户外鸽子生物机器人的设计及初步应用EI北大核心CSCD

视距外控制对具有大范围运动能力的生物机器人意义重大。鸽子生物机器人以在体预编程的方式实现了视距外控制,但尚未形成控制闭环。本研究在鸽子生物机器人控制系统的神经刺激功能之上增设运动监测功能,对鸽子飞行状态实时解算,结合逻辑判据实现户外飞行过程中转向及盘旋的闭环调控。调控刺激位点位于鸽子中脑网状结构(FRM)的两侧,分别用于左向和右向控制;刺激信号具有生物神经细胞膜电位的波形特征并间歇激活;控制系统总重11.8 g。结果表明,该鸽子生物机器人的闭环调控成功率达到90%;辅以在体摄像装置,可方便获取飞行机动时的翼面形态;结合鸽群等级特征,能够实现个体调控对集群演化的干预。这些为发掘鸽子生物机器人在科学研究领域的应用奠定了基础。     

结合磁共振成像和脑机接口的新型在体生物电子鼻的研究

在体生物电子鼻利用了哺乳动物的嗅觉系统,因此具有很高的灵敏度和特异性,但在嗅球中植入电极的过程中其位置主要根据经验确定,因此成功率并不理想。利用锰离子的钙离子相似性和强顺磁性,在10只大鼠单侧鼻腔中滴入锰离子并给予气味刺激,进行磁共振扫描并标记出大鼠嗅球中的对特定气味的响应区域。在该区域中植入微丝阵列电极,记录电生理信号并就行神经信号解码,实验结果表明,受到该特异性气体刺激后,嗅球神经元的电生理信号中LFP信号β波能量增强,spike信号对该气体刺激也会有响应,并且有些通道的spike发放频率变化与刺激气体的浓度有较好的线性关系。此方法对乙酸异戊酯和正丁酸的检测下限分别为0.033和0.007 2 μM。第一次利用锰离子增强磁共振辅助定位的生物电子鼻,未来在爆炸物搜索、食品安全等方面都有广阔的前景。     

基于氧化石墨烯、适配体DNA及信号放大技术生物传感器的研究及应用

基于核酸适配体DNA和氧化石墨烯(graphene oxide,GO)的光学生物传感器因具有快速、准确及灵敏等优点,已越来越广泛地用于核酸、蛋白质及小分子底物的特异性检测.近年来的研究显示,将信号放大技术与适配体-GO检测方法结合可构建超高灵敏度的荧光光学生物传感器,实现痕量底物的特异性检测.文章综述了近年来氧化石墨烯、适配体DNA及核酸放大技术生物传感器的研究进展,以期为该类生物传感器的深入研究及大规模应用提供参考.     

力传导中亚细胞水平的分子FRET成像

体内细胞受到含有化学和力学因素的生理和病理生理的刺激,故研究这些因素在细胞和器官水平如何调节功能就尤为重要。有关细胞和器官对化学因素的反应已开展诸多研究,而力学因素的影响却鲜有报道。近年来,荧光蛋白和显微镜技术的发展已成为阐明力传导过程的有用工具,先进的信号活细胞成像技术促进了力学生物学中分子机制的时空因素研究。本文综述荧光蛋白的基本知识以及其在生物学研究中的应用,特别讨论了以荧光共振能量迁移(fluorescence proteins and microscopy,FRET)技术为基础的生物传感器的发展和特征。基因编码的FRET生物传感器能够实现分子时空活动的成像和定量,使得活细胞中生物化学信号在力学刺激下的反应和传导可视化。同时,本文重点阐述分子水平力学刺激下的活细胞信号传导。     

水生动物机器人的研究现状与进展

生物机器人是人类通过控制技术施加干预信号调控生物行为,从而实现人类可操控的生物,是融合多学科和多专业理论与技术的产物。由于水生动物具有运动灵活、活动隐蔽、适应环境、自主供能等突出的优势特性,而成为水生动物机器人的研发对象,更具科学研究意义与实际应用价值。根据神经科学理论和国际常用的生物控制方法,介绍刺激感受器、刺激神经中枢和刺激效应器等3种类型的水生动物机器人,综述其控制方法及机制,阐述其中的控脑技术,并就发展趋势进行展望。     

基于STM32和USB接口的开放式高性能新型医用信号仪的研制

为满足研究各种细胞、组织等的电生物效应所需的高精度特殊刺激信号,以及科研、教学和医学仪器的调试和维修等需求,研制以内带D/A转换、A/D转换、USB引擎的高性价比、32位单片机STM32F103RD和高性能单频信号发生芯片AD9833为核心的开放式高性能医用信号仪。该仪器能同时输出两路生理信号(如心电波、脉搏波、呼吸波)和特殊波形信号、高频率精度和位相差精度的常用信号(如正弦、三角波和方波)或一路特殊信号和一路常用信号,输出电压幅度可达10 V,电流最大可达350 mA,最高频率可达12 MHz。该仪器具有开放性好、体积小、性能稳定、操作简便,显示直观等优点,可广泛用于电生物效应和医学其它科研、实验教学和医学仪器的调试和维修等。     

细胞骨架与力学信号传导

背景：细胞在感受力学刺激后,通过一定的信号转导机制,将力学信号转换成化学信号,进而实现其生物功能。在这一系列的信号转导过程中,横贯细胞的细胞骨架作为枢纽,发挥着重要作用。 目的：通过系统的分析和总结细胞骨架在力学信号转导通路中的作用机制,为细胞骨架相关疾病的临床治疗提供潜在的治疗靶点。 方法：以英文检索词为“cytoskeleton,microtubules,microfilaments,intermediate filaments,mechanical stimulation,signal transduction ”及中文检索词为“细胞骨架、微管、微丝、中间纤维丝、机械刺激、信号传导”,由第一作者检索 1990至2012年PubMed 数据库及中国知网中文科技数据库,查阅近年机械刺激对细胞骨架影响的相关文献,最终保留 48篇文献。 结果与结论：机械刺激是细胞增殖、生长发育以及凋亡的重要因素。随着对细胞骨架认识的逐渐深入,人们发现细胞骨架在细胞对力学刺激的感受和信息传导的过程中起重要作用。机械刺激作用于细胞后,通过Rho家族蛋白、蛋白激酶C、整合素以及丝裂原激活蛋白激酶等多条信号通路,且各种信号传导通路中存在交联,从而影响细胞骨架的重组,并将力学刺激进一步转换成化学信号,最终完成其生物效应。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

止血防粘连生物纸的生物相容性研究

止血防粘连生物纸是一种采用天然多糖交链制成的新型可降解止血防粘连材料，具有纤维蛋白原活性增强作用和吸水后呈水凝胶结构起到隔离防粘连作用。本研究采用GB／T16886医疗器械生物学评价标准规定的全身急性毒性试验、皮内刺激试验、致敏试验、细胞毒性试验、植入试验和基因毒性试验方法评价生物纸的生物相容性，以验证其安全性和有效性。试验结果显示生物纸无全身急性毒性、无皮内刺激作用、无致敏作用，细胞毒性0～1级；植入肌肉内2周、4周和8周有轻度炎症反应，可见异物巨细胞，细胞内可见材料吞噬体；基因毒性采用鼠伤寒沙门氏菌回复突变试验（Ames试验），哺乳动物培养细胞染色体畸变试验和小鼠骨髓嗜多染红细胞微核试验均为阴性，说明生物纸无基因毒性。结论：生物纸具有良好的生物相容性，没有观察到不良反应，符合临床使用要求。     

基于混沌信号的经皮神经电刺激仪的设计

传统的电刺激仪器都是采用三角波、方波与非对称波等信号作为刺激信号源,或是将一些特定的信号先进行存储、然后再输出作为信号源,这些信号都呈现出周期性,作用于人体时容易使人产生适应性,随着刺激次数的增多而使效果逐渐变差,论文设计了一个基于混沌模型的非周期信号的电刺激系统。首先是在MATLAB软件的Simulink平台下构建出混沌模型,然后借助于DSP Builder软件将混沌模型转换为FPGA的工程文件,通过Simulink平台的模型仿真及Modelsim软件的行为级仿真,仿真无误后将工程文件在Altera公司的开发平台Quartus软件下进行编译、综合,最后生成可执行文件,下载到FPGA芯片即产生了混沌信号;将信号进行电压放大,功率放大,接入电极,实现了基于混沌信号的电刺激系统。所设计的系统获得了新型的电刺激效果,通过改变混沌方程的参数以及改变信号的输出频率,可以改变刺激时的直观感觉,由于人体的生物信号本身具有复杂的混沌特性,用它作用于人体所具有的更深层次的生物效应还需更多的探索研究。     

医用级硅凝胶的生物学实验研究

有机硅凝胶(GNY—514,GNY—515)具有较好的物理机械性能而被用于医学各个领域,但对该材料的毒性及生物相容性研究报道较少,作者参考了有关标准,对硅凝胶材料及制品进行了系统的毒性及生物相容性研究。结果表明红外分析制品内未查出残留单体,从细胞培养试验证实无细胞毒性,Ames试验未见致突变现象,三种刺激试验表明均无刺激反应,硅凝胶的四种介质浸提液无急性毒性反应,小鼠微核试验微核率正常,材料肌肉植入无明显的组织学改变。该研究结果证明了硅凝胶材料是无毒、无刺激、生物相容好的生物医用材料。     

Application of infrared detection in the recording of eyelid movements in rabbits

Classical conditioning of the eyelid reflex has been used for a long time to study associative learning in animals and humans. A new experimental procedure for rabbit's eyelid conditioning was constructed and described. A phonopneumatic stimulator generated conditioned and unconditioned stimuli and a photoelectric transducer acting in close infrared converted movements of rabbits' eyelid to electric signals. An example of acquisition and extinction training is illustrated. This method of eyelid movement monitoring is noninvasive. It may be useful for chronic studies of learning processes in rabbits when used with headpieces for microdialysis probes, electrodes or cannulas which could be implanted into brain structures.     

基于肌电特征提取的智能电刺激仪

为了改善常规电刺激仪的刺激参数不准确、缺少主动治疗模式等缺陷,设计开发了生物反馈式智能电刺激仪。将肌电反馈控制与电刺激相结合,对患者运动肌群的电信号进行无创测量和特征值提取,以肌电特征值作为反馈量控制电刺激仪的输出。创新地实现了基于Delta-sigma技术的肌电信号特征提取及肌电反馈控制,可准确获取肌电特征值,实现了电刺激治疗的智能化,促使患者主动参与训练和治疗;采用刺激电流双向检测技术和可编程式触摸屏人机交互,使刺激参数准确量化。经实验可知:仪器已达到设计要求,实现了既定的功能。     

Antigen-specific helper T cells are essential for cytotoxic T cell responses to metabolically inactivated stimulator cells.

Primed spleen cells respond well to metabolically inactivated stimulator cells while normal spleen cells do not. This observation has been interpreted as showing that cytotoxic T cell precursors are different from unprimed precursors in their antigen recognition requirements for induction. A different model is proposed here which accounts for these observations as due to enhanced helper cell levels in primed populations. Experiments are described in this study which test several predictions of this model. These experiments show that in the presence of in vitro primed helper T cells, normal cells are able to respond efficiently to glutaraldehyde-fixed stimulator cells. The helper effect is antigen-specific. Since unprimed spleen cells can be efficiently induced by metabolically active stimulators (γ-irradiated cells) and can respond to glutaraldehyde-fixed antigen (metabolically inactive cells) only in the presence of specific helper cells, it seems reasonable to propose that helper cell signals are enhanced by a nonantigenic property of γ-irradiated stimulator cells requiring metabolic activity. It is also clear that glutaraldehyde-fixed cells are anti- genically intact as helper cells, primed to antigens on γ-irradiated stimulator cells, efficiently and specifically help a response to fixed stimulators. Conversely, helper cells primed in vitro to glutaraldehyde-fixed stimulators recognize antigen on γ-irradiated stimulator cells. The level of help generated in response to glutaraldehyde- fixed stimulator cells is at least 10-fold higher in primed cells than in normal cells. In addition, primed spleen cells can be induced in vitro to yield helper function by both fixed or unfixed stimulator cells. Normal helper cell precursors are induced at least 100-fold more efficiently by γ-irradiated as compared to glutaraldehyde-fixed stimulator cells. This work supports the idea that a major effect of priming, which allows primed cells to respond to metabolically inactive stimulators, is to enhance levels of helper T cells in the primed population.     

Cortical responses to thermal pain depend on stimulus size: a functional MRI study

Cortical activity patterns to thermal painful stimuli of two different sizes were examined in normal volunteers using functional magnetic resonance imaging (fMRI). Seven right-handed subjects were studied when the painful stimulus applied to the right hand fingers covered either 1,074-mm(2)-area large stimulator or 21-mm(2)-area small stimulator. Stimulus temperatures were adjusted to give rise to equivalent moderately painful ratings. fMRI signal increases and decreases were determined for the contralateral parietal and motor areas. When the overall activity in these regions was compared across subjects, increased fMRI activity was observed over more brain volume with the larger stimulator, whereas decreased fMRI activity was seen in more brain volume for the smaller stimulator. The individual subject and group-averaged activity patterns indicated regional specific differences in increased and decreased fMRI activity. The small stimulator resulted in decreased fMRI responses throughout the upper body representation in both primary somatosensory and motor cortices. In contrast, no decreased fMRI signals were seen in the secondary somatosensory cortex and in the insula. In another seven volunteers, the effects of the size of the thermal painful stimulus on vibrotactile thresholds were examined psychophysically. Painful stimuli were delivered to the fingers and vibrotactile thresholds were measured on the arm just distal to the elbow. Consistent with the fMRI results in the primary somatosensory cortex, painful thermal stimuli using the small stimulator increased vibrotactile thresholds on the forearm, whereas similarly painful stimuli using the large stimulator had no effect on forearm vibrotactile thresholds. These results are discussed in relation to the cortical dynamics for pain perception and in relation to the center-surround organization of cortical neurons.     

基于无线充电技术的胃肠电刺激系统

目的设计一种新型的植入式胃肠道刺激系统,不仅具有刺激功能,还具有肠电和压力检测功能,可用于检测胃肠道刺激的效果,同时增加无线能量供给,以实现刺激器的长期植入。方法系统由体内刺激模块、体外控制模块及无线能量传输模块组成。体外控制模块通过无线射频将控制信号传输到体内刺激模块,体内刺激模块的能量由体外能量发射装置通过电磁耦合进行供给。通过生物反馈控制检测不同刺激参数对胃肠道收缩活动的作用效果,实时调整刺激参数,输出需要的刺激脉冲。以模拟心电信号模拟肠电信号,进行了相关的体外实验。结果在体外实验中,系统可有效检测到2—20次／min的模拟心电信号,并实现实时刺激参数修改输出不同的刺激脉冲。该系统实现了电流检测功能,监测作用部分的胃肠电阻。经皮无线能量在两级线圈轴向距离为22mm时的接收充电稳定功率最大为0．93W,体内锂离子的充电电流为180～240mA。结论系统可检测到最大变化范围的模拟肠电信号。验证电流的作用效应为后续的恒流刺激模式提供参考。该系统的无线充电功能可满足植入式刺激器长期植入的能量需求。     

Self-reproduction in three-dimensional reversible cellular space

Due to inevitable power dissipation, it is said that nano-scaled computing devices should perform their computing processes in a reversible manner. This will be a large problem in constructing three-dimensional nano-scaled functional objects. Reversible cellular automata (RCA) are used for modeling physical phenomena such as power dissipation, by studying the dissipation of garbage signals. We construct a three-dimensional self-inspective self-reproducing reversible cellular automaton by extending the two-dimensional version SR(8). It can self-reproduce various patterns in three-dimensional reversible cellular space without dissipating garbage signals.     

Human growth from the cell to the organism: Saltations and integrative physiology

The Society for the Study of Human Biology has been at the forefront in the scientific study of human growth. The documentation of variability in growth rate, size, and tempo across populations has provoked exploration for sources of this diversity, and the mechanisms by which environmental and genetic factors influence phenotypic expressions of growth biology. At a time when adult health and well-being are posited to reflect early development, the details of early growth patterns are increasingly sought as explanatory domains underlying lifespan health.

A review of recent observations detailing events that occur in growth and differentiation during embryological and fetal development is considered for insights into mechanisms that may be operative in a putative cascade of growth biology operating across developmental ages. Cellular growth and differentiation are posited to be a process of integrative physiology, with increasing complexity in organismic growth achieved through modularity and temporally-differentiated signals.

The flexible patterns of human growth are hypothesized to reflect the variability in timing and amount of growth saltations, which are the outcome of cross-talking signaling systems in an energy/immune integrating complex. This is an adaptive system, flexible and responsive to the challenges of developmental biology in changing environments.     

用于功能性胃肠疾病治疗的植入式电刺激系统及动物实验研究

目的研究可用于功能性胃肠疾病治疗的植入式电刺激系统,通过动物实验研究,探讨不同刺激参数对胃肠道收缩活动的作用效果,为治疗用刺激参数的优化提供初步依据。方法系统由便携式体外控制器和植入式体内刺激器组成,体内外通信采用无线模式。刺激脉冲参数及指令由体外控制器设定并发送至体内刺激器,胃肠道收缩活动由体内刺激器集成的压力检测模块采集并发送至体外以供分析。通过电刺激猪盲肠实验,分析不同刺激参数下盲肠压力的变化,以评价刺激参数对盲肠收缩活动的作用效果。结果系统样机工作正常,输出刺激脉冲信号精确,压力信息记录准确。动物实验表明,增加刺激脉冲宽度使盲肠收缩活动的幅度增大,增加刺激脉冲频率使盲肠收缩活动的潜伏期缩短,增加刺激脉冲幅度同时缩短盲肠收缩活动的潜伏期并增大收缩幅度。结论该植入式电刺激系统参数设定范围大,输出脉冲信号精确并具备压力检测功能,便于进行功能性胃肠疾病治疗刺激参数的筛选和验证。动物实验初步验证了不同刺激参数对盲肠收缩活动的作用效果。     

Blocking Effects of Maternal Serum-IgG and Placental Eluate-IgG on Materno-Fetal Mixed Lymphocyte Reaction and Their Individual Specificity*

ABSTRACT: The purpose of this study is to clarify the problem regarding individual specificity of maternal serum immunoglobulin G (IgG) and placental eluate IgG that block the unidirectional mixed lymphocyte reaction (MLR) in which maternal and cord blood lymphocytes (lys) were used as responder and stimulator, respectively. Both maternal serum IgG and placental eluate IgG were found to include blocking antibodies (BA) which showed similar blocking effect on MLR. But, in the case of serum IgG, individual specificity of BA on MLR was observed to be less great in MLR done using whole lys or T-enriched lys of the cord blood as stimulator, whereas it became greatly significant when MLR was done using B-enriched lys of the cord blood as stimulator. This was the case even in MLR done by using unrelated maternal lys as responder. On the other hand, in the case of placental eluate, it was found to be greater when compared to serum IgG even where MLR was done using not only B lys but also T lys as stimulator. It is thus strongly suggested that BA include individual specific antibodies against fetal B lys having HLA-D/DR locus determinants in addition to individually nonspecific antibodies common to pregnancy which may be produced to a “yet unknown fetal antigen.”     

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The electrodes of an implanted stimulator must be operated in such a way that the task of converting an electron current in metal to an ion current in tissue is achieved without release of noxious chemical species into the tissue, and without significant corrosion of the electrode metal. Both these effects depend on the charge density at which the electrodes are operated. In bringing a newly designed multichannel stimulator into service, the charge densities can only be known when the operating stimulus strengths have been determined. Even then, unless the stimulator is arranged to telemeter out what it is doing, any charge-density figures obtained have the character of estimates, rather than measurements. The first London Mk. V stimulator is used to enable a paraplegic woman to stand up. This note provides estimates of the average charge density and corrosion rate for the Pt–Ir electrodes used. These fall within limits which we believe to be generally accepted as safe.