基于循环抑制CPG模型的蛇形机器人控制器

依据生物利用中央模式发生器(Central pattern generator,CPG)的自激行为产生有节律的协调运动适应多种环境,基于循环抑制CPG建模理论设计了蛇形机器人CPG控制器模型,分析了单个神经元、循环抑制CPG以及该控制器模型的稳定性,并把该控制器应用到一个结合蛇形机器人“勘查者-Ⅰ”动力学特性的仿真模型,得到了实现蜿蜒运动的CPG控制器参数,进而研究了调节S波个数、身体构形曲率、蜿蜒运动速度以及运动轨迹曲率的CPG控制器参数设定策略。此外,“勘查者-Ⅰ”应用该CPG控制器的输出成功实现了蜿蜒运动。该研究结果为设计人工CPG控制器提供了一个可行的方法。

基于循环抑制CPG模型控制的蛇形机器人蜿蜒运动

根据生物蛇和蛇形机器人的结构及运动特点,应用循环抑制CPG建模理论构建了蛇形机器人神经网络模型;利用蛇形机器人模型,仿真验证了CPG模型对蜿蜒运动控制的有效性;提出并验证了实现有目的转弯控制的CPG参数调节方法．最后,给出了今后的研究方向．

基于循环抑制CPG的蛇形机器人运动控制方法

蛇具有细长无肢的身体、独特的半球形关节，使其可在神经系统控制下完成与环境相适应的多种节律运动。模仿蛇的运动机理和行为方式而设计的蛇形机器人克服了轮腿式机器人的缺点，增加了机器人的运动方式，扩大了机器人的应用范围。但应用传统的控制策略实现蛇形机器人运动控制遇到了很难克服的问题。随着社会经济与科技的发展，研究人员把从蛇运动神经系统研究中得到的启示应用到蛇形机器人上，希望不仅可以解决其运动控制问题，更能在构型、步态及控制机制上皆可展示蛇的特征。 生物学家已经证明动物的节律运动是其低级神经中枢的自激行为，是由中枢模式发生器(Central Pattern Generator，CPG)控制的。中枢模式发生器是一种能够在缺乏有规律的感知和中枢控制输入的情况下，产生有节奏模式输出的神经网络。 本文以国家自然科学基金课题《基于CPG的蛇形机器人控制方法研究》和国家“863”高技术计划资助项目《具有环境适应能力的蛇形机器人的研究》为依托，突破以相互抑制机理研究CPG的传统观点，首次创新性地提出应用循环抑制(Cyclic Inhibition, CI)机理来研究蛇形机器人的CPG建模与实现问题。本研究涵概了神经元模型的特性分析、蛇形机器人关节循环抑制CPG建模理论、蛇形机器人循环抑制CPG神经网络稳定性分析以及典型步态的生成方法、循环抑制CPG神经网络控制蛇形机器人蜿蜒运动参数设定策略、应用动力学仿真和实验对该CPG控制方法有效性的验证。 首先，本文介绍了两个用于CPG建模研究的蛇形机器人“勘查者”和“勘查者-I”。给出各自机械系统、控制系统的构成和动力学仿真平台。 其次，详细分析了神经元以及传统的相互抑制(Mutual Inhibition, MI)CPG的特性。从工程角度首次创新性地应用循环抑制建模理论构建了蛇形机器人CPG模型，并对其稳定性进行了深入的分析。首次证明持续型神经元构成的单向循环抑制(Unilateral Cyclic Inhibition, UCI) CPG是能产生振荡输出CPG中微分方程数量最少的，而且其产生振荡输出的机理完全不同于传统的相互抑制CPG。其不需要具备调整功能，只需要神经元之间强的单向循环抑制连接。 第三，首次应用单向激励连接循环抑制CPG构成蛇形机器人神经网络系统。分析了其稳定性，给出其产生振荡输出的条件。通过仿真和实验验证了循环抑制CPG神经网络实现典型步态(蜿蜒运动、伸缩运动和侧向运动)的有效性。首次应用双向循环抑制(Bidirectional Cyclic Inhibition, BCI)CPG神经网络在不同高级控制神经元命令激活下的输出实现蛇形机器人典型运动步态之间的转换。为蛇节律运动生成机制建模提供了新方法。 最后，从实时性、控制方便性等工程应用的角度，对单向循环抑制CPG神经网络实现蛇形机器人蜿蜒运动控制进行了深入的分析。给出了S-波形、幅值、运动速度和运动轨迹曲率的参数设定策略。该系统应用首CPG自激励权重调解成功解决了传统CPG控制系统中CPG的个数比蛇形机器人关节数多一个的问题，并用其实现了一种独特的转弯控制策略。 综上，为蛇形机器人运动控制提供了全新的方法。

Imunização de bovinos com MSP1a e MSP2 recombinantes de Anaplasma marginale com CpG ODN 2006 como adjuvante, e desafio com isolado heterólogo.

A anaplasmose é uma importante enfermidade de bovinos de áreas tropicais e subtropicais do mundo, causada pela riquétsia intra-eritrocítica Anaplasma marginale. A vacinação tem sido a forma mais econômica e eficiente de controlar a anaplasmose bovina. Nos últimos anos, esses estudos têm se concentrado nas proteínas de membrana da riquétsia, sobretudo MSP1a e MSP2. Este trabalho teve como objetivos avaliar o grau de proteção induzido pelas proteínas de membrana MSP1a e MSP2 recombinantes de A. marginale, associadas com adjuvante CpG ODN 2006, perante desafio heterólogo e avaliar a resposta imune gerada. Novilhos da raça Aberdeen Angus foram imunizados três vezes com 200 ?g de MSP1a e/ou MSP2 recombinantes, associadas com CpG ODN 2006 e alúmen. Posteriormente, foram desafiados com 3 x 107 eritrócitos infectados com isolado heterólogo de A. marginale. Os animais experimentais apresentaram quadro clínico de anaplasmose (redução do volume globular, febre e riquetsemias detectáveis por distensões sangüíneas coradas). Não foram detectadas diferenças significativas entre os grupos imunizados e os controles quanto ao percentual de redução do volume globular, riquetsemias máximas e temperaturas retais máximas, indicando que as imunizações não foram protetoras. A despeito da significativa produção de IgG total contra MSP1a e MSP2, detectada no dia do desafio, os animais imunizados apresentaram produção significativa de IgG2 apenas contra MSP1a. As razões para as possíveis falhas de proteção são discutidas. Neste trabalho, é relatada a imunização de bovinos com MSP1a e MSP2 recombinantes de A. marginale, associadas com alúmen e CpG ODN 2006, e posterior desafio com isolado heterólogo, bem como a avaliação da resposta imune gerada.

CD4+ CD25+ regulatory T cells control T helper cell type 1 responses to foreign antigens induced by mature dendritic cells in vivo.

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II-restricted interferon gamma-producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.

Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.

Platinum therapeutic agents are widely used in the treatment of several forms of cancer. Various mechanisms for the transport of the drugs have been proposed including passive diffusion across the cellular membrane and active transport via proteins. The copper transport protein Ctr1 is responsible for high affinity copper uptake but has also been implicated in the transport of cisplatin into cells. Human hCtr1 contains two methionine-rich Mets motifs on its extracellular N-terminus that are potential platinum-binding sites: the first one encompasses residues 7-14 with amino acid sequence Met-Gly-Met-Ser-Tyr-Met-Asp-Ser and the second one spans residues 39-46 with sequence Met-Met-Met-Met-Pro-Met-Thr-Phe. In these studies, we use liquid chromatography and mass spectrometry to compare the binding interactions between cisplatin, carboplatin and oxaliplatin with synthetic peptides corresponding to hCtr1 Mets motifs. The interactions of cisplatin and carboplatin with Met-rich motifs that contain three or more methionines result in removal of the carrier ligands of both platinum complexes. In contrast, oxaliplatin retains its cyclohexyldiamine ligand upon platinum coordination to the peptide.

The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth.

The incidence of prostate cancer is increasing in western countries because of population aging. Prostate cancer begins as an androgen-dependent disease, but it can become androgen independent at a later stage or in tumors recurring after an antihormonal treatment. Although many genetic events have been described to be involved in androgen-dependent and/or -independent prostate cancer growth, little is known about the contribution of epigenetic events. Here we have examined the possibility that the methyl-CpG-binding protein MECP2 might play a role in controlling the growth of prostate cancer cells. Inhibition of MECP2 expression by stable short hairpin RNA stopped the growth of both normal and cancer human prostate cells. In addition, ectopic expression of the MECP2 conferred a growth advantage to human prostate cancer cells. More importantly, this expression allowed androgen-dependent cells to grow independently of androgen stimulation and to retain tumorigenic properties in androgen-depleted conditions. Analysis of signaling pathways showed that this effect is independent of androgen receptor signaling. Instead, MECP2 appears to act by maintaining a constant c-myc level during antihormonal treatment. We further show that MECP2-expressing cells possess a functional p53 pathway and are still responsive to chemotherapeutic drugs.

Structural motifs of cholesterol nanoparticles

The growth sequence of gas-phase cholesterol clusters (Ch(N)) with up to N=36 molecules has been investigated by atomistic simulation based on an empirical force field model. The results of long annealings from high temperature show that the geometric motifs characterizing the structure of pure cholesterol crystals already appear in nanometric aggregates. In all clusters molecules tend to align along a common direction. For cluster sizes above the smallest ones, dispersion interactions among the hydrocarbon body and tails of cholesterol cooperate with hydrogen bonding to give rise to a bilayer structure. Analysis of snapshots from the annealing shows that the condensation of hydrogen bonds into a connected network of rings and chains is an important step in the self-organization of cholesterol clusters. The effect of solvation on the equilibrium properties of medium-size aggregates is investigated by short molecular dynamics simulations for the N=30 and N=40 clusters in water at near ambient conditions and in supercritical carbon dioxide at T=400 K.

Use of synthetic peptides to locate novel integrin alpha(2)beta(1)-binding motifs in human collagen III

A set of 57 synthetic peptides encompassing the entire triple-helical domain of human collagen III was used to locate binding sites for the collagen-binding integrin alpha(2)beta(1). The capacity of the peptides to support Mg2+-dependent binding of several integrin preparations was examined. Wild-type integrins (recombinant alpha(2) I-domain, alpha(2)beta(1) purified from platelet membranes, and recombinant soluble alpha(2)beta(1) expressed as an alpha(2)-Fos/beta(1)-Jun heterodimer) bound well to only three peptides, two containing GXX'GER motifs (GROGER and GMOGER, where O is hydroxyproline) and one containing two adjacent GXX'GEN motifs (GLKGEN and GLOGEN). Two mutant alpha(2) I-domains were tested: the inactive T221A mutant, which recognized no peptides, and the constitutively active E318W mutant, which bound a larger subset of peptides. Adhesion of activated human platelets to GER-containing peptides was greater than that of resting platelets, and HT1080 cells bound well to more of the peptides compared with platelets. Binding of cells and recombinant proteins was abolished by anti-alpha(2) monoclonal antibody 6F1 and by chelation of Mg2+. We describe two novel high affinity integrin-binding motifs in human collagen III (GROGER and GLOGEN) and a third motif (GLKGEN) that displays intermediate activity. Each motif was verified using shorter synthetic peptides.