| 51. |
- Georgiev, Boris, et al.
(author)
-
A Universal Power-law Prescription for Variability from Synthetic Images of Black Hole Accretion Flows
- 2022
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 930:2
-
Journal article (peer-reviewed)abstract
- We present a framework for characterizing the spatiotemporal power spectrum of the variability expected from the horizon-scale emission structure around supermassive black holes, and we apply this framework to a library of general relativistic magnetohydrodynamic (GRMHD) simulations and associated general relativistic ray-traced images relevant for Event Horizon Telescope (EHT) observations of Sgr A*. We find that the variability power spectrum is generically a red-noise process in both the temporal and spatial dimensions, with the peak in power occurring on the longest timescales and largest spatial scales. When both the time-averaged source structure and the spatially integrated light-curve variability are removed, the residual power spectrum exhibits a universal broken power-law behavior. On small spatial frequencies, the residual power spectrum rises as the square of the spatial frequency and is proportional to the variance in the centroid of emission. Beyond some peak in variability power, the residual power spectrum falls as that of the time-averaged source structure, which is similar across simulations; this behavior can be naturally explained if the variability arises from a multiplicative random field that has a steeper high-frequency power-law index than that of the time-averaged source structure. We briefly explore the ability of power spectral variability studies to constrain physical parameters relevant for the GRMHD simulations, which can be scaled to provide predictions for black holes in a range of systems in the optically thin regime. We present specific expectations for the behavior of the M87* and Sgr A* accretion flows as observed by the EHT.
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| 52. |
- Rheinbay, E, et al.
(author)
-
Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
-
Journal article (peer-reviewed)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 53. |
- Roelofs, F., et al.
(author)
-
Polarimetric Geometric Modeling for mm-VLBI Observations of Black Holes
- 2023
-
In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 957:2
-
Journal article (peer-reviewed)abstract
- The Event Horizon Telescope (EHT) is a millimeter very long baseline interferometry (VLBI) array that has imaged the apparent shadows of the supermassive black holes M87* and Sagittarius A*. Polarimetric data from these observations contain a wealth of information on the black hole and accretion flow properties. In this work, we develop polarimetric geometric modeling methods for mm-VLBI data, focusing on approaches that fit data products with differing degrees of invariance to broad classes of calibration errors. We establish a fitting procedure using a polarimetric “m-ring” model to approximate the image structure near a black hole. By fitting this model to synthetic EHT data from general relativistic magnetohydrodynamic models, we show that the linear and circular polarization structure can be successfully approximated with relatively few model parameters. We then fit this model to EHT observations of M87* taken in 2017. In total intensity and linear polarization, the m-ring fits are consistent with previous results from imaging methods. In circular polarization, the m-ring fits indicate the presence of event-horizon-scale circular polarization structure, with a persistent dipolar asymmetry and orientation across several days. The same structure was recovered independently of observing band, used data products, and model assumptions. Despite this broad agreement, imaging methods do not produce similarly consistent results. Our circular polarization results, which imposed additional assumptions on the source structure, should thus be interpreted with some caution. Polarimetric geometric modeling provides a useful and powerful method to constrain the properties of horizon-scale polarized emission, particularly for sparse arrays like the EHT.
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| 54. |
- Eatough, Ralph P., et al.
(author)
-
Verification of Radiative Transfer Schemes for the EHT
- 2020
-
In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 897:2
-
Journal article (peer-reviewed)abstract
- The Event Horizon Telescope (EHT) Collaboration has recently produced the first resolved images of the central supermassive black hole in the giant elliptical galaxy M87. Here we report on tests of the consistency and accuracy of the general relativistic radiative transfer codes used within the collaboration to model M87∗ and Sgr A∗. We compare and evaluate (1) deflection angles for equatorial null geodesics in a Kerr spacetime; (2) images calculated from a series of simple, parameterized matter distributions in the Kerr metric using simplified emissivities and absorptivities; (3) for a subset of codes, images calculated from general relativistic magnetohydrodynamics simulations using different realistic synchrotron emissivities and absorptivities; (4) observables for the 2017 configuration of EHT, including visibility amplitudes and closure phases. The error in total flux is of order 1% when the codes are run with production numerical parameters. The dominant source of discrepancies for small camera distances is the location and detailed setup of the software "camera"that each code uses to produce synthetic images. We find that when numerical parameters are suitably chosen and the camera is sufficiently far away the images converge and that for given transfer coefficients, numerical uncertainties are unlikely to limit parameter estimation for the current generation of EHT observations. The purpose of this paper is to describe a verification and comparison of EHT radiative transfer codes. It is not to verify EHT models more generally.
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| 55. |
- Janssen, Michael, et al.
(author)
-
Event Horizon Telescope observations of the jet launching and collimation in Centaurus A
- 2021
-
In: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 5:10, s. 1017-1028
-
Journal article (peer-reviewed)abstract
- Very-long-baseline interferometry (VLBI) observations of active galactic nuclei at millimetre wavelengths have the power to reveal the launching and initial collimation region of extragalactic radio jets, down to 10–100 gravitational radii (rg ≡ GM/c2) scales in nearby sources1. Centaurus A is the closest radio-loud source to Earth2. It bridges the gap in mass and accretion rate between the supermassive black holes (SMBHs) in Messier 87 and our Galactic Centre. A large southern declination of −43° has, however, prevented VLBI imaging of Centaurus A below a wavelength of 1 cm thus far. Here we show the millimetre VLBI image of the source, which we obtained with the Event Horizon Telescope at 228 GHz. Compared with previous observations3, we image the jet of Centaurus A at a tenfold higher frequency and sixteen times sharper resolution and thereby probe sub-lightday structures. We reveal a highly collimated, asymmetrically edge-brightened jet as well as the fainter counterjet. We find that the source structure of Centaurus A resembles the jet in Messier 87 on ~500 rg scales remarkably well. Furthermore, we identify the location of Centaurus A’s SMBH with respect to its resolved jet core at a wavelength of 1.3 mm and conclude that the source’s event horizon shadow4 should be visible at terahertz frequencies. This location further supports the universal scale invariance of black holes over a wide range of masses5,6.
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| 56. |
- Shah, S, et al.
(author)
-
Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- 2020
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
-
Journal article (peer-reviewed)abstract
- Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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| 57. |
- Yin, X., et al.
(author)
-
Vertical Sandwich Gate-All-Around Field-Effect Transistors with Self-Aligned High-k Metal Gates and Small Effective-Gate-Length Variation
- 2020
-
In: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers Inc.. - 0741-3106 .- 1558-0563. ; 41:1, s. 8-11
-
Journal article (peer-reviewed)abstract
- A new type of vertical nanowire (NW)/nanosheet (NS) field-effect transistors (FETs), termed vertical sandwich gate-all-around (GAA) FETs (VSAFETs), is presented in this work. Moreover, an integration flow that is compatible with processes used in the mainstream industry is proposed for the VSAFETs. Si/SiGe epitaxy, isotropic quasi-atomic-layer etching (qALE), and gate replacement were used to fabricate pVSAFETs for the first time. Vertical GAA FETs with self-aligned high-k metal gates and a small effective-gate-length variation were obtained. Isotropic qALE, including Si-selective etching of SiGe, was developed to control the diameter/thickness of the NW/NS channels. NWs with a diameter of 10 nm and NSs with a thickness of 20 nm were successfully fabricated, and good device characteristics were obtained. Finally, the device performance was investigated and is discussed in this work. © 2019 IEEE.
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| 58. |
- Bastard, P, et al.
(author)
-
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
- 2022
-
In: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 78:7490, s. eabp8966-
-
Journal article (peer-reviewed)abstract
- Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
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| 59. |
- Blondel, A., et al.
(author)
-
The SuperFGD Prototype charged particle beam tests
- 2020
-
In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:12
-
Journal article (peer-reviewed)abstract
- A novel scintillator detector, the SuperFGD, has been selected as the main neutrino target for an upgrade of the T2K experiment ND280 near detector. The detector design will allow nearly 47r coverage for neutrino interactions at the near detector and will provide lower energy thresholds, significantly reducing systematic errors for the experiment. The SuperFGD is made of optically-isolated scintillator cubes of size 10 x 10 x 10 mm(3), providing the required spatial and energy resolution to reduce systematic uncertainties for future T2K runs. The SuperFGD for T2K will have close to two million cubes in a 1920 x 560 x 1840 mm(3) volume. A prototype made of 24 x 8 x 48 cubes was tested at a charged particle beamline at the CERN PS facility. The SuperFGD Prototype was instrumented with readout electronics similar to the future implementation for T2K. Results on electronics and detector response are reported in this paper, along with a discussion of the 3D reconstruction capabilities of this type of detector. Several physics analyses with the prototype data are also discussed, including a study of stopping protons.
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| 60. |
- Broderick, Avery E., et al.
(author)
-
THEMIS: A Parameter Estimation Framework for the Event Horizon Telescope
- 2020
-
In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 897:2
-
Journal article (peer-reviewed)abstract
- The Event Horizon Telescope (EHT) provides the unprecedented ability to directly resolve the structure and dynamics of black hole emission regions on scales smaller than their horizons. This has the potential to critically probe the mechanisms by which black holes accrete and launch outflows, and the structure of supermassive black hole spacetimes. However, accessing this information is a formidable analysis challenge for two reasons. First, the EHT natively produces a variety of data types that encode information about the image structure in nontrivial ways; these are subject to a variety of systematic effects associated with very long baseline interferometry and are supplemented by a wide variety of auxiliary data on the primary EHT targets from decades of other observations. Second, models of the emission regions and their interaction with the black hole are complex, highly uncertain, and computationally expensive to construct. As a result, the scientific utilization of EHT observations requires a flexible, extensible, and powerful analysis framework. We present such a framework, Themis, which defines a set of interfaces between models, data, and sampling algorithms that facilitates future development. We describe the design and currently existing components of Themis, how Themis has been validated thus far, and present additional analyses made possible by Themis that illustrate its capabilities. Importantly, we demonstrate that Themis is able to reproduce prior EHT analyses, extend these, and do so in a computationally efficient manner that can efficiently exploit modern high-performance computing facilities. Themis has already been used extensively in the scientific analysis and interpretation of the first EHT observations of M87.
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| 61. |
- Franklin, RC, et al.
(author)
-
The burden of unintentional drowning: global, regional and national estimates of mortality from the Global Burden of Disease 2017 Study
- 2020
-
In: Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention. - : BMJ. - 1475-5785. ; 26:SUPP_1Supp 1, s. 83-95
-
Journal article (peer-reviewed)abstract
- Drowning is a leading cause of injury-related mortality globally. Unintentional drowning (International Classification of Diseases (ICD) 10 codes W65-74 and ICD9 E910) is one of the 30 mutually exclusive and collectively exhaustive causes of injury-related mortality in the Global Burden of Disease (GBD) study. This study’s objective is to describe unintentional drowning using GBD estimates from 1990 to 2017.MethodsUnintentional drowning from GBD 2017 was estimated for cause-specific mortality and years of life lost (YLLs), age, sex, country, region, Socio-demographic Index (SDI) quintile, and trends from 1990 to 2017. GBD 2017 used standard GBD methods for estimating mortality from drowning.ResultsGlobally, unintentional drowning mortality decreased by 44.5% between 1990 and 2017, from 531 956 (uncertainty interval (UI): 484 107 to 572 854) to 295 210 (284 493 to 306 187) deaths. Global age-standardised mortality rates decreased 57.4%, from 9.3 (8.5 to 10.0) in 1990 to 4.0 (3.8 to 4.1) per 100 000 per annum in 2017. Unintentional drowning-associated mortality was generally higher in children, males and in low-SDI to middle-SDI countries. China, India, Pakistan and Bangladesh accounted for 51.2% of all drowning deaths in 2017. Oceania was the region with the highest rate of age-standardised YLLs in 2017, with 45 434 (40 850 to 50 539) YLLs per 100 000 across both sexes.ConclusionsThere has been a decline in global drowning rates. This study shows that the decline was not consistent across countries. The results reinforce the need for continued and improved policy, prevention and research efforts, with a focus on low- and middle-income countries.
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| 62. |
- Abele, H., et al.
(author)
-
Particle physics at the European Spallation Source
- 2023
-
In: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 1023, s. 1-84
-
Research review (peer-reviewed)abstract
- Presently under construction in Lund, Sweden, the European Spallation Source (ESS) will be the world’s brightest neutron source. As such, it has the potential for a particle physics program with a unique reach and which is complementary to that available at other facilities. This paper describes proposed particle physics activities for the ESS. These encompass the exploitation of both the neutrons and neutrinos produced at the ESS for high precision (sensitivity) measurements (searches).
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| 63. |
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| 64. |
- Kazakov, Ye O., et al.
(author)
-
Physics and applications of three-ion ICRF scenarios for fusion research
- 2021
-
In: Physics of Plasmas. - : American Institute of Physics (AIP). - 1070-664X .- 1089-7674. ; 28:2
-
Research review (peer-reviewed)abstract
- This paper summarizes the physical principles behind the novel three-ion scenarios using radio frequency waves in the ion cyclotron range of frequencies (ICRF). We discuss how to transform mode conversion electron heating into a new flexible ICRF technique for ion cyclotron heating and fast-ion generation in multi-ion species plasmas. The theoretical section provides practical recipes for selecting the plasma composition to realize three-ion ICRF scenarios, including two equivalent possibilities for the choice of resonant absorbers that have been identified. The theoretical findings have been convincingly confirmed by the proof-of-principle experiments in mixed H–D plasmas on the Alcator C-Mod and JET tokamaks, using thermal 3He and fast D ions from neutral beam injection as resonant absorbers. Since 2018, significant progress has been made on the ASDEX Upgrade and JET tokamaks in H–4He and H–D plasmas, guided by the ITER needs. Furthermore, the scenario was also successfully applied in JET D–3He plasmas as a technique to generate fusion-born alpha particles and study effects of fast ions on plasma confinement under ITER-relevant plasma heating conditions. Tuned for the central deposition of ICRF power in a small region in the plasma core of large devices such as JET, three-ion ICRF scenarios are efficient in generating large populations of passing fast ions and modifying the q-profile. Recent experimental and modeling developments have expanded the use of three-ion scenarios from dedicated ICRF studies to a flexible tool with a broad range of different applications in fusion research.
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| 65. |
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| 66. |
- Carlevaro-Fita, J, et al.
(author)
-
Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
-
In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
-
Journal article (peer-reviewed)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 67. |
- Eggink, E, et al.
(author)
-
Prevention of dementia using mobile phone applications (PRODEMOS): protocol for an international randomised controlled trial
- 2021
-
In: BMJ open. - : BMJ. - 2044-6055. ; 11:6, s. e049762-
-
Journal article (peer-reviewed)abstract
- Profiles of high risk for future dementia are well understood and are likely to concern mostly those in low-income and middle-income countries and people at greater disadvantage in high-income countries. Approximately 30%–40% of dementia cases have been estimated to be attributed to modifiable risk factors, including hypertension, smoking and sedentary lifestyle. Tailored interventions targeting these risk factors can potentially prevent or delay the onset of dementia. Mobile health (mHealth) improves accessibility of such prevention strategies in hard-to-reach populations while at the same time tailoring such approaches. In the current study, we will investigate the effectiveness and implementation of a coach-supported mHealth intervention, targeting dementia risk factors, to reduce dementia risk.Methods and analysisThe prevention of dementia using mobile phone applications (PRODEMOS) randomised controlled trial will follow an effectiveness–implementation hybrid design, taking place in the UK and China. People are eligible if they are 55–75 years old, of low socioeconomic status (UK) or from the general population (China); have ≥2 dementia risk factors; and own a smartphone. 2400 participants will be randomised to either a coach-supported, interactive mHealth platform, facilitating self-management of dementia risk factors, or a static control platform. The intervention and follow-up period will be 18 months. The primary effectiveness outcome is change in the previously validated Cardiovascular Risk Factors, Ageing and Incidence of Dementia dementia risk score. The main secondary outcomes include improvement of individual risk factors and cost-effectiveness. Implementation outcomes include acceptability, adoption, feasibility and sustainability of the intervention.Ethics and disseminationThe PRODEMOS trial is sponsored in the UK by the University of Cambridge and is granted ethical approval by the London—Brighton and Sussex Research Ethics Committee (reference: 20/LO/01440). In China, the trial is approved by the medical ethics committees of Capital Medical University, Beijing Tiantan Hospital, Beijing Geriatric Hospital, Chinese People’s Liberation Army General Hospital, Taishan Medical University and Xuanwu Hospital. Results will be published in a peer-reviewed journal.Trial registration numberISRCTN15986016.
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| 68. |
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| 69. |
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| 70. |
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| 71. |
- Chen, H., et al.
(author)
-
Unprecedented non-hysteretic superelasticity of [001]-oriented NiCoFeGa single crystals
- 2020
-
In: Nature Materials. - : Nature Research. - 1476-1122 .- 1476-4660.
-
Journal article (peer-reviewed)abstract
- Superelasticity associated with the martensitic transformation has found a broad range of engineering applications1,2. However, the intrinsic hysteresis3 and temperature sensitivity4 of the first-order phase transformation significantly hinder the usage of smart metallic components in many critical areas. Here, we report a large superelasticity up to 15.2% strain in [001]-oriented NiCoFeGa single crystals, exhibiting non-hysteretic mechanical responses, a small temperature dependence and high-energy-storage capability and cyclic stability over a wide temperature and composition range. In situ synchrotron X-ray diffraction measurements show that the superelasticity is correlated with a stress-induced continuous variation of lattice parameter accompanied by structural fluctuation. Neutron diffraction and electron microscopy observations reveal an unprecedented microstructure consisting of atomic-level entanglement of ordered and disordered crystal structures, which can be manipulated to tune the superelasticity. The discovery of the large elasticity related to the entangled structure paves the way for exploiting elastic strain engineering and development of related functional materials.
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| 72. |
- Goddi, Ciriaco, et al.
(author)
-
Polarimetric Properties of Event Horizon Telescope Targets from ALMA
- 2021
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1
-
Journal article (peer-reviewed)abstract
- We present the results from a full polarization study carried out with the Atacama Large Millimeter/submillimeter Array (ALMA) during the first Very Long Baseline Interferometry (VLBI) campaign, which was conducted in 2017 April in the lambda 3 mm and lambda 1.3 mm bands, in concert with the Global mm-VLBI Array (GMVA) and the Event Horizon Telescope (EHT), respectively. We determine the polarization and Faraday properties of all VLBI targets, including Sgr A*, M87, and a dozen radio-loud active galactic nuclei (AGNs), in the two bands at several epochs in a time window of 10 days. We detect high linear polarization fractions (2%-15%) and large rotation measures (RM > 10(3.3)-10(5.5) rad m(-2)), confirming the trends of previous AGN studies at millimeter wavelengths. We find that blazars are more strongly polarized than other AGNs in the sample, while exhibiting (on average) order-of-magnitude lower RM values, consistent with the AGN viewing angle unification scheme. For Sgr A* we report a mean RM of (-4.2 0.3) x 10(5) rad m(-2) at 1.3 mm, consistent with measurements over the past decade and, for the first time, an RM of (-2.1 0.1) x 10(5) rad m(-2) at 3 mm, suggesting that about half of the Faraday rotation at 1.3 mm may occur between the 3 mm photosphere and the 1.3 mm source. We also report the first unambiguous measurement of RM toward the M87 nucleus at millimeter wavelengths, which undergoes significant changes in magnitude and sign reversals on a one year timescale, spanning the range from -1.2 to 0.3 x 10(5) rad m(-2) at 3 mm and -4.1 to 1.5 x 10(5) rad m(-2) at 1.3 mm. Given this time variability, we argue that, unlike the case of Sgr A*, the RM in M87 does not provide an accurate estimate of the mass accretion rate onto the black hole. We put forward a two-component model, comprised of a variable compact region and a static extended region, that can simultaneously explain the polarimetric properties observed by both the EHT (on horizon scales) and ALMA (which observes the combined emission from both components). These measurements provide critical constraints for the calibration, analysis, and interpretation of simultaneously obtained VLBI data with the EHT and GMVA.
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| 73. |
- Huang, C. Y., et al.
(author)
-
The Cardamine enshiensis genome reveals whole genome duplication and insight into selenium hyperaccumulation and tolerance
- 2021
-
In: Cell Discovery. - : Springer Science and Business Media LLC. - 2056-5968. ; 7:1
-
Journal article (peer-reviewed)abstract
- Cardamine enshiensis is a well-known selenium (Se)-hyperaccumulating plant. Se is an essential trace element associated with many health benefits. Despite its critical importance, genomic information of this species is limited. Here, we report a chromosome-level genome assembly of C. enshiensis, which consists of 443.4 Mb in 16 chromosomes with a scaffold N50 of 24 Mb. To elucidate the mechanism of Se tolerance and hyperaccumulation in C. enshiensis, we generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes. The results reveal that flavonoid, glutathione, and lignin biosynthetic pathways may play important roles in protecting C. enshiensis from stress induced by Se. Hi-C analysis of chromatin interaction patterns showed that the chromatin of C. enshiensis is partitioned into A and B compartments, and strong interactions between the two telomeres of each chromosome were correlated with histone modifications, epigenetic markers, DNA methylation, and RNA abundance. Se supplementation could affect the 3D chromatin architecture of C. enshiensis at the compartment level. Genes with compartment changes after Se treatment were involved in selenocompound metabolism, and genes in regions with topologically associated domain insulation participated in cellular responses to Se, Se binding, and flavonoid biosynthesis. This multiomics research provides molecular insight into the mechanism underlying Se tolerance and hyperaccumulation in C. enshiensis.
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| 74. |
- Jin, Y. B., et al.
(author)
-
Energy production and water savings from floating solar photovoltaics on global reservoirs
- 2023
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In: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 6, s. 865-874
-
Journal article (peer-reviewed)abstract
- Solutions that can support multiple sustainability goals related to clean energy, and resource use efficiency, will be crucial in the near future. The study estimates the potential of floating solar panels on reservoirs globally to generate renewable energy, reduce water losses and conserve land. Growing global energy use and the adoption of sustainability goals to limit carbon emissions from fossil fuel burning are increasing the demand for clean energy, including solar. Floating photovoltaic (FPV) systems on reservoirs are advantageous over traditional ground-mounted solar systems in terms of land conservation, efficiency improvement and water loss reduction. Here, based on multiple reservoir databases and a realistic climate-driven photovoltaic system simulation, we estimate the practical potential electricity generation for FPV systems with a 30% coverage on 114,555 global reservoirs is 9,434 +/- 29 TWh yr(-1). Considering the proximity of most reservoirs to population centres and the potential to develop dedicated local power systems, we find that 6,256 communities and/or cities in 124 countries, including 154 metropolises, could be self-sufficient with local FPV plants. Also beneficial to FPV worldwide is that the reduced annual evaporation could conserve 106 +/- 1 km(3) of water. Our analysis points to the huge potential of FPV systems on reservoirs, but additional studies are needed to assess the potential long-term consequences of large systems.
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| 75. |
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| 76. |
- Nocente, M., et al.
(author)
-
Generation and observation of fast deuterium ions and fusion-born alpha particles in JET D-He-3 plasmas with the 3-ion radio-frequency heating scenario
- 2020
-
In: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 60:12
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Journal article (peer-reviewed)abstract
- Dedicated experiments to generate energetic D ions and D-(3) He fusion-born alpha particles were performed at the Joint European Torus (JET) with the ITER-like wall (ILW). Using the 3-ion D-(D-NBI)-(3) He radio frequency (RF) heating scenario, deuterium ions from neutral beam injection (NBI) were accelerated in the core of mixed D-(3) He plasmas to higher energies with ion cyclotron resonance frequency (ICRF) waves, in turn leading to a core-localized source of alpha particles. The fast-ion distribution of RF-accelerated D-NBI ions was controlled by varying the ICRF and NBI power (P-ICRF approximate to 4-6 MW, P-NBI approximate to 3-20 MW), resulting in rather high D-D neutron (approximate to 1x10(16) s(-1)) and D-(3) He alpha rates (approximate to 2x10(16) s(-1)) at moderate input heating power. Theory and TRANSP analysis shows that large populations of co-passing MeV-range D ions were generated using the D-(D-NBI)-(3) He 3-ion ICRF scenario. This important result is corroborated by several experimental observations, in particular gamma-ray measurements. The developed experimental scenario at JET provides unique conditions for probing several aspects of future burning plasmas, such as the contribution from MeV range ions to global confinement, but without introducing tritium. Dominant fast-ion core electron heating with T-i approximate to T-e and a rich variety of fast-ion driven Alfven eigenmodes (AEs) were observed in these D-(3) He plasmas. The observed AE activities do not have a detrimental effect on the thermal confinement and, in some cases, may be driven by the fusion born alpha particles. A strong continuous increase in neutron rate was observed during long-period sawteeth (>1 s), accompanied by the observation of reversed shear AEs, which implies that a non monotonic q profile was systematically developed in these plasmas, sustained by the large fast-ion populations generated by the 3-ion ICRF scenario.
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| 77. |
- Qin, F., et al.
(author)
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Frailty and risk of adverse outcomes among community-dwelling older adults in China: a comparison of four different frailty scales
- 2023
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In: Frontiers In Public Health. - 2296-2565. ; 11
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Journal article (peer-reviewed)abstract
- BackgroundData on which frailty scales are most suitable for estimating risk in Chinese community populations remain limited. Herein we examined and compared four commonly used frailty scales in predicting adverse outcomes in a large population-based cohort of Chinese older adults. MethodsA total of 5402 subjects (mean age 66.3 +/- 9.6 years, 46.6% male) from the WHO Study on global AGEing and adult health (SAGE) in Shanghai were studied. Frailty was measured using a 35-item frailty index (FI), the frailty phenotype (FP), FRAIL, and Tilburg Frailty Indicator (TFI). Multivariate logistic regression models were performed to evaluate the independent association between frailty and outcomes including 4-year disability, hospitalization, and 4- and 7-year all-cause mortality. The accuracy for predicting these outcomes was determined by evaluating the area under the curve (AUC). The prevalence of frailty, sensitivity, and specificity were calculated using our proposed cut-off points and other different values. ResultsPrevalence of frailty ranged from 4.2% (FRAIL) to 16.9% (FI). FI, FRAIL and TFI were comparably associated with 4-year hospitalization, and 4- and 7-year mortality (adjusted odds ratios [aORs] 1.44-1.69, 1.91-2.22 and 1.85-2.88, respectively). FRAIL conferred the greatest risk of 4-year disability, followed by FI and TFI (aOR 5.55, 3.50, and 1.91, respectively). FP only independently predicted 4- and 7-year mortality (aOR 1.57 and 2.21, respectively). AUC comparisons showed that FI, followed by TFI and FRAIL, exhibited acceptable predictive accuracy for 4-year disability, 4- and 7-year mortality (AUCs 0.76-0.78, 0.71-0.71, 0.65-0.72, respectively), whereas all scales poorly predicted 4-year hospitalization (AUCs 0.53-0.57). For each scale, while specificity estimates (85.3-97.3%) were high and similar across all outcomes, their sensitivity estimates (6.3-56.8%) were not sufficient yet. Prevalence of frailty, sensitivity, and specificity varied considerably when different cut-off points were used. ConclusionFrailty defined using any of the four scales was associated with an increased risk of adverse outcomes. Although FI, FRAIL and TFI exhibited fair-to-moderate predictive accuracy and high specificity estimates, their sensitivity estimates were not sufficient yet. Overall, FI performed best in estimating risk, while TFI and FRAIL were additionally useful, the latter perhaps being more applicable to Chinese community-dwelling older adults.
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| 78. |
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| 79. |
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| 80. |
- Vitelli-Storelli, F, et al.
(author)
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Family History and Gastric Cancer Risk: A Pooled Investigation in the Stomach Cancer Pooling (STOP) Project Consortium
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:15
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Journal article (peer-reviewed)abstract
- Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.
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| 81. |
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| 82. |
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| 83. |
- Zhang, Xueli, et al.
(author)
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CBD2 : A functional biomarker database for colorectal cancer
- 2024
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In: iMeta. - : John Wiley & Sons. - 2770-5986 .- 2770-596X. ; 3:1
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Journal article (peer-reviewed)abstract
- The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.
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| 84. |
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| 85. |
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| 86. |
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| 87. |
- Kamio, S., et al.
(author)
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First experiments on plasma production using field-aligned ICRF fast wave antennas in the large helical device
- 2021
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In: Nuclear Fusion. - : Institute of Physics (IOP). - 0029-5515 .- 1741-4326. ; 61:11
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Journal article (peer-reviewed)abstract
- The results of the first experimental series to produce a plasma using the ion cyclotron range of frequency (ICRF) in the large helical device (LHD) within the minority scenario developed at Uragan-2M (U-2M) are presented. The motivation of this study is to provide plasma creation in conditions when an electron cyclotron resonance heating start-up is not possible, and in this way widen the operational frame of helical machines. The major constraint of the experiments is the low RF power to reduce the possibility of arcing. No dangerous voltage increase at the radio-frequency (RF) system elements and no arcing has been detected. As a result, a low plasma density is obtained and the antenna-plasma coupling is not optimal. However, such plasmas are sufficient to be used as targets for further neutral beam injection (NBI) heating. This will open possibilities to explore new regimes of operation at LHD and Wendelstein 7-X (W7-X) stellarator. The successful RF plasma production in LHD in this experimental series stimulates the planning of further studies of ICRF plasma production aimed at increasing plasma density and temperature within the ICRF minority scenario as well as investigating the plasma prolongation by NBI heating.
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| 88. |
- Kovtun, Yu.V., et al.
(author)
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ICRF plasma production in gas mixtures in the Uragan-2M stellarator
- 2023
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In: Fusion engineering and design. - : Elsevier BV. - 0920-3796 .- 1873-7196. ; 194
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Journal article (peer-reviewed)abstract
- This paper summarizes previous results and presents new studies on the ICRF plasma creation both in pure gases and gas mixtures. In all the experiments, the two-strap antenna was operated in monopole phasing with applied RF power of ∼100 kW. The research for plasma creation was carried out at RF frequencies near the fundamental hydrogen cyclotron harmonic.
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| 89. |
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| 90. |
- Li, Yanping, et al.
(author)
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Brown Algae Carbohydrates : Structures, Pharmaceutical Properties, and Research Challenges
- 2021
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In: Marine Drugs. - : MDPI AG. - 1660-3397. ; 19
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Research review (peer-reviewed)abstract
- Brown algae (Phaeophyceae) have been consumed by humans for hundreds of years. Current studies have shown that brown algae are rich sources of bioactive compounds with excellent nutritional value, and are considered functional foods with health benefits. Polysaccharides are the main constituents of brown algae; their diverse structures allow many unique physical and chemical properties that help to moderate a wide range of biological activities, including immunomodulation, antibacterial, antioxidant, prebiotic, antihypertensive, antidiabetic, antitumor, and anticoagulant activities. In this review, we focus on the major polysaccharide components in brown algae: the alginate, laminarin, and fucoidan. We explore how their structure leads to their health benefits, and their application prospects in functional foods and pharmaceuticals. Finally, we summarize the latest developments in applied research on brown algae polysaccharides.
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| 91. |
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| 92. |
- Moiseyenko, Volodymyr, et al.
(author)
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First experiments on ICRF discharge generation by a W7-X-like antenna in the Uragan-2M stellarator
- 2020
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In: Journal of Plasma Physics. - : Cambridge University Press (CUP). - 0022-3778 .- 1469-7807. ; 86:5
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Journal article (peer-reviewed)abstract
- In support of the ICRF experiments planned on the Wendelstein 7-X (W7-X) stellarator, i.e. fast ion generation, wall conditioning, target plasma production and heating, a first experimental study on plasma production has been made in the Uragan-2M (U-2M) stellarator using W7-X-like two-strap antenna. In all the experiments, antenna monopole phasing was used. The W7-X-like antenna operation with launched radiofrequency power of ~100 kW have been performed in helium (p = (4–14) × 10−2 Pa) with the vacuum vessel walls pre-loaded with hydrogen. Production of plasma with a density higher than 1012 cm−3 was observed near the first harmonic of the hydrogen cyclotron frequency. Operation at first hydrogen harmonic is feasible in W7-X future ICRF experiments.
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| 93. |
- Moiseyenko, Volodymyr, et al.
(author)
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Plasma Production in ICRF in the Uragan-2M Stellarator in Hydrogen–Helium Gas Mixture
- 2022
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In: Journal of fusion energy. - : Springer. - 0164-0313 .- 1572-9591. ; 41:2
-
Journal article (peer-reviewed)abstract
- Plasma production experiments in helium at Uragan-2M have been performed to investigate the role of the hydrogen minority in helium. The experiments presented here were carried on with a controlled minority hydrogen concentration. The hydrogen minority allowed one to increase plasma density more than three times as compared with pure helium. The obtained plasma density is highest for whole time of Uragan-2M operation. The developed scenario allowed to decrease the neutral gas pressure at which the plasma production is possible. This is a requirement for achieving regimes of plasma production with full ionization. Although the initial gas mixture 14%H2 + 86%He can be treated as optimum, there is no sensitive dependence on hydrogen minority concentration, which makes the scenario robust. This study, together with initial LHD experiments, confirm the prospects of target plasma production by ICRF waves for stellarator type machines.
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| 94. |
- Sun, Q, et al.
(author)
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Lenvatinib for effectively treating antiangiogenic drug-resistant nasopharyngeal carcinoma
- 2022
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 13:8, s. 724-
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Journal article (peer-reviewed)abstract
- Nasopharyngeal carcinoma (NPC) clinical trials show that antiangiogenic drugs (AADs) fail to achieve the expected efficacy, and combining AAD with chemoradiotherapy does not show superiority over chemoradiotherapy alone. Accumulating evidence suggests the intrinsic AAD resistance in NPC patients with poorly understood molecular mechanisms. Here, we describe NPC-specific FGF-2 expression-triggered, VEGF-independent angiogenesis as a mechanism of AAD resistance. Angiogenic factors screening between AAD-sensitive cancer type and AAD-resistant NPC showed high FGF-2 expression in NPC in both xenograft models and clinical samples. Mechanistically, the FGF-2-FGFR1-MYC axis drove endothelial cell survival and proliferation as an alternative to VEGF-VEGFR2-MYC signaling. Genetic knockdown of FGF-2 in NPC tumor cells reduced tumor angiogenesis, enhanced AAD sensitivity, and reduced pulmonary metastasis. Moreover, lenvatinib, an FDA recently approved multi-kinase inhibitor targeting both VEGFR2 and FGFR1, effectively inhibits the tumor vasculature, and exhibited robust anti-tumor effects in NPC-bearing nude mice and humanized mice compared with an agent equivalent to bevacizumab. These findings provide mechanistic insights on FGF-2 signaling in the modulation of VEGF pathway activation in the NPC microenvironment and propose an effective NPC-targeted therapy by using a clinically available drug.
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| 95. |
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| 96. |
- Zheng, Yuting, et al.
(author)
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Recent Advances in Bioutilization of Marine Macroalgae Carbohydrates : Degradation, Metabolism, and Fermentation
- 2022
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In: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 70:5, s. 1438-1453
-
Journal article (peer-reviewed)abstract
- Marine macroalgae are considered renewable natural resources due to their high carbohydrate content, which gives better utilization value in biorefineries and higher value conversion than first- and second-generation biomass. However, due to the diverse composition, complex structure, and rare metabolic pathways of macroalgae polysaccharides, their bioavailability needs to be improved. In recent years, enzymes and pathways related to the degradation and metabolism of macroalgae polysaccharides have been continuously developed, and new microbial fermentation platforms have emerged. Aiming at the bioutilization and transformation of macroalgae resources, this review describes the latest research results from the direction of green degradation, biorefining, and metabolic pathway design, including summarizing the the latest biorefining technology and the fermentation platform design of agarose, alginate, and other polysaccharides. This information will provide new research directions and solutions for the biotransformation and utilization of marine macroalgae.
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| 97. |
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| 98. |
- Fustin, JM, et al.
(author)
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Methylation deficiency disrupts biological rhythms from bacteria to humans
- 2020
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In: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 211-
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Journal article (peer-reviewed)abstract
- The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies.
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| 99. |
- Hadid, L. Z., et al.
(author)
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Ambipolar electrostatic field in negatively charged dusty plasma
- 2022
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In: Journal of Plasma Physics. - : Cambridge University Press. - 0022-3778 .- 1469-7807. ; 88:2
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Journal article (peer-reviewed)abstract
- We study the effect of negatively charged dust on the magnetic-field-aligned polarisation electrostatic field (E-parallel to) using Cassini's RPWS/LP in situ measurements during the `ring-grazing' orbits. We derive a general expression for E-parallel to and estimate for the first time in situ parallel to E-parallel to parallel to (approximately 10(-5) V m(-1)) near the Janus and Epimetheus rings. We further demonstrate that the presence of the negatively charged dust close to the ring plane (vertical bar Z vertical bar less than or similar to 0.11 R-s) amplifies parallel to E-parallel to parallel to by at least one order of magnitude and reverses its direction due to the effect of the charged dust gravitational and inertial forces. Such reversal confines the electrons at the magnetic equator within the dusty region, around 0.047 R-s above the ring plane. Furthermore, we discuss the role of the collision terms, in particular the ion-dust drag force, in amplifying E-parallel to. These results imply that the charged dust, as small as nanometres in size, can have a significant influence on the plasma transport, in particular ambipolar diffusion along the magnetic field lines, and so their presence must be taken into account when studying such dynamical processes.
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| 100. |
- Hafdi, M, et al.
(author)
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Design and Development of a Mobile Health (mHealth) Platform for Dementia Prevention in the Prevention of Dementia by Mobile Phone Applications (PRODEMOS) Project
- 2021
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In: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 12, s. 733878-
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Journal article (peer-reviewed)abstract
- Background: Mobile health (mHealth) has the potential to bring preventive healthcare within reach of populations with limited access to preventive services, by delivering personalized support at low cost. Although numerous mHealth interventions are available, very few have been developed following an evidence-based rationale or have been tested for efficacy. This article describes the systematic development of a coach-supported mHealth application to improve healthy lifestyles for the prevention of dementia and cardiovascular disease in the United Kingdom (UK) and China.Methods: Development of the Prevention of Dementia by Mobile Phone applications (PRODEMOS) platform built upon the experiences with the Healthy Aging Through Internet Counseling in the Elderly (HATICE) eHealth platform. In the conceptualization phase, experiences from the HATICE trial and needs and wishes of the PRODEMOS target population were assessed through semi-structured interviews and focus group sessions. Initial technical development of the platform was based on these findings and took place in consecutive sprint sessions. Finally, during the evaluation and adaptation phase, functionality and usability of the platform were evaluated during pilot studies in UK and China.Results: The PRODEMOS mHealth platform facilitates self-management of a healthy lifestyle by goal setting, progress monitoring, and educational materials on healthy lifestyles. Participants receive remote coaching through a chat functionality. Based on lessons learned from the HATICE study and end-users, we made the intervention easy-to-use and included features to personalize the intervention. Following the pilot studies, in which in total 77 people used the mobile application for 6 weeks, the application was made more intuitive, and we improved its functionalities.Conclusion: Early involvement of end-users in the development process and during evaluation phases improved acceptability of the mHealth intervention. The actual use and usability of the PRODEMOS intervention will be assessed during the ongoing PRODEMOS randomized controlled trial, taking a dual focus on effectiveness and implementation outcomes.
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