类风湿性关节炎免疫发病机制的研究进展

类风湿性关节炎(Rheumatoid Arthritis,RA) 是一种以多发性、对称性关节炎症为主,可引起肢体严重畸形的慢性全身性自身免疫性疾病,其发病机制目前尚不完全明确。文章从与类风湿性关节炎发生发展相的免疫细胞( 包括CD4+ T 细胞、B 细胞、先天性免疫细胞)、细胞因子以及微小RNA 等方面对该病发病机制的有关研究进展进行综述。     

胸腺五肽辅助治疗肺癌对免疫功能影响及其疗效的系统评价

为了系统地评价胸腺五肽作为辅助药物治疗各种肺癌的疗效及其对机体免疫功能的影响，利用电子检索收集有关胸腺五肽联合放疗或化疗方案治疗肺癌的临床随机对照试验文献，对符合纳入标准的文献，采用RevMan5.3 软件进行系统评价。最终共纳入文献 9 篇，总样本量 784 例。Meta 分析结果表明，胸腺五肽作为辅助药物治疗各种肺癌提高总有效率的差异无统计学意义[OR ＝ 1.44, 95%CI(0.99, 2.10), P ＝0.06 ＞ 0.05]。在对免疫功能的影响方面，胸腺五肽的使用显著增高外周血中的 CD3+ 细胞水平[OR ＝ 5.88, 95% CI(2.34, 9.42), P ＝0.001]，CD4+ 细胞水平也显著上升[OR ＝8.32, 95%CI(5.22, 11.42), P ＜ 0.00001] , CD4＋ /CD8＋比值也有明显的提高[OR ＝ 0.38, 95% CI(0.18, 0.59), P＝0.0002]，但 CD8+ 细胞水平的差异无统计学意义[OR ＝－3.12, 95% CI ( －9.02, 2.79), P ＞0.05]。总的来说，本研究在一定程度上反映了在辅助治疗肺癌方面，胸腺五肽能显著提高外周血中的 CD3+ 细胞水平、CD4+ 细胞水平、CD4+/CD8+ 比值。而对于治疗的有效率、CD8+ 细胞水平，差异无统计学意义。     

西那美宁电极的研制

分别用磷钨酸、磷铝酸、硅钨酸和四苯硼酸西那美宁制成了 PVC 膜西那美宁电极。磷钨酸西那美宁电极的响应较好,线性范围为1×10~(-5)-1×10~(-1)mol·dm~(-3),检出限2×10~(-6)mol·dm~(-3),硅钨酸西那美宁电极略差,其他性能无明显差别。四苯硼酸西那美宁沉淀颗粒大,易于制备。已用该电极指示,以标准比较法和电位滴定法测定风痛宁片剂和原料药中的西那美宁的含量。     

高阶无静差采样控制系统的动态综合

本文利用"最小响应法"[1,2]给出了N≥2阶无静差采样控制系统的设计公式.作者指 出:对于某类闭环控制系统,在给定阶跃响应最大超调量σmax的条件下,可以找出最佳比值 T/T3э(T为系统的采样周期,T3э为对象的不便克服的等效小时间常数之和),使系统获得相 应阶最大误差系数KN+1,从而可使系统达到快速精密的控制指标.为了在工程设计中应用方 便,文中还给出了二至六阶无静差的σmax,T/T3э,KN+1TN3э最佳参数组,使得这类闭环控制系 统的设计最佳化和简易化.     

基于MEMS微电极芯片的电穿孔系统

报道了一种基于微加工金电极的细胞电穿孔芯片及一套完整的细胞电穿孔系统。该系统能够在多种细胞系中实现高效细胞电穿孔(对典型HEK-293A(人胚胎肾细胞)细胞的穿孔效率高于90%,3T3-L1(小鼠胚胎成纤维细胞)的电穿孔效率高达80%)。并且具有手动模式和自动模式。同时,由于基于独特的电极设计,其所需电压也远低于现有设备(典型工作电压为60 V),成本更低,操作更安全。     

UNIX系统下CD-ROM驱动器的安装与使用方法

TheSetting－upandItsUseofCD－ROMunderUNIXHeXiangyong在DOS和Wq：NDOW系统下安装和使用光盘驱动器是司空见惯的事，一般都很容易使用，安装上也不麻烦，而在tjNIX系统下使用光盘驱动器CD－ROM则稍微麻烦一些。由于ti－M一系统在某些行业如金融保险行业使用较为普遍，因此掌握UNIX下CD－ROM驱动器的安装与使用方法对于提高系统安装维护速度和效率是很有必要的。下面简要介绍一下SCO［JNIX3．2．4．2版本下CD－ROM驱动器的安装与使用方法。IUNIX系统下光盘驱动器CD－ROM的安装首先，光盘驱动器硬件安装与DOS或W…     

产业信息

Imagination Series3NX神经网络加速器助力展锐打造新一代5G智能手机平台Imagination Technologies宣布:领先的无晶圆厂半导体公司展锐(UNISOC)已在其发布的5G业务新品牌---唐古拉系列的T770和T760芯片中采用了Imagination的PowerVR Series3NX神经网络加速器(NNA)半导体知识产权(IP)。此次合作是双方在人工智能(AI)、图形处理等领域多年合作的良好延续。Series3NX NNA将凭借优异的PPA(性能、功耗、面积)特性助力唐古拉T770和T760系统级芯片(SoC)实现行业领先的AI功能。     

直接进入深层子目录的实现程序

目前，大多数电脑爱好者开始学习微机接触到的仍然是DOS系统。而DOS系统中的许多内、外部命令在使用中总感到太繁琐，有些不尽人意，进人子目录命令CD即是一例。CD命令有改变当前目录和进入下一级子目录的功能，但它仅能进入到根目录下的第一级子目录，若要从根目录一次性地进入深层子目录或从当前目录直接进入另外的深层子目录，则必须多次使用CD命令才能完成。为弥补CD命令的不足，笔者编制了一种小程序，实现了可直接改变或进入到深层子目录的功能，并且进入子目录成功时都会有提示已到那个目录下，在不成功时会提示是什么原因，使…     

用于T细胞表位预测的分类器集成方法*

T细胞表位预测技术对于减少实验合成重叠肽,理解T细胞介导的免疫特异性和研制亚单位多肽及基因疫苗均有重要意义.为弥补已有基于机器学习方法的T细胞表位预测模型的可理解性的不足并进一步提高模型的预测精度,首先通过肽的预处理构建出了存储等长肽段的决策表,而后提出了基于粗糙集的分类器集成算法.该算法不但综合利用了基于信息熵的属性约简完备算法和其他属性约简算法的优势,而且将T细胞表位预测领域中的锚点知识融入到了属性值约简过程中.最后利用该算法来预测MHC Ⅱ类分子HLA-DR4(B1·0401)的结合肽,首次提取出了预测精度高且能帮助专家理解MHC分子与抗原肽的结合机理的产生式规则,为下一步的分子建模工作奠定了基础.     

排序学习前向掩蔽模型在T细胞表位预测中的应用

在综述了T细胞表位预测的定义，意义和研究现状的基础上，分析了当前流行的基于误差反向传播前馈神经网络(BPNN)的T细胞表位预测模型的不足，即网络结构较难确定、训练速度慢和难以增量学习等，提出了利用排序学习前向掩蔽（SLAM）模型及其增量学习算法作为T细胞表位预测方法，并给出了构建T细胞表位预测模型的基本步骤。基因HLA-DR4 (B1*0401)编码的MHC II类分子结合肽的应用实例表明，与基于BPNN的T细胞表位预测模型相比，基于SLAM的T细胞表位预测模型不但能在极短时间内完成样本的学习,而且能有效地实现增量学习。     

An integrated microfluidic system for counting of CD4+/CD8+ T lymphocytes

This study reports on an integrated microfluidic system capable of counting CD4⁺/CD8⁺ T lymphocytes from a whole blood sample, which may be further applied for the rapid screening of the human immunodeficiency virus (HIV) infection. This system is composed of a sample incubation module for fluorescence-labeling of the target cells and a micro-fabricated flow cytometry module for cell counting. First, a pneumatically driven, vortex-type micro-mixer has been adopted for the fluorescence-labeling of CD4⁺/CD8⁺ T lymphocytes from whole blood. After the labeling process, different laser-excited fluorescent signals are detected and are used for counting of CD4⁺/CD8⁺ T lymphocytes as they pass through the detection region of the microflow cytometer. A concentration of 963 cells/μl is counted for cultured CD4⁺ T lymphocytes with a reference concentration of 1000 cells/μl. The ratio of CD4⁺/CD8⁺ T lymphocytes is then calculated. Experimental results show that the results from the microsystem are in agreement with the ones from large-scale flow cytometers. In addition, the entire diagnostic procedure, including the sample incubation and the cell counting, can be automatically performed within 35 min. Therefore, this may become a powerful tool for further biomedical applications, especially for fast screening of HIV infection.     

A novel tumor-related protein, C7orf24, identified by proteome differential display of bladder urothelial carcinoma

Proteome analysis of bladder cancer with narrow-range pH 2-DE has identified a novel protein on chromosome 7 encoded by ORF 24 (C7orf24) as one of the highly expressed proteins in cancer cells. C7orf24 is currently registered in the protein database as a hypothetical protein with unknown function. The homologs of C7orf24 in other animals have also been registered as putative protein genes. Western blot analysis using a mAb against C7orf24 confirmed its higher expression in bladder cancer compared with normal tissue. Several other cancer cell lines were also found to express C7orf24. However, the introduction of C7orf24 into Rat-1 or NIH3T3 cells did not cause malignant transformation. A stable transfectant of NIH3T3 cells with recombinant retrovirus vector was produced for a growth rate assay, and a higher growth rate was observed in C7orf24-expressing cells compared with the controls. Six kinds of small interfering RNAs (siRNAs) were then produced, and C7orf24-siRNA#5 showed a strong knockdown effect on protein expression and significant antiproliferative effects on cancer cell lines were demonstrated by the MTT assay. Therefore, C7orf24 may have an important role in cancer cell proliferation, and may be an appropriate therapeutic target molecule against cancer.     

SU-8 microstructure for quasi-three-dimensional cell-based biosensing

A quasi-three-dimensional (quasi-3-D) cell-based biosensor platform microfabricated from SU-8 has been developed and characterized. In this work, SH-SY5Y human neuroblastoma cells were integrated with SU-8 microfabricated microwells with diameters of 100 μm. SH-SY5Y cells were differentiated with 1 mM dibutyryl cAMP and 2.5 μM 5-bromodeoxyuridine. Voltage-gated calcium channel (VGCC) function of SH-SY5Y cells cultured within the microwells (quasi-3-D) versus those cultured on the SU-8 planar substrates (2-D) was evaluated by confocal microscopy with a calcium fluorescent indicator, Calcium Green-1. In response to 50 mM high K⁺ depolarization, cells in microwells were less responsive in terms of increase in intracellular Ca²⁺ in comparison to cells on 2-D substrates. This study shows that VGCC function of cells within SU-8 microwells was indeed different from that of cells on planar SU-8 surfaces, suggesting that SU-8 microstructure did affect SH-SY5Y cell differentiation with respect to VGCC function and that high-aspect-ratio microstructures are not merely “folded” 2-D structures. Furthermore, these results are consistent with previous 2-D/3-D comparative studies carried out in polymer scaffolds and support the hypothesis that cell calcium dynamics on 2-D substrates may be exaggerated. Overall, this work is supportive of SU-8 micropattern as a viable platform for engineering a quasi-3-D cell culture system for cell-based biosensing against drugs for VGCCs.     

Analysis of the HLA class I associated peptide repertoire in a hepatocellular carcinoma cell line reveals tumor-specific peptides as putative targets for immunotherapy

HLA class I molecules present peptides on the cell surface to CD8(+) T cells. The repertoire of peptides that associate to class I molecules represents the cellular proteome. Therefore, cells expressing different proteomes could generate different class I-associated peptide repertoires. A large number of peptides have been sequenced from HLA class I alleles, mostly from lymphoid cells. On the other hand, T cell immunotherapy is a goal in the fight against cancer, but the identification of T cell epitopes is a laborious task. Proteomic techniques allow the definition of putative T cell epitopes by the identification of HLA natural ligands in tumor cells. In this study, we have compared the HLA class I-associated peptide repertoire from the hepatocellular carcinoma (HCC) cell line SK-Hep-1 with that previously described from lymphoid cells. The analysis of the peptide pool confirmed that, as expected, the peptides from SK-Hep-1 derive from proteins localized in the same compartments as in lymphoid cells. Within this pool, we have identified 12 HLA class I peptides derived from HCC-related proteins. This confirms that tumor cell lines could be a good source of tumor associated antigens to be used, together with MS, to define putative epitopes for cytotoxic T cells from cancer patients.     

In silico design of knowledge-based Plasmodium falciparum epitope ensemble vaccines

Malaria is a global health burden, and a major cause of mortality and morbidity in Africa. Here we designed a putative malaria epitope ensemble vaccine by selecting an optimal set of pathogen epitopes. From the IEDB database, 584 experimentally-verified CD8+ epitopes and 483 experimentally-verified CD4+ epitopes were collected; 89% of which were found in 8 proteins. Using the PVS server, highly conserved epitopes were identified from variability analysis of multiple alignments of Plasmodium falciparum protein sequences. The allele-dependent binding of epitopes was then assessed using IEDB analysis tools, from which the population protection coverage of single and combined epitopes was estimated. Ten conserved epitopes from four well-studied antigens were found to have a coverage of 97.9% of the world population: 7 CD8+ T cell epitopes (LLMDCSGSI, FLIFFDLFLV, LLACAGLAYK, TPYAGEPAPF, LLACAGLAY, SLKKNSRSL, and NEVVVKEEY) and 3 CD4+ T cell epitopes (MRKLAILSVSSFLFV, KSKYKLATSVLAGLL and GLAYKFVVPGAATPYE). The addition of four heteroclitic peptides − single point mutated epitopes − increased HLA binding affinity and raised the predicted world population coverage above 99%.     

Identification of B and T cell epitope based peptide vaccine from IGF-1 receptor in breast cancer

The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells. In our previous study, we set a technique based on molecular docking in order to find the best MHC class I and II binder peptides using GOLD. In the present work, molecular docking analyses on a library consisting of 30 peptides mimicking discontinuous epitopes from IGF-1R extracellular domain identified peptides 249 and 86, as the best MHC binder peptides to both MHC class I and II molecules. The receptors most often targeted by peptide 249 are HLA-DR4, HLA-DR3 and HLA-DR2 and those most often targeted by peptide 86 are HLA-DR4, HLA-DP2 and HLA-DR3. These findings, based on bioinformatics analyses, can be conducted in further experimental analyses in cancer therapy and vaccine design.     

Tissue section analysis: Feature selection and image processing

Three examples are given of the state-of-the-art of pattern recognition as regards the analysis of images of human and animal tissue: (1) the counting of cell nuclei of normal and abnormal rabbit kidney; (2) the detection of boundaries of endothelial cells of the living human cornea; and (3) the differentiation of normal and abnormal cells in the human liver. The methodology employed is that of cellular logic matched filtering using the Carnegie-Mellon SUPRPIC image processing system.     

Design of differential TG based 8T SRAM cell for ultralow-power applications

Low power cache memory in a system on chip is in high demand today. With the lowering of MOSFET’s channel length, low-power SRAM design has become a more challenging task. This paper presents differential 8T SRAM cell with minimum power utilization. The proposed cell has one pair of transmission gate as access switches. Due to use of TG instead of pass gate access transistor its write access time (T_WA) is short. The low power consumption of the cell is due to stacking effect. This paper compares design metrics of the proposed cell with conventional 6T (CON6T) and ZIGZAG 8T (ZG8T) SRAM cells. The proposed 8T SRAM cell shows 1.15×/1.17× improvement in T_WA as compared to CON6T/ZG8T at a penalty of 2.65×/2× in read access time (T_RA). The proposed cell consumes 3.22× less hold power compared to both CON6T and ZG8T SRAM cells. And the proposed cell consumes 4.41× (4.44×) less write power as compared to CON6T (ZG8T) SRAM cell. Our proposed cell takes 1.37× lower chip area as compared to ZG8T cell at the expense of 1.49× higher area as compared to CON6T SRAM cell. The proposed cell also achieves 1.5×/3× higher stability during write operation as compared to CON6T/ZG8T SRAM cell, respectively. Read static margin of the proposed cell is same as CON6T but 3.2× lower than ZG8T SRAM cell.