DU, and the ozone mass deficit below 220 DU. Despite the fact that the processes responsible for ozone depletion are reasonably well understood, a wide range of results is obtained. Comparisons with observations indicate that one of the reasons for the model underprediction in ozone hole area is the tendency for models to underpredict, by up to 35%, the area of low temperatures responsible for polar stratospheric cloud formation. Models also typically have species gradients that are too weak at the edge of the polar vortex, suggesting that there is too much mixing of air across the vortex edge. Other models show a high bias in total column ozone which restricts the size of the ozone hole (defined by a 220 DU threshold). The results of those models which agree best with observations are examined in more detail. For several models the ozone hole does not disappear this century but a small ozone hole of up to three million square kilometers continues to occur in most springs even after 2070.
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| 47. |
- Denoncourt, R. N., et al.
(author)
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Burden of Illness for Patients with Hereditary Attr Amyloidosis with Polyneuropathy Begins with Symptom Onset and Increases with Disease Progression
- 2016
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In: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 19:7, s. A436-A436
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Journal article (peer-reviewed)abstract
- Objectives: Hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN), also known as familial amyloidotic polyneuropathy (FAP), is an inherited, progressive disease leading to death within 5-15 years. hATTR-PN is due to a mutation in the transthyretin (TTR) gene. Patisiran is an investigational, RNA interference (RNAi) therapeutic targeting TTR. This abstract aims to further characterize hATTR-PN burden of illness.Methods: The ongoing, patisiran Phase 3 APOLLO trial was utilized to collect patient-reported EQ-5D, Norfolk-DN, Rasch-built Overall Disability Scale (R-ODS), and healthcare resource utilization from hATTR-PN patients with symptomatic disease.Results: APOLLO included 225 patients; median age of 62 years (range: 24-82), median neurological impairment score (NIS) of 6-141.6 and representative of the global patient population (19 countries) with a broad range of mutations and disease severities. At baseline, 57 patients had a Polyneuropathy Disability (PND) Score I and 168 patients had a PND Score ≥ II. By FAP Stage, 104 were FAP Stage 1 and 121 were FAP Stage 2. 41 patients (PND Score ≥ II) reported ≥1 hospitalization of ≥3 nights in duration due to hATTR-PN in the 12 months prior to enrollment. Mean EQ-5D scores were 0.76 (PND Score I) and 0.59 (PND Score ≥ II). Patients reported perceived health status on the EQ-VAS with mean scores of 66.9 (PND Score I) and 51.3 (PND Score ≥ II). Mean Norfolk-QoL-DN scores were 35.5 (PND Score I) and 66.0 (PND Score ≥ II). 145 patients (131 PND Score ≥ II) reported they cannot work because of hATTR-PN. Mean R-ODS scores were 40.9 and 25.9 for PND Score I and PND Score ≥ II, respectively.Conclusions: These data, from the largest controlled study of patients with hATTR-PN to date, further demonstrate that patients experience considerable burden of illness early in the course of disease and this burden increases with disease progression.
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| 48. |
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| 49. |
- Hongo, T., et al.
(author)
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Inhibition of dorsal spinocerebellar tract cells by interneurones in upper and lower lumbar segments in the cat.
- 1983
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In: The Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 342, s. 145-159
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Journal article (peer-reviewed)abstract
- The topographical distribution of interneurones mediating disynaptic inhibition of dorsal spinocerebellar tract (d.s.c.t.) cells from group I muscle afferents in the cat was investigated using both physiological and morphological techniques. Lesions of either the dorsal funiculi or of the lateral and ventral funiculi were made between L4 and L5 segments in two groups of cats. I.p.s.p.s. evoked from group I afferents were seen after both these lesions, showing that the i.p.s.p.s were evoked by interneurones located more caudally as well as by interneurones in the same segments as Clarke's column. Distribution of the caudally located interneurones in the lower lumbar segments was investigated after marking these interneurones with horseradish peroxidase retrogradely transported from Clarke's column. The horseradish peroxidase was injected along L3‐L4 segments of Clarke's column in two cats with transected dorsal funiculi. The marked cells were found in L5, L6, L7 and S1 segments, with a highest density in L6 and L7. They were seen in laminae V, VI and VII. A search was made for interneurones which could be antidromically invaded following stimuli applied in Clarke's column and were monosynaptically excited by group I afferents. Such interneurones were found at locations corresponding to laminae V‐VI of Rexed. The latencies of antidromic and orthodromic responses were within ranges allowing them to mediate disynaptic inhibition of d.s.c.t. cells. © 1983 The Physiological Society
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| 50. |
- Hongo, T., et al.
(author)
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The same interneurones mediate inhibition of dorsal spinocerebellar tract cells and lumbar motoneurones in the cat.
- 1983
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In: The Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 342, s. 161-180
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Journal article (peer-reviewed)abstract
- The aim of the study was to investigate whether inhibition of dorsal spinocerebellar tract (d.s.c.t.) cells evoked from group I afferents is mediated by the same interneurones which mediate the non‐reciprocal inhibition of hind‐limb motoneurones. The origin of inhibition of d.s.c.t. cells from group I afferents was compared in intact preparations, after lesions of the dorsal funiculi (when it could only be mediated by lower lumbar interneurones) and after lesions of the lateral and ventral funiculi (when it would be expected to be evoked by upper lumbar interneurones). In all three preparations extensors were the most common source of inhibition, as in motoneurones. Lower lumbar interneurones inhibiting d.s.c.t. cells were found to be co‐excited by group I (Ia and/or Ib) and cutaneous and joint afferents, and by rubrospinal tract fibres, as are interneurones mediating inhibition of motoneurones. Co‐excitation by group I and rubrospinal fibres was also found for upper lumbar interneurones. I.p.s.p.s were evoked in hind‐limb motoneurones from within Clarke's column in cats with the dorsal funiculi cut between L4 and L5 segments; they were evoked at thresholds as low as 2 microA, i.e. by stimuli with very local actions. The latencies of these i.p.s.p.s were short enough to allow them to be evoked monosynaptically via axonal branches of the same interneurones which projected to Clarke's column. Correspondingly, i.p.s.p.s were evoked in d.s.c.t. cells from within motor nuclei in L7 segments; they were evoked at similarly low thresholds and with similar latencies. In confirmation of previous reports i.p.s.p.s of Ia origin evoked in d.s.c.t. cells were not found to be depressed by Renshaw cells, which excludes their mediation by interneurones responsible for Ia reciprocal inhibition. The study leads to the conclusion that the inhibition of d.s.c.t. cells from group I afferents is, at least in part, collateral to the non‐reciprocal inhibition of lumbar motoneurones. © 1983 The Physiological Society
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