CD8α+ dendritic cells prime TCR‐peptide‐reactive regulatory CD4+FOXP3− T cells

CD4⁺ T cells with immune regulatory function can be either FOXP3⁺ or FOXP3^?. We have previously shown that priming of naturally occurring TCR‐peptide‐reactive CD4⁺FOXP3^? Treg specifically controls Vβ8.2⁺CD4⁺ T cells mediating EAE. However, the mechanism by which these Treg are primed to recognize their cognate antigenic determinant, which is derived from the TCRVβ8.2‐chain, is not known. In this study we show that APC derived from splenocytes of naïve mice are able to stimulate cloned CD4⁺ Treg in the absence of exogenous antigen, and their stimulation capacity is augmented during EAE. Among the APC populations, DC were the most efficient in stimulating the Treg. Stimulation of CD4⁺ Treg was dependent upon processing and presentation of TCR peptides from ingested Vβ8.2TCR⁺CD4⁺ T cells. Additionally, DC pulsed with TCR peptide or apoptotic Vβ8.2⁺ T cells were able to prime Treg in vivo and mediate protection from disease in a CD8‐dependent fashion. These data highlight a novel mechanism for the priming of CD4⁺ Treg by CD8α⁺ DC and suggest a pathway that can be exploited to prime antigen‐specific regulation of T‐cell‐mediated inflammatory disease.     

Aging effects on selective attention-related electroencephalographic patterns during face encoding

Previous electrophysiological studies revealed that human faces elicit an early visual event-related potential (ERP) within the occipito–temporal cortex, the N170 component. Although face perception has been proposed to rely on automatic processing, the impact of selective attention on N170 remains controversial both in young and elderly individuals. Using early visual ERP and alpha power analysis, we assessed the influence of aging on selective attention to faces during delayed-recognition tasks for face and letter stimuli, examining 36 elderly and 20 young adults with preserved cognition. Face recognition performance worsened with age. Aging induced a latency delay of the N1 component for faces and letters, as well as of the face N170 component. Contrasting with letters, ignored faces elicited larger N1 and N170 components than attended faces in both age groups. This counterintuitive attention effect on face processing persisted when scenes replaced letters. In contrast with young, elderly subjects failed to suppress irrelevant letters when attending faces. Whereas attended stimuli induced a parietal alpha band desynchronization within 300–1000 ms post-stimulus with bilateral-to-right distribution for faces and left lateralization for letters, ignored and passively viewed stimuli elicited a central alpha synchronization larger on the right hemisphere. Aging delayed the latency of this alpha synchronization for both face and letter stimuli, and reduced its amplitude for ignored letters. These results suggest that due to their social relevance, human faces may cause paradoxical attention effects on early visual ERP components, but they still undergo classical top–down control as a function of endogenous selective attention. Aging does not affect the face bottom–up alerting mechanism but reduces the top–down suppression of distracting letters, possibly impinging upon face recognition, and more generally delays the top–down suppression of task-irrelevant information.     

Cardiac autonomic characteristics in infants sleeping with their head covered by bedclothes

The risk of Sudden Infant Death Syndrome is increased in infants sleeping with their head covered by bedding items. This study was designed to evaluate cardiac autonomic nervous controls in infants sleeping with the head covered by bedclothes. Sixteen healthy infants with a median age of 12 weeks (range 9-13 weeks) were recorded polygraphically for one night. While they slept in their usual supine position, a bedsheet was placed over their head for about 45 min. All infants were challenged with the head covered and with the head free during both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Sleep, breathing and heart rate (HR) characteristics were recorded simultaneously, together with rectal and pericephalic temperatures. In both head-free and head-covered conditions, autoregressive spectral analysis of HR was evaluated as a function of sleep stages. During the head-covered periods, parasympathetic tonus decreased and sympathetic activity increased in both REM and NREM sleep. Compared with the head-free periods, the head-covered sleep periods were characterized by greater rectal (P = 0.012) and pericephalic temperatures (P = 0.002). Covering the infant's head with a bedsheet was associated with significant changes in autonomic balance. The finding could be related to an elevation in temperatures within the infant's microenvironment.     

Different immunogenicity of H-2 Kb-restricted epitopes in natural variants of the hepatitis B surface antigen

The small hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV) has limited variability, but some serotypes and genotypes have been defined. Although no biological or pathogenetic differences could be traced to HBV serotypes, the clinical picture, response to treatment and long-term prognosis of HBV infection may vary with the HBV genotype, possibly due to differences in specific T cell recognition of HBV antigens from different genotypes. We analyzed murine CD8(+) T cell responses to two K(b)-restricted HBsAg epitopes primed by four different HBsAg variants using protein- and DNA-based vaccination protocols. The K(b)-binding S(208-215) epitope 1 is processed from exogenous but not endogenous HBsAg. Variants of epitope 1 differing at two positions within the epitope (ILSPFLPL in ayw/adr versus IVSPFIPL in adw2) efficiently primed cross-reactive CD8(+) T cell responses. In contrast, the exchange of an N-terminal flanking residue (S to N) completely eliminated the immunogenicity of epitope 1. The K(b)-binding S(190-197) epitope 2 is processed from endogenous but not exogenous HBsAg. A single-residue exchange within the epitope (VWLSVIWM in ayw/adr versus VWLSAIWM in adw2) completely eliminated the immunogenicity of epitope 2. Single, conservative residue exchanges can thus give rise to diverging CD8(+) T cell repertoires, suggesting an impressive complexity and flexibility of the CD8(+) T cell repertoire to antigen variants from viruses with limited diversity.     

Molecular typing of the bacterial flora in sputum of cystic fibrosis patients

Despite recent advances in therapy, lower airway infections remain the major cause of morbidity and mortality in cystic fibrosis (CF) patients. Bacterial colonisation of the lower airways in CF is limited to a few bacterial species, commonly Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae. Burkholderia cepacia colonisation is much rarer, but it has been thought to be associated with more advanced lung disease and increased mortality. A rapid characterisation of the bacterial flora in sputum of CF patients is of great importance for proper treatment. The aim of this study was to establish bacterial profiles and to identify pathogenic bacteria in respiratory specimens by means of molecular methods including temporal temperature gradient gel electrophoresis (TTGE) and DNA sequencing of PCR amplicons derived from 16S rDNA variable V3 and V6 regions. Sputa of 13 CF patients (7 males/6 females, age 19-59 years) collected at the Stockholm CF centre were analysed. TTGE revealed the presence of complex bacterial profiles in all samples. The V3 and V6 PCR amplicons were cloned and sequenced by real-time DNA Pyrosequencing. DNA from Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa, respectively, was identified together with sequences from normal oral cavity flora. The results were in reasonable agreement with those obtained by conventional bacterial culture, considering that only known CF pathogens are included in routine reports. However, the methodology seems too elaborate to be introduced into daily routine     

管道骨骼线三维重建在肝脏可视化的应用

目的 研究三维重建数字化虚拟肝脏的方法.方法 将肝脏管道灌注后的肝脏标本进行螺旋CT扫描,获取CT扫描连续图像数据集.然后使用面绘制移动立方体(MC)算法重建肝脏及其内部管道结构表面模型,并对模型进行平滑和简化.确定出管道树上的关键节点,并使用改进的种子生长法生成管道树.将生成管道的表面模型和管道树相结合实现交互式分析.结果 肝脏管道灌注和铸型良好,螺旋CT扫描获取连续肝脏断面图像数据集242张.基于骨骼线提取的肝脏管道结构三维重建肝脏模型形态逼真,交互性强,通过设定各结构的透明度和颜色能单独或组合显示肝脏、肝静脉和下腔静脉、门静脉、胆囊,并可通过旋转、放大、缩小模型观察各结构.结论 基于肝脏管道骨骼线的方法进行肝脏及其管道系统三维重建可视化肝脏,生成肝脏和内部管道系统,立体空间感强,交互性好.     

Chain Connectivity and Conformational Variability of Polymers: Clues to an Adequate Thermodynamic Description of Their Solutions, 2

In Part 1 of this contribution we have reported how the Flory‐Huggins interaction parameter χ can be modeled as a function of chain length within the composition range of pair interaction between the macromolecules by means of the three parameters α, ζ, and λ. This contribution presents the extension of the approach to arbitrary volume fractions, φ, of the polymer and its application to published data on χ(φ). The resulting equation reads χ = α(1 ? νφ)^?2 ? ζ(λ + 2(1 ? λ)φ) and requires only the additional parameter ν to incorporate the composition dependence. Its employment to experimental data is very much facilitated by substituting for χ_o (limiting value for φ → 0); furthermore, the expression can in good approximation be simplified to χ ≈ (χ₀ + ζλ)(1 ? ν φ)^?2 ? ζλ(1 + 2φ). That is: only two parameters, ν and the product of ζ and λ, need to be adjusted. This relation is capable of describing all types of composition dependencies reported in the literature, including the hitherto incomprehensible occurrence of pronounced minima in χ(φ). For a given system the evaluation of the chain length dependence of χ_o, reported in Part 1, and the present evaluation of the composition dependence of χ yield the same data for the conformational response ζ. Similarly both types of measurements generate the same interdependence between ζ and α. The physical meaning of the different parameters and the reason for the observed correlations are discussed.

Interrelation between ζλ and α for the evaluated systems.     

网络成瘾者失匹配负波研究

目的：了解网络成瘾者的失匹配负波（MMN）的波形特点和变异情况。方法：应用Odd—ball模式在非注意状态下对网络成瘾组和对照组进行事件相关电位MMN成分的检测,分析其波形特点及潜伏期、波幅的变化情况。结果：网络成瘾组与对照组均出现典型的MMN波形,其中以Fz导联波幅最大;网络成瘾组在Fz导联的MMN的波幅明显高于对照组[网络成瘾组为（9．58±3．27）12V,对照组为（7．52±3．36）pV,P〈0．053,但两组潜伏期比较,差异无显著意义[网络成瘾组为（212.00±22．53）ms,对照组为（217．55±25．81）ms,P〉0．05]。结论：网络成瘾组MMN的波幅升高,可能与其对信息变化的自动检测功能出现一定程度的下降有关。     

基于CUDA的快速三维医学图像分割

目的:三维分割是医学图像分析和可视化中的重要组成部分,也是医学图像分割中的一个难点。水平集方法在三维医学图像分割中有很广阔的应用前景,但是该算法的计算量大,不能达到实时处理的要求。针对这个问题,提出了一种基于CUDA的并行加速方法。方法:采用NVIDIA公司的GPGPU模型CUDA,利用图像像素的独立性和偏微分方程求解的并发性,提高C-V水平集算法的分割速度。给出了并行计算的流程图,并对C-V水平集算法在CUDA上的实现进行了详细介绍。结果:实现了C-V水平集并行加速算法,该方法在保证分割效果的前提下,具有更快的分割速度。结论:所提出的方法是切实可行的,实现了快速的三维医学图像分割。     

Rational approaches to immune regulation

Our laboratory is interested in the properties of proteins that render them immunogenic, and how such immunogenicity may be modulated in vivo. We are attempting to enhance the immune response in the design of more effective vaccines against viral diseases, such as HIV, and against tumor antigens expressed on breast, ovarian, and cervical cancer and B cell lymphomas. Our main approach is to use a facultative intracellular bacterium, Listeria monocytogenes, which has the unusual ability to live and grow in the cytoplasm of the cell and is thus an excellent vector for targeting passenger antigens to the major histocompatibility complex (MHC) class I pathway of antigen processing with the generation of authentic cytotoxic T lymphocytes (CTL) epitopes. In the field of tumor immunotherapy, we are also developing nonliving vaccine vectors for tumor antigens.