罕见EGFR L833V/H835L复合突变的肺腺癌患者1例及文献回顾

表皮生长因子受体(epidermal growth factor receptor,EGFR)突变是非小细胞肺癌(non-small cell lung cancer,NSCLC)发生发展过程中最常见的驱动基因,其中18-21号外显子的突变常见,尤其是19号外显子的缺失和21号外显子L858R点突变最为常见,但是EGFR L833V/H835L罕见基因复合突变的发生率非常低,患者数量很少,相关临床数据和治疗方法的证据也不足。部分EGFR-酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)在治疗伴有罕见基因突变的肺癌患者方面同样具有良好疗效。本文报道了1例携带EGFR L833V/H835L罕见基因复合突变的NSCLC患者,在给予阿法替尼治疗5个月后,计算机断层扫描(computed tomography,CT)显示肺部病灶缩小,患者对阿法替尼联合安罗替尼治疗反应良好。同时,我们还对以往报道的EGFR L833V/H835L罕见基因复合突变的NSCLC患者进行了整理,总结了该类患者的特点及应用不同种类EGFR-TKIs治疗的效果。

Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis

AIM:To investigate the expression of co-stimulatorymolecule B7-H3 in gastric carcinoma and adenomatissue as well as normal gastric tissue and to explore therelationship between B7-H3 expression and pathologicalfeatures and prognosis of gastric carcinoma.METHODS:B7-H3 expression was detected in 102samples of human gastric carcinoma and 10 samples ofgastric adenoma and 10 samples of normal gastric tissueby immunohistochemical assay.Correlation betweenthe expression of B7-H3 and the patients'age,sex,gastric carcinoma locus,tumor size,tissue type,tumorinfiltration depth,differentiation degree,lymph nodemetastasis,and survival time was analyzed.RESULTS:B7-H3 was expressed in all gastric adenomasamples and in 58.8% samples of gastric carcinoma.B7-H3 expression in gastric carcinoma samples wasnot related with the patients'age,sex,lymph nodemetastasis,and tumor size(P>0.05),but with thesurvival time,infiltration depth of tumor and tissue type.CONCLUSION:Detection of B7-H3 expression in gastriccarcinoma tissue is beneficial to the judgment of theprognosis of gastric carcinoma patients and the choice oftreatment.

Towards electronic-photonic-converged thermo-optic feedback tuning

As Moore’s law approaching its end,electronics is hitting its power,bandwidth,and capacity limits.Photonics is able to overcome the performance limits of electronics but lacks practical photonic register and flexible control.Combining electronics and photonics provides the best of both worlds and is widely regarded as an important post-Moore’s direction.For stability and dynamic operations considerations,feedback tuning of photonic devices is required.For silicon photonics,the thermooptic effect is the most frequently used tuning mechanism due to the advantages of high efficiency and low loss.However,it brings new design requirements,creating new design challenges.Emerging applications,such as optical phased array,optical switches,and optical neural networks,employ a large number of photonic devices,making PCB tuning solutions no longer suitable.Electronic-photonic-converged solutions with compact footprints will play an important role in system scalability.In this paper,we present a unified model for thermo-optic feedback tuning that can be specialized to different applications,review its recent advances,and discuss its future trends.

Blockchain Technology Empowers Telecom Network Operation

Telecom operators are deploying the fifth generation(5G) networks around the world which promises high information transmission rate, wide network coverage, low communication delay, and easy access to a large number of devices. However, during the construction and operation of 5G, telecom operators face many challenges, such as insufficient frequency resources, low efficiency of network management, information opacity, risks of data interoperability, and network privacy vulnerabilities. As 5G is generally deployed in heterogeneous networks with massive ubiquitous devices, it is quite necessary to provide secure and decentralized solutions. Blockchain is a distributed system maintained by multiple parties with inherit features including decentralization,traceability and tamperproof. These features collectively contribute to a new application ecosystem where transactions are secure and trustworthy. Therefore,blockchain is expected to integrate with 5G networks to build safer and more reliable mobile network infrastructures. This paper firstly discusses the merits of blockchain technology and the benefits of integrating it with 5G networks. Then a variety of applications of blockchain technology in telecom network operation are reviewed, including spectrum sharing, international roaming settlement, network operation management, number selection management and supply chain management. In the end, we show our recently advance in integrating blockchain in 5G by introducing a multi framework based blockchain service network architecture deployed in real environment.

Phosphoinositide-3-kinase,catalytic,alpha polypeptide RNA interference inhibits growth of colon cancer cell SW948

AIM:To investigate the gene knock-down effect by the phosphoinositide-3-kinase,catalytic,alpha polypeptide(PIK3CA)-targeted double-stranded RNA(dsRNA) and its effect on cell proliferation and cycle distribution in SW948.METHODS:Two PIK3CA-targeted dsRNAs were constructed and transfected into SW948 cells.Transfections were performed using lipofectamine TM 2000.The transfection effectiveness was calculated basing on the rate of fluorescence cell of SW948 at 6 h after transfection.Total messenger RNA was extracted from these cells using the RNeasy kit,and semiquantitative reverse transcription polymerase chain reaction was performed to detect the down-regulation of PIK3CA,AKT1,MYC,and CCND1 gene expression.Cells were harvested,proteins were resolved,and western blot was employed to detect the expression levels of PIK3CA,AKT1,MYC,and CCND1 gene.Cell proliferation was assessed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay and the inhibition rate was calculated.Soft agar colony formation assay was performed basing on colonies greater than 60 μm in diameter at ×100 magnification.The effect on cell cycle distribution and apoptosis was assessed by flow cytometry.All experiments were performed in triplicate.RESULTS:Green fluorescence was observed in SW948 cell transfected with plasmid Pgenesil-1,and the transfection effectiveness was about 65%.Forty-eight hours post-transfection,mRNA expression of PIK3CA in SW948 cells was 0.51 ± 0.04 vs 0.49 ± 0.03 vs 0.92 ± 0.01 vs 0.93 ± 0.03(P = 0.001) in Pgenesil-CA1,Pgenesil-CA2,negative and blank group respectively.mRNA expression of AKT1 was 0.50 ± 0.03 vs 0.48 ± 0.01 vs 0.93 ± 0.04 vs 0.92 ± 0.02(P = 0.000) in Pgenesil-CA1,Pgenesil-CA2,negative and blank group respectively.mRNA expression of MYC was 0.49 ± 0.01 vs 0.50 ± 0.04 vs 0.90 ± 0.02 vs 0.91 ± 0.03(P = 0.001) in the four groups respectively.mRNA expression of CCND1 was 0.45 ± 0.02 vs 0.51 ± 0.01 vs 0.96 ± 0.03 vs 0.98 ± 0.01(P = 0.001) in the four groups respectively.The protein level of PIK3CA was 0.53 ± 0.01 vs 0.54 ± 0.02 vs 0.92 ± 0.03 vs 0.91 ± 0.02(P = 0.001) in Pgenesil-CA1,Pgenesil-CA2,negative and blank group respectively.The protein level of AKT1 in the four groups was 0.49 ± 0.02 vs 0.55 ± 0.03 vs 0.94 ± 0.03 vs 0.95 ± 0.04,P = 0.000).The protein level of MYC in the four groups was 0.51 ± 0.03 vs 0.52 ± 0.04 vs 0.92 ± 0.02 vs 0.95 ± 0.01(P = 0.000).The protein level of CCND1 in the four groups was 0.54 ± 0.04 vs 0.56 ± 0.03 vs 0.93 ± 0.01 vs 0.93 ± 0.03(P = 0.000).Both Pgenesil-CA1 and Pgenesil-CA2 plasmids significantly suppressed the growth of SW948 cells when compared with the negative or blank group at 48 h after transfec-tion(29% vs 25% vs 17% vs 14%,P = 0.001),60 h after transfection(38% vs 34% vs 19% vs 16%,P = 0.001),and 72 h after transfection(53% vs 48% vs 20% vs 17%,P = 0.000).Numbers of colonies in negative,blank,CA1,and CA2 groups were 42 ± 4,45 ± 5,8 ± 2,and 10 ± 3,respectively(P = 0.000).There were more than 4.5 times colonies in the blank and negative control groups as there were in the CA1 and CA2 groups.In addition,the colonies in blank and negative control groups were also larger than those in the CA1 and CA2 groups.The percentage of cells in the CA1 and CA2 groups was significantly higher in G 0 /G 1 phase,but lower in S and G 2 /M phase when compared with the negative and control groups.Moreover,cell apoptosis rates in the CA1 and CA2 groups were 5.11 ± 0.32 and 4.73 ± 0.32,which were significantly higher than those in negative(0.95 ± 0.11,P = 0.000) and blank groups(0.86 ± 0.13,P = 0.001).No significant difference was found between CA1 and CA2 groups in cell cycle distribution and apoptosis.CONCLUSION:PIK3CA-targeted short hairpin RNAs can block the phosphoinositide 3-kinase-Akt signaling pathway and inhibit cell growth,increase apoptosis,and induce cell cycle arrest in the PIK3CA-mutant colon cancer SW948 cells.

Development and Control of Underwater Gliding Robots:A Review

As one of the most effective vehicles for ocean development and exploration,underwater gliding robots(UGRs)have the unique characteristics of low energy consumption and strong endurance.Moreover,by borrowing the motion principles of current underwater robots,a variety of novel UGRs have emerged with improving their maneuverability,concealment,and environmental friendliness,which significantly broadens the ocean applications.In this paper,we provide a comprehensive review of underwater gliding robots,including prototype design and their key technologies.From the perspective of motion characteristics,we categorize the underwater gliding robots in terms of traditional underwater gliders(UGs),hybrid-driven UGs,bio-inspired UGs,thermal UGs,and others.Correspondingly,their buoyancy driven system,dynamic and energy model,and motion control are concluded with detailed analysis.Finally,we have discussed the current critical issues and future development.This review offers valuable insight into the development of next-generation underwater robots well-suited for various oceanic applications,and aims to gain more attention of researchers and engineers to this growing field.

Containment Control of General Linear Multi-agent Systems with Multiple Dynamic Leaders:a Fast Sliding Mode Based Approach

In this paper, distributed containment control problems of general linear multi-agent systems are investigated. The objective is to make the followers in a multi-agent network converge to the convex hull spanned by some leaders whose control inputs are nonzero and not available to any followers.Sliding mode surfaces are defined for the cases of reduced order and non-reduced order, respectively. For each case, fast sliding mode controllers are designed. It is shown that all the error trajectories exponentially reach the sliding mode surfaces in a finite time if for each follower, there exists at least one of the leaders who has a directed path to the follower, and the leaderscontrol inputs are bounded. The control Lyapunov function for exponential finite time stability, motivated by the fast terminal sliding mode control, is used to prove reachability of the sliding mode surfaces. Simulation examples are given to illustrate the theoretical results.

The Impact of Restricted Measures on Price Discovery in Stock Index Futures:Evidence from CSI 500 Stock Index Futures

This paper compares the impact of restricted measures on CSI 500 stock index futures market and its underlying spot market.It uses vector error correction(VECM)model and common factor analysis method to study the differences between the two markets before and after the restricted measures was implemented.This paper analyzes the price discovery function through three aspects,i.e.,response to new information,price ratio of new information,and price discovery contribution degree of two markets.Based on empirical results,it is clear that group one in the period of April 17th to September 2nd has an obvious price discovery function.However,group two in the period of September 7th to December 31th does not have.The result shows that stock index futures do have price discovery function to some extent.However,due to the impact of restrictive policies,the spot market price contribution may exceed the futures market in some special time periods,which implies that the price discovery function of CSI 500 stock index futures market is not stable.

Increment of hFIX expression with endogenous intron 1 in vitro

This paper probes into the feasibility of increasing expression level of hFIX gene with endogenous nitron 1 sequence. hFIX minigene was obtained with middle sequence truncated nitron 1 inserted into the relative site of hFIX cDNA, and plasmid vector pKG5i’IX, retroviral vector GINaCi’IX were constructed. These vectors were transduced into target cells of PA317, C2C12, primary rabbit skin fibroblasts (RSF) and primary human skin fibroblasts (HSF). The expression level of mixed colonies are PA317/pKG5i’IX, 151 "g/106 cells/24h; PA317/GINaCi’IX, 308ng/106 cells/24 h; C2C12/G1 NaCi’IX, 186 ng/106 cells/24 h; RSF/GINaCi’IX, 1929 ng/106 cells/24 h; HSF/GlNaCi’IX, 1646 ng/106 cells/ 24 h. These results indicated that hFIX minigene with nitron 1 is able to increase the expression level to about 3 times of that of hFIX cDNA. Meanwhile, in order to study the application of hFIX minigene in the retroviral-mediated gene transfer system and refrain from nitron splicing during viral production, a retroviral vector GlNaCi’IXR with reversely inserted hFIX minigene expression cassette was constructed. The expression level of reverse constructor in PA317 cells was 390 ng/106 cells/24 h with 79% of bioactivity. PCR detection of HT/GlNaCi’IXR cells infected with PA317/ClNaCi’IXR supernatant confirmed the existence of nitron 1 sequence. These results suggested that expression vector with forward-inserted intronl-carrying hFIX expression cassette can be used in directed gene Human factor IX expression with nitron transfer, but when using the retroviral-mediated gene transfer system, reversely-inserted intronl-carrying hFIX expression cassette should be considered.

Modeling and identification of a PEM fuel cell humidification system

A theoretical model of a humidifier of proton exchange membrane （PEM） fuel cell systems is developed and analyzed first in this paper. The model shows that there exists a strong nonlinearity in the system. Then, the system is identified using a wavelet networks method. To avoid the curse-of-dimensionality problem, a class of wavelet networks proposed by Billings is employed. The experimental data acquired from the test bench are used for identification. The one-step-ahead predictions and the five-step-ahead predictions are compared with the real measurements, respectively. It shows that the identified model can effectively describe the real system.

Evolution of defects and deformation mechanisms in different tensile directions of solidified lamellar Ti-Al alloy

Two-phaseγ-TiAl/α_(2)-Ti_(3)Al lamellar intermetallics have attracted considerable attention because of their excellent strength and plasticity.However,the exact deformation mechanisms remain to be investigated.In this paper,a solidified lamellar Ti-Al alloy with lamellar orientation at 0°,17°,and 73°with respect to the loading direction was stretched by utilizing molecular dynamics(MD)simulations.The results show that the mechanical properties of the sample are considerably influenced by solidified defects and tensile directions.The structure deformation and fracture were primarily attributed to an intrinsic stacking fault(ISF)accompanied by the nucleated Shockley dislocation,and the adjacent extrinsic stacking fault(ESF)and ISF formed by solidification tend to form large HCP structures during the tensile process loading at 73°.Moreover,cleavage cracking easily occurs on theγ/α_(2)interface under tensile deformation.The fracture loading mechanism at 17°is grain boundary slide whereas,at 73°and 0°,the dislocation piles up to form a dislocation junction.

Convertible Bond Pricing Based on Exponential Variance Gamma Model

Due to the‘spike and tail’ phenomenon of asset returns,the applicability of the Black-Scholes model for pricing convertible bonds has been questioned,and the variance gamma model can cope well with this phenomenon and solve the ‘volatility smile dilemma’.This paper combines the variance gamma model with the least squares Monte Carlo simulation method to empirically analyze the Everbright convertible bond based on its high activity in the Chinese market.In this paper,the predicted price and the actual price are compared,and the applicability of the variance gamma model in the Chinese convertible bond market is analyzed.Empirical results show that the fitting price predicted by the variance gamma model is consistent with the actual price trend,indicating that the method is applicable to the Chinese convertible bond market.

Numerical simulation of coupling multi-physical field in electrical arc furnace for smelting titanium slag

The smelting reduction process of the ilmenite in an electric arc furnace(EAF)is a commonly used technology for producing titanium slag in the world.It has particular significance to analyze the velocity-temperature-electromagnetics multi-physical field in an EAF for improving its productivity and reducing energy consumption.A transient three-dimensional mathematical model was developed to characterize the flow,heat transfer,and electromagnetic behavior in a titanium slag EAF.For describing the electromagnetic field and its effects on velocity and temperature distribution in the furnace,magnetohydrodynamic equations and conservation equations for mass,momentum,and energy were solved simultaneously by compiling the user-defined function program.The numerical model was verified by comparing with the literature data.The results indicate that the Lorentz force is the main driving force of the velocity and temperature distribution.Moreover,the influence of input current and location of electrodes on the multi-physical field distribution was also investigated.It is found that the appropriate range of input current and diameter of pitch circle are about 30,000 A and 3000-3500 mm,respectively.The mathematical model established can characterize the multi-physical field more accu-rately than before,which can provide valuable guidance for the operation improvement and design optimization of the EAF for producing titanium slag.

Grasp Detection with Hierarchical Multi-Scale Feature Fusion and Inverted Shuffle Residual

Grasp detection plays a critical role for robot manipulation.Mainstream pixel-wise grasp detection networks with encoder-decoder structure receive much attention due to good accuracy and efficiency.However,they usually transmit the high-level feature in the encoder to the decoder,and low-level features are neglected.It is noted that low-level features contain abundant detail information,and how to fully exploit low-level features remains unsolved.Meanwhile,the channel information in high-level feature is also not well mined.Inevitably,the performance of grasp detection is degraded.To solve these problems,we propose a grasp detection network with hierarchical multi-scale feature fusion and inverted shuffle residual.Both low-level and high-level features in the encoder are firstly fused by the designed skip connections with attention module,and the fused information is then propagated to corresponding layers of the decoder for in-depth feature fusion.Such a hierarchical fusion guarantees the quality of grasp prediction.Furthermore,an inverted shuffle residual module is created,where the high-level feature from encoder is split in channel and the resultant split features are processed in their respective branches.By such differentiation processing,more high-dimensional channel information is kept,which enhances the representation ability of the network.Besides,an information enhancement module is added before the encoder to reinforce input information.The proposed method attains 98.9%and 97.8%in image-wise and object-wise accuracy on the Cornell grasping dataset,respectively,and the experimental results verify the effectiveness of the method.

Real-time in-situ monitoring of chiral changes during a reaction at single-molecule level

Molecular chirality is a widespread phenomenon in nature,playing a critical role in various fields such as chemistry [1],life sciences [2], and materials science [3], and has therefore attracted significant attention and research by scholars [4–6].However, the chirality in chemical reactions is often dynamic, making real-time monitoring of chiral changes during chemical reactions at the single-molecule level extremely challenging.

Kinematic Comparison of Forward and Backward Swimming and Maneuvering in a Self-Propelled Sub-Carangiform Robotic Fish

We make a thorough kinematic comparison of forward and backward swimming and maneuvering on a self-propelled robot platform that uses sub-carangifbrm swimming as the primary propulsor. An improved Central Pattern Generator （CPG） model allowing free adjustment of phase relationship and directional bias is employed to achieve flexible swimming and smooth transition. Considering the characteristics of forward swimming in carangiform fish and backward swimming in anguilliform fish, various backward swimming patterns for the sub-carangiform robotic fish are suitably created by reversing the direction of propagating propulsive waves. Through a combined use of the CPG control and closed-loop swimming direction control strategy, flexible and precise turning maneuvers in both forward and backward swimming are implemented and compared. By contrast with forward swimming, backward swimming requires a higher frequency or an increased lateral displacement to reach the same relative swimming speed. Noticeably, the phase difference shows a greater impact on forward swimming than on backward swimming. Our observations also indicate that the robotic fish achieves a larger turning rate in forward maneuvering than in backward maneuvering, yet these two maneuvers display comparable turning precision.

Co‑packaged optics(CPO):status,challenges,and solutions

Due to the rise of 5G,IoT,AI,and high-performance computing applications,datacenter trafc has grown at a compound annual growth rate of nearly 30%.Furthermore,nearly three-fourths of the datacenter trafc resides within datacenters.The conventional pluggable optics increases at a much slower rate than that of datacenter trafc.The gap between application requirements and the capability of conventional pluggable optics keeps increasing,a trend that is unsustainable.Copackaged optics(CPO)is a disruptive approach to increasing the interconnecting bandwidth density and energy efciency by dramatically shortening the electrical link length through advanced packaging and co-optimization of electronics and photonics.CPO is widely regarded as a promising solution for future datacenter interconnections,and silicon platform is the most promising platform for large-scale integration.Leading international companies(e.g.,Intel,Broadcom and IBM)have heavily investigated in CPO technology,an inter-disciplinary research feld that involves photonic devices,integrated circuits design,packaging,photonic device modeling,electronic-photonic co-simulation,applications,and standardization.This review aims to provide the readers a comprehensive overview of the state-of-the-art progress of CPO in silicon platform,identify the key challenges,and point out the potential solutions,hoping to encourage collaboration between diferent research felds to accelerate the development of CPO technology.

Sliding Mode Control for Flexible-link Manipulators Based on Adaptive Neural Networks

This paper mainly focuses on designing a sliding mode boundary controller for a single flexible-link manipulator based on adaptive radial basis function （RBF） neural network. The flexible manipulator in this paper is considered to be an Euler-Bernoulli beam. We first obtain a partial differential equation （PDE） model of single-link flexible manipulator by using Hamiltons approach. To improve the control robustness, the system uncertainties including modeling uncertainties and external disturbances are compensated by an adaptive neural approximator. Then, a sliding mode control method is designed to drive the joint to a desired position and rapidly suppress vibration on the beam. The stability of the closed-loop system is validated by using Lyapunov＇s method based on infinite dimensional model, avoiding problems such as control spillovers caused by traditional finite dimensional truncated models. This novel controller only requires measuring the boundary information, which facilitates implementation in engineering practice. Favorable performance of the closed-loop system is demonstrated by numerical simulations.

Dependence of magnetic properties on microstructure and composition of Ce-Fe-B sintered magnets

In this paper,dependence of magnetic properties on microstructure and composition of Ce-Fe-B sintered magnets with Cu-doped Ce-rich alloy addition was investigated.It shows that the maximum energy product(BH)(max)and coercivity H(cj)of Ce-Fe-B sintered magnet are improved from 6.76 to 9.13 MGOe by 35.1%,and from 1.44 to 1.67 kOe by 16.0%,respectively,via adding 5 wt%liquid phase alloy of Ce(35.58)Fe(57.47)Cu6 B(0.95)(at%).Compared with the magnet without Cerich alloy addition,the volume fraction of the grain-boundary phase with low melting point increases in the magnet with Ce-rich alloy additio n,which is be ne ficial to imp roving the microstructure and promoting the coercivity enhancement of the magnet.In the Ce-Fe-B magnet with Ce-rich alloy addition,Cu and Ce enrich in the grain boundaries of the magnet after annealing,therefore the as-annealed magnet has a higher coercivity than the as-sintered magnet.A distinct Fe-rich layer with the average thickness of 60 nm is found in the grain boundaries in the magnet without Ce-rich alloy addition,but it seems that Fe-rich phase disappears in the magnet with Ce-rich alloy addition.The present work suggests that the further improvement of coercivity in the Ce-Fe-B sintered magnets is expectable by designing the composition and structure of added liquid phase alloys.

Hydrodynamic Analysis and Verification of an Innovative Whale Shark-like Underwater Glider

This paper presents an innovative design for a biomimetic whale shark-like underwater glider aiming at the combination of high maneuverability and long duration.As a hybrid of the underwater glider and the robotic fish,its pectoral fins and tail can serve as not only the external control surfaces for attitude regulation during gliding but also the propellers for agile fish-like swimming mode.To verify the gliding capability of the whale shark-like glider and prepare for future dynamic analysis,the hydrodynamic coefficients,including drag,lift,sliding force,and corresponding moments are estimated through computational fluid dynamics method.In addition,the hydrodynamic analyses of the proposed glider and an equivalent conventional glider during steady gliding motion are executed for comparison.Extended experiments are performed to verify the downward gliding performance.The results reveal that the whale shark-like glider has less drag as well as higher lift-to-drag ratio and a markable gliding capability in practice.It may offer important inspiration for improving the gliding efficiency and performance of an underwater glider in biomimetic shape design.