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乳腺癌相关新关键基因和生物学通路的生物信息学识别

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乳腺癌相关新关键基因和生物学通路的生物信息学识别

作者： md.shahin alam 苏州大学

学位级别：硕士

癌症对世界各地的人类健康有多种影响,它是仅次于心血管疾病的全球第二大死亡原因。全世界范围内不同地区的癌症发病率和死亡率不同,尤其是在不同国家之间,因为人口、生态、文化、环境和遗传变量等因素的差异会导致癌症发病率的异质性... 详细信息

癌症对世界各地的人类健康有多种影响,它是仅次于心血管疾病的全球第二大死亡原因。全世界范围内不同地区的癌症发病率和死亡率不同,尤其是在不同国家之间,因为人口、生态、文化、环境和遗传变量等因素的差异会导致癌症发病率的异质性。根据最新的全球癌症数据,2018年癌症新增1810万例新病例,960万例死亡病例。其中前列腺癌、胃癌和肝癌在男性中最为常见,而乳腺癌、宫颈癌和甲状腺癌在女性中最为常见,肺癌和结直肠癌在两者中都具有较高的患病率。癌症的发病率最高的前三位是肺癌、乳腺癌和结直肠癌,它们的死亡率排名分别为第一、第五和第二。全球乳腺癌发病率自20世纪70年代末一直呈上升趋势,是全世界女性癌症死亡的第二大主要原因,99%发生在女性,男性仅占1%,约占女性所有癌症的26%。早期乳腺癌往往不具备典型的症状和体征,不易引起重视,常通过体检或乳腺癌筛查发现。与乳腺癌相关的危险因素有肥胖、酗酒、更年期激素替代疗法、电离辐射、月经初潮、晚育或不生育、年龄大、患乳腺癌的既往史、家庭乳腺癌史、缺乏体育锻炼等。乳腺癌是一种恶性肿瘤,是由某种基因突变导致的异常细胞的无节制增殖所致,这种基因异常通常发生在乳腺导管（连接乳腺与乳头的导管）或乳腺小叶（分泌乳汁的部分）中。随着科技时代日新月异的发展以及人们对乳腺癌认识的不断深入,乳腺癌的治疗进入了综合治疗时代,形成了局部治疗与全身治疗并重的治疗模式。医生会根据肿瘤的分期和患者的身体状况,酌情采用手术、放疗、化疗、生物靶向治疗等多种手段。外科手术在乳腺癌治疗中发挥着重要作用。但较其缺点来说——把病人体内肿瘤切除,并不能直接“消灭”肿瘤,也不是战胜癌症的良方。控癌是场持久战,不能单独地“一刀切”来解决问题。放疗是利用放射线破坏癌细胞的生长、繁殖,达到控制和消灭癌细胞的作用,但放射性在破坏和杀死肿瘤细胞的同时,对周围正常组织细胞也有破坏作用。手术、放疗均属于局部治疗。化学治疗是一种应用抗癌药物抑制癌细胞分裂,破坏癌细胞的治疗方法,简称化疗。化疗也可能会导致患者出现消化道反应,引起恶心、呕吐、头晕以及食欲不振等。分子靶向治疗是近年来最为活跃的研究领域之一,与化疗药物相比,是具有多环节作用机制的新型抗肿瘤治疗药。因此,更好地应用已发布的生物标志物、发现新的生物标志物以及潜在的治疗靶标对改善乳腺癌的预后和治疗至关重要。人表皮生长因子受体2（HER2）和雌激素受体α（ERα）常常被用于预后和激素治疗反应预测中,是目前最有效的乳腺癌生物标志物。但是,由于某些乳腺癌亚型并不表达ER α或HER2,因此需要应用其他生物标志物。然而,目前并没有发现其他生物标志物与靶向治疗的之间是否存在精准的关联。因此,迫切需要评估潜在的新生物标志物,以用于乳腺癌的诊断和治疗改善。癌症的发生率随着年龄的增长而增加,因此癌症的预防和治疗以及慢性病的管理已成为影响社会经济发展的关键因素。生物医学和信息技术的快速发展,以及主动健康、精准医疗和大数据范式的出现,为癌症的预防和治疗带来了新的机遇。本课题的研究方向包括癌症的异质性和外部综合征、癌症深度表型的挖掘、用于癌症治疗的联合用药算法、癌症的预防和治疗信息模型和慢性病的管理以及系统和平台构建。基于此,本研究的目的是通过生物信息学的方法来评估潜在的新基因作为乳腺癌诊断的生物标志物和药物靶标,并了解其分子机制,改进乳腺癌的治疗策略。首先,通过比较8个乳腺癌组织和相应对照组织的基因表达谱,我们检测到236个具有统计学意义的差异表达基因（包括167个上调基因和69个下调基因）。以***＜0.01和logFC＞1作为上调基因的阈值,***＜0.01和logFC＜-1作为下调基因的阈值,绘制火山图。根据| logFC |的值绘制热图。前20个上调的差异表达基因包括C2、IFITM1、AKR1C1、PCDH7、TIMP3、TDO2、AKR1C1、PMEPA1、IRF9、AQPI、KNDC1、OAS3、DDX60、FAM105A、DDX60、AQP3、IFI27、IFI44L和FN1;下调的差异表达基因包括EVL、CLDN1、CREB5、FBX015、CASP4、NOC2L、ATF6B、RELB、CCDC74B、MATN3、POLR3E、OSR2、CITED4、CASP4、LINC01016、C14orf37、TCTN1、CDADC1、CFAP206 和 C5orf45。为了了解筛选出的差异表达基因的生物学功能和意义,本研究使用了可用于注释、可视化和集成发现的DAVID数据库。使用在线工具“DAVID”对候选差异表达基因进行GO功能富集分析（基因本体论（Gene Ontology,GO）是一种广泛用于整合生物学的方法,它为大规模的基因注释编写结构化、定义化和规范化的词汇）和KEGG途径分析（京都基因与基

关键词：生物信息学微阵列乳腺癌差异表达基因新关键基因

Non-Uniform Doo-Sabin Subdivision Surface via Eigen Polygon

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Journal of Systems Science & Complexity 2021年第1期34卷 3-20页

作者： alam md Nur LI Xin School of Mathematical Sciences University of Science and Technology of ChinaHefei 230026China

This paper constructs a new non-uniform Doo-Sabin subdivision scheme via eigen *** authors proved that the limit surface is always convergent and is G1 continuous for any valence and any positive knot intervals under a minor assumption, that λ is the second and third eigenvalues of the subdivision matrix. And then, a million of numerical experiments are tested with randomly selecting positive knot intervals, which verify that our new subdivision scheme satisfies the *** this is not true for the other two existing non-uniform Doo-Sabin schemes in Sederberg, et al.(1998), Huang and Wang(2013). In additional, numerical experiments indicate that the quality of the new limit surface can be improved.

关键词： Doo-Sabin non-uniform splines subdivision

The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy

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Genes & Diseases 2024年第1期11卷 321-334页

作者： md Rakibul alam md Mizanur Rahman Zhiguo Li Department of Toxicology and Cancer Biology College of MedicineUniversity of KentuckyLexingtonKY 40506USA Department of Medicine(Nephrology) Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAlberta T6E2H7Canada

Exosomes are small membrane vesicles containing microRNA,RNA,DNA fragments,and proteins that are transferred from donor cells to recipient *** cells release exo-somes to reprogram the factors associated with the tumor microenvironment(TME)causing tu-mor metastasis and immune *** evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1(PD-L1)that binds with re-ceptor program death protein 1(PD-1)and promote tumor progression by escaping immune ***,some FDA-approved monoclonal antibodies are clinicallyused for cancer treatment by blocking PD-1/PD-L1 *** notable treatment outcomes,some pa-tients show poor drug *** PD-L1 plays a vital role in lowering the treatment response,showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the ef-fect of cell surface *** enhance therapeutic response,inhibition of exosomal PD-L1 is *** signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion ***-mune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine,nifedipine,lercanidipine,diltiazem,and verapamil were also reported to suppress cellular PD-L1 ***,to enhance the PD-1/PD-L1 blockage therapy response,the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic *** this review,we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.

关键词： Calcium signaling CD8^(+)T cells Exosomal PD-L1 Exosomes biogenesis Immunosuppression Immunotherapy

New structures for closed-form wave solutions for the dynamical equations model related to the ion sound and Langmuir waves

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Communications in Theoretical Physics 2021年第3期73卷 1-13页

作者： md Nur alam M S Osman Department of Mathematics Pabna University of Science and TechnologyPabna6600Bangladesh Department of Mathematics Faculty of ScienceCairo UniversityGiza 12613Egypt Department of Mathematics Faculty of Applied ScienceUnrni Alqura UniversityMakkah 21955Saudi Arabia

This treatise analyzes the coupled nonlinear system of the model for the ion sound and Langmuir *** modified(G'/G)-expansion procedure is utilized to raise new closed-form wave *** solutions are investigated through hyperbolic,trigonometric and rational *** graphical design makes the dynamics of the equations *** provides the mathematical foundation in diverse sectors of underwater acoustics,electromagnetic wave propagation,design of specific optoelectronic devices and physics quantum ***,we concluded that the studied approach is advanced,meaningful and significant in implementing many solutions of several nonlinear partial differential equations occurring in applied sciences.

关键词： the modified(G'/G)-expansion method ion sound wave Langmuir wave closed-form wave solutions

Numerical study on 3D effect and practical design in shield tunneling

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Underground Space 2019年第3期4卷 201-209页

作者： Hossain md.shahin Teruo Nakai Tetsuo Okuno Islamic University of Technology GazipurBangladesh Geo-Research Institute Japan Nagoya Institute of Technology NagoyaJapan Shimizu Corporation TokyoJapan

In practice,different design methods are used in solving geotechnical problems depending on the type of issue such as the tunneling,braced excavation,or bearing capacity of a foundation,that is,the basic mechanism of the design method differs depending on the problems even for the same ground.A numerical analysis using the finite element method has recently become familiar owing to an improved computing performance;however,it is not widely used in the design of geotechnical problems including tunnel excavation owing to the reliability of the constitutive model of the ground *** a constitutive model of soils can properly express the properties of the ground material,a numerical analysis will play a vital role in solving the geotechnical *** this paper,the current state of a numerical analysis and its applicability in tunnel design are ***,the simulation of the ground behavior during tunnel excavation is carried out using sandy and clay ground parameters for shallow and deep tunnel *** paper is mainly focused on the effects of tunnel excavation under three-dimensional(3D)conditions,as well as the current design ***-linear 2D and 3D finite element analyses have been conducted,in which the elastoplastic sub-loading tij model has been used as a constitutive model of the *** performance and acceptability of the constitutive model have already been proven to reproduce the results of various model tests on different geotechnical problems such as the tunneling,braced excavation,and bearing capacity of a foundation,as well as the measured field *** was found that a 2D finite element analysis where the rate of stress release is considered,can be used for the prediction of the ground deformation and surface settlement;however,it does not provide rational information in the prediction of tunnel lining forces such as the stress,bending moment,and axial force,which emphasize the necessity of a 3D analysis with a proper cons

关键词： Shield tunneling Finite element analysis 3D effect

Performance comparison of zero-Schottky-barrier and doped contacts carbon nanotube transistors with strain applied

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Nano-Micro Letters 2010年第2期2卷 126-133页

作者： md.Abdul Wahab Khairul alam Department of Electrical and Electronic Engineering United International University Department of Electrical and Electronic Engineering East West University

Atomistic quantum simulation is performed to compare the performance of zero-Schottky-barrier and doped source-drain contacts carbon nanotube field effect transistors(CNTFETs) with strain applied. The doped source-drain contact CNTFETs outperform the Schottky contact devices with and without strain applied. The off-state current in both types of contact is similar with and without strain applied. This is because both types of contact offer very similar potential barrier in off-state. However, the on-state current in doped contact devices is much higher due to better modulation of on-state potential profile, and its variation with strain is sensitive to the device contact type. The on/off current ratio and the inverse subthreshold slope are better with doped source-drain contact, and their variations with strain are relatively less sensitive to the device contact type. The channel transconductance and device switching performance are much better with doped source-drain contact, and their variations with strain are sensitive to device contact type.

关键词： Zero-Schottky-barrier Doped contact Strain Inverse subthreshold slope Intrinsic cut-off frequency

An evolutionary computational framework for capacity-safety trade-off in an air transportation network

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Chinese Journal of Aeronautics 2019年第4期32卷 999-1010页

作者： md.Murad HOSSAIN Sameer alam Daniel DELAHAYE School of Engineering and Information Technology University of New South Wales School of Mechanical and Aerospace Engineering Nanyang Technological University MAIAA Laboratory Ecole Nationale de l'Aviation Civile

Airspace safety and airport capacity are two key challenges to sustain the growth in Air Transportation. In this paper, we model the Air Transportation Network as two sub-networks of airspace and airports, such that the safety and capacity of the overall Air Transportation network emerge from the interaction between the two. We propose a safety-capacity trade-off approach,using a computational framework, where the two networks can inter-act and the trade-off between capacity and safety in an Air Transport Network can be established. The framework comprise of an evolutionary computation based air traffic scenario generation using a flow capacity estimation module(for capacity), Collision risk estimation module(for safety) and an air traffic simulation module(for evaluation). The proposed methodology to evolve air traffic scenarios such that it minimizes collision risk for given capacity estimation was tested on two different air transport network topologies(random and small-world) with the same number of airports. Experimental results indicate that though airspace collision risk increases almost linearly with the increasing flow(flow intensity) in the corresponding airport network, the critical flow depend on the underlying network configuration. It was also found that, in general, the capacity upper bound depends not only on the connectivity among airports and their individual performances but also the configuration of waypoints and mid-air interactions among conflicts. Results also show that airport network can accommodate more traffic in terms of capacity but the corresponding airspace network cannot accommodate the resulting traffic flow due to the bounds on collision risk.

关键词： Airport network Airspace capacity Airspace safety Collision risk Flow intensity

Exact traveling wave solutions to higher order nonlinear equations

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Journal of Ocean Engineering and Science 2019年第3期4卷 276-288页

作者： md Nur alam Xin Li School of Mathematical Sciences University of Science and Technology of ChinaHefeiAnhuiChina

The present paper applies the new generalized(G/G)-expansion method on three non-linear equations including the fifth-order Korteweg-de Vries equation,(3+1)-dimensional Modified KdV-Zakharov-Kuznetsov equation,and(3+1)-dimensional Jimbo-Miwa equations and obtains some new exact traveling wave *** solutions are checked by putting back into the physical model and are observed to be very advantageous over several existing *** newly method could also be utilized to find exact traveling wave solutions for the other nonlinear evolution equations in the field of applied nonlinear sciences.

关键词： traveling nonlinear wave

A novel (G'/G)-expansion method and its application to the Boussinesq equation

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Chinese Physics B 2014年第2期23卷 34-43页

作者： md.Nur alam md.Ali Akbar Syed Tauseef Mohyud-Din Department of Mathematics Pabna University of Science and Technology Department of Applied Mathematics University of Rajshahi Department of Mathematics HITEC UniversityTaxila Cantt

In this article, a novel （G＇/G）-expansion method is proposed to search for the traveling wave solutions of nonlinear evolution equations. We construct abundant traveling wave solutions involving parameters to the Boussinesq equation by means of the suggested method. The performance of the method is reliable and useful, and gives more general exact solutions than the existing methods. The new （G＇/G）-expansion method provides not only more general forms of solutions but also cuspon, peakon, soliton, and periodic waves.

关键词： (G'/G)-expansion method Boussinesq equation solitary wave solutions auxiliary nonlinear ordinary differential equation