| 1. |
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| 2. |
- 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
-
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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| 3. |
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- 2019
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Journal article (peer-reviewed)
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| 4. |
- Algaba, Juan-Carlos, et al.
(author)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
-
Research review (peer-reviewed)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 5. |
- Beal, Jacob, et al.
(author)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 6. |
- Kim, Jae-Young, et al.
(author)
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Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
-
Journal article (peer-reviewed)abstract
- 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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| 7. |
- Wan, Lu Ming, et al.
(author)
-
Heparanase Facilitates PMA-Induced Megakaryocytic Differentiation in K562 Cells via Interleukin 6/STAT3 Pathway
- 2020
-
In: Thrombosis and Haemostasis. - : GEORG THIEME VERLAG KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 647-657
-
Journal article (peer-reviewed)abstract
- Heparanase (HPSE) is an endo-beta-D-glucuronidase that cleaves heparan sulfate and hence participates in remodeling of the extracellular matrix, leading to release of cytokines that are immobilized by binding to heparan sulfate proteoglycans (HSPGs), and consequently activating signaling pathways. This function of HPSE is correlated to its expression level that is normally very low in majority of the tissues. Exceptionally, human platelets express high level of HPSE, suggesting a unique physiological role in this cell. Using K562 cell line, we found a progressive increase of HPSE during the megakaryocytic differentiation. Analysis of a series of megakaryocytic differentiation-related heparin-binding proteins (HBPs) in the cell culture medium revealed an exclusive positive correlation between the level of interleukin 6 (IL-6) and HPSE expression. IL-6 modulated megakaryocytic differentiation through activation of STAT3. Further, we demonstrated that overexpression of HPSE potentiates megakaryocytic differentiation, whereas elimination of HPSE led to a delayed differentiation. This function of HPSE is associated with its activity, as overexpression of inactive HPSE had no effect on IL-6 production and megakaryocytic differentiation. The role of HPSE is further supported by the observation in an umbilical cord blood CD34+ cells megakaryocytic differentiation model. Our data propose a novel role for HPSE in platelets production by a HPSE/IL-6/STAT3 positive feedback loop that specifically regulates megakaryocytes maturation.
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| 8. |
- Zhang, Yue-Jiao, et al.
(author)
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Probing the Electronic Structure of Heterogeneous Metal Interfaces by Transition Metal Shelled Gold Nanoparticle-Enhanced Raman Spectroscopy
- 2016
-
In: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 120:37, s. 20684-20691
-
Journal article (peer-reviewed)abstract
- In heterogeneous catalysis, characterization of heterogeneous metal interfaces of bimetallic catalysts is a crucial step to elucidate the catalytic performance and is a key to develop advanced catalysts. However, analytical techniques such as X-ray photoelectron spectroscopy can only work in vacuum conditions and are difficult to use for in situ analysis. Here, we present efficient and convenient core-shell nano particle-enhanced Raman spectroscopy to explore the in situ electronic structures of heterogeneous interfaces (Au@Pd and Au@Pt core-shell NPs) by varying the shell thickness. The experimental observations reported here clearly show that Pd donates electrons to Au, while Pt accepts electrons from Au at the heterogeneous interfaces. This conclusion gains further support from ex situ X-ray photoelectron spectroscopy results. The Au core greatly affects the electronic structures of both the Pd and Pt shells as well as catalytic behaviors. Finally, the as prepared core-shell nanoparticles were used to demonstrate their improved catalytic properties in real electrocatalytic systems such as methanol oxidation and oxygen reduction reactions.
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| 9. |
- Akiyama, Kazunori, et al.
(author)
-
First M87 Event Horizon Telescope Results. IX. Detection of Near-horizon Circular Polarization
- 2023
-
In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 957:2
-
Journal article (peer-reviewed)abstract
- Event Horizon Telescope (EHT) observations have revealed a bright ring of emission around the supermassive black hole at the center of the M87 galaxy. EHT images in linear polarization have further identified a coherent spiral pattern around the black hole, produced from ordered magnetic fields threading the emitting plasma. Here we present the first analysis of circular polarization using EHT data, acquired in 2017, which can potentially provide additional insights into the magnetic fields and plasma composition near the black hole. Interferometric closure quantities provide convincing evidence for the presence of circularly polarized emission on event-horizon scales. We produce images of the circular polarization using both traditional and newly developed methods. All methods find a moderate level of resolved circular polarization across the image (〈|v|〉 < 3.7%), consistent with the low image-integrated circular polarization fraction measured by the Atacama Large Millimeter/submillimeter Array (|vint| < 1%). Despite this broad agreement, the methods show substantial variation in the morphology of the circularly polarized emission, indicating that our conclusions are strongly dependent on the imaging assumptions because of the limited baseline coverage, uncertain telescope gain calibration, and weakly polarized signal. We include this upper limit in an updated comparison to general relativistic magnetohydrodynamic simulation models. This analysis reinforces the previously reported preference for magnetically arrested accretion flow models. We find that most simulations naturally produce a low level of circular polarization consistent with our upper limit and that Faraday conversion is likely the dominant production mechanism for circular polarization at 230 GHz in M87*
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| 10. |
- Akiyama, Kazunori, et al.
(author)
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First Sagittarius A∗ Event Horizon Telescope Results. VII. Polarization of the Ring
- 2024
-
In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 964:2
-
Journal article (peer-reviewed)abstract
- The Event Horizon Telescope observed the horizon-scale synchrotron emission region around the Galactic center supermassive black hole, Sagittarius A∗ (Sgr A∗), in 2017. These observations revealed a bright, thick ring morphology with a diameter of 51.8 ± 2.3 μas and modest azimuthal brightness asymmetry, consistent with the expected appearance of a black hole with mass M≈ 4 × 106 M⊙. From these observations, we present the first resolved linear and circular polarimetric images of Sgr A∗. The linear polarization images demonstrate that the emission ring is highly polarized, exhibiting a prominent spiral electric vector polarization angle pattern with a peak fractional polarization of ∼40% in the western portion of the ring. The circular polarization images feature a modestly (∼5%°-10%) polarized dipole structure along the emission ring, with negative circular polarization in the western region and positive circular polarization in the eastern region, although our methods exhibit stronger disagreement than for linear polarization. We analyze the data using multiple independent imaging and modeling methods, each of which is validated using a standardized suite of synthetic data sets. While the detailed spatial distribution of the linear polarization along the ring remains uncertain owing to the intrinsic variability of the source, the spiraling polarization structure is robust to methodological choices. The degree and orientation of the linear polarization provide stringent constraints for the black hole and its surrounding magnetic fields, which we discuss in an accompanying publication.
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| 11. |
- Akiyama, Kazunori, et al.
(author)
-
First Sagittarius A∗ Event Horizon Telescope Results. VIII. Physical Interpretation of the Polarized Ring
- 2024
-
In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 964:2
-
Journal article (peer-reviewed)abstract
- In a companion paper, we present the first spatially resolved polarized image of Sagittarius A∗ on event horizon scales, captured using the Event Horizon Telescope, a global very long baseline interferometric array operating at a wavelength of 1.3 mm. Here we interpret this image using both simple analytic models and numerical general relativistic magnetohydrodynamic (GRMHD) simulations. The large spatially resolved linear polarization fraction (24%-28%, peaking at ∼40%) is the most stringent constraint on parameter space, disfavoring models that are too Faraday depolarized. Similar to our studies of M87∗, polarimetric constraints reinforce a preference for GRMHD models with dynamically important magnetic fields. Although the spiral morphology of the polarization pattern is known to constrain the spin and inclination angle, the time-variable rotation measure (RM) of Sgr A∗ (equivalent to ≈ 46° ± 12° rotation at 228 GHz) limits its present utility as a constraint. If we attribute the RM to internal Faraday rotation, then the motion of accreting material is inferred to be counterclockwise, contrary to inferences based on historical polarized flares, and no model satisfies all polarimetric and total intensity constraints. On the other hand, if we attribute the mean RM to an external Faraday screen, then the motion of accreting material is inferred to be clockwise, and one model passes all applied total intensity and polarimetric constraints: a model with strong magnetic fields, a spin parameter of 0.94, and an inclination of 150°. We discuss how future 345 GHz and dynamical imaging will mitigate our present uncertainties and provide additional constraints on the black hole and its accretion flow.
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| 12. |
- Akiyama, Kazunori, et al.
(author)
-
The persistent shadow of the supermassive black hole of M 87: I. Observations, calibration, imaging, and analysis*
- 2024
-
In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 681
-
Journal article (peer-reviewed)abstract
- In April 2019, the Event Horizon Telescope (EHT) Collaboration reported the first-ever event-horizon-scale images of a black hole, resolving the central compact radio source in the giant elliptical galaxy M 87. These images reveal a ring with a southerly brightness distribution and a diameter of ∼42 μas, consistent with the predicted size and shape of a shadow produced by the gravitationally lensed emission around a supermassive black hole. These results were obtained as part of the April 2017 EHT observation campaign, using a global very long baseline interferometric radio array operating at a wavelength of 1.3 mm. Here, we present results based on the second EHT observing campaign, taking place in April 2018 with an improved array, wider frequency coverage, and increased bandwidth. In particular, the additional baselines provided by the Greenland telescope improved the coverage of the array. Multiyear EHT observations provide independent snapshots of the horizon-scale emission, allowing us to confirm the persistence, size, and shape of the black hole shadow, and constrain the intrinsic structural variability of the accretion flow. We have confirmed the presence of an asymmetric ring structure, brighter in the southwest, with a median diameter of 43.3-3.1+1.5 μas. The diameter of the 2018 ring is remarkably consistent with the diameter obtained from the previous 2017 observations. On the other hand, the position angle of the brightness asymmetry in 2018 is shifted by about 30 relative to 2017. The perennial persistence of the ring and its diameter robustly support the interpretation that the ring is formed by lensed emission surrounding a Kerr black hole with a mass ∼6.5× 109M. The significant change in the ring brightness asymmetry implies a spin axis that is more consistent with the position angle of the large-scale jet.
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| 13. |
- Bond, Alexander E., et al.
(author)
-
A synthesis of approaches for modelling coupled thermal-hydraulic-mechanical-chemical processes in a single novaculite fracture experiment
- 2017
-
In: Environmental Earth Sciences. - : Springer. - 1866-6280 .- 1866-6299. ; 76:1
-
Journal article (peer-reviewed)abstract
- The geological formation immediately surrounding a nuclear waste disposal facility has the potential to undergo a complex set of physical and chemical processes starting from construction and continuing many years after closure. The DECOVALEX project (DEvelopment of COupled models and their VALidation against EXperiments) was established and maintained by a variety of waste management organisations, regulators and research organisations to help improve capabilities in experimental interpretation, numerical modelling and blind prediction of complex coupled systems. In the present round of DECOVALEX (D-2015), one component of Task C1 has considered the detailed experimental work of Yasuhara et al. (Earth Planet Sci Lett 244: 186-200, 2006), wherein a single artificial fracture in novaculite (micro-or crypto-crystalline quartz) is subject to variable fluid flows, mechanical confining pressure and different applied temperatures. This paper presents a synthesis of the completed work of six separate research teams. A range of approaches are presented including 2D and 3D high-resolution coupled thermo-hydro-mechanical-chemical models. The results of the work show that while good, physically plausible representations of the experiment can be obtained using a range of approaches, there is considerable uncertainty in the relative importance of the various processes, and that the parameterisation of these processes can be closely linked to the interpretation of the fracture surface topography at different spatial scales.
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| 14. |
- 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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| 15. |
- Cheng, Shi-Ping, et al.
(author)
-
Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
- 2021
-
In: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
-
Journal article (peer-reviewed)abstract
- Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
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| 16. |
- Deng, Liying, et al.
(author)
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KCl acts as a flux to assist the growth of sub-millimeter-scale metallic 2D non-layered molybdenum dioxide
- 2024
-
In: Rare Metals. - 1001-0521 .- 1867-7185. ; In Press
-
Journal article (peer-reviewed)abstract
- Two-dimensional (2D) metal oxides (2DMOs), such as MoO2, have made impressive strides in recent years, and their applicability in a number of fields such as electronic devices, optoelectronic devices and lasers has been demonstrated. However, 2DMOs present challenges in their synthesis using conventional methods due to their non-van der Waals nature. We report that KCl acts as a flux to prepare large-area 2DMOs with sub-millimeter scale. We systematically investigate the effects of temperature, homogeneous time and cooling rate on the products in the flux method, demonstrating that in this reaction a saturated homogenous solution is obtained upon the melting of the salt and precursor. Afterward, the cooling rate was adjusted to regulate the thickness of the target crystals, leading to the precipitation of 2D non-layered material from the supersaturated solution; by applying this method, the highly crystalline non-layered 2D MoO2 flakes with so far the largest lateral size of up to sub-millimeter scale (~ 464 μm) were yielded. Electrical studies have revealed that the 2D MoO2 features metallic properties, with an excellent sheet resistance as low as 99 Ω·square−1 at room temperature, and exhibits a property of charge density wave in the measurement of resistivity as a function of temperature. Graphical abstract: TOC (Table of Content) (Figure presented.)
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| 17. |
- Eatough, Ralph P., et al.
(author)
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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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| 18. |
- Georgiev, Boris, et al.
(author)
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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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| 19. |
- Hannan, Katherine M., et al.
(author)
-
Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway
- 2022
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 41:5
-
Journal article (peer-reviewed)abstract
- The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal proteins to MDM2, resulting in p53 accumulation. Inappropriate pathway activation is implicated in the pathogenesis of ribosomopathies, while drugs selectively activating the pathway are in trials for cancer. Despite this, the molecular mechanism(s) regulating this process are poorly understood. Using genome-wide loss-of-function screens, we demonstrate the ribosome biogenesis axis as the most potent class of genes whose disruption stabilizes p53. Mechanistically, we identify genes critical for regulation of this pathway, including HEATR3. By selectively disabling the nucleolar surveillance pathway, we demonstrate that it is essential for the ability of all nuclear-acting stresses, including DNA damage, to induce p53 accumulation. Our data support a paradigm whereby the nucleolar surveillance pathway is the central integrator of stresses that regulate nuclear p53 abundance, ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity.
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| 20. |
- Janssen, Michael, et al.
(author)
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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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| 21. |
- Lu, R.S., et al.
(author)
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A ring-like accretion structure in M87 connecting its black hole and jet
- 2023
-
In: Nature. - 0028-0836 .- 1476-4687. ; 616:7958, s. 686-690
-
Journal article (peer-reviewed)abstract
- The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
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| 22. |
- Matsui, Shinobu, et al.
(author)
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Amiodarone minimizes experimental autoimmune myocarditis in rats.
- 2003
-
In: European journal of pharmacology. - 0014-2999. ; 469:1-3, s. 165-73
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Journal article (peer-reviewed)abstract
- Amiodarone, a promising drug for the treatment of tachyarrythmias, was recently found to have immunomodulatory effects in vitro. We hypothesized that amiodarone would affect the immune system in vivo and examined the effect of amiodarone on myocarditis in rats. We induced experimental autoimmune myocarditis in rats by cardiac myosin immunization and treated the animals with an intraperitoneal injection of amiodarone at 25 mg/kg/every other day, 10 times after the induction of experimental autoimmune myocarditis. In the treated group, both microscopic and macroscopic examinations showed reduced heart weights, a mild and localized infiltration of inflammatory cells and fibrosis in the myocardium, and a mild congestion in the liver and lungs as compared with the control group. The phenotypic distribution of lymphocytes in peripheral blood showed a significant decrease in the CD4/CD8a ratio in the treated group, but not in the control group. The proportion of mast cells involved in inflammatory cell infiltration was lower in the treated group than the control group. In vitro, amiodarone inhibited the proliferation of mast cells by arresting them in the G2 phase of the cell cycle. These results indicated that amiodarone minimized the progression of experimental autoimmune myocarditis, suggesting a potential therapeutic role for amiodarone treatment in patients suffering from myocarditis, especially myocarditis complicated by cardiac arrhythmias. One possible mechanism by which amiodarone minimizes the progression of experimental autoimmune myocarditis may be to affect the immune system via the immunomodulatory effects on T cell and mast cell functions.
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| 23. |
- Roelofs, F., et al.
(author)
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Polarimetric Geometric Modeling for mm-VLBI Observations of Black Holes
- 2023
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In: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 957:2
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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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| 24. |
- Roelofs, F., et al.
(author)
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SYMBA: An end-to-end VLBI synthetic data generation pipeline: Simulating Event Horizon Telescope observations of M 87
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 636
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Journal article (peer-reviewed)abstract
- Context. Realistic synthetic observations of theoretical source models are essential for our understanding of real observational data. In using synthetic data, one can verify the extent to which source parameters can be recovered and evaluate how various data corruption effects can be calibrated. These studies are the most important when proposing observations of new sources, in the characterization of the capabilities of new or upgraded instruments, and when verifying model-based theoretical predictions in a direct comparison with observational data. Aims. We present the SYnthetic Measurement creator for long Baseline Arrays (SYMBA), a novel synthetic data generation pipeline for Very Long Baseline Interferometry (VLBI) observations. SYMBA takes into account several realistic atmospheric, instrumental, and calibration effects. Methods. We used SYMBA to create synthetic observations for the Event Horizon Telescope (EHT), a millimetre VLBI array, which has recently captured the first image of a black hole shadow. After testing SYMBA with simple source and corruption models, we study the importance of including all corruption and calibration effects, compared to the addition of thermal noise only. Using synthetic data based on two example general relativistic magnetohydrodynamics (GRMHD) model images of M 87, we performed case studies to assess the image quality that can be obtained with the current and future EHT array for different weather conditions. Results. Our synthetic observations show that the effects of atmospheric and instrumental corruptions on the measured visibilities are significant. Despite these effects, we demonstrate how the overall structure of our GRMHD source models can be recovered robustly with the EHT2017 array after performing calibration steps, which include fringe fitting, a priori amplitude and network calibration, and self-calibration. With the planned addition of new stations to the EHT array in the coming years, images could be reconstructed with higher angular resolution and dynamic range. In our case study, these improvements allowed for a distinction between a thermal and a non-thermal GRMHD model based on salient features in reconstructed images.
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| 25. |
- Shi, Zhi Sheng, et al.
(author)
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Enrichment of Ni–Mo–V via pyrometallurgical reduction from spent hydrogenation catalysts and the multi-reaction mechanism
- 2023
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In: Rare Metals. - 1001-0521 .- 1867-7185. ; 42:8, s. 2700-2712
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Journal article (peer-reviewed)abstract
- Spent hydrogenation catalysts are important secondary resources due to richness in the valuable metals of Ni, Mo and V. Recovery of valuable metals from spent catalysts has high economic value and environmental benefits since they are hazardous wastes as well. Traditional recycling processes including hydrometallurgical leaching and soda roasting-leaching have disadvantages such as generating large amounts of wastewater, long process, and low recovery efficiency of valuable metals. Thus, this paper proposed synergistic enrichment of Ni, Mo and V via pyrometallurgical reduction at 1400–1500 °C. The melting temperature and viscosity of slag were reduced through slag designing by software FactSage 7.1. The phase diagram of Al2O3-CaO-SiO2-Na2O-B2O3 was drawn, and low-temperature region (≤ 1300 °C) was selected as target slag composition. Ni, Mo, and V can be collaborative captured and recovered through the mutual solubility at molten state. Increasing the melting temperature and the amount of CaO, Na2O and C were conducive to improving the metals recovery rates. The kilogram-scale experiments were carried out, and the recovery efficiencies of Ni, Mo and V were 98.3%, 95.3% and 97.9% under optimized conditions: at 1500 °C, with the basicity of 1.0, 13.1 wt% SiO2, 7.0 wt% B2O3, 7.7 wt% Na2O and 20.0 wt% C. The distribution behavior of valuable metals was clarified by investigating the melting process of slag and the reduction in valuable metals. Ni was preferentially reduced and acted as a capturing agent, which captured other metals to form NiMoV alloys. Graphical abstract: [Figure not available: see fulltext.]
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| 26. |
- Wang, Ming-Wei, et al.
(author)
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Expression of PINCH protein in gliomas and its clinicopathological significance
- 2007
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In: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 72:5-6, s. 343-346
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Journal article (peer-reviewed)abstract
- Objectives: Particularly interesting new cysteine-histidine-rich protein (PINCH), as a LIM domain adapter protein, functions in the integrin and growth factor signal transduction pathway, and is upregulated in tumor-associated stroma in several types of cancers. However, no study of PINCH has been carried out in gliomas, therefore we examined PINCH expression in gliomas and its clinicopathological significance. Methods: PINCH expression was immunohistochemically examined in 82 gliomas, along with 26 matched adjacent normal brain samples and 10 recurred gliomas. Results: PINCH was strongly expressed in the primary (35%, p = 0.0001) or recurred tumors (40%, p = 0.004) and weak in normal brain tissue. PINCH expression was significantly increased in high-grade gliomas (55 vs. 24%, high- vs. low-grade gliomas, p = 0.004). There was no association of PINCH expression with gender, age, tumor number, size, histological type and tumor location (p > 0.05). Conclusions: PINCH expression may be involved in glioma development and differentiation. Copyright © 2008 S. Karger AG.
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| 27. |
- Wang, Ming-Wei, et al.
(author)
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FXYD3 Expression in Gliomas and its Clinicopathological Significance
- 2009
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In: Oncology Research. - : Computers, Materials and Continua (Tech Science Press). - 0965-0407 .- 1555-3906. ; 18:4, s. 133-139
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Journal article (peer-reviewed)abstract
- FXYD3, interacting with Na+/K+-ATPase, is considered a cell surface regulator modulating the function of ion pumps and ion channels. The FXYD3 gene was originally cloned from murine mammary tumors and then from human breast tumors. However, no study of FXYD3 has been carried out in gliomas; therefore, we examined FXYD3 expression in gliomas and its clinicopathological significance. FXYD3 expression was immunohistochemically examined in 71 primary gliomas, along with 37 matched adjacent normal brain samples and 8 recurred gliomas. The frequency of strong FXYD3 expression was higher in the primary tumors in either unmatched (p = 0.046) or matched cases (p = 0.02), compared to normal brain tissue. FXYD3 expression was significantly more increased in females than males (p = 0.01), and in multiple site gliomas than single sites (p = 0.02). There was no difference of FXYD3 expression regarding age, tumor location, size, histological type, and tumor grade (p greater than 0.05). The results suggest that FXYD3 expression may be involved in glioma development, especially in multiple gliomas and female patients.
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| 28. |
- Xu, Hong-Tao, et al.
(author)
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Effects of fucosylated milk of goat and mouse on Helicobacter pylori binding to Lewis b antigen
- 2004
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In: World Journal of Gastroenterology. - Beijing : WJG Press. - 1007-9327 .- 2219-2840. ; 10:14, s. 2063-2066
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Journal article (peer-reviewed)abstract
- Aim:To evaluate the effects of animal milk containing fucosylated antigens on Helicobacter pylori (H pylon) binding to Lewis b antigen. Methods:A mammary gland expression vector containing human α1-3/4-fucosyltransferase cDNA sequences was constructed. Transient expression of human(α1-3/4-fucosyltransferase cDNA in goat mammary cell and establishment of transgenic mice were performed. The adhesion inhibitory properties of milk samples were analyzed by using Hpylori. Results: Goat milk samples were found to inhibit bacterial binding to Lewis b antigen. The highest inhibition was observed 42 h after injection of the plasmid. The binding activity of Hpylori to Lewis b antigen reduced mostly, by 83%, however milk samples from transgenic mice did not inhibit Hpylori binding to Lewis b antigen. Conclusion: The use of “humanized“ animal milk produced by the transgenic introduction of fucosylated antigen can perhaps provide an alternative therapy and preventive measure for Hpylori infection.
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| 29. |
- Zong, Zhi-Ping, et al.
(author)
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Involvement of thymus in amiodarone-treated autoimmune myocarditis in rats.
- 2008
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In: International journal of cardiology. - : Elsevier BV. - 1874-1754 .- 0167-5273. ; 125:1, s. 122-9
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Journal article (peer-reviewed)abstract
- We previously showed that amiodarone, an iodine-rich benzofuranic derivative, interferes with the progression of myocarditis using a rat model of experimental autoimmune myocarditis. Further studies have also revealed that intraperitoneal treatment with 12.5 mg/kg amiodarone, which is below the range of its therapeutic plasma concentration, also effectively interferes with the progression of myocarditis using the same model. The relationship between myocarditis and the thymus has not been studied in either patients or animal models. To investigate whether the thymus is involved in the effect of amiodarone on experimental autoimmune myocarditis, we examined its phenotypic distribution in thymocytes and peripheral blood lymphocytes using flow cytometry. We found no significant differences in the proportions of CD4(+) and CD8(+) T cells and the CD4(+)/CD8(+) T cell ratio in the control group compared with amiodarone-treated group. However, amiodarone-treated group induced a decrease in the proportion of CD4(+)TNF(+) and CD4(+)IL-4(+) T cells and an increase in CD4(+)IFN(+) T cells, resulting in a significant reduction of the CD4(+)TNF(+)/CD4(+)IFN(+) and CD4(+)IL-4(+)/CD4(+)IFN(+) T cell ratios. These results suggest for the first time that the thymus is actively involved when myocarditis is treated with amiodarone.
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