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Chen, M.

Publications and source records attributed to Chen, M..

At least 91 records · Page 5

Review article: therapeutic bile acids and the risks for hepatotoxicity

Summary Background Bile acids play important roles in cholesterol metabolism and signal through farnesoid X receptor and G protein‐coupled receptors. Given their importance in liver biology, bile acid therapy enables therapeutic applications beyond the treatment of cholestatic liver disease. However, predicting hepatotoxicity of bile acids in humans is obscured due to inconsistent extrapolations of animal data to humans. Aim To review the evidence that could explain discordant bile acids hepatotoxicity observed in humans and animals. Method Literature search was conducted in PubMed using keywords “bile acid,” “transporter,” “hepatotoxicity,” “clinical study,” “animal study,” “species difference,” “mechanism,” “genetic disorder.” Relevant articles were selected for review. Results Clinically significant hepatotoxicity was reported in response to certain bile acids, namely chenodeoxycholic acid, which was given a boxed warning for potential hepatotoxicity. The chemical structure, specifically the number and orientation of hydroxyl groups, significantly affects their hydrophobicity, an important factor in bile acid toxicity. Experimental studies show that hydrophobic bile acids can lead to liver injury through various mechanisms, such as death receptor signalling, mitochondrial dysfunction and inflammation. Although animal studies play a central role in investigating bile acid safety, there are considerable differences in bile acid composition, metabolism and hepatobiliary disposition across species. This does not allow appropriate safety inference, especially for predicting hepatotoxicity in humans. Exploring evidences stemming from inborn errors, genetic models of disease and toxicology studies further improves an understanding of bile acid hepatotoxicity. Conclusion Species differences should be considered in the development of bile acid related therapeutics. Although the mechanism of bile acid hepatotoxicity is still not fully understood, continued mechanistic studies will deepen our understanding.

Ashby, K.↗

Liquid crystal polymer substrate MMIC receiver modules for the ECE Imaging system on the DIII-D

A new generation of millimeter-wave heterodyne imaging receiver arrays has been developed and demonstrated on the DIII-D ECEI system. Improved circuit integration, allowing for absolute calibration, improved noise performance, and shielding from out-of-band emission, is made possible by using advanced liquid crystal polymer (LCP) substrates and MMIC (Monolithic Microwave Integrated Circuit) receiver chips. This array exhibits ~ 15 dB additional gain and > 30x reduction in noise temperature compared to the previous generation and provide ECEI capability for absolute 2-D electron temperature profile measurements. Each LCP horn-waveguide module houses a 3x3 mm GaAs MMIC receiver chip, which consists of a low noise amplifier (LNA), balanced mixer, local oscillator multiplier chain driven by ~12 GHz input via an RF cable to the enclosure box, and IF amplifier. A proof-of-principle instrument with 5 poloidal channels was installed on DIII-D in 2017. The full proof-of-principle system installation (20 poloidal x 8 radial channels) was commissioned early in 2018. The LCP ECEI system is used for pedestal region measurements, especially focusing on temperature evolution during ELM bursting. The DIII-D ECE Imaging signal has been significantly improved with extremely effective shielding of out-of-band microwave noise which plagued previous ECE Imaging studies on DIII-D. In H-mode ELM bursting, the radial propagation of electron heat flow has been detected on DIII-D. The LCP ECE Imaging is expected to be a valuable diagnostic tool for ELM physics investigations.

Zhu, Y.↗

Multistage Coupling of Laser-Wakefield Accelerators with Curved Plasma Channel

Multistage coupling of laser-wakefield accelerators is essential to overcome laser energy depletion for high-energy applications such as TeV level electron-positron colliders. Current staging schemes feed subsequent laser pulses into stages using plasma mirrors, while controlling electron beam focusing with plasma lenses. Here a more compact and efficient scheme is proposed to realize simultaneous coupling of the electron beam and the laser pulse into a second stage. Furthermore, a curved channel with transition segment is used to guide a fresh laser pulse into a subsequent straight channel, while allowing the electrons to propagate in a straight channel. This scheme then benefits from a shorter coupling distance and continuous guiding of the electrons in plasma, while suppressing transverse beam dispersion. Within moderate laser parameters, particle-in-cell simulations demonstrate that the electron beam from a previous stage can be efficiently injected into a subsequent stage for further acceleration, while maintaining high capture efficiency, stability, and beam quality.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Search for neutron-antineutron oscillations at the Sudbury Neutrino Observatory

Tests on B–L symmetry breaking models are important probes to search for new physics. One proposed model with Δ(B–L)=2 involves the oscillations of a neutron to an antineutron. In this paper, a new limit on this process is derived for the data acquired from all three operational phases of the Sudbury Neutrino Observatory experiment. The search concentrated on oscillations occurring within the deuteron, and 23 events were observed against a background expectation of 30.5 events. These translated to a lower limit on the nuclear lifetime of 1.48 × 10 31 yr at 90% C.L. when no restriction was placed on the signal likelihood space (unbounded). Alternatively, a lower limit on the nuclear lifetime was found to be 1.18 × 10 31 yr at 90% C.L. when the signal was forced into a positive likelihood space (bounded). Values for the free oscillation time derived from various models are also provided in this article. Furthermore, this is the first search for neutron-antineutron oscillation with the deuteron as a target.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Effective Pressure Law for the Intrinsic Formation Factor in Low Permeability Sandstones: EPL law for the formation factor

The effective pressure law for the intrinsic formation factor of low permeability sandstones from the Ordos Basin (northwest of China) was studied experimentally by measuring the electrical resistivity of brine saturated rock samples while cycling the pore and confining pressures, p p and p c . We used a 100,000 ppm NaCl solution so that the results could be directly interpreted in terms of the intrinsic formation factor F. The Response Surface method was used to construct a quadratic function of pp and pc fitting the experimental data, from which the coefficient α of the effective pressure law, p eff = p c – αp p , was determined. We found that the coefficient α generally had low values, mainly from 0.2 to 0.4, thus contradicting the theoretical prediction that α should be equal to 1 for scale-invariant properties, such as F, in linear elastic materials having a homogeneous solid matrix. Since the two underlying assumptions, linear elasticity and homogeneity of the solid matrix, are likely violated in reservoir rocks, we tried to assess their effects on α using simple analytical models, based on idealized geometries of the pore and solid phases. Analysis of these models suggests that non-linear elasticity associated with the formation of solid–solid contacts in the compressed rocks (e.g., during closure of rough cracks or crack-like pores along the grain boundaries), may be more effective in producing the low α values observed than inhomogeneity of the solid matrix.

58 GEOSCIENCES↗

The Intermediate Neutrino Program

The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program (WINP) at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

The JCMT Gould Belt Survey: A First Look at IC 5146

We present 450 and 850 μm submillimeter continuum observations of the IC 5146 star-forming region taken as part of the James Clerk Maxwell Telescope Gould Belt Survey. We investigate the location of bright submillimeter (clumped) emission with the larger-scale molecular cloud through comparison with extinction maps, and find that these denser structures correlate with higher cloud column density. Ninety-six individual submillimeter clumps are identified using FellWalker, and their physical properties are examined. These clumps are found to be relatively massive, ranging from 0.5 M{sub ⊙} to 116 M{sub ⊙} with a mean mass of 8 M{sub ⊙} and a median mass of 3.7 M{sub ⊙}. A stability analysis for the clumps suggests that the majority are (thermally) Jeans stable, with M/M{sub J}<1. We further compare the locations of known protostars with the observed submillimeter emission, finding that younger protostars, i.e., Class 0 and I sources, are strongly correlated with submillimeter peaks and that the clumps with protostars are among the most Jeans unstable. Finally, we contrast the evolutionary conditions in the two major star-forming regions within IC 5146: the young cluster associated with the Cocoon Nebula and the more distributed star formation associated with the Northern Streamer filaments. The Cocoon Nebula appears to have converted a higher fraction of its mass into dense clumps and protostars, the clumps are more likely to be Jeans unstable, and a larger fraction of these remaining clumps contain embedded protostars. The Northern Streamer, however, has a larger number of clumps in total and a larger fraction of the known protostars are still embedded within these clumps.

79 ASTRONOMY AND ASTROPHYSICS↗

Millimeter-wave imaging diagnostics systems on the EAST tokamak (invited)

Millimeter-wave imaging diagnostics, with large poloidal span and wide radial range, have been developed on the EAST tokamak for visualization of 2D electron temperature and density fluctuations. A 384 channel (24 poloidal × 16 radial) Electron Cyclotron Emission Imaging (ECEI) system in F-band (90-140 GHz) was installed on the EAST tokamak in 2012 to provide 2D electron temperature fluctuation images with high spatial and temporal resolution. A co-located Microwave Imaging Reflectometry (MIR) will be installed for imaging of density fluctuations by December 2016. This “4th generation” MIR system has eight independent frequency illumination beams in W-band (75-110 GHz) driven by fast tuning synthesizers and active multipliers. Both of these advanced millimeter-wave imaging diagnostic systems have applied the latest techniques. A novel design philosophy “general optics structure” has been employed for the design of the ECEI and MIR receiver optics with large aperture. The extended radial and poloidal coverage of ECEI on EAST is made possible by innovations in the design of front-end optics. The front-end optical structures of the two imaging diagnostics, ECEI and MIR, have been integrated into a compact system, including the ECEI receiver and MIR transmitter and receiver. Two imaging systems share the same mid-plane port for simultaneous, co-located 2D fluctuation measurements of electron density and temperature. An intelligent remote-control is utilized in the MIR electronics systems to maintain focusing at the desired radial region even with density variations by remotely tuning the probe frequencies in about 200 μs. A similar intelligent technique has also been applied on the ECEI IF system, with remote configuration of the attenuations for each channel.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Synthetic diagnostics platform for fusion plasmas (invited)

A Synthetic Diagnostics Platform (SDP) for fusion plasmas has been developed which provides state of the art synthetic reflectometry, beam emission spectroscopy, and Electron Cyclotron Emission (ECE) diagnostics. Interfaces to the plasma simulation codes GTC, XGC-1, GTS, and M3D-C{sup 1} are provided, enabling detailed validation of these codes. In this paper, we give an overview of SDP’s capabilities, and introduce the synthetic diagnostic modules. A recently developed synthetic ECE Imaging module which self-consistently includes refraction, diffraction, emission, and absorption effects is discussed in detail. Its capabilities are demonstrated on two model plasmas. The importance of synthetic diagnostics in validation is shown by applying the SDP to M3D-C{sup 1} output and comparing it with measurements from an edge harmonic oscillation mode on DIII-D.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Measurement of the scintillation time spectra and pulse-shape discrimination of low-energy β and nuclear recoils in liquid argon with DEAP-1

The DEAP-1 low-background liquid argon detector has been used to measure scintillation pulse shapes of beta decays and nuclear recoil events and to demonstrate the feasibility of pulse-shape discrimination down to an electron-equivalent energy of 20 keV ee . The relative intensities of singlet/triplet states in liquid argon have been measured as a function of energy between 15 and 500 keVee for both beta and nuclear recoils. Using a triple-coincidence tag we find the fraction of beta events that are misidentified as nuclear recoils to be less than 6 x 10 -8 between 43-86 keV ee and that the discrimination parameter agrees with a simple analytic model. The discrimination measurement is currently limited by nuclear recoils induced by cosmic-ray generated neutrons, and is expected to improve by operating the detector underground at SNOLAB. The analytic model predicts a beta misidentification fraction of 10 -10 for an electron-equivalent energy threshold of 20 keV ee . This reduction allows for a sensitive search for spin-independent scattering of WIMPs from 1000 kg of liquid argon with a WIMP-nucleon cross-section sensitivity of 10 -46 cm 2 .

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗