RNA-based NGS检测EML4-ALK融合V1亚型肺腺癌1例

肺癌是全球发病率和死亡率最高的恶性肿瘤。对于肺腺癌而言,识别特定的基因突变并给予相应靶向药物可大大提高患者的生存时间。其中,间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合发生在3%-7%的非小细胞肺癌(non-small cell lung cancer,NSCLC)中。在临床中,多种检测方法可应用于判断ALK融合状态,但存在检测结果假阴性可能。本文回顾性分析1例肺腺癌患者的诊治经过,经多种检测方式判断ALK融合状态,其中,免疫组化(immunohistochemistry,IHC)(Ventana D5F3)、基于RNA的下一代测序(RNA-based next-generation sequencing,RNA-based NGS)检测证实棘皮类微管关联蛋白样4(echinoderm microtubule associated protein like 4,EML4)-ALK融合阳性,而基于DNA的NGS(DNA-based NGS)检测为阴性。本文比较分析判断ALK融合的检测方法,以明确在不同临床案例中选择何种检测方式最准确、最简便,以便于指导后续治疗。

Association between Mental Health Literacy and Workplace Well-Being of Chinese Grassroots Civil Servants:The Chain Mediating Effects of Regulatory Emotional Self-Efficacy and Resilience

This study aimed to investigate the relationship between mental health literacy(MHL)and workplace well-being(WWB)of Chinese grassroots civil servants,with regulatory emotional self-efficacy(RESE)and resilience as mediating variables.A questionnaire survey was conducted among Chinese grassroots civil servants,with a valid sample size of 2673 after excluding missing values and conducting relevant data processing.The PROCESS was used to examine the relationship between MHL,RESE,resilience,and WWB.The study found that MHL among grassroots civil servants was positively and significantly correlated with WWB(r=0.73,p<0.01).RESE partially mediated the relationship between MHL and WWB(β=0.25,95%CI[0.22,0.28]).Resilience partially mediated the relationship between MHL and WWB(β=0.22,95%CI[0.19,0.26]).MHL had a positive effect on WWB through the chain mediating effect of RESE and resilience(β=0.05,95%CI[0.03,0.07]).There is a close relationship between MHL and WWB,where Chinese grassroots civil servants with higher levels of MHL can develop stronger RESE and resilience,leading to higher WWB.The results of this study remind organizational institutions of Chinese grassroots civil servants that enhancing MHL,RESE,and resilience is an important pathway to promoting their WWB.

Permanent Magnet Axial Section Shaping Optimization Surface-mounted Permanent Magnet Synchronous Motor

In this paper, a new type of harmonic injection permanent magnet shape optimization method is proposed to suppress the torque ripple of surface-mounted permanent magnet synchronous motor. The sinusoidal waveform shaping of the axial section of the permanent magnet is added with the third harmonic shaping, and the sine wave and the third harmonic are derived. The optimal ratio is 6:1. The permanent magnet no shaping, sinusoidal shaping and sinusoidal combined third harmonic shaping are compared. The results show that the sinusoidal combined third harmonic shaping design can effectively suppress the torque ripple of the surface mounted permanent magnet synchronous motor and obtain a relatively large output torque. At the same time, a method of using permanent magnet segmentation to approximately equivalently replace sine combined with third harmonic shaping design is proposed, which effectively saves the manufacturing cost of permanent magnets and provides design and research ideas for more economical and effective optimization of surface-mounted permanent magnet motors.

Research on Thermal Calculation and End Winding Heat Conduction Optimization of Low Speed High Torque Permanent Magnet Synchronous Motor

Because of its simple structure,large torque and high efficiency,permanent magnet synchronous motor of low speed and high torque is widely adopted in many fields.In this paper,a 394.5k W mining low-speed high-torque permanent magnet synchronous motor(LSHTPMSM)is regarded as the study object.According to the physical model,a three-dimensional equivalent heat transfer temperature field calculation model of the motor is built to simulate the temperature distribution of the motor under rated conditions.In terms of the serious issue of stator winding temperature increase of permanent magnet synchronous motor of low speed and high torque,the heat conduction optimization of the end of the stator winding is studied,which enhances the heat dissipation effect of the stator end winding,effectively reduces its temperature increase and temperature gradient with the winding in the slot,and improves the practical efficiency and service life of the motor.Finally,the motor temperature rise test platform is constructed for the verification of the feasibility of the optimization scheme,which provides a reference direction for the heat dissipation optimization of permanent magnet synchronous motor of low speed and high torque.

Design of Rotor Magnetic Barrier Structure of Built-in Permanent Magnet Motor Based on Taguchi Method

In this paper,a 20kW vehicle built-in permanent magnet synchronous motor is taken as an example,and a magnetic barrier structure is added to the rotor of the motor to solve the uneven saturation problem of the rotor side magnetic bridge.This structure improves the air-gap flux density waveform of the motor by influencing the internal magnetic flux path of the motor rotor,thus improving the sine of the no-load back EMF waveform of the motor and reducing the torque ripple of the motor.At the same time,Taguchi method is used to optimize the structural parameters of the added magnetic barrier.In order to facilitate the analysis of its uneven saturation phenomenon and improve the optimization effect,a simple equivalent magnetic network(EMN)model considering the uneven saturation of rotor magnetic bridge is established in this paper,and the initial values of optimization factors are selected based on this model.Finally,the no-load back EMF waveform distortion rate,torque ripple and output torque of the optimized motor are compared and analyzed,and the influence of magnetic barrier structure parameters on the electromagnetic performance of the motor is also analyzed.The results show that the optimized motor can not change the output torque of the motor as much as possible on the basis of reducing the waveform distortion rate of no-load back EMF and torque ripple.

The influence of land use change on the spatial–temporal variability of habitat quality between 1990 and 2010 in Northeast China

Land use changes are a direct consequence of interactions between humans and nature.Analysing the spatial and temporal changes in habitat quality brought about by land use change can provide a scientific basis for ecological protection and land planning.Based on the analysis of land use change from 1990 to 2010 in Northeast China,we used the InVEST(integrated valuation of ecosystem services and trade-offs)module to evaluate habitat quality based on watershed subdivision.The results show that:(1)the main land use changes from 1990 to 2010 were the transition from grasslands and forest lands to agricultural lands,which led to a decrease in connectivity of landscape and an increase in fragmentation;(2)areas of high habitat quality were distributed north of the Greater Khingan Mountains,the region of the Lesser Khingan Mountains and east of the Changbai Mountains,while the central plain had low habitat quality;(3)agricultural lands had the largest effect on habitat degradation among all habitat threats.During these 2 decades,the contribution of agricultural lands to habitat degradation were 43.4%in 1990,44.6%in 2000 and 43.9%in 2010;and,(4)at a landscape scale,patch density and splitting index present noticeable negative correlations with habitat quality index.Habitat quality was significantly affected by landscape fragmentation and decreased connectivity.

A statistical analysis of spatiotemporal variations and determinant factors of forest carbon storage under China's Natural Forest Protection Program

The Natural Forest Protection Program(NFPP)is one of the key ecological forestry programs in China.It not only facilitates the improvement of forest ecological quality in NFPP areas,but also plays a significant role in increasing the carbon storage of forest ecosystems.The program covers 17 provinces,autonomous regions,and municipalities with correspondingly diverse forest resources and environments,ecological features,engineering measures and forest management regimes,all of which affect regional carbon storage.In this study,volume of timber harvest,tending area,pest-infested forest,firedamaged forest,reforestation,and average annual precipitation,and temperature were evaluated as factors that influence carbon storage.We developed a vector autoregression model for these seven indicators and we studied the dominant factors of carbon storage in the areas covered by NFPP.Timber harvest was the dominant factorinfluencing carbon storage in the Yellow and Yangtze River basins.Reforestation contributed most to carbon storage in the state-owned forest region in Xinjiang.In state-owned forest regions of Heilongjiang and Jilin Provinces,the dominant factors were forest fires and forest cultivation,respectively.For the enhancement of carbon sequestration capacity,a longer rotation period and a smaller timber harvest are recommended for the Yellow and Yangtze River basins.Trees should be planted in stateowned forests in Xinjiang.Forest fires should be prevented in state-owned forests in Heilongjiang,and greater forest tending efforts should be made in the state-owned forests in Jilin.

Multi-Objective Task Assignment for Maximizing Social Welfare in Spatio-Temporal Crowdsourcing

With the development of the Internet of Things(IoT),spatio-temporal crowdsourcing(mobile crowdsourcing)has become an emerging paradigm for addressing location-based sensing tasks.However,the delay caused by network transmission has led to low data processing efficiency.Fortunately,edge computing can solve this problem,effectively reduce the delay of data transmission,and improve data processing capacity,so that the crowdsourcing platform can make better decisions faster.Therefore,this paper combines spatio-temporal crowdsourcing and edge computing to study the Multi-Objective Optimization Task Assignment(MOO-TA)problem in the edge computing environment.The proposed online incentive mechanism considers the task difficulty attribute to motivate crowd workers to perform sensing tasks in the unpopular area.In this paper,the Weighted and Multi-Objective Particle Swarm Combination(WAMOPSC)algorithm is proposed to maximize both platform’s and crowd workers’utility,so as to maximize social welfare.The algorithm combines the traditional Linear Weighted Summation(LWS)algorithm and Multi-Objective Particle Swarm Optimization(MOPSO)algorithm to find pareto optimal solutions of multi-objective optimization task assignment problem as much as possible for crowdsourcing platform to choose.Through comparison experiments on real data sets,the effectiveness and feasibility of the proposed method are evaluated.

Optimization Design of High-speed Interior Permanent Magnet Motor with High Torque Performance Based on Multiple Surrogate Models

In order to obtain better torque performance of high-speed interior permanent magnet motor(HSIPMM) and solve the problem that electromagnetic optimization design is seriously limited by its mechanical strength, a complete optimization design method is proposed in this paper. The object of optimization design is a 15 kW、20000 r/min HSIPMM whose permanent magnets in rotor is segmented. Eight structural dimensions are selected as its optimization variables. After design of experiment(DOE), multiple surrogate models are fitted, a set of surrogate models with minimum error is selected by using error evaluation indexes to optimize, the NSGA-II algorithm is used to get the optimal solution. The optimal solution is verified by load test on a 15 kW, 20000 r/min HSIPMM prototype. This paper can be used as a reference for the optimization design of HSIPMM.

Cooling System Design and Thermal Analysis of Modular Stator Hybrid Excitation Synchronous Motor

Hybrid excitation synchronous motor has the advantages of uniform and adjustable electromagnetic field, wide speed range and high power density. It has broad application prospects in new energy electric vehicles, wind power generation and other fields. This paper introduces the basic structure of hybrid excitation motor with modular stator, and analyzes the operation principle of hybrid excitation motor. The cooling structure of the water-cooled plate is designed, and the effects of the thickness of the water-cooled plate and the number of water channels in the water-cooled plate on the heat dissipation capacity of the water-cooled plate are analyzed by theoretical and computational fluid dynamics methods. The effects of different water cooling plate structures on water velocity, pressure drop, water pump power consumption and heat dissipation capacity were compared and analyzed. The influence of different inlet flow velocity on the maximum temperature rise of each part of the motor is analyzed, and the temperature of each part of the motor under the optimal water flow is analyzed. The influence of the traditional spiral water jacket cooling structure and the water-cooled plate cooling structure on the maximum temperature rise of the motor components is compared and analyzed. The results show that the water-cooled plate cooling structure is more suitable for the modular stator motor studied in this paper. Based on the water-cooled plate cooling structure, the air-water composite cooling structure is designed, and the effects of the air-water composite cooling structure and the water-cooled plate cooling structure on the maximum temperature rise of each component of the motor are compared and analyzed. The results show that the maximum temperature rise of each component of the motor is reduced under the air-water composite cooling structure.

Temperature Field Analysis of Mine Flameproof Outer Rotor Permanent Magnet Synchronous Motor with Different Cooling Schemes

Aiming at the problem of temperature rise of mine flameproof outer rotor permanent magnet synchronous motor,based on the fluid structure coupling method,the temperature distribution of motor under three cooling schemes of air cooling and water cooling are calculated respectively.For the structure I air cooling system,the influence of different number of heat sink on the maximum temperature rise and pressure drop of fluid channel is analyzed,and the parameters of heat sink are optimized.For the structure II air cooling system,the influence of setting fillet at the turn back of the fluid channel on the head loss in the fluid domain of the motor is analyzed,and the influence of different fillet radius on the head loss and the maximum temperature rise in the fluid domain is obtained.For the structure II water cooling system,the influence of different water flow speed on the maximum temperature rise of the motor is analyzed,and the influence of different assembly clearance of modular stator teeth and yoke on the maximum temperature rise of the motor is analyzed.The cooling effect and temperature rise distribution characteristics of the three cooling schemes are compared and analyzed.Finally,a water-cooled prototype is manufactured,and the temperature rise experiment is carried out,and the influence of the thermal deformation of fluid channel,stator yoke and stator teeth on the maximum temperature of the motor is analyzed.The results show that the calculated temperature field after considering the thermal deformation is closer to the experimental value,which verifies the accuracy of the calculation results,It also provides a reference for the selection and design of the cooling structure of the same type of PMSM electric roller.

Design and Analysis of New Modular Stator Hybrid Excitation Synchronous Motor

Hybrid excitation motor is a combination of permanent magnet motor and electric excitation motor,which can flexibly adjust the air gap magnetic field.At present,the traditional silicon steel sheet core material is widely used,but this material limits the further reduction of stator iron loss.In this paper,a new type of hybrid excitation synchronous motor with modular stator structure based on amorphous alloy material is proposed.The design power is 1kW,and the speed is 3000rpm.By placing the armature winding and electric excitation winding in the stator slot,the slip ring and brush are avoided,and the reliability of the motor is improved.The rotor adopts staggered magnetic pole structure,which has strong flux adjusting ability.The core loss is greatly reduced by using amorphous alloy.Firstly,the structure and working principle of the new motor are given;Secondly,the size parameters of the motor are given,and the principle of flux adjustment is verified and analyzed by three-dimensional finite element(3D-FEM);Finally,through theoretical analysis of the influence factors of the magnetic adjustment ability and 3D-FEM finite element computation,the flux adjustment ability and the torque lifting at low speed are verified,and the advantages of the motor are verified.

REAL-TIME FLUORESCENCE IMAGING OF SIRT1 CYTOSOLIC TRANSLOCATION UNDER THE TREATMENT OF GROWTH FACTOR DEPRIVATION

Sirtuins comprise a family of enzymes implicated in the determination of organismal lifespan in yeast and the nematode.Human sirtuin SIRT1 has been shown to deacetylate several proteins in a NADt-dependent manner.It is reported that SIRT1 regulates physiological processes including senescence,fat metabolism,glucose homeostasis,apoptosis,and neurodegeneration.In general,SIRT1 has initially been thought to represent an exclusive nuclear protein.However,depending on the cell lines and organisms examined,a partial or temporary cytoplasmic localization was observed in murine pancreatic beta cells and neonatal rat cardiomyocytes.Since SIRT1 deacetylates both histone and nonhistone-proteins,such as a number of transcription factors,changes in subcellular localization probably play a role in the regulation of its function.In the present studies,we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidneyfibroblast cells(COS-7).Using SIRT1-EGFPfluorescence reporter,we found that SIRT1 localized to nucleus in physiological conditions.We devised a model enabling cell senescence via growth factor deprivation and found that SIRT1 partially translocated to cytosol under the treatment,suggesting a reduced level of SIRT1 activity.We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation,because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus.Taken together,we demonstrate that growth factor deprivation induces cytosolic translocation of SIRT1,which suggests a possible connection between cytoplasm-localized SIRT1 and the aging process and provides a new application of single moleculefluorescence imaging of the molecule events in living cells.

The structure of TRAF7 coiled-coil trimer provides insight into its function in zebrafish embryonic development

TRAF7 serves as a crucial intracellular adaptor and E3 ubiquitin ligase involved in signal transduction pathways,contributing to immune responses,tumor progression,and embryonic development.Somatic mutations within the coiled-coil(CC)domain and WD40 repeat domain of TRAF7 could cause brain tumors,while germline pathogenic mutations contribute to severe developmental abnormalities.However,the precise molecular mechanism underlying TRAF7 involvement in embryonic development remains unclear.In this study,we employed zebrafish as an in vivo model system.TRAF7 knock down caused defects in zebrafish embryonic development.We determined the crystal structure of TRAF7 CC domain at 3.3Åresolution and found that the CC region trimerization was essential for TRAF7 functionality during zebrafish embryonic development.Additionally,disease-causing mutations in TRAF7 CC region could impair the trimer formation,consequently impacting early embryonic development of zebrafish.Therefore,our study sheds light on the molecular mechanism of TRAF7 CC trimer formation and its pivotal role in embryonic development.

Two-stage stochastic programming with robust constraints for the logistics network post-disruption response strategy optimization

Logistics networks (LNs) are essential for the transportation and distribution of goods or services from suppliers to consumers. However, LNs with complex structures are more vulnerable to disruptions due to natural disasters and accidents. To address the LN post-disruption response strategy optimization problem, this study proposes a novel two-stage stochastic programming model with robust delivery time constraints. The proposed model jointly optimizes the new-line-opening and rerouting decisions in the face of uncertain transport demands and transportation times. To enhance the robustness of the response strategy obtained, the conditional value at risk (CVaR) criterion is utilized to reduce the operational risk, and robust constraints based on the scenario-based uncertainty sets are proposed to guarantee the delivery time requirement. An equivalent tractable mixed-integer linear programming reformulation is further derived by linearizing the CVaR objective function and dualizing the infinite number of robust constraints into finite ones. A case study based on the practical operations of the JD LN is conducted to validate the practical significance of the proposed model. A comparison with the rerouting strategy and two benchmark models demonstrates the superiority of the proposed model in terms of operational cost, delivery time, and loading rate.

Stochastic Joint Replenishment Optimization under Joint Inbound Operational Cost

With e-commerce concentrating retailers and customers onto one platform,logistics companies(e.g.,JD Logistics)have launched integrated supply chain solutions for corporate customers(e.g.,online retailers)with warehousing,transportation,last-mile delivery,and other value-added services.The platform’s concentration of business flows leads to the consolidation of logistics resources,which allows us to coordinate supply chain operations across different corporate customers.This paper studies the stochastic joint replenishment problem of coordinating multiple suppliers and multiple products to gain the economies of scale of the replenishment setup cost and the warehouse inbound operational cost.To this end,we develop stochastic joint replenishment models based on the general-integer policy(SJRM-GIP)for the multi-supplier and multi-product problems and further reformulate the resulted nonlinear optimization models into equivalent mixed integer second-order conic programs(MISOCPs)when the inbound operational cost takes the square-root form.Then,we propose generalized Benders decomposition(GBD)algorithms to solve the MISOCPs by exploiting the Lagrangian duality,convexity,and submodularity of the sub-problems.To reduce the computational burden of the SJRM-GIP,we further propose an SJRM based on the power-of-two policy and extend the proposed GBD algorithms.Extensive numerical experiments based on practical datasets show that the stochastic joint replenishment across multiple suppliers and multiple products would deliver 13∼20%cost savings compared to the independent replenishment benchmark,and on average the proposed GBD algorithm based on the enhanced gradient cut can achieve more than 90%computational time reduction for large-size problem instances compared to the Gurobi solver.The power-of-two policy is capable of providing high-quality solutions with high computational efficiency.

荧光内滤效应技术在生物检测和疾病标志上的应用

荧光内滤效应(inner filter effect,IFE)作为一个重要的非辐射能量转换模型,其作用机理是吸收剂的吸收光谱与荧光剂的激发光谱或发射光谱或两者同时发生谱带重叠,导致荧光剂的激发峰/发射峰的荧光被猝灭。合适的供体-受体对是成功组建IFE传感器检测目标物的重要因素。近年来,IFE技术以其操作简单、灵敏度高,无需修饰供体,无需供体与受体连接,已经引起科研工作者广泛的研究。早期诊断和早期治疗是预防疾病发生和保护健康最为有效的办法。本综述总结了近几年来IFE技术检测酶活、农药、代谢物及小分子化学物质等生物标志物在疾病标志和健康监控上的研究成果,分析了基于"turn-off"法、"turn-on"法以及"ratiometric fluorescence assay"法构建的IFE传感器的独特设计并讨论了各方法的优缺点。最后,简要指出了IFE技术在疾病标志和健康监控上的优点和实际应用时所存在的障碍,并对IFE技术和疾病监控手段未来的发展前景进行了展望。

Adenosine Monophosphate-Activated Protein Kinase,Oxidative Stress,and Diabetic Endothelial Dysfunction

Endothelial dysfunction characterized by impaired endothelium-dependent vaso-relaxation is one of the earliest detectable pathological events in smoking,diabetes,and many cardiovascular diseases including hypertension,atherosclerosis.Overwhelming data from human and animals demonstrate that the endothelial dysfunction associated with diabetes is due to the local formation of oxidants and free radicals.However,the mechanisms by which diabetes instigates oxidative stress,and those by which oxidative stress perpetuates endothelial dysfunction are the subjects of intensive research in the last 3 decades.The studies from us and others have demonstrated that adenosine monophosphate-activated protein kinase(AMPK),a well-characterized energy sensor and modulator,serves as a highly efficient sensor as AMPK can be activated by very low levels of reactive oxygen species(ROS)and reactive nitrogen species(RNS)generated by physiological,pharmacological,and pathologic stimuli(redox sensor).Interestingly,oxidants-activated AMPK feedback lowers the levels of ROS by either suppressing ROS/RNS from reduced nicotinamide adenine dinucleotide phosphate(NADPH)oxidase and mitochondria or by increasing the levels of antioxidant enzymes(redox modulator).Further,our studies demonstrate that AMPK’s functions as a redox sensor and modulator are vital to maintain endothelial cell function under physiological conditions.Finally,we discover that under chronic oxidative stress or large influx of ROS,AMPK is particularly susceptible to inhibition by ROS.We conclude that oxidative inactivation of AMPK in diabetes perpetuates oxidative stress and accelerates atherosclerosis in diabetes.