Digital gene expression profiling analysis of A549 cells cultured with PM10 in moxa smoke

Background:Moxibustion is a traditional Chinese medicine therapy to cure diseases by fumigating meridians or affected parts via burning of moxa floss.Moxa smoke(MS)is one of the key factors in moxibustion.In this study,we adopted digital gene expression profiling,a next-generation gene sequencing technology,to investigate the effect of MS,inhalable particulate matter(PM10),on human lung adenocarcinoma A549 cells.Methods:The effects of MS PM10 on A549 cells,over different treatment durations were investigated in different groups:the 4-h group(4-h MS group and 4-h control group)and the 20-h group(20-h MS group and 20-h control group).Samples collected from the four groups were stored at
80C for subsequent digital gene expression analysis.The differentially expressed genes(DEGs),identified after PM10 treatment,were screened,and their expression patterns analyzed by cluster analysis,Gene Ontology term enrichment,and Kyoto Encyclopedia of Genes and Genomes pathway analysis.Results:Compared with two control groups,1109 DEGs were identified after 4 h of MS intervention and 3565 DEGs were found after 20 h of MS intervention,respectively.Compared with that after 4-h intervention,2149 DEGs were identified after 20-h intervention.Cluster analysis demonstrated that PM10 can significantly inhibit cell cycle process with the prolongation of intervention time.Significant pathway enrichment analysis showed that MS PM10 can inhibit A549 cell cycle process at all phases.When MS PM10 exposure time prolongs,the inhibitory effect on cell cycle process becomes more obvious.Conclusion:MS PM10 has many biological activities,and may cause differential expression of genes involved in various biological processes.Nevertheless,further research on MS is warranted for better understanding of the mechanistic details.

Detecting circulating tumor material and digital pathology imaging during pancreatic cancer progression

Pancreatic cancer(PC) is a leading cause of cancerrelated death worldwide. Clinical symptoms typically present late when treatment options are limited and survival expectancy is very short. Metastatic mutations are heterogeneous and can accumulate up to twenty years before PC diagnosis. Given such genetic diversity, detecting and managing the complex states of disease progression may be limited to imaging modalities and markers present in circulation. Recent developments in digital pathology imaging show potential for early PC detection, making a differential diagnosis, and predicting treatment sensitivity leading to long-term survival in advanced stage patients. Despite large research efforts, the only serum marker currently approved for clinical use is CA 19-9. Utility of CA 19-9 has been shown to improve when it is used in combination with PC-specific markers. Efforts are being made to develop early-screening assays that can detect tumor-derived material, present in circulation, before metastasis takes a significant course. Detection of markers that identify circulating tumor cells and tumor-derived extracellular vesicles(EVs) in biofluid samples offers a promising non-invasive method for this purpose. Circulating tumor cells exhibit varying expression of epithelial and mesenchymal markers depending on the state of tumor differentiation. This offers a possibility for monitoring disease progression using minimally invasive procedures. EVs also offer the benefit of detecting molecular cargo of tumor origin and add the potential to detect circulating vesicle markers from tumors that lack invasive properties. This review integrates recent genetic insights of PC progression with developments in digitalpathology and early detection of tumor-derived circulating material.

Automated Detection and Quantification of Prostate Cancer in Needle Biopsies by Digital Image Analysis

Introduction: Triple immunohistochemical (IHC) stains including antibodies specific for alpha-methylacyl-CoA-racemase and basal cell markers have been a valuable aid in accurate identification of prostate carcinoma. However, accurate quantification of minuscule areas of prostate carcinoma in biopsy specimens can often be a challenge. Here we assessed the diagnostic value and quantitative use of automated digital image analysis on triple IHC stained prostate needle biopsies. Methods: Twelve cases of prostate needle biopsy material including 75 needle cores were stained with triple-antibody cocktail (P504S + 34βE12 + p63). Slides were digitally scanned with the APERIO digital image analyzer and evaluated with the GENIE pattern and color recognition digital image analysis that we developed. A slide with known areas of adenocarcinoma, high grade prostatic intraepithelial neoplasia (PIN), benign glands and stroma was used as a training set for the automated digital image analysis platform. Results: Among 75 needle biopsy cores, 19 (25.33%) contained adenocarcinoma by histology. Digital image analysis recognized adenocarcinoma in 95% of these needle biopsies. The average area of the needle biopsy was 7.63 mm2 and overall the average area of tumor was 0.196 mm2. The smallest area of tumor recognized by the program was 0.0022 mm2 (0.0363% of the core) and the largest was 0.62 mm2 (8.17% of the core) among needle core biopsies. False positives resulted from areas of high grade PIN with patchy basal cells. The false negative was caused by uneven AMACR staining in one area of adenocarcinoma. Digital recognition of areas of interest was improved by three successive image analysis training which increased the sensitivity and specificity from 83% and 89% to 90% and 93%, respectively. Conclusions: Digital image analysis in concert with IHC triple staining may be useful for accurate detection and quantitative analysis of small foci of prostatic adenocarcinoma. Defining methods to increase the sensitivity and specificity of quantitative automated digital image analysis will likely evolve as an area of investigation. Future automated digital scanning and innovative pattern and color recognition technologies may open avenues for classifying a variety of prostate lesions.

Digital television transmission based on asynchronous transfer mode

This paper introduces a method to realize digital television transmission based on asynchronous transfer mode (ATM), a technology based on fast packet switching. Choosing the integral multiple length of an ATM cell payload to equal to the length of an MPEG transport stream packet, an MPEG transport stream packet can be inextenso loaded by several ATM cells and trans-formed into ATM cells. Using ATM virtual connection technology and B-ISDN, the interoperability between ATM and DTV may be realized, and DTV signal transmission may also be realized finally.

Analog-to-digital conversion of information in the retina

We considered the physiological mechanisms of functioning of the retina’s neural network. It is marked that the primary function of a neural network is an analog-to-digital conversion of the receptor potential of photoreceptor into the pulse-to-digital signal to ganglion cells. We showed the role of different types of neurons in the work of analog-to-digital converter. We gave the equivalent circuit of this converter. We researched the mechanism of the numeric coding of the receptor potential of the photoreceptor.

头颈部恶性肿瘤研究模型的演化

恶性肿瘤发生发展的机制探索以及抗癌药物治疗疗效的评估均有赖于各种体内与体外研究模型的建立。近几十年间,随着生物医学技术的快速发展,恶性肿瘤的体内外研究模型也发生了巨大的变化。基因检测技术从单基因到多基因的进展促进了生物信息学飞速发展和恶性肿瘤概念的转变;体外细胞研究模型从单层的二维培养、原代培养向立体的三维构型发展,从而更好地重现肿瘤组织的细胞间交互作用与功能;体内动物研究模型由传统的致癌物诱导、细胞或组织形成移植瘤逐渐演变为基因编辑的动物模型或人源性肿瘤异种移植模型,从而可以针对性地研究相关基因在肿瘤发生发展中的作用;传统的临床研究也从简单的临床回顾性研究更多地向前瞻性研究转变,Ⅰ期/Ⅱ期/Ⅲ期临床研究,研究者发起的临床研究以及真实世界临床研究,这些研究为临床研究增添了活力。目前恶性肿瘤研究模型存在的主要不足包括模型的单一性、对肿瘤微环境的模拟不足、动物肿瘤模型与人类肿瘤差异性,以及缺乏对个性化医疗的考量。未来仍需要进一步研发和优化研究模型,并更有效地将不同模型整合起来,形成一个优化的整体实验模型系统。本文将系统回顾恶性肿瘤研究模型的演化并对相关模型进行阐述,为科研工作者进行恶性肿瘤的研究提供合理的研究模型。

基于OSG引擎的森林火势蔓延仿真系统关键技术研究

针对森林火势蔓延趋势的仿真推演需求,以及森林消防队伍的行动路线选择和实时路径生成的需要,提出了一种融合数字高程信息(digital elevation model,DEM)的扩展晶格模型,将地形的植被、受灾属性与地理高程信息进行结合,通过实时运算得到结果数据并转换为可渲染的资源形式,利用OSG三维渲染引擎将其呈现到最终用户层面。借助这一数据结构以及对应的关键算法技术的研究实现,完成了一套较为完整的森林火势蔓延趋势仿真和灭火演练系统。该系统具有灵活性高,仿真效率和效果较好,支持各种并行计算方法的特点,可以在相关行业和系统中广泛推广和使用。

Novel Perovskite Oxide Hybrid Nanofibers Embedded with Nanocatalysts for Highly Efficient and Durable Electrodes in Direct CO_(2) Electrolysis

The unique characteristics of nanofibers in rational electrode design enable effec-tive utilization and maximizing material properties for achieving highly efficient and sustainable CO_(2) reduction reactions( CO_(2)RRs)in solid oxide elec-trolysis cells(SOECs).However,practical appli-cation of nanofiber-based electrodes faces chal-lenges in establishing sufficient interfacial contact and adhesion with the dense electrolyte.To tackle this challenge,a novel hybrid nanofiber electrode,La_(0.6)Sr_(0.4)Co_(0.15)Fe_(0.8)Pd_(0.05)O_(3-δ)(H-LSCFP),is developed by strategically incorporating low aspect ratio crushed LSCFP nanofibers into the excess porous interspace of a high aspect ratio LSCFP nanofiber framework synthesized via electrospinning technique.After consecutive treatment in 100% H_(2) and CO_(2) at 700°C,LSCFP nanofibers form a perovskite phase with in situ exsolved Co metal nanocatalysts and a high concentration of oxygen species on the surface,enhancing CO_(2) adsorption.The SOEC with the H-LSCFP electrode yielded an outstanding current density of 2.2 A cm^(-2) in CO_(2) at 800°C and 1.5 V,setting a new benchmark among reported nanofiber-based electrodes.Digital twinning of the H-LSCFP reveals improved contact adhesion and increased reaction sites for CO_(2)RR.The present work demonstrates a highly catalytically active and robust nanofiber-based fuel electrode with a hybrid structure,paving the way for further advancements and nanofiber applications in CO_(2)-SOECs.

基于Innovus的局部高密度布局规避方法

标准单元布局是数字集成电路后端设计的重要环节之一,标准单元密度过高影响着工具的布线和时序的优化。采用UMC 28 nm工艺,基于Innovus的两种方法,解决由于局部高密度标准单元导致保持时间违例无法通过工具自动化修复的问题,在实现时序优化的同时降低了动态IR Drop。结果表明,在PreCTS阶段设置setPlaceMode-place_global_max_density value对于后续时序优化效果更好,且动态IR Drop降低8.85%。

High-consistency proton exchange membrane fuel cells enabled by oxygen-electron mixed-pathway electrodes via digitalization design

Proton exchange membrane(PEM)fuel cell has been regarded as a promising approach to the decarbonization and diversification of energy sources.In recent years,durability and cost issues of PEM fuel cells are increasingly significant with the rapid increase of power density.However,the failure to maintain the cell consistency,as one major cause of the above issue,has attracted little attention.Therefore,this study intends to figure out the underlying cause of cell inconsistency and provide solutions to it from the perspective of multi-physics transport coupled with electrochemical reactions.The PEM fuel cells with electrodes under two compression modes are firstly discussed to fully explain the relationship of cell performance and consistency to electrode structure and multi-physics transport.The result indicates that one main cause of cell inconsistency is the intrinsic conflict between the separated transport and cooperated consumption of oxygen and electron throughout the active area.Then,a mixed-pathway electrode design is proposed to reduce the cell inconsistency by enhancing the mixed transport of oxygen and electron in the electrode.It is found that the mixing of pathways in electrodes at under-rib region is more effective than that at the under-channel region,and can achieve an up to 40%reduction of the cell inconsistency with little(3.3%)sacrificed performance.In addition,all the investigations are implemented based on a self-developed digitalization platform that reconstructs the complex physical–chemical system of PEM fuel cells.The fully observable physical information of the digitalized cells provides strong support to the related analysis.

基于数字孪生的铝电解槽三维可视化监控系统

传统的铝电解槽管理存在着管理方式单一、透明度低和参数数据呈现形式弱等问题。为了解决这些问题,本文引入数字孪生技术,将其应用到铝电解槽中,基于数字孪生理论模型及框架进行改进,提出数字孪生铝电解槽的三维可视化监控系统六维模型。基于此模型构建电解槽虚拟模型、场景优化、数据采集及数据映射,通过Java后台提供数据接口,使用three.js三维技术结合JavaScript语言对模型以及数据进行渲染,最终设计实现铝电解槽的三维可视化监控系统。该系统为现场人员提供更加直观的展示效果,使其能更好地了解铝电解槽运行状况,为铝行业智能化发展提供有效思路。

Sphere-forming corneal cells repopulate dystrophic keratoconic stroma:Implications for potential therapy

BACKGROUND Keratoconus is a degenerative corneal disease characterised by aberrant cell behaviour and loss of matrix that can result in vision loss.Cells extracted from peripheral corneas can form stem cell-enriched spheres,which have shown the potential to repopulate the normal peripheral corneal stroma in vitro upon sphere implantation but have not been previously studied in keratoconic tissue.AIM To investigate the therapeutic potential of stem cell-enriched spheres formed from extracted peripheral human corneal cells when introduced to keratoconic tissue.METHODS Stem cell-enriched spheres were formed from extracts of normal cadaveric human peripheral corneal cells.These spheres were implanted into incisions created in full thickness and onto the surface of 10μm thin sections of keratoconic and normal stromal tissues in vitro.Tissue sections were used to maximise use of limited keratoconic tissue available for research.Living cells were stained with Calcein-AM and visualised with stereo and fluorescence microscopy to assess survival and behaviours between the time of implantation day 0 and 14 d(D14)from implantation.Sphere cells in implanted tissues were characterised for stem cell and differentiation markers using immunohistochemistry and droplet digital PCR to assess the potential implications of these characteristics in the use of spheres in keratoconus treatment.RESULTS Spheres were successfully implanted into full-thickness central corneal tissue and onto the surface of 10μm thin en face tissue sections.No observable differences were seen in sphere migration,proliferation or differentiation in keratoconic tissue compared to normal between day 0 and D14.Spheres stained positively with Calcein-AM up to D14.Cell migration increased from day 0 to D14,occurring radially in three dimensions from the sphere and in alignment with tissue edges.Cell proliferation marker,EdU,was detected at day 10.Implanted spheres stained positively for putative stem cell markersΔNp63αand ABCB5,while ABCG2,ABCB5,ΔNp63 and p63αwere detectable by droplet digital PCR up to D14.Double immunolabelling revealed absence of ABCB5 staining in migrated cells but positive staining of alpha smooth muscle actin(myofibroblast marker)in some migrated cells.Droplet digital PCR showed similar expression patterns of differentiation markers but a reduction in stem cell markers between normal and keratoconic tissue with an increase in stromal cell markers and a reduction in epithelial cell markers,indicating an appropriate response to repopulating diseased tissue.CONCLUSION Cells from implanted stem cell-enriched spheres can repopulate a keratoconic corneal stromal surface in a directed manner and exhibit migratory stromal cell phenotypes.

Quantitative analysis of butyric acid-induced nuclear ultrastructural alterations in cells of human lung giant cell carcinoma in vitro

The effects of butyric acid(BA)on the nuclear ultrastructure of humanlung giant cell carcinoma(Strain PLA-801 D)were observed with digital imageprocessing.It was found that the length of the nuclear circumference of the tu-mor cells incubated with 2mmol of BA was approximately equal to that of thecontrol whereas the nuclear area was increased by 1.4times,which implies thatthe nuclear profile tends to become more regular after BA treatment.In addition,the optical density of the nuclei of the experimental group decreased significantlyas compared with that of the control,which indicates that the chromatin in thenuclei was decreased by BA.It was concluded on the basis of the findings thatBA may have a biological effect of reverse-transformation on the malignant cells.

The Viral Load of Epstein-Barr Virus in Blood of Children after Hematopoietic Stem Cell Transplantation

Objective To detect the Epstein-Barr virus(EBV)viral load of children after hematopoietic stem cell transplantation(HSCT)using chip digital PCR(cdPCR).Methods The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain.The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses(herpes simplex virus 1,herpes simplex virus 2,varicella zoster virus,human cytomegalovirus,human herpesvirus 6,and human herpesvirus 7).From May 2019 to September 2020,64 serum samples of children following HSCT were collected.EBV infection and the viral load of serum samples were detected by cdPCR.The epidemiological characteristics of EBV infections were analyzed in HSCT patients.Results The limit of detection of EBV cdPCR was 110 copies/mL,and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid.The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain,and both were more sensitive than that of quantitative PCR.Using cdPCR,the incidence of EBV infection was 18.75%in 64 children after HSCT.The minimum EBV viral load was 140 copies/mL,and the maximum viral load was 3,209 copies/mL using cdPCR.The average hospital stay of children with EBV infection(184±91 days)was longer than that of children without EBV infection(125±79 days),P=0.026.Conclusion EBV cdPCR had good sensitivity and specificity.The incidence of EBV infection was 18.75%in 64 children after HSCT from May 2019 to September 2020.EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.

数字孪生制造单元多维多尺度建模与边—云协同配置

为了解决离散型智能车间多维、多尺度、高保真建模及其软硬件配置与协同问题,以离散型智能车间的基本实现单元——数字孪生制造单元为对象,从数据—知识混合驱动的角度,探明新一代信息技术赋能下数字孪生制造单元的构成要素与关键特征,提出数字孪生制造单元的多维多尺度智能空间模型及其高保真建模方法。进一步从边—云协同的角度构建软硬件集成的数字孪生制造单元配置模型,建立了基于智能合约的数字孪生制造单元边—云协同运行与智能化管控机制。采用Java Web技术开发了数字孪生制造单元原型系统,并以航空发动机整体叶轮加工过程为案例,验证了所提模型与方法的正确性和有效性。

基于数字孪生的智能制造单元仿真实验系统

为丰富智能制造专业课程的实验教学内容,依据数字孪生思想,提出了一种多维模型融合的数字孪生系统模型集成方法,用于智能制造相关知识的实验教学,并以机器人上下料工作站为案例,搭建了基于数字孪生的智能制造单元实验系统。在数字孪生系统框架的基础上,对智能制造单元进行多维模型融合分析,对智能制造单元数字孪生体进行建模与分析,可以准确监控智能制造单元的实时状态,验证了基于数字孪生的智能制造单元实验系统的可行性和有效性。同时也为智能制造单元认知实验、生产过程管控实验等提供基础。

基于低分辨率DAC的IRS辅助去蜂窝大规模MIMO系统联合预编码设计

本文研究了下行链路智能反射面(Intelligent Reflective Surface, IRS)辅助去蜂窝大规模MIMO(Cell-Free Massive Multiple-Input Multiple-Output)系统,其中每个接入点(Access Point, AP)都采用了低分辨率的数模转换器(Digital-to-Analog Converters,DAC)。本文将IRS应用于去蜂窝系统并在AP处配备低分辨率DAC,进一步降低了硬件成本和功耗。采用加性量化噪声模型对低分辨率DAC进行数学建模,进而建立了下行链路用户和速率的表达式。由于公式具有非凸性和高复杂性,本文提出了一个交替优化框架来解决此问题,从而提高用户和速率。特别地,我们通过分数规划解耦这个问题,并采用拉格朗日乘子法和半定规划(Semi-Definite Programming,SDP)方法求得预编码矩阵和相移矩阵的表达式。最后,仿真结果表明,与传统的去蜂窝网络相比,该方案下的网络容量可以显著提高。

MCS HOG Features and SVM Based Handwritten Digit Recognition System

Digit Recognition is an essential element of the process of scanning and converting documents into electronic format. In this work, a new Multiple-Cell Size (MCS) approach is being proposed for utilizing Histogram of Oriented Gradient (HOG) features and a Support Vector Machine (SVM) based classifier for efficient classification of Handwritten Digits. The HOG based technique is sensitive to the cell size selection used in the relevant feature extraction computations. Hence a new MCS approach has been used to perform HOG analysis and compute the HOG features. The system has been tested on the Benchmark MNIST Digit Database of handwritten digits and a classification accuracy of 99.36% has been achieved using an Independent Test set strategy. A Cross-Validation analysis of the classification system has also been performed using the 10-Fold Cross-Validation strategy and a 10-Fold classification accuracy of 99.26% has been obtained. The classification performance of the proposed system is superior to existing techniques using complex procedures since it has achieved at par or better results using simple operations in both the Feature Space and in the Classifier Space. The plots of the system’s Confusion Matrix and the Receiver Operating Characteristics (ROC) show evidence of the superior performance of the proposed new MCS HOG and SVM based digit classification system.

建立数字PCR检测非小细胞肺癌溶酶体相关的4次跨膜蛋白B基因拷贝数变异方法

建立芯片式数字PCR(dPCR)检测非小细胞肺癌(NSCLC)LAPTM4B基因拷贝数变异方法,并初步评估其基本性能和临床应用的可行性。设计LAPTM4B基因引物及特异性探针,建立dPCR反应体系,根据制备的不同浓度目的DNA样品验证该检测方法的最低检测限、精密度和线性范围。本研究首次建立并优化dPCR检测LAPTM4B基因拷贝数的反应体系,分析数据显示,该方法最低检测到12.5%的LAPTM4B基因拷贝数缺失,批间精密度变异系数CV<10%,且缺失比例在12.5%~100%范围内线性良好(R^(2)>0.99)。此外,收集2021年3月至7月于北京大学肿瘤医院就诊的6例NSCLC患者,采用自建方法检测其冰冻组织标本,探究其临床应用可行性。dPCR结果显示,其中5例患者的组织样本存在LAPTM4B基因拷贝数缺失,1例出现拷贝数增加,推测可能与其术前化疗有关。综上所述,本研究成功应用芯片式dPCR方法,建立非小细胞肺癌LAPTM4B基因拷贝数变异的检测体系,并在组织标本中初步证实其临床应用的价值。