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［Objective］To investigate the dynamics issues arising from the frequent lifting and lowering of pantographs in multi-mode hybrid traction trains, the pantograph collision characteristics are analyzed. ［Method］Taking the PC (pantograph-catenary) system as research object, a PC collision test bench is built to study the dynamics characteristics of pantograph collisions during the lifting process. A corresponding dynamics model is established and validated using experimental data. The variation patterns of vertical collision contact forces are also analyzed. ［Result & Conclusion］During PC collisions, collision speed and contact wire stagger value both significantly affect the maximum value, standard deviation, and dynamic coefficient of PC vertical contact force. As the collision speed increases, both the standard deviation and the maximum value of the vertical contact force increase accordingly, while the dynamic coefficient initially decreases and then increases, reaching its minimum when the collision speed is 0.5 m/s. As the stagger value increases, the standard deviation of the vertical collision contact force decreases. At a lower collision speed, the maximum value of the vertical contact force decreases with the increasing collision speed. Conversely, at a higher speed, the minimum vertical contact force initially decreases and then increases, reaching a minimum around a stagger value of 200 mm. Across all speed conditions, the dynamic coefficient is highest when there is no stagger and reaches its lowest point around a stagger value of 400 mm.

[Objective] This study aims to investigate the mitigation effect and physiological mechanism of salicylic acid (SA) on high temperature stress injury of watermelon seedlings, and to provide a theoretical basis for the application of SA in watermelon cultivation. [Methods] Potted ‘K53’ watermelon seedlings in greenhouse were used as experimental materials. After spraying different concentrations (0, 0.5, 1.0, 1.5, and 2.0 mmol/L) of SA on the leaves, the seedlings were stressed at 42 ℃ for 36 h. The growth characteristics, anatomical structure, physiological and biochemical indexes of watermelon seedlings were observed, and the mitigation effects of each treatment were comprehensively evaluated by membership function method. [Results] After high temperature stress, the leaves of watermelon seedlings were wilted seriously, the growth of root length was inhibited, the leaves became thinner, and the mesophyll cell structure was damaged. After SA application, the leaves became thicker, photosynthetic pigment content, photosynthetic gas exchange parameters, antioxidant enzyme (POD, SOD, CAT) activity and osmotic adjustment substances (proline, soluble sugar, soluble protein) content were increased significantly, while MDA content and relative conductivity were decreased significantly. Compared with the high temperature stress group, the MDA content and relative conductivity of leaves under 1.0 mmol/L SA treatment were reduced by 33.70% and 58.58%, while the contents of chlorophyll a and chlorophyll b, net photosynthetic rate, and the activities of SOD and CAT were increased by 22.71%, 21.63%, 98.34%, 23.98% and 19.71%, respectively. [Conclusion] Pre-spraying SA could alleviate the damage of watermelon seedlings under high temperature stress, with 1.0 mmol/L SA had the best effect.

The internal capsule of the basal ganglia is vulnerable to direct pressure from the hematoma and to secondary damage from toxic products of hemorrhage. Our study evaluated the risk and benefits of active strategies including ultra-early surgery and hematoma evacuation through a transsylvian-transinsular approach for moderate basal ganglia hemorrhage.

To respond to the slogan of the national fitness movement, improve the quality of the national fitness movement, and provide scientific reference to public fitness, this paper studies the fitness method of Unity3D technology and somatosensory human-computer interaction virtual reality technology. Firstly, we build a somatosensory HCI virtual fitness system with Unity3D and Kinect technology, verify the data with an edge detection operator, get the simulation results of the somatosensory HCI virtual reality fitness system, and then get the fitness method based on the somatosensory HCI virtual reality technology according to the results. The data show that the fitness industry is seeing new highs as the national fitness membership reaches 75.13 million people as of December 2021, while the growth of women among them increases from 13.5 million in 2017 to 55.6 million in 2021. Among the 800 fitness methods, the physical therapy and rehabilitation category accounts for 1/3, and fitness, bodybuilding and health care each account for about 1/5. The comfort zone of fitness differs between men and women, ranging from 0.6-1.2 for men and 0.5-0.9 for women. The research in this paper can provide reasonable fitness advice to the fitness population and promote the healthy development of the fitness industry.

The information on the two old postcards sent from Peking Union Medical College was studied. Henry E. Meleney and H.F. Hsü, the parasitologists and medical educators of Peking Union Medical College, were introduced. Their experiences in scientific research and achievements were reviewed. The professional ethics of serving patients and the scientific spirit with rigorous research of the medical scientists are of practical educational significance.

With the trend of digitalization, intelligence, and networking sweeping the world, functional safety and cyber security are increasingly intertwined and overlapped, evolving into the issue of generalized functional safety. Traditional system reliability technology and network defense technology cannot provide quantifiable design implementation theories and methods. As the cornerstone of software systems, operating systems in particular are in need of efficient safety assurance. The DHR architecture is a mature and comprehensive solution, and it is necessary to implement an OS-level DHR architecture, for which the multi-kernel operating system is a good carrier. The multi-kernel operating system takes the kernel as the processing scenario element and constructs redundancy, heterogeneity, and dynamism on the kernel, so it has the generalized robustness of the DHR architecture. This article analyzes the significance and requirements of OS-level DHR architecture, and systematically explains how the multi-kernel operating system responds to the requirements of OS-level DHR architecture by analyzing the technical routes of multi-kernel operating systems and develops an operating system solution idea for the generalized functionally safety.

With the development of industrialization, the pollution of heavy metals in soil, such as lead (Pb) and cadmium (Cd), has become increasingly serious. On the other hand, the century old climate warming is considered to be the result of the significant increase in the concentration of greenhouse gases, such as CO2, in the atmosphere. These changes will affect the function and stability of the terrestrial ecosystem. Therefore, in recent years, there are more and more studies on the effects of heavy metal pollution and elevated atmospheric CO2 concentration on plants. But most of them focus on the study of the aboveground part of herbaceous plants under the action of single factor, and the study of the soil microenvironment of woody plants under the combined action of these environmental factors is relatively less. This study summarized the response of rhizosphere microenvironment to the coupling of climate warming and soil pollution, in order to provide theoretical reference for improving soil quality and ecological environment.

Considering the shortcomings of the maximum correlated kurtosis deconvolution（MCKD） method that cannot automatically identify the period of bearing fault impulses,exists the resampling process and the multiple input parameters,an adaptive maximum correlated kurtosis deconvolution（AMCKD） method is proposed.The periodic modulation intensity（PMI） of envelope signal is used to identify the period of bearing fault impulses adaptively.Moreover,the period is constantly updated during searching for the optimal deconvolution filter iteratively,so that the real fault period is gradually approximated.Finally,the filtered signal with the largest correlated kurtosis is selected as the optimal deconvolution signal.Compared with MCKD method,AMCKD method can identify fault impulse period adaptively,avoid signal resampling process,and reduce the input parameters of the algorithm.Simulated and experimental results verify the effectiveness of this method in early fault feature extraction of rolling bearings,and the comparison with fast kurtogram method shows the superiority of AMCKD method in enhancing periodic impulse characteristics.

The epidermal growth factor receptor (EGFR) is one of most potent oncogenes that are commonly altered in cancers. As a receptor tyrosine kinase, EGFR's kinase activity has been serving as the primary target for developing cancer therapeutics, namely the EGFR inhibitors including small molecules targeting its ATP binding pocket and monoclonal antibodies targeting its ligand binding domains. EGFR inhibitors have produced impressive therapeutic benefits to responsive types of cancers. However, acquired and innate resistances have precluded current anti-EGFR agents from offering sustainable benefits to initially responsive cancers and benefits to EGFR-positive cancers that are innately resistant. Recent years have witnessed a realization that EGFR possesses kinase-independent (KID) pro-survival functions in cancer cells. This new knowledge has offered a different angle of understanding of EGFR in cancer and opened a new avenue of targeting EGFR for cancer therapy. There are already many excellent reviews on the role of EGFR with a focus on its kinase-dependent functions and mechanisms of resistance to EGFR targeted therapies. The present opinion aims to initiate a fresh discussion about the function of EGFR in cancer cells by laying out some unanswered questions pertaining to EGFR in cancer cells, by rethinking the unmet therapeutic challenges from a view of EGFR's KID function, and by proposing novel approaches to target the KID functions of EGFR for cancer treatment.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P

This article adopts a research method that combined with theoretical analysis and system design, analyzes multiple dimensions of common safety hazard events, uses support vector machine classification algorithms to filter and mine valuable information in massive data, and establishes a common safety hazard event feature set. This kind of technology can realize the automatic classification of safety hazards and extract their characteristic information, introduce the semantic analysis, word segmentation clustering method to determine the typical processing measures of events, and generate knowledge items to add methods and models to the processing measures database, which can solve the grid safety hazard data entry specifications, In-depth analysis and other issues.

The number of distributed photovoltaic power generation systems connected to the system is increasing, especially for residents and non-residents. A large amount of photovoltaic grid-connected power brings new problems to the line loss management of the distribution network. This paper proposes a theoretical calculation model of line loss for distribution network with multi-distributed photovoltaic access. This paper adopts the actual case of Shanghai Power Grid, calculates based on the mathematical model proposed, and puts forward targeted optimization suggestions by comparing the simulation analysis results.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Co-seismic groundwater-level and temperature changes caused by the Mw9. 0 Japan earthquake in Chinese mainland are described. The recorded water-level changes were mostly oscillations, with some step decreases mostly in the coastal area of Southeast China and step increases mostly in Northeast China and the North–south Seismic Belt. The water-temperature changes were mainly decrease with slow recovery in Sichuan-Yunnan, South China, and lower reaches of Jiangzhong, and sharp increase followed by sharp decrease, or vice versa, in North China and Northeast China. For wells that showed step changes in both water level and temperature, more showed them in the same direction than in the opposite direction.

Tilt and strain meters of the deformation-observation network in Hubei Province all responded to the Mw9. 0 Japan earthquake on March 11, 2011. By analyzing the co-seismic responses, we found that firstly there was essentially a linear correlation between response time and epicentral distance. Secondly, there was some correlation between maximum response amplitude and earthquake magnitude as well as between the duration and earthquake magnitude. Thirdly, the response amplitudes and decay rates were different for different types of instruments. Due to less data-sampling frequency, the deformation instruments, could not display the first motion of P and S waves, but responded mainly to far-field surface waves. Before the earthquake, the NS earth tide component recorded by the cave stainmeter at Yichang was distorted for nearly eight hours. While digital deformation observation did not show complete information about the earthquake source, it still reflected some key features of seismic-wave propagation.

In the United States, more than 40% of cancer patients develop brain metastasis. The median survival for untreated patients is 1 to 2 months, which may be extended to 6 months with conventional radiotherapy and chemotherapy. The growth and survival of metastasis depend on the interaction of tumor cells with host factors in the organ microenvironment. Brain metastases are surrounded and infiltrated by activated astrocytes and are highly resistant to chemotherapy. We report here that coculture of human breast cancer cells or lung cancer cells with murine astrocytes (but not murine fibroblasts) led to the up-regulation of survival genes, including GSTA5, BCL2L1, and TWIST1, in the tumor cells. The degree of up-regulation directly correlated with increased resistance to all tested chemotherapeutic agents. We further show that the up-regulation of the survival genes and consequent resistance are dependent on the direct contact between the astrocytes and tumor cells through gap junctions and are therefore transient. Knocking down these genes with specific small interfering RNA rendered the tumor cells sensitive to chemotherapeutic agents. These data clearly demonstrate that host cells in the microenvironment influence the biologic behavior of tumor cells and reinforce the contention that the organ microenvironment must be taken into consideration during the design of therapy.

Background: This study was designed to investigate the efficacy and safety of apatinib monotherapy in the treatment of elderly patients with advanced colorectal cancer (CRC) who have progressed on the standard regimens. Methods: The data of 106 elderly patients with advanced CRC who have progressed on standard treatment were analyzed. The primary endpoint of this study was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). The safety outcomes were assessed by the proportion and severity of adverse events. Results: Efficacy was assessed using the best overall response of patients during treatment with apatinib, including 0 patients with complete response, 9 patients with partial response, 68 patients with stable disease, and 29 patients with progressive disease. ORR and DCR were 8.5 and 72.6%, respectively. The median PFS of 106 patients was 3.6 months, and the median OS was 10.1 months. The most frequent adverse reactions of elderly patients with advanced CRC receiving apatinib treatment were hypertension (59.4%) and hand-foot syndrome (HFS) (48.1%). The median PFS of patients with and without hypertension was 5.0 and 3.0 months, respectively (P = 0.008). The median PFS of patients with and without HFS was 5.4 and 3.0 months, respectively (P = 0.013). Conclusions: The clinical benefit of apatinib monotherapy was observed in elderly patients with advanced CRC who have progressed on the standard regimens. The adverse reactions of hypertension and HFS were positively related to treatment efficacy. Keywords: Adverse reactions, apatinib, colorectal cancer, treatment, Author(s): Yongjun Yu [1]; Yuwei Li [1]; Chen Xu [1]; Weihua Zhang (corresponding author) [1] Introduction Colorectal cancer (CRC) is the third most diagnosed cancer worldwide.[sup.[1]] Currently, only vascular epidermal [...]

Abstract Linkage maps have been invaluable for the positional cloning of many genes involved in severe human diseases. Standard genetic linkage maps have been constructed for this purpose from the Centre d'Etude du Polymorphisme Humain and other panels, and have been widely used. Now that attention has shifted towards identifying genes predisposing to common disorders using linkage disequilibrium (LD) and maps of single nucleotide polymorphisms (SNPs), it is of interest to consider a standard LD map which is somewhat analogous to the corresponding map for linkage. We have constructed and evaluated a cosmopolitan LD map by combining samples from a small number of populations using published data from a 10-megabase region on chromosome 20. In support of a pilot study, which examined a number of small genomic regions with a lower density of markers, we have found that a cosmopolitan map, which serves all populations when appropriately scaled, recovers 91 to 95 per cent of the information within population-specific maps. Recombination hot spots appear to have a dominant role in shaping patterns of LD. The success of the cosmopolitan map might be attributed to the co-localisation of hot spots in all populations. Although there must be finer scale differences between populations due to other processes (mutation, drift, selection), the results suggest that a whole-genome standard LD map would indeed be a useful resource for disease gene mapping.

This paper proposes a novel integrated guidance and control (IGC) method for hypersonic vehicle in terminal phase. Firstly, the system model is developed with a second order actuator dynamics. Then the back-stepping controller is designed hierarchically with command filters, where the first order command filters are implemented to construct the virtual control input with ideal states predicted by an adaptive estimator, and the nonlinear command filter is designed to produce magnitude, rate and bandwidth limited control surface deflection finally tracked by a terminal sliding mode controller with finite convergence time. Through a series of 6-DOF numerical simulations, it’s indicated that the proposed method successfully cancels out the large aerodynamics coefficient uncertainties and disturbances in hypersonic flight under limited control surface deflection. The contribution of this paper lies in the application and determination of nonlinear integrated design of guidance and control system for hypersonic vehicle.