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- Blach, S., et al.
(author)
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Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
- 2022
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In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
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Journal article (peer-reviewed)abstract
- Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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- 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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- Wang, H., et al.
(author)
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Intruder configurations in 29 Ne at the transition into the island of inversion: Detailed structure study of 28 Ne
- 2023
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In: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 843
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Journal article (peer-reviewed)abstract
- Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.
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- Kondo, Y., et al.
(author)
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First observation of 28 O
- 2023
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In: Nature. - 0028-0836 .- 1476-4687. ; 620:7976, s. 965-970
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Journal article (peer-reviewed)abstract
- Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10−21s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called ‘doubly magic’ nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.
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- Holl, Matthias, 1986, et al.
(author)
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Border of the island of inversion: Unbound states in Ne-29
- 2022
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In: Physical Review C. - 2469-9985 .- 2469-9993. ; 105:3
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Journal article (peer-reviewed)abstract
- The nucleus Ne-29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f(7/2) state, which would place Ne-29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne-29 is reported. The states were populated in Ne-30(p, pn) and Na-30(p, 2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing assignments for the observed states. The lowest lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant l = 3 component, giving first evidence for f(7/2) single particle strength in Ne-29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the SDPF-U-MIX interaction.
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- Mandt, K. E., et al.
(author)
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RPC observation of the development and evolution of plasma interaction boundaries at 67P/Churyumov-Gerasimenko
- 2016
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 462, s. S9-S22
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Journal article (peer-reviewed)abstract
- One of the primary objectives of the Rosetta Plasma Consortium, a suite of five plasma instruments on-board the Rosetta spacecraft, is to observe the formation and evolution of plasma interaction regions at the comet 67P/Churyumov-Gerasimenko (67P/CG). Observations made between 2015 April and 2016 February show that solar wind-cometary plasma interaction boundaries and regions formed around 2015 mid-April and lasted through early 2016 January. At least two regions were observed, separated by an ion-neutral collisionopause boundary. The inner region was located on the nucleus side of the boundary and was characterized by low-energy water-group ions, reduced magnetic field pileup and enhanced electron densities. The outer region was located outside of the boundary and was characterized by reduced electron densities, water-group ions that are accelerated to energies above 100 eV and enhanced magnetic field pileup compared to the inner region. The boundary discussed here is outside of the diamagnetic cavity and shows characteristics similar to observations made on-board the Giotto spacecraft in the ion pileup region at 1P/Halley. We find that the boundary is likely to be related to ion-neutral collisions and that its location is influenced by variability in the neutral density and the solar wind dynamic pressure.
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- Revel, A., et al.
(author)
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Extending the Southern Shore of the Island of Inversion to F-28
- 2020
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In: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:15
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Journal article (peer-reviewed)abstract
- Detailed spectroscopy of the neutron-unbound nucleus F-28 has been performed for the first time following proton/neutron removal from Ne-29/F-29 beams at energies around 230 MeV=nucleon. The invariant-mass spectra were reconstructed for both the F-27((*)) + n and F-26((*)) + 2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the F-28 ground state, with S-n(F-28) = -199(6) keV, while analysis of the 2n decay channel allowed a considerably improved S-n(F-27) = 1620(60) keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of F-28. Importantly, in the case of the ground state, the reconstructed F-27 + n momentum distribution following neutron removal from F-29 indicates that it arises mainly from the 1p(3/2) neutron intruder configuration. This demonstrates that the island of inversion around N = 20 includes F-28, and most probably F-29, and suggests that O-28 is not doubly magic.
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- Akula, Murali K, et al.
(author)
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Control of the innate immune response by the mevalonate pathway
- 2016
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In: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:8, s. 922-9
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Journal article (peer-reviewed)abstract
- Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110 delta. Macrophages that were deficient in GGTase I or p110 delta exhibited constitutive release of interleukin 1 beta that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.
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24. |
- Storck, Sonja, et al.
(author)
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Lifetime measurement of the 26 0 g.s. At SAMURAI
- 2020
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643:1
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Conference paper (peer-reviewed)abstract
- The ground state of the neutron unbound nucleus O is speculated to have a lifetime in the pico-second regime. In order to determine the decay lifetime of the O ground state with high sensitivity and precision, a new method has been applied. The experiment was performed in December 2016 at the Superconducting Analyzer for MUlti-particle from Radio Isotope Beams (SAMURAI) at the Radioactive Isotope Beam Factory (RIBF) at RIKEN. A F beam was produced in the fragment separator BigRIPS and impinged on a W/Pt target stack where O was produced. According to the lifetime, the decay of O happens either in or outside the target. Thus, the velocity difference between the decay neutrons and the fragment O delivers a characteristic spectrum from which the lifetime can be extracted.
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- Broiles, Thomas W., et al.
(author)
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Statistical analysis of suprathermal electron drivers at 67P/Churyumov-Gerasimenko
- 2016
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In: Monthly notices of the Royal Astronomical Society. - : OXFORD UNIV PRESS. - 0035-8711 .- 1365-2966. ; 462, s. S312-S322
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Journal article (peer-reviewed)abstract
- We use observations from the Ion and Electron Sensor (IES) on board the Rosetta spacecraft to study the relationship between the cometary suprathermal electrons and the drivers that affect their density and temperature. We fit the IES electron observations with the summation of two kappa distributions, which we characterize as a dense and warm population (similar to 10 cm(-3) and similar to 16 eV) and a rarefied and hot population (similar to 0.01 cm(-3) and similar to 43 eV). The parameters of our fitting technique determine the populations' density, temperature, and invariant kappa index. We focus our analysis on the warm population to determine its origin by comparing the density and temperature with the neutral density and magnetic field strength. We find that the warm electron population is actually two separate sub-populations: electron distributions with temperatures above 8.6 eV and electron distributions with temperatures below 8.6 eV. The two sub-populations have different relationships between their density and temperature. Moreover, the two sub-populations are affected by different drivers. The hotter sub-population temperature is strongly correlated with neutral density, while the cooler sub-population is unaffected by neutral density and is only weakly correlated with magnetic field strength. We suggest that the population with temperatures above 8.6 eV is being heated by lower hybrid waves driven by counterstreaming solar wind protons and newly formed, cometary ions created in localized, dense neutral streams. To the best of our knowledge, this represents the first observations of cometary electrons heated through wave-particle interactions.
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