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Glytrexate, developed by our team, as a novel multitarget folate antagonist, has inhibitory effects on a variety of cancer cell types, especially KB tumor cells (IC50 0.078 nM), and thus has antitumor drug development prospects. However, its pharmacokinetics and plasma protein binding properties remain unknown. In this study a selective and sensitive liquid chromatography-tandem mass spectrometry (LC‒MS/MS) method was developed and verified to facilitate biological analysis. The bioanalysis method was applied to evaluate the stability, plasma protein binding, and pharmacokinetics of glytrexate. Glytrexate is more stable in human plasma than in rat plasma and in human liver microsomes. The binding of glytrexate to human plasma proteins was higher than that to rat plasma proteins, both of which were less than 30%, suggesting that glytrexate may be at a higher concentration at the pharmacologic target receptor(s) in tissues. Pharmacokinetic characteristics were determined by noncompartmental analysis after administration of single oral (12.5, 25 and 50 mg/kg) and intravenous (2 mg/kg) doses in rats. According to the rat oral pharmacokinetic characteristics, glytrexate had linear dynamics in a dose range of 12.5–50 mg/kg and a poor oral bioavailability of 0.57–1.15%. The investigation revealed that the intravenous half-life, AUC, and Cmax of glytrexate were higher than those of pemetrexed. Pemetrexed is generally produced as an injection preparation. This provides ideas for the development of glytrexate formulations. Therefore, glytrexate injection has clinical application prospects compared to oral administration. This study provides a basis for further investigations into the pharmacological effects and clinical uses of glytrexate.

In order to improve the efficiency of energy recovery of hybrid virtual track train, an energy management method based on the strategy of working condition segmentation is proposed under the condition of known line information. This method adjusts the power allocation of power battery and supercapacitor in different power modes of virtual track train. Based on the environment of MATLAB/Simulink, a simulation system for energy recovery of virtual track train is developed. Then this paper carries on the simulation analysis. The simulation results show that the proposed energy management method can achieve more efficient energy recovery under the condition of meeting the train power demand. After optimization, the power output of the train's power battery is reduced by 9.9%, and the recovery rate of the train's braking energy is increased by 9.3%.

Doudou Zheng,1,* Xiaojiao Bi,2,* Tianliang Zhang,3 Chao Han,3 Tantan Ma,3 Lina Wang,2 Mengmeng Sun,3 Kaiyan Cui,3 Limin Yang,3 Lanfen Liu3 1Department of Psychiatry, School of Clinical Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Psychology, Shandong Mental Health Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Psychiatry, Shandong Mental Health Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lanfen LiuShandong Mental Health Center Affiliated to Shandong University, 49# Wenhua Eastern Road, Jinan, Shandong 250014, People’s Republic of ChinaTel +86 18705317358Email liulf521@163.comPurpose: The incidence of nonsuicidal self-injury (NSSI) behavior among adolescents increases year by year. Patients with a history of both depression and NSSI behaviors tend to have greater risk of suicide. At present, the mechanism of adolescent depressive disorder patients with NSSI behaviors is not clear, epigenetic mechanism may be involved. Proopiomelanocortin (POMC) gene may be associated with depressive disorder. The purpose of this study was to investigate DNA methylation of POMC gene promoter region of adolescent depressive disorder patients with NSSI behaviors.Methods: Bisulfite Sequencing PCR (BSP) was used to test the methylation level of POMC promoter of 15 adolescent depressive disorder patients with NSSI behaviors and 15 healthy controls (HC). Self-made questionnaires were used to collect clinical data of the case group and control group. Hamilton depression scale-24 (HAMD-24), Hamilton anxiety scale (HAMA), Symptom Checklist-90 (SCL-90) were used to evaluate the characteristics and severity of depressive, anxiety and psychotic symptoms. Adolescent self-injury questionnaire was used to assess NSSI behaviors and its severity.Results: BSP analysis found that the POMC methylation level of cytosine-guanine dinucleotide 1 (CpG1) site was higher in the case group than that of HC (P< 0.05). The significance in POMC methylation at CpG1 between case group and HC was gender-independent, and CpG1 methylation level was higher in both male (P< 0.05) and female (P< 0.05) patients than that in HC. The CpG1 methylation level had a little correlation trends with family history of psychosis (P=0.05). We also found that POMC methylation level at CpG17 in female patients was significantly higher than that of the female HC (P< 0.05).Conclusion: There was abnormal methylation in the POMC promoter region of adolescent depressive disorder patients with NSSI behaviors, the methylation of CpG1 may act as epigenetic markers for those adolescents.Keywords: adolescent, depressive disorder, POMC, methylation, nonsuicidal self-injury behavior

Lightning stroke is an important factor affecting the operation of the power grid. In order to improve the accuracy of lightning fault identification, the fault location is based on the information of the tripped lines and the lightning locating system. Real time fault information will be sent to the relevant staff through the fault visual notification system, which provides technical guidance for line operation and maintenance management, operation control, emergency disaster prevention and mitigation. The notification system minimizes the transmission line faults outage time caused by lightning, so as to guarantee the safety and stability of the power grid operation.

Lightning faults are the main faults of transmission lines. Accurate and effective diagnosis of lightning fault can effectively improve the reliability of transmission lines. At present, the determination of lightning strike fault and the location of the lightning strike are determined by manually inquiring the lightning locating system after the lightning strike. In order to improve the real - time determination of lightning fault, the accuracy of lightning strike point positioning and to shorten the outage time due to the lightning strike fault, research on the automatic fault diagnosis technology of the lightning failure of transmission line. According to the lightning fault of the transmission line, the information such as the relevant information of the lightning location system, the GIS information, fault recorder data, the scheduling automation data and the multi-terminal fault location information are used to realize the accurate positioning of the tower and the automatic fault diagnosis function of the transmission line fault. The rapid detection and overhaul of lightning failure is of great significance to the safe and stable operation of power grid.

Taking the reservoir sandstones of natural gas pools in the Upper Paleozoic and the calcite veins in Ordovician carbonate collected in the Ordos Basin, China, as samples, a unique method for geochemical analysis of gases captured in fluid inclusions (FIs) is presented in this study. Geochemical comparison between FI gases and reservoir gases in this basin is conducted. The results show that the gases from FIs developed in Upper Paleozoic reservoir sandstones and from the corresponding reservoirs share similar geochemistry in hydrocarbon gaseous compositions, although there is a high concentration of non-hydrocarbon gases (e.g. CO2) in FIs. The occurrence of FIs in sandstones and the value of the carbon isotopic ratio of carbon dioxide (δ13CCO2 > − 8‰) suggest that non-hydrocarbon gas in FIs originated from primary FIs formed during hosted mineral (quartz) crystallization from magma. Similar geochemistry in hydrocarbon gases from FIs and from reservoirs indicates that the gases pooled in Upper Paleozoic sandstones represent the original state charging from the source rocks and thus experienced a weak or no secondary alteration. Dominating hydrocarbon gaseous components, such as wells Lt1 and Yu9, in FI gases at a secondary formation in calcite veins of Ordovician carbonate imply that the FIs are related to oil and gas charging. The gases originated from the Lower Paleozoic source rock is characterized by δ13C1

Photothermal therapy (PTT) can take advantage of the photothermal effects of photothermal agents to acquire the energy from laser irradiation and convert it into heat. This can intensively elevate the temperature of the surrounding environment to directly destroy the cancer cells. It is expected that PAs with strong absorption in near infrared (NIR) range might possess the ideal tissue-transparent feature and minimal damage to surrounding healthy tissues, beneficial to the practical application. Herein, well-dispersed L-cysteine modified MoS2 (MoS2-Cys) nanospheres with the average diameter of about 422 nm and strong NIR adsorption were successfully synthesized through a facile method. The as-prepared MoS2-Cys nanospheres are composed of nanosheets with the average thickness of about 13.7 nm. The photothermal conversion efficiency of the as-prepared MoS2-Cys nanospheres with the very low concentration of 50 μg/mL was determined to be 35% when exposed to 808 NIR laser at the power density of 0.8 W/cm2, much higher than those of the previous reports with same dose and power density. MoS2-Cys nanospheres possessed the good photothermal ablation effect to significantly inhibit the growth of tumor in vivo. Furthermore, MoS2-Cys nanospheres did not exhibit detectable side effects, suggesting their good in vitro and in vivo biocompatibility.

Automatic generation control (AGC) plays an important role to maintain real time power generation and load balance, and to ensure the quality of power supply. Power system requires each power generation unit to have satisfactory AGC performance. In addition to the design of AGC control strategy, the characteristics of power generation equipment also affect its performance in AGC control. This paper introduces the assess index of AGC performance of power unit, and analyzes the reasons for the poor AGC performance. Based on the AGC control strategy of thermal power units, the paper proposes an optimization method to improve assess index of AGC performance. Through the implementation of typical industrial case studies, the effectiveness of the proposed method is validated.

Primary fan system plays an important role in the operation of a power plant. However, due to the complicated working conditions of the primary fan and the strong coupling characteristics of multi-state variables, it is necessary to carry out feature engineering before using multivariate state estimation technique (MSET). In addition, no-linear operator should be designed to make sure matrix being invertible. This paper proposes an Auto-encoder based model to automatically construct a normal state memory matrix through unsupervised learning of neural networks. It reduces human intervention as well as the difficulty in giving a suitable non-linear operator design. This model is applied to the early warning of primary fan failure in a power plant in eastern Shandong Province.

The primary frequency control(PFC) performance of thermal power units were affected by the problems such as equipment delay, nonlinear valve flow characteristic curve and weak controller parameters etc. Combined with the new integral electricity contribution index method, one dynamic compensation adjustment method of PFC based on real-time evaluation of performance indexes are proposed. The method dynamically adjust the control parameter by calculating the amplitude of PFC at the relevant time and the integral electricity contribution in the corresponding time period. This method not only improves the PFC performance based on the safe operation of the unit, but also helps to improve the PFC performance. It satisfies the power grid’s standard and reduces the frequency fluctuation of the grid system.

With the wide application of UHVDC in long-distance and large-capacity power transmission, the current power grid has developed into a complex AC-DC deep coupling system, which poses a serious challenge to the voltage safety control of the system. Based on the voltage sensitivity of AC/DC system, this paper presents a voltage optimization control method for integrated coordination of AC/DC system control variables. In this control method, a linear constrained quadratic optimization model with minimum control cost is constructed to coordinate the control variables of AC/DC system and correct the voltage amplitude deviation. The potential of UHVDC system to participate in voltage control is studied by optimizing the control quantity of rectifier side and inverter side converters. The simulation results of AC/DC hybrid system show that the proposed optimal control method can effectively coordinate the control quantity of AC/DC system and ensure the voltage operation in a safe range.

The interface microstructure and shear strength of Sn2.5Ag0.7Cu0.1RExNi/Cu solder joints under thermal-cycle loading were investigated with scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD) and physical and chemical tests. The results show that an intermetallic compound (IMC) layer of Sn2.5Ag0.7Cu0.1RExNi/Cu solder joints evolved gradually from the scalloped into larger wavy forms with increasing number of thermal cycles. The roughness and average thickness of IMC increased with thermal-cycle loading. However, at longer thermal-cycle loading, the shear strength of the joints was reduced by about 40%. The fracture pathway of solder joints was initiated in the solder seam with ductile fracture mechanism and propagated to the solder seam/IMC layer with ductile-brittle mixed-type fracture mechanism, when the number of thermal cycles increased from 100 to 500 cycles. By adding 0.05 wt.% Ni, the growth of the joint interface IMC could be controlled, and the roughness and average thickness of the interfacial IMC layer reduced. As a result, the shear strength of joints is higher than those without Ni. When compared to joint without Ni, the roughness and average thickness of 0.05 wt.% Ni solder joint interface IMC layer reached the minimum after 500 thermal cycles. The shear strength of that joint was reduced to a minimum of 36.4% of the initial state, to a value of 18.2 MPa.

PURPOSE: To compare sensitivity in the detection of lung nodules between the deep learning (DL) model and radiologists using various patient population and scanning parameters and to assess whether the radiologists’ detection performance could be enhanced when using the DL model for assistance. MATERIALS AND METHODS: A total of 12 754 thin-section chest CT scans from January 2012 to June 2017 were retrospectively collected for DL model training, validation, and testing. Pulmonary nodules from these scans were categorized into four types: solid, subsolid, calcified, and pleural. The testing dataset was divided into three cohorts based on radiation dose, patient age, and CT manufacturer. Detection performance of the DL model was analyzed by using a free-response receiver operating characteristic curve. Sensitivities of the DL model and radiologists were compared by using exploratory data analysis. False-positive detection rates of the DL model were compared within each cohort. Detection performance of the same radiologist with and without the DL model were compared by using nodule-level sensitivity and patient-level localization receiver operating characteristic curves. RESULTS: The DL model showed elevated overall sensitivity compared with manual review of pulmonary nodules. No significant dependence regarding radiation dose, patient age range, or CT manufacturer was observed. The sensitivity of the junior radiologist was significantly dependent on patient age. When radiologists used the DL model for assistance, their performance improved and reading time was reduced. CONCLUSION: DL shows promise to enhance the identification of pulmonary nodules and benefit nodule management. © RSNA, 2019 Supplemental material is available for this article.

With more and more photovoltaic (PV) power generation connected to power system, photovoltaic power plant will participate in peak regulation and frequency modulation, and then model structure of photovoltaic power plant need to be improved continually. In the paper, a multi-time scale model was proposed, including local controller module, fault ride through controller module, and plant level controller module, while local controller module and fault ride through controller module reflect the RMS transient characteristics of PV power plant, and plant level controller module reflects the medium- and long-term dynamic characteristics. Based on operation data of photovoltaic power plant and measurements of artificial short circuit test, grid-connected characteristics of photovoltaic power plant are analysed deeply, and it is proposed of a universal model of photovoltaic power plant, which is adapt to a variety of analytical needs.

Research on Augmented Reality (AR)/Mixed Reality (MR) remote collaboration for physical tasks remains a compelling and dynamic area of study. AR systems have been developed which transmit virtual annotations between remote collaborators, but there has been little research on how haptic feedback can also be shared. In this paper, we present a Virtual Reality (VR)-Spatial Augmented Reality (SAR) remote collaborative system that provides haptic feedback with tangible interaction between a local worker and a remote expert helper. Using this system, we conducted a within-subject user study to compare two interfaces for remote collaboration between a local worker and expert helper, one with mid-air free drawing (MFD) and one with tangible physical drawing (TPD). The results showed that there were no significant differences with respect to performance time and operation errors. However, users felt that the TPD interface supporting passive haptic feedback could significantly improve the remote experts’ user experience in VR. Our research provides useful information on the way for gesture- and gaze-based multimodal interaction supporting haptic feedback in AR/MR remote collaboration on physical tasks. Refereed/Peer-reviewed

For more than 2 decades, Augmented Reality (AR)/Mixed Reality (MR) has received an increasing amount of attention by researchers and practitioners in the manufacturing community, because it has applications in many fields, such as product design, training, maintenance, assembly, and other manufacturing operations. However, to the best of our knowledge, there has been no comprehensive review of AR-based co-design in manufacturing. This paper presents a comprehensive survey of existing research, projects, and technical characteristics between 1990 and 2017 in the domain of co-design based on AR technology. Among these papers, more than 90% of them were published between 2000 and 2017, and these recent relevant works are discussed at length. The paper provides a comprehensive academic roadmap and useful insight into the state-of-the-art of AR-based co-design systems and developments in manufacturing for future researchers all over the world. This work will be useful to researchers who plan to utilize AR as a tool for design research. Refereed/Peer-reviewed