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Parameter recovery and item utilization were investigated for different designs for online test item calibration. The design was adaptive in a double sense: it assumed both adaptive testing of examinees from an operational pool of previously calibrated items and adaptive assignment of field-test items to the examinees. Four criteria of optimality for the assignment of the field-test items were used, each of them based on the information in the posterior distributions of the examinee’s ability parameter during adaptive testing as well as the sequentially updated posterior distributions of the field-test item parameters. In addition, different stopping rules based on target values for the posterior standard deviations of the field-test parameters and the size of the calibration sample were used. The impact of each of the criteria and stopping rules on the statistical efficiency of the estimates of the field-test parameters and on the time spent by the items in the calibration procedure was investigated. Recommendations as to the practical use of the designs are given.
Species of epiphytic microbiota are closely associated with the fermentation performance of natural forage silage. This study aimed to evaluate the dynamic microbial communities, fermentation parameters, and aerobic stability of Napier grass silage from the same variety and growth period but harvested from three different regions (NGP1, NGP2, and NGP3). After 60 days of ensiling, triplicate silos were opened for sampling and testing aerobic stability. The epiphytic microbiota with higher relative abundances in fresh Napier grass (NGP1, NGP2, and NGP3) were Weissella, Enterobacter, and Lactococcus, respectively. After 60 days of ensiling, NGP3 exhibited higher fermentation quality, indicated by higher lactic acid (LA) concentration and lower pH than that of NGP1 and NGP2. The NH3–N content of all treatments was lower than 100 g/kg total nitrogen. Compared with NGP1 and NGP2 silage, NGP3 silage exhibited a sharp rise in pH and LA consumption during air exposure. After 7 days of air exposure, NGP3 had higher ethanol concentrations and pH. Ruminiclostridium_5, Pediococcus, and Lactobacillus predominated in NGP1, NGP2, and NGP3 silages, respectively, whereas Candida and Monascus predominated in air-exposed NGP3 silage. The bacterial co-occurrence networks from fresh samples to ensiling and air exposure became more complex; however, NGP3 had a higher negative correlation with co-occurrence after air exposure. Different regions had significant effects on the fermentation patterns, bacterial communities, and aerobic stability of Napier grass silage. This was mainly due to variable epiphytic microbiota. Higher fermentation quality of Napier grass silage may also result in accelerated spoilage due to air exposure. Candida and Monascus were primarily responsible for the lower dry matter recovery and higher ethanol contents and air exposure spoilage of Napier grass silage.
The dynamic charge density of KZnB3O6, which contains edge-sharing BO4 units, has been characterized using laboratory and synchrotron X-ray diffraction techniques. The experimental electron density distribution (EDD) was constructed using the maximum-entropy method (MEM) from single crystal diffraction data obtained at 81 and 298 K. Additionally, MEM-based pattern fitting (MPF) method was employed to refine the synchrotron powder diffraction data obtained at 100 K. Both the room-temperature single crystal diffraction data and the cryogenic synchrotron powder diffraction data reveal an intriguing phenomenon: the edge-shared B2O2 ring exhibits a significant charge density accumulation between the O atoms. Further analysis of high-quality single crystal diffraction data collected at 81 K, with both high resolution and large signal-to-noise ratio, reveals no direct O–O bonding within the B2O2 ring. The experimental EDD of KZnB3O6 obtained aligns with the results obtained from ab-initio calculations. Our work underscores the importance of obtaining high-quality experimental data to accurately determine EDDs.
Dual anterior interventricular artery is a rare type of CHD. We reported a fifteen-year-old girl who underwent CT angiography that demonstrated one anterior interventricular artery from aorta and another from pulmonary artery.
The laboratory generation and diagnosis of uniform near-critical-density (NCD) plasmas play critical roles in various studies and applications, such as fusion science, high energy density physics, astrophysics as well as relativistic electron beam generation. Here we successfully generated the quasistatic NCD plasma sample by heating a low-density tri-cellulose acetate (TCA) foam with the high-power-laser-driven hohlraum radiation. The temperature of the hohlraum is determined to be 20 eV by analyzing the spectra obtained with the transmission grating spectrometer. The single-order diffraction grating was employed to eliminate the high-order disturbance. The temperature of the heated foam is determined to be T = 16.8 ± 1.1 eV by analyzing the high-resolution spectra obtained with a flat-field grating spectrometer. The electron density of the heated foam is about under the reasonable assumption of constant mass density.
In preparation for an experiment with a laser-generated intense proton beam at the Laser Fusion Research Center at Mianyang to investigate the 11B(p,α)2α reaction, we performed a measurement at very low proton energy between 140 keV and 172 keV using the high-voltage platform at the Institute of Modern Physics, Lanzhou. The aim of the experiment was to test the ability to use CR-39 track detectors for cross-section measurements and to remeasure the cross-section of this reaction close to the first resonance using the thick target approach. We obtained the cross-section σ = 45.6 ± 12.5 mb near 156 keV. Our result confirms the feasibility of CR-39 type track detector for nuclear reaction measurement also in low-energy regions.
The flying wing is an aerodynamic configuration with high efficiency, but the lack of lateral-directional stability has always been an obstacle that limits its application. In this study, the wing rock motion of a 65° swept flying-wing aircraft is studied via wind tunnel experiments and numerical simulations at a low speed, and various unsteady motion phenomena are focused on. Both the experimental and numerical results show that the flying wing has a bicyclic ${C_l}$–$\phi $ hysteresis loop during its wing rock, different from the slender delta wing, rectangular wing, generic aircraft configuration, etc., which have a tricyclic hysteresis loop. This form of hysteresis loop implies a different energy exchange manner of the flying wing in the wing rock oscillation. Further analysis shows that the flying wing forms a unilateral leading-edge vortex (LEV) under a high roll angle, with its wing rock oscillation driven by the ‘vortex–shear-layer’ structure, which is different from that of slender and non-slender delta wings. Moreover, the quantitative dynamic hysteresis characteristics of the LEV's strength and location for the flying wing and the slender delta wing are also different. These results have proven the existence of a wing rock mode which is different from previous investigations, which enriches the understanding of self-induced oscillation. Present discoveries are also conducive to the aerodynamic shape design and flight manipulation of a flying-wing aircraft, which is significant for its wider application.
The G protein-coupled receptors (GPCR) sensing nutritional signals (amino acids, fatty acids, glucose, etc.) are not fully understood. In this research, we used transcriptome sequencing to analyse differentially expressed genes (DEG) in mouse mammary gland tissues at puberty, lactation and involution stages, in which eight GPCR were selected out and verified by qRT-PCR assay. It was further identified the role of GPR110-mediating nutrients including palmitic acid (PA) and methionine (Met) to improve milk synthesis using mouse mammary epithelial cell line HC11. PA but not Met affected GPR110 expression in a dose-dependent manner. GPR110 knockdown decreased milk protein and fat synthesis and cell proliferation and blocked the stimulation of PA on mechanistic target of rapamycin (mTOR) phosphorylation and sterol-regulatory element binding protein 1c (SREBP-1c) expression. In summary, these experimental results disclose DEG related to lactation and reveal that GPR110 mediates PA to activate the mTOR and SREBP-1c pathways to promote milk protein and fat synthesis.
Instrument delivery is critical part in vascular intervention surgery. Due to the soft-body structure of instruments, the relationship between manipulation commands and instrument motion is non-linear, making instrument delivery challenging and time-consuming. Reinforcement learning has the potential to learn manipulation skills and automate instrument delivery with enhanced success rates and reduced workload of physicians. However, due to the sample inefficiency when using high-dimensional images, existing reinforcement learning algorithms are limited on realistic vascular robotic systems. To alleviate this problem, this paper proposes discrete soft actor-critic with auto-encoder (DSAC-AE) that augments SAC-discrete with an auxiliary reconstruction task. The algorithm is applied with distributed sample collection and parameter update in a robot-assisted preclinical environment. Experimental results indicate that guidewire delivery can be automatically implemented after 50k sampling steps in less than 15 h, demonstrating the proposed algorithm has the great potential to learn manipulation skill for vascular robotic systems.
Several amino acids can stimulate milk synthesis in mammary epithelial cells (MEC); however, the regulatory role of isoleucine (Ile) and underlying molecular mechanism remain poorly understood. In this study, we aimed to evaluate the regulatory effects of Ile on milk protein and fat synthesis in MEC and reveal the mediation mechanism of Brahma-related gene 1 (BRG1) on this regulation. Ile dose dependently affected milk protein and fat synthesis, mechanistic target of rapamycin (mTOR) phosphorylation, sterol regulatory element binding protein 1c (SREBP-1c) expression and maturation, and BRG1 protein expression in bovine MEC. Phosphatidylinositol 3 kinase (PI3K) inhibition by LY294002 treatment blocked the stimulation of Ile on BRG1 expression. BRG1 knockdown and gene activation experiments showed that it mediated the stimulation of Ile on milk protein and fat synthesis, mTOR phosphorylation, and SREBP-1c expression and maturation in MEC. ChIP-PCR analysis detected that BRG1 bound to the promoters of mTOR and SREBP-1c, and ChIP-qPCR further detected that these bindings were increased by Ile stimulation. In addition, BRG1 positively regulated the binding of H3K27ac to these two promoters, while it negatively affected the binding of H3K27me3 to these promoters. BRG1 knockdown blocked the stimulation of Ile on these two gene expressions. The expression of BRG1 was higher in mouse mammary gland in the lactating period, compared with that in the puberty or dry period. Taken together, these experimental data reveal that Ile stimulates milk protein and fat synthesis in MEC via the PI3K-BRG1-mTOR/SREBP-1c pathway.
Streptococcus agalactiae (S. agalactiae) infection is a significant cause of mastitis, resulting in loss of cellular homeostasis and tissue damage. Autophagy plays an essential function in cell survival, defense, and the preservation of cellular homeostasis, and is often part of the response to pathogenic challenge. However, the effect of autophagy induced by S. agalactiae in bovine mammary epithelial cells (bMECs) is mainly unknown. So in this study, an intracellular S. agalactiae infection model was established. Through evaluating the autophagy-related indicators, we observed that after S. agalactiae infection, a significant quantity of LC3-I was converted to LC3-II, p62 was degraded, and levels of Beclin1 and Bcl2 increased significantly in bMECs, indicating that S. agalactiae induced autophagy. The increase in levels of LAMP2 and LysoTracker Deep Red fluorescent spots indicated that lysosomes had participated in the degradation of autophagic contents. After autophagy was activated by rapamycin (Rapa), the amount of p-Akt and p-mTOR decreased significantly, whilst the amount of intracellular S. agalactiae increased significantly. Whereas the autophagy was inhibited by 3-methyladenine (3MA), the number of intracellular pathogens decreased. In conclusion, the results demonstrated that S. agalactiae could induce autophagy through PI3K/Akt/mTOR pathway and utilize autophagy to survive in bMECs.
The optimization of laser pulse shapes is of great importance and a major challenge for laser direct-drive implosions. In this paper, we propose an efficient intelligent method to perform laser pulse optimization via hydrodynamic simulations guided by the genetic algorithm and random forest algorithm. Compared to manual optimizations, the machine-learning guided method is able to efficiently improve the areal density by a factor of 63% and reduce the in-flight-aspect ratio by a factor of 30% at the same time. A relationship between the maximum areal density and ion temperature is also achieved by the analysis of the big simulation dataset. This design method has been successfully demonstrated by the 2021 summer double-cone ignition experiments conducted at the SG-II upgrade laser facility and has great prospects for the design of other inertial fusion experiments.
Taurine (Tau) has many profound physiological functions, but its role and molecular mechanism in muscle cells are still not fully understood. In this study, we investigated the role and underlying molecular mechanism of Tau on protein synthesis and proliferation of C2C12 myoblast cells. Cells were treated with Tau (0, 60, 120, 180 and 240 μM) for 24 h. Tau dose-dependently promoted protein synthesis, cell proliferation, mechanistic target of rapamycin protein (mTOR) phosphorylation and also AT-rich interaction domain 4B (ARID4B) expression, with the best stimulatory effects at 120 μM. LY 294002 treatment showed that Tau promoted ARID4B expression in a phosphoinositide 3-kinase (PI3K)-dependent manner. ARID4B knockdown (by small interfering RNA transfection for 24 h) prevented Tau from stimulating protein synthesis and cell proliferation, whereas ARID4B gene activation (using the CRISPR/dCas9 technology) had stimulatory effects. ARID4B knockdown abolished Tau signalling to mRNA expression and protein phosphorylation of mTOR, whereas ARID4B gene activation had stimulatory effects. Chromatin immunoprecipitation (ChIP)-PCR identified that all of ARID4B, H3K27ac and H3K27me3 bound to the −4368 to –4591 bp site in the mTOR promoter, and ChIP-quantitative PCR (qPCR) further detected that Tau stimulated ARID4B binding to this site. ARID4B knockdown or gene activation did not affect H3K27me3 binding to the mTOR promoter but decreased or increased H3K27ac binding, respectively. Furthermore, ARID4B knockdown abolished the stimulation of Tau on H3K27ac binding to the mTOR promoter. In summary, these data uncover that Tau promotes protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway, providing a deep understanding of how Tau regulates anabolism in muscle cells.
Thermally driven vertical convection (VC) – the flow in a box heated on one side and cooled on the other side, is investigated using direct numerical simulations with Rayleigh numbers over the wide range of $10^7\le Ra\le 10^{14}$ and a fixed Prandtl number $Pr=10$ in a two-dimensional convection cell with unit aspect ratio. It is found that the dependence of the mean vertical centre temperature gradient $S$ on $Ra$ shows three different regimes: in regime I ($Ra \lesssim 5\times 10^{10}$), $S$ is almost independent of $Ra$; in the newly identified regime II ($5\times 10^{10} \lesssim Ra \lesssim 10^{13}$), $S$ first increases with increasing $Ra$ (regime $\textrm {{II}}_a$), reaches its maximum and then decreases again (regime $\textrm {{II}}_b$); and in regime III ($Ra\gtrsim 10^{13}$), $S$ again becomes only weakly dependent on $Ra$, being slightly smaller than in regime I. The transition from regime I to regime II is related to the onset of unsteady flows arising from the ejection of plumes from the sidewall boundary layers. The maximum of $S$ occurs when these plumes are ejected over approximately half of the area (downstream) of the sidewalls. The onset of regime III is characterized by the appearance of layered structures near the top and bottom horizontal walls. The flow in regime III is characterized by a well-mixed bulk region owing to continuous ejection of plumes over large fractions of the sidewalls, and, as a result of the efficient mixing, the mean temperature gradient in the centre $S$ is smaller than that of regime I. In the three different regimes, significantly different flow organizations are identified: in regime I and regime $\textrm {{II}}_a$, the location of the maximal horizontal velocity is close to the top and bottom walls; however, in regime $\textrm {{II}}_b$ and regime III, banded zonal flow structures develop and the maximal horizontal velocity now is in the bulk region. The different flow organizations in the three regimes are also reflected in the scaling exponents in the effective power law scalings $Nu\sim Ra^\beta$ and $Re\sim Ra^\gamma$. Here, $Nu$ is the Nusselt number and $Re$ is the Reynolds number based on maximal vertical velocity (averaged over vertical direction). In regime I, the fitted scaling exponents ($\beta \approx 0.26$ and $\gamma \approx 0.51$) are in excellent agreement with the theoretical predictions of $\beta =1/4$ and $\gamma =1/2$ for laminar VC (Shishkina, Phys. Rev. E., vol. 93, 2016, 051102). However, in regimes II and III, $\beta$ increases to a value close to 1/3 and $\gamma$ decreases to a value close to 4/9. The stronger $Ra$ dependence of $Nu$ is related to the ejection of plumes and the larger local heat flux at the walls. The mean kinetic dissipation rate also shows different scaling relations with $Ra$ in the different regimes.
It is commonly accepted that the breakup criteria of drops or bubbles in turbulence is governed by surface tension and inertia. However, also buoyancy can play an important role at breakup. In order to better understand this role, here we numerically study two-dimensional Rayleigh–Bénard convection for two immiscible fluid layers, in order to identify the effects of buoyancy on interface breakup. We explore the parameter space spanned by the Weber number $5\leqslant We \leqslant 5000$ (the ratio of inertia to surface tension) and the density ratio between the two fluids $0.001 \leqslant \varLambda \leqslant 1$, at fixed Rayleigh number $Ra=10^8$ and Prandtl number $Pr=1$. At low $We$, the interface undulates due to plumes. When $We$ is larger than a critical value, the interface eventually breaks up. Depending on $\varLambda$, two breakup types are observed. The first type occurs at small $\varLambda \ll 1$ (e.g. air–water systems) when local filament thicknesses exceed the Hinze length scale. The second, strikingly different, type occurs at large $\varLambda$ with roughly $0.5 < \varLambda \leqslant 1$ (e.g. oil–water systems): the layers undergo a periodic overturning caused by buoyancy overwhelming surface tension. For both types, the breakup criteria can be derived from force balance arguments and show good agreement with the numerical results.
To determine whether a potassium dihydrogen phosphate (KDP) surface mitigated by micro-milling would potentially threaten downstream optics, we calculated the light-field modulation based on angular spectrum diffraction theory, and performed a laser damage test on downstream fused silica. The results showed that the downstream light intensification caused by a Gaussian mitigation pit of 800 μm width and 10 μm depth reached a peak value near the KDP rear surface, decreased sharply afterward, and eventually kept stable with the increase in downstream distance. The solved peak value of light intensification exceeded 6 in a range 8–19 mm downstream from the KDP rear surface, which is the most dangerous for downstream optics. Laser damage sites were then induced on the fused silica surface in subsequent laser damage tests. When the distance downstream was greater than 44 mm with a downstream light intensification of less than 3, there were no potential damage threats to downstream optics. The study proves that a mitigated KDP surface can cause laser damage to downstream optical components, to which attention should be paid in an actual application. Through this work, we find that the current manufacturing process and the mitigation index still need to be improved. The research methods and calculation models are also of great reference significance for related studies like optics mitigation and laser damage.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
Aims
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Method
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
Results
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
Conclusions
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.