Hydrodynamic approaches that treat granular materials as a continuum via the homogenization of discrete flow properties have become viable options for efficient predictions of bulk flow behaviours. However, simplified boundary conditions in computational fluid dynamics are often adopted, which have difficulty in describing the complex stick–slip phenomenon at the boundaries. This paper extends the lattice Boltzmann method for granular flow simulations by incorporating a novel frictional boundary condition. The wall slip velocity is first calculated based on the shear rate limited by the Coulomb friction, followed by the reconstruction of unknown density distribution functions through a modified bounce-back scheme. Validation is performed against a unique plane Couette flow configuration, and the analytical solutions for the flow velocity profile and the wall slip velocity, as functions of the friction coefficient, are reproduced by the numerical model. The transition between no-slip and partial-slip regimes is captured well, but the convergence rate drops from second order to first order when slip occurs. The rheological parameters and the basal friction coefficient are calibrated further against the discrete element simulation of a square granular column collapsing over a horizontal bottom plane. It is found that the calibrated continuum model can predict other granular column collapses with different initial aspect ratios and slope inclination angles, including the basal slip and the complex internal flow structures, without any further adjustments to the model parameters. This highlights the generalization ability of the numerical model, which has a wide range of application in granular flow predictions and controls.

The target backsheath field acceleration mechanism is one of the main mechanisms of laser-driven proton acceleration (LDPA) and strongly depends on the comprehensive performance of the ultrashort ultra-intense lasers used as the driving sources. The successful use of the SG-II Peta-watt (SG-II PW) laser facility for LDPA and its applications in radiographic diagnoses have been manifested by the good performance of the SG-II PW facility. Recently, the SG-II PW laser facility has undergone extensive maintenance and a comprehensive technical upgrade in terms of the seed source, laser contrast and terminal focus. LDPA experiments were performed using the maintained SG-II PW laser beam, and the highest cutoff energy of the proton beam was obviously increased. Accordingly, a double-film target structure was used, and the maximum cutoff energy of the proton beam was up to 70 MeV. These results demonstrate that the comprehensive performance of the SG-II PW laser facility was improved significantly.

Planting patterns have significant effects on rice growth. Nonetheless, little is known about differences in annual crop yield and resource utilization among mechanized rice planting patterns in a rice–wheat cropping system. Field experiments were conducted from 2014 to 2017 using three treatments: pot seedling transplanting for rice and row sowing for wheat (PST-RS), carpet seedling transplanting for rice and row sowing for wheat (CST-RS) and row sowing for both crops (RS-RS). The results showed that, compared with RS-RS, PST-RS and CST-RS prolonged annual crop growth duration by 25–26 and 13–15 days, increased effective accumulated temperature by 399 and 212°C days and increased cumulative solar radiation by 454 and 228 MJ/m2 because of the earlier sowing of rice by 28 and 16 days in PST-RS and CST-RS, respectively. Compared with RS-RS, the annual crop yield of PST-RS and CST-RS increased by 3.1–3.8 and 2.0–2.6 t/ha, respectively, because of the increase in the number of spikelets/kernels per hectare, aboveground biomass, mean leaf area index and grain–leaf ratio. In addition, temperature production efficiency, solar radiation production efficiency and solar radiation use efficiency were higher in PST-RS, followed by CST-RS and RS-RS. These results suggest that mechanized rice planting patterns such as PST-RS increase annual crop production in rice–wheat cropping systems by increasing yield and solar energy utilization.

We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.

The long-distance stable transport of relativistic electron beams (REBs) in plasmas is studied by full three-dimensional particle-in-cell simulations. Theoretical analysis shows that the beam transport is mainly influenced by three transverse instabilities, where the excitation of self-modulation instability, and the suppression of the filamentation instability and the hosing instability are important to realize the beam stable transport. By modulating the transport parameters such as the electron density ratio, the relativistic Lorentz factor, the beam envelopes and the density profiles, the relativistic bunches having a smooth density profile and a length of several plasma wave periods can suppress the beam-plasma instabilities and propagate in plasmas for long distances with small energy losses. The results provide a reference for the research of long-distance and stable transport of REBs, and would be helpful for new particle beam diagnosis technology and space active experiments.

ABSTRACT IMPACT: This work will standardize necessary image pre-processing for diagnostic and prognostic clinical workflows dependent on quantitative analysis of conventional magnetic resonance imaging. OBJECTIVES/GOALS: Conventional magnetic resonance imaging (MRI) poses challenges for quantitative analysis due to a lack of uniform inter-scanner voxel intensity values. Head and neck cancer (HNC) applications in particular have not been well investigated. This project aims to systematically evaluate voxel intensity standardization (VIS) methods for HNC MRI. METHODS/STUDY POPULATION: We utilize two separate cohorts of HNC patients, where T2-weighted (T2-w) MRI sequences were acquired before beginning radiotherapy for five patients in each cohort. The first cohort corresponds to patients with images taken at various institutions with a variety of non-uniform acquisition scanners and parameters. The second cohort corresponds to patients from a prospective clinical trial with uniformity in both scanner and acquisition parameters. Regions of interest from a variety of healthy tissues assumed to have minimal interpatient variation were manually contoured for each image and used to compare differences between a variety of VIS methods for each cohort. Towards this end, we implement a new metric for cohort intensity distributional overlap to compare region of interest similarity in a given cohort. RESULTS/ANTICIPATED RESULTS: Using a simple and interpretable metric, we have systematically investigated the effects of various commonly implementable VIS methods on T2-w sequences for two independent cohorts of HNC patients based on region of interest intensity similarity. We demonstrate VIS has a substantial effect on T2-w images where non-uniform acquisition parameters and scanners are utilized. Oppositely, it has a modest to minimal impact on T2-w images generated from the same scanner with the same acquisition parameters. Moreover, with a few notable exceptions, there does not seem to be a clear advantage or disadvantage to using one VIS method over another for T2-w images with non-uniform acquisition parameters. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results inform which VIS methods should be favored in HNC MRI and may indicate VIS is not a critical factor to consider in circumstances where similar acquisition parameters can be utilized. Moreover, our results can help guide downstream quantitative imaging tasks that may one day be implemented in clinical workflows.

The aim of this study was to explore the frequency and distribution of gene mutations that are related to isoniazid (INH) and rifampin (RIF)-resistance in the strains of the multidrug-resistant tuberculosis (MDR-TB) Mycobacterium tuberculosis (M.tb) in Beijing, China. In this retrospective study, the genotypes of 173 MDR-TB strains were analysed by spoligotyping. The katG, inhA genes and the promoter region of inhA, in which genetic mutations confer INH resistance; and the rpoB gene, in which genetic mutations confer RIF resistance, were sequenced. The percentage of resistance-associated nucleotide alterations among the strains of different genotypes was also analysed. In total, 90.8% (157/173) of the MDR strains belonged to the Beijing genotype. Population characteristics were not significantly different among the strains of different genotypes. In total, 50.3% (87/173) strains had mutations at codon S315T of katG; 16.8% (29/173) of strains had mutations in the inhA promoter region; of them, 5.5% (15/173) had point mutations at −15 base (C→T) of the inhA promoter region. In total, 86.7% (150/173) strains had mutations at rpoB gene; of them, 40% (69/173) strains had mutations at codon S531L of rpoB. The frequency of mutations was not significantly higher in Beijing genotypic MDR strains than in non-Beijing genotypes. Beijing genotypic MDR-TB strains were spreading in Beijing and present a major challenge to TB control in this region. A high prevalence of katG Ser315Thr, inhA promoter region (−15C→T) and rpoB (S531L) mutations was observed. Molecular diagnostics based on gene mutations was a useful method for rapid detection of MDR-TB in Beijing, China.

The Dimits shift is the shift between the threshold of the drift-wave primary instability and the actual onset of turbulent transport in a magnetized plasma. It is generally attributed to the suppression of turbulence by zonal flows, but developing a more detailed understanding calls for consideration of specific reduced models. The modified Terry–Horton system has been proposed by St-Onge (J. Plasma Phys., vol. 83, 2017, 905830504) as a minimal model capturing the Dimits shift. Here, we use this model to develop an analytic theory of the Dimits shift and a related theory of the tertiary instability of zonal flows. We show that tertiary modes are localized near extrema of the zonal velocity $U(x)$, where $x$ is the radial coordinate. By approximating $U(x)$ with a parabola, we derive the tertiary-instability growth rate using two different methods and show that the tertiary instability is essentially the primary drift-wave instability modified by the local $U'' \doteq {\rm d}^2 U/{\rm d} x^2 $. Then, depending on $U''$, the tertiary instability can be suppressed or unleashed. The former corresponds to the case when zonal flows are strong enough to suppress turbulence (Dimits regime), while the latter corresponds to the case when zonal flows are unstable and turbulence develops. This understanding is different from the traditional paradigm that turbulence is controlled by the flow shear $| {\rm d} U / {\rm d} x |$. Our analytic predictions are in agreement with direct numerical simulations of the modified Terry–Horton system.

Metabolic syndrome induced by atypical antipsychotics is more prevalence in schizophrenic patients. Much less is known regarding paliperidone ER. The objective of this study was to compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. Eighty hospitalized patients with schizophrenia (DSM-) were randomly assigned to treatment with paliperidone ER or olanzapine for 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density level (HDL) cholesterol, low density level (LDL) cholesterol and prolactin. And we also evaluate the body mass index (BMI), homeostasis insulin resistance (HOMA-IR) and homeostasis β-cell function (HOMA-B). 33 patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine completed the entire 12-week treatment. Within-group overall analysis showed that the fasting measures were increased in weight, BMI, waist circumferences, hip circumferences, subcutaneous fat, cholesterol, triglyceride and prolactin for two groups, and fasting glucose, LDL and HOMA-B were increased for olanzapine group. There was significantly difference in serum prolactin between paliperidone ER and olanzapine group. And there was a trend for HOMA-B to increase in olanzapine group over 12 weeks compared to paliperidone ER group. However, there were no overall differential drug effects over 12 weeks on the fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride and HOMA-IR. The study further reinforces the necessity of regular monitoring the metabolic parameters in schizophrenic patients with atypical antipsychotics including paliperidone ER.

Starch digestion in the small intestines of the dairy cow is low, to a large extent, due to a shortage of syntheses of α-amylase. One strategy to improve the situation is to enhance the synthesis of α-amylase. The mammalian target of rapamycin (mTOR) signalling pathway, which acts as a central regulator of protein synthesis, can be activated by leucine. Our objectives were to investigate the effects of leucine on the mTOR signalling pathway and to define the associations between these signalling activities and the synthesis of pancreatic enzymes using an in vitro model of cultured Holstein dairy calf pancreatic tissue. The pancreatic tissue was incubated in culture medium containing l-leucine for 3 h, and samples were collected hourly, with the control being included but not containing l-leucine. The leucine supplementation increased α-amylase and trypsin activities and the messenger RNA expression of their coding genes (P <0.05), and it enhanced the mTOR synthesis and the phosphorylation of mTOR, ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 (P <0.05). In addition, rapamycin inhibited the mTOR signal pathway factors during leucine treatment. In sum, the leucine regulates α-amylase and trypsin synthesis in dairy calves through the regulation of the mTOR signal pathways.

We demonstrate a suspended graphene-(poly(methyl methacrylate) (PMMA) polymer angular displacement actuator enabled by variable elastic modulus of the perforated stacked structure. Azimuthal flexures support a central disc-shaped membrane, and compression of the membrane can be used to control the rotation of the entire structure. Irradiating the PMMA on graphene stack with 5 kV electrons in a convention scanning electron microscope reduces the elastic modulus of the PMMA and allows graphene’s built in strain to dominate and compress the flexures, thus rotating the actuator.

Background: Human induced pluripotent stem cell-derived neural stem cells (hiPS-NSCs) represent an exciting therapeutic approach for traumatically spinal cord injury (SCI). Unfortunately, most patients are the in chronic injury phase where a dense perilesional chondroitin sulfate proteoglycan (CSPG) scar significantly hinders regeneration. CSPG-degrading enzymes can enhance NSC-mediated recovery, however, nonspecific intrathecal administration causes off-target effects. We aimed to genetically engineer hiPS-NSCs to express a scar-degrading ENZYME into their local environment to enhance functional recovery. Methods: A bicistronic scar-degrading ENZYME and RFP reporter vector was non-virally integrated into hiPS-NSCs and monoclonalized. ENZYME activity was assessed by WST-1 and DMMB biochemical assays and an in vitro CSPG spot assay with hiPS-NSC-derived neurons. To assess in vivo efficacy, T-cell deficient rats (N=60) with chronic (8wk) C6-7 SCIs were randomized to receive (1)SMaRT cells, (2)hiPS-NSCs, (3)vehicle, or (4)sham surgery. Results: SMaRT cells retained key hiPS-NSC characteristics while stably expressing ENZYME. The expressed ENZYME could appropriately degrade in vitro and ex vivo CSPGs. While blinded neurobehavioural and immunohistochemical assessments are ongoing at 40wks post-injury, an interim analysis demonstrated human cells extending remarkably long (≥20,000µm) axons along host white matter tracts. Conclusions: This work provides exciting proof-of-concept data that genetically-engineered SMaRT cells can degrade CSPGs and human NSCs can extend long-distance processes in chronic SCI.

This cross-sectional study aimed to examine and compare prevalence and correlates of whole blood Epstein–Barr virus (EBV) DNA between HIV-positive and HIV-negative men who have sex with men (MSM). Five hundred and four HIV-positive MSM and 504 age-matched HIV-negative MSM were recruited from an HIV counseling and testing clinic in Shanghai, China from November 2014 to November 2015 and were administered with a face-to-face questionnaire interview. Whole blood EBV DNA was tested by nested polymerase chain reaction assays on EBNA-1, EBNA-2, and LMP-1 genes. The prevalence of whole blood EBV DNA was 56·0% (95% CI 51·7–60·3%) among HIV-positive MSM and 26·0% (95% CI 22·4–30·0%) among HIV-negative MSM. Whole blood EBV DNA positivity was significantly associated with HIV infection (adjusted odds ratio (aOR) 3·43, 95% CI 2·58–4·57) and frequent intake of pickled, smoked, or salty food (aOR 1·71, 95% CI 1·02–2·86) in the whole sample, and with <200 cells/μl CD4 cell counts (aOR 1·79, 95% CI 1·05–3·05) and pickled, smoked, or salty food intake (aOR 3·14, 95% CI 1·39–7·08) in HIV-positive group. HIV-infected MSM are at higher risk of active EBV replication than HIV-uninfected MSM, underscoring needs of surveillance and research on EBV-related carcinogenesis in this population.

Pig farmers and veterinarians have high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) due to the occupational livestock exposure, while few reported this association on slaughterhouse workers. We conducted this cross-sectional study to explore the phenotypic and molecular characteristics of S. aureus and MRSA in slaughterhouse pig-related workers and control workers in Guangdong Province, China. Participants were interviewed and provided two nasal swabs. Swabs were tested for S. aureus, and isolates were further tested for antimicrobial susceptibility, virulence genes and multi-locus sequence typing. Compared with control workers, pig-related workers have significantly higher prevalence of MRSA carriage (adjusted odd ratio (aOR) 3·70, 95% CI 1·63–8·40). The proportions of MRSA resistant to clindamycin, erythromycin, tetracycline or chloromycetin were significantly higher in pig-related workers than in control workers. The predominant phenotypes of S. aureus were resistant to penicillin, clindamycin, erythromycin and tetracycline. Three MRSA CC9 isolates with livestock-associated characteristics (resistance to tetracycline and absence of immune evasion cluster (IEC) genes) were detected in pig-related workers but not in control workers. For human-associated CCs (CC7, CC59, CC6, and CC188), there was no significant difference in IEC profile or antimicrobial resistance between the groups. These findings reveal that there may be a potential risk for livestock-to-human transmission of LA-MRSA and human-to-human transmission of human-associated MRSA.

A review of Holocene climatic variations in different parts of China shows that they were asynchronous. Proxy data from ice cores, pollen, loess, lacustrine sediments, and changes of sea and lake levels demonstrate that many warm and cold oscillations have occurred in China during the Holocene, including a most important climatic event known as the “Holocene optimum,” a milder and wetter period, and that the duration and amplitude of the optimum period, as well as its start and end times, differed in different parts of China. Uplift of the Tibetan plateau over the past millions of years led to the development of the monsoon climate and to complex atmospheric circulation over continental China during the Holocene. As a result, the Holocene optimum began and terminated earlier in high-altitude regions of western China than at lower elevations in eastern China, and the amplitude of the variations was lower in the east. This suggests that the western higher-altitude areas were more sensitive to climatic change than were the eastern lower-altitude areas. Holocene climatic records in the Dunde and Guliya ice cores do not correspond. Inverse δ18O variations between the two cores indicate that the effects of climate and atmospheric processes on the stable isotopes at the two sites differed. The correlation between the isotopic composition of carbonates in lake deposits in western China and climatic variations is similar to that in the ice cores. The climatic resolution in ice cores and lake sediments is higher than that in other media. The lack of precise correspondence of climatic records constructed on the basis of proxy data from different parts of China is a result of the different locations and elevations of the sampling sites, the different resolutions of the source material, and the varied climatic conditions within China. Further work is needed to confirm both the conclusions and the inferences presented here.