Genome-Wide Association Study of Tacrolimus Pharmacokinetics Identifies Novel Single Nucleotide Polymorphisms in the Convalescence and Stabilization Periods of Post-transplant Liver Function

After liver transplantation, the liver function of a patient is gradually restored over a period of time that can be divided into a convalescence period (CP) and a stabilizing period (SP). The plasma concentration of tacrolimus, an immunosuppressant commonly used to prevent organ rejection, varies as a result of variations in its metabolism. The effects of genetic and clinical factors on the plasma concentration of tacrolimus appear to differ in the CP and SP. To establish a model explaining the variation in tacrolimus trough concentration between individuals in the CP and SP, we conducted a retrospective, single-center, discovery study of 115 pairs of patients (115 donors and 115 matched recipients) who had undergone liver transplantation. Donors and recipients were genotyped by a genome-wide association study (GWAS) using an exome chip. Novel exons were identified that influenced tacrolimus trough concentrations and were verified with bootstrap analysis. In donors, two single-nucleotide polymorphisms showed an effect on the CP (rs1927321, rs1057192) and four showed an effect on the SP (rs776746, rs2667662, rs7980521, rs4903096); in recipients, two single-nucleotide polymorphisms showed an effect in the SP (rs7828796, rs776746). Genetic factors played a crucial role in tacrolimus metabolism, accounting for 44.8% in the SP, which was higher than previously reported. In addition, we found that CYP3A5, which is known to affect the metabolism of tacrolimus, only influenced tacrolimus pharmacokinetics in the SP

Could very low-metallicity stars with rotation-dominated orbits have been shepherded by the bar?

The most metal-poor stars (e.g. [Fe/H] $\leq-2.5$) are the ancient fossils from the early assembly epoch of our Galaxy, very likely before the formation of the thick disc. Recent studies have shown that a non-negligible fraction of them have prograde planar orbits, which makes their origin a puzzle. It has been suggested that a later-formed rotating bar could have driven these old stars from the inner Galaxy outward, and transformed their orbits to be more rotation-dominated. However, it is not clear if this mechanism can explain these stars as observed in the solar neighborhood. In this paper, we explore the possibility of this scenario by tracing these stars backwards in an axisymmetric Milky Way potential with a bar perturber. We integrate their orbits backward for 6 Gyr under two bar models: one with a constant pattern speed and another one with a decelerating speed. Our experiments show that, under the constantly-rotating bar model, the stars of interest are little affected by the bar and cannot have been shepherded from a spheroidal inner Milky Way to their current orbits. In the extreme case of a rapidly decelerating bar, some of the very metal-poor stars on planar and prograde orbits can be brought from the inner Milky Way, but $\sim90\%$ of them were nevertheless already rotation-dominated ($J_{\phi}$ $\geq$ 1000 km s$^{-1}$ kpc) 6 Gyr ago. The chance of these stars having started with spheroid-like orbits with small rotation ($J_{\phi}$ $\lesssim$ 600 km s$^{-1}$ kpc) is very low ($<$ 3$\%$). We therefore conclude that, within the solar neighborhood, the bar is unlikely to have shepherded a significant fraction of inner Galaxy spheroid stars to produce the overdensity of stars on prograde, planar orbits that is observed today.Comment: submitted to A&A, comments are welcom

The Preparation, Characterization, Mechanical and Antibacterial Properties of GO-ZnO Nanocomposites with a Poly(l-lactide)-Modified Surface

Graphene oxide (GO) was employed for the preparation of GO-zinc oxide (ZnO). The hydroxyl group on the surface was exploited to trigger the l-lactide ring-opening polymerization. A composite material with poly(l-lactide) (PLLA) chains grafted to the GO-ZnO surface, GO-ZnO-PLLA, was prepared. The results demonstrated that the employed method allowed one-step, rapid grafting of PLLA to the GO-ZnO surface. The chemical structure of the GO surface was altered by improved dispersion of GO-ZnO in organic solvents, thus enhancing the GO-ZnO dispersion in the PLLA matrix and the interface bonding with PLLA. Subsequently, composite films, GO-ZnO-PLLA and GO-ZnO-PLLA/PLLA, were prepared. The changes in interface properties and mechanical properties were studied. Furthermore, the antibacterial performance of nano-ZnO was investigated

A Novel Mobile Localization Method for Distributed Sensor Network with Non-Line-of-Sight Error Mitigation

Mobile localization using distributed sensor network has attracted significant research interest in recent years. One of the main challenges for mobile location estimation is the presence of the non-line-of-sight (NLOS) propagation. It results in erroneous measurements containing NLOS error due to the reflection and diffraction. The NLOS error could seriously reduce the localization accuracy. This paper presents a novel mobile localization method for distributed sensor network in NLOS propagation scenarios. The aim of the method is to mitigate the NLOS error and enhance the localization accuracy. The transition between the LOS and NLOS is described by two-state Markov model. The interacting multiple model frame is employed to estimate the position of unknown node. The probability data association algorithm is used to filter the estimated location. The simulation results show that the proposed method outperforms the traditional filter method in NLOS scenarios

Functionalization of Graphene Oxide with Low Molecular Weight Poly (Lactic Acid)

In this paper, the hydroxyl groups on the surface of graphene oxide (GO) were used to initiate the ring-opening polymerization of a lactic acid O-carboxyanhydride. GO grafted with poly (l-lactic acid) molecular chains (GO-g-PLLA) was prepared. Lactic acid O-carboxyanhydride has a higher polymerization activity under mild polymerization conditions. Thus, the functionalization of the polymer chains and obtaining poly (lactic acid) (PLLA) was easily achieved by ring-opening polymerization with 4-dimethylaminopyridine (DMAP) as the catalyst. The results showed that with this method, PLLA can be rapidly grafted to the surface of GO in one step. As a result, the chemical structure of the GO surface was altered, improving its dispersion in organic solvents and in a PLLA matrix, as well as its bonding strength with the PLLA interface. We then prepared GO/PLLA and PLLA/GO-g-PLLA composite materials and investigated the differences in their interfacial properties and mechanical properties. GO-g-PLLA exhibited excellent dispersion in the PLLA matrix and formed excellent interfacial bonds with PLLA through mechanical interlocking, demonstrating a significant enhancement effect compared to PLLA. The water vapor and oxygen permeabilities of the GO-g-PLLA/PLLA composite decreased by 19% and 29%, respectively

Static Analysis and Topological Optimization of Steering Block for Mining Shuttle

Taking the steering block of mine shuttle car as the research object, a three-dimensional solid model of the steering block of mine shuttle car is established by SolidWorks. Based on ANSYS Workbench, the total deformation and stress of the steering block of Mine shuttle car under tension are obtained. According to the boundary conditions, the steering block is optimized by topology optimization, and the steering block is optimized by the results of topology optimization, and finally verified by static analysis. The results show that the mass of the optimized steering block is reduced by 11.7%. This study provides a reference for comprehensive performance analysis and optimization of Mine shuttle car steering block