Search

HLA-C*03:597 differs from HLA-C*03:03:01:01 by a single non-synonymous nucleotide substitution in exon 5 (922 AG).

2,4,6-Trichloroanisole (2,4,6-TCA) has aroused a special concern for their odor problem and potential threats. In this study, the degradation of 2,4,6-TCA by UV/chlorination with different UV sources was compared, including low-pressure mercury lamp (LPUV, 254 nm) and ultraviolet light-emitting diode (UV-LED, 275 and 285 nm). The maximum removal of 2,4,6-TCA can be achieved by 275 nm UV-LED/chlorination in neutral and alkaline conditions was 80.0%. The reaction, kinetics and water matrix parameters on 2,4,6-TCA degradation were also evaluated. During UV-LED (275 nm)/chlorination, 2,4,6-TCA degradation was mainly caused by direct UV photolysis and indirect hydroxyl radical (HO•) oxidation, while reactive chlorine radicals (RCSs) had a negligible contribution. The second-order rate constant between HO• and 2,4,6-TCA was determined as 3.1×109 M-1s-1. Increasing initial chlorine dosage and decreasing 2,4,6-TCA concentration or pH value significantly promoted 2,4,6-TCA degradation during UV/chlorination process. The presence of natural organic matter (NOM) and bicarbonate (HCO3-) can inhibit 2,4,6-TCA degradation, while chloride ion (Cl-) had a negligible effect. The kinetic model for 2,4,6-TCA degradation was established and validated, and the degradation pathways were proposed based on the identified intermediates. Furthermore, UV-LED (275 nm)/chlorination also exhibited a promising effect on 2,4,6-TCA removal in real water, which can be used to control 2,4,6-TCA pollution and odor problems.

Paeonia is recognized globally due to its ornamental value. However, the mechanisms behind the formation of distinct levels of lignification in Paeonia stems remain largely unknown. In this study, we selected three representative Paeonia species, namely P. ostii (shrub), P. lactiflora (herb), and P. × 'Hexie' (semi-shrub), to evaluate and contrast their respective anatomical structure, phytochemical composition and transcriptomic profile. Our results showed that the degree of lignin deposition on the cell wall, along with the total amount of lignin and its monomers (especially G-lignin) were higher in P. ostii stems compared to the other two species at almost all development stages except 80 days after flowering. Furthermore, we estimated a total number of unigenes of 60,238 in P. ostii, 43,563 in P. × 'Hexie', and 40,212 in P. lactiflora from stem transcriptome. We then built a co-expression network of 25 transcription factors and 21 enzyme genes involved in lignin biosynthesis and identified nine key candidate genes. The expression patterns of these genes were positively correlated with the transcription levels of PAL, C4H, 4CL2, CCR, and COMT, as well as lignin content. Moreover, the highest relative expression levels of CCR, 4CL2, and C4H were found in P. ostii. This study provides an explanation for the observed differences in lignification between woody and herbaceous Paeonia stems, and constitutes a novel reference for molecular studies of stem-specific lignification process and lignin biosynthesis that can impact the ornamental industry.

Digitally programmable metasurfaces are of potential use in wireless multiplexing techniques because they can encode and transmit information without using traditional radio-frequency components such as antennas or mixers. Space–time-coding digital metasurfaces can, in particular, manipulate the propagation direction and harmonic power distribution of electromagnetic waves, making them suitable for space- and frequency-division multiplexing. However, while digital metasurfaces have been used for wireless communication, these systems could implement signal modulation only in the time domain. Here, we report a wireless communication scheme that uses space–time-coding digital metasurfaces to implement both space- and frequency-division multiplexing. By encoding space–time-coding matrices through multiple channels, digital messages can be directly transmitted to different users at different locations simultaneously, without the need for digital-to-analogue conversion and mixing processes. To illustrate this approach, we have built a dual-channel wireless communication system based on a two-bit space–time-coding digital metasurface and use it to transmit two different pictures to two users simultaneously in real time. Space–time-coding digital metasurfaces can be used to implement secure and low-cost space- and frequency-division multiplexing in a dual-channel wireless communication system.

Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography–tandem mass spectrometry technique was established and validated, which was successfully employed to explore the effects of CYP3A4 inhibitors on alpelisib pharmacokinetics in rats. A C18 column named Acquity UPLC BEH C18 was applied to achieve the separation of alpelisib and internal standard duvelisib after protein precipitation with acetonitrile. The mobile phase in this study had two components, namely, acetonitrile and water having 0.1% formic acid, and a program with gradient elution method was used at a flow rate of 0.40 ml/min. Mass spectrometry in a positive multiple reaction monitoring mode was operated. In the scope of 1–5,000 ng/ml, this assay had excellent linearity. Our newly developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification, selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect, and stability. Then, this assay was used to detect the plasma levels of alpelisib from a drug-drug interaction investigation, where ketoconazole remarkably increased the plasma concentration of alpelisib and changed alpelisib pharmacokinetics more than itraconazole. This study will help better understand the pharmacokinetic properties of alpelisib, and further clinical studies should be done to confirm this result in patients.

Accurately predicting the propagation of hydraulic fracturing arising from the wellbore is essential in petroleum engineering, hydraulic engineering, etc. There are various factors influencing fracture propagation, such as the initial fracture orientation and in-situ stresses, while the limitation of appropriate methods and techniques hinders the further investigation on the propagating mechanism. In the study, a simulator based on High-order Generalized Finite Element Method (GFEM) is introduced to investigate the propagation behaviors of hydraulic fractures arising from the sidewall of wellbore. For better recognization of hydraulic fracturing, several numerical examples are performed based on the simulator. Different influencing factors are studied, including intersection angle between fracture and wellbore, in-situ stresses and fracture interactions. It is found that, regardless of in-situ stresses in the surrounding rock, pre-existing fractures approximately propagate straightforward along their initial directions and finally form planar fracture surfaces. Regarding in-situ stresses, with acute intersection angle between fracture and wellbore, fractures propagate toward the direction of the minimum principal stress. Besides, two parallel and opposite fractures individually arising from two parallel and non-coincidence wellbores always propagate towards each other after passing by each other. Moreover, the interactions between them become strengthened as the distance between them decreases. Finally, the propagating sequences of hydraulic fractures arising from a group of parallel wellbores are discussed. It is found that the sequence can influence the fracture geometry and previously propagated fractures can restrain the nearest fractures embedded in other wellbores propagating away from each other in subsequent stages.

The plasmonic surface is made of metallic surface with deep sub-wavelength decorations, which are designed to mimic the surface plasmon polaritons at lower frequency. Recently, high-order modes in some special structures are analyzed. In order to analyze the dispersion problem of high-order modes of complex lossless structures faster and simpler, a convenient and simple method using the average input wave impedance obtained by a field-network joint solution is proposed. Meanwhile, based on Forster's reactance theorem, high-order modes of the complex structure always exist. Then, the dispersion curves of the high-order modes calculated using proposed method are in perfect match with the simulated results, which can verify the effectiveness and correctness of the proposed method. Additionally, the simulated and experimentally measured electric field distribution of high-order modes have great agreement. Using the proposed method, one can quickly obtain dispersion curve of a plasmonic structure to verify or estimate structure design. Hence, the proposed method may make a big step forward for obtaining the special dispersion relations.

OBJECTIVES Moderate to vigorous physical activity is recommended to prevent hypertension according to the current guidelines. However, the degree to which the total physical activity (TPA) and its changes benefit normotensives and hypertensives is uncertain. We aimed to examine the effects of TPA and its changes on the incidence, progression, and remission of hypertension in the large-scale prospective cohorts. METHODS A total of 73,077 participants (55,101 normotensives and 17,976 hypertensives) were eligible for TPA analyses. During a mean follow-up of 7.16 years (394,038 person-years), 12,211 hypertension cases were identified. TPA was estimated as metabolic equivalents and categorized into quartiles. Cox proportional hazards regression and multivariable logistic regression were used to estimate associations of TPA and changes in TPA with incident hypertension and progression/remission of hypertension. RESULTS Compared with the lowest quartile of TPA, normotensives at the third and the highest quartile had a decreased risk of incident hypertension, with hazard ratios (HRs) of 0.86 [95% confidence interval (CI): 0.81−0.91] and 0.81 (95% CI: 0.77−0.86), respectively. Hypertensives at the highest quartile of TPA demonstrated a decreased risk of progression of hypertension [odds ratio (OR) = 0.87, 95% CI: 0.79−0.95], and an increased probability of hypertension remission (OR = 1.17, 95% CI: 1.05−1.29). Moreover, getting active from a sedentary lifestyle during the follow-up period could reduce 25% (HR = 0.75, 95% CI: 0.58−0.96) risk of incident hypertension, whereas those becoming sedentary did not achieve benefit from initially being active. CONCLUSIONS Our findings indicated that increasing and maintaining TPA levels could benefit normotensives, whereas higher TPA levels were needed to effectively control progression and improve remission of hypertension. Physical activity played undoubtedly an essential role in both primary and secondary prevention of hypertension.

Ethnopharmacological relevance Paeonia plants have been widely used as traditional Chinese medicinal materials for more than 2,000 years in the treatment of cardiovascular, extravasated blood and female genital diseases; paeoniflorin and paeonol have been implicated as the plants’ primary active ingredients. Aim of the study Previous studies have been singularly focused on the chemical constituents and content variation of the Paeonia roots in the advancement of traditional Chinese medicine, with the plants’ stems and leaves considered useless. This study aims to explore the chemical constituents, content variation, and antioxidant capacity in Paeonia stems and leaves for the future utilization of traditional Chinese medicine, given that current practices of digging and trade endanger Paeonia in the wild. Materials and methods Herein, secondary metabolites from the stems and leaves from six developmental stages of the annual growth cycle of Paeonia ostii T. Hong & J. X. Zhang, P. ‘Hexie’, and P. lactiflora Pall. were qualitatively and quantitatively analyzed via high-performance liquid chromatography with a diode array detector (HPLC-DAD) and high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Antioxidant capacity at each stage was also evaluated by various free radical scavenging assays. Results A total of 24 metabolites were detected and identified, including 5 monoterpene glycosides, 4 tannins, 5 phenols, 9 flavonoids, and paeonol. Excepting paeonol and the phenols, the levels of each metabolite category were significantly higher in the leaves than the stems during all developmental stages. The paeoniflorin content in the P. ostii leaves was the highest during the first developmental stage and higher than the standards of the Chinese Pharmacopoeia, suggesting it to be the optimal harvesting stage for medicinal uses. Notably, the antioxidant capacity of the leaves was significantly greater than in the stems, particularly for the leaves of P. ‘Hexie’. Conclusion Our study indicates that the leaves of P. ‘Hexie’ have the potential to be a worthy medicinal substitute to Paeonia roots due to their high monoterpene glycosides, phenols, and flavonoids as well as their strong antioxidant capacity. Further, this study provides a theoretical basis for the development and utilization of non-root Paeonia plant sections as medicinal plant resources.

Warfarin is a widely prescribed anticoagulant but the doses required to attain the optimum therapeutic effect exhibit dramatic inter-individual variability. Pharmacogenomics-guided warfarin dosing has been recommended to improve safety and effectiveness. We analyzed the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes among 120 patients taking warfarin. A new coding variant was identified by sequencing CYP2C9. The novel A > G mutation at nucleotide position 14,277 led to an amino acid substitution of isoleucine with valine at position 213 (I213V). The functional consequence of the variant was subsequently evaluated in vitro. cDNA of the novel variant was constructed by site-directed mutagenesis and the recombinant protein was expressed in vitro using a baculovirus–insect cell expression system. The recombinant protein expression was quantified at apoprotein and holoprotein levels. Its enzymatic activities toward tolbutamide, warfarin and losartan were then assessed. It exhibited changed apparent Km values and increases of 148%, 84% and 67% in the intrinsic clearance of tolbutamide, warfarin and losartan, respectively, compared to wild-type CYP2C9*1, indicating dramatically enhanced in vitro enzymatic activity. Our study suggests that the amino acid at position 213 in wild-type CYP2C9*1 may be important for the enzymatic activity of CYP2C9 toward tolbutamide, warfarin and losartan. In summary, a patient taking high-dose warfarin (6.0 mg/day) in order to achieve the target international normalized ratio was found to have a mutation in the CYP2C9 gene.

HLA-A*30:171 differs from HLA-A*30:01:01:01 by one nucleotide substitution at position 821 in exon 4.

Due to the abilities of remarkable field confinements and enhancements, plasmonic surfaces supporting spoof surface plasmon polaritons (SPPs) are important artificial structures with many potential applications. In this paper, we propose analytical derivation to the dispersion formulation of metallic surface with complicated subwavelength decorations using a field-network joint solution, which offers a new scheme to obtain the dispersion relations of plasmonic surfaces. Based on the proposed method, we could predict not only the dispersion relationship between the frequency and wavenumber but also the approximate near-field distribution on the plasmonic surface rapidly and accurately. As an example, we analyze a series of complex-decorated metallic plasmonic surfaces, with comparisons to the full-wave simulation and experiment. The analytical, numerical, and experimental results show that these plasmonic surfaces support electromagnetic surface modes that are similar to the SPPs at the optical frequency. Meanwhile, the calculated dispersion curve and field form have great matching to the simulation and measured results.

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid β peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

In view of the importance and complexity of international crude oil price, this paper proposes a novel combination forecast approach that captures a variety of fluctuation features in crude oil data series, including change points, regime-switching, time-varying determinants, trend decomposition of high-frequency sequences, and the possible nonlinearity of model setting. First, product partition model-K-means (PPM-KM) model is used to detect change points in the oil price sequence. Next, we apply a time-varying transition probability Markov regime switching (TVTP-MRS) model to identify the regime-switching characteristic. Then, we use Bayesian model averaging (BMA) to filtrate main determinants at each regime. Finally, the time-varying parameter structure time series model (TVP-STSM) is used to decompose the oil sequence, capture the time-variation of coefficients in “volatile upward” regime, and forecast the crude oil price. Compared with some other competing models and benchmark model of ARIMA, the newly proposed method shows superior forecasting ability in four statistical tests. Besides, we make scenario prediction on WTI crude oil price to examine the implementation effect of OPEC cut-off agreement at the end of 2016. OPEC production and U.S. shale oil production are used as two scenario variables, and the WTI price is forecasted fluctuating around 50 dollar/barrel based on three scenario prediction. We conclude that WTI crude oil price would take a shock upstream tendency in the short-term but the rising scope would not be large.

As China’s high-speed railway featured by low-carbon quick prospers rapidly, railway transport has been regarded as a crucial means to replace the aviation transport. Selecting the data from 156 routes of China's 48 major cities from 2001 to 2014, the paper takes the aviation mileage as the threshold variable and the operation time as the control variable to build a panel threshold regression model. Firstly, under the consideration of the economic, demographic, environmental and railway indicators, the paper analyzes the influence of China’s railway on the aviation passenger volume and the flight number; secondly, under the condition that the railway speed is more than 250 km/h, the paper analyzes the shock effect of China’s high-speed railway on aviation transport. The conclusion shows that the higher the level of the economic development is, the more developed the aviation transport of the region will be. when the aviation mileage is below 1132 km, as the aviation mileage increases, the influence of China’s railway to the aviation transport fall into a decline; China’s high-speed railway has a positive shock effect on the aviation transport, and the shock effect reaches the maximum when the aviation mileage is from 650 to 755 km. This paper is of great practical significance to study the optimization of transportation structure.

Coding metasurfaces allow us to study metamaterials from a fully digital perspective, enabling many exotic functionalities, such as anomalous reflections, broadband diffusions, and polarization conversion. Here, we propose a tensor coding metasurface at terahertz (THz) frequency that could take full-state controls of an electromagnetic wave in terms of its polarization state, phase and amplitude distributions, and wave-vector mode. Owing to the off-diagonal elements that dominant in the reflection matrix, each coding particle could reflect the normally incident wave to its cross-polarization with controllable phases, resulting in different coding digits. A 3-bit tensor coding metasurface with three coding sequences is taken as an example to show its full-state controls in reflecting a normally incident THz beam to anomalous directions with cross-polarizations and making a spatially propagating wave (PW) to surface wave (SW) conversion at the THz frequency. We show that the proposed PW-SW convertor based on the tensor coding metasurface supports both x- and y-polarized normal incidences, producing cross-polarized transverse-magnetic and transverse-electric modes of THz SWs, respectively.

A time-domain (TD) line-integral (LI) representation of the physical-optics (PO) radiation integral is developed for the scattering from a perfectly conducting surface illuminated by an electric Hertzian dipole. The proposed LI representation, which is valid and singularity-free for all near-field observers, is derived directly in the TD by introducing dyad potentials. This TD representation can be further expressed in terms of geometric-optics and boundary-wave components of the scattering mechanisms, as in the conventional frequency-domain LI representations. Using the proposed LI representation, the computational complexity is reduced by an order of the scatterer’s linear electric size, compared with the straightforward numerical quadrature of the PO surface integral. Simple and complicated numerical examples are presented to demonstrate the efficiency and accuracy of the proposed TD-LI algorithm.

HLA-C*15:219 differs from HLA-C*15:02:01:01 by one nucleotide substitution at position 17 in exon 1.

HLA-DQB1*03:01:45 differs from HLA-DQB1*03:01:01:01 by one nucleotide substitution at position 636 (C>T).

HLA-DRB1*11:245 differs from HLA-DRB1*11:01:01:01 by one nucleotide substitution at position 505 (A>G).

Coding metasurfaces, composed of an array of coding particles with discrete phase responses, are encoded with predesigned coding sequences to manipulate wavefronts of electromagnetic (EM) waves and realize novel functionalities such as anomalous beam deflection, broadband diffusion, and polarization conversion. Such a new concept can be viewed as a bridge linking metamaterial and digital codes, yielding the investigation of metamaterials from a digital perspective and eventually the realization of real-time control of EM waves. Here, we propose and experimentally demonstrate a transmission-type coding metasurface to bend normally incident terahertz beams in anomalous directions and generate nondiffractive Bessel beams in normal and oblique directions. To overcome the larger reflection and strong Fabry–Perot resonance that usually originate from a thick silicon substrate, a free-standing design is presented for the coding particle, which is formed by stacking three metallic layers with four polyimide space...

This letter introduces the concept of regression structural similarity index measure (regression SSIM) and builds a supervised graph framework of automatic detection of small-size ultrawideband (UWB) radar targets. The twofold contribution made in this letter includes the following: 1) The regression SSIM is proposed to measure the similarity of the local pattern between a test image and a reference image; and 2) the framework of a supervised graph, together with the regression SSIM, has been developed to address the automatic detection of UWB radar objects. As opposed to other detection techniques reported in the literature, our methodology does not rely on statistical modeling or imposing typical shape parameters. Selected results of processing simulated and real UWB ground-penetrating radar data are provided, which verifies the state-of-the-art performance of the proposed methodology and provides important potential for a wide class of target detection.

To evaluate the urinary levels of 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in liver injury patients with hepatitis B virus (HBV) infection and to explore the relationship between urinary 8-oxo-dGsn or 8-oxo-Gsn and degree of liver damage. We enrolled 138 liver injury patients with HBV infection and 169 age- and sex-matched healthy controls in this study. A sensitive and accurate isotope-diluted liquid chromatograph mass spectrometer/mass spectrometer (LC-MS/MS) method was used to measure the urinary levels of 8-oxo-Gsn and 8-oxo-dGsn. Simultaneously, pathological analysis of liver biopsy tissues was carried out, and immunohistochemistry was carried out for 8-oxo-Guo, 8-oxo-dGuo and MTH1 protein in some liver injury tissues. We analysed the correlation between the degrees of inflammation and fibrosis and levels of 8-oxo-Gsn and 8-oxo-dGsn. We also analysed the levels of urinary 8-oxo-Gsn and 8-oxo-dGsn with clinical data of HBeAg, HBsAg, and HBV genotype and detected the levels of plasma aspartate aminotransferase, alanine aminotransferase (AST), platelet, alkaline phosphatase, prothrombin time (PT) and HBV DNA, and calculated the aspartate amino transferase-to-platelet ratio index (APRI) score. Nonparametric correlations were used to evaluate the correlation between 8-oxo-Gsn, 8-oxo-dGsn or APRI and various laboratory biochemical indicators. Results showed that the levels of urinary 8-oxo-Gsn and 8-oxo-dGsn in patients with liver injury were significantly higher than those of healthy controls (both p .001). Urinary 8-oxo-Gsn was significantly associated with AST, APRI and PT (p = .013, p = .026 and p = .049). The receiver operating characteristic curves of 8-oxo-Gsn were 0.696 (0.632-0.759) and 0.731 (0.672-0.790) for inflammatory activity and fibrosis, respectively. Patients with higher levels of urinary 8-oxo-Gsn are more likely to have a high degree of fibrosis and urinary 8-oxo-Gsn may have a great potential in assessing liver fibrosis.

HLA-C*07:02:107 differs from HLA-C*07:02:01:01 by one nucleotide substitution at position 978.

HLA-A*30:01:13 differs from HLA-A*30:01:01:01 by one nucleotide substitution at position 756.

Lesinurad is an oral inhibitor of urate-anion exchanger transporter 1 and has been approved by the US Food and Drug Administration for combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with refractory gout. In the present study, a sensitive and specific ultra high-performance liquid chromatography with tandem mass spectrometry assay was established and verified for the determination of lesinurad in rat plasma and was described in details for the first time. Chromatographic separation of lesinurad and diazepam (internal standard, IS) was performed on a Rapid Resolution HT C18 column (3.0 × 100 mm, 1.8 µm) using methanol–water (70:30, v/v) as the mobile phase at a flow rate of 0.3 mL/min. Lesinurad and IS were extracted from plasma by liquid–liquid extraction using ethyl acetate. The mass spectrometric detection was carried out using an electrospray ionization source in positive mode. Multiple reaction monitoring was used for quantification of the precursor to product ion at m/z 405.6 → 220.9 for lesinurad and m/z 285.1 → 192.8 for IS. The assay was well validated for selectivity, accuracy, precision, recovery, linearity, matrix effects, and stability. The verified method was applied to obtain the pharmacokinetic parameters and concentration–time profiles for lesinurad after oral/intravenous administration in rats. The study might provide an important reference and a necessary complement for the qualitative and quantitative evaluation of lesinurad. Electronic supplementary material The online version of this article (10.1186/s13065-017-0353-6) contains supplementary material, which is available to authorized users.

HLA-DRB1*07:01:22 differs from HLA-DRB1*07:01:01:01 at position 244 (CT) in exon 2.

HLA-A*02:07:10 differs from HLA-A*02:07:01 by one nucleotide substitution at position 117.

Aim: To systematically investigate the genetic polymorphisms of the CYP3A4 gene in a Han Chinese population. Materials & methods: The promoter and exons of CYP3A4 gene in 1114 unrelated, healthy Han Chinese subjects were amplified and genotyped by direct sequencing. Results: In total, five previously reported alleles (*1G, *4, *5, *18B and *23) were detected, of which one allele (*23) was reported for the first time in Han Chinese population. Additionally, seven novel exonic variants were also identified and designated as new alleles CYP3A4*28–*34. Conclusion: This study provides the most comprehensive data of CYP3A4 polymorphisms in Han Chinese population and detects the largest number of novel CYP3A4 alleles in one ethnic group.