Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis

Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis--experimental autoimmune encephalomyelitis (EAE) in the mouse--either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis.     

Paramyxovirus SV5 and multiple sclerosis

Multiple sclerosis is commonly associated with a local humoral immune response within the central nervous system. A hallmark of this intrathecal response is the presence of electrophoretically demonstrable oligoclonal bands of IgG in the cerebrospinal fluid (CSF) of up to 95% of patients. Observations indicating that a major part of the CSF IgG in some patients may represent antibodies to SV5, a simian virus closely related to human parainfluenza type 2 virus, were recently reported by Goswami et al. We have studied thirty patients with multiple sclerosis, but although we find intrathecal synthesis of IgG antibodies reacting with SV5 in seven of these, the antibodies were not associated with oligoclonal CSF IgG bands and could in each case be explained as potentially cross-reacting antibodies to other paramyxoviruses known to be human pathogens. We have therefore been unable to confirm that SV5 may be a major intrathecal immunogen in multiple sclerosis.     

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.     

单元机组协调系统的多模型自适应解耦控制

针对火电单元机组被控对象多变量、强耦合及模型参数随负荷显著变化的特点,提出一种基于多模型自适应解耦控制的协调控制策略.采用多个固定模型和2个自适应模型并行辨识机组对象的动态特性,在每个采样时刻基于切换性能指标选出最优的局部模型作为当前模型,并据此设计解耦控制器,从而实现全工况运行的自适应控制.同时对多模型控制系统的全局稳定性进行了证明.通过对300MW亚临界直流燃煤机组协调控制系统的仿真表明:该控制策略对负荷变化适应快,且可获得良好的动、静态解耦控制效果.     

Functional epistasis on a common MHC haplotype associated with multiple sclerosis

Genes in the major histocompatibility complex (MHC) encode proteins important in activating antigen-specific immune responses. Alleles at adjacent MHC loci are often in strong linkage disequilibrium; however, little is known about the mechanisms responsible for this linkage disequilibrium. Here we report that the human MHC HLA-DR2 haplotype, which predisposes to multiple sclerosis, shows more extensive linkage disequilibrium than other common caucasian HLA haplotypes in the DR region and thus seems likely to have been maintained through positive selection. Characterization of two multiple-sclerosis-associated HLA-DR alleles at separate loci by a functional assay in humanized mice indicates that the linkage disequilibrium between the two alleles may be due to a functional epistatic interaction, whereby one allele modifies the T-cell response activated by the second allele through activation-induced cell death. This functional epistasis is associated with a milder form of multiple-sclerosis-like disease. Such epistatic interaction might prove to be an important general mechanism for modifying exuberant immune responses that are deleterious to the host and could also help to explain the strong linkage disequilibrium in this and perhaps other HLA haplotypes.     

交通污染排放的纯语言型多属性群决策模型

为了有效评估不确定性交通污染排放控制方案的优劣,针对客观事物的复杂性及人类思维的模糊性,在构建影响其方案选择的指标体系基础上,利用语言变量刻画其不确定性,考虑决策者的主观偏好,研究一类该问题的多属性群决策模型。该模型有效地避免了传统方法无法处理交通污染排放属性权重完全未知、属性值和对方案的主观偏好值的缺陷,从而使得交通污染排放管控决策更具有科学性和合理性。以某道路的5个交通污染气体排放方案评估为例,并与无决策者主观偏好的方案排序结果比较,验证模型和算法的有效性。     

Analysis of human T-lymphotrophic virus sequences in multiple sclerosis tissue

Several observations suggest that retroviral infection is involved in the pathogenesis of the human demyelinating disease multiple sclerosis (MS). First, lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III), the agent of acquired immune deficiency syndrome (AIDS), has been shown to be neurotropic in man. Second, the genetic organization of the lentivirus visna, which causes a chronic demyelinating disease of sheep, closely resembles that of LAV/HTLV-III. Recently, Koprowski and colleagues reported that MS is associated both with raised levels of circulating antibodies to HTLV-I and with the presence of HTLV-I-specific RNA within cell lines derived from the cerebrospinal fluid (CSF). Here we report that no HTLV-I-like or LAV/HTLV-III-like sequences can be detected, by in situ hybridization, in central nervous system (CNS) tissues from MS patients, and that nonspecific HTLV-I-like signal in peripheral blood mononuclear cells or in CSF cell lines is characteristic of MS. Furthermore, enzyme-linked immunosorbent assay (ELISA) analysis of circulating and CSF antibodies for HTLV-I reactivity fails to distinguish between MS and control groups.     

多通道多业务媒体接入控制协议研究

提出了一种优先级控制的多通道多业务随机接入协议,协议将信息分组按照优先级高低顺序从空闲信道中随机选择信道发送,理论分析和仿真实验表明,该协议能提高系统资源利用率,并优先为高优先级业务提供服务,是一种有效的多通道多业务MAC协议。     

一种新型访问控制模型的研究及其应用

针对NIST RBAC参考模型的局限性和当前DBS中安全机制不足等原因,提出一种可扩展的、基于角色的、多种访问控制安全策略组合实施的EMC-RBAC访问控制模型,并将这种安全模型应用于Web数据库系统的访问控制中,建立一种基于角色的自主访问控制和基于属性标记的强制访问控制相结合的B2级Web数据库管理系统的应用原型.     

Lack of evidence for involvement of known human retroviruses in multiple sclerosis

The recent report by Koprowski et al. that human T-cell lymphotropic retroviruses (HTLVs) may be involved in the development of multiple sclerosis (MS) has aroused much interest. The report was based largely on immunological evidence, using enzyme-linked immunosorbent assays (ELISAs) with viral antigens or disrupted virions. We have accordingly sought confirmation by screening sera and cerebrospinal fluid (CSF) samples from MS patients against cell lines infected respectively with adult T-cell leukaemia (ATL) virus (ATLV/HTLV-I) of Japanese cells (MT-1 and MT-2 lines), our own isolate from British black patients with ATL, the MoT cell line which produce HTLV-II, and our own T-cell line containing a local isolate of acquired immune deficiency syndrome (AIDS) virus (C-LAV/HTLV-III). We have failed to find antibodies against these retroviruses in the sera or CSF. Furthermore, neither virus could be isolated from the peripheral white blood cells of two MS patients.     

A mathematical model for optimized operation and control in a CDQ-Boiler system

Based on analyzing the thermal process of a CDQ (coke dry quenching)-Boiler system, the mathematical model for optimized operation and control in the CDQ-Boiler system was developed. It includes a mathematical model for heat transferring process in the CDQ unit, a mathematical model for heat transferring process in the boiler and a combustion model for circulating gas in the CDQ-Boiler system. The model was verified by field data, then a series of simulations under several typical operating conditions of CDQ-Boiler were carried on, and in turn, the online relation formulas between the productivity and the optimal circulating gas, and the one between the productivity and the optimal second air, were achieved respectively. These relation equations have been successfully used in a CDQ-Boiler computer control system in the Baosteel, to realize online optimized guide and control, and meanwhile high efficiency in the CDQ-Boiler system has been achieved.     

具有多种传播方式的介水传染病模型的稳定性

建立了一类具有直接传播和间接传播两种传播方式的介水传染病模型,讨论了感染的水资源对疾病传播行为的影响.定义了模型的基本再生数R0,给出了各类平衡点存在的条件阈值.利用二阶加法复合矩阵,分析了模型地方病平衡点的全局渐近稳定性,给出了疾病持久的条件.     

基于强跟踪多模型估计器的作动器故障诊断

在多操纵舵面飞机的自修复飞控系统中,快速准确地获得作动器的故障信息至关重要。该文将多模型思想与强跟踪滤波器相结合,在多模型自适应估计方法的基础上,提出了一种基于强跟踪多模型自适应估计器的作动器故障诊断方法。该方法改进了多模型自适应估计方法的不足之处,具有较好的鲁棒性和较强的自适应能力。它适用于非线性系统,能在线快速地检测出故障,并能较准确地估计出故障的大小。通过对各种作动器故障的仿真,验证了该算法的有效性。     

煤矿测控网络模式选择

选择测控网络模式,实现煤矿企业的信息化网络化,是构成煤矿企业网络的基础.通过比较,采用工业以太网,以其成本低、传输速率高,加上其技术成熟、应用广泛,又有丰富的软硬件资源和广大工程技术人员的支持,是很有发展前景的测控网络.     

T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis.

Multiple sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral encephalomyelitis and because of the presence in the blood of multiple sclerosis patients of in vivo-activated T cells reactive to myelin basic protein. Immune involvement in multiple sclerosis has been further suggested by the association with the major histocompatibility complex class II phenotype DR2, DQw1. To define the T-cell specificity toward myelin basic protein, 15,824 short-term T-cell lines were established from multiple sclerosis subjects, subjects with other neurological diseases, and normal controls. Here we report a higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84-102 in patients with multiple sclerosis compared with controls. A second region, identified between residues 143-168, was recognized equally in multiple sclerosis patients and controls and was associated with the DRw11 phenotype. These DR2 and DRw11 associations were also observed among T-cell lines generated from family members of a multiple sclerosis patient. The immunodominant 84-102 peptide from myelin basic protein was both DR2- and DQw1-restricted among different T-cell lines. These results raise the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals.